Synthesis of Certain Disubstituted Peperidines

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PURDUE UNIVERSITY

T H IS IS TO CERTTFT T H A T T H E T H E S IS P R E P A R E D U N D E R MY S U P E R V IS IO N

BY

E N T IT L E D

Raphael Otto Bachmann ________ SYNTHESIS OF CERTAIN DISUBSTITUTBD PIPERIDINES

C O M P L IE S W IT H T H E UN TV ERSITT R E G U L A T IO N S O N G R A D U A TIO N T H E S E S

AND IS A P P R O V E D BY M E A S E U L F IL L IN G T H IS P A R T O F T H E R E Q U IR E M E N T S

FO R THE DEGREE O F

Doctor of . Philosophy

P

H

T O T H E L IB R A R IA N :---IS T H IS T H E S IS

r o f e s so r in

eab of

Charge

S O H o o ii OR D

of

Th

e s is

epartm ent

TO B E R E G A R D E D A S C O N FID E N T IA L .

P S O F E S S O B W S ORABGB

GBAO. SCHO OL F O B U 9—3 . 4 9 —IM

THE SYNTHESIS

OP CERTAIN DISÜBSTITUTED PIPERIDINES

A T h e s is

S u b m itte d to th e F a c u lty

of

Purdue H u iv a r s ity

by

R aphael O tto Bachmann

I n P a r t i a l F u l f i ll m e n t o f th e

R equirem ents f o r th e Degree

of

D octor o f P h ilo so p h y

F e b ru a ry , 1950

ProQuest Number: 27712198

All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is d e p e n d e n t upon the quality of the copy subm itted. In the unlikely e v e n t that the a u thor did not send a c o m p le te m anuscript and there are missing pages, these will be noted. Also, if m aterial had to be rem oved, a n o te will ind ica te the deletion.

uest ProQuest 27712198 Published by ProQuest LLO (2019). C opyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States C o d e M icroform Edition © ProQuest LLO. ProQuest LLO. 789 East Eisenhower Parkway P.Q. Box 1346 Ann Arbor, Ml 4 8 1 0 6 - 1346

ÂCKNOUVLEmEMBNT

The w r i t e r w lsh e a to e x p re s s h i s s in c e r e a p p r e c ia tio n to Dean Glenn L« J e n k in s and Dr# John E» C h r i s t ia n f o r t h e i r I n t e r e s t and as* s i s t a n c e I n t h i s w ork. Acknowledgement I s a ls o made to th e Ameri­ can F o u n d a tio n f o r F h a rm a c e u tlc a l E d u c a tio n f o r th e f i n a n c i a l su p p o rt o f t h i s p r o je c t*

TABLE OP CONTENTS

Page IBTBODCCTION...................................................................................................

1

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

6

E xperim ent

I# S y n th e s is o f d i e t h y l d l p h e n y l g l n t a r a t e .. . . . . . . .

E xperim ent

...

2# p r e p a r a tio n o f two Iso m e rs o f 2 ,4 * d lp h e n y lg X u ta rlc a o l d .

E xperim ent

. . . 10

...............11

B. A tte n p te d s y n th e s is o f «!, ■'0=0 0-CH J l S - 0 OnC

(XV)

X

IC-

(XVI) Hydrogen Copper C hrom ite (1 9 ,2 0 ) H pHg ^»0H

CHg ^OB-0

'0 Hg

and (XVII)

• ^NH-CHg-|ÿ OHg ^ H g JÏ-QH CS~0 Ho

(X V III)

7. p ro c é d u re g* a .)

NaOEt

GHg(GE)COOEt + CHg(OH)CN

(2 3 )

CH( CN) ( COOEt ) -CHg-CH( CN ) ( COOEt ) (XIX) b .)

R-X + CHg (Gïï) COOEt

N.aOJB.t . ^

R-CH(GN )CÛOEt

( 21 )

CH(CN) ( COOEt)-GHg-CH(CN) ( COOEt) o r R-CH(CN)COOEt R-X NaOlt

NaOE

R-CH(CN){COOEt) -CHg-CH(CN) ( COOEt) -R (XX)

S a p o n ify , a c i d i f y and d e c a rb o x y la te R-CH(CN)-CHg-CE(CN)-R (XXI)

Raney N ic k e l Hydrogen ( 20)

ÇH2

\

CHg

R-CH CH-R '^ C '^ I Ho (X X II)

8. P ro c ed u re 5. 0-OHg-CN + CHoIp

0CH(CH)-CHp-OH(CK)-^ / (X X III)

(1 8 ,2 2 )

Raney N ic k e l Hydrogen ( 20)

CHg

\

CHg

jÿ-CH OH-0 ^C I Ho (XXIV)

The m ethylene io d id e (25) and co p p er chi^omite (26) a re p re p a re d a c c o rd in g to p ro c e d u re s d e s c i'ib e d i n •O rg an ic Syntheses**

The g l y c c l o n i t r i l e o f P ro c ed u re 2 (a ) i s an

e x p e rim e n ta l sam ple from th e A m erican Gyanamide Company,

9,

F ro p o se4 meth®4 f o r S y a th e a ls o f 8 .6 * b is “ (l**hydrpxyalkyl) p i p e r i d i n e s and 2 . 6 - b l a - ( a r y l h y droxym ethyl)p_lperl_dlne (XXIX)_>

°®5|

5 ^ t ral> K O O C | ^ C O O K

5 5 2 ^ HOOC^^COOK

(XXVI) N HOOO^^COOK -------------- >

N C 1 - ( 0 ) C |^ ^ C ( 0 ) C 1

(XXVI) R-B»+ Hg

E th e r ^ K atm os.

01-(0)C|/ \C(0)-C1

IL J (XXVII)

(XXVII) BMgBr

-----^*^^8---- >

gfidpl ^ Benzene N atmos* (29)

RCdCl.

E-(0)c/\c(0)-R

I

J

(XXVIII) H

Ô

C(0)-R

B H2_drogen ^ R-(HO)C-pH

C a ta ly s t

H CH-C(OH)-R

yCHg &

(XXVIII)

(XXIX)

R = e t h y l , p r o p y l, b u t y l , amyl and p h e n y l.

2 , 6 - l u t i d l n l c a c id ( d l p i c o l i n l c a c id ) (XXVI) i s p r e ­ p a re d by o x id a tio n o f 2 , 6 - l u t l d i n e (XXV) w ith p o ta ssiu m perm anganate i n n e u t r a l s o lu tio n (2 7 ).

I t i s c o n v e rte d to

10. th e a e l â c h lo r id e (XXVII) by r e f l u x i n g w ith t h io n y l c h lo r id e (8 8 ).

S in c e th e a c id c h lo r id e even decom poses on s ta n d in g

i n a d e s s i c a t o r o v e r p o ta ssiu m h y d ro x id e ( 5 0 ) , i t i s alw ays fre s h ly p rep a red .

The p r e p a r a t i o n o f an a lk y l cadmium

c h lo r id e and i t s su b seq u e n t r e a c t i o n w ith 2 , 6 « l u t i d i n l c a c id c h lo r id e a re ru n i n a manner su g g e ste d f o r t h i s ty p e r e a c t i o n by Cason and p ro u t ( 2 9 ) .

R e d u c tio n s o f th e d ia c y lp y r id in e s

(XXVIII) a re b ro u g h t about c a t a l y t i c a l l y .

A ll r e d u c tio n

m ix tu re s a re p r e t r e a t e d w ith Raney R ic k e l to a s s u r e rem oval o f p o is o n s .

L in s te a d (51) shows t h a t where a number o f i s o ­

m ers a re p o s s i b l e , c a t a l y t i c r e d u c tio n may y i e l d a l i m i t e d number o f fo rm s. p r o d u c ts .

T h is f a c i l i t a t e s s e p a r a tio n o f r e a c t i o n

G e n e ra lly , th e d ia c y lp y r id in e s a re re d u c e d i n

th e p re s e n c e o f p la tin u m b la c k i n a P a r r R ed u ctio n A p p aratu s (32) a t th r e e atm osp heres o f hydrogen p r e s s u r e .

E xperim ent 1 . S y n th e s is o f d i e t h y l 8 j 4 - d ip h e n y lg lu ta r a te (1 8 ). To a s o lu tio n o f 1 4 .5 (kc. o f f r e s h l y c u t sodium d i s ­ so lv e d i n 200 CO. o f anhydrous e th a n o l, 130 Gm. o f d i e t h y l p h en y lm alo n ate and 73*5 Gm. o f f r e s h l y d i s t i l l e d m ethylene io d id e were added.

T h is m ix tu re was r e f lu x e d on a steam

b a th f o r seventy*»two h o u rs o r u n t i l th e m ix tu re became n e u tra l.

The e th a n o l was th e n s tr ip p e d o f f u n d e r vacuum

and th e r e s id u e p o u red i n to 200 e c . o f w a te r c o n ta in e d i n a s e p a ra to ry f u n n e l.

A f te r a l l th e s o l i d m a t e r i a l d is s o lv e d ,

th e o i l y l a y e r was s e p a r a te d , and th e aqueous la y e r was

11. e x t r a c t e d w ith s e v e r a l p o r t io n s o f e th e r#

The e t h e r e x -

t r a c t s w ere eomhined w ith th e o i l y l a y e r , and d r i e d o v e r calc iu m c h lo r id e f o r tw e n ty * fo u r h o u rs .

Then th e e th e r was

s t r i p p e d o f f and th e r e s id u e d i s t i l l e d u n d er vacuum i n a C la is e n d i s t i l l i n g fla s k #

The d i s t i l l a t e b . r . 186«*189^/8mni

w eighed 71 Gm. (83J^ o f th e t h e o r e t i c a l ) .

A fo re -ru n o f

d i e t h y l c a rb o n a te was c o l l e c t e d a s d e s c rib e d by S o u th e r ( 1 8 ). E xperim ent 2 . P r e p a r a tio n o f two iso m e rs o f 2$4 - d i p h e n y l g lu t a r ic a c id . Seven gram s o f d i e t h y l 2 , 4 - d ip h e n y lg lu ta r a te was added to a s o lu tio n o f 1 .5 (M. o f sodium i n 20 c c . o f 95^ m ethanol. S h o r tly a f t e r m ix in g , th e e n t i r e m ass s o l i d i f i e d .

The n e x t

m orning anhydrous e th e r was added and th e s a l t f i l t e r e d o f f . The d r i e d s a l t was th e n d is s o lv e d i n w a te r and d e c o lo r iz e d w ith N o r ite .

On dropw ise a d d itio n o f 10^ h y d r o c h lo r ic a c id ,

th e o rg a n ic a c id p r e c i p it a te d #

The h y d ro c h lo ric a c id was

added slo w ly enough to a llo w c r y s t a l l i z a t i o n to ta k e p l a c e , o th e rw is e a p u t t y - l i k e mass form ed. w h ite pow der, m .p. 164-165®.

Y ie ld ;

P h y s ic a l p r o p e r t i e s ; 3 Gm.

The m other l i q u o r o f th e sodium s a l t and th e wash e th e r were e v a p o ra te d to d ry n e ss on a steam b a th .

The r e s id u e s

were ta k e n up in w a te r and d e c o lo r iz e d w ith N o r ite .

P ro

c l p i t a t i o n o f th e a c id was c a r r i e d o u t a s d e s c r ib e d above. T h is a c id was r e c r y s t a l l i z e d from c h lo ro fo rm -p e tro le u m e t h e r . P h y s ic a l p r o p e r t i e s ; 1 .5 Gm.

w h ite pow der, m .p. 185-186®.

Y ie ld :

12. B m erlm em t 3 . A tteaqsted s y n t h e s i s o f

,«/- d lp h e n y lg lu t a rlm l de*

' T hree grams o f th e lo w er m e ltin g Isom er o f 2^4*"dlphenylg l n t a r l o a c id was c o n v e rte d to th e ammonium s a l t by d i s s o l v ­ in g i n an e q u iv a le n t o f ammonia w a te r and e v a p o ra tin g to d ry n e s s .

The d r ie d ammonium s a l t was p la c e d i n a s u i t a b l e

d i s t i l l i n g f l a s k s e t- u p f o r downward d i s t i l l a t i o n .

H eat was

a p p lie d to th e f l a s k slo w ly a t f i r s t and th e n th e te n ^ e r a tu r e was r a i s e d u n t i l d i s t i l l a t i o n o c c u rre d . c o m p o sitio n to o k p la c e .

C o n sid e ra b le d e­

The d i s t i l l a t e (1 Gm.) was a brown

u n c tu o u s mass which s o l i d i f i e d on s ta n d in g .

A ttem p ts to

c r y s ta lliz e t h is m a te ria l f a ile d . E xperim ent 4 . S y n th e s is o f N -benzyl

,* ^ d ip h e n y lg lu t a rlm l de and N, N*-

d ib e n z y l 2 , 4 - d ip h e n y lg lu ta r d ia m id e . A m ix tu re o f 34 Gm. o f d i e t h y l 2 , 4 - d ip h e n y lg lu ta r a te and 4 2 .8 Gm. o f benzylam ine was ch arg ed i n t o a h ig h - p r e s s u r e bomb u n d er an atm osphere o f h y d ro g en .

The bomb was ro ck ed

f o r - f i v e h o u rs a t 250® G and a hydrogen p r e s s u r e o f 1500 p s i.

A f te r th e h e a t e r was s h u t o f f and th e bomb had c o o le d

to room te m p e ra tu re , th e r e a c t i o n m ix tu re was removed and ta k e n up i n e t h e r .

The e th e r s o lu tio n was washed fo u r tim e s

w ith 50 c c . p o r tio n s o f 10)^ h y d r o c h lo ric a c id to remove any un< r e a c te d amine and th e e th y lb e n z y la m in e form ed d u rin g th e r e ­ a c tio n .

W hile w a sh in g , p ro d u c t (A) c r y s t a l l i z e d o u t a s w h ite

f la k e s and rem ained suspended i n th e e th e r l a y e r .

The e th e r

13, p o r t io n was s e p a ra te d and f i l t e r e d ,

p ro d u c t (A) w eighed

3«5 Gm., m .p , 260-S61® (aluminum b lo c k ) .

On e v a p o r a tio n

o f th e f i l t r a t e , a b ro w n ish mass rem a in e d .

T h is mass was

d is s o lv e d i n e th a n o l and r e f lu x e d f o r fo u r h o u rs w ith N o r ite .

A f te r f i l t e r i n g , th e h o t a lc o h o lic s o l u t io n was

a llo w ed to c r y s t a l l i z e s p o n ta n e o u s ly .

Twenty gram s o f a

w h ite c r y s t a l l i n e m a t e r i a l (B) was r e c o v e r e d . F iv e gram s o f (B) was f r a c t i o n a l l y c r y s t a l l i z e d from a lc o h o l y ie ld in g p ro d u c ts (C) and (D ).

P ro d u c t (C) w eighed

2 .5 Gm. and m e lte d a t 164.5-165® ; p ro d u c t (D) w eighed 1 .5 Gm. and m e lte d a t 149-150^. A n a ly s is ; (A)

N ,N *-dibenzyl 2 , 4 - d ip h e n y lg lu ta r d ia m id e. C a lc u la te d f o r OgiHgoNOg: N, 6«05J^. Found:

(C)

N, 5*90)^.

N -benzyl

- d ip h e n y lg lu ta r im id e .

C a lc u la te d f o r Og^Hg^NOg: N, 3#94)^. Found; (D)

N, 3#91)K.

N ,N *-dibenzyl 2 ,4 - d ip h e n y lg lu t a r d l am ide. C a lc u la te d f o r Cgj^EggNOg: N, 6.05)^. Found;

Comment ;

N, 6.91)K.

About 20 Gm. o f p ro d u c t was l o s t i n s e v e r a l

a tte m p ts to s e p a r a te (C) and (D) by f r a c t i o n a l d i s t i l l a t i o n o f (B ).

The p ro c e d u re o f t h i s e]q)erlm ent i s e s s e n t i a l l y

th e same a s t h a t u se d by paden and A dkins (19) i n p r e p a r ­ in g o th e r g l u t a rlm l d e s .

14.

 ttenqpteâ p r e p a r a t i o n o f 3, 6—d ip h e n y lp lp e r id in e hy hydro* g e n o ly s ls o f a m ix tu re o f N ,N * -d lb en zy l 2, 4*»diphenylglu* ta r d la m ld e and N *benzyl

- d ip h e n y lg ln ta r im id e .

A m ix tu re o f 11 Gm. o f N ,N * -d ib en zy l 2 , 4 -d ip h e n y l­ g l u t a r d i ami de and N -benzyl

- d lp h e n y lg lu ta r im ide (B o f

E xperim ent 4 ) , 20 c c . o f d io x an and 1 .8 Gm. o f copper c h ro ­ m ite c a t a l y s t (26) was c h a rg e d i n to a h ig h - p r e s s u r e bomb# Hydrogen g a s was in tr o d u c e d a t 1900 p s i and ro c k in g o f th e bomb was s t a r t e d .

A te m p e ra tu re o f 263 to 284® C was m ain­

t a i n e d f o r a p e rio d o f n in e h o u rs . ra n g e d from 3000 to 3100 p s i .

The hydrogen p r e s s u r e

A f te r th e bomb had c o o le d

to room te m p e ra tu re , th e hydrogen was allow ed to e sca p e and th e r e a c t i o n m ix tu re removed and f i l t e r e d .

The d io x an was

e v a p o ra te d o f f on a steam b a th and th e r e s id u e ta k e n up i n a b s o lu te e t h e r .

Dry hydrogen c h lo r id e was p a s s e d i n t o th e

e th e r e a l s o l u t i o n , c a u sin g an o i l to s e p a r a te . to s o l i d i f y t h i s o i l f a i l e d .

A ttem p ts

The o i l and a c id ic e t h e r

s o lu tio n were a g a in combined and e x tr a c t e d w ith w a te r to remove any w a te r - s o lu b le h y d r o c h lo r id e s .

The w a te r s o lu tio n

was th e n n e u t r a l i z e d w ith X0% sodium h y d ro x id e and e x tr a c t e d w ith e th e r#

A f te r d ry in g t h i s e t h e r e a l s o lu tio n o v e r c alciu m

c h lo r i d e , th e e th e r was s t r i p p e d o f f .

The r e s id u e was

t r e a t e d w ith b e n z e n e s u lfo n y l c h lo r id e to d e te c t and remove any seco n d ary amine (3 3 ).

No seco n d ary amine was found

p re s e n t. Comment:

The h y d ro g e n o ly s i s o f s u b s t i t u t e d d l am ides

15. and la d d es i s reeoBtmended by A dkins f o r p r e p a r a t i o n o f sub­ s t i t u t e d p i p e r i d i n e s ( 20 ) . E xperim ent 6 . S y n th e s is o f 2 ,4 - d i p h e n y l g l u t a r o n i t r i l e (1 8 , 2 2 ). One and o n e - te n th gram s o f sodium was d is s o lv e d i n 100 c c . o f f r e s h l y p re p a re d a b s o lu te e th a n o l.

To t h i s so­

l u t i o n was added 26 Qm. o f r e d i s t i l l e d p h e n y l a c e t o n i t r i l e and 2 9 .4 (M. o f f r e s h l y d i s t i l l e d m eth y len e io d id e .

The

m ix tu re was th e n r e f lu x e d f o r e ig h te e n h o u rs o r u n t i l n e u t r a l to litm u s p a p e r. u n t i l b u s s in g s t a r t e d .

The e th a n o l was d i s t i l l e d o f f At t h i s p o in t 50 c c . o f e th e r was

added and th e m ix tu re f i l t e r e d .

The r e s id u e on th e f i l t e r

was washed w ith s e v e r a l 20 c c . p o r t io n s o f e th e r#

The f i l ­

t r a t e s w ere combined and e v a p o ra te d on a steam b a th .

If

any e th a n o l re m a in e d , i t was s tr i p p e d o f f u n d e r vacuum b e­ f o r e th e r e s id u e was su b m itte d to vacuum d i s t i l l a t i o n i n a C la is e n d i s t i l l i n g f l a s k . was c o lle c te d #

A f r a c t i o n b . r . 220-227®/5mm

T h is f r a c t i o n was d is s o lv e d i n e th a n o l,

d e c o lo r iz e d w ith N o r ite and a llo w e d to c r y s t a l l i z e spon­ ta n e o u s ly .

T h ir te e n and f o u r - t e n t h s gram s o f 2 ,4 - d ip h e n y l-

g l u t a r o n i t r i l e was c o l l e c t e d from th e m other l i q u o r ; m .p. 66®; y i e l d :

Comment:

4:9% o f th e o r y .

S o u th e r (18) p r e p a re d 2 , 4 - d ip h e n y lg lu ta r o -

n i t r i l e by c o n d en sin g e th y l e y a n o a e e ta te w ith m ethylene io d id e i n th e p re s e n c e o f sodium e th o x id e . m e ltin g p o in t o f 66®.

He r e p o r te d a

Z e lin s k y and Feldman (22) condensed

16. p h .eaaylaeô'boiiltrlle w ith m ethylene Io d id e i n th e p re s e n c e o f sedlnm hydroxide*

They r e p o r te d a m e ltin g p o i n t o f 70**71®»

E xperim ent 7 . S y n th e s is o f 3, 6- d ip h e n y lp ip e r id ln e and 2,4«i»diphenylpenta« m eth y len ed iam in e by r e d u c tio n o f 2^ 4« * d lp h e n y lg lu ta ro n itrile » F o u rte e n gram s o f 2 ,4 « d i p h e n y l g l u t a r o n l t r i l e , 100 cc* of d io x an and 0»7 Om* o f f r e s h l y p re p a re d Raney n i c k e l c a t a l y s t w ere c h a rg e d i n t o a high**press u r e bomb w ith a ro c k in g mecha«* n i am*

Hydrogen g as a t 1660 p e l was in tr o d u c e d , th e h e a t e r

was tu rn e d o n , and th e ro c k in g mechanism was s ta r te d *

A

te m p e ra tu re o f 200® C and a p r e s s u r e o f 2500 p s i were m ain­ ta in e d f o r a p e r io d o f f i v e hours*

A f te r th e bomb had c o o le d

to room te m p e ra tu re , th e hydrogen was allo w ed to escap e and th e r e a c t i o n m ix tu re was removed and f i l t e r e d *

The fll**

t r a t e was s tr i p p e d o f d io x an and th e n d i s t i l l e d a t re d u c ed p r e s s u r e I n a G la ls e n d i s t i l l i n g fla s k *

A f r a c t i o n weigh*

In g 10 (ha* b* r* 200*238®/15 mm. was c o lle c te d * t i o n was r e d i s t i l l e d a t 2 mm», b . r* 169*179®*

T h is f r a c ­ Dry hydro*

gem c h lo r id e was p a s s e d i n t o an anhydrous e th e r s o l u t io n o f th e r e d i s t i l l e d p ro d u c t u n t i l p r e c i p i t a t i o n no lo n g e r oc­ c u rre d . The p r e c i p i t a t e d h y d ro c h lo rid e was d is s o lv e d i n abso* l u t e is o p r o p y l a lc o h o l and allo w ed to c r y s t a l l i z e i n a vacuum d e s s i e a t o r o v e r c alciu m c h lo rid e *

P ro d u c t (A) con­

tin u e d to c r y s t a l l i z e u n t i l th e is o p r o p y l a lc o h o l had p r a c ­ t i c a l l y evap o rated *

On t r e a t i n g th e r e s id u e w ith anhydrous

17. e t h e r , p ro d a e t (B) p r e c i p it a te d *

(A) was r e c r y s t a l l i z e d

from is o p r o p y l a lc o h o l th r e e tim es*

(B) was r e c r y s t a l l ! z e d

tw ic e from a m ix tu re o f is o p r o p y l a lc o h o l and e t h e r . m. p . 319*320® (alum inum b lo c k ) , w eight 3 (pa*

(B );

(A): m* p .

231*232®, w e ig h t 1 Gm# A n a ly s is : (A)

2^ 4* d ip h e n y lp entam eth y le n e d ia m in e d lh y d ro c h lo rid e ,

C a lc u la te d f o r GiY% 4% G lg : Found: (B)

N, 8*655È.

K, 8*42)^.

3 , 5 * d ip h e n y lp ip e rld in e h y d ro c h lo rid e * C a lc u la te d f o r C^t^HgQÜICl: Found:

N,

M, 5*14^*

E xperim ent 8* S y n th e s is o f e th y l n * b u ty lc y a n o a c e ta te * One h u n d red t h i r t e e n and o n e * te n th grams o f e th y l eya* n o a e e ta te was p la c e d i n a f l a s k f i t t e d w ith a r e f l u x con­ d e n se r w ith a c a lc iu m c h lo r id e tu b e a tta c h e d , a m ercu ry s e a le d s t i r r e r , a therm om eter and a d ro p p in g funnel*

A

s o lu tio n c o n s i s t in g o f 137 Gm. o f n - b u ty l b ro m id e, 10 cc* o f d ry e th y l a c e ta te and 400 cc* o f anhydrous e th a n o l i n w hich 2*5 Gm* o f c le a n sodium was p r e v io u s ly d is s o lv e d was added to th e e s t e r w ith c o n s ta n t s t i r r i n g and a t such a r a t e t h a t th e te m p e ra tu re d id n o t r i s e above 60® C*

When

th e a d d itio n was c o m p le te , th e m ix tu re was r e f lu x e d f o r one h o u r.

S u b se q u e n tly th e e th a n o l was d i s t i l l e d o f f , th e l a s t

t r a c e s b e in g removed u n d e r re d u c ed p re s s u re *

Enough w a te r

18, was t h e n added to d is s o lv e a l l s o l i d m a te r ia l#

The o i l y

l a y e r w hich s e p a r a te d was ta k e n up w ith e th e r and th e aque­ o u s l a y e r was e x tr a c t e d s e v e r a l tim e s w ith sm a ll p o r t io n s o f e th e r#

A f te r th e e th e r s o l u t io n had b e en d r i e d o v e r D rie*

r i t e , i t was e v a p o ra te d on a steam b ath #

The re m a in in g

o i l y r e s id u e was d i s t i l l e d u n d e r vacuum and th e f r a c t i o n b* r# 90*139®/13 mm. was c o l l e c t e d .

T h is f r a c t i o n was th e n

f r a c t i o n a t e d t h r u a V ig reau x column and 83 (ha. o f m a t e r i a l was c o l l e c t e d , b . r# 113*122®/ I 3 mm# ( c h i e f l y 117*118®)# Comment:

H e s s le r and H enderson (21) p re p a r e d e th y l

n - b u ty lc y a n o a c e ta te i n t h i s m anner u s in g b u t y l i o d id e . E xperim ent 9 . Attenq>ted s y n th e s is o f d i e t h y l 2 , 4 * d ic y a n o * 2 ,4 * d lb u ty l* g lu ta ra te . (A)

From e th y l n * b u ty lc y a n o a c e ta te and m ethylene io d id e # F i f t y * s i x and o n e * h a lf grams o f e th y l b u ty lc y a n o a c e *

t a t e was p la c e d i n a o n e * l i t e r , th re e -n e c k e d f l a s k f i t t e d w ith r e f l u x c o n d e n se r, c alc iu m c h lo r id e tu b e , m e rc u ry * se a l­ ed s t i r r e r and d ro p p in g f u n n e l.

A m ix tu re o f 6 6 ,9 (kn. o f

m ethylene Io d id e and a p r e v io u s ly p re p a r e d s o l u t io n o f sodium e th o x ld e i n e th a n o l (12 Gm. o f c le a n sodium , 200 c c , o f a b s o lu te e th a n o l and 6 c c . o f d ry e th y l a c e t a t e ) was added slo w ly to th e e s t e r so t h a t th e te m p e ra tu re d id n o t r i s e above 60® €•

When th e a d d itio n was com plete (a b o u t

two h o u r s ) , th e m ix tu re was r e f lu x e d f o r one h o u r.

Then

a l l th e e th a n o l was d i s t i l l e d o f f and enough w a te r was added

19# %o th e r e s id u e t o d is s o lv e a l l s o l i d m a te r ia l#

s e p a r a te d was e x tr a c t e d w ith e t h e r .

An o i l w hich

The e t h e r e a l s o l u t io n

was d r i e d o v e r D r l e r l t e and e v a p o ra te d on a steam b a th .

The

r e s id u e was d i s t i l l e d a t 13 mm, t h r u a v ig re a u x colum n.

No

c o n s ta n t b o i l i n g f r a c t i o n was c o lle c te d # (B)

Prom e th y l n - b u ty lc y a n o a c e ta te and m eth y len e b ro m id e, p a r t (A) was r e p e a te d u s in g m ethylene brom ide v ic e

m eth y len e io d id e *

I n th e d i s t i l l a t i o n s t e p , 23*4 (kn, o f

e th y l b u ty lc y a n o a c e ta te was re c o v e re d and 2 3 ,4 Gm. o f ma­ t e r i a l b# r . 150-204® /13 mm, was c o l l e c t e d , (C)

From e th y l n -b u ty lc y a n o a c e ta te and m eth y len e brom ide

w ith p ro lo n g e d r e f l u x , p a r t (A) o f t h i s ex p erim en t was r e p e a te d e x c e p t t h a t th e r e f l u x tim e was in c r e a s e d from one h o u r to f o r t y - e i g h t h o u rs .

S im ila r r e s u l t s were o b ta in e d .

Comment:

Z e lin s k y (24) r e p o r t e d th e s y n th e s is o f th e

homologous d i e t h y l 2, 4 - d im e th y l- 2, 4 - d ic y a n o g lu ta r a te by con­ d e n sin g e th y l 2« c y a n o p ro p io n a te w ith m ethylene io d id e ,

in

view o f th e d i f f i c u l t i e s e n c o u n te re d i n t h i s e x p e rim e n t, i t was c o n s id e re d a d v is a b le to a tte m p t a n o th e r m ethod o f syn­ th e s is , E xoerim ent 10. A ttem pted s y n th e s is o f d i e t h y l 2 * 4 - d lc y a n o g lu ta ra te (2 3 ). (A)

From e th y l c y a n o a e e ta te and m ethylene i o d id e . F i f t y - s i x and f i v e - t e n t h s gram s o f e th y l c y a n o a e e ta te

20, was p la c e d I n a o n e - l i t e r , th re e -n e e k e d f l a s k f i t t e d w ith r e f l u x c o n d e n se r, c alciu m c h lo r id e tu b e , m e rc u ry -s e a le d s t i r r e r and d ro p p in g fu n n el*

 m ix tu re o f 6 6 .9 (kn. o f

m ethylene Io d id e and a p r e v io u s ly p re p a re d s o l u t io n o f sodium e th o x ld e i n e th a n o l (12 Om. c le a n sodium , 200 c c . o f a b s o lu te e th a n o l and 5 c c . o f d ry e th y l a c e t a t e ) was added slo w ly w ith s t i r r i n g t o th e e s t e r so t h a t th e te n ^ e r a tu r e d id n o t r i s e o v e r 60® 0 .

When th e a d d itio n was c o sq jle te d

(a b o u t two h o u r s ) , th e m ix tu re was r e f lu x e d f o r one h o u r. Then a l l th e e th a n o l was d i s t i l l e d o f f and th e r e s id u e ta k e n up I n enough w a te r to d is s o lv e a l l s o l i d m a t e r i a l .

An

o i l was th e n e x tr a c t e d from th e aqueous m ix tu re w ith e t h e r , The e t h e r e a l s o lu tio n was d r ie d o v e r D r i e r i t e f o r tw e lv e h o u rs and th e e th e r e v a p o ra te d o f f on a steam b a th .

The

r e s u l t i n g r e s id u e was d i s t i l l e d th r u a V ig reau x column a t 13 mm, 25 Gm, o f e th y l c y a n o a e e ta te was re c o v e re d and th e rem a in d e r o f th e m a t e r i a l decomposed and c h a r r e d i n th e d is tillin g fla s k , (B)

Prom e th y l c y a n o a e e ta te and g l y c o l o n i t r i l e (2 3 ), Two h u n d red and t e n grams o f a b s o lu te e th a n o l was

p la c e d i n a o n e - l i t e r th re e -n e c k e d f l a s k f i t t e d w ith r e f l u x c o n d e n se r, c a lc iu m c h lo r id e tu b e , m e rc u ry -s e a le d s t i r r e r and d ro p p in g f u n n e l.

S e v e n te en and f o u r - t e n t h s grams o f c le a n

sodium was th e n added to th e e th a n o l.

When s o lu tio n was

com plete and th e m ix tu re c o o le d , 5 6 ,6 Gm, o f e th y l cyanoa c e t a t e was added w ith s t i r r i n g .

The s o d l o - d e r i v a ti v e o f

21# th e e s t e r p r e e l p i t a t e d and c o n s id e r a b le h e a t was g e n e ra te d * f i f t e e n gram s o f g l y c o l o n i t r i l e was th e n added g r a d u a lly to th e h o t m ix tu r e .

S t i r r i n g o f th e m ix tu re was c o n tin u e d o v e r

n ig h t to a llo w c o i ^ l e t i o n o f th e r e a c t i o n .

Then th e e n t i r e

m ix tu re was p o u red i n t o a l a r g e e x c e ss o f w a te r and n e u t r a l ­ iz e d w ith 10^ h y d ro c h lo ric acid*

The r e s u l t i n g s o l u t io n was

e x tr a c te d w ith s e v e r a l p o r t io n s o f e t h e r .

T hese e th e r ex­

t r a c t s w ere comd)ined and washed w ith a c o ld , d i l u t e s o l u t io n o f sodium c a rb o n a te and s e v e r a l p o r tio n s o f w ater#

A f te r

th e e th e r e a l s o lu tio n was d r ie d o v e r c a lc iu m c h lo r id e i t was e v a p o ra te d on a steam b a th .

A sm all amount o f n o n -

d i s t i l l a b l e r e s id u e rem ained* (C)

From e th y l c y a n o a e e ta te and g l y c o l o n i t r i l e w ith re flu x * P a r t (B) o f t h i s ex p erim en t was r e p e a te d e x c e p t t h a t

th e r e a c t i o n m ix tu re was r e f lu x e d d u rin g th e a d d itio n o f g l y c o l o n i t r i l e and f o r an a d d i t i o n a l hour#

An o i l y r e s id u e

was o b ta in e d from e v a p o ra tio n o f th e e th e r e x t r a c t .

T h is

o i l was d i s t i l l e d a t 15 mm. to y i e l d 10 Gm, o f e th y l cyano­ a e e ta te and 5 Gm. o f m a t e r i a l b , r , 180-165® /15 mm.

The

l a t t e r f r a c t i o n was i d e n t i f i e d a s e th y l 2 , 3-d ic y a n o p ro p ano a te by h y d r o ly s is and d e c a rb o x y la tio n to s u c c in ic a c id . Comment;

g ig son and Thorpe (23) p r e p a re d d i e t h y l 2 ,4 -

d ie y a n o g lu ta r a te i n th e manner o f p a r t (B ),

They r e p o r te d

t h a t i f th e r e a c t i o n was ru n i n th e c o ld e th y l 2, 3- d i c y an opropanoate r e s u lte d #

The g l y c o l o n i t r i l e u se d i n p a r t s

(B) and (0 ) was d i s t i l l e d from an e x p e rim e n ta l sasqple o f

22i

a p r e s e r v e d aqueous s o lu tio n o f g l y c o l o n i t r i l e f u r n is h e d by th e A m erican Cyan ami de Company. E xperim ent 11# S y n th e s is o f 2, 6- p y r id ln e d ic a r b o x y lic a c id ( d i p i c o l i n i c a c id , 2, 6- l u t i d i n i c a c id ) ( 2 7 ). I n a 2000 c c . b e a k e r were p la c e d 1500 c c . o f w a te r , 1 0 .7 Gm. o f 2 , 6 - l u t i d i n e and 6 5 .2 Gm. o f p o ta s siu m p e r ­ m anganate.

The m ix tu re was h e a te d to a g e n tle b o i l on a

h o t p l a t e w ith c o n s ta n t e f f i c i e n t s t i r r i n g f o r f i v e hours# At t h i s p o in t th e s o lu tio n was c o m p le te ly d e c o lo r iz e d by a d d itio n o f sm all p o r t io n s o f e th a n o l and was f i l t e r e d w h ile h o t. b a th .

The f i l t r a t e was th e n e v a p o ra te d to d ry n e s s on a steam S u f f i c i e n t w a te r was added to th e r e s id u e to e f f e c t

s o l u t io n .

A f te r f i l t e r i n g th e c o n c e n tr a te d s o l u t io n o f

th e p o ta ssiu m s a l t was made s tr o n g ly a c id w ith c o n c e n tr a te d h y d ro c h lo ric acid*

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

and washed w ith s e v e r a l sm a ll p o r tio n s o f c o ld w a te r.

T h is

p ro d u c t was a p p a r e n tly th e complex CgggNCOgH(COgK) ^CgEgN (C0gH)g*3Hg0 r e p o r te d by P in n e r (5 4 ).

By su sp en d in g th e

c o i^ le x i n 60 c c . o f w a te r and a g a in t r e a t i n g w ith concen­ t r a t e d h y d ro c h lo ric a c id , th e f r e e a c id was o b ta in e d .

The

c r y s t a l s were f i l t e r e d o f f , washed w ith s e v e r a l sm a ll p o r­ t i o n s o f w a te r and d rie d #

The f r e e a c id m e lte d a t 236®,

Y ie ld s w ere 46 to 56^ o f th e t h e o r e t i c a l ,

A sm a ll amount

o f th e f r e e a c id was re c o v e re d from th e m other liq u o r s # Comment; a y i e l d o f 60)K#

Hess and W essing (27) r e p o r te d m .p, 236® and

23i Experiment 12#

S y n th e s is ©f 2 , 6- p y r id ln e d ie a r b o x y lic a c id c h lo r i d e (2 8 ) . I n a 200 c e . round -bottom ed f l a s k f i t t e d w ith a r e f l u x co n d en ser and c a lc iu m c h lo r id e tu b e w ere p la c e d 21 Gm. o f 2 ,6 - p y r id ln e d ie a r b o x y llo a c id and 44 #6 Gm. o f t h io n y l c h lo rid e .

The m ix tu re was r e f lu x e d u n t i l s o l u t io n o c c u rre d

(a b o u t 24 h o u rs)#

Any e x c e s s t h io n y l c h lo r id e was s t r i p p e d

o f f u n d e r re d u c e d p r e s s u r e w ith th e a id o f a w a te r b a th a t 50® G#

Then th e a c id c h lo r id e was ta k e n up I n th lo p h e n e -

f r e e benzene and f i l t e r e d #

At t h i s p o in t re m a in in g t r a c e s

o f th io n y l c h lo r id e were removed by a d d itio n and su b seq u e n t s t r i p p in g o f f o f te n s u c c e s s iv e 20 c c . p o r t io n s o f th lo p h e n c f r e e b en zen e.

I n o rd e r to c r y s t a l l i z e th e a c id c h l o r i d e , no

h e a t was a p p lie d d u rin g th e l a s t benzene-w ash step#

The

r e s u l t i n g c r y s t a l s w ere th e n d r ie d I n a vacuum d e s s i e a t o r o v er p o ta ssiu m hydroxide#

The p ro d u c t m e lte d a t 60-61®.

Y ie ld s w ere 95-99)^ o f th e t h e o r e ti c a l # Gomment: 61®.

W o lffe n s te in and H artw ich (2 8 ) r e p o r te d m#p#

S in c e th e a c id c h lo r id e decomposed w h ile s ta n d in g i n

a d e s s i e a t o r o v e r p o ta ssiu m h y d ro x id e ( 3 0 ) , i t was f r e s h l y p re p a re d each tim e i t was u se d i n a s y n t h e s i s . Experim ent 13. S y n th e s is o f 2 ,6 - d ip r o p io n y lp y r id in e . A t w o - l i t e r th re e -n e c k e d f l a s k was f i t t e d w ith a r e ­ f l u x co n d en ser h a v in g a t a k e - o f f w ith a c a lc iu m c h lo r id e tu b e a tta c h e d , a m e rc u ry -s e a le d H ersh b erg s t i r r e r and a

24# 500 e c . d ro p p in g fu n n el#

A n itr o g e n i n l e t tu b e f o r e q u a liz a ­

t i o n o f p r e s s u r e was a tta c h e d to th e m outh o f th e d ro p p in g fu n n e l as w e ll a s to an open in g i n th e s id e o f th e m ercury se al#

I n th e f l a s k was p la c e d 4*86 Gto. o f magnesium t u r n ­

in g s*

The e n t i r e f l a s k was th e n warmed w ith a s o f t flam e

w h ile a slow s tre a m o f d ry n itr o g e n was p a s s e d th ro u g h th e f l a s k and o u t th e d ro p p in g f u n n e l.

The i n l e t e q u i l l z a t l o n

tu b e was th e n a tta c h e d to th e opened d ro p p in g fu n n e l and th e f l a s k was allo w ed to cool#

A f te r th e f l a s k had c o o le d ,

th e r a t e o f n itr o g e n flow was a d ju s te d so t h a t a s l i g h t p o s i t i v e p r e s s u r e was e x e r te d on th e system .

Then 200 c c .

o f d ry e th e r was in tro d u c e d from th e d ro p p in g fu n n el# Twenty-two and f i v e - t e n t h s gram s o f d ry f r e s h l y - d i s t i l l e d e th y l brom ide was p la c e d i n th e funnel#

S e v e ra l cc# o f th e

e th y l brom ide was added to th e f l a s k and th e m ix tu re was warmed w ith a l i g h t b u lb u n t i l th e r e a c t i o n c o n tin u e d spon­ tan e o u sly #

The s t i r r e r was s t a r t e d and th e re m a in d e r o f

th e e th y l brom ide was added a t such a r a t e t h a t r e f l u x d id n o t become to o vig o ro u s#

When th e a d d itio n was c o m p le te ,

r e f l u x was c o n tin u e d w ith a m a n tle u n t i l a l l o f th e mag­ nesium was consumed. b a th .

The f l a s k was th e n c o o le d I n an i c e -

T h i r t y - s i x and s e v e n - te n th s grams o f anhydrous

cadmium c h lo r id e (A.R. g ra d e ) was added i n sm a ll p o r t io n s w ith th e fu n n e l rem oved.

A f te r a l l th e cadmium c h lo r id e was

added th e m ix tu re was r e f lu x e d f o r one h o u r w ith v ig o ro u s s tirrin g .

At t h i s p o i n t , a l l o f th e G rig n a rd r e a g e n t

sh o u ld have b e en consumed.

E th e r was d i s t i l l e d from th e

25. f l a a k u n t i l a v is c o u s m ass rem ained when 100 cc* o f d ry th io p h e n e - f r e e benzene was in tr o d u c e d and a n o th e r 50 cc* o f d i s t i l l a t e was c o l l e c t e d .

The a p p a ra tu s was a g a in s e t up

f o r r e f l u x and a second 100 c c . p o r t io n o f benzene was in tro * duced.

Here i t was i s ^ o r t a n t t h a t th e m ix tu re was s t i r r e d

v ig o ro u s ly to form a smooth suspension*

When th e m ix tu re

a p p ea re d homogeneous i t was c o o le d to room te m p e ra tu re w ith an i o e - b a th .

Tw enty-one gram s o f 2 ,6 - p y r id in e d ic a r b o x y lic

a c id c h lo r id e d is s o lv e d i n 100 c c . o f d ry th io p h e n e - f r e e benzene was in tr o d u c e d th ro u g h th e d ro p p in g fu n n e l o v e r a t h i r t y to f o r t y - f i v e m inute p e r io d .

When th e a d d itio n was

oonç)let©, th e m ix tu re was r e f lu x e d f o r two h o u rs w ith v ig o r ­ ous s t i r r i n g .

A f te r th e r e a c t i o n m ix tu re c o o le d to room

te m p e ra tu re , i t was decomposed by adding 200 Gm. o f an i e e w a ter m ix tu re and th e n slo w ly ad d in g an e q u iv a le n t o f 20^ s u lfu ric a c id .

The d eco m p o sitio n was c o n s id e re d com plete

when two c l e a r l a y e r s a p p ea re d .

The aqueous l a y e r was

s e p a ra te d and e x tr a c te d w ith s e v e r a l sm a ll p o r t io n s o f b en zen e.

The benzene e x t r a c t s w ere combined w ith th e ben­

zene la y e r and washed s u c c e s s iv e ly w ith two 200 c c . p o r t io n s o f w a te r, one 100 c c . p o r tio n o f 6^ sodium c a rb o n a te s o lu ­ t i o n , two 200 c c . p o r t io n s o f w a te r and one 100 cc* p o r t io n o f a s a t u r a t e d s o lu tio n o f sodium c h lo r id e and th e n f i l t e r e d th ro u g h a l a y e r o f anhydrous sodium s u l f a t e .

On f l a s h i n g

o f f th e benzene an amber to brown c o lo re d o i l w eig h in g 1 4 .5 Gm. rem ain ed .

T h is o i l was d i s t i l l e d and r e d i s t i l l e d u n t i l

c o l o r l e s s a s fo llo w s ;

26# F i r s t d i s t i l l a t i o n b # r . 125-160® /5 mm* R e d is tilla tio n b . r . 120-125®/1 ram*

7 Gm. 6 Gm.

The f i n a l y i e l d was 22^ o f th e t h e o r e t i c a l and th e c ru d e y i e l d was 52)K o f th e t h e o r e t i c a l . Comment :

I n g e n e ra l t h i s ex p erim e n t was c o n d u cted i n

th e same m anner a s p r e s c r ib e d by Cason and F ro u t (2 9 ) f o r th e p r e p a r a tio n o f k e to n e s from a c id c h l o r i d e s .

The r e ­

a c tio n betw een th e a c id c h lo r id e and th e cadmium r e a g e n t was t r i e d a t 0®, 25®, and 80®. about 10^ i n c r e a s e i n y i e l d .

H igher te m p e ra tu re s gave T h is s te p was ru n u s in g d ry

e th e r v ic e d ry benzene a s th e r e a c t i o n medium w ith o u t i n ­ c re a s e i n y i e l d .

However, th e u s e o f benzene f a c i l i t a t e d

s t i r r i n g th e r e a c t i o n m ix tu r e .

R e p la cin g 0 .1 1 mole o f

cadmium c h lo r id e by 0.2 mole d id n o t seem to a f f e c t y i e l d s . I n a l l c a s e s , th e c ru d e y i e l d v a r ie d from 45 to 55)^ o f th e th e o re tic a l.

I n g e n e ra l th e o rg a n o m e ta llic complex was

d i f f i c u l t to decompose and a w h ite s u b s ta n c e , w hich ap­ p e a re d to be a cadmium s a l t , p r e c i p i t a t e d from th e aqueous la y e r on s ta n d in g . E xperim ent 14. P r e p a r a tio n o f th e b is - 2 ,4 - d in itr o p h e n y lh y d r a z o n e o f 2 ,6 d ip r o p io n y lp y r id in e . The d in itro p h e n y lh y d ra z o n e was p re p a re d by th e p ro c e d u re p r e s c r ib e d by S h r in e r and Pu son (3 6 ).

One and o n e - h a lf

grams o f 2 , 4 * d ln itro p h e n y lh y d ra z in e , 1 Gm. o f th e 2 , 6 - d i p ro p !o n y lp y rid in e and i.00 c c . o f 96% e th a n o l w ere b ro u g h t to b o ilin g .

Then, 2 c c . o f c o n c e n tra te d h y d r o c h lo r ic a c id was

27# added and b o i l i n g was c o n tin u e d f o r s e v e r a l m inutes# G r y s t a l l l a a t i o n to o k p la c e im m e d ia te ly .

The m ix tu re was

a llo w e d to c o o l to room t e n p e r a t u r e b e fo r e th e o ra n g e c o lo re d hydrazone was f i l t e r e d o f f .

On r e c r y s t a l l i z a t i o n

from 96% e th a n o l two tim e s th e hydrazone m e lte d a t 272273® i n an aluminum b lo c k . A n a ly s is ; C a lc u la te d f o r CggBg^^OgNg: Found:

N, 2 2 .8 6 ^ .

N, 22*82%; 22*96%*

E xperim ent 1 5 . C a ta ly t i c r e d u c tio n o f 2 , 6* d ip r o p io n y lp y rid in e h y d ro c h lo rid e to 2, 6- b i 8- ( 1- h y d ro x y p r o p y l) p ip e rid in e h y d ro c h lo rid e w ith p la tin u m o x id e . (A)

U sing p la tin u m o x id e c a t a l y s t and c o n c e n tr a te d hydro­

c h lo r i c a c id . Two grams o f d ip r o p io n y lp y r id in e , 30 c c . o f concen­ t r a t e d h y d ro c h lo ric a c id and 0 .1 Gm. o f p la tin u m o x id e c a t a l y s t were in tro d u c e d i n t o a P a rr h y d ro g e n a tio n a p p a ra tu s . The m ix tu re was shaken w ith hydrogen a t th r e e atm ospheres f o r tw e n ty -fo u r h o u rs . Comments

No hydrogen was a d so rb e d .

2 , 6» d ip ro p io n y Ip y rid in e h y d ro c h lo rid e hy­

d r o ly s e s i n w a te r.

I n a s i t u a t i o n o f t h i s k in d . Crook and

M cElvain (11) u se d enough e x c e ss o f h y d ro c h lo ric a c id to p r e v e n t h y d r o ly s is i n w a te r s o l u t io n . U sing p la tin u m o x id e c a t a l y s t and a s l i g h t e x c e ss o f d ry hydrogen c h lo r id e gas i n a b s o lu te e th a n o l.

28*

Two grams o f d lp ro p io n y lp y rld in ® , 100 c c . o f a b s o lu te e th a n o l, 0 .1 Gm. o f p la tin u m o x id e and a s l i g h t e x c e ss o f an e q u iv a le n t amount o f d ry hydrogen c h lo r id e w ere i n t r o ­ duced in to , th e r e a c t i o n b o t t l e on a F a r r h y d ro g e n a tio n ap­ p a ra tu s .

The m ix tu re was shaken w ith hydrogen a t t h r e e

atm ospheres f o r tw e n ty -fo u r h o u rs .

A drop i n hydrogen p r e s ­

su re o f 60% o f th e t h e o r e t i c a l o c c u rre d .

A f te r f i l t e r i n g

o f f th e c a t a l y s t th e e th a n o l was s t r i p p e d from th e r e a c t i o n m ix tu re u n d e r re d u c e d p r e s s u r e a t 60-60®.

The r e s id u e i n

th e f l a s k was d is s o lv e d i n enough h o t e th a n o l to e f f e c t s o lu tio n .

A b so lu te e th e r was th e n added to th e h o t s o lu ­

t i o n u n t i l th e c lo u d p o in t a p p ea re d .

On sta n d in g 200 mg*

o f a h y d ro c h lo rid e (A) c r y s t a l l i z e d , m .p. 223-224® a f t e r one r e c r y s t a l l i z a t i o n .

The m other l i q u o r was c o n c e n tra te d

u n t i l ab o u t h a l f o f th e a lc o h o l was rem oved.

A gain abso­

l u t e e th e r was added w h ile h o t u n t i l th e c lo u d p o in t ap­ p e a re d .

On s ta n d in g , a h y d ro c h lo rid e (B) c r y s t a l l i z e d ,

m .p. 208-211®.

A f te r one r e c r y s t a l l i z a t i o n 5 mg. o f (B)

rem ain ed , m .p, 211®.

F u r th e r c o n c e n tr a tio n o f th e m other

liq u o r y ie ld e d s e v e r a l mg. o f a h y d ro c h lo rid e (C ), m .p. 199-203®.

Mixed m e ltin g p o i n t s ;

AB 197-200®; BC 200-205®.

A n a ly s is : C a lc u la te d f o r ; pound; Comment;

OnHg^OgNCl:

N, 6^93%*

N, 6*14%; 5*09%* C ra ig and Hixon (36) have u se d a s l i g h t

ex cess o f d ry hydrogen c h lo r id e i n a b s o lu te e th a n o l f o r c a t a l y t i c r e d u c tio n o f am in es.

The y i e l d s o f th e r e d u c tio n

29. de n e t c o rre sp o n d to th e amount o f hydrogen a p p a r e n tly a b ­ so rb e d .

T h is e x c e s s iv e drop i n p r e s s u r e i s a cc o u n te d f o r

by te m p e ra tu re changes# S u f f i c i e n t q u a n t i t i e s o f (B) and (C) w ere n o t a v a i la b l e fo r a n a ly s is .

From m ixed m e ltin g p o i n t s (C) was assum ed to

be im pure