Flow synthesis of oxadiazoles coupled with sequential in-line extraction and chromatography

Kian Donnelly; Marcus Baumann

doi:10.3762/bjoc.18.27

Flow synthesis of oxadiazoles coupled with sequential in-line extraction and chromatography

Beilstein J Org Chem. 2022 Feb 25:18:232-239. doi: 10.3762/bjoc.18.27. eCollection 2022.

Authors

Kian Donnelly¹, Marcus Baumann¹

Affiliation

¹ School of Chemistry, University College Dublin, Science Centre South, Belfield, Dublin 4, Ireland.

Abstract

An efficient continuous flow process is reported for the synthesis of various 1,3,4-oxadiazoles via an iodine-mediated oxidative cyclisation approach. This entails the use of a heated packed-bed reactor filled with solid K₂CO₃ as a base. Using DMSO as solvent, this flow method generates the target heterocycles within short residence times of 10 minutes and in yields up to 93%. Scale-up of this flow process was achieved (34 mmol/h) and featured an integrated quenching and extraction step. Lastly, the use of an automated in-line chromatography system was exploited to realise a powerful flow platform for the generation of the heterocyclic targets.

Keywords: chromatography; flow synthesis; in-line purification; oxadiazole; reaction telescoping.

Grants and funding

M.B. thanks the Royal Society of Chemistry for a Research Enablement Grant (E20-2998) as well as Science Foundation Ireland for generous support of our research program through grants 19/IFA/7420, 18/RI/5702 and 12/RC2275_P2. Support from the UCD School of Chemistry in the form of a Ph.D. Demonstratorship to K.D. is gratefully acknowledged.