Selective Acylation of Polyamines with Acid Anhydrides and Acid Chlorides in Water

Abstract

Mono-acylation of polyamines can be difficult due to the side reactions of poly-acylation. Using large excess of polyamines can hardly alleviate the problem. This letter reports a simple method to solve this problem. We found that simply using water as the reaction media, several polyamines could be mono-acylated with acid anhydrides and chlorides at low temperature in acceptable to excellent yields. Because the reaction is simple and uses readily available starting materials, it is expected to be useful for conjugating different molecules together using polyamines as the linker. Keywords: Amine, polyamine, diamine, acid anhydride, acid chloride, water, mono-acylation, electrophiles, 1,4-butanediamine, Boc protected, piperazine, Thin layer chromatography, Flash column chromatography, MeOH