Formylation

Formylation is a chemical transformation that introduces a formyl group (-CHO) into a molecule. The formyl group is commonly added to amines to form formamides, or to aromatic substrates to yield aldehyde-functionalized products. Formylation thus provides a versatile handle for further synthetic transformations and, in some cases, serves as a temporary protecting group for amines.

N-formylation of amines is one of the most widespread forms of formylation. It can be accomplished with formylating reagents such as formic acid, formyl chlorides, or formic anhydride, often using coupling additives or dehydrating conditions. N-formylation is frequently used to protect amines during multistep syntheses and to prepare formamide derivatives for subsequent transformations.

Aromatic and heteroaromatic formylation targets carbon frameworks bearing electron density that can be attacked by electrophilic formylating species. The Vilsmeier-Haack reaction, which employs a formylating agent generated from POCl3 and DMF, is a common method for introducing formyl groups onto activated rings. Classical alternatives include the Reimer–Tiemann formylation of phenols using chloroform and base, which yields ortho-formyl phenols under stringent conditions.

Other routes include specialized reagents and protocols designed for selective formylation of particular substrates or positions, often leveraging the same underlying electrophilic formylating species. In practice, choice of method depends on substrate sensitivity, regioselectivity, and the desired downstream chemistry.

Applications of formylation span organic synthesis and biochemistry. N-formyl protection is widely used in peptide and small-molecule synthesis, while formylated aromatics serve as intermediates toward aldehydes, alcohols, or further functional groups. In biological contexts, formyl groups appear in natural products and in certain translation initiation processes.