Posts Tagged ‘Anomeric effect’
Monday, August 8th, 2016
The previous post contained an exploration of the anomeric effect as it occurs at an atom centre X for which the effect is manifest in crystal structures. Here I quantify the effect, by selecting the test molecule MeO-X-OMe, where X is of two types:
- A two-coordinate atom across the series B-O and Al-S, and carrying the appropriate molecular charge such that X carries two lone pairs of electrons (thus the charge is 0 for O, but -3 for B).
- A four-coordinate atom across the series B-O and Al-S, with X-H bonds replacing the lone pairs on this centre in the previous example, and again with appropriate molecule charges (e.g. +2 for SH2).
The donor in the anomeric interaction always originates on the oxygen of the MeO group attached to X. The acceptor is always the X-O σ* empty orbital. The results (table below, ωB97XD/Def2-TZVPP calculation, NBO E(2) in kcal/mol) confirm that as X gets more electronegative, the X-O σ* empty orbital becomes a better acceptor, and so the NBO E(2) interaction energy which quantifies the anomeric interaction gets larger. Eventually (with X=OH2) the donation of electrons into the X-O σ* empty orbital becomes so effective that the X-O bond (in this case O-O) dissociates fully and the NBO perturbation cannot be computed. Also for reference, a “normal” anomeric interaction (such as is found in e.g. sugars) is around 18 kcal/mol. Anything larger than this could be considered especially strong, and anything less than ~10 kcal/mol would be regarded as weak.
| X[1]* |
| BH2 |
CH2 |
NH2 |
OH2 |
| 12.5 |
17.7 |
18.5 |
dissociates |
| AlH2 |
SiH2 |
PH2 |
SH2 |
| 6.9 |
12.9 |
21.9 |
31.3 |
| B |
C |
N |
O |
| 8.3 |
11.7 |
12.9 |
14.2 |
| Al |
Si |
P |
S |
| 4.8 |
6.6 |
11.2 |
18.2 |
For the entry X=S, the E(2) term is actually larger than for the oxygen. I should note that the Me group itself is not passive in this process. The C-H bonds can also act as significant electron donors, but here I am not going to analyse this additional complexity.
This table reveals that there is nothing special about carbon as an anomeric centre, and here also the normal intimate association with the term anomeric and heterocyclohexanes such as found in sugars.
* Here I introduce a refinement to my normal process of citing the data produced for any specific calculation. Rather than including 16 individual citations for each cell in the table, I have gathered all these calculations into a collection and cite here only the DOI of that collection. When resolved, the individual members of that collection can then be inspected for the actual data.
References
- H. Rzepa, "Anomeric interactions at atom centres", 2016. https://doi.org/10.14469/hpc/1221
Tags:Anomer, Anomeric effect, Atomic orbital, Carbohydrate chemistry, Carbohydrates, Chemical bond, chemical bonding, Chemistry, Hydrogen bond, interaction energy, Lone pair, Physical organic chemistry, Quantum chemistry
Posted in Interesting chemistry | No Comments »
Saturday, August 6th, 2016
In the last few posts, I have explored the anomeric effect as it occurs at an atom centre X. Here I try to summarise the atoms for which the effect is manifest in crystal structures.
The effect is defined by X bearing two substituents, one of which Z is a centre bearing a “lone pair” of electrons (or two electrons in a π-bond), and another Y in which the X-Y bond has a low-lying acceptor or σ* empty orbital into which the lone pair can be donated. This donation will only occur if the Z-lone pair and the X-Y bond vectors align antiperiplanar. Here is the summary so far.
As required of a good periodic table, it has gaps that need completing, in this case X=N and X=S. Firstly N, for which the small molecule below is known (FUHFAP).
A ωB97XD/Def2-TZVPP calculation[1] yields an electron density distribution, which can be collected into monosynaptic basins using the ELF technique. There are two oxygen lone pairs (17 and 20) that are close to antiperiplanar to the adjacent N-O bond, having E(2) interaction energies obtained using the NBO method of 15.1 and 15.8 kcal/mol, typical of the anomeric range. The basin labelled 13 on X=N1 below is also perfectly aligned antiperiplanar with the adjacent O3-C2 bond, but its E(2) interaction energy is only 7.3 kcal/mol. Thus a strong anomeric interaction on the anomeric atom itself does not seem to occur. The same effect was noted for X=O in the previous post; the explanation remains unidentified.
With the X=S gap, we have lots of opportunity with polysulfide compounds, a good example of which is the C2-symmetric and helical S8 dianion TEGWAF[2]
Each of the 8 sulfur atoms exhibits antiperiplanar orientation of an S lone pair with an adjacent S-S acceptor σ* orbital;
1:2-3=23.7 kcal/mol;
2:3-4=18.5;
3:4-8=11.7, 3:2-1=7.4;
4:8-7=11.4, 4:3-2=9.2.
This just surveys the central main group elements, and it is possible that this little mini-periodic table may yet grow.
References
- H.S. Rzepa, "C 2 H 7 N 1 O 2", 2016. https://doi.org/10.14469/ch/195294
- Rybak, W.K.., Cymbaluk, A.., Skonieczny, J.., and Siczek, M.., "CCDC 880780: Experimental Crystal Structure Determination", 2012. https://doi.org/10.5517/ccykj88
Tags:Acetals, Alkane stereochemistry, Anomer, Anomeric effect, Atomic orbital, Carbohydrate chemistry, Carbohydrates, Chemical bond, Chemistry, interaction energy, Lone pair, Physical organic chemistry, Stereochemistry
Posted in crystal_structure_mining, Interesting chemistry | No Comments »
Friday, July 8th, 2016
The previous post looked at anomeric effects set up on centres such as B, Si or P, and involving two oxygen groups attached to these atoms. Here I vary the attached groups to include either one or two nitrogen atoms.[1]
.
The plot below shows aminols, C(NHR)(OR”). A torsion along either the C-O or C-N bond of ~60° implies that (at two coordinate oxygen or three coordinated nitrogen) there may be a lone pair with a torsion of 180°, which would set up an antiperiplanar alignment between that lone pair and the adjacent C-O or C-N bond (the anomeric effect). The clear hotspot is at angles of ~80°, which does raise the issue of why it deviates from 60°. Only a location of the lone pair centroid (using eg the ELF quantum mechanical technique) would cast light on that. There is a less distinct region for which the C-N torsion is 60° and the C-O torsion 180°, and an even less distinct region for the reverse (C-O torsion is 60° and the C-N torsion 180°). This tends to imply that a nitrogen lone pair is a better donor into a C-O bond than the reverse. Electronegativity suggests this should indeed be so, with the N lone pair less bound by the N nucleus and hence easier to release into a C-Oσ* orbital which is a better acceptor than then equivalent C-Nσ* orbital. 
This plot is where both heteroatoms are nitrogen (geminal diamines). There are about twice as many examples, resulting in more distinct clustering. The anomeric hotspot is now around 70° and there are equally populated clusters where only one torsion is ~70°. There is another cluster for which both torsions are 180° (no stereoelectronic alignment of lone pairs) and three small clusters where the torsions are either 180° or 0°. There is finally an intriguing cluster for which both torsions at ~120° (again no stereoelectronics). 
Searches like this seem to be good at creating more questions than they answer. Clearly, the origins of the various hotspots need to be investigated, ideally using quantum mechanics to quantify the stereoelectronic interactions involved. So this sort of (ten minute) exercise is very good at raising research project investigations.
References
- H. Rzepa, "Anomeric effects at carbon, involving lone pairs originating from one or two nitrogens", 2016. https://doi.org/10.14469/hpc/936
Tags:Anomer, Anomeric effect, Carbohydrate chemistry, Carbohydrate conformation, Carbohydrates, Chemistry, Nitrogen
Posted in crystal_structure_mining | No Comments »
Friday, July 1st, 2016
The anomeric effect occurs at 4-coordinate (sp3) carbon centres carrying two oxygen substituents and involves an alignment of a lone electron pair on one oxygen with the adjacent C-O σ*-bond of the other oxygen. Here I explore whether other centres can exhibit the phenomenon. I start with 4-coordinate boron, using the crystal structure search definition below (along with R < 0.1, no disorder, no errors).[1]
The result shows two prominent clusters, one with both torsion angles being 180°, and another with both being ~60°. This latter is the one that implies that there must be two lone pairs, one on each oxygen, that are anti-periplanar to the adjacent B-O bond. There are two more diffuse clusters where only one antiperiplanar alignment is seen. So yes, 4-coordinate boron can exhibit an anomeric effect!
This compares to the carbon-anomeric plot which is shown here for comparison, where the top right cluster of 180° torsions contains proportionately few hits than with boron.
The next centre is at 4-coordinate silicon. Again three significant clusters are seen; one with two antiperiplanar lone pair alignments with Si-O bonds, and two more with just one such alignment. The previous hotspot for which both measured torsions were 180° is largely absent. So here, the anomeric effect is much stronger. Notice also that whereas the torsions in the region of 60° for the carbon centre lie along a ridge coincident with the diagonal (bottom left to top right), that for the silicon centre show a ridge running orthogonal to the diagonal. An interesting point to follow up perhaps?
Since the off-diagonal clusters are relatively prominent, implying just one anomeric interaction, it is of interest to see if this results in any asymmetry in the two Si-O bond lengths. If its present, the effect is small.
Finally 4-coordinate group 15 elements. Most of the hits are in fact for P; there are none for N. This shows four clusters; the two on the diagonal show respectively two and no antiperiplanar interactions. The two off-diagonal clusters show just one such orientation. As with Si, the ridge in the 60° region run orthogonal to the diagonal.
So this little exploration shows that the anomeric effect, best known for sugars and at a carbon centre, is in fact more general to the adjacent elements.
References
- H. Rzepa, "Anomeric effects at boron, silicon and phosphorus.", 2016. https://doi.org/10.14469/hpc/696
Tags:Acetals, Alkane stereochemistry, Anomer, Anomeric effect, Bond length, Boron, Carbohydrate, Carbohydrate chemistry, Carbohydrates, crystal structure search definition, Ester, Physical organic chemistry, Stereochemistry
Posted in crystal_structure_mining | No Comments »
Monday, May 30th, 2016
This is a follow-up to one aspect of the previous two posts dealing with nucleophilic substitution reactions at silicon. Here I look at the geometries of 5-coordinate compounds containing as a central atom 4A = Si, Ge, Sn, Pb and of the specific formula C34AO2 with a trigonal bipyramidal geometry. This search arose because of a casual comment I made in the earlier post regarding possible cooperative effects between the two axial ligands (the ones with an angle of ~180 degrees subtended at silicon). Perhaps the geometries might expand upon this comment?
The search query is shown above results in 394 hits (May 2016) and is presented with the three variables in the query plotted as below, with the O-4A-O angle indicated by colour (red ~ 180°; blue ~90° and green ~120°).
- The cluster at distances of 4A-O of ~1.9Å represents silicon compounds, and tends to suggest that the pair of distances 4A-O are quite similar in value. The angles correspond to a di-axial arrangement around the silicon. In this scenario, one might imagine a stereoelectronic effect similar to the anomeric effect when 4A = C operates and which has the potential to strengthen both di-axial oxygens.
- The bulk of the points come at higher 4A-O distances of > 2.1Å and consist mostly of 4A = Sn. There are two a clear-cut distributions, one for angles of ~180° and a separate one for angles of ~90° and both are qualitatively different from the Si distribution. The 180° set corresponds to a di-axial arrangement for the oxygens, whereas the 90° set suggests an axial-equatorial geometry. Both distributions have prominent tails which reveal that as one 4A-O distance shortens, the other lengthens, equivalent to asymmetric anomeric effects at O-C-O.
- Noticeably absent are any green points; these would correspond to bond angles of ~120° and hence would correspond to di-equatorial ligands.
This quick exploration (with potential variations that I have not explored above) can be added to the collection of “ten minute explorations” I have described elsewhere.[1]
References
- H.S. Rzepa, "Discovering More Chemical Concepts from 3D Chemical Information Searches of Crystal Structure Databases", Journal of Chemical Education, vol. 93, pp. 550-554, 2015. https://doi.org/10.1021/acs.jchemed.5b00346
Tags:Anomer, Anomeric effect, Carbohydrate chemistry, Carbohydrates, Ligand, Molecular geometry, Physical organic chemistry, Stereochemistry, Stereoelectronic effect, Trigonal bipyramidal molecular geometry
Posted in Chemical IT, crystal_structure_mining | 3 Comments »
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.
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.
- 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.
- There is a tiny cluster for which both RO-CO torsions are ~180° and hence neither oxygen has an antiperiplanar lone pair.
- Only slightly larger are clusters where one torsion is ~65° and the other ~180°, meaning that only one oxygen has an antiperiplanar lone pair.
- 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.
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.
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.
‡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.
Tags:Alkane stereochemistry, Anomeric effect, Carbohydrate chemistry, Carbohydrates, Carbon–oxygen bond, Chemical bond, Ether, Lone pair, Physical organic chemistry, Quantum chemistry, Stereochemistry, Technology/Internet
Posted in Chemical IT, crystal_structure_mining | No Comments »
Friday, June 12th, 2015
In the preceding post, I discussed the reaction between mCPBA (meta-chloroperbenzoic acid) and cyclohexanone, resulting in Baeyer-Villiger oxidation via a tetrahedral intermediate (TI). Dan Singleton, in whose group the original KIE (kinetic isotope measurements) were made, has kindly pointed out on this blog that his was a mixed-phase reaction, and that mechanistic comparison with homogenous solutions may not be justified. An intriguing aspect of the (solution) mechanism would be whether the TI forms quickly and/or reversibly and what the position of any equilibrium between it and the starting ketone is. This reminded me of work we did some years ago,[1] and here I discuss that.
It involved the addition of phenyl hydroxylamine, PhNHOH to acetyl cyanide at 215K. Because the CN group is poor at leaving, the tetrahedral intermediates do not collapse and instead accumulate in seconds to the point of becoming detectable by NMR (both N-C and O-C isomers). The position of the equilibrium clearly favours the TI rather than the starting materials. In another context, both the rate of reaction and the equilibrium can be driven towards the TI by the application of pressure.[2] Hydroxylamines are known to be super nucleophiles, enhanced by the so-called α-effect from buttressing of adjacent lone pairs on the N and O. This reminds that a peracid also should exhibit a related α-effect; it should be a better nucleophile than a normal carboxylic acid. So I decided to take the TI formed from cyclohexanone and mcPBA and look at the NBO orbitals, which should tell us about the anomeric effects present in this TI, and in particular if they might be larger than normal (which could be equated with greater stability for the TI). Here are the relevant NBO energies.[3]
- The conventional anomeric effect in O-C-O manifests as a E(2) perturbation energy of ~16-18 kcal/mol between one oxygen lone pair and the antibonding C-O orbital. There are two combinations, and these are normally similar in energy.
- For the system above, the O1-C2-O6 interaction is 25.6 kcal/mol, much larger than normal, but partially counterbalanced by:
- O6-C1-O2 =13.0 kcal/mol which is a little lower than normal. This is overall an unusually strong anomeric effect for the O-C-O motif!
- The energetic asymmetry is matched by the two computed bond lengths, 1.381Å for the larger interaction and 1.455Å for the smaller. The pseudo-α-effect has desymmetrized the anomeric effect, but nevertheless strengthened it overall.
NBO 103 for O1(Lp)
NBO 97 for O6(Lp)
NBO 123 for C2-O6 antibonding σ*orbital
One concludes that the asymmetric anomeric effect makes the TI resemble the reactants. The transition state leading to the TI must be even earlier. In this context, I note that the (mixed phase) 13C effect reported for the carbonyl by Singleton and Szymanski[4] was quite a large one for carbon (1.045-1.051), a magnitude which argues against a very early transition state under these conditions. But the calculated value for a homogenous solution state model of ~1.023 is certainly more in accord with an early transition state.
Finally, a search of the CSD reveals 12 molecules containing either a O-O-C-O-O or a O-C-O-O sub unit This one[5] shows a bis HO-C-O-O-C-OH structure at room temperature; these species need not be unstable! There are none however with Ac-O-O-C-O. And of course the potent antimalarial artemisinin contains a O-O-C-O-C-O-Ac unit, for which stereoelectronic effects may also be important.
References
- A.M. Lobo, M.M. Marques, S. Prabhakar, and H.S. Rzepa, "Tetrahedral intermediates formed by nitrogen and oxygen attack of aromatic hydroxylamines on acetyl cyanide", The Journal of Organic Chemistry, vol. 52, pp. 2925-2927, 1987. https://doi.org/10.1021/jo00389a050
- N.S. Isaacs, H.S. Rzepa, R.N. Sheppard, A.M. Lobo, S. Prabhakar, and A.E. Merbach, "Volumes of reaction for the formation of some analogues of tetrahedral intermediates", Journal of the Chemical Society, Perkin Transactions 2, pp. 1477, 1987. https://doi.org/10.1039/p29870001477
- H.S. Rzepa, "C 20 H 20 Cl 2 O 6", 2015. https://doi.org/10.14469/ch/191327
- D.A. Singleton, and M.J. Szymanski, "Simultaneous Determination of Intermolecular and Intramolecular <sup>13</sup>C and <sup>2</sup>H Kinetic Isotope Effects at Natural Abundance", Journal of the American Chemical Society, vol. 121, pp. 9455-9456, 1999. https://doi.org/10.1021/ja992016z
- A. Kobayashi, Y. Ikeda, K. Kubota, and Y. Ohashi, "Syntheses and crystalline structures of several aldehyde peroxides as new flavor compounds", Journal of Agricultural and Food Chemistry, vol. 41, pp. 1297-1299, 1993. https://doi.org/10.1021/jf00032a025
Tags:Anomer, Anomeric effect, Carbohydrate chemistry, Carbohydrates, Chemistry, Dan Singleton, homogenous solutions, Ketone, Meta-Chloroperoxybenzoic acid, Organic chemistry, Tetrahedral carbonyl addition compound
Posted in reaction mechanism | 2 Comments »
Sunday, July 11th, 2010
The title of this post merges those of the two previous ones. The tunable C-Cl bond brought about in the molecule tris(amino)chloromethane by anomeric effects will be probed using the Laplacian of the electronic density.
Laplacian @0.67 for tris(amino)choromethane. Click for 3D
The figure above shows the Laplacian for a conformation of tris(amino)chloromethane with one of the nitrogen lone pairs antiperiplanar to the C-Cl bond, and the other two lone pairs antiperiplanar to C-N bonds. The features visible at an isosurface of ± 0.67 include
- (a) The Laplacian here has a value of -0.67 (= red isosurface), which indicates an accumulation of (covalent) shared density along the C-N bond (underneath this surface, you can see the blue sphere representing depletions from the nitrogen atomic region). This bond has the lone pair antiperiplanar to a C-N bond.
- (b) Contrast this with the C-N bond which is antiperiplanar to the C-Cl bond. A greater volume of the covalent C-N region is bounded by this isosurface. More of the N lone pair on this atom is donating into the C-N, as more conventionally represented below.
- Notice how the red isosurface associated with the N lone pair and the region associated with the C-N bond are in fact contiguous, and not separated basins!
Anomeric donation
- (c) represents the lone pairs on the chlorine, which have been augmented by the donation from the nitrogen. Notice how they come out as a torus rather than the conventional double dot representations!
- Notice the absence of any features along the C-Cl bond! This would be typical of a fully or even partially ionic bond, but it also illustrates that with a property such as the Laplacian, one does not get a complete picture by inspecting at just one isosurface value.
The next isosurface chosen is 0.3. At this lower value, more depletions (blue = electrophilic regions) are seen and a tiny feature now appears along the C-Cl bond, which is the covalent accumulation of that bond, a feature that grows @ 0.2. This nicely illustrates the variable covalency/ionicity of the C-Cl bond. Notice also how the lhs is all red (anionic) and the rhs is mostly blue (cationic), showing the formation of in effect an ion pair.
 tris(amino)chloroethane @ 0.3 |
 tris(amino)chloroethane @ 0.2 |
There are many other features which can be explored in these Laplacian maps, but I leave those for the reader to indulge in. Just click on any of the diagrams above,and start your exploration.
Tags:Anomeric effect, Chemical Energy, Interesting chemistry, Laplacian
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