Amide Synthesis by Transamidation of Primary Carboxamides

Abstract

The amide functionality is one of the most important and widely used groups in nature and in medicinal and industrial chemistry. Because of its importance and as the actual synthetic methods suffer from major drawbacks, such as the use of a stoichiometric amount of an activating agent, epimerization and low atom economy, the development of new and efficient amide bond forming reactions is needed. A number of greener and more effective strategies have been studied and developed. The transamidation of primary amides is particularly attractive in terms of atom economy and as ammonia is the single byproduct. This review summarizes the advancements in metal-catalyzed and organocatalyzed transamidation methods. Lewis and Brønsted acid transamidation catalysts are reviewed as a separate group. The activation of primary amides by promoter, as well as catalyst- and promoter-free protocols, are also described. The proposed mechanisms and key intermediates of the depicted transamidation reactions are shown.1 Introduction2 Metal-Catalyzed Transamidations3 Organocatalyzed Transamidations4 Lewis and Brønsted Acid Catalysis5 Promoted Transamidation of Primary Amides6 Catalyst- and Promoter-Free Protocols7 Conclusion

Reductive cross-coupling of N-acyl pyrazole and nitroarene using tetrahydroxydiboron: synthesis of secondary amides

“…This is because amides are much more stable than other acylating reagents such as acid chlorides, anhydrides, and esters. It has been reported that amides bearing various N -substituents were employed and reacted with amines to afford the desired transamidated products under the conditions with 4 or without transition metal catalyst. 5 Reactions of nitrogen-, carbon-, oxygen-, and sulfur-based nucleophiles with amides have been described.…”

A one-step base-free synthesis of N-arylamides via modified pivaloyl mixed anhydride mediated amide coupling

“…[15][16][17][18][19][20][21][22][23] As one of the oldest approaches, amide bond formation via mixed anhydride has been widely applied on the plant scale, 8 including amine condensation with anilines. [24][25][26][27] In the presence of a base, namely Et 3 N, NMM or N-methylpiperidine, carboxylic acids are first transformed into the corresponding mixed anhydrides using acid chlorides, such as pivaloyl chloride (PivCl) [28][29][30][31][32][33][34][35][36][37][38][39][40][41] or isobutyl chloroformate (IBCF). [42][43][44][45][46][47][48][49][50][51] The advantages of PivCl for scale-up include its relatively low cost, wide availability, and nontoxic pivalic acid as a byproduct after aqueous workup.…”

Amidic resonance not a barrier for transamidation of N-pivaloyl activated amides: catalyst, base and additive free conditions

“…Although, transamidation is very well documented with planar and resonance stabilized unactivated primary amides. 28 Nevertheless, it has at least one or more of the following shortcomings: it requires heavy metal catalysts, additives, peroxide activators, strong bases, microwave irradiation, a long reaction time, and an inert atmosphere or it is limited to primary amides, with limited substrate scope, formylation/acetylation, low yields, high reaction temperature, and excessive use of additive/reagents. However, in the present work, a simple N -pivaloyl activation overcomes the above limitations.…”