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To AVOID FINES return on or before date due.
MAY BE RECALLED with earlier due date if requested.

 

DATE DUE DATE DUE

DATE DUE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

6/01 c:/CIRC/DataDue.p65-p.15

s SCIENCE

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By

Robert James Fawnatt

L T”; " 3

Submitted to the School for Advanced Graduate Studies of Kichigan
State University of Arriculturo and Applied Science
in partial fulfillment of the requirements
for the degree of

[FCICTQJE 0F PIEILGSt-‘PEYY

{apartment of Chemistry

 

The author wishes to express his timers
appreciation to Professor Robert 3. Sonnet:
for his friendly counsel timghout the
course of thin wax-3..

*WHW

ii

VITA
Robert James Fawc ctt
Data and Place of Birth: June 9, 1926, in Halbridgc, Ohio.

E'Aucation: Public School of ”naléziricgn, Chic. Graduated from
Bowling (Ix-can Stats Univsrsity, Bowling: Green, Ohio,
19135-1950. Bachelor of Soiencs, this Lauoo, 1950.
iiicI-Iigan State University, hat Lansing, Michigan
1950-1955.

Professional Positions: Student Assistant, Bowling Green State

University, 1959.

Research Assistantship, Bowling Green State University,
1950.

Graduats Assist-an Michigan State University, 19570-19355.

Chemist, Research and. E's-velopmnt iopartmant, tycth Inc.,
Mson, r-izichigan, summer 1952.

Research assistant, hammering ilwtpormcntal Station,
Kichigjm State University, sum-not- 19534.

Research Chmfist, The B. F. Goodrich 00., Brcoiesvilla,
Ohio, 19:15.- ~

Professional and Honor Societies: American Chemical Society.
The Society of the $151.19. Xi.
iappa Itu £4.psilon.
Boob: and Rotor Scholastic Honorary Society.
Chemical Journal (limb of Bowling; Grssn Stats University.
Chemical Follow, Bowling firm Stats University.

111

 

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Page

Ixraasucrzcx.....................................................
HISTGRICAL.......................................................
Lxscussxau...........;...........................................
EXPERIEEE? ........;............................................
2,5-c1nnthy1thiopheay......................g..................
Preparation of 2 ,S-IT imthyl-3dbhioph enemlfomrl C hloririe . . . . . .

Lotemzmtion of the llwtrclization Equivalmst of _ _
2,S-Limethyl-B~thiOphen68ulfonyl Chlorifiioooooooooooo0000.0

2,S-Dinothyl-B-%hiophanosulfcnamifia.o.......o..u.......o..u-..

fraparauan 0f 2.5-1Methyl-S-miophenethicl. o o o o o o o o o c o 0 o o o o o

Attempted Synthasia of 2 , S-Eimt‘uyl-B-thiophaneth 101 by Zinc
Sulfuric Ac 1d Rw‘uc non of 2,5fimflzy1-3-thiophenmlfom'1

Chloride...................................................
Attmptod Efionobromimtion- of 2 ,S-Ejimamyltl’xiophena.u...u.....
Proparation of 131101: Msrcnrie 05116000000000.0000.0.0000000...
Preparation of 2.5-2! methyl-J-imthiophmo................ ...

Attmptad Synt‘zxasis of 2 ,S-I inetlwl-3-tiziopizsamthiol by. the

1
h

96
91
92

Grignaré RGQCtion on 2.S‘CififlthYl'B‘iOCOthiCphenao.09.on... 130

2,5.Simethyl'3'thicphenQCIbeXYIic Afifioooooooooooooooooooaooo 13$

Pra’flr‘ticn Of Pctassium F firfifan Sulfide.....................
A) a

Attempted Syntz-xuia of 2,5-1‘Lmt1y1-3-th10phenethiol by the
Reaction 01’ Potassium E‘Iydrogan Sulfide with 2 ,S.;'-i:aathy1-

12-7

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Pmemfion of 2 ,5-Ein::?31a:rov-3 Map? amzmlfamama . . . . . o . . . . . . 113
Isolatinn of Seaman 2,5m..-..13ro-3¢..a.x .mmfi'mta. . . . . . . . . 1...‘ ""

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Preparation of Qi‘hwgrlfi‘AOpfiana from Sasha 9 .Bflflfig'y'l.

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Frwwatian of Z-F'nanylthioiiwm by the 1.1.13.0 Brmtim..uuu 3.2?
Pr aflwation a: 2-1‘? 1--..1mt1u.............3.................. 132.
The Reaction of 2-?lesodium vim cfiloz.a:znmm............ 133
Preparation of 30:39.31 Amiga in Either.............‘.a........... 13?

Preparation 0: S‘m'lw&siwmém.0.00000.00.000.009000co Ba

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TABLE (f CttlT'32‘l‘3 - Continua-:3 1433553
Prwuation O! 241-":21319-37933."1) tizicphsnfiouuuno"...n. LA}
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Preparation of S-thl-Q-tfzirsgmne ‘1101.................. .... ll.)
Propagation of S‘fimfib-fi 42*: Maybe 531031.123 Prof-11:36 . . . . . . . . . . . . . 1573
Tho Fmparati on c! S-Ih'cm-iz-(l' -c;.'c... CF";- 33;;1” 013‘...) tfziognfaam. . . . 117:.
Frapmtion of S-Bmm-E-(l' anti-3333:». my” -) ti: ' 04:19:25 . . . . . . . . . . 1513

Attosptad Pehfromtfion of Sq?m'~o-2.(l' .cwlsanml)
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Lithium Winn“ Wyv'd‘itia Raf-UCtiOn O: 541' Jyu10333xrfifil-l).
2“}113113'1 z-‘isduii‘QOQOOOOOOOOOO'OOOOOIOIOOOOOOOOOOOOOOOOOOOI 1’1

Prapfiration 0f 71”“:{1 fl'i2.n:1:~"391£tfi............................ 1'3
l’ref-arfiion 0f riflfi131 Thimflfi Ulfiteoooooooooooooooootoo-coo 13’1“»!

Fregaration of the Macadam Salt cf ; ._ icwbgmmmv-
Jikfifi‘fim4mfiiopi'im30oooooooooooo:o00.900.000.000.coco... 1%,)

3.4- LmW‘szy-Qp {hfi‘fiOuALWIOQ’L 10:")? iifiufiooooococoooooout... on 1‘-

Attmptm’ mtheaia of 2, ’5-2 ..crx‘xzmt‘ {rm-1 iiéhgfl‘hmm
“1103753113 Vital“! “3‘" 5'1 101-153...00000000000000.0000...coo... 1?J

151'me Of COP-135? Chmflim Cam’atooooooooooooooooooocoo. 17,5
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Preparation of 3,1:cr'1mtkowfi-bmctm optame {Iain-2.; F untam-
UJccinL'fiiLTQ ” f3?! 1““‘5‘fua‘ 1".“ ’= "wit-000.000.00000000000000 1:22

x11.

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“1.3 Ci CA 14’1"}{1‘3 - Continued- Page
Attempted Synt‘wslt of 3,114.12“:-oxy-2-t1tlo;)hgnat3~iol.."up. 13k
Z-Acatyltlaiophanau"nun-nun.nuan...“.3..."”u... 1‘35
24thmpimnocurboxylic Aeid...'....;...;........................ 13-7
11.5-31bromo-2vtfziOphmortar-bowl“ Minna...”............... 158
2.3;:ibmm0u310phflnao00000000000too¢¢oooocouoocoonccogoo.cooo. 13?
Praparation or 24’1paridmod-othlnol...uand......an"... 13‘].
Preparation of Qqurpizolino-l-pthmql...g...t.........¢....... 2193
Preparation of h-Farpholino-l-butanolguuuuuuunoun... 19h
jdbrpholino-lwhloropropmauu..t...‘.§..u.'..uu.....;nu... 19$
3-(§,E-iliamylminc)~1-cLloropropano.”.1....gt..g..g......... 137
3% lper 13:130‘1‘Ch10I‘VODI‘UPHZQOcoooooccoooOooo000009000000000000 193
Fraw‘ation of h-zicrpholino-l-cmarcfiutam Eyérocmorléa....'.. 199
Prapu ation of“ us“ .rp..g.......0‘u-L. lcz‘cetfmna Hydrochloride...... 2:1
Preparation of Zi’mriaigao-l-chlmoo time Eb’dI‘OChlflrmaooaooo 2:11
Fraparatlun of .a‘oramu,u£.o 61:10:02 .j,drin..uuuu....n.uo 2111-2

Pr “33313131011 0: Y .2 tarp: -°131°"n‘?1‘°§33'1-2,Sdlmthylfi-thimyl
Sulfide flyfirOChloridfioooooooooo............................ 2C3

Preparation of Y~Piparlfihm-mpropfl-Z,Sqlhmflnylflfimgfl
SUIflde Hyflrochloridaoooooooouosooooooooooo-ooo00.0.0000... 2b;

Preparation of Y -(.~-.',": so? iathylmho)cn-progayl-fifl-dmzat‘xylo
B-thierg '1 Sulfise LytirfichloriCa............................ 2J6

I’rg-araticn of P 42 ,2: ~27 19 £2313:an ) ethyl-2 541.261.}:on _
3"d1&ny1 Sulfide HfflffiCthTiCO-oooococoon-o0.0.00.0.coo... 2L8

Preparation of P-(E’,1‘J-Ii2:eti 2ylar~L*':o)et1:yl-2 ,S-d imflxylo
B‘thiaflyl Salfid. 33d? chloride.......................o.... 2C9

Preparation of F-Fiparidino-athyl-l’,S-dbaxa’myloj-vfiaiwl
Sulfide HydrOChloriéooo-ooo00-00000on...aoooooooooooooooooo 211

xiii

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Preparation of f.‘ cz‘twpfiolinoctizyl-E ,5 -ci L1i3fil¥1¢3¢iflf$1
SUlfid. HyflPOChloridBooooo00000.00...cocoooooo:ooooonone-o.

Preparation 01‘ 9-05, 11-1 139313? lawincha-cxetkzyleflv’l-Zfia
cinet 2¥1"‘L.1133f1 Suiting :W- rccnlorif -0000.ouoooooocoooooo

Preparation of 5 «ifomfizolino-n-bu tad-2 ,S-d 1mt‘or1-3-‘mimvl

ii“. A ‘K: $- ‘ l '5
unlfibc nJfiICCu—Cr1¢000coco-0.00.03000-oooooatuccvooooocooo

I reparati or: of " fivazzriclincet3l -2 ‘7' -c21c1.loro~3~t.h1m3'1
331:163 Hyuro-110F110..oo....o........o....................

Frmat ..on 01' 9 11-4, 2’ -." *at}~yla.'mo)a+‘~v1o2,5~c10110m-
3""33313ul:ii; HJLrLCulCriL3.ooooooooooooooooooooooooocn

Pru, taxation of ?-(13,!I-€T;’.zwth}1.¢ 1:10)-c~:.cth3rlatl.yl-2,S¢
fichlorD-B¢tu1anyl SlLfiita EynroctloriGO..................o

Prwamticn of Y {13:22-1‘Jzo-zdrcmrl-2 E-d..cE~J.oro-3dt.h1m3'1
SUlfidO fiYfiPDCh10?iCGocooooacooooooczo00000.009000000000000

Pmration of r «£10.21011no-nmropy1c2 ,S-dichloro-y-thienyl

1“ 0!. L
4 in, JLfiabu19.&~Soooooooocuooooooooooooootooooooooio...

Prmrati- n c! v-(V, ‘1' -:‘i 2121;“ m*v~c)«n‘rrt'r*‘-2 Sékfilma
B'thifinyl 301:150 Hytroc“loriuaiOOOOOOOOOOOOOOOOOOOQIQOcoo.

Preparation of fi-Piperminoethz'l-S-phml-Q-thiml Sulfide

:JfiPQChloriJaoooooooooooooootoooooouoooooococoocoo-o-out...

I 1221212" ation 01' Y’ -E ipariz. ‘13:: {.mpy‘b- 5-1;"...1'2, 122-11322}.
331515. fildrOCfilD”lu.uoooooooooo‘cofoooooocoo-000.00.00.00.

Fraparation of 2' ,h' émitmp21wgln2 ,5” «'1 123211.319 «kiwi

SUlfidDooccooouoocooooooooooooooooocooooooooooooooooooo-ooo

Preparation of 2' ,h' drummer-9'14,S-dichlcro-C: ~t1.1m~.:;1

'2‘.‘ ‘9 .:
h33$£1£fl°000§00000000.0.0.000...0.00.00...0.000%ta0.0.00.0...

Praparation of 2',1.' oi:1n1t1‘pp2221'1y1-Z-fpimvl-fl4:219:17}. 3 ”ice.

SU-J-I-I‘un-IO.OOOOOOOOOOOOOOOOOOOQIOQOOOOOOO.OOOOOOO000......000000000

BIXIUR’).P1.0.00.0.....OCOOCCICIOOI0.0.0.000...00.000.000.000...

T1133 CF CSI‘E'KL‘S «- Contizmod 13830

215

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LIST C! 132133

g
E")

2,5‘5'113'4‘3 Itimtad-Bdfidoflxma Sunnlumiéefi o o o 0 I o o o q o o o o_ o a 0

$1».

2,1:tZ‘I-1nitro'pheny1 Sulfifia formative! of Ring Substituted

.P‘siiophanau'iiouoooo0.000000000000000000000.000000000000000

B

Chlcromflfozmtion offlS-fi‘.‘ 16311013321093an with Chloro-

lulfonic ACido-oonooo.ooooooo000000.090cocooOooctogogoogoo
IV fiMlfiiCfll Rmzjo’ With Substitutmi 71110;):1‘31393 o o 0 at O O. I o o o a
7 Km: Bruno Derivativaa or Substimfiad Thiophanos . . . . . . . . . . .

VI Sumry of the £7ocarbozq’lation of 3,};«ifiimathmqr-
2,5-iicarbcxythiophenn...o....o.............ooo...........

VII w 433,31-I‘1alkylammo) nlkyl-LS-dimt’uyl-Bdthiwl
3ul£iuo EyCrOCthPidB‘oooocoooooooooocooonooooooocoo...coo

VIII w ~(3,fi-lrinlkylmmo) ulkyl-Qfi-diohloro-G-thiml
Sulfida ”yfirOCthYISGCooo-ooooc00.00.00.000.cocoa-00.00...

IX w ~(R,E-Ii-1.al‘q'lmnino) mcyl-S-phm-Q-thianyl Sulfide

HydTOChloridaflc00000-000000.000.00.00.00.oooocoo-000000.00

F333

25

2?

LIST 63? 1"”3
T ' E rag-2
mam 53ow 0f 2 ,1..¢\JiZ-36t.l}'l‘J.tfliopaA333 {32.13.01 0 0 o o o u o o o o 31
Gmwmtim 01' 2,54. 102110Nfiiiop'22en9. . o o g Q o o o o o. o o o o o I J}
In!” SPOOW‘ of 2 ,,y£310.}110P0.3"fi“aiOphfiRét-Elifil - a o c o o o o o o #2

Infra-rod Spectra. of S4’21m'v1o2-t1110phmmthiol. . . . . . . . . . . . . . (>1

mruuwg

Infra-rad Spectra. of S-(l'dfi'yclohwsrzm'l)~2-téziophmwthiul... 64

and

1.1473033 CT ION

Simo the diIcovory Ind isolation of thiophom in 1302 by Victor
rigor, tho history of 153110th chozaiatry chow periods of rapidmd
soda-Ito youth. Tho discovery and isolation of thiophemo m not tr.
um beginning of thicphono ohmiatry. Laurent (1), in 15134, 1.51am
I Ionpmnd formed dun polymeric thiobmsaido‘zxyxio m dosh-actively
«sun-d. his so; until 1891, homer, that this compound as sham
tI ho 2,3,h,5~totraphowlthiophmo by Bowman and From (2) who Iynthosiaod
it from Itilbm Ind Iulfin‘. Fofioflng the period of diocovozy and. study
It Mom by Victor Mayor (3), higalightod by tho publication of MI
hook " oi. MOW," intent m generated in thicph one c2 wintry
II Ihm by tho 1‘ 11‘1")! IrticIII thick oppoorod in tho litomturo during;
tho knowingtwo yum.“ 1'22. next. period or development in thiophom
W I. initiated in 1915 when amen Steinkopi‘ began I lifetimo
Ihdy of thiovhm Ind itI dIriVItiVII. Thin period reached it's peek
If M in 19141 lith tho fiiblioition by Stoiniwpf of MI book
'DiI MO d0. Thiophons',‘ (15)- Th mix-mt warmed intoront in t‘rzioo
phm MI: in 1955if‘olloving thI diIooij and development by Socomr-
Vault: Oil Co... mo. of I commercial method for producing; thiophono from
nlm and butom. YhiI hu made ovailoblo, in onrzi cor moroial mantitioa,
Mono and I mini: or or itI derivatives. By 19 50 the chief cozmorcinl
III for unaphma and HI dorivnti‘voo m an intomooiatoo in the drug

industry. This period in the oonOpmnt of thiOp‘nmo chmiotry woo

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him by W“ book, 'Thiophm Ind ItI Mutt"? (S), which
mmmuaamiauaopnmnmmymmmu
mum. mt filo. - '

mmmutigIt-ioa dIILI IithInth-v Ipooirie bunch of
W W; mly, tho mthooio or III thiopbonothiolo Ila
m mum». II um II thiophm dwintim mob and In!" II
Wtor the mwumfi‘iophmoflnoh. .htilthomt
MytianmodytEm-I WWW!!!“ scaly,
W01,” 3W“ III cam-mm“- m ,
quuIWi-thommophmo
gun-u. ”ImthMtydW1MIIhW’
II“ 191:0“ Ind IIrly 1.930“ from tho thi'ophene prooIII, I good dad of
MIIWIIMImwmItIWMWWI
mgmntmmmmnmwudmmmi
”Moth-r mommim.’ mmmmmmu
“NWQIWWWWMM. Tholithiun
WWMMqumeImhfiMI
W mgr-round qpfiofih, fox-Writ” sin-gum
WIINWWIWWPI‘WIIWWI
ting. lawn-mm M'thIflMtiaIIithothor
wammnmmumehuuam-I. Moi
um). m.hddifluuobmmunuthiophuthiohm
-WMme'Imwmm’It-Mmtor
wring additional m thiaphmotMolI.

 

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Tho oooom phuo of tho promt imootigotion involvm‘. tho synthoaio
of IO!- N 0(N,E«3.1Ilkyl&u1m)alkyl-2 and 3 t‘z'xio‘m'l Iulflo‘o 2131?.roc‘aloridoI
tron tho horotoforo unknown trdophonothiolo prepared for tho first mm
u ”do ofidy. Tho interest in thin claoo of sulfur hot-orocyclio
WI rowitod from tho discovery by Schuota and Hour! (4,?) tEiot
Ion. N -(N,H-diIlklefino)IJJ<y1-3-C'Li 81"qu aulfido hydrochloric? on had
local moothotio Ictivity com-.3. to or groator than procaino in tho glinon
pig when toot. On the other hand, those Iona im’ootigotoro domnotrotod
Wt Iom I) 43,3-dialkylamino)IJl'yl-Z-thiervl sulfide mfirochlorizios did
not poomo looIl aesthetic octivity. In vim: of this fact, grants:-
who-is III phcod on tho preparation of nucloarly mbotitutod 34:11::-
phoaothiolo.

Tho Ilkyl oido chIinI II well as the terminal tertiary amino group
in tho w 0(21,E-dialicylmuino)allcyl-2 and 3-thiom'l rolfirio h‘fdrochloriz‘os
vol-o Iyotmtionlly varied to oscortoin their irfluonco on tho pharm-
ooutiool activity of tho tor—3 xix-y amino mlficio.

Thio investigation doalo only with tho study of mow-soon for propor-
ing thiophonothiol compounc‘o, on well on preparing; sovoral codes of tho
dorivotivoo to ho tootod for thoir potontiol pharmacological value.

Tho Ictuol tasting and. evaluation of those oonpvmrto as ciruijo is not
included in tho work herein ropertoc’... Their noomlnooo on now phonon
«19M Igmto mot omit tho laboratory and clinical tasting much

all ho done by on independent laboratory anti reportofi oloouhoro.

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Tho mom-to 3* 3 of £18 Love-3313113 on im- too :3 .1111: mmz-oooo. 2333.3
1‘ irat- , and cor-937;: 332-3133 to ram imprmtmt, 16:19 I start-3 of tho (3330511333?
loan on: to tn Iflt‘ 311519 of.‘ now rim; 33‘3ot3tltozi fill-€73.33!’32133'353-1318o The
oooond was to utilize the mm t i . ”-13.1an to yrojo m c‘ ori3mt3' ..voo or
pat-0:13.111}. pf-mfiomologinal vain-o.

3: mm and f3mfi‘ ('7 ,1?) 65 .1: 393-3 .. :3 t?- at soy-313w 43:3,12-aml;,-1m§m)
IL;31~33:3:13311,,o3.1..1‘;'-.3o 3:32? recall; 331.; 3:: 110- {31 mos 1.21.33: mot: 1-33.13:
that oqzolm or moo-1391:! grocoino in tin £115.wa pig wool test.

In contrast to t: :33 t‘ or also tom t: at too“ 431,513131’, 33‘ mammal :31-
hum-(,1 3111... 331:" o 3133 hoof... ~“ 9:31:33 3.12.: none or. vow little local moougotio
Ictivity in tho 33:33 toot. Fro-1 thooo rooulto it was omtioipoto-d

tut W .g-m Btl‘bfi’ml U 0(31,.h-(; 1317‘} '19: 1.30)al 3’1“?)43133‘" ’1 Elfl? 3
Wroo‘zaoridoo would be of particular inmost "booms-o of the pimp-.m-
oolngiool doth-31w of mo unsubstitatod 341119231 Ialfido ciorivotivoo.
mirth-or, than was no comma that bocouoo the 09 flan-cialt-yloomo)
Ilia’demi-myl mlfielo E1322: oi'ioxi-Sm proviouoly ctoooribod ( 7) had no
local mootlwtic activity fiat 031-313 ring In?- 1331mm: U -(?¥’,I'I-L i-ol- ylo
malnohll 5'1-3-‘tILl ‘1,- l 6111515.!!‘33331‘063133252'15399 10.:- 11:1 not‘z ova 543‘ 31:33:33. ty.
moroforo, it was or intoroot to program 80.319 of the tor-£1,511? I3“-'-;‘.'.-'Jla
dorrmtivoa of tiziophcmo rim; oa‘ootita. to! 2-311-3331,” 113-131 8431:3339 for

pE-aarmcologiool ovoihaotion.

A

marl Ira—r. animal-9 tm methods, or want-ion. of those, by winch
the term uaim derivatives 01., thiopism rim; mLatitutm-i, 2 1-1-3 3-
tllauylalkyl mlfid as could I). preparefi. Thu-y can be rare-eaten}. by
tho tanning; tam Iaqaamaa 61' reactions ,

afiama o c1(:;{.)n-:zz ---a- R‘3(ma)§3 0 330-01
/ .

 

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b)

185(0239133 + 5131' .._... RHSCCflahf-‘l o as, o 3-2;;
3 - 5. ,

flfl 5(ca)nk1 9 2111.13. a” 38803. 3.)nzq. '0 3353103911
. s 1 _ s, .

2.1.1. '11! 0 Aim-333)“ 4.33}! ---c- 3’, " C" in) OH 4- R 12311-1131

aficca):ca-U““‘ -----~ ‘11,” "’3‘“ . 11:1
. _ 3/ .

 

 

II

The first mama-.1 involves 3m comiowaiion of the 303.1131 salt of the
mi-O'tituteai tidflg-iiin'éthiol 3.131 {.11 9. 13.111133131713111 to f 0131:: t‘: 1-: GJ dum‘roxyall-Jlo
3¢fi1iany1 minds. 71319 was than Ill-3w: to ram-ct with many]. chloriéo
to cum-1n 111.6) ochloroalkyl-Bdmimwl dmvaun. In the nan. Itep or

— .._-

-Io“ .. 1II.

. x a. .
. l I Illi'a \ ‘1!
A-.- ll v ‘ 4 .H

' bl‘lxu IL

1“

tho mumo tho taunt-y dm‘intin «a ho W by Mag the
summary “no to rust with tho wnhlomdkyl-afium sulfide.
rho mmmnarnnmmwwywyl
Maximum“ dimmnth tho indium alto: tho
nun-1.1mm “mutual.

In tho, pram Wigntion, the lattar 80:111me of reaction Item.
‘I «flayed mural: time the over-van yield of the 11m pmmct
Ilia tomcat in tho “1213111th 12110111111111.1111): m mater won in the
am nomad. I'M. II n comidmtion of print: We: We
It tho mac-111.111“ unwind in synthesizing taro mm mtitim
at tho ”minted WWO]...

Seward methodl we wailablo for the ayntimois of the interr-
uluta tax-tiny amim 0.1602101: and their chloroa-srivutives. Brena: (3)
and 111: collaboratoro reported a mam-1:111 :11:- 1111 Iyntheaia of (111111111-
dno (11201101! by 11.1 roaction at 1317;1de with othylcna crflgmhchrL-u

in acetone) at a solvmt.
.19 .
m o (imam; m < - .mxacazaerman

Clinton (9) and hi: Malta'- used o mm mm, chtoming
Win parcmt guide, using av]. annual 1111 I mlvmt and a mi].
witty of sodium iodides. The sodium 1:16.169 shes-Lama the mtien
In. by 11163231159 at iodine far the chlorine: atom in the c! lax-02' ycirin.

man and mesh. (2.11) W fi-al‘ioroativl mrpholim by reacting
p-ffimn'flhyl when» with thiamrl 111101-1111».

“3

V .11 (Hut-5'1 . 1 o :oo 1.
\_/

Abs-1'3 um ‘2n1itmro (1.1) lama-13812013 y -c}1lorprom'1 mrpholim by
the interaction 01 mrplaulirw .1113 trimiéxylama clxlorabx'o1dzle in abs-slut.
bansano, to obtain the desired product and the hydrohromifio of morpholino
in stoichiometrie qnnntitiea.

Until the presant work, only thFOO different thiaphanethiolo havo
been raportafl 1n_thn literature. Listed in the ordar of their diocavary,
they no, 2-tliophsnati‘icl, 2-!3t213r1-2-ti119pi1m9taiol anti 3%.iophanatqiol.
Biodermann (12) praporod 2-th10phan0thiol in 19:! than a three percent
yield by reducing é-thicphensulfonyi chldrido with sine dust and hydro-

chloric acid

. . . _ 1 ”$0331 221,? I ‘43:!
s I-\'

V. mayor and lime (13) discovered Z-tMOphanati'xiol 1n the alkali-

Iolnblo portion resulting from the preparation of thfinp‘nene from succinic
acid and phDSphom pontnmlrido. Quasar om Branton (11;) prepared
adhiqwimnethiol in .1 20-31.; yield by the addition of sulfur to 2-11-4112,).-
ngnuium 10:11:39. some“ and Hour: (7) prepared Zothiophanetz 1101 from
2-bromoth10phono by a Grignn'd reaction with sulfur and from 2-u’1icphene-
”11011171 chloride by a sine dust sulfuric acid refluction. Thaw obtainad

a 67% yield by the Grignard route and I. 59% yield by the metal acid
Motion of 2-tlaiophonesnlronyl chloride.

..1.I{l1

inn. 1.

' Iv.‘

 

Granary-1111' and Earthen (15) prepared aesthyl-B-thmphanothial
by refining thiono [3,2-bJ-t2dopham with podium in alcohol.

   

The mamaptan, 3-f1hiopé1gnatl 1101 ’m obtaihad from the: tar. romad
in the commercial production of thispE-‘mm. Yl’aiofahmza in obtaimd by
allowing 1:11th and mm:- to met .1. noo° F. (113). The press”
pmhwaa approximately 5 LG} yield of thicpmfié and an equal amcmnt of
tar (1'11). Patna—15h. (intimation of the far 213 m gives n 3341132?!
yield 01‘ 3-u1iophonothiol. 73:13 following motion scheme has bean

prepoaod to mommt for the Bdhiophanatmol produced in $211. process:

wvduhuu/ 1 . 1.11...
13.13.") run“? .\ . w w \ .

‘

H
u '1‘!" n “
3" i

./

.-...--..-/ m .1 2H- / m 7 , —1..1l.u...r
- -- \ ”1.x .12

H

w 11r~°3 . 3
6.53. M. . 13233-3129311-9;.3+ 1133 -—--u- bi: .gggw'zgwfin

 

T3113 rwact'lcrn a ..za'nca was 1'11" 3111111113 a; 1.3:- the chaser-ration 13:13 1:31:53 that
l

Bulb-3r 3:11.111; 11‘" 13:! 811151-313 $111,115: to 313.1311; Ult': t?‘.1.o;1?1=.1r1.9 11:13:11:- t.3

.1139 c011.-- tins u in 1.213 313.321 1.13.119. 31.11.2111 £11311 .3113 93003351333351?

tad Breatan (1L) preparafi an 331333113 31: 19 of 3-12139132115131 by

MEL-13 311115.11! to S-tfi-arg'lrmgn'mium 1063.13.

M
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1:5

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at 1‘

 

I I + 11:1 .._...» I l + 11.13::

3

The sans tuthorn re rted the infrarad s¢3ctra ct Z-th10359m .3131
L .

and 3-1.31103121111-13‘11101.

1 .l .l’d
.u...IuIJ

r .. i...\
.r. ‘ v'
t

Brooks ( ..7) and his c0113.. crate-r I report. .313 a. 13:33 amiss: or
derivativu of J-tuop1mat..1ol.fall 0f the derivatives; w. u 11.111.111.321:
and aid not have any substituunts on 1.1.1 111191.11. ring 0211131133. tan C110.
nth-3r 11:11- 033.

T'so t-‘miaphmmt": 5.01:3 polyvarim 0116?.01‘339. to cimflc 3:12'13'1111-‘111213.
1'21: (13.: m- or 3-t. 11011-1sn6t21301 can be pmlyzed in psrt to gin t 119
original mrcaptan. The 3-'t?133312.an9t1.101 has bean 831mm to exist in
both $21.0 minus. md £11101 forms. In neutral and baaio solutions the
thiol fox-1n pmoominatas, but in acid the 3115mm 10m in praacz'at. 1n largo

mount-5 (13) .

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liar-ml and 133.911: (19) prepar-fit' p~ti1iocr11lol and n-butyl «sarcég .an
by (.119 lithium alum hydride red-notion :3. pdtolnencsnl. ”1.....1'1 cE-Jerise
and n-imtylmlfom'l chloriée rasumtively. T313 procmur-a Gavel-:1" 31‘. for
them pregm‘abiorm mm 11151311 in $1.1: rr11.:.11t 3.111.181.3ng 1.3.011 as s 112.131 to
reams 2,5‘411' 1e ’31-3-417. 10133.111115111. 1?" .211: l chloride an: 2,;'-1?.i1:2.3.or0-3-
t21‘-;0:11111n1131'.-1"’or1'rl 11131011119 with 1111:1111; al-minw hys‘ri 1.3.3 to {2.10 airma-
pending mhutitutod thiephem 1.113.018.

Since the numer of t. icz3ioz1etziuls‘111m m vary liniwd it 11113
11131331111113 to prayers I xmxhor of fizio;;~i.1111at.2111113 11 1.1.1.113 111111-13"... $433331:-
uents in the magpie-3m r1133. The “11.113er of the trdswhcnat‘uall had

to be: Imam unaqaivocally. The mlfimryl group was of greatest interest

 

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than in tho tax-II position of tin thiophene ring II prwiouI work
(5,7) indicated that derivItiveI of web coupIundI mm have pharm-
«logical 7&1110. Homer, tho thiol group in thI tun position of the
”nephew ring III of intaraat Ilse Iinco only on. previduI thicphenI-v
thiol of WI typI had previously been prapmd.

A t‘MOphInati-uiol with way]. gram and tin this]. group in tho threI
position m firIt Iought. A limaturq Ian-ch for th mathmsa of
introducing In alkyl group into the thiophona ring VII made. The:
max-tat mthodl of mItorical mterut will be briefly discussed Ind
tau rIIIonI for Ioloéting the prooedurc Inployed to cbtam the alkyl-Jo
'mIphonomu will b. indiutod. .- '

v. Mayer Ind KrdI (20) m thI fix-It invIItigItorI to prIpIrI an
my]. thiaphonI by Ipplying I Hurts-Pita: typI reaction to thiaphana.

I]! IZI-JIIRIm-o “a I ISL-II
'I

They tound that t2» two puitinn or thiophem III nos-I active than the
film politic]: Ind thIt thI iodq darivativI III but wit“ to thiI
Ma but that tho bronze derivathI would undergo tho Ilkylation
m N‘. we 1mm 71M:-

Stdnkop: Ind Schubart (21) ha" mom that IcyltmopnmI can be
mated to IlkylthioPhInII by I flmanm ”daemon o: the may).
dainty".

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31.an that: original tor! a large nmnbar at alkyltt-AOphenol hurt been
pron-rad in this um"; * ‘

Shapcrd (22) 11erqu flathylv-S-mthylthiwhm by the action of
mu man on tho mémmm a: 2aeny14muy1mopnem.

I c _ 503 II a :1
EL: ‘63; W 033 a “.633

3333302?!

Other Ilkyl thicphonol In" bean prepared in this manner.

A largo m of my}. thiephmu have been prepared by a Frieda
and Craft. typo nation. This ha- been ammpliahod with alkyhnlidal
II veil u with clonal. Schlaichar (23) m the first to investigate
thi- ruction 1n 1%. Ipplication to th10phone. . , _

the no“ common method for synthesizing wry}. thicphemo is by the
ring 010mb! an uppropruto intermediate. A very excellent review of
am- pmochru bu boon mum by 5011' and Folk”. (23) and includes
nu mm” h «pair-cum detail. “than ”thud: can b. divided
in“ m MIL W. Th. fir“ group ennui-b of the reactions of
Ilium or 91km- um sum: or compound: containing mli'ur. such :0
Wm ulna. animal“: dioxide. Such mthuu are usually anly
a «mid. imam-tau. The ether man}. method and to obtain

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13

olkylthiophms is to affect. s ring closurs of s‘ -dicarbony1 compounds
um phosphorus mind...“ Ths immowl W. my be in the
for. o! a r-dikstons, Y-ditldshyds, «com. acid and loss of its
dsrintins, or o Y-ksto acid. _. _ ‘

An .11:qu thiaphsno m required tron which an slkyl-zothio-
Wummmmhmnmmtmmuy
“mommthodsotssuiuorms, «abutment.
W, for biological tasting. ‘I'hs mophm derivative, Lynn-um-
W, W tho moss-17 rsquirmts. This compound is
Wool sud thus, tbs 9 positions of tho thiOphms melons».
minim. A padhlo stating mm for its motion was
“Mariano“ which as mil: sumbls in sufficient qusntitiu to
chitin the necessary amounts of ~tho dosirod final product. Bun-Roi,
[mu-Host: (2S) and Pal (2'5) mthuiud 2,5-dinothylfiuophms in an
nun-ago yisld of 60:3, from no ”muons, by tho ring closure of
Watson.

6
cuécwnfimcoca, 121:- ca, 3
3

.Q; - n

In the prosont work the experimental proosciuros vars wifisd to obtain
better yields, than any previously reported, of 2,5-dimthythiophons
fro: somnyhootons and phosphorus ponuafltido.

Tho lryl thicphom, 2-phczv1th10phsno, as required for the» prop-
mtioa of S-vphorwl-Z-thiophonothiol. The tumor compound has been
pix-apnea by several methods. fines and Pool (27) and Chruszcssvoim (28)

.i

 

 

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preparsd 2-phccvlthiophcns from P-bonzoylpropionic acid and also from

“I Codi“ salt, by cyclizotion mactiom with wlfirios of phosphorus.

05313606 503.3%»; --3-39 '1.

chzwws (23) and sand as s cilurmt to accents tho rotation
curing fhs pyrolylis phase. has and Pool (27) also :2er 2-phcny1-
thiopbsno from s substituted nolonic acid cud phosphorus pcnmulfids
in 1." m ten percent yield.

cdagcmaacamoan}, iii-
, .- 3

Monica cod Berger (29) prepared what they describo‘iu A mixture of

2- sad 3€phsrg1thiophcncs by the interaction of bcncsncdiuonium chlorids

with thicphcns in the, pruoncc of clmninma chloride. ' -
Bombers” (30) reacted Hmitrosoccctmilids with 13110911an to obtain

1 mixture of mono and diphcwlthiOphsnoa. '

 

c l! [I O c H, 4 03300.11

.q'

. Jr:

’1'.)

_ c
(”Nix

Gembsrx and Bacimnn (31) prepared Emhmylthiogrhcns in an eleven
psrosnt field tron bsnaanscliasonima chloride and thiophans in ths
prssmcs of sodium rydmxico. Tho activs intermediate was banned-

asonium hydroxics forms-:3 from tbs bcnamsdiaaoniuo chlorido.

8 ,

Bruno and Voronkov (32) hairs dons cox-mi dora‘ols work on tho synt‘ ssia
of 2-9hmylth10phons from lvhavlbutane, l—p mnylbntmss, and 1-9216 «1-
butaciions by allowing ths lcttor thros compoumfs to react with sulfur
re.- ton to fifteen hours an. tor-.pisraturos of zoo-zifc. in sealed tubos.
Tho yields vars, sit}: phcrgrlbutamo 5?», with l-fihomr'lbutadicnc 5;. ," and
with ldphmylbutsnos from 25 to 3531. i -

' Tbs 2,5dmstifirl-3dti1iophmcmlfoziy1 chlorids was synthcsissd as an
iota-masts usadsd to prspars 2,5-dimtiw1-3dthiophsnsthiol. :l'his could
hs dons tor first taming tbs 2,5-dimsthyb3dthiophmmlronic acid and
sown-ting this to its ”Howl chlorids with phosphorus psatachlcrids
or tbs anemia acid shim-ids ssuld bs obtains by tbs dirsct interaction
at its 2.5-dinstby1thiophm Iitb a solar access of Wade acid.
II ”I fill mm and in woman: or shlmfilhnsting thiOphons
s. so Ilss .06 tcr'anylthiophsms. -:~

miss. 8W (33) um mm mmum acid by treating
ossl w buns-u- no. duty-six psrcsnt sulfuric acid. em: (31.) ,.

0

Eli...
I.‘-a. /

.-.¢v
\

(us’u‘ \.

r Iain-1.. ..

Ola. .g
-ln. -

L

prsparsd Z-tmcaphanaaali’onic acid- by t2... coma: of gays: acid cE‘mactm‘isad

. I s Hafici‘ws- | | o 19:30
3

S

iioysr and iron (31:) obtain-mi Estifiop-‘ueznooulfcmrl chlor'i'fo from

sodium-awopmnwolfomto and pizocptwrns pontachlorixio.

0 P51, -------r s P0313 s HoCl
. . O’Ka 0.81

5

Tbs mo chloriéss 2411iophrmoaulfom'l oixloricls was synthesized by
Map! and flopnsr (3S) and also by Burton or" lavy (37) by allowing

Manic acid to react with ti'Liopizons at a tazsporaturo of -l§° C.

‘doc.

l A _ _s 23350.01 «SJ—«I- 0 2131 s :i ”33‘

Lang‘s! ($8)"first proparod 3-thi0phonoaulfonio by the sulfonation
of 2 ,S-dibrmoothiophsns with pyromlfuric acid to obtain 2,5-iibromo-3e
thiofiumssnlfsnio acid. Tho brow groups wars subsequently removed by
a {it's parssnt Galina moalgam rociuctiozn.

Stoinkopf, Jacob and Fans (39) and than Kaiser (1.0) sulfonatod both
2.1. ..u zfi-cmtnynmopnams with sulfuric acid to obtain mono and

dimlfonick acid derivatives of those dializylthiophonoo.

il’t’u
- ’..I..so

m‘akfl

..I. at:
101‘-

I
“ova—,1.

. . '1' ill
3...»... .1er . rally...
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J
i.) I

.1

a a

L7

1?

In tho present sock 2,3-6Lathylthiophmo was criorwclxonatad
mu; with an access of ahlomsali’onic acid using a modification of
tbs min-ital mom dsvalopoo by Stainkcpf and 501m (33) and
alas or Barton and may (37) to obtain 2,5-dimafi1y1-3-thi01manamlfony1
an“.

.03. 0,01
. I s 2HOSK3331 edit—aha. I ‘ s 331 s- fire—39‘
11,0 «on, 3,0 3!,
8

“ms compound, S-phcnyl-iZ-bronothiophans was praparsd as an inter-
ssdiats in dis synthsais of Swhorvl-thhiophoncthiol. Thiophcnc
broninstos such mars readily than bananas but tho bromination of Zephczvl-
mophcas with bromino could. not be cheated hazclusivcly to tho thiophons
male!“ (27). The para position of ths p zonyl group had a tomm omy to
be brominatoi.1oc3.auativs bronination of 213333.31” .fllt 110133. 2:13 yiolciod a
tatrabromt‘rdophsno. This has been reported to ho 2-(n'cbromophew1h

LL», 3~tribronothiOphmo .

[310 ”.._... 811C}. .3.

33.1mm, Pctcrscorrf, and Gorc in; {.31)- raga-tad they laminated
21933.ne- 1thiophcns with c; anogsn bronincs as the brorinating .5... to
obtain anyl-R-bromthiormcns in a ninsty pmant yiolxi .

 

‘4‘.

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5.4
(.23

15113 101‘! mm nut be: regattas: e‘.’ 4.11 1.1.111 9.221.231.1th p.113 2 ...1..w;...1.w-
111m I38 used. L‘l the prdiunt 9021., E‘s-bromoaam £111. his in 01:13? 013123
II I .0le as found to 11301111151111 2 .1111, 11111391191111, in 1.213 5'- position,
in 03:11!qu 31.31.69. A n11:-.1:g point of 83-330 =3. for 1.1.1: profiuct was
M, which was the “use an that royortad for S-phorg/l-u-Enbrow-
thug."- .9113 by the: 0111110.; .311 hrs; 21.62: 11161.. ‘.::.t of 211': ".1111 1101'. T11.- 2:251:11
nubile mafia; tar-.1. 11:31.1. .2. -121. 0011.13.16. $.13: 21-5 3:3 1: :1-2-zi..-.:1:.:.3 was
the mm‘amzw tax-1.111111% of 23-93121; lti: 1.11.1--.

A new 11161.; 013 was 69111-119113; in 1.2.3 praserxt work for preparing
Euphamrltmopim‘zs by the aromatiwtion of 2-(1-0;;aloha:-.cnyl31111011313119.
The carting utgrial for '1. ins" 331311111315, 2-(l'-c:.'1clohax; e1~"1)tl.iopi‘.mm,
was firut prepared by x iasur 6111’: 133121131; uric: (1.2) 9.1113 1.321111 lat-31' by
Tilforti and his co-mrkars (.13). T113511 1111:3313: .:ator-s treat“: ”at-i. 1611;;
manaaim bmvicie with cycloiznzcano 11:3 to obtain 2-(l'-c:;cl ohm-.3131) 1‘10-

pfmns which ms cleffiqirntad to 2-{1‘ «13.112101191111131)thiop‘.23m during its

mil‘icau on by :11 Milkmen,

 

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1;:

Tu mtmm, ”44130124101. 'thiOphem has been“ ,1“ ”and by I-Zinsburg
(ids) using; a ring closure method. Pager (hf) pregwad 3,1;«iimatimsy-
thiopham by the ‘follmdng Iaqmma of rmtlona, im‘clving n ring claws
reaction explain; the Masha-g matixod, a matzvlauon with dimm'lmlfma,

renewed by wax-01min am: finally a é-acarbozquatién Itap.

F-i‘a“?! $3.0. .‘Eia‘.
5(c: {20:7 3.). o 02-111»ng -:-‘-'-:-'-o
5:13:20: 3002:,
a .
' 11,6 “2:;
9 (c: 1,).30. --. | _ + 33,530.
tycoocIs Em; 33138061 Iowa,
3
H.C H, H363 c0811.
0 Eat)?! ——- - I - o (:2! 0:;
nacom cogs-z, Na 00:: co m

H.C R,
u | 7:21 at. o 21-h
HI DOC 00 .131 Hi. DC
| H3 eager Chroma: 0::130 :’ 33C | A ‘33 . Cr.
m '13 5311:10le U’

3

 

mm ('46) prepared 3,1;«imet‘noxyt2'zioréwno by the dacmfiorqflat ion
of 3,u-¢1hycroxy-2,-dicarboxytmophm¢ in refluxing pyridine tonaww

by a ankvlauon of the 3 ,hxiihydromhi oph am with diametham .

aé

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| 11 M51... H 3 2‘0
W300 I ca 1193451513 Tamsgmg’ | O x, .

‘ 8W3 . on}. was T107

0“}ng And L111 (147), . prepared Liz-dimethmgthiophona by I
nut-bod 31mm to ham". with I alight modification or t} a procedure.
they and copper power .0 t. a catalyst. in tho decarboxylation of
JAWq-Qfi-dicarboaqthiophm without the aid of an ergmic hue
“ch as pyridinc or mimline.

min); a .2. x
. .
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.:ufllh..‘\ hill-II!

21

‘C'ISCUSSIUH

AM carom comma-anon of tho to main objaeto of thia invooti-
ption; nasal], tho unthaoio of previous): mm thiophmethioll and
an promotion of no! tertiary minoalkyl thiowl sulfide hydrochloride:
from tho thiaghohothiola, it no fiacidmi to attempt that W proparo .
mum Bathiophonathioh in via! of tho proviaua work 01‘ Batman and
Hour! (5.7). than immigaton round that tho spawn mlfida
dorivativao haw local anesthesia activity mu. tho iwmaric Zdhisml
“Ride deritativu failed to ohcw ouch activity. Tho problap or propan-
iu J-uxiophmthiola io complicated by tho fact that tho thrao and four
{Initial of Wm aro oomidarably loa- raactivo' thao tho tan and
tin politic». fro Wat thio difficulty moral pathoda vex-a
attmptod. Thahoandtiwpooitinnootthiopmoauldboblockodby
tint introducing pupa in than positions. up” mupo could to at
tootwoo, mouddohcouldlatorbarmadoromovhichomldba
an intact in tho final J-Ithianyl which dopiyati'va. Tho mpo
introducod in tho m and rm poaitiona had to to atablo toward axporiw
“MWhthhiMaothothiolmintothom
artmpaattim. choblmkingmmlataomvodmer
maamnmthonmormofiawmwmntaba
Mmmwmmmwdorwmammm
plat. fail prompted an adéitional problem oinoo the thin]. group to

 

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$30 Other mothers. in animals for obtaining 3-tioic;..‘:.rxmtfai:18 with.
other nib-times“ on tho rim. 3.13.3 mtg-0:3 111?G- was a rim closure» of
a Liz-dioubom'l oormmmd which will form thiophemo derivatives with two
”1101 M? 83 well aa ethan- mbstituanta in piano on 1.319 thiop‘mno ring.
Tho only tin Jdiuogahmetticlo rogortod 12-1 the literature were first
wood by 9210 mood (15,15).

(at i‘ N 3
(If?aua.aUHa«-1 is 11!:100 Q-’
or a 8 —-——-E-L-o I I a l I a taro
CZifCLé-CZHCE-Ta
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I, Ill a death]. ’ II ‘I
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s ’ a

fin an! “M mthmio, in the present atudy, of a new

 

mm W thiol no accowmhod by aubutituting the two and
{in M“ of tho thiozfixwo ring with idmticnl groupo and than
Mains tho thin]. group in tho throo position which 1a ocpnivalmt to
tho {our petition thoroby eliminating the isomer problom and tho ltmcturo
it tho with; amount was unequivocal. Tho first comm proparw
by W u‘thod In! 2,5«3mathy1-341110phonothiol. Tho follmdng Wazoo
at random N W.

float-
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no ' , a ' real L .. a »
3 3

Tho ring closuro of anatomy). acetone! with phosphorus pantsaulfifo
m a Miticntion of wmfl “method. W in tho litmtum “3‘19“
. mirror“ trimlfic’o had been and as tho mining agent (23,25).
Theo no claim in the liter-own that Wa Wm!» in not
I ottootivo in tho ring clam. rotation! to mhmo thiopheno deriva-
8300 an phosphorus trimli‘iéo, hmor, it has boon ohm that phoogfimo
Mull-tick to really a mixturo or WI WW and mm (21;).
In tho pro-mt investigation tho on of phosphorus Wis?!) mo
yuma onion .1! hotter than thooo mm for tho plmaphma trioulfido
In” I Wanton? marina-ital proooduro had been devologm. A yield
of IMlfi'domwm or over oigisty porcmt in obtainod. Tho
phosphomo pontmrido m a coma-om grade am no need without
Mzor pn'ification. It no found that tho boot 7191ch woro chumm
by adding o 8518.11 mt of mutual aczztcno to tho fimly mattered.
p3-‘.osphoma pontazmlfida and “51113 the 123511? dry power? mixture was
stirred it no nwfiomly heatad until tho reaction had initiator].

‘I all! 0
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Tho oootonyl woman: was 1213:: 3:11:21: circpwiso to tho ot-irrof. :z‘ixturza at

a rato mi'ricio‘nt to muster." t'xo roost'ion mixture at its ronux
tworu’mro. than all of £12 “33:31:31 acitono Fad boon Mai-3:11 the rag-
action 2:5:mro was hooked at its reflux to<¢oroturo for a prior? of
flirty nimztao uni finally $21.3 Iii-.153 pro-..Imrt was isolatod hf; (Tistillxzilon.
Tho precinct was l‘or-tfizor purified by max-zip; with a oodiup bgiroxicio
oolution, drying and. fractiomtim; the procflct. Tho rats of reaction
boom vary violent if too inrgo a qwmtiv of acotcm'lacotmo was

mow prior to the mutation of the reaction.

The omoroouli‘onotion'of 2 ,Ei-dmotfgltrlopbm to $1.313 1’ ,Fi-dimo'oiu'lo
3—thicphonomlfomvi chlorifo was accomlioimd by adding 2,55-ribocthy1c-
thiophono to chlorosulfonio acid at tmporpturoo bolou negro dogma
Cmtigracfo. This prooofinro was a poéification of tho promo: of StoinE-mpt
and Hogan r (1.8) . I! tho t'aztoraturo of tho reaction mixturo mo ollmd
to rioo ouch abovo zero dogma Contimdo thoro m conoiderablo chewing
am taro would form. Tho cmdo martian mixturo always had a mop red
color. The product was isolated by pmri. 1; tho reaction harbors onto
ioo, extracting with carbon totmofiorido,‘ washing with water, mm,
and fractionating t3'2o cm: proc’mct. Tho 2 ,S-dimotm'lthiofimno-Qo
3211501151 chloriio mo cz-mroctoriood by tom: ' :3 tho omonmiéo darivativo
on: also by it: snponification oq‘iivolom. Sons proportion of tho
mMormid-o do ..vatiro are moors'ot! in Tablo I.

"Suo Wot-ion of 2,5«’:imt¥~y1~3~t?fiophmosnflforg'l oifiorifio cauood
comidorablo do? frioul‘: . :‘my ottonpta mro ran-do to rofiuco this acid

chlorido with zinc that and ulna-1c acid. Thia pothod of reduction m

;Ma“€m - v" _ "gén. g‘m‘ “Wm
. 91:19:st “a: stir-N7

   

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61102193352117 used byi Giant's am} i 111:“ (7) for t 13 [reg 1::1 11.12?! 0..
24.11.1031‘mwt21101 $111331. 2471.2 " spires ms 213' 5,11 c? 210112313 without 1:21" 5.13.2.1;
tit-3 int 11121.3(;iata aflcryl 13:15:11.? 3. 1‘19 minor: is an a. 2.1;)" 11111212: of“ L1.)
2131;131:2523 of 138313931 ”3152.153'11'1 chlzn‘ifa c'19$:tI‘'-.‘a‘.'-111:1.t by Gil zen. (13/.

3"

31:31:3sz (12') was 5;: 3-353. :.-.~1.. 1:1 {1:131:13 ' :13 2-".

‘

1 1 ..3: ,3 1
A 31:1 ‘311'53'01-iva. 3.31 1J1)»:

yield by a 31.11:: Cast react-inn of Z-tl-iop? 31-3313L .amc 3313.1213th 1121.1211-
attangtl to mince 2,54 i1‘xat7'.y'l-3~t".1‘11;;‘131‘22151112‘021311 631102113 by 1412113111113;
the reaction times, 60:5013‘7‘t1‘fitifiw , M 9.226911 sis-3 of zinc the 3-31.231-1-1‘221
meth‘- 1! of raducti on was 1113;121:135 '23:: pro-.1313” from tires-3 11:13:33st
mctlcns agpaarad ta be 2,?mi1rtfigxl-j-t} 3111 1111113331511er 3331:: and
pager-sly 5011.9 cormajvm’ing 3211212221: acid. 73:3 2 ,5-(11,.—mtl;yl-3-ti21011213213.
mania acid could b.2130 been for-11.92:: by hyngJIysia of 1.2113 2,5-dLmtixyl-3-
thiofmnzmlfamrl c1112r1133 c311 wing 111.223 ttta: um 131.: racucv 111.11. To cat 1a 11:33:19
1! the zinc natal an the can” far the {emu-o of this rwfiuction,
24h13p21ene3131frmyl (371110115.ch was pmpamd am? minced by this awn-13 met‘nosi.
11332.5: comspcmilng to t‘1 at £01133! .2: the lit raturo var-a 01131111133 for
tha 2dthioph3netflol. 1233112502113 it 1133 concluded that neither» "’ .23
tactniqus nor rengmta warm at hunt, but t‘at tE-«a 1112-1511232 It'd-.8 not applic-
nbla to prwgara a2, 7-6‘12-3‘: z;.'1-3-1t..‘:d:1;13::1111::tLiol.

The method which was 3.111 33931 far the 1131413313 cf tn 32115-3231
chins-139 to £311.?! thiol 9012:1113: an fiapfa’cion of 11.7.13 mix-0.1 o: Yaw-131
tun-:3 Caesar (19) for the min-1.1mm of p-t-rflfiminmulfonyl 3711011130 and
1-1331. 31139.1.1f01171c flcza to pets-J 11:22-95:11 p.113 n-butz-l r: :21:.:a:...1n
Pemctivaly. The 333131.10 autism pro 1333:! t}. n 9111331113.! 6.131.311.1132 for
‘11-! rmhctlon. Roam”, the staid-21:32:31.1? of this mntion has net

hm verified.

C.
u\

9.)

'9 -: ~911-v v:1“ .’-1-" ’11-- Maw-'1
P3 ”2321 . 3. Ao‘L-t- " w ‘3, ‘..-"..... 1 ’1 f’ " "' .1'. J. ..

The product no thou 1393.91.99. by acidifica’nion. Tho p.999 91.71.1119 9991'; for
tho promotion of 2 “-93.99"; 1.11-3-19‘139. 911199913921 3;]. 9" .-o. ;:9 was to
diesel-«o s largo oar .9939 of 179912913113. 3.11.1.9 911.921.91.113 hydriata in 92:1;
091% «16 than 399' on 91119199]. 921.111.1021 of 2 ,EC-dL13=2tf'1;-.'1~3~t"ir,1;1 92239121592911
93110111 0 to the 11mm: 911111.111": 213119139 solution 2:91;: at 11129 reflmc
$91933119turo. 3. ""129 2,,m...22..q,1-,-w 9.9.191; ‘ 9-1 was 159199953 by Cazstrgsying:
the 92:995. 13.19.919.13 911.139.9129 tgiirico with water, 9999219919: the otter
195.19. , “tr-acting the pmmct from tho at? 29:1 11:1 an"! a 001115.119 Mfroxldo
00121151913, acidifying the basic salt, extracting it from t“:o 992199115 21.1.3.1:-
tur! vith other, trad-1117?, and 99.111.11.13 frectionating £119 crafts {331.191. The
flak?! obtained 1191119 no big? as 91:; ht ty-oigzht paramt boa-9d on tho
2,31‘inot’9y103-t21109‘29219591139.:3'1 o :1 91.199191 in tho rafuction.

Tho 2,5-91399122311-3- 2’99}; 921.2%.1'2191 was characterized by tho for-antic}:
of the 2,12-rfiinitz19phazvlsulfido d-arit’ativa and 91 aztfintal analysia. The
results of thin ”1:32.118 are to bo foam-.2 in Table II. T213 2 ,fff-dirsyat‘1-zyl-
J-fiziozwiumtiziol m fwnd to be mlati voly 11219992319 at. room 11.929192199112192
especially in contact with air. I‘a appeared to have a tend 2121.91; to
oitbor oxidize or 91311911199. Miter standing; in an 99120313329119 of nitrcgm
for moral Hook: 1:: o rofrisy'amt or, so .9 of tho mtorial would no 19:: 12:1-
disoolvo in {1:11 sod-.1129 2:39.3:1093259 , 19.".3. 999 it cozfiglet'zlyd 3.911923 1.12;.21
initially propane.

The infr- rod 899913119 was ( 1t.9:.~:1.‘.r1.3'3 on a 5112:3133 {1219;191:199 3.917919

of 2,Sdtmfiwloj42110131192191.2130].. An almorption band at. 3.?wn'iicatod

 

 

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.1 II 9.2 9:5 g.“ S.” 3.8 8.3 9.39.9.3 «94.99.3930 H09999..M90993?a§?m
8.8 3.9.. 3...: £3: «3.. 3.3 9.3m gin 33.9.3.2 umvouwaanowmnu 90.330.999.93un29539. am.“
1.. II 9&8 9.5“ SA mud 3.9... 43...»... 9932.3 «3.33.99 ..3». d...9998.9...9u3amépfigawm.a

m9 953.6939.

 

 

EM 2.0.9.. 9.9.... . 3...... . .
8.9099 .. Fm! ..N...... .. .. . 6°63" 399939 PH?- .n... 8338939....N
£698.“ £89.89 9,9989% . 95099.3

 

 

3.9999896 £5.55» 95 .3 9925...; 2339999999213.
n :3.

the Inl‘wdryl group prev; .1“ sinfm red spectra of 2,,x2‘mk‘1-9-
thiophsmthiol is alt-own in Fit-arc 1.
he 03132111931! 01‘ 2,5-c1mtq 1.3%}.101‘9 .anethiol WI 32.223.122.325 vitae at
access by two utmtive assumes. Ono math-ad involved the preparation
of 2,3«2jaeoflvlej-iodot2fiaphm and 2.5919822...“ pl-j-broeoté‘ 19:22 am. An
“mm. was mm." to react the halo derivafivo with magnesia: and finally
with calm:- to give t“ $1.101 map on hydrolysis.

The 2 SNL‘aattvl-J ~bromt2110p:.sno ml pmarei by bromnating
2,5‘dizmaylfld0phena in carbon 6182113160 0.: I solver-1' .9. Even fi‘xmgh the
product in. weaned with aqua-cud 00511118 Cl. wants to rams the 91.3.3 pz‘oaiuet
fir-mt malted $9.... 90.92999 of the nutty]. group: rather than the 1:? tree
poaitiono... 0.2.219 thiopfzm 11:23, the final prod‘ act readi 1:; drawer: an
“airline and mm when moped to the air. Because of tide c iffiamlty,
a well u the desire to take advantam of the greater reactivity of the
10:20 paup, the experimental war! with t‘m brow derivative was dis-cen-
timad and the minder of the we“? was done with 2, wdient‘ “1-3-1060-
0110990110. Tao 2,,«21991. Vl-j-domtudoweas was eastbasiaad by a
mantra adapted from I method reported by 22242918 (:33) for true aynflzeais
or 24999909994.

I ' .t,“
2 | I L. :21, o HgO .£......:.... 2 l o 2231, o 1-236

8

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ar-

The iodine and freshly prepared yells" awe-.221 iodide were aide/.2 alters
nut-31y, in small 9.9.2.219, to t .e 2,,a-c‘inet‘qlthiephens dissolved. in

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banana. Tho rotation was easily followed. by the dmwama (:1 tbs
yellow mercuric oxide color and the ammo of the crimon mrcuric
10613.9 color. The yellow mercuric cxicfe'l flmctien was to remava the
1117:.ng iodida 23363.13me 0: it was formed, ta prev-ant redaction of
the product. An ext-113?. m min.) ta obtain the 2,3-C‘iaetizylr3dtizio~
3332911012301 {ma the loan derivative by running a Grigmrd ”agent uni
than reacting the: latter saith altar. mo meme: 0: fwd 0.21:: Frau: (51)
ill W to prepare the Orig-am remgmt. A mole quantity or 2-1930-
prom was used in conjunctim with the 2,5«iimtf'yl-J-ioéc tiziogsheno.
Addition of sulfur to the resulting Stigma reagent, {anew-ad by
byérolyaia of the reaction mixture, $21163 to 3131.3 my 2 ,Eqiizmth-S-
thiaphanetiziol. A second aura-n was m3.) using only 3 trace of 2-1030-
WI‘OPQI” to initiate the Grier/m reaction) how-aver, the mas-alts were
again negative mam altar ms 5:13:33 to tan Griggzzard reaction 2:.i5'tura.
In order to detamxim uiwmxar the 2 , SQWCvl—J-thiangmgmsiwu imiica
rammed umjar the cozfiiflonn twig-2‘63, the Grignard reaction with 2,3-
dimtqyl-Jdioxiotfslopham m repeat-ad and thus resulting Griggmrd coraplauc
ho carbomm, renewing the method 61' marry (:2), by pouring the
himard roagmt war portal-ad dry ice Mpam'ad in ethar. A vary 3:22.13.
mm. or 2,543Lmtl'ar1-3-tldcplxmo carbmlic 8313 ms iaolated am!
mmwioa by its ting point. Further, activa {Brig-m3 mag-mt. was
probably formed during the reaction of 2 ,SxiineflyhB-iadotuophma wit.
again «I m 01mm by the very a-totiwmdc martian an will as tho

reactivity of the resulting ooluticm when a small portion was allowed. to

 

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react with water. 3000000 01’ the 1023-10111 previowly raj. acrtsd by Guest
and Branton (11.) , t0r thy -0paration or Bdthioplmnethiol wrong?! 1.130
Grignard reaction 0. wall a: £10 fact tlmt u better mthod was dqvalrsped
by the litizium flut'imat hydride raéuction of the 2 5-31.:th .yl-j-vtiici.»?.0na-
lulfcm'l chloride fits Criggm-ci 00111.00: was not in': ostiigtui farther.

A 01ml; nttaznpt was 30.30 to matizesizo 2,E-Cimtivia-1.3103310210-
$2.101 by allowing 2 “an met. 9.1-3-10 0t. t;».io 0;»E.ena to rant with potassium

Wrogan 91111130 in pr

«L

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. wmwfiw 7n n a
l I O h 13 A 3 3:“ch 1»
H. ‘3’ 150,0 CO

5 33 hr!-

0031310 glycol as a solvent.

 

 

T00 90% Wan lulfmo m froflxly prewar! by tho method of
mm. (53). man mom-a “mung a pan-um wax-om: lamina
dammgmmmdondlrwmutom. madam-inn
Woman “kid. It! dissolvad in prowlm glycol. The W ro-
tation, u inc-E icata-fi in t'. :0 equation, failed t0 occur and the 2,5-31mthy1-
3406.0t2110pha0u was isolated mtmgéd. 1:0 further attempts were rude to
develop thin wti'lod. for introchzcing the mmmto group into the thicphana
ml”.

The mom new t: dogmas" £13.01 amt? 08120:! m 2, S-dimlcro-Bdt.‘ 13.00
330000 .101. Share mm two reason- ufiich prorszptod the imaatiggatian
into the nmthosil of this particular t‘xiophenathiol. A variety of (311‘-
termxt mhstitucmts on the par-ant t‘.-.io;>‘.-.0net2.i01 car-1330.01! was sought.

That” first synthaais im'olved 031;, 1 groups, tux-010:0, t.0 imostigation

‘1' |-.

 

3;;

cf 0-351110%]. t2. £0;-‘::-:7.:»..:t‘ ..f- :1: i.- rr“"*r~ 01:001' 0.:1=0tit»..0nts than all-'3'].
(50005-0 1.0.0 ..3-30. A 1.010 t—‘tioy‘. 200000101 1:10 t‘m 0 .0100 £00 the 00000"-
nit: 45.03 £001.}sz 01' a 0m: €91"? M" 3.01. “11:0 2, "'- «01.0.0101; 100“?“ 1-0...
62000:: 000mm 0f it. 03.000030)! M in Us 0-000 of tits 2.3311005: 14.31.30.-
;:T.0na. This c210 .1071: was 01.0000 1!: 3:00! 0011000 ta Cm 6101-000 or (21.1030
darirntirrs 0000000 0: 1.3.0 00.100100 maflfit 1as 01‘ t‘ 0 c‘ 0.00, 000.01,
00. 10.40 gmitumta on 0?... Exit-30000 ring, the 00101-0 3:00;: being the
lust mauve 01' t‘.0 1.00.03. .. “--3 was 0:3 L007twt 00.101 0m~.r.t!.0 1:00.000
it 1.03 plan-.00 to 1100 1&0 0.....- 0mm... bf mfitm as w: 001mm

01.31 t? 0 2,3—01: 01.0.1. 001-92 0:13 an: it.‘ 0 {rastfi‘fitym 00:00:01 0! t3 0
03:10:00 @0093 01.1310 11.3.1.0: 0.100010 1-2.1. 0 r05 m». 03.00 02101.01.

I. previously W00 00:01:10 01' 3 02-1000 group 1:01.115; mums: {m0 0...
two pmitidn 02 1.1.5.0; {Mam mas may by 3003:0150: 0:10 Baum-001.: (3..) .

may Egon-0d that the 0010130 3000p WIS-.8 raucad rm 1.1.0 12.1.0900...) ring
1:000 I 00.00131 3:00;: in #320 £003 pmitton w: 00331;; ”$00.01 to 0 32300020"-

szattyl what-3.0mm 0.0 1.0 111.100.001.03 1:. the removing equation-a.

  

.03! - ' 0.0.!
Q. ‘ '1‘! I?
93529? t

30.3 8

 

1.1.1" - a; -
I
€3.13" ‘3’!"
1‘3“: ,
s

.0000 was no magmas that 1:... 00-...) 1.3....- vraid wt .00.... 0:. v.12. 1,37.

0?... W?J’J¢.LU,£ML.3—L“J¢ql 0 1001.10. The: reactivities 01? the 2.13::

its, .1.

~ ‘5'." ln/

1
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110‘"

02110011.»! atom: toward 1112311111: 01.10.1120: 10:11:11. 32.101111: not be 1.311.103}.
with 0 different 011.301.101.000 in ta £21100 p03 0100 0:1 1:10 udapbm ring.
Tho 19110213; 00016100 01' mastic-m an avatar: aims-m for he

mm.um of 2 ,Sqfichlom-jw 109.010.2001.

.- __ )31'21
0 23030.81 ---9- ~ 3 0 13.30. 0 15141.
C]. - Cl -

' Q a“ f - v 1-
Lqub. . (>5. 1 . . 2111,1110; a
2

4. ‘53
1.11.131. 0 2113.1 --—- 2 4 L1C1 0 2.1.31;
C1 81
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The 2 , 54.103.10r10ti'd0p31wm was coaxavzmcinlly availabla £3.10... The
lichigm 6110 10.1.1 Corporatim and was pm'ii‘ied by fractional distillation.
T210 chloromliormtim of 2.5431011101'0121103111000 did mt pm 00:1 00 00:15.1:
u with 2,5—dinot'rgrl’dic1p'0000. T110 yield! of 2,3«11011101‘0-3-0110021021eo
tulforvl chloride were consiéaralfly 101.00 £210.11 in the correspomim c.1130
with 2 ,S-dimtlwltlziophm. I. cursor; £10.11; was 11.3.70 of this reaction.
T100 mole ratio of 2,54110hlomtm09210m to chlorcmlfonia mic: was varied
and the yielhio of 2,5-1-110010111.}«bigic'pzwmmlforyl 0? 21031.20 was datarndmad
by isolation of the product. Tim 1001011011 0! t0.) pro-11.0% 1010 00.01.17.

out in 0.. £000 1111mm :1: 1:11;». 2 , 3-61.02“; 1:01-21 d1.1.0.1..03:12". 0110311110.»ng 01110111..." .

91:

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n m found that 1119 311331311 £113 mull ratio of 0313.0?!)8213301113 113151 to
2,5cdichlorothiaphom the greater:- tho yiald of 2 ,Sa¢113111:11*o-3-t3113p‘. 11.1m-
mlfonyl chloride obtained. For 1111111031300! discussion this rim'bion

an be comma-ad to proceed -11 two ”31* a; as to?" .._...ouax

. "3513’:
| o HOS-03E]. ---—u o 1m
Cl .1 (:3. .1
8
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91‘“1(‘1----u- (12' Ill 01'32113‘

Unis: t’m ccnéiticns of $7.11 3113111133., ti") first 813;: is "v.1..31' .111 *1-

 

'versibb. "3.11 5:130:11 31.11 of 1.1-1 r: 111:1 10.1 c0113 11:) r1.- 1:31:11. TI...

‘4‘—

. ‘ - «1-» -‘_-\5»‘.~
$111,511.11: 11011111 b3 1333;141:123... 0-? 3411...} 31113--

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mlfcm. 21. 1132111111136 1:17.1‘ 1. $311213; 33:1;1'3111'afimn of 331.011.3111.. ”11111.3 11111.3.
This 111111.11. 31.13.11 t‘sa i: 1111:1119 in 3:11:11 vfi.‘ 1.1571311 (191111711112: 1:11:11 (1..
c211.*1':.:r..lfo:113 11111.1. 333213 «.11. 1331'130511.o:*s t11362 1.11.1311: .1311 11111.12: fizz-.11
an 6151.11.11.31 :1 1:“: 331 1113:. 11.1.1113 t»; 311111.}. 33.11;) is t 9 c1111; '1 31‘ 111*?"
yields. T113. 2,3-1213‘1 133:1; '- c;:“~s1:*.3 rat-1.313 1111’ 0110:3811...” 331111 36.31"}. 13"?
1:133:31111; to give a r1112..’6.13?‘1 b13111. {10.131133 1113:1111:ch 33.131139. T113“
formation is greatly ”minute-:1 1.1312111 t5»? reaction t-mmtara is 1111311311
to rise: 111.3311 above 0° C. This 1 ”1.11.111! that c3110m51lf3211111¢11 11-..2
2,5«113‘. 131191131111 “1171:3113 1111115113? rmact, 111: 1 aces 113% 1111'..ats 1.3 at tin-.3
11:19:11,111: promct 19 the (161513113 03.13.. In 1111 cases a want-Wrath

@3211 7 of 2,1210%...31'0-“411‘10’11311 m1..‘-“onic acid was fomfi, 3:121 11-.-.

1:115 1332.31. 311 as eit c.-: it: 1:21-... 11.1.1 :1- 1111.3. 3.2111 21:133."... Uni 1:111" 11*1'11‘ 1, 1:.."23
1.1.7 -1 ..'t :13. 11:11:23 0.? 1.1 53-171.: .13::13-3-t‘15.o1*11*11'1133..1f:2.1i'.3 11:11:}. 1:11:13 1.13";
Cetaztrmwi 11.111 11.115 the-1113 .13 m 1:1.‘1-13t13-n or 1:). 31:21:11- t-‘m 11'11LZ :13? "17:13.11
rat-1:131 :15 33:31‘21 affects-f by 3:13:123111331113 acid cmcmtmtion. 3’11
all of ‘E e rat-”-033 31:11:55.3}. 3.3.1133 (3111:1115, "5-15 cf1""r1*'1'1** c 13 5.1131 $1113
1131... 11:111.). via: . halt-1:) '1 .1112. 1.13“: 131.11 ":13. .:st 3131; 5.11 t‘. 3 61:11:10-
(1.11.3: tiara 911311-31116 as Witt-.1111. The: 111.131.13.111; tha c2:.3.3rcs1115311.11t5-:1n

”'63.“

0.11111: . wants am 611.11 11.11..) 1:13 III , 3:11 51.33 3'1““ .31. the 11:13.9
ratio? or: chums-'1" 1" 3111-3 9.1113. to 2,‘ I‘m '13 13.01-11.43" 1.11.13 are p "2’1- :11:

‘13:: m c:- ti‘? or 2,:«1131191-11-3 «311152.333... any]. c}:1~1*1313
11133513131 ml was: my}. the; 31.11.11.173 of tit-1.311.121.1131 (fits-1.11111 by t‘:-e1‘3.1*«-1<:t

61123131112130.1311 3.6:“. of 2,'mf..iofi.lm*oi£’1i:1phmm 31:11:) ratémr 101-: 321:? t3: 2,5:-

61.11." ..31*3-3~t1-0p£;321-3s.11.f‘01113 £13 -1. 11:13 a. 11,113; 1.1.". as 5.11 1.13-3.13" 1t3 L1 L3

anthmm o- 2,51-11'1“n'*o+ 11112-31131: .1101. $192 «1131.1110- ~t-.-o~: 3-111-
61.1-3.2112h13, c.1te'. 1:16 :13 a 11:11-11:11} net of t. :1 c 3.31:1'11111- 11.011 1‘3-

assticn, who 133151133 by 1““ ..11-1 its 69135.11 1 5:11. 1151112131;- 1111‘...1.1:1 3 the acid.
301111.133 1111.11 33:31:11 11311112113111, r). 113.411: 11:1: m1t,:1:115. t 1311 31.3132": ".113
t 19 soc-11.11:! 2, 51-: -.1110110-4-t-111n1112-1n'18uli‘o-1H from he sodium 311 ..fata
1th m1'1gfimw ~13 1.1131131. It was tom-1:1 hat 11:13 (111:: 111.11 salt was mm
easily mans-:1 11111111 8.11: 12111 alfata $111.11 1113 30111111113011.1135; {rte-33:11:11:
salt was £11321 1131-3931111: 11.13.331.13 .
A 35111510 attmngt was 11:21.33 ate) phat-111:3 Llamas-109w 5.0...87131-

3.13.1":111111 acid div-1136:1511);- the interaction of «11.11111101311 gamma-.13 of

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CHLOROSULFONATION 0F 39

2,5-DICHLOROTHIOPHENE

 

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PERCENT. YIELD OF 2.5-DICHLORO-3-THIOPHENESULFONYL CHLORIDE

 

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I 2 3 4 5
MOLE RATIO OF .
CHLOROSULFONIC ACID TO 2,5-DICHLOROTHIOPHENE

FIGURE 2.

 

LO

ehloeeeulfmm acid and 2 , 54113:.1152-9 Lhiophene . Control a! the ems.-
hre e: the Men mixture m net efficient smug?) for the quantitiee
e! mesquite employed em! e med-en vim reaction eat in yielding
“My tam fatal-me m3 e. very low yield of the desired product we
M.

be Iodine end when“ eelte et 2,5-‘d1chleree3-th19phenemfoaio
said were ”averted to 2,5-dich1oreo34hiopheneeelfewl chloride by men:
e: pheephme made by e evaluation or Adm end Flu-rel (SE—J)
peeeme. The 2,5-d1ahleroe3-emmmennouy1 ehlertde we Mined
by tum-emu er the exeeee phoephme penienhloride, 'ufireefioa of the
produce an: urban mnuuae, drying, end traction]. dietflletien
t. m the were prodmt.‘ The 2,5d10h1m-34h1ephmnm1 chloride
in max-1m by the {oration of m unmet“ end‘elmntel
can“ 0: the letter. '- Theee ’neulee ere ehm 1e Teble II.

" ‘ The 11th:“: elmainun hydride reduction of 2,S-diei'doro-B-miophene-
«1:01:71 chloude to LSWMJW in mm by
the me method ee eee' «played for the reduction 0! 8.5-dllethy1o3o
Wand chloride. the reduction nee ion-e ”some for the
«W curative than to: the m1 Mauve. When the
«bored eelutieu er t,S-diehloretmmmec}éeultmwl chloride «me into
eenteet with the ether-eel eolution of 119113: alumimm hydride the
man; incensed precipiute gloved e fiery red color. Eben this
men-1 edhered to the inside of the flank menu-an; tee chewable
for were). eeoonde. The redueuon er the ehImnHonyl group no

eccompliahed without the reductive removal of the chlorine new from

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he ti'xiOphons ring. The resulting 2 ,Eqiichloro-B-thimhenotix101 was
characterised by forming its 2 , ‘i-dmitmphenyl sulfide derivative and
making so elemental analysis of this derivative. . "te results of t}- ie
molyeie are to on found in Table II. .. The intro-red epoctre of 2,) “(ii-

.loro-3-thiophsnsthiol was determined on e fresh ample uhich is sham
in Figure 3. The infra-rod spectre indicated e eulfhydryl group present
by the absorption band at 3.9m. The 2 ,S-diohloro-3dtixiophmothiol an
unstable even when stored in e freezing cheet moor en etnosphare of
nitrogen over e iom period or time. is the uteri“. need it become
pertielly ineoluhle in e eodiun hydroxide collation.é Thin instability
could be due to oithsr dimer isetion or to oxidation of the toiol to the '
corresponding oieeulride from residual oxygen loft in the container ertar
weeping it with “nitrogen. flower, oxygen could hove mtoreo the
container since it we opened frequently for rmol of Muriel to pre-

pere derivatives; . 3'12. - NW”... ..

After two ponioonly mleeoribed Hhiophmothiols were successfully
eynthoeised en ottenyt one node to synthesize eons hwotofore' omnown
2dth10phexxethiole. These were of interest for the ewe reasons es the
Hiaphenothiolfe; namely, to study e method for profiting than on well
u to inventigeto eone of timir derivatives for poeoible phemologioel
eotivilty. Eva: :though the work of Schuste end Hour! (3,?) indicated
that the 2mfioplienothiol derivetivee showed no loco]. anesthetic activity

\Ihsrees the thiophonethiol derivatives did, there was no assurazme that

nxbetitutod 2-thioxflmnothiole would follow this some pattern.

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In order to obtain thiole with 1 different eubotitnmt than an
arty]. or halo group, e phenyl grcmp was chosen as the next. group to have
present in the thiephene ring with the tidal gram. After e. careful
search of the literature it was decided to synthesise S-phenyl-i’cthio-
phenothiol. This compound. could be obtained by may of the previously
reported S‘pbenyl-Z-bromthiophone (2.1). Altlwagh the “mature oi‘
S-phonyl-L’dbronothiOphme had not boa: vigorously proven previously, the
present investigation supports the earlier m of Steirfltopf em hie eo-
mr‘norl (1:1). They brominated 2-phenylthiOth by omega: bromide $0-
obtain the nono‘arono 2-phony'ithiophme. The point or ettnok or the
bronine would be expected to be at the moot active poeition mining,
which is the five position. When elemental bromine we need, Knee and
Pen) (27) reported difficulty in exclusively bromimting the thiephme
melons. Presumably the pare position of the phonyl group one else
easily bromimted. In the present investigation Peeverel ettenpte were
made to broninate 2-phemrlth10phone with cyanogen bromide, but all
ettonpte hileci. “min one even true men Wioeny pure 2-phonyl-
thiop‘none we employed. Whatever In inhibiting the bronimtion could
only be present in trace amounts in the 2-phom'lthiophom or use present
in the freshly purchaeod white label Eastman Chenioal Company oyemgon
bronide. The bromination one tried with two different samples of
oymognn bromide. The other possibility. oxiote thnt an impurity wee
present in the previous work of 8tein2mpf (2.1), which catalyze-:1 the
reaction to give exclueive attack in the five poaition of the thiozzhono

ring. The 5-phonyl-2-bronothiophano me propuo: by break-toting

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2-phony1thiOphone with fldhromoouccinimiéo in carbon totrachloriéo ea tLo
eolvunt. fhe product cbtuinoo had the some uniting point as that
roported by the cynnogon bromide mothod enfl analyzed correctly'for mono-
bromo Zephamylthiophene. A forth . attempt VII mode to prove the
Utmoturo of S-phonyl-z-bromothiophm and will be elaborated upon
following the diocueeion or the eynthoeie of 2-pbonylthiophene.

T213 synthesis of 2¢phem~*lthiophene hoe been ecoorpliehed by moral
different oethode. Hone of the methode already reported in the liters.
Cure gave very high yields of 2-phonylthioohono. After the verioue {
nethode available wore tried, a method we: dovoloped for the oynthoeie
of 1-pbonylthiopfiene which gave bettor’yielde and also no. applicable
to large quantities or motoriel. Tho first method.uoed.lue e ring
closure at deenaoylprOpionic acid Iith phosphorue pontesnltide (27).

c..n.coca,ca,coox-wfi- v s *7 ' . :
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The 9~bonsoy1propionio acid was prepared by'e procedure reportaé by
Somerville and Allen (55) which involved e Frisdol Crafts ecylntion of

benzene with succinio enhyorido in tho prosonoo of enhyfiroue aluminum

chloride.
ng “C
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The ring closure reaction of this material to yiold quhonylthiophono

gave very poor yielde. The f-bonzoylprOpionic acid and phosphorus

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pmtamlfids ms intimat'zly sixsd and than hsatsd in e Warts flask.
After ths mstion bar! has: initiatoé by carsf‘ully heating the mixture
it Moms var-y vigowu and consider-31313 shat-ring of t‘us reagents
snmsd. Only hall quantitiss of 2-p‘n-onylthiophms could be distill-ad
from the reaction mixture. To nodsrets tbs reaction, the P-benssylo
mums ecid ves convertsd to its sodium salt by malts-snails: than

said with a sodium hyfimndo solution m3 mapossting the manning
sodium P-bmeaylprogsiomto solution to dryness. The dry Mina P-bmsoylu-
prepiamte tits? mixing, with pHsSpbonm pmtsmlfiae was en 11pmvsmsnt
ms: the ass of the fres acid, but was with t‘sie modificatim the;
yields ms only slight-1: improved. cruezsswsm (2.9) rmdad the
use metian with isprovsd yields by using; send as diltmnt is the
rustic: liming This masthead m suploysd using- sodium a-bsnsaylo
Monte, and, and phosphorus haste-nines. This madlfioation moderated
the tactics but the proéuct obtained me very 1mm and the yields
me still very poor. Th3 prosefiure was slightly hpmed by confiuctir;
ths ring clam metian in an evacuated mm ms}: so that as the
I-phenylthiozahm forum it was invadisuly distilled from the reaction
W to mmnt its thou-ma]. decomposition. This proceefixre gave a
crude pmmct thet see more easily Immune. Altar preparing 2uphsmr1-
“110th by ths ring closure pmosdurss using fi-bsnsofipmpionie acid
or its sodium sent, it was, conclufiat'. that e bettsv method was usedsd to
commimt‘ly prepare the mg” quantiti. as of M-amrlthiw’mm Meant-1

in tho prssmt mm.

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More and Bachmnn (31) proper-ad 2-phanylthiophone in an elovon
puma-1t yield by react“ bmmthMOniun chloride with thiophwe in
the presence of a two parcmt moose of caustic. than this reaction
was otta-‘ptao on 5 cos mole scale tzm yielo of 2¢poemvlthiophana was
less tiwan six percent. It» success of the method Canada on using e
largo enough excess of tldophone so that when the heterogeneous aqueous
mixture of bensar.e.iazorfim chlorine end traioyoono is vigorously stirred ,
the suspension at Mayhem will extract the turntable bmzonoo‘iezo oxide
from tho mixture so rapidly as it is famed from the bonsonsdiosonium
chic-rid own the: cool“ Iguana is elouly eodod to the reaction
mums. The yellow solid formed when the be" is added has boon
postulated (3.3) to be the (31330 mzyaricio, 3513-6433, which undergoes
hyLrolg'sis to give the native species. These compom'e ere sxcesdincly
unstable and titan“ in the cry or moist state} therefore, it is
imparativs that the active intormouiato be oztroctsd immediately into
the thiophona pooos whore it forms the erylthiophone cooyouxd. Tbs
reaction mixture is hazardous life lug-o excess Tim the botmonodisoo
oxide is ollowod to accumulate in tho roaction suture. “The product
as iscaatao by flash atom distill-Luca vita the distillation flask
hum-sod in an oil bath, kept at 130° .C.‘to provost foaming. The proc‘ruct
no very slowly atom distilled, necessitating. largo quuititios of
distillate having to bo oollaotofi. Tho Gomborg and Beohnnn method is
an slogzmt synthooia of aryltlziogxixones, ospocielly tho erylti-ziophsnoe

that are substitutad with other groups such as halo, nitro end oysno.

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2'47

am with substituted eniline, Gomborg end Baohnnnn (31) obtainod
epmximtely tmty‘five percent yields of the emoepoming eubotitutod
withiopheuee.

The difficulty in undying thie motion to e large scale properation
lice in the feet thet very efficient etirrin; ie moo-ed to “$1.;in
«treat the Medina oxide into the thiop’aeno phone before it under-b
goes dummeition. Thi- IIIB probably the min factor reeponsible for
the 1m! yield obtained in tho one attazot to apply this method in the
mt inversige‘tion.

A limle nth-apt In: med. to eynthaeiee S-phonyl-R-bronothiop‘nexm
divinely rm SWMWI Iodine! ee ans-mud in the following

emetic:- .
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Q _ ' a M . 1/1”- ? a
car Re

8

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BoI lb! : 1-0 -e lie!
3 _ 3

Refinish end Schick (57) discovered tint m Wing‘s-team ere
erected nth Mounted eodiun and et the "no: more or oiethyl
m S-beio-thhiervleodinn 1e fox-nod. If the reaction ie oer-nod out
in when or benzene ee e eolvent et the reflux Wei-am of the
reeotion mixture, then the halogon ie replaced by the coding: atom to
yield 24mmylaodium. Apparently at the lover More end with

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6!. to‘yl oft :3: no t? a 301.33%. t’za 32232303323 in tbs five ponition of
2-";:.1.2t‘.'~.ic;2‘23n.2e is wide enough to be 2333313332.: by t‘2 3 93:11.2" 3.32:1.
Vnrtsug‘t :..'1:."..’-':‘-i'3" attofip‘r‘ t‘: 3 33:23 mutton with 01.23? £31233.”
523,—“. ago-.2331 32'23:r2,: u“.-.5|0p*'2:2;'1 emf-r, dip‘2-3ny1 ot‘wr, 8‘113-1‘123,
Manna, bar- eons en'.‘ 5.312.223.23, but worn 21223229332339.2231 in netalatin: tho
1:319:32” 3223.33.23.13 2:31:22: V2333 adv 33:11:.

1"») 3312.1. manta-.1 £381,213 nan-'3 ms 322-2233232223 by e method 622323231133" by
Raptor}: ('57). 7‘19 22"?232233' and $565.22“. 332390?“ 3.2.3 1:336. in (3‘3! to 1119‘26 and
22332.23. to 117.; 2... at 2251.3": 2.1.22 24- waters: 3?: 2,-2222-222222322 roastion ocmrrad
3321:9125; t":o rmc‘tio-a 3:1.3t12333f3 33-23113: spontanocusly for er'proztirrzt 31:;
e 125.332.2293 Tho 2222222222 3212:1233» was 7152323022221}? 222222-23 until two
tax-2.; 213.35.22.23: {:211 to 35°13. Tbo toluemo was 31.2.2 23:22:26. from v2.9 3731 :39; 21AM!
3232.23.22 33:32:! t‘rou. :‘2 n 1331531.)" £12: 3 e325. t .311 t‘: e (1186.! ranted 33.213233 m
coy-22:23:: nit": dry 6125:3311 oi‘or. The Z-bromot‘iopl one we 1222:2236. to this
ethorcal mixture at t‘ze 133112.32: 2222;222:2322er of tho et'..;er. The 33-42mm-
2-t‘:13ny1 223221333 we not 3.33133 21 but was use! 5:323:13: 5532 £3.23 323263
reaction. A tbm and e. 3332!: 330‘ 21' «32:32:23.: of iofobonzano was 9.6213?! to
the siJorom-thbtrmylsoaiun M'rfm'e 2222:! the mirrtom wee. not at its
2-25.12: 22222292122223.2229 for flu hams. 252.223 9.29 react ion 1225.: 3222-2.- may -.3-36
up by, destroying 9.23;! sodium prmnt with 0.395201 and 223553. , new dia-
t5.ilat5.on, end- Notional 65352111223102: of 02230223332 3 portion of the
8‘...an 55.59.11th wish has? boon eta-«113:? with tho 33351622221 rant-321221 in
the at ease». distill; ion pct, 823 10229 . 39.33223 on." 32:23“ or t.‘ e 2-3233322-
thiopftone m roomy-3d umheng-ed. Bo 933-3323: atterzpto were 12236.3 to

propere S-pbenyl-Q-bmothOpB-ma by tbie mt‘xcd.

 

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. -.z‘d I; ‘2 .'é."~ ‘2 ve-A-i'n‘y. ‘~5&0J “as“ £315 1‘3de M2“ in)" &-£ ‘2’“‘Jtom0fio cii'w U34“! L-\ U‘ «5.5.:

.1 4-3.. . .222 2.. ..4 -'. 1.. - -' .,~. ...;'.....
‘ ' 2 ~ ' . - . .~ . h .
.. .L 5‘3 2.2 ‘.. 2... o." 52.3 4.4.3.325. an .3. ...}... {.J 12.. J .5 must I. L... 1%, .1234“ u..L...b .

- 222212.2an ,

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(are
M3 ‘ "" ‘UO

Tbs Edb‘fimlsodbm ma mma £31332: 1332133323336 scrum 32332:", 33
described previaualy, and. ZahlnrotbiOphc-me in 1223513335333 12421033229 as a
”3.315.321 medium. The emigrated 9065.213: sand was pvt-23332332.! 5.22 belt-3m
Ind than the toluene was replaced with. dry benzene. The 2 -hlcrothh-
$912!! was adds-r5 to the 33813931215935 5065.213: 522.2263 02232322222222.2101: 5.3: the
bans-232329. The mafia: ms wcntbarr'ic which cans-:26.- t-‘w b18133}!!! to reflux
90331432902331, aft-:23: t‘ze 333223531322 had been 1321 2.3.1.3232! by ext-33222.1 heating.
The freshly 3:23-0:23er 2.2322222232133232)» 2335 2:33:35 65.th L13 (.5322 33225.2t5cn
with qwlo‘mmne vit‘zmt 1.23310? 150135212331. The (1.1310533132320323 was adéod

to the z-tbmnylaotimm 3295233231331 in benzene while the mixture was

s!

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coolad in an lea bath m ...n‘cained betas... 1.- and 12 C. $1.12:- tfaa re—
action 1:11:11“? 1:11.- 1...? .21: 1.12 1.22:: 1.2"; 13:11:32 1.11:: it 2.11:: ‘32;- 21 1:111:12.

‘ -.-r-n vw~."--. .n 2.
;J 5.9-...“ cu“ ~'~'»‘&-J ”a S-J- -—4

to was 1. an a" :1.t:.:.-12.:.. 1;: '-:.;1.2 ;.1..‘.-.'.t:.-.3
dmlxativat mid- “lb“; 12.119. :2. 1.1 {2. 13.21.12 kLs ...... W": Eel-t} c.‘a£"';-;1. 12.1111.
inter. 1.12 mm 1.5.2 ....Lure 12:... .121.- .1 as- 1131:: 1:11.}. I.;.-:Z::2.:‘..l:::i: 1233.12.
The orgmlo portion was was; 3:; , .lri. ., 1:113 1'.“ 12.11: " *‘-.131'.lt3*.1 1.13.13;

'0 011:) foot Vlgz'a'aL-s. 00112.11. :‘uu fruziona Ham‘s 9011.13.21.11: 1:". 1-3;; 11;;22121‘3-1
to be the: desired 1911012th 33.5.“... .111 a... ..3 l:::; 12-13.: .:3. L’.1L 11.1.1113;
boiling at. Ill-115° C./l.5 2:11. 1-; mail: -.2:lc-1-2.2:1 a 12:13:11.3 car"; 92*.
tetrachloride solution with no visa-ale alga: 0. 13:11:33: 3:11.213. 2 37:13.-
tion. Another grac Lblon filling; a iii-17'2" C./2.j. 1.7.1. 71;; 1...}; ..--.:'21~..;:1 zed
mall 2.10.2.1. of bro;.'.'ziu 311.221.1011. T121 5.: Ira :32: 1:13-31:11 I 1323 first.
fraction indicated unnatural-an while mat cf the 1:33:11: $1.111: £111; 2.
“3.31221le1 veal wscr .Lloa 1:212:21: fur mmatx ail: :1. mar-31.3 1.1.3 {list
{nation had only a 11.11;: abszarpucn for 1...: 53.11.2191}. 12...: t1": 23:12:16
fraction hm a stronger abmzptian for 1.1.3 afirczwl tax-1:1. It was 5:21:-
oludsd that. tho- first fraction 11.2.: 1al:.'i;, 2(1'~c5':lc..:..:;.x,"l}Lil-:fiana

Inf! the 831.10sz was mainly ECU-L wg'clm I..~a.w...,2...)..-.. ... .115. 111.1211 2-7.3 c.211-
mum-.13.: with no.» of 1.2.0 ota‘ar 12.2cm of tin-.2 33001111113111.1121.” of La
tmtlomtln; column.

1.1. lever balling fraction was in. “1.1.12.1- transact 1.3.1.} 5.11.1? to
daimirogamto the 2(1'ooyclo‘uaxanyl)thicphana to 31:23.; 2-1“- .au'l'ulaglzam
by a named reportw by Shamwocz 8.21:1 111- comoraurs (5:). '11.: tag-
Htical 11mm; of fluh‘ur 111112.331; to £153.11; out two 5112113111328 of ., rag--111

.‘J

Wu haat-ad at ISL-220 0. 9:11.21 30.2.: of the lawn: balling Ix‘aculon.

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In??? trbwmturns, mw‘ly 173° 8., ma foam} to give only partiéal
63“:rt‘rn-:nr.ntion. Th? profit-t, isclatod by distillation, solidified
ark-“1': ellmr.‘ ta cool. Hts":- mmtgllizim; the material several times
f2"?! 0919.301 1% wn‘ltafl sit 59-...30 é. dtich ill the reportad (27,253,231) _
mitt-:57: point fer 29%my1thiopfiem. fall was mrther avid-anon that. the
19s.: 5:111:21 {Nation cantaimd 2-(1‘ mlohaxmlhhiopheno u the min
mfivonmt. . ..

'I'hs 3'11'3’10'9' boiling fraction Wick was slammed to be 2-(1' -cyclo«-
hevmclylhticphma ma trusted with {outdo acid to dammirtto it to
2-(1‘ m'clarertarglhhicpwm. man this was carriad out a very exothmic
ram-tie?) guru-«i am." a “Mm-in). we isolatefi Wish boiled in the prepnr
I‘m-1‘9 fr):- ‘F-(l' -rj-;clo‘:@vmy1)t"‘ioj~‘mna, along, with nth-Ctr mtarialo. The
mt’tzt rozr’fly Memories“ hwdne in carbon tatmchloricia without
visibly si-fie 9f hy‘rogm brewide baring evolved. Tl'wia 13mm support.
t‘rirt fin?! higg'fwr boiling fruition could ba partly 2-(1'-cyclo"1m'anolyl)
tricficna. “3'“: material was rat immatigatad myths”, bacaun I better
rzvatké’j was 21:39.6 to prepare tins are-:9 pro-Anetta in pure form with good yields.
Tris ms t'wa firat the that 2vhw1thimhena was synthesized by the
swim ream.

him? it was fimonstvthefl that. QfivF-m'ltfuophma could ha mmtheeiaod
£1.31 9.03 .czmlosmmrylhhim‘yme by da‘tydmgpmtinn with sulfur a better
mafia: for ohmirifig P-(l'~13m10‘w‘vvéfly1”3.13391an ms Might. Thin was
azTPCC.’1:TtL'.!35'ZL3 t‘rmagh a art-313%! rm: aticm or 2~thiony1 mgrxssium broaddo

~ .

vi :3: y’alrvfwmrme follamr‘ b" a fishy-Waiter: raaction, an rapmacnted

by tics fallmring eqxations.

 

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f“ " ......~.. 31-315»
«w 9 70
‘ 62931- 1.2-.
U C) ‘ I: II 0
£ ‘14“.- SU 81.).»
3 .

 

:2'0.3 oar-'1'.” of reactions pram-31.312 vary- umtfii‘q with 511 mar-«313. 35.3ch
of batter than eighty percent in the first “tam. At the: tins.
2—(1'ccycloi-mawlfihiog1hém am prepared it was thmght that this: was
an urinal Wain, because of an car-1133101: at a rein-moo to it. in
Hartmab'a mmh. However, a later vary cm). march of the
literaturo disclosed that Planar- and Samsshavias (1.2) had unwashed
241'ucycbimzwlh‘ai0phm by O 813313.? xaettxod. The Grimm nastier:
procwuro m 333311313113 tan 33:33 11093:”, try 33: wanted the int3r~
artiste tertiary 0.100101 by 711331.111: it. in a vacuum. The boiling paint
am alumni-.31 31111le13 of the ca: 4.3.1.1115 obtainad by 1.21.3 oxalic 331;:
dotwdintinn 1231:1133 m in 3.333331% with #413 previmly report-33' 3.3311011
or unmask.

T113 Zgi‘xwltidofiamw m tynmmizod by ciaiwogumtion of
2—(1‘wyclohezzm15’l)thiopl:18na with mlfur. The “11111“ and 2(1' «12,1010-
humylhnicphm m "mermaid: 1111133 in a. flask and than manned in

Mir..- 1/ ._ 0.1:...)
a 5
r1... _ .--...

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fin...)

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m on lath. The (Set-15311333211135.1111 started 1.61am the tmyeratura rename!
maximize]: 260° C. In 31:13-33:23ch by tha evolution of hfiromn 31115139.
The ”nation was continued at 263° C . for tum hours and, finally the
temperature 31' the bath 11113 171113.112 to 220° C. for five hours. 13:33:13,333
220.0 3., 1.22 moles, of 2-(1'«.:yclohmm‘lmdowphma the yield of
thawlthiomam m 1211' ty percent wit-1 recwary of, 8.33. 3., 0.051
mole, of mung mtarial. In 0. 334202111 preparation of Z-v‘phfiyltzuoghano
where the temperature was held at 223° C. for four and three-quarter
ham, th. yield was easentially 12:3 31:11.13. In all c3333 the 2-511-13131-
thiopl‘lem n. 1301111136: by fractimml (Eiatillation. The: product may
further purified for some of the 31311613141311“ with cyanogen bromide by
Ming 1% from 011301th «fix-anal.

Tho m It» in tha synthesis of Evfxewldflziwixmthiol was
the preparation of S-ph-Wl-Zcbromotdephmo. The method of swamp:

(511) which involves reacting 2-1ah3ny1thioph3nc with cmgan bromide ms

 

1.11311 'bE-‘aia rmfiion was carried out. 31'. 30° 0., broadnation did not occur
and the 2?}1my1t2-1iophm m ischtad 111132" c: . To eliminate the
possibility of failure or the reaction due to impure Zacharglthiophane,
the material isolates”. was furt'imr 1711113 1011 by mmballising it from
0122232101 and analyzing the prociuct. The analysis, reported. in Table 1"! ,

indicated. that the 2-pt1w1té1iophane 1%! very pure. The analyzed pure

..35333133333go533ufi3333f
_ .. .3938 84.9 .238 inn-84.25:

 

. . .. .3933
3.9“ 3% 8.... as 8.90 32s, #8480 . .o ..3 agggganmp
5.9 3.9 93 3A 4.3.... 33 .433 ,.._ 449.3 .4354 4932184484
«4.9 9.9 9% R.“ ER 3% magic ..3-mac ggTSxfiuuu
3.8 6.2 .3 «am 8.4.. a...» . 51.4 . 4.98.3 . 33.458433

 

9.9 39 a: 4.3. ad. «19 mama—o 3.010% 111.11.34.41“. . .cua

 

 

4.,4 4 . . 4.4 4.. u. ., .... 4.... w ... v. u
4 m .. u. .. ill-Bar . fig... .
.. ..m a v ... ”m. m... ., ..M .... m .u u... . w .

a. . . .a .1 I

 

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0 009.10..

r75?

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0'"

2$mmnpnm m then moployad 1n the reaction, using a racontm
W umplo of East-mu Chanda]. Comm Whit: La'bsi cyenogon bmaficéa.
The mixture m beam at 60° C. and again bz-ordnation failed to occur
and tho 2-phany‘li34109’uem Int iwhtod umhangod. Following {fit-a amoral
mm.- to obtain bromimtion of 2-93: 'lthioohono with cyamgon brook-fa
thin authod an abandoned.

The afimlthiophm val bromimtod in excellent. 31318.: with
[Manama in dry carbon tetrachloride as I. solvent.

 

The qurlthiomom and H-bwmouocinimdo, in equal molar quantitioo,
m diagolvod in carbon htmhlorifio at room tamporaturo and vigorously
m (It apprommy an hour, and than heated at the reflux
Wanton-e of the reaction mixture for a patio-:1 of five to ten hours.
Inning the coarse of the reaction the mocirdmicza cm‘o‘ualliwfi from the
reaction mixture. Aft-or cooling the reaction mixture the succinindCa
no romvod by filtration. . The Sap?:onyl-fi-bromotE'AOphono was isolated
by woman; the carbon tetrachloria‘e and rmmrotalliaing 1.5.9 solid
obtained in this manner from absoluto atom-:1. The vaulting point. narrow
with that. reported and product. snow-aw cox-roam as is s‘:.om1 in
table IV. _

The Srioloa‘cf 5va.mrl-2-brozao‘hhiofiana was approximately eig‘rs’oy-

eight. percmxt witmut. recovery of mtcmial from me no the? liquor from

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Mmmw,MmMMhfi1omth
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wwuwummm. WM
WmioWMWQMWUIMto
”Ii-"5.12.41? “"T‘“ mumwutu
motmmmmuMmMV-hmummaz
uwmumntuoumybmummzum
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Ammmwuumuomdswm-
WWWiahrnntv-QWMUWH
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31.37 334!
35-" 35.61

Lem- Simon's W F! bu:-
r‘xg It. an; m on tho:

* «game-Mwakxasd mm
Fmfl’mssb’nfla 1.»... ”8:59;. -

:bp. are.» tun {. Mtg-Ly
pqrfiwrwflau m -.
um:

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could be 133125.25 mi a semi: math aunnt b: *wrry 2:533er was 1:355: in

the sham: dist Tllntion 1714-153. ‘15. spam-wad 1.3 €101,137}: by: 1::ng ’mm"-:5."z:3

@115. out frag: tin 2-(1'my:.¢.:axen:,-)-"-t~momt‘.i fiena 5.1 a warmer that

tom-2c s pol; maria swim-...]. was...” .1312 1:513 tarry regime. 150 9411343?

“tau-pi: was :5. :60 be m: vfirommta tl‘m 2-(.. 'rwhhmvwfi ){abmrrbkinphenm
Tim dong-mum}, 5-53: :~"vl-2-4..ua.,::mnt2.iol was a; 515.} mi: "At! from S-ghsznyl-

l
1‘

zfirazwtiziopcamm thunk}: s Gfigmwfl Traction hummus! b r 5.37:: :rac 5.5.0:: cf

the 0:13:12: dras- zctt v1. .51 E51311"

351%»-
5 ' 3.

 

     

This ammonia not may 131-06.:ch Smfiam'l-Z-fii cylanat: 2.501, but. also a
consi: oxabla qzmdty of? a pro: not awning; at 11:6. >-1.7:7.0° C.w which
amalgam: for the d5. made, 2 ,2‘-<i1ph%nylditlsiwl fiisulficia, an in
15:01:11 in Table I?" . This compoum 50:11:! 1.20535.ny lbs 1 dLmr of Sepia-argu-
243133;. .... 1:1, 5me, 3:9 analytical ramlta agtsead battar with tiéw
dim. s; an V115}: t; s (15.2%. 5503mm, ‘25: could b9 command within
expat-15mm error. Dimitri: {emulation began tuned-hwy upon t‘m
addition of sulfur to the S~pf1fiz1vl~2~vwiaaykm311685.321 brands. Th-a c31-

sulfida um rmmvad by filtration aft»? scifiification of the Grigtmrfi

R“.

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9535.75.17 .m .5;

....,... .. ...... .a 3" .... ~...-. . . .. ... A . $3 , 9 v 9.9 y , . o .
co..:-t:3.;;.s_. ’1“: nth-9.1“. Pat-#113,: 1:1. 5"5. 3. 71:33 5.31:: 355:3... 32,," 9.3.. 9.95.5.1; it
from tie 95.22.31: layur with a. 817:3}?! 32y. 9;?! :1 5'3. ' 25:31:” 11.9: :7: by

931.75.173.99551'7, 13' 9939; n it 02 95.93.15,; 2:;If'..""1tf;9ma::.;m:9 :51': 9:75 197:3
933.954 rec.'<>"-*“ . 3:3 by filtratian. 332-3 :diszzlf 1.7.9 991133.: 31:99
2-991: 15'. 95‘ 0::1" Minn 56:9 99.3.3.1? 3:399:33: 6":ring 91:99-fsfitffin 9.? t":

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The outarification of thiogqucolic ' acid was accmpliehgc by a
method first eraployad by Fla—13m- (31). This involves heating a mixture '
o! tillaglycolic acizi and. ethanol at its reflux temperature for eight
hours in a. presence of mum-ac acid as ’a «amt; The sum tuna
glycolata was 1:10th by mam; esteem: finiwdm 00611111: Carbon“ to ’
neutralize the We acid and 3331:0110 hotel as well u absorb “tear.
Ethm' m added to precipitate the inorgmic nits am! tha ethyl thic-
glycolato was finally iaclaw and purified by htrncticml distillation.
The yum of ethyl thioglycolata (flap-main largely on the ratio. of thioo
5137:0110 acizi to ethanol 52:310ng in {.336 aatification. mam the male
ratio ma 11.3.1? the field was 523.9,: mad when the mole ratio was 1:33.58
the yield was 59.59:.

Matty]. thifiiglycuiata was matheai am! by rowing the sodium salt
or emyl thicflycolats by interchange with sodium ethoxido 1n 02.3mm). u
a solvent. The ramming sodium derivative was ccnpled with ethyl
‘chlcroacatato in ethancl as n levent. The rang-ants me nixed at 50°
C. uni the mixture tad haa‘aed to it. reflux tea'maraturo to? a half
hour. Soc? 1m: chlorida precipita‘tcfl 13:10:23.3me upon mixing the magma.
Ethar we finally addud to the reacticn nurture to precipitate the
partially tolubla sodium chloride am: attar filtering the am the
4516th fifiociiglycolate was isolated in good find: by fractional

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distillation. The yields were nppx'ozclminly oigxty percent and higher
yields could have ham obtaiawd by refine mounting the form from
um distillation.

The dimdiun salt of 3,h-fiL“:c‘r027-2,5tdicarbomthmthiophmo ml
prepared by mixing tho Maury]. ti'tiOéigJyoohu with an ago” at dimtl'wl
mut- and adding this pump. to a mum ablation mmtmo
the m1” Miter of medium notaexién compared to 61mm Quinta. at
a tcpemtun balm! 10° 0. The yellow anodim an of 3.h-dihyfi.rm-2,
Memumfiziophm began precipitating morn: m tho We
mmmm. The fixturcmfimllqhutadfiium
muntwcpcriodof fmmMQWtotmmnhalfhm.
After 60011113 $qu reaction mm tin product m fluent: from tho -
mum mm and. waned with mammal. A Ovc one hundred parent
11:16. we obtained because of an ammuun or mum“:
”Gina mthozido and possible imcmpletc mule: notéxanol. The .
miniatumtpurified mater, butwddimtlyinthonmm
a: the W1..-

l'no M’vlation at the Iodium salt at Lit-tawm
WILOPM was mated by using 311 exam at dammit“...
m named a: Marga: and m (1;?) proved mm m the M.
Manon. They heated a mixture of WW and the medium:
“1‘ of 3,h«iflzydroW,S-diem-bomat2mflaim Cb 1%.- reflux
mm“ for flirty mm. ‘n‘hw this “I “mud in the prmnt
mg, m. maction mixture charred uni Mantel. difficulty in

 

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capsrimsdin Altman; to bola to the 3,h-G:L2wt?w:qr~2,5-diwbmy-
this;+ . Atta- wuummwemm,
mlynlhfifiyisldaftbansidmsbmm.‘ Itmfmwattha
guilty a: 0061131! 8.31% of 3,h-dii'xytiiwqr-fi,Sficafisonstxwythidyé'mm
taken to be stats-232121535 cow not ha m urgsr than three gar-ma or a -
ml» 11' high yield: of the: 3,3-(flmflmzqa2Jnciw‘baxythisphm wars ts
be obtained. Thin In true beams of the large heat of the martian.
mxsn the rmtisn who initiated the interior cf the reaction mixture
tcndad to quickly swaths“ and, char. mat-sail nth will mastitis: the
heat could easily bu dissipated to the outer all; of £2. reaction vessel
by vim stirring. The beat yialezis was. sbtslmd by Idling the MR
and cilwhylm“ Pats at room tavernm; a and than H! ils It. irring the 2222.2:-
ture, as oil bath, at approximatfly 1533 (3., me ruined. m‘mmfl the!
reaction that. Eaten tho insist twat-stare of the reaction nfixtum
ham to quietly rise the oil bath mo myidly lanai-es. A vary exothsmio
reaction mm casting was rsflmng of the vacation saxtum. The re-
actisn suture tsrpsrsmro usually rose to 125-135.- C. After ths teams.
turo had {all .m to 213° C. ti 2; all bath was rspucsd and. his reaction
mixture was hastaé for tasty Limit-so .122 119° C. The reaction mixture—2's
color chmgsd from ysllsv to units whim the showcase mstion occurred.
It mfficisnt 0001’ 215 m not sifscwd it rshitfly tum-ad ta :1 1115222322: sclsr.
It t‘s a intmisr temsraturo of $22 a mix?» ”it didn't rise slams 125° C. t‘ns
mixture staysd n 11.th color. Tim chess: 22122.22; laulists was r... 20'. ad by

vacuum distillation. The 2,4q‘la2t‘2my-t ,5-2 isnrbsmet 2cm. laments was

nc-t inflated but hyr. rolysm‘i directly with moons ("1 90:33.11 .0122" “ion
The 3,4(iflt-1--:}”~,,mgC&"JC.\W~JOJ who who 13:. “slot :1 bry ocid-Uiootion
of the mention mixturo with hydrochloric acid. rho product was bani-2231'
purified by railsml sing it in bass, Emrolorio log with chooses). £1.12: ti: zoo
moid'lriootion with acid. Tho L13: oat purl y was ob“ alum! be me .3 stal-
mm; the acid from 0. onto:- methanol nexus: with a charcoal pmfificotion.
Yiolr‘n of slat-24:23 pennant or batter mm'obtsinsd by this method of
methylation. It the 3,12-dimtf2m-‘4fiqflsafimi wills-jg memo mo not. 31211-0 it
had a madam? to bocozzo gray on aunt-.22. 3, ottoman it rmoinod Write.

A single attmpt was mass to mthylsto the whim-2 salt of 3,2241%
Mug-2,S-dioaz-tmmthomhiophono vim notify]. 106116223.

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133‘- .Na 0213 1:3
‘ 4- 2:23.)! ---- I t 23231
CE;3C320.C s .CTEnC?!$ I c: Yapizaotc 3 'a:, gain-’13

The not: 111.12 salt and mothyl 106.1629 mixture m 22th in absolute
methanol at the reflux twp-erratum of the roost-.1011 mixture for sights-on
hours. as yellow sodium salt was very insoluhlo. The reaction mixture
III flltm'od and from tho filtrato‘ a small mount of t Units crystalline
mtorinl was isolated which when in the tespmtm range lira-vs" c.
That 3,2441an logy—2,54?“ carbonothoxythio'phmo has not boon previously
reported in the literature. The 3,1;«3Lmt1mw-2,Sf-Cienfisethoxyfiliophma
1| tapomd to molt at. 52-530 C. (12?). Estate the asirmsly low yield
and wide slums in melting points, as wall as tho availnbility of a
befits:- matiwd of nought-lug involving disotl'xylsllfata, the reaction

. ¢ . w . . .

J

m5... 112/

. I»).
In "I

77

0.223103%; 220923? iodide was not imesi‘.“..g0t0d fizz‘t‘ar in 1:729 1:722:22y2t

“11%;.
The“ ...; «£1.2t‘202; 3210; '1‘. m0 m2: 122192032322. 12;, t'13932’..‘§'10.‘4;" .tirm
. ‘ ‘: L «fix 0 ‘ : . .I --. ~ .‘ ‘,-., 2 o,
of 5.292.102; .2; .9 {5-01-2022 027,1“.15233320 2.20.1.2,” 0:29;. '22: c 2:22.212-1 as a

cat-:2 yet mar-0.2213 in (1221001200. 7:3 trig-3'21“ arcane catalyst was
tram-.1; 12300212023. by the 2201:2027“ of Comer 0:21“. 1.10 1.20“" ...;“1022atf2r0 (’2) .

T120 62 .311“: '22:.‘23tion was 00..-..0 2:? cut “2,22 m cuffs-rant pmcmnrn. Th-
!irst 009.102.“. 13-12206 heath; 2 t.‘ 0 2,3.” -r 1:222. 2‘202'2-2- 3- ~27 . “mt' 2.0223052122123030
wit: copper chmnfla catalyst 3.2.22 92122-211229 as a rmctian 210231222 unis?

an 0th: 03.22000 01‘ nitmi'; :n for 0:212: 12.22.2122 ...7' t‘:::i*ty 223.322.4203. 11:0 reaction
mixtfi'c was 2 'il ut0:“ .wit“: 0t“ 02" 0.":219-3 ca talyzt 2:22.20 rvnc'x'ar.“ by filtration.
T220 quits-":20 was qr-tnctad from the pZ'OCHCt wit“: rag-2223120610010 acid an?“
the uni-00.2.1202“. starting; wharf. a). was 120.22.02.11.“ by l 00223121222 hyclmvdrfe
attraction. ‘1“.20‘“ ,..~c 1'23“"02'21..-op-.0..- wan £1.00 11y isolated by fractional
'utfllation. Tim filtration ate? in the above errpndmntal prom-“2.2.220
was scrwttima difficult tea-mes of t“: 0 taz- a 313-21“ .0“: fomx? during t“:0
120001.100. in 0031012 method of cal-2:21.03 out the decarboxzrlatim: reaction
an! 10011212130 of the pro-Bust 1m: to 222.2: the reagrmta 03' rims-xiv:

1:120?“ 02101:! am? than 0f 3r 1.22.0 mac. tian “2.06 been 0:222:210terl to (5.20.211 {.320
product and a 00201:“ 02:01:10 vacant 0f qzizlclino from the reaction 2042321220
“.223: 31‘ red 20-22:! pix-0002300. This gave a very 01322.21 mixture of win-2211.220

r221 3,22%”15t‘firr“ “0:2“0210 from which it was 0225102- to Cx‘mot the
(122122011220 the 1822'“ .0120 the promct 00:. 02.20310 0.1.02.0. 172:2 tut: 220*.32222220

"0?: 0022:202' 02.10 2:101:23. “he 2:203:02 022:2 Iii-311.! 02:0 02222220221020 in". . 022-0 VI.

271

“32212-2. 32232232222242“ 7 2

~ .2412». mm . m.
mflvdbmuwcamwswutmm m2.
2.121. 252222220 =.'fmm «Mafia-m W

msfiwxmmu was; madam

-~ .. a: an n d 4 1 ‘ ‘ ‘ _

2.2.20 EM 22102520291th *3 m0
3‘22!» m«w.u2.ww

 

. ... 100220.22. 2!};in
r “.12 1‘1»: ~ marry! ‘P. 32.23%}: mm 2Q 2 l
. .. 4 ,2,..—«:w.¢' W) 1.: mug... ...; Iii" ".2

2 01km? 0?.- ' £1220 mum“ 21"? '4

..t .:2 ram-.3 '2. mm“. 12222 «“01391 3,

-n) 25:22." 2.36 #3 mg)“ 1" m

Ahfifihfiflfifl

22222222

 

 

 

 

2'3" 3’“ Hi 2% ‘1 ‘"
O ‘
~- 7 4013 '24:)“ .:6 0232212253. -_ . V

2222, 02420202222 1.» 22202.2 22.222229. 22:22.0, uh J " 5
22120: 3,2022- 2W“ motivate“ 2' 0
. “2-22.02: 21.x! 22.272201222224217 1.5a C . “.000 MA“ 0 it“

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72

The yields var. 10733.81. 737m 13:33: qmntitial 0f 77377777777777 mm 6779103376: 7
l comidm‘a‘ula amount of tar £01,337. '3 7127131773 1.273 dacarboagrlation rmct1m1.
177777-77 was always an 177333333 117 77317373 of the 331733333 during tit-a reaction.
In 3773 case were 2 {gm-33 of copper cE-a‘oniua 0731733333 and, the agent
catalyst was isolated by filtration, followed by 37 7777777737733 washing with
‘33:- mi' 3 final 671373173 in man. Tim £12717]. 777713771. of 3373711; cat3ly3t.

m 5.35 grams. The 17731-737733 in mi" ‘1'. “as probably the result of tn‘
327cc; :tion of 1.137731%“: 77772“ng th 73 traction 1:917:37 7mm not (177177311113 or
0153731“ 301777713.

The 3 Aim-30351111771377.3713 ml bmainatad by two affix-ant experi-
mnta‘l nets-7:77:37 The first proca‘uro 18 11.1773 rated by the following
equation.

:7". L "-

   

. s: 7 3., a my J..‘ I 3
1173‘ 7.33 ..1“. , 7 3277:7717: 2 7.7 g..:...--.771 37-77:! 337.71, 77773 77.7.-

. .. .' - "b“\ «u' Ju~~ .37.‘ my ‘- 1 “up ,‘ " LA ,5. 7
77-133 “377:. 1y... 7‘3: r3777: 3,2«717777-77333 7. 5““ 7713577773.. 3.71 55.7.3 3.77.31 . 3.71.17;
.- ‘ ’1... I! [on "_ A j 3‘
3 r9371 3 1.3.3213“: .733 (:7 337331;!- 733-. 2.- .‘fimn nan-“W7.- $3773.73 3373;171:373

.77 1,! 17.“). .77 A :1’ 'H- “s .. 3.....-31. ,, u. 3 7.. .
3 4:72.73.- 3:e.-.-.3 37; 3- 7. a! ti“. 3 7.7.3.7???"'“-.-.-«ts:.-.-.3-3’7u713r7.337 {ac-.77-.

O

3.3 W: s 1:323:1me 17;.“ 1377:: v.1. .‘3 2":2132 ’. ‘7“7-'3‘..1€.: '7’ 1337' "1‘73 of ‘3‘ :4 I"-.‘:-7..‘-77‘:173.
803m masct‘x'. ,7’3. -; ‘.-1' “7t “ 312.177.3132 7m 7373 13721:.137 3.77:: $3770 371732731? b7111-
Lfig 777373.73: mama-3:? $172. the 71151211137173.0777 v“.-cI7 var“! 2773777. V7373

the: ‘37-}? “c. 10 7.3.7:“:‘7'3171‘13. ‘1" 7a 371* 17377.1 yi 71:. cf ‘5’. .97" 1.173% Sty-243.3771:-

$2717.32 7:73 07.71.77 77:73 7.77:3.

_

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l.’ ’ . 4' " ‘ “‘ , ‘. - ‘ -’ ‘ V 9 "~'.- N 5 E ‘*H "‘« -‘ fl“ 3“ 1 . '3 1 “" "- ' T ‘ ‘ . '-- V' '1" ‘
m 3.». U ‘a..~ a, ax. . . .9 :5, .- ~:. ’ 0.. o, -... NJ L .. . ‘v _ .. v .1 a . -.L. . .~ '9 - .,- . .w . , - .‘ .~-
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“J ”you. b ‘33:. d o x .1 v a a ‘30... an rum-M U9 v. ...-“4 ow .1. :A. a}! u ..3 u}. .4 .t - .. x. s-1 3 -.4.- -- ‘ Q

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‘\r 4. Hf." ’ ,4... A .‘r' ' ‘ - 0 ._. ~.- \vua -. my: a: \n-q’ ..3“ ' - "VI: ,9 4' , \ 5.. ”a ‘
$-60 smb dun-Lu—h‘w— vdfiu U U —.‘ «II-- 4. — 7v n l: 'viv . v w —t.--- ~.— .'-3 - ...s .. a 1. -) a ‘4‘ ~~‘ J h‘~ -‘ ~-- ‘1' 7" ~_ ' ’ ‘ '1‘

 

¢- - -..gv - _ an. ...a, 13 f' ... . '_ ..9 en -,.- .43 .9 ..e, ....
651...“...3’ . .- u ‘1'3i7fo1K’J fl 1 2.» ‘ '.. s . :3 "2.94.... O... 2'37”»7H ..1" .3." :"wu u ...‘73 P "its“

.9 ....~ I! $331-4 ~ “ I"! a. -.* :- A9. .2 a at
&w-Lifl34~ U_ t::.:.3 an.) 31.8%- “'33 \7.‘~,' Q T~J3 fiWG’...At3 a} {“53 3t. mutt-..3. .3 I}... 7’} ..r.3

.- a 3 .. .-.; a... a m- .. i _ - , - 9 .~,
ant-321.3... ..3 to be: £311.33 1.22 ...-..3 V. .-.: .:«Jr 333 est-3. 13.x: 71-395.;0. “"33

.3, .,1.
’ ..f 1’

3‘ ‘3 . .A ‘ 7' .I- . ..n 7- . '_ - .0.
to 23-3 3.13 tea-tn" of t‘ a 3'...) m? s. ....1 (.333. (2:35.?! tar»: cut ’3 W2»-

‘0

. -. _ . 5 ._ .. ..~._ .1 A - .. 2,- .'. ,.. .9 ‘ ,. fi ,0 .7 . - ._.
“.3 t.’v-11‘l"«iw‘.lj’ “$43.;er At»... a 8&1... ..u :1 ..7‘....‘J..4Lm173 834.313.1133 to" r =~ 3’70 0-3.

‘7'4' ~‘-. ."” \U. 3‘, I ‘~‘\ ‘. I. ...,-
J 3 * . 3.3.2.33 cf." 9 .3. M ”9'

..t.’ .O-l~" '. v

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pm; \lct 33"};‘JO-3": f-‘Qu: t-."~! b?‘3 h~whhv.asf\}bi r.

q

‘ Q
moist: of £13 3313:1113. ‘32:: 3, .‘."".Z.l..‘.'i-’-.":.‘..‘:-C)’g"$fi*’71"31’3’3'f;-;i9:§2it"??? 2:3 net“ -3221

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pf.l~flf3ub3.j 1’3.“JL ”'3‘.- is} t ‘3) 14..."; “Eur“...

5 -30 ”on

’1‘ .‘. v.3 - -..~* .... - " . p , _n\; .. n ‘1‘ .._. -. -.
A a...&;3.*3y GL‘OUJU x‘3 “ “d8 :Hiz-O'n' a to 33““: 5!; &\-‘ a ;:J 3 3’ .‘3 .v~.. 'u‘l 5“- ';’. .Z. -7-fl‘l ,i('- :7 f}!¢-

’. .. q. n- ’ 1 J n. i. “5-? - a ‘ '. ‘fv- . 'u 1‘ "' 2‘ "I’i" , '-
tiauc'lo 3.33 “$32.35. 6.31.1342”... 3.3 J..a.i3CtJ-- L’,’ ILA? 1.9;;C‘fl'mlu fife...» 4.3315.

 

Th9 prom: use 993d v.5 t'. :5 5'3 :5 as ‘L': .9139 ._ 3.;9 m9: 1; tho .;:-3.....:= .2199 of
Sfihmg'l-E-thi 99'. 953+. .191. The 611:5}.er 99.5.3311. 9.3339391 t9 $93.93 3.3
evidmcad by the apcntanacus r9313: .13.; of ti 9 3' 1:1; *0 5.3 33.9 3,143.-
mfi':o3;!-2«bmmot‘uiorp‘zmm was: 35': to t :3 3929339 burnings in ’95
61.3259. Homer, the 9599.]. 35.399 :19 9959 3.1931, 9139:: sulfur in 3:31.35 1.: 3
(Edward r99; 7951., did not: 3332;93:- to 09cm in $195.99. 1.199 t..- e 159-
htfi. on of product 3538 “tr-3:13:13} by 52. 511315 3. traction, acir'iii‘icatfidn,
Other actracticm, and a final distillation, only a tarmr residue was
Obtained 21.1933 was unifi 31‘3“" ~19. Th9 proca‘fizra was not rag-3951.991.
P9951231: 13:9 3,1«31-1932-3233- ”-5) 1913‘ 1-5951. :191 1:3 wztrarzaly active and
dimrizad or dacompoaw on hinting to give {39139339195321.9541 la. i‘iw oth-‘ar
pouibmty .1... that tiza t1':‘101 derivatim did not form. 1309:3999, if this
“to t. a can the start :2; mtarial would bar-‘9 been lost during the
mama. actuation procaiure. No attaqrt to obtain 9 55993154 13519319 9
on the “action 93.193159 was 339.33 in this 9559.

511399 flbltitutad 3421193323911. 911.31.211.91 c 9315591553 3:999 3135* “95 during
tho initial mixes of t‘ .13 izwdstigation the: various synthetic routes to
3-thiagimmfl-doh $19113 002351553395. Una such route was 139551.159th but
fin-l]: abandoned for the reasons indicataad. The following 693135 of

tactical as used to obtain a 3-bmmt1119932999 derivative .

no, ‘I Q, A "5-? C.
| 'l. \J.1'~L0)20 “"""~ .843 ukrdué 3
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332-55
l 53,
«30921
5951.19 3
--l
l» 1 3 (993909353 «Eka- o (332,999.91. cc,
4:033 - crifgjoitmna

8

a?! I] Mr”, * 3:0 + $3531 m , 0 94551999911, 3 2339::
.1”me 1'14."
..., ,3 U l
5 - - -_ . -- - - . . , s .

T135 aoetylation of 9555.55 ma 39995391151195. by the 139123.95 of
5599333. ms: toga: (33) in 4». 113313 me than a nixty parcont yield.
Tho oxidation of 1.229 2499.}rltE-d9phmo was 95.99155 out by 127:0 mttzoci of
11911911331 ma 003115? (5.1;); 35:19!) 95112103.!!! the lmlo- from reaction, to give
on 9.1.9951. 53333133559 yield of 2¢?:-o;3?:enocarboxylie acid. Tho brom-
mtion or 2-t3119p335nracarbozcrlic acid was done It; the 1:912:03 of Sta-311115053!
(39,635), Tic procoduro m not 3 way 5951151219 999 as a large 53:99.59
01' bromine and Z-tiiiopi'2e:539 oz‘bozrylic acid had to be mm}, which cat-135:1
a atioly tE-aio}: 19553 to form. The moction mixture was allmci to remit:
in the Open to permit 192:9an bromide and meal bromino to escape.
Th9 lost traces of bromine ma mam-9:! with on 3939115399 carbonate
solution. A yield of almost ems-111.3? porcmt of 11.5-dibrm-e-mioghano-
subatglio .5191 ms obtained. mrtlm‘r coz'zalioatiorl in this prooochu‘o
m t‘zat the hydrogen 13:93:15.9 am 99:999.! bromine are difficultly removed

and o. wormgh mine; of the mogmts m rather difficult.

Ill--.
fl D i I

Biz...
. x

'3’.

r-I.ov-o..‘

75

The brominntod acid to. docorboxylotod by replacing the carboxyl
group with a ooronriooototo group and than ronovnl of tho lattsr group
by hosting it in I 20% oqooono podiun ohlorido Iolotion at the reflux
tumour. of mo): a Iolntion. T2110 1.0 followed by acidification
and Itoun diotillotion of tho relation niztnro to obtain the product.
Thin nothod failed when the norcuriooototo dorivntivo Ino'not isolated
baton its final decompooition. khan tho muiocototo don-ivntivo was
ilolntod from tho norcurio cantata solution nod than oubjoctod to
done-pooition in a sodium chloride solution, [OIIOI'd‘h¥W...tIII=dil‘il‘
lotion. and £19911: a fractional diotillotion o: the product,'n,botter
than fifty percent yiold of 2,3-dibromothiophono III obtained.

The original intantion Hal to rooovo or roplnoo the bromine in the
tin petition through a lolootivo ariunord {unnotionyhr taking odvuntoao
of the rolotivo difforcneoc 1n the roootivitioo of tho‘hronino ates.»
in tho two ond throo position.

 
  

‘ | . 2*. E 9th or rmval
I El: . Br or
‘ ' 3 replace Hgar

3

This on: to ho folloood by the conversion or the 3-bronothiophono
derivotifo to its corresponding Grignard tangent 9nd interaction of
the latter with 0.11th to give 3-t‘hiophonethiol. when it was found
that‘vary low yields resulted from the formation of tho thiol group in.

the three position through tho Grignnrd reaction the method was

lb

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77

abandoned or a useful mthoois in mumblo montitiu of oubotitntod
3-Ithioxahonothiolh- The wtity of filial. thnt were needed in the
initisl imootigstim to uk- tho nooossu'y qnsntity or final dorivn
tivoo for biological any would have and. this method. a rather
lnboriouo proooduro. For the may of new ubstitutod 3dwiophmtlziolo,
tho method in. utility am can molar be and. tie mm innstigoo
tions on this nothod m mo.- in tho promt work.

The s” (HJ-dialkylsminohlkyl chloridoo worn proporod by two
general methods. The thrco carbon ohnin 1m slkyl group. are pro-
psmd by I vary (:1er method indium in tho tailoring motion.

. P n‘ _ . y
Cl(CHa)3 Br 0 2:13:51, -—4-—9 61(czz.),z~rrz, o Fig-Shim).-

hvo moles of the secondary oozing were allowed to intoroct with one mole
of trimatm'lono ohlorobronido in mtmirous bonsono. {The reaction as
exothermic and refluxed opontanoouoly for o moderate period of time.
m. monfinry amino hydrobromido crystallised from the reaction mixture
and was removed by filtration. The secondary train! was rooovorod from
tho min- hydrobronido. The U (B,S-&iulkylsnhxo)slkyl chloride In
inland by attraction of tho benzene ”Elation with hydrochloric acid,
mipitntod with bsso, «motion with othor, drying, sud traction).
diltillstion. Too tron amines urn not otoblo during long porioéo of
Mg. in the refrigerator. Intormlxuhr mm “It. formed
Ihioh malted in high mlooulu night poms. to ovoid thin the
tr" mines are convortoo to their mmoblormu by What with

é

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75

anhydrous hyrlrogm c‘s‘alorido in nnhyciroun other Bolutionn. The hydro-
chloride noltn worn vary nto‘slo and the mines vorn rcgonorntod with
base when used in the nynthosin of the u.) (21,ri-cicllq'lninokllcyluziom'l
nulfic‘on hydrochloridon. Tho piporiniino, diothylmrino, and norpholino
analog warn prop-nrod by the method just donoriboxi. Tho method was
roccosnml because the brooo group in mfi'iciontly more rooctivn toward
tho aminos than the chloro group that mixturon of the halo compaction
worn not formed.

The nocond gonarnl method, nos-:1 to prepare tho w(r,:~:-ouiz:y1mmo)-
alkyl chloride compounds. coplcyod ohlorohydrinn an tun ntnrting
materials. The two and four cnrbon homologies wore prepared by thin

method, and it canon represented by the following equationn.

absolute
012281101'

bid,

EiC(oZ§a)nCl 9 Zara, HC(CE{3)n!R, o 333393-151

9 an Cn61 r H QC;
rags-(Maker: 9 52:1, ._....a, 9. ‘I-(C;1,)nCL . so, o “(.1

Tho chlorohydrin was allowed to react with, tho reconfiory mine using a
ratio of one mole of chlorohydrin to too moles. of secondary amine; one
3101.: of amino being consumed. in forming the amino bydrochlorido. Thin
reaction woo-very exothermic u’non piporidino iron :rployod on tho
amino. Aftor the initial reaction subsided the reaction net-flours was
stirred and heated at. its reflux temporcturo for twenty-four hours.
when morpholin-o van usod on the aria-a componont no initial exothermic

reaction occurred, which indicates the rolativn basic ntrongth of

 

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79

norpholine and piporidine. Tho product won isolated by neutralising
the reaction mixture with sod inn otnoxirfe, adding other to precipitcto
tho sodium chloride which bod famed, removing the latter salt by
filtration and finally fractionally distilling tho product. Yields of
sorority-five percent or higher were obtained by this procedure. The
compounos prepared by this method were 2-piperidino-l-et‘mnol,
2-morp‘nolino-l-ethnnol, b-piperidinom-bntnnol and qurpholino-n-
butonol.

The (A (fifi-diolF-Iylamino)aDenols were converted to the correspond-
ing b) '(NJ-dinlirylomino)olkylc‘::lorides by the Barron reaction employing
thionyl chloride in onhydrous clloroi‘om on the reaction medium. The
hydrochloriéon of the w (Hfi-rtinli'yhminohlkyl chlorides crystallized
from tbs reaction medime end they were incloted by filtration and
purified by repented rocrystollisntionn from absolute alcohol.

The tertiary onino derivatives of the substituted 2 no 3-thienyl
an’yl sulfides were obtained from the U (N E-dinlr'ylnni-io)o1}yl
chlorides by treating t? e lster with ti. o mbetituted tI--10pmnot3 in]. in
an oquomn soluti on containing moor -ceen or sodium hycroxioo. This

synthesis can be represented by too following equation,

11‘ o R2fi(CI~1,)r fl RC1 o misc}! ‘4 aosl't
3

o 2373?). o 2‘33!)

me mot convenient mothod {or occonplinhing this synthesis in to use

an excess of too thiopnonothiol with respect to the w(!€,N-dis1_‘<y1onino)

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alkyl caloriio hydrochlorico. In this mannar tncro is no axons: of
the tertiary amino loft in tLo reaction mixture to cause dif‘icultioo
in tho isolation preoccuro, Cue to it: precipitation on a hydroctlorico
vita tho hyd. caloric. of tno product. From tho mixture of hynro-
chlcrlooc it is sumothos difficult to obtain tan pure hydroclilorixo
of tho orccuct. gran thougn this an: o potonticl difficulty, equal
molar quantities of the tnicphanotniols and “U (E,x-oinlhylanino)
alkyl chloriooo or their Amino hydrochlorioeo war. employed in most
instances, nine. it an: prefarrod not to oacrifics any or the substi-
tuted thionhonathicl. 'Ths reaction was carried out at the reflux
tanparaturo of tho reaction medium. Tho sodium salt of the substituted
:iophonothiol was fir-t preparod by dissolving the thiol in the sodium
hydmxido solution. :.'.rwug;‘a Bedlam hydroxide was «uployod to form the
oodiun salt or the substituted thiophonctniol 19 wall :0 to liberuto tho
w(H,N-di&l£ylamino)all~.yl ciderido fmn its hydrochloride and to he?
left o small «icon: of soalun hyoroiico. whore the free amino as: used
instead of the hydrochloride the Iodiun nycroxiCo concontrotion was
3‘3ij accorfiingly. The U) (21' ,li-diuLaj'lMlnoX-Jkyl calorido solution
was mddod dropwiao to the stirred, refluxing, alkaline nercapton solu-
tion. The reaction mixtures ware stirred at their reflux tanparaturoa
for on acuitional tnroe to aignt hours, at the can of union time o
ycllou'oil had ooparated from the roaction solution. The oil was
axtractod with othor, unshod with an alkaline oolution, cried and
finally the prouuct was proclpitotod from an othar solution as tuo

hydrochloride by adding anhydrous hydrogen chloride. Eifficultioo Hero

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strperiencad if hydrogm c. lor11’9 “as 512:. ‘0." to t'. 0 et‘. arsl 531‘ 1.:r. Ln
execs: of the amount. necessary for the hydrcchl-cridn salt! crrattcu.

Wen ‘13 occurred oily pro: ‘ucta fcrrn' 31111.21: were 11‘1“ icult or 11:91.1:-
311319 to erg, stalliac. To 3101:? 9118 t‘. a hyflrcc‘ lcr‘ ...: 1"..1r'1tt11m was
accomplished in several she? 13, by scaling mall accounts of dry byi‘rcgen
c‘rloric‘a, filtering; the procuct formed, and then stir. ‘ing another quanti‘ y
of dry hydrogan chloride. T is procacuro was rep 331521 until no 5.1.31-
tionclv (21,?«1-disllcylsm1nchlk’yl disul‘stitutad fizianyl sulfide Maire-
chloriris formed on Earths:- sd-c’. tin of gar-outs hydrogan chlorii 3. Ta
:17sz -ns nature of the pro; act was rrntlv 1:2}:va bv satt‘m ~

wide the fir-33211;! precipi-ated lurc‘rochlorida in £11.19 et‘28raal mixture

for camera]. hours at 0° C. barorc 1’1... Waring. T13 b303, 15-21-111 :ylauim-
cllqlhisubatimtcd thing-l sulfic'ca 3:71. rcc .loridcs vars purified. by
racrystc ..lizing in most instant: ca fro-.1 m‘zyfirv 2: imprcpyl alcohol.

It was s‘esolutaly Mammal to maintain anhydrmxs conditianu during

the handling: of tbs hydrochloric-39. Fara? of the crude: products wars
vary hygroscopic and on vary humid days, they had s tandm to liquify.
In such cams the filtration: wars carriafi out using I pleas frittad
mmaal with s calcium chlori a tuba 1'4 mm in the: top of the tunnel.

The can. chm chlorids tuba was quickly put in “lacs after tha matarial
had Imam placed in t‘m funnel mc‘ dry air ms drawn own- t‘m crystalline
product. The purifiod tydrochlorides had mm or only 1 slight. tendency
to be m'groacopic. Ingmar-31 the 31-1239 in than reacticns mm

91g? ty parent. or shove. 1111933111” , sin: n-w W(3,?Iqiiallq’ln'nmcal“:yl)

2,5-dichloro-2-‘L‘iiwl ml! 169 hydrochloriclea, nine nmr

82

W(n,l-dunn-nmuui)2,s-dmmyio3-miw1 mind. hydrochloride.
ad in N(l,l-didkyhnmnlkyl)-6¢phawlo2-fiziwl lurid. hyuro-
chlorldn var. mm.“ for tho tint time. I. usury or some of

moi:- mm mun md analytical remit. are given in Table.
VII, VIII. and IX.

83

 

 

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The preparation of 2 ,S-cimstivlfiniophm In art-13d out {our
times with only slight .‘zac-difications in the ”perinatal procedure and
mm mum in lane variations, in the yields. Into I three liter,
three neck reams. bottom flair fitted with a reflux ”Men-or, stirrer
and dropping funnel was placed 2w 3... 0.90 min, of phosphomm. penta-
mlricfo. A 300 3., 2.53 moles, quantity of 2,5-hcxmodiono as phase!
in the dropping mm]... Stirring Am gamma and tpprumatoly 50 to
66 ml. of tho 2,5-huanadiom m added grand]: to tho stirred phos-
phom. mumlficla. M. this point there In no indication 01f m
nation taking place, and the 33431131021 of the 2,5-henneciiono was dis--
cantimcd. Stirring was contimed and the reaction ml}: was gently
heated by means of In llectric mtal. This procwiure initiatad l
vigom rmtion mandating removal or the hurting mantel and
1mm of the “action flu}: into n inter bath to control the re-
lation. firm with this precaution tom of tho proéuci was unreactac'.
2,5-hoxumdinno escaped wrong-h the condenser. khan the initial rmtion
htd nbaidoci the ice brain was ream“ and the remimiar of 1.3-2: 2,5-dlaxan9-
diam was aided dmpuisa at a rate afficimt ta minim a gentle

reflux 01‘ thus stirred reaction mixture. Following tins cowlata addition

Jul" .lc.\1..

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37

of the zfimnmediono the rout-ion mixturi Iii kept. at its reflux
tower-taro for an addition]. tuna: m At this point external
heating of ti:- rooction mixturo In mm and it! rem: condonm
Ill "planet! with I distillation fink. 01'! tab. confining a that-2102mm
Ind : comm-or. Tho crud. out bran thick Wet m dittillod

with aim-1n; using a mu]. :1 the mm. a: but. Distillation a.
discontinued won decomlition at in ii induct-d by tho We

of demo mm mm... charting or «no atrial, and I vary rapid
dark-nag 1n ooh: 01 tho maid!" in flu W a... m migE-xt
or the crud. elm use: mu product at lJc-dimthylthiophmo in
153.5 g. and it no a boiling point. mg. at so" to 125° c. m. crud.
2,5‘Limofi'w'lthioplmna Ia: placed in I motor: mama, “and with

80 ml. of 3 N sodium .m-droxida solution follow ‘1! 50 ll. of distilled
at». The crude pram“ m cried by hung at low. mr night in
cmfi lith mwdrml mama sultan utter which 1% II reciiatillad.
fno fraction boiling at 1313' .00 C. amp, with 3 rotractivo incur, n39 -
1.50%, m collated. it. weighed 122.8 3., 1.1 m1“, Bid represented
I 1.1.65 yield. ‘

The mend preparation of Eifiwmothylfiiiophenc m womliahod
with better yield. by varying than outdo of phonphornl- pontmlrido to
2,5chaxanodiono. The com apps-.1164. as previously described III
unployod noopf. for to: use of a more officiont bulb typo condom”.

In this oraparation to; roacticn was initiatod with at mild m from
I mason Elmer, which gave bottom contra}. of the initial vigorous

reaction. The interaction of 25’.) 5., 1.12 melon, of phosphomg

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pontaailfido and 3m: 5., 2.63 males, 1‘ 2,5-‘éwxanociono follovod by
“elation at tho product a! prmrimxsly «inscribed gave 156 .5 3., 1.65
melon, I 63 .31 yield or pure 2,5-C anotzylthiophmu mic}: boiled at.
133-138" c. nu: ma n nfmtivo index, n36“ :- 1.50%.

A third preparation or 2 ,S-dimfivlthmhmo carried out on just
previously described and starting with the m wnutm of mutant:
gum, 239.5 3., 2.13 moles, on 81.15 film of the desired thiophono
derivatiw with a mfroctivo index, mg“ II 1.913).

To. final [marotlon of 2,5«flnntiv ohiophm’w was carried out.
wloying twice tin. quantum. of tomcat! as in the two provious
prefix-“ions, amok, 5.20 3., 2.2:. mien, of phosphor-um. pmtawlfico
and 600 3., 5.25 moi”, of 2,5aheotmodiono. The yi-alsd obtalnod in thin
«to as, 2.37 .5 g., 3.93 molaa, 73.3% or to. theoretical no the product
boiled at 13.3.- 35° c. The reported boiling range for 2,5-anmw1-
thiamine is 133-1350 C. (2'3).

Preparciion of 2,5-iizrzcfi‘yl-3-fiuoyhonomltom'l Chloride

 

A 500 ml... fibre. neck round bottom flask m equipped with a
stirrer, mozwimotor, and u 125 ml. dropping rumol. The witty
121.1 g... 1.0:. melon, of crzlorooolrcnio acid was placed in tho flask

and the latter was than placed in an ice salt. mixture bath and coolod

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to 0° C. A 3.3 .3 5., 1’3.27] 31.1151, quantity of 2,5-d1‘aet2'g'lthlophana was
placed in tha cupping rural. 1:0 2,:-..-1c‘:.;-.. 5.3311315 was aid-ad
circpwiaa to fizz figure-1:13;: min-mi 1:01.: chagcrosulfgnic $0.0. T1110
ranked mix-“tum minutaa (11:54:; Kiel-1 tiz~1 tn. target-aura o! the
reactian 11:30:11; ran: to 2° C. After ma 11.113.11.100 01’ 1.110 0122;31:110-
pimna m 00.11213“ the ramticn Lat-dam was stirred for an 022111102111
22311: to insure 001;, 1.3.; 21039 of ma. tlon a}: .0: 1.1.1.011 111 1GB pcumd onto
830 g. of 01-11372}: 1:13. 1113 caused a p113: precipitate to form and an
natanpt was r-io to 15.31113 tit nave 131. It was 0011th on a
1:111 11° but as soon :13 1.1.0 hate-rial Rm" ‘ up to roam tagsrature it.
l‘q.1-"1a* .- “‘11 pin}: mtwm 11:13 1.1.011 up 1.11 carbon tatmciflorida and
tea 110,1qu filtrate u 1.1.1130th with tar-.19 1121-3 1121. portions of:
cafaan tatmcalzrkia. Tina 00.:“11103 oafion “tract-.10 1120 extracts wax-o
(.2101 in contact with 3112.y0r0us mymsi‘m sulfate. 1210 carbon tetra-
c lormc van 1'1:sz 1101:. g a. 1:.th aspirate: and 12-10 2,5«110fig 1-3-
t:ic;13.anosulfcny1 03.10.0139 ml fracti canted tnployin; a one foot. heat
3... “ate-1d 115:7: a: column. The: :‘ractiop boiling at 1.3.3.1033 h/fim.
IE3. was collected. The m...;.t of ti is fwctim m 25.05 3., which is
1.1.8}? of tho thaioretical yield. Tm: 2,,v-01..c.. f1¢J*‘i 10p11enm1f3m1
ctilorido was cmert-ad to 2,S-cmeuzyloj-thicphmsulfommo and
31111172011. The neutralization 0%" aivalant of 2,9-611201J1t'110p1oaoo3-
mlfonyl 0111011.}: no detain-fined. T110 result. of those dataminatione

am given in later e..-;1ar5.:ants.

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[,rat-smirution of the Rmtraliuhlon wivalant of
2 ,5 --3 i=1 1131931-} -t.‘:i::;1?:mcmlfm'l c" 110:1ch

1 SO :11. valuao 51’ 3.1233 1'! Melina Mlmxida wluticn was pipetted
into I '56 311. round bottom {11133: fitted with I r3111: con-Jensen
1 0.115310 5. maple of thy 2,S-ciimcté1yl~3¢110p11anuulfamrl chloride
was weighed in a amll V1111 am“. Itnppcreci. 7319 stopper of tho vial uni
named and char removing the reflux ccnchmmr the vial and its con-
tan“ var. dropped into £319 stamiut’s codimi lvdroxlén contained in the
flask. The reflux ccmza‘chr m net. in place and the; rcacticn mm
was kept. at its reflux tmpomturc by means or : micrcburnar for two
und a (garter hours. 'fim oily mtcritl in tho vial won dissolved in
1.210 Itamhrd balm. The flair: and 5011th ‘H'BZ‘O cooled md .. £31! drop.
or phmlptmlun var. aided. rho chalice mixture .uu titrated with
0.15512 fl hydrocfloria acid to a colorlau and polni which required 12.39
:11. volume of acid. A 113.911 1111-. 7011112.. 01‘ the 00.11. acid an roquirai
to tin-nu 3 SC 111. volume at the sodium )‘gdroxmc aclntica used in
the above hyciwlysin. From this at. and the fact that one oquivalcn’c
of 2,5-dLnatHyI-Bdufiicphmumlfwl 01110111113 require! two equivalmta
of 001110.13 hydroxide it‘s“ $011121 that the «marl-swam molecular weight
of the product isolated m 212. The theoretical value in 211 which

in an error of 1 unit or 0:1erth 0.117 percent.

 

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A SC?) 13. quanti t3I of 2,,«34wt 'I"-3-t:1iop1m1r3eul£ony1 chlorific
11'.) 11.1. of cancmtrctr-t‘; 6:;189’113 3210:1111. hr-Lrozziza and 2 g. of pow-Acre:
...... .. ..n: ma cal-‘30: ate 1:: .«3 chem in an 91 fat inch tact tuna. T2113 crtctur
'1... ctirrad 11...: 1 a {#1133 85211.14; mi which c0111; ~33 a virjomus evclutic
of {3:15. 11‘: an i; a gas m 3111131211 3111:: (20113-021 tine mixture mm team-2?. 131 a
Water bath at m" C. for fiftsm 13.- 111.115 £12121 1.211121 at 80-1700 C. for an
a-i "ixioncl tam 1111131111129. .A 11111.11 airstallinc solid tom-11’. and it was
1‘va from t“ :3 .mt r13: Mai-3+1 ratctura by filtration. T1113 clcar filtrate
was-.0 000106. in en in: bathr 5133 +220 2,52115.11111121116thdcp‘zxcmmlfonc 71.11:.)
cwvtallizcri fro»: the. I 1235mm as a mite (rt-ya 1.1151111 solid. The
(-13qu ware filtered 91-113. 111‘: 1:1. T1113 cry-'stezllir.c caterinl obtained
Ivan the hot rtect‘. 3:1 11:: tum 1.33.1.3: at t 3 311.111 trp-araturc as the
mtc‘r‘ial 0331;111:1311 £10111 tm cold filtrate. fi'xemforc , we”; were cor-1101114321
and. recrystallized once {3212-1 act-W. Tiza “(311.3 point of this procuct
m8 ILLS-13.251": C. '3‘113 r1‘1;'\ortv1€ mlthg: point far 2,5«31'1-11‘315'1-3-
t“!cp‘rf-Jmamlfrrmrziz' '73 is 1359 C. (3.33}. fillerzantal analysis of the (10.11-
m.:111«:"1 for cam-:11, 11;?" P0333 11:12.. 311311? gave 5-113 following results
Calc'd tor c W3“: 2:, 3.7.53; 11., 1.7).; :1, 3: .5. F0111; :2.7 .42;

a, 1.;13 5, 33.37.

:02

P re; ration of 2’. ,5 J? 123-3121 $1.31 43310;). 3:333:13].

 

A am 1132:, time: 31-3312 $352: was 1‘1th 31th a reflux “33:39:23
raving a 0:313:12: c::2_1;-r:i.2:‘sa 123133 nth-331194 to €7.23 top and, a stirrar, and.
a Cngping flannel. T33 apynmtam w. dries-.1 an oven at 1150 C. prior
to its being meet-33133. A 13.5 g... 0.23;; 130123, taunting; of lithium
8313:1123; "I‘M-.1313; ms 331713313133 in a 31V mm 11132113.? an Lavartud flame].
#2121: 339.3 :3 8122-2333: of 3.2-3: 331132303331 flowing fies-0:131: it. Tia-3 pulverized
11.32.11.133. 3111;313:321 1.31.3133 mi: 31.3 3.1. of dry 91.1.61: mm 3.333! to the
raactian £132.52; . T130 stirred 3mm“ m 23.331233 at its reflux mammatum
far time hours to (313330179 the lit"21.uga: almuism 19:63:19. A 23.0 g.,
0.053279 mole, qumti‘q; of 25-33323-233 1-3-thisphwuzulrowl ctglorizie dia-
lclved in 100 1-21. 01’ dry other: was placad in the cropping funnel.
This lolntion was 363.3233 firoywisvau t: ’62:: littima 9.13.11.11.33 1333316 salu-
tion at a rat-.3 sufficient to keep the stirr‘ml reaction mixture at its
reflux amperamw. F ’12,! 12:13:32“ Ware I'GQLKLZ‘M to M 1:320 2,5«11319‘3‘1y1-
B-shiophcnemlfaml chloriio sclntian. The mmm 1m stirred and
23.131113} at it! r2431“ targmrahuz‘o an wizlitimzal half hour am: film 501’.
0.2133 ovemig;3:t-. The rolloumg 33;; 1:20 3:1. of Hut-er were slowly added
to tha stirred mactinn xfixtura tram tins (trapping hmnel while the
viz-action {13331: was 1.31333623- in an ice bath. 1‘. S]. :31. quantity of 93}

sulfuric acid was {33.111531 with 330 :21. 01' unta'r, fiphcad in a heme-m.

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and chillsd in :3 in.) bath. T's-3 2:33-21:7sz mast-inn fixture m slowly
poured into the m1]. stixro-i mlfurir: cit! sciatica. The ether layer
we Sfiiiial‘ltOd 1:; a Niger-star? funnel and the 2.2110ch phase was mummy!
with. two, ICC ml. [artists a! ether. the ether ecttt': ta and original
otter imam var: cmhirmé ma}. vtflittm; with two, 25' m1. 9. lion: of a

15 5 aquamn smilzm hyr’mtride solution. ' In 0133' 1113'” aapnrabm'i {mm

the corabinaal 3125.13.10 aghast: on sciéifhtatim of the him with a
6 molar sulfuric 101d solutian. After separating the oily layer the
mama port?! on was mrbmotod with two, 15 m1. portiom of otrxer. T319
amiairm-i oily layer and other extracts mm dried in contact. wit}.-
mifiygu‘cua magnesemm waffle. After removing the magnesium aulfatu by
filtration be 1139: was removed by (intimation on a stanza bath. Tho
red-jug was diuiillml using a wx‘ifiod Imimicro (1131mm dist‘maHz-m
flask. A fraction boiling: n. 70-75" C./E-.m3. Hg. weighing 19.59 5.,
.Ou'T'ILQ min, was ocllactafi utic‘t ”prawns a 145.2?! yield. at 2,541.-
new,1-34hicphenethiol based on the initial noun? of 2,5-diraoflzrl-3-
t7“. 10p?)- manna: 131 chhfid 9 .

The name gsnml mart-Lama]. procaa-furo was used in a moon-i
mpaxation of 2,S-dirat‘ryl-jdtr3.012531219151321 la in tho lithium alas-15.1mm
hydrtio raiuctimm of 2,5-fimat} 31-3‘tlxioyhammlfov1 chlorifio just
described. Thu qmnttthl of natwial: ul-Jd mam 87.5 g., 0.311") Innis,
of 2,S-dLmthyloB-thiophcnasulfowl chloride and NJ: 5., 1.2:? moles,
of lithium duyzimu mtrtia coniuia ‘ in I total of 230 m1. of dry

0th.”. The 111':th alum-mm hyx' r160 oolution “am- prepared by refluxing

Sis

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tum 1.21.3,134 2.41.1. .1- '...I L. -: -..: 3:: r 2:11.033‘

M
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.-

3: in.) Ext-are, than

«may; it 3:51:33.- c*.;‘rv':.‘.:._,?.-‘... A ‘13-'41 :31." a half ficur part-c; was re quired
to az‘fi 13.11 of tits: ?,§-—.1:295;;'1-3-!:.?:icphmasnlfcm'l cl:191'ic.’o 1.9 the

livzmm alumina hytfréirfa solution. T‘w 2,5-{1153t3231-3-t?:10p‘rnmefliol was
isolatac! as previmaly fiascriheci. fit?! fraction boiling bat-wean 5:96:30 C./
1.5-1.8 mm. 3.1:. wadrmd 1135.12 3., 0.3353 magi!“ ...ici. in 3.13:?- of the
fluoreticel 3:”. 91:2. Try.) yiclci was lam-2r than in fine first pr:‘spa.x'a't ion

of this material Btu-.6 Men though 1.35:3 crude; 2,5-dinetiyl-3-t32-10phene-
£23.01. was EtCI‘GC in ether un; er an at}; aware of nitro gm for tween (inc/I,
trara ware 1.32:. Lanai-37:3 at“ some oxim‘ticn and dammpoaition. ’3'123 reduction
01' 2 ,,-<,L..»3tr."‘-”--tT‘.iop?.c-12t«.a.z1..‘7‘om'1 chloribia 33.3.3 bagmatad & third and

fourth 1.1.3::3 on a. (2.7...) mole 3:26.13 an {33.731 yis 1;? of t. .9 me meg-tan was

(attained and or: a 0.11’» m 1:) sea 13 az: 85.1”: yial-ci of 2,S-:.‘Lrnathyl-3-

t:-.f..3 Emmet: 121‘. was obtained. Tao-r git o of 11mm alum 11mm 12;: ride: to

‘2’, -:-Li=:.:9 t‘:grj1- 4.7213; .31.: lfcrzyl 9‘2101‘11: .273 was t‘: e cur-3:3 u in t; a
wrenact m. Tm refractive incest of 2,5-ctmfrg'1-3-

v

Pf:
Viiophaneticl was detnvfinad, n53.” L" " 1-5771.

“th synthesis of 2,54“: mothyh'a-hhiophmeflziol by Zinc
Sulfuric 121:} ”tac’uct ion of 2.5-1 methyl-
B-taiOp;mnaIu1£ow1 ( florid.

A 175' 3., 1.5 moles, quantity of Wonk “it! I. pit-cod in
a on: liter beaker mpportedin tn loo nah nth Incl ooohd to «:150 C.

A turret val filmrsa‘. in tho cold acid and 85.2 3., 0.5 mole, of

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2 ,S-dLaefifiyILuCphem were 2.3.2132: drag-atlas, from a dropping farms].
upper-ted above the beaker, to the vigrmaly nth-rad acid,‘ at a ram
sufficient to keep the meticn temperature balm! ~10° C. max-mg

the addition or the thme derivative to the acid the reaction '
mixture turned a bright m‘color. A 3L3 33., 3.5 13013:, quantity of
com commmtod mL’uria acid wa- poured onto 900 g. of ice cantainad
in a three liter flame hock flask equipped with 'n stirrer and reflux
maimaar, and 3:1er mm ice-salt. bath. 'l‘ha reaction mixture of
chloroaulfonic acid and 2,5«fiLmthdthiophano ml muted into the. I
vigorously nun-ad ice and sulfuric acid; Followixig this, 153.5 g.,
2.5 moles, of a mixture of zinc dust and 30 math zinc powder vars

added to 1m nth-red mum” during i one hom- pariod. After the
addition of the zinc had been completed tha. reaction mixtaro no otirrod
an additional tin-ea hour. at apprqxbmtaly ~10° C. to complata the
reduction. The reaction mixture m that cmtiously allow to mm to
room tmperamm at which point than valuation of hydmgm nu quite
vigorous; mm the gas evolution Ind make: the stirred mama
mixture was heated by means or m electric mute]. at its reflux
tamer-3min for two hour-a, allow to coal to room wmmuture, loosely
“append, and set aside overnight. Tm W reaction 31m” an
ant refluxed until :11 or the mine had dissolved at which point. $229
mixture had turned red in colar; 1'33 animus:- m maxim for

Item distillation, 3nd after an additicmal quantity of water had been

”dad to the stirred reaction mixtures 11. ins. ltm 65.3th. The any

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layer In the distillate m takun up in other and the aqumo 1.3.3.1:-
hl extracted with Dovetail 100 ml. portions of other. Tm crammed.
.010? mu hr. driod over mhfirouo mgrmlitm sulfate and than
distilled using I Hm comm we” mm 01' the other. Following
a .311 {mm or 0.51 g. boiling bola! 130° c... a motion which
mated to 2:..23 g. m collected mm: ballad at 130-337" 3. and! had
I mun man of ab" - 1.56324. this "W m identified a
1m” Ifimuniophme and that”. no appmiablo yield of
2,5adlaoflay1p3cflxiophondhhiol who obtained. Apparently a very ml].
amount or an desired 2.5-umthy1-3waop3anam1ol an tamed as
indicated by on strong typical odor of a thiophmathiol which no noted
Mid-01y {alloying the aim vacuum. he recovered 2541139931-
miophm muted v: 28.5: or that initially used.

Attmpted Eonobmmmation of 2,5-1’1'mot?rylthiophsano

A pollution containing 37 .6 3., 0.33 solo, of !,S~6Lmt‘:y1thlophmo
dunno: an 200 n1. at carbon 41:21:15. on plane in as am 11w
m nook round beam nun: equippad with 3 ram ccndemm, um,
tad dropping funnel. R 9:13 vigorously Ibis-rod mum In added,
during u to and . nut hour period, 53.5 3., 0.33 1.01;, of broaino
dimlvod in 100 ml. of carbon disulfldo. Tho reaction flue: was cooled
in on ice bath of. intervals to prmént loss of carbon c’isulfico and
brutal!» through tho condenser. Following tho complete addition of the

tam-1m Iolntlon tho reaction mixture was nix-red an maumu hour

 

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am a mark: to hung-o completmo at ”action. After being set
lilac tbr five hours -%o ranc‘ien mixturo an. washed, in I separatozy
ma, can an, 150 :1. pox-noun or tmty gamut. aqua—ma 31am
carbonic Caution and one, 100 :1. portion of (113111196 water. The
urban mm. lam m muted and 6:1“ by being set name marv-
nigbt in cannot with WW.“ ugnasinn sulfate. Daring tho making
proceduro that. IIP'”V1V1d color ahangsl observad in tan carbon disulfida
Caution. the rmnon'uixm boron tubing m M and copious
mum. a! hydrogen bromide: 1m“ omitted; The cam aimincio
muQChmgflwmmmgmmgfrmgrmtomrpu, than“
pink and finally'to u lizht.ynllou'oolar. Hhilo the oolutiah Ina being
dried tho min altit- turned pink that purple and the Deletion
m a a pun-p1. «1a: £30.13. um b01333 at um. Might the
ninth: gun gm artful. tho miion‘ulntian mi fractionated
‘Ilkng n.0na foot heated Vlgrunx udlunn in gira, tho solvent cnfbcn eta
ammo, 313.5 g. of amounted 2,5-dinwt‘1ylflaiophona boiling an, 135-1390
6., u h.7 g. internodinto fraction.ih1§h who dincérdod and finally

36.1; g., 0.19 male, a 57.1 yield of; 2,5-dmethyl-3—bromothiophma was
collootod boiling in the range 194-23$° c. at atmospheric pressure.

In. ”portal boiling point or this material is 195-195° c. (63).
Prep-mums: our Kalle! Emma-1c 0x16.

The quantity, 159.2; g... 0.5 mole, of mercuric acetate vars file-solved
in L50 ml. of distilled water. A ‘42 3., 1.05 moles, quantity of

oodiun tutu-oxide, n 53% «can of tho theoretical mount. near-led, ms

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4110061736 in 200 ml. of distinct! mm! m'. tho ramming basic solu-
mu m chilled in :1 1c. bath. 1'32. mercuric acetate caution mu
mod into tn. vigv-maly rein-rad cold Indium hydrmdfia solution
rmltlng in tho 1.qu precipitation or the yullmt mercuric oxide.
AM moving tho W12 mic oxide to min in an in bath
to: W hm: 1% ‘- recovered can I manner m1, transformer-:1
b O We, fished with MO 251. of at» and thin ignin filtered on a
3mm: mil. E31110 use precipiuu m an the farms). 1% was washed
fir” filth 956 ethanol to rm. mm as! then with ot‘m‘l ether.
m ”00191th m :3: dricd and stored in a vacuum desiccator. Tm
product m 3 var: fine yellow pan-:32 M the yield an quantitative.
In I lacuna preparation of uremic ma. it no- found wdimt
h uplq I W {titted glut. filter in place at the Buchan- mu
In all {flu-tum mum, mm: (rum rumum tho filmtion
and “thing a: m ”llama mm.

Praparatlon of 2 ,Sdsbmmyl-J-iodothiophana

‘_ l I

8 w
mo quantitiea, 50 m1. of benzemo and MJ. 3., (51:2 3019, of
2 ,Sémfixylflzicphena were plan-ad in». 300 m1. wick mnthed bottle.
'l‘ha bottle was showered and coolad in In 150 water huh. I. 75 3.,
0.35 nola, qumtity, of fraimy prepared. yellow im‘cuflc oxide und

109 g., 0.343 mole, of iodine mo mighod into two separate beaks“.

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The bottle ccatafilw‘xg the beam-ma sciatica of 2,5«“1mthylthiczmene

in! shaken contimmaly m ml]. pcr'tianl of tha iodine and a—az‘cu‘rio
02163 were cltmcircly cdzicfi. to the. macticn battle. Ra ‘ccttlc and:

its? contents were occasionally cooled in an ice water bath ta lump the
tcspcratura on the mticn bottle an ’00 tn £293. of the mm. The
pram-u of tit-c rcaction ms tsunami by tho eclcr changcc cf the ra-
cction mixture. After all of hp 13.25.12. and max-maria ozi‘sc had bmm
added thc crimson colored reacmzm Mature m 63.3th an Mammal
fifteen Emacs to. incur-c complatamacc of reaction. Tim marcuric 10616.3
was collected on c Bimimcr funnel my“. washcd with thrcn, 23 a)... mrtions
of othcr. Tue oil-ac? makings and filtrcto tiara co;;bin9d and aTm'ccm

with 90 al. at a ten pare-cut solution of sea-33121.1; missulfctc. The; organic
layer was cpcratcd from the tat'q-Jéa‘ccs~ Myer, dricd over calcium: chlorici‘c,
t‘uc cthcr am bcnzmc were rczmcd by distillation, and the product

was “can distilled mmfing 3 (21333611 typo head. The. initicl fraction
boiling; in the tcnpcrcturc rang-:9 25.6? C. at 2.5 In. Fig. mighc-fl. 5.2 g.
and m (Elana-daft. The next fraction distilling at. 62433" c./2.e mm. Hg.
weighed 7.1.0 g., 0.311 cola, 73.3, was collectcd u precinct. L 3.8:. 3.
quantity of residue rant-113:1 m t‘ze flask. ma product had a slight
iodine color and remixed M‘zcr gratification. I. small want of
freshly prepared 1011011 mourn mice and calcium chloriflo vars added
to the product and 1% an act. ”1:39 for a day. Tm sex-cum 031.16 and
calc 11m chloride were removcd by filtration and the product. can again
distilled using a Chum typo flack. The untericl boiling bctwcan
68-70" c./2.o mm. Hg. m comma. 7.39 purified 2,5«cmacm-3-

 

 

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100

mommnmo island (2).? 3., 0.2;} mole, men in 69.71; or me.
fixmmtiml yield, is: mfractive mm was 1.5275, at. as" 9.

Isle pragmz-niion was winch: again, exactly an ficmriINd abavc
mm mat the product. was distilled using; a beam-:3; one foot. 3152-311};
«hum. ”fix-9 fmtim boiling bahmm 6713f C./S m. 233. 'm coll-x tee.
It '91ny 72;.i; 3., 0.312 tabla, which 1- 73.11.; of the tincorctical
71m. The rai‘ractivc imam: of the product was 1.533? at 24.50 C.

The maxim boiling range for 2,:j-tiinzztizrl‘3-iciothicfizcnc 13
9945/11.; m. fig. (7a).

Attmpbad Ssmtf‘acaia of 2,Séstwtfiyl-j-fiziophcnctibial by tho
Lirimard cmma on 2.5%.M'Jlajdocoflxiammw '

. I “a

a .
A. can liter, taro: neck flack was equipped with an efficient
r0111»: comimscr, stirrer, and a '3" tube containing a gal inlcc tuba
at 125 :11. d‘rcppmg fumwl. Tbs: amass-misled £5211»;th um dried awr-
mgat in an oven at. no” :3. A 74"! 3., 0.29 mole, quantity of Cried
mine: taming: wcrc placcti in the flack and miles. «in! nitrogen was
“pt filming; the apparatus it was :3th £1323 dried as an extra
maceration to meow any trance of moisture from the mpammn that
n have commuted mm 11: was being “gamble-1!. my nitrcgcn wan
Capt throng; the tppm'ltzm curing the rmminlcr of the experimxt.
A 25.5 3., 0.15 male, qzmxicr at training" distinct: zmacpz'angmc,
div-01nd in 1w :1. of unfair-cu other, in placed in the dropping

 

1
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ct

191

fennel. Approximately fivo milliliter: of the 2-iodopropano ctr-mox-
solution was wood to two nognoaiuzn to. Logo. T323 reaction flask was
heated gontl: on a “can both mus tho mansion turning: .2225 two
2-iodopr0pano other solution were vigorously stirrod to initiate tho
reaction. As soon as to race ion had started 120 ml. or amoydrcus
nth-or we ail-nod to the mention flask" and tho rcmahulorof tho 9-1:):‘0-
propane either solution was coded dropwlac to tfio vigorously stirraj
contents of tho reaction flnslf: owor a half hour period . The quonti‘cg,
23.5 3., 0.1 mole, of 2,S-oimotnyl-fi~10dothiophcn3, discolvod in lfio
ll. of atyo‘oouo other, was placed in the drooping funnel. T-slia solu-
tion was called orcpuioo to tho vigorously stirred racotlon :v-Lixtuz‘a
over a period or a half hour. Tho roostion was sofficimtlgr exothermic

‘I

to hop tn. reaction - mm at its tofu temperature cox-Log; to
addition of tho 2,Sqlloothyl-J-iodotulophono solution. mo roaction
mixture was stirred. an additional half hour, while being kcpt. at its
reflux totporaturo, by applying external boat with an oloctrio mental.
At this point the reaction mixture was allowed to cool to room
temperature, stopporod unfior an atmosphere of nitrogen ml out enli-
ovomight. A 6.35 3., 0.25 cola, quantity of. sulfur, which is a 0.01
ml: execs: of the thaorotical awunt needed, was ozidogi in small
monies to tho stirred Grieg-lard roogont by means of a dry addition
tuba. ho audition of the sulfur caused too reaction to rsflux mildly.
Tho roaction mixture was stirred '13 kept at its reflux comparator-o for
on additional four hours. 2:17 nitroaon was slowly swept. through 029
reaction oppu‘atus during all the above operations. The reaction

mixture was cooled in an ice but: and a cold culfuric not: solution,

15:2

prepared fro: 13 ml. of comazitratoo valiuric and 255'- :ll. of your,
thioh corresponds to a li..2;3 by weight solution of sulfuric will, was
Slowly wood. from tho oroppix‘zg Formal into the cold, Itlrrssu, Grignard
reaction mixture. After all .: t2... 9.1mm. acid solution 2...; Loan
mid-ad the other layer was sap-aroma from the scan-sous laym'. Tho aqaoous
layor was extracted with two, ,3) ml. port-lone of other an; call-sod with
the original Qthor layer. Tho (205$an other sulntlon was «attach»;
with throat, 23 ml. portions of 20 percent mom hydroxides. The coalinad
aqueous basic gamete, while being kept cool in an ice but}, wax-s
scioifiod with 12 2! mlf‘ario acid. There was only a slight. cloudiness
when tho basic extracts were achlod; indicating thorn to: little 11‘
In}? 2,5-cimtm'l-3-itfiiophonethiol being relauzxi. Tho cloudy mums
um attractor! with turoo, 25 ml. portions of tutor. ‘fim €0.31)Ll’f:§:i‘9tli'3r
examts were drier} in contact with motyzirous magnesium sulfate mi than
distilled wrong-1 a. semi micro modules! Claison East-z. Aftor all of
the etc-or has; ‘oacm room's. Via-are was only a very soc-ill mount of
region. rmim’azg in the distillation £13.33... Apm‘mtly the procedure
was Lufisquato for to proforatiun of 2,545.36urgl-3-leophono{21.5.01.
T113 snipermont was ropeawd with swam]. £1qu icotions. The saga

apparamou in the prsvimxa oxpeerent was Griz-x; thoroughly and used
in this mtparimont. A b.27 3., (7.3.76 mole, quantity of Gris: ammonium

. 1.2;: was placed in the flask and while swophzg dry altrcgm through
the apparatus the) magnesium anti apgaratus wore carmmy haatod with a

small flame from n Runs-3n tumor to Laws Cfiviplata rag-..ov-al of misturo.

 

 

A"

 

 

 

163

A 33 g" 0.125 mole, Quantity of 2 ,S-dimatI13'l-3-1odotitiopheno was
dissolved in 1w ml. 011‘ dry etimr and placed in the dr'opging {41221;}...

A few milliliter: of tail late: solution war. mic-w tc t‘ua stirred
namesimn turning: in the reaction flask. Khan tlm reaction $8113.; to
start even after limiting it was initiatmi by 5.32313 to it a rauctmg
mum‘s, from I six inch teat. tuba, Elie: consia‘wai of 3. 1w agililiwrs
of dry Other, 3 fan: manila burnings and several (3:093 cf 2-icaOprcwno.
A 133 ml. volume of other was adumi to the reaction mixture mu“. than the
2,50dmatl’orl-3-iodom10pam was new lczropwiac at I rate Bui'i‘ici’snt to
maintain tn: nation mixture at it.- roilux temperature. An aux-35pm“
of dry nitrogen was R‘spt in the apparatus fixmugizcu-b tbs aaparimnt.
“CW .13. 01' the 2,5fiimfluxyld-iodothiopnezw had been used, the “him?
In stirred ma karat at its reflux temperature for an hour and was than
Cot wide for Imrml hours. A 5.0 3., 0.156 mole, quantity or tuli’ur
as carefully almanac: inta me reaction vessel. An ammonia reaction
not in mic): caused tau reaction mixture to rsflux. Slightly more men
5.0 3., 0.156 mole, of mlfizr maxifi-u;aic;ad before any viaibla sign or a
toactian occurred. The “action. mun-*0 m «5.2:»; an: haste: at its
reflux temperamro for m waitional hour. After the flask and mutants g
hm been 09013:! in an ice bath, 150 ml. of j H kqdrochlorio acid were
Clouly cdéod to the reaction mixture to hydrolysa w Origami sulfa;-
uddition product t‘ut might have formed. The aqueoul layer In naparawd
from the other layer uni extracted with two, 50 ml. portions at «finer.
The ofiaer extras“ and original other layer were combined and attract-ad

with four, 20 ml. portions of 3 i sodium lag-druids solution. Tao confismod

 

'lw

0'1"

’3

151;

hula extra“ rare cooled in an ice bath and acidified with 6 R hydro-
chloric Icid. has notified solution which contained only I small.
amount of oil as Ixtractm with three, 25' ml. portiaxsa of atfier. The
combined other extracts were drmd in cantact with. Inhydz‘oua mafleslum
InlrIt-I and distilled using I semi-micro (Slalom flask, mocfified with

I Vigrm typo aide Ira. After the “3131* had been rarnovad by distillation
on]: I trace of rmiduo remind 1n the flag}: which wieatad that. no
2,S-dinet-zyl-Jdmiophenethiol had hem produced. Apparently tbs prachmt.
of the reaction was not. notable in bass Ind vac lost. in the original
Ithor solution that m “G‘s-th with ban. In later expat-manta].

hark it III discoverad that flicphmemioh readily fan-a diuulficzes in
thc presence of minn- in In ether mama. This could explain the: lack
of yield of 2,S-dimefiny-B-thiophanathiol.

A time (back. EJG ml. round butt-0:: flank m equippw with I stirrer,
“flux comimm, and I “I" “who containing I dropping tunnel Ina gas
inlet tube. The (margins m dried in tho mm borer. mum.

A half» 3.. 0.2 83213, quantity of mgneniua val dried in an even Ind 13.321
placer. in tau reaction mm. kitrogan 11:11:11 as first dried by bubbling
it. tu‘ough a crying tower containing concentrated" sulfuric mm, m

swept urea-g1 no Ipperatuu mile I small gas flame nu used to gas-lily

3‘.-

It'l.’
.II:

1:35

but tho IppIr‘ItuI Ind “gamma. Ana: the apparImI had coolad,

23.8 3., 0.10 I010, of 2,5vdmuzy1-3cdodamiophms (insolvent: in 100 ml.
of dry other m 191ch in than dropping mane]... PM of tin 2,5-dinamyl-
J-clodothiophm Iohtion m aided to the vigorous]: stirred magnolia-2:
hmingu. Dry nitrogen in: “any swept tin-ouch tho apparItuI during
tho «nun mimic a: the: experiment. mm the mtian failed to
aux-t, an an boating, n In manna by adding to 115, Iran I six
nah an tube, I routing 111:?an or man). drop- “ Mops-09m,
other and I tow nanom- Inning“ m tho reaction of the 2,5 $.13:-
S-Mothiophm tub "main hId MM, 100 II. or “he as added .
to tho tactic: this Ind the rmaindor or me 2,541mw1-3-mmm-
Wantinmmufizevigumhlmmmum
MumnInu ntthilnfibknpihoncnmmmn its
panama-taro. Immammmmmwu
Ina I11 or the 2,5dw1-14odommm.wm . 2210 WI at y
m-wimmmmmummuIm-Inorm
nth-om VII mad mmgh tho Ippmtnl. It the ad of thin tine
chm III Ici- mm insolubu nus-m Idhoflng II tho “do. or the
WM, mIlIrglImtofmImIrhIdepm-Im. That
filmmstmmtinoumrd mtprmlulhmbyId-ding some
of tho «In: Ichtion Io rum mm: «and I vigorous reaction to tax-a
pm. Imon.whmotmummtotmmtmmm
It»? stirring m distinct mun ton-nod inch could possibly hm bean
m h fin ”Minty at tho 2,5-dimthyl-3-fitiophtmmgwoiun iodido.

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1136

The addition of 30 ml. or bmzono followd by stirring mg the mixture
camplotoly miscible. Tho Grignard roagant nae carbonated by employing
the method of Huang (5'2). A 253 g. qmntity of dry ice m pulverized
in I mortar and placed in I one liter, three nook round bottom flock
mipp—od with I high opood stirrer. A 2C0 :21. volume of dry ot‘ocr me
Idded to the dry ice Ind the mixture m Itirrod vigoroualy to form I
Ilury. The 2 ,5-6 mot?xyl-3-t£:iozmcm~mgmeamm iodide collation van
transforrod to I dropping funnel and added to tho vigorously Itirrod

dry ice other Ilurry over I five mimte period. There was I vigoroui
evolution of carbon dioxide during tho Iddition or the GrignIrd reagent.
the rocction mixture use Itirrod until Ill of tho dry ice had disappeared
thick reqpirod titty minutoe. The reaction flack Ind its contontlvae
plIoed in In ice‘both Inc while the lItor was being Itirred 100 ml. or

6 H Worden-inc Icid val Isidod elouly to hydrolyze the Origin-d Iddition
product. Tho othor‘bonzono layer Hal separated from the Iqocoue layor.
The 1.1m:- ms extracted with two 50 ml. portions of other end the
combined other extract: wore added to the original other boncono eolntion
contIinina Irv possible 2.5-dimctlvl-3-vmiophm cIrbomlic acid. The
Iolntion In: extracted first with I he m1. and than with I 30 m1._
portion of 3 H Iodium hyfiroxido coluticn. The codbinod alkaline extracts
were Icidifiod with 6 H hyfirochlcric acid which resulted in the

immediate formation of I.brcun procipitatc. The crystalline motorial
me set ”his in contact with the swoon: medium for nine (ism, tE-zcn

filtered and recrystallized from hot water. Some of the solid would not

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dissolve in the hot water am: was rmovou as on i. :p ;.-t;, by filtration.
After tbs Iolution had cooled I 5" “ 3111.13] gallon colored crotall no
eolid repented from solution. Iacolo; izin . c -orcoul was a: .1:- 94. to

'10 muture Ind it was again heat-ad to its b02311“ t"3.'fl§..18 aturo and
filtered. Crystallino not-wial fails-3:3 to fi‘ipfil‘ate after to solution
had been not aside overnight in I refrigerator. Two drape of concou-
tratod hyfiroc‘nloric acid were mood to the cold solution and. immiifitoly
I white crystalline solid famed. After cooling; in an ice bath for I
half hour the it. its c1“ rstallino colic-4 was filter-”cl and dried. {Italy
Igproximtoly 0.1 g. of mat-aria]. was obtained. The molting; point no
carofally taken on I molting po'mt block was 117-3130 C. T323 ropcrtofi
(71) melting point of. 2,5-dLthJl-3-t311cms- ocarbcrjlic acid is ll“)-
123" 0.

Preparation of Potassium is'drogon Sulfide (53)

A 500 g., 7.85 330133, qaantity of raagant gym-fie, 635.1, pctossion
hydroxide were dissolvod in 325 ml. of water. A cylinder of Igflz‘cgon
8111:1139 m cormoctafi to I trap which was two cozuxoctod to I gas
dilpa'sion tube. The potassium IW'ciroxziuo solo ion was cool-ea in an
ice bath. The hydrogen nulfic-io was buqualod into t .o potasa: um 13m retico
eolution until there appoarod to be no further ansm‘ption of lvfirogrm
Iulfide gII u imiicatoc‘ by the rapid. evolution of tho hydmgan sulfide
gal. ThiI roquirod appro: :imtoly Liz-co Laura. T33 potassima hwérogen

sulfide Iolution van transformci to I roacmr vcsso eqaippou witn I

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1138

pound gnu lid containing standard ignored ground glans openings.
The reactor an: equip;- ed with I comienaor for distillation and the
reuse]. was placed in I amoral oil bath box-2303mm between the limits
or 150-15c° C. and boat-3d by two knife electric 1:13:20 heaters. The
can: enser was equipped wit. ... I new: tel-go off and I receiver, the
vacuum in the oppIrItuu being obtained by I voter espirator. Boiling
Items were Island to the vessel and the rate: was ram-ad tron tho
potassium . 'dro: 5m solid... ‘3 by vacuum distillation. The product, solid
potassium hyfiromn sulfide was heated timer 1:: mm at. 153° =“ .for four
hours to remove the last. tree as of mte-r. The dried potassium hydr gen
id-o adheres-.3 talmiouely to the inside of the vessel after the lid
m moved. and considerable diffi cult; one trip arionoeo intrymg to
scrape 12.0 product from the vessel. To circunv-mt this, 150-0 ml. of
prop; lone glycol ma c.1330 , I calcium chloriis $21!: a was place-:3. on the
reactor vessel to protect t2: cont-ants ron moisture on: he vessel
W! placed on I swam bath overnigbt after which the potas-eiun byfirogon
sulfide was easily renovegt. 3.0.. '- fir. 3.2:“;itional prop; lone glycol was
video to completely dissolve 12:3 potasshm fg'rirogen 6113.55.39. 11:23 result-
ing whtion had I concentration of more: 119.00.}; 3.5‘ no lor wit}; respect

to potassium hydroggfln null ”i=5

A
..9

Attempted Synthesin of 25-33%?.3'l-3~thicphmetbiel by the
Reaction of Potassium Iiydmgm Sulfide with
2 ,5 «E. usual-3 dove 0.110932%

 

A SOC.- 101., tree nae}: flask was mapped with I Itirrer, reflux
comiensar Ind I 'Y“ tube fine." with I cropping funnel Ind gas inlet.
tube. A 206} ml. volume of propylene glycol containing 0.7 mole of
potassium hydrocen sulfia‘w, was plIcarfz in the flask. A 2.0 53., 0.17
mole, quantity of 2,54?3.139%?:yl-3-iofiat3fifipbeno ml placed in the
(ix-awry; funnel. The stirred museum txyr‘rcgm sulfide Iolution ml
heat-ad to 150° C. by means of an electric mantel and the 2,5-dibmt3glw
3~iociothiophena Hus Iéded drop'dse to it over I thirty minute period.
A slight. pct-alum pressure of nitrogen was naLntatned 1n the Inner-am:
during the echerf'ment to prevent. air frem entering: the Imratns and.
oxifilnlng my 2,3-dimet7239143-é- logbmethtol formed as I result of the
reaction. The stirred. reaction mixture was kept It I temperature of
130° C. for I total of twenty hours by heating in I I-eriaI of four hour
intervals over I £3er day period. A mmmm distillation apparatu-
m ”ambled consulting of I Claiaen flask and In oil bath heated by
meal of I hot plate. All of the promrlmglycol 001th Ind unwanted
2,S-dLmfixbe-iofiotbicpbene 3m: removed It I pressure of fivo milli-
mtm'l of mercury. The head tempm‘hm in the Claism flask rose to

101° c./s an. Egg. A considerable mount. 0: unreacted

L

 

2,541.00 '*‘1-3-100000004010 1:118 17.01.11,-.. as 6........ .1. by" t.“ 0 .. 3-1.1.1
phase of u a diet? ...-Llate #01130...“ 110.11 L411 1.015.130 1.0ility :11" prcvfi 1.11:0
glycol Ind t2; 0 2,5-‘31'011.yl-3-io.c...10..21111.1. A t; .01. 11:0 :11 1:371:91“: .3
routine rmined in the distillation flask. A 3.3:; 1.3.. ‘r01-1.'1:a 0;? 32:12.11?
was added to the r2231; 11:1, 111.... 1.1. 11.3 11.2 23.1.11.» 1.1.5.8 :....:.‘t.;113 arc-:1 it. was
Iciniifiod fit?) 5 11‘ 1135100: loric acid 1.1 5.011 1008.13.21.11 in 1.2.0 13.721.111.100

fl‘ . .
- (5'
‘A ~13."

of hydrogm 31112100 011.3 1113 1'01~.....':.i.211 01‘ I 111901111 p:.1--,11:..t..1.
material will til/care; 22:.- ~021t3a0 1.3.: first 81.“. I 2 C :11. :3. tier: 8:...

than with three, 1...: 11:1. portions 0.1? 0:41.115 Zia 00121111100 131121.11” 0.1.1.9118
were in 1mm untreated 1111.11 two, SC .211. port. 10113 of 3 ."1' 13045... 21. 313-110.111.13.
T119 c0501. '- 16... basic 0.11.1000; In. 0 “3.4.1.101 1.5.1.11 ‘5 I; ”301001....1'10 110;...

I00 utmcm first vita I 5.) .111. 11011111011 1111.1 0.1111 115.1111 two 2;; 1:13..
portions of other. laying 1.7.10 Ici.iificati011 1:11.11 113-.31‘0c21101'ic I051.)

wry little 111001111110 111110011211 3:11.)me from 302.111.1011. The 00.210.311.10
other extracu were dried in contact with 11.1.3.2.1'0113 0111;310:1100 0111:1110,
Ind star '5. twin mmveu‘ on I 61.01110 bath. Only I 8;.ig..t 1.23:1. :1 0f
reels-P110 rm-minofi in 1.19 distilling £111.11: , indicating fled 110119 of {1.0
desired product. had. formed. '1‘ 1a 1:.- 10.101.10.31 2 ,,-:.l..1.1t..yl-3-ioz.‘.0 1131031110119
collected faring £10 initial distillabion of ti 11111111031.“ 11:11. 3232;313:10-
glycol m recovered.

Frapanticn 01' 2,-1.5 ic flora-3431103131 enemlfonyl Chloride by
ire-ct.’ 1. 13.01-03.11... 0:12.11 011

t».

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r:

A 01.“: 1*, 1.81133 2230?: mm! hotter: flask was fitted. with n

Ours-432', 112203531213 mm}. and a. ”‘1'" tab» containing a ti: monetar- which
roach-:11! to. 1.2.3 better: 01' 12:: £19.32: and an outlet. tuba to confluct gas
1:13;: from 2.23 32293123323. T329 119.31: was (Paar-39331 vim 313.5 g., 3.0

1210139 01' $123321? (21.51.11.138. 0111022032111'01110 acid and than 1322123123313 111 an

ice 33.1.3 31.2.2. 5.13:! 3.12.: to coal t0 -2. o" 0.1 153.0 g., 1.0 mole
quantity of 25413112122123.1232 mm was placed 1:: the Crommg 9.121.311 and

£103.? r’:*c-::1:1.123 to 11:3 sizrrm? MM can-cmlt‘nnic acid mr 0 01.321?»
£133 minute p1- 131' . 1.9313? 13-11 a: the 2 "-:‘112‘1102'ot‘21rp sun had been
£233.31- t1: 0 re! (:31 M31 reaction 2312311199 was stirred an additional
tin-13;: 23.33.23.131: reasrtim mirhzm was pound onta two liters of
ex 1:12.. 1:2 0 (21203522.: gram colored precipitate and oil to fem. The
132-3111913111: 3.21:1 0.1 were act-tuxw into 391231231 portions of carbon
tetac‘ 13:3. to 12.122. ware combined cred ma‘md with 100 ml. a! tutor and
than (2:12.; in Contact with 1112‘ 321220213 arr-'10.. .1121 3111.. at». T126 carbon
tev:;:..o. ~13 was re-zcv'x‘! on 3 913-0323: 1291131 using n 6111313331 {.3126 {1331:
m: the 2211313213 12213 tractirmatad 012:1].an 1 one foot heat .1 321:9th
V1 r3123: 1231...... A 11mm term 1201112211 at 68-111°/31 m. 11:. which
3121121331 to 11.17 g. was 12! 52292-51323. 'E'ha colorless, fraction boiling; in '3
2.113 :32; :0 ill-113° -. .:1 .3. 3m: 1201130306. and on cooling 3011131151 1.
T120 31.01:: wan 231.113: 5., 0.01291 32.33.93 which is 9.813! of the vasomtical
yielfi. A 11.00 g. r331.” us r8230: 'nM. in t‘. a flea}? after the distillation.
T110 c11101‘om11fonation 0f 2 ,S-dicflnrothiophm was repeated using
‘23 311.139 apparatus as described them. A diff-:2mnt ratio of reactant

and reaction times were 213.333. A 233.1 3., 2.0 320103 quantity of

‘l

g"!

I.

«+1
I
‘1
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.

112

{1113321131 distilled :32 12031111130211: 1:. 1.2.1.5 planar: in he flu}. 2.21.2

0 ... - , ,
U. in In 1C0 Gait b31110 ‘ 13;ch E.’ 1.1.] “91.) (iiaIi-u if",

coolofi to -5
of 25-0210 1011013.- 10922; 0.210 was plat-.111 in the 1:110; ping [1.111101 011:3 0.21;:
cropuisa to tLo star-ac! 0010 0.12... 2121 120011113 2.10 00.13 on: a 0.10 1.32 :1 00:10.1.
1'11: 1'0 motion mixture was stirrer: an 0.011.111.2101 0112-1910120 2111111013 ,
£2011 5:10 1:130 011310 02:31:?- 0:1 100, an: mtrac .011 with three 10.3- 1111. 002.211.3113
of carbon tetrachlnrhia. 7:110 001:3;311121 carbon “0.220021101111313 0'2ata2acts
Item 15051101 with 50111. of water and tan 1111100 in contact with wig-11120118
1103110010.: oulfat-a. Tia: 00.20011 tux-ac: 10121.30 11.13 011.301.1101! 1120111 2:310
product. on a “00211 bats: and t2. 9 121101.000 1.08 A fimtimwmd 1101.13 0 021-3
foot haat jackets-.1 114120111: column. T320 10120121111 fraction, 130132.315
5.33 g., boiling; at 22.1190 C./0.5 111.1... 275;. was 001.100 -_'i which 131213.100.
1:13.: g., 0.0;;911010 x1! comoapomia W a ”0.2... yieiu. A 5.53 3.
11031121100 rmminezt 111 the distillation flash.

To determine the 0 iact of ratio 01‘ 1100.,0211203 on ,1 01:: the wt
proceu um was 1211.00.00 as 01.50.1101. 0101.20 118.11.; 51.12.51 3., 53.0 01:21-23
01' 112033134; distilled c Aer-03111101110 00.1.1 Ma..- 1;}. 0 g., 1.0 1.2.01.3 0‘1”
2,3-1ichlomti:icp?1mn. T210 franc-1:10:11 b03311; at 2.;-117°/.‘..1 3.115;. 313.
wig-.1103 9.57 a. 11113 01312111211012, and the fraction boiling at Eli-12.301: ./
21.1 91:1. fig. 0131;311:15; L3.19 fig" 0.12:2 1001.6 t 19 .2); 1103 0011060001.

A 5.33} . 120316110 ram-'36: in tbs distillation £003..
8

 

 

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Pmpxauwn 01 2,3- is; 1036', 4}: tartan $11-05;; 4c .2 ( .4)

f -- , "3323;,
C1": [:1

. 5

A 125' 30.. Emma flani-z m titted with a "an! ”aim.
A mum” of 8 g. or a monivrl 0:1th and no :11. of cone mutated
arm-02mm hydroxiéo m plaza: in t?» flask and 2 g. of 2,5-dichlom-3-
1%.:chme chlurma m adds-d. The mixture was lath-rad and set
aside for fifteen Maltese at noon tmnmhm, with occasional finding.
me reaction flask was imrsmfi 1n n m:- bath at. 60° 0. tm' five
minutes, tho bath m then taut-3d to 86° C. and held bet-mm 'IO-fiizc’ G.
for In waiting). ten afinuw. rm flats}: and 1t.- com‘antl tm'e simian
occnafmally (hiring tho heating period. The hot 3011mm was £11119»er
to m the amass mom: emanate and on cooling the tummy,
smite Walling 1:00:21» 0! 2,Sdichlom-tj-thioyhmmlf‘mmma
nmtallilod from the Kantian. The: pznc’a'wzt m recrylte-lliaad three
time. I‘m 7'5 :1. of he: rum:- to 3431:“. 2,5admhlm-3dthiopéxane-
sulfinufiria melting n. :L,30--13o.5o c., max. each recryitalliution.

Analysis or time nospound for carbon, 12-36mm, sulfur, my:
atfiorina gave the following ”lulu: Calc'd. for “33330131133:
9, 20.70; E, 1.3173 (:1, 27.63) 8, 30.55. Found: C, 23.83; H, 1.1:?!
31, 35.753 3, 30.75.

 

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filtered from the hot solution. The clear filtrate was evaporated to
dryness in a bukor an n stem bath mile a stream of air was blown
mm the beat-tor to accelerata we wapara’cim. The: solid react-no was
mm to a cmtmizmg dish and dried in an oven at 110° 0.,
wmight. Th. yield of sodium 2 ,S-(E ichloro-B-‘thmphenemllfmts was
199.5 3., 0.133 13010. The dried Int-arm bumad readily leaving only a
hull want of residue, Lmilcat‘ :3 the 1'3.qu cf the major part. of
€19 Indian «rune.

The aqueous wlutionn from all previous chloromlfomtion reactions
m combined and mtralizad with forty percent sodium hydroxide and
fit. mu are filtered. T53 filtrate: was evaporated to dryness on 3
than both 31th occasional rmal of Cara salts by filtration as thay
erytullim from the concmtratrad solution. fi‘za salts were (Erica: and

mud nth mthanol as described above.

Preparatian of Potassium: 2 ,S-r.’sicElem-3%::iopéwncsulfonate

' C ’U.?t.
m- x 1

8
A one liter, three neck flash: hemmed. in an ice salt. bat7=‘s, was
fitted with & machmical atirraar, an outlet tuba (302131th to a Izgn'frcgm
adoricfia trap, and a '1" tube finish containad a Emmomawr mxd (l.'33‘:;jing
tunnel. A 2% g., 2.55 mine, quantity of freshly distilled 03110130-
«11‘0an acid was mam: m tiafl 11.3%. and cooled to -3.5° c. A 31.4»; g.,

2.0 moles, quantity of 2 ,S-dicliorotlzicphma was add-xvi dropwlaa to the

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00141 stirred chloroaulfonie acid from the dmpphg tunnel. m5:- adding
tho 2.5-diehlnrofi‘uiopheno for I half hm the rmfiofi tamporature had
m so 6.0° c. and mum addition or um Mafiaiophmm m 01:9?de
until tho mam had dropped. to 1.0" c. m mm mung rm.
011091109. for a third or an hour tho mum: mum boom vary mic}:
mt! than fin flirting n“ at mama!“ 1% 0011311106 and tho mature
mu rapidly. It In wrmn u dozen-m the 1,me mm the
film-mm mid not be 1W into the reaction sodium. An additional
omen minutes were required to finish miéing the 2.5-dichlorot‘210phmo.
A: web of the contents of tho name as paucibh m poured onto
amazed ice. After cooling the 112133: in an ice bath, ice and. tater ware
added cautiously to the auction flunk. A vigorous reaction enema! and
than the reraaimier of the natural in the flask was nuptial unto the

ice with flat original mtg-m. The aqueous mixture at untrained

with pot-angina hydroxide and the mum-.1 ulntion a crude Mum
2,5-dichlorofixiophmwl‘u1fomh mil inorganic «It. in. moramd to
dryness, “dated by u up stream: bloating am- it, on u «.4» bath.
unwawmmmmwmummuimmumn
110' c. for ta» am. The dry gamma an mm” m mm, with
the, um um partial. or absent» methanol. During «oh Minn,
um «11.. m stirred In this refluxing methanol for :1: a. night noun,
has filmed and the filtrate m anger-aka on a “on bath, «W
by a CW 0: .5: blaming ever tho surface 6! the methanol to human
the evaporation. The whim 0011:: obtained in this name:- m» the five
mam. gamma 125.1 g. m crying overnight in m m at 110° c.

 

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117

If the solid was pure potassium 2,5-dichloro-3-thiophanmlfomte, the
yiald was 0.3452 male or 23.1; which chm tha‘ the golubility of the
patassima salt of 2,5-dichloroti'ioymnemli‘omta ml" not nearly an
affactive in its isolation by natfiazwl utraction as $323 Bog-3.3m Gal?“
Adéitionnl mount: of the pmmct could have been obtained by flux-the:- ’
mthanol attraction as m them by this fact that fin ems}: cult mixtum
atten- ezctraction m Itill glitz comma lawn ignited over a Human
burner (lama, schich indicated organic mistrial meat in the mm.
Praparatim of. 2,S-Eichlcrofiufi:iophmeauli‘ml Chloride from
Sodinn 2 ,S-rpichlom-B-thiaphmsulfmta
. 03Cl
Cl 1 .

The est-:06. caployed far the preparation at 2,:3-dichlore-3-fi110phano-
miller-:31 china-1&0 m a Mflicatian at that dmlomd by him and.
Earn}. (55) for the! preparation of benmmlfwl chlorirh. A 109.l:7
3., 03.28 min mummy a: sodium 2,5-dichioro-3-tmophm1rmm,
Which conuméd a little 30:11:25 mm as tap-army, m pulverized. in
a mortar. A 52.1 3., 0.251 mole quantity a! phosphoma" pmtacuorifie
m also pilveriztx! in a mortar. The pulverized aoéium 2,5-dichlom-3-
thicphmltomto and phosphorus v pantschlarigio vars mixed intimtaly
mamolimmndbotmnmk. mom‘sttiueéuithumfm
continuum containing a calcium chloride drying who to protect the
contents of the flask {mm amcepheric mummy. The 11313: as men
lama-ed into a mineral rail constant imperamz'e bath mt at 175° 0.

 

 

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117

If the solid was pure potassium 2,E-éichloro‘fi-t‘!iopi‘mmmlfonate, the
yield was 0.1.62 ml: or 23.13 which 33mm taut the uolnbility at the
potassium salt of 2,5-dicblomthiophmesulfomte m not nearly an
effective in its isolation by mammal axtmtion as tho 00:31:12: salt.
Editions). amt: of the promct. could have been obtained by mr‘hhar
mthanal mantles: a was shown by the fact tint the crude salt mixtura
utter attraction no 312111 wits 0033mm. than ignited over a Bunsen
humor flame, which inflated organic ataxia]. present in the swim.
Prnparatim of 2 ,S-Esichloro-fii-thiap}:anesulfom'l Chloris-7‘33 from
Sodium 2 ,S-.«.Jichlom-3 axiommaulrmta
0,51
Cl 1

The M109! nploy‘d for that preparation of 25-dichloro036thiofimnm-
lulfozvl chloride at I modification of that davmlogaed by Adam and
Haml (ES-'5) for the preparation or bmzenemlromd chlorida. A 199.32.?
3., 09:28 mole mum at sodium 2,S-dicffiore-B-thiophenmmlronata,
which contained a. little moz-Tim: sulfate as bylaw, ma pulverimd in
I mm. A 52 .1 g., 0.251 mlo qmmtity oi’ phosphmrus pmtacifisrifio
m 21m pulverized in 3 mm. 1'39 pulverizad sodium 2,?3-éichloro-3w
thiephmamltonnto and phosphorus " pantachlori-La var-3 min-29d iattnately
in a one 1.1th round mm flea-Er. The flask was fittad with a reflux
:29:de containing I calcium chloriéa daring tub-a to protect the:
contents or the flan: from atmcmpmric mum‘s. The: Elam: m than

10mm into a mieral oil constant. tczrz-pmramre bath sat at 115° C.

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113

After four hours the :::£;;t:;z"3 ma 1: film‘: viii-3 :mzte, but F3133} t1:

flask was stapysred m2? aim-gm t‘n 332.5% bar-am a liqui; slimy. After
flaking matter fiftam nirmfiaa will: occasionally relaxing tfzc pr-zsmra
in 13:39 flask the liquid cool-3d mad again bagw'ra 3 Eric}; mate. T16: flask
was rammod to the constant fagmvetxwe bath and was he: tad an miditioxul
fiftam houro, being mad from the oil bath at four hm intervals

and shaver: in t3 a manner just iri‘a‘. ”to: tits first. eight. hours

2'3 3., 0.096 mole of wéiticmal phosphorus ., pmtacidoriéa were midis-'2 ta
the flask. At the and of rifts-an hen" the ranction We was poured
onto crushed ice and tn oily layer for-nod on 1:313 bottom a: ting beaker. ~
The mixture was uxtructod with firm, 100 ml. portions of carbon tetra-
cE'JorLt-a. The combined extracts were washed with 50 ml. of salts;- and
(Brio-:1 in contact. with amzydm masm sulfate. The carbon tetra-
chlori="='.a was removed on a. 83335?! bath. ha residua was nationally
distilled using a one {cat heat 58.3mm: Vims: colmm. tan fraction
distilling; "batman 119~l22° C./3.7o!..0 m. 23. was collectad. 11:5 yimld
m 30.85 3., 0.3922 mole. 75.13! or the theoretical. Th3 starting
mtarial in. Have been“ of tha extraction sneezed of obtaining it,
therefore the yield of 2,3-dlchlcro6-micpbenamlfonyl cast-1:33 would
bu higher 1! a corrocticn were mafia for V2243 Indium mlfata present an

an meurity in the ltarting matfn‘ia .

The reaction nu repeated on I largar acala using 320.0 3., 1.2533
sols, mantifiy of sodium 2,5dichlcro-3-tzlomanamlfcnem and 11:33.0 5:...
0.7 1:015, of ph-oap‘vm" pmtachlcriém I‘m reaction time was twenty
ham at 173° 6. ’ms pmiuct was isolated as before. The reaction

.I.
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E.

119

boiling It iii-120° c./3.6 m. fig. m comets: mien mun: to
212.5) 3., (3.81.6 5013, a 6'! .51 yield of 2,5-diohlm-3-Uiiophmli’om’1
culprits. flu worms dorivntin of hi. Wt was prepared for
11mm amlytis. The rmlyticol (in: m W wider the prepara-
tion or to 2,5-dlc1;lorooB-thlophenmltmaido.

Preparation of 2, fi-T‘ichloro-BAhiophormmlfmvl (tram-trio from
you-am 2 ,Sqila.:loro-3-$..iopkmoultonato (55)

0.61
C]. * 1

TM gramme! uscx: in this proguation was the tam an that. described
in tho previous axpériamnt. A 1253.]. g., 0.}.62 mole, quantity of potassium
2 ,S-dichlaro-J-thiophonasuli‘onata was firmly W in a mortar and
lined thorouggoly by choking in a 590 ml. ”append round bottom flank
with 1.3.2 3.. 0.231 mole, of previously ground phosphorus: pmtaichlorido.
A prunro’ m continually dmlomd and had to be "loosed every few
mimtu to put” me W he: being; forced out or the flame. The:
this containing the intimto mixture of mist-ed rang-ants no fittofl
with a condmer and placed in union bars. at 175° c. for tmty hours.
Tho flask was moved from the oil bath every four hour: and after
cooling 1% in: “append and Ihakon for a mum oi‘ an hour. tuning
the shaking the procure in the {look bad to very frequently be rolouaci.
In tho and or tmty hours the tympy 5112mm was poured onto 5'30 3. of
ice contained in I two lit-3r baker. A dark 01137 Mar forum: on the

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120

bottom of the beaker and was separated. The oquoouc layer was mtractod
vim toroo, 100 ml. portion: tat-carbon totrachloricio. Tho ooobinod
carbon totroosloriu mtmtc were aimed to the original oily portion,
than nomad with 50 ml. of water am cried in contact mitt-1 arflzyorouc
Mgneslun ”Hate. The nmosiun sulfate was tutored from the carbon
tetrachloride solution and the carbon tetrachloride m roamed from

the crun-To mm... by alatillation oo a steam bath. The rocifino was
fractionated orrgloying l bani-union m'iifiod 0131835 distilling malt.
Tho tor-arm boiling between {Si-122° C./h.0 mm. Hg. no discordod and

the fraction boiling at 127.1300 C./S.3 m. Hg. was collectoo. A 3.90

g. roaiéuo rmlnod inltl-za distillation flock. A 35.21 3., 0.1;. mole,
31.23- yiold or 2 ,S-dichloroojdmiophonoaulionyl chlorioo was obtained
based on the potassium 2,S-c?ictzloroojdtniofihonomlfoonto and in tho
reaction. In. low yield indicates the possibility that potauiua sulfate
was prosont in the motkianol extract-ed potusiom 2 ,S-dicbloro-B-thiophmo-

culfonote.

Pranotion or 2,Sé'ficEfioro-J‘thiophmotziol

Cl 1

A two liter time. nook flask was fitted with a bulb typo reflux
condenser, containing a calcium chloride crying; who, stirrer and I ”I”
who containing o dropping mu in om sic. of the '1‘ and the other
Cid. was atopporod. The entire class orlpmtuc to: dried in an oven

at 110° C. prior to usoafiJling. in 13.1 3., 04.77 mole quantity of

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121

lithium alumna hgrzlri'ic was pulvcrizod in a mortar anzi aided to the
{lack tin-cog}: the am of the 'l‘_ tube otter rmving we stopper.
A 5753 ml. qwutity of sodium dried, othor was uldod to tho £183:qu
the lithium almim 12,1?riéo woo stirred in the rofluxing other until
it had dissolved. A 2.0 3., 0.15) mole, qaautity of 2,5-oichloro-3-
fidofimncmli‘om-‘l chloride diuclvod in E0 :91. of dry other, was ICE-(30d
dmptriao to tho vigorously stirred lithium alumina: hydride: colution at
a rate cufficimt to maintain a gentl- rcflux of the other. Luring the
coalition of the 2,543ichloro-Juthiophenomlfonyl chloride occasiomlly
luz-‘qu of reacting mtu'iul would adhere to tho man: and took on c
glowing red color. After the udffiition of tho 2.5-(iichloro-3-tmophcnc-
alforwl chlorifio no complete the reaction mixture was tuned at it.
roflux temperature for an additional two noun. It mo than coolod
cm: 250 ml. 01' wot-3r was cautiously add-ad dropwiao to the ctirrcai con-
tents of the flock while the latter was imam-oval in an ice both.
A gray procipitcto form which won roéiccolvod by aiding 6 N hyéro-
chlorio acid mo stirring. The other layer was “pirated from tho
cocoon: lag-or and the lattor was extracted with three loo ml. portion.
of other. 'i'hc other extracts were combined with the original other
layer. The resulting other solution was attracted with two, 1% ml.
portions and one, 50 :1. portion of “it room hydration. The combined
Ioéium hyciroxidc extracts were acidified with 1‘5 X Sulfuric acid which
(sunset: com oily material to I'mroto from solution. not: was attracted
from the aqueous solution with tom; 50 I11. portions of other. The

combinod other mtractc were memo with SL‘ :1. or water and dried in

122

contact with mfimirouo mgnasiuo sulfate. The other wan removal by
cistillation using a modirioci Claison flask. The regions was fraction-
ctvrd using; a arr-all Vigrmx modifier; Liaison flask. The fraction boiinz
batman 55.;3°c ./S.O mm. .3. was collected. The vsight of 2,53-dicE-aloro-
34hiophammiol W1. 11.35 3., 0.0613 mole, which in a 35.5,?! yielr’i. rm.
pit-«met wan stored under a hiking-rm «Members in I refrigerator.

The two reaction was repeated twice using difl'mt logic! of
reactants and in each 8059 a dirrorant.yiald was obtaincd.' Tho guanrdl
procedurc and «momma mc the m O. in tho hm upoert with
the exception flat I 6 l sulfuric 101d ”hum III mod to acidity the
reaction nixturc in plan of 6 I Yq'flmcl‘ilw acid. 1.55.9 3.. 1.5
who, quantity of lithium alum war-1a. ma 125.8 3., 0.3 nolc,

mutiw at 2,5«dichlnrcd-3dthiophma—mli‘awl chloride war. Imployco.
’ that hour: wuro roqgired to mix the roagcnto Ind the rocction nixturc
‘1 lit “1d. Wifnight. Following €11. it “I hand it 1” mnux
separators for one hour. - A fraction boiling at 73~7S° C./l.h m. Hg.
Volga-.1123 22.53 3., 0.1217 mole. m 100119-06 winch il 3 211.113 yield of
2,5-dichlorGo3-fixiophmziol. Tho retrofit“ indoor of the product in:
nr'f‘oc 1.6231.

In tho other prcpmtion using; 56.? 5., 1.32.1 moles, of lithium
“manual hyfirldo and 112 .3 g“ 0.24147 £301., of 3,5-dichlow3‘fi'llophene-
Inlronyl chlorido with c h.5 hour mixing tint, Chroc hour period of
being set. aids "and a. two hour heating period at the reflux tampcnmro
of tho reaction Irir’mrc, I 22.0 g” (5.11? min, 26.6}: yield of
2,5(ichlnro-3-thiophanofiaiol boiling at 35-830 C./S .5 m. 123. with

0 -.
n§° I 1.5253 was comma-J.

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Preparation of E-fltmmyhropionic Acid ((23)

(«222332313412

3.! in litar, t roa nae:- , m- “a? bottom flask was fitted wit-2 a
Firebox-sorter mechanical atiz'ror, rolfiux con'.‘enmr and. a pow” addition
£31.52 2:...53 3b.; coma-ct...’ to; :12? two 2..-L.;‘j Burrow top-222' mints with
clout 013:1. inches of ru‘ubar twin;- of tzs ems €13,ch n the standard
joints. or»: moor .ioint was 1712.22.22.22 to the five liter [13227: and 12.9 other
to a 503.4 32.3.. romni both“ flask ”wile": coniaimmi the power to be «ideal
to $6 reaction flank. the m2: arr 21113 was 1.01.1359...” seal of! t. o
tmllar f 133%.: from to; five lit-3r roaction flasks. A 2'23; 3., 2.27:}. 22231.99,
qzmnhi ty of powuorod mccinic an virigl 3 anti 12.28251" 1337-»: 3., 13.55
1201.28, of banana ware p130 :43 in to! 12:23 1.1th £1.38... A "CG 3., 32.5
who, qumtity of anhydrous 512mm... calorific was quickly pow? are: in a
mortar to {wart-mt ficiaturc in the air froa Warming 1'. a m‘zyt‘muc

was (3:222 in 13:) 3. portions w 312:2

Eb

llwmlmra chlor ill-9. The 22‘302‘tari3 3m
mm tznfzaiatnw 5:3de to to: 53"...) :21. pomior orifii'tion flask fro-a which
it 2.1.! in turn 8.3.3921 to the at irroc’ benzene 1-:an also 2212: 3217231139
rttttara. Fig-"Jr 3m chloricm was rapia‘ly evolvczf from 1’.‘ e stirred roost on
atrium... 7222:1113 the as.1».31tinn of to last 1533 3. portion of mfg-rims
&s.'.‘..‘.§..‘lll cleoririo, t. 5 reaction 221.1739 ‘noca. a co viscous t.‘ at stirring
v.3 79'1“] v; Ji‘imlt. fifi‘fi-‘l‘ all of t3 a an 3;: rous 1112.14. 22* c. lcri'f a had
been 22.13%; to £29 rmcti-on £19.31: to stirrer atoll-9.1 because of the

vary viscous lrg'cr on the bottom of to their. “1"“: stirrer was mind

to the upper portion of the reaction medium. The powdm' addition flask
woe may! and replaced with a bill) type reflux concimcor. Tho roacti
mixture finally became eo viscous that it was impossible to stir my
portion of it. the c! the remote condcnecre was ctcgaporcd and tr... (rumor
m fitted with e calcium chloride 6nd. 22;; tube to prevent Mir-mm from
momma; the motion mixture while it we not nit:- o-cernig-fi-at umfcr I
hood. The following day the rcection flask m gmtly heated on a

stem beta, 2321c}: canned cop cue quantities of hydrogen c: ~2:1!232-ilc to be
evolved. ‘ Aftcr fleeting on the stoma both for an hour tic-o viscous mass
became quite fluid so that it was easily stirred. T220 ctca-x bath 21:22.9
regzleced with e heating mtcl and tho stirred mixture was kept at its
reflux imperative for 3 half hour. The mental me replasoc by on ice
bath and one of the reflux: comma. was mused with e drawing fumel.
A 3220 ml. qu. tity o! ......- woe slowly or? ..ed to the cold etirrocf roactlon
Hinton-c free: the dropping- fmmcl. Mtar tho tutor hed been 91.1333, 300
al. of commtratcd Wrochlnric acid were slowly added to the mixture.
foo (romping funnel was 2'23?th with I confionsar fittod to the flask
by mom of e 145 dame ol‘oow and the eponratue ... mung-rod for atom.
distillation. Tm reflux condensa- was rmcd and e atom inlet tube
we fitted to the reaction may... The reac ion mixtxrre become vcry dark
on fire mace benzene wee racidly atom distilled from the reaction
We. The hot non steam volatile racists we. ”afar-ad to e tar-cc
liter beaker mi on cooling the ofi-bmoylpropfi ..onic acid cry‘etallizo-E
from solution. me content: of c... Molar was cool-ad to (1° 0. and fine

loll-1 9 mmcgrlprepionio £11! an rscororod by filtration. he cruc‘; e

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acid “I “that! V112: I cold Iolntion of 100 ml. of ooncmtratod hya'ro-
ammo um 31mm with 30:: ml. a: water, arts:- which 12. was aired
hump); with 1200 :1. or com mm:- in I baakar m again filtered.

Tho product. an I very duh brown color. The crude B-bcnacylm‘oplonic
Icm nu dunked in I boiling Iolntion prepared from 253 (3., 2.12
U193, o: autism antenna mammary” In: 1500 £13.. a: water. . Tin-3 mall
mm 9: 8121111311?! 12333130321220 which form-:1. III filtered fro: the arson-ad
.3121 Ind “Shad lit}: tour, 50 n1. portion- Ii’ hot minor. l'ho filtrate
u acclaimed with chmoal m2 again filtered. The decoloz‘lzod

:11th was tramfcrrcd to a four lltar banter, cools-:32 to 52.1."

C.,
am (3th Icidiflad with 390 n1. 0! oomontratod hydrochloric etc-.123.
Tho pmlpitated {lobanzoylpmplonic Icid was (32301322 to 0° C. in an ion
«3.3 bath, filtered and was-30¢ with £021:- 306wa quantities of «212‘
um. 3m F-bmamxlpmrlonic net-2‘: ma; ciriod (wax-night It r0023 1.322233.-
hn‘c and finally for I day 13 an oven Iti'w 0C. to give 290.52 3., l. ’23
ml”, In 80.01 mm at B-bmmylprcp‘m Icid meaning It ilk-115° C.

1‘“ W melting your. (-35) a; 115°

/

Preparation of 832123.22 f—in-mmylpmpiomto

ecu 392232222012 1‘

 

~ 4"- !" N . ’ as O .- r (3“: O -
A 923211112231 of 2.3 3., .(3- 3:13 , cf sac-2’.“ 13.323.393.123 dies-3313.621 1::
13-3 ml. at 2:222:23 13223 32222323232322. A $53.3 :3., 1.0 233393, quantity at
-vs '9' 7a an, n -. . -h~ 1-09 - ~ 3‘ '-
f'A, 223133133223, .3133 acid 2.2.3 2331:: 01.22.: in £223 “.23 £23;de 621...?)1... .

1'12. 3 82.11.11.132: was trans: 33:33:! to a $2.33 11‘; 3? mac-tier: ”333241 31‘; t3:

 

 

11th I «:11de Ind vacuum war/tor for distilling under Wed
me. the IppIrItuI an mud by man a: I water Iaplrator.
turmtlmmalmlmarm inmoilbath beanie Imam
affluent to owe gentle diltillIt-im. um tho W: M evapor-
Imudxyneu, wammmummmemww
mathInManMmmmdhmmtmnguupwcd
mammuEB‘CJoz-mm. mmmummmvmmm
O cox-3.2. 33. yield of new B-bmoylmpicmu obtained In mun--
M118.

Preparation of 2-thylti‘2ioplwm from

e-Bmoylpropiaun Acid (27)

r _ a
2.
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Isou.mnfiutltwumawmmaon¢mmd
aguwhmmmuIm-uammmamuw
to any at thn vellum man. I 9.00 2., 0.0525 3291:, “1.1333
ate-buluylpropm Iciddellfi 1.. 0.0503 301:, mafia:
memmwmnwmmwmm
inIm. motmnmmumnmmm
mfimmImmuMld.~-Ammmmhwto
Mammmwmm‘nmwmmw
twthuadrtbcbottmatt‘umnuk. mommtm
w to malt and than manly I WI mum com Ind tho
menu at fimtlafibagmu chum tom. Theron had Itcmfency

 

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327

to club up the aide am of the Nuts flask. The reaction mixture was
heated gently to distill mtarinl from the 11332:, but clue to excess
fawning, heating €20 maiden Mr. M to be discontinued. At this
pcint. only I £22911 33322122., lass than I gram, or I rod-dish calorcd
mwmmmmmmmm. Thu-Item”
mumm ml. origin-ma inakenrlgomly. 110:1.qumt1ty
of “ha-maddfl b mmmmfixfimmfimmmg, flow
In: transferred to Ian]. «pant/my banal, ad mother «train:
mud 22m $22. mm phase.“ The ether valuation no trains-Id

so I50m1.baakarmd mmsnmeWonIuw-um. The
call want. of residue :2thde 12: thin m’m MW in I
12111th a: hot m1. filtered throng: I air-ch rum, Ind thu
thomly‘mltiuwm. mmlinginmhahthI
tn ems-21:5: ”mm m. chum which malted um 38 Ind 22"
c. The W 3.12.3222; point of Mkauylthinphm 1. 32-33" 0. (27).
Tho emu-mus m rcpaatcd naing . Lo :21. mm flank to that the foam
produced during tho mum could be nor. bully retained in the flask.
The gamut; nt F-bmoy‘lxoplom mm and In. tho lama, but me want
of Mayhem meI III mus-ea ‘- 5.60 3., 0.6251 mlc, Ilia:
tho am of roaming tho mi; of charting during 32». reaction. Homer,
the Milan Iixtnro chums! m tho" reaction III initiated filth hat
a 1:: cm prm Wt. 2‘33 713122 of m. m2mmuap22m

h. 0.30 z. Ind '1‘ III not wflfiad fin-that. This method of preparing
I-pimlufiophm hi IbI-m‘scnai Imi Indian 33 «vbamoylmplomto m
Inplayad in plus or the free 3.33.22.

123

Fraparaticm o: hfhmvlwiophana from
50:; in 2" igenwylpm 3310mm ( 231: )

I 13-5 n1. tam-ta distillation flack fitted with In Iir coolm con-
denser and i 50 ml. Erlmaynr flask and In I receiver ccmtitutm
the apparabn upland in this synthesis. I 30.70 3., 0.15 mole, qxzmtity
of dry Icahn-I f-bmzaylpmpionata Ind I 15.0 3.. 0.129 mole, muw
at phospz‘xoml wwmo, 19.5., , III $3:wa mixed in I m Ind
pmnmmamm. mam: ”heated gamuthIBmm
burner. wcmgwmmmmmm W, hum-
mhuuith uhofmmiduthQanmmio
mats. Tho mural. III collected in three tram wishing 0.20 3.,
0-33 8.. and 0.35 x. in tho War in which the, In. ”W. muons
tin Ind tin-II 00111311136 on ceding to I "whim hm «lam Iona.
AM combining fruition trio Ina tin-II and maintaining Ira decomm-
12»; with charcoal. in strum]. II I solvent, Ipproadmtely OJ; g., of I
material was obtained which melted It £243" 0., 1n Igrment with the
reported melting point for 2-9E‘aétg' lt‘nioph we.

The (apartment. in- reputed, using the mo Ippm-atus and qumzti-
tin of materials II above, mapfi that 23.0 g. or and VII £1?de (a I
diluent. The dry materials mm inthfily mixed in I mortar and placed
in the Warts M. Tao mwimm meow. and for tho We
of tha expaflmt- III tin m II um dear-find in ”II M aperi-
mt. mam III not u Imh warring of the ration mum I‘B tho
initial pbuei a: ma pgrclcmu u in the prev-1m Wu. I 2.61;
2., 0.81135 3033, 11.02% yield of mu. thmylfiaicgmma m ebtninofl.

‘I’

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129

W loom-I1 non-'Italliaauom {rm ethanol I mall quantity of
material an chums: mien malted It. mm" c.

Soul-I1 other “tempts to obtain higher yiolc‘zI mo moo. The
qzantity of and II I diluent. IlaI increased but. this ruled to give
h1g2” yiolda. um “um o: phOSphom hoptemlfme to Indium
B-bonsoylpropianato m varied, but on: 11km” failed $0 Woo
the yieldo. Tho uporimontons remand enact]: II in the previews
oaoo wept tint I Imam: III applied to the sarcoma, using I Iido cm
lb: inch test. @300 II I receiver. the tut inb- IiéI I!!! III ammo
“SEW minim-throngs Itnp. mmomummnm
m not II oolorod Ind m min to purify, omueqnmtlfw I Mainly
highor mm or you zqhavltmopham III comma II loll I-I loot
aluminum thIdtobotIkatfiuImntthIpmJJm
ILnoI iha mm flux Me. I W to all” m hates: moor
rorhzood pressure.

Preparation of Zi‘hmwltifiopi'xmo by
the [31330 Reaction (513.73.27h)

 

A mhmmd Itirror m arranged Ibo“ I ha 3.1m- bon'ur so that.
Officimt mixing a: tho canton“ of tho beaker could be Iocoxapliaimf.
A 93.12 g... 1.00 mlo, qnmti‘w of freshly datum Iain» Ind ‘60 ml.
of water m! mixed in €30 beaker and 200 ml. of mumiod hydro-
ohlorio acid m «food Io the turrId mm. 221- beakafl iII wt in

 

 

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I pan of 10. “to! and am notation was anatomically stirred as it
cooled in order to procipitoto the anilino rt‘drochlorido in I fine
crystalline form. A solution of 72.0 5., 1.53;; mole, of aodium n! tr-ito
eiIoolvod in 1...; m1. of orator no: placed. in I 250 m. drooping formal
Imported 8'00” the beak-or contoirjng tit-a aniline Izydroohloriéo. Sow
In. no minim! to fiw reaction mtfimro'mm oft-on its tertporamro has?
mum to 2.5" c. the 00511:]: cits-1w solution was 3:25:35. to t‘no contents
of the booka- over I 75 21mm poricri, at the and of which time I Item):
iodide pop» ma point was obtained with I few drops of the motim
mitt-om. Too dmotiooo mum woo tranofmod to I one gallon moo
mouth Jar and ice was packed mm: the for mo an officiont moor-onion
Itirrcr m ”ranged over tins for so that flzorouigh mixing of the con-
mu 0! the jar could be obtained. A 5'30 3., 5.915 moles, (mantity of
thlophono, mic}: had been previously coolo". in on too both, so! woof:
to the jar. A 21.2 ml. qmtitar or 5 1!. Indian bydrmzioo solution was
added from I dropping formal to the vigorously stirred reaction mixture,
kept. of. 2° 0., during a perm: of on m: a half hours in which time
tho reaction mixturo had turned red in color. Tho sun-ad mutton
mixture In! allowed to an to room toztpomtum $15195 caused it. to change
to I deep reddish brown in color. It. was tronofmod to I three 11m:
Iopamtory mono}. and £32.43? «Loafing with hydrochloric acid tho
amnion broL-zo mo tho organic loam:- Ioa aoporatoé from the aquomo
Levon A two litm- firoo nook, mmfi bottom flask was oquipyoé and
wrong-ad for Item dismtion. um- flm reaction mixture woo trons-

iorred to the throat liter flank, it was moorood almost cor-gleam)“ in

 

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1.31

m oil bath, wt 6?. 179° C. 15:) {313636226 61661161176 $69.21!. :' drug the
item ciatJlntion and to hasten the distilhti an. The a: 6633 112116;; "3:23:18
no steam distilled from fire mastinn mixture vary rapidly. It was
collectsd and fmtionatafl for mrt‘mr use. .6 Zfifihffi *1thisr.‘; 112-6
“9321 distilled vary 610111 . It 2‘26: I. ten-361103: t6 crysmn‘! 36 111 the
661136216611. A $013310 L.;‘">’3""C-.i".'543-§' 133' lit-31‘s f distill-.1153 1:62:16
631166391. Arte-r 672-1213 ..6?616216 61’ it 5.21 an 1:16 3361,1216 562.123.
car‘s 2-:fi.ar1;,'ltizio-1;2T1666 was £112,363: $321.1 1.- -6 11:13... 363 distillata an a
fluct- 6.61- 1’11.- 116]. and 1.316614 121111253 31-16.! to an .‘E'rlmxtm‘ar £11133: , as

ti.- o pro‘uc t 111611.111 at r3311 1.611; 2111.136. "“16 mum (2136111636 was
extracted with 1:66 liters of 3’22; '1: 121port16na 13336 62611:. 2 to ta...
03811.? in I. 6‘1 r66 11:2 :33 3132111666237 £26116]. . T126 6626:- 6.2213116 1.: 1161-6
63321212161 1111.21 £26 crime; 1:111:26 36116. #21621 had “be-2m 1' {191"551 £33.11 127126
mucous pox-um, and t}: .6 1-9613;ng 612231' 66 ...uiien 11:13 63166 in 6011‘ 3t.
'1th L‘fi“j’-"'r0u8 363168166 66.13:. t3. T716 1116;362:1216 Surata was 1'11“ :36:
from U16 63233626111 solution of 6131.16 263.311 l‘flo‘mme and L3 6.11: ms
human: on a 3666.31 bath. Th6 r-atzsifwe 11313111216 23 .92"; g. ‘31:"- 1.101131186114117
if 606166113311 1C6 bat-1. It 1:66 a light rmizfjh brown 6:12.31”. :131‘3
was a tmdmcy for two phases to form in the. 632262: 8131216210!) 11:32.61 knic-
eatnar? all of the: 113th had not him-16.226626. by 251.7111; Q26 652216 363.211.1611
in contact. with mime-1616.23 carats. T226 r661166 was r 1.8661 13.111 not

6‘621361 and docs." 33136:}. with chaz‘caal. -.16 2-11. .311; “...9"‘*'JI13 cry ailinw

on cool 11;; @211 6112121161 solution. ""26 2-311361 inwae 1:36 ruler; Eta-.1.»
1121-3121 again fmn et'Isanol give €3.12 3., 5.3333 .1 61.6 , a 3.33:, 32,1311

0! 2-19-10 61136 09316 6, halting at 2.2-. .. .16 22:: :42 2::- 3.3326 to

recover additional promct from $.26 mtiwr liquors.

132

Preparation of Z—T‘uiamrleodim (58)

| | _Y

)3
3

A free lifm, tire-3 nod»: flag-r, azppertad in a heating mental,
was fitted mm: a nachmtcal sun-er, reflux condm, and a. “1" tuba
containing; a karma-zeta:- am! dming funnel. A 750 :11. q'mntity of
“1:23“?! , prm‘mmly (1‘31 3:3 wit-‘1 aorfijn, 1mg “3.73435. to the {15.3%. To the
tolurm-z', 2'? (3., 0.12; arc-la, of mmu-g: 3.21 50 3., 2.17 1101-93, of sodium
var-2| :1.-Ema? and tins Fair-tum was tramm?‘ rapidly to 93° C. av? firm slowly
to 1'30 C. It miflz tarma'r‘vhv'a the; tolume mil-rad fipcntannously far
ugpz-odmtaly a minute am“! a half artsy? t‘rza heating mantel had bmn
ro:-.:o~mé. that was main applied and the ”action pitting was kept at.
its raft-.11: wry-Brahma fer an m’z’ittcml two mimt-os. '52:; reaction
ntdaré was attrrmi vizier-911313 and slime-3d to cool to 245° C. fie
tolufiizno was removed from t‘m armlgjamtad Wilma by (”31-11th it thmurh"
a frr‘. 5-5-4 glass tube into a trap by mans of a. mtar aspirator. After.
removing the balm-rm cans lttar of 30:31:13: Grim benzmn, was aimed to
the ar-*a1;_mzwa,te«.i :36 film. A 113 3., 1.0 male, quantity of 2-chlorc-t3do-
prim-9 was “and to the? am}. 3m: tea-:3 an. inn mop'm-cted 1:: banana. This
mixture reflux-ac? apmtanammly far a. cpm'tm' of an hour, vitbcut 5:191?-
ing «~"t::*rma.l Mat, aft-71- 1*. Em? berm initially Mata.” at. its mflux
targmr-sta‘w for 8".‘G‘Jt fivs mir‘mtrafl. 551m tins, raactflnn mi'vcture had

:1.-3:252“: rafl‘rttzxg sycatantmufly it 11-“. a black pearEemr appearances.

I"

r

turns; To at .3 1.213 "335.?! a. .,.....J t: '25.: r; mtian £15.32: m" 1.2.3

3 firm-r! 101"". mm» was 1:21» “pt at. t3 reflu... tang-arc? .11er an rational

gm“. hours. 1:19 2’555—31'3—332'iun 1:11.13 use»: fl'm:.i:.t 3' £113- ” an). to
.1“

:33. t mu c'rclc2;crm'3.z1a 1"... “ fut momma-~13 c. gum 23' 3.41.. (.....WM»

frcrx . .a raga-3r. 3:212:21.
The fixation of 1-1.4.m13-auuzn with (..3: bhwzamne (73’)

T: :53 12;,- :ra‘ms 61‘1'9M1L19J1-3 -1:-ally we; .1:“ u...:..3::tl»'>....::,
wigs-'9. prfipwaticn 15:13 Just sfiascrib-z-fi, was used in the pres ant 8:411:31.
to wok". transferr‘w ti' .3 o:'*;;m axwitiva organs swim-3 comm.

T113 ”1" tuba was tibia: with a. £17231; at»: uni c": mtw‘afi-JLI into La
macticn mix-2, a :13. c arr. acme: fzrn. nitrcgsn 1211‘:de u drawing
farm-91. T1: 3.1:: :tusm ” «35.23131: 1m in: a 312:1. posit iv: mean-s of
fry niimwn to 92" went ail: fur: m: 22.3.11; ta cmztact 1:5. .11 t: a reaction
:aLzmr-a. The apyaratua was cums-tam: in an 12:) bath and 1.13 ZJuhiJw'l-
iufl; lama-3:23 .._:g‘me 23:18 c2313.: to Lo C. A 137.25 g., 1.1 moles,
qamxt-lty cf C"r:10re.-anfmc , which Lac? been Cried ova: ankycmms magmas-373;:
silicate and 52.31.12.131, was amalgam 5.11 3.3-3 :11. of 121;: 36112011») am:
place-(‘- in tin: drawing; 9"“:21“. 1‘31: c, 313.35.330.13 mint ..3: 11.3 s3. ”'35:
aide-:5. to the: 32"?111 :mht'loa cf ”-2....imymc ' cm“ a far" ' 1.11.111:
mum-2:1. it 9:23 am: of $.19 the, that .cwtlcn may: mm Linc}; in
{321;}: "1:1 its v.59; ..tuw 1w: 1-13-31: t: 12.30 C. Tim 1:0 hat; was
text's-'3. an". the mactim z... .4. :3 was mirror: an a; :2" b.1131 31%:- x ..7 a
31...? mm: -.._, {£12m wt mi: 3 for tJ'.:-::3 q..3~t:rs 61" an .201. . '12.: flash

0 ”Q Q

was again an: pgmrtm—l in an ice bat}. ;; '..... at etfgmsl mam 5.13:2;

’Q

33.20:}. to the reaction r-Lthure, to clestrcy my :1.-.0958 soiling: press-ant,
fell-31:23:! by 101‘.- 1.1. or water. Aft-3: an um: and a. quart-412', 1.00 ml. of
6 N byLz-ochlaric arid were ads-:2 to the stirred reaction mixture. It
was than transfermd to a capa'a'stoz-y mil-3&1 and the organic lay-er was
separated, and washed first. with 1.10 :11. or water, than with 130 1:11. of
3 1: 60:11.13 I‘gfimzido nolution and finally with mo :21. of water aft-3r
which it was erad in contact ":55; miyamus paw-main: sulfate: to:
twelve hours. 1"... mgxasiwa sulfate was reamed from the benzmaa Bola-i
tlan by Iiltratioa and the filtrate was humane! using a. one foot
heat. .:acketéd Vigrmx calm-.31. ma aifitillato was collected in six
fractions. The first four frwtiwxs contammi banana and unraactad
2-c1.lorot.hi.cp2.ane. The two fractions collected at 103-1150 C./1.3 In.
2:3” 27.21 g. (I), and 153~m° c./2.3 m. 1.1;... 15.72 3. (II), were
investigated for the presence of 2-(l' acyclnh'wamlhhmphma ms!
2-(1' VJrclohiaxmxylol)tf.10phm13. Both frac'ticns: decoloriaed a carton
tetraciioriia 801::an of bromine. 22¢m'3r, (I) fipkiq' daccloriz -".
lama mammta mm (II) cnly alum-.3; érmoloriaed small mam-its, ~13.
noifiz-ar one was there any 115:: of hydrogan brozaiJm evolutizm. T1118
Lmlicatad (I) probably contain-ad n largo pmwtage of an mmmatad
compound were u in (II) there ma c1133 tracaa of the manhunt-3'3.
conpozmfi preacmt. Infra-rad analysis vm'ifi‘iod th in, u (I) slash-ad a.
strong absorption band and (II) ma}: absorption for unsaturatizm, and
harms: (I) had I. very weal: absorption and (II) a. stg dam-puma
for the byway]. group. The tuft-active inflame were: (2) x1300 C‘-

a
1.57:3 ald (II) 1130 G. . 1052270

1'31. do?vdmti® of the highm‘ boiling nation, II, “I Ettaztrptéd
in use {allowing mar. :- 54: ml. round two-tum; flwx m fit-'t-*x: with
a mafia: eorumm ms: @3an in A heating; mum]... A S g. quantify
of (II) an; 25' ml. of cwmzl‘at» foam acid. wart-3 pigeon in tut: map.
In}. beaten gently. '32-'18 Mafia? rah: 4:: very viwwaly for approxi-
111un a Mute. um: $.10 ixfiti-afa. ruwismn mlaigaé, the WWW-:3
was Luyi} at. its main: magma.» 1;? 53;: 30-11:: gnaw, man coal-52;: and.
diiutuu with 2w ml. of WW", and. atmctac nit: area, 3.90 ml. partisan
of char. l'na comma: «ii-aw: mk‘acu awe Rem-am with two, 1w :1.

$

pus-$3.013 of 6 3% mm hyu’oxha Gelatin: Incl dried in contact viii.
anagram “55min swam. Utar the gamma was was 2‘0»me
ire-re 1.30 «mm salutiun by iiltoi‘fltim, the arms: :33 rmvor‘: an a
stem beam. Tm realm: m [mummtad using a semi micro mfifim
cum; than. Tm frautium boiling at mug-nu" c./1.3, m. 17g., 0.1:;
3. am 120-1525" u./1.3 m. 21.3., 9.6:. g., were collected. Bum fractions
mm dwelorimd broaina carbon tatrwhloricio ablation time“ any
visLblu evidence of hyérOgan brawn being: evolved.

1.3me 1m dag-Jame“ m not cos-uplam. Tim auction was mt.
313m. ind hum-32' by this mum: of he: gdratiun. Sub-aquamt delay: rat-1m
We aceozwllaimd um; 2L5 may: acid.

To esmblifi: that (I) was 2-(1qyelnfixmeml) tuophem its
691:1:og‘muim to 2-pgutg‘imofiz-‘m was gamma (5:) in 1m follow-
mg vascular. A. 23$ fl. romn‘ bottom flask m fitted with a mflxtrz cam-
flaw-4:! and the: final. was Liwt‘éwfi in a urge-mum vaguwtala 01.3. hath

map-ac vii... tau blew heats-3:8 and an alum-5.0 stirrer. mo blade

hostar was a 33-32 watt encyacit , If'?3 c :nwolleu: by a. pouarswt. art-.22 tze
cfiiar with a 122' watt. ca pacity 333 car: rolled by u memostat. A 11) g
0.2;:211 1101a, (rmtity of (I) , lat-2:: prm'an to be 2-{cycldmwm2n thia-
ph-me, and 3.? 3., 0.12 mole, of 341m:- ware mixed in the £19.52: and
heat-32.3; to 23° C. , at which paint wueg‘m to by: evolved from the
wit-m raaction man. It had the odor of h‘firogm suiting and. it?

‘

3:913:2madlaratlacctaba 9:21: was 13.5:er ova: tin anti, of ti? rflux
coma-2.512313 it. iii-335185333 tum.) black, indicating the prosance 0:? m3" "39
ion. “ii-.3 tea-2.3m? “a of thew-.1 bath was raisad fwm 171° to 12-: 5° C.
cm“ 3.33 tm ind : quart-33' hours. At ”2:0 and of £43.: period O positive
13:31:? wetate hast. was etLll in: 13:11. the reactlg .01: was c.8001}...m, ..

Tine crude: rgaction mixture was autumn from g 25 :71. mm: flag}: .2
c3... L'Mxis :ad prasauro. I‘m [:33 22:10:13 mm ccllectaci, ona mum; at 3523-»
1270 C ./2 5m. 23., 1..C2 g. and £1.21 char at 1J:-l~'i° C./5.3 mm. Hg"

3.2.35 3. The first. fraction 54% I wry positive teat far unsaturaticn
vim bmmine in carbon tetraczmms. The second fraction {yam a very
final: positive but with brmfine, 12:: eating; 0 13 c 2:- .111 mac-uni. of
unsatxatmi mtarial was present and this fraction pmtially en's-milked
on cooling it. in an ice bath. 172.9 first. tractioz: appeared to be mainly
unchangad 3mm; mtarial and £32143 second mainly 2 Emmdfiziqifzane,
contaz— 1:13th with starting mate: is]. and 854.73 reaction products. Tina
man smut. or crystallms mun-1&1 1n the 3223ch [mac L120 :1 ma isolated
by rzp‘lzi film ion on a mall I'irac‘n fumal and after recr- ,rstalliz atoni
{ram ethanol it. nwltad at LIL-mo C. The litaratura reports tan with:

9:»:an for 2-pizam21tinioyhene, 2.2-.3" c. (27,23,31) am: 3:.-32..S° c. (32).

137

The dehydrogenation of (I) was repeateo using the same apparatus
and quantities of reagents as in the previous experiment, but at a
higher temperature nnd 3 longer reaction time. The oil bath temperature
reached 180° C. before a positive lead acetate test for sulricsa was
Obtained in the open and of tro reflux condenser. The temperature of
the bath was raised to 230° c. and raintained at that tanperatum for
three hour. and than it we: finally increased to 220° C. for an hour
and three quarters. The reaction mixture was cooled and transferred
to . semi micro modified Claisen flask for distillation. A fraction
boiling 3t its-110° C./1.h mm. Hg., 3.0; 3., solidified in the conéenser
and otter leveral rocrystallizatione from ethanol its melting point
an. hZ-hjo C. which indicated the product was 2-phenylthiopheue. A
large soul. preparation of 2-phenylthiophene with its physical constants
and chumion1.annlyeel are given later.

Preporation of Sodium Amalgam in Ether (58)

The preparation of the sociun amalgam was carried out2using a
modification of Eartough'a (38) method. A three liter, three neck
flaskuoo fitted with a reflux condenser, mechanical stirrer, and ther-
mometer. To the flask uore added, .00 m1. of toluene, 17.2 3., 0.75
mole, of sodium, and 12.5 g., 0.6fi25 mole, of mercury. The vigorously
stirred contents of the lash were heated rapidly, with an electric
mental, to 95° 0., then slowly from 93° to 196° C. at uiich point the
toluene refluxed vigorously for approximately a minute. After the

toluene stopped refluxing due to the heat of amalgamation of the sodium,

 

 

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138

the sixturs was vigorously stirred and kept st its reflux temperature
by'sxtornsl netting for three minutes. The hosting mantel was removed
and the mixturs_uss vigorously stirred until the temperature had fallen
to 35° C. A tritted glass filter stick, connected to s Hater sspirstor
through s trip, was placed in tne reaction mixture. The toluene was
removed fronzthe Iodine smslgnm by drawing it through the filter stick
into the trap. A 300 ml. quantity or awaren- ether was udded to the
flask to cover the sodium Inslgnn, protecting it {ran attack by moisture
and air.

Preparation of S-Bromo-Z-thienylsodium (57)

H

The sodium amalgam Obtained a; the previous preparation was used
in the present synthesis, utilising the same Apparatus employed in the
sodium amalgam preparation, exceyt that the thermometer uns replaced
with s '1' tube containing a dropping tunnel and nitrOgan gas inlet
tube. i solution of £1.52 2., 0.5 mole, of freshly distilled 2-bromo-
thiophene dissolved in 500 ul. of enhyfirous other was placed in the
dropping innnel. A continuous strean of dry nitrogen fies swept slowly
through the apparatus. The ether soniun smslgsm mixture was heated to
its reflux temperature End the 24bronothi0phene was added dropuise to
the stirred refluxing ethersl nirture ever s.period of two hours.

The reaction mixture was kept st its reflux temperature for an

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139

additional two hours, under an atmosphere of nitroggjen, to complete the
much. The relating product S-brmno-zdthienylsodizm, use a

”pension of brass: colored pol-der- in the other medium.

Attempted Preparation of S-i‘hemrl-2-bronothiophene

 

The apparatus already containing the S-broao-Z-thimrlsodiun,
those preparation has Just previously been described, one used in the
pram preparation of S-phimyl-‘é-bromthiophene. A' L58 g., 2.25 moles,
quantity of freshly distilled iodobeneene, which boiled at 155° c., m.
placed in the dropping Dermal. The phwliodide m added drowise to
the stirred refluxing ethereal am...“ SémM-thiaxylsodiun,
over a one hour period. The stirred reaction mixture was kept at its
reflux tnperamre an mum four hours and after cooling, it ...
stoppered, and set aside overnight. The excess sodium was destroyed
by adding 100 m1. of ethanol followed by 50 m1. of tater and stirring
the mixture for an Em. A 500 ml. «entity of eater was then added
to the flask and the apparatus 3"“ arranged for vacuum steam distilla-
tion by replacing the reflux condenser nit}: an L5 degree elbow, condenser,
side ar- adaptor and receiver. The steam distillate boiled at 51° C./

101 m. Fig. The non-steam volatile residue was trsnsferred to s

separatory funnel and the aqueous layer separated. The organic layer

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was washed Iith 200 ml. of enter end than lose ml. or etnanol res
added to the organic leyer. fine to the‘blsck dirty eppeerance of the
solution, at this point, it use decolcrised euth charcoal.° The sloo-
holio solution.ves fractioneted'ssing a one foot heat jacketed Vigreux
volunng‘but no S-phenyl-Qchronothicphene III obtained. A 225.? 3.,
1.10 eoles, quentity c! iodobenasne see recovered tree the frectiono
eticn, leering e‘bleck terry residue in the distilleticn tlelk. The
Adistillete tree the steam oistillsticn was transferred to e separetory
funnel and the ecueous phase was removed from the organic eateriel end
the letter wee dried in contect with mnydroue ugz'aeeme mlfete.

the nemesinn sulfate m remorse by filtration. The organic material
was tractioneted using a one foot heat jacketed column. A 223.23 3.,
1.09 soles, (lo-entity of iodobonsme and e 55.1.5 3;, 0.3:; mole, quentity
of z-crooothiophm were recovered. The totel recovery or nnreecteo
icdobensene amounted to 97!. The 26.06 g. of unreccvsred 2W
thiophene probably decomposed during the reaction thich accounted for
the black terry residues obtained.

Preparation of 2-(l'-Cyclohexeny1) thiophene

 

A three liter, three neck (leek eel fitted lith e reflux condenser,
nechenicel stirrer, end e "I“ tube containing e gel inlet tube end
dropping funnel. ‘All of the glassware was dried at 110° C. for epproxi-

nately twelve hours prior to assembling. Nitrogen gas which had been

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dried by bubbling it through a concentrated sulfuric acid tow-3r, was
elawly swept through the apparatus during the entire experiment.

A 53.50 3., 2.20 moles, mantity or nognosinn, previously dried in an
oven at 110° C. for twelve hours, was placed in the__ tree liter flock
and the entire apparatus was furthm dried by heating with a small
Bunsen burner flame mile sweeping dry :11ng Wrough it. After the
apparatus had cooled to room tonpercmre, 1:10 :11. or dry ether and

2 ml. of freshly distilleci etlwl bronioe we added. After the reaction
batman the ethyl bromide and magnesium bed started it was diluted with
750 ll. of ether. To this vigorously stirred reacting mixture was
video, free e dropping funnel, a solution of 325.1 3.. 2.0 moles, of
2-brcte‘othiophene dissolved in 3.0-0 ml. at ctr: ether over a three hour
period. The 2-bronctniophene was added at a rate sufficient to main-
tain a gentle reflux or the ether in the reaction flask. After the
addition of the halothiop‘nene was complete the reaction mixture we
kept at its renur tanpcreture for en coditional hour and forty aimtes,
and then cooled to room twperature. A solutions! 215.91 3., 2.20
mles. of fresh]: distilled cyclohexanone, oiseolved in 2130 ml. of dry
ether see slowly aided from the dropping humol to the stirred. reaction
nixture ever a forty-five :31th period. The stirred reaction mixture
was kept at its reflux temperature an additional thirty minutes. 1:- ring
the addition of the cyclohexenone, the reaction mixture changed from a
bleak to e broun color and finally s tan precipitate formed as the

last of the cyclohaxencne was being weed. The reaction mixture was

cooled in an ice bath and hydrolysed with 6 I hydrochloric acid by

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adding the acid slowly from the dropping mm. The reaction mixture
res transferred to e separator-1r formal no the aqueous phase was
separated from the organic phase. The aopeoue lever was .Ihid with
three, loo nl. portions of ether and the ether flashing! sore corn-bingo
with the original organic portion. The ethereal solution was cried in
contact with amwdmus magnesium sulfate. The drying agent was
filtereo from the ethereal solution and. the filtrate was transferred
to a distillation wparatus where the other was distilled from the
product on s steam both. “me dark viscous residue of crude

2-(1' -cyclohexanolyl) thiophsne was treosi‘orred to a one liter, three
neck flask fitted with a reflux condenser and stirrer. A 500 :51.
Quantity of a 2;}; by weight aqueous oxalic acid solution was added to
the flask and the stirreo mixture was heated at its reflux tenperature
for an hour. The reaction mixture was cooled, transferred to s
separatory flannel, and the aqueous phase was separated and extracted
with two, 300 ml. portions or other which were added. to the original
organic phase. The ether solution was washed with 53 ml. of a 3 3!
sodium hydroxide solution, than with 55 r . of water and dried in contact
with anlryfirous magnesium sulfate. The drying agent rues filtered from
the solution, and the other was removed from the crude product by die.
tillation on a steam bath. The liqeid residue was fractionated using;
s one foot-heat jacketed Viggreux calm-n. The fraction boiling at
11942.20" C./3.C m. £23., with e rotroctive index or 11:50- l.f£‘l-.’:.5, was

collected. It weighed 2-733 .93 3., 1.62 moles, which was an 81.0.! yield,

 

 

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ban-3d on 2-brcmothioph-3n3, of 2-{1'«cycloiwxmvl)tiziopiona. The

9 q - e -‘ .-i 0
reported. boiling paint for 2-(l'~c;.‘c10~'33;;'.;,3r-'i) tnicyuena is {lg-)1 C./
6.1 mm. Hg. (13.2). Iilemmtal 5.3313333! cf the pro:‘:uc:t for carbon,

drown and sulfur ”333 tho following vaults: Calc'd. for C '.--t .15:
_ - ' it a 1-0 13

C. 73-12} J. 7.3” 5, “.552. 1:311:33: (3,713.34; I! 7.32; 5, 19,39,

Propamtion of Z-I-‘hanyltiwicphom

O

A 5-9-0 ml. round bottom 231333: was fittm .a reflux cons;.-.:msar
and supportad in an oil bath equipped with a thmnostat, a 53,; watt om":
e 125’ watt boat"1 '13 b19133, and a at war. A 1%.?) 3., (Make; 3:013,
quantity of 2-(l'ccgrclc33x3nyl) thiop‘ncne and s 39.1 3., 1.22 moles,
quantity of mlmr w3 r3 adiod to the flask and thoroughly 1:- dby
stirring with e glass rod. 37:19:! 1'. 3 {Reaper aturo of 1.18 b3 at?) roazz'nrz-d

.-o . , .
2'.» C. en ofmlution of goo 133.3 3.5.31.1; and e :30 Sit 1:3 tsat for wiring

we obtained by holding 301833.331" i: 31 mtata pa *3: over tie-o tsp of
the condmnr. T‘ao bot-Hr ~ mi: ts. . at QUE-300.13.? two homo, than

raieod to ??C 00. for £3". hours, :1.”? tin-m the £1.33}: was ran-373.3 from
1:519 oil bath, “opp-31:91:? , arr-..3 eat aside ovarnigh‘t. The: following 33;; tip-.3
oil bath was hoa‘d 923° C. 32165 the ...-.3232 t‘:1 1:13 603;?)3‘13‘317' 1.7.8
egain placed in it for an 31-:- air. Iéo 5:13-33 cezrld be 33m risi'zg from the
surface of use reaction 35113323,}31; a. positi 3-33 toot 31.11.511.13 at

the top of the cominesar was still obtainasblo. 1‘13 raaact ion mixture

I!

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was transfarraé to I distal t on arparetus and fracticnatad using a
can foot heat Jacketed Yigrcux cclunn. n ferarun of 6.L§ 3., O.£Slh
mole, of 2-(1'mytlohum‘rl) tiicpr'ana um recovered. A fraction
boiling in tho range 133-133;" :1./2.3 m. 1-13.»; collected which
oolifiifieé 1n the receivar. Ifiis reprasanted I, hho?5 3., 0.??? mela,
50.?! yield.based on 2-(1'ccyclnhaxaxyl) thiophcna. The profiuct,
2-?‘mrazrlthitzp‘mna, had a mitt-'33 point of i;2n‘.3° C. aftm' racrys‘mlliza-
tion from ethanol. The reportad melting points of this corpounfi was
19-1.? 0. (27.23.31) and 324-32.? c. (32). It. boiling point in
reparted (32) to be 25.4.1" c.

Inc to 1.1.9 Largo). mount. of msflrffua ramming in the distillation
flask, an attempt was maria to isolate aciditicnal quantities of 2~phanyl-
12210;»?!ch by heating the maiden an additional five and a third hour:
in an oil bath at 23u° C. A very weak positive sulfide test was still
duuinad from the vaporl being evolved from the mains. I‘Fawvar,
iman the mixture was éictilled only a snail unsunt of material distilling
at. 159-151" c./2.2 an. F3. mu obtainod and this remained liquid at
room t9:s~p9:*atxre. Following the nxpermsmtal pmcmlro Just doacribad
the prapamtian of Zaphanyltfiiomsna was repeat-3:3. A 130.}: 3., 0.932
mole, qnantity of 2-(1'-qyclohaxanyl) thiophcno and I 63.0 g., 1.93;
mole, quantity of sulfur were used. The raacticn $212:er was hex-.tmi
in in oil bath for fear and threa-quartar hours at 229° C. khan the
rmtioa :xixmro was tractionaw, a fraction boiling; a 136-107" c./
2.9 mm. Hg. was collacfiad. This represantad a 77.97 5., 0.h55 mole,

£9.53; 311313, or 2-pi‘sanylthicphwa based on the amount of

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2-(1' -oyclol:axmyl) tfdophem moo. Thu gwodnct melted at t2.o can)
tazpmturo u in the previous preparation.
Attmptod Bl‘emination of 2-i-‘hom'ltidogshono
with Cyanogen Bromide 1.1)

A 232;; r . one neck flask was Into-<3, with a roflux comfoasor and
mpportod in an oil bath. Tho latt-or was 11:3:th with a blade; hoatar
regulated by a moment. The top of too oondmsor m connootod by
moons of glass tubing to a trap containing an mucous ”din-:3 hyn‘roxim
Iolntion. A 10 5., c.0525 mole, quantity of 2-phorylttz’mphma and a
6.52 3., 0.6625 mole, qumtity of cyanogm bromide voro placac‘i 1n the
flan}: and the apparatus was ”ambled. The oil bat‘a was placed unim-
the reaction flask and beam to 140° c. men were no visible mei-
cations of gen being liberated. According to work rsportod by
Stammpf (141) a groan color uhould have developod 1n the faction
mixture, but 1:18th it became a reddish brown. moroactlon mixture
was hoatoc‘. for three and two-mix: hournot mo C. and than loo m1.
of a 3 E looms: hyfiroxLio solution was acid-o: to the £13321... The
reaction mixturu m heated at its reflux towel-own for an “minor-m
two hour! and then transferred to n 5% :31. three moi»: flask arranged
for stoma distillation. ‘mo distillota from tho stoma diatillntlon
val coolao in an ice but}: and {I'm your: motel-rial m iltazreci from
the aqueous mspa‘naion. The solid tutorial was cmrstalllzoc: from
ethanol to yield- 8.65 g. of unchanged 2-phomrlthiophsano melting
sharply at ans-343.6 c. Etilemantal analyses for (swabs gave the

following result...

 

11.6

Calc'da c, 715.94%; E, 5.03; 5, 20.01. Foam?! c, 73.5% 1:, 5.1-3.3
8, 23.11;.

The roaction ms mooted. using the some apparama and morimtal
groom”. A 5.68 53., (3.053% mole, quantity of newly gmrchasao Eautsm
Chaaical Company white label graham}: bravado and 8.50 53., 0.0335 mole,
of uncovered and ”purified thsnylthiophono were added to the flask
no the puma was heated- nt 80° 0., but once at this ”rapist-own the
mmgan bromide ”porn-ad and. coll-acted in the reflux comfianaor the ‘
tnporatzro at tho both an lowed to 60° c. The circulation or mtor
1n the rorlux eondmsor was discontimad until the crystallised magm-
bromido melted mo rm back into the reaction flask. The reaction
mixture was heated at 60° C. for four and a quarto:- houri and than
70 :21. of a 3 N oolution of sodium hydroxide m Added to the flank.

The reaction sis-mum was heated at its reflux tmaturo for an miciitional
two hours. Afton- 1oolating the prmhwt in the m manner as described
in the provioua experimt and crystallizing it from ethanol n 6.80 g.,

o! manhunt-god thmwlthiomme m obtainad Ihich melted at 1:24:39 C.

Preparation of Zd’hoxvl-S-bmmtticphma

Br

A two neck, 200 ml. round bottom flask was flttod with a mimoioul
Itirror and reflux wndmoar, contnlning n caloimn chlorido tub. tttachod

to the upper and at tho eondmar. A 10.0 3.. 0.0525 mole, quantity of

L7

2-phonylt‘aiofixmo was atomic-oi 1:: 5-3 ml. of dry carbon tot;'ac2:lor-ifio
and placed in the flock. A 1.1.12 3., (3.0523 cola, quantity of fl-brorxo-
mount-nice ml coded to tl-za 2-3132omrlt’2:iop‘rnmo carbon totmc‘slorh‘c
lolntlon. Tho Iolution vac vignmusly oth'rcz‘z for a half him: at room
tnparltm-o and than it was hootod vith a heating mantel at its reflux
tangents“ for ten hours. The rosction mixture changoci from a 115;? at
yellow to rod And finally to a bromish red color. Succ 5:113:11“ cry: ..3.-
1139:! from the reaction mixture on two aides or the racction flask.
Imam brmddc gas was m‘olvoo from the reaction mixture dur1n3 t‘2..3
course of the reaction. The reaction mixture was coolcd in an ice bath
and the cryltallino mocinimlda was filtered from the carbon totracidorida
by annotating it on a Buckner tunnel. Th racclnimldo m washed- with
35 :11. of cold carbon totmchlorlcéo and this was combined with the
original film“. The carbon tatrachlorma solution was (.‘ifioui in
contact with anhydrous nvagmsmm sulfatc. A 50 ml. modified Cloison
distillation flask was czpportcd on 3 atom bath and o. 50 m1. cropping
Mme]. m fitted in the top of tie Cloiem flask. The dricr} cache-n
tetrachloride solution was trmaforrcc‘i to the dropping mmcl and than
it no Olav]: added to the Cloiscn final: as the carbon totrcchlorifio
In unfilled. Tho mixture had a tem'imcy to foam during the distil-
lation. 11‘“! all of t‘m carbon tetrachloride solution had beam mica-'32
and most of tho carbon tetrachloride hot! beam distilled- from the
Chi-on flack, the appamma was evacuate-J to 2.0 an. E3. pressure and
$1110 tho diutilllng flask was being heated in a warm vats-3r bath fin

last traces of carbon totracidurioo more rc;.:ovcd. The recline in the

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flask co11£3.floo to c broanish gray coloreJ solid w loo he? a noltlng
rings of 79.330 0., wcia*6* l?.LS 3., which reprocgntcd a 115.3:
yiald of crude 2~pfienyl~§~broncthiopkcnc. rho Cruse 2-ph .yl-S-bromo~
thiophcac after {£11790 roomtollimtiozm from ethanol. 3?...3 13.1 3.,
0.0513 mole, on 87.53 yield of 2-37‘Porry1-6Jsronot 13.033125216, wilting at;
BS.§-€5.0° G. The reported melting point for 2~phcn:1-54bromcthioyhono
10 85-86" C. (1.1), :mcparod by bromincting 21>hszrxyltoicphmc with
(2313:9333 bromide. Analyses for C1 05,5317 gov-c tho following results.
Celo‘dl C, 50.221 11,3523; 3, 13.4.1.- 3 Br, 33.1.2. Foam: C, 53.2?)

F, 3.13) 3, 13.223 Br; 33.25.

Tho bromlnatim of Emhonylfizicyhmo with Rdwrotaoouccininldc was
repeated tflco 71th 113 {0110333313 variation!) in mtitlol o! recs-saute
and 11:39 of roaction. Th3 apparatus 1m: mantles]. to tho amiarotus
used to tho initial proporation.

A solution of 20.52 3., 0.123 mole, of 2-phonyl’a11oohcm (iocolvod
in 100 ml. or dry cmfim t-atrach 10:31.15 3... placod in tho rose tioo flock
and to this, 22.8 3., 0.128m mlo, of H- bromsuccininidc was 36.363. The
mixture was stirrod for on} our and tan mfmutos at roan temporcturo
0nd than at its reflux tanpora‘ouro for five hours. Tho isolati cm of
tho product, on doccrib-od previously, 313111313 215.6 3., 0.3.1.1 mole, an
87.6% yield of 2~phauyl~5~bromoohiophono, melting at o,.§-o .Oo c.

The largest scale propxntion of 2-331'.om*l~5~bromott.iophone was
made using 57.0 3., 0.32 mole, of 2-pionylthiophonc dissolved in 3&6
ml. of dry cw‘oon totroch" 1.1.19. A ELL-i) ml". round bottom roactlon flan};

I
was [about-7.11.35? for tho 2.11.) 1:7 '. f 1.131;. Tho 2-331omyltédophono solution

 

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was placnd in the 5.7.7.373 ml. flag}, and $1.37 3., 0.32 27:91.73, of 340177.:73-‘20-
mac 1111:1160 was add-7x! to it... 12.3 reaction mixture was stirred for an
hour and n quarter at. room temp-graham and rum at its rsflux
mgramro for five hmt'.‘ . 753.3 17723.17 ion muffin butmfi 61135177737771.15'
than t‘m previous one in that lf‘b‘fi‘ the retention mixture was hat-:78 to
its reflux fitperamra, the rats or raflux beca‘w so vignrano flat. the
berating mantel had to ha ramvod. l‘he mutton mirmra cmtinued to
reflux spontaneously for advert-.1 mimtes. The product was iaclated in
the usual mane): to yiald 88.19 3., 0.359 E3013, a 115.23 349161 of a
yellowish gray nolored era-7:20 matarlal. ”tar two racrystallizatians
from ethanol, decolcrlzing with charcoal during the first. crystalliza-
tion, a 62.18 3., 0.260 mole, 81.33”. yield of colorlmn 2-371:myl~5~

bromot‘ciog‘wna was obtained which melted at sang-7.75.0" c.

Prapnration or S-Phanyl-ozd-vmmphmthlol

 

A ans liter, tiara-as neck romai bottom flask was fitteé- with a raflux
com-2.3187317 Which had a calcium chloride tube fitted to the upper an}, a
mec2'2,anlcnl atlrrsr, and l '1“ tube containing a gas inlet tuba and
dropping fungal. The uneasmldad glass apparatus was driad for thrm
hours in an oven at 115° C. After the 0:73. rains was asswz-blmi, a stream
of nitmg ., dried by bubbling it thrwgh a concenwateai sulfuric 9.2.7.23.

tower, was slowly “apt fizrouggh the apparatus. A [”52 3., 0.1723 male,

Q1221.1LJ of 1.237.. .2522 1:172, w ...-.7; . he... b.2322 32713.: ..‘or a Lia; is: .121 071.321 3‘7.

l-lo _ I! n ‘7.
1.1.; C. was lacs-7.72.2 1.7.77. 132.9 3227.21.12.77: 177.22.31.32: £177.35". ' 2-41.7.2 12:7. :2
I
”mtg: m beifisgc «zit Yin. L: ...J fiwvuuss, .'LU “(2.3 08.11313 $13.1? L735?!"

91. fl“: a Man burr-.317 £122.32 12:7 :72: 2.5.x}: ...237 .3.-.2232: that 2221.332. 37.22.77.273
accus'als; .96.. Hurting tho 37......3 7.1;;2-31 ...”... dzJ" 111317;. :32: was 81:22:13“
passed fizz-mgr: E23 3;.-;7:.7:27atus. 1.32227 1: .a a7 33.773133 was 72:. 3013., 17.. :31.
of 903.133 (11713:. sti 327 was a .32.: to t; .73 1’13... ma t777m177.. t." .3 3.7.7977“:
funnel. A 1.2.33 g., 0.13:; 2.72313, quantity of 5.. «£1. w.LJ7J."c."Us 0.32....u77n77220
1:3: dismlvsd 1.71 206 ...1. ::::.£ '33. 3121.327 3.15. plsmad 17.71 £17.73 3.7-7.2; 7:31.137. fur-2:21:21.
mural 151.121.112.227: cf this 3': 1717:1331 2.773273233572133 to t': :3 £13333. 3.717;. 533222.157
heated on a stem: bath. 27.137.777.21 tin: 13.43.33 27:22.5. st..;'-t:2:l, 5:3 i2'3.i.:'23,t::7;. by
I. contiguous rsi'luz cf t‘z-e 07.23.3277 3221.32:- t‘ :22. steam bass i..7..:i 123- 22. 17:. 2:27.73: ,
2550 ml. of dry 3.37.32: were 32.93;: to 3.23 273332.132: $13.72.: 33:21:33.2...
vim 1707:2313". Th3 372177.327 67721117213172 of Salami-24.217337 7:. -.i :77: was 37.03::
8107:2131 to t}; 3 3.1277273: 3712.73.57.22: 2:;12-27‘9212737 at 22 27732.3 873551313772“: to 273.132.35.21
a 37:72.19 reflux of the 31723317. 27.21 2:27.227 1.777 ..3 regs 2.17371 to 3.2:: 17.3.73 atlas-27
aviation of 5-7777. 071,7l~"-?77737.ot3.is;‘2.:n-. 31’an 77.737.33-517: 221.37.31.73 was 22331.34:
at its ruflnx tamer-3:231:73 for an 33.25.225.033}. hour. 15.7.7... . t..3 2.7.3337. 2.7.27. '3
ttlrrer m stag-sped an 0113,77 {£227.33 832273105 to “23 bottom of the raactlon
flask, from the 113$ 37731107.: 3013:7732: reaction 2212:3333. T123 drawing
hams). was 27391337373: by a pawn er 3:1;17‘7’77 .322 (53:71:23, 22:22:33 by ccxmectlng two
ltamiard tapered intur Joints 1:73.77 a rubbar t7 bin .77; of #27723 33.7373 :3 313-7237122317
and. attacfiag 57.3 37-1. 53722332713 tapered. 12:27:77.7}: 1707' 2.3. be ttom 1’1. 77 77}: on one
smam join . The: other 3mm: flint was 33.3333 5:. the neck 31’

the rusctlon flask. A 5.73 5., 0.1.. 22.313, 07.22.3277}. 3.22:; of :17777 7799237 3173';

“120.": was pm‘*"3z.: in tin I: 2.3... $2.05.:. T13 601.50: :33 0...: "..3 01;; 3:5 t0
t1}: sic-m 0c"; 000001320 3015;“.020 at. a 1"" m " 12's.: :2. 0 31:01:. 3‘111010.

of 0'...» 91.23:. The a.;-<~.i...aa o: 1.2: 0.11.342: 1-01-41. "1 ' {11“33'1 01.10293

Nona: as

The last awn; 0.11:4: in t‘ra :1.-0;};- ...-Man ...-.033: was 1:032:03 into
tit: 003.31.19.21 mixture with La.‘ '01.. 01‘ 0:11.20. .‘. 13:1;2’: y 110;“ racipttnta,
Vidal 0‘15. not appear to 1:3 in: 5.11:” Al‘, 1‘0: .236} w 2.0: t‘: o 9:13” was
c.5500 to 1.5.3 reac":m mast-1:0. $1.0 01.13333 faction Fianna was twat-ad
at. its reflux Migra- are far twanty 31.30453: 0:10 1.1.0:: 03:13:... 31:3
tp'mratus was a»: 07:13:01 33:3 set as -'._25 $0? an hour. ‘1" n rwnrtisn {3.031;
was their. packed 5:; ice v.3 1:‘ s2; :01. 01‘s R h .051'00‘114. "aria acil was 0.11:1

to t‘s .45»er *y‘ r: p- actJn ”’1 int, u :‘Paa‘b t: 3 “to—"FA—u“, fI=L'.;1;1. r‘“ ' brill“

pruipitst-a which had £017.05 0.2:.- 3t1-2 r0...) 3.12:0 mm 1'00: *v0fi £3020 the
rcactio.. mixture or. a flat-12d filiar. ”3's y':~'1..ow 3300’. 1.0000 .3

rear: 8%....- i“ 1201‘... '1‘: t: 1 07010510300 01.10.2101 mixture: to 30 0121 10.1.1.- 3. 0f
mtmial. Aftar tre- mm-ztcllizatiana 13m 030103; czma t3 is rat-01:10.1
nit-31 at 11-3-1‘.i.° C. his was 1.0 .0:- 05:91.11 (:0 he Sephestl-Q-‘fifimy’l-
disulflde or £11": (ff-001° cf f-f-I"3191-2-931035:7311-115 5.0 . . "'33 wateril was
er-nd in a 61:11:; pistol at. 305 100.115. at. tho 1201:0111 .1130 of 1-2010; :ing
0 0:00:01. 1.00:0...va anal-35.: f3:- car‘ma, 115012;»;20 and sulfur $95.61 the
£01100.ng r0 wlu. Analysis for Eng-'34”... Calc'dd .52 .75; 1?, 3.6.}:
8, 33.52. F0003: L, $13.97} "'3 3.933 3, 33.3. . Tin 3m.‘*‘at0, from
which 1:115 yallov prmipitata had bear: char-$394, m3 t'mxaf'zr'rai to a
s-txgm'ab ry farm-'91 mad the cquwus 3)? 10.90 was swarmsd from 13-43 0:110:03].

1:50.30. 1'210 aquacu- 333.030 mm extra... mta-tf with Cr rec , 334.3 011.00 p0.-1'tiom of

at). a: and t‘. 0:: co:::1.1n0£: with ta origmal 9th.: partisan 00:5: .1 -0003:

 

 

\
1
_ I
- .
o
..
9
' - . _

15-2

with threa, 30 ml. portions of 6 ll Minn ray-fireman eolutim. The
confined alkaline ”tracts ms acidifhd with 116 m1. of 6 91 Afro-
chlo-rtc acid aeration. faring the acidification of tho carbimsd 50:31:23
hydroxide extract-s a yellow merely-imam femad. T229 yellow pracipitem
was filtered from that laid solution and washed with smart-11 porting: of
cold mtar. The crime (Fry pracigzitat‘a mlth at 753-1350 C. as detarmiusd
on a melting; point block. T329 yellm: precipitaie was initially soluble
in methyl 3.109%]. but on continuefi heating a yellow precipitate crystal-
11nd from 00121151021. Aftar this mun-in]. was cryshllized frog a methyl
alcohcl cyclohmzma soluticn three: times and dried in a vacuum piste-1
at the reflux: tamperi’cura of ethanol a material was detained flmt

melted at. 13.3.5-LE;° C. hydra-xi melting point of this what-mesa with
the 01'1ng yellow laud obtain-m! from ma initial reaction described
above gem no dapresaion in melting point. Amaranth tim- fi—plm'xyl-Z-
fidoplmneth 101 oxidized to the (iisulfiua or (intern-ad during the
recrystallization procafiura. A 19.72 3., 0.152 mole, 52 .11}?! yield of
Sup?gam'l-z’ctzziOpEmnothiol was obtained when a correction in ma for

the previously isolated Swizmgfl-aofiziamrl diamh‘icia. mmmtal analy-
811 for ma recrystallized mtm'ial gave in» following results! Calc'ri.
for Cmfins‘: C, 62.79; IE, 3.6“); :3, 53.32. Foam: C, 62.1.5?’ If, 3.5334;

3, 33.29.

A tum-.3 Liar. three main ilwx waa mm with .3 11:13qu comma-er
ooutais’m‘sg a Galena c1 11011.10 tine «is the top, Q maimicu stirrer,
In: a. "1’” tube “mum-x; . an mlat tum and t 5.9 all. drappmg funnel.
All 73.3.35 arts of .3 agmum tiara driau' for twelve hours in an oven
5
-J3 ._.. - . Q‘ - -q ~‘_.1- Q'v: _-> ~ - - ‘--n
at 1.2,. u. an)... that ans-amalw u.-L-&¢3 not. hl'ta‘figfln gas, wine by Dilofllllig
it .'...‘au .1 a can; ..Jtrzswd 5.11“»; Gala tun... , m alouly s. ...;at through
ti 3 upper: rat-.15. A 25.5 3., 1.3.4 salsa, (gum-tit}; a: manila, mica had
* -¢ ‘ ~ - .H . ‘ ~1 g m - a
gar-Inna; 1:33;: cause. for 1.; ileum in an 0.1..) at a... 9., m 9.1.3639 m
tho £1.23... “I a La .‘..zr :quin 1;}... "‘ wt wlatura La unusual and
1» a
mtg; 5.9.1.3 3.123111“; :fi “3; 6 CMDWLLB‘J hhga}; “it.“ . iii-“1.1333 Dian-1U}. “1.5.5.3
dz“! nlbrvflm UN! 5013’ [hurt {...-“mm the r'sm'a.uua. A 84.0w “Nazi mi
- u n t a D'
(31:, 11;L;‘o.;4r. VHS panda; ‘LLLL'au‘j. his. mfg... aims Liu'iiig the antlre (go-4:33
of t...» arggrltmn’an £23.? 1.1.: aging-..tga 2m; 0001.»; to mam Wap-uuume,
award Myers of L. '3' star and 10 g. of freatsly uia'tillad my].
bro. :1.-.13 wurva alive.“ to tha $13.33.: by mmaw of w: crappmg furnwl.
A restate; m Lax .utsly sure. as was by lam-3 by tr: :3 ruilm: mg u’.‘ wr
and ta: quaaranca of a grqymh pmaLar out in the cum: solvamt.
A 1.3.3 ml. (11.13;?th of sauna an; etuar, was 9.43;} to the mm.
A 2.3.35: 55., 1.x}. 5.01:3, qwxul'by of imam; (Listlllmi 2,5:7-(lerozwtidoo

ping-.13 dissolu'm; in ...-u :5... 03 6355.1 was 3.4!...) slowly to t..e vi;_{u:'ozm1y

I'. 4’10!

— {rul-
o-.0.

i

CW reaction mixture from the trapping funnel. .’i'hs 2 ,5-ctihromo
filfiophm van added gt a rate «Efficient to pro-dug. a math reflux of
tho aflzar, which required- an hm and ten minutes. ”the reaction mixture,
thick. at this point. m In light brown in color, an stirred tor an
wifimnl half hour at. its raflm: mapamtm. than the mimxical
flirts: m stopped a brown oily 1W anti-ad in tin. bottom of tin:
reaction metal. This raw-rial m comma: to be Shmmévfidimyl- ~
nag-”main brand: and m magmas: reacted with mmhmo without
further isolation.

Tho Preparation of S-firom-E-(l'myclohaxanclyl) miopheno

 

The apparatus just described 1n.tha preview pmparatian was employed
in the garment. synthesis“ The Sibmm-é-uhiwmmesium browse, pm.
pared prmiously and tter-3'3- m a 115.th “mayhem wa- cooled to 0° c.
by bra-mung ‘L’xe reaction flash in an ice bath.“ A 107.95 3., 1.18 210103,
“may cf hyclohacmona, mien had been dried in contact with armyjmua
3mm sulfata and distilled, m" din-aim: in Lao ml. or dry ether
and placed in tho drapping fumai. Tm cyclohmcmns collation mu IL3L’EGd
slowly to the stirred Grimm-d tea-3.3mm over t thirty manta pariod tearing
which. @1259 flu mast-15m nirtm‘o tumor! yellow and a large mmmt of a
yellow prec ipflmto format}. After the ketona had. been wdod 122:9 stirred

O

a,»

1'55

reaction mm was heated at its reflux taxparaWa for an additiorml
m: hour. After cooling the reaction aim" 5CD ml. of 6 H hydro-
chloria mm m slowly added to it follow by hep ml. or inter.
morwummmtnmfmd hamstoryfmmalum the
other by» was mated, washed 11th 166 m1. tutor, and dried in con-
“at with WW! amenity: wlfate, The W “33390 was filtered
from the ethos“ common cm: the mm“ is warm Go a éiatilo
um Impartial. the other was dutillad from thin solution on a

“on hath. Th0 uniting 65.1: routine, amides-ed to be and. S-branso-
2-(1'-eyv.lohmlyl) thiolafm, m not W106 War but us and
directly in the am premium.

Preparation of E-Elrom-Q—(l'ccyclohwzwl) fidepham

 

A ta liter, three me}: flag}: was fitted with a reflux conc'ensar
and mmpanical stirrer and mppcrtcd in a heating mantel, The cmfo
S-t-mm-Z—(l'-c;mlohaxew1)t :33.“ 22:, 1:205:13 prapam’oion is éznscribm
in the premium wzpaz'ment, mm tmmfermz! to tha two litar reaction
flask. A 10-0 3. qumtifcr of oxalic acid was diamlvad in ism ml. of
hot water am! the acid Solution m poured into the raaction flaak,
I?» vigrr-ously curred reaction szfixture ms haatad at its reflux

tmparatara for m hmr. The reaction 3:113:er was coolaci, trmsrwrad

S!

..f

.I ... t .I.

I {.15 ll

ms

to a separator-y tmml, and the orgmio phase as lopmtwf. It ms
was: with two, 100 ml. portions or water and than c‘fried in contact
trite: mm: ngnanm sulfate. Tho Mgmilm sulfate m filtarm:
from tho solution and the filtrate; was {antiquated using I one foot
mt. jacketed Vim com. in 13.949 3., fax-em, boiling between
w~1sfs° c./3.7-h.5 m. 12g. , was discarded. rho fraction boiling at
155-155" C./3.5 In. Hg. which solidified on cooling Ill collected.
It immmtod to 117.35 3., 0.1533 mole, mick m I h8.3;€ yield of
fibrous-24 1' myolchmcanylkhioph—mo bums an the mount of 2 ,S-dibromo-
thiophmo mm}. The Sobromo-z-(l'ucpplomwlnhiophm melted our
tn. mg. 33.5-35.1“ 0. Elemental min for clpznsnr gave the
fondling result... WM“ 0, 1:53.39) H, 13.55; 8, 13.181 Br, 32.87.
round: 6, 19.32; H, ham 3, 13.03; Br, 33.08.
Attmptad Dahydrogmtion of S-arom-z-(l'ccyclohexwl)
fiziophm to form flflrom-Svphuvlfiliophma »

A 250 1:11. mm: was fitted with 5 reflux condenser and immar!
Ln an 01.1 bath whose Wimmro was controllad by he blade hasten.
. A 500 watt b13130 heater was controlled by a 'Pmrltat' and t 325 watt
heater was controlled by a them-went. The “PM? control was
used to ram tho bath tmramrc to within 5° c. or the desired
unparam aid tho thermontafi nu ma obtain $215 :35de temperatur
by fumid*:.1ng thaacidltionnl heat. needed. A 10- g., 0.0m 13919,
quantity of 5-bmm-2-(1'mplohaxwlfihiophuno and I 3.02 3.,
0.0933 mole, quantity of sulfur ware placed in the flask and thoroughly
mixed. when the bath WW9 reached 176° 0. there we a rapid

evolution a: tuna. Tho mm gov. I positive toot for wide; with
32015me lead Icotam paper. This positivo load acetato teat
woos-load m be much slower than in the proviso: doivdrogonation wai-
mnu, however, the evolution of gas“ was met: more rapid. The mm.
had In irritating odor similar to I hydrohalifio, unaware, they were
tested for new, and it was found that blue litm- roadily turned rod
than hold some the oomiansor. The temperature of the bath was raised
to 230° c. and kept there for tun ma. a quarts: hours. The tongum‘amro
Ian than rain-ax! to 215° c. tor In additional two and a quarter hours.
At the and of 1532le um, Ivan thmgh tho load Icon“ test am still
positive, tho reaction nlxturo m cooled to roan mmmro. A 60
ml. quantity or buxom m wood Ind tho mm. was filtered through
I Buchnm' filter to MI I call mi. of loud lantern]. from téao
Iolutionf ThI tun-.5 an Item distillad which wad tho human
and only I mull mt, leu than 0.5 8-; of I tutorial which oolidii‘ied
on cooling to Ipproadmtoly 10°C. A largo mount of tarry residue
minor] in tho max: Ind could not I» Item's diatillod. me raportaci
mlting point of 2-br‘omo-S-phom'lfloio'gmono 1a 85-85° 9. (L1) m2 it

in Item distillablo. I: In? 2-bromo-5-phenyltiziophmo was form-3o: in
the Inm- dehydrogenation mction it w mob loss than 0.5 g. Z'E-ze

material in tho dehydrogenation reaction was not lnveotigatod further.

hmtion ct S-(l’Cyclchum'lfie-thimylmmsm
{memos and Its Eleaotim with Lultur

 

.1 {.‘.-mo litor, flax-co coo}: round bottom flask was mom wits. s.
taxz‘a'aical stint-or, I confionoor contoini. ; I calcium caloric-'13 Crying
tifua and I "I" sicfs cm. tubs carrying I 3.12: 1.11221. tubs aux-.1 (rowing;
fouml. The unoco—oszloz‘: gloss ooparatus was dried overnight in an oven
at llefa'o C. A 9.3.3; 3., 0.3333 hole, qzmntity or :mfiom'm tunings.
which had boom. (3; too for I day 131 on ovon at 1.1530 6., was plate-3d in the
vacation flask. 3.31113 nitrogm, orlod by bubbling it through I
concontratod mlfurio acid drying tower, was slowly swept through tho
apparams, “rm lattm' was cautiously f“- mad with I Duncan humor to
drive out «my moisture tI'aot may hora collect—ad in the apparatus tor
it had boos assembled. “tar mac apparatus had cooled BS‘Olml. of dry
; other was added to the reaction £19.st by moons of tho dropping tunnel.
try nitrogon ms slowly swzpt through tho apparatus continuously to
prov-amt Iir from tutoring the cmarotaas. A 10 g., 0.621 mole quantity
of ctfil‘orowlfis, was abide-:1 to the other and. magnolia tamings Ind
stirs-9d vigoroooly until t‘rrzs Grimm-d rocction was initio'tso. An 85.22
3., 0.3373 mola, mmntity of S-(l'wyolof-z-Jxmyl)~2-brozaothlophmo was
dissolved in 5C0 :11. of dry otter and added during In hour, to the
vigorously Itirrod motion mixture through t'2s dropping funnel.

The reaction mixture tux-nod I brownish yellow color. The reaction

mixture was stirred Ind hosted It its reflux to'gom'awrs for In hour

15?

I31 fortu- nimztml. khan ma stirrer was stoppofi I alllow brown oil
tamed on the bottom of tho rmtion flack. Tho dropping; Mal was
replaced with I power Mifion tube prepared- from tun :1.-oc- inmu'
Immm taper Joints connected by I six inch length of mbbor mbmg.
on. sumo tapm‘ joint was connected to the reaction flock and the
other was fitted to I 50 33.. room: boom flak. A 13.0 a... 0.143!) mole,
qmuw or war, dried by generating one pzmpeoru pmtoxifio m

I mums oooiccator for two cars, was placed in the 50 :31. flwo. the
sulfur was cox-1&3, during I fifteen Bimbo ported; to the Itirrori
reaction mm" in tall portion It. I «to utilelmt to maintam the
other It its “£11m memo. tho no traces or alias flora uni-red
into the rwtion mixture with 5G ml. of dry other. 15::- reaction mixture
was stirred and banked If; its reflux Whirl for a sodium hour
«mm: time Mun-Ibrightyollo'mcolch marmouumsk no
pmodmmicebath Ind 20:: n1. 01’6le Iota ”Intimates
placed in I dropping Mel Ina-.3 the lItt-ar HI! fitted in tho Imam.
in plan. or the own-m Itic‘lium tube. Tho acid solution was coded drop-
viu to tho sun-so tactical mix-time. A bright yIllow procipitoto
famed mommy. A 1'00 :31. quantity of tutor ms stifled m tho so-
action mixturo and the yellow precipi‘faato m filtered from the othe‘arsal
and moons solution- with I flntod filter. Tho yollw precipitate; was
oligitly oolublc in other czar?- imsolnhls in 10,1; and int: harmonica.

ma other photo of tho rocctim mixture was I bright yellow color, moi-r
outing it as saturated with the yellow precipiuta. Tins Igneous Icid

pins as sopmtoc‘ from the star phase in I Iopantcry funnel.

Tia-3 cqcocuo pit-Jase was attracted viii-z twee, 5.0 m1. portions of ooze»:-
“if! 1.120 othor ore-tracts mac combing: with us orighw-l ofi-ror phase.
2.3 otivr plazas was attractor: with firm, 130 ml. portions of 3.9::
potassium rmiroxioo solution. Tho cominod potaccm fair-oxide solo-
tiona worn 8:13.3in wit": 6 l‘.’ hyairochloric 3.21:3. 33:3; brown 011
tamed. Tho oil was extracted free: 122.9 aqueous mom wit": cures,
12'2".) rel. portions of ctitar and tho extinct fitfi‘flr coatmcts mm Crim
Overnight in contact with ailmiroua compassion m ."eto mic: I nitrogm
Itszospimrs to prevent air oxiietion. The otror was ciiatillod firm: tics
crude product using I mdii‘ic-d (liaison 83:11 micro distillation flask.
The: rosiziuo was fractionated coin-v tho was distillation apparatus.
A traction boning It 133.c" c./2.2 m. fig. m collected. I. 23.3.6 3.,
0.13 tools, 36.51;! yield of S-(l'mvolohaxam'l) -2-t!:13p2.aflat£1lol ms
Gounod. .1:: analysis was mt mode on talc pro-duct because of its
instability. An Mrs-grad spectra cos Gotta-remod, sinking that I
flulfr‘syjryl group was present inioaoax’ by In absor‘gtion bowl It 3 .35 fl.
All attsrzpts to prayers I 2,1.«v-iliritroymm'l sulflio dar'itrativo of tho
prcwct failed to yield I crystallins dodvetiva.

The follow prankyitata mic?) m: found Khan tho Grignwd vacation
mums!» was 1’.-;‘(§"Ol}'2~ifi was purifloql. ‘l'lro cruis yellow precipimto
melted in the tame 123-13o" c. on a suiting point block. M‘tcr
rom73tallizing tszo mat-twin; twlco from iocprcpyl alcohol anti ore” from
notion-cl I omtcrial mltlng at 133-133 C. was obtained. The.) olswsontal

analysis for 33(13'333. 3mm: Cam’oJ C, 51.34;?) IE, 5.1:?) 3, 32.8}.

f .
I
I

Fume?! C, 51.23; H, 5.673 3, 32.36. ’i‘lzo ctiaor portion of the {1:1ng

 

 

 

 

 

.
u

131

"action mixture was evaporated to err-mass on a tat-93:2 bath $9 33191::
12.30 g. of ammo S-(lh-c 'clo‘: .9.ar:;,rl)-a~t.n--.. g1. ciazxififie. A 130.921.7339
OI cu material was racrystallizaé from 18013199391 £932.01 my}. if. 3:290
. {in was “lung point as the or 51.9.91. prscipitate. I. mix-:93 999193.213
point. 31? mi: mun-is]. with we original precipitata 83.01939 no 99. 3 9.3331091.
The S-(l'mmluflwa-Z-miamrl dimlficle) um: warhead vial litisim
Minna hydridc, a! show: in the Subsequent pragmration, for fur'timr
proof of it. ltruc mm.

1. ...t-i' in?! Alu-fiuma ’fyr. ‘91.:79 fi'ar’uctflnn of.“ 5-(1'433910‘93:39:71.)-

2 ~tiz'11'3zy'l 1 15111116 3

A one litur,‘ .z. 393 11997»: {19.37: was f1 turn? with a raflntzt comiensnr,
mechanical 1!th and m;9m~ final. T113 117293.393“ 3d 51.9.99 an? 3 91:93
val, c’friad ave:rn..1:':t in an oven at 119° C. before 5259999251199. A ".73 3.,
0.01335 1101., quantity of 1:“! 9.713.112: 9199:5939: 323-9723193 was f.‘ 21313.3 mtm'i in
a caremlly 6.91. 9:: mrmr 11.4: 99 1 33:99.9. of dry nit-.99 3991, by p19. 91:17: tw
mortar under an inverted 9.19.2191, which was connect-99%. to a 99:; 12.19.9999:
”urea. Th. £139,133 mam 11.9.7631“: 91-319191: 13.399159 was ~911va it: a
litar reaction 1133’: and ? 0 9.1. of CW at 91:.- “993 r: 591w t 9 939917.021
fink. The lithium 913.15.199.39 “9913*" -. 9.1- mixture 999 .9 3:12:99”: 9?. its
reflux Weratazr3 for fiftem nimtas to dissolve tit-3 lit-311m 913.191.139.92
hyfir‘lfie. A 6. CO 3., 0.6153 9319, Qlfin+-1tj§' of E-(l' «7:3919‘-9~»rr:331.)4?-
thimtd (2131111933 was (1133019991 in 200 m1. of (3:7 eff-13': 9.92:1 3519.99.91. 1.21
the dumping mrmcl. T720 ether solution of f‘(l"¢f'€lflf7€ffifi?1)~20

t’r lewd dimlf .c‘ '9: was a: 9199‘. c mmdm t-o ti: :9 919999129139 3+. .11"er 1132911131

Illusimlm hydride at A 2‘th 1.1311: hat to maintain the reactim mLatura
at it. reflux txgreraturo without mammal heatiflg. lawn all the
5-(1'cyclohexemrl)-2-thieny1 a’imlfi-fia hm: haen ”tied, the rascals!)
mixture was oth'roufi and heated at. it: raffle: tarrperam‘a for an midi-
ticnal hour and. a (patter. T33 reaction mixtura was cooled in an ice
bath and 50 ml. of mtézr were slowly added to (59$th any mccaas lithium
tlumimzra hycrlge. Tho reaction mixture was tuon poured into 1&0 ml. of
vigorously stirred 6 ll hvfiroc?~lorlo acid. The mention mixture was
transfened to. I separator-y rmal and the aqueous phase was s'apnratad
from the ether pkmaa. The aqxeoua phase was extracted with three, 56;:
n1. portions of eater and the atzur m-:tracto were ch-lnud with the
oril'vinal othar pm.” and extract-ad with three, 25 ml. portions of 11:1:
potassium mtfmt’o salutim. T59 combines} aqueous potassium hydroxide
extracts ms acifiifled with 6 E hgairoci'xloric acid, mar-wpon a brown
011 formed in the acidified aqueous mains-u. The all m utmctmi from
the aqueous solution with tune, 50 ml. portions or other and the cou-
izmc‘ cuter extracts Hero (triad in contact with animlrous maximum
luli‘au under an mmpmm of 31:12-ng. Tim other ml distilled from
tit-a swarm uclution using I. 33:11 mien: modified (11.112911 distillation
ammratua and a sample was “fit [rm £93 1'ng resign. for an
unit's-fired 11131311.. 79:26 titre-trad spectrum contained an absorption
bani at. 3.96 p indicating a calfwdm'l group was present. The residue
was not fractional]: distillao in cum" to premt either timrml do-
cuvgroaiti or air extant-Lon. All stigma to gar-mare O 2,1;m21111t1‘0‘
phenyl 'lflcio ciarlvatlva treat the residue fallad to give a crya'mlllna

martial o

*1
L.

Preparatian (31' {5:31 ‘51'1ajljrcolata (-5.1)

U‘Ef‘i' (‘3‘! PTLP"
.- J‘ ..3!.- . a-=.~ug$rmaa

.5
'5'
'4
..3-
(f

J
'3

, cm 1132!: mum hot. tea {2.31535 was tittad with a re. 7.13
mafia-“.33: carz'tzg an a‘*~~“::2 3: 3.13111 chlarlr‘a éryfzzg tube. A 3313*...2

5., 5.33 3301335, qaa. .tf-fiy of 3233333... 'r-clin mic“ ma diseralvad in 03.3

liter, 7?. 2 3., 17.1 31:21:35, ci' absalnu r“ “anal contained in 12333 {La-.33.

A 1.1;- g., mst‘lty of ccmmstratud sulfuric acid was carefully stir-i323! to
the: 1.303513333327311.) acid ablation. The rmst‘ian 3:..1xture was 3: 01:33 at its:
raflax 33.3.33333'333a333 for 913‘. t. 3303339 am: than set. «aid: at room banqusrawra
:3: tan 322-38. The mixture was poured. into u tarea liter 135391.392: .3333

11-1113 it was nth-r0353, msz-tyéma 330*;in camonata um «idem in portions

until carbon dioxide evolution had 3333333331. After the: caiditim of todium

cza'bcmto hat: baa-m ccnpletac, a litar of anhyt'waa 933.3:- m added to

the ads-$1M to precipitam t‘m excess 8033mm carbcmte, and 692.1332...
$415333) £3923 2.2.3 (3‘5. 3'1 {31033;m018t3 13*. .3323 was 3331313139 in tha 5.1339301}

3.3333103. 731:3 1::33-.33i:i.p£."‘“.ta we (30113333313 on a 333:: :.-".-’Jr fur-.2361 3.23:? 333-... ad

with edua: 33.1313 was mutiny. wit: t:- 3 (33'1de fl ltrata. The filtrata

was trmai‘crrtai to a :‘isiillaiim afgatm‘t’as 933.33.33de with a 0:333 {out
twat Vial“: "'14.“.11'21 Col; :3. 1". 33.3 338.51.? p33 “'6 321' $3.13 atlar 3:315 I‘s:33cs*.:'33;‘;

b3 3 1.11.13.33.42: an a at 3.1-3 bath at 333323 “whwic prcsmzm 9:333 tea r2323“ ..ndar
at 54.} 23:3. F133. 3333.} a. bra-warms. a 01 3.33 C. Tim r3331: 33: 33.9 312.333.31.31! to

YafLL’2;iL£-£ {11.53.11 33.5. :11 £21.; “£3: 31' fraht on 131.11.?" at ’31" 3° C ./..2.'3' 3232.. fig.

.~--- ‘ _._ _ ‘ ..-1 3'
Uta; €L21Wt23/Q. r4414. 2"“; F'I‘Smlu3d 8 l, 20:} 80’ 2-9; 1331.38, 51...,“Av

of :fi.‘.‘1 t... 0......Jla2w. Tia fiesta-.7373 1.35.222: cf ‘ .3 pmrmct mg,

C I O s
213°0' 1- 1.1.3? . The r3302: 3.: haul-3.3.; point 51‘ 231'." :1 t...’. Huh”
1. 1:7 -..‘“'\.-‘a C ./t‘...: ‘05; 4.91.9 priéfiflnrfi (?f) o

n‘

1739 praparation of eat-3'1 3;..10313332313233 was r't-;~-33t~3a:1 32812:; a ..3-'2'
excess cf 32... ‘322301. The 0.23:3 32:?pu;'i.323.;t..\l prccaxim'a 333.3 $231,133.31.
A 12.73301 3., £7.33 moles, (gammy 01' {...}.oiglg'uolic acid, 237'.) 3., 11.3
23301715, 3 liters, of absoluta ati'zafwl as)... 13.3 .5 3., 1.13- $103.? 32', of
con mar-.5332 calm:- ic acid 3mm used in t- 0 Synthesis. T2233 reaction
2221:. 'taz'a 3:329 1:31:33 at its rafhlx w.:.~;;<3rat=:2ra for 01:35:. Mara and 3.53.3 ~
con-1111:; it was neutralize; with a 3.33 3., 1.3.3 32.133.33.32, ,..22-.. city of
wig-Cream Emilia-carbonate. A {:30 113.32" gaunt}. 2.3-" of“ {332333330213 0333-:
was 3233‘. to 173.335.33.339 tit-3 salts. 7‘13: ramimiar of tax 12.333.33.303: of
En profiuct ...-3.3 curb-3:- out an C~39:3"‘.‘3-33 9.13033. 1133 fraction 3303.15.23;
at ’73-’39 C ./19 2333. F3. 8338 33011003332} as transact am”. rmwamu..2 a,
1.23.?! 3., 3.53 2:301:33, €3.63 yield: of 3.231 £213.31 3133;}. 333. Its x'ui‘ractivo

o C ‘ .'
1:35.32 was r.” ' 0 1.1571.
..i
I’r-zzgm 33.1.32: 0! Lfirs'dgl 3.123.131]wa
c.3333 3.c;-;;::,:;r..zaacz..:::;:,: .1,

A flaw-33 113-30}: , hr.» 1.13.332: {3.323313 ma tithes. with a atirmr, a £35122:
can: 3:133." git}. (2233.33.21 malarh‘e tube, 313‘ "1" 133.39, can fighting 3 than-
maxim: m2 :3 ‘7‘ C? ".1. 33:91:" .223 33223131. A 57.5 3., 2.5 salsa, mmtity
o. 333.21.3- 9239 333133;} '30 a 1.13.3.1: cf (1.360111% eta-anal canfainmi in the
was: 3.3.323 £13.33: at. a rats wn‘flcmnt to 1:33;: fin 33136201 112 13.: reflux

1.53.3;- raturu. Aitar preparing and c.3913": he 3933.11.33 33131337130 solution,

hum-LL“

1‘ pd
1” »

I 313 3., 2.5 320193, qua-32% .’.}; c! 11:31 1.5.3.95; “36131.; ~13 was ray! .13 c.-
m 11'. E114. a it. was Vigz‘filédi 1:; stirre‘i. A 3.? 5., 2.35 3:21:43, .‘.:‘Ttiiy
of «1:351 snowmen-"... was 31:52:93, we: a 0113 hear prim, frcm t :-

dropping fume}. t1) the atz'uvwc‘s 903. 3.1111 61'; ..3’1 {1135232013122 misfits-.1 at

4 rate which kept t.» “action tagm fun helm DC. .9. 1:119.) 353;:-
cipitaia of 521.14: ciloriga 1:713:31; 35‘". t: 3 11731511 11 i5.t.-m cf

GL‘“ 3'1 c- .10 01.54 at». ..:-1..;.‘;.-«.°:‘ {no 1...1..;";.;.:=-.1 01' {.11. 634131 c‘ .1 1* .1213
bani ba‘m oaswlutrszi fiat stirred ranchlon mixturfl was 2.11311. 13% its 122.141.
txwem‘aro is: 4 half 1.011;, t. an it. ms c0013.": 1:1 an ice 1.5.1.3., 53:.) a.
lit-1r of other mm 42119211 to it to 1:. Image: 11.9 3* 111111112: (:1 511:: 12.1.11
cE-Llorido. 1211; 94:31:31 chlorifa was flit-1‘63; h*c»::1 L’zs rmm‘izlon .1171 we
on a Duel-mar mnnal end 11mm on that 111me titt- urea, 1‘40 :21. pardons
of et‘mr. A one foot ”fiestas comm: Vim: 301mm, was used to
frmtionatr the distillate. Tue «11.11%? m rm; by distillation on
4 sis-.111 bath at nfimsfimfic presume and than at ruined pmamwa,
obtained Lit}! a water 3&371rator.'fha ruidua m3 fragments-1:. tax; the
fraction boiling ai‘. 11,-115‘: C./1.5-‘- mm. fig. um collacwzi. A 333.3} g.,
13:33 13512313, 7"." ._; )2 3191:. of 111-31.:131 11314411.}:1301 1.315 m obta’dud 111110
0 ,
had I. miractin 12:92: or 2130” " . 1.11311. The ragmrtm 12011122,;
3.3131 c: 12.3 «:31 1:»1oc1 31:31:11.1.» 1; 2-37-39 .2. (7:7).

7...; 33:11.2 21.1513 of ($1111. 31 t2 3.011133%};114 was re. mated on a my»?
kale. 4L: ma 5., 3.33 11:33.05, (3de er M41411, 3.3.3 1.1. or $331313
111.114., 1.23.83 .3.;3 mice, a: 3111,11 Czicfiv‘cohta, an: 4.32.1.1 5..
3.5,} 13431013, of etfiol c.1lorometcte Vera used in than lac-301211 pragmatism.

1'91: €21;st of an hour was rag. U617 to 13er t1.» atfiyl ci'llamuccz‘u: L4 3:1?

 

'9

the reaction nurture m heated gt it! reflux ergmro for an hour
Ind ten nir‘mtao. Tm cruéa proéuct was 51°“thth and the fraction
boiling ut n7-119° (.3./2.0 In. fig. m collected 1:214:23 mounted to

1196 .7 2.. 2.31 mm, c 68.65 yum of diathyl tziofliglyoelato. It hag!

o
a refractive influx of 113° '3' II 1.11%.

Prepara ion of t‘ a I 1306 111333.11. of 2,5«1 iambomethow~
., ,b'LL W101: none (35A?)

«- . o
, fia ‘ 1 “in
CI‘ 31 "333088 .grLCXé-Ifa

A f1" liter, t me use}: ronnz‘ ho who: flask was f1 tad witi: a
mechanical Itirmr, I reflux comianam‘ containing a calcizm cum-mo
vibe, and: a "I” tube containing a dropping mane]. and I timrmmtar
“Erich mmcied inta the five liter reaction flask. 1 solution of
ӣ11m methoxizia was prepared by allowing 115 5., S .0 moles, of 00:21am
to react with LG} m1. of absclnta methanol in the five 111.431. flask.
The w'fhm ms 536m to tag mitt-mm]. at a rate wmimt to limp the
methanol at its rail-1: tmemtui . Aftar all of tho noziium hm
reacted with the matimol, the solution m ccolad to 5° C. in an ice
bath. A palatial: containing 235.0 3., 2.5 220138, a: draw-23*]. oxalate
and. 396.5 3., 1.92 who, of 6119152131 fiiiodiglycolata in 1.5 liter: of
absolute methanol was max-ad. 15210 golntion as added mpviso from
tit-o (impping flannel to use stirred waif-m: mthixia solution during a

per-Led or two hours. The reactian tezmramrn was kept below 1u° c.

”...-..--.. "

 

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12.7 1

During the first mortar hour of tie macaw, the roaction 211nm
booms bright yellow in color 13:1 the roller 122301211310 omen»: salt
of 2,5-61oorbomothom3,bqiifiyfirowtgiiophono hogan to precipitate.
“tor all or the roactanto had been mid-oi: to the flash the stirred
reaction We was kept at its reflux tomoroturo for whom and a
half 1nd him it no: not aside: womigfizt. The z'gisotimt 111::er m
ooolod to 0° C. in an loo bath and the yollow colored soc-111m salt m
1‘11th from the mot-zonal solution on a frittod gloss film:- by a
"manor-mm with a inter upirator. The yollov colt m Woo
from tho filter and whoa with 530 3311. of com absolute methanol and
man filter-22d again. The cruéo mtwial was air fined for a ciay and
than gimme! to a fine power. It £2.me to 62.1.3 3., 2.2-5 melon, a

3; yield of tho crud-o éiaoiiima salt 01' 2,5~dicarbo:ootfiio:Qr-3,h<ii-
hydro x31; dophone .

Tho preparation or this profiuct m ropoatod 113111;; different
qimntitiol of mutants am a {mm-em reaction time. The amorous
and procedure followed tor. tho am a (3er above. A 167.0 5.,
7.25 moles, 'qumuty of ”(1111.11 mo mm to react in 15:31) :11. of
(buolnto methanol. A 1490 3., 2.353 who, quantity of d1otégzyl thiodin
glycohto and 3.21; 3., 3.5? moles, of dimtizyl oxalate voro 613391qu in
1590 m1. of absolute methanol. Tho romlting mlution W 31363:! crap.
true, mm o two and a half hour porno, to the loom Bottoms collarb
Hon kept at a martian below 13° C. The yellow pron: wit-ate, as
before, was Itirrod and rofluxoii for an hour of for all the roacmiltl
hod- boon mood to the reaction 11351:. The reaction solution and

 

m3

prooipitato Hora ooolod to 0° C. and filtoroci through a coarao glass
untamed tutor. Tho yellow colored solid product no. minimal with; co :3
not @101. Aftor the yollov solid had boon a1r oriai! for tizroo (Boys with
occasional stirring mm on to dag; to 81x: wayorotion, tho yollou 'cmzio
"to-rial m mod to a fino pcuo‘or in a starter. This wifiofi 7557.5
3.. 2.72. moles, a 11:}: yield. of tho cruflo (515061133 salt of 2,54i1cnrboc-
3:32:03?ng«fiifiycrozr—Q’tfdoph-mo was ohtoinod. Again thin 51:91.1- 1. 1:19.31:
and compares to too proviouo proparation, oven though the ratio and
quantity of reactants mloyod ore dfiformt. Tho Logaxrity could be
ugiaorbod moti'mwl 1!: to prooipitoto as veil as (Sietizyloxohto. Tho
mtorm was not won drimi bacon” of the odor producod curing the
(3:71:13; procoss. No physical constants are roportod for tho (Eiooe’iun

salt of 2 , S <iicwbomthow-3,L—-<i fizy-droaq'fiziophono.

3 , Lafirttothowbz , 5 «11¢ arboaothoxythm phone (1.3.1247 )

cu, ' " :3
{32-13% ’“ _. mm,
s

This Iyntnoain was carried out six timo- md tho yields of product
ranged from poor to good. has to the Ienoitivity of the synthesis to
tho quantity of roagontl employed, t‘zo proporotion v1.11 be described
lovoral tinsel to give an indication of the oifficultiou involved in
thin mmtiiooia. .

A throo liter, three nook roumi bottom flask was futod with a

curror ancl reflux oorxionoor and the apparatus was support-3c: on i

hating motel. A 621. 3., 2.25 wlot, quantity of previously prepared
Ind alight]; input. W salt of 2 .Sdficarbomfliw-Jfi-dmma
«ammo is; plIood 1n the rmum flank. A 1:63 a... 11.6 melon,
1030 m3... quantity of Sushi: dictmod éimtivlouli'ato on quickly
added to tho Iodiun salt my» to. I160 nook of tho faction 11333.
the Irish neck or the nation ruin m Itopporu no I «10mm chlorioo
mmbnmntmmwmummumtmum
from uttering tin. mum flock. Tho. rotation Intro In! stirred am
hosted gently with I hating mm. m- yino' an anomaly ItIrtod
tobacmblIckinlmIlnodmmttothommotthofhok.

The bastion: mate]. ‘1 mick]: mod . To. block 00101! noon spread
thmgnwt the nation :1.-“acme. n... W boom. very difficult to
our. 1110 hating onto}. an replaced an: tho mum incur-s was
but“. to 11», reflux mature Ind alumina] It tint torr'gmraturo for
1.0 Imam. Tho reaction voII‘ol ii cooled, otoworoo, Inc“: not Iconic
«mam. . in MI in mind for vacuum distillation by placing
I 3.5 dogma 01b" in $11. I169 m of the reaction flask Int: fitting I
conduct: with I Did! It: adaptor Ind waiver to the £5 degree slow.

I 13W Iipbator VII «mated to the .1658 Ira or the adaptor through
I w. m. roam m I: hated Ind Lilia}: 3., 3.68 molou, of
dimmg'lmlhto III new diItillod from tho resection mumps. The
ruiduo in tho vocation flak hi I black 0011A man. 1116 reaction mix-
two on hydrolysed by «5:11:13 m liter of I 6 8 com-um hyfirouoo
Iolutmn to it in the reaction that. The reaction mixture woo hootoa

It 1t: reflux tommturo for an hour and I half. It has: I black color

 

 

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3.70

and cammwahln u:- can present. mu black tar mtarisl wag m-luowd

by aollacting it. at a mam” mmml. The filtrate was acidified with

a 6 E maimc‘nlgrin acid caution. we}: cam-god a black precipitate to
tm. The law-arr was very drums to rm: by filtration on a:
MLmr tunnel. The original tarry material obtains»: in tha initial
filtration in: again hon-hm at 11:: rating temperamro with 500 m1. of

I 6 F! 00:31:11» What“ aviation. The mixtm-o was filtered an: the
filtrate an acid flied u in the previous can but no solid product
could 15. isolated. Tho buck precipitate non-m char. Ira: tea
acidification m ditflanlfly soluble in at». The precipitate m
but purified by 61000171113 it in hot new“), treating it tit}: charcoal,
filtering and warm 1am to tho hot filtrate to ammo the proéuct.
m mm. m envied to 0" c. m u in. bath um! um finned. me
email I!" payilh black colored flood]... The W]. charcoal
What In matted We to yum guy colored undue. men tho
WMummmmquw-wmum
thaw darkened nonddmbly. A ”35.26 3., 0.328 3010, “‘61 yield of
JA-dmflwqch-dimqtmaphmo as am this): aw at
WW 2925’ e. um um “1311.:me m 290° :2. m. mam
«mum a: mu sat-rm. is above 250° a. (1:5). mm a. mu
wm at the ”mm ‘0‘ GM in I “the lug. quantity of hot
afar, tram with W, lad #001015, 11‘. yield“ a. wry mite
prodnc‘ finch 6W with “timing at WW fire um
um it did ham. 1% was rocmtmisod has aster.

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171

T713 33.1079 mt‘:3313 was fizzy-331.3%!- on a 33.313.31- 33e._:‘.3 and 1.7113 33:23 33-

tars 1133 811311113! 31051.11 .3, 133111;, ' 132.3 3333 3.235191. twat a 5330. 3.1 . mum:

1.13:: 11331: 1:33 1:333. far 121-3 reactim V0533}. and 3 11.131310311131172: 1:35
13.11.33 in cm of the 3163 11-3323 in 3.13}: {mm}??? that. 1313 3213:13333131-
bulb . 31.311533 1:311 121.0 the mac 1133 31 1:11:33. 11:3 mac 1.1011 {133}; was
12113333 V11... .1;- ".0 3., C. ‘- ’3 3: 331-, or 2.113 fin-31y ground 3133:3133 salt.
a! 2,5«11331313‘1 3 ‘11-: ,‘.,-.‘:i‘-.;r:fmtgwflicrmm 33:1 120 $3., .952.) 333. 3, of
h~as“:l‘-' (5.5111133 (11.311171313315313. T13 mar-3:! macmton 35.31.1133 1333
113313;: 1:11.11 a heating 33.31331, 113.31“ 11.3 ”ta 21.11.133.113 rwc‘wfi. 12.0 U. at.
111.1331 poi-:11. it ran 3.15%:me to 12,.- "00. (133 to 3 14:33:33 330131311313
I'm-3:13.33 occurring which c3133! the mac 3131-1133133 to raflmt. 11:3
21331.; .3.-3 want 31 3139 quickly 333131.31 #3331 1.113 1331131311133 began to 3133.
1213 33331103 3114:3133 was 31.1.3333 until 11.3 te-~=.:->31~3mrs had £31133 to
13.19.3311 12 an the 3311331 1333 replami 1311:: art 1.13 r3331; on £13.31: and
2163?. 1330 my“ ,1136 to maintain 0‘13 reaction tewpnratnra at. 110° C. for l.

1.31 of flirty 3.31.1133, 1.1.30. 1‘33": t .3 p011. 1.11:3 react-1011 31.3mm 113:1
react-.36 0. 3.331113 0! 121° 0 . f“£‘““” the half hour interval the 333031021
61321336.! from its 031313.32. 31311011 39101- to 1:11.113, 33‘ than to 1.13316.
The mention 31:43:30 1133 333133 and. 1:23 apgaratua 1313 arranged for
17mm distillation 33 13:3 done in 1‘23 previms magnum-33 except. that.
o. :3 5331.331 pump 131.3 333:? 1113133.: 3.! a 931.33 333.133.1423. A 36.11 3.,
0.2315 31313, quantity of (Tigrmthylmlf‘at-a 111-13 11.131.111.33 from the mantion
3.327.133 at. 550° C./’2 m. 1173.. Tim 3.1;?" 31:13 1133 c003. .312 3.31 157-0 131. of u
6 1! sodium ...,Jrozziz‘a 3311131311 was 3.3373” and .1:-7.3 133911.323 :31:er was

1133136 and stirred at its 311.113: 1.312333511111113 for 3 3311‘ hour . A 112-311

 

 

 

 

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0:10-0:11. of a tan 00100.10 "01.1.;130 3 50.10 pm. 1:00:51. 1:: £1313 £13331. '51: "0:110

1010 1‘13: 13171313. by collecting 1.1. on 8 fl‘itbni glass $115100}... '1'1‘13 {31.11:}.
00103311 £111.51: 1603 11:31:11.3 513.1112 0 .m'c 0311 m1; than £1.130:31£. ISL-.0
1'2..."rata 31:10 0011-5."121 .....1 £23 2.1.0.3113110503113 main/0:10:10 03111
$51.12}: 25:021. :.1! 113120-31 a 0:30.20 111111.113 11.1.13 . T1113 0110.31.31 11233 0011150030
5.15.3511 111.175.1001 11;: Ly vacuum filtration 0n 0 $1111.31 $1.560 f‘ ...l‘ 5:? 031.15:-
uhch-L it 51:13:: wast-3:3 11.03.17.131; with 001.2 5:31.121“. Tim 5:71:10 praclpitam
1311:11021011 Ii 5.118 0.1.: (if '11? -', ...:...1 -11 was n30: 1y 1111.133: 1 00102? 11115511 (my.
T353 biz-{.3}: 111.31.31‘1111 was r31“. 1151115113313 h 6 3 $0111. 11 1 30.30;...0 031115.101: and
trmtfi 91.1111 155.1130 511.111. 0210 10590031 by 0:111:13 the 02.03:: 0123., 11301.1. .g fcr
tam to f “15:33 minute—3 01.1.1 $1100 filtm’m. “2.119 £11133. [1.1003110 110-10
(70011111 02331 8.615.153.1511 1311511 00001-111113 15-511 1152131331.”..10'10 0.31:1 t0 5:13:13 {1
r1-5a:"3.;,r 3511.153 p300 345110113. The: [13301351151110 51:10 Genoa-tail or: 0 9110.10.23
I'm-5:131, 10152103 033331 £1230 thoroughly with 00115. vat-3r and 05.: 1131.30.
The city 15100313101 ma 0 53.13:," lifizt. gray in color. 1’113 01:01 1-"15. y 01‘ 2,3-
0 1033’ 11-01;, ~3,.1-.....501.10r~'t11 3.0;5‘ 10.10 abtalnoi was 15' .711 3., O. 5’ -1010,
1.1.6:: 5101:3- , 5.3.5.035 6000121903311 at. up; 5:031:50 00hr 52.153 00:10 3x35030533: as
t: 0 25:11:31.3]. 0‘.- 511.1111: in ti 0 preavious 033.002.00.153 001.

"3‘3 {.1:-3 :riald was 12103003041 3".1'0131‘0111 on €10 0000.731 attrx;1;'>t,
001353233. £0 1:10 orig-1.15:3. 05011350010 01‘ 2,5«1’ 100.3150 53—3, 115-111303102- :yti: 1.0-
1:33:20, the pragmr 011.00 1130 05153011313 with 0. fut-:13? 01515310011100 of the
mgmra’ma to obtain battcn' 11051511311111” central. 1753 0:190:33th no
identical in this pragaraticn 05101-513 first £353 113011.511; manta]. m0 replamd
by an oil batizeu pporterd on. 0 151301201033. 13110 watery 501:}: 0'0 it. 00111.1 b0

0:101:13 raised and Mara}. T110 0153151111100 01‘ rel-03001.0 0111.". £38 05q:10r1.5100t01

173

1 - scamm Isa-:21: mm.» the: Isa-.16 as in ti 1!! “ravawatim mgr. wearabazi.
f w

, , - . . ...0
Tim ail {141+ 21 m heat-5‘ mm a 111321.20 11.03.2212:- to 1.112

C. 229512113 ra‘shzrt
it smxmi the reaction I 12:35.1; 7722'945 minutes after? the oil bat: was
rats-.112 tit-2.1m wanna 121312312: 31.31:; of a mac ion a‘mm by ta 31:11:31.1
calm £331.15 to whim. 11119 1111.111 :23 sitar the 0.1.1 hath "hex: team m 19-1312

' ‘3": Co fi’f'j t5"! Oil

tin-a reaction mixture ta'gwrntam r1111 mly rum; to 1:9
bath was qxiak‘iy lmwai. 112nm t‘m tarqpaz‘sblrs of the WM £11m. 3112,3111”
Ina-12 13mg; :1 w 112.)” C. two bat: was mum am! £119 tamramm was
...touad at 13.1.10 C. 101' a 211.11“ haw, tLvM fr .125 12:13 paint 32:51:11 .2113
initial Nani-an 22111: oacurrat. 1‘213 amass 11-1 13t.‘-.-- 1312‘ “' .119 at: 1‘ am- 323
by damnation at. 573 C./3 ran. 2:3. After coaling £23 r3311-“ 1:: 13:13
111321;, 211.:- 121. Cf 5 R 51-21;..21112 223111.:1'~:3"':113’3 was 011.61.": and fixatfisfimfi 1n?)
east at. its: rainy: beauezvaatxra far a :m'2111w. $2.13 p211a;.'iu<;t new is :-
law by 301.11? 1.13:; 't. 0 2.11.1 mm of 2.11: it, 2122-2 bran 4391;321:111 an ice
bath with 125 m1. of commtmtaé mammoth mid. 5 cream" at? its
91.131313111121153 {12112011, but it 13.217231; hit-.1:}; on air cits-'11: 3:; and it pom»: ‘3
l pmgmm 01m“. 12..) pm: 412%. u --.s 5.1.11; 3: 11.13.11" 1131:" by (312430111215; 1%. L”
a w 112;: 1137‘ roads 9011:“ ...:m, dwelarismg wit-'1 mammal, [and than
rfiwmipitating by acidification. 21.32:” wash in;- am: 1: 2711.11; :1, 2.3.7:? 5.,
0.1.2. :wle, 73.12,; 11.2111 of ...,gm-a.a.,w .3313...- ..3: 33333 3:21;" 2:31:42.» mus;
obtainaci 12:11:12.1 2311: the “no swam-3512.13.01: trimarnWa as 2.211 1::J.'1:'1:12.::
pragemd 881111-28.
its preparation was r'rpw‘wd a am, 113111;; the km .Eadqw:

" ~'- ‘ v .. fl 3 I- u «’2' r- 15", .' :l" . : ' h" I." ’3" t" ‘*‘J": "
(11115011111111 but an 8. 42:11.4 M321. 5:19.116. A 2.11.”... 3., 05:12) 11112.12, q1.,..,,._,..,,..y

of t; .3 “MA: 51...: t, of 2.5-1" ...car‘z: 211-13.,22-1 11".; 5:9: xii: 10:2: 11:21:: cm" 5’12 3.,

{uh-'3 moles, of freshly disfillnd dbnrzthwrlmlfgte mg 2139'}. Tim
reactant: mixture! tm'nad black in £12.13 mafimnt became Mat could
not b0 nominated my fro: the initial: a! the reactim 222mm mica?
.200 5:11. A 1.“ .52 53., 0.5.23 mic, 51.6125 yield of profiuct was obtained.
13218 Rafi-rial bum. dark on being sat with in tho laboratory for
”rural dag-1. It ma rmmtfllizad rm 1 water .223 2221331 mimm
being treata‘! with (thercogl in each mmmllmatim. A vary wits
prot'Tuct was antenna. The final "01.52% of this mug-1.1 ms £29.12 5.,
.21.]. E118, a ”7.715 yiald.

Tao adfiitisnal mmtiuna of 2,5-riicm‘bozq-3 ,h-dimmm40921w
Item can-1m cut. using appmzimtsly 260 g. mmtitios of the (2.2mm
salt a: 2,3-d1carbmthomjr-3 ,h-dfl'y’wm‘dcp‘xme, obtdning annually
the 3:1. “is ramlta as tho» csacribad chm.

Attazfiatsci 53;..22 than: of 2,"? -E 12:22 “hoafiww-fik-L “motto‘y-
thing} 2m with 2292.“ng India.

 

1 am lib-2r, tin-as neck $12.62., mmorwd in a heating mutal, was
titty? w: th 1 stirrer and rtfluth aon'fanscr. A 30. 0'? 3., 0.2.). mole,
Qt. 312222;- of £23 finflyw $022.35: (2132an 5.2.. t of 2 ,Sxficarmfwthmiy-B ,1”
2’... 1 '~ “.MNt whine, 242. 5 3., G.C3 2.019, of fr~:aZ".-.;r flotilla} met. 3].
1062.229 @222 25222;} 1.21.. of? 2323912122 mammal were plan 22 in 2.220 flask. Tm»

34.1:er y'allaw mar-.02: digit in the {22:212. :21 and 2:3“ dwliocim was

)zuaiaxi at it... reflux Mayer-am” far 01 52.1.3311 hem-g. Tm fellow
aygmu'anuu of €16 reaction 2.142511% We.» Slit-1.1.3.; 11531»! in (202.0?
during the «1.2mm. taut period. The 21231102: 6013:; we {111.5390 £2202:
the hot solution. The 2:232me was vac-m thfi hm: the 342122.th
using a what upirgtnr. ‘k-‘uhur ma 0.339.: to the bot. raga-1.3.1.3 mat-ll a
cbuuiy appearance éaValD'tn/é, than the mix-We 25.8 02211106? in an 11.5
bath. A “Lita crystalline: material wanted from the solution.

2'... cry: b.1111» mwid was collected on 0 L311 Bau‘rmaz' funnel arm
rucrysiallhad £qu a murwfiawwl mixture. A 2.8 5., 171.2111 01' 3
mm: crystalline mat-322131 m 022.22.11.52, ...-2.2.2:». mltad war n 1:34:31" 0.
tam-cram" range as dabamined on a waiting point black . no :2? 22.115.22.21
Wiwmfluu 1' or 2 ,Sdicm‘bnmrfinqu-{i ,Z.~L’. 13263232.th 10.232.222.13 we g1”: an {21
1.223 litaraume. This mtwm m not unmet, mum time I. battor
unis-.06. was dwelomd to ohmin the was proéuct. “Eh-3 123.303.02.13,
3,1;«ans'b’w2q-2 ,S-(licu‘bafiaqrthioyhana , malts at 52-530 C. (1.57) which
macaw: that the crystallma 22.331212]. may not. hem ham the (7.3.35: 2222?

product.

nap-2.125.222: of 03;:2322 Chromita Cc Lemmy,

r":

The experimntul procadww raga-1.3:! by 3% . Cannor (...) am: his
comrkm doacrlbimg the prawntion of anvil-yet. 3‘33}, 2.22: $011223-)
A :ECJ ml. qaantitgf of an quoua wlution, contairng; 2.31 5., 1.213 3:201:23,
of cuprw Junta-:23 baby-”rate and-31.1 5;., 0.11.? 22.219, of barium nitrate,
16:28 125.2th to 812° C. In}. pczu‘od into 92!.) :21. of a second &‘§11§€3119I-:“ -
tion cont-(Lining 151.2 g... 0.613 2-2013, of ogmmmm 63.32.222.222}: and 223 2-23..

of a 2355 mmnium lzydmxia‘ia 001.112.1012 .

175

An owls-2 procipitata famed 1121.312 van oalloctaci an 3 132133319:-
Ifltar and partmly (312135 by drawing air tiu‘ouz‘h 11‘. with a water
winter. 1123 proclpitata w subsequently 62213:: ovamijn in an oven
at 60° C. and than finely pound in a matter. The praciyitata m
612116913 into approximately four equal portions and each was time-2.2203022
maul: by placing it. in a porcelain anaemia and heating; the
latter war a Bunsen human The (33302320931022 UI-l 00632132113322: by
flirting tho precipitate with I mulls while it In hem; heated.

After flu dmmsifion was well started the: flame!“ mad and the
precipitate nu confixmmly stirred, until than in l madden evolution
of was moonpmied by the: martial taming black. The pant—“Son was
reamed from the “starch and allowed to. 9001. After the four panics:
Ina-o lapm‘utaly (3900me in this mar $3231 vars moszbinefi and
leach-cc, far thirty 2312211233, with .233 :21. a: n 10" new 3012.1th pro-
parod by dissolving 60 g. of glacial math Acid in 5220 g. of water.

ma blank material m filtered from the Donation, am"! mheci with 312:,
1:20 211. portiom of am. After 6225121533:- black: capper crmmte in
121 oven overnight. at. 125° 0.. it an finely ground in 3 mm. Follow-
ing to above procedure, 133.90 3. of copper chrmi’w catalyst were
obtained.

Fraparatim of 3,32-i-L23flm23t221032‘2ma (2.3:,L7)

.:v 2’22?
C...30UL..3

3
A 250 321., but: mack find: an: fitted with 3 Ward tape: tube

having a 123° 31:23 am. A mohwical stirrar was fitted. throng: the

177

straight. part. of the ”ward taper an: mttmu’aad to ‘82: batten or the
21:0 221. flask. me :1.-£3 1233;; of the: flask ms {1%sz with a gas inlet
who to permit nitrogan to be swept twougfi the mama. A water
cooled commaar was tittad 1n the 36" side gm of €223 cum-arc} tam?
am: the commas.” was fitted with A 1153 m 1.1.2an and. race fiver.

m tilde am of the adapts? was codmctod to n dry Leo trap, 222.302.32.312,
and n water agitator. Th3 raact‘lon flag}: was mpported above an oil
bath mm. could be easily raisaci mum. 1.2.. reaction that. 11.. .21
bath was heated to 180° C. with two heating bladaa, 0:580 can! 125 watt.
capacity. I. SO :31. quantity of freshly distilled. quinolma was 0:15.392!
to the ram: titan flank fimfil the 01:29 neck. A 15.5 13., 0.071 220162,
quantity 0! 3 ,32-diwfi2-ozqf-2 ,Z-dicarbomrt‘dogvhmo and 2 g. of (20:25.23?
chromium oxide me $63.: to the stirred (1213101111.. The gas 1:12.222 tube
was wt in place and the appmms ma fight-02232213: amt with nitrogen.
7.2.. oil bath, £2223}sz to 133° 6., we raised. aroma? the. reaction
flank. T223 sun's-.2 mum mum was $2332.31 for a half hour period.
At. the and of this period 1229 nitrogm inlet tube ma clap-22d shut. 312}
the name mph-stin- was away: and 2.111. then stirred rmtim 2312th23
was heated £1. 922122011223 and Liz-dimthmrythiophme mum” diatill- 2
batiem 66 and 22 m. 2.13. pressure: 115 233.. quantify of (35.32.111.223
was collected. 22.. distillate was 610303233 in 200‘ :41. of strum am:
the rename Imitation m ecu-com first with. a 160 221. portion of a
6 I hyfirochloric acid solution and than with tam, ‘50 ml. portions or a
3 H hgnfirochloric lucid solution to mien the quinoline. £220 sawm- solu-

tion was then naked ‘71“. I 50 m1. rtion of a 3 R Sufi-122:3 122 5222022158
PO 1

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178
001:.- ion fallow: by a 25' n1. portion of Hat-3:. The «ether aclutian was
(tried in cantata: with ammhwa magnesium unat- and aft/arr tar-naval of
the 1mm: by filtration thy etha- mm mm} by distillation m a
new; bath. Tn: raisin. 1m: fracticmtad using: a Bar-Li micro modified
Chum dist-imam head. mm, a mall foreman was discarfied a
fraction m (:0an bailing at ICE-115° C./11 rm. fig. It weighed
LGZ 3., 0.033. mole, tad rap-resented I 3.7.11 yield of 3,1.«fimethow-
fixiOp‘nano. The reported boiling points for 3,h-dimethowt?.iophma are,
110° c./17 m. Hg. (:.7), 123-11.? c./12 m. 123. (LS) and 1210-1221.? c./
10.11 m. (5.7).

The starvation of 3.3411 hamquthicp‘nune ml :3qu «igloying
the apparatus deocrlbed than. In trail case 2 g. 0! copper cimomiun
021d. catalyst, so ml. at guinea-11m and 15.71. p, 0.0721 mole, of
3,13-cinathaw-2 ,S-dicarban-fizicphm ma mound to intaract for a
parted o: 20 nimtu » 1539" c. A 5.75 3., 0.033? mole, $5.33 yum of
Liz-dimmoxywiomem boiling at. JAG-115° C./12 m. Hz. m obtainofi.
The residue in the “notion flaw: m diluted with 9mm, altered using
a null Bucimer fumol to mover the! catalyat and. 111001111110 material.
After fishing this with several 50 ml. portions of other, am: family
drying it overnight in an even at 110-11? 0. 1t «sigma 5.35 g.
Apparently tha catalyst gains might by abaorbina iviritiel {bring the
reaction.

In A m preparatiaa of 3,}.qfiimthemziophmo the «mammal
mascara was mania") to c‘atmino the affect. on the yialci of product.
A 230 m1... two me}: 1183?: m oquiyped. with I 129021311011 ltirrer in

 

179

one nook and tho other was fitted with c ItanQard taper having a side
arm for a gal inlot and a reflux condenser. A 65 ml. quantity of
froshly cistillcd quinolino, 16.5 3., 0.071 mole, of 3,5-cinothory-2,S-
dicorboxythiOphonc cnd 2 g. of coppor chromium oxide catalyst were
placed in tho reaction flask. The stirred reaction mixture was kept

in an atmosphere of nitrogen while an oil bath at lSU-lfifio C. was unoo

to host the reaction mixture for 30 minutes. After cooling the

reaction mixture, 200 ml. of ctfior was added to it and the very dark
colored solution was filtaroi through a flntod filter to remove the
catalyst and residue. no filtratc was extracted first with n 133 m1.
portion of 6 B hydrochloric acid Iolution, than with two, 133 m1.
portions of 3 M hydrochloric acid Iolution, naxt Hits two 100 ml.
portions of 3 fl sodium hyoroxido solution and finally with a 50 m1.
portion of water. Tho other solution was dried in contact with anhyoroua
magnesia: sulfate and filtered. The other was removed by distillation
on a Itoam bath. The residue from the cthor cintillation was fractionated
using a semi. micro Cloison flask. to give a fraction boiling at 139-1150
C./ll mm. Hg., rtioh weighed b.51 g., 0.6313 mole, and represented a
LL.11 yield of 3,5-d1mothoxythiophano.

It is notoworthy that shon n largor quantity of 3,h-dinothoxy-2,S-
dicarboxytLiOpheno was docarboxylatad the yiolé was very poor. The
procedure for vacuum distillation of the crude reaction mixture,
oosoribod in the proviouc propara ions, was used. In n fourth prepara-
tion of til: compound a 65 g., 0.23; mole, qpontity of 3,3-dlmothoxy-2,S-

cloorboxythiophone, 8 g. of copper ciromiun oxide catalyst, and 230 m1.

 

Vi

of quinoline wars usad. Tho reaction time was a half hour and the
isolation procedurs was tho some so described abovs. A fraction boil-
ing st 85-95° c./1.s mm. Hg., woighing 1.09 g., 0.00755 mole, which 1:
s 2.55! yield of 3,h-dimctboxyth10phonc was obtained.
Five sfiéitional preparations of 3,5-dimothoxythiophcno ware mafia.

Tho vacuum distillation procedurs of the crude reaction mixture was
followed in s11 those syntheses becanao of tho case of purification of
the final product. For the purpose of sssy comparison, tho quantities
of rcogonts togathcr with tbs yields obtained src tabulstcd in Tabla VI
slong with ths prsvionaly described preparations of 3,h-dicothoxya

thiopheno.

Synthesis of 3,h-§imothoxy-Q-bromothi0pbens

cu,o H,
I
‘- ,, 3r

8

A 500 31., three nook round bottom flask was equipped witn s
stirrcr sno dropping funnel. A 5.0 g., 0.03%? mole, quantity of
3,h-dimcthcxythiophcns was dissolved in 200 ml. of glacial acetic acid
containod in tho reaction flask. A 5.5; 3., O.C3h7 mole, quantity of
bromine was dissolved in 100 ml. of glacisl scetic acid snd tho solu-
tion was cooled to 1.6.00 6., the temperature at which it startod to
crystalliss due to frosting. Ths reaction flack Inc its contents wors
cooled to 15.00 0. in sn ice bath 1nd the rsacticn mixture was coin-

tainod at this tooporaturo'hy rsising sné lowering tho ice bath ss

 

l4.

31

noooss‘ary. Tho cold bromine solution was added to too dropping funnel
in small portions in order to hoop tho solution cold until it so:
used. Tho bromine solution vos some dropviso to tho vigorously stirrod
cold 3,h-dinothorythiophono solution over s h? minute period. Tho
motion mixture was s light brown color anon s11 tho bronino solution
bod boon stifled. Tho ios both was rmovod from tho roootion flask snd
soils tho roaction nixturo was stirred for 23 minutes it was sllonod
to warm up to 22° C. Tho reaction nixmrs m poured into 900 :1. of
voter and the aqueous mixture was oxtrsctod first with s no :11. one:
than with tm, 15') ml. portions of other. Tho combined other extracts
IBPO washed with s 100 mi. portion and than with s 230 m1. portion of
s 6 i! sodinm hydroxide solution. 'Eho otnorosl solution was dried in
contact with sn‘zmrons nognosiun sulfate. Tho other non moved by
distillation on s steam'both and tho rosiéno ins fractionntod using s
somi micro modified Cloison flask. Two fractions were colloctod; ono
st 83-03" C./O.S m. '33., 2.11 3., and tho other at SPILL-21.111O (.3./0.? on.
$3., 3.5? g. This continod vary impuro material snonntsd to 5.73 g.,
0.C2§9, s 7h.8“ yiold of 3,h-dinothoxy-deromothiopnone. Duo to tho
largo rsngo in tho boiling points of too frsctions, tho mmorioont was
ropootod by adding the bronino solution st s slower rote. Actually tho
shove fractions distillod mainly'st 98° C./O.5-O.7 mm. Hg.

Tho rspoatod broninotion of 3,3-oinothoxythiophono was oono on s
larger scale. Tho apparatus used was tho oar-no with tho exception twat
s ono litor reaction vosool was employod. A 15.0 5.. 0.19n nolo

qumtity of 3,h-Cimotl~.oxythio;mono dissolved in 3'30 m1. of glacial

 

 

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sootio said and s 16.6 3., €3.th solo mmtity of bronino diaoolvoc.
in 230 ml. or glauisl sootio scid oars employed in this «pennant.
The procedure was tho me as in the previous aperinont. Tim brooms
solution as sided slower, over an hour and s hsli' poriod snci tl-xon tho
nixturo sss stirroo for on attentional 35 minutes at union time t‘.-.s
rosotion mmro was out: brown in color. 'i'no reaction mixture was
poured into thrso tins its vellum of water and than ontructod first
with s Soc sl. portion snd than with two, 2w ml. portions of otter.
The oombinad stbsr sstrnots wars mood with three 1W {:1. portions of
s 6 H sodium hyr‘roxios solution one finslly with s L30 :1. portion of
s 3 H souinn hydroxixis solution befors tho ushings tasted bssio to
litnus. Tho sthorssl solution was then “shod with Bros, 100 37.1.
portions of tutor notion moved most or the block color that hm
dorolopod. Tho sthorosl solution no oriod in cont-sot sit-1 magnesium
sulIsts sno distilled ss describod show. A small forum was dis-
osrdod snd. tho romaine-Ear of the product boilod. in s rolstivoly narrow
tongs, 79.32? c./o.3 no. 5:. An 1773.15 3., c.0313 sole, 78.2,: yield
of product as obtainsd. Analytical dots on this product is recorded
st tho and of tho following orporismt. ‘
Preparation of 3 ,h-liisaothoxy-a-brcmothiopnono lining
hodromsuccinxaico as too Bro:- * .nting Agent
A 500 ml. thros nook flask was fittsci with s condenser sud
anatomical stirrer. Tho remaining side nook Opening was used to sod
tho reagents. An 13.19 3., 0.126 mole, quantity of 3,}s-dizoofixonr-

thiophsno was dissolved in 200 ml. of dry carbon tetrachlorifls and tho

resulting solution uss placed in tho roootion flask. A 22.h g., 0.125
solo quantity of H-bromosuccinimioo was slowly coded to tho stirred
solution of 3,h-dimothoxyth10pnono. Tho rooction mixturo one stirred
for on hour with no oxtornnl.hooting, and than it was booted st its
reflux tooporoturo for tivo hours. A consiooroblo quantity of solid
succinioids formed during tho reflux period. Tho roocting mixture was
cooled in on ico bstn to to C. and tho insolublo succinimido uus
tiltorod from tho carbon tetrachloride solution of 3,h-oimothoxy-2o
brooothicphono by means of s Buchnor tunnel. Tho filtrate nus soohoo

in s separator? funnel with throo, 130 :1. portions of s 6 H sodium
hydroxido solution, sno finally with 50 ml. of water. The carbon totro-
chloride solution was driou in contact with anhydrous magnesium sulfsto.
After tho mgnouum sulfates m rmoo by tiltrstion, tho carbon totrs-
chlorioo was removed by distillation on s steam both. Tho residue was
froctionally distilled using s sand micro modified Cloison diotillotion
sppsrstno. Tho frsotion boiling st “Ia-61° C./0.'u-0.S m. Hg. was
collected. A 25.07 3., 0.112 mole, 59.0; yiold of 3,u-dLuot&:ox.y-2-
bronothiOphsno was obtained. Elomontsl snalyois of tho product gave

tho following rooults. ‘Cslo'd. for CéH,0.55flt C, 32.30; H. 3.16;

S, 13.3?! Br, 35.22; Found! C, 32.51) H, 3.193 S, 1h.201 Br, 35.61.

H‘.

'wi-o

of

Attmztaxi Synthesis of 3,32 irotrtliorw-Z -t‘r:io,">hrmatliol

(‘3
L:

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0

1: III

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31

U

A 530 £11., torso nook. flask was fittod with s condenser in one of
tho sido nooks, s moclmnicsl otirror in the center nook, and a 'Y“ tubs
containing s dropping mnnol am; s gas inlet tubs. Tho gloss portion
of tho apparatus was dried in an oven overnight st llo0 C. prior to its
sssoziiling. Tho open sod of tho comionsor was fitted with s calcium
chlorioo drying tubs. A 1.17 3., 0.0.1.5 solo, quantity of dry ongmosiun
sets]. chips was aided to tho rssction flask through cm are: of tho "I"
tubs si‘tdr removing tho dropping funnel. mails dry nitrogen was slowly
swept through tho apparatus, tho ontiro apparatus was cautiously heated:
with s mall Bunsen burner tlsno. The dry nitrogon was swept slowly
through tho apparatus during tho entire courso of tho experiment.

After tho apparatus had cooled to room taper-stairs s 10-3 isl. portion of
snhyurous otnor was mom:- to tho reaction flask through tho drapomg
funnel. A 10.0 3., onus nolo, quantity of 3,1l-dimothoxy-2-bronotuio-
phone was dissolved in 30 m1. of snhyrirous other and. won placed in tho
dropping funnel. _ Tho 3 ,1;-dinothox§-2-bronotuiopoano solution was mean
dropwiso to tho rapidly stirred suspension of magnesium in other.

Tho reaction was initiated by gently hosting it on s steam bath. Too

3 ,h-dinstimoxy-Z-bronothiophono was added at s rats sufficient to main-

toin o gontls reflux of tho reaction nixturo, which roquiroo

3
l’.

spproximtaly 155 22:22:12,165 to a... fin 11.315. ;' L.'2...~;'.'..ti"::. .-.-:"Z-Lss 11...:
3,3.«ZEL'oothuqr-2Jm“ .3330 t ...o, Tam 7.1.11.1“: Eon} bzon adder.) ":25. nL 17:33.?
reaction mixtu'o was Eze'r-atL—LZ at. its I‘t-LflUJC to; ::‘wr:-.t.’.z‘o 2.23 3.1 2.1-:‘s'3-os.
A 1.2.... g., 6.22.5 Kola, qnnntffiy of my sulfur was c.... to to ci.-:.'.*.'-e.~.~d
.c'tionr nix'wr r: in 3:223:21 [firtlv'és 4:. 3w... 2-. 3f-:::«:c"-:z-r nzftglaisggi 2.2%»...
The. otiz‘rm reaction 2. new a Lia-2.1.622 at its rsi’luL-z toiznsrshzre for
3'0 ninutoo and than it we. cool-on in an 2.28 b.3121. A 1L3 :21. ports-on
" s 6 I»: kgnfroctlorlc acid. 3.212.231: ms ntfcezd to t :3 r-: articn 1:11....‘118.

9 ‘91 a . . .3 m} '3 ,. ..,. .; . .'.-:4. . ..' '5' ..
1. yellow so“... form... 11...: t...s 1.5.3 r132... em, 1': ' ...-...trnuon. .t mu.

‘- "s s.
U' I

NI s

between ll2—ll',‘° (I. and (32332.2. are: to be sulfur. Tho nguoous 32.3.51: woe
so“ ,nrntec'. from the newer wane. The aqueous 12.3.»: was extractor with
ti... 9o 65 ml. portio:.s o. awe. ....»3 utE-eor extracts and or ..{jii‘ :1 other
layer were contain-ac! ma! (minnows 2:12;. t2 roo £31311. (alt.-. of 3 22
soc'iion moronic: solution. The, confine-.'.? alkaline extracts m. :5

so units-J. with 1.011. of s 6" 55 2.3.31" .:c L3. in 3.3.1.2 5C? .....-a... {lily a
sllj; 'Ltly clouc y mom... mum to mas-J. in 12m sol-“tiara. -213 31.1.»: ..8

mt?" 131 was atr acted with seniors). 1.23 xii. pr. rticnc of otmr. Tho

1 fi

other extrsc to were cc..;’:: in u and drier? 2:. contact with ¢::":.".~;-,::"r::us
magi-onion sulfato. fitter tho IALt..rZ :33. been rafizov «.'i‘cy 1' filtration
tho cthar was I'm-Lover. by 615112.113 tum on s 311.11 both. 01.31;; a sligt

amount of s colcroz". Nolan-<3 romainorz in “one distilling flash, $11.31. was

tarry and could not ho 16.2.:- 1....23...

15 t3

2-daetylt‘i110pham

A one lit-3r, three me}; $133}; was fitted with a stirrer, reflux.
condenser, electric heating mantal, am! 3 “1" tube. The latter was
oquipped with I tl'temnatar and a 125 m1. circpping {11113181. The quanti-
tiao, 335.5 g., 1.3.0 moles, of thicp‘nano and 510.5 3., 5.0 moles, of
acetic awn-firms were placed in the flask and brought initially to a
temperature of 60° C. by means of the heating mantel. A 50 5., 0.531
mole, quantity of ortho phosphoric mid was placad 1n the Cropping
[mans-31, and added dmpvise to tho stirred thiaphana acetic entzyzirigis
mutants, with be maternal heafsourco éisconnectm‘, at a rat-a
tufficiemt to maintain tm reaction mixture tmparatum b91011 99° 5-.
Following the acid «Editor: the utirrod reaction mixture was mintainaci
at a tamper-awn of lez'uo-lloo C. for thrash hours. Aft-er allowing the
reaction mixture to cool to room tanperatura it sat transferred to a
time liter beaker $116 one liter of mtar mo wit-Sad after which the
content. val 3’01er for an hour. The oily organic layer In! separated
from the aqueous lmr and washed three times with 2w m1. portions and
once with a. 1x20 :11. portion of 101; sodium carbonate solution, follow?
by drying in contact with maxim-on- magnesium sulfate. The crude prou‘uct
was financially distilled mic:- vammn using 3 one foot. heat Jacketed

Vigreua colum. 1‘09 fraction boiling at 72-73" C./3 mm. Hg. was

collected, and wanted to 232.5 3., 2.247 moles, of Z-ccctyltniofizm,
c 61.73 mm. The rcportcd boiling point for chwlthiophm is

2’21'110ph‘32’10 oarborjlic Acid

.. 3

The Z-ccctylthiOphcnc m origin: to z-thinphcncocrbomrlic acid
with c notably prwod mam. codiun hypochloritc collation. In a
fibre. litcr, turn neck m, I 218 5., 5.5 ml”, qmmtity or codiua
hydroxide m discolvod in 300 ml. of inter. The reaction flack cod
itl contents more then cooled to 0° C. in cm ice bath and 1250 g. of ice
ware coded to the reaction flask cftcr which tho flask and its contents
were tarod on a trip balance. Chlorine gas In. rwicily hobbled into
tho cold codium hydroxide colntion, by man: or A glass tuba ccnnoctod
to a trap thich in turn as connected to c chlorine cylinder, until
the reaction solution has! absorbcd. 1531 g., MS moles, of chlorine.
Ho external cooling of the reaction flask was necessary curing the
chlorine acidition. The flask was then fitted with a reflux oomlonser,
ItlrrGr, and I '1'" tube containing c Eler‘czrametar and C 125 ml. dropping
mmcl. -A 63 .0 3., 0.5 mole, quantity or chtyltbiophonc m plan-cc
in tho lotiition funnol. The stirred contimtl of the flask was booted
initially to 55° C. by moan- 01‘ a canto]. and than the 2-ccowlthio-phmo

no aided dropwicc, over a half hour period, at a rate adjusted to

J

 

158

maintain a reaction tmpereture at 55° 0. ronwLng't-e addition of
the Z-ecetylthicphme the reection mixture we! Itirred an add itionel
1.5 minutes while keeping m Waters below 55° c. The excess
sodium bypochlorite was destroyed by abiding aqueous 2G,! by weight
Iodime bimlfite until eeverel drops of the reaction mum” gave e
negative test when aided to en acidified potassium ioéir‘e solution.
acidification of the reaction mixture with 200 ml. of concentratot!
hydrochloric acid remitted in the mediate precipitation of 24211::-
phone carboxylio acid. The precipitate mu chilled in en ice bat-h and
collected by filtration on e Buchner formal. trter recrystallization
frore 600 ml. of water, cm drying it weighed 62.}. 5., 0.2.3593 mole,
which in a 97 .Ilfi yiel. . It melted at lZS’wlZm‘Jo C. The previously
reported melting point for one material 1: 127430" c. (5;) and 129°
c. (79). ‘

h 5-1311)me cthiophenocarboxylic Acid (39,65)

5

\

In c three neck hel! liter round bottom nu: equipped with e
etirrer and reflux centimeter wee placed 1.38 3., 23M soles, of bromfme.
The ctirrer we Started incl 58.5 g., 0.15 mole, of 2-th10phenocerboaqlic
acid were added in smell portionl airman a tide neck or the flank.
um all the acid had been (video to the reaction mixture it one set
aside overnight, in the hood, in an Open £13.81: {a permit the ozone

bromine to evaporate. The resulting sticky material was then transferred

. N
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1*???

to an 0pm banker and a ctr-om of air was blown acrosa it to mrfizor
rcmon rm bromino. The last traces of tree bromine were removed

from the erotic laminate-i 2-tiifiophonocnrbon'lio acid by stirring it
into a half litor of 0.5 mom uni-onion carbonate. Tho aqueous solu-
tim on acidification with 6 I chlorio acid yielded a uhito prorfiict
which was collocted by filtration on a Buchnor mum]. and dried. Tho
cmdo promo 1’. after a single recrystallization from ammo}. mounts-.’. to
a 67.71 yield, 88.2 3., 0.30 mole. Tho ropor‘ d melting point of
h,5-dibromo-2-thiophm¢rbmylio acid (39) is ”Mac a. and that -
courted for tho ohm material as 2:25-2:27" c. with some sublimination
occurring abovo 21o° c.

2 , 3...; F‘ibroroo ti‘siophcno

U:

5

A solution containing 83.2 3., 0.31 mole, of 13,5-dibrono-2-thio-
pfzonccarbon'lic acid dissolved in 7‘» ml. of glacial acetic acid was
placed in a three lit-or, three nook flask equipped with a stirrer and
reflux comiozisor. To this Itirrod solution 219 g., 0.69 sac-lo, of
mercuric acetate m addod aftor mic!) tho reaction mixturo was hootoé
at its reflux twaporaturo for four ifxonz‘o curing which tizm there was
WL‘EGILCG of carbon dioxide being liberated a: imiicotod by t‘m forzmtion
of gas bubbles. The mixture on: allow-cc: to cool to room torqsoromra
whore upon a white insoluble salt squares-too which was recovered by

filtration on a melami- funnel and prosaic-d as dry as posoiclo.

190

“the omic out derivative m placed in one liter of on aqueou- 23;;
Iodine! chloride collation contained in the origin]. apparatus and

mud with curring gt ,1:- reflux mm. s... an hour. it on.
point 1:20 :1. or menu-gm hydrochloric acid on wood to tho
reaction mixture and n an atom distilled. Sm difficult; a: in-
mtmmmmummmoucmmumomu
tea. wummmuacmmtmamwm
mmmmmgampwmtumm1uummm.
“111mm. ommmmmum-w.mawmmg
mated to 97.59 3.. 0 night which no groom tun that of tho.
Iurting man-m. m. mural had a My to mom- » 222.9 0.
an alt“ in tho mg. 225-229° c. with” the Norma: a melting at
227° c... which nu 1m 1m: tho melting point or the nursing comm-ad.
However. inn c nixed melting point or m. origin“ “Sadibm-fl-thio-
mammal!» lucid and the docarbcwlated product no nude than
resulted a vigorous evolution a: can u zoo° c. with decompositim,
indicating that the two $15qu were not iciootical. A 5.7 a. quantity
of the product m not uiée for future reference while he remind-or

or the material was eobjoctoo to cocarbcrs'lation and again placed in
the origircl apparams. frnc liter of glacial acetic acid and 23") g.,
0.537? mole, of mercuric acetate wore act-ted. and the stirred mixture

was rafluxoc for five hours. Aftor allowing the mixture to cool to
room manure the white prccipitctc val collectod, lacked th

vat-3r and dried. This white cmWJW material did not molt or

dccorposs at. tamer-cones up to 393° C. but did turn slightly brown.

191

no. material we again otirred and refluxed in one liter of e 213‘; by
reign aqueous! oolntion or sodium chlorioe for three heart, after
much loo ml. or comma-aw Wochhrie acid in: mood, and the
Idaho. In Inflected to Item distillation. he oily profit“ in!
mated fro: the ammo distillate and on additional gamut; of
mommwumzmmmmmumnw
min: dzloride. “the combined oil. we dried in contact with calcium
chloride and distilled from n Cleioon flack collecting the mterial
boiling at Zea-2.23" c. coco weighed no.7 g.. 0.159 mole. a 53.65 yield,
discounting the m1]. mat of the initially mum nun-bl
but aside for term. The reported boiling point (80) of 1,341.
mitotizlophm is 212-233" C. hyper-mil: the WW tailed
market“, butdmmepwefinucond Wuhan thalamus-1o
alt me tool-coax]: dried prior he ammunition will) 20% by weight

aqueous Doom; chloride solution.

Preparation of 2-Piperid ino-l-ethanol

32220333334 ' >

A two liter, three nook flack val equipped wit}: auntirrer, reflux
cumming: and upportod in a heating watel. The quantity, 2.3.1.6 3.,
3.0 melon, of 2-chloroothanol was dissented in 7:30 ml. of absolute
alcohol canton-ed in the flank. A 30 g. quantity of Iodium iodide was
next dissolved in the 2-chloroetimrwl Iolution and finally to m1:

15

192

Iolution m odour! 1130.9 3., 5.05 11191119, or piperiiine. the reaction
311:.er no flirted mo on no 1114311111: reaction set in $211.15 0111131311 the
661ml to reflux 1‘0: qumdmtely five nit-mt“. After 910 initial
tpontanoonl reaction notified the stirred reaction mixture V28 )1an
at its reflux temperature for a twenty-four hour period. Piperirfine
hyt’. rochlorico cry-tanned from the reaction mum on to 9 reaction
proceeded. A no liter, three neck flask was equipped «with a. reflux
comma and the 0th or waning: in 121 a flea»: wore flowered. Tho
qmtity, 6? 3., 3.6 moles, of nod-111m wore clieeolvod in mil portions
in 115’»; ml. of “tunnel in the flock of. a moo sufficient. to ammo a
gentle reflux or the ethanol. The sodium sol-101163 solution m allow
to oool to room toworature and. tho 2-95.;19ririino-1-othanol, piporidine
hydrochloride reaction mixture was poured into a 3 liter hooker and
cooled to room wiperamre in a cold water both. The freshly pro-game
soc-111m ethoxido solution was poured with “in-in: into the reaction
mixture in 1:1. beau-1r. The romlting mixture was vim-ad for eovornl
11111111110 (toting 115111111 time sol-113901 sodium ehlor1c34 cmtallieod from 1:20
elooimlio solution. The reaction elurz'y m 1111111111 in an ice but?
and filtered on a Incl-11111“ 1‘in to moon the insoluble 80611111
01101:.) 11.1.171ch t‘ 1111 111137133. 11131.1 fizreo SO :11. {101“th :15 of ot:1;,
ot? 131‘. Tho 110.112.2196 filtrato and otI-zor makings after 11:71:13 in

11" *1. 11‘ m 11.1 yr r311: mar-1111.31.13 wife-.113 vrzro ciotf’lloo using a. one
foot. Vi you. - column and tho amruorial :Ziltllling b11101! 117° C. was
telnet“ for memo .7 cf mifoootsd pip-arid 1:13. The mater-1:11 rofmino

in; in 1.311 distillation flash we (11111111113. with torso than 11.311.13.113

1323

with 11111151 at: or, oust-.3; U o p."-c..,....t1.tion or 12101311131 Bolts whim
wore removed from to: solution by filtration. ’21:- other was rose-mo
by distillation on 3 151911;: '21:: not? 1;. a racial-1.19 was £21m frao 1111.11.11.11

f5

um 1r m‘ucad proamro 111.11g a one of. ’igroux whom. no unto-1m

.. o
1112‘ 41:13 in tho twoiutaro mm :9- -;-.. C. at 23 111111. of mroury 11:3
collected. The yiol-zl was 231.0 5., 2.25 1110198, 733.111,?» of tho i; t-oratic a1.

'11... 1'1.‘1port£.:1 boilhxg point of the pro; .uct iii 39-110 0 ./1:1.1. 315;. El).

Preparation of 2-!‘31'312501130-1-01‘. anal

1:31.?" ....2._/ \U

A two liter, taxes nook flan}: m oquipp with a atirrzr 11.1.1?
roiling comionnor. Tho Quantities, 23.1.5 3., 3.0 110193, of 2-chloro-
ethanol and 35 3., 0.20 mole, of 30121111 iodiezio wore dissolvofi in 7.30 111.
of ethanol containod 1n the reaction flask. 1522.? g., 5. (1 12011111,
mantity of norpholino was aédod'to the reaction mixture and it. me
then kept at its reflux tarpon-turn for a poriod of twenty-four hours
3.113. won cooled to room Wanton. 11o ouantity 53.0 11., 3.0 moles,
of sodium more carefully dissolved in llS O 1111. of absolute ethanol con-
tained in a two liter 1 a}: equipped with a mflmc oomionsor. Tho
cooled sodium 01210111110 solution was poured info 12119 Zmrpholino-lo
ethanol, morpholino hydrochloride mention sanctum which had boon
transforrod to a tin-roe liter boaisor. l'ho resulting mixturo was sting-.1

for several minutes to allow the '51.;er chloride to crystallize from

1):;

he Balaton. Aim: 6301.sz m an 3.3:: bat-:3 1:13 mute-ca m: i‘iitsru:
on a Luciana {mat}. to raw“ @2113: wily: mutter: prwiglzah uni the
mu: was kwm viii» tween, 33 m1. permits of ether. T313 filtrate
was mun-x. 11512; a. one 230% ‘a‘ ri‘r‘mx 301.2321. 215mm m collacted
to a heat: imaraturo of Duo mic}: ra'nvad the ether and are as:
mrpholim, at which paint entails bag-an to fan 3.12. the distillathzz
flask. the material in a... {Slur-L was raw“; mi tho filtru’oa was
diluted to three times 11;: 7121mm vita amar to inure cowlata
preemitation or my giitioml salt. After chilling in an he but:
the salt. was £31.11: renewal by filtration and the filtrate m {Brim-'1 in
contact with madman magnesium Water is: several 1.54:3 before the
final deflation of the filtrat-a. Tia magnesium mliata an: ultra}.
from u... oihural ”nation and the other was remand by a’istillation at
atoswaric measure. A are. foot Vigram column as mmnfié fur a
new dawns-n. 73a 11213451 fraction of mtarisl boiling b61211

m-

1350 (.’./13.6 mm. m imam-fled. ma Zawrpiaellrwol-efimnol distilling
on A .01] O A an - _. . , _ . . 1 .1 ; nu nq.

at w.“ C. m. 3.7.5 mu. mama m cullectm. we wig-tau $3.2 3.,

2.32 ml“, mic}; is 77.3}; of the meorotical 31133.5, The “apex-tad boil-'-

. v I n .- O "‘ t - O * . “
inc range [91' Zwrpzzehno-i-atwnol n Lib-4.20 0J2; m. kg. (:2).
Preparation of hfizorpf'mlflno-ldiutmol

'f 4“! 5“.' £2! I‘Z! ‘ ‘5
A-;.1:_a-i_.45<.,43- ‘; b

In a can litar threw nae? £14957: fi'bt'rfi with a mfluic ccnsfmmtara

otlrrmr am“? a Heatmg ranml, 2i) 5., 0.12 mole, of penguins; imiia m

‘
ul
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“‘31)
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(1‘33!)le 1.": 3’0 :31. of (’37 ethanol. “1‘3 Via asltxtim, .3 35-1"! 22.0:
1 32013 01' Eye ....33‘3'2'313133- 31.2 H.123 :., 2 93.31.33, 3.? 31223331312133 $323.3
062333.. 1'13 rtact ion 35.313199 3?‘ 35 31.13.3333 at i a r31” 1.13.: 33":i;3.63‘tir3 fer-

. .

one 635'. A solution of 5231’.‘ 1:: 33:33:31 :3 in 31.3331 3:233 :37: 3.33. by
allogir g 23 5., 1.0 330.3, 0... 33113.13: 3 to raachv viii: 363; std. '3 12.3: efiwml.
Eta-33' 1:23.. I 2.1.1133 macaw 241.332.1133 331131.34 ‘32 c3333 1.315313» 1. ’ 1.13-
mtml was (33111133 in an 123 2.331323, tine precocla‘ 301411133 {1:311:23
.316.th 12113 £10161)" £1633“: to it. titar talent :1 m 313.3338 t 6 13213333. 31*
Mimi 33213113 :2" 13. 1:13 1313 6311.23.33.32. 3.1 3 33323113 I 1.. 3; 313;: $332.23.: with
“her. T236 ultra 3 2:1: 63,233.1- 33.321112333133 cc 1131.213: 3:351 6.13.5.1; to

I boa” myramm of 1350 .to r-fzmm t 3 0‘3”; 3-3301 an”. 33.331. of €23
unrmtac' mmbollna. T233 1333132113 5213331 t‘rzn 31.32.111.331 13: a 223.13 2.3..
wit“:- than 31:23: it: V‘Oh“‘:fl or 33".33" to 131333.933. 53 31312.3; 3.1 33:13.13:
cumin which again ma coll/3333': on a 313:1331- £11t3r 6.33 3132133 with
033.33. Tho filtrate and 3125..., m3 ‘31“:ng 63333-6 cmfimm 3.13;: «3.653.113 on
I Item bath to remove the at? 333,133.! the 23331.3sz was 3133:. ”3;: 1.181335

3 one foot Viarm 4201311331. 1123 fractim 3313.1. 1:; at 13-12;? C ./2.:‘Jto

3.2 mm. Hg. was collectari. T23 rag-.:nrtui 1305.13.11; paints: of 2.433333331130-
1£Uutunol arc 131-133° c ./7 3:10;) 333 113~3379 c./t 313 (3;). 119

o

Macaw 1:23.33: of tar-.3 1213213133: 331133333 was, 1333'? -- 1.1.7;22 ,‘ 33:: it

'91"506 79-2? z-, which is £3.33 31 315 31 33331211 yialfi.

1:1.

3 4201'??? ems-1 «3? 31:33:30.3: 33333313

€132,333 3 4231300
A two litar mun-d better. £2.33: mag-4131:1333. with 6 13311313: car. 2333.3 .. .
A 3.33.5 g., h. 0 39213, qmsut‘: * of rec-"pr. .1133 1333 31392133113 5.3.2 .31.
of banana contained in the reaction £13.33. A 3134.9 3., 2.0 11331333,
quantity 3..." trtaeti-ylena 32.1 "113mm: 3 m a 3.1333. to the 33331331011113 531m-
tion. The resulting 631113.133 3.31:6 12.13.433.24» *0 3" .3332: at mom tww" M1233,
viii: occaficnal shaking of 19-3 1‘13 ‘1 . *’ .1'1 5 can‘mts, 5'33“ 3.: 2233;:
{Earring mic}: tins 0011.3 33.3: 9332.351" .. ~3c-33-31utisn. ’1?» 33731. 3333 of £1
11333: w‘n'a part-€331,333 from 333131.333 by 333332723 01' a cal-.3: 5.2.133 (23.3.3 «1‘3 £1236
6:33. 931. 3:31:23 3*. room try-333331333 far a V3323 3.. .‘~. The 3333312221 mixture-3
w: {2733.1 1333.31.63 at its mflux tmprgtum £3333 £31333 hours, 33-3133 in an
ice bath and the 13631331319 3330:1333”. 3.11:3 13:3" 3 ‘o‘wn. " 3 was r3 333.:334‘. by
filtration and 63333.33 with :1.-"3.3313333: 34:23-33. $33 33233::- 33333111. :3 an:
filtmta 1mm combing-.’. mi extracted with £3333, 3‘13: :11. 3:313:16 of
J R 313fitfm331101".c mid. A f 311' quantity of haunt W33 mark-3:3 in U245 initial

part of 1:333 amnion. Tho om hit-333 301:3. 31313.33 tr: mm m a at? 3:3 1;;

basic with 10 1'! 6333111231 kfimfiia 031333.331 33:13}: m ”3.03 in $.33 far-3:33.131:
of} 6.3.1 3335313113133 011:; Law w:- 3.3:: m 81': 3.3::‘3 rrom t 3 333383316 13 331‘.
The aqueous Layer was a; "trachea first with 1'." P33 03.1.3313‘32331‘; with

one, 550 ml. portion of cuter. T3333 original Gib" mtm‘ial am‘i ether
extracts were: ctr-3b .’nez , C‘s-ind 2L": cent-act with an. unhmw 1.30.4.3. 1.13

carbonate, and 6-30 other: val 1%va by distillation on I 33733-333 bath.

...r-nv‘w

 

 

 

 

137

The crime pmducs m {.mtlamtad, 113111;; a one foot Viggwm cohmz,
mm new. rm manna boning: 1...-1.. c./11 m. :23. ms
cemented. The mortal boil ...-1; paint 18 113-11? C./25 ram. Hg. (1.1).
11.0 refractive imlax m 1213'“ :- 1.1.730. mo yield was 130.9 3., 1.1.1

ache, 1.1.15}: m 55.5.: of tha timers .icsl yialfa.

3633:- 13t"’ls_-....o)-l-c..l.“o‘.. 5:123

1'1": 1!

fifi U.
(5‘ '5” "9'1 (-wy 1 a

- “r43"! 22" V -2
12:31:11,

A ho liter 115% m equ'wml 11h a ruflu 130211512542: 5.523 232.6 g.,
13.0 moles, of cliefiiylsnizao dissolved in $7151) :11. of banzma was with:
to the 11531:. A.) "" “.9 g., 2.3 moles, quwtity of what; :ylanc 0.1.010-
bmica m mic-ed to tho solution in tno £155... Th5 mm: m 5325.: an
fmxmtly during a one hour 93121051 1mm pmtactad from 2591-23er with
a calcium chloric‘so tube, and set. aside for two day: 513 ram: 1.5729515 ":29.
The reaction 111::er was then kept at. its reflux tampere‘ma for a period
of time hours, cooled in an ice b.5111, ark-.1 132+: cry 9* 11.2m fiietzy“ .1:2.
1.421.120.2121.» was ranM from 1.3.5 303111.151: by {111.275.1011 511.31.25.52-
with ether. 11:55 1.2.51" washings an. £111.. “51.8w m: acct. 551.32. 11151131121
twee, 2:113 :21. pox-1.15213, than UP .21 two 133 :11. p01 1.1055, and £121....y

1.21 a 100 5-3.. partied of 3 1: hyrirochlcric c216. T113 1305311556. 5.5.1.3

matracta were mafia basic 1:11.221 13 H sodium hy..1ro:.-:i-9 50‘ ...ution man." 121;;
in the form 1.15210! an oily layer. The lama: m n-awatmi an." the

aqwous layer was :ctractac‘. with three, 153 ml. portions of 01.71.51:

193

7:29 any mum and othar muracta ma mined, dried in omuct
with 3112':de potassium carbonate, and tho can? an mod on a
Item bath. The arm“ precinct m wumtad using . one foot agree:
001mm and the: fraction 5011213 betwixt: 60-630 c./m an. Hg. in.
counctod. A 55.: g., quantity or sum-1n boiling mm 66-85" c.
an: (thawed. The yield ms 137.? 3.. 1.01 moles, uhioh in 50.7% of
the them-cued r1916. mo ratmtiva mm: at tho product a nay-’-
1.h3’39. the reported boiling rag- for 3(Hfiatiwyum4nm
program to 75.3075o C./25 m. “3. (135).

3+ ipar 1:? ino-l-cifloropropam

«9:9. r‘IY'I "Y'
C1“: 225.0. ‘akdl. ‘

A two liter round bottom flu}: m ogippxl with I "flux caflmwar
and 330.6 3., 1;.0 mien, 01’ {2.113911de Cissolvod in 91!.) :11. of banana
m placed in tho flask. A 3114.9 3., 2.0 moles, quantity of trimtzylana
calm-shrank}: m added rapidly to tin aoluticn in the reaction that:
and mag“ val]. to u-orougffly nix tt-m'éclnuon. The reaction m laft
unattmdod far tumty 33:12.23: and inland 05310917 reacting u in tea
cm. of tho previously described sacrpmlhm and filetfi'zylanino xierimc-
titres it. beam ratimr vigaroul and a hrg-a taunt of the bani-5:339 ma
driven out a: the madman 30:23 of the raactanu very probably are
loot ut the same time. A 5:»: ml. qmtity of national argm‘lmuo
banana wu 05:30»: to the reaction mixture am after it had, subsided it

was kapt at its raflux twenmro for three hours. After cooling; use

 

’ .._- -.

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reaction mixture in an 14:93 2424.94 the en'stalll. ~43 p ..paricim ‘tvcfrobro: 41:6
was removed by filtration and 4:5an with star. :4: cor-4:454 “:43 was. 1.4 a
and £11 mm mm cxtractad with 3 R Egfimhlaxic acid. The car'mLm:
acid garnets were made basic wan 1'3 N sodium 33:12:13.: ‘2: which canals:
in eily 1.35:4 to tspmte. 1249 has 4.4-: 34:34:90“ law was extract-9:1 with '
other ind £240 0124m- axtraet and oily portion were combined and dried- in
cornea 441.14 an! .yflroul potassium cu-bonet . Th: ethn- m resume: on
I Mm bath and the oily residue was metamtsd using I on. foot.
Vim (2911144444. The frmtian hailing at 83-320 (Ll-5 2442:. Hg. was
collected. A 12.1 3. {Drama (34‘! a 1'3 a. (1:43.. tity 0. 143913443 9:444: 4315-
emw. the kitty appeared to 1443 a qamtarmry salt pols-mar or 3-
piperkiino-l-ohloroproma. The yialfl m 130.07 3., 0.9?” w mole, of
3-p13nz4mL4io-1-omomprogm which is 1.6.1.5 or the fl'zeomtical yum.
rho repented boiling; range far 3-pipwidino‘1-crloromane is 954-133"
c./25 m. Re. (85).

Praparstion of 14-1 brp‘slm-l-c‘lommtma ‘Bsuchndm

Cl? “131...? 334.4443 .ii i 00:33:]-

U

A one litar, three mat: flask mo fitted with a reflux confisnmr,
mac Harlin]. stirrer am! I "I" tube can tannin; I tnsmomtrzr wit-74:45 534.;
into the reaction £13.33: m? a dropping fume]... A 79.0 g., 0.3.33 44:43.3,
qmttity cf hqrxpfimlmmt “.91 was disscl'md 1:4 13:40 .411. of dry chlam-

fom and placed in the rescuer: 11333:. A «antics: of 81.5 43., €4,535?

4'

,—
8-th

«.d‘fi

W14, 01' ."1‘33 39' Cristi .134; t. 5.341;). (3....3‘41 canals-4‘ 43.4 .:4 5474 4.3.1. of dry
c211... £0313 van preyeu‘oi in t: s (1:995:53: Pam-.31. The --:>:‘.‘é.4:4:1ta of $1.9

‘ E _. ("-ofl - -1 1...? 4.
$12.23.: wars 44:44.4: 2:... C . an I 4:441:44 Laéz at“... than the ‘4‘. 1:43;]. a lame

cilomfom aviation was a: dad- dragnin ta ta fibres: mmtian mixture
at a rat 4: 54:55:544‘1: t0 4:441; 54.1.: t. a rmtion mixture “EH-13°C. 4.4114-
out titre 641: cf a steam bath. One hmw and: [1544444 mm“: were mqaimd
to 4.3:! all or the mluticn. A cm 1:43: 435413141319 mm was tittad in

ylace cf ‘40 dram; ‘33 Camel and a ma: 13min; to a mtar aspirate:

was covna-cttrd to the top of the confismar. $45.10 I slaw stream of air
u‘cal drawn 1'; rough $5444 mm‘W‘a. 4.! to ‘m: we at: 45424-4 (5.035414: Cums, the
martian mixture was stirred was! hast-3:1 at. its 2'an taagm'a‘wa fer
tm hours. Em up: mama m3 m1‘5:.5%:3 for {’itztilhtion and agprorimataly
75 2:41. 01' ct: lorefam ma ‘41.:3‘3411135.5P’J.fi the: nation yam‘im'a. The
reaction mm: was 43901346., 1154— amp-an cmtala for" ...-24:3. The crystalline
solid. was contacted on I. Bucimar funnel. The precinct. was wary cruria

and fcmr recrystallization: from 130mm], 1 0.120.401 .‘.th charcoal
£449th in each recrystallization, wararaquired to obtain I proauct
melting 444. 120421" c . rm reported iiwrabua value a: to 444414.444;
point. 4.. 120-124? a. as). 44 641.0 5., 0.235 min. 57.5% arms as
obtained.

no

’3
C ‘9
H

Frwshion 01‘ 2-631. -p:.u1:11o-l-ci wréduwfi 143;...4». 16::

1:13:53}: 34:01 .131

he same gmora.‘ prsceaux emit. par...” 11:: variously c:acribad
wars attplaysd, using; 735.6 1;" 0.54772 1:11:10, 01‘ 2%:1p31clkzc42tlgaaal 6-in-
solvmi in 1.30 421.1. of C117 chlarofura 11:45 82 .14 3., 0.1373 11101.9, of tfiionyl
6.41.3.5: ..sr‘Lia diam-km". 11133-3 1.31.. c. 6'“; 1:2.-.1019 ‘1“ ...11. '4‘1:o hours war-a raqairzsd
to :11: the rasgants and the mastic-n mm. was 51:14. mad at 1.3 talus
trawnraume for 11225: Lrty 1-112%:- :1. £331.11 1301411315; the prodact in to
usual manner 41“: reczp‘sfiallialng it fram- improb WI «10011131 I. j ..17 3.,

..., o
v. 9' J-‘I 7"- ... “ ..‘_..‘ “v? .‘-, l.. f.
' .512 121016, 8,, ’. .4111: of a 11. 08.1.1.1. ...altiug st. 1.2 ~13} C. v2.3

0
%

0.11.41.41.11. ‘1“.‘13 malting pomt a. ..van in tins" 11:11—11:41- 04‘ this six-13119.net)

‘31:..93 n ....
is 132-1...d v. (.112).

Prspa‘r anion oz t-Fipn‘icnrmul-clbmataana Zydmcalsrids

c1 (341224523: . >413}.

The use gas-411ml ptmadws sad Apparatus as pra‘viously dancribad
‘me mloysd except. that. 1 two litar sanction fins}; m used instead
of s one liter {1115242. A 12?.2 g” 1.0 1.1019, quantity of 2¢piparisiho~
otémnol dissolve-:1 in 2440 ml. of 12:7 chloroform and 1142.3 3., 1.2 moles,
of freshly distilled tzionyl cl‘iorids required one hour and fifty-five

minutes to combine followed by s flirty minute reflux period. A 1513.5 3.,

”J

fi—b I- -“C.

. ‘ '~,. ~ 1 $1: ~

.
4.
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'1.
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.

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., n , ‘ . u
v A I Q
- a
,1 1 x 4.
. . ,4

0.99) mole, 11.1.; $101.: of .:a'Lcrfil rth-zg; at. 2211-221 3., after:
rucr 51.111.11.11... from aims-.11, was 02: 111111113. 1'21. {agar-trad ml‘uirg

2,.41 \ n . J.-- -' .p A' G a ":n
9611wa til. 114294141511 L. (Lu-8 \1. (4.).

Preparation of Tamra-sat} 15213213 Chlorohymm (33

A‘ A ooooo a" 10'.
11

b.5113, .'.‘xu ..zv 13'

A 0119 11-322 , t‘. rec use}: flask was equip pad with a raflux condenser,
gnu diaparaicn tube, mc‘. a mazmmtar. The open am of the reflux
com: maar was connected to a dry ice mpropy 1 alcohol trap by u seven
11.111th glass tube. A 115171203913 chloride smarataor no corm‘uncted
by fitting a rubber Itoépor 20%..ng o. figuratory fumel in a one
11m mction nus... ma side at: of the motion flask was connected
to 11%.. gas dispersion who in tha reaction flank. 506111111 (11.110.11.59 was
placed in the motion “as: am cow-weft with cementratsd rmirociluric
new. Commhttad 3111111211: 9.12.12 was placed “1 the 3212:32’4213' #112231.
1119 wantity, 2132.6 2., 6.0 91131116, or butMgw’mfixm ma 93.212212“ in the
taxation flank and 11011be to its reflux tut-21129222121126, {111° C. , by 1:113:13
of an elect: ..c Emmi. me comma-awn! sulfuric acid was slowly added

to the mama-1101212 aciri 3025.112: 032111222163 Fixture, 111.110 1.1211; 322:2 .-:-

2;}

.9. u..- .-
“.'.”.

1252 me: 1101210 00%! 14? to?» ma 5.01.13" 111121211312 into the 1‘11..qu Lu; 1
Ezydrofarm. T12. lay-1:225:11: 113115123...» 321222‘ was 8:11.33‘1 occazicrd‘g'
to give an even now of 5213. 1‘21!) prcc 315 W: was cuntinn 36. until 1:15
tarry-2.1mm” of tho mrtiun 1111111226 1232131122 116° C. 321L191. 1229...: as:

@prorimtely fmu‘torm hours. Fractionation of the 1201102161“. 1252; {are

9-

\I

 

2.)}

mar 325.3001: prawn 3.103.000, a Ca) 1:133.“ 52123023111, a 0.2.2.113. product
boiling at iii-9.10 CJl’S m. 115;. The mam-tad boiling point. for ma
fraction oolluctod an 60-91.” c. 2 .11. fig. "12:11: tutorial m 129-19-111-
killed to $11!. 2 3511.5 3., 3.26 mien, 321.3; yield, of para tetra;-
mmylana 11111212014ch 11021111.; 111-52" :1./2.. m. 11;. 2.2... reported 2102.1-
11211;; point for tam-2210213311113 011101203; :22121 in 61-51:") chi; 1113. 12:22.. 012
723-710 (.’./7 2.2213. £13. (£3).

Preparntfinn of Y .39.»;1: 31.110122012022214,gmizzotyl-
3411110121,]. 811111110 2m.ro01.loz Lie

42".? ("VI'Q n1; va‘hl
«M: 1‘" a ‘3‘“ -. ...-01
2’223

A ESL-3 1:1. thrao. 22.002: .105‘: was $111.11»: with I flirt-2.2.2:, 120111;}:

00212112212312, 011:1 (.'.-1209222222 1111212101. .1 6.5.5 5., 0.155 22.013 1121122212132 05'

'r'22-20
nod:‘.'12_1.‘~2;n12r_>2'1’<1 2’15501201 in 1 3 .122. .. of 2:02.22: was 22’2-23 ts) {2‘0 £1.33.
A 9.135 5., 0.131" 3 22.010 Q1m2tity of 3n21023‘2011:20-1-021012022120 311m was
placed in fine (frigging {41:21:31. A '1 ..- g.,0 .23.: 2.2.31.2: quantity of
2,; 1.2.2.232" Vie-2.22.12. 2:? 23319:;1101 112.215 013001212911 in the swim 122.22.220.2120
80111112231 8:123.- hnatar! to its r.:.i"711.x'2: Unparatzm. T? 4% ”—222222‘2211 21.2.231-
‘S-q“ '.- .

. . . a .2 .1 -. 2.. n . ”C' s A I
c .loi‘ap1‘a‘ 5' “-:., «as a. 1.2-? v ‘1}av.u: ta t- .3 Vulgar 15"? c 0*»?3’. am-flkeouxa

51111111011 02.21212 11 1351121213 01’ fiftc... 121.212.1203 aft/3:2 V1122 t‘L-a 1222212: 2:02.21

{11:19.26 v.33 720.1... at). a r‘ifirmal tar-.2: 32:22.! a 32:11.? 3.011123 1.21:3: 2.2132221118
3121121211152. Cu 02.2.1221; 5112-. 0:111: .21.:- 9.23.2.1. Lats: 121-11 12.3 122.: 5.02.1012: 721.11.;‘8

012.1: til: 2.2.2121 3.193.121.1311 £122.11 the 2.7.2.2011 3 12:20:22. -1:-.3 2:100:13 portion

V. ‘ _ .
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.- :
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was a; use. data; git; tr :3 2;; 4. pc- tiara c: and: {LL c922: ...:ci via;
the original oily Muriel. 1213 “actual Deviation win maxed wits;

2'3 ml. of five 34-31 ‘csir amt 8.3;.1LL2; ...,udwma ti.- +‘:-:1 with ,‘J Jiblo of vat-:3,

and triad in contact Him army. 1W4: ma $95.12;: chlor ida. A tree mad
5%.. ml. flu—L. was ‘lttad vita a rim-“Jr, V‘- inn (2 llUI‘iLG Cry‘uu titre
am a. 6 m. 1411913 mm ems" *icted to agpz‘dmixiaiily one mwmfiu" at
be mat. Fry 2.4:.1‘Ogui'l c.1aiida was windmt by crowd.“ covxm..mci;3
ml? r12 acid ante a sodium chloride «accurate: gig-owls?“ 35.3.
mixture comma in I and liter suction fuel. '22-»: at: an ad” by: .zc 2:;
ciJaridva Item tile cadet of the: suctimn flu . 156.8 pasw: ulnar, 1 a

60133 avatar; unfair; acid drying tom-3: 3...: tum 313m bubbled into
the vie-proudly stirred .Uifirfi-fil sol-tics; a; r max-p} 0.».JIOM" ,... ~1~
2,3-«11-30313'1-3dfiximlyl sulfide. Midi the ml .131 a sit-an ymdipiiaia
had for-gum he Imam @3311 do was bubbled into ti.» ether cal-41.13:; an
additional in: mm aftar mile?) the find: a. Mmrmfi and sat
acid. in m in bath for :1: hour; to facilitate cwatalliutlm of

€10 precipitate. Tim mite prmipitau in then filtered on a manner
mmal Ind “shad with other. me cm in produc 1; much malted at 137.-
ML)" C. will mmfllisad {mice from Wogyl 31092 01. Tim yield of
mnsfillimod Yucca-phallnomdpwl-Zfi-cimfi;yl-3¢aimy1 dull u: 3
hyr.?rocI'-.1.orida m 12.77 3., 75.033 of the theoretical yield. The mlt. -
point of the product arm- drying warnight at 63° 6. in an mam-5.3 her:
fining pinto}. filled vim calcium china: 0 and Wfin um 3.14.6.0-1330510

C. Analysis of the compound for carbon, hfimgrm, and auli‘ur gave um

NJ

EU
in.

, . 5 ’ "d D ‘I g“ ‘.’__ v. " * ".“ I. _"' a 0.. . .
iqufihe‘Oa r; Jo-t$. -- {tut-‘3' "I" 0 “ .,‘;.‘ ’ 12 ‘ ‘ao’ 8' ---; n, C .‘ 1" I

5'.

r~ a- 'A r- ---... I' :7'7 n h-‘ f
U’ bargvhq 3U U‘k: v, ’«dei ::, ‘0’;- ‘5 3’ d. .k‘

Prepar :1th or Y-f‘ip-aridimffn-m-opy‘ ..-2,S-d.um7t..;. 1t imp. ~"‘
Emilie-9 .-.;'..-':70c..:.la.. i a

g: 31:3 '73, 0142.1

 

A 500 m1. terse neck £11m; was fitted with a stirrer, reflux con-
denser end dropping {11:31:01. A 60109103 con-him“ 6.7? :5 3., 0.136 mole
of 0011113 hydra-.1“ (1186.13.21.33. in 152-; ml. 61' mm was prejaafi and
place-1'. in tin flak. To this salution 8 3., v.0,f5 and-ls of 2 ,5—61m.-1t‘:;y‘1-
S-finiophmefiniol m added and disallvei by during. A1: 3.95 5.,

Oo‘w'L'S' mole quality of 31:11»: dine-lawloroprma m plea-ad .:1 t. a
dragging meal mi; misled drapvua during a maul?! Minnie period to

he vigomsly 0&1de refluxing 39117.net: cent mine: 1:: $31! mutation
flu-Sm. sm- all of the 3-15“.per1=.linc-I-chlemropmne hen”. been o. 3596:.
the reaction mLxmro was stir-r7726 at it! ruin->7: tervperehme an additienal
three Mars. 321 cm: ling 'L a 17321ch M12291?!) In 011 layer famed
#1103: ms aegmtet‘. and the awards writer: was advanced with tree
Im’rt -.7: 7:3 o- 25 n1. c‘.’ $51711“. T'aa c73.':3.;"-.m:.£ math-er matrar ta 'rm‘fle Vin-{.‘.
ta 7'7‘ a 027.". 73.3.3]. cm: ’63 OLJ Y in? 13?: “Mm-Trev -",’3'-*“7:!t‘7'1t‘:wmyl
g

e . . #4 ,
5:151:79. Tie r'mzlti. r efflcr 5‘81 5.03:7 . 1:: was was-mm: with 2;, 57:1. :2! "

I

he;

33:413. 7. 1.4 :7: re .7. 10 club. fuller”: ’ry ' :21. cf wt. :2»:- an" 1:. an r 77‘.7 :1“.
in cant-met with 3:9: . are: 277.11 3051.12: ml... fist-e2. m: 5271:2423? . ...}. 5:121.

time m then transferred to a fizz-ea neck, 5&0 m1. mum bottom flask,

i}. it- \.
K

‘o

2.. J

2:75

in)

11966“. with I calcinn cilarir'o @17411277 {221.3, 77.;'¢T7~7o4;z'.7:2 (23.37.033.76 gas inlet
tuba 52:22! a sum-or. 23:7; 3232:3322: (31.7 77:13:: was babble... 12:79.0 to stirred
storm solution villa be $122.72: m3 1717131757313. in an ice 12:22:... Altar

tie mitts]. mite procipltata {02:72:23, tiee 17.37.7170; 3:: of 71.0271. 3 has inf 71.7133.
th0 no solution on ...:2..:.-.:2.~.1 two mans-as after 122.133. the {13.52: was
storms-a7} a2: .71 not 9.31:2: in ice for six 22::- 77: to ct: tam a. nor-o (:27: o7 7"! 712:9
prowet. Tho 0:12:79 Y -pi.pa:7§.x. 11.77.0712rop;71-¢ ~ch .7237... .yl-B-thienyl sulfide
hya'roohlori: a was 5.1%.“ {fax} and mamad 171.52: at 617F727 275179321 chloride
was again bunt-319.? arts-the filtrate to obtain .21 0.233103: 371.21.. :27.
cmia product. 12:9 total 13733.3: t of arm-e Y-pipo Lino-narrow 9.3.1-
mté:yl-3~t?7ziewl min-7:3: hydrochloriéa was 15.2.2 3. aft):- two re:
cmtallizationl from 6273' 1339270333771 model 1.3.2: 3., 0.1.33 27.7.9137, a

73 .1:! yiald of a procuct mutiny at 1715-13.. .1." C. was :3me

E1777 23:2 tel Will of t) :9 command for carbon, hydrogen, and salmr mm

t2": following rasults: ' Calc'd. for Cuftusarsls C, 32:.9-33 E, 7.91

3, 230950 3’33." C," 2,: roCl’" 3}, 802‘: ' 3. 22.73.
Fraparati on or Y -{3—: ,22-; ofiiurla=7sizzo)q:-1)ropfi-2 , S -di:7:at2 .ylo

Bat: 17.321371 15:23.! do Hyairocfdarioo

WI.S,I.CL31 VAA'H'EQ‘ ' .ESCl

I

:2," ~63,
3 .
[I
A 6.735 3., 0.17375 solo, quantity of sodium halter do was dissolved
in 1:20 fl. of water contoimaci in a time nae-2:, 5730 ml. flask itteci

with a stirr .er, reflux mucosa, and drop .1223 rowel. In the 453.311.2729

.
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3012:. tics 8.75.73 3., O .QL-S mom, 0:. 2,,-:.._.777°77'l-"7-t 10;) 1312:2717. 3‘10]. m3
6139012731.}. An 0.2) 5., 0.C,-,,'37 2.01:2, qumtity of 377.2.oturmz21no-L-c 1:230-
prawn m piano: in t‘: 3 drop ...22. 172222121 and mid-.321 eadcopw‘ no to t :2
vigorously stirred ref 1112:1223 momma 377131.193 071317 a poriozti of Ithaca
winters. Tue roacti. on 7727 77317.73 1.72:3 37‘: 7.27273: at its 173517.17: 7.722732327312333
for $217333. 551731 a. qwtor hours at 9:21:72: pcmt an oily 13.7-77.2}: ‘23:; 13:77:32.
127.... m lopamtod after coo.-.7 4.7.1.3 17-3....77 72.2.72 2.213122. 7773 121 on lea Lats;
m the aqzmn portion 2.7-2.3 mtractoc‘ with firs-a, ,3) 1:71. portions of
ofizar. Tao canninad 37132327 37.:- .tracta 2.772 .73 cad-$3.3 to t: o 077 .3.-72231 oily
mtwial. The maul got: .2. 7:231 3:212:17. 37.7.72 :1 of cm to Y -(:.-,‘7.7-. .:12.i.;.1-
mind-977970;; 14,5777; «“7773 "i777” ~3-t1;1...;71 sulfi «:73 m mafia: with 2:3 :21.
of 23730131123 fvdmfido solution, follow-m..- by r .1 ml. of wa‘ war and rm
213:3 in contact with anhydrous: 272132581213 Mate. Zry hydrogen“: c‘lerLI-O
in 32:27:21.: twang-:7 Lo 31.127272237124527.on solution containod 1.72 a ‘ 3“ 27.71.
{77:17:23 nook £13.33 1212713273361 112 on 1:33 both 322:3 fitted with a stirrer,
calcium c‘fiorh‘o tuba, md 3535 5.23.2.2 tube. A gray crm‘a Y -(‘.‘:,:7=:-c::’2~
Ifixylmino)-o-prcvpyl-2,5-6133631-3-31333771 37.13.111.13 hydrochlooido
procipitato fox-2.22061. 1:212 after being; sot 3.72133 1.7.7. t?- 3 3327227331 solution
3% 0° C. for 5.71: hours was tutored am'.‘ washed 1273:; et‘uor. Efry hytirfigrfm
oljnrmo in again bubbled t3- rough. . tio orig-final filtrate to obtain 8
Boom glantity of gray crude mount, which when 30.713112 :1 with £7723
12321.2 crude product 537.73 I tote-.1 wig" t of 27:3 .3313]. mount 1.77.; to
13.1.1 3. “£220 our-.‘. product was fixmotmizod twice from dry ioopmgyl
alcohol. The yiold of rocmotollizad r-(t‘,.“-:Z4 .223. 777" ..71211720)-12-p77~7;1-

2 ,Eaéimfizyb-B-t‘dmi 57.2111 :‘o 1:37: 17037110271: 3 was 10. .’S 3., (3.071.!) mole,

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a 72.2: 61’ 1:2.: firecroticnl yialci, mum; at 193-113" 0. Analysis of
ti: a compound fer carbon, ‘m-firogem, an: sulfur gave the fallout; 3
malts: Cal-:2 'd. for Cufiui' 31:31: C, 53.121 5:, 3.233 5, 21.52.
rams: c, 52.90] a, 8.2:, 3, 21.70.

Preparatian a! $413,132?lati-53-13:;sz)etrfi-Qfiaflimthylo
3~thiaavl Sulfide 1;";- roe: .lo': 1: a

1. {‘71
*' -:I::1
3.1m: r arr?"

 

The Id 0 q), rams was mad 85 1:315:10 prm'iaun praparatrozw of
bymrociioridc unit 3 cf amino mlfiéuo. A Gammon at 8.2 3., 0.2125;
501.3 of 0033411: gamma in SO :21. cf Vim: m praparafi and placed in
he macaw flan. A 8.0»; 3., Ca.£j‘,',4 mole (5.1:... but: of {many pmpared
2,Sqfir-aattiyl-S-t‘fiophanat§ziol was éissalvafi. in the stadium Emirazida
solution. A 9. 55 5.,0. GE?” 4 21:91! quanmty 01' 2451312 ‘qylaninflat’: 23?].
Gloria‘s Wochlormo m assumed Lu 50 m1. of water and placed in
the dmpping £1me Lila the commute of me that... m vigorously-
ntirrefi at ita reflux temmfim, the 2-(Jiethynvmzo) athyl chloride-r3
1W roe:- zloricie so lution m 0.66.961 drum; over t we hear pox-19:3. The
rem-chm auburn was mm at it. reflmz “twat.” an audition].
ei;;t hours, than cooled md in any material was extracted with three
1C0 2:1. portitma of eta-gar. Th3 canbmod smear attraca were washrad Him
20 2:31. of 5'13 sodium milrozzma and than vita: as: £5.1- of inter. ’i'z'zo e‘umreal

mum-an of 1:229 crude B (E ,H-diatm'lminohtbyl-e ,Smimafizyl-B-fidemyl

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£33 533 (Erie—.'. cvmxzht in mutant wit-J grim-mm: memeaiw mire-rte.
The manaaina militate was tube-wag hora ha dry ethereal saluiian and
dry Ramos-an clflmiis m as“: fro: the apparatus described in ta
wan-3.3“ preparation. The 01min {3 (3,:3-éiefityhaine)ethyl-fi-tiziarg‘l
sulfide hydrochloride was precipitatud in m portiam, rmtg gash
by filtration to prwcmt the: midi-flan of mm: luring—:32: chlorate. In:
corizlmrl dry and. 1313th “6153503 13.!23 3. After tea recrystalliu-
$.qu from €117 180mm"). flannel the flaw in 13 .12 g... 0.015;? male,
83.72: of ma madman—cal :1.-.:ch . I'm pare protuct has! 1 melting point
of 1%? .G-ILZJO C. analysis 6f the awry-“M3 for carbon, Wit-ohm, an;
mh‘ar gave the fanning roman 6.110%. for 61333.3353'313 C, {1&3}
ESE, 7.323 3, 22.31. Faumi: C, 51.62: H, 7.2“?! 5, 22.56.

Preparation 01‘ 9 (1‘?,.»'-ni‘»iwt‘:.r1mnino)sytbyle,§.¢i_mtggfl.
Bmdargl m ’iJ-a Kym hlcricfie

‘nt A?! tr not ._Ih§
6‘2“. 'i‘b“;}?‘ 9353);.3‘5.’

  

The mm apgmrama was e'mlcyaJ a: 1n the prwloua pregnant-firms
or t‘m afime hylmdlwida 331111.603. m: 8.2 3., 0.2-3.5 male mzmfixy
of 30:15:31 mama-11m was. (23.3961va in 50 ml. of mm 6mm in I
5'33 ml. flmk. Ta this stirred soluflmfifi 3., 0.05171; m1- of
2,5«12wt323rb3-t‘: imitmot‘uiol ms ar‘xflaé am! the vdsztum was haatnci to

{a reflux tas'qzm‘atura. A mlntion ccntain‘. 1:; 9.555 g. , CAI-£32; mole of

-r" i-‘tvzthylmimrrfirgrl ctzlarlda hyfiz‘cc‘wlorizfla dismlvad in 15-0 511. of

Int-gr as p13: 53 1:1 firs Crap; ._ .24? I1 £71.41 33.1.3.2 ta t- : rail-.1 ... ‘1;
Iii-"‘11:": salt win'on of 2,3~.'1.~;12y-I.. 3“» 1 x > .6931. .101 over a M 310:1
of a"; Lear. Art): tiza mtg-.1293 he": mime-J m aJJitir ma. hear and a

half it was discovered tint an was: of 2-(LmettIQIlmLLnoatIyl cflcriI‘o

1:33ch 1rd: 9 bar) ham in I‘m. art. I1“ “....s-I, the: dare, I 1.5? 5-. 0.11.11
1.13 5:15 .land (11“ .:mtifgI "‘-' 2,5«1133‘ J-;,:I1-3 ~t.1-.;;-.-I-I:.. 1.32101 m 36.1301:

and the $1.1: a: mantis-I mix-.4 3 1228 3122.13: at 1123 r3 films: taI-I'pnrat 33:3

‘

tar as 5.:l‘itiznzl lei-1:11: town. I331? aligning it to carol, tbs manual:

fi-‘n‘

man was «$221313! tam!) tma with fiat.) 211. pa tiers of shim. T‘rxo

$221333. thar tI—Itrncts mm var-.235 with 2’} m1. of o. 5,“: 63311:: FayrhIIOIJJ’Lo
saluting 8:31. "In... as: mtzr, in: 8:13.} in contmt wit: 13-3.3qu
mam-2911:: [1333111, car "23:17,;3.’ . 2:7 Emma-gym chlorilo Ia-Iaa bubbled into
1.2.35 1.1.61 11:3. 01" mar; 613113.103 as pr", I~-II‘ "1131.)" a ’aac; 15.2.1. '31.; 21151.21
yer-3:121:33 of end-3 yrs-12:3 1:33 1‘11 3332:“ .-.- .I‘I-t .a nine: 2: Lion rm;
1.7.53.3: with stirs: after $3.31; a carton: precigitaw was. 3.33;} by
11:25.1 1113M]. treat neat. wiia. 311-2:an cleric-3. Tin: again-33 Elie-fie rm‘a
prwipltatoa wigbezi 12.33 g. 11:3 cmda product m r-ac—rysummd
tri.‘ a from dry issprcfi-Il Limits). to at. ...-.1211 l 12.37 3., 0.01;": Ian-la,
7;.2}, 35.9135. 03' .: “..3-Ln“. :13. ”018*.y1-J.,-LL 1111.3, ’21- “1.1113?"
6.113320 ‘I nix-0c:- " Irlzlo withxg GIL MILE-132 .30 C. finial/$3.5 a: 1.115 ecu-
pans; far c3333.; III-l. *cgsn, mi. EJLar [:33 1.1.3 Hmong.“ results:

nu-l I f

0‘ «c. D . ."h f - it. ' fii“"._. a
C‘&ZC';. .101“ C10: .uS’iu .L. a. “Vodj' (I. 7.2») Q. ...} on. J. iUu-L:

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C. 8.7:“), 5;. 7.2.”; a. 5.11;).

 

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Frag-63a on of 54193131; 351-332; 3."'*l-2, 3‘11. thy]. -3-t‘.13;,~.;r1

Jul; 4“ J j»... Uta-.193 and

4? :2ng >r "7.1
Iago U .1

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....
Timplming tum apparatus and. in tho firmious preparation or 1333
€an hfiimhloride 321151230. a mint-ion containing 8.2 5-2., 0.25}; mule
of calm: Emiroxicio dissolved in 532:1. of water was prays-aw: 1?: tag
SLAB ml. raactlon flask. An 8.120 13., 63.053 9’94 mola qmnti ty of 2.5-61mm3r1-
3~t1'-10plzanet2 101 was 61330le n the 8071sz 1'23'i3rorvtifa comm-Gt: and {21-3
latter was heated to it: reflux tar-3.39222. ant-um. A solution 20:11:21 “11.323
1.2.20 3., 0.651; mole of 2-piper121Ln'a—atf'1yl cfior-ide hyLi-rociglari'fie
(7.19801va in Si) 120.. of WW m placafi in his ($011913: funnel and
.4323“! dmpwiso to the utirred reflmriztxg 0351811318 solution of tut: sodium
salt of 2 ,S-L 1:23.; yl-B-t. 10': :3n3Lml over a om hmr period. The
nun-9d reaction mLmre was kept at its reflux t’mmuro an national
six hours, and than coolod. 5.!) an ice bath... The oily mtarial which had
separates? m m: tractod with urea, 1C0 n1. portions or :3 “her. Tao
Mined «mgr (ma-met: m 9252; ad first with 20 ml. of a, r" u so: 12m
mma oolution, than wit‘: ‘23 :21. 0:? water, In? driod in con tact wit?
cfiayfiruuo nay-905.2113 all-1am, memifim. 1713 93712133931 solution ma
filtered to mm the (17133 Infant than tranMam'wi to 1.213 waviously
clencrlbad mm: for aiding c‘ry m'vm-vcn chloria-Ea to the etharmal

Iolution of the crud o Hm 93'1“ o)at¥:yl-2 ,5-(T‘Lmt’gl-3-t'3ifixvl l‘xlfific.

The F-plpm‘idinocté ;yl-2 , 5-21 but? . ;’l-3~t':-.1myl sulfide h;airm:hl0r:2:‘a mag
pracipitntm by two separate 1322:0333 chloride additions. T210 c

product was filtered fmn tau: aolutian aftrsr each pmcipiimflorn t0
prevent. excess hyuro :00 01:10:“ 12.30 froa twinge, $13000 to the mammal era-lac
non. Tim fresh pracipi temps, was: 2 time, 1mm stored in an 103 hat;

for three harm‘s ta facilitaw crmmmct..m mic-r t0 filtm'inar. 2:23
dry cmfin Papipnarlaiinoatlyl-z,5-613—31 ’ y21-3-tzi- myl sulfide 333,1?~m0223..01~3-f‘0
magma 131.80 3. After tun max“ 01.113.103.10 23 in on dry 1333.)? 0:31 34.133 01
the 13315115 cf pure at"; gwiparid moat:- ale-:2, S-ciiact‘g'lfisj-mximrl 30151:: a
by! whlortno was 13.11 5., 0.63123; r1010 an 57.5% $1016. It raralt-‘pr? at.
173-171? C. 111111331 0 or... a co: Wan” fur cmfimn, ““’r€“""2"!, ma. 81152213
gave €10 tollmring rasultss Calc’d“. mr Cu “3,5,.2'61: C , 5'3.‘ '3 23., 7.5393

5, 21.97. Foams: c. 5.5-“ :3 It, 7.1.5; 8, 21. 72.

«n .71

‘ A = 3 ' 2 ' '3 r” r" .- a :1 a 2 . I ..
{v.31}. 1"" ' 3's 0". ' . h .o " 1 . ~ ~ .' .1 , ~~ . - '9 ’3 ' .9. V
”. v4. 3.... ..vfiv ..W v "db- 'J .5";- ,’. “.- ‘...Mu V: ‘J 5-,!“U-LA'JpIQ‘ .fi

Sali‘izia 11;,”me 1101‘ 12:23

la, :.-. .... : I ... .'1-.o¢
l | ddoowl£~ii::‘ . 'b .‘.;i

‘S I ‘
g 1
"3‘“ v.2 7.3

3

.‘.. ’V ,9, a. ‘

1’1sz app-mam “05.42: in 2.13 32.;‘22342w0‘353m 32:33 ta $430.0 as “at; mgsuxuw
m t 9 p1‘9’5'&0118 r13. ZEIG-Chbw.» Cd. “hi; 3 Enlist} :Vwm.-10- .‘.L-’J uw+_& 5. M £302
3., 0.2«5 mule (310,194.; 0:: no: im 19W? ::i a was ”Nam.“ in :9" :01. of
4.20 hzi‘tially mum; to ”mu 51);: ml. 1*0m'ilan flask of £120 0.3-2:01.; baa.
A1: 3.3:) g... 6.35:0 2:20.10 gwwi’; of 2 ,:;-«;L;~pugl~3~t:.1cr2.11.234 .101 was
‘ 7‘

dissolved in the 602-1102; 2;: ;o:.iza 331.111031. A 8013.11.10 on c rawirzkg ....-.3

IF ."I "."“ i 0 ’ aA-..~n .~ ‘ q fO'-" "‘3 ‘ ‘(l 1“ Q ‘3. ... - v.2 -Otl|r“ \' “o“: 3 ii. I ‘ l“ ‘ ,9
6-, b.ug,ma 3434.8 OJ» afi-.~.3;;.bs.g.uu~uuu_, CéwUL 4.3.5) M23 ‘ntAUU‘JJ-VUO 4.23 ,»u flu... Us

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21.3

1 ._. ‘1 ‘3 .3 1..~ '5 ._-. ..) _ n. , - 5"! 5.0.. ,3 ... - 3 . .4. 3.
$2.155 .1:.-- p15: .._:1 t3 ":- .. .5,“ “55:23. . 2.5. m--.5:5 2.1.21.3.1 0. t 0
.-!' \' g ...-2 I ‘, ‘LI‘ " ¢I J‘ i

so. .3.... salt 31'” ..,_,~.~ 55.05 351-: ~ 55‘ 5.55.. 5 01 5552.9 M155 at 1...: Man;

1.43 51.401.45.50 4... '. .19 1.55 .-. 230.41.15.51 5:? 2-5.5:355‘;;; '3 35.0015. 351 c 1.55.51.“ 3 was 9.15.5.0

fragrae ever a 5:": z‘. of a .... 5:05;“. 12:0 1523:1219 ..on $55.4 ...:ttvt'a 5:53 83:73?"
. " V. . J , .‘fi- vo 5: ' ' '. 0'. E " ‘"
...-.51).. at its 15.5.1.5... 1»? 3.5352515.» 1'05: an 05 5.14:1- cnnl 553550251 25. am,

3

5.. ~~ . ..5 .. .4. '5- .95 ...- b :- ‘ . “
Ln (1.510550.- 50 220.1. .55.. .3 5.: 1:15.. we. 05"" :5. «‘5 V . ‘t‘l‘fi’fl 1-0 .~53..

_, ' “ma .. .«...!1....5 3.2..-. .45-... x. .2, t r’
pfizy. ‘5 0:13 of .'.:5. 1" 52 :5... .~-5.-- :3- o .3.-.013 5:53.553 mam. with. 2 .1.

O

4' ' 5' '1 . \~. 5......4 ' ‘3“: v t ' 5.. in"? p . .. = .; ....x
c, ...» 3;...‘tn .f'. 1.53 32...... .351, ‘7‘“. :3... -. 55.1.0. v.11: an. 5.151... 1r.

‘ ‘t v”; 5 . 5......- . v 11,- ._ . -. 5". - '5' 5
531.0; - ... 5.55.5.2 5.53m..- 3.--.303, 055.515.513.51. .‘.5.. I 111.0250“ ;._~r

’a‘ . .1... -'..‘55011.’ -/ 3. ." 1.: ~y-9 ' ~J\
00:122.... 3.1.2100 14;.8 t; “WW {.9 t... ppm-51.1.1153}! c 05041053.. 155.530.35.108

.1:? LEA—2.3 553-? 3333'“: 31"5 r-'--'1~~T-“‘.I'-”f. 3'33 0:75:33 ‘5‘#5537?“3121C~rzt‘af'l~?,.'7-

r1 :2; “fig-ii ~5 .1:->551 :35“ ‘,“:"* 5 35:23 {gaunt .5". as (“fly-55” time.
A 12.1.7 .1 . (5.1::“.£’.fi;' of «fit-":3 55.55513. '54.. was (51.55.15.1-55tfiz" was 25°15 511555235513. 3.
2......) $.57: 23' 5-3.. 0.” (157:: 33""~Z‘7‘;’,‘,"1 3.7.5:? 51 t) 3,5531? 11.9". 3.5., 0.1.3? r5013,
1 '57.Z.,".'- ;,-'i‘:1c‘. of $1.53 “-55551501125054 5;"5 ”,5' ~61- 35?. 71-1-5: 1- ~5.-51:1 91151 0

’ I‘ I' . ‘q hfi-‘D 39‘ $ .. I 1 t. ‘ ‘ ’ “A... 0," ~ ‘ o A ‘
h, . 5.50.1.3. 10.5.. . .0 3.55.50 .1:. t 5.5.55.1 5:» c3 .. 11-? 2 C. .1:-2115:5313 01' turn
7 5 :5. ;- t - v w. , 1 ... I 3 ' I - o.
0b.5.“_“4‘.L1~1 .24.? 2.2.355 5:, 3,311.3“ L... 31.119115 3370 b.3115: loving 25.3.11. 543:
II '1‘. ’7 . H ‘l’ . ar- I'~.' ' a fi! 5‘ 1 a ' .. 1 ,3
E—A—v'u .‘C1&:£3J"2‘“l: C’ «,3.- 3 1'-" «40.13 t. 2.6.0:-0 r“ d’zuh' : L, L../.173

l."

I
E. 30-4. g; 2’ 110:1.

21:;

-. -‘ .

Prflpmwticn cf 4’ .( TI ,5: .5. 1.51.5. 2315311110155. 1.52:3 a. grunt.- ; 3551-52 ,5-1- 23.52513. 5y].-
3 -th_ .’.-52.51551 531:1: 3.5.51 5.9 Saying 21153.55: 1:: 9

an!" P‘ffi'W :- ft. ".515
)4a‘a3«.-...xi.3?. 5,as§g)a.flv
:5 c 5:
"5 .513

9

Thu puma“ user. in the prasuat. pmmmtion m tun mm as 15.3.1.5.
used in the pram-1m. skum'pz-ezpm-nmwa. A winner; of 6.2 1;” but-...;
mole of 00121113.: hydroxida in 5,535) 5.5.1. of WW was propuec} m be 5m; 5.111.
flask 01‘ the quantum. An 6.0!) 5., mafia Bola quantity of 2,5«21uathy1o
3-fiicphmefir-lol was dissolved in two mains: 51515111595153 solutisn an;
hmtea? to its reflux bmonma. A ”laden 0:: 6.76 3., 0.1.5554 mole:
of éLmthylminoWil cl’JGE'iCia 2155:1500} 355.151.2153 diaaolval in £3 3:1.
or water was placed. in the dropping fume]. and mm to the stirred
rafhxzing W mama: minim over a Emir 11m pan-ind. The 15-:-
actdcm mu m nit-rod .1:. its 25:1me mummm for an miciitioml
half hour, than oeulod and extracted um; times, 160 El. portions of
Other. The 002be 94531015 “tracts WIN! mgheci with 25 ml. of I 5.53"
sodium hydroxiéa sciatica and than «11.21 25 ml. of later. The mam
«liberal solution u drier: in contact 2:35:52 91115576356110 21831in «new.
file Mineral autism m filtered to 15mm tan drying mam: am hxa
We fi-(Hm-cflmthylaminmwflvlofiwl—éfi-Chafiu’l-J-h.imvl NBS-.69
Wanna. m mmwd u in prwim magma-mien: by ten fitpa15r;m
precipitaflcna with We Wimgan amend» each pragmatic:
being followed by storing the sigma]. in an $26 bat: prior to tilt-wing.

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23.5

A 12.97.} g. yield of 1 var: crud: hygroscopic mtarial melting at

Q) —- t s 1
12.x) U. M3 .LJv-JILLV'A'. .1:-L..)! um "9.) L -X’i: S~Wu£.202.5 1. '1”; w...’ ;U\o‘

..“l £33u;l a 5.»; E0. bng,‘ J‘wLHJ, 1.10,} ' J‘Lviu 01:41.0?) 2. “(:2’6.‘

T -“'.-—'2 .r‘ —r " ”.’.... u. -.‘ -.‘ ’ Ii --: '- i D 1 - '1‘ -. 3;. ' it“. -
01.3.". to ..., at. cup—w" 'nu... ""V 4-H *4 .‘.-s’)‘ LinfigA’d‘kI-hdiyb Era-Jud. Jug-J A?“ -¢‘v$tn¢.ué 18

Q I . I '1.- “who .1" ._.” _ I- h ‘I q _ G. “b 1 In. .. -.'_. I {.'_
I'mtuefi 8v J-f» “in". 9. “W iuwwuw‘uo W‘béfi U: L-AJ fitting-OHM .Lv‘S'

“ -‘ 't"---"-x 2'24"“- ‘r ’- -" - w! 4-2 . 'n ‘ 31."; .. as ...-‘ 'r " r
car-.20“, wash-.2.” 22.2... 22d... 5.2222: the fchomb malts: Celc'... fer

'- *fr'f ' v ’ .. .'. j" -_~ --. “'2' " . _ -- . r'v‘ 2: r 9“
0“." “-3 'v’ W’.R...‘," 3” {tie} 9. 4.40.5.5. £02122»! ‘4, ans/0‘45 n, (or-«3

8’ 2.: 0.31.

Pragmation of 6Jeep?.elfit'rom-J'eztyl-QJ 23.25": 2;,‘3-2-vt3: 13m“ '1
It; Ill—fa? 9 31%,;420 c3 CLO}; i;.- a

a" flu ("I I"? x 9.72
‘;;,‘ .--.3 g .11”... 3‘ C.-t~
... n
r'.;"-I “JFK;

. 222.5 92222-2 22321252223". :3 and 572.232.7133. 1222;223:1129 were 22:: ‘ 2222 that r’emci’mi
in “the previous! merm‘m‘t—s 22521;: 8.0 3., flflf'j'b, 220122, of 2 ,3” ~73teetfij'1-v
3dfi=i mew; 2.01 ’3385" wad in 3.220 2211.01? m‘er P"“*"“1 ~23 3.2 g. ., {.‘.-37;,
male, 01’ 80312153: 12323220153 aid 11. 9 g. ., 0.127351; mlaa’ of hmrg‘mltno-
l-c‘zlorc‘camm .15”.r*.....".la- .-. ‘3 :52 Les alvasii in 5.3 2:11.. of water. fifty mint-ea
were reqxtre! to 0.6-2"- t: a 2222;192:223 WWW“ ol‘:2~1-<~‘1~M‘222+ .'13 5032229422222 to
the 2 , :5 «2.1.202; 231-3 ~t?~.5.o;wt:.enet‘.; 12:21 sebum. 15:13 22:3 Ellyn-22:3 by M
613.22: hm” mflmm perioz‘. 5.2%..” iselati._ 22* t 3 mete- 3.221 in t."-.a 222322223.
23mm: 3, 0.?2; 53., 0.0023 role, 22.15“; 5'2 22.3. of a pmcfuct 32:2: ting; at
1.23-1.25“ .50" m, art's“: tun: News ......1 Mathews i‘mn 1.5032901; 1 alcohol 22.23

cm; 2'2 221532111118 of tho (20222522272 for cafbon, Etifimfifln, unfi- 2!le

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mo tats fallowing 1-13.1.3: Cah'd . 1 .2' PH .335? .:I all: C, 395,;
H, 705:1, 5’ 19-92. ’i~.w~' (1, 5‘2 9",}, I}, 0:.?; £231: 8’, 1.90:3».
h'eparation of {q 1")"1: unot ".L-e: “‘11:“.101'0-‘41 18:213.
5'31le 1 a “rm-- .111? 1:";
' " .’V'1
8‘ 3:. 13 .2 18.
I3
d
'3.” a ”he 6:27:11“:ng rr>:*cr1‘-3mi in tha '?I‘£*18 “3‘"“" 0'5". r“?

aim haired-13:15:23 mlfkea was 1152-313. A 803.211.1711 of 5.5 gu, 0.1.3; memo,
of Wilma hy."rm:iua in 1.21:: 1:21. of? matey: mm prtayut'od 1:1 t’ve {3:10 r-l.

rem {:1.-1m filial; of the autumn. A 7.1%.; 3., 0 f .73 male, c; mi. 11.1! of
2,384inhiomfl-thiuphmum21.01 ms dimolvad 1n the ”dim: mail-oxide
{Elation mi. 12:9 1.21.1.2:- ma };-.3e\;'.a.3;‘3 to its rest“! at: 1.1- yet-at. m. A 5-3112-
ticn of 6.95 3., 6.0373 13:13, 01' 2-(p1.;13:r1diao)et.‘zy1 ct:- crlsfe EWJmchlort‘io
Ciasclvad in 55-7} :11. of vat-er was 9.15.94. (ray-«:93 fro-.‘.: the; 6033:5111: 151nm].
into the vignmmkr 91:1“er reflux- :3 80111111311 during a flirty minute
pat-fled. Th: r921... ~ 19': tilt!!! us at? "and at 1%: reflux tam nature for
m aid-11:15:19.1 It: hears, than 6:901:21. and n5 untested tit}: fcur, 15)") m1.
p<r~himn of et‘wr. the coughinad ether mtrmts vars mixad first with
20 m1. '3 5‘1 sciatica e! Ian-m hyfiraxim, met! that 1111.: 2-13 :1. of
afar. The ethereal r3 .ntion was {tried 1:! cantacb with m‘zfivwa
magfiezatm 921.5310. 1'19 cmi‘ea fm’mrix Emotr glar'é’, wca,c‘zlaro~3d‘tdwnrl
83.151 #73 hyfirocfww 1m 1.0 mm 13431;: 3:11 in tho mxmr already (14:33:21041 tram

the £1th red eta-r3111 acluticn by passing 6.1:: 1.3mm c.- 1151-1119 into

 

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bun-L

1223 cold ethereal cola-‘tinn.'1‘i.a precinct am: very bayoacopic and all

on- '\‘V\_~'~ .3. ~13 a:-i PA?J«.,§.J~.«¢~ t’f t:.33 raw} T‘r‘t ")1...‘ (3 in.) fur: a ‘- :9

Q-Aeks .'-‘ ...-90.1..1

b
ca-

fi'l‘..:.;".-:: P 3 " g 11.31" a t". ‘ ‘ f? 1. 4.!» ° (.’.:6‘17 11,1170 in a 711?‘='='=-'31‘ Bt”?‘.=’*“r

"the “7 W013 use: in 1:23 $111.:=r.t:'-.-s:r.s. A. 11.3"“ E'- Trialx‘. c: a white

....-.
.3 xi. “*5-5'39- 1...; G H.316 13.17!“ 1.227;» rrzctfis’ml'dz .93... ’9.-- "71:3 3‘ -.

in't-‘tfi‘rl .1.+.~.~c1 *1 953’: 3.. 0.“??? wiv. 71.1171, trial". a: a. was

641 1'.» a I'V“ r:-

‘..‘ l " ." “I H ..v~‘..“~" A ‘ ....
(‘0;OSNa1LL-1) r¢\:.: 'gr: -Jg|)-.‘v..v"l-' .- ‘1’ J.““O-.._J‘_ Si‘ri“

‘0-

. (v '. 9. 1‘0 3 ' i , a.
c.::3.:-r:‘.m, ...2-.t.i‘13 a: l?=.-.’i=--1.’:. 2 55., ms C'-t«112..-3€'.. mach-:13 cf .3 o

49
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C’.‘ 1:911:15. f3?! earner, ., 63172::me 33:15:12? at???) t .3 {...-1' Wt‘”-"1‘g

.'.. - q 3 f" c pix-'5 1. u, a“ ”Q ‘1.

Ilakllfl’ Calc’d. £03" C;;'13r‘za--J.;: 1", .3.}"7. :3 1:, L.~~'.} LA, ...Lari)
9 ' -.. ‘ "3" Ci; .\‘ '." ‘

a, 4-9‘27. P‘s-MC: C, ifogk.‘ £3, £...;..l.’h ~L, :31071- ,5}, 13.1?20

f.' ‘" . N .— ... p «as ‘ ‘- -’ ‘ «
41-53: “$1172: of 9%”, ' - {ft '15); .1! ..)tz'i'. 31*? ,3-:1.=3 .._ ‘3. AW ~L........,,.L
an. \ ' - ' o - ‘ ‘1r- .
‘71.: ‘19 a.“ 3’ =

A a \v 's ~h 01-};- ‘W

“A‘. an»..- .I I.-- (A.-. . ... ,
-J-‘,;.;c..n..l.~:o.(z..., 3.41:5); ...ul

A aslntim of 5.5 g” 0.11, 23.143 (2:? 89.43.1153 33,7 :0: it's) 0111 £32; :1. v."
mt‘m «:35 pray-ares? in 193:7 r-zac '13.}: flash 3:? tr) aggrar'aizzs p‘..‘J-Ji-.mibly
1937:1139" A 7.00 3., (53:78 ans-la grant}. ..3; 1" 2,5fliiczllaifl‘fi't.101}..’Elil‘3‘
$313.93. was (€19 gselvcfl in t2 7 f: ‘i!' '11:“. ¥:=y=.’I'c::.i-‘Fea .3313" 3.0:: 5:31? the.) latter 1:545
fiesta! to itzs reflux fo'vfazrs‘rlgazm. A saint-gm of 6.3-1 5., t’ .33; 3 3.4...)
of 2-6 3:31: zylnfimccx “in? "’ ...-7': .9 1.317.301.2132‘3121 3.93.1»). in 5.7.3 13.. cf L..-.m'

r. -‘ ' t .9... “.... ...-..¢ ‘ ., ..‘3 .5.)- q . *
m :1.-l... 3. aroma-:19 tr; 1:13: 31.1.. “2 9.”, 2:91.. ..3-.33; 5...; 411:: .t‘J.’UC...‘24-CL} 0.....11-

r).
E?

- ' u . " ”I. o - .---. n . . s. . . , ~.. ~ -1
ti-m or. a? I thirty 271.7,»: ..3 pwin}- . .7 .7=:=;.=.:L‘..<-:n :2.-..‘2‘.1.~e 1r. '3 1:: >1. 3...

ream t. 3373mm an as. -32.; 35.2: 2.02m, tea-a mule; an...‘ ...-=1... .:‘1‘...

It‘l. . Cu;

53:...
1:11.22 2.33am, 17‘: :21. ---‘-2. 5.3.2:: cf 1:51:53. T's»? C“""".'":.'. 31.217: 1.2317235
.. 1 - n4 ." a . .1: v , .. 'JA.
Rum anaxid £.rat 1.6.12.1 ...: :-*.. c... we w, an (“L 6‘1 13 0712.11 14;.»

Q

. 0" «1- ,8" . ' ...” r ..

tam-.3:..:~..~.:.8 33.7.1135 ...: sulfa .15. T21: hi 71319:]. 8:31 L1. .1 11.29 £11103 an.
. 1.31M! -. , 7 .. G 0" ‘0 km, , ° 9 .... ,10-4. 2.. ..-~

t: 3 cm a "‘(fii atledaL.-d.3b)~t }'l-..,..=-! .‘.r; gait-:2“ ....2...1 ...-.... 2 . ..z‘cv

a!

02.1911” van 13:2th in €29 usual 11211:: n‘ by ”rei‘ivfi 1411.1“ 1:: t1.

....-. .x. .:- 7' 3.7. 4 " .. ",7- .. .. . 1 ' 3 ‘ . 1' 9 F». f" :-
mummy: a. magma of L3: 3?- 2.1-: (L ....owa to mugs] 3.». '~..’ 8.. o. e.

’ a. uuuuu '3 ' -.' .‘x , , ‘u .. j". “, '0 u 0' .' " " . ‘9‘
on”; 1:12. act. .’...‘L-a‘r tame.- ruc..*v__ ..m..--:..t1:2r.a r1211 (13-; £77. :1“. .77.- ..

w ' . r, ~¥ ”fl .. fl _ "i‘ d n " a I ‘Q‘ ‘ .0 --.“- “‘W’q

“ I Q

2.55:2": ”’1‘?“ "-1.." 62;". 841.....1-«3 {"3301 "2.11"" -.:'.. 11.. :3 L:

‘Q
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t '.:.;»‘. £191??? a

. 0
25(21ng 13:31.11. f IVS-1:1 C. {.33.}.‘313 CI 1.3 63-75131. 71.21:? for 611.3177

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33:23.3, c-.i'. "Lac, 12:... 52.2.3.1- gave. tin fillwim; main: 1151.296.
f9: ‘12} 1=:Sa==-1a" C, 37.43 ""5 ENE? 53-: 33-""3 53; 19.1"". “21:7,"!

c, 37.1.}; 3!, .‘..333 CI, 3;.313 3, 213.133.

 

}‘-=f.'- d". 0‘ ;'- t L” C "T "-.- Q :'" . ‘3 ."" ' 'h' . :“ ~ " " L" -" '."O-‘.“
¢ -‘./W‘U-rJJ .- . -\A9’- ‘ G'H°V~"'--.. limb. «:1»; “-54%.a... ..-'*‘I..J ‘ vp‘wt‘iuAV
HI .1 '5 Q i I, f'.’ «V ‘ .1: J
3-" :I-‘DED ‘."J.+..L.&n'- "‘3 .‘. —:\-.~.’:La:n)*:-AZ "3
‘ v ‘3, “ 0 \ . "V'¢
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m. 1 " .1 ’11 .0 .-~ . .m 9 -v ..‘_” ‘ .~ 3 ... J. . ,‘ _.. V .. J. .“ .~ a“ .‘_, 4‘
Anti: ti;";'?kl 3:13.23 Lattfbx- ..3. 13’") ";~'-.' "f'.4.a".’ “I .'.?Ti'f'u. 57.34.35 .931 .3 1”- tr Matti-24. \r.»

that dc 55:21.1“: 3 L" t a yr: :21: 2112“» L”.t1'2‘.'.3 -.f auras It;"".:‘ot:' 1211...:
.A ‘ - .'.r w ...-.. T. - . v a. .1! . . . - 0.." . .. . .v
'11 "'22-" 18. .’. 7r“-" 3'50: (“Elf-2' 7191-3"! $2123.11.-qu 13- 3;. "' ...-.:"'.!.f~:“.:-~-.., 3.1- ‘3'".1‘3"

.'e. 3.x. . . , . . .-. 2" .‘f. . ‘1", .
in a 8-1:...1; ...-22., :1‘372‘}. 3,287.1; .. :9 ~ . Him. (.1’

$211 I '5: 3155931:
,.1 \ 4’ :‘x ., .- ..3 . .1 .. . .' ‘ F . .8.
”Cl"; ‘a'.\L‘-"' thn" 1- ~ C}.- me.‘ :J maids‘ 1‘1"“ 3'- l . (:3: m1 U631‘ ’ C. «M ~~ ' V‘ L>L " ‘ 3"» in t' ".‘l' f'ins 4‘" ‘0')

‘ . 'v r“—‘ ‘ ° .'." H“. ' 3""'.:'i' Q ~, I r. - an ".
0f "“5 ”mat-‘5' 1‘ 33-9-4141! 31" .‘.; (to: M2». M 50-0, if .312? L..-1‘11:-

. , 'P 2 . 5 ”.._ 3 ’ " 39 . 1, .. -" ... .-.. . 3 ‘ 3
”mew‘ 11911.29 :1;7.m..<fi.10r1 .9 r man" {:7 ‘31.: n". cf 12:. .42» m r ”an

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5...:
‘0

to L.. m rmmg mums mmaptm gamma over . 22211-23;
mama perimz. The sun‘s»; raaeuan mixbm‘a wan kept at its reilmz
taayammro for an 16:25. timed. o x hmm, 1.2.011 cooled at! 9.2mm: Win
£232»), lu-u‘ 22:1. purtiona of ”Law. Tins confirm”. «ti-sat entree“ 372179
“55.51"". initially vita 20 1:1. cf I 5:; 006m maroydxa solution and
than wit: 2-.) :21. of 2.21%. . T52»: 0:525:72}. 302.3102: 212:- ("$122222 2:. contact
3.12.32 mimwoua ruzgwsima sulfate, .1" Llhzroé, and dry 2m:rc:gun (22:10:75.2.‘0
ms Luljglud tron}; $229 astimz‘ filtrate. 1:15 I? iculty m mcpesri’ cad
1'1 isalatt'mg t‘fa cam-Lia f-(rl 33.25312.- ‘T'lrr' )mw3+‘**r ethyl-2,?gfq’ichlom-
34.13.237.31 mil 15’s hyér:-¢‘:ltn'ifia. T215 first 27:.th 1:322:32 precipitn‘bmi,
duritg the: a:i:~‘.5.t1.*m of (3:7 Eastman 32.102759, Va. -' (111123}; 1:; 67:27:37.3. iv:
an oil. 1‘19 {last-c was 3159:3277: and p122. L5 in an 123 222.32, wwmysm
£77 on 80115221721. T329 nits-3:373 3222;232:2132: of the crude maturial ma
ct «32.23, warnig‘nt, in a m1"2‘1ff‘}'fff"£f to 71.17:: it to crgmtnll'i.z<3.
751-3 21: tor-131 a. hand 6%.: 0.71;: to t .9 final. , 122927220123, tie 225.317? was
dacantad from 11'. am! the crude mtarial aft 6231125333 min-r71: ed in the
{La-3‘2: by cififwrmcs and fmmd to 129 15.37 a. 412.62: threw r5.)¢1‘3’$"fifllli33-
flown from (‘17 197m~cm [1 0.16521 a, (2.31 5., ($5223 2.7.13, :90“: . 1, yulL
of f-{¢,..~ «2172:3t5.“ “330)‘C-mfit" :3"; t.“‘1-€,2-L“‘ run-t... .am'l mlfiaa
WT2WF‘102‘12'29, melting; at 1312.645» C. was ohm: new . Analysil of 12:29
cos-29022715 far car-20:1, 33.7279373, cf-hzrina, 322:2 sulfur, gave the following

In.

remitsl 6:16:53” 892! “13:15! 6, 335.2...) 1., 1:53; C1, ELSLJ S,

,1"

2L993’10 Palm"! C, 33; gm ' 05:"; {‘1’ 3:5."31’ 3’ 2:).:.50

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2:51.133.

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4- .. .‘ (‘14- "-1- ’. 5..l‘...n‘1
Irma: . ..3-an (21‘ Y J: ‘ v.3 -1:-911* “~021'1-?,.~-. 1': ...a. row-13-11-;-
wed—5.5.x .3 1g ..3 LJ-a‘fidrh. a
- w’ \m 3"”:
if ya "‘ f’ a;
r’l
.- -. ..‘_; . ..J'...‘ . .‘ ...- .v a; - .‘. ...- -.. ...... .‘.», _ .. 3 . .—-~ “
3 8:11. 3-3.1.1...9 as Lit .; -..-.._. .... 3.11 p. -13....3 p? ..3-.11-..-13 0..

.1...‘..‘. :2 311 .. ..‘- #3.... H.’ ‘3' 3
£11.27 1.3394: '23’1?‘ 3 9311‘- 9’.“ 31‘7": .” - . is a..m..h.n of ,:.a 3., (..., :11....3

F. .‘. o ‘1; --"0o . . ‘9 6". .‘1 . ‘ "I . In” .‘.->3 ' 3‘ . -'. ..'1" ‘
:3. 3:3: .153 1.1 ".1 :3 <....~..»c.:...'.1<. S...) ,- 21. 1.. Viva? was 133,113.33," in ...:9

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:5!

.1113 liter rem-£1011 £11111: 4;: giant--3. A 7 g., Cali}.

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'-' ‘ h ‘ .'.: “a r 2!. ‘ ‘ ‘ N‘ o. .r J
of 2, .-.-i---.cro-J-..:i pal--11 1.93 .-.-1 35?. 71's.. in h. an and .1131 :.,*..*o.:-.-.~.:

4

As..-— O

mintlhz. 11 5011113011 of (.u.) rj., 14.4.3 3:19.113 cf 34:: '3‘1l”\i310.1.a'..mm‘

. 1. 1* ..3 ...-...; 9 r'r- p -.3 1..-: t. '.
{17:01:13.3 syn 1'53 . .:>:.°... '3 c...:1t(..-....s:.... ..3. ..l. a. 1.1.1-11“ 1111: fax... ...; to

...... . 3 v: C.‘ I. '. ......e 4.. - .1. . ~ .«s-s- - g -, 1 .g ,
61"., ...-in; 9.1....21. 2:... Li: ..1 L 4:1,. ..-:3 .11 11.3 8.323: ran-.1. “- 23.2.: -.3-3'-
" J- ‘ H 0‘ " . a .s < 0 ~ I . 0! . ‘ 1‘ . D
(tag-An mid." rm 0 r .11" 02.9....1' 1:” 1“: r1 . '3" .1 s... .‘9 1' s! :21 35.11133;
. ‘ 0' " ~“‘ -‘~ ' ‘ ‘ . . 4‘? Q r ’t‘ o ‘19 ‘ .
9729 3.33%. :1.. it»! reflux 3.: .....L.1:.....1m :32‘ at: :1--.1133: ...;1 .3.-.‘..- .'.-.11 3, than

0.12131? 93.! 9:."- “cxztcc‘: with firms, 13;? 2.1. 3?:7:*".:1:13 of ct‘.:r. The Ctr-3;" 35d

0"..." 31:- mrtmct: ware 1915293413. wit?! 1}. :1.. :1 5'."- amt-.311 ;M‘.‘G‘T*...‘9 {snowed

1‘3! :30 T11. of vat-:3: . T113 c-t 23‘3”" a;1'*tf.:n nut-..3 tiff-)3 in rum-3t 1.”‘.'-'*.‘L

a . '1 P (”-31 '. 3 .~—‘ \ ,1 ..m. 7. .4 .'
$9.3. r5215 2.19.3223 .513: :1.-.._. 5.11-, ...... 33133;, 3.12211 cry hyxcnn c... :1--.5:

. - .. . .. ‘ . . , .. ‘34.: .. .f....'&...
3:: :53? :31 1.23.3 t1: 5.: cell-11-11 L1 3 amm.:‘ .1103? Czar-.‘...- to :1" .1: ...-.....t9
1.251:- .3311? rw"5"1'i’.no-n~“"‘*“' -._ I’d”... *’ "..1:r'r:j;- d‘ 1.115131 311.1... 1:??? $1357.35;-

c‘ ““1- £1122, 31'1 3m px'tixl :1r331:.1*;”‘~'"=6, ”“""""" ’3' 1'31 .;:~.”‘ pz‘x‘fi-

.‘-.» .-. thd-H' A ‘hwiJ-w bani) WJV*-~ :. 3'
1.3121211. 12:3 cmza pI‘DELf.'.:.‘t 1.91:3 13:32.31": 11:11.3: £52111 (1:112 1:11.112 to yigzl.’
I x ‘ 1“ ' r1 “_. ' a . ..
11.1. 5:. of a c311»: pmmc’c. 1.1. '1': t'. rem rec- spa-...}.unums “Tar? . ”‘91-

~p\ ‘ r- r N ~~Nl
pm; "‘1 alcc 1 a, 8.1.7 5., 8.1.3.!- ...cl.1, 5.3.32; 31-31.: of y

f’“"\

..../

3..

‘

1’ 2-13-1933" 2. woman's-333;. ~2, «2. .’£2.11 3233-3-25. 12-3.. .2; 1 8:11:13 I‘M" .'2c33 1331. 3

5

1

23:11.13; 22.. 1334350 C. was $033111 .'. 22.4.222-‘233313 of the «33333313.: for
0333232311, hydrogen, 031.32.31.33, 6:3! 32.23.1122. g'ma the $31.13*: .3; resume:
‘ u ’1 ~ ‘71‘1 . ,

C‘LJ,UC :5" Gig; 14w; vlfl‘ C, wolf?» ; 5., 5.: '0'" C1, , ..‘(:"; 5, 18.1.9.

A‘

Found C, 31.52;} 2!, 5.2;; C1, 3.2-2.912; 5, 13.51.

2 322322423332 12 0.2; Y -£ .212 3:15.113 «2.2-: m3,1-2,C-«fici.loro~3-th1mtfl

“hm-“‘- ; d-JxavCL-udvfi 1.:‘Lflo-M"

2’33 appm'nmn 2.2.5.2.; in 224.23 2,3.‘233323t. 5.7.31.2...23313 mm the 8323.23 as m
mphym 1.. £223 prewioua §2r23pmmiio¢m of the 93.21.1229 mammary... sulfides.
A 7.80 {9, 0.8373 223C319,- (p.3.t1":.y of 2,5q‘1...lo.‘o- d'*'1'32““2""4'2'*"‘r:¢11. vs!
dismlvad in a aalnticn prw'mad frets 5.5. g... 9.154 mole, of 10.39.3331
.;,x 123:- »:ié-a 333:3 100 331. of wghn- and t} :3 32.113.215.913 "wwmtan salution ma
23339.36. ta 1%. rant»: ‘tmpemiura 113 £33 mutiny. £1352: of €223 3331353323333.
A 32312331.... cf“ 6.11.85 ,0 03??» 33:13, 2:! 3~3cmolmmlacfglompmpcm
62.2323. 31.214 in 5". 92.2.. of water- ma £38 <. 32' dram-:4 so tn the mflumz alim-
131213 raw-ca:- mm whii -on (31111215 3 ’(2' .rbv-f 11m samba patio: . The reaction
22.232.333.233 hm sum-32% at its refills: 2:233:23.me 33* an 5:2..-3101151 33.x Ems.
I... 332* be I‘S‘CMOI! 30113231023 hm! cooler, the oily mammal we: <32:th
3:1... 1: rm 15123 2.3.. 13034330323 of 69:32.2;23. 113 ems-33:73:23“ ether (mi-rm?» $33339
3232:: 32-2 $2.23!.- with 2-3 3.2.1. :3! .23 3'53. cm'im 3.9.3.2313; mmum, than with

2:2 33‘... 0112* water, and the: «team nation 3.2.2.3 3....-. in contact vim

7:371..- mus 331313991213 carats. T3 9 c ”In: a Y «warpfaclfinom-uprc‘jglo
2 , S«31c':31 ere-3%}:- 1‘3"“). 82:. 1.31130 33y: met-z“ aria a was moist-.5. in the mama?
describmfi above by bum-311:1; dry Imfmgm chloride ti‘tl” 333': 13:9 fry
swarms}. mlution. Arty thme racqzatallimticns from 190 32'039'1
nlcohcl A field of 9.337 5., 0.3335 mola, 75.733 of Y «rmrp‘wlinomu
gamma-2,5,1 in": lore-Bum 1cm]. v1.1.3 ”1(3- 9 1w roe hlorLJ-n 33233111,; at 1
115.50 C. was 03- tsined. kmlgmia of the conpovmxzi for: carbon, 333': rag-3n,
ordering, and 3.11131:- mm the follcu'mg results: Calc'd. for 01.3?1 5 3. 30313 a
C: 37.35] H, 11.53) Cl, 33.: 2.43 5, 13-3. 9. Founc’: C, 33.0.} H, 11.3353
61, 30.27; 5, 13.13).

Preparation of r «Rm-£193: ‘lazdm)-n«rr0pv1-2-diczfl.orco
B—thiem'l Sulfia. o mares. Aerie-.0

er! (11' A91 Qt r1"

.lab-Aru' 4li.)a.;:c
c1 ‘ 1

I'm same apparatus We. «played no that used in the previous synt‘tm-
net of the hyimcmnrifiaa of 1131116 U ”PL-Tea. A solution or 5.5 5.,

0.1.; mole of sodium 3:;er "13‘s VII dissolved in 50 .3 . of water in the
reaction flank of the Appenmdt A 7.00 3., 0.6378 9013 quantity of
2,5-c1chloro-3-tfiiophm01hiol m dismivad in the sodium hydroxide
wlution and. hastod to 1ta rails: twp‘s.r rams. A solution of.” 7.03; 3.,

0 .0373 mole of J-fiiatfzyhmino-l-chloropropsne hyfirochloriéo in 53 m1. at
aster wan aim-ed from the drop; mg animal to the vigorously stirred
raflmdm 311331.153 manta: collation m a period of mm mm.

My.

:3
w

E19 motion mm” m “in-ml at 1130 reflux wqawnwro fer an
s‘ditioml 91.1: hours, 60016:: Inc? outflow with three, 1C0 3:1. pox-time
of Omar. The combined other attests war. mad first with 10 m1.

of I. 5.! mm Ivar-oxide solution, fem with 20 m1. of water, md éried
in contact with anhydrous ammonium sulfate. The “hand Iolutian -
m awn-ed m: cm crud. Y -(R,I€-diefl7;y1&11m)-n-pmpy14,S-¢ichlom
Jdthtemfi. sulfide Wrochlorwo an isolated in tho previously floweribw
mamm- uuing two separate ar‘éitlom cf dry mucus Emit-03m ehlorifie.
The crude pros-Met was mat-sad with «hat. after threo racrywtnlliutiom
rm dry inopmpyl alcohol I 7.945 3., 0.0223 mob, 59.0%; yield of pure
Y dasthylamino )cn-groy;r1-2,5qfiomoroo3~m1inyl untido bmzrocflorido
melting at 117-113.? c. m obtain“. Win or the em for
aux-m, kmimgm, uncaring, and calm:- gave the following remit-s
Calo'd. for 011313333615: c, 39.2»!!! H, 5.142; 61, 31.73) 5, 1?.l5’.
meds 0, 39.62, H, 5.1.81 51, 32.02; 3, 19.01.

’ Praparatian of 5-?epermmoefizylaS-pE-mrgvlofidthiam'l
3x11521130 Byflrmbioricto

_ 3 ,

A three nook, 500 Ill. rmi bottom flask, sum-Omani in a hmfing
mm]... wan fitted with a reflux comimw, machanical stir-fir, and
firepning manual. 1 6. 20 5., 0.151: mole, qumztity of sod 12m M't’aroxizié
{halved in 10"?) 31. of "Inter." 33:6 placed in 15.416 reaction flea}; . An 3.0:)

g., 0.0.3.5 mole, quantity of 5-1-22;mgvl-z-udoymzat;do). m3 mammal in

 

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1.2m mum-a m‘ofizflo Ic'iutim. Tina quantity, 7.35 5., 0.62.0 mole, of
211peridfmo-l-cidomattam hyrimci‘iorufi, was dissolved in 100 ml. of
water and placed in the camping mnml. The stirred alkaline caution
of Sqahmyl-ZE-t‘. iop‘:r.mt&iiol m hafwd to in reflux tergwratm'a and
tit-a 2-121p9riciino-1-chlm‘omheno bgfifrochloridw aolntian was East: to it
dI‘D‘p‘H'JG over I fifteen 1:33.th period. Th. reaction mixture was etirred
n its reflux Wmmm for an uiéitional fivo and. a half homo. M.
the and of this period stirring was strapped, and an 35.1 pew fox—mm

on the batten: 31' E19 reaction flask. Mm: mung the nation nature,
M. was transferred to a separator? fume}. and the 011 3:25:50 mo wanted
fawn 9.1.3 aqmmza phase. ‘1'in nqmms page m extract-3d with three, 30
ml. pox-time of other and wrinkled with ths all plans. The ether-gal
”inflict: was washed first with m :21. 5' 6 N 3051113 hyr‘rozida than wi‘h
23 :11. of water and (Triad in contact with mflxyrirmzw mgnaei‘m mlfaw.
flat the magnum: Inmate had ham filtered Iran the awn-all solution
the EL'wiperiiinoefiz'ldjwhwi-Z-vtiimnd sulfida gamma. m

pres-1;; {haw from the ethar by bubbling into the oth wohtion mam-ma

m

racy-03321 chloride in the swap mrmcr u in the previously (3.225“:de
marina”. The product was isolated in two precipitation: to want
830933 M‘rogm chlorigia trot: biasing whim! to the «hm-u). colutim.

1.1" tar £1.13 f-piysrizf 111,063 Q'l-SfiszUl‘Q-‘fi Amy]. mlfit’: ea hylmhlnr‘lda
was recrystallizsd twice fro: 180m; 5'1 alcohol a, 10.512 2., 0.031 33019,
7?.1‘; 3191:: a! product. was 0‘23th which mum: at 161.2-161.S° c.

flak-alt of the campmmi for car’tvn, kgfimgm, m3 nlmr ma 122a

225

{ensuing results: Cain's. '..r our? 33"...9133: C, (33.31.; :7, 5.312;
B, 15.95. Foam: C, 60.23. 31', 6.53933 ,1?.;l

?raparation of Y q“ip¢31‘x..’1nom-profi3;-V cph-‘x ”1*
2dthiany1 3311”}. a 3' ‘drcc‘lcrifi a

Q flmzfixfix‘ am

A '1' 0 m1... tins-o. nac‘: mum‘s bottom flask, rapportod in I batting
natal, m rittcci with a I‘m comma, mechanical Inner, and
@309th ma. A nlntion mum.“ 6.26 3.. 0.153; mole, of Indium -
meido ciiooolvod in 1'60 :1. of “W wu placad in the reaction
this. An 6.00 5., 6.0.5515 2min, quantity of up: mv1¢2dtidap£zemtflol
m added to tho mmlm aolutitznm ti 1:: rmtion flask. A 7.93.. 5.,
0.64.5 mole, quantity of 31:1paridino-l-c‘a loraproxsax- o 1;,- rec 1151's.: a was
discolvad in 100 ml. of water max placed in ma dragging funnel. Ladle
1.- 0012811119 maptan mixture m vigorcua‘q stirred and heated at. its
reflux Woman's, tho 3m...l ”sari; mod-c1119 repropazxa mrflmscszlorim solu-
tion was «Mac! dropwiso to it. ow:- an eight minute parioé. m reaction
mixture was nun-ac: and heated at its r43. flux ta-zp-oramre an miditional
five hours to convicts the taxation. um: t2: .3 react: can... mamaw has.
cooled, 1t wac transfer 312) a capaxato‘g funnel and t? :a lowsr organic
puma was anmratod from {:13 aqueous plan. T118 aria-sous p?.aae was
asttaacwd with two, 53 m1. portions of east)? and the err'wacts we: coas-
bmad with the original organic 9mm. The ethereal solution was

named first. with 20 .51.. of 6 R Soc? in: 171%: 13.8 mint. on, than with

.... .4

.. ...

.. . n

’V .\

.'.. \‘
aIII..‘

.... - I
. V .. I a

.'l

20 ml. of water ms was in contact with easy-firms mimisiun 3:111:42.
After the Ws‘m mlfata has been tutored fro: the eta-areal 303.11-
tion tit. product was isolated ky bubbling at} ratings: chloris'o into
the delusion in this same:- may seat-215%. The f qsiporidino-n-
myfl-fi-pmlé-thiml sums. msmomriil m hoisted. 23,7 two
mar-ates adcitiono of twmgm chastise to prevent mes: hydrogen
chloride from being added to £1 ethereal. solution. After two ro-
crystallisation has 633’ isopropyl alcohol a, 32.1.) 3., 0.03732 .'.-ale,
8? .2! yield, of Y opipriflno-ndpron 1-5‘933m'1-Zjhi0w1 5:13:15 3

13:. ‘WrooaorLlo as obtained $1.101: what} at. 1.3.:5'15453 C. Elam-mm]. mlys
81.9 of the proCuct for cartmn, hyrirogm, and sulfur gave the following
res-ans: {.‘.alo'd. for cmrzmsgniis C, 61.11221 :1., 6.331 3, 18.12.

Props-re don of 2',.'-..nam~ww1-e Wino t2w1~3~tixioznrl 5mm;

 

A 0.643 3., G. "1330 sols , qsanti‘" of Liz-”inn”... s- 1‘; car-sass was
dissol'md' in 1;. ml. of absoluto Miguel in an 02.5.22. 1:121: twat tubs.
A 6.3;} 5., $9433? 32-13 qsmtity of 25-02223“ ;-’1-3~t‘: isp‘ 1Q“.QJ;131 us...
(313302335. 111 8s .1. of mt: 3:123. and tan (Emmi of. a 6.. " sodiun‘ “3:; “0::1; a

s a '-

1 ’1" ‘ ‘s’ * 0. -‘~ ”._. ‘ ‘a ‘ -. - ...! .. - 5-. . '3 ..'fi

V

tits. ass :uowkxx‘ into 1,-1.3 2,3,1. ultra» 9-1:. ‘.0:s0':s;.1 “1... 13011:. 10:: ., a bailing

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c3319 m aided, and the 33.212“ ms heated at it. reflux tmpm-amro
for five rimtu mat-1g 2 micro Mean burner. A yellow precipitate
for-mod mirfily upon mixing two tun calmness. The hot solution In:
£3.le using 3 Hirsch formal and the filtrat-a was allowed to 3001
tampon a yellow crysfllligm solid form-£41. After mryttalliuuon
of the solid. twice from m-anol 1% m dried at the rails: tomammre
of 3317:2231 in a drying #31331 31:. 17 m. Fig. T313 melting point. of the
profiugt was 1335-133 .60 C. flwrmfoal £315,331. of thin mus-3.31 gave
he fellas“ 3 results! Cain's. far ouzrnfigzac“ c, 1.5.33.3 1:, 3.257;

Prmmotion of 2',l:'-‘1-'iz~:itr0::1:2m- ~3,if-ciichloro-B-v-t'vi3:311 Sulfir’o

in eight. inch toot tube was 533.3134: with a 33.3.: inch reflux: can-03:53.:-
md 1.3 g., 0.013 3013 of 2,2.1.3.3113233:1.1.0331:221:2.mo was, flog-31:33:? in 3.2
m1. of absolute metfimgwl, wide? initially to two toot tubs. In. a 33335:."
night. inch to” subs, 1.5:? 3.3., 5.3331333: mole of 2,Efq-Eic‘;zlom-E-t‘dags?tme:a
£333.91 13:: (31550le in 2;: :1.-:1. 03‘ at: solute cast-mm]. coz'msinmg: 2;? aims
of 6 3 00:31:13 writ-02:31.33 solution. 133:6 alializm solution of 2,5«310§=.lo:~o-
3%:1op339nothiol was {30:13:33 into the: 2,134333':three-3&0rob-mmms 003113.331,
I boiling stone was whim}, anti firs rasctian afix‘imo 1mg hast-23:3 at its
reflux tatmoramre for £23: minutes using; a 53:33. micro borne-r. Tm

solution was filtoroi 13.23.12; hot 32.3 as: 60015.33; 1.33:: yollow

- A
flat 9-
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Ausfi

$12.4

2‘ ,".-'dLnitmphzmyl-tghdiz‘florot‘1:222:21 92.213139 crystallize". ‘32::
crude cierintiva was mom-stamina (2.22m 2.122% {mm firmluta 2:22“. 22:2:
to give I product Belting 12$ 1355-1370 C. 2.22;:1323122 222‘ 1:35 0021:“:‘3222‘.
1'31- carbon, h.--og::u, c2213:- 22¢ an: 22:21.. ’22:: gm tks {allowing results.
Calc'd. for clc-IE‘SQCInEEO" 2:, 33.2.3"; ‘2, 1.153 Cl, 227.19) S, 1.3.223.
Found! 21, 33.2.2123 II, 1.32; (:1, 20.213 3, 13.13.

Prapsration of 2’ ,14' «ixbfltrop;:ay'lvjupE233'2ylu2-t‘1123:2321 52.21.!an

222:,
{DU-2022-

A" *3 ml. 51212322222323: £13.33»: was fitted with I 8232.33. 22:12:32; .3.-.:me
6022.23.23an 13:11 suppartafi on a 1:22-23 «52:23 £12930 3 82221122.. 03"!) 122211832: burner.
A (2.? g., 12.5 milflmivahnt,camn;1ty 01‘" .. ,. «.114 wecizlarobmzma was
{1833122232} in 5 ml. of 312250122223 222325231202. contaixmd in the 50 ml. Erlrsmwyer
Cash. In 3 03:22:23: 5'3 12:2. 31:12:22.2:3M’ flash 3 l. 2.5 5., 5.2: 2:511:32:-
22:13:22., qmti’w of ;~,- ~91.2:221;‘l-3-‘.3-i:;?.:.:.2.22:1 was £219.30 lac-.‘. in 1: 22- . of
8522391323 22:22: 32me by ail. .23 12: 2.3220; 3 of 6 I! sorlizm .3320: 1.22 mint-32.021
to L..: material to £333: L123 £341.33 Bait: c: S-ghazyl-C~221.i¢,‘:'..ux‘...-ti.131.

Th3 2,1..«151 true:- 202033223113 33132432: was “3.2.3:: to 1.3123122; 2-1 spam-2212's

tiza filialfifio 5g2fzczzg'l-2-t7..i':;2 3.31.2-2 8:122 1.4.021 was q; ...: Ly , 12.2.:
12210;...3 Eflot ..,:.-2 12.53.3322 .laz~2.‘....:.....3 2:..-..‘.L-:.. 7‘23 2... 2.2.2:; 32:22:25.1):
{um-:22: and than 2:331:22; (“1.22.3 . “2:11.22; t2»..;:-.2;-ata:c 2:32- 3:22: 2.2.2.3223.

2' ‘l i‘ ‘ u: -q ‘1 ...-.2- . 1‘ «a A 2 I ‘ ‘ .. '2‘.\ ¢ ' t. ..3 u ‘ 3 - .'. . I".
.- ”2: ...:223 p: 332;.Lta’w’ .0... 3;. L:.3::2:..13 w...:.:2 2...: z”..::..-: ...:m 32.222222: was . t.

it

-. _ .....-

223

The pracipltata was filhar‘ed from the black colored solutién on a
Hirsch flannel. T29 yellow practpitste was 0.. 232.223.11.33 021223 120:: a
22512222222122.2723 1220922012221 alcohol 222112:er an... 2.22321 2.22103 from 33.22122 2322:).
Aft? .23 material wan 21-1-1921 in a 6212:1223 piste]. at 1 2:23. 22;. {22223252221229

at 2:229 mam: tmpermmro or 0.. ‘ml 12. 22:31:32! at. 1 4-141? .20 LL.

I1..:32~*.2:-.1 analysis of the cow tor carbon, 2322.120: 222.3: Bali-.222
gave the following basalts: (222122.21. {or Chgimfiaihc‘: C, 53.C.-£5 1, 2.313

s, 17.2). rm: 2:, 53.222; 22, 2.972 3, 17.6.1.

1.

'2.'i"

3.

is.

03.?" lb’21.
Ci'..(, 2. r‘ . \.

The 002313022221. 25112292222194;.1912.2222e2.2.1..1 and LES-elation)-
J-vmiophmAOI m mam-.2321 tar tho fir-It time by the lit-5.11m
alumina: Wide Mazatlan of 2 , Sidnetryleduuiwhmmifomi

chloride and 2,5-tlici.loro-3-vt‘raiopZ-2mmlfom'l cE'213r1213 mapoct’waly.

23 cc; 3130212‘22‘32—32‘22223'1t 11‘? M13 3238 agmt‘m'fl... 32.1 by a 32341:" ..3 12.22;”
previously Ila-:32: for 121215 cart-1:321:22: which 912222119 larger giantitiszs
of tin 0222;231:221 to be synt‘ 2222122221 canvmiantiy. 11:1. was SECS???"
13.8?292‘2 t‘;.m'21ffh 1:23 0211311373.”?! of t? 122-2231 31353322333313} 132322221? 3 to (3‘2: -0-

113132229223, 19110 .12.: by d: . ‘::;22 129.123 022 and are. “.22. 2.311322 with 25:21.11“.

The 0022290222123 S-phanyld-Edophanathicl wan prepared for £23 first

1.1.223 and diaractariaed.

T1123 aompamds Sctrm-‘Z-(l’mfizl 2:32:321)t.‘1..ap 2.13 an: 3,2«11 1:21:23. 23.2-

3422292222: 122101312 .222” um gathasism: 1‘92- t‘ze first the.

A nor-ion cf w-(B, 21-22111} yltrinohrgrj. substituted 122122231 121111222
132211222221.htm” mm prawns-22d hm £223 M22122 33-21. 2223122232! 3212222222222.“
2 and 3 13110932222232.1210”.

1"
«f.

13.

2; g

231

A. Laurent. Ann... 2“ 3L: (1 ‘44).
5.“... human and 53-. From, 3991-" 21;, 125.3”; (1‘91).
V. “49 gr, " .019 Tfiiopmnggr .ppe' 3m mnciwmig (1~l”'i?'i).

w. Stainropf, 'EQGC r2tio can Thiophsns, ' Stain opf . Le iptig, IEQI.
Litficprintaé, by :L-fiwmrd 33:01:: am, Ann Arzcr, 3 to wits-n.

H. E. Vartnug‘, “T icp ans and Its Larivativaa,‘ Interscienco
P31211353”, 132., ll. Yo, 1520

w‘ 5‘10 Heart and R. D. SCT‘E‘JQtS, J. A13. C‘"‘:e.f'-., 309., I?” -31', (1;:53}.
J. Eémun, C. Drummer! am .21. Sing, Ben, 23', 1231’ (1:22).

R. O. Clmton, V. J. Salvador and S. C. Lac cm a, J. A1. (1:212.
500., Z}? 3324 (12u9). -

J. P. aacn and V. U’. ?lne , J. A*. 3*QM. 308., __, 1&43 (lzLL3-
3. R.L ASA». and F.C d. v41t~ere, J. L1. 0:91. 500., _j, 735 (lzL,).
A. Maxim“, nan, y, 1211:; (lit-”2.).

9'. 329,23: and it. fimro, 132312., 2;", 1‘25’3 (135:7).

P. D. Caesar and P. D. Branton, Ind. Eng. C‘mm,‘ .1:.» 122 (1:32} -2).

(193:).

m

C'rallngm' and Van-inn, J. Inst. Fetroleua Tao 2nol.,?1. 131’

:1.. .53.. Rumnm, R. 0.: 21:.nafor, and A. 2%. 3w: 2mm, Im. Sing. Gina-22.,
:3, 3?6 (19u2).

J: ”0 81'00*., ”O G: pf“. 01123 Jo Jo hfil‘lfl' J. *1. C3331. 56(30,
”352 9 (15' ~..).

:1. D. TTartcug-t, ”Ti-aicpimne Md Ito I’:»ariz'atiw'es,' Intarscianco

Publirorn, 1116., E. Y., 19:12, 9. 1:2)“.

(2. 8. rat-val and P. D. Caesar, J. A222. 0:20:22. Sam, 72, 1L3} (15.23;).

V. ;{_.J A." m 3'}. 'rla.’ 49”., 1., 1.1:: (1:?L§)U

c ocu

25-
2:3.
2' o
2?.

29.

3c.
31;

32-

232

w. Stoilli'opf and I. Sc1.u‘aert, m... 52,-, 1 (1321:).
A. r. Sham, J. Ara. 6513371. 303., 2“. 2/51 (1}32).
Ii. Schloiu‘ar, ham, 1;, 372 (1535’).

D. 3. Vol! and 31;. Fallerl, ”:Jx'grallic Reactions, 701. VI,“ Jo‘an
ilty ind Sons, 1130., N. 13., 1.131, p. 1.10, Gupta:- 9.

I .
33. t1. Sun-2303' and Ham'm-ann, Ree. truv. Chum, f1, 30? (19346).
c. Pun, 3.15, 1:, 2231. (Li-:55).

A. Chrzaszcam' a, Rocsni’i Chem, 5, 1,33 (1925): Chen. Abate.

g1, law (1923).

3. 2:02am: mcl R. Bax-gar, Sen, L, 199%. (133)-

a. Baubargar, 5924.. 13,. 35-3 (1:97).

M. Gonbm'g and W. E. Baci'um, J. A5. Chem. Soc., £1, 2339 (19294).

3.1mm) and .‘i . O. Voromwov Lo lad a ad.1{auk (11.5.8 71.)“) E?
129; (1.21.1). Guam. Mast... a}, 2 :14 (123).

v. bieyer, as... 1:, 1.472 (L363).

' L.“ Eéaitl, 2%., E 7/2 (Ii-:3“). I

V. hog-or and. ii. in“, Iii-an, 1;, 2172 (153.3).

1:. Staimopf rd 1. f‘cpnm‘, Am, g___,‘<‘1 171. (1933).

H. Eaton and W. A. MW , J. C‘mm. Soc" 5253 (1)93).
Lager, “32“., 11, 1,15» l (1 mu).

w... smug-opt, .3. Jacob and 1:. Pam, Ann... 51;, 136 (1931;).
3'... richer, Ber" 23, 25-50 (15395).

W. Stojn‘. opt, Y. J. Patermicrff and R. 39rd! ,Ann., 7:2“ ,
2’2 (1.93 3).

3.2. L. F. T1833”: md J. Ensmsiscvicl, J. Am. Chem. Soc., 15:, 3352 (1’39?)-

153.
a"...
’45 o

57.

5-3.
59.
50.

61.?

c. ”0 fine”, L. A. LOOI‘LB, 3‘1. CO V“ Ca- an. Lyr.’ ”161;. 3.
Shelton, J. Am. Chem. 500., 11, 17.35 (17;;

o. Han-berg, Bar., 15, 2113 (1912).

E. W. the”, J. Am. 61:53:. Sam, fl, 2217 (1.95:).

S. G. Turrfimll, Jr., U. 3. Pat-mt 3,303,133, .iaa-x'zbor 2,1941. ‘
C. G. Cvarbargar and J. G. 19.1, J. 131.3103. Soc" 2;, 2'35: (13 1)
W. SfiqinE-opf and T. Hem-3r, Ann" L1, 17L: (1933).

R. Aziméa and c. 5. I’mal, 'Crganio S,:1rhheaea, Col. Vol. I,’
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H. Pfimil, 'Organic Sgn’o‘am, 4301. V01, fi,‘ Eran 91110;! and Song,
IMO, R. It. 1943' p0 3570

C. 13.31er sad? . L. Erma, J. Ate. . C? m. Soc., L, 5513 (195:3).
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10212114119: and Sons, 1119., u. 1., 193.3,, p, 22;“
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anflhm. Inc" 3. Yo, 1952' 2. 506!

I. R. wimod, W. H. firefit, and F1. Stunsfiam, J. Chem. Soc.,
1332 (1932).

R. C. Arnold, A. 7. Liam, a. K. Alm, J. Am. Chan. $090115? 731
(195 O)-

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65. R”. E. I’nrt'mff'a, 'Exiaphma and Its [arivatlveafl Intarscianca
' Puhliahars, Inna, “0 Yo, 1952. Pb 509.

63. L. F. Sommervillo and C. F. E. Allen, " A“39ni c 5,111.3 anal, Col.
Vol. B," John Riley and Sons, Inca, N. 1., 13M, 1). c1.

67. l. D. Chmnia md J. B. Tntri’wn, “Baghxicro Qualitative Crganic
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37. L. Ehorr, H. florloin and.P. 33th, Bar., 3:, 3133 (1933).

82. D. fitarr and a. R. Hi:on,'Crganic Synthoaes, Col. Vol. II,‘I
J01)“ 36115:! and 30:13, 13010, £0 Io, 1,243, p. 571.

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