VilsmeierHaackformylation

The Vilsmeier–Haack reaction is a chemical transformation that installs an aldehyde group onto activated aromatic rings or heteroaromatic compounds via formylation. It uses the Vilsmeier reagent, generated in situ from dimethylformamide (DMF) and phosphorus oxychloride (POCl3).

Generation of the Vilsmeier reagent occurs when DMF reacts with POCl3 to give a chloromethyliminium chloride–type electrophile. The arene undergoes electrophilic aromatic substitution with this reagent to form an iminium intermediate, which is hydrolyzed during workup to yield the corresponding aldehyde.

The method is most effective on electron-rich substrates such as anisole, anilines, phenols, and certain heteroaromatics (furan, thiophene, pyrrole). Regioselectivity is influenced by existing substituents, guiding formylation to specific positions. Reactions are typically performed in DMF at low temperature, followed by aqueous workup to hydrolyze the iminium adduct to the aldehyde. Yields are generally moderate to good, though deactivated rings may require alternative approaches, and excess reagent can lead to polyformylation.

Applications of the Vilsmeier–Haack reaction include the preparation of formylated arenes and heteroarenes for dyes, fragrances, natural product synthesis, and pharmaceutical intermediates. It is a widely used and reliable method for introducing formyl groups when direct formylation is challenging.

History and naming: The reaction is named after Wilhelm Vilsmeier and Albrecht Haack, who developed it in the 1920s.