Jump to main content
Jump to site search

Issue 32, 2018
Previous Article Next Article

Computational study of the mechanism of amide bond formation via CS2-releasing 1,3-acyl transfer

Author affiliations

Abstract

Reactions of thiocarboxylic acids and dithiocarbamate-terminal amines provide a linker-traceless method for amide bond formation under mild conditions, whereas the reaction mechanism is not clear. A systematic study was performed herein with density functional theory (DFT) calculations to elucidate the detailed mechanism, the substitution effect on the proposed CS2-releasing 1,3-acyl transfer and the differences between CS2- and CO2-releasing 1,3-acyl transfer. Relevant results indicate that this type of reaction proceeds via the nucleophilic addition of an in situ generated dithiocarbamic acid on thiocarboxylic acid, H2S elimination, rate-determining 1,3-acyl transfer and CS2 release. For the generation of secondary amides via the 1,3-acyl transfer, a thiocarboxylic acid- or dithiocarbamic acid-assisted pathway, in which both the carbonyl group and amide nitrogen are activated, is the most favored. For the generation of tertiary amides, MeOH-assisted carbonyl-activation is the most favorable pathway. N,N-Dialkyl substitution of the mixed anhydride intermediate promotes the 1,3-acyl transfer by the steric effect. In contrast, N-phenyl substitution and using thiobenzoic acid as a substrate slow down 1,3-acyl transfer by both the conjugation effect and steric effect. Furthermore, CS2-releasing 1,3-acyl transfer was found to be favored over CO2-releasing 1,3-acyl transfer in the aspects of both kinetics and thermodynamics mainly because the S–COR bond is weaker than the O–COR bond.

Graphical abstract: Computational study of the mechanism of amide bond formation via CS2-releasing 1,3-acyl transfer

Back to tab navigation

Supplementary files

Publication details

The article was received on 07 Jun 2018, accepted on 24 Jul 2018 and first published on 25 Jul 2018


Article type: Paper
DOI: 10.1039/C8OB01338A
Citation: Org. Biomol. Chem., 2018,16, 5808-5815
  •   Request permissions

    Computational study of the mechanism of amide bond formation via CS2-releasing 1,3-acyl transfer

    Y. Jiang, T. Liu, X. Sun, Z. Xu, X. Fan, L. Zhu and S. Bi, Org. Biomol. Chem., 2018, 16, 5808
    DOI: 10.1039/C8OB01338A

Search articles by author

Spotlight

Advertisements