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

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.

Read the rest of this entry »

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”

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).

Read the rest of this entry »

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

WATOC 2025 report – extending the limits of computation (accuracy).

June 25th, 2025

This are just a few insights I have got from some of the talks I attended. As usual, this does not represent a report on the WATOC congress itself, but simply some aspects that caught my personal eye. Read the rest of this entry »

WATOC25 and its (Dr Who like) regeneration to Young WATOC25.

June 21st, 2025

The WATOC congresses occur every three years. WATOC25, the 13th in a series which started in 1987  takes places tomorrow in Oslo, Norway, The day before the main event there is something new – a session just for early career researchers or “Young WATOC”. As an “old” WATOCer, I dropped into the opening session and was delighted to find a packed auditorium, with literally standing room only comprising mostly young researchers in their 20s.

Read the rest of this entry »

Mechanism of the dimerisation of Nitrosobenzene.

June 14th, 2025

I am in the process of revising my annual lecture to first year university students on the topic of “curly arrows”. I like to start my story in 1924, when Robert Robinson published the very first example[1] as an illustration of why nitrosobenzene undergoes electrophilic bromination in the para position of the benzene ring. I follow this up by showing how “data mining” can be used to see if this supports his assertion. I have used the very latest version of the CSD crystal structure database to update the version originally posted here in 2020.[2]

Read the rest of this entry »

References

  1. "Forthcoming events", Journal of the Society of Chemical Industry, vol. 43, pp. 1295-1298, 1924. https://doi.org/10.1002/jctb.5000435208
  2. H. Rzepa, "The first ever curly arrows. Revisited with some crystal structure mining.", 2020. https://doi.org/10.59350/c6thp-wqe69

How many of the compounds that appear in the chemical literature are mentioned just once?

June 6th, 2025

Tom recently emailed me this question: Do you know how to find out how many of the compounds that appear in the chemical literature are mentioned just once? Intrigued, I first set out to find out how many substances, as Chemical Abstracts refers to the them, there were as of 5 June, 2025. There is a static estimate here (219 million), but to get the most up to date information, I asked CAS directly. They responded immediately (thanks Lee!) with 294,778,693 on the date mentioned above. It is not actually possible to answer the first question itself using CAS SciFinder, but again CAS came up with a value: “there are 113,383,649 substances in CAS Registry with only one CAplus citation” equivalent to  “38.5% of the current substances have only 1 reference.” I should add this estimate was qualified by “that can be misleading, since that includes salts, multicomponents, etc. But that’s a first pass.” I am actually impressed that as many as 61.5% are mentioned more than once, since before learning the answer, I had intuitively guessed that percentage as being much lower.

Read the rest of this entry »

Cyclo-S6 (Hexathiane) – anomeric effects again!

June 1st, 2025

I thought I was done with exploring anomeric effects in small sulfur rings. However, I then realised that all the systems that I had described had an odd number of atoms and that I had not looked at any even numbered rings. Thus hexasulfur is a smaller (known) ring version of S8, the latter by far the best known allotrope of this element of course.

Read the rest of this entry »

Forty (one) years on – The pico-mac-nano and Chemdraw.

June 1st, 2025

Last year I reminisced on the occasion of the 40th Anniversary of the Macintosh computer.[1] Four decades of advances in technology now mean I can do a fair amount of computational quantum modelling on a recent Mac (one from 2022 with M1 processor), and since then they have only got even (~2 or 3 times) faster with the M4 processor. Many of the recent calculations done for these blogs have included at least one or two that were done on the Mac. So I was intrigued to find that a real working version of the original Mac is about to be released for sale, but with a twist. Its called the “Pico-mac-nano” and from its name it is truly diminutive, being only 6.2 cm high – half the height of a can of cola – and with a 2″ LCD display. It comes with a connector for a keyboard and mouse, although currently it has no sound.

Read the rest of this entry »

References

  1. H. Rzepa, "The Macintosh computer at 40.", 2024. https://doi.org/10.59350/f11dr-93t29

S7I1+: The largest anomeric effect exhibited by sulfur.

May 21st, 2025

In this series of posts about the electronic effects in small sulfur rings[1] I have explored increasingly large induced geometric effects. Here is the largest so far, for the compound S7I1+[2]

Read the rest of this entry »

References

  1. H. Rzepa, "5-Imino-5λ<sup>4</sup>-heptathiepane 3-oxide. More exuberent anomeric effects.", 2025. https://doi.org/10.59350/rzepa.28615
  2. J. Passmore, G. Sutherland, P. Taylor, T.K. Whidden, and P.S. White, "Preparations and x-ray crystal structures of iodo-cyclo-heptasulfur hexafluoroantimonate(V) and hexafluoroarsenate(V), S7ISbF6 and S7IAsF6", Inorganic Chemistry, vol. 20, pp. 3839-3845, 1981. https://doi.org/10.1021/ic50225a048

5-Imino-5λ4-heptathiepane 3-oxide. More exuberent anomeric effects.

May 20th, 2025

The two previous  posts[1],[2] on the topic of anomeric effects in 7-membered sulfur rings illustrated how orbital interactions between the lone pairs in the molecules and S-S bonds produced widely varying S-S bond lengths in the molecules, some are shorter than normal (which is ~2.05Å for e.g. the S8 ring) by ~ 0.1Å and some are longer by ~0.24Å. Here we extend this to the unknown molecule shown below.

Read the rest of this entry »

References

  1. H. Rzepa, "Cycloheptasulfur sulfoxide, S<sub>7</sub>O – Anomeric effects galore!", 2025. https://doi.org/10.59350/rzepa.28515
  2. H. Rzepa, "Cyclo-Heptasulfur, S<sub>7</sub> – a classic anomeric effect discovered during a pub lunch!", 2025. https://doi.org/10.59350/rzepa.28407