Institute of Chemistry, University of Tartu, 14a Ravila Street, 50411 Tartu, Estonia.
J Org Chem. 2010 Oct 1;75(19):6436-44. doi: 10.1021/jo101061u.
The study of the polyfluorination and polytrifluoromethylation effects on electronic structure and intrinsic acidities has been performed using DFT B3LYP and NBO calculations for the valence isomers of benzene and phenol, i.e., the structures of prismane, benzvalene, Kekulé, and Dewar systems. Also the isodesmic reaction analysis approach to estimate the effects of the substituents on the acidity of the compounds has been used. Although in some systems the additivity of fluorine substituents was more than 100%, the acidifying effects of the fluorine substituents were comparable to that of the CF(3) in only one case. Isodesmic reaction analysis of substituent effects shows that steric effects of poly-CF(3) substitution in the alicyclic cage compounds are significantly smaller. The relative thermodynamic stabilities of the valence isomers of Kekulé benzene were significantly lower than that of the aromatic cycle. The introduction of fluorine substituents often destabilized the compounds even further. Out of the fluorinated hydroxy derivatives of prismane, Dewar benzene, and benzvalene, not all are predicted to be stable enough to be able to undergo a reversible protonation-deprotonation process. In the case of several hydroxy derivatives deprotonation is accompanied by the rupture of a C(α)-C(β) bond and in some cases by the rearrangement to the corresponding phenolate anion. The isomerization of benzene derivatives resulted in more cases where the acidities increased compared with the respective phenol derivatives. The only hydroxy compound with significantly higher acidity than the respective phenol was pentafluorinated 2-OH-Dewar benzene, which was expected to rival the gas-phase acidity of perfluoro-1-adamantanol, currently the most acidic experimentally measured perfluorinated alcohol.
这项研究探讨了多氟化和多三氟甲基化对苯和苯酚的价电子异构体（即棱柱烷、苯并环丁二烯、凯库勒和杜瓦系统的结构）电子结构和固有酸度的影响。此外，还采用同系物反应分析方法来估计取代基对化合物酸度的影响。尽管在某些体系中，氟取代基的加和性超过了 100%，但只有一种情况下，氟取代基的酸化效应与 CF3 的酸化效应相当。取代基效应的同系物反应分析表明，多 CF3 取代的脂环笼化合物的空间位阻效应要小得多。凯库勒苯的价电子异构体的相对热力学稳定性明显低于芳香环。引入氟取代基往往会进一步使化合物不稳定。在棱柱烷、苯并环丁二烯和苯并环戊二烯的氟化羟基衍生物中，并非所有化合物都被预测具有足够的稳定性，能够经历可逆的质子化-去质子化过程。在几个羟基衍生物中，去质子化伴随着 C(α)-C(β)键的断裂，在某些情况下伴随着向相应的酚盐阴离子的重排。与相应的苯酚衍生物相比，苯衍生物的异构化导致更多的酸度增加的情况。唯一酸度明显高于相应苯酚的羟基化合物是五氟化 2-OH-杜瓦苯，预计其与气相酸度最强的全氟-1-金刚烷醇相当，全氟-1-金刚烷醇是目前实验测量得到的酸度最强的全氟醇。
