Non-Catalytic Low-Cost and Sustainable Amidation using a Twisted Amide

Abstract

Cost reductions and environmental friendliness have been strongly desired in amide synthesis. In this study, carboxylic acid was converted to a twisted amide using inexpensive tosyl isocyanate and bromoacetate. The twisted amide was then reacted with an amine to give the desired amide and commercially valuable tosylglycine esters. Epimerization-suppressed amidation, application to the peptide synthesis, column chromatography-free amide synthesis, and solid-phase amide synthesis were established. Moreover, effective use of the co-product tosylglycine ester was demonstrated by the sustainable peptoid synthesis. The established method can become a practical amidation that solve the cost and sustainability issues in amide synthesis.