Crystallization and Resolution of cis‐Permethric Acid with Carbon Dioxide Antisolvent

Abstract

Crystallization and resolution of cis-permethric acid (cPA) with (1R)-1-phenylethanamine (PhEA) as a resolving agent was investigated by means of gas antisolvent (GAS) and supercritical antisolvent (SAS) methods. A significant pressure effect on both the yields and diastereomeric excesses of the crystallized cPA-PhEA salts was observed in a defined pressure range. The pressure effect was found to be related to the structure and dissociation of the salts. Both methods yielded diastereomeric salts with excellent diastereoselectivity, compared to data reported in literature, and a fibrous structure of uniform fiber diameter.

Towards Diastereomeric Pure Salts with Antisolvent Methods

“…Our and others' previous works did not achieve more than 0.88 enantiomeric purity in one step in case of resolution of IBU [34]. IBU forms a racemate [28], which has an eutectic composition at 0.88 enantiomeric purity. Higher enantiomeric purity could not be achieved by recrystallization.…”

“…Antisolvent methods have been applied for chiral resolution in relatively few cases [26][27][28][29]. In principle, supercritical CO 2 is added to an organic solvent to achieve selective partial precipitation of the dissolved compounds.…”

Gas antisolvent fractionation based optical resolution of ibuprofen with enantiopure phenylglycinol

“…The amount of diastereomeric salt used to prepare the organic solution was set by changing the amount of racemic ibuprofen and (S)-phenylglycinol while the amount of methanol was kept constant. The mass of the precipitated salt is determined either by the apparent solubility of the salt, or as reported in previous papers [32] [46], by the dissociation of the salts. Figure 3.…”

Gas Antisolvent Fractionation: A New Approach for the Optical Resolution of 4-chloromandelic Acid

“…This new method allowed substantially higher selectivity than the crystallization from organic solvents [13]. Carbon dioxide-involving experiments have even been conducted using the supercritical fluid as an antisolvent and as a reaction medium in diastereomeric salt formation as well [14][15][16][17][18][19]. Antisolvent methods have been studied in the production of enantiomerically pure compounds too [6,14,[20][21][22].…”