A Continuous-Flow Method for the Desulfurization of Substituted Thioimidazoles Applied to the Synthesis of Etomidate Derivatives

Baumann, Marcus; Baxendale, Ian R.

doi:10.1002/ejoc.201700833

A Continuous-Flow Method for the Desulfurization of Substituted Thioimidazoles Applied to the Synthesis of Etomidate Derivatives

Baumann, Marcus; Baxendale, Ian R.

Authors

Marcus Baumann

Professor Ian Baxendale i.r.baxendale@durham.ac.uk
Professor

Abstract

A simple yet robust flow set-up for the efficient desulfurization of a series of thioimidazoles is presented, which generates the corresponding imidazole derivatives in high yields. The strategic choice of peristaltic over piston pumps allowed reliable delivery of the heterogeneous stream of the thioimidazole substrate into a T-piece where it reacted with NaNO2 in the presence of acetic acid. This approach enabled the controlled and safe formation of the reactive nitrosonium species without uncontrolled exposure to hazardous nitrous oxide by-products as observed in related batch protocols. The value of the resulting imidazole products was further demonstrated by their conversion into various esters representing new derivatives of the known analgesic etomidate through an efficient one-pot Corey–Gilman–Ganem oxidation procedure.

Citation

Baumann, M., & Baxendale, I. R. (2017). A Continuous-Flow Method for the Desulfurization of Substituted Thioimidazoles Applied to the Synthesis of Etomidate Derivatives. European Journal of Organic Chemistry, 2017(44), 6518-6524. https://doi.org/10.1002/ejoc.201700833

Journal Article Type	Article
Acceptance Date	Jul 9, 2017
Online Publication Date	Aug 16, 2017
Publication Date	Dec 1, 2017
Deposit Date	Nov 20, 2017
Publicly Available Date	Aug 16, 2018
Journal	European Journal of Organic Chemistry
Print ISSN	1434-193X
Electronic ISSN	1099-0690
Publisher	Wiley
Peer Reviewed	Peer Reviewed
Volume	2017
Issue	44
Pages	6518-6524
DOI	https://doi.org/10.1002/ejoc.201700833

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Copyright Statement
This is the peer reviewed version of the following article: Baumann, Marcus & Baxendale, Ian R. (2017). A Continuous-Flow Method for the Desulfurization of Substituted Thioimidazoles Applied to the Synthesis of Etomidate Derivatives. European Journal of Organic Chemistry, 2017(44): 6518-6524, which has been published in final form at https://doi.org/10.1002/ejoc.201700833. This article may be used for non-commercial purposes in accordance With Wiley-VCH Terms and Conditions for self-archiving.