This paper describes a novel method for efficient synthesis of amides through reaction of carboxylic acids with amines by activation with P(OEt)3 and Iodine. The novelty lies in easy amidation of several primary and secondary amines to synthesize amides including peptides without racemization. One major advantage of this procedure over earlier ones, is that it does not produce the difficult to separate byproduct triphenylphosphine oxide (Ph3P=O). The method for screening the base and the solvent for the reaction is well documented.
The Reactions of Interest:
The reaction documented in this paper is between a carboxylic acid and an amine. However, the focus is on the reaction conditions.
The solvent and base have been standardized for amidation of benzoic acid as listed in Table 1.
The Table 2 lists Synthesis of various amides using P(OEt)3 /I2
The trend of non-polar solvents like dichloromethane, chloroform and DCE performing well with high yields was reproducible. Trimethyl amine is the suitable base as the authors have noted.
Following the Table 2, reaction of dicarboxylic acids was tried. The desired product with amination at both sites was observed.
All the reactions were reproducible, although with slight variation in yields.
The reactions of dicarboxylic acids were not done by the authors. The results are the expected ones, and should be tried.
I have not tried it, but the reactions with para-phenylenediamine, ortho-phenylenediamine and para-amino benzoic acids will be interesting to study.