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Updated: Jun 29, 2025

Preparation of Contiguous Bisaziridines for Regioselective Ring-Opening Reactions
Published on: July 28, 2022
Regioselective quinazoline C2 modifications through the azide-tetrazole tautomeric equilibrium
Dāgs Dāvis Līpiņš1, Andris Jeminejs1, Una Ušacka1,2
1Faculty of Natural Sciences and Technology, Riga Technical University, P. Valdena Str. 3, Riga, LV-1048, Latvia.
Abstract:
2-Chloro-4-sulfonylquinazolines undergo functional group swap when treated with an azide nucleophile: 1) the azide replaces the sulfonyl group at the C4 position; 2) the intrinsic azide-tetrazole tautomeric equilibrium directs the nucleofugal sulfinate from the first step to replace chloride at the C2 position. This transformation is effective with quinazolines bearing electron-rich substituents. Therefore, the title transformations are demonstrated on the 6,7-dimethoxyquinazoline core, which is present in pharmaceutically active substances. The methodology application is showcased by transforming the obtained 4-azido-6,7-dimethoxy-2-sulfonylquinazolines into the α1-adrenoceptor blockers terazosin and prazosin by further C2-selective SNAr reaction and azide reduction.
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