Synthesis of new optically pure tetrabromobenzotriazole derivatives via lipase-catalyzed transesterification

An efficient and convenient approach to synthesis of new, enantiopure hydroxyalkyl derivatives of 4,5,6,7-tetrabromo-1H-benzotriazole (TBBt) has been developed. Prochiral ketones synthesized through alkylation of TBBt were reduced to racemic secondary alcohols, which were separated by kinetic resolution carried out by lipase-catalyzed transesterification. After optimization of solvent, lipase and acyl donor group, the highest enantioselectivity factor (E > 200) and optical purity of the products (>99%) was achieved with lipase Amano AK from Pseudomonas fluorescens in tert-butyl methyl ether.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Racemic N2-hydroxyalkyl-4,5,6,7-tetrabromobenzotriazole derivatives were synthesized. ► Kinetic resolution by lipase-catalyzed transesterification was carried out. ► Optically pure (S)-alcohols (ee > 99%) and (R)-esters (ee > 99%) were obtained. ► After optimization of conditions, very high enantioselectivity (E > 200) at 23 °C after 24–96 h was achieved, with lipase Amano AK.