Dipartimento di Scienze e Tecnologie Chimiche , Università "Tor Vergata" , Via della Ricerca Scientifica, 1 I-00133 Rome , Italy.
Dipartimento di Chimica, Sapienza Università di Roma and Sezione Meccanismi di Reazione, Istituto CNR per i Sistemi Biologici (ISB-CNR) , Sapienza Università di Roma , P.le A. Moro, 5 I-00185 Rome , Italy.
J Org Chem. 2019 Feb 15;84(4):1778-1786. doi: 10.1021/acs.joc.8b02571. Epub 2019 Feb 1.
Evaluation of polar effects in hydrogen atom transfer (HAT) processes is made difficult by the fact that in most cases substrates characterized by lower bond dissociation energies (BDEs), activated from an enthalpic point of view, are also more activated by polar effects. In search of an exception to this general rule, we found that the introduction of a methoxy substituent in the 3-position of 2,6-dimethylphenol results in a small increase in the O-H BDE and a decrease of the ionization potential of the phenol. These findings suggest that the enthalpic effect associated with the addition of the m-methoxy group to 2,6-dimethylphenol will decrease reaction rates, while the polar effects will increase reaction rates. Our model analysis of polar effects has been experimentally validated by comparing the reactivity of 2,6-dimethylphenol with that of 2,6-dimethyl-3-methoxyphenol in HAT promoted by a series of radicals (cumyloxyl, galvinoxyl, 2,2-diphenylpycrylhydrazyl, phthalimide- N-oxyl, and benzotriazole- N-oxyl radicals). In line with our predictions, the ratio of HAT rate constants ( k / k) is larger in cases where there is a greater contribution of polar effects in the HAT reaction, i.e., in HAT promoted by N-oxyl radicals containing electron-withdrawing groups or when more polar solvents are employed.
评价氢原子转移（HAT）过程中的极性效应很困难，因为在大多数情况下，从焓的角度来看，特征键离解能（BDE）较低的底物更易受到极性效应的激活。为了寻找这一普遍规律的例外，我们发现，在 2,6-二甲基苯酚的 3 位引入甲氧基取代基会导致 O-H BDE 略有增加，而酚的电离势降低。这些发现表明，与将 m-甲氧基添加到 2,6-二甲基苯酚相关的焓效应将降低反应速率，而极性效应将增加反应速率。我们通过比较一系列自由基（枯基氧自由基、戊二酮氧自由基、2,2-二苯基苦基肼基自由基、邻苯二甲酰亚胺-N-氧化物自由基和苯并三唑-N-氧化物自由基）促进的 HAT 中 2,6-二甲基苯酚与 2,6-二甲基-3-甲氧基苯酚的反应性，实验验证了我们对极性效应的模型分析。与我们的预测一致，在 HAT 反应中极性效应贡献更大的情况下（即，在含有吸电子基团的 N-氧化物自由基或使用更极性溶剂促进的 HAT 中），HAT 速率常数（k/k）的比值更大。
