N-Dealkylation of Amines

Abstract

N-dealkylation, the removal of an N-alkyl group from an amine, is an important chemical transformation which provides routes for the synthesis of a wide range of pharmaceuticals, agrochemicals, bulk and fine chemicals. N-dealkylation of amines is also an important in vivo metabolic pathway in the metabolism of xenobiotics. Identification and synthesis of drug metabolites such as N-dealkylated metabolites are necessary throughout all phases of drug development studies. In this review, different approaches for the N-dealkylation of amines including chemical, catalytic, electrochemical, photochemical and enzymatic methods will be discussed.

Light‐Induced Dealkylation of Benzamides in Aqueous Solution

“…[5][6][7] High activity of natural systems in N-dealkylation reactions has been successfully imitated in synthetic chemistry. In particular, the dealkylation of amines has been widely adapted, [8][9][10] giving access to many N-containing compounds, mostly via reaction with cyanogen bromide [11,12] or oxidation [13][14][15] . In contrast, the removal of N-alkyl groups from amides, which are ubiquitous both in nature and in agrochemicals or drug molecules, remains poorly developed.…”

Electrochemical transformations catalyzed by cytochrome P450s and peroxidases

“…The dealkylation can be initiated either by single electron transfer or hydrogen atom transfer. [328][329][330][331][332][333][334][335] For oxidative N-dealkylation, [336][337][338][339] two elementary steps are involved, i.e., hydrogen atom transfer and single electron transfer. N-Oxidation proceeds through charge transfer to the oxo-ferryl group, followed by the formation of radical cation and homolysis of the iron-oxygen bond to generate the new N-O bond.…”

“…The dealkylation can be initiated either by single electron transfer or hydrogen atom transfer. 328–335 For oxidative N -dealkylation, 336–339 two elementary steps are involved, i.e. , hydrogen atom transfer and single electron transfer.…”

Mechanistic Aspects of the Electrochemical Oxidation of Aliphatic Amines and Aniline Derivatives

“…Due to the large variety of amine-containing molecules available and extensive research on them over the past seven decades, it is impossible to discuss and cite all work performed in this area in a single paper. Nevertheless, several review articles and book chapters have been published summarising the impressive advances in this field over the years [ 3 , 4 , 5 , 6 , 7 , 8 ]. However, a detailed discussion of the different mechanistic aspects of the electrochemical oxidation of amines is still elusive.…”