Archive for the ‘reaction mechanism’ Category
Friday, June 12th, 2015
In the preceding post, I discussed the reaction between mCPBA (meta-chloroperbenzoic acid) and cyclohexanone, resulting in Baeyer-Villiger oxidation via a tetrahedral intermediate (TI). Dan Singleton, in whose group the original KIE (kinetic isotope measurements) were made, has kindly pointed out on this blog that his was a mixed-phase reaction, and that mechanistic comparison with homogenous solutions may not be justified. An intriguing aspect of the (solution) mechanism would be whether the TI forms quickly and/or reversibly and what the position of any equilibrium between it and the starting ketone is. This reminded me of work we did some years ago,[1] and here I discuss that.
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References
- A.M. Lobo, M.M. Marques, S. Prabhakar, and H.S. Rzepa, "Tetrahedral intermediates formed by nitrogen and oxygen attack of aromatic hydroxylamines on acetyl cyanide", The Journal of Organic Chemistry, vol. 52, pp. 2925-2927, 1987. https://doi.org/10.1021/jo00389a050
Tags:Anomer, Anomeric effect, Carbohydrate chemistry, Carbohydrates, Chemistry, Dan Singleton, homogenous solutions, Ketone, Meta-Chloroperoxybenzoic acid, Organic chemistry, Tetrahedral carbonyl addition compound
Posted in reaction mechanism | 2 Comments »
Wednesday, June 10th, 2015
I have blogged before about the mechanism of this classical oxidation reaction. Here I further explore computed models, and whether they match the observed kinetic isotope effects (KIE) obtained using the natural-abundance method described in the previous post.
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Tags:ATM, Baeyer–Villiger oxidation, Chemistry, Dipole, energy, energy gradient, Kinetic isotope effect, Physical organic chemistry
Posted in reaction mechanism | 4 Comments »
Wednesday, June 3rd, 2015
My PhD thesis involved determining kinetic isotope effects (KIE) for aromatic electrophilic substitution reactions in an effort to learn more about the nature of the transition states involved.[1] I learnt relatively little, mostly because a transition state geometry is defined by 3N-6 variables (N = number of atoms) and its force constants by even more and you get only one or two measured KIE per reaction; a rather under-defined problem in terms of data! So I decided to spend a PostDoc learning how to invert the problem by computing the anticipated isotope effects using quantum mechanics and then comparing the predictions with measured KIE.[2] Although such computation allows access to ALL possible isotope effects, the problem is still under-defined because of the lack of measured KIE to compare the predictions with. In 1995 Dan Singleton and Allen Thomas reported an elegant strategy to this very problem by proposing a remarkably simple method for obtaining KIE using natural isotopic abundances.[3] It allows isotope effects to be measured for all the positions in one of the reactant molecules by running the reaction close to completion and then recovering unreacted reactant and measuring the changes in its isotope abundances using NMR. The method has since been widely applied[4],[5] and improved.[6] Here I explore how measured and calculated KIE can be reconciled.
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References
- B.C. Challis, and H.S. Rzepa, "The mechanism of diazo-coupling to indoles and the effect of steric hindrance on the rate-limiting step", Journal of the Chemical Society, Perkin Transactions 2, pp. 1209, 1975. https://doi.org/10.1039/p29750001209
- M.J.S. Dewar, S. Olivella, and H.S. Rzepa, "Ground states of molecules. 49. MINDO/3 study of the retro-Diels-Alder reaction of cyclohexene", Journal of the American Chemical Society, vol. 100, pp. 5650-5659, 1978. https://doi.org/10.1021/ja00486a013
- D.A. Singleton, and A.A. Thomas, "High-Precision Simultaneous Determination of Multiple Small Kinetic Isotope Effects at Natural Abundance", Journal of the American Chemical Society, vol. 117, pp. 9357-9358, 1995. https://doi.org/10.1021/ja00141a030
- Y. Wu, R.P. Singh, and L. Deng, "Asymmetric Olefin Isomerization of Butenolides via Proton Transfer Catalysis by an Organic Molecule", Journal of the American Chemical Society, vol. 133, pp. 12458-12461, 2011. https://doi.org/10.1021/ja205674x
- J. Chan, A.R. Lewis, M. Gilbert, M. Karwaski, and A.J. Bennet, "A direct NMR method for the measurement of competitive kinetic isotope effects", Nature Chemical Biology, vol. 6, pp. 405-407, 2010. https://doi.org/10.1038/nchembio.352
Tags:Allen Thomas, calculated activation free energy, Chemistry, Dan Singleton, Deuterium, Diels–Alder reaction, Isotope, Isotopes, Kinetic isotope effect, Nuclear physics, Physical organic chemistry, shell solutions
Posted in reaction mechanism | 6 Comments »
Sunday, April 26th, 2015
Allotropes are differing structural forms of the elements. The best known example is that of carbon, which comes as diamond and graphite, along with the relatively recently discovered fullerenes and now graphenes. Here I ponder whether any of the halogens can have allotropes.
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Tags:Allotropy, Bromine, Carbon, Chemical elements, Chemistry, free energy barrier, Fullerene, Halogen, Hypobromite, Matter, Nonmetals, Oxidizing agents, Oxygen, pence
Posted in reaction mechanism | 9 Comments »
Sunday, April 12th, 2015
Sodium borohydride is the tamer cousin of lithium aluminium hydride (LAH). It is used in aqueous solution to e.g. reduce aldehydes and ketones, but it leaves acids, amides and esters alone. Here I start an exploration of why it is such a different reducing agent.
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Tags:aqueous solution, Chemical bond, chemical bonding, Chemistry, Electronic effect, energy, final product, free energy barrier, Hydride, Hydrogen bond, immediate product, Lithium aluminium hydride, reduction
Posted in reaction mechanism | 2 Comments »
Friday, April 10th, 2015
Previously on this blog: modelling the reduction of cinnamaldehyde using one molecule of lithal shows easy reduction of the carbonyl but a high barrier at the next stage, the reduction of the double bond. Here is a quantum energetic exploration of what might happen when a second LAH is added to the brew (the usual ωB97XD/6-311+G(d,p)/SCRF=diethyl ether).
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Tags:computed free energy barrier, energy, energy surface, final product, flat energy potential, free energy, lower energy pathways, metal exchange, pence, potential energy surface, reduction, Yes
Posted in reaction mechanism | 1 Comment »
Wednesday, April 1st, 2015
The reduction of cinnamaldehyde by lithium aluminium hydride (LAH) was reported in a classic series of experiments[1],[2],[3] dating from 1947-8. The reaction was first introduced into the organic chemistry laboratories here at Imperial College decades ago, vanished for a short period, and has recently been reintroduced again.‡ The experiment is really simple in concept; add LAH to cinnamaldehyde and you get just reduction of the carbonyl group; invert the order of addition and you additionally get reduction of the double bond. Here I investigate the mechanism of these reductions using computation (ωB97XD/6-311+G(d,p)/SCRF=diethyl ether).
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References
- R.F. Nystrom, and W.G. Brown, "Reduction of Organic Compounds by Lithium Aluminum Hydride. I. Aldehydes, Ketones, Esters, Acid Chlorides and Acid Anhydrides", Journal of the American Chemical Society, vol. 69, pp. 1197-1199, 1947. https://doi.org/10.1021/ja01197a060
- R.F. Nystrom, and W.G. Brown, "Reduction of Organic Compounds by Lithium Aluminum Hydride. II. Carboxylic Acids", Journal of the American Chemical Society, vol. 69, pp. 2548-2549, 1947. https://doi.org/10.1021/ja01202a082
- F.A. Hochstein, and W.G. Brown, "Addition of Lithium Aluminum Hydride to Double Bonds", Journal of the American Chemical Society, vol. 70, pp. 3484-3486, 1948. https://doi.org/10.1021/ja01190a082
Tags:Al-H-Li bridge, dihydrocinnamyl alcohol reduction product, free energy, Imperial College, independent researcher, low energy escape route, lower energy alternative, metal, pence
Posted in reaction mechanism | 5 Comments »
Saturday, February 14th, 2015
According to Guggemos, Slavicek and Kresin, about 5-6![1]. This is one of those simple ideas, which is probably quite tough to do experimentally. It involved blasting water vapour through a pinhole, adding HCl and measuring the dipole-moment induced deflection by an electric field. They found “evidence for a noticeable rise in the dipole moment occurring at n≈5–6“.
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References
- N. Guggemos, P. Slavíček, and V.V. Kresin, "Electric Dipole Moments of Nanosolvated Acid Molecules in Water Clusters", Physical Review Letters, vol. 114, 2015. https://doi.org/10.1103/physrevlett.114.043401
Tags:energy, gas phase models, Java, pence, similar energy
Posted in Interesting chemistry, reaction mechanism | 1 Comment »
Sunday, December 14th, 2014
These posts contain the computed potential energy surfaces for a fair few “text-book” reactions. Here I chart the course of the cyclopropanation of alkenes using the Simmons-Smith reagent,[1] as prepared from di-iodomethane using zinc metal insertion into a C-I bond.
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References
- H.E. Simmons, and R.D. Smith, "A NEW SYNTHESIS OF CYCLOPROPANES FROM OLEFINS", Journal of the American Chemical Society, vol. 80, pp. 5323-5324, 1958. https://doi.org/10.1021/ja01552a080
Tags:computed potential energy surfaces, di-iodomethane using zinc metal insertion, Simmons
Posted in reaction mechanism | 1 Comment »