Flow Photo-on-Demand Synthesis of Vilsmeier Reagent and Acyl Chlorides from Chloroform and Its Applications to Continuous Flow Synthesis of Carbonyl Compounds

Abstract

Phosgene and the Vilsmeier reagent (VR), which are used in a wide variety of organic reactions, are unstable in air. Phosgene also has an extremely high toxicity. Their safe use, especially in industry, is an important issue in flow organic synthesis. The present study reports the flow synthesis of acyl chlorides and VR with phosgene (COCl2) produced from the flow photochemical oxidation of chloroform (CHCl3). This system is applicable to the continuous flow synthesis of esters, carboxylic anhydrides, amides, aryl aldehyde precursors, and β-chloroacrolein precursors. The confined space in the flow reaction system is preferable for safe and efficient conversion of (1) CHCl3 to COCl2 and (2) DMF to VR as well as (3) the subsequent chlorination of carboxylic acids, formylation of aromatic compounds, and chlorination and formylation of acetyl groups with VR.