Imperial College London

Henry Rzepa

This, the fourth candidate provided by C&EN for a [vote for the molecule
of the year](http://yearinreview.cenmag.org/molecules-of-the-year/) as
[discussed here](http://www.ch.imperial.ac.uk/rzepa/blog/?p=17168), lays
claim to the World's most polar neutral molecule (system **1** shown
below).\[cite\]10.1002/anie.201508249\[/cite\] Here I explore a strategy
for extending that record.  
[![](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2016/12/polar.svg){.aligncenter
.size-large .wp-image-17207 decoding="async"
width="400"}](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2016/12/polar.svg)

The claim for **1** (**3** in \[cite\]10.1002/anie.201508249\[/cite\])
is on the basis of its measured dipole moment which is 14.1± 0.7D in
THF. This is qualified by the note that the dipole moment might be
exalted by complex formation with dimethyl acetamide; the authors report
a calculated smaller dipole moment of 9.6D (B3LYP/aug-cc-pVTZ) for the
isolated molecule. 

Inspection of **1** suggests that it is impossible for both the amino
groups to be co-planar with the benzene ring due to steric clashes
between the H...H atoms and that they must be twisted to avoid this. If
so, the conjugation with the ring would be reduced and so would the
charge transfer from the amino groups to the cyano groups (the
phenomenon responsible for the polarity). I re-optimised the molecule
myself (ωB97XD/Def2-TZVPP/SCRF=THF) and it has C~2~ symmetry, with both
amino groups rotated to avoid those steric H...H clashes (DOI:
[10.14469/hpc/1989](http://doi.org/10.14469/hpc/1989)). The calculated
dipole moment (the basis set is a bit better^‡^ than in
\[cite\]10.1002/anie.201508249\[/cite\] and also the geometry is
re-optimised in the solvent field) is
**[13.6D]{style="color: #ff0000;"}**, which is rather closer to the
measured value. An alternative explanation for the original mis-match
between theory and experiment of 4.5D could be simply the lower quality
basis set^‡^ used in the calculation and no modelled geometric
relaxation in the thf solvent field.

![](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2016/12/033.jpg){.aligncenter
.size-full .wp-image-17209 decoding="async" width="400"
srcset="https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2016/12/033.jpg 560w, https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2016/12/033-300x184.jpg 300w"
sizes="(max-width: 560px) 100vw, 560px"}

The NC bond lengths shown above will be used as a probe to reveal the
extent of conjugation. I tried **2** (R=H), a method of avoiding the
steric clash and allowing both amino groups to fully conjugate (DOI:
[10.14469/hpc/1987](https://doi.org/10.14469/hpc/1987)). Note how the
amino CN bond length contracts by 0.017Å, whereas the o-cyano CN lengths
also contract slightly. The calculated dipole moment for this variation
is [**16.1D**]{style="color: #ff0000;"}, which seems a rational outcome
of increasing the conjugation. However, measured dipole mment values of
10.9 and 12.2D are reported for **2** (**5a**, R=Me and **5b**
C~7~H~16~) respectively.\[cite\]10.1002/anie.201508249\[/cite\] This is
surprising given that these systems avoid any NH...HN steric clash and
should therefore allow better conjugation and hence an increased dipole
moment. Perhaps it is these molecules rather than **1** where the
measured dipole moment is perturbed by other effects?

![](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2016/12/034.jpg){.aligncenter
.size-full .wp-image-17211 decoding="async" width="400"
srcset="https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2016/12/034.jpg 552w, https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2016/12/034-300x278.jpg 300w"
sizes="(max-width: 552px) 100vw, 552px"}

Inspired by these molecules, I thought: why not start with a base
aromatic ring that was already polar and sprinkle amino and cyano groups
around it? Thus **3** and **4** above. The latter is derived from
azulene, which is well-known to have a [noticeable dipole moment of its
own](https://en.wikipedia.org/wiki/Azulene), with the five ring carrying
excess charge to aspire to 6π-electron aromaticity and the seven ring
losing charge to again create a 6π-aromatic ring. The cyano and amino
groups would serve to stabilize those respective charges.

Firstly **4**: Amino groups on the azulene 5,7 positions twist out of
plane and do not conjugate (long NC bonds) but all the remaining groups
show effective conjugation (DOI:
[10.14469/hpc/1988](http://doi.org/10.14469/hpc/1988)). So one could
probably dispense with 5,7-amino substitution. The calculated dipole
moment is [**21.4D**]{style="color: #ff0000;"}, which elevates the
previous value significantly.

![](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2016/12/036.jpg){.aligncenter
.size-full .wp-image-17213 decoding="async" width="450"
srcset="https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2016/12/036.jpg 583w, https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2016/12/036-300x235.jpg 300w"
sizes="(max-width: 583px) 100vw, 583px"}

Seven  2- or 3-substituted cyanoazulenes are known in the CSD (Cambridge
structure database) and likewise seven 4, 6 or 8 nitrogen substituted
derivatives are known. So it should be possible to combine these two
groups onto an azulene ring.

Finally **3**, where the amino CN bonds are even shorter, indicating
increased stabilization of the cyclopropenium cation ring formed by
charge
transfer (DOI: [10.14469/hpc/1990](http://doi.org/10.14469/hpc/1990)).
The amino groups no longer clash sterically. The central CC bond
(nominally a double bond) is lengthened considerably to facilitate the
charge transfer between rings and hence mutual aromatization, the five
5-ring bonds are 1.405Å (typical aromatic values) and the 3-ring
1.367-1.38Å (again aromatic values). This candidate has a dipole moment
of [**21.7D**]{style="color: #ff0000;"}, despite its smaller size
decreasing the separation of the charges and hence the moment.

![](http://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2016/12/037.jpg){.aligncenter
.size-full .wp-image-17215 decoding="async" width="400"}

If the function of a molecule of the year is to inspire ideas in others,
this one has certainly achieved its purpose! Now for the syntheses!

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

^‡^Anionic systems always benefit from better basis sets, much more so
than neutral or cationic molecules.

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


This, the fourth candidate provided by C&amp;EN for a vote for the molecule of the year as discussed here, lays claim to the World’s most polar neutral molecule (system
<strong>
 1
</strong>
shown below).[cite]10.1002/anie.201508249[/cite] Here I explore a strategy for extending that record.

Rogue Scholar Beiträge

Molecules of the year? The most polar neutral compound synthesized…