The Same but Not the Same: The Case of (S)-Naproxen/cis-1-Amino-2-indanol Chiral Resolution via Diastereomeric Salt Formation

The solid state of four novel S-(+)-Naproxen (S-Nap) diastereomeric salts with cis-1-amino-2-indanol (SR-AI and RS-AI enantiomers) is reported. The anhydrous SR-AI_S-Nap_A is the only obtained phase in all the experimental conditions used, while the kinetically preferred diastereomeric salt RS-AI_S-Nap_A1 forms only in certain conditions and undergoes an irreversible phase transition to RS-AI_S-Nap_A2 after melting; this second phase was obtained even by dehydration of the monohydrate salt RS-AI_S-Nap_W. The preferred crystallization of SR-AI_S-Nap_A was observed when S-Nap was introduced in a solution containing equimolar quantity of the racemic cis-1-amino-2-indanol, in spite of the strict similarity of the crystal packings of SR-AI_S-Nap_A and RS-AI_S-Nap_A1. With the aim of trying to explain the preference of S-Nap for the SR-AI enantiomer, an in-depth analysis and comparison of the diastereomeric salt crystal structures were carried out.