Electrophilic Activation of Carboxylic Anhydrides for Nucleophilic Acylation Reactions

Abstract

Nucleophilic acylation of symmetrical carboxylic anhydrides has inherited limitation of reaction efficiency along with relatively poor reactivity. Traditionally, one equivalent carboxylic acid is generated during nucleophilic acylation of a symmetrical anhydride, which always limits the yield of final product to 50% or less. This is a major drawback, which discourages the use of anhydrides for laboratory or industrial applications. Electrophilic activation of carboxylic anhydride using methanesulfonyl chloride is found to be an efficient method for nucleophilic acylation, which increases product yield by restricting the formation of corresponding acid as a side product. The developed protocol found to be a mild and high yielding methodology for one-pot nucleophilic acylation of carboxylic anhydrides with several type of N- and S-nucleophiles demonstrating appreciable functional group tolerance.

Palladium‐Catalyzed Synthesis of Carboxylic Acid Anhydrides from Alkenes via in situ Generated Carboxylic Acids

“…Using our procedure, the formation of symmetric acid anhydrides from alkenes comes within reach, if a catalytic system can be developed that exhibits high regioselectivity. Moreover, a recent report on formation of two molecules of acyl derivative, instead of one, by electrophilic activation of symmetric acid anhydrides [15] further adds to the future scope for sustainability of this reaction.…”

Decoration, Characterization and Antimicrobial Activity Evaluation of Novel Nano‐Based 1,2‐Phenylenediamine Functionalized Maleic Anhydride‐Allylphenyl Ether Conjugate

“…Copolymerization reaction of maleic anhydride and allyl phenyl ether depicted in Scheme 1. The reaction of acid anhydrides with amines (Scheme 2) to form the corresponding amides is represented by a four-step mechanism (Scheme 3): [6,77] 1) nucleophilic attack of the anhydride group by the aromatic amine molecule, 2) ring-opening reaction, 3) deprotonation by aromatic amine after nucleophilic attack, and 4) proton transfer/ intramolecular assembly, each as per spectroscopic measurement and water-solubility test results for the structural characterization of the designed alternating copolymer and the fluorescent dye-functionalized conjugate. The ring-opening reaction occurred after nucleophilic acylation of a symmetrical carboxylic acid anhydride group, which undergoes a nucleophilic acyl substitution reaction, resulting in an amide (neutral carboxylic acid derivative).…”

KF-catalyzed direct thiomethylation of carboxylic acids with DMSO to access methyl thioesters

“…2 A number of synthetic methods for the synthesis of thioesters have been reported. 3–8 However, synthetic approaches for accessing methyl thioesters, featured in many bioactive molecules, 9 remain scarce.…”

“…Classical procedures for the preparation of methyl thioesters generally rely on multistep syntheses or nucleophilic substitution of acyl compounds with difficult-to-handle methyl mercaptan, and suffer from great limitation, narrow substrate scope, and reliance on multistep and stoichiometric reactions. 8 It is thus clear that the synthesis of methyl thioesters remains challenging. To address these issues, Li and Tian reported a palladium-catalyzed carbonylative thiomethylation of aryl halides/aryldiazonium salts/amines with 4-methylthio-2-butanone as a sulfur precursor (Scheme 1a).…”