Issue 17, 2024

Rapid in situ generation of 2-(halomethyl)-5-phenylfuran and nucleophilic addition in a microflow reactor

Abstract

2,5-Disubstituted furans are frequently found in pharmaceuticals and bioactive natural products. Nucleophilic substitution reactions on the carbon atom adjacent to the furan ring are useful for producing various furan derivatives. However, the formation of 5-substituted 2-halomethylfuran and the subsequent nucleophilic substitution reactions are often limited by severe undesired reactions caused by the highly reactive halomethylfurans. This paper reports the successful rapid synthesis of various 2,5-disubstituted furans using microflow technology, which suppresses undesired reactions including dimerization and ring opening of the furans. We observed that Brønsted acids had a significant effect on the nucleophilic substitution reaction and the use of HBr and HI gave the best results. A plausible mechanism of the Brønsted acid-mediated nucleophilic substitutions in the developed approach was proposed.

Graphical abstract: Rapid in situ generation of 2-(halomethyl)-5-phenylfuran and nucleophilic addition in a microflow reactor

Supplementary files

Article information

Article type
Paper
Submitted
05 Mar 2024
Accepted
03 Apr 2024
First published
10 Apr 2024
This article is Open Access
Creative Commons BY-NC license

Org. Biomol. Chem., 2024,22, 3448-3452

Rapid in situ generation of 2-(halomethyl)-5-phenylfuran and nucleophilic addition in a microflow reactor

Y. Matsuura and S. Fuse, Org. Biomol. Chem., 2024, 22, 3448 DOI: 10.1039/D4OB00358F

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