Dealkylation, nitrosative

The reaction of tertiary aromatic amines with butyl nitrite has been investigated in detail. The main products arise from 7V-dealkylation/7V-nitrosation, e.g. equation 91270. 

Figure 2. Nitrosative dealkylation of tertiary amines (a) mechanism postulated by Smith and Loeppky (2) (b) composite of proposals by Lijinsky et al. (S) and...

A similar mechanism was invoked by Ohshima and Kawabata (2) to account for their results in the nitrosation of tertiary amines and amine oxides. In applying these concepts to the nitrosative dealkylation of tetraalkyltetrazenes, Michejda al. 5) introduced an interesting variant by suggesting that immonium ions could be formed in two successive one-electron oxidation steps (for example by ferric ion oxidation of tertiary amine to the radical cation followed by radical abstraction of a hydrogen atom from the alpha position), rather than exclusively through the one-step removal of a hydride ion as nitroxyl. The resulting immonium ion was again considered to react directly with nitrite to produce the N-nitroso derivative. These reactions are summarized in Fig. 2b. 

Thus the postulate that a-amino nitrite esters could form and fragment to nitrosamines has provided a useful construct for explaining some aspects of the nitrosative dealkylation of tertiary amines and their derivatives. 

Nitrosamine formation is not the only conceivable fragmentation mechanism for compounds of structure I. By analogy to the nitrosative dealkylation reactions discussed above, one might predict that such compounds could also undergo cis elimination of nitroxyl in amide-forming reactions. Such a transformation has possibly been observed (14). During an attempt to synthesize the nitrosamino aldehyde VIII from immonium ion IX, Hecht coworkers were able to isolate only 5-10% of the desired product. The major product proved to be N-methyl-2-pyrrolidone, as shown in Fig. 10. We interpret this as evidence that an intermediate such as li can fragment not only by the Fig. 1... 

Michejda, C. J. Tipton, T. J. Campbell, D. H. Nitrosative dealkylation under oxidative conditions as a possible source of nitrosamines. In Walker, E. A. Bogovski, P. Griciute, L., Eds. "Environmental N-Nitroso Compounds. Analysis and Formation" lARC Scientific Publication No. 

As a result of our previous work on the scope and mechanism of tertiary amine nitrosation (X), we became interested in the behavior of N-alkylaziridines toward nitrous acid. Possible modes of reaction are illustrated in Scheme 1. The operation of either path A or C would be consistent with our previous studies of oxidative dealkylation of tertiary amines (1 ), while pathway B would be akin to the observed cheleotropic transformation of N-nitroso-aziridines (2). 

In the aliphatic series, primary amines are deaminated by nitrous acid, secondary aliphatic amines are A-nitrosated, while tertiary aliphatic amines form salts in the acidic medium followed by secondary reactions such as dealkylation [1, 21a, b]. 

Recently [35a] it has been found that, contrary to common belief, tertiary aliphatic amines react with aqueous nitrous acid to undergo dealkylation to form a carbonyl compound, a secondary nitrosoamine, and nitrous oxide. Base-weakening groups markedly reduce nitrosative cleavage, and quaterniza-tion prevents it completely. Several examples of this reaction are shown in Table II. 

Phenolic ethers, dealkylation of, 287 Phenols, nitrosation of, 394 Phenoxypropadiene, 11 3-Phenylamino-l-butyne, 97 Phenyl azide, 281-282 Phenylazoalkanes, 327 Phenylazodiphenylphosphine oxide, 328 Phenylazoethane, 308 Phenylazohydroperoxides, 331 2-Fhenylazo-l,3-indandione, 299 Phenylazo-l-naphthalene, 304, 311 PhenyIazo-2-naphthaIene, 304, 311 Phenylazonaphthalenes, 310... 

Aromatic A A -dialkylamines react rapidly with HN02 and undergo ring nitration and nitrosative dealkylation both reactions are linked through the formation of a nitrosammo-nium ion R1 RiV—N=O (R1 = Ar, R2 = Aik). This nitorosoammonium ion then undergoes reversible homolysis to NO and a cation radical (Loeppky et al. 1998). 

Reagents for amination, nitrosation and nitration of tertiary alkylamines are discussed in the appropriate reviews listed in Sections 6.1.3.1.4 and 6.I.3.I.5. Tertiary amines can be nitrosated with dealkylation by dinitrogen tetroxide for example, 1-methylpiperidine gave 1-nitrosopiperidine (80%). lliis reaction probably starts by one-electron oxidation of the amine, the aminium ion then undergoing dealkylation. Other oxidative d ylations and dealkylations include the formation of iV-nitrosodibenzylamine in high yield from the acid chloride (PhCH2)2NCOCl and sodium nitrite and the conversion of the amine (43) into the nitramine (44) with nitric acid. ... 

Tertiary amines react with the nitrosating agents in an acidic aqueous solution to form A -nitrosamines but, in general, only after the complete formation of dialkylamines through dealkylation. 

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