Minds (and memories) can work in wonderful ways. In 1987[cite]10.1021/jo00389a050[/cite] we were looking at the properties of “stable” tetrahedral intermediates formed in carbonyl group reactions. The reaction involved adding phenylhydroxylamine to acetyl cyanide.

Proton transfers are amongst the most common of all chemical reactions.

In another post, a discussion arose about whether it might be possible to trap cyclopropenylidene to form a small molecule with a large dipole moment. Doing so assumes that cyclopropenylidene has a sufficiently long lifetime to so react, before it does so with itself to e.g. dimerise.

In the preceding post, I looked at a computed mechanism for the hydrolysis of a ketal by water. Of course, pure water consists of three potential catalysts, water itself or [H ₂ O], and the products of autoionisation, [OH ^– ] and [H ₃ O ⁺ ]. The latter are in much smaller concentration, equivalent to a penalty of ~11.9 kcal/mol on any free energy barrier.

The previous post was about an insecticide and made a point that the persistence of both insecticides and herbicides is an important aspect of their environmental properties. Water hydrolysis will degrade them, a typical residency time being in the order of a few days. I noted in passing a dioxepin-based herbicide[cite]10.1039/P29890001265[/cite] which contains a ketal motif and which in water can hydrolise to a ketone and alcohol.

In a recent post, I told the story of how in the early 1960s, Robert Woodward had encountered an unexpected stereochemical outcome to the reaction of a hexatriene, part of his grand synthesis of vitamin B12. He had constructed a model of the reaction he wanted to undertake, perhaps with the help of a physical model, concluding that the most favourable of the two he had built was not matched by the actual outcome of the reaction.

I asked the question in my previous post. A computational mechanism revealed that AlCl ₃ or its dimer Al ₂ Cl ₆ could catalyse a concerted 1,1-substitution reaction at the carbon of Cl-C≡N, with benzene displacing chloride which is in turn captured by the Al. Unfortunately the calculated barrier for this simple process was too high for a reaction apparently occuring at ~room temperatures.

In 2010 I recounted the story of an organic chemistry tutorial, in which I asked the students the question “ how would you synthesize 3-nitrobenzonitrile “. The expected answer was to generate a nitronium ion to nitrate benzonitrile, but can one invert this by generating a C⩸N ⁺ ion to cyanate nitrobenzene?

These four posts (the box set) set out to try to define the energetics for a reasonable reaction path for the Willgerodt-Kindler reaction. The rate of this reaction corresponds approximately to a free energy barrier of ~30 kcal/mol. Any pathway found to be >10 kcal/mol at its highest point above this barrier was deemed less probable. The first three efforts at defining such pathways all gave such a result.

The two previous surveys of the potential energy surface for this, it has to be said, rather obscure reaction led to energy barriers that were rather to high to be entirely convincing. So here is a third possibility. The red section corresponds to the previous exploration, in which a 3-membered sulfur ring intermediate was mooted. Here we go back to a 3-ring with nitrogen instead.