The mechanistic origin of regiochemical changes in the nitrosative N-dealkylation of N,N-dialkyl aromatic amines.
The mechanistic origin of regiochemical changes in the nitrosative N-dealkylation of N,N-dialkyl aromatic amines.
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N,N-二烷基芳香胺亚硝化N-脱烷基化区域化学变化的机制起源。
DOI：
10.1039/b418457b
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Loeppky,RichardN
中科院分区：
文献类型：
--
作者：
Teuten,EmmaL;Loeppky,RichardN
亚硝酸介导的4-取代-N-乙基-N-甲基苯胺脱烷基化的区域选择性是反应混合物酸度的函数。在高酸度下，脱乙基化占主导地位，而在pH 2及以上时，脱甲基化是亚硝胺形成的主要反应。在某些情况下，亚硝化脱烷基化的区域选择性随着操作的进行而变化。通过使用相应的4-硝基苯胺作为主要底物，CIDNP，动力学，动力学氘同位素效应和其他涉及在非质子溶剂中与NO2或NOBF 4亚硝化的转化，叔胺亚硝化的新机制已被推导和提出来解释区域选择性脱乙基。该机制涉及NO+将底物氧化为胺自由基阳离子。随后通过NO2从与胺氮相邻的碳上夺取氢原子以产生亚胺鎓离子，亚胺鎓离子进一步反应以产生相应的醛和亚硝胺。根据酸度的不同，这个过程与其他三种机制的途径竞争，其中两种通过亚胺离子产生亚硝胺，一种导致C-硝基化合物的形成。亚硝胺形成的竞争途径包括从亚硝铵离子中消除NOH以及自由基阳离子的去质子化产生α-氨基自由基，该α-氨基自由基迅速氧化为亚铵离子。主要的，但不是高度区域选择性的去甲基化发生这些途径。硝基化合物的形成主要由NO2与自由基阳离子反应，然后去质子化产生，但也可由帕拉C-亚硝化反应，然后氧化产生。
The regioselectivity of the nitrous acid mediated dealkylation of 4-substituted-N-ethyl-N-methylanilines is a function of the acidity of the reaction mixture. At high acidity deethylation predominates, whereas demethylation is the predominant reaction in nitrosamine formation at pH 2 and above. In some cases the regioselectivity of nitrosative dealkylation changes as the run proceeds. Through the use of the corresponding 4-nitroaniline as the primary substrate, CIDNP, kinetics, kinetic deuterium isotope effects and other transformations involving nitrosations with NO2 or NOBF4 in aprotic solvents, a new mechanism of tertiary amine nitrosation has been deduced and proposed to explain regioselective deethylation. The mechanism involves the oxidation of the substrate to the amine radical cation by NO+. This is followed by the abstraction of a hydrogen atom from the carbon adjacent to the amine nitrogen by NO2 to produce an iminium ion which reacts further to produce the corresponding aldehyde and the nitrosamine. Depending upon the acidity, this process competes with three other mechanistic pathways, two of which give the nitrosamine through the iminium ion, and one leads to the formation of C-nitro compounds. The competing pathways to nitrosamine formation involve NOH elimination from a nitrosammonium ion and deprotonation of the radical cation to give an α-amino radical which rapidly oxidized to the iminium ion. Predominant, but not highly regioselective demethylation occurs by these pathways. Nitro compound formation principally arises from the reaction of NO2 with the radical cation followed by deprotonation, but also occurs by para C-nitrosation followed by oxidation.