Continuous flow synthesis of alkynes from isoxazolones

Abstract

The development of a continuous flow approach for the generation of alkynes from isoxazolones under diazotisation conditions is reported. The underlying transformation has been known for several decades; however, in batch mode, it is plagued by variable yields, excessive use of sodium nitrite and limited scalability due to its exothermic nature and the release of copious amounts of toxic nitroxide gases. The presented flow approach overcomes these limitations and delivers various alkyne products in residence times of less than 1 minute with productivities of ca. 2 g h⁻¹. This demonstrates the value of continuous flow processing in miniaturised devices and renders this alkyne forming method an attractive addition to the limited synthetic toolbox towards this important functional group.