Use of Programmed Damped Temperature Cycles for the Deracemization of a Racemic Suspension of a Conglomerate Forming System

作者：Suwannasang Kittisak; Flood Adrian E^*; Rougeot Celine; Coquerel Gerard

来源：Organic Process Research & Development, 2017, 21(4): 623-630.

DOI：10.1021/acs.oprd.7b00028

The current research has developed a potential route toward process optimization for the deracemization of a racemizable conglomerate forming system. The use of damped temperature cycles where the magnitude of the temperature cycles is reduced as the enantiomeric excess (ee) in the solid phase increases is a promising methodology for optimizing the temperature cycle induced deracemization process. This process requires significantly less time and energy to reach an enantiopure state compared with the use of constant amplitude temperature cycles. There was evidence of some crystal breakage occurring in the system; however, the limited amount of breakage did not produce any change in the enantiomeric excess in the solid phase in the absence of temperature cycles in the system. Hence, the primary mechanism in this process is neither Viedma -ripening nor Ostwald ripening. Scanning electron micrographs of the crystals taken during the series of temperature cycles show that the amplification of the ee in the solid phase is caused by dissolution and growth phenomena induced by the temperature cycles. The promotion of the larger or faster growing crystals at the expense of the smaller or slower growing crystals during the cycles and entrainment from a mother liquor having ee = 0 are both responsible for this deracemization.

• 出版日期2017-4