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.
Step (e) reminded me of a mechanism we had recently investigated, involving desulfurization of epidithiodioxopiperazine fungal metabolites in which an S-S bridge is reduced by one sulfur atom by the action of triphenyl phosphine. Dimethyl sulfide in turn is used to reduce a O-O fragment of the trioxolane intermediate produced from ozonolysis by one oxygen. The transition state for path (e) is shown below (ωB97XD/6-311G(d)/SCRF=dichloromethane).
Transition state geometry for step (e). Click for 3D.
The reaction IRC for this step is shown below
- Notice how the sulfur atom approaches more or less along the axis of the O-O bond.
- At the transition state (IRC=0) the three atoms are almost collinear. This might have some steric consequences for sterically congested alkenes.
- At IRC = -4, cleavage of the O-O bond is almost complete, an the system is starting to resemble the zwitterion shown below (the calculation is done with a solvent continuum field applied, to help stabilise any ionic intermediates that might form). One might be tempted to ask how this species could be stabilised to the extent of having a less transient existence.
- Still, it is highly transient, since there is no actual minimum in the IRC energy profile. Instead, between IRC -4 and -15, the remaining bonds cleave to form the final product shown in the scheme above. As with the previous post, which illustrated the Baeyer-Villiger rearrangement, this reductive elimination is also very asynchronous, with the pair of C-O bonds cleaving after the O-O.
This again illustrates the reactions where several bonds are either forming or cleaving, the relative dynamics can be quite unpredictable. It may even be strongly influenced by substituents and solvation. All text books of organic chemistry I know of rarely if ever address this aspect of mechanism. With new generations of interactive and dynamic text books about to spring upon us, it might be time to rethink what goes into them. I would hope it is not just a rehash of what one might call the classical arrow pushing representations of mechanism.
Tags: 200th post, pericyclic
Posted in Historical, Interesting chemistry | 3 Comments »
April 30th, 2012
During the 1960s, a holy grail of synthetic chemists was to devise an efficient route to steroids. R. B. Woodward was one the chemists who undertook this challenge, starting from compounds known as dienones (e.g. 1) and their mysterious conversion to phenols (e.g. 2 or 3) under acidic conditions. This was also the golden era of mechanistic exploration, which coupled with an abundance of radioactive isotopes from the war effort had ignited the great dienone-phenol debates of that time (now largely forgotten). In a classic recording from the late 1970s, Woodward muses how chemistry had changed since he started in the early 1940s. In particular he notes how crystallography had revolutionised the reliability and speed of molecular structure determination. Here I speculate what he might have made of modern computational chemistry, and in particular whether it might cast new light on those mechanistic controversies of the past.
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Tags: computational chemist, computational chemistry, pericyclic, sigmatropic shifts, tracer labelling
Posted in Chemical IT, Historical, Interesting chemistry | No Comments »
April 22nd, 2012
Astronomers who discover an asteroid get to name it, mathematicians have theorems named after them. Synthetic chemists get to name molecules (Hector’s base and Meldrum’s acid spring to mind) and reactions between them. What do computational chemists get to name? Transition states! One of the most famous of recent years is the Houk-List.
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Tags: condensation, energy, gas-phase optimised geometry, Houk-List, smallest steric exchange energy, so-called single-point solvation energy correction, steric exchange energy
Posted in Historical, Interesting chemistry | 3 Comments »
April 6th, 2012
Chemists love a mystery as much as anyone. And gaps in patterns can be mysterious. Mendeleev’s period table had famous gaps which led to new discovery. And so from the 1890s onwards, chemists searched for the perbromate anion, BrO4-. It represented a gap between perchlorate and periodate, both of which had long been known. As the failure to turn up perbromate persisted, the riddle deepened. Finally, in 1968, the key was found, but talk about sledgehammer to crack a nut! It was done by alchemical-like radioactive transmutation of selenium into bromine:
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Tags: alkaline sodium hypobromite solution, chemical synthesis, metal catalysis, present chemical knowledge, speculative chemist
Posted in Historical, Interesting chemistry | No Comments »
March 13th, 2012
I wrote in an earlier post how Pauling’s Nobel prize-winning suggestion in February 1951 of an (left-handed) α-helical structure for proteins was based on the wrong absolute configuration of the amino acids (hence his helix should really have been the right-handed enantiomer). This was most famously established a few months later by Bijvoet’s definitive crystallographic determination of the absolute configuration of rubidium tartrate, published on August 18th, 1951 (there is no received date, but a preliminary communication of this result was made in April 1950). Well, a colleague (thanks Chris!) just wandered into my office and he drew my attention to an article by John Kirkwood (DOI: 10.1063/1.1700491) published in April 1952, but received July 20, 1951, carrying the assertion “The Fischer convention is confirmed as a structurally correct representation of absolute configuration“, and based on the two compounds 2,3-epoxybutane and 1,2-dichloropropane. Neither Bijvoet nor Kirkwood seem aware of the other’s work, which was based on crystallography for the first, and quantum computation for the second. Over the years, the first result has become the more famous, perhaps because Bijvoet’s result was mentioned early on by Watson and Crick in their own very famous 1953 publication of the helical structure of DNA. They do not mention Kirkwood’s result. Had they not been familiar with Bijvoet’s result, their helix too might have turned out a left-handed one!
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Tags: California, chiroptical spectroscopies, computational chemistry, Imperial College, Institute of Technology, John Kirkwood, Pasadena, spectroscopy
Posted in Interesting chemistry | 1 Comment »
March 9th, 2012
The equilibrium for the hydration of a ketone to form a gem-diol hydrate is known to be highly sensitive to substituents. Consider the two equilibria:
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Tags: anomeric effects, ELF, free energy difference, interaction energy, NBO, O Lp
Posted in Interesting chemistry, Tutorial material | 2 Comments »
February 27th, 2012
Sometimes, as a break from describing chemistry, I take to describing the (chemical/scientific) creations behind the (WordPress) blog system. It is fascinating how there do seem increasing signs of convergence between the blog post and the journal article. Perhaps prompted by transclusion of tools such as Jmol and LaTex into Wikis and blogs, I list the following interesting developments in both genres. Read the rest of this entry »
Tags: API, chemical terms, chemical/science-savvy blog, chemical/scientific, citation management, Digital Object Identifier, Dublin, Java, LaTex, Sometimes
Posted in Chemical IT | No Comments »
