Imperial College London

Henry Rzepa

The [previous
post](http://www.ch.imperial.ac.uk/rzepa/blog/?p=4030){target="_blank"}
set out a problem in conformational analysis. Here is my take, which
includes an NCI (non-covalent interaction) display as [discussed in
another
post](http://www.ch.imperial.ac.uk/rzepa/blog/?p=2230){target="_blank"}.

[![](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2011/05/problem_sheet_answer42.jpg "problem_sheet_answer4"){.aligncenter
.size-full .wp-image-4058 loading="lazy" decoding="async" width="300"
height="503"
srcset="https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2011/05/problem_sheet_answer42.jpg 1408w, https://www.ch.ic.ac.uk/rzepa/blog/wp-content/uploads/2011/05/problem_sheet_answer42-610x1024.jpg 610w"
sizes="(max-width: 300px) 100vw, 300px"}](http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2011/05/problem_sheet_answer42.jpg)

The lowest energies of the four diastereomers **A-D**, each in two
conformations (**1/2**) were calculated at the
ωB97D/6-311G(d,p)/SCRF=ethanol level, and are shown here relative to
**A1** (kcal/mol) as free energies. The values of ΔΔG of each pair
(relative to the lower energy conformation) are converted to relative
concentrations using ΔΔG = -RT *Ln* K and these are shown in blue. Those
conformations where a C-H bond is aligned anti-periplanar (*app*) with
the C-NMe~3~ bond are highlighted in red. Various aspects of the
questions posed include:

1.  Those conformations with two *app* combinations are likely to result
    in a mixture of two alkenes **E** and **F** (shown in the [previous
    post](http://www.ch.imperial.ac.uk/rzepa/blog/?p=4030){target="_blank"}),
    and likewise those with only one *app* alignment will give a single
    alkene.
2.  The concentration of the neomenthyl system (C) favours the conformer
    **C1**, which is also the one with *app* allignments. This will
    react readily. The menthyl system **A** has only a low relative
    concentration of **A2**, and so will react slowly. The experiments
    show the rate is about 10 times less than **C**, whereas the ratio
    of relative concentrations is larger. This may be due to difference
    in the transition state for the elimination, or possibly effects due
    to the presence of a counterion.
3.  The concentration of **D1** is the lowest of the four pairs of
    conformational isomers. This might be due to buttressing, in which
    the relative proximity of the NMe~3~ and iPr groups forces the
    former into closer proximity with the axial methyl than is found in
    **A2**, the other conformer with an unfavourable 1,3-diaxial
    interaction.
4.  The relative energies of most of the pairs of combinations of
    conformers/diasteromers are interesting, and I leave it to you to
    play with them and draw conclusions (or detect mysteries).

I thought I would finish by adding an [NCI
analysis](http://www.ch.imperial.ac.uk/rzepa/blog/?p=2230){target="_blank"}
using a wavefunction computed for ωB97D/6-31G(d,p)/SCRF=ethanol. The
green surfaces are indicative of regions where ***non-covalent
interactions*** are occurring (which include electrostatic and van der
Waals effects). The colour scheme is set to blue(ish) to indicate more
attractive NCIs (such as strong hydrogen bonds), green to indicate
weak(ish) NCIs, with a red or orange tinge indicating a repulsive  NCI.

<table data-border="1">
<colgroup>
<col style="width: 50%" />
<col style="width: 50%" />
</colgroup>
<tbody>
<tr class="odd">
<td><div id="attachment_4047" class="wp-caption aligncenter"
style="width: 210px">
<img
src="http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2011/05/A2-RRS.jpg"
title="A2-RRS" class="size-full wp-image-4047" loading="lazy"
decoding="async" aria-describedby="caption-attachment-4047"
onclick="jmolInitialize(&#39;../Jmol/&#39;,true);jmolSetAppletColor(&#39;goldenrod&#39;);jmolApplet([600,600],&#39;load wp-content/uploads/2011/05/A2-RRS.xyz;isosurface wp-content/uploads/2011/05/A2-RRS.jvxl colorscheme translucent bgyor;&#39;);"
width="200" height="200" />
<p>A2 diaxial. Click for 3D.</p>
</div></td>
<td><div id="attachment_4060" class="wp-caption aligncenter"
style="width: 210px">
<img
src="http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2011/05/B2-SRS.jpg"
title="B2-SRS" class="size-full wp-image-4060" loading="lazy"
decoding="async" aria-describedby="caption-attachment-4060"
onclick="jmolInitialize(&#39;../Jmol/&#39;,true);jmolSetAppletColor(&#39;goldenrod&#39;);jmolApplet([600,600],&#39;load wp-content/uploads/2011/05/B2-SRS.xyz;isosurface wp-content/uploads/2011/05/B2-SRS.jvxl colorscheme translucent bgyor;&#39;);"
width="200" height="200" />
<p>B2 Axial-equatorial. click for 3D.</p>
</div></td>
</tr>
<tr class="even">
<td><div id="attachment_4049" class="wp-caption aligncenter"
style="width: 210px">
<img
src="http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2011/05/A1-RRS.jpg"
title="A1-RRS" class="size-full wp-image-4049" loading="lazy"
decoding="async" aria-describedby="caption-attachment-4049"
onclick="jmolInitialize(&#39;../Jmol/&#39;,true);jmolSetAppletColor(&#39;goldenrod&#39;);jmolApplet([600,600],&#39;load wp-content/uploads/2011/05/A1-RRS.xyz;isosurface wp-content/uploads/2011/05/A1-RRS.jvxl colorscheme translucent bgyor;&#39;);"
width="200" height="200" />
<p>A1. Di-equatorial. Click for 3D.</p>
</div></td>
<td><div id="attachment_4061" class="wp-caption aligncenter"
style="width: 210px">
<img
src="http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2011/05/B1-SRS.jpg"
title="B1-SRS" class="size-full wp-image-4061" loading="lazy"
decoding="async" aria-describedby="caption-attachment-4061"
onclick="jmolInitialize(&#39;../Jmol/&#39;,true);jmolSetAppletColor(&#39;goldenrod&#39;);jmolApplet([600,600],&#39;load wp-content/uploads/2011/05/B1-SRS.xyz;isosurface wp-content/uploads/2011/05/B1-SRS.jvxl colorscheme translucent bgyor;&#39;);"
width="200" height="200" />
<p>B1.Di-equatorial. click for 3D.</p>
</div></td>
</tr>
<tr class="odd">
<td><div id="attachment_4063" class="wp-caption aligncenter"
style="width: 210px">
<img
src="http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2011/05/C2-SRR.jpg"
title="C2-SRR" class="size-full wp-image-4063" loading="lazy"
decoding="async" aria-describedby="caption-attachment-4063"
onclick="jmolInitialize(&#39;../Jmol/&#39;,true);jmolSetAppletColor(&#39;goldenrod&#39;);jmolApplet([600,600],&#39;load wp-content/uploads/2011/05/C2-SRR.xyz;isosurface wp-content/uploads/2011/05/C2-SRR.jvxl colorscheme translucent bgyor;&#39;);"
width="200" height="200" />
<p>C2. Equatorial-axial. Click for 3D.</p>
</div></td>
<td><div id="attachment_4064" class="wp-caption aligncenter"
style="width: 210px">
<img
src="http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2011/05/D2-SSS.jpg"
title="D2-SSS" class="size-full wp-image-4064" loading="lazy"
decoding="async" aria-describedby="caption-attachment-4064"
onclick="jmolInitialize(&#39;../Jmol/&#39;,true);jmolSetAppletColor(&#39;goldenrod&#39;);jmolApplet([600,600],&#39;load wp-content/uploads/2011/05/D2-SSS.xyz;isosurface wp-content/uploads/2011/05/D2-SSS.jvxl colorscheme translucent bgyor;&#39;);"
width="200" height="200" />
<p>D2. Equatorial-axial. Click for 3D.</p>
</div></td>
</tr>
<tr class="even">
<td><div id="attachment_4066" class="wp-caption aligncenter"
style="width: 210px">
<img
src="http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2011/05/C1-SRR.jpg"
title="C1-SRR" class="size-full wp-image-4066" loading="lazy"
decoding="async" aria-describedby="caption-attachment-4066"
onclick="jmolInitialize(&#39;../Jmol/&#39;,true);jmolSetAppletColor(&#39;goldenrod&#39;);jmolApplet([600,600],&#39;load wp-content/uploads/2011/05/C1-SRR.xyz;isosurface wp-content/uploads/2011/05/C1-SRR.jvxl colorscheme translucent bgyor;&#39;);"
width="200" height="200" />
<p>C1 SRR. Axial-equatorial. Click for 3D.</p>
</div></td>
<td><div id="attachment_4067" class="wp-caption aligncenter"
style="width: 210px">
<img
src="http://www.ch.imperial.ac.uk/rzepa/blog/wp-content/uploads/2011/05/D1-SSS.jpg"
title="D1-SSS" class="size-full wp-image-4067" loading="lazy"
decoding="async" aria-describedby="caption-attachment-4067"
onclick="jmolInitialize(&#39;../Jmol/&#39;,true);jmolSetAppletColor(&#39;goldenrod&#39;);jmolApplet([600,600],&#39;load wp-content/uploads/2011/05/D1-SSS.xyz;isosurface wp-content/uploads/2011/05/D1-SSS.jvxl colorscheme translucent bgyor;&#39;);"
width="200" height="200" />
<p>D1 SSS. Axial-equatorial. Click for 3D.</p>
</div></td>
</tr>
</tbody>
</table>

Amongst the many features visible in these plots is the strong
1,3-diaxial NCIs seen for **A2** and particularly **D1** and the
conformational variability in the NCI between the iPr and NMe~3~ groups.

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


The previous post set out a problem in conformational analysis. Here is my take, which includes an NCI (non-covalent interaction) display as discussed in another post. The lowest energies of the four diastereomers
<strong>
 A-D
</strong>
, each in two conformations (
<strong>
 1/2
</strong>
) were calculated at the ωB97D/6-311G(d,p)/SCRF=ethanol level, and are shown here relative to
<strong>
 A1
</strong>
(kcal/mol) as free energies.

Rogue Scholar Beiträge

Updating a worked problem in conformational analysis. Part 2: an answer.