Imperial College London

Henry Rzepa

Following on from Armstrong's [almost electronic theory of
chemistry](http://www.ch.imperial.ac.uk/rzepa/blog/?p=5411){target="_blank"
rel="noopener"} in 1887-1890, and Beckmann's radical idea around the
same time that molecules undergoing transformations might do so via ***a
reaction mechanism*** involving unseen intermediates (in his case, a
[transient enol of a
ketone](http://dx.doi.org/10.1002/jlac.18892500306)) I here describe how
these concepts underwent further evolution in the early 1920s. My focus
is on Edith Hilda Usherwood, who was then a PhD student at Imperial
College working under the supervision of Martha Whitely.^1^

The doctoral degree itself had only been introduced into British
universities in 1919,^1^ and so Usherwood was very much a forerunner of
the modern system of training.The academic staff and students at
Imperial totalled 30, making it one of the largest research schools in
UK chemistry at the time. Usherwood's project was on tautomers, or
isomers of molecules which differ only in the position of a labile
hydrogen atom. The then quite novel electron-pair symbolism introduced
by [G. N.
Lewis' ](http://dx.doi.org/10.1021/ja02261a002){target="_blank"
rel="noopener"}in 1916 was adopted to represent two [tautomeric
equilibria](http://dx.doi.org/10.1039/CT9222101604){target="_blank"
rel="noopener"} (the supposed mobile or tautomeric hydrogens being
enclosed in \[...\])^2^

1.  \[H\]C:::N ⇔ C::N\[H\]
2.  \[H\]C:::CH ⇔ C::CH\[H\]

or in our more modern representation (in which lines replace colons, and
charges are used to ensure the octet rule is adhered to when possible):

1.  H-C≡N ⇔ ^--^C≡N^+^-H
2.  HC≡CH ⇔ :C=CH~2~

Modern structural techniques such as electron diffraction or microwave
spectroscopies not yet existing, the problem was tackled using specific
heat measurements as a function of temperature. This method suggested to
Usherwood that for **e.g.** equilibrium **2**, the concentration of
iso-acetylene (we now call this vinylidene) was insignificant at
ordinary temperatures, but it became appreciable between 200-300°C.
Further evidence was claimed for the formation of the "unseen"
vinylidene by observing ketene as a by-product of the oxidation of
acetylene. This article very much set the trend of (an almost mandatory)
speculation on the outcome of (nowadays much more complex) reactions by
the need to formulate a reaction mechanism in which various (otherwise
undetected but) plausible intermediates are involved.

Moving on some 90 years, and how might one approach such a problem
nowadays? Well, I have oft argued on this blog that a good place to
obtain [an immediate reality check on a proposed
mechanism](http://www.ch.imperial.ac.uk/rzepa/blog/?p=4751){target="_blank"
rel="noopener"} is a calculation. It will come as no surprise that a
very accurate calculation can be done on the systems shown above. For
example, CCSD(T)/cc-pVTZ will yield a free energy for the equilibria
with a pretty small error (\< 1 kcal/mol). We use ΔG = -RT Ln K to
inter-convert free energies and equilibrium constants. If we are
generous and state that in order to observe an appreciable concentration
of a minor species, the equilibrium constant can be no smaller than
10^-3^, its energy cannot be greater than 4 kcal/mol above the more
abundant isomer. Our reality check will be to see if the free energy of
vinylidene is indeed no more than 4 kcal/mol greater than acetylene.
Well, CCSD(T)/cc-pVTZ predicts vinylidene is 41.3 kcal/mol higher @298K,
reduced to 33.8 @2000K (and before you ask, these results took a total
of perhaps 30 minutes to obtain).

In 1924, the concept of calculating the relative energies of two species
using first principles was not even a glimmer on the horizon. The nature
of mechanisms was slowly and often painfully established by recourse to
experiments alone. And many of the unseen intermediates often remained
just such, their existence only inferred indirectly from the models one
constructed (of specify heats in Usherwood's case). It is perhaps no
great surprise that these models do not always stand the test of time.
In this case, within a year of Usherwood's publication,
[Partington](10.1080/14786442508634648){target="_blank" rel="noopener"}
was suggesting that the model for the specific heats of acetylene should
have included allowance for polymer formation.^3^ The modern take, armed
with the calculation I note above, might in fact side with Partington
after all. As for the formation of ketene by oxidation, it is indeed
known that (peracid) oxidation of an alkyne will produce ketene, but the
modern mechanism (an interesting exercise in arrow pushing for a
student) does not involve vinylidene intermediates.

I will add at this point that Hilda Usherwood was married to Christopher
Ingold, and the pair of them subsequently published many of the seminal
articles in what became known as physical organic chemistry. That legacy
continues to this day with (as I noted above) the almost mandatory
speculation about the mechanism of any new reaction. But it is only in
the last five years or so that these speculations have started to be
increasingly tested against reliably accurate computation. A new era is
underway.

------------------------------------------------------------------------

^1^ My post was inspired by reading W. H. Brock, "The case of the
Poisonous Socks", chapter 28, RSC Publishing, 2011, 978-1-84973-324-3.

^2^ These representations are taken from ref 1, p 225 (and include a
correction of replacing C:C as drawn there by C::C. The original article
apparently appeared in the proceedings of the British Association of
1924, which is not yet available online.

^3^ Brock, in ref 1, p226, suggests that Usherwood stood her ground on
this one, and won her case by showing that Partington's evidence for
polymerization was valid for only a small part of the temperature range
she had investigated. I have not managed to track down the original
sources for this exchange.

::: {.wp_orcid_field}
[https://orcid.org/0000-0002-8635-8390](https://orcid.org/0000-0002-8635-8390){target="_blank"
rel="author"}
:::


Following on from Armstrong’s almost electronic theory of chemistry in 1887-1890, and Beckmann’s radical idea around the same time that molecules undergoing transformations might do so via
<em>
 <strong>
  a reaction mechanism
 </strong>
</em>
involving unseen intermediates (in his case, a transient enol of a ketone) I here describe how these concepts underwent further evolution in the early 1920s.

Postagens de Rogue Scholar

The dawn of organic reaction mechanism: the prequel.