An investigation into novel methods for amide and peptide bond formation is herein reported.
Firstly, methyltrimethoxysilane (MTM) has been demonstrated as a reagent for the direct
amidation of carboxylic acids and amines. It has been shown that a range of different amides
can be formed in moderate to high yields, where the work-up consists of just an aqueous base
and acid wash to provide pure amides. Moreover, certain secondary amides can be isolated as
crystalline solid by a simple filtration protocol of the reaction mixture. This investigation also
explores the use of MTM for di- and tripeptide formation, demonstrating that tripeptides can
be formed as a single diastereomer and isolated pure without the requirement for chromatography.
This thesis also explores the use of trimethylsilyl chloride (TMSCl). It has been shown that TMSCl cannot promote room temperature amidation of carboxylic acids with amines. Through
the authentic synthesis of the proposed trimethylsilyl ester, it has been shown that TMSCl does not promote conversion of carboxylic acids to TMS esters. However, the reaction of TMSCl with DMF provides an in-situ Vilsmeier salt which can formylate amines at ambient temperature, and therefore offers a novel method for formamide formation. The last section of this thesis explores the use of a thianthrene and N-chlorosuccinimide (NCS) combination for a stepwise amidation of carboxylic acids and amines. It has been shown that addition of a carboxylic acid to a solution of thianthrene and NCS will result in acid chloride formation, which will form amide on addition of amine.