Vilsmeier Reagent

Unstrained neutral amides are notoriously poor acylating agents. However, electrophilic attack usually occurs at oxygen, and 3º-amides are activated by such an event. A useful application of this concept is the generation of an electrophilic formylating reagent by reaction of dimethylformamide (DMF) with phosphorus oxychloride, as shown in the green shaded box below. Note that the structural formula of the resulting complex resembles that of an acyl chloride, with the iminium double bond providing additional electrophilic character. This reagent, known as the Vilsmeier-Haack reagent, attacks nucleophilic substrates to generate formylated products. Two examples are shown below the reagent box.