Direct Transamidation Reactions: Mechanism and Recent Advances

Abstract

Amides are undeniably some of the most important compounds in Nature and the chemical industry, being present in biomolecules, materials, pharmaceuticals and many other substances. Unfortunately, the traditional synthesis of amides suffers from some important drawbacks, principally the use of stoichiometric activators or the need to use highly reactive carboxylic acid derivatives. In recent years, the transamidation reaction has emerged as a valuable alternative to prepare amides. The reactivity of amides makes their direct reaction with nitrogen nucleophiles difficult; thus, the direct transamidation reaction needs a catalyst in order to activate the amide moiety and to promote the completion of the reaction because equilibrium is established. In this review, we present research on direct transamidation reactions ranging from studies of the mechanism to the recent developments of more applicable and versatile methodologies, emphasizing those reactions involving activation with metal catalysts.

Keywords: amide; amine; catalysis; catalyst; transamidation.

Scheme 1

Transamidation of a secondary amide with a secondary amine.

Scheme 2

Proposed catalytic cycle for transamidation reactions between primary or secondary amides with primary amines.

Scheme 3

Proposed catalytic cycle for transamidation reaction between tertiary amides with secondary amines.

Scheme 4

Proposed mechanism to explain the transamidation reaction catalyzed by l-proline.

Scheme 5

(a) Transamidation of amides (alkyl, aryl, Het-aryl) with amines catalyzed by Fe³⁺-mont. (b) Transamidations of α-hydroxyamides with amines.

Scheme 6

Transamidation catalyzed by Fe(III) and water of (a) carboxamides. (b) α-amino esters. (c) Synthesis of 2,3-dihydro-5H-benzo[b]-1,4-thiazepin-4-one by intramolecular transamidation.

Scheme 7

Catalytic transamidation of (a) N-alkyl heptylamines with benzylamine and (b) N-aryl amides with aryl amines.

Scheme 8

Transamidation reactions in the presence of sulfated tungstate of (a) cinnamide with alkyl and aryl amines and (b) α-amino esters with formamide.

Scheme 9

Transamidation of DMF derivatives with aniline.

Scheme 10

Transamidation reaction catalyzed by HfCl₄/KSF-polyDMAP.

Scheme 11

(a) Boron-mediated transamidation of primary, secondary and tertiary amides with different kinds of amines. (b) Formylation of amines catalyzed by a boronic acid. (c) Transamidation catalyzed by boron between α-amino esters and formamide.

Scheme 12

Hydroxylamine hydrochloride as a catalyst of the transamidation reaction of (a) substrates with a Boc protecting group and (b) α-amino esters with a benzyl group.

Scheme 13

(a) Benzoic acid as a catalyst of the transamidation reactions of heterocyclic amides and heterocyclic amines. (b) Selectivity of the transamidation reaction using benzoic acid as a catalyst.

Scheme 14

(a) N-Formylation of α-amino esters promoted by K₂S₂O₈. (b) Natural products and drugs obtained by transamidation reactions using K₂S₂O₈.

Scheme 15

(a) Synthesis of N-aryl/heteroaryl pivalamides via transamidation catalyzed by H₂SO₄-SiO₂. (b) Synthesis of procainamide.