The Syntheses of Pharmaceutical Intermediates in Supercritical Fluids

Abstract

Reactions such as ammonolyses of esters to amides and of mesylates to amines, asymmetric hydrogenations, and the condensation of trimethylhydroquinone with isophytol to d,l-α-tocopherol in supercritical fluids are reported. Ammonolysis of a mesylate with anhydrous supercritical ammonia can lead to the corresponding amine in high yield (up to 96%), representing an interesting alternative to the normally practiced azide substitution/hydrogenation sequence to introduce an amino function. The synthesis of d,l-α-tocopherol in supercritical carbon dioxide or nitrous oxide by condensation of trimethylhydroquinone with isophytol in the presence of various Brönsted or Lewis acids, especially an imide or its metal salts, as catalysts is an interesting alternative to existing processes.