Dealkylation

Dealkylation is a chemical reaction in which an alkyl group is removed from a molecule. It most commonly refers to the cleavage of carbon–nitrogen (N-dealkylation) bonds in amines and carbon–oxygen (O-dealkylation) bonds in ethers, but can also involve sulfur or carbon–carbon bonds in thioethers or other substrates. In biological systems and in organic synthesis, dealkylation is used to modify activity, polarity, and metabolism.

In enzymatic contexts, oxidative dealkylation is typical, especially via cytochrome P450 enzymes that remove alkyl groups from nitrogen or oxygen atoms, often releasing an aldehyde or ketone corresponding to the removed alkyl chain (for example, demethylation releases formaldehyde). O-dealkylation of aryl ethers similarly yields a phenol and an aldehyde or alcohol depending on the alkyl group. In chemical synthesis, dealkylation can be achieved by hydrolysis under acidic or basic conditions, hydrogenolysis, or demethylation reagents, depending on the substrate.

Applications include drug metabolism, where dealkylation can deactivate or activate compounds and influence clearance; environmental chemistry, where dealkylated products may be less persistent; and organic synthesis, where deprotection or modification of alkyl groups is required. Examples include caffeine metabolism by N-demethylation to theobromine and theophylline; and codeine O-demethylation to morphine.

See also deprotection, hydrolysis, oxidation.