I was intrigued by one aspect of the calculated transition state for di-imide reduction of an alkene; the calculated NMR shieldings indicated an diatropic ring current at the centre of the ring, but very deshielded shifts for the hydrogen atoms being transferred. This indicated, like most thermal pericyclic reactions, an aromatic transition state. Well, one game one can play with this sort of reaction is to add a double bond. This adds quite a twist to this classical reaction!
Di-imide reduction with a twist: A Möbius version.
November 26th, 2012The regiospecificity of di-imide reduction of an alkene.
November 25th, 2012Not a few posts on this blog dissect the mechanisms of well known text-book reactions. But one reaction type where there are few examples on these pages are reductions. These come in three types; using electrons, using a hydride anion and using di-hydrogen. Here I first take a closer look at the third type, and in particular di-hydrogen as delivered from di-imide.
The “unexpected” mechanism of peroxide decomposition.
November 18th, 2012A game chemists often play is to guess the mechanism for any given reaction. I thought I would give it a go for the decomposition of the tris-peroxide shown below. This reaction is known to (rapidly, very rapidly) result in the production of three molecules of propanone, one of ozone and a lot of entropy (but not heat).[1]
References
- F. Dubnikova, R. Kosloff, J. Almog, Y. Zeiri, R. Boese, H. Itzhaky, A. Alt, and E. Keinan, "Decomposition of Triacetone Triperoxide Is an Entropic Explosion", Journal of the American Chemical Society, vol. 127, pp. 1146-1159, 2005. https://doi.org/10.1021/ja0464903
Thalidomide. The role of water in the mechanism of its aqueous racemisation.
November 10th, 2012Thalidomide is a chiral molecule, which was sold in the 1960s as a sedative in its (S,R)-racemic form. The tragedy was that the (S)-isomer was tetragenic, and only the (R) enantiomer acts as a sedative. What was not appreciated at the time is that interconversion of the (S)- and (R) forms takes place quite quickly in aqueous media. Nowadays, quantum modelling can provide good in-silico estimates of the (free) energy barriers for such processes, which in this case is a simple keto-enol tautomerism. In a recently published article[1], just such a simulation is reported. By involving two explicit water molecules in the transition state, an (~enthalpic) barrier of 27.7 kcal/mol was obtained. The simulation was conducted just with two water molecules acting as solvent, and without any additional continuum solvation applied. So I thought I would re-evaluate this result by computing it at the ωB97XD/6-311G(d,p)/SCRF=water level (a triple-ζ basis set rather than the double-ζ used before[1]), and employing a dispersion-corrected DFT method rather than B3LYP. 
References
- C. Tian, P. Xiu, Y. Meng, W. Zhao, Z. Wang, and R. Zhou, "Enantiomerization Mechanism of Thalidomide and the Role of Water and Hydroxide Ions", Chemistry – A European Journal, vol. 18, pp. 14305-14313, 2012. https://doi.org/10.1002/chem.201202651
Mechanisms of carbon monoxide insertion reactions: A reality check on carbonylation of methyl manganese pentacarbonyl
November 4th, 2012When methyl manganese pentacarbonyl is treated with carbon monoxide in e.g. di-n-butyl ether, acetyl manganese pentacarbonyl is formed. This classic experiment conducted by Cotton (of quadruple bond fame) and Calderazzo in 1962[1] dates from an era when chemists conducted extensive kinetic analyses to back up any mechanistic speculations. Their suggested transition state is outlined below. Here I subject their speculations to a quantum mechanical “reality check“.
References
- F. Calderazzo, and F.A. Cotton, "Carbon Monoxide Insertion Reactions. I. The Carbonylation of Methyl Manganese Pentacarbonyl and Decarbonylation of Acetyl Manganese Pentacarbonyl", Inorganic Chemistry, vol. 1, pp. 30-36, 1962. https://doi.org/10.1021/ic50001a008
Secrets of a university tutor. An exercise in mechanistic logic: second dénouement.
October 29th, 2012Following 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.
Secrets of a university tutor. An exercise in mechanistic logic: first dénouement.
October 28th, 2012The reaction described in the previous post (below) is an unusual example of nucleophilic attack at an sp2-carbon centre, reportedly resulting in inversion of configuration[1]. One can break it down to a sequence of up to eight individual steps, which makes teaching it far easier. But how real is that sequence?
References
- T.C. Clarke, and R.G. Bergman, "Olefinic cyclization at a vinyl cation center. Inversion preference for intramolecular nucleophilic substitution by a double bond", Journal of the American Chemical Society, vol. 94, pp. 3627-3629, 1972. https://doi.org/10.1021/ja00765a062
Secrets of a university tutor. An exercise in mechanistic logic, prequel.
October 27th, 2012The reaction below plays a special role in my career. As a newly appointed researcher (way back now), I was asked to take tutorial groups for organic chemistry as part of my duties. I sat down to devise a suitable challenge for the group, and came upon the following reaction[1]. I wrote it down on page 2 of my tutorial book, which I still have. I continue to use this example in tutorials to this day, some 35 years later.
References
- T.C. Clarke, and R.G. Bergman, "Olefinic cyclization at a vinyl cation center. Inversion preference for intramolecular nucleophilic substitution by a double bond", Journal of the American Chemical Society, vol. 94, pp. 3627-3629, 1972. https://doi.org/10.1021/ja00765a062