H_:___.__:::_

 

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i
’z". : .'
‘5.. a .

-aJ-o

QSBZOb??

IIIIIIIIIIIIIIIIIIIIIIIIIIIIIII

III/WIN HI 1’fl}Ul’I/IHNII/HIHIWllllll/l/I/W |

 

A

 

 

MICHIGAN SYATE umvm

RECEIVED

wilt: ‘L 0 59

DE". .F CHEMISIIY

 

.___—

 

COEBISATICH PRWUCfi 0'." Z'PIEEDINECAFEOXAIDI'HIDE
mm VAR-10031.! SUBSHWTED PBBIMCETOHITmES

By

win-11.30.13”

A THESIS

Subdttod to tho School of 801mm and Art.- 01 Michigan
Stat. Unimdty o! Amman Ind Applied Science
in partial fulfillment of tho ”gunman:
for tho demo of

iVIAS‘ER OF SOME

BM 0: Ghoul-try

1959

ACKHMEDGLEIT

The author wishes to «1me his mum
nppmution to Dr. Mon 1.. Goal-m for his
almanac and ”313qu througzout the courts
0: thil work.

VITA

Home: William 0 . Day
Born: October 28, 1930, in New Album, Indiana
Ammo Cm: Now many High school. 191:5“l9h9

Indiana University, Rhondngton,

Elohim Stat. Unimity,
Eat Loafing, Michigan, 1956‘1959

Dog-u- and: B. 3., Indiana Uninraity. 1955
military 8mm" Arm, Jamal-y, 1951*er1: 1953

mloymtt Him“ 8. Harrell 00., cmmu, mic,
“hm, USS-869m”, 1956

CWD3¥SATIW Pflfb‘UUE3 0? 2"PECZLJIE' "‘ 31";{1133133
E1113 $3.35wa SUBSTIIUTQ LQTMV dxlumm

3?

m ESTRAG?

admitted ”mamasmcmmonmm
Stun Uxflvanity of mm. and Applied $01“.

mmmmmotmw
forum down-of

2mm 03* W W 3
W15 0: Chm

I’m 195?

mm £45»ng

1331*ch

A mien of dim]. mlomwileo was pmparad by canaeming

WWW with variously mutated phamlaoatonitrnu .
mmmmmm meow; to the Imam.

 

rho nun-nu used m phuvhoetonltrflo 1am. ma Mzoxr',
W. rm. rum-mm. WW, WW,
“HM-harm)“. 0-311 3": 3‘: 9‘3 WWWMW.

m WI‘HZWWMW mo row! to pound.“
wmwmnlvmmflmprmotma.

AW ‘9 mm WMMWIWW by
Wanting tbs cumming 30:310th ran umfiufwtory due
to em mm: to reduction at m amm- me new a» manic

m.

Efiiylmgmmm brands reacted with a-phaml-fifl $931333}. )nczvlo"
mm by lkmflimon to give ems-252731134 amrimfi )valaramtrilc
Wish m magnum into a 5:13.33 and 3 11:43.16 tamer.

vi

TIBLE OF COHTEETS

Page

INIRUDUCIIQR...................................................
.HISTORICAL.............................................;.......
EXPERIZMTAL..........”an..."..............................‘..
1. Reagents................................................

II. Preparation of Mandates...-.........................
111. mu maximum Intel-mutton”.....................
IV. causation Wotan...“...............“nu"...

'0 mnWOOuvoOQ000d000coauootoooouoaooouoooco-oeoQoo
Dmssxwoooocooooooooboaaooooaoooot-acotooto...cocoooooooauooo
mMCQ¢oloooovuoOOOoatoonocouootoaaocooctooo000.00.00.00coo.

WEOOOOCU.IOCOOIOOOCOOOCOOUOOIOOCOOOOOOOOOOOOOOOOOOOUOOO

I

vii

39
ho

9...

QOOOII

‘cq¢09

.0.0Q.U

v.0...

 

INTRDEUC TIGN

Since the discovery of their cytotoadc action, nitrogen maul-d:
have become the eubj act of wide investigation as possible chemotherv
patio egmte for cancer.

In wait of nomads at thin type for Downing for antiwar
mum Richy am am (1) prepared n,n-bn(a~omomthy1)p, h-
diphewl'n-propyMne end the corresponding diminl comma! .

  

H-GH,~u/GH'CH'01
\Oflfiflfil

RI. 3'. H, CH30

It the dedded to ettmmt the pmtim or duller ASH-11mm-
We having e heterocynlic ring in place of Qhe . phony]. or
m pmfi in the fl‘position of the propylmdne. The preparation of
W*Hé'pmdy1)‘wwlomm was mad m by condemns
ZWdede m4 phmleoetgnitflle . Hm, because of
Wm difficulty in reduom the double bond in the emlonitrne,
mpmpymmdhmemmmgmmme orthedeeired whom
he W in thin munch.

It hue been reported by film and Karma (2) that hirdmthyl-
unmetyryl)ginoline caused regression of tumre in test. animals.

0 NH O "\CH

Since the condensation promote or 2Winecerbaxamehyde iith phenyl-
mum-mmmwahmummimmmpmu
the mun. group, n m decided to upend the eeriee of substituted
(“.1171 «mm» for etudy at possible phnmologcel properties.

mu paper report.- the preparation of each a eerie. o: dieryl
«momma. eone or their chemical properties and the ettewte to
we 5W1. X‘Cz‘wmdylbropym“ . The acrylonitrilee were nede
by confining 2-pyridineurbomdehyde with e. variety or albatituted
mum.

{ESTORICAL

The cytotoxic behavior of nitrogen matarda has made these mapounde
3. 31131901: at Mandy in recent years 3.31 possible» chmmtherapaztic agents
for cancer.
‘ l,N-bie(B-ehlomet1v1)*$.Y*diphmwl-n'pmpy1uine and the eon-ee-
wmgdimiaflwmmmebmmndbyhcmamnmn (1)
for amening 191- anti-tumor activity.

 

It mama to “mm the preparation or linihr aomounde pom

I pyridine ring in place of the phezvl Oar anilyl group in the B-pmition.
There are man]. known route! available. for the anthem or

$, fmwmoe. mo Kwanzaa reaction can be employed tor

mm; .171 Aldehyde» with mwmmm 31mg mam

nits-um. ambleqmnt reduction tux-nun“ w. fl, T-mem.

here are e110 methods reported for pmring the “MM «made

by aim-ting phnylmetomtrilee . The muting ¢,§-di.erylp®pion1tflle

m then be reamed to the amine.

Aminee end Iodine! alcohoh‘bco are mallyulad e8 catalyete’i‘or
the meenegcl madmtion reactions .

Front (3) m thet Wehyde comm with phmynoetonitrile
inthepreeenoeoteodiuncthcxide, givingenemcclientyieldote-phml-
mmtrile. Salim: ethcxide m (Lac ma to prepare h-nethm-o-
Wtrile from phenomenon. end phenwhcetmitrne (h) .
hemmmwloyedbydaneIiatmdStephentomfln
Mew-Mon producte o: 2,14'dawthoxy", simma- end 2mm- 1
lawman eith Whale (5). Hm, peer yieide
are obtained with kW and h'mdrcxr3‘mthoxybemfldehydca
whenecdiueethoxidemneed wowmmmtmmmmuo:
thehydmbmadmydumepennmeombieinelcahol. nun-m
W to anélnwholiepomlhymndemw. non
neeinehleto commephwwmeeithmrmnlto give
mmmmo m Iodine ethane (6) .

mum mmmmm mu: mat with Wu in
momma-“Wuhan mam-manning (when __
W emetilbm rm rmthmphuwleoetmitrile. Lil-Mutiny-
end SA‘nethflencdimphenyieoctonitrfle end venous mastic aldehydce
in yielde ranging between 30 end 110% naing ecdine nacholetee ee consent“
in; W n—mu-ophmmm mm nth raitrobenefldehyde
to 1;.»me ma rnitro end 3-221th fleet
my. _

new and Emu (1) mat-ed e, Ir-dlphozvlpropym tron
mowicimemnitflle [obteimd in 95% yield by condensation of Wehyde

nth phcnylmatonitrilc ”cording to Root (3)]. by catalytic reduction
in 21mm acetic acid with Adam' platinum oxide catalyst . The radium
product In obtained in héfl yield.

Phillipa (8) 1?qu that cinahonineldchydo mated rapidly with
e. misty o: mutitutod phewucotonitrnce to produce to. Hmmwm
-phcwl)*i5-(h-q11noly1)-ncryiozfi.tfllea in 80:; or groom yield- .. Amt
pomeztnn hydroxide m the m1 cam... among: c more weakly heals
outcast, such It: dictum or pipcridme was need with n-nitmphenyP
WW» Amt];- the Itmngm' basic amt m aux-1mm
with more mm Infinite ... ‘ , , i

, ‘ufi‘DiPhWJ-Pmfiimitrfln can be mood moms: mm by

nmcting mommceommlc with bcml chloride mung e‘odiun mine (9).
3m” (10) rented tint 6.3-diphaw1propion1tflle an be obtained
mesmyiddoyuzc Mm orbonsyl chlorideend prom-um-
mmwweotupmpotummmdeend triathynnnc. maul)
mud autumn" mum o: mach with 2- an 1;“th
mm pmflofing low yield. at the nonnative mtylpiperldine‘l (11)
ans m 61mm product (I). who tonouug equilibrh would appear
a. be involved.

 

H

”W? 3- QUE)

*.

, a , H“ .

filemuutyorthehydrogmetom oreuthyimpinthev
end r’poeiuom otehetemoyolio unambcenutflizcd nonmetal
condensation reaction. Modlmdcr (12) was able to prepare f-etyryl.
pyfldim (embuolc) by moms e mourn or bmuldohyde and r-vpioonm
with mac chloride. sham end Wagner! (13) reported that acetic mhydrldc,
need an the condensing cgcnt for 2- or h-pioolme with aromatic aldehydcc,
W0 purer products and higher yields than did mine chloride. (human and
Ell-nu (2) 9011:501qu variously substituted benzeJdehydcc with piconnco,
mimidinc and icpidina using either acetic anhydrldo or Iino chloride.
my were oblate proparo Hrdimthylandnoatml)-qumo11ne according
to the following «nation .

 

Bahmr Ind oomrkorl (11;) reported preparing tho iloquinoljno analog
and variously substituted command: or this type of tho nine chloride
method. Bold. from this reaction are oocuionllly law and often the
product mat be mooted Iron the resulting tar.

Sim. tho pyridineoubonldehydeu hm roomtly become available
company, it was decided to condemn 2-pyridinocubonldehydo with
1 main:- oi‘ phorwlaootonitxilu in the manor omployod by Phillip: (8).
In the com. of this investigation it was loomed that @phonyl-fi‘
(Whoorylomm could be prepared in pod yield mm
2-pyridineoubonldehydo and phwlnootonitrilo min; aqueous potassium
hydronao u the oondonning agmt. The following function illustrates
thi- motion.

”.0 . i O “in.

carom

 

mo reduction condition: and by beKay and Brownian (i... Adm'
phtdmm ofido outalyat in glacial some acid) could not be applied to
”hawk-{H Z'mmldyl )1orylonitrilo boom” the vilepyridim utmotura
it mocptiblo to polymerisation in the presence or wide. ma double
bond in a-phwl-M 2-pyridyl)*ncrylonitrilo was also found to be very
mist-rm to otlur methods of graduation and .m uttenlptl to toure-
sent. the «mound mo unsatisfactory mut- .

Sunni Wl-fi-uwlpmmonitrflu ham bum obtained in
unlpooitiod yield: by roduotion o: the corresponding «Momma with
now mau- (m). Ava-amt: on 3pm (15) mostly reported tho
Motion of gfi-diphmhomontriln by We Uitb bonnyl alcohol
and M We. Although the add m :3th in lost um,
tho lam-011:1! o: ‘5‘ mm could to mppmud by momma out tho
tutor tron tho bowl aloobol Iolntion mu adding tho borylonitriu
mummhodaotnduotionmmtut‘wtodintbum

Robin:- (16) showed that an mmont of WWII: bromide
addod to Wmtrih to produoo ¢,B-dipbawlv&lmnitrilo (III)

“aim... .358 «E. W

0:53: 0 i-{fl

It, ill-tend or hydrolysing the addition product, I align mole:- com

of ethyl iodide were added and the mixture renamed, the resulting product
we the dieubetitnted compound (IV). ran disubetimted product, bonnet"
in; of only I. Dingle colid isomer, we obtained by liable: in 98% yield.
1mm (17) doing e ”investigation or Kohler'e mrk obtained 90;: of
Iolid product which oould be Iepmted by fractional crystallization and
mobmioel picking into two isomeric mun».

In Iddiflon' to the nitmgm meterde certain other 15pr of command:
hm been reported to pouoee mutt-moor and anti-tumor activity. 011m
and Kai-ale (2) reported that h-(rdimethyludnoetyryl)-qainolim admnietered
in e diet of rate bearing Lyntphom 8 tumors brouglt about regression of
the tumors. Behner and coworkers (11:) stated that e eerie- of
h—(hanimstmikeummm end ieoqximline maloge‘ oi‘ h~(rdmothy1§
.3111“me moved mum degrees of anti”: activity.

Gino. W-Hi-pyndyihorylomtrilu are lililu to the above
comm, Wingewridineringinpleoe of the (31111011116 group-ad

10

I1” possessing the double bond between the aromatic aubetibiente, it
W dmflblo tan-tannins this series of compounds for anti-*bmor
Ind mem nativity.

this pupa therefore, deal: with efforts devoted to the preparation
of the eeriee of compounds posses-sing e pyridine ring in e related struc-
ture in hopes that they may exhibit eindlar pharmacolo glee]. properties .

Benn 1nd lepworth (18) first tormleted the aldol-like mechanien
for the Kmevemgul madman which was later mpmrted by Kohler and
Cuban (l9) .

The W probably Wolves the following steps:

1. mountion of the methylene coupons! by dissociation of a.
hydrogen ion: '

vex-1.013;: H‘" e [Rhea-CHI"

2. Addition of the anal, probably through its ions, to the carborvl
eonpoundj

Rae an o + [Ruched]- 4- H‘ m RfiCH-CN

3 . ElimnItion of water from the aldol'like intermediate .v

RIF ’ . _ '
BfiH-CN H, H’ e 0H'(or 330) e 3,0 A 0—01!

: Beeee pmduce at higher oonomtretion or the enolete union in the
Inclination emilibrinn (stop 1) by removing the hydrogen ion. he ate

of the addition reaction (step 2) depends upon the demo to which the
~m‘bom'loonpoundiehindemd. Reactioneeimmto etepzin‘mioh
water is eliminated one «tally-zed by both acids and been, but genemuy
wide one more effectivethan bodes.

-. mammm’

I. REAGENI'S

rcme—W by a. Crock ,b. p. 123.1260
(5 me), 1356105113“, mfled (20) lope 1.1.:b.p. 261 e

rChloropherwiwetonitrilv-Premred by D . bp .p . 11.54%?”
(5-7 mm), 11133 1.6808, reported (20) n.p.2 211° , b.p. 25]. (2M)

n‘flhlmhmllcetonimmpflfl I. Pwlgok,b ope 127 ’1380
(8 me), lb” low, mom (20 iepe' 30 ’ hep. £65.26

The above chlorophuylecemnitrnee were W by W W
in the Organic Preparations Cour-ea, Chad-try 510, et Hichigan State
University. They were prepered from the corruponding chlorobenzyl
chloridee end eodiun We in eqzeone eleohol eolntion by the mthod
ehewn in Ormie Syntheses m).

Acetic anhydridwm white moi. Heed ee received.

mun Molrrw white label. Bed ee received.

m1 bmm .white label. Read as received.

Lithium madman hydride-dicta Wee, Inc. around to a powder and
etered in bottlee in e deeeioetor.

Wmmm Colmendneu. Redeem.
Methyl iodide-'3!“ white label Used ee remind.
PWWW white libel. deed as received.
PW nominee-hum white label. need ee received.
Wench, calm and Bell. and a: received.

bWMe-dmm Chancel Co... Deed ee reedved
Stored under nitrogen in the retrigeretor until needed.

A

“111 man.- were by Micro‘i'ech immune. Stone, mama.

Potassium Wee-Baker Wed Reagent. Used as received.
5% Palledinn en charcoal arm.

mango Remy nickel demystnpmviamy prepared by a... method
deecribed in Organic Syntheses (22)

Sodium Cyanide-dank? Analyzed Reagan. Heed as received.

11. PMABAflCH CE' WWW ‘

 

u deemed in We SmbheeesmB). In this method enieyl nacho].
in com into» the ehleride by vigeroee thin-in; with WW
hydrochhric acid and the remnant dhlcride in eede into the nitrite by

haunting with seem We in Inhydme acetone. Fran 138.2 g. (1.0
mole) of anieyl eldohol there was obtained 1111.6 1. (78%) of rumour
phero'ltcetonitrile, b.p. 99~102° (0.1. n.3, an” 1.5290. Organic 8mm»:
reports mp. 91-97” (0.3 1313.), r535 15285-15291. mm- or. 71-81:.
by In... madam (an) by the-continuation a: We
'withrheduflneudngemdificnfionci m-qum
We use dyntheeil (25,26). In em werk WWwo
wee W by amen a: ‘rnmmumummm with Wm
WM

murmur gene (0.31. min) of dry pyridine wee clinched in 300
Ibeddryetheeendhydronchloride'emminheheeolnm
mmmddo menace-pm. manna-mm.
wwwmmmumu mewithdryether, animated

 

 

to e 250 ml. flask fitted with an air condenser and thermmeter.
mmmncatommle (111.7 g., 0.10 mole) m then added and the
reaction mixture“: heated to 130° on e mile for tour hours. After
decline the melt was taken up in enter, about 50 ml. of 6 N mdrochloric
widenedded, addendum medbytw’o other menu. The
conbined other Mommmhed mooted. aw, dried-over
mmu,em the «harm mendedottonel’deenbem.
Wen at the residue “gave 9.5 g. (71$) 01' rhydrcaqrphexvleceto-
mum, hm. 118-150" (0.5 m). The mum-1.1 «audition! in the mew
ing and: and gum n.p. 69-70“, reported (27) b.p. 330°, mp. 69-70".

Mummflynole)
of wmutrile, 11.9 g. (0.09 Idle) e1 endin- ”incline
endloon.o£um1mdxedinei~1itermekntudwithem
endcdndm. mmmmmmnmtmmm
Wendtheuebemlmthmbeimefl.

PW chloride hydretheride (23.2 3., 0.135 nah)
weediewlvedinendnimnemmotweterineupmeorymmei. Two
nmdrodnmitmotwlmmphimdmedrymommbm,
dememthmwdedtotheupemtorymml. Potassium
hydroxide (7.6 3., 0.135 midweedineclvedineninimnotntermd
wmmummaddedtonnmnmi,mxy1mthmmguedto

 

memelihmtedneemm. anenmtioneeeremdewith
thermin'ingceldxylene. mommies! Wemedriedever
Alumni“ sulfate for 30 ween.

The xylem lentian a! the m was 0000:! to the motion flask
and W for harbour» mammrnngup the Wmmo
film mention an mad with war, was with 10% sodium hydroxide
”mum, and twice can with mm. The organic mutton was dried u
tundmtaomnwmmnauw thoxylanom “rippedosftnndor
Woodman. mwurmmautmadmaamm
um 001nm mm. 11.1. g. (55%) 01' a light 131101: 011 was collected,
hp. 15h"'.'155o (0.5 m.).

Am... Galo'd. for ounmnam x, 12.06. rounds I, 11.60.

W amtmhmmotoaiufiu ~4- m u
Mama Ln osmium...- (28). mum-mum (153.0 g., 1.28
mu)mmmtoumm'mum.s mucous-m-
mm: mm “id (Up. gr. 1.3.2) and 1312.5 at hominid We add
(up. p. 1.81.) with vigorous tun-ins. Upon ablation and Mimi”
hum, 110.: 3. (SM) or mmpmmutrm, mp. m.5«-n6.0°,
m obtain-d. Org-n10 3W mom -.p. 115-116", 50-th yiddu.

W. rmphuwmmmmu m mar-d by .
mutation at tho ”that! warm hr cm. mu «mark-fl (29).

. 3mm» pun (04:0 I010) at gamma-mum» In reduced
Willi: 1am Om“ am! of 35.0 g. and 30.0 g. A won
at manummmmmamu 150.1. at cm
«duo—Ind so :1. «95$m1m Munmtupunmuth

0.3 g. o: 51 pawn- «hum-d mm a 50 1.1. no mm m

16

abnorbad the theorotiofl W of twdrogan after four hairs; the other
mnrequirodonlytmondom-hmm. mutflmmoflm
«want the bio Donations were continua Ind the Iolvant was removed under
rudnood gar-unto. me any miduo was distilled an now; through a 21""
inch Vigrm column giving 1.6.1 3. (90%) otwa oohrlou oil, b.p. 139-1L0°
(0.8 mm). m. hydrochloride malted at 229-230“, reported mp. 230-231"
(29).-

W mm. m (0.061 ~10) of mmml"
main-i1. ... dimmed in 5 an. o: mm... mm... acid in
200 :1. of water. Lactic anhydrm. (7.5 3., 0.073 Ion) m then added

to the solution tenured WW by the addition of 9.2 g. at Iodinn
mute. within 0 abort. time whitewash-mind tho mum mm".
Tho Madam collected on o. rum, when! with cold Inter 1nd dried.
manna. yield was 9.3 3., mp. 69-73°. This material In W
mm» (a. 200 m1.)t1th onlyntumnmw a: m1 add to
.10 thumbnail. - m. maven-ed mam wish-d 9.1 g. (811), mp. 73-713.

Ann.0o1o'd. to: cmnmnfi. I, 16.09. row. a, 16.06.

W. mlmmumpmbywomod
dimmed. infirmio Synthetic. (30), for the premium of Ilkyl
phosphates. '
mum(3h$x.,1.som1u)mm1pmumaawm1y
toEOOnl.otuthm11nclflitarm-kfltmuthum, non-
dmmddroppingmnml. marmaftholodinnhadructodtho
Manuela-Watt. mwwmwnlmmaddod

17

during tha mu of 000 Jul: 01 the 301211110100 pram «king 01' the
We. An additionll ~100 :1. 0f xylem; m then added, the flask was
cooled in n 100 bath, and 76.6 3. (0.503010) 0! phosphorul mahlorido
in film (0:. 190 ml.) were added drum“ to, the stirred rotation nu:-
m-o keeping the temperature below 20". war the addition a: complete
thoracuonmmnmadonnmbathnthmtorlo
hon". MWmthenmmdmdthondiuchloridoonm
Intern-mind mmmuw. nthcr, thatthnrushbdncaddod
to th- filtrate. m. solvent. was mod under reduced m and the
pawn“ n: W by damnation. fin mm o: the com]... on
u 31.1 g. (bk-11$). hp. 90-91° (20 an), up” 1.3950. m mm
mm; pom :- 97° (36 u.) (31).

www- Mwwwwbrm
mwwam—nmwmn(3z,33)tormt1um
udnzphomhm-m

mum. (17.1 3., 0.086 .01.) was mad with 12.0
g.(0m6un)ammhylmmun01mmnmntwuwu
um. meMmum-lymuthtmm
Madman-.m'uonmm. .mmnmw...
nymuwmmam. mmMmowm
MummmmuthmeQSLKom
ummmmmmuuMWu-nmw. an
mmunmuuumfiudmmmu
wmwflmmntodoftonthoflmbath. Mama-aid“.

18

in W 11mm 5!." 8.3 g. (1101);: l 1.14:0 5701101! 011, b.p.
119120" (0.5 mm). (m hoax-00:00:10. melted at 166-7°.
' 1.1.1. 0mm for‘GImHquzl B, 10.25. rm. 1:, 11.4.7.

III . 0m mmmm IM‘MQHW

am. Phillipa (a) reported that ammumuohydo' 00mm mm.
Vithnrim Wain-11.- in nun-”um mm, 10m
ration-bl. 1.0 MM. um R‘pyridimmonldohfio ma bah-in in 111:.
m. In order to 6W0 mat «mm mum b. a... mimic for“
this nation, 0 «rial or 0011;10:30qu an aim with WW
unbound-Jayne tad phwmmmh in ethanol using 0mm pot-Iain:
W. piporidina, 01W ma lodin- authentic u tho condensing
030111;). I; In 000”. did tho product precipitant. fro:- the 001001011 0.
rapes-bod by Phillipa. It m but hand that warm I"
In won-mu choice, um WI-fi-(z-mmnmqhmnh m
mutt-horn ummmdum otthcuuiufiflfmod to
precipitate in: thc motion We.

-. The m affective pmcociuro :0: th. propmtim 0t marl-9'
(g‘pyridylkwrylonitrilo m as follows: mm. amount- a:
ammo-aw. and pbmymotonitrfln m aired in 0 5:1
WWI solution. ‘Whilo the mien m sun-ed vigorous):
uthaummmmuruwammorwpow
hydroxide m 000001.30 .0116 product which tamed in a n- mm.
m inland, dried, Ind Wad fmm SOS uqmoul 0151101101.

1 m cm“... method later adopted for the Wtion of
6*ph01w1‘$¥(2-pfiidfl)*acxvlomtmo involved carrying out the condemn“
am in inopmpyi 11001.01. m. reaction mm was allmred 1:0 mm
for Appmtaly an hour to assure completion of the: maximum.
Itm thawed into mum: of icomthltin'mg. tramway
precipitated may as a. solid. New to mm precipitation or
the product by adding inter to the 130::me almhol caution forced the
pmctmtotnlutimumoflmmotmmcmtmim
material. A

7 Emily the maimed mam-1m tom: «animation
prochm with 2W0 which maipiuw no: inopmpyi
Alcohol 0011101011 A! 017900.10 within mm m being camped tith
mama potassium hydroxide.

mm pound.“ We as: In 0300“" catalyst for no“ at
m- cadmfim. PM m and smith gmmmmmmi. _
been” bm.m_uod u my aolvqt 1’00 tho rotation. minnow: -
Win-110 m M0 m to alt-0W. its «Indentation with
ZWWM

Inpmpyl lloohol. proved to be a good 801m for curving out. the
reaction ml for mum of the products . When hopmpyl ..
Alcohol sad 0 pipcridino «Wt m used to condense rail-owl'-
”mm... and awnmmm. 311 Mm: mm): color
develop“ in th. rmtion mum. Hhm barium was used as the solvent
the solution did not W 00101. appreciably. The 0000010100" and

20

mmmumm product- «do wit. imlnhlo in tho almholl and
0mm, and momma an: employed as tho mimic. W
ing the» Mata.

IV. CWTmN P33330333

 

‘. Seventeen gram (0.157 28010) of
Wei-gym and 18.1: g. (0.157 10010) 0: phawlwetommo
mmwmlSOfl.atmpmpy1flmholinnSOO-M.Eflm
M. i solution or 5.0 g. 01’ 11on hydroadda in 20 :0. a: mm
m thawed, the madam“: nix-lad 0101000011818 “allowed
to ma 87mm. 0.. ”mm as W on m (on. 500 3.)!!1th
M.mummmwmu. mu Mm
0811mm 0110mm. mm MAM-imam to m trans. a:
m,mdriad. Wmummammtmnlso-i.
.11an Mom mined 20.8 g. (78.51) a: .818. mm. 3.1:.
63-613. 1 mu: Wm mm 23.2 3., mp. 65-66°.

inn. ‘ mm for 0.481918... 0, 81.52; R, 0.89; a, 13.59.
m: (c, 81.61; H, 5.01; a, 13.50.

 

11W (3? .9 3., 0.25 ml.) Rid 26.8 g. (0.35 ml.) of ZWW
Woven mu 111500-11. ofiaopmpyl alcohol. Himsmu
Wadinguu.0:20$upmpomumhymemmlbopn
mating in... tho 0031:2100. After am (rm-night the mm
«mm pradnflm separated by mini-mi. was one. with cold

impropyl 0106:.on thrao mammm. Thu dried mmmpm
55.3 g. (671 yidd),‘l.p. 121.1270. After Ella mmtflliutim tron
inopropyl 01001101 um product. mltod 01b 126-127".
Ami. 0.1010 for union; 0, 69.8753, 3.77; I, 11.65.
Found: 0, 69 .56) H, _ 3.90; E, 11.58-

. ._ '. Thnmndemtionofls.2
g: (0.10 mi.) of Wmmiahctonih-m and 10.7 g. (0.10 mob) of
2Wd¢hado m carried out in 175 ll. of inopropyi alcohol
ndngtqim petunia: hydroxide (1 pin 5 :1. a: at») to «nine
the reaction. “mummmmnummhuonw '
1110111: We and mu;- pucipittbed uithih I nimtu mm min-
mmmmm thapmduatwiaxod 19.5 3. 111011.01an
81.6 mm and tho whit. cry-hm melted at 103-10. ”5° 00 roux-yum
nation! tronuopmmmmldidmtm thou-imam.

m. mm :8. 0,312,021; 0. 69.81; h, 3.77; I. 11.65.

Mahdi 0, 70.00; a, LG]; I, 11.1.2.

 

. , . . . .- , . ' .' h-chlomphmncmnime
(15.2 g... 0.10 :01.) and 10.7 g. of. away“ m 013*
mind in 200 11.01 mph-om Ilcohol, £01m by the addition a a
.mln‘hion a! 1 x. of pomhydroddo in 5 I11. 01' water. 1110 motion
momammtoctmdfimontampommtotthrcomabutm
pMpiufim took pm. my mm us than pimd in the «trimmi-
my». 0. m1”. ”“8 PM 1:00 follow: 301111113. The
muonmskmmowdto “and 1:101:0aner 0001mm

 

diva before the product was isolated. The white crystaln were collected
mimosa-,mhadwiihnmw Wad formdm. 11:.
”015.811 maxed 16.0 g. ((67%) m0 melted oven:- 1 13h’152° my. Sacral
Wan: tron inopmpyl 01001101 only mmwod the win-anon
to nit-111°. Booms-1110mm ma 0mm and 1210:: .0191 m1:-
{wild to 1mm. the limiting point. ~

Ami. 00.10% for onion... 1, 11.65. hum: I, 10.72.

m m (0 .062 min)
01'. n‘mtmphmmtrilo and 6. 6 3. (0.062 10010) of 2m

aldehyde were 0111001700 in 1150 ml. of bum.- ‘mirty dJ'OpI or W
maddodmd tho mtionodxbummmmoo “and on: day. “has
munch tornadwarnoollooted annulus-madam. The crude
product «131.8 11.3 3., mp. 1305’. me mum nun nary-W
tron 8mm (8... 800 ml.) and 7.0 g. a: an mums, (mp. 138-200"
In mood in th- fir-t crop . £10 oonbinod nothwr limoro Iron tho
motion m and the recrystflliutim mm ah «diam 6.7 g.
whoa to. wins. a! minimum was "fined. n10 Mal ylold was 13.7
3.,82 82.55 0: W001. mt. amt-la from moth-r ”110111301100
unit-d at 1984.99 .5".

Ami. 0.1018 tor 033.030,. 0. 66.95; H, 3.611 x, 16.73.
round. 0,, 67.03; R, 3.77; x, 16.92.

 

0.. ' ' a... q.- 1. —n~

0! WWW was 00:10:! to 8.0 3. (0.025 mole) of

 

23

gmptmlma’wni’snll in 75 ml. of isopml Alcohol, precipitation
of tho 1011M crystalline product 000}: 1111.00 attain Amos without the
“cinnamon catalyst. wumocrystfllwanoowadonn
m m m... my mom 8.5 g. (85%) ado-hood .1 9:.‘95"
Roan-When W 0.1001101 gave 7.3 g. of wit. W,
I 13.9. 95‘96°. 4 .

1m. maul. for 638,317,: 0, 75.99) a, 5.01: 3.18.99.

rounds , 6. 76.1141 B. 5:15} 13. 19.07.”

m- m or 9(rmnowxawll-fi-(Wfl)wlommlt m added
to abaakdr coat-11:111. 25:11. otuw. mum drops 0: 0000mm
hadroolflorio Acid were added with stirring remind by 000 Addition of
15 dmpn 0: acetic W0. A water nolntion of 0.6.3. of Dodzhm
«mum added immune! the aostylntod pmdnct found as thou-y
pmipihuo. 1m: potassium hydrozddo was added until tho solution
moo-iota 11m. mommohmoonoohodohom. thrice
nahodoihhmwdriod. myonoomomnhopromctmtod oh

Ida-197° . mmmmnim nioodflmmiiing
pong to 211.5-212.5°. ”axis 10 identical with tho mm; point o:
«firmlekHWdyuymomm W tron
Wommhommtrila and 2Wehydn. A nixed
melting point ottho hm product- Ihmd on depression.

 

(0.05 301.) of (Miamophwmmnitrfln was 001100110011 with
5.3 g. (0.05 mole) of 2 .. m - -a in 175 ml. of inopropyl

 

21.;

alcohol using aqzeous potassflm hydroxide (one gram in five annular-3
of. mm) as catalyat. Inflow crystals precipitated from the solution
within minntea after tho alkali was added. Upon oomletion of precipi‘
totion the product was oouootod on o filter, whoa ohoo nth oold‘
ilopmpyl alcoholfiund twice with water. The dried 'yonow ammo nighed
11.7 3., mp. 130-1313. When the material an mmmnzed my not
mm alcohol 9.3 g- (15%) was mad. n.p..135-2.36.5°. m- pm
Most «1m Qt 1.35.5“1365o ~

m. 0.10.66 for c‘alax’. C, 77009, H. 6.07, H. 16.86.
‘ rm. '. c, 71.26; a, 6.13; x, 16.95..

- flMOW‘
'uetonitruc (55 to. 0:032 hole) and 3.5 g. (0.032 non) of 2%!”
W m wound m 1m :1. of W1 alcohol. tow
wmmflnno: 0.5 potpomhydmainS n1. oratorto
titanium. Manammhrmd mmmmthouw
.1... wood. m..- otonangmmoom opmtoto «who...
«W on I mm, mo with cold mpmpyl alcohol, water, and
mod. rho 11-14 m 7.0 g. (81.5%) o: ”no: maul. up. zoo-210°.
“hm Wounm tron ammo an ”no! pktolota, mp.

2115-212 5" '

m. Calo'd. for 01,63,150: H, 15.96. Fahd: H, 16.18.

 

- o Th1! 1717717110 m Med
u : luxur- with fiWW)~BflW)WfiflJa

 

25

, by the following pmcednre. Fourteen and seven-tenths grams (0.10 mile)
or Wmmkoebomtrfle and 10 .7 g. (0.10 role) of 2mm
Mouldwyde were mixed in a. eolution of 75 m1. of iwpmpyl alcohol
in 200 ml. or water. mree game or potassium hydmxide dissol'xed in
Sui. or water“: thenodded and the Wm swirled vigorously:
few edmtee until the eoiid product meeipitated. me reaction mixture
mthmmowedto stand emmerebefore filtering Marthe
emdepmdnctwnlmhedendnirdned 1t mason 21.3 :- W“
tiara tron nopmpyl Mahatma We type. of email... me (the
mommymtodot'zws‘: mammhhmtehmm
hm mm) united ot 118-132°. much or tho ammo-u.
:roatho W’flmifil oohtmdbyrodtooolmthoomtho nothi-
nqm and mtm tho mention to atone. no month-no metal:
mar-t mam krplyemtd memmumohrdmt?
'i‘nzee mmempmoipimed mutt-11o. noumoutruono
W from fresh impropfi. alcohol, 1m g. (53%) being
mod, mp. n.5«73.o°. Tue mm Wm thou-mo
tho swag point to 124?.

an. - Gale'd. tor 0,531,179: a, 11.86. Found! a. 11.73.

. 8m m (0.053 aole)

 

of amnewmmdtme was dumbed in a ”lotion or 3-1; “. (0.06
ml.) or pom hyomndo in 125 h. or ntoo. mm
115611360 (5.? 3., 0.053 holdmthenlddodwthemtiondxmom
WhMefimWahron-dq. momma"

26

pmdpimed by adding when dioxide (dry ice) to the Iolntion. me
n¢e brown solid was ooneotod on n filter, washed with water, in:
dried. The yield at crude product will 6.1. g. (1435‘): I.p. 155‘1580.
Wei“ tron inopmpyi alcohol we 5.0 g. of an mettle
mung ot lob-165°. o oooond Mme» did not change the
melting point.

Anni. We'd. tor oufimnfic O, 75.67; 3, £51.; I, 12.61.

rm: 0. 75.66; H. ham; x, 12.55.

 

phonyloootommlo (36.8 3., 0.25 min) no 28.0 g. (0.25 min) or
amuse-Immewmaddod to trutcm-kmqernuk contain-
ins 100 :1. of 95$ ethanolond 500 ml. of m. too you a! petunia
mandomntomthmoddoauummmmmmm
mm until the pellets dumbed and the solid communion product

formed. m filtering, washing with new and drying, the crude material
mangled 58.9 g... mp. 118-1306. Won than my]. me.
ammo 51.2 g. 01' white man. no yield no 88% and tho melting
point no 1.1.8'150" . in additional momma» wood tho melting
point to nee-150.5"
moi. «nova. tor 01533179,: 0, 70.85: H, 5.55; x, 11.02.
tone: 0. 70.71.; H, 5.621 x, 10.91.

_ ‘ ‘3 h_ I a 1'! --o o up}! nu“ so.o_ru' 3- «no one: ’ ~~HVDU I ' .I i...” 9.! 'or a
Three end mm mm (0.015 mle) of n’fi-diwxylminoethoxybhmvl‘

2?

clinched in 75 all. of ieopmpyl alcohol. Ono pellet of potassium
hymndonoduoolyodtnommmoorntorondm oddod to flu obooo
tension. muwemfionldrbnreetoodtormdqe organ-pro-
osrdtotod non tho oozntioh. Upon nrndhg them only port o: the
m0 went into solution. Mohammhtionwu filtered 0.8 g.
or orange email, mp. 156-159", we obtained. Arterreoqetflliution
tron ocotonitrno tho resulting om noodloo halted ot 157-159". in
main mootodthot tho noted-inns won-anon. m. reportod melting
points-156°(3h). W '

- = Anni. Calc'd tor 01,11,985)“ 0, 67.27; H, 1.111.

Fund. 0, 67.59: H, 1.32.

' me nether ligmr from the obove product gave n white precipitate
upon standing. mo Wm. connotedonnm,wed1dwith cold
mmmolmn dried. The yield at «(a-(methymhoomoxy)-
mkrmm-Hnmmwmmm m 1.2 o. (25:). mp.
lot-109° . Ween from inopmpyl alcohol mind tho mlting
point to 108.5‘109°o

Anal. Odom. tor Cfiflaotl c, 70.78; H. No.
MI 0, 70.68; H, 7.145.

   

(0m wok) e2 Mp’ehlompnem)-fl'(2'pyridy1)aeqlonitrm in die.
Iolved in 200 ml. of dwbename, 6 g. of methyl iodide was added end
the oontm wee allowed to stem st noon tmmo Predpitatim or

WI

ammo! Pmcrs or 2-9me
mm unwed! mnmm mom-mm

28

 

 

 

a - m H.p.°0.
. 1. a 75 65‘66
2. 261 .. 6? 126.127
.3. 301 , 82 mos-101.5
1.. 301 67 13m"
5. are: a; 193-399.;
6: an: 8.5 - 95.96
7. 2m 85 2115-2115
8- 21708.). 75 1355-1365
9. good. 58“ ' 72-73 '
19. 2MB. -- . 55- WoS‘lE'flJ
3.1. 1G! 10 WW
12- ? 06.15.170.719.“ as 108-5‘109
:PW wood or mum

bloat-anew
finmuwmmiwnmmmmmm
memottmwlmwkundthedmtdmw.
Whmlmmuo
Winn. rm impropyl noohol, m, and
Mlmumldtordmthonlmmt.

29

momma-unimamwwmmmmtionmmod
fwmmbdonmnttewtmmdemieokteflmomg cry-lull.
After filtration, washing with dry benzene and drying, h.5 g. (5635 yield)
of anemia III damned, hp. 211-212". Reoryetmiseticn iron on ._
ieopropyl alcohol‘eootommn eolwm'i: gave orange needles, 1.13.2115"
212° deo. ‘ _
Add)... some. tor anthem,» 0. 1.7.08; H, 3.16.
' mm: o, h6.891 H. 3.03.

a "4 " ,- - I. “

:‘ lt'l‘ t'PQ'E OUT”: LI Q’p l ‘ -' ”015.1 or n)“ t) o n a nu .oo o o ‘0 o ..

31! 81'!” (W21. lab) at 5W(WW1H'(2W)*
pmpiomtrilomdiswlvaliaZOOnl.otdqWIdthemmunt
of m1 oddod to toko tho noted-m into mutton. . mo hydrochloride
mmmpmipihmwmnznmptmletowmmgm
oh1or1do. mmmmmgnthdrymmmmpor
emdeprodnotmobm. Monitingpointmetmtodfilemle
modemiliozypemndmundzoo°. moaningpointotme
ataxia-l m «tutu-bed at 2257-230" by the following Intend- me oil
Mthmgrmmtonrimtmmmmmdmulungpointoitho
Wtootodhymorodhgthotsrotthooommry. Brawn-Men
WWetmiohmmhhokmmhmtm
enmitpownhommpomww. 131011th
mwummmomwwuatynmmttum
’anmuntom. Dryethummioklyoddod

30

forcing the “if. wt of Mint-ion. 85.1: mm (88%) of anemone platelets
was moved, n.p.231*232° doe.
Anal. 683.0%. for 0351131730: 0, 61.963 H, 5.21.-
? rm. 0, 62.1313, 5.25.

.- Twenty and m-tontho m (0.10

 

mole) of e‘phonyvfii Z‘pyridyi)~ooryiomtrik was diuoine in 120 ml.
01' 8120031116.. eon-n01 end added to the rink tor high pressure mommaon.
The ”Intima- chilled inedryiomtonebnth uni WWW
m1. of mono-muons added. two mor‘amaymokumoddodohd
the WWW “hydrogenated of. 3500131!” murmurs at an
elevated temperature (on. 100°). mo catalyst m filtered off and the
solvent was removed under reduced presmro lowing a. rod‘vellm oil as
midue. This mterinlwu distilled at 0.5 on. pressure “in; a four
inoh Vim column. A form 01‘ 0.7 g. of e light yellow oil W
at 60-d1°.n1roo other fractions wot-o then collected: 5.7 g. at 130-3330";
5.11 g. M; 1502:1155"! and 2.1 g. on 159165". The fraction with b.p.
150-155" (0.5 no»), on“ 1.57215. was tired to identity the preach” me
.11 round a. yellow crystalline salt with piorio laid, mp. 215.5‘2165".
Phanwlieothiooyau-be was and to prepare the We: darn-tire.
(30:1: :13th to have auditing pointbelow WW.
Hm, the hydrochloride salt of the pherwlihienrea dominate no r
o nito mot-111m out, may WW0, which mtod ot
176‘17700 M It“ fit the following “3311!.

5' £31.0n10'd. tor cur-13.011733: H, 10.91.. round: x, 10.95.

 

31

«- .—.o , a.

W. Mamm- mugs (2.9 g., 0.12
moon) m placed in o ene‘liter- nook fitted with o sun-or, don-
dmeeppodwithnuidnnohloridlhhe,nndedmppingfml, and
thomtireayltenmmnedpnfly. odohundrodndnmtoroordzy
othy1othornooddod oo thongaoodmtntho nook. Ethyioromdo
(12.7 3., 0.12 mole) no dawned 1d 150 ml. or dry othorond m...
intothedrewdnsml. MWofthee‘thylbrome Deletion
mthouoddodtothonmunondthomuonmemnomrrod
vigorously. m..- the reaction how {the ethyl brands oolnflon was
thonmeddropodutothosurmmnmonenuutowmn
ooiowunnxwhonmtoo). mmnoomumodonowmhr
ottorthooddmodmmto. indenting too-innitmot othyl
branch m added to convene the mounted nonunion.
”mi-p-(mfidyimrylondmo (20.6 p, 0.10 oo1o) wu dir-
mindinzoo-lmrdrrbmmdthnoointienmmdromoto
mmmuthlfin'ingmnamume. momma
meuotmodunmmdonootmbothtornuhouro.

. me oomph was enameled by adding m1: e dim-ltd solution
(a. 100 all.) a: amnion chloride. The organic layer we washed three
to... with out», dried our potoom'ooromto for too ham, one th.
1101va it. «operated. . , . .

www.mmmled 11m». 51qu 16.8 g. (79%) a: o
yellow oil at b.p. 11.0-11.2" (0.8 ”J.- m new to proper.
n nibble We mid alt from hydrogen chloride or piorie mid

32

were unsuccessm. Tna salts may be. too hymscopio to befimily
amazed and purified. me 011 m mdiatmed at 126-128" (0.2 mm).
The diltilltto comm upon W in tho ramgemor, mp. 61'3°,
mmuomxcryatmuatmnmmn-hmmgmmpdguw
isomer. 81: mm of 901016.083 chunky crystals, mp. 67.5'690, um
ohm tram 10.2 g. o: distillate. , Recrystallization of the solid
1mm did mt change the melting point. ‘

m. Calc'd.‘1'or 0163145: 0, 81.32; H, 6.82.

round: a, 81.19: H. 6.83.

33

DISCUSS! C31

_ Tho ooxfionntion of 2'pyfldinaolrbmldohydo and ring motivated
Wan-nu pmcudn according to the mum. mum.

 

Tho tlblo onpago 28113153an prepared tam-m.

Bunny tho Lotus-nudist“ undo]. coma: in this and is unable
m (put: out l mm or untu- lpontanmly during the motion
yielding m mum. on the m1 product. Honour, when Mon?
phmy‘llcvtomtrfln was condensed with ammohydo the moi
tumultuous M10 mom tho onlyproduct W mm the no"
lotion mixture. Law, when this condensation no mood, tho and.
pmézatmIWofthOMOIinWmd the «hydrated
30W. rlw-mmmmmawfl-mmmm and 2W
Wool-eterwnltabhfldoloommmohmtho solo
product from the commotion Mon. ‘

Evil. and 1mm 100m of tho oondemaation product: on possible,
although in no Won: than evidence of more than one 130m: produced.

Presumably the isomer isolated from these comimsations is the 5m;-
mdirioauon where the cyano group lies adjacent to the pyridine ring
(the phemrl map on! the pyridine group an trans to one another).

.3 _ Q;—

CH
N

/\

.5.

ELI-Pm Inns-For-

Dafladst and Stephen (5) Ian unable to hydrolyze nit-1'11” obtunad by
mu: continuation: 1nd assumed that tho product.- m the Wm.
It. had been sham by Preifl'or .(33) that 313 tom 0: cm olnfinio
morn." mmm-Wmmwmmmwmw
without difficulty.

It 1. poo-ma for m moleculaa o: 2W1nocarbomdehyde to
"not in I Won‘tpr common to for. rpm-idem. In only one of
tho lint-ed condo-among. 711., tho propmtion or rWfl-diatnym'
'WWWJ’PWF1W)WV'&0: I“ “I." W
2W WW tron the "when firearm 2“Pyr1doin my havn
hm found in mu reaction boom” of tho slow precipitntion of the
hydroow attain. or bonus. from 2mddnocmonldohydo m not used. ’
m com-motion product, 1.0., the hydra: 1211.21.13, did not precipitate
until “in m dawn. m tho trim-11a hon tho other conduction
mom pnoipimod within mm. If this dolny 1: due to a slower

35

rats of much, perhaps this allows time for tree 21mm?
fldnhydo to condemn to for: rpmdoin. Also, when old 2'pyrid1na’
cuboxnldahydo is added to ioopmpyl flcohol an insoluble material is
611mm mama“: 1'11. Iolntion. _Paxhapa the mom substance in
Win union in formed by lelt'oondmsation of. tho memos upon
standing. mo insolubl- Iotcnal m not in suffioimt quantity to he
collectedonifiltlr.

11' Wl‘?‘(W)Wm-W “1' W 01 “I. W Nb”
mmwwegumwnnmmm,mwum,md
nmmumnm,mummmmuaum
“humoowmthobottonlndliduotthooom. mutation
ilk” plan. may. within I am or ”coal: undu- opumn conditions.
rorthnullonnhmiwodmtpomutmmoumthn
ommmwmmmm. tool-roam
wubmmmmo polymiuflon. mo hydrochloride alt
armommmmbowamwmwwmm
WWmmofldouammunIotthooowudryothor.
mmwmt,m,muommnmmcm
prom moo-Inno- damning the W in I ooh-no. Sim-on;
ammubmmomommuuonwmumumnm,
ammommmmnummnomm.
“munmmutdmnmtmtorpom.
in W 1.! mm: In 1mm pawn” line. i polar Iolvent
Ind n In“ N! mink! for the Mon. a,§-Diphm1m1on1trilea

36

do not bohovo 1n thil lunar. thoroforo, 0M tho pyridino ring in
tho otmcuro plm o nannicont who in promoting tho poWon.

ma hydrochloride oolt o: fiWflpa-thomhowlrflmrmfl)‘
pmpionitnlembopropuod olthoufin one mum cautionuhm w
cmtallioingthoultinordutomiddohydmtionondmooquont
polymerization of the compound - _. ..

no donblo bond in Wl-fi-(mdyl):ury1omtrnu appear! to
ho wry mm: to Induction. Whoa o-phoxwl-fifl ownwlonitrne
mom-“dun; olorgomoloof ummmmmanmm
mmungpoodnot. nW-mumoummu
tho audio mpthourodnood. .W.Mthodoub1obom
mmmwmmwmmonmmmnm
pom inthopmomoofonooid ondfitttwt hammofl.
tam romltod “ammonia. Lttonpto to Managua tho doohlo
bondoithourylommoonxthooudmm {motho 11mm-
mmmmmwmmkahmln
mm“ sommmmm. 80. per-
(WW I” “W in 1" 73014 by mine WWI-‘5’
(W)Wmnum mmnkaansoommmom
mom. _

, um Wmmm 1o unnamed anon 2W
WWWMMmW. moddehydonlnmt
81% tho noun Iothylono of tho. gmmmtrflo by tho
mm mention in tho mar com with tho other mbotitutaed

 

 

o .
.
:
... - _. ._ _. «. ._.
u
o- u .. -
. >77 ._ .-
\
__
o
o . . O
I
.
I
.
o
o
_. . .-
l .

3?

phenymmnimlai reported in this work, or the amino group can react
with the memo» to tom the sewn hose. Simeon Womamon
product found from Emmetonimo and Z'pyfidinaomoamdehyde
precipitated within o mammoth“ tho tan reactants in
impropyl oloohol with no added catalyst, it was mononehlo to ban.”
that the Manage). commotion took wooden“ over the taxation at
tho Sohirt'o m..,m, in ordor to ootobluh magnum pmot of
Ihieh oondmofion product m'ohtaim, 1 m1: of the material one
matzlotod. Tho monsoon-mug. no the m ulna; point oo cud
Wophem‘lkB’u-pyfiemmnitulo oynthoeiud by oondoming

' ' m-ooith Woman. (pogol‘l).
Mmmdopmdoninommflnzpom.

nutmmmms) WMwum-tionotmu

one: Wain Wmmmmm
WW“ oloopromrohydrom. MW! W
mwnunmonnnuummmom Wm.-
Monldohado the experiment on unsuccessful, ond than no qxanutouvo
rmuwotthophmvmotomm. wax-mono“: almond remind
unmotomommmormmmmormmm mm, inthio
mummififiotthothoorotiaolomuntofhflmmmtokmupmw
quotas. AM there no no intermediate room between the
WWo and plmwlacmnitmo as one the case with
W, and tho absorption of hydrogen was due to hydrogenation of the.
aldehyde.

 

38

Q'thrfii 2-pyridy1)faorylonitmo no mood with othylmgneaium
bmflde in on “tempt to W a-phenyl’fi12‘pyfldylhaleromtrilo.

‘rho vaultingoilypxodnotm minted bydiotimngum. the
W“ oolidifiod upon otonding o too doyo in tho wanton ._
Frictional minimum tron n'hm provided 1 and one o 13mm

 

Wofltombompwmhthooorfionimmuflmthyl
iodidobut thormtdpnprooood! m. uthooorylonitnloondon
”mummyliodidomdumlndinmiuortoolmtgouohubouom,
mmwnmdotmonmm.omtmombogmtotom
WWI“. Thoroportadmthiodidootoodtorhooomho
MumpMotmimhtodmmertommmmottho
pneipitotion.

39

:flfififlflflf

WWW oondm rapidly with powwow _
mm- an «new... mmmmmloo in tho memo or on our
lino ootolyot to giro good yioldo of or(snbotitutod phonyi)-$'(2'pyridy1)‘
WW. Inhmontiouthointomdiotondoloommm
«mum mm to to now .

WW'9’(W)WMW no POW by ooidoin
polor'oolmonto

no. m1. bond balloon tho mm a... an whom-H W)-
mumhummtomtm Mutantodoomonm
momuoiwmwummmgtmuisoomw
on mm mm. , .

W mm mt- we marl-fimnmr
Wm b? 115%“ m W‘91W)Wnfinlfi .
mummmefthemaotmooommonwid
honor.

ho

mmm

1. A. r. W m: n. a. Brawl, J. on. 612633., a, 61.8 (1950).
2. a. mud 0. Karma. J. Am. Gm. 38¢... .61, 31.2 (191.5).

3. H. 7. Front, hm... 25g, 156 (1889). . j '

1.. x. samba 0.10m. J. pm. mm... (2), 1m, 359 (3.925).

5. r. do mm m n. .1. Stephen. J. 81103.8”... 639 (1931.).

6. a. 1. I'M. m., 259, 15? (1889). .

7. 3.33. nun-m1 m! A. flaring, 3.1... cm. 300., an 835 (291.2).
a. A. P. runny, J. An. Chem. 558.. 12» 5230 (1952).

9. a. 1.- Hon, 1m. chin. (Peri-2, f3, 31.10953).

10. J. Jul-mm, cm. rand... gag, MI; (1951).

n. 1. r. em, J. 011. m... 23. 1.153 (1958).

n. a.‘Wer,,Bg.. 3g, :59 (1905).

3.3.3.13. 3m mm. 1. mm. J. cm.5oo., n (1933).

18. c. '2. am, J. Vilma, 8. Unit, a. W. J. a. (loan, c.0001,
J. Pain, 2. mm and A. man, J. Org. chem... g, 683 (195712;,
1060 (1953). A ~ ’

1.5. a. 1m And I. W. J. n. at... an... an. 103 (1958).

16. a. P. ram». 1.. Chen. 1., 35, 386 (1906). '

17. s. wan-om, J. 1:. cm. Sam. 68.. 1157 (191.6).

18. A. c. o. m and 1. mm, J. cm. 800., .35. 1.5 (1901.).

19. E. P. Kohlsr an a. a. Canon, J. ya. man. 800.. as, 1.975 (1923).

no. I . Haubron. mutton-.11 o: erg-ma 611mm, Oxford University
m; M 1m (1953), Vol. I; p. 551.

o

vs

210 R. ada-im and A. F. m. Org. Syntheses), Coll. Vol. I, 107 (19141).
22. R. )‘iozingo, Org. Synflxaaes, 0011.. Vol. III, 181 (1955).

23. K. Rorig, J. D. Johnson, R. W. Hafilton an: T. J. 19mm, Org.
Syntheses, 1Q, 50 (1955).

2].. L. Ioder E. H. I. Ch mad W. Bun-011?, Pros. Iowa. Acad. Sci.,
Q, 271 (195).); a. A... 13236 (1955

25. C. Grumher, Halv. Chim. Acta, 5, 610 (1922)} C. A... 1.6, 3896 (1.922).

26. c. Gaucher, 14. Sam A. ormr, A. mppamtamam E. 3mm,
Helm Chino £0158. é. 53'67 (1923)! c. in. 1-1. 21.21: (1923):

27. I. Hdhmn, Dictionary of Organic Chamiatzy, Oxford Undxmiw Pmu,
Kw Iork (1953), Vol. II. p. 807. -—

28. a. a. Reba-tun. Org. 3mm, Gall. Vol. 1, 396 (191.1).
29. B. H. Chase, J. P. Thurston and J. Walker, J. cm. 806., 3139 (1951).
30. Ga Button 1nd cc ”0113’, 01". Synthm, Coll. V010 II, 109 (19,43).

31. I. Hafibron, Dictionary at Organic Chafing. Oxford University Frau,
NW tor}: (1953), Vol. IV, Pu 190‘

32o€i91$)3mmn, ‘6 We m 30 Hg 1m, in ”0 Ch”. 8000’ Q" 2977

33. D. G. moms, J. H. Billmn and C. E. Davis, J. Am. Chem. Soc... Q,
895 (191.6).

31.. a. 3. Lemma, Aha. up, 1.06 (1915).
35' PI P13113035 10 Wt 01‘ “a ma,- m: m 162 (1928).

CHEM? ITRR AR?

 

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