Henry Rzepa's Blog Chemistry with a twist

April 4, 2019

Smoke and mirrors. All is not what it seems with this Sn2 reaction!

Previously, I explored the Graham reaction to form a diazirine. The second phase of the reaction involved an Sn2′ displacement of N-Cl forming C-Cl. Here I ask how facile the simpler displacement of C-Cl by another chlorine might be and whether the mechanism is Sn2 or the alternative Sn1. The reason for posing this question is that as an Sn1 reaction, simply ionizing off the chlorine to form a diazacyclopropenium cation might be a very easy process. Why? Because the resulting cation is analogous to the cyclopropenium cation, famously proposed by Breslow as the first example of a 4n+2 aromatic ring for which the value of n is zero and not 1 as for benzene.[1] Another example of a famous “Sn1” reaction is the solvolysis of t-butyl chloride to form the very stable tertiary carbocation and chloride anion (except in fact that it is not an Sn1 reaction but an Sn2 one!)



  1. R. Breslow, "SYNTHESIS OF THE s-TRIPHENYLCYCLOPROPENYL CATION", Journal of the American Chemical Society, vol. 79, pp. 5318-5318, 1957. http://dx.doi.org/10.1021/ja01576a067

February 18, 2019

The Graham reaction: Deciding upon a reasonable mechanism and curly arrow representation.

Students learning organic chemistry are often asked in examinations and tutorials to devise the mechanisms (as represented by curly arrows) for the core corpus of important reactions, with the purpose of learning skills that allow them to go on to improvise mechanisms for new reactions. A common question asked by students is how should such mechanisms be presented in an exam in order to gain full credit? Alternatively, is there a single correct mechanism for any given reaction? To which the lecturer or tutor will often respond that any reasonable mechanism will receive such credit. The implication is that a mechanism is “reasonable” if it “follows the rules”. The rules are rarely declared fully, but seem to be part of the absorbed but often mysterious skill acquired in learning the subject. These rules also include those governing how the curly arrows should be drawn. Here I explore this topic using the Graham reaction.[1]



  1. W.H. Graham, "The Halogenation of Amidines. I. Synthesis of 3-Halo- and Other Negatively Substituted Diazirines1", Journal of the American Chemical Society, vol. 87, pp. 4396-4397, 1965. http://dx.doi.org/10.1021/ja00947a040

October 1, 2017

Dyotropic Ring Expansion: more mechanistic reality checks.

I noted in my WATOC conference report a presentation describing the use of calculated reaction barriers (and derived rate constants) as mechanistic reality checks. Computations, it was claimed, have now reached a level of accuracy whereby a barrier calculated as being 6 kcal/mol too high can start ringing mechanistic alarm bells. So when I came across this article[1] in which calculated barriers for a dyotropic ring expansion observed under mild conditions in dichloromethane as solvent were used to make mechanistic inferences, I decided to explore the mechanism a bit further.



  1. H. Santalla, O.N. Faza, G. Gómez, Y. Fall, and C. Silva López, "From Hydrindane to Decalin: A Mild Transformation through a Dyotropic Ring Expansion", Organic Letters, vol. 19, pp. 3648-3651, 2017. http://dx.doi.org/10.1021/acs.orglett.7b01621

May 25, 2016

The mechanism of silylether deprotection using a tetra-alkyl ammonium fluoride.

The substitution of a nucleofuge (a good leaving group) by a nucleophile at a carbon centre occurs with inversion of configuration at the carbon, the mechanism being known by the term SN2 (a story I have also told in this post). Such displacement at silicon famously proceeds by a quite different mechanism, which I here quantify with some calculations.


November 12, 2014

A computed mechanistic pathway for the formation of an amide from an acid and an amine in non-polar solution.

In London, one has the pleasures of attending occasional one day meetings at the Burlington House, home of the Royal Society of Chemistry. On November 5th this year, there was an excellent meeting on the topic of Challenges in Catalysisand you can see the speakers and (some of) their slides here. One talk on the topic of Direct amide formation – the issues, the art, the industrial application by Dave Jackson caught my interest. He asked whether an amide could be formed directly from a carboxylic acid and an amine without the intervention of an explicit catalyst. The answer involved noting that the carboxylic acid was itself a catalyst in the process, and a full mechanistic exploration of this aspect can be found in an article published in collaboration with Andy Whiting's group at Durham.[1] My after-thoughts in the pub centered around the recollection that I had written some blog posts about the reaction between hydroxylamine and propanone. Might there be any similarity between the two mechanisms?



  1. H. Charville, D.A. Jackson, G. Hodges, A. Whiting, and M.R. Wilson, "The Uncatalyzed Direct Amide Formation Reaction - Mechanism Studies and the Key Role of Carboxylic Acid H-Bonding", European Journal of Organic Chemistry, vol. 2011, pp. 5981-5990, 2011. http://dx.doi.org/10.1002/ejoc.201100714

September 19, 2013

Patterns of behaviour: serendipity in action for enantiomerisation of F-S-S-Cl

Paul Schleyer sent me an email about a pattern he had spotted, between my post on F3SSF and some work he and Michael Mauksch had done 13 years ago with the intriguing title “Demonstration of Chiral Enantiomerization in a Four-Atom Molecule“.[1] Let me explain the connection, but also to follow-up further on what I discovered in that post and how a new connection evolved.FSSF3-gen



  1. P.V.R. Schleyer, and M. Mauksch, "Demonstration of Chiral Enantiomerization in a Four‐Atom Molecule ", Angewandte Chemie International Edition, 2000. http://doi.org/d8g2nw

January 10, 2013

A conflation of concepts: Conformation and pericyclic.

Filed under: Uncategorised — Tags: , , , , — Henry Rzepa @ 11:09 am

This is an interesting result I got when studying the [1,4] sigmatropic rearrangement of heptamethylbicyclo-[3.1.0]hexenyl cations. It fits into the last lecture of a series on pericyclic mechanisms, and just before the first lecture on conformational analysis. This is how they join.


October 29, 2012

Secrets of a university tutor. An exercise in mechanistic logic: second dénouement.

Filed under: Uncategorised — Tags: , , , , — Henry Rzepa @ 7:37 pm

Following on from our first mechanistic reality check, we now need to verify how product A might arise in the mechanism shown below, starting from B.


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