Case of Chiral Resolution through Converting Two Racemic Compounds into a Conglomerate

The formation of a conglomerate is always attractive, which is a prerequisite for chiral resolution by a flexible and productive preferential crystallization. This present study is aimed at exploring the possibility of chiral resolution in a two racemic compound system. The racemic conglomerate of S–S and R–R was prepared by slurring RS-naproxen (RS-NAP) with RS-1-(2-naphthyl) ethylamine (RS-NEA), which was determined by powder X-ray diffraction, differential scanning calorimetry, single-crystal X-ray diffraction, and ternary solubility phase diagram. Moreover, comparative analysis of the molecular structure, stacking patterns, thermodynamic properties, and intermolecular interactions of S–S and R–S indicates that the S–S crystal is more stable. Finally, the feasibility of chiral resolution in isopropanol was explored through a seeded isothermal preferential crystallization mode, and alternative crystallization of S–S and R–R was achieved with recycling the mother liquors.