Posts Tagged ‘Ether’

A visualization of the anomeric effect from crystal structures.

Thursday, August 27th, 2015

The anomeric effect is best known in sugars, occuring in sub-structures such as RO-C-OR. Its origins relate to how the lone pairs on each oxygen atom align with the adjacent C-O bonds. When the alignment is 180°, one oxygen lone pair can donate into the C-O σ* empty orbital and a stabilisation occurs. Here I explore whether crystal structures reflect this effect.

Scheme

The torsion angles along each O-C bond are specified, along with the two C-O distances. All the bonds are declared acyclic, and the usual R < 5%, no disorder and no errors specified.

  1. You can see from the plot below that the hotspot occurs when both RO-CO torsions are ~65°. From this we will assume that the two (unseen)‡ lone pairs at any one of the oxygens are distributed approximately tetrahedrally around each oxygen, and if this is true then one of them must by definition be oriented ~ 180° with respect to the same RO-CO bond (the other is therefore oriented -60°). This allows it to be antiperiplanar to the adjacent C-O bond and hence interact with its σ* empty orbital. So the hotspot corresponds to structures where BOTH oxygen atoms have lone pairs which interact with the adjacent O-C anti bond.
  2. There is a tiny cluster for which both RO-CO torsions are ~180° and hence neither oxygen has an antiperiplanar lone pair.
  3. Only slightly larger are clusters where one torsion is ~65° and the other ~180°, meaning that only one oxygen has an antiperiplanar lone pair.
  4. A plot of the two C-O lengths indeed shows an overall hotspot at ~1.40Å for both distances. If the search is filtered to include only torsions in the range 150-180°, the hotspot value increases to 1.415Å for both. If one torsion is restricted to 40-80° and the other to 150-180° the hotspot shows one C-O bond is about 0.012Å shorter than the other.

Scheme

Scheme

I also include a further constraint, that the diffraction data must be collected below 140K. The hotspot moves to ~ 55/60° indicating values free of some vibrational noise.

Scheme

Interestingly, replacing  oxygen with  nitrogen reveals relatively few examples of the effect (C(NR2)4 is an exception). Replacing  O by divalent S produces only 13 hits, with the surprising result (below) that in all of them only one S sets up an anomeric interaction. Arguably, the number of examples is too low to draw any firm conclusions from this observation.

Scheme

‡Most diffractometers measure low angle scattering of X-rays by high density electrons. These are the core electrons associated with a nucleus rather than the valence electrons associated with lone pairs. Hence very few positions of valence lone pairs have ever been crystallographically measured.

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A new way of exploring the directing influence of (electron donating) substituents on benzene.

Friday, April 17th, 2015

The knowledge that substituents on a benzene ring direct an electrophile engaged in a ring substitution reaction according to whether they withdraw or donate electrons is very old.[1] Introductory organic chemistry tells us that electron donating substituents promote the ortho and para positions over the meta. Here I try to recover some of this information by searching crystal structures.

I conducted the following search:
xray

  1. Any electron donating group as a ring substituent, defined by any of the elements N, O, F, S, Cl, Br.
  2. A distance from the H of an OH fragment (as a hydrogen bonder to the aryl ring) to the ortho position relative to the electron donating group.
  3. A similar distance to the meta position.
  4. The |torsion angle| between the aryl plane and the C…H axis to be constrained to 90° ± 20.
  5. Restricting the H…C contact distance to the van der Waals sum of the radii -0.3Å (to capture only the stronger interactions)
  6. The usual crystallographic requirements of R < 0.1, no disorder, no errors and normalised H positions.

The result of such a search is seen below. The red line indicates those hits where the distance from the H to the ortho and meta positions is equal. In the top left triangle, the distance to ortho is shorter than to meta (and the converse in the bottom right triangle). You can see that both the red hot-spot and indeed the majority of the structures conform to ortho direction (of π-facial ) hydrogen bonding.

benzene-xrayHere is a little calculation, optimising the position that HBr adopts with respect to bromobenzene. You can see that the distance discrimination towards ortho is ~ 0.17Å, a very similar value to the “hot-spot” in the diagram above.

benzene-HBr

This little search of course has hardly scratched the surface of what could be done. Changing eg the OH acceptor to other electronegative groups. Restricting the wide span of N, O, F, S, Cl, Br. Probing rings bearing two substituents. What of the minority of points in the bottom right triangle; are they true exceptions or does each have extenuating circumstances? Why do many points actually lie on the diagonal? Can one correlate the distances with the substituent? Is there a difference between intra and intermolecular H-bonds? What of electron withdrawing groups?

The above search took perhaps 20 minutes to define and optimise, and it gives a good statistical overview of this age-old effect. It is something every new student of organic chemistry can try for themselves! If you run an introductory course in organic aromatic chemistry, or indeed a laboratory, try to see what your students come up with!

References

  1. H.E. Armstrong, "XXVIII.—An explanation of the laws which govern substitution in the case of benzenoid compounds", J. Chem. Soc., Trans., vol. 51, pp. 258-268, 1887. https://doi.org/10.1039/ct8875100258

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