Amides in One Pot from Carboxylic Acids and Amines via Sulfinylamides

Abstract

An efficient method has been developed for the direct amidification of carboxylic acids via sulfinylamides preformed in situ by the reaction of pure amines with prop-2-ene-1-sulfinyl chloride. The method can be applied to aliphatic acids, including pivalic acid, aromatic acids, and primary and secondary amines. It is compatible with acids bearing unprotected alcohol, phenol, and ketone moieties and applicable to the synthesis of peptides. It does not induce their α-epimerization.

Nonclassical Routes for Amide Bond Formation

“…In a different approach, the use of sulfinylamides was recently described by Vogel and co-workers allowing the one pot amidification of carboxylic acids with amines (more than 70 examples) . As illustrated in Scheme , amides and Cbz-protected dipeptides have been obtained in good to high yields in the presence of 20 mol % of DMAP (chloroform at 70 °C).…”

“…208 In a different approach, the use of sulfinylamides was recently described by Vogel and co-workers allowing the one pot amidification of carboxylic acids with amines (more than 70 examples). 351 As illustrated in Scheme 129, amides and Cbzprotected dipeptides have been obtained in good to high yields in the presence of 20 mol % of DMAP (chloroform at 70 °C). The reaction probably proceeds via the formation of an activated mixed anhydride 187 of sulfinyl and carboxylic acids, through the addition of carboxylate/amine exchange on the sulfur center.…”

Unexpected Reactivity of N‐Acyl‐Benzotriazoles with Aromatic Amines in Acidic Medium (ABAA Reaction)

“…According to these results, we decided to select toluene as a reference solvent. We then evaluated the role of TFA equivalents on the conversion rate into the final amide 3, after 3 h reaction time ( Table 1, entries [8][9][10][11]. The TFA amount did not have a major influence on the formation of amide 3.…”

“…Numerous studies have been devoted to the development of efficient methods for the construction of amide linkages, most of them resulting from condensation of carboxylic acids with amines. Some other methods involve transamidation, carbamates, S‐nitrosothiacids, sulfinyl‐amides, oxidative amidation of aldehydes, and amidation of esters . However, despite the efficiency of these methods, the coupling of aromatic amines is still problematic due to their low nucleophile character.…”

Direct amidation of carboxylic acids with amines under microwave irradiation using silica gel as a solid support

“…Amides are undeniably among the most important functional groups in organic chemistry; they are present in many naturally occurring molecules, synthetic polymers, peptides, and pharmaceutical agents, among others. 1 Traditionally, amides have been prepared by coupling activated carboxylic acid derivatives and amines, 2 from carboxylic acids using stoichiometric amounts of condensing reagents 3 and more recently by innovative methods such as transamidation, 3c,4 employing carbamates as the amine source, 5 via S-nitrosothiacids, 6 oxidative amidation of aldehydes, 7 and very recently via sulfynilamides 8 and amidation of esters, 9 in addition to the more wellknown named reactions. 10 Despite all these existing methodologies, new synthetic efforts have been made in order to obtain amides directly from carboxylic acids without using any coupling reagent.…”