Chromatographic Optical Resolution on Polysaccharide Carbamate

Chapter 5

Chromatographic Optical Resolution on Polysaccharide Carbamate Phases 1

1

2

2

Yoshio Okamoto , Yuriko Kaida , Ryo Aburatani , and Koichi Hatada

Downloaded by UNIV LAVAL on May 6, 2016 | http://pubs.acs.org Publication Date: August 14, 1991 | doi: 10.1021/bk-1991-0471.ch005

1

Department of Synthetic Chemistry, Faculty of Engineering, Nagoya University, Chikusa-ku, Nagoya 464-01, Japan Department of Chemistry, Faculty of Engineering Science, Osaka University, Toyonaka, Osaka 560, Japan 2

P h e n y l - , a r a l k y l - , and alkylcarbamates of p o l y s a c c h a r i d e s , c e l l u l o s e and amylose, were p r e pared by the r e a c t i o n of the polysaccharides with corresponding isocyanates. The carbamates were adsorbed on silica gel to use as c h i r a l s t a t i o n a r y phases f o r HPLC. Optical resolving abilities of the carbamates were evaluated by using a hexane-2-propanol mixture as eluent. Alkylcarbamates of both c e l l u l o s e and amylose showed low c h i r a l r e c o g n i t i o n . Optical resolving abilities of phenylcarbamate derivatives having a substituent on phenyl group depended on the kind and p o s i t i o n of the s u b s t i t u e n t , and 3,5-dimethylphenylcarbamates of both p o l y s a c c h a r i d e s gave p r a c t i c a l l y u s e f u l c h i r a l s t a t i o n a r y phases. 1-Phenylethylcarbamates a l s o e x h i b i t e d interesting chiral recognition. Optical resolving abilities of 3,5-dimethylphenylcarbamates of o l i g o s a c c h a r i d e s were a l s o evaluated. In the past ten y e a r s , many c h i r a l s t a t i o n a r y phases (CSP) f o r high-performance l i q u i d chromatography (HPLC) have been developed ( 1 - 3 ) . CSP can be prepared from both o p t i c a l l y a c t i v e small molecules and polymers. These are usually chemically bonded or adsorbed on s i l i c a g e l . In the chromatographic system with a CSP of a small molecule, the mechanism of c h i r a l r e c o g n i t i o n can be estimated through s p e c t r o s c o p i c s t u d i e s on the i n t e r a c t i o n between the c h i r a l compound used f o r CSP and the compound to be r e s o l v e d . On the other hand, i n the system with a CSP of a polymer, the understanding of c h i r a l r e c o g n i t i o n mechanism i n a molecular l e v e l is

0097-6156/91/0471-0101$06.00/0 © 1991 American Chemical Society Ahuja; Chiral Separations by Liquid Chromatography ACS Symposium Series; American Chemical Society: Washington, DC, 1991.

102

CHIRAL SEPARATIONS BY LIQUID C H R O M A T O G R A P H Y

OCONH-^


Cellulose tris(phenylcarbamate)

OCONH-^^

Amylose tris(phenylcarbamate)

u s u a l l y d i f f i c u l t b e c a u s e i n many c a s e s t h e e x a c t steric s t r u c t u r e s of a polymer is not a v a i l a b l e . Nevertheless, polymeric CSPs are i n t e r e s t i n g because their chiral recognition depends on the h i g h e r - o r d e r s t r u c t u r e o f the polymer and unexpected high chiral recognition ability may appear due to the higher-order structure of the polymer. Polysaccharides such as cellulose and amylose a r e the most a c c e s s i b l e o p t i c a l l y a c t i v e p o l y m e r s . These polysaccharides t h e m s e l v e s show r a t h e r low c h i r a l recognition, but their derivatives, particularly carbamate derivatives exhibit high chiral recognition and can separate broad racemic compounds into optical isomers (2,4). In t h i s article, optical resolution by tris(psubstituted phenylcarbamate)s of cellulose is briefly described, and then c h i r a l r e c o g n i t i o n by 3,5d i s u b s t i t u t e d phenylcarbamates of c e l l u l o s e , and amylose, and t h e i r o l i g o m e r s i s discussed. Optical resolving powers o f a r a l k y l c a r b a m a t e s such as benzylcarbamate and 1-phenylethylcarbamate of the polysaccharides are also evaluated. Experimental P o l y s a c c h a r i d e carbamates were p r e p a r e d by the reaction of polysaccharides with corresponding isocyanate derivatives. *H-NMR and elemental analyses indicated that hydroxy group were almost quantitatively converted to urethane moieties. The derivatives were adsorbed on macroporous s i l i c a gel (particle size 7 or 10 | / m , pore s i z e 4 0 0 nm) w h i c h h a d b e e n treated with 3-aminopropyltriethoxysilane; the weight ratio of the carbamate to silica gel was 25:100. Each of the packing materials o b t a i n e d was p a c k e d i n a s t a i n l e s s - s t e e l tube (25 x 0.46 ( i d ) cm) b y a s l u r r y m e t h o d . C h r o m a t o g r a p h i c a n a l y s i s was p e r f o r m e d on a JASCO TRIROTAR-II c h r o m a t o g r a p h i c e q u i p p e d UV a n d p o l a r i m e t r i c (JASCO D I P - 1 8 1 C ) detectors using a hexane-2-propanol (90:10) m i x t u r e as an e l u e n t at a flow r a t e o f 0.5 ml/min at 25°C. Dead time (t ) was determined with 1,3,5-tri-tert-butylbenzene. Most columns e x h i b i t e d t h e o r e t i c a l p l a t e numbers between 3000-6000 f o r benzene. Q

Ahuja; Chiral Separations by Liquid Chromatography ACS Symposium Series; American Chemical Society: Washington, DC, 1991.

5.

OKAMOTO ET AL.


Resolution

on

Chromatographic Optical Resolution

4-Substituted

Phenylcarbamates

of

103

Cellulose

Optical resolving abilities of various 4-substituted phenylcarbamates (1) of cellulose have been evaluated (4-6). T a b l e I shows t h e s e p a r a t i o n factors (a) for 9 r a c e m i c compounds ( 3 - 1 1 ) on eleven 4-substituted phenylcarbamates (la-k). The s u b s t i t u e n t s a r e a r r a n g e d i n the increasing order of electron-withdrawing power f r o m left to r i g h t i n the t a b l e . The o p t i c a l r e s o l v i n g a b i l i t y is i n f l u e n c e d v e r y much b y t h e s u b s t i t u e n t i n t r o d u c e d on the phenyl group. Phenylcarbamates l a and l k containing a h e t e r o a t o m show v e r y l o w c h i r a l recognition. The best chiral discrimination is attained either alkyl-substituted o r h a l o g e n - s u b s t i t u t e d phenylcarbamates. This results indicates that inductive effect of substituents influences the c h i r a l r e c o g n i t i o n of CSP. t-Butylphenylcarbamate le exhibits particularly high optical resolving power. In t h i s case, sterical effect of t-butyl group may a l s o p l a y a n i m p o r t a n t role. A schematic hydrogen bond i n t e r a c t i o n between a phenylcarbamate group and the carbonyl or hydroxy group of a solute is depicted i n F i g u r e 1. B o t h NH a n d C O o f the carbamate moiety can i n t e r a c t with a solute through hydrogen bond. The i n t r o d u c t i o n o f an electron-donating group l i k e t - b u t y l p r o b a b l y i n c r e a s e s the e l e c t r o n density of the carbonyl oxygen, which may facilitate the hydrogen bond on this oxygen. On the other hand, an electron-withdrawing substituent like halogen increases t h e a c i d i t y o f NH p r o t o n . T h i s has been c o n f i r m e d by the d o w n - f i e l d s h i f t o f NH r e s o n a n c e in H NMR s p e c t r a o f the cellulose phenylcarbamates (5). The i n c r e a s e of acidity o f NH p r o t o n s h o u l d e n h a n c e the c a p a b i l i t y of the hydrogen bond f o r m a t i o n o f t h i s p r o t o n w i t h an electron-donating group l i k e c a r b o n y l . Thus, the i n t r o d u c t i o n of alkyl or halogen group is expected to r a i s e the c h i r a l recognition a b i l i t y of cellulose tris(phenylcarbamate)s. Polar substituents like CHoO a n d NOo t h e m s e l v e s c a n interact 1


104

CHIRAL SEPARATIONS BY U Q U I D C H R O M A T O G R A P H Y

CM

Ο

r*

!Z3

• ο

•Η


CJ

rH

^

k{ 3 4 5 10 11

a

2.42(-) *1 2 . 4 9 ( - ) 1.30 1.00(+) 1.36 not e l u t e d not e l u t e d

k

0-•CD a i

1.46(-) 1.76(-) 0.87(+) 2.50(-) 7.75

1.15 1.22 1.37 1.15 1.00

Amylose

7 - CD k

i

0.95(-) 1.36(+) 0.66(-) 1.83(-) 7.34(-)

a 1.52 1.05 1.16 1.11 1.10

k

a

i

5.63(+) 1.30(+) 1.39(+) 2.98(-) 2.67(-)

1.42 1.15 4.29 1.11 1.10

c

a) E l u e n t : h e x a n e - 2 - p r o p a n o l ( 9 9 : 1 ) , 0 . 5 m l / m i n . b) E l u e n t : hexane. c) E l u e n t : hexane-2-propanol (90:10). (Reproduced with permission from reference 8. Copyright 1990 T h e Chemical Society of Japan.) Chiral recognition by t h e 3 , 5 - d i m e t h y l p h e n y l c a r b a mates (14) o f a - , / ? - , and y - c y c l o d e x t r i n e s (n=6,7, and 8) a r e q u i t e d i f f e r e n t from that o f the amylose derivative (Table V ) . The h i g h e r - o r d e r s t r u c t u r e o f the c a r b a mates o f c y c l i c o l i g o s a c c h a r i d e s must be d i f f e r e n t from that of a l i n e a r polysaccharide amylose. The e x i s t e n c e o f these s t r u c t u r a l d i f f e r e n c e s and s i m i l a r i t y between the carbamates o f o l i g o m e r s and p o l y mers i s a l s o e x p e c t e d f r o m t h e CD s p e c t r a o f t h e carbamates (8) . Optical Amylose

Resolution

on A r a l k y l c a r b a m a t e s o f

Cellulose

and

T r i s ( a l k y l c a r b a m a t e ) s such as methylcarbamate and c y c l o hexylcarbamate of c e l l u l o s e show r a t h e r l o w c h i r a l recognition. Optical resolving a b i l i t i e s of aralkylcarbamates



110


such as b e n z y l - (15), ( i ) - l - p h e n y l e t h y l (16), ( l ) - l - ( l naphtylethyl)(17), and diphenylmethylcarbamtes (18) have been tested (Table VI) (9). Three carbamates 15, 17, a n d 18 d i d n o t efficiently separate 5 racemic compounds i n t o o p t i c a l isomers. A l t h o u g h f o u r columns had similar theoretical plate numbers for benzene, 15, 17, and 18 e x h i b i t e d b r o a d p e a k s f o r t h e r a c e m i c c o m p o u n d s in Table V I . H o w e v e r , 16 s h o w r a t h e r h i g h o p t i c a l resolving power f o r 4 compounds, and c a n s e p a r a t e also completely into enantiomers. Among f o u r a r a l k y l c a r b a m a t e s , o n l y 16 forms lyotropic liquid crystalline phase i n tetrahydrofrane. Regularly-ordered structure of the cellulose carbamates seems t o be e s s e n t i a l to o b t a i n an efficient CSP. Analogous results were a l s o o b t a i n e d on the four aralkylcarbamates of amylose. Only (RS)-l-phenylethylcarbamate (20) e x h i b i t e d high optical resolving power (Table V I I ) . Optical resolving a b i l i t y of 20 i s higher t h a n t h a t o f 16 i n m o s t c a s e s . 1-Phenylethyl g r o u p o f 16 a n d 20 is c h i r a l . Xhe i n f l u e n c e o f c h i r a l i t y o f t h i s group on o p t i c a l resolving a b i l i t y was investigated. In case of 16, ( R ) or (RS) derivative showed higher resolving ability than (S) derivative, and on 20, (S) or (RS) derivative shows higher resolving ability (Table V I I I ) . The compounds w h i c h c a n be b e t t e r r e s o l v e d on (S)-20 than o t h e r polys a c c h a r i d e c a r b a m a t e i n c l u d i n g p h e n y l c a r b a m a t e s a r e shown i n T i g u r e 2.

PCONH-R -O

OCONH-R

OCONH-R

OCONH-R

Cellulose derivative

OCONH-R

Amylose derivative

CH

—CH

I

CH

3

CH

3

6

Cellulose

15

16

17

18

Amylose

j9

20

21

22

- Q



5.

Chromatographic Optical Resolution

OKAMOTOETAL.

CeHsCHCaHs

CN

^yOCOC

H

5

\^OCOC H

5

6

6

111

_I C

« 5~V^ H

HO-^Y°

0

O

a=1.35

CH3CH-CCH3

a=1.13

a = 2.03

a=1.23

{

/

a=1.42

C H -S-CH:CH 6

a=1.56

F i g u r e . 2. Racemic compounds r e s o l v e d tris((S)-l-phenylethylcarbamate).

5

2

a=1.52

on

amylose


112


Table V I . O p t i c a l

r e s o l u t i o n on c e l l u l o s e 15

k[ 3 5 9 10 Benzoin

a

0.39(+) 0.27 2.57(-) 0.57(+) 2.03

a r a l k y l c a r b a m a t e s (15-18)

16

-1 1.00 -1 -1 1.00

k{

17

a

0.62(+) 0.52(-) 3.18(-) 0.61(+) 3.67(+>

-1 1.12 1.20 1.37 1.18

18

a

k{

1.00 -1 1.00 -1 1.00

0.51 0.62(-) 1.80 0.25(+) 4.22


The s i g n o f o p t i c a l r o t a t i o n o f t h e f i r s t - e l u t e d in parentheses.

Table V I I . O p t i c a l

3 5 7 10 Benzoin

-1 -1 1.08 -1 1.00

isomer i s shown

*1 -1 -1 -1 -1

k

a

l

22

21

20

a

0.66(+) 0.43(+) 1.00(+) 0.41(+) 2.41(+)

0.97(+) 0.50(-) 1.54(-) 1.25(+) 3.58

r e s o l u t i o n on amylose a r a l k y l c a r b a m a t e s (19-22)

19

k\

a

k{

-1 0.72(+) 1.68(+) 1.15 1 . 6 9 ( - ) 1.24 0.75(-) -1 3.51(+) 1.41

k

a

i

-1 -1 -1 -1 -1

0.79(+) 0.66(-) 1.16(+) 2.50(+) 3.33(+)

The s i g n o f o p t i c a l r o t a t i o n o f t h e f i r s t - e l u t e d in parentheses. Eluent: hexane-2-propanol (90:10).

a

k{

1.0K+)

^1

0.67(+) 1.60(-) 1.92(+) 4.11(+)

1.09 -1 -1 1.21

isomer i s shown

T a b l e V I I I . O p t i c a l r e s o l u t i o n o f racemates on ( R ) - , ( S ) - , and ( R S ) - 2 0 (R)-20 k

3 4 5 6 7 9 11

i

0.74(+) 1.97(+) 0.61(+) 4.46(+) 1.93

Chromatographic Optical Resolution on Polysaccharide Carbamate

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