Continuous-Flow Preparation and Use of β-Chloro Enals Using the Vilsmeier Reagent
“Continuous-Flow Preparation and Use of β-Chloro Enals Using the Vilsmeier Reagent”, Org. Process Res. Dev., 2012, 16, 1442-1448.
The Vilsmeier reagent is used in the preparation of a wide variety of heterocycles, such as pyrazoles, via formation of β-chloroacrolein intermediates. However, use of this extremely reactive reagent on large scale requires special precautions to avoid potentially dangerous exotherms. This article describes the safe preparation at room temperature of the Vilsmeier reagent under flow conditions for the formation of β-chloroacroleins and 3-formylchromones, as well as the use of these in multistep, continuous flow processes for the syntheses of β-acrylonitriles and polysubstituted pyrazoles.