Nitrosation chemistry of pyrroline, 2-imidazoline, and 2-oxazoline: theoretical Curtin-Hammett analysis of retro-ene and solvent-assisted C-X cleavage reactions of alpha-hydroxy-N-nitrosamines.
Nitrosation chemistry of pyrroline, 2-imidazoline, and 2-oxazoline: theoretical Curtin-Hammett analysis of retro-ene and solvent-assisted C-X cleavage reactions of alpha-hydroxy-N-nitrosamines.
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DOI：
10.1021/jo050856s
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发表时间：
2005-07
期刊：
影响因子：
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通讯作者：
Hong Wu;R. Loeppky;R. Glaser
中科院分区：
文献类型：
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作者：
Hong Wu;R. Loeppky;R. Glaser
对吡咯啉1(X=CH2)、咪唑啉2(X=NH)和2-恶唑啉3(X=O)的亚硝化反应进行了理论研究。亚胺1-3通过N-亚硝胺离子4-6转化为α-羟基-N-亚硝胺7-9。7-9的NN-顺式异构体可能与三角洲-氧代烷基重氮酸10-12发生逆烯反应。有了微溶剂化的机会，8和9的C-X裂解成为可能，并导致N-(2-氨基乙基)-N-亚硝甲酰胺15和16的形成。NN-异构化势垒与开环反应的势垒相当，需要考虑两种Curtin-Hammett情景：7-9的NN-反式异构体进行C-X裂解或NN-异构化的CH-I，以及NN-顺式转子异构体进行C-X裂解、C-N裂解或NN-异构化的CH-II。我们测定了7-9的逆烯反应的底物、产物和所有过渡态结构的所有立体异构体，微溶剂8和9的C-X裂解，以及8和9的NN-异构化。在B3LYP/6-31G水平上探索了势能面，并对结果进行了讨论，重点比较了C-N裂解和C-X裂解的动力学和热力学。研究表明，所有的分解都非常快，活化势垒低于21kcal.mol(-1)，比较分析预测，1和3的化学毒性应该与2相似，但明显不同。
The results are presented of a theoretical study of the nitrosation chemistry of pyrroline 1 (X = CH2), imidazoline 2 (X = NH), and 2-oxazoline 3 (X = O). Imines 1-3 are converted to the alpha-hydroxy-N-nitrosamines 7-9 via the N-nitrosoiminium ions 4-6. The NN-cis isomers of 7-9 may undergo retro-ene reactions to the delta-oxoalkyl diazotic acids 10-12. With the opportunity for microsolvation, C-X cleavage becomes possible for 8 and 9 and leads to the formation of N-(2-aminoethyl)- and N-(2-hydroxyethyl)-N-nitrosoformamides 15 and 16, respectively. The NN-isomerization barriers are comparable to the barriers for the ring-opening reactions, and the consideration of two Curtin-Hammett scenarios is required: CH-I for the NN-trans-rotamers of 7-9 to undergo C-X cleavage or NN-isomerization and CH-II for the NN-cis-rotamers to undergo C-X cleavage, C-N cleavage, or NN-isomerization. We determined all stereoisomers of the substrates, the products, and of all transition states structures for the retro-ene reactions of 7-9, the C-X cleavages of microsolvated 8 and 9, and the NN-isomerizations of 8 and 9. The potential energy surfaces were explored at the B3LYP/6-31G level, and the results are discussed with emphasis on the comparison of the kinetics and thermodynamics of C-N versus C-X cleavage. The study shows all decompositions to be very fast with activation barriers below 21 kcal.mol(-1), and the comparative analysis predicts that the chemical toxicologies of 1 and 3 should be similar and remarkably different from that of 2.