Total Resolution of Racemates by Dynamic Preferential Crystallization

Abstract

Crystallization-induced asymmetric transformation (CIAT) of axially chiral materials is summarized on the basis of our studies. CIAT can be classified into two categories, Crystallization-Induced Enantiomer Transformation (CIET) and Crystallization-Induced Diastereomer Transformation (CIDT). Racemic mixtures or diastereomixtures that exist as a mixture of stereoisomers in solution converge on a single stereoisomer by dynamic crystallization. Many axially chiral materials, such as N-arylpyrimidine-2-(1H)-ones and -thiones, were crystallized as conglomerates, and total resolution was performed with high enantiomeric purities from the solution by CIET. Dynamic resolution of aromatic amides, such as 2-alkoxy-1-naphthamides, 2-quinolone-3-carboxamide, coumarin-3-carboxamide, and nicotinamides, was also successfully achieved by crystallization from the melt with high ees. Furthermore, optically active materials tend to crystallize in a chiral fashion, and CIDT is useful to obtain single diastereomers from a mixture of many diastereomers. Many types of aromatic amides with chiral auxiliaries were crystallized in a chiral fashion and were easily resolved by dynamic crystallization from the melt. Salt formation of oily racemic nicotinamides with enantiopure acid involving racemization during salt formation also gave diastereopure salts. The optical activity of the materials resolved by dynamic crystallization was effectively transferred to the products by many kinds of asymmetric reactions.