A-value revisited: ring flip energy of chair structures in halogenated cyclohexanes by quantum chemical methods

A-value is conventionally defined as the ring flip Gibbs energy of chair conformers in monosubstituted cyclohexanes. It is well accepted in organic chemistry as one of the proxies of steric hindrance of a substituent group with respect to hydrogen. In this paper, the ring flip energy of mono– and dihalogenated cyclohexanes was investigated by high-level quantum chemical methods. Satisfactory agreements between calculated values and published experimental values from NMR were established before extending the concept to ring flip energies of polyhalogenated cyclohexanes. We assessed the qualitative and quantitative accuracy of prediction of ring flip energies by A-values in two models: a simple and intuitive model based on linear combinations of A-values and a proposed extension of this model to include geminal substituent interactions. The simple model results in poor predictions of ring flip energy in polyhalogenated cyclohexanes, and the extended model provides only slight improvement. Our data suggests that simple linear combination of traditional or extended A-values may not be appropriate for the energy prediction of systems in this study.

A值（A-value）通常被定义为单取代环己烷椅式构象的环翻转吉布斯自由能。该指标作为有机化学领域公认的空间位阻表征参数之一，可用于衡量取代基相对于氢原子的空间位阻效应。本研究采用高精度量子化学方法，对单、双卤代环己烷的环翻转能展开了探究。在将该概念拓展至多卤代环己烷的环翻转能研究前，我们先验证了计算值与已发表的核磁共振（NMR）实验值之间具有良好的一致性。随后，我们在两种模型中评估了基于A值预测环翻转能的定性与定量准确性：其一为基于A值线性组合的简单直观模型，其二为我们提出的拓展模型，该模型纳入了同碳取代基相互作用项。研究结果表明，简单模型对多卤代环己烷的环翻转能预测效果欠佳，而拓展模型仅能带来小幅性能提升。本研究的数据显示，采用传统A值或拓展A值的简单线性组合，并不适用于本研究涉及体系的能量预测。