Posts Tagged ‘Enol’

The conformation of carboxylic acids revealed.

Tuesday, April 11th, 2017

Following my conformational exploration of enols, here is one about a much more common molecule, a carboxylic acid.

The components of the search are shown as four queries below, which will be combined in various Boolean senses (DOI: 10.14469/hpc/2462).

  1. Query one defines the carboxylic acid, with 3-coordinate carbon specified at the carbonyl along with 1-coordinate for the carbonyl oxygen. Then the HO-C=O torsion (o° for the syn conformation shown on the left above and 180° for the anti-conformation shown on the right) and the length of the O-C bond as variables.
  2. Query two defines a contact as ≤ the sum of van der Waals radii between QA (=N,O,F,Cl) and the hydrogen of the carboxylic acid (pink).
  3. Query three defines a contact as ≤ the sum of van der Waals radii between QA-H (QA=N,O,F,Cl) and the oxygen of the acid (pink).
  4. Query four defines a temperature of <100K for the data collection temperature.

The first search uses just Query 1, with additional constraints of no errors, no disorder and R < 0.05.

This can then be focused by combining Query 1 + Query 4, which shows a clear preference for the syn conformation.

Next, Query 1 with NOT query 2, which restricts the search to carboxylic acids that do not have contacts to the hydrogen of the OH group. This excludes carboxylic acid dimers, as shown above. The predominant hot-spot now corresponds to the anti conformation.

Again this is narrowed using Query 4, which removes almost all the syn examples.

Now using Query 3 (as shown above), which restricts the search to examples where the oxygen of the HO group is itself not in contact with an acidic hydrogen. This allows carboxylic acid dimers. This now reveals the syn preference again.

At <100K reinforces this effect.

Finally, Query 1 and NOT query 2 (no dimers) and NOT query 3, where a smaller preference for anti is seen.

So it seems that an interesting difference emerges between enols and carboxylic acids in that when no hydrogen bonding to the HO group is allowed, an anti preference emerges. The electronic origins of this effect will be probed in a future post.

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The conformation of enols: revealed and explained.

Thursday, April 6th, 2017

Enols are simple compounds with an OH group as a substituent on a C=C double bond and with a very distinct conformational preference for the OH group. Here I take a look at this preference as revealed by crystal structures, with the theoretical explanation.

First, a search of the Cambridge structure database (CDS), using the search query shown below (DOI: 10.14469/hpc/2429)


The first search (no errors, no disorder, R < 0.05) is unconstrained in the sense that the HO group is free to hydrogen bond itself. The syn conformer has the torsion of 0° and it has a distinct preponderance over the anti isomer (180°). There is the first hint that the most probable C=C distance for the syn isomer may be longer than that for the anti, but this is not yet entirely convincing.
To try to make it so, a constrained search is now performed, in which only structures where the HO group has no contact (hydrogen bonding) interaction are included. This is achieved using a “Boolean” search;

The number of hits approximately halves, but the proportion of syn examples increases considerably. There is an interesting double “hot-spot” distribution, which amplifies the lengthening of the C=C bond compared to the anti orientation.

The next constraint added is that the data collection must be <100K (to reduce thermal noise) which reduces the hits considerably but now shows the lengthening of the C=C bond for the syn isomer very clearly.

A final plot is of the C=C length vs the C-O length (no temperature, but HO interaction constraint). If there were no correlation, the distribution would be ~circular. In fact it clearly shows that as the C=C bond lengthens, the C-O bond contracts.

Now for some calculations (ωB97XD/Def2-TZVPP, DOI: 10.14469/hpc/2429) which reveal the following:

  1. The free energy of the syn isomer is 1.2 kcal/mol lower than that of the syn. The effect is small, and hence easily masked by other interactions such as hydrogen bonding to the OH group. Hence the reason why removing such interactions from the search above increased the syn population compared to anti.
  2. The syn C=C bond length (1.325Å) is longer than the anti (1.322Å). 
  3. The syn isomer has one unique σO-Lp/σ*C-C NBO orbital interaction (below) with a value of E(2) 7.7 kcal/mol, which is absent in the anti form. As it happens, a πO/π*C=C interaction is present in both forms but is also stronger in the syn isomer (E(2)= 46.8 vs 44.2 kcal/mol).
    unoccupied NBO, σ*C-C
    Occupied NBO, σO-Lp
  4. The overlap of the filled σO-Lp with the empty σ*C-C orbital is shown below (blue overlaps with purple, red overlaps with orange).

    To view the overlap in rotatable 3D, click on any of the colour diagrams above.‡

It is nice to see how experiment (crystal structures) and theory (the calculation of geometries and orbital interactions) can quickly and simply be reconciled. Both these searches and the calculations can be done in just one day of “laboratory time” and I think it would make for an interesting undergraduate chemistry lab experiment.

‡ This visualisation uses Java. Increasingly this browser plugin is becoming more onerous to activate (because of increased security) and some browsers do not support it at all. The macOS Safari browser is one that still does, but you do have to allow it via the security permissions.

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Posted in crystal_structure_mining, reaction mechanism | 2 Comments »