Alcyclic carboxylic acids: The dialkylaminoethyl esters of some 1-methyl-3-alkyl-cyclohexane carboxylic acids

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ALICYCLIC CARBOXYLIC ACIDSs THE DIALKYLALUNOETHYL ESTERS OF SOT® 1-METHYL-3-ALKYLCYCLOHEXAHE CARBOXYLIC ACIDS

By M an d e ll S ta n le y Z i e g l e r

A THESIS S u b m itte d t o t h e S c h o o l o f G ra d u a te S tu d i e s o f M ich ig an S t a t e C o lle g e o f A g r i c u l t u r e and A p p lie d S c ie n c e i n p a r t i a l f u l f i l l m e n t o f t h e r e q u ir e m e n ts f o r t h e d e g re e of DOCTOR OF PHILOSOPHY D e p a rtm e n t o f C h e m istry

1950

ProQuest Number: 10008693

All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion.

uest ProQuest 10008693 Published by ProQuest LLC (2016). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code Microform Edition © ProQuest LLC. ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 4 8 1 0 6 - 1346

ACKNOWLEDGMENT The a u t h o r w is h e s t o e x p r e s s h i s g r a t i t u d e t o Dr* R o b e r t M* H e r b s t , w hose g u id a n c e was t h e i n s p i r a t i o n o f t h i s problem *

s|«sj< a}cs|e%)t£>f: %

**** ** *

344590

TABLE OF CONTENTS P age INTRODUCTION..........................................................................................................

1

DISCUSSION...............................................................................................................

7

EXPERIMENTAL..........................................................................................................

15

PREPARATION OF INTERMEDIATES........................................................ 15 3 - M e t h y l - 5 - a l k y l - Z ^ - c y c l o h e x e n o n e s .......................... 15 3 -C y a n o -3 -m e th y 1 - 5 - a lk y Ic y c lo h e x a n o n e s .................... IB M ethyl 3 , 5 ,5 - r t r i m e t h y l c y c l o h e x a n o n e - 3 - c a r b o x y l a te . 21 PREPARATION OF NEW COMPOUNDS........................................................ 22. M eth y l 1 ,3 ,3 - t r i m e t h y l c y c l o h e x a n e c a r b o x y l a t e . . • « . 22 1 , 3 , 3 - tr im e th y lc y c lo h e x a n e c a r b o x y li c a c i d * . . . . . . . 23 l - M e th y l- 3 - a lk y lc y c l o h e x a n e c a r b o x y lic a c i d s . . . . . . 25 A cid c h l o r i d e s o f l- m e t h y l - 3 - a l k y l c y c l o h e x a n e c a r b o x y l i c a c i d s .................................................................. 2 7 D ia lk y la m in o e th y l 1 -m e th y 1 -3 - a lk y I c y c lo h e x a n e c a r b o x y la t e • h y d r o c h l o r i d e s . . . .......................... 29 P i p e r i d y l am id es o f 1 -m e th y 1 -3 -R -3 -R * -c y c lo h e x a n e 32 c a r b o x y l i c a c i d s . .............................. Amides o f l- m e th y l- 3 - R - 3 - R ’ - c y c lo h e x a n e c a r b o x y li c a c i d s ........................... 34 MISCELLANEOUS SYNTHESES.................................................................... 36 B e n z a la c e to p h e n o n e .................................................................... 36 c< - P h e n y l- (3 - b e n z o y l p r o p i o n i t r i l e . ................................ 37 c< , ^ - D ip h e n y lb u t y r ic a c i d .............................. 38 SUMMARY.........................

41

REFERENCES

42

LIST OF TABLES TABLE I

PAGE 3 -M e th y l-5 -R -

^ - c y c lo h e x e n o n e s ....................................

17

II

3 -C y a n o - 3 - m e th y l- 5 - R - c y c lo h e x a n o n e s .................................................

20

III

l- M e th y l- 3 - R - 3 - R * - c y c lo h e x a n e c a r b o x y l ic a c i d s .......................

26

IV

A c id c h l o r i d e s o f l- m e th y l- S - R - S - R 1- c y c lo h e x a n e c a rb o x y ­ l i c a c i d s ................................................................................................ •

28

D im e th y la m in o e th y l 1- m e th y l- 3 -R -3 -R 1- c y c lo h e x a n e c a r ­ b o x y l a t e * h y d r o c h l o r i d e s ..........................................

30

D ie th y la m in o e th y l 1 -m eth y 1 -3 - R - 3 -R 1 - c y c lo h e x a n e c a rb o x y ­ l a t e • h y d r o c h l o r i d e s . ...............................................................

31

P i p e r i d y l am ides o f 1 -m e th y 1 -3 -R -3 -R ’ -c y c lo h e x a n e c a r ­ b o x y lic a c i d s . ........................................................................................

33

Amides o f l- m e th y l- 3 - R - 3 - R f -c y c lo h e x a n e c a r b o x y li c a c i d s .

35

V VI V II V III

INTRODUCTION The s y n t h e s i s o f some t e r t i a r y a m in o e s te r s o f t h e l - m e t h y l - 3 - a l k y l c y c lo h e x a n e c a r b o x y l i c a c i d s i s d e s c r i b e d i n t h i s t h e s i s .

T h ese a c i d s

a r e r e l a t i v e l y s im p le compounds w h ic h , i t i s h o p e d , m ig h t s i m u l a t e t h e c a r d i a c a c t i o n o f t h e e ry th ro p h lo e u m a l k a l o i d s ( l ) . The c a r d i a c g l y c o s i d e s , o f w h ic h d i g i t a l i s i s a n e x a m p le , i n c r e a s e t h e to n e an d t h e w ork o u tp u t o f t h e h e a r t , w h ile s lo w in g t h e h e a r t b e a t . P h a r m o c o lo g is ts h a v e lo n g b e l i e v e d t h a t th e p r e s e n c e o f a n u n s a t u r a t e d l a c t o n e r i n g i n a s t e r o i d s t r u c t u r e was e s s e n t i a l f o r t h i s t y p e o f c a r d i a c a c tio n .

H ow ever, r e c e n t s t u d i e s o f t h e s t r u c t u r e o f some o f t h e c a r d i a c

a l k a l o i d s i s o l a t e d fro m t h e b a r k o f e ry th ro p h io e u m g u in e e n s e h a v e d i s ­ p ro v e d t h i s h y p o t h e s i s .

T h ese n a t u r a l l y o c c u r r i n g a l k a l o i d s h a v e b e e n

shown t o b e mono met h y la m in o e t h y l an d d im e th y la m in o e th y l e s t e r s o f m onoc a r b o x y l i c a c i d s o f h y d ro g e n a te d p h e n a n th r e n e d e r i v a t i v e s .

B lo u n t and

c o w o rk e rs ( 2 ) h av e s u g g e s te d a s t r u c t u r e f o r e iy fc h ro p h le in e , one o f t h e m ore a b u n d a n t o f th e e ry th ro p h lo e u m c a r d i a c a l k a l o i d s s -h = 0

OCH,

HC

CCU —CHo-CHn-NH-CH.

The p o s i t i o n s a s s ig n e d t o t h e m e th y l g ro u p s i n t h i s s t r u c t u r e h a v e b e e n q u e s ti o n e d by R u z ic k a ( 3 , 4 , 5 ) , b u t no new f o r m u la t io n h a s b e e n p ro p o s e d . Many o f t h e e ry th ro p h lo e u m a l k a l o i d s have a d i g i t a l i s - l i k e a c t i o n , l e a d i n g t o a n i n c r e a s e i n t h e work c a p a c i t y o f t h e h e a r t .

-1 -

M alin g and

K ra y e r ( 6 ) h a v e d e m o n s tr a te d t h a t t h e e s t e r l i n k a g e i s e s s e n t i a l , a s t h e f r e e a c i d c o u ld p ro d u c e no c a r d i a c a c t i o n i n d o s e s 100 tim e s a s l a r g e a s th e e f f e c t i v e dosage of e r y th r o p h le in e .

I n c o n n e c tio n w ith t h i s d i s ­

c o v e r y , K r a y e r , F a r a h , and TJhle ( 7 ) h av e shown t h a t b o th m e th y la m in o e th a n o l a n d d im e th y la m in o e th a n o l im p ro v e t h e w o rk c a p a c i t y o f t h e f a i l i n g m am m alian h e a r t , A s u r v e y o f t h e c h e m ic a l l i t e r a t u r e h a s f a i l e d t o d i s c l o s e any s y s ­ t e m a t i c i n v e s t i g a t i o n o f s y n t h e t i c a m in o e s te r s s t r u c t u r a l l y t h e e ry th ro p h lo e u m a l k a l o i d s *

re s e m b lin g

A lth o u g h t h e a m in o e s te r s o f num erous

a l i p h a t i c , a r o m a t i c , an d h e t e r o c y c l i c a c id s h a v e b e e n p r e p a r e d , t h e s e compounds h a v e b e e n i n v e s t i g a t e d p r i m a r i l y f o r t h e i r l o c a l a n a e s t h e t i c p ro p e rtie s ( 8 ) .

I n o r d e r t o s tu d y t h e s t r u c t u r e e s s e n t i a l t o t h e a c t i o n

o f t h e c a r d i a c a l k a l o i d s , t h e p r e p a r a t i o n o f some a l k y la m in o a l k y l e s t e r s o f s i m p l e r a l i c y c l i c c a r b o x y l i c a c id s i s ' s u g g e s te d .

The p r e s e n t w ork i s

one o f t h e f i r s t s t e p s i n t h a t d i r e c t i o n . The f o ll o w i n g s y n th e s e s i l l u s t r a t e some o f t h e p o s s i b l e m ethods f o r p r e p a r i n g c y c lo h e x a n e c a r b o x y li c a c id s s A.

T hrough h e a t i n g and d e c a r b o x y l a tio n o f t h e a l k y I c y c l o h e x a n e - 1 ,1 -

d i c a r b o x y l i c a c i d s , a lk y lc y c lo h e x a n e c a r b o x y lic a c i d s may b e o b t a in e d . The i n t e r m e d i a t e s a r e p r e p a r e d by t h e a c t i o n o f s o d io - m a lo n ic e s t e r on a l k y l - l ,5 - d i b r o m o p e n t a n e s .

A lth o u g h 2 -m e th y lc y c lo h e x a n e c a r b o x y l i c a c i d

( 9 ) has b e e n p r e p a r e d fro m 1 ,5 -d ib ro m o h e x a n e , t h i s m ethod i s s e r i o u s l y ham pered by t h e u n a v a i l a b i l i t y o f t h e n e c e s s a r y d ib r o m id e s .

B.

R e d u c tio n o f t h e a l k y l b e n z o i c a c id s h as b e e n a c c o m p lis h e d by

c a t a l y t i c and c h e m ic a l m eans.

M e t a l l i c so d iu m i n b o i l i n g am yl o r c a p r y l

-2 -

a l c o h o l (1 0 ) h a s b e e n u s e d t o re d u c e t h e r i n g i n b e n z o ic a c i d and i t s h o m o lo g u e s.

Low p r e s s u r e h y d r o g e n a tio n u s in g AdamsT P la tin u m C a t a l y s t

(3 7 ) h a s a l s o b e e n u sed *

The a l k y l a t i o n o f a r o m a tic a c i d s h a s b e e n

d e s c r i b e d ( 1 1 ) , u t i l i z i n g h y d r o f l u o r i c a c i d a s t h e c o n d e n s a tio n c a t a l y s t . A l k y l a t i o n g e n e r a l l y y i e l d s t h e m e ta is o m e r .

Low y i e l d s an d th e p o s s i b i l ­

i t y o f i s o m e r i z a t i o n a r e s e r i o u s l i m i t a t i o n s o f t h i s m e th o d . C.

T c h u b a r a n d S a c k u r (1 2 ) p r e p a r e d t h e 1-m e th y lc y c lo h e x a n e c a r ­

b o x y l i c a c i d by w h a t th e y te rm e d " a s e m i - b e n z i l i c r e a r r a n g e m e n t’* o f 1 -c h lo ro -l-a c e ty lc y c lo h e x a n e .

| J ; cooh CC

The u s e f u l n e s s o f th e r e a c t i o n a s a g e n e r a l p r e p a r a t i v e m ethod i s l i m i t e d by t h e u n a v a i l a b i l i t y o f t h e s t a r t i n g m a t e r i a l s . D.

The 1 , 3 - d im e th y lc y c lo h e x a n e c a r b o x y lic a c i d was s y n t h e s i z e d by a

p i n a c o l r e a r r a n g e m e n t o f l- m e t h y l - 3 - c y c l o h e x y l i s o p r o p y l p in a c o l and s u b se q u e n t o x id a tio n (1 3 ).

NaOBr

a c id

CH, I ^COOH

o f

-3 -

The s t a r t i n g m a t e r i a l s f o r t h i s t y p e o f s y n t h e s i s a r e n o t r e a d i l y a v a i l ­ a b le .

F u r th e r m o r e , t h e r e p o r t e d y i e l d was lo w . E.

C y c lo h e x a n e a c i d s i n w h ic h t h e c a r b o x y l g ro u p a p p e a r s on an

a l i p h a t i c s i d e - c h a i n a r e p r e p a r e d by t h e same m eth o d s t h a t a r e u s e d f o r th e s y n th e s is of th e f a t t y a c id s .

S in c e th e c a r b o x y l g ro u p i n t h e a c i d s

d e r i v e d fro m th e c a r d i a c a l k a l o i d s i s a t t a c h e d d i r e c t l y t o a n a l i c y c l i c r i n g , t h e c y c l o h e x a n e - f a t t y a c i d s w i l l be d i s r e g a r d e d i n t h e p r e s e n t w o rk . F.

The a d d i t i o n o f h y d ro g e n c y a n id e t o a l k y l - s u b s t i t u t e d c y c lo -

h e x an o n e s p ro d u c e s c y a n o h y d rin s w h ic h may b e h y d r o ly z e d and re d u c e d t o y i e l d a lk y lc y c lo h e x a n e c a r b o x y lic a c i d s .

The e y e lo h e x a n o n e s may b e ob­

t a i n e d by t h e c a t a l y t i c r e d u c t i o n (4 2 ) o f t h e 3 - m e t h y l - 5 - a l k y l - Z ^ ? - c y c l o h e x e n o n e s w h ic h a r e p r e p a r e d by a K n o e v en a g el r i n g c l o s u r e ( 1 4 , 1 5 ) .

The

3 - m e th y l- 5 - a l k y lc y c lo h e x a n e c a r b o x y l i c a c i d s w ould r e s u l t fro m t h i s s y n th e s is . G.

The s y n t h e s i s o f 1 - m e th y l- 3 - a l k y lc y c lo h e x a n e c a r b o x y l i c a c i d s i s

a c c o m p lis h e d by t h e h y d r o l y s i s a n d r e d u c t i o n o f 3 - c y a n o - 3 - m e t h y l - 5 - a l k y l c y c lo h e x a n o n e s .

These k e t o n i t r i l e i n t e r m e d i a t e s h a v e b e e n p r e p a r e d fro m n

t h e 3-m et hy 1 - 5 - a Ik y 1- Z ^ - e y e 1 oh ex ©none s .

I t is

o f i n t e r e s t t o n o te t h a t

t h e 3 - m e th y l- 5 - is o p r o p y lc y c lo h e x e n o n e , i t s e l f , h a s d e f i n i t e p r o p e r t i e s o f c a rd ia c s tim u la tio n .

H e x eto n e ( 2 6 , 2 7 ) , a s t h i s

compound i s know n,

h a s a p h a r m o c o lo g ic a l a c t i o n a lm o s t i d e n t i c a l w ith t h a t o f cam p h o r. The re a d y a v a i l a b i l i t y o f t h e s im p le a ld e h y d e s was a p r im a r y f a c t o r i n t h e c h o ic e o f m ethod G f o r th e s y n t h e s i s o f t h e a l k y l - s u b s t i t u t e d

-4 -

c y c lo h e x a n e c a r b o x y l i c a c id s *

The h i s t o r i c a l b a c k g ro u n d o f t h e r e a c t i o n s

i n v o lv e d i s su m m arized i n t h e p a ra g ra p h s w h ic h fo llo w * I n 1894 K n o e v e n a g e l ( 1 4 , 15) s y n t h e s i z e d a num ber o f 3 - m e th y l- 5 p

a l k y l - Z ^ - c y c lo h e x e n o n e s b y c o n d e n s a tio n o f a c e t o a c e t i c e s t e r w i t h some s im p le a l i p h a t i c a ld e h y d e s i n t h e p r e s e n c e o f d ie th y la m i n e o r p i p e r i d i n e * R e c e n t i n v e s t i g a t o r s ( 1 6 , 1 7 , 1 8 , 19) h a v e som ewhat s i m p l i f i e d t h e o r i g i ­ n a l K n o e v e n a g e l te c h n iq u e *

By 1904 K n o e v e n a g e l (2 0 ) and H ann and L apw orth

( 2 1 ) h ad s u c c e e d e d i n a d d in g h y d ro g e n c y a n id e t o t h e e t h y l e n i c d o u b le bond ° f c< , y - u n s a t u r a t e d a ld e h y d e s and k e to n e s *

M ic h a e l an d W e in e r (2 2 ) s u g ­

g e s t e d t h a t t h i s a d d i t i o n o c c u r r e d th r o u g h a 1 , 4 - a d d i t i o n o f t h e a l k a l i c y a n id e , t o w h ic h t h e y a s c r i b e t h e i s o c y a n id e s t r u c t u r e , f o llo w e d by a k e to s h i f t . K n o e v e n a g e l (2 0 ) h y d r o ly z e d 3 - c y a n o - 3 ,5 - d im e th y lc y c lo h e x a n o n e t o t h e 3 , 5 - d im e th y lc y c lo h e x a n o n e - 3 - c a r b o x y lic a c id *

No f u r t h e r w ork was

a tte m p te d w ith t h e s e compounds u n t i l 1 9 4 8 , when W hitm ore an d R o b e rts (1 9 ) p r e p a r e d a s e r i e s o f m e th y l e s t e r s o f 3 - m e th y l- 5 - a l k y lc y c lo h e x a n o n e - 3 c a r b o x y l i c a c i d s by t h e a l c o h o l y s i s o f t h e c o r r e s p o n d in g n i t r i l e s * The c o m p le te r e d u c t i o n o f t h e k e t o g ro u p o f X - k e t o a c i d s h a s b e e n d e s c r i b e d by num erous i n v e s t i g a t o r s *

I n 1912 W o lff (2 3 ) re d u c e d t h e

h y d ra z o n e o f l e v u l i n i c a c i d w i t h so d iu m h y d ro x id e *

V a rio u s m o d i f i c a t i o n s

o f t h e W o lf f - K is h n e r te c h n i q u e h av e b e e n em ployed i n th e r e d u c t i o n o f o t h e r k e to a c id s *

R e c e n tly , H u an g -M in lo n (2 4 ) p r e p a r e d y -( p -p h e n o x y p h e n y l)

b u t y r i c a c i d i n 95% y i e l d by a m o d if ie d W o lf f - K is h n e r r e d u c t i o n o f t h e Y -k e to a c id *

He u s e d p o ta s s iu m h y d ro x id e and t h e r e l a t i v e l y in e x p e n s iv e

85% h y d r a z in e h y d r a te i n d i e t h y l e n e g l y c o l s o l u t i o n w h ich p e r m i t t e d t h e a t t a i n m e n t o f a s u f f i c i e n t l y h ig h te m p e r a t u r e t o d r i v e o f f t h e w a t e r an d

-5 -

c o m p le te t h e r e d u c t i o n .

Newman (2 5 ) re d u c e d

- p h e n y l - (3 - b e n z p y l-

p r o p i o n i c a c i d by t h e Clemmenson m e th o d , u s i n g a m alg am a te d z i n c and h y d ro c h lo ric a c id . re d u c tio n of

Newman a l s o a tt e m p te d a s im u lta n e o u s h y d r o l y s i s an d

- p h e n y l - ( 9 - b e n z o y l p r o p i o n i t r i l e a n d o f m e th y l

(3 - b e n z o y l p r o p i o n a t e .

-p h e n y l

H ow ever, t h e y i e l d o f t h e h y d ro c a rb o n a c i d was

lo w , c o n s i d e r a b l e q u a n t i t i e s o f t h e s t a r t i n g m a t e r i a l s b e in g o b ta in e d i n each c a se . A s e a r c h o f t h e l i t e r a t u r e f a i l e d to d i s c l o s e any s u c c e s s f u l a t te m p t t o p r e p a r e a h y d ro c a rb o n a c i d by a o n e - s t e p h y d r o l y s i s and r e d u c t i o n u s ­ in g t h e W o lf f - K is h n e r m e th o d s .

6

DISCUSSION P r e p a r a t i o n o f t h e 1 -m eth y 1 - 3 -R -3 -R r -c y c lo h e x a n e c a r b o x y l i c a c i d s in v o lv e d t h e s e r i e s o f r e a c t i o n s diagram m ed below s R-CHO

+

2 CH3 -C0-CH2-C 00-C 2H5

C

CH.

/ \

CH CH

R-CH

\ /

C - CH 3

/

^2

/\

CH., , 2

CH n

C

C -

\ CH/

CH,

N 1> Clip

R*^ \

fH 9

/ ^C H , CH.

0

I!

A

CHo I "

CH, I jcOOCH„ q

R |/ \

^

S

^C H g

CH.

C

A

CH. CH. W o lf f - K is h n e r R | * | “.COOH C C' r e dJ ______ u c4_* t i o_____________________________ n ” ^ ^ Rr \ / CH< CH,

Clemmenson re d u c tio n

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-7 -

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The f o l l o w i n g r e a c t i o n s w e re a l s o c a r r i e d o u t:

C 6H 5 -

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CO

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-

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CH -

CO

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CHg -

The p r a c t i c a l i t y o f e a c h o f t h e a b o v e s t e p s I s e v a l u a t e d i n t h i s s e c tio n #

The e x a c t p r o c e d u r e s a r e d e s c r i b e d i n th e s e c t i o n t i t l e d

’’E x p e r im e n ta l” •

-8 -

The / \

- c y c lo h e x e n o n e s ( r e a c t i o n A) p r e p a r e d i n t h i s

a l l b e e n p re v io u s ly d e s c rib e d (1 4 , 15, 16, 17, 18, 1 9 ).

r e p o r t h av e

The o r i g i n a l

p r o c e d u r e o f K n o e v e n a g e l (1 4 ) was c l o s e l y f o llo w e d e x c e p t f o r o n e m a jo r v a ria tio n *

W hereas t h e b i s e s t e r was o r i g i n a l l y s a p o n i f i e d and d e c a r -

boxy l a t e d b e f o r e s te a m d i s t i l l a t i o n b y b o i l i n g u n d e r r e f l u x w i th co n ­ c e n t r a t e d a q u eo u s a l k a l i f o r f o u r h o u r s , i t was fo u n d t h a t t h e y i e l d was n o t d im in is h e d by b o i l i n g f o r o n ly f i f t e e n m in u te s p r i o r t o s te a m d i s t i l ­ la tio n .

The r e f l u x p e r io d c o u ld n o t b e e l i m i n a t e d e n t i r e l y b e c a u s e t h e

i n i t i a l s a p o n i f i c a t i o n was a h i g h l y e x o th e r m ic r e a c t i o n w hich p ro c e e d e d w ith c o n s i d e r a b l e r a p i d i t y when s u f f i c i e n t h e a t h a d b e e n a p p lie d * A lth o u g h m ost o f t h e y i e l d s w e re u n ch an g e d by t h e s h o r te n e d r e f l u x tim e , a 10% i n c r e a s e was n o te d i n t h e y i e l d o f 3 ,5 - d im e th y lc y c lo h e x e n o n e . 3 - C y a n o - 3 ,5 ,5 - tr im e th y lc y c lo h e x a n o n e ( r e a c t i o n B) was s y n t h e s i z e d by d i r e c t a d d i t i o n o f h y d ro g e n c y a n id e t o is o p h o ro n e ( 1 9 , 20)*

Two

a t t e m p t s t o p r e p a r e t h e sam e compound fro m t h e so d iu m b i s u l f i t e a d d i t i o n p r o d u c t w e re u n s u c c e s s f u l*

A lm ost q u a n t i t a t i v e r e c o v e r y o f t h e s t a r t i n g

m a t e r i a l was o b t a i n e d . W hitm ore an d R o b e rts (1 9 ) r e p o r t e d p o o r r e s u l t s on t h e d i r e c t a d d i­ t i o n o f h y d ro g e n c y a n id e t o 3 ,5 - d im e th y lc y c lo h e x e n o n e .

H ow ever, th e y

p r e p a r e d t h e 3 - c y a n o - 3 - m e th y l- 5 - a lk y lc y c lo h e x a n o n e s ( r e a c t i o n C) s u c c e s s ­ f u l l y fro m t h e b i s u l f i t e a d d i t i o n i n t e r m e d i a t e s , a lth o u g h i n a l l c a s e s , 20-30/£ o f t h e s t a r t i n g m a t e r i a l was r e c o v e r e d . th e p ro d u c ts , c o n s id e ra b le t a r i y

A fte r d i s t i l l a t i o n of

r e s i d u e re m a in e d .

-9 -

The h ig h r e c o v e r y o f s t a r t i n g m a t e r i a l s u g g e s te d t h a t t h e k e t o n i trile

decom posed (2 0 ) a c c o r d i n g t o t h e e q u a t i o n 0 CN II | -C - CHg - C H ---------------------HCN

0 n 4> - C - CH : CH - .

The r e p la c e m e n t o f t h e s u l f o n i c a c i d r a d i c a l by t h e c y a n id e g ro u p "was o r d i n a r i l y c a r r i e d o u t on a b o i l i n g w a t e r b a th *

I f t h e a b o v e d e c o m p o si­

t i o n a c t u a l l y o c c u r s , i t m ig h t b e r e t a r d e d by u s in g a lo w e r te m p e r a tu r e * One e x p e r im e n t was p e rfo rm e d i n ■which t h e 1 ,3 - d im e th y lc y c lo h e x e n o n e b i s u l f i t e a d d i t i o n p r o d u c t was h e a te d o n ly t o 65° C* i n t h e p r e s e n c e o f a q u eo u s so d iu m c y a n id e .

B ut f o u r h o u rs o f h e a t i n g w e re r e q u i r e d f o r a

s i z a b l e o r g a n ic l a y e r t o fo rm .

D is tilla tio n of th is

y i e l d e d m o s tly 1 , 3 -d im e th y Ic y c lo h e x e n o n e *

o r g a n ic m a t e r i a l

I n a n o t h e r e x p e rim e n t w it h t h e

same b i s u l f i t e a d d i t i o n p r o d u c t , 60 m l. o f b e n z e n e was a d d ed t o t h e f l a s k j u s t a f t e r t h e a d d i t i o n o f t h e a q u eo u s so d iu m c y a n id e *

The p u rp o s e o f

t h e b e n z e n e l a y e r was t o d i s s o l v e t h e k e t o n i t r i l e a s i t s e p a r a t e d fro m t h e a q u e o u s s o l u t i o n o f t h e b i s u l f i t e a d d i t i o n p ro d u c t*

The r e a c t i o n

was c a r r i e d o u t on a b o i l i n g w a te r b a th w ith t h e te m p e r a t u r e o f th e i n ­ t e r n a l aq u eo u s p h a s e a t 90° C*

The y i e l d o f 3 - c y a n o - 3 ,5 - d i m e th y lc y c lo -

h e x an o n e was 60*4%, a n i n c r e a s e o f m ore th a n 12% o v e r t h e m ethod n o t mak­ in g u s e o f th e b e n z e n e l a y e r .

A p p r e c ia b le im p ro v em en ts i n t h e y i e l d s o f

t h e e t h y l and t h e is o p r o p y l hom ologues a l s o w e re a c h ie v e d by u s e o f t h e b e n ze n e l a y e r .

H ow ever, t h e n - p r o p y l compound showed no im p ro v ed y i e l d

an d t h e r e was a c t u a l l y a d e c r e a s e d y i e l d i n t h e c a s e o f 3 - c y a n o - 3 - m e th y l5 -p h e n y lc y c lo h e x a n o n e .

-1 0 -

The im p ro v ed y i e l d s may b e t h e r e s u l t o f ( 1 ) lo w e r r e a c t i o n tem ­ p e r a tu r e , (2 ) d i l u t i o n o f th e p ro d u c t, o r (3 ) b o th .

T h at t h e d i l u t i o n

e f f e c t d o e s p l a y some p a r t i n t h e g r e a t e r y i e l d s i s d e m o n s tr a te d by t h e ab sen ce of t a r r y

r e s i d u e a f t e r t h e d i s t i l l a t i o n o f th e k e t o n i t r i l e s p r e ­

p a r e d by u s e o f t h e b e n z e n e l a y e r . The 3 - c y a n o - 3 - m e th y l- 5 - c y c lo h e x a n o n e s p r e p a r e d i n t h e p r e s e n t w ork have a l l b e en p re v io u s ly d e s c rib e d (1 9 , 2 0 ). Of t h e a l i c y c l i c a c id s p r e p a r e d i n t h i s t h e s i s , t h e 1 , 3 , 3 - t r i m e t h y l c y c lo h e x a n e c a rb o s c y lic a c i d was t h e f i r s t p r e p a r e d b e c a u s e o f t h e e a s y s y n t h e s i s o f t h e 3 - c y a n o - 3 ,5 ,5 - tr i m e th y l c y c lo h e x a n o n e fro m i s o p h o r o n e . M e th y l 3 ,5 ,5 - t r i m e t h y l c y c l o h e x a n o n e - 3 - c a r b o x y l a t e was p r e p a r e d by t h e a l c o h o l y s i s ( r e a c t i o n D) o f t h e k e t o n i t r i l e by r e f l u x i n g a m e th a n o ls u l f u r i c a c i d s o l u t i o n o f t h e c y a n id e f o r s e v e r a l h o u r s . of t h e k e t o e s t e r was o b t a i n e d .

A y i e l d o f 65%

The c a r b o n y l g ro u p o f t h e k e t o e s t e r was

t h e n r e d u c e d ( r e a c t i o n E ) , u s in g z in c am algam an d h y d r o c h l o r i c a c i d a c ­ c o r d in g t o t h e m ethod of Clem m enson. t i o n was a b o u t 37%.

The a v e r a g e y i e l d f o r t h i s r e d u c ­

The a c i d p r e p a r e d by h y d r o l y s i s ( r e a c t i o n F ) o f t h e

re d u c e d e s t e r m e lte d a t 5 1 -5 2 ° C. when r e c r y s t a l l i z e d fro m 50% is o p r o p y l a lc o h o l.

B ecau se o f t h e lo w o v e r a l l y i e l d , a m ore s a t i s f a c t o r y m ethod

o f p r o d u c in g t h e a c i d was s o u g h t. A s tu d y o f t h e l i t e r a t u r e p e r t a i n i n g t o t h e W o lf f - K is h n e r r e d u c t i o n (3 3 ) r e v e a le d s e v e r a l i n s t a n c e s i n w h ic h

y - k e t o a c i d s h ad b e e n r e d u c e d .

The H u an g -M in lo n m o d i f i c a t i o n (2 4 ) was t r i e d b e c a u s e i t e l i m i n a t e d t h e h a n d lin g o f m e t a l l i c so d iu m ; made u s e o f t h e r e l a t i v e l y in e x p e n s iv e 85% h y d r a z in e h y d r a t e ; was a p p l i c a b l e t o l a r g e r q u a n t i t i e s ; an d a c h ie v e d

-1 1 -

h ig h t e m p e r a t u r e s w i th o u t t h e u s e o f p r e s s u r e *

U sin g t h i s m ethod f o r

t h e r e d u c t i o n o f m e th y l 3 ,5 ,5 - t r i m e t h y l c y c l o h e x a n o n e - 3 - c a r b o x y l a t e ( r e a c t i o n G-) p ro d u c e d a y i e l d o f 60.3% o f t h e 3 , 5 , 5 - t r i m e t h y l c y c l o h e x an e c a r b o x y l i c a c i d , m e ltin g a t 5 0 -5 1 ° C. when r e c r y s t a l l i z e d fro m 50% i s o p r o p y l a l c o h o l .

The m ixed m e lti n g p o i n t s o f t h e a c i d s p r e p a r e d

by t h e Clem m enson and t h e W o lf f - K is h n e r r e d u c tio n s showed n o d e p r e s s i o n . A lth o u g h t h e W o lf f - K is h n e r r e d u c t i o n o f m e th y l 3 , 5 , 5 - t r i m e t h y l c y c l o h e x a n o n e - 3 - c a r b o x y la te g a v e a f a r b e t t e r y i e l d o f t h e a l i c y c l i c a c i d t h a n t h e p r o c e d u r e u s i n g t h e Clemmenson r e d u c t i o n , t h e f e a s i b i l i t y o f a s im u lta n e o u s h y d r o l y s i s - r e d u c t i o n o f t h e k e t o n i t r i l e was i n v e s t i g a t e d . U sin g t h e Clemmenson m ethod o f r e d u c t i o n , Uewman (2 5 ) h ad f a i l e d t o ob­ t a i n t h e h y d ro c a rb o n a c i d i n one s t e p fro m trile .

^ - p h e n y l - (3 - b e n z o y l p r o p i o n i -

The W o lf f - K is h n e r r e d u c t i o n o f v a r i o u s k e t o n i t r i l e s

( r e a c t i o n H)

was c a r r i e d o u t by H. F i s c h e r and c o w o rk ers ( 3 5 , 3 6 ) u s i n g m e t a l l i c so d iu m a n d h y d r a z in e h y d r a t e i n a l c o h o l u n d e r p r e s s u r e a t 1 6 5 -1 8 0 ° C ., b u t t h e s im p le re d u c e d a c id s w e re n o t among t h e p r o d u c ts r e p o r t e d . H ow ever, t h e W o lf f - K is h n e r r e d u c t i o n was v ie w e d w ith i n t e r e s t b e c a u s e t h e a l k a l i n e - a q u e o u s c o n d itio n s o f t h e a f o r e m e n tio n e d H u an g -M in lo n m odi­ f i c a t i o n s h o u ld h y d r o ly z e t h e n i t r i l e p r i o r t o

re d u c tio n o f th e c a rb o n y l

g ro u p . To t e s t t h e p r o c e d u r e ,

- p h e n y l - (3 - b e n z o y l p r o p i o n i t r i l e was p r e ­

p a re d ( r e a c t i o n s J an d K) and c o n v e r te d t o o ( , y - d i p h e n y l b u t y r i c a c i d i n 63% y i e l d by t h i s one s t e p m ethod ( r e a c t i o n L ) .

The 3 - c y a n o - 3 , 5 , 5 -

tr im e th y lc y c lo h e x a n o n e was s u b j e c t e d t o t h e same c o n d i t i o n s , w h ich p r o ­ d u c ed a 69% y i e l d o f 1 , 3 , 3 - tr im e th y lc y c lo h e x a n e c a r b o x y lic a c i d .

-1 2 -

The

d i s t i l l e d p r o d u c t s o l i d i f i e d an d w as r e c i y s t a l l i z e d fro m 50% is o p r o p y l a l c o h o l , m e ltin g a t 5 0 -5 2 ° C.

The m ixed m e lti n g p o i n t w i t h t h e a c i d

p r e p a r e d b y t h e Clemmenson r e d u c t i o n show ed no d e p r e s s i o n . I n a d d i t i o n t o t h e h y d ro c a rb o n a c i d , a s m a ll am ount o f a h ig h m e l t ­ in g b y - p r o d u c t was o b ta in e d i n t h e W o lf f - K is h n e r r e d u c t i o n o f (X ,-p h e ry l(3 - b e n z o y l p r o p i o n i t r i l e .

A z in e s h av e f r e q u e n t l y b e e n o b s e r v e d a s b y ­

p r o d u c ts o f t h e W o lf f - K is h n e r r e d u c t i o n ( 3 5 ) , c o n s e q u e n tly , i t was th o u g h t t h a t t h e h ig h m e l t i n g b y - p r o d u c t o b ta in e d m ig h t b e t h e a z i n e o f (3 - b e n z o y lp r o p io n ic a c i d .

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A c id c h l o r i d e s o f l - m e t h y l - 5 - a l k y l c y c l o h e x a n e c a r b o x y l i c a c i d s

/ \ ce9

R \>i R'

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CH *

I n a 50 ml* C l a i s e n f l a s k , w h ich s e r v e d a s t h e r e a c t i o n v e s s e l , ■was p la c e d 0*05 m ole of t h e c y c l i c a c id *

By means o f a d ro p p in g f u n n e l ,

1 8 .0 g , ( 0 .1 5 m o le ) o f t h i o n y l c h l o r i d e ■was a d d ed d u rin g f i f t e e n m in u te s* D u rin g t h e a d d i t i o n , t h e r e a c t i o n f l a s k was k e p t a t room t e m p e r a t u r e by im m e rsio n i n a c o o l w a t e r b a t h .

The w a t e r b a th was th e n b r o u g h t t o b o i l ­

i n g , t h e r e a c t i o n b e in g th u s h e a te d f o r two h o u rs*

A f t e r re m o v al o f

e x c e s s t h i o n y l c h l o r i d e t h e a c i d c h l o r i d e was d i s t i l l e d d i r e c t l y fro m t h e r e a c t i o n f l a s k , u s in g d im in is h e d p r e s s u r e an d a f r e e f la m e . c o n ta i n s t h e d e s c r i p t i o n s o f t h e a c i d c h l o r i d e s .

•27-

T a b le IV

TABLE

IV

A c id c h l o r i d e s o f l- m e th y l- S - R - S - R * - c y c lo h e x a n e c a r b o a y l i c a c id s CH. CH

|

CH

l^coci

2

J fi E 1'

c \

/

X CH

CHZ

R

R1

Y ie ld

% M eth y l

M ethyl

M eth y l

3

B o ilin g p t . Mm. °C.

C h lo r in e * % Found

% C a lc d .

9 0 ,5

9 4 -9 7

15

1 8 .8

1 8 .6 , 1 8 .5

H

6 6 . 6

87-88

16

2 0 .3

1 9 .9 , 2 0 .1

E th y l

H

B 8.9

1 0 0 -1 0 3 14

1 8 .8

1 8 .9 , 1 8 .5

n -P ro p y l

H

9 2 .9

1 11-113 15

1 7 .5

1 7 .2 , 1 7 .3

Iso p ro p y l

H

9 0 .4

1 1 0 -1 1 1

13

1 7 .5

1 7 .1 , 1 7 .3

Phenyl

H

9 1 .6

15 5 -1 5 6

5

1 5 .0

1 4 .8 , 1 5 .0

C h lo r in e was d e te r m in e d by t h e V o lh a rd m ethod ( 3 9 ) .

-2 8 -

D ia lk y la m in o e th y l l - m e t h y l - 3 - a l k y l c y c l o h e x a n e c a r b o x y l a t e . h y d r o c h lo r i d e s

R R'

I

I -C00-CH9 -CH -UR • HC1 w u £

2

\

/ 'N th, CHg

To 0 .2 0 m ole o f t h e d ia lk y la m in o e th a n o l i n a 50 m l. g l a s s - s t o p p e r e d E rle n m e y e r f l a s k , 0 .0 5 m ole o f t h e c y c l i c a c id c h l o r i d e was a d d e d d r o p w is e .

The s t o p p e r was w ire d on an d t h e m ix tu r e was s h a k e n v i g o r o u s l y

f o r f i v e m in u te s .

W ith i n t e r m i t t e n t s h a k i n g , t h e f l a s k was th e n a llo w e d

t o s t a n d f o r tw o h o u r s .

The c o n te n t s o f t h e f l a s k w e re p o u re d i n t o a

s e p a r a t o r y f u n n e l c o n t a i n i n g 25 m l. o f s a t u r a t e d so d iu m c a r b o n a te s o l u ­ tio n .

The f r e e a m in o e s te r w h ich s e p a r a t e d was d i l u t e d w ith 25 m l. o f

e t h e r a n d th e n w ashed f r e e of t h e w a t e r - s o l u b l e a m in o a lc o h o l w i t h t h r e e 25 m l. p o r t i o n s o f w a te r .

The e t h e r s o l u t i o n o f t h e a m in o e s te r was d r i e d

o v e r a s m a ll am ount o f a n h y d ro u s so d iu m s u l f a t e f o r tw e lv e h o u r s .

The

d ry a m in o e s te r s o l u t i o n was th e n d e c a n te d i n t o a tw e lv e in c h t e s t t u b e . An e t h e r e a l s o l u t i o n o f h y d ro g e n c h l o r i d e was ad d ed d ro p w is e , w i t h c o o l­ i n g , u n t i l t h e s u p e r n a t a n t f l u i d i n t h e t e s t tu b e was d i s t i n c t l y a c i d t o Congo r e d p a p e r .

A l a r g e e x c e s s o f h y d ro g e n c h l o r i d e was a v o id e d .

The

w h ite p r e c i p i t a t e was f i l t e r e d q u ic k ly th ro u g h a B u ch n e r f u n n e l , w ashed w ith d ry e t h e r , a n d d r i e d I n a vacuum d e s i c c a t o r .

The f i l t r a t e was t e s t e d

f o r c o m p le te p r e c i p i t a t i o n by a d d in g a few d ro p s o f e t h e r e a l h y d ro g e n c h lo rid e .

The e s t e r - h y d r o c h l o r i d e s w e re r e c r y s t a l l i z e d fro m a n h y d ro u s

e th y l a c e ta te .

P h y s i c a l c o n s t a n t s a n d a n a l y t i c a l d a t a f o r t h e d im e th y l-

a m in o e th y l e s t e r s a r e g iv e n i n T a b le V.

T ab le VI r e c o r d s s i m i l a r d e s ­

c r i p t i o n s o f t h e d i e t h y la m in o e th y l e s t e r s .

-2 9 -

TABLE

V

D im efeh y lam in o eth y l l- in e th y l- S - R - S - R 1 - c y c lo h e x a n e c a r b o x y l a t e • h y d r o c h lo r id e s

A

CH? CH R ^ l |^COO-CH 2 -CH2 -H(CH 3 X C R' \ / ^C H CHrt ^

3; R

R*

)2

• HCl

n itro g e n * % Found

M e ltin g p o i n t °C .

%. C a lc d .

M eth y l

M eth y l

159

5 .1

5 . 0 , 5 .0

M eth y l

H

1 5 0 -1 5 1

5 .3

5 . 4 , 5 .4

E th y l

H

1 0 9 -1 1 1

5 .1

5 . 0 , 5 .0

n -P ro p y l

H

1 0 9 -1 1 0

4 .8

4 . 9 , 4 .8

Iso p ro p y l

H

147

4 .8

4 . 8 , 4 .8

Phenyl

H

136

4 .3

4 . 3 , 4 .3

* H itr o g e n m s d e te r m in e d by m acro - K j e l d a h l a n a l y s i s ( 4 0 ) .

-3 0 -

TABLE

VI

P i e t h y l am ino e t h y l l-m e th y l-S -R -S -R * -c y c lo h e x a n e c a r b o x y l a t e » h y d r o c h l o r id e s yCHn

/ H

R.

CH I

R*

\

CH | 3C00-CH 2 -CH2 -H(C 2 H5

/

) 2

* HCl

X CH

N ® 2

R

R*

M e ltin g p o in t °C .

** N itr o g e n % C alcd* % Found 4 .6

4 . 7 , 4 .6

M eth y l

1 2 0 -1 2 1

M eth y l

H

1 2 8 -1 3 0

E th y l

H

1 1 4 -1 1 7

4 .6

4 . 7 , 4 .7

H

1 1 2 -1 1 6

4 .4

4 . 7 , 4 .7

Iso p ro p y l

H

1 3 0-133

4 .4

4 . 6 , 4 .2

Phenyl

H

1 1 6-119

4 .0

4 . 2 , 4 .0

n -P ro p y l

j|c

CO •

M eth y l

5 . 0 , 4 .6

* M e ltin g p o i n t was d e te rm in e d on c ru d e p r o d u c t w h ich was v e r y h y g ro s c o p ic * ** N itr o g e n was d e te r m in e d by macro - E j e l d a h l a n a l y s i s ( 4 0 ) .

-3 1 -

P i p e r i d y l am ides o f 1 - m e th y l- 3 -R -3-R * -c y c lo h e x a n e c a r b o x y l i c a c id s CH

A

CH R

I 2

H'/ C \

/ ^

CH l/

CH C0C1

+

> _ R \ I

/ ^C H ch 2 a

CH |^ c o - h ( c h 2 ) 5

R-/ C \

/\ ( H ch

3

^

T h e se s u b s t i t u t e d am ides w e re p r e p a r e d b y t h e S c h o tte n -B a u raa n n te c h n i q u e ( 3 0 ) .

E q u im o la r am ounts o f t h e a c i d c h l o r i d e s and p i p e r i d i n e

w e re s h a k e n t o g e t h e r v i g o r o u s l y f o r t e n m in u te s i n t h e p r e s e n c e o f a s l i g h t e x c e s s o f 1 0^ p o ta s s iu m h y d ro x id e *

A g la s s -s to p p e re d E rle n -

m ey er f l a s k w as c o n v e n ie n t f o r t h i s p r e p a r a t i o n . o i l y l a y e r Had fo rm e d .

W ith in two h o u rs a n

T h is was d i l u t e d w ith a n e q u a l volum e of b e n -

\

z e n e , s e p a r a t e d , d r i e d , an d d i s t i l l e d u n d e r d im in is h e d p r e s s u r e .

Only

t h e p h e n y l hom ologue was a s o l i d , t h e re m a in d e r b e in g y e l l o w i s h , v i s ­ cous l i q u i d s .

R e c r y s t a l l i z a t i o n o f t h e p h e n y l compound fro m is o p r o p y l

a l c o h o l y i e l d e d t a n c r y s t a l s m e lti n g a t 5 5 -5 6 ° C. a r e d e s c r i b e d i n T a b le V I I .

-3 2 -

The p i p e r i d y l am id es

TABLE

V II

P i p e r i d y l am id es of 1 - m e th y l- 3 -R -3 - R 1 - c y c lo h e x a n e c a r b o x y l i c a c id s CH

/ ^

CH H

|

\

R*

CH | JCO-H(CH )

2

c

C^

\

/

2 5

CH

CH2

R

RT

B o ilin g p o i n t °C . Mm.

if. if.

n itro g e n % C a lc d . % Found r

M eth y l

M eth y l

128-131

2

5 .7

5 . 7 , 5 .6

M eth y l

H

12 8 -1 3 1

2

6 .0

6 . 2 , 6 .3

E th y l

H

1 35-138

2

5 .7

5 . 9 , 5 .8

_ n -P ro p y l

H

141-145

2

5 .4

5 . 4 , 5 .5

Iso p ro p y l

H

/ 14 3 -1 4 7

2

5 .4

5 . 6 , 5 .5

Phenyl

H

*

5 .0

4 . 5 , 4 .6

* M .p. 5 5 -5 6 ° C. ** H i t r o g e n was d e te r m in e d by m acro - F J e l d a h l a n a l y s i s u s in g m e t a l l i c m e rc u ry c a t a l y s t ( 4 1 ) .

-3 3 -

Amides o f l-m e th y l-S -R -S -R * - c y c lo h e x a n e c a r b o x y l i c a c i d :

A

CH I

R*^

\

A

OH MCOCI

+

CH I

HH O H

C C

/ x CHch2

r

CH I IcO-NHCC

1

\ / N :h ch2 3

One gram o f t h e a c i d c h l o r i d e was a d d ed t o 20 ml* o f c o n c e n tr a te d ammonium h y d r o x id e c o n ta i n e d i n a 50 m l. g l a s s - s t o p p e r e d E rle n m e y e r fla s k .

The s t o p p e r was w ir e d on a n d t h e f l a s k was sh a k e n v i g o r o u s l y

f o r f i v e m in u te s . o c c a s i o n a l s h a k in g .

The m ix tu r e was a llo w e d t o s t a n d f o r 48 h o u rs w ith W ith t h e e x c e p tio n o f t h e e t h y l h o m ologue, t h e

s im p le am id es w e re w h ite c r y s t a l l i n e s o l i d s .

S in c e t h e s im p le am id e

o f t h e e t h y l compound was a n o i l , t h e a n i l i d e was p r e p a r e d b y s u b s t i ­ tu tin g

10

m l. o f f r e s h l y d i s t i l l e d a n i l i n e f o r t h e ammonium h y d ro x id e

in th e above p ro c e d u re. l i d e m e lte d a t 8 0 -8 1 ° C.

The l- m e th y l- 3 - e t h y lc y c l o h e x a n e c a r b o x y l a n i ­ The am id es a r e d e s c r ib e d i n T a b le V I I I .

-3 4 -

TABLE

V III

A m ides o f l- m e th y l- S - R - S - R 1- c y c lo h e x a n e c a r b o x y l i c a c i d s

/

R R*

s

|

| lc o -m

c

cc

*CHr \ / x' CH3

R

R1

M e ltin g p o i n t °C .

N itr o g e n

% C a lc d .

% Found

M eth y l

M eth y l

9 1 .5 - 9 2 .5

8 .3

8

,2 ,

M eth y l

H

7 4-75

9 .0

8

. 8 , 9 .0

E th y l*

H

8 0 -8 1

5 .7

5 . 7 , 5 .7

H -P r o p y l

H

1 3 6 -1 3 7

7 .7

7 . 7 , 7 .5

Iso p ro p y l

H

8 2 .5 - 8 3 .5

7 .7

7 . 7 , 7 .7

Phenyl

H

131-133

6 .5

6 .5 , 6 .4

8 .2

* A n ilid e . ** N itr o g e n was d e te r m in e d b y m a c r o -K je ld a h l a n a l y s i s ( 4 0 ) .

-3 5 -

3.

MISCELLANEOUS SYNTHESES B e n z a la c e to p h e n o n e 0

II CgHg - CH = CH - C - CgHg A s o l u t i o n o f 109 g . ( 2 .7 5 m o le s ) o f so d iu m h y d ro x id e i n 980 m l. o f w a t e r an d 630 m l. o f 95% e th a n o l (3 1 ) was in tr o d u c e d i n t o a 5 l i t e r ro u n d - b o tto m f l a s k f i t t e d w ith a m e c h a n ic a l s t i r r e r * c o o le d e x t e r n a l l y by i c e .

W ith s t i r r i n g , 260 g . ( 2 .1 5 m o le s ) o f p u r e

a c e to p h e n o n e was p o u re d i n t o t h e f l a s k * USP b e n z a ld e h y d e was a d d ed a t o n c e . 1 5 ° C. f o r tw o h o u r s .

The f l a s k was

T hen, 230 g* ( 2 .1 5 m o le s ) o f

The te m p e r a t u r e was k e p t n e a r

The m ilk y l i q u i d was r e f r i g e r a t e d f o r tw e lv e

h o u r s , by w h ic h t i m e , l a r g e y e llo w c r y s t a l s h ad fo rm e d .

The p r e c i p i ­

t a t e was f i l t e r e d th r o u g h a l a r g e B u c h n e r f u n n e l a n d w ash ed w ith t h r e e 100 m l. p o r t i o n s o f w a t e r a n d o n c e w ith 100 ml* o f 50% e th a n o l*

A fte r

a i r - d r y i n g , t h e y i e l d o f l i g h t - y e l l o w b e n z a la c e to p h e n o n e was 403 g . (9 2 $ y i e l d ) .

jfc

M .P. 5 1 -5 4 ° C .*

uncor re c te d .

-3 6 -

1 3 - 7 "Pound j

C l, 1 3 . 4 , 1 3 .5 .

The a m id e was p r e p a r e d fro m t h e a c i d c h l o r i d e .

“VSIhite n e e d le s w e re

o b ta in e d u p o n r e c r y s t a l l i z a t i o n fro m m e th a n o l, m e l tin g s h a r p l y a t 9 6 ° C. C a lc d .

f o r C^gH^yUOs F ound:

N, 5 . 9 . N, 5 . 8 , 5 . 8 .

o n e s y n t h e s i s o f c