Enantiomeric enrichment of cyanohydrins

Abstract

A method of enantiomerically enriching chiral cyanohydrins is disclosed that involves selective cleavage of the unwanted enantiomer into its cleavage products HCN and the corresponding aldehyde or ketone by use of an enantioselective dehydrocyanation catalyst, coupled with simultaneous removal of at least one of the dehydrocyanation products.

What is claimed is: 
     
       1. An enzymatic process for the enantiomeric enrichment of a chiral cyanohydrin of the structure ##STR16## comprising the steps: (a) bringing said mixture of chiral cyanohydrins into contact at a pH of 3.5 to 5.5 with an enantioselective dehydrocyanation catalyst selected from the group consisting of (R)- and (S)- oxynitrilase and cyclic peptides until one of said chiral cyanohydrins is converted in a dehydrocyanation reaction to dehydrocyanation reaction products comprising hydrogen cyanide and an aldehyde or ketone of the structure ##STR17## (b) simultaneously reducing the concentration of at least one of said dehydrocyanation reaction products by a method selected from a liquid-liquid extraction, a liquid-gas extraction, a membrane-based separation, a chemical conversion, and combinations thereof where (i) R 1  and R 2 , taken together, form a diyl hydrocarbon chain containing 3 to 5 carbons, or   (ii) R 1  and R 2  are different and R 1  is selected from straight and branched chain alkyl, cycloalkyl, heterocyclic and aryl groups, said cycloalkyl, said heterocyclic and said aryl groups being unsubstituted or substituted with a substituent selected from the groups consisting of halo, hydroxy, lower alkyl, lower alkoxy, lower alkylthio, cycloalkyl, carbamoyl, trifluoromethyl, phenyl, .Iadd.phenoxy, .Iaddend.nitro, alkylsulfonyl, arylsulfonyl, alkylcarboxamide, and . .acrylcarboxamido,.!. .Iadd.arylcarboxamido, .Iaddend.and R 2  is selected from hydrogen and R 1 .   
     
     
       2. The process of claim 1 wherein step (a) is conducted in a liquid phase selected from an organic, an aqueous, an organic/organic mixture, and an organic/aqueous mixture. 
     
     
       3. The process of claim 1 wherein step (b) is conducted by a liquid-liquid extraction and the liquid in said extraction is an organic liquid. 
     
     
       4. The process of claim 3 wherein said organic liquid in said extraction is a cyanohydrin. 
     
     
       5. The method of claim 1 wherein step (b) is conducted by a liquid-liquid extraction and the liquid in said extraction is a mixture of immiscible liquids. 
     
     
       6. The method of claim 1 wherein step (b) is conducted by a liquid-gas extraction utilizing gas as a sweep or a sparge. 
     
     
       7. The method of claim 1 wherein step (b) is conducted by a membrane-based separation selected from a method utilizing a supported-gas membrane or a membrane contactor. 
     
     
       8. The method of claim 7 wherein step (b) is conducted by a method utilizing a hydrophilic supported-gas membrane. 
     
     
       9. The method of claim 7 wherein step (b) is conducted by a method utilizing a hydrophobic supported-gas membrane. 
     
     
       10. The method of claim 9 wherein a polymer is coated on said hydrophobic supported-gas membrane. 
     
     
       11. The method of claim 10 wherein said polymer is poly(dimethylsiloxane). 
     
     
       12. The method of claim 1 wherein step (b) is conducted by a chemical conversion of the dehydrocyanation .Iadd.reaction .Iaddend.product hydrogen cyanide to form a cyanohydrin, said chemical conversion being selected from hydrolysis, alkylation and hydrocyanation. 
     
     
       13. The method of claim 1 wherein step (b) is conducted by a chemical conversion of the dehydrocyanation reaction product aldehyde or ketone that is selected from reactions with compounds selected from the group consisting of bisulfites, amines, diamines, hydroxylamines, hydrazines, and oxidants. 
     
     
       14. The method of claim 1 wherein said dehydrocyanation catalyst of step (a) is dissolved or immobilized. 
     
     
       15. The method of claim 1 wherein R 1  is m-phenoxyphenyl, R 2  is hydrogen and said dehydrocyanation catalyst of step (a) is (R)-oxynitrilase. 
     
     
       16. The method of claim 1 wherein R 2  is hydrogen and R 1  is selected from m- and p-methoxyphenyl; furfuryl and 5-methylfurfuryl; and piperonyl. 
     
     
       17. The method of claim 1 wherein step (b) is conducted by contacting said cyanohydrin dehydrocyanation products with one side of a two-sided supported-gas membrane and circulating an aqueous alkaline solution on the other side of said supported-gas membrane. 
     
     
       18. The method of claim 1 wherein step (b) is conducted by extraction of said aldehyde or ketone cleavage product into an organic liquid. 
     
     
       19. The method of claim 1 wherein step (b) is conducted by a membrane-based separation utilizing a combination of a supported-gas membrane and a membrane contactor.