Imperial College London

Henry Rzepa

I have
[mentioned](http://www.ch.imperial.ac.uk/rzepa/blog/?p=2559){target="_blank"}
Lewis a number of times in these posts; his suggestion of the shared
electron covalent bond still underpins much chemical thinking. Take for
example mechanistic speculations on the course of a reaction, a very
common indulgence in almost all articles reporting such, and largely
based on informed * [arrow
pushing](http://www.ch.imperial.ac.uk/rzepa/blog/?p=2737){target="_blank"}*.
This process is bound to follow the rules of reasonable Lewis structures
for any putative intermediates. Here, I suggest that we are now firmly
in an era where such speculations must of necessity be backed up by
quantum mechanical estimates of the energies and structures. I would
propose that journals routinely encourage referees to insist on such
(additional) checks. Let me give one specific example of the need to do
this (part of a follow up to an earlier article I [blogged
on](http://www.ch.imperial.ac.uk/rzepa/blog/?p=2828){target="_blank"}
previously).

::: {#attachment_4880 .wp-caption .aligncenter style="width: 345px"}
[![](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2011/09/nsch001.gif "nsch001"){.size-full
.wp-image-4880 loading="lazy" decoding="async"
aria-describedby="caption-attachment-4880" width="335"
height="254"}](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2011/09/nsch001.gif)

Scheme 1 (reproduced from 10.1002/chem.201100693 )
:::

The example is found as **scheme 1** of an article written by Legrand,
Gilles, Petit, van der Lee and Barboiu entitled "*Unprecedented
Synthesis of 1,3-Dimethylcyclobutadiene in the Solid State and Aqueous
Solution*"
(DOI: [10.1002/chem.201100693](http://dx.doi.org/10.1002/chem.201100693){target="_blank"};
 Scheme 1 reproduced here  with the permission of the publishers).
Structures **1** -- **3** are my additions, and are not present in
**scheme 1** of the above article.

::: {#attachment_4756 .wp-caption .aligncenter style="width: 310px"}
[![](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2011/08/scheme1.jpg "scheme"){.size-full
.wp-image-4756 loading="lazy" decoding="async"
aria-describedby="caption-attachment-4756" width="300"
height="309"}](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2011/08/scheme1.jpg)

Possible species involved in the mechanism for photochemical irradiation
of dimethyl pyrone.
:::

The scientific problem is to identify what the products are of
photolysis of **Me~2~1**. The species is contained as a guest inside a
calixarene host, the whole assembly being dissolved in water (D~2~O).
This was photolysed and the products characterised by (*inter alia*)
their [^1^H NMR spectra, Figure
7](http://onlinelibrary.wiley.com/doi/10.1002/chem.201100693/full){target="_blank"}.
Focus in particular on** 7b**, which shows a set of five spectra that
are claimed to identify the consecutive species **Me~2~1**, **Me~2~2**,
(**Me~2~3** or **1**), **Me~2~CBD^S^/CO~2~**, **Me~2~CBD^R^** and
**Me~2~4** as the outcomes of photolysis at "*different irradiation
times at l=320--500 nm or at l=190--500 nm*".

::: {#attachment_4882 .wp-caption .aligncenter style="width: 449px"}
[![](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2011/09/nfig007.gif "nfig007"){.size-full
.wp-image-4882 loading="lazy" decoding="async"
aria-describedby="caption-attachment-4882" width="439"
height="714"}](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2011/09/nfig007.gif)

Figure 7 (taken from 10.1002/chem.201100693, reproduced with permission
of publisher )
:::

How might one apply a computational reality check to this scheme? Lewis
himself might have ventured to suggest that representation **Me~2~3**
does not adhere to his rules; a modern chemistry student would draw it
instead as **2**, a vinyl zwitterion. This species in turn could either
eliminate carbon monoxide (red arrow) or ring close to give the unusual
ylid **3** (blue arrow). In fact DFT calculations on the isolated
molecules in water
([ωB97XD/6-311G(d,p)/SCRF=water](http://dx.doi.org/10042/to-9341){target="_blank"})
indicate that the C-O bond in an isolated molecule of **Me~2~3 **does
not persist and fragments to carbon monoxide and an alkoxy
zwitterion, making it around \~36.5 kcal/mol higher in free energy than
the [alternative
zwitterion](http://hdl.handle.net/10042/to-9341){target="_blank"} **1**.
The third species **3** is somewhat more stable, being \~20 kcal/mol
above **1**. Calculations also reveal that whilst rectangular
**Me~2~CBD^R^** is obtained on the singlet surface, the square
**Me~2~CBD^S^/CO~2~** can only be obtained on the triplet surface. This
state however is \~8-10 kcal/mol higher in energy and unlikely to have a
long lifetime before it decays down to the singlet surface. One could
study all the species in the scheme above in this manner, but that
analysis is for another place and time.

Until relatively recently, such reality checks would be all one might
attempt computationally. But these experiments were NOT conducted on
isolated molecules in solution, they were done in the presence of a
calixarene host. Could that change things? Zwitterion **1** can be
[placed inside this
cavity](http://hdl.handle.net/10042/to-9313){target="_blank"} and the
calculation repeated (again simulating solvent water), as can **2**. In
fact the latter spontaneously collapses to **3**, and now has an energy
\~ 27 kcal/mol higher than **1**. Whether **1** itself (or indeed
**Me~2~CBD^R^**) has any persistent lifetime is another issue, and one
not addressed in this blog post.

In fact, the reality check has another purpose, which is to stimulate
other ideas. In this case for example one could regard **3** as a
carbene, in which case one might ask if coordination of the carbene to a
suitable metal might be a stabilizing mode. Amazingly, a number of such
systems are known! I show just one below.

<table data-border="0">
<colgroup>
<col style="width: 50%" />
<col style="width: 50%" />
</colgroup>
<tbody>
<tr class="odd">
<td><div id="attachment_4796" class="wp-caption aligncenter"
style="width: 197px">
<a
href="http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2011/09/schxfe10a.jpg"><img
src="http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2011/09/schxfe10a.jpg"
title="schxfe10a" class="size-full wp-image-4796" loading="lazy"
decoding="async" aria-describedby="caption-attachment-4796" width="187"
height="173" /></a>
<p>SCHXFe structure diagram.</p>
</div></td>
<td><img
src="http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2011/09/schxfe10.jpg"
title="schxfe10" class="size-full wp-image-4795" loading="lazy"
decoding="async"
onclick="jmolInitialize(&#39;../Jmol/&#39;,true);jmolSetAppletColor(&#39;white&#39;);jmolApplet([600,600],&#39;load wp-content/uploads/2011/08/SCHXFE10.cif;&#39;);"
width="245" height="235" /><br />
SCHXFe. Click for 3D structure.</td>
</tr>
</tbody>
</table>

There is a lot more that could be said (and written) about [this
article](http://dx.doi.org/10.1002/chem.201100693){target="_blank"},
including discussion of the ^1^H NMR spectra, but I will stop at this
point. Hopefully, I have shown how simple computational reality checks
on a proposed mechanism can easily result in both unexpected outcomes
and ideas for new chemistry!

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


I have mentioned Lewis a number of times in these posts; his suggestion of the shared electron covalent bond still underpins much chemical thinking. Take for example mechanistic speculations on the course of a reaction, a very common indulgence in almost all articles reporting such, and largely based on informed * arrow pushing*. This process is bound to follow the rules of reasonable Lewis structures for any putative intermediates.

Messaggi di Rogue Scholar

Computational “reality checks” for mechanistic speculations.