Archive for the ‘reaction mechanism’ Category

How does methane invert (its configuration)?

Thursday, March 16th, 2017

This is a spin-off from the table I constructed here for further chemical examples of the classical/non-classical norbornyl cation conundrum. One possible entry would include the transition state for inversion of methane via a square planar geometry as compared with e.g. NiH4 for which the square planar motif is its minimum. So is square planar methane a true transition state for inversion (of configuration) of carbon?


Forming a stabilized m-benzyne.

Friday, January 20th, 2017

The story so far. Inspired by the report of the most polar neutral compound yet made, I suggested some candidates based on the azulene ring system that if made might be even more polar. This then led to considering a smaller π-analogue of azulene, m-benzyne. Here I ponder how a derivative of this molecule might be made, using computational profiling as one reality check.


The smallest C-C-C angle?

Monday, October 31st, 2016

Is asking a question such as “what is the smallest angle subtended at a chain of three connected 4-coordinate carbon atoms” just seeking another chemical record, or could it unearth interesting chemistry?


σ or π nucleophilic reactivity of imines? A mechanistic reality check using substituents.

Sunday, October 9th, 2016

Previously, a mechanistic twist to the oxidation of imines using peracid had emerged. Time to see how substituents respond to this mechanism.


σ or π nucleophilic reactivity of imines? A mechanistic twist emerges.

Wednesday, September 28th, 2016

The story so far. Imines react with a peracid to form either a nitrone (σ-nucleophile) or an oxaziridine (π-nucleophile).[1] The balance between the two is on an experimental knife-edge, being strongly influenced by substituents on the imine. Modelling these reactions using the “normal” mechanism for peracid oxidation did not reproduce this knife-edge, with ΔΔG (π-σ) 16.2 kcal/mol being rather too far from a fine balance.



  1. D.R. Boyd, P.B. Coulter, N.D. Sharma, W. Jennings, and V.E. Wilson, "Normal, abnormal and pseudo-abnormal reaction pathways for the imine-peroxyacid reaction", Tetrahedron Letters, vol. 26, pp. 1673-1676, 1985.

σ or π? The ambident nucleophilic reactivity of imines: crystallographic and computational reality checks.

Wednesday, September 21st, 2016

Nucleophiles are species that seek to react with an electron deficient centre by donating a lone or a π-bond pair of electrons. The ambident variety has two or more such possible sources in the same molecule, an example of which might be hydroxylamine or H2NOH. I previously discussed how for this example, the energetics allow the nitrogen lone pair (Lp) to win out over the O Lp. Here, I play a similar game, but this time setting an NLp up against a π-pair.


Molecule orbitals as indicators of reactivity: bromoallene.

Thursday, September 1st, 2016

Bromoallene is a pretty simple molecule, with two non-equivalent double bonds. How might it react with an electrophile, say dimethyldioxirane (DMDO) to form an epoxide?[1] Here I explore the difference between two different and very simple approaches to predicting its reactivity. bromoallene



  1. D. Christopher Braddock, A. Mahtey, H.S. Rzepa, and A.J.P. White, "Stable bromoallene oxides", Chemical Communications, vol. 52, pp. 11219-11222, 2016.

An alternative mechanism for nucleophilic substitution at silicon using a tetra-alkyl ammonium fluoride.

Friday, May 27th, 2016

In the previous post, I explored the mechanism for nucleophilic substitution at a silicon centre proceeding via retention of configuration involving a Berry-like pseudorotation. Here I probe an alternative route involving inversion of configuration at the Si centre. Both stereochemical modes are known to occur, depending on the leaving group, solvent and other factors.[1],[2],[3]



  1. L. Wozniak, M. Cypryk, J. Chojnowski, and G. Lanneau, "Optically active silyl esters of phosphorus. II. Stereochemistry of reactions with nucleophiles", Tetrahedron, vol. 45, pp. 4403-4414, 1989.
  2. L.H. Sommer, and H. Fujimoto, "Stereochemistry of asymmetric silicon. X. Solvent and reagent effects on stereochemistry crossover in alkoxy-alkoxy exchange reactions at silicon centers", Journal of the American Chemical Society, vol. 90, pp. 982-987, 1968.
  3. D.N. Roark, and L.H. Sommer, "Dramatic stereochemistry crossover to retention of configuration with angle-strained asymmetric silicon", Journal of the American Chemical Society, vol. 95, pp. 969-971, 1973.

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

Wednesday, May 25th, 2016

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.


Kinetic isotope effect models as a function of ring substituent for indole-3-carboxylic acids and indolin-2-ones.

Wednesday, January 20th, 2016

The original strategic objective of my PhD researches in 1972-74 was to explore how primary kinetic hydrogen isotope effects might be influenced by the underlying structures of the transition states involved. Earlier posts dealt with how one can construct quantum-chemical models of these transition states that fit the known properties of the reactions. Now, one can reverse the strategy by computing the expected variation with structure to see if anything interesting might emerge, and then if it does, open up the prospect of further exploration by experiment. Here I will use the base-catalysed enolisation of 1,3-dimethylindolin-2-ones and the decarboxylation of 3-indole carboxylates to explore this aspect.