Archive for July, 2025

Why an Electron-Withdrawing Group is an o, m-Director rather than m-Director in Electrophilic Aromatic Substitution: The example of CN vs NC.

Tuesday, July 22nd, 2025

In the previous post[1] I followed up on an article published on the theme “Physical Organic Chemistry: Never Out of Style“.[2] Paul Rablen presented the case that the amount of o (ortho) product in electrophilic substitution of a phenyl ring bearing an EWG (electron withdrawing group) is often large enough to merit changing the long held rule-of-thumb for EWGs from being just meta directors into being ortho and meta-directors, with a preference for meta. I showed how Paul’s elegant insight could be complemented by an NBO7 analysis of the donor-acceptor interactions in the σ-complex formed by protonating the phenyl ring bearing the EWG. Both the o– and m– isomers showed similar NBO orbital patterns and associated E(2) donor/acceptor interaction energies and also matched the observation that the proportion of meta is modestly greater than ortho substitution (steric effects not modelled). These interactions were both very different from those calculated for the para isomer.

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References

  1. H. Rzepa, ""Typical Electron-Withdrawing Groups Are o, m-Directors Rather than m-Directors in Electrophilic Aromatic Substitution"", 2025. https://doi.org/10.59350/rzepa.28993
  2. P.R. Rablen, "Typical Electron-Withdrawing Groups Are <i>ortho</i>, <i>meta</i>-Directors Rather than <i>meta</i>-Directors in Electrophilic Aromatic Substitution", The Journal of Organic Chemistry, vol. 90, pp. 6090-6093, 2025. https://doi.org/10.1021/acs.joc.5c00426

“Typical Electron-Withdrawing Groups Are o, m-Directors Rather than m-Directors in Electrophilic Aromatic Substitution”

Thursday, July 17th, 2025

The title of this post comes from an article published in a special virtual issue on the theme “Physical Organic Chemistry: Never Out of Style[1] There, Paul Rablen presents the case that the amount of o (ortho) product in electrophilic substitution of a phenyl ring bearing an EWG (electron withdrawing group) is often large enough to merit changing the long held rule-of-thumb for EWGs from being just meta directors into these substituents are best understood as ortho, meta-directors, with a preference for meta. I cannot help but add here a citation[2] to the earliest publication I can find showing tables of both o,p and m-directing groups and dating from 1887, so this rule is 138 years old (at least).

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References

  1. P.R. Rablen, "Typical Electron-Withdrawing Groups Are <i>ortho</i>, <i>meta</i>-Directors Rather than <i>meta</i>-Directors in Electrophilic Aromatic Substitution", The Journal of Organic Chemistry, vol. 90, pp. 6090-6093, 2025. https://doi.org/10.1021/acs.joc.5c00426
  2. H.E. Armstrong, "XXVIII.—An explanation of the laws which govern substitution in the case of benzenoid compounds", J. Chem. Soc., Trans., vol. 51, pp. 258-268, 1887. https://doi.org/10.1039/ct8875100258