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

Baumann, Marcus; Baxendale, Ian R.

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
• Public URL: https://durham-repository.worktribe.com/output/1343958