Calculating Accurate Proton Chemical Shifts of Organic Molecules with Density Functional Methods and Modest Basis Sets

The purpose of this paper is to convince practitioners of 1H NMR spectroscopy to consider simple quantum chemical calculations as a viable option to aid them in the assignment of their spectra. To this end, it is demonstrated, on a test set of 80 conformationally stable molecules of various kinds carrying different functional groups, that, in contrast to what is claimed in the literature, large basis sets are not needed to obtain rather accurate predictions of 1H NMR chemical shifts by quantum chemical calculations. On the other hand, modeling the solvent by an SCRF-type calculation may improve certain predictions significantly. The best accuracy/cost ratio is provided by GIAO calculations in chloroform as a solvent with the specially parametrized WP04 functional of Cramer et al. using the cc-pVDZ or 6-31G** basis set, closely followed by similar calculations with the ubiquitious B3LYP functional (both predict 1H chemical shifts with an average deviation of ca. 0.12 ppm, if the results are scaled linearly). A slightly higher accuracy can be attained by adding diffuse functions to the basis set, but going to the triple-ζ basis sets which have invariably been used hitherto in calculations of chemical shifts does not lead to any improvement. The popular increment schemes such as those implemented in the ChemDraw or ACD programs do not do nearly as well and are often incapable of correctly distinguishing stereoisomers.

本研究旨在说服氢核磁共振波谱学（1H NMR spectroscopy）从业者，将简易量子化学计算作为辅助其完成谱峰归属的可行方案。为此，本文针对包含80种带有不同官能团的各类构象稳定分子的测试集开展验证，结果表明：与已有文献中的论断相反，通过量子化学计算获得高精度1H核磁共振化学位移预测结果，并不需要使用大基组。另一方面，采用自洽反应场（SCRF）型计算对溶剂环境进行建模，可显著改善部分预测结果。在氯仿溶剂中，使用Cramer等人开发的专用参数化WP04泛函结合cc-pVDZ或6-31G**基组开展规范不变原子轨道（GIAO）计算，可获得最优的精度/成本比；紧随其后的是应用广泛的B3LYP泛函的同类计算——若对结果进行线性缩放，两者预测1H核磁共振化学位移的平均偏差约为0.12 ppm。向基组添加弥散函数可略微提升预测精度，但沿用此前化学位移计算中普遍使用的三重ζ基组，则不会带来任何精度提升。ChemDraw或ACD程序中内置的主流增量方案，其表现远不及上述量子化学计算方法，且往往无法正确区分立体异构体。