While computational prediction of chemical reactivity is possible it usually requires expert knowledge and there are relatively few computational tools that can be used by a bench chemist to help guide synthesis. The RegioSQM method for predicting the regioselectivity of electrophilic aromatic substitution reactions of heteroaromatic systems is presented in this paper. RegioSQM protonates all aromatic C–H carbon atoms and identifies those with the lowest free energies in chloroform using the PM3 semiempirical method as the most nucleophilic center. These positions are found to correlate qualitatively with the regiochemical outcome in a retrospective analysis of 96% of more than 525 literature examples of electrophilic aromatic halogenation reactions. The method is automated and requires only a SMILES string of the molecule of interest, which can easily be generated using chemical drawing programs such as ChemDraw. The computational cost is 1–10 minutes per molecule depending on size, using relatively modest computational resources and the method is freely available via a web server at http://www.regiosqm.org. RegioSQM should therefore be of practical use in the planning of organic synthesis.

中文翻译：

---

快速，准确地预测亲电芳族取代反应的区域选择性

虽然化学反应的计算预测是可能的，但通常需要专业知识，并且台式化学家可以使用相对较少的计算工具来帮助指导合成。本文提出了用于预测杂芳族体系亲电芳族取代反应区域选择性的RegioSQM方法。RegioSQM质子化所有芳族CH碳原子，并使用PM3半经验方法作为最亲核的中心，识别出氯仿中具有最低自由能的碳原子。在对525多个亲电子芳香族卤化反应实例的96％的回顾性分析中，发现这些位置与区域化学结果在质量上相关。该方法是自动化的，仅需要感兴趣分子的SMILES字符串，可以使用化学绘图程序（例如ChemDraw）轻松生成。使用相对适度的计算资源，取决于分子大小，计算成本为每个分子1-10分钟，该方法可免费获得通过位于http://www.regiosqm.org的网络服务器。因此，RegioSQM应该在有机合成计划中具有实际用途。