Recent Developments in Amide Synthesis Using Nonactivated Starting Materials

Abstract

Amides are unquestionably one of the most important functional groups in organic chemistry because of their presence in numerous interesting molecules such as peptides, pharmaceutical agents, naturally occurring molecules, proteins and alkaloids, among others. This synopsis surveys the diverse recent approaches to amide synthesis from nonactivated carboxylic acids and derivatives as well as noncarboxylic compounds, highlighting the most innovative methodologies and those that are more eco-friendly compared to traditional methods while focusing on recent developments during the past two years.

Solvent‐Free N‐Alkylation of Amides with Alcohols Catalyzed by Nickel on Silica–Alumina

“…The formation of an amide C–N bond is one of the key processes for the synthesis of peptides, pharmaceuticals, polymers and natural products Amides are generally synthesized by condensation of carboxylic acids (or their esters, anhydrides or acyl chloride analogs) with amines, or by the reaction between an amide and an aryl or aliphatic halide . However, those methods exhibit a poor atom economy, as they inevitably lead to the formation of stoichiometric amounts of waste.…”

“…[1][2][3][4] Amides are generally synthesized by condensation of carboxylic acids (or their esters, anhydrides or acyl chloride analogs) with amines, or by the reaction between an amide and an aryl or aliphatic halide. [5][6][7][8][9] However, those methods exhibit a poor atom economy, as they inevitably lead to the formation of stoichiometric amounts of waste. Though less explored than the previously cited methods, reductive alkylation of amides with aldehydes has been reported by our group as a greener alternative, [10] along with other nitrogen nucleophiles.…”

Synthesis of Amido Esters and Amido Phosphonates through Carbonylation of Diazo Compounds Followed by Nucleophilic Addition Reaction

“…[1][2][3] The amide functionality can serve as a directing group in a synthetic method [4][5][6] and is related to other groups such as esters and phosphonates, which are more useful in total synthesis. [11][12][13] Widely used methods include: (i) carbonylation followed by amidation and (ii) the hydroamidation of alkynes and nitriles. [11][12][13] Widely used methods include: (i) carbonylation followed by amidation and (ii) the hydroamidation of alkynes and nitriles.…”

New Efficient Eco‐Friendly Supported Catalysts for the Synthesis of Amides with Antioxidant and Anti‐Inflammatory Properties

“…More than forty research articles have been dedicated this year only to the synthesis of amides . Classical synthetic pathway to access amides include the use of activated carboxylic acid derivatives such as activated esters, acyl halides or anhydrides in the presence of various amounts of coupling agents, generally expensive and/or toxic . Recent developments in amide synthesis using nonactivated starting materials have been described .…”