Archive for the ‘Historical’ Category
Sunday, January 6th, 2013
The benzidine rearrangement is claimed to be an example of the quite rare [5,5] sigmatropic migration[1], which is a ten-electron homologation of the very common [3,3] sigmatropic reaction (e.g. the Cope or Claisen). Some benzidine rearrangements are indeed thought to go through the [3,3] route[2]. The topic has been reviewed here[3].
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References
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H.J. Shine, K.H. Park, M.L. Brownawell, and J. San Filippo, "Benzidine rearrangements. 19. The concerted nature of the one-proton rearrangement of 2,2'-dimethoxyhydrazobenzene", Journal of the American Chemical Society, vol. 106, pp. 7077-7082, 1984. http://dx.doi.org/10.1021/ja00335a035
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H.J. Shine, L. Kupczyk-Subotkowska, and W. Subotkowski, "Heavy-atom kinetic isotope effects in the acid-catalyzed rearrangement of N-2-naphthyl-N'-phenylhydrazine. Rearrangement is shown to be a concerted process", Journal of the American Chemical Society, vol. 107, pp. 6674-6678, 1985. http://dx.doi.org/10.1021/ja00309a041
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H.J. Shine, "Reflections on the π‐complex theory of benzidine rearrangements", Journal of Physical Organic Chemistry, vol. 2, pp. 491-506, 1989. http://dx.doi.org/10.1002/poc.610020702
Tags:higher energy, Historical, Interesting chemistry, π-complex, pericyclic, Reaction Mechanism
Posted in Uncategorised | 4 Comments »
Thursday, December 20th, 2012
I have written earlier about dihydrocostunolide, and how in 1963 Corey missed spotting the electronic origins of a key step in its synthesis.[1]. A nice juxtaposition to this failed opportunity relates to Woodward’s project at around the same time to synthesize vitamin B12. The step in the synthesis that caused him to ponder is shown below.
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References
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E.J. Corey, and A.G. Hortmann, "The Total Synthesis of Dihydrocostunolide", Journal of the American Chemical Society, vol. 87, pp. 5736-5742, 1965. http://dx.doi.org/10.1021/ja00952a037
Tags:dispersion energy, free energy, Historical, Interesting chemistry, pericyclic
Posted in reaction mechanism | No Comments »
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, Historical, Interesting chemistry, Reaction Mechanism, simulation, zero-point-energy
Posted in Uncategorised | 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, Historical, R. C. Cookson
Posted in Uncategorised | 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, Historical, Interesting chemistry, σ/π orthogonality, nitrosyl, non-polar media, o/p director, o/p director of aromatic electrophilic substitution, Reaction Mechanism, Tutorial material
Posted in Curly arrows | 8 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, Historical, Internet time-warp, Internet/Web terms, Reaction Mechanism, Skolnik, Web day
Posted in Uncategorised | 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, Historical, Indiana, Nick Greeves, Reaction Mechanism, Robert Robinson, Tutorial material
Posted in Curly arrows | 12 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, free energy, Historical, Interesting chemistry, Internet era, London, pericyclic, perturbation energy, re-analysis using modern algorithms, Reaction Mechanism, Skolnik
Posted in 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:Chemical IT, Historical, Interesting chemistry, MPEG, Peter Schreiner, Skolnik
Posted in Uncategorised | 3 Comments »
Monday, May 28th, 2012
Streptomycin is an antibiotic active against tuberculosis, and its discovery has become something of a cause célèbre. It was first isolated on October 19, 1943 by a graduate student Albert Schatz in the laboratory of Selman Waksman at Rutgers University. I want to concentrate in this post on its molecular structure. Its initial isolation was followed by an extraordinarily concentrated period of about three years devoted to identifying that structure, culminating in a review of this chemistry in 1948 by Lemieux and Wolfram.[1] This review presents the structure as shown below (left). The modern rendering on the right is based on a crystal structure done in 1978.[2]‡
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References
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R. Lemieux, and M. Wolfrom, "The Chemistry of Streptomycin", Advances in Carbohydrate Chemistry, pp. 337-384, 1948. http://dx.doi.org/10.1016/S0096-5332(08)60034-X
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"The crystal and molecular structure of streptomycin oxime selenate tetrahydrate", Proceedings of the Royal Society of London. A. Mathematical and Physical Sciences, vol. 359, pp. 365-388, 1978. http://dx.doi.org/10.1098/rspa.1978.0047
Tags:Albert Schatz, candidate for its formula, Historical, Interesting chemistry, laboratory of Selman Waksman, MS, muse, pence, Rutgers University, tuberculosis, X-ray
Posted in Uncategorised | 1 Comment »