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!
Posts Tagged ‘free energy’
Di-imide reduction with a twist: A Möbius version.
Monday, November 26th, 2012The “unexpected” mechanism of peroxide decomposition.
Sunday, 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. http://dx.doi.org/10.1021/ja0464903
Thalidomide. The role of water in the mechanism of its aqueous racemisation.
Saturday, 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. http://dx.doi.org/10.1002/chem.201202651
Dynamic effects in nucleophilic substitution at trigonal carbon (with Na+) revisited.
Monday, August 13th, 2012This reaction looks simple but is deceptively complex. To recapitulate: tolyl thiolate (X=Na) reacts with the dichlorobutenone to give two substitution products in a 81:19 ratio, a result that Singleton and Bogle argue arises from a statistical distribution of dynamic trajectories bifurcating out of a single transition state favouring 2 over 3. On the grounds (presumably) that the presence of both the cation X (=Na+) and H-bonded solvent (ethanol) are uninfluential, neither species was explicitly included in the transition state model used to derive the dynamics. I speculated whether in fact the spatial distribution of counterions and solvent (set up by explicit hydrogen bonds and O…Na+ interactions) might in fact be perturbed from un-influential randomness by co-ordination to the carbonyl group present in the system. I also raised the issue of what the origin of the electronic effects leading to the major product might be.
More joining up of pieces. Stereocontrol in the ring opening of cyclopropenes.
Thursday, July 12th, 2012Years ago, I was travelling from Cambridge to London on a train. I found myself sitting next to a chemist, and (as chemists do), he scribbled the following on a piece of paper. When I got to work the next day Vera (my student) was unleashed on the problem, and our thoughts were published[1]. That was then.
References
- M.S. Baird, J.R. Al Dulayymi, H.S. Rzepa, and V. Thoss, "An unusual example of stereoelectronic control in the ring opening of 3,3-disubstituted 1,2-dichlorocyclopropenes", Journal of the Chemical Society, Chemical Communications, pp. 1323, 1992. http://dx.doi.org/10.1039/C39920001323
Transition state models for Baldwin dig(onal) ring closures.
Sunday, June 10th, 2012This is a continuation of the previous post exploring the transition state geometries of various types of ring closure as predicted by Baldwin’s rules. I had dealt with bond formation to a trigonal (sp2) carbon; now I add a digonal (sp) example (see an interesting literature variation).
The mechanism of the Baeyer-Villiger rearrangement.
Monday, May 7th, 2012The Baeyer-Villiger rearrangement was named after its discoverers, who in 1899 described the transformation of menthone into the corresponding lactone using Caro’s acid (peroxysulfuric acid). The mechanism is described in all text books of organic chemistry as involving an alkyl migration. Here I take a look at the scheme described by Alvarez-Idaboy, Reyes and Mora-Diez[1], and which may well not yet have made it to all the text books!
References
- J.R. Alvarez-Idaboy, L. Reyes, and N. Mora-Diez, "The mechanism of the Baeyer–Villiger rearrangement: quantum chemistry and TST study supported by experimental kinetic data", Organic & Biomolecular Chemistry, vol. 5, pp. 3682, 2007. http://dx.doi.org/10.1039/b712608e
Spotting the unexpected. The hydration of formaldehyde.
Monday, March 12th, 2012In my previous post I speculated why bis(trifluoromethyl) ketone tends to fully form a hydrate when dissolved in water, but acetone does not. Here I turn to asking why formaldehyde is also 80% converted to methanediol in water? Could it be that again, the diol is somehow preferentially stabilised compared to the carbonyl precursor and if so, why?
The dawn of organic reaction mechanism: the prequel.
Sunday, November 13th, 2011Following on from Armstrong’s almost electronic theory of chemistry in 1887-1890, and Beckmann’s radical idea around the same time that molecules undergoing transformations might do so via a reaction mechanism involving unseen intermediates (in his case, a transient enol of a ketone) I here describe how these concepts underwent further evolution in the early 1920s. My focus is on Edith Hilda Usherwood, who was then a PhD student at Imperial College working under the supervision of Martha Whitely.1