Archive for the ‘reaction mechanism’ Category

Is cyanogen chloride (fluoride) a source of C⩸N(+)? More mechanistic insights.

Friday, December 4th, 2020

I asked the question in my previous post. A computational mechanism revealed that AlCl3 or its dimer Al2Cl6 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. Comments on the post suggested using either a second AlCl3 or a proton to activate the carbon of the C≡N group by coordination on to nitrogen. A second suggestion was to involve di-cationic electrophiles. Here I report the result of implementing the N-coordinated model below.


Is cyanogen chloride (fluoride) a source of C⩸N(+)?

Saturday, November 28th, 2020

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 Willgerodt-Kindler reaction. Completing the Box set.

Monday, September 7th, 2020

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. Here I try a fourth pathway in search of the hitherto elusive appropriately low energy barrier.


The Willgerodt-Kindler Reaction: mechanistic reality check 3. A peek under the hood for transition state location.

Thursday, August 27th, 2020

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 Willgerodt-Kindler Reaction: mechanistic reality check 2.

Friday, August 14th, 2020

Continuing an exploration of the mechanism of this reaction, an alternative new mechanism was suggested in 1989 (having been first submitted to the journal ten years earlier!).[1] Here the key intermediate proposed is a thiirenium cation (labelled 8 in the article) and labelled Int3 below.



  1. M. Carmack, "The willgerodt-kindler reactions. 7. The mechanisms", Journal of Heterocyclic Chemistry, vol. 26, pp. 1319-1323, 1989.

The Willgerodt-Kindler Reaction: mechanistic reality check 1.

Tuesday, July 21st, 2020

The Willgerodt reaction[1], discovered in 1887 and shown below, represents a transformation with a once famously obscure mechanism. A major step in the elucidation of that mechanism came[2] using the then new technique of 14C radio-labelling, shortly after the atom bomb projects during WWII made 14CO2 readily available to researchers. Here I am going to start the process of applying the far more recent technique of quantitative quantum mechanical modelling to see if some of the proposed mechanisms stand up to its scrutiny.



  1. C. Willgerodt, "Ueber die Einwirkung von gelbem Schwefelammonium auf Ketone und Chinone", Berichte der deutschen chemischen Gesellschaft, vol. 20, pp. 2467-2470, 1887.
  2. W.G. Dauben, J.C. Reid, P.E. Yankwich, and M. Calvin, "The Mechanism of the Willgerodt Reaction1", Journal of the American Chemical Society, vol. 72, pp. 121-124, 1950.

Curly arrows in the 21st Century. Proton-coupled electron transfers.

Wednesday, June 10th, 2020

One of the most fascinating and important articles dealing with curly arrows I have seen is that by Klein and Knizia on the topic of C-H bond activations using an iron catalyst.[1] These are so-called high spin systems with unpaired electrons and the mechanism of C-H activation involves both double headed (two electron) and fish-hook (single electron) movement. Here I focus on a specific type of reaction, the concerted proton-coupled-electron transfer or cPCET, as illustrated below. These sorts of reactions happen also to be of considerable biological importance, including e.g. the mechanism of photosynthesis and many other important transformations.



  1. J.E.M.N. Klein, and G. Knizia, "cPCET versus HAT: A Direct Theoretical Method for Distinguishing X-H Bond-Activation Mechanisms", Angewandte Chemie International Edition, vol. 57, pp. 11913-11917, 2018.

Choreographing a chemical ballet: what happens if you change one of the actors?

Friday, May 8th, 2020

Earlier, I explored the choreography or “timing”, of what might be described as the curly arrows for a typical taught reaction mechanism, the 1,4-addition of a nucleophile to an unsaturated carbonyl compound (scheme 1). I am now going to explore the consequences of changing one of the actors by adding the nucleophile to an unsaturated imine rather than carbonyl compound (scheme 2). 


Discussion of (the) Room-temperature chemical synthesis of dicarbon – open and transparent science.

Wednesday, May 6th, 2020

A little more than a year ago, a ChemRxiv pre-print appeared bearing the title referenced in this post,[1] which immediately piqued my curiosity. The report presented persuasive evidence, in the form of trapping experiments, that dicarbon or C2 had been formed by the following chemical synthesis. Here I describe some of what happened next, since it perhaps gives some insight into the processes of bringing a scientific result into the open.



  1. K. Miyamoto, S. Narita, Y. Masumoto, T. Hashishin, M. Kimura, M. Ochiai, and M. Uchiyama, "Room-Temperature Chemical Synthesis of C2", 2019.

A databank of molecular dynamics reaction trajectories (DDT) focused on undergraduate teaching.

Wednesday, April 22nd, 2020

In a previous post, I talked about a library of reaction pathway intrinsic reaction coordinates (IRCs) containing 115 examples of organic and organometallic reactions. Now (thanks Dean!) I have been alerted to a brand new databank of dynamics trajectories (DDT), with the focus on those reactions taught in undergraduate organic chemistry courses, some of which are shown below.