Diazirine

Diazirines are a class of organic molecules consisting of a carbon bound to two nitrogen atoms, which are double-bonded to each other, forming a cyclopropene-like ring. Upon irradiation with ultraviolet light, diazirines form reactive carbenes, which can insert into C-H, N-H, and O-H bonds. Hence, diazirines have grown in popularity as small photo-reactive crosslinking reagents. They are often used in photoaffinity labeling studies to observe a variety of interactions, including ligand-receptor, ligand-enzyme, protein-protein, and protein-nucleic acid interactions.

Synthesis

A number of methods exist in the literature for the preparation of diazirines, which begin from a variety of reagents.

Synthesis from Ketones

Generally, synthetic schemes that begin with ketones involve conversion of the ketone with the desired substituents to diaziridines. These diaziridenes and then subsequently oxidized to form the desired diazirines.

Diaziridines can be prepared from ketones by oximation, followed by tosylation (or mesylation), and then finally by treatment with ammonia. Generally, oximation reactions are performed by reacting the ketone with hydroxylammmonium chloride under heat in the presence of a base such as pyridine. Subsequent tosylation or mesylation of the alpha substituted oxygen with tosyl or mesyl chloride in the presence of base yields the tosyl or mesyl oxime. The final treatment of the tosyl or mesyl oxime with ammonia produces the diaziridine.