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Updated: Oct 13, 2025

Preparation of N-2-alkoxyvinylsulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines
Published on: January 3, 2018
Flash chemistry enables high productivity metalation-substitution of 5-alkyltetrazoles
Jeff Y F Wong1, Christopher G Thomson1, Filipe Vilela1,2
1Institute of Chemical Sciences, Heriot-Watt University Riccarton Edinburgh EH14 4AS UK graeme.barker@hw.ac.uk.
Abstract:
Tetrazoles play a prominent role in medicinal chemistry due to their role as carboxylate bioisosteres but have largely been overlooked as C-H functionalisation substrates. We herein report the development of a high-yielding and general procedure for the heterobenzylic C-H functionalisation of 5-alkyltetrazoles in up to 97% yield under batch conditions using a metalation/electrophilic trapping strategy. Through the use of thermal imaging to identify potentially unsafe exotherms, a continuous flow procedure using a flash chemistry strategy has also been developed, allowing products to be accessed in up to 95% yield. This enabled an extremely high productivity rate of 141 g h-1 to be achieved on an entry-level flow system.
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