Vilsmeier

Vilsmeier refers to Wilhelm Rudolph Vilsmeier, a German chemist whose name is associated with the Vilsmeier-Haack formylation reaction. The term most often denotes the Vilsmeier reagent, a chloroiminium species generated in situ from dimethylformamide (DMF) and phosphorus oxychloride (POCl3). This reagent serves as an electrophilic formylating agent used to introduce formyl groups into aromatic and heteroaromatic substrates.

Mechanism and scope: In the Vilsmeier-Haack reaction, DMF is activated by POCl3 to form a reactive chloromethylideneiminium species. The substrate, typically an electron-rich arene or heteroaromatic compound, undergoes electrophilic attack by this species, forming an iminium intermediate. Hydrolysis during workup then furnishes the corresponding aldehyde. The reaction tends to favor activated rings and often yields formylation at ortho or para positions relative to directing groups such as methoxy or amino groups. The Vilsmeier reagent is valued for enabling formylation under relatively mild conditions compared to some alternative methods.

Applications and limitations: The Vilsmeier-Haack formylation is widely used in organic synthesis to prepare aromatic aldehydes from readily available arenes. It is particularly useful for substrates that resist other formylation strategies. Limitations include limited reactivity with deactivated rings, potential over-formylation or side reactions, and the necessity for anhydrous, carefully controlled conditions due to the reactivity of POCl3 and the chloriminium species.

See also: Vilsmeier reagent; Vilsmeier-Haack reaction.