Computational Methods to Predict the Regioselectivity of Electrophilic Aromatic Substitution Reactions of Heteroaromatic Systems

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• 作者：Monika Kruszyk ; Mikkel Jessing ; Jesper Langgaard Kristensen ; Morten Jørgensen
• 刊名：Journal of Organic Chemistry
• 出版年：2016
• 出版时间：June 17, 2016
• 年：2016
• 卷：81
• 期：12
• 页码：5128-5134
• 全文大小：528K
• 年卷期：0
• ISSN：1520-6904

文摘

The validity of calculated NMR shifts to predict the outcome of electrophilic aromatic substitution reactions on different heterocyclic compounds has been examined. Based on an analysis of >130 literature examples, it was found that the lowest predicted ¹³C and/or ¹H chemical shift of a heterocycle correlates qualitatively with the regiochemical outcome of halogenation reactions in >80% of the investigated cases. In the remaining cases, the site of electrophilic aromatic substitution can be explained by the calculated HOMO orbitals obtained using density functional theory. Using a combination of these two methods, the accuracy increases to >95%.