Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 May 11;20(18):3717-3720.
doi: 10.1039/d2ob00589a.

Solvent-free amide bond formation using a variety of methoxysilanes as coupling agent

Thomas Lainer  1 , Frank Czerny  2 , Michael Haas  1
Affiliations

Solvent-free amide bond formation using a variety of methoxysilanes as coupling agent

Thomas Lainer et al. Org Biomol Chem. .

Abstract

A solvent-free procedure for the formation of amides without exclusion of air and moisture is described. Using tetramethoxysilane 1, hexamethoxydisilane 2 and dodecamethoxy-neopentasilane 3 as coupling agent carboxylic acids and amines are reacted to form amides in good to excellent yields. The formation of these amides was confirmed by NMR spectroscopy and mass spectrometry. Remarkably, neopentasilane 3 exceeds the performance of the currently used monosilanes as coupling agent in terms of group tolerance and yield.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1. Postulated silyl ester formation as intermediate.
Chart 1
Chart 1. Used methoxysilanes as coupling agents.
Scheme 2
Scheme 2. Amide bond formation of the optimization reaction.
Scheme 3
Scheme 3. Different carboxylic acids coupled with benzylamine.
Scheme 4
Scheme 4. Different amines coupled with benzoic acid.
Scheme 5
Scheme 5. Plausible mechanism of the fragmentation of 3.
Scheme 6
Scheme 6. Isolation of the insoluble polysiloxane.
Chart 2
Chart 2. Proposed structure of the polysiloxane.
See this image and copyright information in PMC

References

    1. Roughley S. D. Jordan A. M. J. Med. Chem. 2011;54:3451–3479. doi: 10.1021/jm200187y. - DOI - PubMed
    2. Bryan M. C. Dunn P. J. Entwistle D. Gallou F. Koenig S. G. Hayler J. D. Hickey M. R. Hughes S. Kopach M. E. Moine G. Richardson P. Roschangar F. Steven A. Weiberth F. J. Green Chem. 2018;20:5082–5103. doi: 10.1039/C8GC01276H. - DOI
    1. Boström J. Brown D. G. Young R. J. Keserü G. M. Nat. Rev. Drug Discovery. 2018;17:709–727. doi: 10.1038/nrd.2018.116. - DOI - PubMed
    1. Brown D. G. Boström J. J. Med. Chem. 2016;59:4443–4458. doi: 10.1021/acs.jmedchem.5b01409. - DOI - PubMed
    1. Kumari S. Carmona A. V. Tiwari A. K. Trippier P. C. J. Med. Chem. 2020;63:12290–12358. doi: 10.1021/acs.jmedchem.0c00530. - DOI - PMC - PubMed
    1. Modern Crop Protection Compounds, ed. P. Jeschke, M. Witschel, W. Krämer and U. Schirmer, Wiley-VCH, Weinheim, 3rd edn, 2018

Publication types