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Using the general-purpose reactivity indicator: challenging examples

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Abstract

We elucidate the regioselectivity of nucleophilic attack on substituted benzenesulfonates, quinolines, and pyridines using a general-purpose reactivity indicator (GPRI) for electrophiles. We observe that the GPRI is most accurate when the incoming nucleophile resembles a point charge. We further observe that the GPRI often chooses reactive “dead ends” as the most reactive sites as well as sterically hindered reactive sites. This means that care must be taken to remove sites that are inherently unreactive. Generally, among sites where reactions actually occur, the GPRI identifies the sites in the molecule that lead to the kinetically favored product(s). Furthermore, the GPRI can discern which sites react with hard reagents and which sites react with soft reagents. Because it is currently impossible to use the mathematical framework of conceptual DFT to identify sterically inaccessible sites and reactive dead ends, the GPRI is primarily useful as an interpretative, not a predictive, tool.

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Acknowledgments

PWA and JSMA acknowledge funding from NSERC and computational resources from Compute Canada. PWA, JM, and JSMA would like to thank Sharcnet for computational resources. JSMA would like to thank his FPR fellowship from RIKEN.

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Authors and Affiliations

  1. Computational Materials Science Research Team, AICS, RIKEN, Kobe, Hyogo, 650-0047, Japan

    James S. M. Anderson

  2. Computational Condensed Matter Physics Laboratory, RIKEN, Wako-shi, Saitama, 351-0198, Japan

    James S. M. Anderson

  3. ASRC Federal Technical Services, 289 Dunlop Blvd, Huntsville, Al, 35824, USA

    Junia Melin

  4. Department of Chemistry & Chemical Biology, McMaster University, Hamilton, Ontario, L8S 4M1, Canada

    Paul W. Ayers

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  1. James S. M. Anderson
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Correspondence to James S. M. Anderson.

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The authors declare no conflicts of interest and that there are no potential ethical breaches in this purely computational work.

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Anderson, J.S.M., Melin, J. & Ayers, P.W. Using the general-purpose reactivity indicator: challenging examples. J Mol Model 22, 57 (2016). https://doi.org/10.1007/s00894-016-2910-7

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