Structural basis of solid solution formation during chiral resolution

Abstract

A systematic study of crystal packing in a series of structures is presented: an isostructural triplet of an optically active compound {( R)-2-(6,7-diethoxy-1,2,3,4-tetrahydro-1-isoquinolidene)-2-[2-hydroxy-3-(4-morpholinyl)propyl]mercaptoacetonitrile hydrochloride, C 22H 32ClN 3O 4S} 1, its racemate 2 and their achiral dehydroxy parent compound {2-(6,7-diethoxy-1,2,3,4-tetrahydro-1-isoquinolidene)-2-[3-(4-morpholinyl)propyl]mercaptoacetonitrile hydrochloride, C 22H 32ClN 3O 3S} 3. Based on the structures we suggest some requirements necessary for an optically active compound and its racemate to be isostructural. A generally used resolving agent d-champhor sulphonic acid was unable to provide full separation of the racemate. The crystal structure of a partially resolved product (C 32H 47N 3O 8S 2) 4 sheds light on the possible reasons of this failure. We suggest a few criteria for solid solution formation of diastereomeric salts.