Dealkylation amines

Deall lation. Chloroformates such as vinyl chloroformates (40) are used to dealkylate tertiary amines. Chloroformates are superior to the typical Von Braun reagent, cyanogen bromide, because of increased selectivity producing cleaner products. Other chloroformates such as aHyl, methyl, phenyl, and trichloroethyl have also been used in dealkylation reactions. Although the dealkylation reaction using chloroformates is mostiy carried out on tertiary amines, dealkylation of oxygen or sulfur centers, ie, ethers or thioethers, can also be achieved. a-Chloroethyl chloroformate [50893-53-3] (ACE-Cl) (41,42) is superior to all previously used chloroformates for the dealkylation reaction. ACE-Cl has the advantage that the conditions requked for ACE... 

The second type of oxidative biotransformation comprises dealkylations. In the case of primary or secondary amines, dealkylation of an alkyl group starts at the carbon adjacent to the nitrogen in the case of tertiary amines, with hydroxylation of the nitrogen (e.g lidocaine). The intermediary products are labile and break up into the dealkylated amine and aldehyde of the alkyl group removed. 0-dealkylation... 

J.H. Cooley u. E.J. Evain, Synthesis 1989, 1-7 Amine Dealkylations with Acyl Chlorides". 

Cyclization of haloamines (cyclic amines) dealkylation of quaternary salts of nitrogen heterocycles 0-45 Reaction between dihalides and cy-anamide (cyclic amines)... 

Anilines (23 R = 2-Pr, PhCPfc X = Cl, Br, I) have been obtained in high yields (40-95%) from the reaction of the primary amines 2-propylamine and benzylamine with the ethers (24 R = Me, CH2=CHCH2, CH2-oxirane) in EtOH at room temperature.127 With secondary amines dealkylation of the aromatic ether to the corresponding phenol took place rather than SNAr dealkoxylation. 

An example of a tertiary amine dealkylation via oxidative degradation is seen with diphenoxylate hydrochloride (Fig. 32). An example of a secondary amine dealkylation via oxidative degradation, the API brinzola-mide undergoes a dealkylation reaction converting the secondary amine to a primary amine in the presence of heat, light (neutral pH), and peroxide... 

In the presence of light, dorsolamide hydrochloride also undergoes amine dealkylation from a secondary to a primary amine, which presumably occurs via oxidation to the hydroxylamine, dehydration to the imine, and subsequent hydrolysis to form the primary amine (Fig. 40) (61). 

It was believed that a sequential electron-proton-electron transfer mechanism would result in small isotope effects and that a hydrogen transfer mechanism would result in large isotope effects. Because small isotope effects were observed for amine dealkylation by cytochrome P-450, a sequential electron-proton-electron transfer mechanism was proposed for the reaction [67, 75-77]. The magnitude of a single isotope effect provides only limited information about a reaction mechanism, however, and isotope effects might be logically consistent with any type of C-H cleavage reaction. 

P-450 amine dealkylation mechanisms. Because kn/ko values for A -demethylation of / -substituted A, A -dimethylanilines by cytochrome P-450 are nearly identical with those for the hydrogen abstraction reactions of t-BuO , it was proposed that P-450 reacted by a direct hydrogen-atom-abstraction mechanism (B) rather than a sequential electron-proton-electron-transfer mechanism (A) [78, 80]. Identical relationships between A h/ d values for reactions of t-BuO and P-450 has been expanded for other substrates including />-xylene, toluene, benzyl alcohol, and tertiary trialkylamine [78]. It has thus been suggested that all these P-450 reactions proceed by a common hydrogen-atom transfer mechanism [78]. 

On ingestion prometryn metabolizes, producing amine dealkylation and side chain oxidation. It affects the tricarboxylic acid cycle. 

SB Karki, JP Dinnocenzo, JP Jones, KR Korzekwa. Mechanism of oxidative amine dealkylation of substituted N,N-dimethylanilines by cytochrome P-450 application of isotope effect profiles. J Am Chem Soc 117 3657—3664, 1995. 

The versatility of the P450 oxygenases is summarized in Figure 9.3. Epoxides can be introduced into aromatic rings or across double bonds. The former reaction leads to a hydroxy or dihydodiol. It is most unlikely to observe aldrin in environmental samples since it is rapidly converted to dieldrin, a common environmental contaminant that is very stable. Aliphatic chains can be hydroxylated and ethers, thioethers, and substituted amines dealkylated. The conversion of parathion to the more reactive paraoxon is a factor in the mechanism of toxic action, as well as its environmental stability (see Hydrolysis, Chapter 8). The situation can be complicated by the fact that a substrate can often undergo more than one reaction. 

Cooley JH, Evain EJ (1989) Amine dealkylations with acyl chlorides. Synthesis-Stuttgart 1-7... 

Amine Dealkylations with Acyl Chlorides" Cooley. J.H. Evain, E.J. Synthesis, 1989, 1. 

Alkylated anilines Amine, aldehyde Synthesis of amines dealkylation of methyl or other secondary amines Monooxygenase, Peroxidase... 

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