Dealkylation of amines

Dealkylations of amines by means of acyl chlorides have been reviewed (equation 90)260. 

An oxidizing agent. Useful for the dealkylation of amines and the conversion of pyrimidines to purines. It is most often associated with triphenylphosphine (TPP) in the Mitsunobu reaction. Examples ... 

DEALKYLATION OF AMINES f-Butyldi-methylsilyl triflouromethanesulfonate. 2-Chloroethyl chloroformate. 

Dealkylation of amines. Most amines (primary, secondary, and tertiary) form crystalline salts with benzeneselenol. When heated (150°) some of these salts decompose to form the dealkylated amine and an alkyl phenyl selenide. Salts of primary alkylamines for unknown reasons undergo dealkylation very slowly hindered, tertiary amines are dealkylated most rapidly. 

Electron-transfer reactions of amines are of significant importance in biochemical systems. Enzymes known to catalyze the oxidative dealkylation of amines include monoamine oxidase [16, 17], cytochrome-P450 [18, 184-186], horseradish peroxidase [187], hemoproteins [188, 189], and chloroperoxidase [187, 188]. N-dealkylation of amines by peroxidases are generally accepted to occur via one-electron transfer, whereas the role of electron transfer in reactions catalyzed by enzymes such as monoamine oxidase [16, 17] and cytochrome P-450 [18, 184, 185] is currently a topic of debate. 

Silverman s studies on mechanism based MAO inactivation have provided overwhelming support for the role of electron transfer in the MAO catalyzed dealkylation of amines. It must be mentioned however that spectroscopic attempts for detecting the radical ion intermediates have hitherto been unsuccessful. Yasanobu and coworkers could not find EPR spectral evidence for radical intermediates in MAO-catalyzed oxidation of benzylamine [205]. Miller et al. failed to observe the flavin semiquinone or an amine-flavin adduct in rapid-scan-stopped flow spectroscopy [206]. The only time-dependent absorption change observed in this study was the bleaching of the oxidized flavin. Furthermore, no influence of a magnetic field up to 6500 G was observed on the rate of MAO B reduction. The reaction rates of systems with kinetically significant radical pair intermediates are known to be altered... 

Search for new mechanism based investigations for deducing the mechanism of the enzyme catalyzed activity continues to be active area of research. Mariano and coworkers have used activated flavins such as 5-ethylflavinium perchlorate, whose ground state reduction potentials are high enough to promote oxidative dealkylation of amines, as enzyme models [209]. Studies on the inactivation of the model enzymes by cyclopropylamines and a-silylamines suggest a polar mechanistic model. Silverman attributes this result to the drastically altered nature of the flavin used in these studies, which could favor a nucleophilic mechanism [16]. 

In the catalytic cycle in Scheme 1, details of the reaction between the high-valent iron-oxo porphyrin n radical cation [(P)Fe =0] + and a substrate have yet to be clarified [66]. Three possibilities have survived after extensive studies of the mechanisms of the reactions of high-valent iron-oxo porphyrins, in particular the dealkylation of amines by cytochrome P-450 (A) a sequential electron-proton electron transfer (B) direct hydrogen transfer then electron transfer and (C) electron transfer followed by hydrogen transfer (Scheme 2) [67-74]. 

Figure 10.8 A common mechanism for quasi-irreversible CYP inhibition. A-dealkylation of amines and subsequent oxidation to nitroso compounds can lead to MI complex formation.

Further reactions which may be used for the dealkylation of amines are included in section 82 (Amides from Amines) and section 81 (Amides from Amides)... 

E. O Reilly, C. Iglesias, N.. Turner, Monoamine oxidase-w-transaminase cascade for the dera-cemisation and dealkylation of amines, ChemCatChem. 00 (1-4) (2014). 

Dealkylation of Amines. Treatment of a secondary or tertiary amine with diethyl azodicarboxylate in nonpolar solvents followed by acidic hydrolysis leads to the formation of mon-odealkylated amines. The mechanism of this reaction is believed to involve the formation of a triaza adduct (by Michael addition) followed by a two-step ylide rearrangement yielding an alkyl-substituted hydrazocarboxylate. Research on unsymmetrically substituted amines suggests that benzyl groups are more easily removed than alkyl groups methyl groups are the hardest to remove except in cyclic amines like iV-methylpiperidine (eq 3). The Al-dealkylation of imines has also been reported. ... 

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