Dimethyl ketal hydrolysis catalysed by hydroxide and hydronium ions

April 7th, 2021

In the preceding post, I looked at a computed mechanism for the hydrolysis of a ketal by water. Of course, pure water consists of three potential catalysts, water itself or [H2O], and the products of autoionisation, [OH] and [H3O+]. The latter are in much smaller concentration, equivalent to a penalty of ~11.9 kcal/mol on any free energy barrier. Here I take a look at these ion-catalysed routes to see if that penalty can be overcome.

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A computational mechanism for the aqueous hydrolysis of a ketal to a ketone and alcohol.

April 1st, 2021

The previous post was about an insecticide and made a point that the persistence of both insecticides and herbicides is an important aspect of their environmental properties. Water hydrolysis will degrade them, a typical residency time being in the order of a few days. I noted in passing a dioxepin-based herbicide[1] which contains a ketal motif and which in water can hydrolise to a ketone and alcohol. The reverse (acid catalysed) formation of a ketal is a staple of the taught organic chemistry curriculum. Here as a prelude to looking at the hydrolysis of that dioxepin, I take a look at a possible computational mechanism for the hydrolysis of 2,2-dimethoxypropane using pure water, without the help of acid or base.

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References

  1. P. Camilleri, D. Munro, K. Weaver, D.J. Williams, H.S. Rzepa, and A.M.Z. Slawin, "Isoxazolinyldioxepins. Part 1. Structure–reactivity studies of the hydrolysis of oxazolinyldioxepin derivatives", J. Chem. Soc., Perkin Trans. 2, pp. 1265-1269, 1989. http://dx.doi.org/10.1039/P29890001265

Deltamethrin – a polymorphed insecticide.

March 24th, 2021

Deltamethin is a pyrethroid insecticide for control of malaria which has been used for a little while. Perhaps inevitably, mosquitoes are developing resistance to it. So what could be done about countering this? Well, perhaps surprisingly, form a polymorph![1] These crystal structure isomers are often highly undesirable; thus Ritonavir, which changed its polymorphic form during manufacture to become far less active (due it has to be said to insolubility). Now a polymorph of Deltamethin has been discovered, which when applied as a powder, increases its effectiveness more than 10 times against Anopheles mosquitoes and provides a potentially new affordable malaria control solution for countries that are loosing protection.

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References

  1. J. Yang, B. Erriah, C.T. Hu, E. Reiter, X. Zhu, V. López-Mejías, I.P. Carmona-Sepúlveda, M.D. Ward, and B. Kahr, "A deltamethrin crystal polymorph for more effective malaria control", Proceedings of the National Academy of Sciences, vol. 117, pp. 26633-26638, 2020. http://dx.doi.org/10.1073/pnas.2013390117

The small-molecule antiviral compound Molnupiravir: an exploration of its tautomers.

March 14th, 2021

For obvious reasons, anti-viral molecules are very much in the news at the moment. Thus Derek Lowe highlights Molnupiravir which is shown as a hydroxylamine, the representation originating from the Wikipedia page on the molecule.

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The chemistry of scents: Vetifer oil.

February 28th, 2021

I have occasionally covered the topic of colours here, such as those of flowers and minerals, since it is at least possible to illustrate these using photographs or colour charts to illustrate the theme. But when Derek Lowe took a break from his remarkable coverage of the COVID pandemic to highlight a recent article on the active smelling principle in Vetifer oil[1] I could not resist adding a tiny amount to his must-read story.

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References

  1. J. Ouyang, H. Bae, S. Jordi, Q.M. Dao, S. Dossenbach, S. Dehn, J.B. Lingnau, C. Kanta De, P. Kraft, and B. List, "The Smelling Principle of Vetiver Oil, Unveiled by Chemical Synthesis", Angewandte Chemie International Edition, vol. 60, pp. 5666-5672, 2021. http://dx.doi.org/10.1002/anie.202014609

Non-covalent-interaction (NCI) surfaces for two large annulenes (revisited).

February 7th, 2021

The last post addressed the concept of “steric clashes” in a pericyclic reaction transition state as an extension of the time honoured practice of building molecular models to analyse reaction outcomes. A modern computer generated model might express this in terms of a NCI (non-covalent-interaction) surface. A few posts ago, I had looked at some “molecules of the year” for 2020, one of which was a “figure-eight” twisted dodecaporphyrin in which an aspect of the reported[1] geometry had struck me as potentially lacking features due to the so-called non-covalent dispersion or van der Waals attractions. So I am revisiting here by adding the NCI surface for this molecule and one other.

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References

  1. M. Rickhaus, M. Jirasek, L. Tejerina, H. Gotfredsen, M.D. Peeks, R. Haver, H. Jiang, T.D.W. Claridge, and H.L. Anderson, "Global aromaticity at the nanoscale", Nature Chemistry, vol. 12, pp. 236-241, 2020. http://dx.doi.org/10.1038/s41557-019-0398-3

The thermal reactions … took precisely the opposite stereochemical course to that which we had predicted. A non-covalent-interaction view of the model.

February 3rd, 2021

Another foray into one of the more famous anecdotal chemistry “models”, the analysis of which led directly to the formulation of the WoodWard-Hoffmann (stereochemical) rules for pericyclic reactions. Previously, I tried to produce a modern computer model of what Woodward might have had to hand when discovering that the stereochemical outcome of a key reaction in his vitamin B12 synthesis was opposite to that predicted using his best model of the reaction.

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The Stevens rearrangement: how history gives us new insights.

January 29th, 2021

In a recent post, I told the story of how in the early 1960s, Robert Woodward had encountered an unexpected stereochemical outcome to the reaction of a hexatriene, part of his grand synthesis of vitamin B12. He had constructed a model of the reaction he wanted to undertake, perhaps with the help of a physical model, concluding that the most favourable of the two he had built was not matched by the actual outcome of the reaction. He was thus driven to systematise such (Pericyclic) reactions by developing rules for them with Roald Hoffmann. This involved a classification scheme of “allowed” and “forbidden” pericyclic reactions and his original favoured model in fact corresponded to the latter type. When physical model building in the 1960s was gradually replaced by models based on quantum mechanical calculations from the 1970s onwards, the term “allowed” morphed into “a relatively low energy transition state for the reaction can be located” and very often “no transition state exists for a forbidden reaction”. The famous quote “there are no exceptions” (to this rule) was often interpreted that if a “forbidden reaction” did apparently proceed, its mechanism was NOT that of a pericyclic reaction. Inspired by all of this, I recollected a famous “exception” to the rules which is often explained by such non-pericyclic character, the Stevens rearrangement[1],[2],[3] by a 1,2-shift.

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References

  1. T.S. Stevens, E.M. Creighton, A.B. Gordon, and M. MacNicol, "CCCCXXIII.—Degradation of quaternary ammonium salts. Part I", J. Chem. Soc., vol. 0, pp. 3193-3197, 1928. http://dx.doi.org/10.1039/JR9280003193
  2. T.S. Stevens, "CCLXX.—Degradation of quaternary ammonium salts. Part II", J. Chem. Soc., vol. 0, pp. 2107-2119, 1930. http://dx.doi.org/10.1039/JR9300002107
  3. T.S. Stevens, W.W. Snedden, E.T. Stiller, and T. Thomson, "CCLXXI.—Degradation of quaternary ammonium salts. Part III", J. Chem. Soc., vol. 0, pp. 2119-2125, 1930. http://dx.doi.org/10.1039/JR9300002119

The chemical synthesis of C2: another fascinating twist to the story.

January 20th, 2021

Last May, I wrote an update to the story sparked by the report of the chemical synthesis of C2.[1] This species has a long history of spectroscopic observation in the gas phase, resulting from its generation at high temperatures.[2] The chemical synthesis however was done in solution at ambient or low temperatures, a game-changer as they say. Here I give another update to this unfolding story.

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References

  1. K. Miyamoto, S. Narita, Y. Masumoto, T. Hashishin, T. Osawa, M. Kimura, M. Ochiai, and M. Uchiyama, "Room-temperature chemical synthesis of C2", Nature Communications, vol. 11, 2020. http://dx.doi.org/10.1038/s41467-020-16025-x
  2. T.W. Schmidt, "The Spectroscopy of C2: A Cosmic Beacon", Accounts of Chemical Research, vol. 54, pp. 481-489, 2021. http://dx.doi.org/10.1021/acs.accounts.0c00703

The thermal reactions … took precisely the opposite stereochemical course to that which we had predicted

January 20th, 2021

The quote of the post title comes from R. B. Woodward explaining the genesis of the discovery of what are now known as the Woodward-Hoffmann rules for pericyclic reactions.[1] I first wrote about this in 2012, noting that “for (that) blog, I do not want to investigate the transition states”. Here I take a closer look at this aspect.

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References

  1. R.B. Woodward, and R. Hoffmann, "Stereochemistry of Electrocyclic Reactions", Journal of the American Chemical Society, vol. 87, pp. 395-397, 1965. http://dx.doi.org/10.1021/ja01080a054