Archive for the ‘Historical’ Category
Saturday, November 10th, 2012
Thalidomide 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. 
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References
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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
Tags: 298 4.7, aqueous media, ATM, energy barrier, energy barriers, free energy, simulation, zero-point-energy
Posted in Historical, Interesting chemistry, Reaction Mechanism | 1 Comment »
Wednesday, September 12th, 2012
All organic chemists are familiar with the stereochemical notation for bonds, as shown below. But I had difficulty tracking down when it was introduced, and by whom. I offer a suggestion here, but if anyone reading this blog has got a better/earlier attribution, please let us know!
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Tags: Derek Barton, R. C. Cookson
Posted in Historical | 4 Comments »
Monday, July 23rd, 2012
Recollect, Robinson was trying to explain why the nitroso group appears to be an o/p director of aromatic electrophilic substitution. Using σ/π orthogonality, I suggested that the (first ever) curly arrows as he drew them could not be the complete story, and that a transition state analysis would be needed. Here it is.
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Tags: free energy activation barrier, σ/π orthogonality, nitrosyl, non-polar media, o/p director, o/p director of aromatic electrophilic substitution
Posted in Historical, Interesting chemistry, Reaction Mechanism, Tutorial material | 7 Comments »
Friday, July 20th, 2012
Twenty years are acknowledged to be a long time in Internet/Web terms. In the early days (in 1994), it was a taken that the passage of 1 Web day in the Internet time-warp was ~≡ 7 for the rest of the world (the same factor as applied to the lives of canines). This temporal warping can also be said to apply to computational chemistry. I previously revisited some computational work done in 1992, and here I rediscover another investigation from that year[1] and that era. The aim in this post is to compare not only how the presentation of the results has changed, but how the computational models have as well.
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References
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R.A. Batey, P. Grice, J.D. Harling, W.B. Motherwell, and H.S. Rzepa, "Origins of the regioselectivity of cyclopropylcarbinyl ring opening reactions in bicyclo [n.1.0] systems", Journal of the Chemical Society, Chemical Communications, pp. 942, 1992. http://dx.doi.org/10.1039/c39920000942
Tags: computational chemistry, hardware tools, Internet time-warp, Internet/Web terms, Skolnik, Web day
Posted in Historical, Reaction Mechanism | No Comments »
Friday, July 20th, 2012
I was first taught curly arrow pushing in 1968, and have myself taught it to many a generation of student since. But the other day, I learnt something new. Nick Greeves was kind enough to send me this link to the origin of curly arrow pushing in organic chemistry, where the following diagram is shown and Alan Dronsfield sent me two articles he co-wrote on the topic (T. M. Brown, A. T. Dronsfield and P. J. T Morris, Education in Chemistry, 2001, 38, 102-104, 107 and 2003, 40, 129-134); thanks to both of them.
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Tags: Alan Dronsfield, Indiana, Nick Greeves, Robert Robinson
Posted in Historical, Reaction Mechanism, Tutorial material | 9 Comments »
Thursday, July 12th, 2012
Years 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.
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References
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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
Tags: Cambridge, chemist, conformational analysis, Internet era, London, pericyclic, re-analysis using modern algorithms, Skolnik
Posted in Historical, Reaction Mechanism | 1 Comment »
Thursday, July 5th, 2012
Back in 1994, we published the crystal structure of the molecule below (X=H), a putative anti-malarial drug called halofantrine. Little did we realise that a whole area of organo catalysis based on a thiourea catalyst with a similar motif would emerge a little later. Here is how the two are connected.
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Tags: MPEG, Peter Schreiner, Skolnik
Posted in Chemical IT, Historical, Interesting chemistry | 3 Comments »
Monday, May 7th, 2012
The mechanism of the reaction of alkenes known as ozonolysis was first set out in its modern form by Criegee. The crucial steps, (a), (b) and (d), are all pericyclic cycloaddition/eliminations. The last step (e) is known as reductive ozonolysis, and this step is often treated as an afterthought, part of the work-up of the reaction if you like (it is not illustrated in Criegee’s review for example). Here, I will attempt to show that it is actually a very interesting mechanistic step.
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Tags: 200th post, pericyclic, S bridge
Posted in Historical, Interesting chemistry | 3 Comments »
Monday, May 7th, 2012
The 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!
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References
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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
Tags: final product, free energy, stereoelectronic, X5
Posted in Historical, Tutorial material | 5 Comments »
