c m c m L d ^ iv a tiv h s o f tm o m m .
m o m a a s B m k c tim

past x ~ m

pm

xx

- m

a c m rz r eeactxck

By
m

i s

h,

A THESIS

SabiriLttod to %im School ot Oraduat© Sto&U* o f M ichigan
S tato Collogo o f Agriet&tur® mm%A pplied Selene©
in p a r t i a l f u lfillm e n t of ih© ro q u irejssn ts
f o r th e degree o f
w o r m m p r a o s o p ia r

Department o f Chem istry

1955

ProQ uest Number: 10008335

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iC S S M J B O t fM r

Tbe au th o r wtahoa to oxg»i*®a* Mo a p p re c ia tio n
to D octor Bobarfc 0*
f o r Mo f rie n d ly counsel
t l m g b u t th& co urse o f fchia in v e s tig a tio n .
B» i s « is s in deb ted to Mis n if * # Donna, f o r h»r
eyngw thetlc tsM oratandling vMofa helped to »ak»
p o ssib le th® com pletion o f th is theai**
ilTMhi ih
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T O

^ iU ia a H arper fira ff
!

C andidate f o r th e degree o f
D octor o f fhllosopfegr

Major Subject* Organic Gbamleiry
A n aly tica l and B io lo g ic a l Ciaoniotry

Minor

B io g rap h ical Data*
Bate o f B irth *

A p ril 27* 1928 in Mow Hbpe* V irg in ia

E d u c a tio n *

B# S , in Cfcemietry* th e C ollege o f W illia® and Mary* 195$
M* S. in O rganic C henistry* MicMgan .State C o lleg e , 1952
A dditional G raduate S tudy, M ichigan S ta te C o lle g e , 1955
s » p e r i* n o « f

G raduate
ftegeaveh
Beeearefe
M re o to r

AaidLetant, M ichigan S ta te C ollege* 1950-1952
C hew let, M ichigan S ta te C ollege* 1952^1953
O te d o t* B enito F la s tic e , Iins«* 1953*1951*
o f fteeearch, Tylene F la srtio a , Xm *9 195i~F reee»t

F ro fe e sio n a l A ffilia tio n s *
A n e r le a n O t a d o a l

th e Society o f

S ociety

8l&m 11

ill

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Pag®

i <* f m w m m & m m ^ n m
m m o m c r im .

.......... . ..............

x

m s n m u i* ...* .* ...,* * * * ............ . . . . . .............. . ........................ . .

3

................
6
j& ^idbooatal C osdlU ans
@14# Enaction® o f tho tt#t&rm%&yqr f a c t i o n
. . . . . . . 10
Mmkm&m o f the? K«fom&t®lQr H o a o t l c n . * 12
Provioua X ttw o tig atlo n o f tho TM003& Carbonyl
Ckjfi^oi3$ySs * .•* * •* .•..* •» « .•* •* # •« ..ft.* # * .* * .* * .* .* * .. X6
............ .......................... . . . . .

20

o f Ih to x m d la to o . ..............
Hoaetiox) o f * *B *o»oo«t«ro..#. . . . . . . . . . . . . .
m&otton o f SUqA ^ ^ Iro n o o ro to n a te . . . . . . . .
B oaotioa o f O ly l B ro m id e ,,............... ..............
f a c t i o n o f Frop&rgyl Broa&d®, . * * „ . . . . . . . .*

30
2h
3$
hi
h6

m scvsaxoit
P re p a ra tio n
lo fo x w to V
BeformatolQr
B o fo rm to l^
Koform&toiQr

c b e k r u l u u f f ln d « M M ..........................................
sjFHsmanrA 1. . .
P ropagation
Kofonra&t$!$r
Itefom atgiky
B efoacm to^
!&fom&tsRy

h9
.

5X

o f X ntonsodiatos................
51
.........
63
R eactions o f v*>*$rom&®&teP8
ao& citons o f Stfeyl ^9r©©oorotonat© .......... ?8
Reaction® o f *Xlyl B r o ^ i o . * . * . . 85
Re&otioos o f F ropargyl Bron&d*........ . . . . . . . . 89

m m .m *

................

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9R8OD0CTZ03l%##..................................................
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9

T.iBtK OF COHTlSTi - Continaod

Page
108

DXXCSSXOH..,.................

th e :<itaa£d% R»»otl©n w ith t b e n a ls ..
..................
106
the SelwitJt R eaction with the ^cyltMophensi 9 .................. I l l
c h b m ic u l

g ^ i o a r r s .................................

m

1

sxp aa M a sm .....................................................
F ow ution o f T e tr a s o le s ..................
sum jar
H a rw a K R s...

133

.....................................................

138

......................................

139

sdl

ix js o r

tm & s

TAate

p*g®

Z ZtigrX 3-(2«TJslo«yX)->»Q|fl4nosy*llMffloat®a
ZZ

.........

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ZZZ BM pl 3>(2*7M «i^X )>>^iliW (yal1eH »at«s....................

27
28

.

29

. . . . .................

30

V

Sttsyl (S-(Thtonyl) icjryOato#.........................................................

36

VI

EMiyl 2»s*toB!jrl-3»%0*,O 3qr-3«(tht^3rl)-JU eaa»at*s and
Etlgft M T M 0n ^)-5 -% dj*«Jij^» P M rt«n oates................. ... .........

»2

IV iitiy l > (3 -T M 9 i^l)-> ^d F o ay saS csn o * t« 8

VIZ
V III

£ « « * 5 * ( t)3 iw X ) ^ tW »Zkadiaiw «te«
U«(Tld«n7 Z)«li>^(iKM(y~Z-* ilfewnoa.

...........................

1*3

.....................

1*5

IX l-(T h len y l)-3 -b 'u ty n » -l-o l8 ......................... . ..................

W

X 3 m u q r o f Prochwfco and Methods f o r tho T h e n a lo ....

XX 3mmwry o f P*odaata tram %t» .cy ltb lo p h en as............

33.0

H7

1

t h » fteforw atcky in a c tio n inv olv es t o

in te ra c tio n o f an

~balo~

* * t* r w ith i carb o n y l e o n p m i such m m aldehyde, k eto n e, o r act
e a te r in t o presence o f o im under ankydroo* condition® (I ) * ft* th is
re a c tio n a now oavtaNMNutara bond la c re a te d and a p p a re n tly tbo follo w ­
in g aequoae* o f atcp a and latex w d l& tea a re involved (2)*
l^ -G O O R

*

*

In

-------------- *

M a*k«Qm$L

l£n*C~GOQR ----------- *> ^ -$ **C 0 Q B

p&nl

(1 )

(2 )

PH

♦ Hi ---------- > ~q*$mQQm * Enf4

(3 )

fhB»t fro® aldehyde* and ketone*, ft *hydroa^w»«toro.are o btained
oo t o f in a l product*

Hndor c a rta in easpertontaX co nd ition * o r w ith

*o»* typo# o f re a c ta n t* , dehydration occur* d u rin g th e re a c tio n and
rootalt* in an u n sa tu ra ted e a te r ,

to m

dehydration does n o t occur

d u rin g tb@ re a c tio n , t o <* -hydr& syeatcr n a / bo converted to t o
© oswapoodlng * , c* -unaatnr& ted e n te r d u ring a imbue queni at© p.
PH,
- QmCmOOm ----------- *

-C«0*C00H

*

K3Q

t o r * mi o u te r 1* need in ste a d o f m aldehyde o r ketone
appear* to i n v t o t o
m (><*kebe*at*r*

(W
to

pro****

fo llo w in g atop* (assum ing eq u atio n 1) and y ie ld *

2

+ XZ»-G-C001i

mC««0«4
-COOK

(5 )

OB

*

> j L m s q q b + m n + z n iA

m

(6 )

V htle th e m o ti o n 1a g e n e ra lly considered to proceed between
th e re a c ta n ts in d ic a te d , numerous v a ria tio n s in th ese have been success*
f u lly ^applied* The halogen eonponent may be a (3 - h a lo s s ts r O fit) , a
vlstylog o f an *s - h a le e s ts r ($*X8) f on a l l y l h a lid e (1 9 ), a propargyl
h a lid e (2 0 -2 3 )f a feensyl h a lid e (2 li), a n * , <* -d lh ttlo e s te r (1 6 ,2 5 ,2 6 ),
o r a a ^ *haloaztdde (27)*

lik e w is e , o i eth y len e oxide ( 2 8 ,2 f) # a S h lff

base (16,30) , op an e d d i (11) may be need a* th e second r e a c ta n t,
Bae to th e sy n th e tic u t i l i t y o f th e Eeform atsky re a c tio n , i t emu
th e purpose o f th e work d escrib ed h ere to In v e s tig a te e x te n siv e ly the
re a c tio n s o f th ie c y l aldehydes and tb ie n y l a lk y l ketones w ith a v a rie ty
o f halogen components in an e f f o r t to determ ine p o ssib le c o rre la tio n s
between th e y ie ld o f p ro d u c t, s te r io f a c to rs in th e r e a c ta n ts , re a c tio n
so lv e n t e f f e c ts end s u b s titu e n t e f f e c ts in th e r e a c ta n ts ,

P rev iou s

s tu d ie s o f th e HefoxMtsfey re a c tio n w ith carbonyl d e riv a tiv e s o f tM o*
phene have been rep o rted (i»,16,21,6$,66) ,

However, th ese a re o f a

s u p e rf ic ia l n a tu re in th a t o n ly th e two s u b s titu te d isom ers v e rs In*
m s t i p t e d | th e v a r i e d o f re a c ta n ts wm r e s tr ic te d to th e aldehyde and
n a tty ! ketone Of thlophsns and c e r ta in o th e r a s p e c ts o f th e In v e s tig a ­
tio n s mush a s rearranged p ro d u c ts, b y p ro d u c ts and so lv e n t e f f e c ts
were in need o f f u rth e r stu d y .

3

T i* RofOSKatohf wmmMm

f tr s r i re p o rte d in o e e rle e o f paper*

bgr B efo x m ts^ f and K U soonoff and issBedistoXy because th e
eu b jeo t o f a v ide and o&riesi in v e s tig a tio n by mmmr&m people (3 ?) *
I t repr#*©tSt* SO ftiXt©JJ#i©fS Of $$20 POSOtiOOS ©f ©F{g*4JRQ$in© C08tpQ’tlif)de
wStli ooiSbOKg^l. OdffipoioSii bob hftff th e advantage© th a t t foXotiowf o f tb*
SxitofM Otato orgM»>ssim compound io «©t re q u ire d ,

th e re a c tio n ia »

oodooo tb* in te ra c tio n o f a ©srbwayX ©oapooad w ith no aotiv© Imlogon
eonpoimd in th e papeooo©# o f vino tander aoh^tircttie ©o&iibioita*

io inter**

nediab© w $ m m $ m h a lid e in I m S oM oh then a tta c k s %ho carbonyl
eceopoiioiib t o y ie X d s o

eoKpX#y»

Srideao* th a t m w&ama&m h a lid e %» trn m d wm provided by
D ata (36) whs** ho no* Obi* to tao&ob* and anaXy*© th e produot tvm th e

♦ 5£n *1 '"•—

jj**C**C0OC

BsJji f u r th e r de»©«»ir&ied th a t th e a d d itio n complex r e s u lts front th e
in te ra c tio n o f tlto carbonyl w m pm m t w ith th e organojsinc h alid e
in te r w e d ia te .

c* % * 4 t

* { a % )^ j^ o c io o A
2W r

OSu&r
^ C# %^H«G<»COOGa%

(c v »

h

Oecorapoaition o f the addition complex

hydrolysis y ie ld s the

aorrespoiidtGg Iy&mw conpeiswI ,
Q&x&r
^O G C *%

ODC^%

♦

The o n ls r o f r e a c tiv ity o f th e h a lo e s te rs ± a# a s would bo expected
iodo > hmtm > ohlnrc*

E ster* w ith secondany o r t e r t i a r y <* ^halogens

a rc co n sid erab ly nor* re a c tiv e th an th e corresponding prim ary d e riv e tiw e s , b u t in sutaaor in sta n c e s t i n r e a c tiv ity o f * given halo compound
m y be m odified by a ta r i* fa c to rs o p e ra tiv e in tin e s te r ,

4s th e

carbo ny l ©exponent th e aldehydes mm ao w re a c tiv e th an th e In to n es
and t i n l a t t e r compound* in tu r n , a re a c re re a c tiv e th an th e e s te r s (3?) *
f in o v e r-a ll re a c tio n o f e ith e r a ketone o r aldehyde w ith m
a c tiv e halogen compound under i& fom als$gr co n d itio n s r e s u lts in th e
form ation o f a ^ -h y d ro a y estsr which nay be converted by dehydration
to th e corresponding ^ m a tu ra te d e s te r ,
J

t

-&« ------ S»—» ftt

M* y 8*-fe£WB

N*»n «a a s te r i s assd as the carbonyl coraponsnt the produot i s
generally a

0 -k a to e ste r.

B -C -i

♦ S'

*

B«-O H

5

H U I«r

mad Bond (U) wmmded in utilising

fo r

M&fnrmtstky reaction eh*m oth&ns (3 f$) rep o rted m m n r only isodsrate

msmnm ty ettbnt&tniing i*mgn®ei«i» fo r s i m md carrying ***> ^
actio n in tetraly d ro fu ran ,

c«

% Ib

♦ B vcauB ^osoeaib — n — ^ c ^ ^ s s t y c ^ o o o c ^

th e viaayloga o f th e ^ -haX eectore undergo tig® Refora&tglgr re a c tio n
(S**1B) *

fdm m iviporie (8 ) th a t e th y l * -io d o cn o to n aie, p -eM o ro -

h em d d elC ’d * , m d e lm r e a c t to for© Alio expected condensation in a
fa2$ y ie ld ,

Cl«^

^ la

* IC^*CH<!B-&>B+ —^5-> Cl4 ---ch«cb J os+

Grew© i%9) found M
t i n t i n d leA tyl e th e r

c y c lic ketones r e a c t v itii 4 l ^ l tra n !4 e and

md

m tm ln to give a ty p ic a l E efom atoky

p ro d u c t,
500 %
0

coo&t
* C% «aa43% 8r —

£n

r v

°H

I S p CISa-OS-CHa

A** a c tiv e I d & p eenpcusid analogous to a l l y l bromide to p ropargy l
brcanide*

A nesteor o f in v e s tig a to rs have re p o rte d th a t i t fu n c tio n s

in th e R efom aisky re a c tio n to give good y ie ld s ( 20- 23 ) .

Banfcset and

c o -m rk e rs (20,21) found th a t a v a rie ty o f carbonyl compounds could

6

bn SMaStoeywd tfcltSi w o stw iy l bf@nid.d6*
9
C%QC% 4- CHiC-CSy-ap

z™
.■■£".•■■»
% »*

9a
CJU-C-CH--C--OH
o i^

Fuaon aad Cook (2b) oboonrod that bonajn h*lld«a roaet wifch
arom atic oX&mto&4m to yjU ld otH bo sa darivatiinsa?*

The u asatttra to d

ecBBpcMaod* in s u l t through ifeo « n j d&S^lrat&m o f tb® carfclnola cNsdug
d le ilX la iisw i.

T hus, bomttldohyd® romeio w ith b o n sai c h lo rid e to y io ld

aiXXbom isi a 2W yt&ld*

c#%as * c«%Q£yca

—^5-s> c„ifeciLc«yc.jfe
•V y

C*%OB«CRS«Jfe

Xb a pa?oa»#» romicdlsoont o f th e O m en* g ly a id ie o s to r sand<m&at±on
( |9 ) * l^ ro a y o l& c ^ sa i& ro aro obfc&imd vitas* % ®( -K& haloooters a re
aXlowodi to ro a o t v itli cajrbopyl eoiapoijoada (16*25*26).

f o r ©xarapl® tb s

in te ra c tio n o f aooiogtliomm® v iih o th y l dlobtoroaootA to g iv es tb s
product in a f0$ y ie ld (25) *

BmiQmmtMkp
0

CEj
* G l^ tT O S C ^ — ^> 09%0*^880@Ci %
OH Cl

Sbpleyittg a «XiS8**e©pp»r a llo y in pX&ae o f *Xne# DraM (2?) prepared
$ ^H^dXdllg'l^ (3«4aydroaqr a s id e s by th e fcroatraeal o f aarfeottyl oempcwmdsr
v i t h ^ ^ ro m o s s & d e ® .

7

0
0
BrCH-|CNEa •+ ECS
C e rta in epoxides r e a c t w ith

r

OS
0
ECJWH8CNK3

-h a lo e s t e r s in th e presence o f sin e

to produce hydroixyesters analogous to those o b tain ed from carbonyl
compound® in th e normal Kefo m a ts ky re a c tio n (2 8 ,2 9 ).

E thyl l~hydroxy~

cyelopentylaest& te i s formed from oyelopentene oxide by condensation
w ith e th y l bromoaeetat® (2 8 ).
OH
+

0
B rC ^ S 0 %

CHaCOEt

The in te ra c tio n o f S h lff bases w ith ^-broiooestere in tb® preeenee
o f sin e proceeds in an expected manner w ith sim ultaneous lo s s o f an
alco h o l to give a 2-aaetidinon© (16,30) # Thus, M ille r and Word (16)
prepared 1-phenyl -3 -ae th y l-h - ( 3-metiiy l ~2«*t h ie n y l) ~2-ax e tid in o n s In $$%
y ie ld by re a c tin g 3**methyl*2*th©nalaniline w ith e th y l o(-brom opropionate
under Reform atsky re a c tio n conditions*

♦ BrCH*C00 £ t
B*UC3 %

CHaCH-C*0
4. 0 9% OS

la k e s (31) has o b tained e th y l lH n e tiy l^ -p y rro lo n e -5 -a e e ta te in
about 20$ y ie ld by tr e a tin g K-methyl succtnim ide w ith e th y l broraoa c e ta te and sine*

8

cn ^ co

CH-^-CH-jCO OCaHe

IW %

*

SrGHjjC0 0 0 * %

c h ^ -co

c jv c o

iS&pefdjHftltal C ondition*
In th e e a r ly

on ( l f2,3&*36)# th e K eforaatsky re a c tio n , i t

m s c a rrie d o u t by m ixing tb s m o te « ts a t mom tem perature w ith o u t
m so lv e n t follow ed by e x te rn a l coo ling o f th e o p tio n to m oderate tb s
f ifm tt M IM

re a c tio n ,

A fte r feeing a lie n e d to sta n d a t room

tcnpsiwlM M to r varying p e rio d s o f t i n s , tfee re a c tio n m ixture m s
b r ie f ly b o ated , 60*60° 0 #f and then decomposed w ith d ilu te s o ld ,

X»

tb s store re c e n t a p p lic a tio n s o f tb s m c t l o n a so lv e n t has bom
employed and o m o f tits re a c ta n ts so y bo added p o riio n w ise w ith s ti r r in g
and a t tb s r e f le x teaqjem tore o f tb s s o lv e n t,

I t i s e s s e n tia l th a t

tb® so lv e n t employed be on# in which tb s p ro du cts a re soluble? in o rd er
to p rev en t s e a tin g o f th e se rfag e o f th e sin e which g re a tly I n h ib its
th e re a c tio n ,

Prolonged re a c tio n tim es a re to be avoided s in c e ,

seen a t le v tem p eratu res, extended re a c tio n time r e s u lts in an in c re a se
in tb s amount o f h ig h -b o ilin g by-products (UOjkl) ,
S tr ic tly anhydrous c o n d itio n s a re req u ired f o r su c c e ssfu l u t i l i ­
s a tio n o f tb s befefM tsSgr reacM on,

In th e presence o f m inute q u an ti­

t i e s o f m oisture th e re a c tio n may be I n itia te d only a f t e r an in d u c tio n
p erio d o r tb s use o f c a ta ly s ts such as io d in e , amalgamated sin e o r
tb s copper complex o f a e e io a c e tic e s te r (h2) #

9

The q u a lity ©f c in e used in th e re a c tio n la o fte n re sp o n sib le
f o r d iffe re n c e s o f o p in io n concerning re a c tio n tim e , y ie ld , c a ta ly s t
and p u r ific a tio n procedure*

I t should he o f a high degree o f p u r ity

and hove % fro th c le a n s u rfa c e ,

dme o f th e b e tte r procedures f o r

eo n d ltlo fiin g th e s in e I t re p o rte d bgr F i t t e r and Johnson (1*3), who
ad v ise iM srato zi o f 30-m®sh slo e In hot co n cen trated s u lfu ric a c id
to which a few drops o f n i t r i c ac id have been added* The e lm i t
washed w ith w ater and acetone and then d rie d in an oven*

In c e r ta in

in v e s tig a tio n s amalgamated a i m , m ixtures o f cin e and copper powder
(hO) o r sine~aopper a lle y s (2 ? ,hh,h5) have been used*

dim erous in *

sta n c e s are re p o rte d (14,20,21,1*6,1*7) in which m ercuric c h lo rid e was
used in co n ju n ctio n w ith cin e to Improve th e y ie ld s in th e Beformatel^r
re ac tio n *

O ther m etals o r m etal com binations which have boon in v e s ti*

gated a re aluminum (1*8), magnesium (I* Jk9,$Q), m gnosium ^lodine (5 1 ,5 2 ),
eium ^eebal'km s c h lo rid e (h) and »api®slum -eopper (53) *
The so lv e n ts most g e n e ra lly employed in th e Befo n se ts fey re a c tio n

art d ie th y l o th e r, b e m s m , to lu e n e , p y lo n s, dtoxane, d ib u ty l o th e r,
a n ts e le and ia tra iiy d ro fu ra n * The c r i t e r i a fo r determ ining th e so lv e n t
to bo used in a s p e c ific case a re s o lu b ility o f re a c ta n ts and p ro d u c ts,
re a c tio n tem perature d e s ire d , and. in c e rta in e a s e s , th e e f f e c t o f th e
so lv e n t on th e course o f th e reactio n *

D loxane, f o r om&ople, i s sa id

to promote enolle& iion o f th e carbonyl component, th ereb y d ecreasin g
th e y ie ld o f p r e im i (5&)*

10

Sid# Hoacttems of the Itafevmatslgr Benetton
Various aid® reactio n s re su lt vhenever tb® MtoSonmt&kp reaction
i s executed (3?) * The orgam tinc halide inisrsa&diat® i » j odd to the
<* ~haXoestar forming an aceteaceit® e a te r.

Haon and hapeorth (55)

observed th at vino and sth y l brcm& eetate in te rn e t to give ethyl
~bratt*coteacetate *

t BrC»aC00Ca% + t n

(SSi$r
i> BrCH^CH^COOCaS®

00*%

-^ ->

B fc a J c a y jo o o ^

+ C a ife o z riB r

f h is re a c tio n mjuXc! bis o f minor concern when aldehydes and batone®
a re used sin c e th e y p o ssess g re a te r carbonyl r e a c tiv ity th an th e e a te r
g ro ssin g o f th e b a lo e o te r.
Another aid® re a c tio n wliioh l a o f Im portance o n ly where tb®
carbon yl cojnparwmt l a an e a te r la the coupling o f tb® halo® a te r by tb s

sin e ,
0%C000%

2 BrCHaC00C% + 2n —> |

* 2nBra

CH^G0DS%
has rep o rted (5b) th a t th e organeasinc compound may induce
e n o lla a tio n o f th e carb ony l component* T his r e s u lts in recovery o f
th e o r ig in a l carbonyl caaspound and th e reduced e s te r .

n

Q & ii8 r
ICflyR ♦ B r O B ^ O O C ^

CH«CO<KaJLj ♦ HC-CHl

m e SUH ♦ ZaABr

The amount o f « n o lis« tlo ii has been found to he % fu n c tio n o f th e typo
o f so lv e n t § th e halogen d e riv a tiv e er^ lo y ed , and th e s t s r i e blocking
by groups in th e ketone (S6,S?) * D iom ne, fop in s ta n c e , I s i« id to
promote e n o lie a tio n (51*) *
Who© a lip h a tic aldehydes and ketones a re u se d , th e se may undergo
a ld o lle a tio n through th a in flu en ce o f th e v ise s a l t s ,

2

[T > o

0 = < 2 3

♦

H ,0

In a d d itio n to consuming aldehyde o r b ato n s, th is sld o X lsa tio n t follow ed
by deh yd ratio n o f th e a id s ! produces w a te r, which in tu rn causes do*
com position o f th e srganoslnc h a lid e in te rm e d ia te .
The form ation o f a rearrang ed product du ring th e Bsform ateky
re a c tio n has been im ported in two c a s e s ,

E nglish and Qregory (18) and

Jo n e s, 0 f S u lliv a n and W hiting (1?) Is o la te d two isom eric p ro d u cts f vm
Bsfom & lsky re a c tio n s employing m ethyl V -brow o© rotoiute.

The products

were id e n tif ie d as b ein g th e normal product and an isom eric <* -v in y l
d e riv a tiv e .

OH
ECH-CH^IS^C HSOOG%

38 + BrC%CH«CH300C%

-- ^
mB-cmoQeH*
6n 6h«c^

F re ra a a b ly , th e <* ~ vtqyl d e riv a tiv e r e s u lts through a charge m ig ratio n
i n th e n eg ativ e sp ecies o f th e orgaaoslxio halide*

B rZ n .C H ,-C H -C H -C -^ C %

#

mm

9

rib& e& £«octt
m *cn9

Meeh&itinn o f th e Heformatslgr R eaction
Very l i t t l e d ir e c t In v e stig a tio n has been rep o rted concerning th e
mechanism o f th e Reform atory reactio n *

Evan# and P earson (5 8 ), eho

made a thorough stu d y o f th e G rignard re a g e n t, M g l, a lso conducted
a c u rso ry e s m ln a tio n o f the Reformat# fcy re a g e n t, R2»X. R esu lts o f
tra n e fe re n c e s tu d ie s conducted by these In v e s tig a to rs in d ic a te th a t
th e h alo orgaxiBSHitaSlle complex in e th e r so lu tio n may be rep rese n ted
by th e fo llo w in g e g re s s io n s
m nX

~ ±

Hi ® + ^ n X

I t m is found th a t bensens so lu tio n # o f &!*© reag en t do n o t conduct,
w hile e th e r so lu tio n # a re e x c e lle n t conductors*

t h i s may be a ttr ib u te d

to s o lv a tio n by e th e r o f th e o rgano m etallic cos&plox,

13

?ii$ re a c tio n o f th e KefonaatsEy complex i s presumed to preoemi
by m I n i t i a l earbanion a tta c k on tb s carbonyl carbon*

01
C£*
U u

♦

®
Jit* ------ $>

&
E-9 -H*
a

Thor# may bo c e rta in reasons to b e lie v e th a t fre e ra d ic a ls are
Involved in th e h e fo im isk y reactio n *

These a re suggested by the

is o la tio n o f e s te r s o f su c cin ic and s u b s titu te d su c cin ic ac id s as a
r e s u lt o f a coupling re a c tio n between two m olecules o f ^ - lu lo e s te r .
However s th e re i s co n sid erab le co n tro v ersy as to w hether coupling
re a c tio n s o f th is type proceed by a fre e ra d ic a l o r io n ic mech&n*
law ($ 9 ).

nnoajm&t —^ so* * •caycoost
2 -CHjjCOOEt

--------5>

(CBjCOOEt),

or
2KaC%C0Q£t ----->>

(?)

En

®

jCHaCOOEt

then by Sg2 displacem ents
*c» ye o o E t

*

K ^coost

-----------*■ (c H g C O O s t),

♦

aP

The re c e n t in v e s tig a tio n s (60) on th e "tarta re a c tio n tend to in d ic a te
an io n ic taech&nlsm.

IU

Evidence su p p o rtin g th e io n ic mechanism o f 1ihe Reform ats ky
re a c tio n so y bo found in a study o f th e p ro du cts formed from th e
v tay lo g s o f th e e s te r s o f hrome&estic a c id .

S ngliab and Gregory (18)

c a rrie d o u t re a c tio n s betw een c y c lic aldehydes and e th y l V -bromoorotonuto and rep o rted th e Is o la tio n o f two isom eric p ro d u cts 9 and a
p o ssib le mode f o r th e form ation o f th ese p ro d u ets through an loxxlo
mechanism (17) has a lre a d y been discussed*
The i l l a t i o n o f u nreaeted carbonyl compound and nonhalogenated
e s te r In th e B efom atsky re a c tio n has been explained by Keuman ($h)
on th e assum ption th a t s n e liz a tio n o f th e ketone i s promoted by th e
org& nom etalllc complex follow ed by in te ra c tio n o f th e l a t t e r w ith th e
e n e l to y ie ld nonhalogenated e s te r and th e h alo m etallic complex o f
th e en o l which re g e n e ra te s th e ketone when th e re a c tio n m ixture I s
hydrolysed*

t h i s mechanism, however, f a i l s to account f o r th e is o la ­

tio n o f u n reaeted carbonyl expound and nonhalogenated e s te r In th e
numerous cases where the ketone o r aldehyde i s Incapable o f e n o lis a tio n *

In such o ases i t i s more p la u sib le th a t th e io n ic form i s

re sp o n sib le f o r the is o la tio n o f uxireacted carbonyl compound (17) *
»

O H *-? -# 3

oa

CBa«C-0-C-iR
SC i
I
ob ft

♦ II

i>

CHaCOOR

*

KCH

IS

<2>

l a view o f m io n ic sp e c ie s o f th e type #CHaCOO&t, i t i s n o t
s u rp ris in g th a t th e is o la tio n o f C la lssn type condensation pro ducts
has been re p o rte d ($$)«

T his may be rep rese n ted a s proceeding by a

ty p ic a l C laisen mechanism (6 1 ).
Jm
OjBrCh**C
OSt

♦

&
tQUffiOQEt

©
0
-*> BrC IIa-C-C HgCOOEt
OEt

0
9

BrCHa-C-CI^COOEt
0«t

----=>

9

BrCHa-C-CH^COOEt

o

+ &%Cr

Since aldehydes and ketone* a re much more re a c tiv e than e s te r s , th is
sid e re a c tio n i s im po rtan t only shore th e carbonyl component i s an
e s te r ,

In f a c t , th e re a c tio n o f a Reform ats ky reag e n t w ith an e s te r

may be rep resen ted by th e same s o r t o f mechanism a s d escrib ed above *
Most

($ -unsatw rated ketones undergo th e norm al Bsform atsiqr

re a c tio n ,

however, K ohler and co-w orkers (62) observed th a t m ethyl

brom osinem alonate adds l , h to benssalaeetophenone,

Iy e r (63) found

th a t when acetone i s tre a te d w ith th e same Reform atsky reag e n t th e
only p ro d u ct Is o la te d i s th a t corresponding to 1,1* a d d itio n o f th e
h a lo e s te r to m e sity l o x id e.

A pparently, th e f i r s t s te p o f th e re a c tio n

i s th e condensation o f acetone to give m e sity l o x id e .

The occurrence

o f th is a ld e l type condensation and deh yd ratio n o f th e a ld o l may be
re p re se n te d by a mechanism s im ila r to th a t o f a ty p ic a l a ld o l
condensation (6h)«

16

© /COOK*

0

iQg
''COOEt

+

0 r"
CJJ,-j?

©

9

+

9

C%-9-C)%CC%
0%

J30OI1

„ BL—
L h
—
—■■■> -<C|^|
'COOBfc

+

© ro 9

sCHgCCH^

(»
<?
^ 9
tCHg&CHg ----- > CHj|-C-CKaOCHa
0%

©

9

+ 2 n ir ------ » C K ^^m G H a
C%

♦ Zr®rQM

th u s* th e v a rio u s p ro d u cts is o la te d from th e Beform&tsky re a c tio n
may be eaqpXelmd on th e b a s is o f a stngl© io n ic s p e c ie s ,

Only more

e x te n siv e In v e s tig a tio n w ill confirm o r disprove th e se p o s s ib ilitie s *
P revious In v e s tig a tio n o f th e »efe*m tsfey R eaction on T hienyl
Carbonyl Compounds
In a s e r ie s o f p u b lic a tio n s (b *16,23,65,66) Herd and c o lla b o ra to rs
re p o rte d th e a p p lic a tio n o f th e Reform atory re a c tio n to a s e rie s o f
2 ~ th isn y l be to n es and ald eh ydes.

th e se in v e s tig a tio n s were conducted

on th e m m r e a d ily a v a ila b le ketones end aldehydes and no attem p t was
mad# toward th e in v e s tig a tio n o f the more d if f i c u lt ly prepared
3~tM.«nyl compounds*
The f i r s t o f th e se pap ers (65) d isc u sse s the in te ra c tio n 2~ac#tyXtb io p h en # , 2 ~ ih o n al, and some m ethyl and halogen s u b s titu te d 2 -th s n a ls
w ith th e e th y l e s te r s o f broraoacetio a c id , <=* -broraopropionic a c id ,
^ ~brom eisovaXerle a c id , bromomalonlc ac id and ^ -bromoHEi-butyric
a c id ,

lin e m etal and a bsm ene^toluene m ixture were th e o th e r

17

Gimpimmle o t th e system ,

Ttw

rep o rted « er» c o n s is te n t w ith

ex p e c ta tio n s d m m by analogy &mm th e corresponding bem eae d eriv a­
tiv e * # b ein g 10-63# depending on th e n atu re o f th e re a c ta n ts •
e th y l fereetsaeetats, e th y l

f^here

-broaoisovalerafce mid e th y l brojaanalonabe

were enployed* th e se in v e s tig a to rs wore unable to is o la te th e (3 - h y d r o x y
e s te r s , h u t o b tain ed In ste a d th e corresponding im m tu m ted e a te r s ,
As a f u r th e r p re p a ra tio n , th e p ro d u cts from rsao tlo ise y ie ld in g
0 -hydroxy e s te r s were reflu x o d w ith 6# om X ie s o lu tio n to y ie ld the
dehydration products*
th e second paper^ by K©»ld.n# M ille r and lo rd (23) t d e sc rib e s th e
p re p a ra tio n o f seme a o e ty le n io d e r lm tlv e s o f thiophene in which
l-(2 -tfa i« i^ l)-3 -b u fc y r^ l-o l and l-(2 -ti& eny l)-l~ b ex »n -5-jm ~ 3~ ol were
sy n th e sise d through th e re a c tio n o f s i m mod p ro pargyl bromide in a
b en sen o -tetrah y d ro fu ran M ixture w ith 2 -th e n a l and (3 -2-tldU M ^rlacrolein
resp e ctiv e ly *

I !j

oh

H

♦ Br-CHa-C£CH

Zn.„

w :»-ch3- c=ck

S

i /

No in v e s tig a tio n m s conducted on th e re a c tio n o f th ie n y l ketones w ith
proper g yl b rm id e*
th e th ir d p u b lic a tio n (h) concerns th e © election o f a condensing
agen t f o r th e u til is a tio n o f
B sfem atsk y re a c tio n s*

-© blare and ^ -brosao ester© in

The only carbonyl d e riv a tiv e o f thiophene

In v e stig a te d was 2-aee ty lth io p h e n e ,

I t was found th a t sie re u ric c h lo rid e

16

• • w w s a tis f a c to r i ly m a prom oter in heferm atsky re a c tio n s in v o lv in g
th e above BMmtlomd halogen wmpamd* g iv in g expected p ro d u cts in
a s high a* $&$* T l» re a c tio n a t 2«*oetylthiopheiie w ith e th y l
d ic h lo ro a c e ia te to give a 23$ y ie ld o f e th y l ^ -© eth y l-( 2 «*ihiex3yX)
a c ry la te l a re p o rte d .
Xn a stu d y o f th e sy n th e sis o f some iM ophene polyenes (66)*
M ille r m i Mord employed th e ir p rev io u sly d escrib ed procedure (b ) o f
th© in te ra c tio n o f

(X*2*%MooyXaoroXoin w ith m ethyl

Br^HaCKaCOClCHa

(S^romopropionat© .

h c i « h«c ih : h3cooch3

The f i n a l paper (16) by M ille r and Herd re p o rts tb s p re p a ra tio n o f
mmm 2~tM #pyl polyene a c id s by tb s re a c tio n o f 2*»thenal and (*~2~thieuyl~
a c ro le in w ith e th y l Y^rom ecroton& te and m ethyl

JM n

* Br-C %-CH-DH-CODSt

(x) in „

-brom oaorbate .

H-CH-CH«€B-COOH

(2) IhiDH
They m m unable to I s o la te e ith e r th e corresponding hydroxy o r uns& turated
e s te r s and so sa p o n ified and dehydrated th e re a c tio n m ixtures w ith
m ethanolie sodium ty d ro x id e to o b ta in th e lan satu rsted a c id s .

D espite th e

fin d in g s o f doxies* O 'S u lliv an and W hiting (XT) and those o f in g lls h and
Q regoiy (IB ) f o r s im ila r re a c tio n s w ith b em ald ehy ds, th e se in v e s tig a to rs
could n o t fin d any evidence th a t th e rearran g ed <~vXnyX a c id s were
formed alo n g w ith th e normal p ro d u c ts.

They do, however* support th e

19

awtohatilwa propoeud toy*

and c o lla b o ra to r# f o r tfee is o la tio n o f

vfcoro en o liisatlo n cannot o c c u r.
kotono* were #tudiod I d th t» i n s t i g a t i o n .

Ho th ie n y l

20

m m sm m
P re p a ra tio n o f Xntetmadi&tes
The 2« and 3 -th ie p y l aldehydes and he to m s employed in th is
in v e s tig a tio n imr© sy n th esised by stand ard procedures d escrib ed in th e
lite r a tu r e .
The p re p a ra tio n o f 2~ th sn al oaa m em plteh& d by two d if f e r e n t
m ethods.

fk rtough and B ic& srt (6 ?) prepared 2~ th sn al through on

a d a p ta tio n o f th e oasii«m etliylatiori re a c tio n to th lo p b em (6 6 ).

T his

In volv es %h» in te ra c tio n o f th lo p b en s, 31% fofm ldobydo and a®moni\£&
ct& ertds g iv in g th e in te rm ed ia te 1 8 -^i* (2 ^tbi© n yl)-X #3*Klia««kcyclo-«
b u ta n e , which i s n o t Is o la te d b u t i s hydrolysed

d ilu te a c id so lu tio n

(pH * 3 #0*6#8> to give a U8$ y ie ld o f 2 -th e n a l end a hl% y ie ld o f
$H ^thyl~2~tJi© nylaraine .
r

C!%0 * KH,C1

> I*

JX-CHJi' ^KC%
3
OHe

pH 3 * 6 .8 ^

The b e e t y ie ld o b ta in ed in th e p re se n t in v e s tig a tio n wm
4 b e tto r procedure frees th e sta n d p o in t o f y ie ld s end s im p lic ity o f
re a c tio n ooxiditione f o r th e p re p a ra tio n o f 2 -tb e n a l I s th a t d escrib ed
by C am paigns and A rcher (6 9 ).

T his sy n th e sis in v o lv es the d ir e c t

21

£#m pjk% im o f th e thiopfeen© isnelsus by d law tl^lfo rw aaid e In th e
presen ce o f phosphorus oxycKlerld e*
72#

Champaigns and U reter re p o rte d a

o f t*tbirasX f th e p re se n t stu d y confirm ed tla is w ith a ?fc# y ie ld

o f th e aldehyde.

* (0 % )#

flie E^aeyltM oplsem e were o b tain ed by th e a e y la tio a o f thlophene
w ith ac id anhydrides in th e presence o f c a ta ly tic amounts o f o rth o
phosphoric a c id acco rdin g to a method d escrib ed by fferlough and Kbsak
(70)*

Af t e r e x tra c tio n o f th e phosphoric so ld th e pro du ct i e is o la te d

in good y ie ld by vacuum d i s t i l l a t i o n .
2 * aeety l U iiopbam

mm p repared

Bmployini? th is p ro ced u re,

In 86$ y ls ld f 2~prc^© nylthl© pheiie

mm

o b tain ed in 72*7# y ie ld and th e y ie ld o f 2~buty?yXthlophens one 7h.5$
whm tfaiophen® woe a e y la te d w ith a c e tic an h y d rid e, p ro p io n ic anhydride
and b u ty ric anhydride re s p e c tiv e ly .

Using th e same process* S««w%l<*

tM ophene was a c y la te d w ith m « tie anhydride to g le e a 66$ y ie ld o f
2~ac«tyl-3-raethyltI& ophane a s w e ll a s a 12# y ie ld o f th e isom eric
2^ae© tyl^h*«@ thylthtophene *
Since d ir e c t s u b s titu tio n a t th e 3 p o s itio n in th e tM ophene rin g
does n o t o ccu r len g th y procedures m m req u ired f o r th e p re p a ra tio n o f
m d 3^aeetylthlo|>hcm e*

By re a c tin g 3*metiiy ltid o p h en e w ith

H-bromosuceiniiBido In th e prosenee o f bemaeyl perox ide in carbon te tr a o h lo rld e m so lv e n t seconding to th e method e lu c id a te d by B ittn e r and

22

c o lla b o ra to r* (1 1 ), a maximum y ie ld o f 60*6& o f 3~thenyl bromide « u
obtained*

The re a c tio n to q u ite exotherm ic m l th e product is o la te d

i s 2^ro^^3*m tI^X tM opJi9iso i f th e bettsoyl peroxide I s em itted o r
deCOStpOSCCi* In

th e normal p ro d u c t, )* th » i^ l brom ide, i s *

stro n g Imhtymato r and nos fro n d to bo u n s ta b le , decomposing u ith
v io le n ce a f te r a sto ra g e p erio d o f se v e ra l m onths.

The S o m o let r©~

m otion p ro v id es a eesmm&enb method f o r th e p re p a ra tio n o f 3~ihe«yl
from 3~thenyl bromide (?2) * A s o lu tio n o f 3 -th en y l bromide in ©fcloro~
form m i tre a te d w ith h esm etli(flro etetram in e to form a complex s a l t
vhlch m s hydrolysed by ho t e a te r to give a b6$ y ie ld o f 3 - tlie m l.
The aldehyde, 3~thexisl m s converted to l^ th a n o ie so ld by o x id a tio n
w ith s ilv e r oxide fo llo w in g a p re v io u sly d escrib ed method (7 2 ),

S ilv e r

o x ide m s formed by th e treatm en t o f a s ilv e r n itr a t e s o lu tio n w ith
aqueous sodium i^ d ro x id e .

To th e r e s u lta n t brown suspended s ilv e r

oxide i s added jM tem al and tb s p re c ip ita te d s ilv e r i s removed by
f iltr a tio n *

A fte r a c id if ic a tio n o f th e f i l t r a t e a 95% y ie ld o f s o lid

3-lhsmQic so ld 1® o b ta in e d .

The 3-theisoic acid m s oonvsrted to

> th o n o y l c h lo rid e by tM o h y l c h lo rid e w ith th e p ro d u ct being is o la te d
in 80$ y ie ld by vacuum d i s t i l l a t i o n a f te r removal o f excess th io n y l
eh&orlde (? 2 ),

Campaign© and leS eu r (72) used a procedure developed

by GlXmam and le ls o a (73) to conv ert 3~th©noyl c h lo rid e in to 3 -a c e ty ithiephsm s,

A prepared s o lu tio n o f m ethyl magRosltam bromide m s tre a te d

u lb h f in e ly ground cadmium c h lo rid e to give a s o lu tio n o f dim ethyl
cadmium to ’which m& added slow ly and w ith co o lin g 3*tbenoyl c h lo rid e .

23

A fte r liy iro ly e ie o f t&e roaetioi* m ixture u itfe d ilu te et& ferle m id
t k X i/faid p ro d u ct wa* o b ta in ed by i m t u d i s t i l l a t i o n in a y ie ld
w hich m # 73S o f th e th e o r e tla a l.
th e trw ^ o m a tio n a involved in the preparation® o f 3~thenal end
3*^etyX thiopb*ne a re repreeented by th e fo llo w in g equation*!

:%

+

0
0% <

B«Br

a**.-**
■"'■
'*>
fwea&n#

•eiyfe*

"o

■9

P
c% *cN
/W
c s^ -c
'b

E3

•CSyBr
goroaelyt v
nW eSm on"'”

•coax

•OO0H

aooi.
S 6-

8-

0
-C X I

♦ (CH3) 3Cd
■s

Of th e a c tiv e halogen compounds used f o r th e fteform ataky re a c tio n s ,
e th y l brom eaeetabe, e b h y l^ -brom oproplonate and aXXyl brom ide ware
com m ercially a v a ila b le *
E thyl ^ **bro®E>isobntyrate m o prepared in good y ie ld * by a r a t t e r
e le g a n t ad a p ta tio n o f tbe fStlX -A tolbard^Z elli^^ reac tio n *

Bromine was

2h

added Bitw&p to a s tir r e d s o lu tio n o f phosphorus p en lao h lo rid e i s
ie e b u ty rio sold*

a f te r b ein g s e t «iM d overnight* th e m ixture was

tr e a te d m th m ex cess o f th lo n y l c h lo rid e to glare °< ^ ro m ts o b u ty ry l
6 K M # hfts&vh m m m% Is o la ie d # b a t , a f t e r removal o f exsess tb io n y l
c h lo rid e , *aa tr e a te d v ith a b so lu te e th a n o l.

By vacuum d is ttlX a tS s ii,

a 71V e v e r m ll y ie ld o f e th y l ^ •^ n rem lso b u ty ra te woo O btained.
B eing tb s method d escrib ed V Setm&dt and K arrer (7h) , sifcyi
^ "fersoMwretofiato area p rep ared from mth&t oroton& ie through 1&e in te r*
motion o f S ^ r e o o a e i n l i d # n l t i e th y l e ro io n a ie in tb s presence o f
hsn so y l peroxide em ploying carbon te tra c h lo rid e a* a s o lv e n t.
y-brotaocro to m te m o is o la te d by d i s t i l l a t i o n in a 622 y ie ld .

B thyl
IlbyX

e ro to n a ts m o sy n th e sise d f a 722 y ie ld by th e e s ta r if io a tio n o f c ro to n ic
aold s t i l t 222 e th a n o l and s a lf o r te a s id .
H i m 1! method (72) f o r th e sy n th e sis o f p ro p arg y l bromide from
pirepargyl alco h o l m o used su c c e s sfu lly to produce a 72% y ie ld o f
p ro p arg y l bromide*

Flaoepherus tiih ro m id e m o added dropwise to

pro p arg y l a lc o h o l d isso lv ed in d ry p y rid in e a s a so lv e n t and th e alleyne
h a lid e m o Is o la te d by d i s t i l l a t i o n *
tsfem a& sfey E m o tio n o f c<*0romoeat©ire
tim

K*baremeasters employed m th e a c tiv e halogen c o n s titu e n t m ire

e th y l b rem eao eiate, e th y l o<-biremoproplcumte and e th y l tC rbrcoioloobutyrate .
t h i s e e le e tto n o f bromoeeteire a lls e e d an exam ination o f th e r e a c tiv ity
o f a prim ary h alo gen , a secondary halogen end a t e r t i a r y halogen.

25

tb& carbonyl d e rim tiw s o f thiophene ©aoanined mm 2 -th en al,
3-thsnaX, 2^motyk%Moph»m,
2*lm iyi^lthi0plieae and

2-propiouyltfalophotwi$
ttyltidophono* th e v a ria tio n of

tfeisnyl d o iiw b iw s ««i in tli® p o sitio n of sirtMrbitoiiiStti on the
tMfifSwio rin g , the length o f th@ alfcyl chain Im tb s g-acylthiopfcenas
and the presence o f * methyl group adjacent to the acyl group*
f l i t so lv e n t snploycd m « tosm om sin e s m nr©a c tio n m s found to
occur I n otfeyl o th e r and om soo£vt decom position took p la ce i s toluene*
th e mvo o f a boms era*-to lu e n e m ixture nan found to o f f e r no advantages,
% th e lo fo rm ts k y re a c tio n o f carbonyl d e riv a tiv e s o f tftteptan o
vith** -b*m oosb® ro a v a r ie ty Of b m e h chained e th y l 3-(2«*thle»yl) o r
3~( 3 -th ie n y l) *3»)^rdro3i3ralkaf5oat#s worn produced*

:*eO03fc

t

Equim olar q u an tities o f th e th ie n y l carbonyl compound and

-bromo-

e s to r wore d isso lv e d in mltydrm& h®m®m and to th is s o lu tio n , v ith
s t i r r i n g , m o added a s im ila r q u a n tity o f d ry acid msked tin© Oust*
f ho re a c tio n m s in it ia t e d by a s lig h t a p p lic a tio n of hoot to tho
bottom o f th e re a c tio n v e s s e l, and ©nee s ta rte d th e rig o ro u s e so tb e ra te
re a c tio n had to bo m oderated by b r ie f iism rsdon o f th® ap p aratu s in an
1m bath*

^hm tb s i n i t i a l r u c t i o n had s ^ s ld e d tbo a&xtur® m s

h eated a t i t s rofXo* toa^®ratar@ f o r one hour and then hydrolysed by
th e a d d itio n o f an loo co ld 10$ s u lf u r ic acid so lu tio n *

The non-

aqueous la y e r m s se p arate d and eombimd w ith a subsequent o th e r

26

e x tr a c t ©f th e m ueous p o rtio n *

The cosfcim d e x tra c ts m m given

<3<mm<mUv& txm^mma^s w ith m b e r, 10% mdlxm carbo nate and m te r in
o rd e r t© i w v i tr a c e s ©f © alfurt© a c id ,

After th e s o lu tio n m

d rie d

w r m h ^ tv m m d tm railfat® , th e e th e r and beraene v ere rsaovad a t
r e d d e d p& m m m m d th e re sid u e m e d i s t i l l e d trader vacmai*

A q u a n tity

o f mmvrnmd ketone o r aldehyde m e f i r s t receiv ed follow ed by th e
(>-hydbr©3sy e s te r*

E>iatiXlati©n pm m \ire® o f le s s th an one s d lllis e te r

©f jaercury m r© u s u a lly r e t i r e d i© a m id dehydration o f tb s (3 -hydroaye s te r to th e corresponding u n sa tu ra te d e s te r*
in a l l o ases th e (3 ^ d r o a y o s to r e m r® is o la te d in a pure c o n d itio n .
A pparently th e v m ©f a lo m r b o ilin g so lv e n t and low er d i s t i l l a t i o n
teapem turs© acecu at f o r th e su c c e ssfu l Is o la tio n o f th e (3 ~Jiydr©xr~
e s te r s a s compared to H ille r and Hopd<« $6£) fallu r© to is o la te th em
oewiK^simds

e t l y l b rsn o so e tste w ai used*

11 to g e th e r 9, te n ©tlyX > -(2 ^ tid ^ iy l) ^3^%drojs5yalk^noat3s and s ix
e t l y l 3~( >*tM e n y l) ^3-hydifmyalkam»at©e #M oh have n o t p rev io u sly been
re p o rte d

p rep ared and sons o f th e ir p ro p e rtie s a re ma&Mri&ed in

fa b le s 1 and XX re sp e c tiv e ly * Tt$s y ie ld s and percentage o f recovered
batons a re re p o rte d I n T ables 1X1 and I f .
th e y ie ld s shorn e th y l bm noacetat® m s in to rs o ted sd ih the unsubs tltu te d fchicmyX d e riv a tiv e s ranged tm m $$ to 68$.

l i t t l e change in

y ie ld o ccu rs w ith v a ria tio n s in th e le n g th o f ac y l group attach ed to
tb s th io p h em n u c le u s,

A fcsrksd decrease in th e aaount o f product

ob tain ed occurred, sh a re 2 -a e e ty l-3 H n stly l thiophsno m s used a s only
a 25$ y ie ld re s u lte d from th e In te ra c tio n o f th is compound w ith e th y l

27

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29

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30

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31

bremoaootat® under noZommtBtey conditions?.
tm%m» mm high (1$$) ,

The amount o f recovered

Th® low y io ld * m d high rocovory o f a le r tin g

m o to ria l ar® presuma&iy 4u© to bh® blocking e f f e c t o f ih® 3«mothyX
group m bh® th iop ho m rin g *

A s im ila r r e s u lt was ro p orto d by Homan

($6) f o r bho B afofm toisy r o ta tio n In volving a c e ty l megigpXone.
Homan a ttr ib u te d bho high reco v ery o f unchanged a c e ty l aoaitylen© to
enolift& tioa o f th e baton® by th e os’gnnom®t a l l l e d e riv a tiv e which thon
ro a ste d w ith th e ©no! form o f th e ketone to produce a redwood a® tor
and th e kaXooim eoraple* o f th e ®**©X# On h y d ro ly sis o f bh© re a c tio n
m ixture the halass.ino complex regenerate® th e keton e»

JU C % J-R

XZn-Cy-OOOH

jm -hJ

01

I

OZnX

Zi-CH«€-*K ■+ M u^O U ^O O B
OXal

f

+ C%~C0OR
OH

+

Si

JM3S*fc~K

*

fb® amount o f onollo& tlcm ha® boon found to bo a fu n ctio n o f th®
typo o f aoXvemt, th® haSmgma m p leyed* and th e aterl® blo cking by
groups In ib© koton® {$&*$?)*

U sually th e © m llsa tio n re a c tio n proceed®

a t a alm ier rat® th an th e norm al re a c tio n except in th o se case© where
o to rlo fa c to rs h in d er form ation o f th e normal p ro d u ct.
from th e reaction® in v o lv in g th e aldehyde® o f thlopbene gssm on*
re a c te d aldehyde was reco v ered ,

fh io recovery* 5-10$* mao accompanied*

a s w ith th e ketone® by a CQwrparable amount o f reduced o o to r.

32

&$ enolist& tioji &&m n e t occnr w ith aldehyde# e f ttrfeptatB e, th ^ ir
m m m r& in ib® B efoxm iehy r a ttl e r * muet be aeeoiiaated f o r by m m •
e th e r eagtiUittftt&Qii* tts& id e a s o ffe re d by Jo in s end c o lla b o ra to rs (X?)
fin* th e jpom m ry o f l^ m e ld e l^ d e front Xh«» re& eiien w ith ntebhyX
V ^roaaoarotenai© m& be o ffe re d m m exg&ana ile s * Tfc© erg*mesl*so
d e r i^ a iiw o f the e a te r dl»eeei^t@ s in to Io n ic specie® * A reeoaagiee
s tru c tu re edits th e n eg a tiv e elm rgt on th e m afom tfl ©^ygem th en a tta c k s
th e aldehyde mtd m m &in In a p rod uct w hich, when hydrolysed, would
y ie ld th e a ld et^ d e end reduced e a te r .

G

Br£®

-

<2»
9
* a % -c -a it

<— r

n

0&

(S)
4* C%:X o i t

U ?0
p»
JWB-O-C-CS^

•s

c% < M 8t

"C%

•B

3*0

y -c*

♦ w y jo a s t

•s

When eth y l <* •^bromopreplom'^ ©erved &s 'the aetlne ImXogen oom~
pom®% in the B efensatsly reactio n , y ield s ^or® s lig h tly low er, 5b~63$,
exeept where 2-&eaiyl-3-«*?ieifcyl thlopbone m e used In which cane the
y ield m e only 20$*

apparently any incna&sed s te rle e ffe c t of the

longer oitrbon chela in the haleeoier i s overcome by the increased

33

o f tlw i M k r j r k lfig e n .

The

o l recovered

• b e rtin g m o r t a l were n e t aptw eeiably d if fe re n t tr m tfeom where ettyX
braoftoootat* wee used*

One© og«ii*# no liaporbasit v a ria tio n i s y ie ld s

wee m tk m d w ith th e e w U tla a i s th e le n g th o f th e oarbon ch a in its th e
a c y l group o f th e carbonyl d e riv a tiv e .
The um o f e th y l

^ rw o is o b u ty ra tc re s u lte d in co n sid erab le

flu c tu a tio n o f y ie ld s o f product® o b ta in ed » f r m t end 3~ihenal y ie ld s
o f 6k and 6 0 m m e h tx ln e d , w hile w ith 2 and 3**e«otyl thlopben*
y ie ld s o f only IS end &£$ w m o b ta in e d .

The lo n g er chained

%h$j&phmm $mm only' la rg e m o u n ts o f reoevered keto ne.

a ts d la r r e s u lts

m m observed i*hero <?~aoet,yl~3-«*ifoyl ilstopkeoe m a employed. The
resu lt® w ith th e a c y l tMopfeojae© a re due to th e heavy blo ck ing e f f e c t
o f th e two *lHnetfcyl groups in th e h a lo e e te r.

The enoliz& tlon re a c tio n

i e th e o n ly one th a t proceeds a t any reaeoneble r a t e .

In creasin g th e

re a c tio n tim e end r a is in g th e te n p e m ta re o f tho re a c tio n re su lte d in
rnm&mlm d@<30$s*po®ltXon and no da^noromont in yield® ,
A» «n © ver^aH m m r w M m , com s lig h t inpravemtt&t in y ield s was
noted f o r th o se oaoea where th e 3 - t l d ^ y l d e rtv a tiv e e waro employed in
com parison w ith the. corresponding 2 -th ie n y l eocpowndo.

T his d iffe re n c e

may hove boon g re a te r in view o f th e fa c t th a t th e sael-ir q u a n titie s

w tllieod In the roaet&one o f the 3«4h£eoyl d eriv ativ es wire only oneh a lf o f the m&mt® used few the Jvtl& enyl carbewyl compound®. The
p ero o n tafe lo o t through? sseofc&nXeai m anipulation® wu® c e rta in ly la rg e r

in th e e a se s o f 3-*thionyX ccmpomi® w hich m m used in ssa&lXcr o u a n tltle s
because o f the wmh g reater d if f i c u lt ie s involved in th e ir preparation.

3h

d iffe re n c e i n f ie ld s between th e %m groups o f I s o m

m y be due

to %lm in c re a se d ^ lo a tp o m g a tiv ity o f ih© two p o s itio n in tb s tldophen©
r in g m c o h e re d to th a t o f tb© th re e p o s itio n r e s u ltin g In a s lig h tly
d ecreased tendency f o r th e n eg ativ e sp e c ie s to a tta c k tb s carbonyl
e a fb e a .

T hus, according to th e p o ssib le nsebanicaa,

^>C~H

+ IC^-QOGB*

th e m m eXeotTOiesgative th e

— *

-CHa-COOKt

carbon th e lo o s i s tb s lik e lih o o d

th a t th e an io n ic a tta c k w ill occur*

Tbs moo o f diox&m m a reactio n solvtm t was studied to dotorsain®
1f y ie ld s m m decreased due i© th e preiBoiton o f e n o llm iio n m was
re p o rte d , by Jtsssey and 3® m m ($ ? )# in the pfmt&l ks tones*
iiiv e s ilg a te rc found th a t y ie ld s were reduced by m wmh

These
h®$ w ith

tho reco v ery o f noroaotod ketone b ein g p ro p o rtio n a te ly h ig h e r, M aintain*
in g o th e r condition® c o n sta n t 9 dloxans m e used in ste a d o f boneon^ m
a so lv e n t In th e E efo m atsk y re a c tio n o f th e ih ie n y l k e to m s, and i t
was observed th a t y ie ld s w w rodoood by only 10-20$ f o r th e thlophene
d e riv a tiv e s .

C ^rroopoi^iiigly g re a te r red u ctio n s were observed in th o se

oases where e th y l tovM sseeteb* was used t hm in th o se where e th y l
^ ^ ix m p ro p lo iis te was tb s halogen component,

Mo s ig n ific a n t v a ria tio n

was noted in th e aatoont o f e m u la tio n in dioxaaae w ith t$j© v a ria tio n
in th e e ls e o f th e a c y l c h a in ,

Tbs use o f d i® m m a s a so lv e n t f o r

th e reaction® o f th e J3~tid©nyl ketones was n o t in v e s tig a te d beoause o f

35

tb s lim ited qu a a tity o f th ese compounds a v a ila b le .

The result® o f

th is study are recorded la Table XU.
The dei^ydrablam o f the BeformsissQr product® to the corresponding
u»saturated e ste r s was carried out according to a procedure described
by M iller and herd (6 5 ).

f iv e grtm q u an tities o f the (2-hydrcxyes ters

wore ^ flu x e d in 6$£ o x a lic *so lu tio n fo r s ix hours.

The product was

extracted w ith eth y l eth er and a fte r drying and concentration o f the
so lu tio n , the eth y l £~ {4M e»yl) acrylate was d is t ille d under reduced
p ressure.

The use o f a c e tic anhydride, B$% form ic acid (7 6 ), sin e

ch loride in a c e tic acid (7 7 ), or bensene so lu tio n s o f iodine (78) as a
dehydrating agent resu lted in the formation o f ta rs and h igh ly colored
reaction f ix tu r e s .

The unsaturated products are presumed to be <*,£ -

unsaturated, but there i s tbs p o s s ib ility th at in certain in stan ces
(*, X-unsaturated e s te r s may have been produced (79) ♦ In no ca se,
however, were two isom eric masatnra&ed e ste rs is o la te d .

Through the

dehydration rea ctio n , e ig h t eth y l (3~(ihlenyi) a cryla tes which have
a c t been p reviously reported were prepared.

Some o f th® p rop erties o f

these compounds are recorded in Table 7 .
Beforraatsky Enaction o f IthyX
The reaction o f eth y l

^-Broiaocrotonate

y~brom©er©t©nate w ith th ie n y l carbonyl

d eriv a tiv e s under BeformaiaJy conditions y ie ld s a v a riety ©f products,
the o rig in o f which are dependent on the nature o f the carbonyl
component.

The carbonyl compound® In vestigated were 2 -ih en a l, 3-th en a l,

2*&cetyltht©ph@ne, 2-propionylthioph@ne, S^butyrylthiophene and 2-acetyl-*
3 -« eth yl thlophene,

36

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37

Borneo* mm ftwmi to be the boot reaction nadlon t«r the itaforaatsky
pooetta* a t ttkgdL * •brM M rotaate a itb tte th isn yl oertoonyl darivn*
tlv M . £tbgrX otAor, tolaene or bemena-toluene alxturee offered no
adVllllfoffltfftWft ,
Id tto® oaoo o f $<* add 3 -tfe en a l, th e hydroxyeetera wore is o la te d
Id a ymm co n d itio n £ rm th e re a c tio n m ixture b y vacuum d is tilla tio n *
H i jkitNlooli o f

2*bw tyr|X , m i

tM&pham m m eim i& aiim ted b y th® corresponding d e h ^ ra tio n p rod ucts *
f he d o h ^ rc tlo n i f th e bydroTQ^mbttrm la pmmmmI to tmm OQOiirtd
d u rin g th e ir d i s t i n c t i o n , ein ee re|>eatad d i s t i l l a t i o n f a ile d to linprov®
th e p u r ity o f th e products* and o n ly re s u lte d I d f u rth e r d eh y d ratio n ,
fh eee p rod ucts w ore, th e re fo re , converted to tb® usioattsratod c e te ra by
refXua&ag f o r e ig h t hours id a $$ o x a lic ac id s o lu tio n ,

H ille r and

{ford (id ) were unable to I s o la te e ith e r tk e kydresgr o r u n satttrated
e s te r s add oo sa p o n ifltd add dehydrated th e p ro d u cts w ith m ethaaolic
lygtyffKl ^

to Ototalii th® oorrespondidg a c id s *

By th e U®tomm%»ky re a c tio n o f e th y l V ~broi»e>erotenet© w ith c a rb o n ji
emnpeen&s o f tid ep h sn e a v a rie ty o f branched e th y l S*(tMoiQrX)^S«aXli^,X«
a ^ p e n ta d ie n o a te s ware sy n th esised *

m'B. + Sr*C%*CH«CB-a001t —^2aU,

4 - *C«CH*CH*CIWOGEt
> &

th e In teractio n o f tooth 2~ and 3-thenaX with e th y l * -toremo-*
eretosiate re su lte d In too iacm eric f^d ro x ^eto rs whose bo ilin g points

3e

d if fe re d by a p p ro x im te ly 285° C# ftm low er b o ilin g o f th e p ro d u c ts,
w hich va* iis lA t« 4 in tb s la r g e r n m l f ra p id ly adsorbed m& mole o f
b re n tn e .

f u r th e r , th e tre a tm e n t o f th e low er b o ilin g e s te r w ith

osone f o U M t by h y d ro ly sis o f th e o so n td e , re su lte d In th e form ation
o f form aldehyde. t h i s l a t t e r o b serv atio n I s in d ic a tiv e o f a te rm in al
iw altip le hood lin k a g e , w hile tb s ra p id re a c tio n w ith bromine I s
o h a rs o to rls tle o f a double hood shdoh i s n o t ad jacen t to an e le c tro *
n eg a tiv e

Gonsid&ratlni* o f th ese two re a c tio n s stro n g ly suggest

th a t & rearran g ed p rod uct having a te rm in a l v ltjd group was fo rc e d ,
th e h ig h e r b e llin g Isom er re a c te d w ith bromine a t a much slow er r a t e ,
a p ro p e rly c h a r a c te r is tic o f a double bond a d ja c e n t to o r In co n ju gatio n
w ith m e le c tro n e g a tiv e group.

Although M ille r and Herd (16) s e re

unable to is o la te m y p ro d u cts corresponding to

* v iiy l e s te r s , th e

is o la tio n o f such i v i m s y d p ro ducts have been e ffe c te d b efo re in
le f e r e a is ly re a c tio n s employing m ethyl V -brem ocrotonate (1 7 ,1 8 ).
th e se In v e s tig a to rs re p o rte d th a t th e

* v in y l isom er b o lls a t a con*

slderafeSy low er to a p e ra tu re th en does th e normal p ro d u c t. The p re se n t
in v e s tig a tio n confirm s th is o b se rv a tio n .

Presum ably, th e

-v in y l

d e riv a tiv e r e s u lts through a charge m ig ratio n in th e n eg ativ e sp ecies
o f th e organosinc h a lid e ,
<&
ArCSH^%-*CH«CIMOOgt ^ = ±
Fi
n$
®
U
>e*H + iCB-COMSt
^ a /
CB*C%

/I
lC ^C B <.fK 300Et

+
fl
I!

il ^
JJ*CB*CIW%)0&fe
OH«C%

39

Sh l b

cm® o f S H b b l , the y ield o f ^ -v in y l- (3-hydto*©3^»ter

was &$!& o f l b th e o re tic a l while th a t o f i t 10 normal product m o
o f tit# th e o re tic a l.
were

W th 3~the«»al tii® y ield s o f the vinyl Iso h ijo

m d 17% re sp ectiv ely .
The iCm&Mm o f «** ^ -v ii^ rl te e n e r was noted to have occurred

w ith 2-aoetyltM opiauie altho ugh to & le s s e r e x te n t t hm w ith th e
aldehgdOg f-tb e n a l * Th© normal hydrossy e s te r tended to dehydrate upon
d is tilla tio n

tsftoo

c’C-vipyl d e riv a tiv e could be Iso la te d and

c h a ra c te rise d m th e l^ d ro ^ o s te r*

th e normal product one dehydrated

end c h a ra c te rise d m th e alk ad len o ie e s te r ,

th e y ie ld o f *< -v in y l

Isom er was 1$ o f th a th e o re tic a l w hile th a t o f th e normal prod uct m s
76% o f th e theoretics*!*

There were no isom eric products formed in

th e se re a c tio n s where 2 -p rap io n y l and 2-butyrylthioph^n® served as the
carbonyl compound* Presum ably, the in c re a se in e ls e o f th e ketonic
a lk y l group ten d s to in h ib it the a tta c k o f th e more bwligr an io n ic
sp e c ie s b earin g th e charge on th e K -carb on .
ta rg e q u a n titie s (5?«62%) o f recovered th ie n y l ketones re su lte d
from th e ir in te ra c tio n w ith e th y l ^-brom ocrotoiute * A comparable
q u a n tity o f e th y l c ro to n a te was is o la te d from each, o f th e reac tio n
m ix tu re s« th is may be ascrib ed to sno lis& tlon of th e ketone by th e
organosine h alid e in te rm ed ia te r e s u ltin g in red u ctio n o f the h a lo e ste r
and th e recovery o f unchanged k eto n e.
A sm all amount (10-11$%) o f recovered aldehyde was found in those
re a c tio n m ixtu res in which th® th e n a ls were employed.

Jo n es, 0* S u lliv an

10

and v h itio g (IT ) observed a s im ila r occurrence when benzaldehyde ,
w hich e m m %

underw ent th e h efo raatsk y re a c tio n w ith m ethyl

* ~briwweF©tei*ate* The ex p lan atio n was advanced th a t th e Is o la tio n
o f bem aldehyde was due to th e form ation from th e

-brcm oerotonate

o f an in te rm e d ia te which l e a resonance hybrid and a® such can re a c t
to form an o d o n ie sp e cie s o f th e erganoeino h a lid e which on h y d ro ly sis
y ie ld s bene&ldehyde and reduced e s t e r «

Br£»~C B^-C H*CB-GOOKe

(2) cS)
Sr£n + »C%^g-OfiWJC«e
© 9

€%*Cii»C

G«jHfc-CH * €Ha«CB»Q
9

*«•

•> Gb %-OB-O^C«CH-CH«C»8

>

0 6%-Cft>

* GKaCH-CB-COCM©

4 s im ila r mechanism accounts f o r th e is o la tio n o f tb s then& ls from th e
re a c tio n m ix tu res in th e p re se n t in v e stig a tio n *
The H efom atshy re a c tio n s were c a rrie d o u t by m ixing ©ouimolar
q u a n titie s o f carb o n y l eengxrand, e th y l ^ -brom oerotonate, and sin e
d u st in d ry bem ene*

4 sm all c r y s ta l o f Iod ine was added as a re a c tio n

i n i t i a t o r , s t i r r i n g was commenced and th e bottom o f th e re a c tio n v e sse l
was h eated g e n tly to s t a r t th e reactio n *

Xt was n ecessary to m oderate

th e vigorous em athemi© re a c tio n by tem porary immersion o f the f la s k
in m Ic e bath*

The re a c tio n m ixture was heated a t I t s re flu x

hi

tom jwiraiure f o r ©as hour A fter th e spontaneous reflu ad n g had subsided
to com plete th e re a c tio n *

A fter hydr©2y®ing th e re a c tio n m ixture w ith

an loo so ld 10# s u lf u r ic so ld soluiium th®

©us la y e r was

se p a ra tfd and e x tra c te d su c c e ssiv e ly w ith w ate r, sodium carbonate so lu ­
tio n and w ater*

The o rg an ic so lu tio n was d rie d over sodium s u lfa te

and th e so lv e n ts were removed, a f te r which th e re sid u e was su b jected
to vacuum d is tilla tio n *

The fo reru n contained e th y l ero to n ate and un~

re a c te d carbonyl compound follow ed by th e pro du ct o r products*
A lto g e th er, fiv e th le n y l s u b s titu te d itydxwxpwtars which have n o t
p re v io u sly been re p o rte d were p rep ared .
m terJU d s a re sussnarlsed in T able VI*

The p ro p e rtie s o f these
In a d d itio n , s ix e th y l 5 -(th len y l)«

$~hXysyl~2,^ p e n ta d le n o a te s m m sy n th e sise d .

A suonsarlsatlon o f the

p ro p e rtie s o f th e se compounds I s shown In Table VXX*
Jtsfo iM tslg r R eaction o f * lly l Bromide
The condensation o f a H y l bromide w ith carbonyl d e riv a tiv e s o f
thiophen® under th e co n d itio n s o f th e Reform at s ty re a c tio n le a d s to t Im
form ation o f h~

(

*
OH

S:
The use o f a l l y l bromide In th e E efom ataky re a c tio n has receiv ed very
l i t t l e a tte n tio n (19) p rev io u s to th is In v estig atio n *
T h is a c tiv e bromine compound was found to r e a c t w ith th e th ie n y l
c&xbomyl d e riv a tiv e s to give e x c e lle n t y ie ld s o f the expected p ro d u ct.

la

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Since «w*3t®r v ery S ia ll q u a n titie s o f wnrsacbed ketone were reco v ered ,
I t way be sp ecu lated th a t th e e n o lix a tio n re a c tio n i s o f minor Ibk
p o rta m e when a l ly lle brom ides are u sed .

There was no in d ic a tio n th a t

th e p ro d u cts o b tain ed underwent any degree o f dehydration during
d i s t i l l a t i o n a t low p re s s u re s .

The y ie ld s o btain ed were o f th e o rd e r

70 * 80 $ and v ary l i t t l e v a ria tio n in y ie ld s was noted between th e

then& ls and acy lth lo p h sn es nor between th e 2-tM e n y l and 3 -th ie n y l
d e riv a tiv e s .
The re a c tio n was c a rrie d o u t by th e In te ra c tio n o f equlm olar
p i s t l U d s o f carbonyl compound, a l l y l bromide and einc d u st in a
w in te rs o f eq ual volumes o f beneene and te tr & l^ r o f u ran .

The presence

o f th e te tra h y d ro fu ra n prevented th e p re c ip ita tio n o f th e a lly ls in c
bromide in term ed iate which caused e a rly term in atio n o f th e K eforaatsky
re a c tio n ,

lif te r th e i n i t i a l A W thsm lc re a c tio n had subsided th e

*

re a c tio n m ixture was heated a t i t s re flu x tex ^arab ure f o r an a d d itio n a l
hour.

Ic e co ld 30$ a c e tic ac id was used to achieve h y d ro ly sis o f th e

re a c tio n m ix tu re,

i f t e r th e aforem entioned w ashings, drying and

rem oval o f th e s o lv e n ts , the re sid u e was d i s t i l l e d in vacuo to y ie ld ,
f i r s t , a v ery sm all amount o f u nreacted carbonyl compound follow ed by
th e pure liq u id p ro d u c t.
A lto g e th er, seven p re v io u sly unreported h-tldenyl4i*JU ydroxy*l*
a lk e n ss m m prepared by th is p ro ced u re.
a re euam arieed in Table f i l l *

T h eir p h y sic a l p ro p e rtie s

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C

M*form*%*ky Emotion o f I¥op*rgyX 3imid*
4 previous rep o rt ( 6 6 ) describes only the in te ra c tio n of propargyl
bromide w ith 2 -tb anal to y ield the expected l - ( 2 **tM®iaya>*>btttyii-.l-el*
This arMS? rep o rts n

mm ea&enslve in v estig atio n of tid e p a rtic u la r

aspect o f the Jtefbmsttsky r m t t i i to a wide v a rie ty of carbonyl deriva­
tiv e* which included 3 -thexial,

2 -& eetylthiophene, 2 -propio*srltMophene

and 2 -l*atyrylthi©ph«me * th e reactio n was found to proceed ee s p o rte d
w ith 2 -th en al r e c i t i n g in a 60$ y ield o f the expected product.

lik e w ise th e re a c tio n ’w ith 3 -th e n a l took p la c d w ith a 62 £ y ie ld o f
th e eerreep en d lsg 3 ~ th ie« y l d e riv a tiv e *
^ I th th e 2-tIsie n y i k eto n es, however, even though the re a c tio n
appeared to proceed v ig o ro u sly , w ith th e «t»c b eing com pletely consumed,
i t m e im possible to o b ta in any Heform&tsky type product*

The recovery

o f u nreacted ketone was f o r 2-ace ty lth io p h ea e Bh%$ 2-proplonylthiopliene
76 $ and f o r 2~bufcyrylthiophem 7 31 ,

4s assail q u a n titie s o f n o n d is b ill-

a b le m a te ria l rem in e d In th e d i s t i l l a t i o n f la s k i t i s p o ssib le th a t
sm all amounts o f th e e j e c t e d pro du cts may have been farm ed, b u t were
d estro y ed by p y ro ly sis du ring th e d is tilla tio n *

The use o f a higher

b o ilin g so lv e n t such m to luene o r th t in c re ase o f re a c tio n tim e up
to fo u r hours gave no bhienyl a lk y n o ls, b u t only re s u lte d in wore
ex ten siv e decom position in th e re a c tio n m ixture * Based upon th a la rg e

n

percentage® o f unreao ted batons reco v ered , i t seem® th a t th* in te r ­
m ediate pro$m*gyl a im bromide promote* co n sid erab le enoXAg&tion o f
t l » 2 «*tidUmyl ketone**

t h i s r e s u lt to In sh arp c o n tra s t to the aa& ll

amount o f e x p lic a tio n which m m stm d in the &ef©mat«lqr m ic tio n w ith
a lly ! bros& de,
wrmmr*w

Ho s u ita b le e j^ la n a tio n may bo offered fo r th is

W,PH
>mt

The Befom&toky mm%%om o f propargyl bromide were a a rrie d o a t
in th e aam manner am m m th o se in v o lv in g a lly ! brom ide.

The re a c tio n s

proceeded v ig o ro u sly &n& w ith o u t the a p p lic a tio n o f boat*

I n itia lly ,

co o lin g o f t bm re a c tio n v e s s e l w ith an lo o b o th woo r e t i r e d to m oderate
th e re a c tio n *

% drolysi® o f th e re a c tio n m ixture was accom plished

w ith m im m M 30$ a c e tic a c id eo latio n *

A fter th e u su al e x tra c tio n s ,

m a k in g s and d ry in g th e co n cen trated re sid u e m e d i s t i l l e d tinder reduced
p re ssu re .
th e p ro p e rtie s o f th e Km 1~( th ie n y l) ~>4m tjti»l«»ols which m m
prepared a re rep o rted In Table IX* .One o f th ese compound® ha® not
been re p o rte d p re v io u sly .

TM£ XX

1*3

h9

ewmni& m a m a
TM ephsm e~PraetlcaI g ra d s, Eastman Kodak Co.
lo s tto

Mmfmm Kodak Go.

h « p io R l 0 ^ ^ i d d « - F 2^actic«il g ra d s, I&ststaa Kodak Co*
B u ty ric i«Apd*£dfeM#0t m®tmm Kodak Co.
lim e dusb» 30O m esh, a c tiv a te d by immersion in hot eem oentrated s u lfu ric
so ld to wbteh a fe v drops o f n i t r i c acid has been added. Tbs sin e
mus mashed w ith d i s t i l l e d m uter and acetone and d rie d a t £0° c .
f o r bmsnty m in u tes.
Bensene^-C. P . g rad e, d rie d by d i s t i l l a t i o n from sodium,
T a ir ahydrofuran~C. P . grad®, d rie d by d i s t i l l a t i o n from sodium.
i^xafk #« £. P . g ra d e , d rie d w ith magnesium s u lfa te and sto re d over
to lu e n e -0 . P . g rad e, d rie d by d i s t i l l a t i o n from sodium .
3#U ethyl thioph<me«Courtesy o f SoeongMfacutsn OH C o ., p u rifie d by
d ry in g over magnesium s u lf a te and d i s t i l l a t i o n from sodium.
E thy l b ro m o ao etate^ M te li& s l, Eastman Kodak Co,
K tbyl < K ^roja^a?op iO ttate^^te la b e l, &astnaa Kodak Go.
Form aldebyde«>Praotieal, 3I f s o lu tio n .
Iso b u ty rlo letd -P ru o l& e al, b atm an Kodak Co,
C rotonic A e ld -P m c tle a i, Eastman Kodak Co,
H ~B roittom ieciJ^idtf-*M te la b e l, Eastman Kodak Co.
Bensoyl F erosd U le^cm erolal g ra d e , Luoldol Corp.
Carbon T etrao h lo rid e -C . P . g ra d e , a b s o lu te , Kerek & Co.
ijiy i B rom lde^M te la b e l, Eastman Kodak C o ., p u rifie d by drying over
magnesium s u lfa te and d i s t i l l a t i o n through a C lalsen column.

50

la b e l, Eastman Kodak Co*
K exam & tfoylem tetrajiii^^

la b e lf Eastman Kodak Co*

Chlor©for3n**0 0 p . g rad e 9 a b s o lu te , Merck & Co,
T hieuyl ehle**id*M>, P , g rad e, p u rifie d by d i s t i l l a t i o n tram <gttlnoline
follow ed by d i s t i l l a t i o n from b o ile d lin s e e d o i l .
M ethyl B reaide-^liii© la b e l, Eastman Kodak Co,
Hagaeslun«C, P , ta m in g s , Baska&n Kodak Co,
Cadmium e h la rtd e -C , F , anhydrous, Baker Chemical Co,
P ropargyl

la b e l, Eastman Kodak Co,

F y rid in e -F ra o tic a l# Eastman Kodak C o ,# d i s t i l l e d from barium o x id e.
Phosphorus frib ro a id e ~ P ra c t:ic a l, Kastman Kodak Co,
Phosphorus T ric h lo rid e -lra c ticoO.# Kastman Kodak Co,
Phosphorus 0 x y e llo rid e ~ F ra c tlc a l, Eastman Kodak Co,

£L

anaeam m
P re p a ra tio n o f In term ed iates
M h rn a l

Method A «— A w ell e ltr r e d m ixture o f 252 g , ( 3*0 m oles) o f thlop hene,
1020 g , (12 moles) o f 37 $ form& ldsl^de &**$ 321 g . (6 m oles) o f ammonium

c h lo rid e was heated to 67 ° and allow ed to co o l to 55 ° * At 67° th e
cloudy re a c tio n s l x t u e c leared and became straw colored*

By the care*

f o l a d d itio n o f 10 $ potassium hydroxide e o la tio n w ith ra p id s t i r r i n g ,
th e re a c tio n m ixture was brought to a pH o f 6 (U n iversal In d ic a to r
p a p e r),

th e m ixture was steam d i s t i l l e d j the p o rtio n b o ilin g above

98? was c o lle c te d and n e u tra lis e d w ith co n cen trated hydrochloric ac id
to a pH o f 6,5#

A fter se p a ra tio n o f the o ily la y e r , th e aqueous la y e r

was e x tra c te d th re e tim es w ith 300 m l, p o rtio n s o f e th y l other*

th e

e x tra c ts were combined w ith th e o i l and d rie d ov er anhydrous calcium
s u lf a te .

A fte r rem oval o f th e e th e r th e re sid u e was d i s t i l l e d

in vacuo through a Cl& lsen column to y ie ld 153 g . ( 1*37 sto le s| k&%) o f
c le a r p le a sa n t sm elling p ro d u ct.
$1° (1 sam,)}

product i n i

1*5927*

I t s p h y sical p ro p e rtie s were*

The re p o rte d p h y sical p ro p e rtie s o f the

b .p . 72.5® (7 * * .)|

1.5920 (67>.

b ,p .

52

Method B mm in % one l i t e r tiiro e-m ck ed f la s k f i t t e d w ith a re flu x
co n d en ser, s t i r w

m i dropping fhimeX were placed 126 g* ( 1*5 m oles)

o f thlophene and 136 g* (1*92 m oles) o f d i m e t h y l f * Fro* th e
d r e e in g f w e l 266 g« ( 1*66 m oles) o f phosphorus o ay eld o rid e wee added
slow ly to th e ra p id ly s tir r e d and seeled re a c tio n m ixture*

A fter m

i n i t i a l h ea tin g on th e &tmm h a th th e re a c tio n commenced end proceeded
v ig o ro u sly w ith th e e v o lu tio n o f hydrogen c h lo rid e .

When th e i n i t i a l

re a c tio n had subsided tin? re a c tio n m ixture mm heated f o r one hour
w ith e t ir r la g on th e steam h a th and th en cooled to room tem perature*
th e d a rk a d o re d s o lu tio n wee poured ov er 1500 g . o f eraeksd io e and
tr e a te d w ith 300 a i . o f sa tu ra te d sodium a c eta te*

th e o ily la y e r

whioh eeparatod wae combined w ith subsequent o th e r e x tra c ts o f th e
aqueous la y e r m d washed thoroughly w ith 10 # sodium b icarb o n ate s o lu tio n *

A fte r d ry in g o v er amhydrous sodium s u lf a te , th e e th e r so lu tio n

was co n cen trated on th e steam b a th and th e resid u e was d is t ille d under
reduced p ressu re*

I fo re ru n o f u n rela ted ttd ep hsn s was follow ed by

I 2ii g* (1 *11 m olesi 7k%) o f d e a r liq u id *
were b.p* l»7 -U8° ( 0 .3 WB*.)f

I t s p h y sical p ro p e rtie s

1,5906.

2«Aoetyltb3ophene

To a m ix tu re , heated to 70° $ o f 3?8 g . (h*S m oles) o f thlophene
and 175 g* ( 1*55 m oles) o f 955 a c e tic anhydride contained in a one

S3

X lt* r th ree-n eck ed f la s k f i t t e d w ith & re f le x condenser and thermometer
wee added 1 5 g , o f 855 phosphoric a c id .

4 vigorous re a c tio n s e t in so

shaking th e f la s k and I t s c o n te n ts n e c e s s ita tin g immersion o f th e m ~
a c tio n v e s s e l in m le e h a th to c o n tro l th e tem perature o f th e s o lu tio n
which ro es ra p id ly to 50° # A fter being s e t a s id e f o r a h a lf hour th e
m ixture was reflu x ed a t 94? f o r tarn hours and a lie n e d to e e e l to 5 0 °.
A volume o f 300 m l, o f w ater was added to tb s re a c tio n f la s k follow ed
hy shaking o f th e m ixture f o r f iv e m in u tes,

th e organic la y e r was

sep arated and washed w ith 300 m l, o f 105 sodium carbonate follow ed by
washing w ith 300 m l, o f w a te r. The so lu tio n was tra n s fe rre d to a
C lalse n f la s k where a ttxlephem e-m ter e se e trsp e was removed by d i s t i l l ­
a tio n a t 68° follow ed b y th e exsese thiophene a t 8h ° # th e app aratu s
was arranged f o r vacuum d i s t i l l a t i o n and a w ater c le a r p ro d u ct was

obtained. Ita ptyrtoal properties w n i

b .p . ?5® (3 a » .)j n*S 1.563?.

A t o t a l o f 168 g , {1,33 moles $ 865) o f 2 -acsty lth io p h cn e was o b ta in e d .
The re p o rte d (7©) p h y sic a l p ro p e rtie s o f th is compound are*

b ,p , 77°

(h w »„)| njj^ l,56hO .
2 -Fropion 3rltbiophen©

S
0 ain g th e ap p aratu s and procedure A sc rib e d above, $01* g , ( 6 ,0

m oles) o f th io p h en e, p i g, ( 2 ,2 m oles) o f p ro pio nic anhydride and
20 g , o f phosphoric a c id were in te ra c te d a t a re flu x tem perature o f 100 °,

Sh

& fter th e a d d itio n o f w ater m d w ashing th& cntde pro duct 1b th e manner
its ifiM

in th e p m t o i j ^ a m l l o s i th e o rg an ic la y e r was co n cen trated

«nd d i s t i l l e d a t reduced p ressure*

th e re was receiv ed 22h g . (1*60

n e le s f 7 2 *7 $) o f d e a r liq u id whose p h y sic a l p ro p e rtie s were*

b .p .

8t * 8l 0 (1 w »*)| t§f> 1 «$y*2 * th e re p o rte d $50) p e a l e d p ro p e rtie s are*

b .p * 88® (7 m j $ »§# l*S b35.
a ^ u ty ry lth io p h en ©
9

^>0

The ap p aratu s and procedure employed here were th e sane as th a t
used In th e two previous p rep aratio n s*

th is compound was p repared by

th e re a c tio n o f $0 i* g* ( 6*0 m oles) o f thlophen© w ith 366 g* ( 2*2 moles)
o f F$# b u ty ric anhydride in th e p resem e o f 20 g . o f phosphoric acid*
t h i s re a c tio n m ixture was heated a t I t s re flu x tem perature o f 106° fo r
two hours*

Follow ing th e se p a ra tio n procedure used In th e form er

p re p a ra tio n s , th e crude p ro d u ct was fra c tio n a te d , y ie ld in g 2$k g*
( 1 *6$ m oles| 7 i**5 $) o f pure product which feed the follow ing p h y sic a l
p ro p e rtie s*

b.p * 83- 8$° (1 wm*)|

p h y sic a l p ro p e rtie s are*

1*3*08.

b*p, 8?~92° (3 m®.)|

2 ~Ao@tyl~3 ^sj«?tfcyX tM ophene

■C%

I t s rep o rted (80)
1*3*18.

55

b eing th e

g en eral procedure d iscu ssed above* 29b g . ( 3*0

m elee) « f 3-* e th y l th l^ iM fn t, ITS g* <1*55 m elee) o f 955 a o e tie
a liS ftrld i m d 1 $ g« o f phosphoric

m i t in te ra c te d and th e erode

p ro d u ei mm is o la te d in th e u su a l M r n r ,

F ra c tio n a tio n o f th e erode

p ro d u ct through a solemn 30 m m in height* 12 me, in diam eter peeked
w ith l/S * g lo a t h ello es* yiaXded lb 3 g , (1.02 m olesj 665) o f 2~aeetrX*
3 -*H*thyl IM flp te m , r e f ra c tiv e Is d m » |^ l,560l*f b o ilin g a t lk ~ lh *5°
(1 m t«)# and 26 g , ( 0 *X§5 m oleaf 125) o f 2 -*«etyl~b~Bratbyl thhepheue*

r e f r a c tiv e in d ex njj^ 1 ,5 5 8 1 , b o ilin g a t 77»5»tS»5° (1 « » ,) •

The

re p o rte d (61) p h y sic a l o o m tm ts f o r S - a c e t ^ ^ - i^ t h y l fchiopheis© are*
b*p* ?9° (It a » ,) f

are*

b .p ,

86° (3

l* 56X8 j and tim e# f o r 2 ~ac# ty l-h - re th jr l %hi&ph®m

m»*)|

1 *5 6 0 0 *

F or f u rth e r © h& roeterisatloii th e thiosam learh& sone s o f 2- a c a ty l3-m©thyl and 2-<M»©tjX~hH®efc^KL fchiophene ware p rep ared .

The sm itin g

p o in t* f o r tim e d e riv a tiv e * were 206 *207° and 219-220° re s p e c tiv e ly .
The re p o rte d (81) m a ltin g p o in ts f o r th e tl& nrem ieaihaeem s a re f o r
2 «aeebyl*>m atf$& thiophen® „ 287 - W ,5 ° and f o r 2 -a e e ty l-b -« e th rl

th io p h e m , 219*220°,
3~Thenyl Bromide

*GHjj8 r

b a t w llt« P th«»-necl«d flask fitte d with an e ffic la n t reflux
condanear tad sttxrar wiro placed 282 g , (2.88 moles) o f 3-raothyl

$6

tfctophens

3 $ g* o f foemoyl peroxide d isso lv ed In TOO m l. o f d ry

eastern te tr a c h lo r id e ,

To th is so lu tio n n o t added, w ith s t i r r i n g ,

$00 g* ( 2 .8 8 m oles) o f ^brcm osuceinim ide co n tain in g an a d d itio n a l

q u a n tity o f h g . o f b e m e y l p ero x id e.

Th® hremtm&tiiag agent woo added

d u rin g a to o hour p erio d and a t such a ra ta as to allow a ste a d y
re flu d ln g o f th e re a c tio n M ixture * Follow ing th e com plete a d d itio n o f
th e K ^r< «^suoeiniinide th e re a c tio n m ixture was heated a t I t s re flu x
tem perature f o r fiv e hours and th an allow ed to cool to room tem p eratu re,
The in so lu b le soeelntm ids was removed by f i l t r a t i o n and th e f i l t r a t e
was co n cen trated a t reduced p ressu re * The re sid u e on vacuum d i s t i l l a ­
tio n y ie ld e d jOp g* ( 1*75 m oles; 60*6$) o f pungent sm elling 11 <$014
b o ilin g a t T5~82° (1 urn*)« The rep o rted (? 2 ) b o ilin g p o in t o f 2-th a n y l
brom ide i s ?5-78° (1 m®*).
Of two previous p re p a ra tio n s o f 2 -th en y l bromide one became so
v io le n t th a t the re a c tio n m ixture was l o s t through th e condenser, th e
o th e r gave 178 g* ( 1*01 m oles) only a 35 $ o f the expected product *
I t should be noted th a t a sto re d sample o f about 200 g* o f 3 ~th®nyl
bromide decomposed w ith co n sid erab le v io len ce a f te r s e v e ra l months o f
standing*
3 -Tbena!
0i«

To 177 g . ( 1 .0 mole) o f 3~tbei^rl bromide in 350 ml* o f chloroform
co n tain ed in a one l i t e r f la s k f i t t e d w ith a re flu x condenser was

57

added 138 2 * ( 1*0 stole) o f hexanethyX enet^trasdne. The m ixture was
fe»*W a t i t # re f lu x tem perature f o r on© h ou r, cooled and f ilte r e d *
The w hite c r y s ta llin e s o lid w&e d isso lv ed in $00 ml* o f w ater and
•too® d i s t i l l e d u n til one l i t e r o f d i s t i l l a t e had boon c o lle c te d *
A fter im tr a lie a tle x i o f th e d i s t i l l a t e w ith d ilu te hydrochloric acid
th e o ily o rg an ic la y e r wee sep arated and combined w ith th re e subsequent
o th e r e x tra c tio n s o f th e aqueous layer*

Using calcium s u lf a te , th e

o th e r s o lu tio n was d rie d and then co n cen trated on th e e tc sen both*
By d i s t i l l a t i o n a t reduced p ressu re $h g , (0 ,i *8 m olsj U8j$) o f c le a r
liq u id pro du ct m e obtained*

It® p h y sic al p ro p e rtie s w erei

b,p*

76 -T?° (12 me*) * th e rep o rted ( 82 ) p h y sic a l p ro p e rtie s o f 3~ ih en al

are#

b ,p , 78

( lk u a O .

This p rep a ra tio n was rep eated to y ie ld 55 g*

(0,1*9 mol® | 19$) o f 3 * tlm sl*
>»ThettQie acid

th e com bination o f a s o lu tio n o f 150 g* ( 0*883 mole) o f s ilv e r
n itr a t e in 300 ml* o f w ater w ith a so lu tio n o f 70 g , (1*75 m oles) o f
sodium hydroxide l a 300 m l, o f w ater gam a brown suspension o f s ilv e r
oxide*

To th is suspension was added, w ith rap id s t i r r i n g , h ?,5 g .

(0 *li2h mole) o f 3 *»theml o v er a 25 mtmuts p e rio d , d u rin g which tim e i t
was n ec essary to co o l th e re a c tio n m ixture to m oderate th e exotherm ic
re a c tio n *

At th e com pletion o f th e a d d itio n o f th e n a l th e c h a ra c te ris tic

58

•dv*

th is aldehyde had disappeared and a heavy p r e c ip ita te o f

s il v e r had s e ttle d to the bottom o f th e b ea k er.

The m e ta llic s ilv e r

woe removed by f i l t r a t i o n and washed w ith WO ml* o f w ater which m s
combined w ith th e b a sic f il t r a t e .

A cid ifica tio n o f tlie f i l t r a t e w ith

co n cen trated h y dro chlo ric acid canoed th e p re c ip ita tio n o f a w hite
s o lid ,

The m ixture vac n e t a sid e in th e r e f r ig e r a to r f o r tw elve hours

d u rin g which tim e 51 g . ( 0 .U0 mole5 9 5 0 o f product c r y s ta llis e d from
s o lu tio n .

I t m s f i lte r e d and dried*

The product had a m eltin g p o in t

o f 135*5-137°. th e im ported (72) m e ltin g p o in t i s 137-138°*
c h lo rid e

The- a d d itio n o f 59.5 g* (0.5® m ole) o f thionyX c h lo rid e to 51 g ,
( 0 . 1*0 mole) o f 3-th e n o ic acid over a two hour p e rio d , d u ring which
th e e 1die re a c tio n m ixture mm kept a t i t s re flu x tesg& r& ture, gave a
d e a r yellow s o lu tio n .

A fter removal o f th e ex cess th ie n y l c h lo rid e

on th e steam b a th th e re sid u e m e d i s t i l l e d u nder reduced p re s s u re .
At a tem perature o f 99-101° <3® mm.) th e re m s o b tained J*6.7 g . <®.32
m ole) 8 0 0 o f s lig h tly yellow liq u id product Which s o lid if ie d to a
s o lid having a m eltin g p o in t o f 1*9-51°,
c o n sta n ts f o r th is a c id c h lo rid e are*
51-58°.

The re p o rte d (72) p h y sic a l

b .p . 110 - 111 ° 0 6 mm.)) m .p.

$9

0

M ethyl magnesium bromide was prepared by th e in te ra c tio n o f
k$ g . (0 ,b 6 mole) o f m ethyl bromid© w ith IX g* (0 ,b 6 mol®) o f magnesium
tu rn in g s in 300 ml* o f anhydrous o th e r.

To tid e ra p id ly s tir r e d and

cooled G rigm rd reag en t was added b h *7 g . o f f in e ly p@Kdo.rod ^ h y d ro u s
cadmium c h lo rid e * The re a c tio n m m & l was removed from %ho co o lin g
b o th and th e ih d u r e s ti r r e d f o r am a d d itio n a l hour a t room tem perature*
A fter re p la c in g th e re a c tio n v e sse l l a a co o lin g b a th , 1*6*7 g# ( 0*32
m ole) o f >»tbesiQgrl c h lo rid e was added in sm all p o rtio n s ,

dion th e

sjwmtsneous reJHUndiig had subsided tb s re a c tio n m ixture m s heated a t
i t s re flu x tem perature f o r am tiour and then allow ed to co o l to room
teeg*er&tur©.

The ImUtragtmmm s o lu tio n was p ou red , w ith vigorous

s t i r r i n g , onto a m ixture o f d ilu te s u lf u r ic acid and erao&sd ic e ,
A 300 ml* e th e r e x tra c t o f th e m ixture was washed tw ice w ith w ater and
d rie d ov er anhydrous sodium s u lf a te ,

-*ft@r removal o f the o th e r th e

re sid u e was d i s t i l l e d under reduced p ressu re to y ie ld 29.5 g» ( 0 , 23 b
m ole, 73$) o f c le a r pro du ct w ith the p h y sic a l c o n s ta n ts« b .p , 77 *76 °
(is * * .) j «^5 1 , 5621 .

(6 an .)f

Thfl rep o rted ( 72 ) b o ilin g p o in t i s « ,- 8 S°

1,5612.

The 2 ,1 dii& ti^pheiylhyira& oira o f th e product had a m elting p o in t
o f 265,5*266°. The rep o rted (72) s a ltin g p o in t i s 265°,

60

E th y l ^ -brom oisobutyrate
ch 3
Br-C«*C00 Ca%

Ini© a one l i t e r th re e necked fla s k f i t t e d w ith an e f f ic ie n t
re f lu x co n d en ser, th eraom ster and dropping fu n n el were added $75 g .
( 3 ,1 3 m oles) o f is a h u ty ric so ld 5 &* o f phosphorus pentaoK Loride*
To th e s ti r r e d s o lu tio n , m aintained a t a tem perature o f 7 8 °, w et added
c a u tio u sly 525 g . (3*28 m oles) o f brom ine. The re s u ltin g d ark colored
re a c tio n m ixture was h eated on th e steam b ath f o r seven hoars d arin g
which tim e th e tem perature o f th e m ixture ro se to 87° and th e red
c o lo r o f brom ine p r a c tic a lly d isap p eared ,

lif te r being s e t a sid e over­

n ig h t th e m ixture was warmed to remove any onrc&oted bromine and I t was
th e n tre a te d c a u tio u sly w ith JbhO g , ( 3 .7 0 moles) o f th io n y l c h lo rid e
follow ed by h ea tin g o f th e re a c tio n m ixture f o r a two hour p erio d a t
i t s re flu x tem p eratu re.

The condenser was then removed and th e excess

tM o n y l c h lo rid e allow ed to b o il o f f .

To th e s o lu tio n , a f te r allow ing

i t to coo l to room tm p e r^ tu ra , m s slow ly added 181* g . (h.O m oles) o f
e th y l alco h o l w ith an o cc asio n al shaking o f th e re a c tio n v e s s e l.
Follow ing th e a d d itio n o f th e alco h o l th e so lu tio n m s heated a t re flu x
tem perature f o r f if te e n m inutes and th en tra n s fe rre d to a one l i t e r
O laisen d i s t i l l a t i o n a p p a ra tu s.

The eth an o l and a sm all q u a n tity o f

u n rese ted e th y l b u ty ra te were removed by d i s t i l l a t i o n a t atm ospheric
p re ssu re and th e app aratu s was then arranged f o r vacuum d i s t i l l a t i o n ,
D is tilla tio n under th ese co n d itio n s gave 1*6? g . (2 .ho moles j 77%) o f

a

e lttw lig n id prodnct d ia tillin g a t 5Q*£X° (10 a n .) which had a
ra fra o tlv a Index o f

14U*07. Xha reported ( 8 3 ) boilin g p o in t i s

63-6S0 ( I t a n .) .
E thyl e m to a a te
Cf^CMH»C0 OC*lfe
i m ixture o f 25$ g , ( 1 ,0 m oles) o f o ro to n ie acid* 750 m l, o f
eth a n o l and 250 g , o f s u lfu ric acid m o p laced l a % two l i t e r fla s k
f i t t e d w ith a re flu x condenser and heated a t i t s re flu x tem perature
f o r th ro e h o u rs.

The r e s u ltin g s lig h tly yellow re a c tio n m ixture was

th en poured In to a th re e l i t e r beaker co n tain in g 1000 g, o f cracked
le e and n e u tra lis e d by th e c a re fu l a d d itio n o f 2$% eodits# hydroxide
s o lu tio n u sin g litm u s paper to in d ic a te n e u tr a lity .

A fter removal o f

th e eassess eth an o l by d i s t i l l a t i o n th e two la y e rs were sep arated and
th e aqueous la y e r was e x tra c te d w ith 2$Q m l, o f e tly l e th e r ,

The

e th e r e x tr a c t m s combined w ith th e sonaqusems la y e r and d rie d over
anhydrous sodium s u lf a te » A fter removing the e th e r on a steam b a th
th e re rem ained a straw co lo red o ily liq u id which on d i s t i l l a t i o n
y ie ld ed 266 g , (2 ,2 6 moles* 75%) o f product b o ilin g a t 137-139°•

The

re p o rte d ( 63 ) b o ilin g p o in t i s 1 3 6 , 7° ,
ftth y l

^rc»soorot«m ate
Br~C%»CH«C E-C0 Q0 *%

To a one l i t e r f la s k f i t t e d w ith a re flu x condenser was added

62

1 X8 g , (%m0 mole) off e th y l eroton& te, 1 ?U g . ( 1*0 mole) o f K-bromo-

suoclnim ide , 1 .1 7 I* o f benscyl peroxide and 1*00 a d . o f carbon te ir a ^
c h lo rid e .

T&U m ixture was heated a t i t s re flu x tem perature f o r an

hoar and a h a lf and then tre a te d w ith an a d d itio n a l 200 m l. o f carbon
te tra c h lo rid e follow ed by Immediate f i l t r a t i o n to remove th e in so lu b le
suooinim ide.

The f i l t e r cake was van bed thoroughly w ith carbon t e t r a -

c h lo rid e and the combined f i l t r a t e was co n cen trated and d is t ille d
under reduoed p re ssu re * i f t e r a fo reru n o f a few m i l l i l i t e r s o f
e th y l cro to n a te th e re was ob tain ed 158 g . (0.82 m oles* 825) o f a
c le a r p ro d u ct having th e p h y sic a l con stants*

b .p . 7 4 *5 - 76° (2 mm.) j

af 1 M m - Th8 r8portad <7W p * ^ 91 oonst;^ t s o t th is cw8pound
b .p . 92-93° (1 0 am .) n^S l.l»9i0..

n

F ropargyl bromide
8 r~C%~CsCH

to a s o lu tio n o f 119 g« (1*0 mole) o f p ro p arg y l alco h o l and 12 g .
o f p y rid in e contained in a 500 ml* th re e necked f la s k f i t t e d w ith a
dropping fu n n el and r e f lu x condenser w ith an attach ed drying tubs was
added d ro p s ie s , w ith o cc asio n al shaking o f the re a c tio n f la s k , 95 8 *
(0*35 m ole) o f phosphorus trlb re s d d a .

The tem perature o f th e re a c tio n

m ixture was im ld a t - 10 ° b y means o f an ic e - s a lt b a th d u rin g th e
a d d itio n o f th e prom inating agent*

A fter th® com plete a d d itio n o f th®

l a t t e r th e re a c tio n m ixture was im m ediately d i s t i l l e d to y ie ld 86 g ,
(0 .7 2 m olsf 725) o f a w ater c le a r product b o ilin g a t 81.5-84°*
re p o rte d ( 75 ) b o ilin g p o in t o f propargyl bromide i s 82 - 85 ° *

The

63

kef ornate kp f a c tio n s o f ^ -Bromoeetem
life y l 3^(2^t!dex^l)^3«hjrdx^x^pi*op{inoikt«
H
B^CHa-COOCaHt

Stoder sntpdm is condition®, l l . t g* (0.10 nolo) of 2-thexm l,
X6 .T g* ( 0*10 n o lo ) o f e th y l bromo&oetate and #0 ml* o f dry beasone
were placed In a 250 m , th re e necked fla sk equipped w ith m e ffic ie n t
s t i r r e r and a r e f le x condenser f itte d w ith a d ry in g tabs*

To th e m ix-

taro in th e f la s k m s added 6*5 g* <0 *1© n o lo ) o f dry so ld washed sin e
d u s t, and a sm all c r y s ta l o f iodine*

i f to r s ta r tin g th e s t i r r e r , th e

re a c tio n f la s k m s heated lig h tly to i n i t i a t e th e re a c tio n a f te r
which i t was n ecessary to m oderate th e rig o ro u s re a c tio n by a b r ie f
immersion o f th e re a c tio n v e sse l in an le e b a th ,

^ e n th e i n i M ai

exotherm ic re a c tio n had su b sid ed , th e m ixture was h e a te d , w ith s t i r r i n g ,

a t i t s re flu x tem perature f o r an hour* The re a c tio n m ix tu re , a f te r
b ein g allow ed to co o l to room tem p eratu re» was hydroiyxed by th e
a d d itio n , w ith ra p id s t i r r i n g , o f ?5 m l. o f an ic e cold 10 $ s u lf u r ic
acid so lu tio n *

th e non-aqueous la y e r was sep arated and combined w ith

a subsequent e th e r e x tra c t o f the aqueous p o rtio n *

The combined so lu ­

tio n s were given consecutive treatm en ts w ith 100 m l. o f w a te r, 100 ml*
o f 10 # sodium carbonate so lu tio n and 100 ml* o f w ater follow ed by
d ry in g o v er anhydrous sodium s u lf a te ,

Tim e th e r and bem ene were

removed a t reduced p ressu re and th e re sid u e was d is t ille d under vacuum*

6k

A t 63 ~0fa° { k am*) 0*7 g« o f 2-th e n a l v « i recovered follow ed bgr 12*6
0 *062 mole* 62$) o f a el®«p c o lo rle s s p ro d u ct b o ilin g a t H 3~H k 0

(0*2 o n .) w hich bad * r e f ra c tiv e index o f

1.5220*

A nalysis o f

tb® compound f o r carbon and hydrogen gave th e follo w in g r e s u lts i
Oalo*d* f o r O ^ ^ a t 0 , Sk.Of Hf 6 . 0 .
Foundi Ct 5 k*lj H, 6 .2 .
4 p rev io u s p re p a ra tio n o f th is m a te ria l fo llo w in g th e above
>

procedure re s u lte d in a 51*5$ y ie ld o f th e expected p ro d u c t,

m

to lu e n e was employed os tb s so lv e n t w ith o th e r experim ental co n d itio n s
b ein g h eld c o n sta n t th e y ie ld dropped to 7 *5 $ o f th e th e o re tic a l amount
ra£ tb s q u a n tity o f u n d is tilla b le re sid u e in th is ease was 1 0 .0 g .
S ib y l 3- ( 2 -tM e p y l) «3^ l^ ro x y ^ 2H ^thy lpro pan oate
9» ?«»
OH-CH-COOC.Hb

a
u

Using th e ap p aratu s and procedure d escrib ed above, 1 1 .2 g . ( 0 .1 0
m ole) o f 2 ~ th e n a l, 10 J l g . ( 0*10 mole) o f e th y l <* -broinopropionatfc and
6*5 g« ( 0*10 m ole) o f * im d u st were allow ed to in te r a c t in 50 m l. o f

d ry tosmene as a re a c tio n m edia.

After h y d ro ly sis and se v e ra l w ashings

th e crude p ro d u ct was d i s t i l l e d to y ie ld 0*3 g* o f 2~ th sn a l follow ed
b y 9.7 g . (0.057 aoloj 575) o f s l i ^ t l y yellow p ro d u c t, w ith a r e f ra c tiv e

ln d .x at

1.5129* **4 b oiling nt 108-110® (0 .5 w i.). Th* reported

(85) pfcyiltal proportiaa o f th is oubotano* < n i b .p . 119-122° (tt * n .)|
a*5 1.5151.

65

I t t y l 3^ 2^ tM e i^ ) ^ 3*l3ydroxy^ 2 , 2-dim ethylpropanoate

f fee ap p aratu s and procedure employed v s r t th e same a s in previous
p rep aratio n s*

fb o above compound was prepared by th e in te ra c tio n o f

5 ,6 g , ( 0 ,0 5 mole) o f 2 -tfc e n a l, 9 ,7 5 g , ( 0 . 0 $ mole) o f e th y l

-bromo-

ie o h u ty ra ts and 3,25 g , ( 0 ,0 5 mole) o f d ry sia o in 25 m l, o f anhydrous
b em en e.

Follow ing th e se p a ra tio n procedure used in th e form er ejqpexi*

m eats, th e erode p ro d u ct wee fra c tio n a te d to y ie ld 7*3 g . ( 0 ,0 3 2 n o le f
6k%) o f straw co lo red product whose p h y sic al c c n sta n te were*
113-1X1^ ( 0 ,1 s e i,)i

1,51X2.

b .p .

A nalysis o f th e compound f o r carbon

and hydrogen gave th e fo llo w in g re s u lts s
C a lo 'd . f o r C ^ l^ O aS * C, 5 7 ,9 | H, 7 , 0 .
F ow l* Gt 5 7 *9 j 8 , 6 , 1*,
i£ihyl 3~( 2«tldenyl)^3^l^rojytm tai)cate

Yfc* In te ra c tio n o f 12*6 g* ( 0*10 mole) o f 2 -a c e ty l th io p h en e,
1 6 ,7 g« ( 0*10 mole) o f e th y l brcsaoacetate, and 6*5 g . ( 0 .1 0 mole) o f

s in e in 50 m l. o f d ry feeasene proceeded vig o ro u sly and spontaneously.
XfUs* th e u su al se p a ra tio n th e resid u e was su b jected to vacuum d i s t i l l a tio n , and th e re mm ob tain ed a t 86- 88° (2 urn,) 2 .0 g . o f 2- a c e ty l
thlophsxie follow ed by th e c le a r c o lo rle s s product w ith the p h y sic a l

66

* H *pertlM i

* .» . 93-9k° (0 ,2 dm .)i n *5 1 ,5 0 6 3 . Th» y ia ld o f product

wm Xb.2 g« (0*066 m olef 6 65 ). A nalysis o f th e compound tor carbon
and hydrogen gave th e foiUewing r e s u lt* »
CaleM * f o r Ciofiu ° a Sl c j S6 * l| H, 6 *5 .
Found* c* 5 5 .5 i H, 6 , 6 .
?b©

nsm o f o n ly

25 m l. o f bem ene as a re a c tio n a d v e n t w ith th e

o th e r experim ental condition© and amounts of re a c ta n t* b eing hold
c o n sta n t re s u lte d in a 32 $ y ie ld o f th e same p ro d u ct.
A tld r d p re p a ra tio n o f th is m a te ria l in v o lv in g i n i t i a l l y th e same
reag e n ts and amounts a s above tollmmd by th e a d d itio n , a f te r f if te e n
m inute*, o f m a d d itio n a l 1 .6 g . ( 0 .0 2 5 mole) o f sin e .aid h .2 g .
( 0 .0 2 5 m ole) o f e th y l brem eaoetate r e e d te d in 11*.0 g . (o .065 m olej 655)
o f th e expected hydroxy e a te r and th e recovery o f 2 .3 g . o f unreaoted
2**aeetyl th io p h en e.

Nhen 50 ml* o f anhydrous to lu en e was need in ste a d o f beneene &e
th e re a c tio n so lv e n t th e y ie ld o f product was reduced to 1 ,2 g . ( 0 .OO65
mole! 6 *5 $) m i 3*6 g . o f unchanged ketone wae reco v ered , v lth th e
amount o f high b o ilin g b y p ro d u c ts being 8 . 1* g .
The in te ra c tio n o f 1 2 .6 g . o f 2 -a o e ty l th iop hen e, 16,7 g . o f e th y l
brom oaoetate and 6 .5 g , o f sin e in 50 m l. o f d ry diox&ne wa« vigorous
and enotherm le,

% .rklog up th e product in th e u su a l manner y ield ed

5*1 &• o f Ufsroactod 2~ a e e ty i thlephena m l 6 .5 g . (O.ObS mole! 1*2 $)

o
o f product b o ilin g a t XO2~10b (1 am .) which had a re fra c tiv e Index o f
1 JW T .

67

I

^M q— qm cco o ^

th e »mm g en e ra l procedure m p rev io u sly d escrib ed m e employed,
u sin g 12*6 g , ( 0*1 zaolo) o f 2 ~aoetyltklQph©»$, 18.1 g . ( 0*1 mole) o f
etlgrXc* -brepopi^opioiiat® end 6*5 g . ( 0*1 aoX©) o f sin e d u st in 50 m l.
o f d ry b em tm *

Follow ing th e se p a ra tio n procedures d iscu ssed above,

vacuum d i s t i l l a t i o n o f th e crude p ro d u ct gave lt .1 g , o f 2«&eetylthioph&n&
sad 12*5 g . ( 0*055 o o lo j 555) o f s lig h tly yellow liq u id b o ilin g a t
102 - 103 ° ( 0*1 mw*>*

I t s r e f ra c tiv e in dex m o

1 . 5122 . tb s rep o rted
u
( 65 ) p h y sic a l p ro p e rtie s f o r th is compound ere * b .p . 123 - 117 ° (3 am*))

a®* 1 . 5 X6 8 .
'^hm th e su m re a c tio n was c a rrie d o u t in 50 ml* o f dioxane i t
gave 3*8 g . o f u arcao isd kutone end 5*8 g , (0.0J3 m ole; 535) o f th e
expected $u»fo;maicfcy re a c tio n product*

iSihyl 3 -( 2-i'ilonyX ) -3-!|ydr©xy»2 #2-dijaethylbutanoat«
08 OHa
1 *0 — C~C00Ca 2%

/iUL

■

U sing th e turn eagMSrtnenteX technique ste in she above re a c tio n s ,
12*6 g* ( 0*10 mole) o f 2-ocetcsdLtlii«pl^ii»f 15*5 g* ( 0 .1 0 a o le ) o f e th y l

-b rc n o ls ^ u ty r e te end 6 .5 g* ( 0*10 stole) o f sin e were allow ed t©
in te r e s t in 50 « 1 . o f mhp&ram bencene.

A fter h y d ro ly sis and

66

separation the residue m

d is tille d under reduced pressure to y ield

3*3 K. « f e th y l isobutyrate end 3,9 g . o f 2*aeetylthl0pheiw followed
fey 3 .6

g. (0.01? am lej 15M) o f lig h t yellow liq u id product boiling a t

100*101

........................
(0,1
mb.) w ith

.25 1.5S3lt.
a re fra c tiv e index o f n*

-UislyuiB

o f tb i product fo r carbon and hydrogen gave the following rw aultai
Calo»d. fo r G&.E ]^ ),3 i
Found.

C, 59,S| H. ? J t.

C, S 9.fli H /T .3 *

Ethyl 3~{ 2-ihicfQ rl) ~3~hydrox^«t&m&t*

5^

an^n*

To a d ry tb rce-n sck sd 250 ml* fla s k f i t t e d w ith s t i r r s r and re flu x
wmdmnmr was added 11**0 g . (0 .1 0 mole} o f ^-propiox^liblophon©, 16.7
g* (0 .1 0 stole) o f e th y l
< tot sod 50 o il. o f d ? / bam om .

6 .5 g . (QA® stole) o f dry sin o
Tb® erode product was Isolated in the

usual m<mmr sod subjected to xaeuuss d is t illa t io n to y l s l d 2 .1 g . o f
wnrcaetcd ketens b o ilin g a t 62-83° (1

s b s .)

o f c le a r l i m id p rod uct b o ilin g a t 95-96

o

and lh .8 g* (c ,065 n o lo | 65$)
( 0 ,2 am .)# which had a r e ­

25 1 . 5105 . A nalysis o f th e compound fo r carbon and
D
hydrogen p m th « follow in g r e s u lts s
f r a c tiv e index o f

Calc»d. fo r GtxHxeOs Ss 0f 57 .9f H* 7 .0 .
Foundi

0 # 58*2| I # 6 .9 .

\
Vhsn tb s shorn sy n th e sis was rspcotod u sin g o n ly 25 w l. o f bsracnc

os a reactio n solvent the m ount o f usreaeted 2«propioz3grlthlophons
was 5 .9 g . and the y ield o f product was 8 .2 g . ( 0 ,0 3 6 «ol©f 365).

69

tim

o f Mm«m fo r toemem m * reactio n media and

m aintaining o th er experimental conditions sonataat gave $,2 g . of unreacted ketons ami 9,2 g , (0,043 mole* k3$) o f the expected product.
ith y l 3^(2~tM © nyl) -3~fcydT^xy-2^#t*^p#m tan0& i«
pH
0^SJ*O©OCj*%

6

Follow ing th e p re v io u sly d escrib ed method, 11*.0 g . (0 .1 0 nolo)
o f 2 -p rop ion yl U dophem , 18 ,1 g . (0.10 nolo) o f e th y l

-bromo-

priaploxi^to oiid 6 .5 g . (0 .1 0 n o lo ) o f *ime were allow ed to In te rn e t in
§0 ml* o f d ry b « m « in .

I f to r o b ta in in g th e erode product by methods

a lre a d y d iscu ssed I t mm d is t ille d a t reduced p ressu re to y ie ld 1 .0 g .
o f 2~prapiCttjyX thlpphem# and 12.1 g« (0.062 m olej 62$) o f y ellow ish
O'
liq u id p ro d u ct whoso p h y sic a l p ro p e rtie s w orst b .p , 103 -101* (0 .1 »»«)}
1.5Q1S.

.Analysis o f th e compound f o r carbon m d hydrogen gave

th e fo llo w in g r e s u lts t
a d o M , f o r 0*sB *#as*
Found*

a # $9 *$$ u, ?.i*.

C, 59*6* f , 7 ,4 ,

H o p etitio n o f th e above re a c tio n usin g dloxanc as a re a c tio n media
in ste a d o f brnmmm gave 4 .8 g . o f mnroaoted feeton# and 1 1.1 g . (0.O1S5

mole I 55$) o f the expected hydroxy ester*
E naction o f 2-propio^ylthiepl4#n# w ith e th y l^ -hrom otsobutyr& te
^e^Xcylmg th e o ap srim en tal technique described p re v io u sly , 11*.0
g . (0 ,1 0 mole) o f 2 ^ ro p io i^ lth io p h # n ^ $ 19.5 g* (0 .1 0 mole) o f e th y l
^ -brcm olsblratyr& be and 6 .5 g . (c .10 mole) o f sin e wore allow ed to

70

in te r a c t l a S© ml*

benzene* th e re a c tio n proceeded vigorously*

b u t a f t e r working up th e re a c tio n m ixture l a th e u su a l manner and
d i s t i l l i n g th e crude p ro d u ct, on ly 9 .5 g . o f unreacted 2 -p rop ion ylthiophen© was o b tain ed b o ilin g a t ?6-?7° {©.§ am .)*

There remained in

th e d i s t i l l a t i o n fla s k 5*6 g . o f m u n id e n tifie d high b o ilin g re sid u e .
The same re a c tio n m s rep eated again u sin g tlt.h g . (0*125 nolo)
o f e th y l © (-broBioieobutyrate, Xl*„0 g . (0*10 {sole) o f 2 -p ro p io n y ltM ophane and 8 . 1 g , (0*125 mole) o f d r y sin e and h eatin g th e re a c tio n
m ixture a t i t s r e f lu x tem perature fo r th re e hours*

ig a in th e re was

o b tain ed by d i s t i l l a t i o n 8*7 g . o f unreaoted ketone w ith 7.2 g . o f
n o n -K iistillab le resid u e rem aining.
Sthyl 3~( 2-titLenyl) ~3-hydFoxyhexano&te
n
i*

n^H
JL 4*cg^coo0#%
8
CH3CHaCH3

The ap paratus and experim ental procedure were the same a s o u t­
lin e d above,

The re a c tio n o f 15*1* g . (0*10 mole) o f 2 -b u ty ry lth lo p h en e,

16*? g* (0*1© mole) ©f e th y l brom oaoetate and 6 .5 g . (0.10 mole) o f
zin c d u st in 50 m l. ©f bernene gave 2.1* g, o f u nreacted ketone and
11**0 g . (0 .0 5 6 molcf 565) Of a straw colored liq u id product b o ilin g
a t 97-58° (0 .2 m n jj

1.506i*»

The result® o f a n a ly sis fo r carbon

and hydrogen were*
C a lc 'd . f o r Cla Hiep 3Ss C, 5 9 .5 | H, ? .h .
Found* 0 , 59.9$ ^ 7.1*.

71

4 I m i n i j»rep«»ti<m o f th lo sttbstanea using the

mho

exp#ri-

aen to l conditions owl p t a d t i l n o f reactan ts so su ited In 3.1 g . of
unnsacted totems and 12.7 g . (0,052 mole; 52?) o f product.

Vvom a sim ilar synthesis o f th is conpound in which dioxans was
used as the reootlon solvent there was iso lated 5.5 g . o f 2-butyrylto*

thlophen© and 10,6 g* (O.Obl mol$f h3$) o f product b o ilin g a t 115*116
(1 wn.) which bad a re frac tiv e Indojc

1 *5 0 ?3

.

stfeyft,

'

m vn *
‘iif**ei|.C0DCa%
08^% C %

th e in te ra c tio n o f 15.li g, (0 ,1 0 mole) o f ?~butyryXthiophon®,
18*1 g* (0*10 no lo) o f e th y l

-bstm opropioaate and 6 ,5 g« (0.10 nolo)

o f d ry s la o d u st in 50 m l. o f d ry bom cm procotsdod in a manner s im ila r
to p re v io u sly d escrib ed E ofosm tsky re a c tio n s .

A fter th e u su a l

se p a ra tio n and d i s t i l l a t i o n under reduced p re ssu re th e re was obtained
£ JL g . o f unrcaotod b tto m and 13#5 g« (0.06k n o l« | 6h£) o f a yellow
liq u id p ro d u ct b o ilin g a t 112*113° (0*1 tm m) which had a re fra c tiv e
index o f n ^ ljb 9 ? 0 .

A nalysis o f tb s compound f o r carbon and hydrogen

gave tb s fo llo w in g r e s ta te s
G aloM . f o r Cj3 Haa0 aS* 0 , 6 0 .9 i H, 7*8*
Found# 0 # 6 0 ,? j Hf 8*0*
tfesn th e above re a c ta n ts were allowed to in te r a c t in 50 m l. o f d ry
d lo m n s a s a re a c tio n media tlmr© was obtain ed 5*3 g* o f ?*butyrylthioph©n©
and 9*7 g . (0.01*6 w alej IM ) o f th e expeeied p ro d u ct.

72

iieaotion o f 2^uty?ylthloph<m © w ith e th y l

^ reiw isob u tyrate

A ccording to thm p rev io u sly d escribed experim ental c o n d itio n s,
15

g* (0*10 mole) o f 2~hutyryltM c^phene, 19.5 g* (0 ,1 0 mole) o f e % l

(A ^broj^lBobuiyrab© and 6*5 g , (0*10 mol#) o f sin e d u s t were allow ed
to I n te r a c t In §0 ra l. o f dry b e m w ,

Although the re a c tio n proceeded

v ig o ro u sly , th e re was is o la te d fey d i s t i l l a t i o n 10*7 g , o f unreaotad
S ^ u iy ry ltM e p lie n a b o ilin g a t 79-82° (0*5 aw*)*

A to ta l o f 6 .1 g* o f

u n id e n tifie d and no n-d ls t i l l a b l e resid u e remained in th e d i s t i l l a t i o n
fla sk *
&thyl 3*( 3 ^ th ie n y l)

OH

Using no change i n experim ental c o n d itio n s, the in te ra c tio n o f
5*6 g* (O.OS mole) o f 3-th@ m l w ith 8*1* g* ( 0*05 mole) o f e th y l bro»o~
a c e ta te and 3*3 g . (0*051 mole) o f sin e in 50 ml* o f anhydrous bem ene
took plane viforot& O y.

A fter th e mmm se p a ra tio n procedures as

d escrib ed sh o w , vacuum d i s t illa tio n gave 1*1 g* o f 3 - t t a i a l d i s t i l l i n g
a t 63*6h° (li mm*) follow ed by 6*5 g . (0.0325 molej 6$%) o f c le a r co lo r*
le s s p ro du ct b o ilin g a t U i*-U 6° (0 .5 mm*) whose re f ra c tiv e ind ex was
n j^ 1*5202*

a n a ly s is o f th e produet f o r carbon and hydrogen gave th e

fo llo w in g r e s u lts t
C ato'd* f o r © #% #*$* C , 5h.0f B, 6*0.
Foundi C# 5 h .0 | H, 5,9*

73

Bths^t >*(
9» 5%
pCB^CB^COt^^

Using t o *s$&rato and prooedar® do*erlbed afeovo, 5 ,6 g. ( 0 ,0 5
awl®} o f 3~tom alf 6,1* g* (0 *0$ sk&sj) o f eth^l^S ~broiBopropton&t» and
3*3 g# (0#Q§I nolo) o f 4 1 7 &1&0 powder ooro allowed to interact in
50

xnl, o f dry booiono# After hydro!?*!*, washing, dzylog and removal

o f t o reaction solvent t o en*d* product wsa d istille d to yield 0.7
g , o f unre&oted 3~to**al followed bp $ .9 g , (0.0275 »w>le| 55%) o f
p ro d u ct b o ilin g a t 1XIi-X15*5° ( 0 .5 asm,) whom r e fra c tiv e iadox m e
aS
*1^ X,5XX0* A«aXy*i» o f t o pro duct f o r earbo** and iydrogon gave t o
fo llo w in g re s u lt* !
C ale*d, f o r C*aHH G*Si

G# 56,1* H, 6 ,5 ,

Found1 C# 56.1; 1* 6,®,
>*( 3~thi«ggdL) «3^iiydro^-2 #2«Kiim®tiyipropa3!K»at©
OH ?%
JW~COOC*%
6^

To a 2$P0 a d , toeoH O eeksd H ank vo® added t o

q u a n titie s , 5 ,6 g ,

( 0 ,0 5 wfido) Of 3 ~ to m X # 9 ,8 g* ( 0 .0 5 nolo) o f e th y l <* ^ferdffloisobutyrate,
3 ,3 g , (0,05 1 nolo ) o f s in e d o st and 50 m l, o f b em en e,

A fter t o

u su a l vigorous ro a e tio n , se p a ra tio n procedures® and removal o f bensene

Ih

th e <3rude p ro d u ct was d i s t i l l e d under reduced p re ssu re t© y ie ld 0 .5
g , o f u n reacted 2~th®nal and ? .2 g# (0.0316 molej 63%) o f a s lig h tly
yellow liq u id p ro d u et b o ilin g a t 116-118° (0 .5 mm.) which had a
r e f r a c tiv e index o f

1 .505 8.

A nalysis o f th e pro duct f o r carbon

and hydrogen gave th e follo w ing r e s u lts t
C alo*d. f o r CE^E^OnSi Cf 57,5 | Hf 7 .0 .
Found* G$ 5 8 ,0 | H# 7 ,2 .
E thyl 3~( 3 -th le n y l) ~3~hydroxytmt&ttoate
GH
*q-GI%CO0Ca%
8

fti© in te ra c tio n o f 6.3 g . ( 0 .0 5 n o lo ) o f l-a o e ty lth to p h e n e , 8.h g .
( 0*05 stole) o f e th y l b re n o a e e ta te , 3 ,3 g , (0,051 mole) o f sin e in 50
m l, o f bem ene a s a so lv e n t proceeded spo ntan eo usly .

S eparation o f

th e crude p ro d u ct in th e u su a l manner and I t s vacuum d i s t i l l a t i o n re ­
s u lte d in 0 .5 g . o f u n reacted 3-acetyltM ophen© and 7.3 g . {0 . 03 h molej
68%) o f c le a r c o lo rle s s product d i s t i l l i n g a t 93~?h.5° (0 .1 mm.) whose
r e f ra c tiv e index was

1,5067,

A nalysis o f the product f o r oaifeon

and hydrogen gave th e follo w ing r e s u lts 1
C a lc 'd . f o r
Found 1 Gj, 5 6 .I f

G,
6*®*

S 6 ,lf %,6 .5 .

IS

E'thgrl 3**(3‘*tfct©nyl)

tly lb u tam & te
OH
*c— ce*o0oc*H&
CK* 6%

II 10 re a c tio n o f 6.3 g* <0*0$ m l® ) o f l^ e ty ltM o p fe e n © t 9*1 g*
{&&$ msX®) o f e th y l c*

and 3 ,3 g* (0,051 mole) of

«i*ws lift 5® ml* o f d ry feem aae took plae© riipicCly,

A fte r th e u su al

s e p a ra tio n , th e ©rude pro du ct m o d i s t i l l e d to give 1 ,6 g , o f unamaeted
3 -^ # ty ltM © $ ^ n s to ilin g a t ?G*7X° (1 am*) follow ed by 5*3 g , (0,026
m olef %$%) o f liq u id p ro duct o o llo eto d a t X 0M £6° (0*5 msa,) which had
a r e f m o tiv e ind ex o f njg* l*511h«

A nalysis o f th e product f o r carbon

and hydrogen gave the fo llo w in g reeru liet
C alo*d, f o r C>aiH^OaS# C $7.9* B, 7 .0 ,
founds G, 56*0| H# 7*0*
Btlgrl 3~( 3 ^ th lc n y l)

,2 ^ iiM tt^ lto t& n Q ate

^ 0 — C ^O O G ^

Follow ing p rev io u sly d escribed experim ental co n d ltio n o , 6 ,3 g ,
(0 *0J noils) o f 3-"««3otyltlii©p)i®ii#, 9*6 g . ( 0 .0 5 mol®) o f e th y l ^ -bromoia o b u ty ra te and 3 ,3 g . (0*051 mole) o f d ry s im mr@ allow od to undergo
in te ra c tio n in 50 m l. o f dry to m e n e ,

Th© crude product m s Iso la te d

from i t o re a c tio n m ixture by th e u su al method and on vacuum d i s t i l l a t i o n

76

§*vt 3 ,5 $* o f

> ac® tyltfeio 3>h€a>@ and 3*1 g , ( o ,013 raolej

26&) o f * « t* m colored product b o ilin g a t 105*107° (0 ,5 ran,) which

bad * n f w t t w Index o f

xtf 1.5521. iatl&Aa o f tbe prodaot fo r

carbon and l^ d n g to gave tbe follow ing reou lto t
O ale'd. fo r C gA 4>,s* 0 ,
Found* c , S9.it K, 7 .5 .

S»,S$ K, 7.1*

K%fcgp& 2»(2-( >«wtbfXtiAmarl) -3-l)0*lnMybut*noata

UnploptHf tho prev io o o ly doaorlhod ap p aratu s and onporlnontftl
proccdtar®, U*,0 g , (0 ,1 polo ) o f 2*ao®tyl*3*n®thjl thiopbon® were
aUcwcd to r e a c t w ith 16*7 g# (0*10 tool©) o f ethgrl bromoaeotat® m d
6*5 g , (0,3/j n o lo ) o f glno d o s t l a 100 sal, o f d r / ben®e»«,

There poo

obtained b j d i s t i l l a t i o n , a f te r h ^ ro l^ e i® , waefciiig* and reasoval o f
th e re a c tio n m edia, 6 ,8 g* o f trareaebed 2 * a o e ty l* 3 ^ th g rl thtoptam e
d io tm in g a t ?>?& * (1 » . ) follow ed bar 6 ,6 g , (0,025 mol®* 2$%) o f
a s lig h tly yellow p ro d u ct b o ilin g a t H W 1 6 ° (0 ,5 m u )

1*5137,

ia a iy s to o f th e p ro d u ct f o r carbon and iiydrog&n gave the follow ing
i® o d ta*
Cslft’d* f o r
C, 57.9? H, 7*0,
Found* a , 58*0| B, ? £ ,

77

K%
£H
.

9»cooca
0% C%

>9

A a&xtMM Of lh.O g , (0,1® no lo ) o f 2 -aeo ty l-3 -® etM l
1 8 A g« <0*10 mole) o f oihjrl** ^»amw^^|»lfCmato and 6*5 g« (0,10 mole)
o f r i m in 100 *1* o f anhydrous be»s©m re ac ted v ig o ro u sly ,

A fter th e

d escrib ed h y d ro ly e ie , washing and ao lren b removal prooedures th e m ixture
m o d i s t i l l e d in v m w y ie ld in g 7*1 g , o f uareao ted ketone and 1**9 g*
(0.020 a o b | 20«) o f Xlejald prorfuot d ia tllU a g a t 117-118° (0 .2 a n .)
whose m ir m ttm index warn
$ o e t a and & ^ j p a g m

1,5083*

A ttaly tls o f th e pro d tiet fo r

th e l< d M a g resu lt* *

Calc*d* f o r 0 ao % IM * 0 f 59*5f Ht 7#h*
Found* C# 59Jk$ H* 7*3*
R eactio n o f 2*m& tyl~3**9^tbyl ti&ophon© w ith e th y l ^ ^roraoisobutyrata?
The in te ra c tio n o f %k+0 g* (0*1 mol®) o f ?-Ac©tyl~3-js0 th y l thiophsne
w ith 15*5 g* (0*10 n o lo ) o f otbyl** -^rogaoioobtttgrrato and 6*5 g , (0 ,1 0
no lo) o f d ry sin e powder in 100 m l, o f ben&ene prom&d&d upontaneoualy*
4ft«sr th e u su a l s t i p u l a t i o n s , th e erode product was d i s t i l l e d to
y ie ld 7*6 g . o f f*aootyl*3-*is^thyl thiopbene b o ilin g a t 7?~7h° (1 am *),
a**i le a v in g in th e d i s t i l l a t i o n v eseal 1 2 ,a g* o f a a o n * d ia tilla b le
m a te ria l*

73

uaJtamMtafey Ha*cUoiui o f

V «4iro»aoerofc<mat«

BtlqA. ?( ( 2«*tbiemyl) -tardfoxym athyl) -jl-fcuteroata

<?£
> 0•ca
^ * 0 0 * *
■ s"

ea*c%

E th yl 5~{ 2 *tld e n y l)
9 it
^^CMHarCS^CB-COOC 8%

Xa « ty p ic a l re u e tto n , H ,2 g , (0 ,1 $ mole) o f 2 -tb $ n * l, 19.3 g .
(0 ,$D mol©) o f e th y l

V ^ r t M m r e t e a a t * and 6 ,5 g , (0.10 mol©) o f sin e

t e s t were added to 100 m l. o f d ry betissen® m d th e re s u ltin g m ixture was
p u t in & ttr o o « te o M f la s k equipped w ith a s ttm » r and a re flu x
condenser w ith a oaleltsia c h lo rid e tu b e ,

A sm all c r y s ta l o f io d in e wee

added, s t i r r i n g woe ©©*»m*ced end tins bottom o f th e re a c tio n v e sse l
wan healed lig h tly to I n i t i a t e tb s re a c tio n , a f te r which I t wee n eseso aiy
to m oderate th e vigorous exotherm ic re a c tio n by te e^ o rery Immersion o f
th e f la s k i n m le e b a th ,

A fter spontaneous re flu x ln g had (subsided f

th e re a c tio n wee continued f o r a h a lf hour a t th e re flu x tem perature
o f th e re a c tio n m ixture a f te r which th e co n ten ts o f th e f la s k were
allow ed to co o l to room tem p eratu re,

% dro3ysie o f th e re a c tio n m ixture

was accom plished by th e a d d itio n , w ith vigorous s t i r r i n g , o f 75 m l. o f
m te e co ld 10$ s u lf u r ic a c id

so lu tio n *

th e nm~a%mom la y e r was

se p arate d and combined w ith a subsequent e th e r e x tra c t o f th e aqueous

n
p o rtio n *

t i n eoOhinsd io ltitlo tu ) im m e x tra c te d (ro o o e tsiy e lj w ith 100

»&* * f m W , 100 wtkm ©f i m m m m ©automate and 100 w l. o f w ater
follow ed by d ru tn g o v er anhydrous sodtiam su lfa te *

A fter ren o v al o f

th e solvent® on a s t m i b a th , th e re s id e s mm d i s t i l l e d in vacuo,
fh® fo re ru n m ® m m & 1 .3 g . o f e th y l © rotoaate b o ilin g s i 30 - 1*0°
{00 m m) mmI 1*9 g . o f 2-td*®nalf b«^v

{9 w e .).

Follow ing those

f ra c tio n s o f unreaoted natevlaX woo th e f i r s t p ro d u ct which waowsbsd
t® 6*9 g« (0*098 n o lo ; 20g) o f e th y l 2 * ((9 -tM w ^ l)# lb ^ 3 ^^ y n o tb y l)-3 *
bubenoat© , b o ilin g a t X32 - lA ° (1 raa.) which hod a r e fra c tiv e index o f
fig
||0 1*5970. A nalysis o f tid e p ro d u ct f o r carbon and hydrogen gave
th e fo llo w in g re s u lts *
CaXs*d* f o r O^iMjuPaS* 0 , 5®*3l
Found* 0* £ 6 *6 f ft, 6 . 3 .

6 .2 .

th e second p ro d u ct asaounted to 3 .6 g , (0.016 mole] 165) o f e th y l
5- ( 2-tM « « ^ l)- 5^ h ^ re x y - 2-p an ten o ate and d is t ille d a t 160-161° (1 w r .) .

95
I t s r e f r a c tiv e index was ftp 1 *5 573 .

A nalysis o f th is p ro du ct f o r

carbon and hydrogen gave th e follow in g r e s u lts #
C*2c»d. f o r Cu 3i*0»3t C, 58.3J Hf 6 ,2 .
Found! 0 , gi.O f it, 6 .0 .
th e f i r s t o f th e se p ro d u cts re a c te d ra p id ly w ith hmmUm in carbon
te tra c h lo rid e w hile th e second d id not*
Follow ing a p re v io u sly rep o rted procedure f o r o so n sly sio (1?) ,
0 .2 g . o f e th y l 2^ ( 2 «tM enyl)^bF 6 ro x y m el^ ji)- 3-bute& oate was d isso lv ed

in 10 sal. o f a c e tic a c id and tre a te d w ith a strew s o f ©stone f o r an hour,
fiw osonide was deeostpoasd w ith a im d u st and w ater and then d i s t i l l e d

m fflX 30 ml* o f d i s t i l l a t e had been eolXeoted*

th e d i s t i l l a t e was

tr e a te d w ith 0*2# g* o f ddmadoise sad s e t aside fo r a tw elve hour p erio d
l a the r e f rig© r a to r d urin g w hich time an in so lu b le m a te ria l c ry sta lliz e d
from so lu tio n *

IM « was removed fey f iltr a tio n and recry® tallized from

a metlu n c l-w a tc r miaeture of equal p a rts to y ield about 0*1 g* of a

m aterial which melted sharply a t 187-187 *5° * Thera was m depression
in the m elting p o int when the l a t t e r substance was mimed w ith the product
o b tain ed on in te ra c tio n o f formaldehyde w ith dimedone,
E th y l 2-BbJ^nyl-3*hydroxy-3-( 2-thi@ ayl) -b u tan o ate
9H

O l

6% CH*CHS

E thyl 5-<® -tbieuyl)<*2<jh-tae^eneut@

8

J

.f*
13.n ts-sy
pr,.,^nnn
Oi
'Y—w*v
««%»js
—
vsAJva*%

0%

B^ploying the usual procedure# 12*6 g , <0*10 mol©) o f 2 -a c e ty lthlaphane, 19*3 &* (0*10 mole) o f eth y l ^-feromocrotonate and 6 ,5 g.
<0,10 mole) o f cin e d u st were allow ed to in te r a c t to 100 m l, o f anhydrous
bem ens*

A fter ca rry in g o u t th e is o la tio n procedures d escrib ed above,

th e p ro d u cts wore vacuum d is tille d *

The f i r s t f r a c tio n o b tain ed was

7*1 g* o f e th y l erotonat® follow ed fey 7*8 g , o f 2-acetylth io ph em s.
Follow ing th ese fra c tio n s o f u n reacted s ta r tin g m a te ria ls th e re was

obtained 1,5 g* (0.007 n e te j

7%) o f ethyl !•« tlwB3rl*3,>M

< ^ 7 ’}*

(2-thtenyl)<*ataH®ate b o ilin g « | 107-108° ( 1 aw.) which ted a wfrwUvs
ted** o f Up 1,1j959. Analyai* o f t t e product fo r carbon and hydrogen
8**w t t e fo llo w in g n « a t »
C alsM , fo p Cla % #0aSi

Fmmdt a , S9.7» H, 6 .8 .

C, 59 .9 i H» 6 .7 .

T te n ex t f ra c tio n b o ilin g a t 155-156° (1 «m.) d id n o t give &
e© rree$ a n a ly s is f o r t e iaamorl® © te r and m a r e s u lt va» r e f l u t e
f o r ©Xgjbt te r © i» a 6$ o x a lic acid © olutloa from vhldb te r© ua»

iso la te d 5*8 g . (0*026 mole? 26$) ©f ©bJ^rl 5^(2«*thi©nyi)^ fb ~ te te ie m a b c
bciXirsg a t Xkl^lkti^P (1 a m .),

te l y o i # o f th e p rod uct fo r carbon and

hydrogen pv® tlio fo llo w ing rom slts*

CaX©*d* fo r C**1**40*31 Cf 6 M f H, 6 .3 ,
Fouudi

C, 6 b ,?f 8* 6 ,5 .

Th© f i r s t o f t e t e w product took up b r o t e rapidly wbile the
©©•©end re a c te d only ©Xwly,

JSiliyl 5*(2*thX©»yl)~2 #k~h©pt*dd&n0te

tioing t e proiriouoly doooribod n o te d , Xb.0 g . ( 0 ,2£ mol©) o f
2-propionylthiophoB 9, 19.3 g . (0 JLO n o te ) o f e th y l ^ -broooorotonato
and 6 .5 g . (0 JLO n o te o f sin e m m allow ed to undergo re a c tio n in 100
mL. ©f d ry ta s s o n e .

S ia U lla tio n o f t t e is o la te d cru<i» product gave

7.8 g . o f e th y l orotem ate and 8.7 g . o f 2 -p ropionylthiophsno, follow ed

82

toy

$.9 ft. {0,0*$ ml»t 25#) at product b o ilin g a t 1U9-1S0° (1 a s .) .

tim re fra c tiv ® Index wae a

1*577?*

4 m ly sle o f th e p rod uct f o r

cartoon am! hydrogen gave th e follow ing r c a o lts i
CxLe*d« f o r C ^S^O ^S#
Feuiad*

C* 66«Xj H* ?*6«

0 , 6S * ?f n , 7 . 8 *

Tt&g X&ter product reacted slowly with brosalno in cartoon te tm # '
chloride *
Ethyl 5«*(S^tl& enyl) •*£ fh«Krotadteaoate

•C M B K 2M 00G A
%G%G%
The re a c tio n o f 15 M g* (0*10 a o le ) o f 2-toutyrylthiopb»«o w ith
15*3 g* (0 *1G Bide) o f ©tohyl ^ **tor0®®oorotoaate and 6 #5 g# CG*10 iftol©)
o f wine powder in 100 ml* o f d ry bem enc o ec w rsd spontaaeoaaly*
A fter to e uauaX is o la tio n procedure t there was o btain ed toy vacuum
d i s t i l l a t i o n 6*8 g* o f e th y l croton& to, 8*8 g* o f u n rcacted ketone
and 8*3 g* (0*032 iqcIoj 32#) o f a p ro du ct tootling a t 162«*l6h° (1 bbO *
A m lyaia o f th e p ro d u ct f o r carbon and hydrogen gave th e follow ing
re c u ltn t
C«X«»d* fo r Ou % ^ aSi C, 6?*9j H, 7.2*
Found* 0 , 6 8 ^ | St 7 A .
A w ry alow re a c tio n occurred between the p ro d u ct and bromine In
cartoon te tra c h lo rid e *

83

on

E thyl S*{ 3 *tM ei|yl) ^S^hydrox^S-^penienoafce
an
^B^JH^H-GH-COOC^Hg
-0 Follow ing t&m « te w d escrib ed pro cedu re, 5*6 g . (0 .05 stole) o f
3 -tfe en a l, 3 #t$ g* (Q*®$ mole) &£ mine m d 9*7 g , (a ,05 stole) o f e th y l
V ^ z m o o ro to n a to w ere allow ed to In te r a c t in $0 m l. o f d ry bensone
a s a iP X vin i to y ie ld too loforatabsliy p ro d u ct* .

The f i r s t enounted to

3 ,3 0 , ( 0 ,0Xh6 xsoXof 2W> o f e th y l 2*{( 3~tht®r*yl)~tigrdroaQP»eth y l)- 3 o
b u te n o a te , and had th e fo llo w in g p h y sic a l p ro p e rtie s* b .p . X3h*X35
25

(X * . ) , *3 1.5255.

W j » l» o f tb« prodaot for oorbon and hydrogen

gave th o fo llow in g re s u lts *
C alc*d, f o r
C, 50.3$ H, 6 .2 ,
Found* C, 5T*S| B, 6.1*.
The geeoid p ro d u c t, d i s t i l l i n g a t 158*160° (X n o t.), anemntod to
X*9 g* (O.OOSii no lo | 17$) o f e th y l 5 * (3 * tM o i^ )* 5 * t(riro j^ 2 -^ » tsrn o a tc
and had a r e f ra c tiv e Index o f

1*5555.

Carbon and hydrogen an&ly*

s i s o f tfc* p ro d u ct gave th e fo llo w in g re s u lts *
O alo’d . f o r 0**% e°*s * e # 5 $ .3 j H, 6*2.

Found*

c , 5 8 * 3 | I , 6 . It.

The l i n t o f th e above p ro d u cts re a c te d ra p id ly w ith a carbon
te tra c h lo r id e so lu tio n o f bromine w hile the second reacted only
slow ly*
S thyl $ - 1 , > « e th y lth le i^ y l>}*&

t#
rc *

P

JM f *CB*Cn*CB*G00ast88
GE*

U sing th e same procedure m in th e above s y n th e s is , lh ,0 g ,
(0*10 saole) o f t^ so iy lrlH B ie th y i tl&op&ma, 19,3 g , (0,10 so lo ) o f
©thy! ^ ^rcaao o ro to m te and 6 ,5 g« (0 ,1 0 aaole) o f d ry sin e were
allow ed to in te r a c t in 1©0 m l, o f anhydrous be&eene,

A*

th e re a c tio n

proceeded a em ail q u a n tity o f p r e c ip ita te formed w hich d isso lv ed on
th e a d d itio n o f $0 m l. o f a d d itio n a l h m m m *

A fter h y d ro ly sis and

w ashing, th e re a c tio n M ixture mm d i s t i l l e d under reduced p re ssu re to
y ie ld 7 #3 g* o f enreaoted 2**acetyl-3-»wethiirl thiophene follow ed by 5 ,5
g , o f a p ro d u ct which gave ra th e r poor a n a ly sis f o r carbon and hydrogen.
The product mm subsequently dehydrated by 6$ o x a lic a c id s o lu tio n to
give 5 ,1 g* (0,020 itiolsf 20#) o f y ello w ish product d i s t i l l i n g a t 16h165° (1 » » ,) •

The a n a ly sis o f the p ro d u ct fo r carbon and hydrogen gave

th e fo llo w in g r e s u lts which were high in carbon and low In hydrogen.
G a in 'd , f o r
c f 66,1* H, ? ,6 ,
Foundi 0 , m $% K, 6 ,9 ,
t& th th is m a te ria l o n ly a very slow re a c tio n occurred w ith bromine
in carbon te tra c h lo rid e s o lu tio n ,

8$

Reform atsK r R sao tio as o f .d ly l Bmrnlde

ii
‘3

Vnder anhydrous c o n d itio n s, 31*2 g« (0 .1 0 mol#) o f 2-tbsnail*
13*1 g* ( 0 4 .0 mole) o f a lly ! brom ide, 6 .$ g . ( 0 4 0 mole) o f slo e d u s t,
SO i&* o f b«am m and SO s&» o f anhydrous to tr ^ d r o f o r iia went placed
in a tSO m l. ihree-neebed f la s k equipped w ith am e f f ic ie n t « t e r and
a re flu x condenser hairing an attach ed dryin g tab®.

& sm all c r y s ta l o f

Iodine moil added and th e re a c tio n was in itia te d by lig h t ly h eatin g tb®
bottom o f th e re a c tio n v e s s e l,

iffcer tb s agxmtanseu# re flu x in g had

su b sid ed , t t e re a c tio n m ixture mao heated a t I t s re flu x tem perature
f o r m h m r and th an allow ed to co o l to m m %smperabore*

% d ro ly sis

mas c a rrie d o u t by tbs* a d d itio n , w ith rap id s t i r r i n g , o f 100 m l. o f an
ic e so ld 3©$ a c e tic a c id ,

tb s re s u ltin g too la y e rs mors sep arated and

tb® «gm*6us la y e r mas e x tra c te d w ith e th e r which mas combined w ith
tb s me»*«tm *m p o rtio n *

^ h is so lu tio n was washed w ith su ccessiv e 100

ml* p o rtio n s o f w a te r, 10$ sodium carb o n ate, and ag ain in m ater and
th e n d rie d over aisl^drous sodium s u lf a te ,

th e so lv e n ts mar® retsoved

ts s ls r reduced p re ssu re and th e erode prod a©t was th an d is t ille d under
reduced p ressu re to y ie ld 12*0 g , (« *0?8 moles f ?8$) o f c le a r c o lo rle s s
liq u id b o ilin g a t 89-9$ *5° (1 am .) whose re f ra c tiv e ind ex was *4^ x *5^39*

86

C*rfee& ^

ly dro gen a n a ly s is o f the p ro d u ct g u n th e follow ing re su lts*

0a io ’d , f o r
G$ 62,3* &* & J .
Found* 0 $ 62.1* H, 6*$*
6*{ M ?hl® nyl) -X~pontaa~6~ol

>W3WSHg-<!H«C&|
. K &%
Follow ing th e eajpHsrlmeutal procedure weed in th e above s y n th e s is ,
12*6 g . (0*10 mole) o f 2-aaetylfchlopbsne, 1 2 ,1 g , (0,10 mole) o f a l l y l
bromide end 6 .5 g . (0 .1 0 mol©) o f d ry s i m m m allow ed to in te rn e t in
a a ta ta r e o f $0 m l, o f bsnssns end 50 ml* o f te trs h y d ro fu ra n ,

A fter

ly d ro ly isis w ashing, th e credo pro du ct was d i s t i l l e d to y ie ld 11.8 g .
(0.0^0 a o lo f 10%) o f li-vnid p rodu ct d ie tH lin g a t 82~8h° (2 m « ) , lt»
2$
re f ra c tiv e index wan n0 1.5512, Carbon end hydrogen anaXysl# gave
th e fo llo w in g re s u lts *
C alcM , f o r G ^ O S t C , 6h ,3 i H, 7 .1 .
Found* c , 6 6 .5 f I , 6 ,7 .
fc*( 2*fM enyl) ~l-fa^x«m~6-61
9&
>C*C!L-*GH*0E2
S ^ 6% cj%
th e procedure deployed urn* the same a® th a t p re v io u sly d e sc rib e d ,
th e in te ra c tio n o f 16 ,0 g« (0,10 mole) o f S-^propioryXthiophen®, 12,1
g , ( 0 ^ 0 mole) o f a l l y l b ren id e end 6 ,5 g , (0,10 mole) o f c in e in a
so lv e n t m ixture o f 50 m l« each o f bem eae and fcatrahydrofuran proceeded

87

ilg n w u lr.

A fter th e usual asp iratio n method the oruds product was

d is tille d e n te r e n e n to y ield 13,2 g, (0.0725 mole} 72.5*) e f
• le e r 11**14 p re te s t.
(1 .5 am*)j

1 ,5 2 6 0 ,

I t s pigm ies! p ro p erties

w ni

t . p . 9h-95®

A nalysis of the product f o r carbon and hydrogen

the fo llo w in g re s u lts *
QiOm U * f o r e tftS u M l G, 65*^1 Hf 7,7
Fom di o , 6 5 * ?* % 7.9*

a<

J-a^GH-CHa
CBaPHaCI^

th e p re p a ra tio n o f th is compound was accom plished by th e In te r*
m otion o f 1SJL I* (0.10 mole) o f 2*bntyryittiioph© n«, 12*1 ®. (0*10
s&ole) o f a l l y l browid© and 6 ,5 g , (0*30 nolo) Of sin e in 300 sal, o f a
m ixture o f ogtMl p a rts o f bammm and to tm l^ d ro fu ra n ,

A fter h y d ro ly sis,

washing and removal o f ib® re a c tio n so lv en ts tteo rem ainder was d is t ille d
to y ie ld l b , 3 g , (0*0 73 isoloj ?3#> o f liq u id p ro d u c t,
p ro p e rtie s o f tld s m a te ria l wore*

th e p h y sic a l

b .p , 9h»9!f (0*5 s* s,)| n ^ l.S ? 0 5 .

Carbon and hydrogen a n a ly s is o f the pro du ct gaw® th e follo w in g re s u lts s
C aleM . f o r C^H^OS* C# 6?*3| B, 8*2,
Found* 0 , 6 6 .8 j &, 8*1*
!«*{3-T hienyI) *“3-bnt© n^l-ol
OB

•s

88

M b * the previously developed experimental Method, 5*6 g.
( 0 ,0 5 m l® ) o f 3«tlie»& l, 3*3 g* ( 0*05 a d o ) ©f tin© d u st ami 6*1 g .
(0*05 mole) o f a l l y l bromide were allow ed to undergo re a c tio n In 50
wil* o f a ©a© to on© m ixture ©f anhyttam# bemten© and t^tm h jd ro fu rajs*
The ro a o tto a m ixture was worked u© according to th e p rev io u sly d escribed
p ro ced u re,

th e product was d is tillo d to y ie ld 6*1 g , (0*01*0 wolej

805) o f a c o lo rle s s liq u id w ith th e follow ing p h y sic a l p ro p e rtie s*
h * p , SfD^Fl* (1 m * ) |

1*$2i2S,

A nalysis o f th e product f a r c a rto n

and hydrogen gave the follo w in g r e c u lt# »
C alcM , f o r 0»% p$* C, 62.3 1 H# 6,5*
Found* « , 6 2 ,7 | H, 6*3*
!*•( 3**Tfei«h3rl) * l« p en ten ^l^o l
9fi

The in te ra c tio n o f 6,3 g» ( 0 .0 5 mole) o f l^acetyliM op hen e f 6,2
g* (0*0$ mole) o f a l l y ! broB&d© and 3 .3 g . (0 ,0 5 mele) o f d ry *lno
d u c t in §0 n l* o f a one to one m ixture o f bem sne and tetro h y d ro fisran
to ok p la c e v ig o ro u sly ,

a llo y in g

mum se p a ra tio n procedure us

p re v io u sly d escrib ed i ‘elXo**d by vacuum d i s t i l l a t i o n o f th e crude
pmdm% y ie ld e d 6*0 g* (0*036 n o le f ?25) o f c le a r o d o r le s s product*
I t s p h y sic a l p ro p e rtie s were*

b ,p . 8CM£t° (1 w m Jl n ^ 1*52*98,

A nalysis o f th e p ro d u ct f o r carbon and hydrogen gave th e fo llow in g
re s u lts *
C alc1©* f o r
G, 6 h .3 | H, 7*1.
Found* Cf 6h*5j H, 7,2*

89

li*C

)-l* p o n to n -lt-o l

—

s

i T<?«^
itG-CH»-CS-CH,

6%

Aocordlng to tb s a lre a d y d escrib ed experim ental c o n d itio n * , lb.O
g . (0 J.0 m ela) o f 2 » aeety l* > « « « ^y l th iop hen e, 12.3. g . (c J.0 mole) o f
a l l y l bromide and 6 .5 g . (6 .1 0 mole) o f d ry sin e w&&& allow ed to
satds&r&o in te ra c tio n in $0 wX* osoli o f dry bsnscns and d ry tetrohydro*
fn m t*

Thor® m o is o la te d by th e

p rocedure, from th is re a c tio n

rnd xtev 12*0 g* (QJ)T0 jsolcf W > o f * c le a r liq u id p ro d u ct.
ptysloaX p ro p o rtio # wore*

I ts

b.p* 9 7 ^6 * 5 ° (0 .5 m&*)| njj^ 1,531*0.

^ m ly s ia o f tfes p ro du ct f o r carbon and hydrogen gave tb s fo llow ing
re s u lts *
C alo'd* f o r
G# d5*9| Hf ?*?*
Found* C, <5*Tf H, 7 .B .

B ofozm tsby Be& eiicas o f FropArgyl Bromide
X«*(2«f hl@nyl) ^3^utyn»l*K>X
OH

ttm co n d itio n s used f o r th e fttfo sm tsliy re a c tio n s o f propargyl
bromid® mors id e n tic a l to those used f o r a l l y l brcBstd®,

According

to co n d itio n s p rev io u sly d e sc rib e d , 11*2 g . (0 ,1 0 w ols) o f 2 ~ th e tu l,

90

13US> g* (0 ,1 3 mUM o f prop*kpgyl bromide m d 6 m$ g* (0,10 mole) o f
aim® mw® interact® *I In a m ixture o f 50 m l. o f a n u r o u s b em em and
§0 m l, o f di^r ta tr a J ^ r o f to a n ,

4 fio r s e p a ra tio n , th e crude product

was d tsO H o d In rrn m to jd«U t 9JL g* (Q*060 m olsi 60$) o f liq u id
p ro d u c t,

'This compound had th e follow ing p h y sic a l p ro p e rtie s*

Sii-85*1, (0 JL taw*)| a |^ 1,52 20 .
f a r thla aofflp<«md a re i

b*p,

The rep o rted (66) p h y sical p ro p e rtie s

b .p , 98-100. 5® (3 a n .)} n„ 1 .5235.
a

X«*{>*Thicnyl) *3^1^yn*X*<&X
OH

A spontaneous re a c tio n took pl&os when $ ,6 g* (0 ,0 $ mole) o f
> th o n a l# $ M g« <®*®§ n o lo ) o f pro pargy l bromide and 3 ,3 g , ( 0 ,0 5
M l® ) o f a im d o s t war® added to a m ixture o f 25 ml* o f bsmerns and
2$ ml* o f te tra iiy d ro fm r^ i,

l f t * r h y d ro ly sis, washing and removal o f

th e re a c tio n so lv e n ts th e o r d a product was d i s t i l l e d a t rsdmosd
p ra o c m i g iv in g h ,6 g , (0 jOjQL mcloj 62#) o f a p ro d u ct which had thse®
p iy s io a l e e n sta a to f

b .p . 63oSk.lT (0 .1 w - ) | Sq 1 .5207.

Carbon and

hydrogen n a l T i i i o f tho pro d u ct gem fcte follow ing r a s u lts i

Calo*d. tmr G * ^ )si C, 63.2} B, 5 .3 .
Foundi C, 63.2} K, 5 .5 .

91

Meaoblei*

w ith propargyl bromide

A H s o i m re a c tio n ensued when 22*6 g . (0*20 mole) o f 2 -a c e ty lH * ? g* (0*20 mole) o f j^ e p arg y i bromide m i 6 .5 g* o f
ftlmo d u ct wore added to 200 m2* o f a one to em b o s s m m i letrahy dro ~
f o r m m ix tu re ,

A ll o f th e sin e mm © etspletaly consumed and th e ro~

a c tio n appeared to bo co&iplefce a f te r th e u su al p erio d o f h e a tin g .
^hsa bfcm re a c tio n m ixture ww hydrolyzed. washed and re a c tio n so lv en ts

w a » w i, dlotl2la1& sm y ie ld ed 10.Ji g, o f urm aobed 2«&o*tyX thiopiiene
0

b o ilin g a t SS^$6 (0 .1 mm.). Ho f u rth e r products could be obtained
from th e 2*2 g* o f high b o ilin g re sid u e which remained In th e d i s t i l l otdon f la s k ,
Vtm re a c tio n woe rep eated u sin g a lo n g er re a c tio n period o f th re e
hours in s te a d o f th e u su al o m $ b u t th e re re s u lte d 9*1 g* o f wmreaebed
2» acetylthiophene end no f u r th e r dJjsti l l a b l e m aterial*

In th is ease

tii# re s id e s amomted to 2 .9 f#
H epatibion o f th e above re a c tio n using 100 m l, o f to lu en e a s the
so lv e n t re s u lte d in th e form ation o f a p re c ip ita te eM ch d isso lv ed
upon th e a d d itio n o f SO «&, o f d ry tetrelgdrmfOrmft*

th e re a c tio n was

com pleted and a f te r th e u su a l treatm ent o f th e re a c tio n m ixture th e re
wm o b tain ed $ .6 g# o f unreacted 2«aoetyltM oph®ne and h .2 g . o f a non»
d ie t i l l a b l e m a terial*

/

th e use o f 100 m l, o f te tra h y d ro fu ran ae a re a c tio n medium gave
no b e tte r r e s u lts w ith th e only is o la ta b le m a te ria l being 1 0 .6 g . o f
txskroaeied 2«*acctylthioplmne •
b o ilin g re sid u e rem ained.

&i th is in stan ce v eiy l i t t l e high

n

rn m U m t o f
^

*&tfe jn ^ a r g y l bromide

w » ttIto Of th e in te ra c tio n o f U*.0 g . (0,10 male) o f

8^2*opl©ijgrl<ti3l€^lifi*j®

w ith l l , f g ,

6*5 g« (0 ,1 0 mole) o f dry* elm*
cedin g e^erlw em fe,

(0,10 mala) o f propargy! bromide mad

&w% verf? s im ila r to those o f th e p re ­

^ ie tllX a tle n y ield ed 1 0 ,6 g , o f mjm&eted

prioicrltl& ophen© b o ilin g a t 6t«*65° (o.T »wu).

The amount o f reatdure

a f te r d i e t l l l a t i o n <me $»6 g*
Kftaat&on o f 2-b nty rylb hieph em and propargyl bromide
The r e s u lt O btained here mm oompereble to th a t o f t i e o th e r
teetonee, m i$ * b g . (0 ,1 0 mole) o f 2-butyrgrlthiophene appeared to
r e a c t td b h 1 1 ,9 g* (0 ,1 0 mole) o f pnopargyl bromide end 6 ,5 g . o f a lso
I s SO m l, o f hem tese and. 50 m l, o f te tra h y d re fa m i,

to w e r , d is till­

a tio n o f th e m ixture

g&ira 11,3 g ,

o f 2-botyrylthlophene w ith 3 ,1 g , o f

fe lfb -b o ilin g re sid u e

rem an in g in

th e d i s t i l l a t i o n v e s s e l,

KewertlOKi o f g~aeei/l*3«e^bto& thloph^m end prop arg yi bromide
The in te ra c tio n o f 14.0 g , (0,10 male) o f 2- a e e iy l- 3-» eib 3rX
tM®pheHO# 11,9 i , <0,10 mole) o f propargyl b r^ id ® and 6 ,5 g , (0,10
m ole) o f r i m i s 100 m l, o f a one to one m ix tu re , b j volume, o f bem ene
and ta tra b jv lro fb ra n m o u lted i s th e is o la tio n o f 10.3 g . o f unreacted
ketone and 2 .5 g , o f re o id n e , which could n o t be d i s t i l l e d .

n
Bohydr&ttoi* o f 0 *% dr03© 'eatars
32o a typ lc& l p re p a ra tio n , § «&* o f th© (3 ~hydr©3Qrester was placed
In a 100 w l# fla e k f i t t e d v lth a r e f le x contieiwier and $0 »X# o f a 6£
o x a lic a c id e o la tio n m s added*

The re s u ltin g isw is c ib le li<?nid

nttfhare waa heated a t I t s re flu x teiaperatune w ith o ccasio n al a g ita tio n
•for th re e Iwmra and th en allow ed to oool to room ta o p o ra to ro .
o f SS n l« o f e th e r m s added and th e n la tn re oa* ehaken*

a qfu&ntity

Follow ing th e

e e p ie a tto n o f the to o la y e rs* th e o t t e r la y e r n « d rie d ov er anhydrous
sediu® s u lf a te and th e e th e r oas rewored cos th e a te m bath*
was d i s t i l l e d under reduced p re ssu re ,
re a c tio n s m m tiSmmt Q u a n tita tiv e .

The pro du ct

The y ie ld s In thoee dehydration

A

mmm
I* Tit#

reaction® o f th e ^ ^ rc s s o e s te rs j o % l bromo-

a c e ta te * e t h y l ^ ~br0Ex>ju*opion&t<s> and e th y l ^ ^ rcatt-ied b tttg rr a te |
u ith %» <m& > *tha»alf

m d 3^^etyX thi© phsm , 2~j^opi© j^lthiophen© ,

2«4*utyi^Xtbioph®ne and 2~aoet;^<*3»*«ietl&l thiophmae were c a rrie d out*
f ie ld * o f 0>

e s te r s m

la rg e ly & p ro p erty o f th e amount o f

s b e rie hindrance involved in th e fcassation o f tb s product*

The use o f

dloxaxse in ste a d o f bam ene m th e re a c tio n media caused only s lig h t
re d u c tio n in y ie ld s through e n o liz a tio n o f the ketone employed. The
p ro p e rtie s o f th e (3~hydroagr e s te r s formed as w ell as th e p ro p e rtie s
o f th e correspoKKiing unsatur& ted e s te rs ere re p o rte d .
2 , The h efcm aisk y reaction® o f e th y l

•b ro ao cro to n ate w ith 2*

and >»thefijgl, 2~aaetylthlopb*m© , 2~propic»crltM ophezie, 2-butyxylthiophana
and 2»acetyX*3*^M»tXyX thiophene were c a rrie d o u t.

f ie ld s were r e la tiv e ly

low and in th e case o f th e f i r s t th re e thiopkene d e riv a tiv e s mentioned
th e re was s h e lv e d seme isom eric rearranged product along w ith th e
expected p ro d u ct.

The p ro p e rtie s o f tfe® products a re re p o rte d ,

3 , The B ftfesm tslgr ta c tio n ® o f i& ly l bromide w ith 2 - and 3~ ib»na!#
2«* and 3~»eetylbhlophen«, 2-p rop lon yX tld .o ptee, 2*butyrylthloptieno and
2~&cetyX~3«**i®ihyX tbtepbene were c a rrie d o u t.

The y ie ld s o f b~(TM enyl)~

b * i^ ro x y » l^ k e tift£ were unifoim ly high w ith v ery l i t t l e unre acted
ketone being reco v e re d . The p ro p e rtie s o f the p ro du cts are re p o rte d .

95

li. th& M to m eta k y reac tio n * o f pmp&pgpl b ro aid a w ith 2 - and
3~thm aX , 2~acetylt!&oph*m©, 2-propior^lt*iiopfaena and 2Wfcuty*yltbiopheae
were c a rrie d o u t.

Only in th e ease o f th e th e rn le vac any Hefem&ieky

ty p e p ro d u ct is o la te d In good y ie ld s .

Fro® th e to to n e s no produet was

fernerd, h u t la rg e q u a n titie s o f unreaoted ketone were reco v ered .

th e

p ro p e rtie s o f th e products re s u ltin g fro® th e tto n a ls are re p o rte d .
5* V berscw f e a s ib le , y ie ld * are c o rre la te d w ith s te r le consider*
ationss, in d u c tiv e e f f e c ts and re a c tio n so lv e n ts.

rm

xz

r m s e n t m a m a ttm

96

m aosucT icm
The in te ra c tio n ©f equtm olar q u a n titie s o f hydragoic a d d w ith a
carbonyl compound in th e presence o f a stro n g acid has become known as
th e Schmidt re a c tio n *

Through i t , i s a v a ila b le a convenient method

f o r th i p re p a ra tio n o f a m w ber o f organic n itro g en compounds*

Time

so ldo y ie ld amines according to th e fo llow ing eq u a tio n ,

IMX30H ♦ M* -JL*

k-NHa

♦ CO* * «*

from aldehy des, th e re are o btained d t r i l s s and formamides w hile
feetcoos y ie ld am ides,
ii~Cf£>

RCOH

*
4.

1^3

M*

JL *

Bfig

and

BCOHm

+

S-SJB-C®
8a

The re a c tio n was f i r s t recorded by K arl Schmidt in 1923 when he
observed th a t bensene had an a c c e le ra tin g e f f e c t on th e decom position
o f hydraasoio a d d in th e presence o f m ineral a c id (81,85) and th a t
v a ria tio n s in th e re a c tio n tem perature re s u lte d in d if f e r e n t p ro d u c ts,
Jfe found th a t th e a d d itio n o f hsnsopbenone to th e m ixture re su lte d in
a vigorous re a c tio n and an alm ost q u a n tita tiv e y ie ld o f b e a s a n ilid e ,
^Xac© th a t tim e th e scope o f th e re a c tio n has been broadened c o n sid e r­
a b ly to in clu d e n o t o nly carbonyl compounds b u t o ld f la s , la c to n e s ,
an h y d rid es, e s te r s , a c id h a lid e s , quinonas, d t r i l s s , imldo e s te r s ,
am ides, leo cy an ld es, oximes and many o th e r types o f compounds (8 6 ),
alth o u g h when m ost o f th ese l a t e r compounds are a re a c ta n t w ith
hydrassoic acid such in te ra c tio n # a re n ot g e n e ra lly considered as
c o n s titu tin g a tru e Schmidt re a c tio n .

9f

There 1ms been re p o rte d v ery l i t t l e work on th e Scheldt reactio n
o f carbonyl d e riv a tiv e s o f fcaiaroeyoli© compounds and only one of
th e se d e a ls w ith tfclnpten© d e riv a tiv e s (8?)*

In th is stu d y , Bard sad

H o ffa t conducted a r a t t e r cu rso ry exam ination o f tb s Sefcoidt re a c tio n
o f 2 ~ ao ety ltiteg tei$ e sad found th a t s m ixture o f th e two p o ssib le
p ro d u c ts, 2'N%oet&sddoifttapten$ and ^ f e h & n c ra s t^ ^ iie , re s u lte d .
I t mm th e purpose o f th e p re se n tly desoribed in v e s tig a tio n to
grtowfyr th e S ehaidt re a c tio n o f th e ketones and aldehydes o f thiophene

under a v a r ie ty o f co n d itio n s*

Both th e two sad th re e s u b s titu te d

IM sp y l carbonyl d e riv a tiv e s were stu d ied and a la rg e nusber o f ooids
were es^ley ed m th e c a ta ly s t.

F u rth e r, se v e ra l d if fe re n t so lv e n ts

were In v e stig a te d sad co n sid erab le v a ria tio n in re a c tio n tem peratures
was exam ined.
Tfcs thiophens d e riv a tiv e s in v e stig a te d in th is study Included

fattens*! , l^ tten a l, ^-acetyl thiopb^s®, ^»ppoplD«ylthioptens, 2-n«butyryl»
tM ophsns and 3 ^ ao o ty lth ic p te n e ,

The re s u lta n t p roducts w ere, in a H

o a s e s , known eeispownda which had been p rev io u sly prepared by unequivocal
m ethods.

The aldehydes o f thiophsn® gave uniform ly high y ie ld s , o f

th e e j e c t e d n i t r i l e s , w hile only ra th e r poor y ie ld s o f amides were
o b tain ed from th e k eto n es.

98

m sm m jo *
The fiefciftrft re a c tio n has found i t s mm% o x to salv e a p p lic a tio n in
to n »*»bho#l» o f amines from a c id s .

i t h s tr a ig h t chained a lip h a tic

ta ld ft th e y ie ld o f am im g e n e ra lly in c re a se s w ith th e le n g th o f the
a lk y l o b ata ( 8 i#BT) * t a t 00 such g e m rs llz a tio n cm be wade In the case
o f th e mere oompaioeted bram h*oh«dned a d d s ,

In g e n e ra l, d ib a sic

a c id s y ie ld th e cori^aponding diamine® (90,5ft) w ith the exception th a t
m&lnmle ac id e ta s u b s titu te d m alonie asid e y ie ld * -amino asid e (9? ,93)
which do n e t undergo f a t h e r re a c tio n w ith )*?drasole a c id ,
OCSOH

„ ♦ SK. . K

COOH

j ,

?

U^JMXX>U
Ml%

The reco ils® proceeds re a d ily o w n w ith a c id s in which th e carboxyl
group to r e la tiv e ly in e rt*

Th® numerous dogaoriures and exceptio ns (86)

to th e se & o**er«lioaiiosii w ill n o t be d iscu ssed here sin ce th is p a rtic u ­
l a r stu d y woe n o t concerned w ith th e teatw ic so ld o .
The ao tetid t re a c tio n i s known to proceed more re a d ily w ith aldehydes
e ta ketones th an w ith a c id s .

The d iffe re n c e in th e r e a c tiv ity o f hydra*

s o le acid w ith carfcoxayl compounds and a c id s i s la rg e enough th a t a koto
ac id w ill r e a c t w ith one mole o f iydraE olc acid in tb s presence o f an
a c id c a ta ly s t to give e a n lu siv e ly two amides w ith no m&am re s u ltin g

99

o^-a-e^aPHaCOOH ♦ m* — * dJLsiEHgCi^cooH ♦ cfyHic-cji.aj^cooH
tb& mooting* o f aXdohydn* id tli hydrasoie m id h&s n o t boon no

e x te n siv e ly IwootdLg&tod m th e re a c tio n o f tkm X ator r e g e n t w ith
koiom a*

tli# prim ip.& l product roswxlttng from aldehydes i s tb& c o rre o -

ponding g A tr tlo , bust in e e rto in in sta n c e s * fom snid® I s o b ta in e d ,
H n s f from bemdXde%de 1m

m e n tio n prodaot»f b e m o n iiril# and for*®-*

a n llid o f o re o btained {©5*9$).

Tt» r e la tiv e y ie ld s o f th e se products

s m dependent on th e n r a t o f e a lfu rlo acid need &* * c a ta ly s t,
JUnngor smoomts Of th is eab& lyst em m th e form ation o f a g re a te r pro-*
p o rtio n o f fo m a n llld e .
fi® eorrospondlitg m i d m!4®$ r e s u lt «b®» sym KstdGal ketones
undergo tli® flo ta td t r e a c tio n ,

Thus acetone I s rep o rted {©5) to give a

a u sm tlta tiv e y ie ld o f mstlg?&aest*Mld* w hile o^relohoxanon® and ey e lo ootancM give W

y ie ld # o f 6 -cap ro la o tan and a*-aminooopryiio lactam ,

m a jM tiv e ly lf© ,£T)#

In th e se

stiem OT»3fs«»etriooX ketones am M & hyed th e re to

tho p o s s ib ility o f m& o r bo th o f tm d if fe re n t products r e s u ltin g .

100

ip n oted above* ls m ilin lc acid re a c ts to give tb s two p o ssib le amides*
fewever* sin c e tb e la rg e r p ro p o rtio n o f product r e s u lts through tb s
m ig ratio n o f th e p ro p io n ic ac id group* th e n atu re o f th e mein produet
i s in many e a ses la rg e ly dependent m tb s r e la tiv e e le c tro n e g a tiv itie s
o f th e to o groups involved*

From aeetophenoas th e re i s obtained & Tf%

y ie ld o f a e e ta n ilid e w ith none o f tb s o th e r isom er being is o la te d (9 2 ).
^ s tih re p o rts (98) th a t tb s p ro p o rtio n o f isom ers produced i s dependent
upon th e a c id ity o f th e medium as determ ined by th e a c id ity o f th e
c a ta ly s tt b a s ic ity o f th e s o lv e n t, b a s ic ity o f the carbonyl compound
and b u lk fa c to rs o f th e groups attach ed to th e carbonyl carbon*
i b r ie f d isc u ssio n o f th e p re se n tly accepted id eas concerning a
m echanistic p ic tu re o f th e Schmidt re a c tio n I s in order*

Schmidt

proposed a mechanism (85) in which he suggested th a t th e bydra*oic so ld
cleaved th e stro n g a c id c a ta ly s t to y ie ld n itro g en and Hie ia id e ra d ic a l
which th en a tta c k e d th e caubonyl group, follow ed by a rearrangem ent
s im ila r to Hie Becksan re a c tio n .

k
— >

(»H>
N>

0
ft-c-n m

HOB
E-C-E

In 19h8, nmmm and O ildenhom (99) proposed a carboaium io n
mechanism w hich was more accep tab le in lig h t o f more re c e n t evidence*

101

According to th e ir tlo o iy , th e

group o x jp n i i protonated

y ie ld in g a carbonium Ion which 1« attac h ed by on® o f the resonance
gpsele* o f hydrasolo a d d , follow ed by th e elim in a tio n o f n itro g en
and th e m ig ratio n o f one o f th e groups attac h ed to the carbonyl carbon.

O M f*
OH

Hswman end O ildenbcro p o stu la te d th a t th e group which m igrated
wm th a t which pda*sssed the g re a te r m igratory ap p lied * .

T his th eo ry

was a p p a re n tly stren gthened by th e result® o f a stu dy o f th e re a c tio n
o f im sym m otrieal d ia ry le th y len es w ith hydrasoic acid in th e presence
o f s u lfu ric acid conducted by HcEwen* O illand and Sparr (1 0 0 ),

From

th is p a r tic u la r work i t seemed ra th e r evident th a t the group which
m igrated from carbon to n itro g en was th a t p o ssessing th e g re a te r
in tr in s ic m ig rato ry a p titu d e .

They found th e o rd er o f m igratory

a p titu d e s to be according to th e follow ing sehemst
p~*nl*yl> p ~ te ly l> p-bipfa»*yl> phenyl^ p^hloroph®isyl^> m ethyl
T his o rd e r i s in q u a lita tiv e agreem ent w ith th e m ig ratory a p titu d e s
V

found in th e F in aco l rearrangem ent.
Almost sim ultaneously 9 & tiib (98) proposed a s im ila r mechanism
in which th e em phasis was n o t upon th e m igratory a p titu d e s o f the

102

groups, Iw l n t k f

th« reU U vs bulkinase of the two groups,

tM m mechanism was postulated to account fo r a number of instances in
which the group m igrating woo not th a t which w old bo expected to have
tbo g reater m igratory a p titu d e , but the one haring tho la rg e r bulk,
m o soasspl o f a bulky group to also disouisod by Sobusrofa and ftm tross
(101,102), lb s distinguishing fa cto r in b d th 's asehaoisn lo th a t i t
presents an interm ediate species exh ib iting geom etrical Isosw rlsn
to tho oadittoo.
9
Ri - c- r ,

„+
8 >

OH
a l -6 -a ,

^ e , jf%

^ t»0*

«

« * « •
II ©
W1IB

•* »,.>

^

® ® ,
ttM taB t>

©
? -« ,
%-H

0
E^MS-ft^Ra

OB
a*-9-«»
I®
OMMf
g. _
(S'
—I S » * - 9 - a ,
^ K ,^H
*

®
♦ %0

th e dehydration atop o f tho mechanism causes tho form ation o f a
sin g le sp e c ie s w hich nay have two geom etrical c o n fig u ratio n s about tho
double bond*

I t would be expected th a t a preponderance o f tid e sp e cie s

would bo in a form eo th a t tho la rg e r group would be tra n s to th e ago
group causin g lo s s s tr a i n .

Coneequontly, in th e succeeding a to p ,

proceeding through th s lo s s o f n itro g en and s h if t o f an E group to
n itro g en * th e group which would be expected to m igrate would be tho
one bMMR to She ase group.

I t I s e v id e n t th a t th e la rg e r group does

103

m ig rate ja 'e fe re n tlO ly tn m l a t e r work by SWLth ( 103 - 105 ) .

I t is

s ig n ific a n t th a t In th e { ^ su b stitu te d bensophenona s e r ie s , alm ost
eq u al amount* a t am h rearrangem ent product a re o b ta in e d .

T his i s

Im sx p lleab ls in te rn s o f p u rely e le c tr ic a l f a c to r s , b u t I t I s in
m & m m m t w ith tb s c te r ie eon sideraU ons which have been d e sc rib e d .
Since th e p a ra s u b s titu e n ts do n ot in e re a se th e b u lk o f a phenyl group
a s f a r a s th e ase group i s concerned, an equal m ixture o f isom eric
p ro d u cts would be expected.
th e re a re th re e g en eral methods fo r c a rry in g o ut th e Scheldt
re a c tio n w ith a carbonyl oospound. The f i r s t o f th ese e n ta ils the
a d d itio n o f a benssne o r ciilorofbrm so lu tio n o f bydraaolo ac id to th e
o rg an ic compound d isso lv ed in about btdos i t s volume o f co n cen trated
s u lf u r ic a d d .

T his method i s most g en e ra lly ap p lied to th e p re p a ra tio n

o f amines from a sid e and i s n o t u se fu l where th e organic compound I s
s e n s itiv e to high co n cen tratio n s o f stro n g a c id .

The speed o f the

re a c tio n i s observed by load ing th e evolved gases through a wash b o ttle
arranged m a babble c o u n te r.

The amount o f hydrasoio so ld employed

i s u s u a lly 1 to 1 .2 m oles par carbonyl group and follow ing the com plete
a d d itio n o f th e hydrasoie ac id s o lu tio n , s tir r in g o f th e re a c tio n mix*
to r s i s continued u n t i l gas ev o lu tio n has ceased (8 9 ,9 1 -9 3 , 1 0 6 -H 3 ).
The second g en eral method and th e one app lied m ost fre q u e n tly in
th e case o f aldehydes and ketones in v o lv es th e a d d itio n o f co ncentrated
s u lf u r ic a c id to a s tir r e d so lu tio n o f th e carbonyl compound and
brdram U a c id in chloroform o r b sm e n s.

Prolonged co n ta c t o f th e

101*

o rg an ic
i s th e

w ith s u lfu ric a c id i s avoidsd*

tM i l a t t e r procedure

one th a t has been auoeoM hiU jr ap p lied to th e re a c tio n o f

aldehydes w ith hydrasolc a d d < S 5 ,9 2 ,6 6 ,m , l l h ,! ! $ ) •
1 le a s commonly employed procedure re q u ire s th e a d d itio n o f a
v o lu tio n o f th e carbonyl compound and hydr&soic a c id to a w all « U m d
q u a n tity o f co n cen trated s u lf u r ic a d d o r to a d a t u r a o f s u lf u r ic

mid

and chloroform {85#9 ? ,U U ),
F re q u e n tly , a v a ria tio n o f th e f i r s t Method can be su c c e ssfu lly
ap plied*

In th is p ro ced u re, s o lid sodium a sid e ia added in m i l

p o rtio n s to th e carbonyl compound contained in s u lfu ric a d d o r o th e r
ao id c a ta ly e ta f o r i t m i be added to th e a d d c a ta ly s t d isso lv ed in
so lv e n ts end* a s a c e tic a c id (90*103,XOJi,10? ,!G 8 ,ll6 « a i8 )*
a v a rie ty o f so lv e n ts have been deployed in th e Schmidt re a c tio n ,
th e a o s t common b eing chloroform and bemsene*

Hecexxtly, tric h lo ro a c e tic

a c id has a tta in e d sens prom inence, both a s a so lv e n t and c a ta ly s t
( 96 , 1 0 3 , 1014)*

th e re has been a t le a s t one in stan ce in which a c e tic

a c id served s a tis f a c to r ily a s a f a c t i o n media (119) and th e use o f
t i ^ l t o m t l ^ l e n e a s a so lv e n t h as been rep o rted (120)*
is not

a s a tis f a c to r y

so lv e n t

(92),

m h yl e th e r

although i t s use has been claim ed

in a few p a te n ts ( llh ,1 2 l) *
m m o th e Schmidt re a c tio n i s norm ally quit® exotherm ic c m
method o f tcsp cratur® c o n tro l i s re q u ire d ,

th e re a c tio n w ith aldehydes

and hetonss I s u su a lly c a rrie d o u t w ith cooling o f th e re a c tio n m ixture
in

m

ic e b a th , and c o n tro lle d a d d itio n o f th e hydras®ic sold*

Only

10$

when th e re a c tio n i s H o g g ish i* a higher tem perature o f any advantage.
tem ever, w ith aldehydes and leeto nes M i l a lik e ly to le a d to excessive
decom position and th e re i s the f a r th e r danger ©f lo o sin g hydrasoic
aeM ( b .p , 37*)*
C onsiderable work has been devoted to a s c e rta in in g th e type o f
n ttlis a b l* c a ta ly s t and th e co n cen tratio n s d d e h *111 give th e h ig h e st
y ie ld s * C oncentrated s u lf u r ic so ld in a sse n ts o f about double th a t o f
th e carbonyl compound has been need meet ex ten siv e ly a s th e c a ta ly s t.
D ecreased y ie ld s r e s u lt from th e nee o f d ila te s a lfu r lc acid (8 5 ,9 2 ),
b a t th e re I s co n sid erab le evidence te a t te e use o f 9S% s u lfu ric ac id
I s th e meet s a tis f a c to r y fo r ketones (122)»

Smith and o th e rs (9 8 ,1 03 ,

10k ,122,123) have shewn th a t tric h lo ro a c e tic acid I s e x c e lle n t c a ta ly s t
f o r th e S cheldt re a c tio n .

O ther c a ta ly s ts which have been m entioned

a re hydrogen c h lo rid e (9 7 ,1 0 7 ); phosphorus tr ic h lo r id e , phosphorus
p e n ta o h lo rld s, phosphorus oxychlorlctei f e r r ic c h lo rid e , sta n n ic c h lo rid e ,
th io n y l c h lo rid e ; su lfo n ic ac id s (9 5 ); phosphoric a c id (H it); altaninura
c h lo rid e (9 5 ); and u ltr a v io le t lig h t (1 2 k ). There I s no evidence te a t
ai*y o f te n se c a ta ly s ts serv e a s w e n ae s u lfu ric o r taicK Loroaceti©
a c id .
The most eenncn b ip ro d u ct re s u ltin g from te e re a c tio n o f a ketone
o r aldehyde w ith hydraaeic a c id In te e presenee o f a stro n g m ineral
a c id i s a te tr o s o ls .

T ide i s o f m iner im portance where te e m olar

r a te s o f carb o n y l compound to hydraaoie acid i s o n e, b u t in th e presence
o f la rg e ex cesses o f hydras©!© acid te tra e o le s may be te e m ajor p ro d u ct.

106

in im ported (9S) to r e s u lt irem th e in te ra c tio n o f
benzaldehyde w ith hydr&zoio a a ld .
Cs % *cm

* 2H2* --------^
EH

K

Iki tin presence o f excess hydraaotc a c id , acetone re a d ily jfia ld t 1 ,5 d i» e t^ lt© tra » o le ( iS #U S ) # C yclic ketone# are ffcmid to re a c t in a

s im ila r mmmm (95,123,126*128).

A ccordingly, tit* h e a rt atd n u lan t

H eir& zel* i s prepared from cycXoh*x&rK5»© end hydra#oic ac id (8 5 ,1 2 5 ),

/ O H * G % - C l i ts
§4
6

&
OH*

* *»#------ >
6

OH*
£=■¥
h*«g%- ®n
™

I t has bseek e sta b lish e d th a t th e te tra s & e s re s u ltin g from ketones
do a c t r e s u lt from th e f u rth e r re a c tio n o f excess hydragole a d d w ith
t i e a s id e , w hich would be tb s eaqpaeted product o f th e S e ta id t re a c tio n ,
nine# i f th l# amid© i e su b jected to treatm en t w ith hydr&eole aoid
under th e ease «op*rta«**taX co n d itio n # , m te tra s o le r e s u lts (8 5 ,1 1 5 ).
th e o r ig in o f te tra s c le # r e s u ltin g from aldehyde# i s even le e s w e ll
e s ta b lis h e d ,

th e re i s m m in d ic a tio n th a t a n itril® i s n o t th e

In term ed iate sin c e th e re a c tio n o f a n i t r i c w ith hydrasoic a c id in
th e presents* o f co n cen trated s u lfu ric ac id y ield # a 5 ~ < ^ ii» ~ l-a lk y lte tr a s o le {129-132),

Ptoenyltetrasel© has been rep o rted (9 3 ), as the

107

IM3 f * at* ------ *

*0 ^ 0 =

H

p ro d u ct r e s u ltin g £*oto b enaalW hyic.
I t a t m d M offat (8T> made th e only re p o rt o f th e Schmidt re a c tio n
W in g c a rrie d c u t v ith a carbonyl d e riv a tiv e o f th iophane.

These

in v c o tlg a to ro wore cooking a alsjple one atop p re p a ra tio n o f 2-ace tam idothlopW ao from 2 -ao© % ltl2ioph®»a and made use o f th e iohaidfc reactio n *
My th e ir p ro ced u re» a co ld so lu tio n o f 2~&©@tylthiophsm© d isso lv ed in
ohlorofim # m e tre a te d w ith 96# s u lf u r ic acid end a chloroform so lu tio n
o f l^rdra®oio a c id ,

pmtzm

They m m ab le to re c ry e ta llle e from benseme end

a e u te c tic m ixture o f 2*^@ tam iW thtophette end 2~then©mett$&«

amide which wm sep arated by so lu tio n o f the p ro du cts in a m ercuric
ecetetO H ^dium a c e ta te s o lu tio n and e x tra c tio n o f th e ^-tfceacaftsttylam lds
w ith chloroform *

‘tibsit th e m in v e s tig a to rs c a rrie d o u t th e re a c tio n

a t e le v a te d tc n ^ e re tu re s th ey o b tained ©tOy a minute m ount ©f
f^tlienom etl^lm dde end a ©oguddersble amount o f m a te ria l which th ey
presumed to be m eo etm ld othio pW iieeiilfo iiic a d d .
std s ro b le decom position in th is l a t t e r reactio n *

th e re wee eonSince th e ir in te r e s t

m s e t r i o t l y In th e sy n th e tic n a tu re o f th e re a c tio n , Hard and M offat
made no f u rth e r in v e stig a tio n *

108

i&so&a^oif
The Schmidt R eaction w ith Theim ls
l a MnrariU* o u t th e Schmidt re a c tio n cm 2 -th e m l m d 3 ~ th en al,
tb® m ost r e a l l y executed ®xpsiim®ntaX procedure was examined.
4 h&mm® so lu tio n o f 2 -th en a l having a s lig h t excess o f hydraeoic
so ld smd contained In & beaker was tr e a te d , w hile being s t i r r e d , w ith
a sm all m®mt o f co n cen trated s u lfu ric a c id ,

A stead y stream o f gas

■was evolved and mt I t s com pletion a m ixture o f too and w atsr was added
to th© re a c tio n m ixture and th e re s p itin g la y e rs wars separated*

A fter

washing w ith d ilu te sodium lydroxid® , the bem ens la y e r was tre a te d
w ith a co n cen trated sediimt b is u lf ite so lu tio n to remove unreaoted
aldehyde and was th en d ried o w anhydrous sodium su lfa te *

The bensem

was removed by ev ap o ratio n and th e resid u e was d is t ille d under reduced
p re ssu re to give m

y ie ld o f 2 * th en © n itrile which was id e n tifie d

by means o f i t s b o ilin g p o in t, re fra c tiv e index and conversion o f a
sample by b a sic h y d ro ly sis to th e known 2«thenoic acid*
I second p re p a ra tio n o f 2 ~ th e ix m itrils was c a rrie d o u t except
th a t Sirupy phosphoric a c id was used as the c a ta ly s t*

The re a c tio n

seemed to proceed somewhat d ow er a s determ ined by th e ev o lu tio n o f
n itro g e n , b u t a f te r th e above d escrib ed is o la tio n method th e re was
o b ta in ed a dO$ y ie ld o f 2 -tb e n o n itril® .
These same two procedures were ap p lied to 3~ tbenal and whore
s u lf u r ic a c id was employed as th e c a ta ly s t a 19% y ie ld o f 3 -th e n o n itrile

109

re s u lte d w hile from lb s phosphoric a c id cataly sed re a c tio n , th e re was
o b tain ed & 62$ y ie ld o f tb s expected p ro d u ct.

The Id e n tity o f th e

p ro d ao ts was determ ined by b o ilin g p o in t, r e fra c tiv e index and e&n~
v e rsio n t© th e s o lid 3-th eao io m U .
/T ^ J -o a s
^

♦

ft

a s*

.g-at *

s ,

s

* Sffi

J$C>

ff^ JJ-COOH ♦ KH»

The p ro p e rti* * , d e riv a tiv e s , y ie ld s and methods o f p re p a ra tio n
o f th e se p ro d u cts ere summarised in Table X.
In e l l o f th e above d escrib ed stu d ie s th e tem perature was held
a t 20° 0 , o r le s s .

One stu d y was conducted in which 2~ thsnal and

hydraoeic rnM wore allow ed to undergo re a c tio n in th e presence o f
s u lf u r ic so ld a t liS °,

T his re a c tio n was c a rrie d o u t in a fla s k f i t t e d

w ith s t i r r e r and re flu x condenser to p rev en t the lo se o f hydrasolc a c id .
As th e re a c tio n proceeded co n sid erab le decom position was in ev id en ce.
^hsn th e ev o lu tio n o f n itro g en had ceased th e m ixture was worked up
in th e u su a l maimer to y ie ld a ra th e r la rg e amount o f ta r r y m a te ria l
and o n ly 21% o f th e th e o re tic a l amount o f 2 -th e n o n ltriX e . There was
a lso p re s e n t a la rg e amount o f a base so lu b le m a te ria l which y ield ed
a yellow in so lu b le p re c ip ita te w ith barium c h lo rid e s o lu tio n .
was pro bably a s u b s titu te d tM ophene su lfo n ic acid s a l t , b u t m
f u r th e r exam ination o f th e substance was conducted.

T his

110

&
<%
m

31 3
R

a

u>
3

XA
*

r*

$

*

XS *
•■=*t*>
£*
.'S ^
%
T
fc

i
I
H

i

M

*»*>

&

1W
1

V|

M
J

'■*

§I I

f4

%,
B

.

O*"*
m p
w
% ~

&

s %
IIII

%
tif f
• *
**%

«s *a
s

-i

I ll

Tbs Schmidt ite ac tio n w ith th e Acylthiophenos

4

o f th e Schmidt re a c tio n o f th e aoylthtcphsnes i s b o o st

b y co n sid erab ly more d if f ic u lty th an i s th a t o f the th e n a ls ,

F ir s t,

th e work o f Hard end M offat (87)* which was n o t com pletely s a tis f a c to ry
l a th a t th ey receiv ed a m ixture o f products from which th ey were able
to I s o la te only t^thenom ethyla«ilde, was repeated*

The in te ra c tio n o f

2~aoetylthiophene w ith hydrasoie acid in th e presence o f s u lfu ric acid
w ith chloroform a s th e so lv e n t proceeded re a d ily a t 0*10®. follo w ing
th e se a u th o r1® procedure* th e m ixture m e poured onto Ice and th e
zqm om la y e r m s re p e a te d ly e x tra c te d w ith chloroform which m s eon*
blued w ith th e o rig in a l chloroform la y e r and. washed w ith d ilu te a lk a li*
A fte r ev ap o ratio n o f th e chloroform Che produet was r e e r y s ta llis e d
tr m bensone and a second crop o f c ry s ta ls m s obtained by th e a d d itio n
o f p sn t& is.

The f i r s t product m elted o v er a rang® o f 1O8~1390 w hile

th e second had a sh arp m elting p o in t o f 101~102°* Bepeated r e c r y s ta lllc a tio n s o f b o th p ro d u cts from v ario u s so lv e n ts fa ile d to e f f e c t any
f u rth e r separatism *
and M offat*

Them o b serv atio n s follow ed c lo se ly those o f HUrd

The m ixture o f th e two crops o f c r y s ta ls was su b jected

to b a s ic h y d ro ly sis to y ie ld a v ery dark colored so lu tio n from which
I t was p o ssib le to I s o la te a low y ie ld o f 2-theno io acid by a c id ific a ­
tio n *

T h is in d ic a te d th a t th e m a jo rity o f th e product was 2~aoetamldo~

tktophsfiO w ith a m a ile r p o rtio n being 2-tfcenom«bhyla*5id®.
I t m s thought th a t changing th e re a c tio n so lv e n t to bem em
m ight r e s u lt In a preponderance o f a sin g le product and th e re b y avoid

m

a im y d i f f i c u l t s ^ r a t o n ©f th e two isom eric am ide*, The a d d itio n
©f

s u lfu ric acid to a feemen* so lu tio n o f )fd r« so lo so ld

and 2~ac© tylthioj>hen*, a t ©*, re s u lte d in a d ark rod eo latio n *

A fter

th e p re v io u sly d o w lb o d o p e r a tio n t o benzene was removed by ©vapora tlo n to y ie ld a d ark rod o i l which m© taken
and tre a te d w ith Kerit© A*

in ab so lu te eth an o l

Slow evapo ratio n o f t o

ethan ol re su lte d

in tb e form ation o f the same red o i l which was taken up in h o t bonsene
and c e d e d s l c d y .

% e * few w hite o iy sta l* appeared th e se were

lia s e d ia td y sep arated and d rie d ,

They m elted a t 159-160° (1 1 6 ),

to n

no f u rth e r c r y s ta ls could be is o la te d from th e benzene s o lu tio n i t
m s © en eM to ted and tr e a te d w ith a barium c h lo rid e so lu tio n which
caused m immediate p re o ip lta tlo n o f a yellow s o lid .

T his was presum­

ab ly due to th e form ation Of th e b eritas s a l t o f a su lfo n ic a c id ,

Tin

rem aining bm nem s o lu tio n was evaporated to a lig h t red o i l which
was d i s t i l l e d a t rodeoed p ressu re to y ie ld some 2~4cetyl th iophene,
b u t no f u r th e r p ro du ets o m ld be is o la te d ,
Bspei&tdoti o f t o sh ow procedure re s u lte d in th e form ation o f a
f i y ie ld o f f-aoetifisidothiopfeen® , a f3S recovery o f 2-ac©tyltbl©ph®ns
and a la rg o m m m t o f a b a rto s s a l t .

There i s a re p o rt in t o

l i t e r a t u r e (137) o f t o form ation o f red ams&stm* between 2 -a c e ty lthleptsem and s d fu ri© a c id .
to

I t was thought t o t th is may account f o r

I s o la tio n o f some w nreaoied tl& ophsm * A ecordisigly, a beseems

s o lu tio n o f t- a c e ty lth io pbmm was tre a te d a t 0 C, w ith a sm all amount
o f s u lf u r ic acid to y ie ld an immediate dark red s o lu tio n to * * in te n se
c o lo r was lig h te n e d co n sid erab ly by d ilu tio n w ith w a te r.

113

ias attem pt to employ phosphoric sold so s c a ta ly st fo r the w »
so tto o o f 2<Hfte*tylth±oph«m sod fcydragole o d d was unsuccessful because
o f th e form ation o f s c ry sta llin e complex titr n m phosphoric sold o d
which in h ib ited th© Schmidt reactio n . Tide white
so lid complex i n i f i r s t reported by Stages sod lU oodorf (138) oho
noted th a t i t m olts a t 92«#6*.
€H
CH
11
II
CH
a-COC%*%FO.
^ $
Xm «n e f f o r t to Improve tho y te ld o f products o b ta in ab le from
2-M8^1ylbhdophe»e in th e Schmidt re a c tio n th e method o f Semant and
KeXntoefc m o employed ( U p ) .

The a d d itio n o f s o lid sodium asid e to

a m ixture o f 2-acetylttelG phene mt1 s u lfu ric so ld in g la c ia l a c e tic
so ld re s u lte d In a rap id and vigorous ev o lu tio n o f n itro g e n ,

4 fte r

a h a lf hour th e re a c tio n m ixture m s poured onto ice* n e u tra lis e d
w ith ammonium hydroxide, and e x tra c te d se v e ra l tim es w ith bensene.
The bensene s o lu tio n m s d rie d and concentrated to a brownish o ily
l i quid wMoh was poured onto crushed ic e to y ie ld a ta n s o lid m elting
a t 110-133*.

The s o lid m s d isso lv ed in a s n a il volume o f benssne

and tre a te d slow ly w ith boseae
i

f u r th e r re o ry » ta lli« a tio ii
\

to give a m a te ria l

m elting a t 152-1$?°.

o f th is m a te ria l tram a w ater and eth an o l

m ix ture re s u lte d in a m a te ria l m elting a t 158 .$-!$$>.S °. T his m eltin g
p o in t was n o t depressed when th e product was mimed w ith «e$Sfcpl« o f
p u rs 2-aoeta»idothiophene •

lib

VtowMvw* v a ria tio n # o f IM s procedure were examined w ithout any
®9^

i

^

***» mf l ^ | e r w a i t s o f e u lfu rle

mid earned

mere ex te n siv e decom position o f th e re a c tio n m ixture aa d id prolonged
re a c tio n tin e god e le v a te d

The re a c tio n proceeded

r a th e r alugglal& y a t 5° and y ie ld # were n o t improved,

IMmg th e procedure o f tenant and KeXntesb (119) on 2«o»jdnqrl*
tMephm© and 2~n-butyryltkioph©ji« resu lted la aJU and 22$ y ield s
resp ectively o f 2-j»m pioam ^

and 2-butyramidotM0pl*m«.

Hi b o th ease# t h f f f wa# evidence o f ex ten siv e deoonpoaltioa o f th#
re a c tio n wfaxtem*, There v m obtained M a g tb s reery ctiO X iaatio n o f
b o th o f th e erode p rod ucts an o ily m a te ria l which when c e d e d to low
io^poratmvm# gave a cem loelid o f In d e fin a te m eltin g p o in t.

B asle hy*

d r d y c i# o f th le m a te ria l r o o s te d in th e form ation o f a m a l l m ount
o f' 2**tbmols mold in d ic a tin g th a t am # tbanm ld# M

romaLtad I n th#

Schmidt roamt&em o f thee# aoylthiophtm aa.
I^om

th e y ie ld o f ^ acstm sid eth lep b cn a mm o n ly

%$%9 8 » m , mm in th e above experim ents* a m a ll amount o f th e oorr«is~
ponding thomel® m id

wm is o la te d

by b a sic h y d rd y s ie .

The mao o f trie h le ro & c c tic a c id a# b o th c a ta ly s t and so lv e n t w&»
examined*

ih l# procedure was attem pted on 2-^o«tylthioph#m w ith

th e hpdreaolo meld being generated in th# re a c tio n m ixture by th a
a d d itio n o f sodium o tid c # m alm ost Immediate g e la tio n and ch arrin g o f
th # mymUm ooeorred*

T his was found to be dm to th# hig h a c id ity

m d r e lfttiv o ly high m eltin g p o in t o f tric h lo ro a c e tic m id {$9°} nine#
d iss o lv in g 2~ae#tyXtM©phsm® in th e liq u id m id reim ltad In a s im ila r

US

•WKun«WM»* Accordingly, th is pdadM liV m s abandoned.
I t was thought th a t tr ie llo r e s c e ilc m M ml$fa% serve s a tis f a c to r ily
m a c a ta ly s t i f a so lv e n t were employed to allow th e m ixture to rem ain
ll^W&i a t low er tem p eratu res„ "$mn feemeiie was employed as th e so lv en t
th e s v m tlm f a ile d to occur even a t elev ated tem p eratu res.

th e ad d i-

tI o n o f sw ifte io sa id caused th e u su al vigoim m re a c tio n w ith deeomposM U tt*

fy p a re n tly th e 4SMP&«*tSm e f tric h lo ro a c e tic acid in hensene

wm e ffe c tiv e in i t t o i o g

a c id ity o f th e medium to each a p o in t

th a t th e S o ta ld t re a c tio n d id n e t o ccu r.

A, s im ila r phenomenon occurred

when chloroform carved as th e re a c tio n medium.

In b o th ca ses o n ly

f-a c o ty ltld o p h e iie and a sm all anaant o f decomposed m a te ria l could be
is o la te d from th e re a c tio n m ix tu re.
A cetic ac id was examined f o r I t# s u ita b ility as a so lv e n t where
trlo l& o y eao stlo a c id in used as th e c a ta ly s t in th e Schmidt re a c tio n ,
A m ixture o f 2 -acety ltld tep b sn e, tric h lo ro a c e tic a d d and a c e tic acid
was tr e a te d w ith f in e ly powdered sodium aside w ith m apparent re a c tio n
o c c u rrin g ,

th e tem perature was in creased from 20°C, to $ti0 C. w ithout

in du cin g m y re a c tio n to o ccu r.

Wm& a sample o f th e re a c tio n m ixture

was withdraw n as»I tre a te d w ith concentrated s u lfu ric a d d an immediate
and vigorous e v o lu tio n o f gas took p la c e .

The rem ainder o f th e so lu ­

tio n m s n e u tra lis e d w ith mmx&xm hydroxide and e x tra c te d re p e a te d ly
w ith beacons.

The bens one e x tra c t was con cen trated and th e rem aining

llg u ld m s d is t ille d to y ie ld a 95% recovery o f th e s ta r tin g m a te ria l,
2«aeetyllHof$h®&# *

116

Booaitaa o f i t s low n s ltin g p o in t and high a c id ity , tr if lu o r o a o o ito so ld n as stu d ie d m a reag en t to s e m both a» c a ta ly s t and
solw oat in t i n Sehnidt re a c tio n .

th e a d d itio n o f 2-s^«$yltl& ophene ,

in afesotats o f h p irw o i s a c id o r sodium a rid * , to th is acid re s u lte d
in a w r y ra p id decom position and c h a rrin g in d ic a tin g th e f u t i l i t y o f
n tts a p tla f to conduct th e Sch»idt re a c tio n in th is medium.

i» w ith

tr ic h lo ro a c e tic s o ld , a re a c tio n would n o t occur between 2 -a o e ty ltM o p h sn s, to d lm oaddo and triiln o ro a c o tic ac id l a a c e tic a c id .
4 soMBKarlaotlO!! o f th e p roducts re s u ltin g from the in te ra c tio n
o f th e aoylttdophosio* w ith hydrassoie aoid and s u lfu ric acid in a e o tie
m id io to ho found In M O * XX.
The id e n tity o f th e saddes re s u ltin g from th e Schmidt re a c tio n
w ith asyltM ophw aes m s asc e rta in e d by a comparison o f th e products
w ith tb s m m m&dm prepared by th e follow ing sequence of- re a c tio n s i

on— ch
I)

on

II

+ m *

* (c % c o )^

on

01

0~«V B n.

C'fL.COQB

CH— CH

||
CB

a
& - « ),

( iX c ^ c o ^ o
w ra s — »

CB— CB
II
II

The n itr a tio n procedure* ^

c a rrie d o u t to g l? s an 82$ y ie ld o f

^^^trothlopsfesns by tr e a tin g tM opbeits w ith a m ixture o f a c e tic

117

€}

u#a
».
o

G•&
«*•
o

H

*
N)
***
o

«K
#*t

V>*
a

&

#5*

4

M
#*

m

#
O

9

*

♦

H

rfl

GO
m
i*4
O#

05

304
CSI

HI

4*
M
I

#
5

lu*

P*

ij3

ra-

CV

04

x

llf i

anhydride m l

m id in m ail* m id a t m m tMwqwsWe, The

product was iso la te d by pouring the reaction mixture onto crashed ioe
and c o lle c tin g the yellow

mXU by f iltr a tio n (139). th e 2«**Xtr©~

thiophaae e o reduced to the aSamtle efclorlde~h7drogeB efclerlde dodde
• a l t o f 2-m W M ophens by reaction w ith m etallic t i n in the preeenee
o f concentrated hydroeiiloric m id (136) a t hg°. th e product, wfcieh
p f« d |d tftM as a itU o d s h so lid , m

separated by f iltr a tio n , ta ile d

w ith eth er and deled, th e desired acylai^dothlophens wee obtained

t*m the 2«*au*ii!©iM&phen* s a lt by treatm ent w ith the appropriate *etd
antodrlde dissolved In m e^nal volume o f eth er (136). A fter the
in itia lly emtlmrxttlo reactio n hid •wbsldsd, the mixture was trea te d
w ith a ooooentrated aalu tlo n of ©odium hydroxide and crashed le e . the
p ro elp lt^ted product
w ith e th e r. The

wm quickly f ilte r e d , washed w ith water and then
was reerywbaXXlsed tmm water and d rie d .

The p re p a ra tio n o f th e acyithlopheiiaa and tbaneXe i« dism issed
in F a rt 1 o f th is diom rfe& tion.
A r a th e r a w e a ry e m d s a tio n o f th e re a c tio n o f 2~ttoen«l w ith
eaeess h yd rasoie a d d to y ie ld th e b s tra s e le was conducted.

ita

2«th«mal was tre a te d w ith a two fo ld excess o f hydrasolo a e ld l a
bwmrnm and

e u lfu rlo m U a rig o ro u s ev o lu tio n o f n itro g e n a o m m d .

Tin re a c tio n m ixture was poured onto loo m d tre a te d w ith a 2Q£ sodium
earhensib* o e la tio a .

The ralam e o f th e r o t a t i n g so lu tio n was reduced

by e ra ^ & tio i* and w thanol was added to p r e c ip ita te sodium s u lfa te
which was removed by f i l t r a t i o n .

A fter c a re fu l treatm en t o f the

u*

co n cen trated ^ t l A n w ith 6 normal l^ id ro eid M e a o id , a yello w ish
S o lid se p arate d which was f ilte r e d o f f and i!« d ifl8 o M in sodium
e&yben&te s o lu tio n and f ilte r e d ag ain to remove a co n sid erab le anoofit
o f yellow amorphous s o lid ,

C arefu l a c id if ic a tio n o f tb e carbonate

s o lu tio n a l l h 6 normal h jd m M o d s a c id , caused th e product to sep arate
00 O w h its s o lid which s o s c o lle c te d toy f i l t r a t i o n ,

o lilt# p la id o f

Thor* was reso lved

2*iM .e»yl) t s t r a e d e which m s id e n tifie d by I t s m elt­

in g p o in t and cenpax&nm w ith tb s rep o rted (13b) w eltin g p o in t o f tb s
m m compound prepared by a d if fe re n t procedure,
tio n fo llow ing tb s above p rocedu re, o

10 o second prep ara­

y ie ld o f tb s sans te tra e o le

d e riv a tiv e m s o b ta in e d ,
in attem p t was made to determ ine w hether o r n o t th e te tr a s e le
s m e lte d tr m t i n re a c tio n o f an in term ed iate n lM L e w ith th e excess
hydrocele s o ld .

Using th e earns sa jp ariaen tal procedure and co n d itio n s

m d escrib ed above, f ^ tb s n o n ltr ile m s allow ed to in te r a c t w ith hydra*
so lo so ld and s u lf u r ic so ld in feem sns,

D istin c tiv e from th e p reviou s

re a c tio n s m s th® f a s t th a t the s u lfu ric la y e r d isco lo red ra p id ly and
^appeared to c o n ta in co n sid erab le decomposed m a te ria l,

TJrn re a c tio n

sd a c tm mm poured onto %m m d slow ly n e u tra lis e d w ith sodium carbonate
s o lu tio n y ie ld in g m amorphous b la c k t a r which was © lig h tly so lu b le
in e th a n o l and cceg& etely so lu b le in d ilu te s u lf u r ic .

T his l a t t e r

p ro p e rty was eom pietely opposed to th e base s o lu b ility o f 5~(2-»th±eisyl)~
te ir a s e ls *
a b o rtiv e ,

i l l e f f o r ts to d ec o lo rize o r c r y s ta llis e th e product were

120

Booed m th e d if fe re n t s o lu b ility o f %he prod uct re s u ltin g trm
th e a l t r i l e , i t m aId m m th a t the n l t r l l e vm n e t m in te ra e d lo te
in th e y«aeti(m o f 2 *bJ»jaaX w ith m tm m hydrasolc ac id to y ie ld th e
ia d e r th e co n d itio n s «s*ploy*d, n t t n i e e t s a O ^ y ie ld
l~substituted~$**«a& not.etyar,ol03 which o re so lu b le in stro n g acid end
In so lu b le |» boeet*

Prem aeably, th e te tre e o l* r e s u ltin g fro n 2 -th e n o -

a i i r t l e wee deeospeeed through i t s s o lu b ility and re a c tio n v ith
ma&imiM sold*

Xt would he expected th a t th e thlophene rin g o f

1 * ( 2*thio»yX )~$*ea& ietotra& ele would he e a s ily attack ed by s u lfu ric

so ld lo a d in g to s u b s titu tio n end probable rin g ru p tu re , v isile 5 *
{2*tM enyl)t-etr& 7ol© ehsmld be co n sid erab ly wore s ta b le in th e re a c tio n
■factere due to th e d e a c tiv a tio n o f th e ihiophana rin g by th e e le c tro *
n e g a tiv e te tr a e e le rin g end th e lo o s o lu b ility d f th e compound In

ew&fbrie ocld«
The probable re a c tio n s o ccu rrin g between 2 -th en o l end 3*thsne~
n l t r l l o w ith essseso hydreeoie ac id e r e ,
OH

CH— OH

0H

OH
^

C~*0 =
KK

OH
II
OH

N « /

H ow evert oin© e
MM1$ Oo&^JUiO
e p e c u lu t i £*»&

CH
!i
Qmmfffl ♦ SWa

>

B
II
H

OH---- CH f?H aC = H
IIII
I I
It
CH
C
*
*

m

cmmoM* n o w m s
% d * m o i© M id o o l n t lo n o
Fr® paared b y th « a d d i t i o n o f tr a l f ia r l c a o l d
to a s o l u t i o n o f so d iu m mMm o c w o re d w ith a X a y o r o f b o m o n * o r
c h lo r o f o r m * f k o o r g a n ic l a y e r n o s s e p a r a t e d a n d d r i e d o v e r
a n ly fd ro u o o o d iu n s r a l f a t a ,

SodXtaa agtde — ly&elie&X grade* Bastn&a Kodak Co*
X oetin Acid ~

G, F* $rad®# Herek & Co*

T ric h lo ro a c e tic a c id
C hlorofom

tQi&te la b e l, Kaefcaan Kodak Co*

C# P , $?adof Horok 4 Co,

T j^lnO foaoelX o ooid «*** O btained on stu d en t p re p a ra tio n .
M b y te

ao id ( f u s i n g ) -**<P ractiooX grad®, S a e tn a n Kodak Co,

f i n (obob) ** P ra c tic a l grad#, laetm an Kodak Co*
A ootio anhydride «** T^Mt® la b e l* 3a®t»«n Kodak Go,
F ropionio aiaiisi'dride *•» FraotloaX grade* Hatha eon Go,
anhydride *** %Mi« la b e l, Eaotaiia Kodak Co,

122

ita p M M Mjawi t .

2~Theti©*sitrlXe
an — oh

u

it

CH C-OK
''S ''

4 100 ml* b m m m s o lu tio n o f U *2 g . (0 .1 n o lo ) o f 2~ th»n*l,
and 1*0 m olar In tytirm m U so ld contained to * bGO m l. beaker woo
tr e a te d e le e ly , w hile b ein g s ti r r e d , w ith
a u lfu r ic

sold* 4 vigorous ev o lu tio n

k a l . o f oonoeiitrated

o f gae occurred ufalofe subsided

t o t o i t 20 minute®. i l t o feeing s a t aoida fo r an a d d itio n a l 1$
m inutes 200 g« o f lo o m otor mm added to th e re a c tio n m ixture and th e
v a u l tin g %m la y e rs m m sep arated w ith tb s benzene la y e r feeing
th o ro u g h ^ washed w ith d ilu te sodium hydroadde so lu tio n follow ed by
d ry in g o v er anfcydrmx* sodtom s u lf a te .

ffee b&mene mm removed by

ev ap o ratio n and th e re s u ltin g o i l mm d is t ille d under reduced p ressu re
to y ie ld 9 .2 g . (0 #08b molef 81$) o f c le a r c o lo rle ss product wbea®
p ly sie& l c o n sta n ts w orst b .p .

(21 « m .)|

1.5653.

The rep o rted (133) p ly s to a l co n stan ts o f 2-t&ononitr±lf& ere
77*S*?8® (12 m a .)| n |^ l*S6bl*
A q u a n tity o f S .0 g . o f the p ro du ct moo reflu x ed f o r o n e-h alf
hour to $0 8& * o f o 10* sodiu® l^drei& do so lu tio n d u ring which tto o
th e Odor o f ammonia moo v eiy ap p aren t,

ffea s o lu tio n was co o led .

123

oafcraobed otom w ith e th e r anti th en c a re fu lly tre a te d w ith d ilu te
i^ d re e b h e rie m M which caused a w hite p r e c ip ita te to ra p id ly s e ttle
o u t o f eo lu iio t) in th e form o f needle shaped o * y » ta ls. th e l a t t e r
were c o lle c te d and d rie d , and amounted to M

g . o f a product w eltin g

a t 1$8JM U t9j/* In d ic a tin g th a t th e n l t r l l e had been converted to
2 * t t o d « mold* th e rep o rted (13?) m eltin g p o in t o f 2-tbsm oic acid
l a 129-430®.
2h a re p A tttie n o f th e re a c tio n o f f ■
- ih sn a l w ith fy draeo le a c id
th e mam

o f re s o ts n ts were ewplo^ed w ith th e exception th a t

W *&. o f airtspy phospljorlc a d d was used me th e c a ta ly s t in ste a d o f
s u lf u r ic a c id ,

The re a c tio n proceeded sromcwhat wore Slowly » h u t a f te r

to o hours th e re a c tio n m ixture was awfejeeted to th e same w p a ra tlo a
pw eed u re to y ie ld 6 ,? g* (0.060 molef 60S) o f 2~ihf?txjnitrlXe d i s t i l l ­
in g a t 86*86,5° ( I f
l# $ 6 5 i.

bum.

) ,

and wMeh had a re fra c tiv e index o f

th e pfoduot m e su b jected to th e saws method o f h y d ro ly sis

to y ie ld 2*thsnolo m id w eltin g At 128,5-130°*
3 -T h e n o n itrile
c h — c~m
Sb
£h

Follow ing th e above d escrib ed procedure, 5*6 g , (0.0$ mole) o f
3 ~ th sn a l, 50 ml* o f 1 m olar hydr&eelc so ld In bensene and 2 m l. o f
co n cen trated s u lf u r ic acid were allowed to in te r a c t.

JT tsr the u su a l

se p a ra tio n scheme th e re was is o la te d , by d i s t i l l a t i o n , 2.15 g*

12lt

(0*0395

m

2 . j T9I) of > U n a a ttr tl« wfaoae physical constants w n i

l»,p. 6ii.S-86 (18

hb. ) |

1.5551, Tbs reported (13b) physical

eonstanta o f 3-tbK ionitrne a n 203- 205° t

l.» A .

A sample of the product was converted to 3-thenoie acid tty
b asic

hydrolysis. I t s m elting point was 136-13?*5°. The reported

m elting p o in t of > * h sm ie acid la

1 3 7 - 1 3 8 °*

In * second study o f th e re a c tio n o f > th e n a l w ith hydrasoio so ld
th e same q u a n titie s o f reag e n ts were need as Above except th a t $ m l,
o f phosphoric ©old were a llo y e d In ste a d o f s u lfu ric a c id ,

A fter a

re a c tio n p erio d la s tin g two b u r s th e product was sep arated and is o la te d
according to th e p rev io u sly d escrib ed procedure.

There was obtained

by d i s t i l l a t i o n 3*38 g« ( 0*031 m elej 62%) o f a c o lo rle s s liq u id produet
which had th e follow ing p h y sic al constants*
^

1.S538*

to.p . 88-89° (20 im .)j

B asle h y d ro ly sis o f a q u a n tity o f th e product y ield ed

3 -th sn e le so ld which l i l t e d a t 136*S*138°*
The S cheldt E naction w ith 2-4c#iylthiophens
Follow ing th e procedure elu cid a ted by Hurd and Hoff a t (U) $.h g .
(0.013 stole) o f 2 -acety lth io p h en s d isso lv ed in 100 m l, o f chloroform
was tre a te d w ith 5 m l, o f 96% s u lfu ric acid and ho m l, o f a 1 ,9 m olar
s o lu tio n o f hydrasoic ac id in chloroform .

The re a c tio n so lu tio n was

kept a t 0-10° f o r IS m in u tes, w hile being s ti r r e d , and then poured
onto ic e .

The re s u ltin g two la y e rs were sep arated and th e aqueous

la y e r was e x tra c te d re p e a te d ly w ith chloroform .

A fter the combined

chloroform s o lu tio n s had been washed w ith d ilu te sodium hydroxide the

125

was re»OT«d on a steam b a th to y ie ld a y ello w ish brown
s o lid which was tak en up in hot hensens.

th e f i r s t crop o f s lig h tly

yellow c r y s ta ls amounted to 1*13 g* end m elted over a range 108-139°*
The a d d itio n o f pentame to th e rem aining bensene e o la tio n caused th e
se p a ra tio n o f 1,22 g* o f yellow ish c ry s ta ls m elting sh arp ly a t
0
101-102 . That th is second crop wae n e t a pro du et expected from the
Schmidt re a c tio n l e In d ica ted by th e fo o t th a t the expected products
2~aceiam ldothtophene m elts a t 160-161° w hile 2-thenoi^tfcylam lde has
a sm itin g p o in t o f 113-XHa°* Followixig Herd and M offat1* suggestion
th a t t h i s m a te ria l was a e u te c tic m ixture o f the two p o ssib le p ro d u c ts,
th e two crop s o f c r y s ta ls obtained were combined and su b jected to
h y d ro ly sis by reflo atin g f o r 2 hours In 50 ml* o f a 105 sodium hydroxide
so lu tio n *

The d ark colo red m ixture was eooled and e x tra c te d tw ice

w ith $0 m l, p o rtio n s o f e th e r,

Cpon a c id ific a tio n o f th e aqueous

p o rtio n and co n c en tratio n to a relum e o f 15 m l. th e re m s obtained
0*29 g* o f 2 -th en o lc a c id which m elted a t 129-130°.
2-icetam idothiophene
CH
8h

To a w ell s tir r e d m ixture o f 12.6

CH
b-HH-C0C%

g . (0 .1 mole) o f 2 -« c e ty lth io -

phene in 110 ml* o f a 1 m olar bensene so lu tio n o f hydraaoie a c id ,
a t 0 ° , was added It stL. o f con centrated s u lfu ric a c id ,

Tim ev o lu tio n

o f gas was so vigorous th a t a 20 minute period was req u ired to

126

e o a p lste

a d d itio n o f matd A fter which tte le e eo ld re a c tio n

iid x io re has Allowed to m m to roost tem perature and I t nee then
poured In to a n l x t t r t ©f le e end w ate r,

The r e s u ltin g two la y e rs

m m se p arate d and th e bem ens la y e r was e x tra c te d w ith a I t# sodium
b icarb o n ate s o lu tio n and th en d rie d over anhydrous sodium s u lf a te .
When th e benzene was removed by evaporation a rod o i l sep arated and
t h i s was tak en up in ab so lu te eth an o l and tre a te d w ith K orlte A.
Slow ev ap o ratio n o f the eth an o l caused th e red e l l to sep arate again
and I t was taken up In h o t bensene and th is so lu tio n was allow ed to
oool slo w ly.

A fter a few c r y s ta ls had separated th ey were im m ediately

removed by f i l t r a t i o n and d rie d .

They had a m elting p o in t o f 159~160P.

^hen a sample o f th is m a te ria l was combined w ith an authenic sample
o f 2~aostafflidothtophsne th e re was no depressio n in i t s m elting p o in t.
The rep o rted (lliO) m eltin g p o in t o f 2-acetarald© thiophene I s 160*161o .
i s th e bem ens so lu tio n was cooled fu rth e r the red d ish o i l again
sep arated and i t was re d tsso lv sd in a la rg e r volume o f bensene and
e x tra c te d w ith $% barium ch lo rid e so lu tio n which caused a yellow
p r e c ip ita te to form in th e aqueous p o rtio n .

T his m a te ria l was assumed

to be th e barium s a l t o f a su lfo n ic a c id , b u t was n o t examined f u rth e r.
The rem aining bensene s o lu tio n was concentrated to give a lig h t red
o i l which on d i s t i l l a t i o n y ie ld ed 5.h g . o f 2-ftcsiylthiophene b o ilin g
a t ?5~76° (3 mm.)* ho fu rth e r m a te ria l could be is o la te d .
A second a p p lic a tio n o f th e Schmidt re a c tio n to 2-ace ty lth io p h en e
re s u lte d in a 1% y ie ld Of 2-*U5etas8idolhiophene and a 2%% recovery o f
tm reacted 2 -ace ty lth lo p b en e.
amount o f a barium s a l t .

There was a lso obtained a ra th e r la rg e

127

Im m attem p t to decrease the amount o f su lfo o a tlo n which was
a p p a re n tly o ccu rrin g whan s u lfu ric a c id w « used a s a c a ta ly s t, a
m ixture o f 12*6 g . (0*1 no lo) o f S -aeetylthiopbane and 110 m , o f a
1 molar* beneoas so lu tio n o f bydrasoic a d d was tre a te d w ith 10 n il,
o f phosphoric a d d ,

th o a d d itio n o f th e a d d re su lte d In the

in stan ta n eo u s form ation o f a w hite p re c ip ita te w ithout any gaa evolu­
tio n ,

fh e s o lid warn recovered by f i l t r a t i o n and d rie d under vacuum.

I t had a m e ltin g p o in t o f 9$~97° which agrees c lo se ly w ith th e m elting
p o in t re p o rte d by Khages and A H ondorf (6h) fo r th e complex formed
between 2«acetylthiophene and phosphoric a c id .
4 d if f e r e n t procedure f o r the re a c tio n o f 2«*aeot^rlthlophene and

hydraaoie a c id was tr ie d which involved th e a d d itio n o f 8*b &.
(0*13 mole) o f sodium a sid e to a s tir r e d so lu tio n o f 12,6 g» (0 ,1
m ole) o f 2-ace ty lth io p h en e and 10 m l, o f s u lfu ric ac id in 10O m l. o f
a c e tic a c id a t 35° * das ev o lu tio n had ceased a f te r approxim ately
two hours and th e d ark red re a c tio n m ixture was poured onto crushed
ic e and n e u tra lis e d w ith ammonium hydroxide, to th e n e u tra lise d
m ixture was added 100 m l. o f beroten© and ib® la y e rs were se p a ra te d .
The aqueous la y e r was e x tra c te d th re e tim es w ith 100 m l. p o rtio n s o f
bensene and th e se m m combined w ith th e o rig in a l benzene e x tra c t and
d rie d over anhydrous sodium s u lf a te ,

th e bmmem was removed and tie

r e s id u a l red o i l was poured onto crushed le e where upon I t s o lid if ie d
to a ta n s o lid .

A fter one s e c r y s ta llis a tio n from bsnsene th e product

m elted o v er a range o f 110-133**

Th© m elting p o in t in creased to

1S2-1S7* a f te r a re c ry s ta llis & tio n from a m ixture o f e$ual p a r ts o f

128

hwmmm and hexane,

There was obtained 2*8 g . (0.02 mole* 20*) o f

m bits c r y s ta llin e product a f te r a f in a l re c ry a ta llis a b io n from a
m ixtu re o f e th a n o l and w ater.

The w aitin g p o in t was 158.5-159.5° and

i t ia « n o t depressed whan a sampL© o f th e product wee mlxnd w ith an
au th en io sample o f 2»m%imdM%Mjsfphme m The rep o rted (lW>) w aitin g
p o in t o f 2*&oefcasddo thiopfcen© i* 160-161°.
A r e p e titio n o f th e above n a ta tio n using 20 m l. o f s u lfu ric
maid re s u lte d in a rad o ily p la s tic appearing produet which could n o t
bo induced to s ip m ts lllte »

I t was com pletely soluble in eodluni

hydroxide and gave a yellow p r e c ip ita te when tre a te d w ith 0 barium
c h lo rid e s o lu tio n .
o
Hhtn th e re a c tio n wee c a rrie d o u t a t 5 th e ev o lu tio n o f n itro g en
was extrem ely alow and only by warming the m ixture to approxim ately
35° could i t be censed to proceed a t a normal r a te .

Isp lo y isg th e

is o la tio n method which m e 4uet described th e re was obtained a 175
y ie ld o f 2*aoetam ldothiophene»
2-Froplonamidotijdop3iene
CH
CH
^3

CH
C-4SflW30C,|%

To a s tir r e d m ixture o f l&.O g. (0 .1 mole) o f 2 ~ p ro p io s^lth io p l» n e,
20 m l. o f co n cen trated s u lf u r ic acid and 100 m l. o f a c e tic ac id was
added, in sm all p o rtio n s , 8.1* g . (0.X J mole) o f fin e ly p u lv erised
sodium a s id e .

A fter approxim ately two hours a t th e re a c tio n tem perature

129

o f IS

gas evolution bad oo«i«d and the iw l reaction Mixture vm

poured onto crushed Ire and neutralised with d ilu te ammonium hydroxide,
deploying the previously described reparation procedure there was
obtained t a f te r two re o ry etallisa tic o a from a mixture of benssne and
hexane, 3*5 g* ( 0 , 0 2 b w d«|
m elted a t 109 ,5-110 .5 .

2t f )

of a c ry sta llin e product which

a sample of the preduct when mixed w ith

a^proplonamidethiophen® had a melting point of 109-110.5°| the re ­
ported (ihO) m elting point of 2-propionamldothiophene la 110-111°.
E vaporation o f th e benssne so lu tio n from which the i n i t i a l crop
o f c r y s ta llin e p ro d u ct was is o la te d yield ed a sem isolid m a te ria l
which mac reflu x ed f o r two hours in a 10$ sodium hydroxide so lu tio n ,
bpon n e u tra lis a tio n o f th e re s u ltin g so lu tio n th re e was obtained
0 ,9 I# o f 2 -th en e ie a c id which m elted a t 129-130°,
2 - 8 utyraa&d©thi0 phens

CH
CH

CH
^S-HH-GOC HaCfiy3%

Follow ing th e m m g en eral method described p re v io u sly , l$ .b g ,
(0 ,1 m d e) o f 2-butyrylthiophen® „ 20 m l, o f 9S% s u lfu ric ac id and
8,h g . (0 ,1 3 mole) o f sodium asid e were allowed to in te r a c t in ICO
m l. o f g la c ia l a c e tic a c id a t 35°.

A fter approxim ately two hours

th e re a c tio n m ixture was processed to y ie ld 3.7 g . (0.O22 molef 22$)
o f s lig h tly yellow c r y s ta ls which m olted a t 128-129 ,

A mixed m elting

p o in t o f 128-129° was o b tain ed when th e product was interm ixed w ith

HO

m auth ettio *m pl* o f 2-butypaaddotM ophooo.

Tho rep o rted (ikO)

m e ltta g p o in t o f th e product i s 120.5-129.5°.
The o r ig in a l bem ene m other liq u o r was evaporated to y ie ld *
sem iso lid mass which was ^ydrolysted in a sodium hydroxide s o lu tio n ,
to y ie ld 1 .2 g» o f 2 -th*noie acid which m elted a t 120.5-129°.
3-Ace tam ldotM ophene

CH— G-NB«GGGHa
CH
CH
"* &

The in te ra c tio n o f 12.6 g . (0 .1 stole) o f 3-ao© tylthiophene„ 20 m l.
o f 95# s u lf u r ic ae id and S.b g . (0.13 mole) o f sodium asid e in 100 m l.
o f a c e tic a c id proceeded in a maimer s im ila r to the re a c tio n o f
2 -acetyltM op tm n e.

A fter n e u tra lis a tio n o f th e re a c tio n m ixture w ith

ammonium hydroxide and e x tra c tio n w ith se v e ra l p o rtio n s o f bensens
th e re was o btained a f te r two re e ry sta llissa tio n e from a m ixture of
hssmetts and cyclohoxane 1 .6 g . (0.013 molej 13#) o f a product m elting
a t 11*6-11*7.5°, The re p o rte d (ihO ) m olting p o in t o f 3-aoetaa»idothiophone
i s XliS-lbS0 ,
Treatm ent o f the o r ig in a l btntseae e x tra c t re sid u e w ith b o ilin g
sodium i^droxXdo and n e u tra lis a tio n o f th e m ixture w ith d ilu te hydro­
c h lo ric a c id re s u lte d in th e form ation o f 0.7 g . o f 3-tbeno ie acid
which m elted a t 136.5-137.5° *

131

?hi

o f 2--ve<»tyltidophene in M e h b m e t t k Acid
A

m ixture o f 3 g , (0,021* mole) o f S^aeetylthiopben© and

35

g, of

tflftld iW D ifittlo acid 109 v a n e d to 60^ to e f f e c t a booog^noooo so lu tlo ii
to which was added in m a ll p o rtio n * 2 g . (0*031 so le ) o f powdered
sodium a s id e ,

t$U & a fiv e m inutes a f te r the f i r s t two components had

b e m brought in to s o lu tio n th e re a c tio n m ixture charred b adly and
became se m le o ltd , th e r e s u lta n t mass was in fu s ib le and in s o lu b le .
I t was found th a t a m ixture o f 2-aeetyltM epben* and tric b lo r© a c e tlo ao id a t 60& ra p id ly reached a charred s o lid s t a t e .
To 12*6 g , (0 ,1 0 s o le ) o f 2-aeety ltM cphens d isso lv ed in HO m l,
o f a 1 s o la r bem ene so lu tio n o f hydra*©!© a e id erne added 10 g , o f
tr ic h lo ro a c e tic a e id .

Ho gas ev o lu tio n was observed even a t tempera*

tu re s a s high as 1 6 °.

F in a lly $ m l, o f con cen trated s u lf u r ie acid were

added w ith th e r e s u lta n t expected ev o lu tio n o f n itro g e n ,
deploying 1 2 ,6 g , (0,10 mole) o f 2~ acstylthiophone, 8J* g , (0,13
m ole) o f sodium a sid e and 10 g , o f trie K lo ro a c e tic aold in 100 m l, o f
ehloroform gave a r e s u lt id e n tic a l to the one ju s t d isc u sse d .

The

a d d itio n o f 5 m l, o f s u lf u r ic caused th e re a c tio n to proceed.
In a v a ria tio n o f experim ental procedure 1 2 ,$ g . (0 ,1 0 mole) o f
2 -acety lth io p h en e and hO g* o f b riefcloro aceiio acid d isso lv ed in 100
m l, o f g la c ia l a c e tic meld were tre a te d w ith 8 ,h g , (0,13 mole) o f
sodium a s id e .

The s o lu b ility o f sodium asid e in th e re a c tio n medium

sms r e la tiv e ly low and no re a c tio n seemed to o ccu r.

Vhen th e tem pera-

tw o was ra is e d to SO0 th e m ixture became homogeneous, b i t no gas

132

f ^ u U o n o r d tlw f evidence o f re a c tio n o ccu rred .
^ lWS#

F in a lly , a f te r two

so lu tio n was n e u tra lise d w ith ammonium hydroxide and

e x tra c te d tw ice w ith ISO m l, volumes o f bemems which were combined,
washed w ith w ate r, d rie d over anhydrous sodium s u lfa te and evaporated

to le a v e an o ily liq u id re sid u e . T his liq u id wee su b jected to die*
tilla b le * ! a t reduced p ressu re to y ie ld a sin g le liq u id fra c tio n which
has th e fo llo w in g p h y sic a l co nstants*

b .p . 92-9k° (12 w O f n ^ 1.563ii.

These p ro p e rtie s agree w ith those o f 2*acetylthlophsne o f which th e re
was 1 1 .? g . ^ co v ered *

Ho o th e r m a te ria l could bo Iso la te d from th e

re a c tio n m ix tu re .
th e Schmidt R eaction o f 2-A cetylthiophem in T rlflu e ro a c e tie A dd
to determ ine th e c o m p a tib ility o f 2 -acetylthiophene In tr if lu e r o a c e tic s o ld , 2 g . o f th e form er were dissolv ed in § m l. o f th e acid
a t 0 °.

An in stan tan eo u s ch a rrin g occurred in d ic a tin g th e f u t i l i t y o f

c a rry in g o u t th e S o h d d t re a c tio n w ith trlf lu o ro a e e tie acid as so lv en t
and c a ta ly s t.
In a se p arate experim ent, 6 .3 g* (0.0$ mole) o f 2~*o*tylthlophene
and 20 m l. o f tr lf lu o ro a e e tie ac id disso lved in 50 m l. o f a c e tic ac id
was tr e a te d , a t 1 0 ° , w ith h 9Z g . <0.065 ®ol®) o f f in e ly powdered
sodium a s id e .

Ho evidence o f re a c tio n occurred so th e m ixture was

warmed to SO0 r e s u ltin g in a darkening o f th e s o lu tio n , b u t s t i l l
m e v o lu tio n o f n itro g e n .

133

o f T otraselft*

S® — c s

6m

g**c —

3

m

k

A

t o 5*6 g . (O.Og r a le ) o f 2*thenal d isso lv ed l a 150 m l. o f a 1
m U r b em em s o lu tio n o f ty d r a w ic acid mm added 8 a l . o f 9$$ s u l­
f u r ic m id w ith ra p id s t i r r in g .

The w l t i t l a a o f n itro g e n m o p ro sp t

mA v igorous and a f te r an hoar th e mlafeur© nos poured onto lo o g . o f
loo follow ed fejjr n e u tra lis a tio n w ith a 201 mdivm carbonate w d a lio n ,
th e m u tra U sed s o lu tio n m o evaporated to a volume o f 50 a l . and
tre a te d w ith 30 a3L* o f eth an o l to p re c ip ita te sodium s u lf a te which
mm rumored by fiX fceratlon .

The a d d itio n o f 6 n o raal hydrochloric

so ld to th e f i l t r a t e earned a w hile p r e c ip ita te to fo ra which m s
se p arate d and re& U solved in 50 w l. o f to # so d ira carbonate end re*
f i l t e r e d to re w m a s n a il m ount o f y ello w ish snorphotis s o lid .

The

c a re fu l a d d itio n o f 6 m vm X hydraohlorio to th le second f i l t r a t e
caused th e product to re p re e ip lb a t* .

f t m e recovered by f i l t r a t i o n

end a f t e r drying amounted to 3.29 g . (0.022 molcf hh$) o f w hite
e ry s ts tllin e s o lid m altin g a t 2O2*g~20h.5°. The rep o rted (60) r a ilin g
p o in t o f 5*(2* tM enyl)totra* eli» i s 2 0 t.7^205°,
l a a second p re p a ra tio n by th e san® procedure th e re was is o la te d
3 .21 g . (0.021 m olei fc2$) o f 5^(2*tM ® nyl)tetra«ole which r a ile d a t
2Q >20S*.

1&

H eaction o f S -T h e m id irtle w ith

Acid

&«P&>yi»g th e came esp eriin en tal co n d itio n s a* wore ju s t d e sc rib e d ,
a m ixture o f 3 ,2 g* (0*020 mole) o f E -th e n e n itrile and 00 ial* o f a
1 m olar bam ene s o lu tio n o f hyirasoi® acid wore tre a te d w ith 6 ml* o f
£5$ s u lf u r ic o d d *

Tigprsme gas ev o lu tio n continued fo r about a h a lf

hour d u rin g which tim e the s u lfu ric acid X ^ o r became very dark in
o d o r*

The m ixture m e poured onto $0 g , o f ic e and n e u tra lise d w ith

a £0$ sodium c& rbom te s o lu tio n which caused th© p re c ip ita tio n o f a
b la c k ta r r y m a te ria l*

The l a t t e r m s s lig h tly so lu b le in eth an o l and

com pletely so lu b le in 6 normal s u lfu ric a c id . The b la c k ta rr y m a te ria l
m e b a te s up in hot eth an o l and tre a te d w ith ttorit© A w ith l i t t l e
enceeee in d e e o lo rls a tio n , m the ta r r y m a te ria l sep arated from so lu ­
tio n ag a in ae th e eth an o l cooled*

I t m e then d isso lv ed in d ilu te

s u lf u r ic ac id and ag ain tre a te d w ith S o rite i .

n e u tra lis a tio n o f th e

a d d s o lu tio n w ith a sodium carbonate so lu tio n re su lte d in the
se p a ra tio n o f the o r ig in a l ta r r y m a te ria l,

A re p e titio n o f th is

procedure n e tte d th e same re s u lt*

2«^itrothiephene
CH
'CH

CH
8-1*3*

In to a f la s k f i t t e d w ith a re flu x ©ondenser was poured one h a lf
o f a s o lu tio n oompos&d o f 160 g , (2.1* m ic e ) o f fuming n itr ic acid

135

mA 1200 i

o f K ittle

to tM j w u added alo v ly , At 10° and

one h alf o f a solution o o n tain in g 168 * . (2 moles) of

*****

thiophene and 680 ml* o f acetic nafaydildt, The ad d ltln s o f tho
l a t t e r s o lu tio n in q u ired too and a h a lf hours during which tim e the
tem perature o f th e re a c tio n m ixture was n o t allowed to ris e above 2J®,
At th is p o in t In the p rep a ra tio n t i e re a c tio n m ixture woe again cooled
to 10° and th e i^ c sln d e r o f th e n ltr lo acid and a c e tic ac id e l u tio n
was added,

T his nan follow ed by th e a d d itio n , during an how and a

h a lf , o f th e rem ainder o f the th icp hen s a c e tic anhydride so lu tio n
under th e easts condition® a s were described above „ After th e reaction
m ixture had been m% asid e f o r an a d d itio n a l two hours a t roost tempera­
tu re th e lig h t co lo red so lu tio n was poured onto 2000 g , o f cracked
le e which caused th e form ation o f a lig h t yellow p re c ip ita te o f
2 « n itro th lo p h sn e,

T h is was recovered by f i l t r a t i o n and d rie d ,

2^KriUsobMnph<ssss % drocM orido Stassalo C hloride S a lt

P«

CIS

CM

G-M%*Sm* * « 1 4

a s o lu tio n o f lhO g« (1 ,0 9 m oles) o f 2 ~ n ltr 0 thicphena> and 2500
ml* o f co n cen trated hydrochloric aoid contained in a isQOO m l, beaker
was waw®d to h5°* To th is s o lu tio n , w hile b eing s ti r r e d , was added
270 g , o f 30 mmh t i n sh o t d u rin g a h a lf hour p e rio d .

A fter an

a d d itio n a l hour and a h a lf o f s tir r in g th e re a c tio n m ixture was
f i l t e r e d to renews th e w hite In so lu b le product which wae mixed

136

w ith o th y l e th e r and r e f ilte r e d .

A fter d ry in g , th is

m a te r ia amounted to M l g* (0*86 anOaj 7W> o f a «Ughfcly ta n
co lo red p ro du ct d d o li w u ato re d in a brown b o ttle under n M g sm t& o n ,
2*Acfciaf8idatldoph«ne
pH

ch

CH

^c^iuomn^

$e & ra p id ly s tir r e d so lu tio n o f 1*2 g. ( 0 ,0 7 9 mole) o f 2~aratno~
hydrochloride sta n n ic c h lo rid e s a l t in 120 *ol. o f w ater m s
added JO g # (0*268 mole) o f m e tis aidiydride d isso lv ed in JO n l . o f
e th y l e th e r .

i f to r IS m in u tes, a. s o lu tio n o f $St g . (1 .3 no lo ) o f

sodium hydroxide in 0 m l. o f w ater was added slow ly s id le pooling o f
tb s re a c tio n m ixture*

Th© so lid which aeparated m s im m ediately

removed by f i l t r a t i o n and washed w ith w ater follow ed by e th e r .

A fter

a sin g le re e ry w t^ & ig a tlo n from hot w ater th e re was obtained 9*87 g.
(© ,(?( wo&sf 8ftt) o f product which m olted a t 160.5*161.5°. The
re p o rte d (UtO) m elting p o in t o f fc^aoetafflidotMopheii® i s 160*161°,

2-Fi^lomoBidot}jioptene
g n — -CH
CH
S-M*'C0Cs&

According to th e above ©xperlaacntal method, 1*2 g , (0.079 mol®)
o f 2*aRtlr»thlophene hydrochloride sta n n ic c h lo rid e s a l t in 120 is l.
o f w ater and 33 g . (0.25h mole) o f p ro p io n ic anhydride in JO m l. e f

117

•W w » w allowed to l a t o n s t ,
th ere was obtained
1 1 0 *1 1 0 . 5 ®,

9 ,2 0

After w n tra U M tlsa of tin a ix ta n

g . ( 0 . 061» isolej 81$) of * product m elting a t

T|«o reported Melting point (lUo) o f 2 -propionamidotblo-

phene io U 0 -U 1 ®.
2»autyr«Bldot hlcphetwi
pH
OH
^

CH
, C-MH-COCHjCH^CHj
8

The reootion o f ItS g . <0,07? nolo) of 2 -aminothiopbeae hydro­
chloride stann ic chloride s a lt with
anhydride in

120

aO., o f water end

30

36

g . ( 0 .2 3 w l« ) of b utyric

n l. of e th rl other re sta te d In

the form ation of 9AS g . (0 . 0 5 b melef 67$) of 2 -butyranidothiophene
which had * B e ltin g p o in t o f 127.5-12? . th e reported (lUO) m elting
p oint o f a-butgrsmidothiophene i s 128.5-129.5®.

13«

mmm
1* The ^ehn ld t re a c tio n w ith %<* and 3 -th sn a l were c a rrie d o u t
u sin g hydra*ote cold In hausens.

Good y ie ld s o f th e expected nitriX e®

n e re o b tain ed when e ith e r co m e a tra te d s u lfu ric acid o r phosphoric
ac id was used m th e c a ta ly s t.
2* The Schmidt re a c tio n w ith

and 3~ aoatylthtopbena, a-propioniyl-

tidoplm se and 2-bu ty r y l tblophena gave only low y ie ld s o f the aeylam idotM ophenes and «m 11 amounts o f th e thenoalkylam ldes,

The low y ie ld s

were la rg e ly due to sid e re a c tio n s such as complex form ation w ith the
c a ta ly s t, su lfo n a tlc n o f the products and la c k o f s ta b ili ty o f th e
tM ophsne derim tiw © toward th e reag en ts employed. The use o f so lu ­
tio n s o f hydtr&solc a c id and suspensions o f sodium asid e in bexsene,
chloroform and a c e tic ac id was in v e s tig a te d .

A v a rie ty o f a c id s ,

In clu d in g s u lf u r ic a c id , phosphoric a c id , tric h lo ro a c e tic ac id and
tr lf lu a r o a c o tic a d d , were stu d ie d m c a ta ly s ts fo r th e re a c tio n .
3 . The form ation o f to tre a c le s through th e In te ra c tio n o f excess
ty d ra s d o a c id w ith 2 -th sn a l send 2~th© nonitril© was studied*

The same

te tr a s o le was a c t Is o la te d fro® th e two s ta r tin g compound® in d ic a tin g
th a t th e n t t r i l e probably I s n o t an in term ed iate in the form ation o f
a ts tr a s o le from 2~ th sn al and excess hydrasoic a c id .

139

aMPBBEHCiSS
1 . S. Jtaforaatsky, Bur., £ 0 , 1210 (1687).
S . S. Beforoatelqr, J . prekt. Chan.,

169 (1896).

3 . 6 , gaharlaad and B. Heinrloh, 8 er ., 2 2 , 1222 (1939).
1*. R. K. M iller and 7 , 7 . Mont, 4 . Org. Chan., 16, 728 (1951).
5 . <1.

Cook and B. P h ilip , 4 . Ctea. Soo., 162 (1968).

6 . <1. ■*’. Oooie and B. Sofaawatal, <1. Chm. Sea., 288 (1965).
7 . 4. anglleb, 4. m . Qhan. S ac., 2 1 , 615 (1951).
8 . a. C, Tueon, 4 . in . Chaa, S ee., ^0, 2272 (1938).
9 . B. 0 . Paeon and P. 1 . Soatiadek, 4 . im. Chan. S ee,, § 6 , 679 (1966).
10. f^ S N P a r ,

a b b .,

I S , 80, 120 (1968).

11, 'J. £ . Bactaaa and a , S, Braiding, 4 . Org. Chan., H , 317 (1968).
12, B r it. P a t., 626,712 (1969).
13. S. X. Beilbroo, 4 . Chen. S ea., 866 (1966).
16. 3 . H. Barper and 4 . 7 . Onghton, Chan, and Ind.,576 (1950).
15. i , B. Mnttall and v . c. Shea, 4 . Pham. Pham asol., I , 971 (1969).
16. R. S. KUlar and 7 , 7 . Eford, 4 , Org. Cham., 1£, 1720 (1951).
17. &. B, 4aaaa, 0 . 0 . 0‘aWUtran and V. C. m t ia g , 4 . Chan. S a c .,
1613 (1969).
18. 4 . KagUeb and 4 . 0 . flragory, 4 . in . Chan. S ee., 6 |, 2123 (196?).
19. B, Qrawa, B ar., 708. 1076 (1963).
20. 8. B . ibnbaat, £ . B. Jonas, and X. M. aU a, J . Chaa. Soc., 2696
(1969).

UtO

21* H* B. Baifeftat, 4 , Cbesn, £©©,, 36fe6 (195©).
22. 9 . 2* Jfcbar and 9* 0 , M alagar, B* S. Pat*, 2,5140,116 (1951).
M . H . ^ k i * i , t , £*
21*. 9 .

and P . F* E ord, 4 . 0*g. O h**., J 6 , 199

C. f t e n and 8 . 0* Cook, 4 .

in . c t m , 3o© „

U 80 (19bQ).

t 5 . Stef*****, Compt* m a d ., 80J, X3?b (1936)*
2 6 . I . 8 . i t o i t and ft* C*

4 . 0**, C l» * .t £ , 29 (I9 b 3 ).

27* » . 1* M » | 4 . An. C9«». ®&©#*22, 677 (19b8) •
20. 0 . 8 . Clan© and 4 , Orasten, J . Cham. So©*, 362 (1933).
29* 7 . I . Atfemm 9 4 . Gaa. 01m * (8.3*S .ft.), jf , 2$$ (1939).
|0 . H. Otomm and H . %©*t©p, 4 . in , Cfea®. 3»©.f 6g# 22$$ (191*3).
31* B* t o i # © o il. €*©©&. CEsm, O o w a ,, 1 . i t (19 32 ).
32* 0 * IM tosnatakgr, 4* pr& kt. C!»at«, j$ |, k7? (1096)*
3 3 . s* M f o jm ts k r, ® «r„, |S , 3262 (1095).

3 b . ®* BsPornaiaksr and 8 . P lo seo n o ff, B e y ,, J 0 , 2030 (1095).
35. ®*

M to y n a ta k f, 4 . ta a a . Phy®.

©feta. S©©#, 2 2 , 19b (109©).

36. S .

Betfomafca^f, B a r., 20, 2@b2

(1895).

3 7 . a* Mm&t *Q*gmiM M & e tio n s11, V o l. 1 , 4©la* VUagr and 3©n», 1n o . ,

ISaw f o r k , H* I . , 191*2 * p p . 1*30*
38* X. 0 . B ain, 4 , M a s, Phgra. ©Iwoa. So©*, jjg , 593 (1896).
39. E , Adana, "Organ!© MacM«maw, 7©1, 7 , 4oim m © ar and a m , I n s .,
S«s X ork, » , X 1 9 h 9 * p p . bl3-bb© .
b©. 4* A. BlouaBJiasd and S* F . Balgr, 4 . An, Ohm, So©*, jJJ, I8b2 (1931).
b l« 0 . X ipkin and t , D. a to m ic , 4 . An. Cfcea. So©,, 6 1, 3295(1939).
b a , B. F . K ohler, 0 , X. H eritage and A, 1 . H aeleod, An* CImhb* 4* , b6,
221 (1 9 H ) •

Ib l

lt». I*, f . t i* **r and V. s . Joisaott, 4. An. Own. Soc., <£, 575 (19bQ).
bb . «J. H. Oladetona and a .

TtUrn, 4. Ohm, S ee., 567 (187?).

hs. W. Kraaee and A. von Oman*. “Die Chon&e der Retailor*anieh«B
twMagmem*, adrorde & « * ., I n s ., ;«n Artier, M ieh., l f t ) , p .

63 .

b6 . v . a , %»fast An. Ftntfraer £smb6. O il B ar., ]&, 85 (19b3).

4. P . UmwI, BuU. so c. cM a., (b) 2£, Sb5 (1921).
b 8 . A. C* Kay and S. B. P u tt, 4. Indian Chaa, See., £ , 109 (1928).
b9. 8 . ZeUwlqr and 4, B a tt, B a r.,
21b0 (1902).
b7. K; Sawnelet and

50

. a . v ix u ta tte r and D. B ait, A m ., b ! 8 . Ib 8 (1919).

51. s . Lesiasekn, Perfw »ry Saee«rt. OU Keeord, J £ , bb (192b).
52. A. voo Baeyer, B a r., J £ , 8759 (1905).
53. H. GUnaa, J , H. P etersen, and P . -Joh o lts , Bee. tra v . a id * ., b ?,
19 (1928).
*J ‘
*8*. H . S . ftewnoa, J*

Cliero. Soo», 6 2 , 870 (191*0).

0 * 4« C« t a n and A, L ap so rth , t a c * 0 1 m . S a c ., 19, 189 (1903).

0 , M* S.

Wmmi, J* 4»* 01m . S ee., 61, 2131 (191*2),

0 , 4* I . t a m y and M* S# t a e m , J. iw* Qbmm S a c ., jJO, 3021* (19U8).
0 * w, 7 . H$sn$ and &• F e srsc n , <1* An* Che». S e e .,

2865 (191*2) *

59. I , E. ilcsiw ider, »I«ntc Organic Be*ietions*, John

and Sena,

I n c ., Sew to r k , H. X ., 1951, p p . 20 > 20 6.

60* B. 1 . le te in g e r, J . An. Cfaem. Saw., J g , 1*06 (191*8).
61. R* Adajna, "Orgiwite Reactions**, V ol. X, John ^&l*y and Sons, I n c .,
Sew XorR, IS. X ., 191*2, p p . 266*302*

82* R* ? . Kohler,
2 2 1 (1911).

8

* I*. t a i t a f * «nd *. X». MeeXwed, ^s*. Chen. J . , 1*6,

63* 0* E* Iy e r, J* Indian a im . S e c .,

22, 2 i^ (191*0).

81$. I* B . H m n d e r , "Xante O rganic R eactio n s* , John ^ e y and Sons,
I n c ., Sew X erk, S . X ., 19 m , p p . 176*179.

6®, E , S. M iller and r . p . Hord, 4 , Op*. Chut., J g , 8? (1950).
66. b . s . i m » «m r . f . Horn, 4 , org. c b m ., j 6 , 1380 ( 19S1 ) .
6? . 8 . p . Bwtoagh and 4 . 4 . D isto rt, 4 , 4». Cbm. S ee., 71, 3922
66 . B. r>. Bartough, S. 4 . XAskmiewie* and S. H. Murray, J . 4b . Chon.
. | 70. 111*6 ( 19 U8 ) ,

69. B* CmpaPgna and « . 1 . Arebrn, J . 4a . Cbm. d o e., J £ , 989 (1953).
70. B. D, Hsrtough and A. I . Koeak, i . 4n. Cbm. See.. jgg>, 3093 (191*7).
71l K. a m e e r , J . 4a» cm®. S ee., a , 1201 (19b9),
72, 8 . Canpalgno and w. h , u a r a r , J . be. Ohm. S ee., 22 , 1557 (191*8).
73. 8 . O&aaa and J . 9 . Kelson, Bee. t r a r . e b in .,

518 (1936).

71*. 8 . SeMUIt and 9 . JU rrsr, Belv, Cbln. A cta., 2£, 573(191*6).
75. A. Kironan, B a ll. See. Chi®.,

698 (1926).

76. H. Kup», A m ., ^ 1, 321 (1909).
77. 1 . T etay,

Mil. See. Cbm
., Z L

600 (19°*).

78. 8 . HUJbert, 4 . 4 a . Ohm. S ee.,

l? i *8 (1905).

79* 0 . A. pen and X, s . S aap n d , J . Cbm, S ee., 2l*6l (1932).
60. O,

w.

Sielsteo$1 and 3 . 8 . SeJaftart, .Am., l*2i*. 1 (1920),

81, 8 . 0 . Jfeirtoagb and C. 3 . Conley, 4 . An. Cbm. S ee., 6g , 309 (191*7).
82. 0 .

SteiAleepf and B. Setnddt, a n . , 533 . 261* (1938).

63. S . S . B m jrlaats, B o ll. Soe, Chi®. B elg ., J g , 138 (1929).
fib. K. S eln ld t, Z, aagew. C bm ., J 6 , 511 (1923).
85 . K, selw id t, B en., SI* 7Oh ( 1921*),
86 . I . Adana, "Organia Keootlene” , Vol. 1X1, John ’Hl*y and Sens,

I n c ., Ben Yarte, B» Y ., 191*1*, p . 307.
87. C , 0 . Rim and 4 . M offat, 4 . An. Cbm. Aoc., 73. 613 (1951).

UO

88. 3 ,

idaaeon and

J.

Kenner, J , Cha*. t o o . , 838 (193lt).

8 9 . a . v . B ra u n , 4 m . , jjg o , m o (1 9 3 1 ).

90. H. O M tw lin, S . *n®»w. Chan.,
» . 0 . 3 . Patent X,926,796 (0 ,

4

536 (193?).

., £ £, 5792

92. s>, S. Orlggs, Q, C. Baith am

s.

(1933).

» . a l i a , J . Cbm, 3 m ., 61 (1 9 l2 ).

93. Q«*“. laten t 5I&,890 (Fw Jl., J 8 , y»gk (1933).
9i». V. Hayer and w. K . ’•Sniff, Oasa. ebte. I t a l . , 21, 189 (191CL).

IS , 0 . S . Patent 1,637,661 ( 0 . i . , a , 3057 (1927).
96. J . v . Binmw and 1 . Hajmons, B a r., 6£, 502 (193°).
97, 1 . Raaietea, M. W* Goldberg, M* i&irteija Mid H* A* BoecIsanoogen,
M r.
98* P .
If*

CMh *

£ 6 , 1323 (1933).

A* S* « L th , 4 . * • Cb®m* S o«„ JO , 320 (I9 h 6 ).
3* Mwmm mud0* 1 . Oildenhefrn, I , am* Ctm * 8 o e .f Jg> 317 (19l>8).

100* '/* BmMuBwetu H* G llllla a d and B* X* %ar*% 4* a»»C h a a . S&o,#
u » 3212 (X #> )*
W&m C* Sefcuereh m i S .

2*

102* C* Schuereh Mid S*

0.

<1*

B*

J U A fe jr ,

IQl** ?* 4* &* 3 n lth and
(1950)*

J.

P . HMWwltft,

A*

103. P* a*

Am.C hm . 8am,$ J l f 2233 (I9h9) .

*1* am* C |a » . Sw&.# 7 1 , 2238 (191*9).

s* a d t h m i

1P3*

P*

Bastr®*®,

J,

Am *

s# e#,

|£ ,

2303 (1930).

4* A®* Chew* S e c ., J £ , 3212

a d t h , 4* las. Chsaa. 3wt*f J 6 , 1*31 (I9 $ b ).

106* 4* v* B r a t m l E* Anton, & e r,y 61*, 286$ (1931)#
107* D. V* .kfamon, 4* Ct*e»* 3 » e .# X$6t (1939).
108* 4 ,

v* i s m

and B* F a d e ta s li, B ar*, 66, 681* (1933)*

109* E, E . Buchnaim, 4* 0 , Betme, T* &n»l manI H* 4* S c h la tte r, 4* aw*
Chaw*
Jjfc# 2696 (191*2).
110* 4* fa Bmira end H. X ttm ayar, B e r.# 6£, 1739 (193U).

3 J jl(

111* l . » , Snigga Mid Q, C . D a ith , 4 , C bea. S e e ., 156 (19 37 ).
1 1 2 . 4 , v , aren a and w. P tn k w n eU o , B w „ 6 £ , JCg6 (1931).
113. C . 4ans«n and A, I . Fopa, F n e , Boy. 3oc. London, 0 5 1 , 53 (1 93 6).
H i . B . S . P a te n t, 1,561,631 (C . A ., JO , 123 (1926).
11$. B . A. M a la w i and F , 1 . M e iin , 4 . Mi. C bm . S e e ., 59 , 2658
(X#37/*
1 1 6 . 7 . P ro lo g , B . Beisfe&ek a n t a . Resets, .m b . , «&£, 231 (19lO ).
117. £ . Cerlwvnikov ami 7 . P ro lo g , B e r., J ^ , 1616 (1 9 & ).
118. E, R. te w a M , G oss. ehim . i t a l . , JjJt, 175 (1 9 H ).
139. S* H. S m m t and 4 . 4 . H elnto ah , 4 . 'on. Chets. S o e ., J 2 , 1835 (1950).
120. 1 . B. S rigge and 4 . V. Ijrttle tc m , 4 . Chew. S o e., 121 (1913).
121. O ar. P ’tJ n i., 127,058.
122. 4 . k . Dies and P . A. 5 . S adth, 4 . O rg. C b m .,

179 (1919).

123. 0 . 7 . M igfattagele and M. H alsm th sl, 4 . l a . Cbm . S e e ., 72, 1823

(1 9 0 ).
121. R . K. K e lle r and P . A, s . $ * ith , 4 . .be. C bm . S e e ., 66, 1122

(1911).
125. B . S . P a te n t, 1,599,193 (C .

20, 3 I 6 O (1926).

126. L . R usicka, H. V. Goldberg and X . H arbin, Holy. Cidjn. .e t a ., 1 6 .
1335 (1 93 3).
127. B r i t . P a te n t, 555,HO (c . A ., J>2» 911 (19 15 ).
128. 0 . 3 . P a te n t, 2,029,799 (C . A ., JO , 1950 (1936).
129. 4 . y . Srwa» and V, K e lle r, B e r., 6g, 1677 (1932).
130. K, S to H e , B e r ., Jg£, 1289 (1 9 2 2 ).
131. C . O H verU H an elala, O w e. c h in . i t a l . , *>?, 139 (1 92 2).
132. S . ’S te lla and S . B*nke»3tank, 4 . p ra k t. C b m ., 121. 261 (1930).

133* K* Patuktda and
ggomns* 4* Oem, Cbesa#, (tJ#S#3#a J . IS ,
1866 (19U9)* (G . 4#, &£, m & (191*9),
“
13k* 8 , H |w » anti F , C , t a t e t , J , smmChm9 sa c* , £ 2 , 3379 (19S0),
135* H. i>. HarfeouQh and 1 . Q, Cc-alay, 4 . Abb* Cba»* 3©o*f 69, 3^96
<19fc?).
136, &,
S M ritapf, nl%U»
1 9 i l , p* 59*
137*

B* Ikrtcm gl*,
Praaa,
X&rk, 8* 1*

dm f h&opiiana*, Stalnleopjr, Breaden,
asd Xia Dar&vativaft*, IntsjraoiMJco

138* A* SOag®a and F* J t ta s t e r f, * * " » & »

(1898).

XJ9* »• Clitaan* *Qrf«iil* %ifti»«lft”# WL. U*, 4o*m m «gr and 3cmst,
3&®., Itear f a r k , 8 , X.„ 193k, p* 76,
ll|0 , ©*

■*«»»« t o * 1? (1911*) •