Separation of optically active amides

Details Separation of optically active amides Separation of optically active amides

1998-01-27

1999-05-18

Killos, Paul J.

Organic compounds -- part of the class 532-570 series

Organic compounds

Carboxylic acids and salts thereof

564384, 564385, 564424, C07C59/125

Patent

active

059051671

DESCRIPTION:

BRIEF SUMMARY
The present invention relates to a novel process for cleaving optically active amides.
The hydrolytic cleavage of optically active amides which have a center of chirality in the amine part of the molecule cannot be carried out, or can be carried out only under very elaborate conditions, to result in retention of the center of chirality.
Devant and Braun (Chem. Berichte 119 (1986) 2197-2207) describe the impossibility of eliminating chiral amines from acetamides without destruction of the center of chirality (page 2194). The authors furthermore find that numerous attempts to hydrolyze the amides with alkali or acid to the carboxylic acid and optically active amine were unsuccessful, and that only reaction with dinitrogen tetroxide as described by White (J. Am. Chem. Soc. 77 (1955) 6008) leads to the desired result. However, this reaction with N.sub.2 O.sub.4 is complicated and therefore unsuitable for industrial processes.
WO 95/08636 describes an enzymatic process for the resolution of racemates of optically active amines, in which the amines are acylated enantioselectively with an ester, then the mixture of acylated amine (amide) and unreacted amine is separated and, if required, the optically active amine is liberated from the acylated amine (amide) by amide cleavage. However, no parameters for process in which the amide cleavage can be carried out are given.
It is an object of the present invention to provide, precisely in view of the efficient process described in WO 95/08636 for the resolution of racemates of amines, a low-cost process which can readily be carried out industrially for the hydrolysis of optically active amides with retention of the center of chirality.
We have found that this object is achieved by a process for cleaving optically active amides to carboxylic acids and optically active amines with retention of the center of chirality, wherein the amides are hydrolyzed in the presence of a polyol or of an amino alcohol and of an alkali metal or alkaline earth metal hydroxide.
The process according to the invention is suitable for virtually all amides which can be prepared from optically active primary or secondary amines. It is particularly suitable for amides whose amine part consists of an optically active arylalkylamine.
It takes place particularly well with primary arylalkylamines, for example those of the following structures: ##STR1## where X is any conventional aromatic substituent, in particular halogen, nitro, cyano, C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkoxy and C.sub.1 -C.sub.4 -alkylthio.
The process according to the invention is furthermore suitable for cleaving amides whose amine part consists of an amino alcohol of the general formula ##STR2## in which the substituents have the following meanings:
R.sup.5, R.sup.6 =independently of one another H, branched and unbranched C.sub.1 -C.sub.10 -alkyl, C.sub.1 -C.sub.4 -alkoxycarbonyl, phenyl, phenyl-C.sub.1 -C.sub.4 -alkyl, it being possible for the phenyl groups to be substituted by halogen, nitro, cyano, C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkoxy and C.sub.1 -C.sub.4 -alkylthio. It is furthermore possible for R.sup.5 and R.sup.6 to be connected by a carbon chain, which can be interruped by oxygen, sulfur or nitrogen and in turn be substituted, to form a mono-, bi- or tricyclic system
R.sup.7 =H, C.sub.1 -C.sub.10 -alkyl, C.sub.1 -C.sub.4 -alkoxycarbonyl
R.sup.8 =H, C.sub.1 -C.sub.10 -alkyl
n=0 or 1.
Where the carbon atoms substituted by OR.sup.7 or NHR.sup.8 are stereogenic centers, the process according to the invention relates both to the syn and to the anti isomers.
Examples of amino alcohols of the above general structure which may be mentioned are:
2-amino-1-butanol; ephedrine; pseudoephedrine; norephedrine; norpseudoephedrine; tert-leucinol; phenylglycidol; 1,2-diphenylaminoethanol; cis- and trans-2-aminocyclopentanol; cis- and trans-1-amino-2-hydroxyindane; cis- and trans-2-aminocyclohexanol, statine, 2-hydroxy-3-aminophenylpropionic acid.
Preferred amino alcohols which may be mentioned are: cis- and trans-

REFERENCES:
patent: 3592854 (1971-07-01), Potts et al.

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