Structural basis of solid solution formation during chiral resolution

A systematic study of crystal packing in a series of structures is presente d: an isostructural triplet of an optically active compound {(R)-2-(6,7-die thoxy-1,2,3,4-tetrahydro-1-isoquinolidene)-2-[2-hydroxy-3-(4-morpholinyl)pr opyl]mercaptoacetonitrile hydrochloride, C22H32ClN3O4S} 1, its racemate 2 a nd their achiral dehydroxy parent compound {2-(6,7-diethoxy-1,2,3,4-tetrahy dro-1-isoquinolidene)-2-[3-(4-morpholinyl)propyl]mercaptoacetonitrile hydro chloride, C22H32ClN3O3S} 3. Based on the structures we suggest some require ments necessary for an optically active compound and its racemate to be iso structural. 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 (C32H47N3O8S2) 4 sheds light on the possible reasons of this failure. We suggest a few criteria for solid solution forma tion of diastereomeric salts. (C) 2000 Elsevier Science Ltd. All rights res erved.