Though not quite germane to this blog (Computational Organic Chemistry), the recent commentary by Rzepa¹ does deserve mention. Henry takes on, in a nice breezy style (note the title: The importance of being bonded), the nature of bonding in 1, which initially was thought to be of structure 1a but subsequent x-ray structural analysis suggested the presence of an S-S bond, i.e. 1b. Schleyer has applied NICS analysis to suggest that the compound is bishomoaromatic.² Henry utilizes AIM and ELF analysis to discuss the nature of the bonding, including the possibility of H^…H interaction between the methyl groups and trishomoaromatic character. What I liked about the article is that Henry rightly makes the case that exploration of the notion of “bonding” can be quite opaque and often leads to stretching the models we commonly employ. Well worth the read!

References

(1) Rzepa, H. S., "The importance of being bonded," Nat. Chem., 2009, 1, 510-512, DOI: 10.1038/nchem.373.

(2) Zhang, Q.; Yue, S.; Lu, X.; Chen, Z.; Huang, R.; Zheng, L.; Schleyer, P. v. R., "Homoconjugation/Homoaromaticity in Main Group Inorganic Molecules," J. Am. Chem. Soc., 2009, 131, 9789-9799, DOI: 10.1021/ja9029285

As mentioned in Chapter 2 of my book, many post-HF methods predict that planar benzene has an imaginary frequency, whereby out-of-plane bending leads to a lower energy structure.¹ This anomaly was suggested to result from intramolecular basis set incompleteness.

Asturiol, Duran and Salvador provide more evidence that the root cause is intramolecular basis set superposition error.² They propose an extension of the standard counterpoise correction, which has been widely applied to interacting molecules. They divide the molecule into small fragments and apply the counterpoise correction to these fragments. For benzene, they use C-H or (CH)₂ fragments. With this counterpoise correction, the imaginary frequency corresponding to an out-of-plane distortion is removed for all combinations of either MP2 or CISD with the 6-31+G*, 6-311G or 6-311++G basis sets. The planar indenyl anion, which is found to have 4 imaginary frequencies at MP2/6-311G, has no imaginary frequencies when the counterpoise correction is used.

These authors have now shown that nucleic acid bases suffer from the same intramolecular superposition error.³ Uracil, thymine and guanine suffer from spurious imaginary frequencies with certain combinations of MP2 and Pople basis sets. However, all of these out-of-plane imaginary frequencies become real when the counterpoise correction is applied. The take-home message is to carefully mate the post-HF method and basis set combination – or else make the counterpoise correction!

References

(1) Moran, D.; Simmonett, A. C.; Leach, F. E.; Allen, W. D.; Schleyer, P. v. R.; Schaefer, H. F., III, "Popular Theoretical Methods Predict Benzene and Arenes To Be Nonplanar," J. Am. Chem. Soc. 2006, 128, 9342-9343, DOI: 10.1021/ja0630285

(2) Asturiol, D.; Duran, M.; Salvador, P., "Intramolecular basis set superposition error effects on the planarity of benzene and other aromatic molecules: A solution to the problem," J. Chem. Phys. 2008, 128, 144108, DOI: 10.1063/1.2902974

(3) Asturiol, D.; Duran, M.; Salvador, P., "Intramolecular Basis Set Superposition Error Effects on the Planarity of DNA and RNA Nucleobases," J. Chem. Theory Comput. 2009, 5, 2574-2581, DOI: 10.1021/ct900056u

One of the great longstanding dreams of synthetic and theoretical organic chemists is to prepare a stable molecule containing a pentacoordinate carbon atom. Bickelhaupt and co-workers propose a novel series of compounds that hint that this might be possible.¹

Their attack is to first find a CR₃ radical that is stable in its planar form. The nitrile group perfectly satisfies this goal. Next they look at the series of compounds X-C(CN)₃-X^– (1) where X is a halogen, searching for a stable D_3h structure. This is found with the halogens: Br, I, and At, at the ZORA-OLYP/TZ2P level. Seems like case closed, except that inspection of the supporting materials shows that the nature of the D_3h structure is sensitive to computational method. So, with the larger basis set ZORA-OLYP/QZ4P or with ZORA-OPBE/TZ2P, only the I and At compounds are local D_3h minima. And with ZORA-M06/TZ2P, only the At compound is a local minimum. The authors do mention these points at the end of the article. So, what we have here is a tantalizing suggestion for how to prepare a hypercoordinate carbon species, but further computational (and experimental) work is clearly needed.

1: X = F, Cl, Br, I, At

References

(1) Pierrefixe, S. C. A. H.; van Stralen, S. J. M.; van Strale, J. N. P.; Guerra, C. F.; Bickelhaupt, F. M., "Hypervalent Carbon Atom: "Freezing" the S_N2 Transition State," Angew. Chem. Int. Ed., 2009, 48, 6469-6471, DOI: 10.1002/anie.200902125

InChIs

1(F): InChI=1/C4F2N3/c5-4(6,1-7,2-8)3-9/q-1, InChIKey=LBDHZXPWKBFYBC-UHFFFAOYAX

1(Cl): InChI=1/C4Cl2N3/c5-4(6,1-7,2-8)3-9/q-1, InChIKey=NMFGEVWEEWBFSS-UHFFFAOYAU

1(Br): InChI=1/C4Br2N3/c5-4(6,1-7,2-8)3-9/q-1, InChIKey=FHKJQJBDHAEQES-UHFFFAOYAC

1(I): InChI=1/C4I2N3/c5-4(6,1-7,2-8)3-9/q-1, InChIKey=FWKBAUUEXUSUNH-UHFFFAOYAO

1(At): InChI=1/C4At2N3/c5-4(6,1-7,2-8)3-9/q-1, InChIKey=BJQBFKCUAROAAS-UHFFFAOYAK

Bond-stretch isomerism refers to isomers that differ simply in their bond lengths. Seppelt and coworkers suggests that the hexafluorobenzne radical cation C₆F₆^.+ exhibits bond-stretch isomerism.¹

The oxidized C₆F₆ with O₂⁺SbF₁₁^– and obtained C₆F₆^.+Sb­2F₁₁^– as a crystalline solid. X-ray diffraction identified 2 structures. B3LYP/TZPP computations confirmed the identity of two isomers, a “quinoid” form 1 and a “bisallyl” form 2, shown in Figure 1. The two structures are nearly degenerate, with 1 predicted to be 0.09 kcal mol^-1 more stable than 2. The computed two unique C-C bond lengths are 1.371 and 1.427 Å in 1 and 1.449 and 1.389 Å in 2, and these distance agree well with the X-ray experimental values.

1 – quinoid	2 – bisallyl

Figure 1. UB3LYP/6-311+G(d) optimized structures of 1 and 2. Note once again the article and supporting materials lacked the full description of these structures!)

The potential energy surface in the neighborhood of these two isomers is like that of a sombrero. The two isomers lie in the circular trough and movement around this trough is nearly flat. The peak of the sombrero is the D_6h structure, which is a transition state interconverting 1 and 2, with a barrier of 3 kcal mol^-1.

1 and 2 are clear examples of bond-stretch isomerism, though it is likely that the complexation with the counter ion is what freezes out the rapid interconversion of the two.

References

(1) Shorafa, H.; Mollenhauer, D.; Paulus, B.; Seppelt, K., "The Two Structures of the Hexafluorobenzene Radical Cation C₆F₆^.+," Angew. Chem. Int. Ed. 2009, 48, 5845-5847, DOI: 10.1002/anie.200900666

Jan Martin and his group at the Weizmann Institute continue to push the envelope in developing a computational rubric that produces computed energies with experimental accuracy. Their latest attempt tries to balance off computational accuracy with performance, and they propose the W3.2lite composite method,¹ which includes, among other things, an empirical correction for including triples and quadruples configurations.

Amongst the test molecules they discuss are the benzynes (the ortho, meta, and para diradicals) discussed at great length in Chapter 4.4 of my book. The W3.2lite estimate heats of formations are 112.06 ± 0.5, 125.06 ± 0.5, and 139.03 ± 0.5 kcal mol^-1 for the o-, m-, and p-benzyne, respectively. This compares with the experimental² estimates of 108.8 ± 3, 124.1 ± 3.1, and 139.5 ± 3.3 kcal mol^-1, respectively. This demonstrates nice agreement between the computed and experimental values. A similar sized difference is obtained for the singlet-triplet gap of p-benzyne: 5.4 ± 0.6 with W3.2lite and 3.8 ± 0.5 kcal mol^-1 estimate from ultraviolet photoelectron spectroscopy.³

References

(1) Karton, A.; Kaminker, I.; Martin, J. M. L., "Economical Post-CCSD(T) Computational Thermochemistry Protocol and Applications to Some Aromatic Compounds," J. Phys. Chem. A 2009, DOI: 10.1021/jp900056w.

(2) Wenthold, P. G.; Squires, R. R., "Biradical Thermochemistry from Collision-Induced Dissociation Threshold Energy Measurements. Absolute Heats of Formation of ortho-, meta-, and para-Benzyne," J. Am. Chem. Soc. 1994, 116, 6401-6412, DOI: 10.1021/ja00093a047.

(3) Wenthold, P. G.; Squires, R. R.; Lineberger, W. C., "Ultraviolet Photoelectron Spectroscopy of the o-, m-, and p-Benzyne Negative Ions. Electron Affinities and Singlet-Triplet Splittings for o-, m-, and p-Benzyne," J. Am. Chem. Soc. 1998, 120, 5279-5290, DOI: 10.1021/ja9803355.

InChIs

o-benzyne: InChI=1/C6H4/c1-2-4-6-5-3-1/h1-4H
InChIKey=KLYCPFXDDDMZNQ-UHFFFAOYAO

m-benzyne: InChI=1/C6H4/c1-2-4-6-5-3-1/h1-3,6H
InChIKey=MDEXXEPHAKMVNO-UHFFFAOYAG

p-benzyne: InChI=1/C6H4/c1-2-4-6-5-3-1/h1-2,5-6H
InChIKey=AIESRBVWAFETPR-UHFFFAOYAI

Gronert¹ has published a scathing criticism of the concept of “protobranching” (see my previous blog post) put forth by Schleyer, Houk and Ma² – SHM for short. As a review, protobranching is the term coined by SHM for attractive 1,3-interactions in alkanes. They argue that these attractive 1,3-interactions are the reason for the energetic stability of the branched alkanes over the straight-chain alkanes. Their argument largely rests on the fact that Reaction 1 is exothermic by 2.8 kcal mol^-1.

2 CH₂CH₃ → CH₄ + CH₃CH₂CH₃           Reaction 1

Gronert’s arguments are many and I will discuss only some of them. First, he notes that choosing ethane and methane as the reference molecules leads to all alkanes being stabilized. The stabilization energy of n-heptane is 5.7 kcal mol^-1 and that of n-heptane is 14.1 kcal mol^-1; is this a difference that is meaningful? Under the protobranching method, the stabilization energies of norbornane and n-heptane are quite similar (13.8 and 14.1 kcal mol^-1, respectively) – does that mean they are equally strained? Similarly, protobranching leads to an extraordinary prediction for the resonance energy of benzene: 69 kcal mol^-1. (I find these arguments quite compelling – the use of protobranching extenuates to magnitude of many chemical effects like ring strain, π-conjugation and resonance energy to the point that they become unusable.)

Gronert notes that the C-C-C angle in propane is larger than 109.5°, suggestive of a repulsive force, and one that is in fact much larger than suggested by SHM. The “attractive interaction” is not reproduced in intermolecular models. He points out the SHM attribute the attractive 1,3-interaction in alkenes to hyperconjugation and not to protobranching, and further notes that SHM correct for the strength of the C-H bond in ethyne but not for the C_sp-C bond in propyne, nor do they make any such corrections for the alkenes.

But Gronert’s main complaint rests on the fact that there is simply no evidence for an attractive 1,3-interaction. All previous suggestions for this have been refuted by many others over the past 30 years. SHM’s main support rests on the ability to fit the thermodynamic trends, but Gronert points out that many other possibilities exist for doing so, including a repulsive model. There is ample evidence to support a repulsive interaction. It seems to me that Schleyer, Houk and Ma have their work cut out for them to carefully rebut Gronert’s arguments.

References

(1) Gronert, S., "The Folly of Protobranching: Turning Repulsive Interactions into Attractive Ones and Rewriting the Strain/Stabilization Energies of Organic Chemistry," Chem. Eur. J. 2009, DOI: 10.1002/chem.200800282

(2) Wodrich, M. D.; Wannere, C. S.; Mo, Y.; Jarowski, P. D.; Houk, K. N.; Schleyer, P. v. R., "The Concept of Protobranching and Its Many Paradigm Shifting Implications for Energy Evaluations," Chem. Eur. J. 2007, 13, 7731-7744, DOI: 10.1002/chem.200700602

The paper I will discuss here is a bit afield from computational organic chemistry, but it raises some interesting issues that tangentially touch on the main theme of my blog.

Roger Sayle of OpenEye describes a software tool for translating chemical names from one language into another, for example a name in English to the corresponding name in German or Japanese or Chinese.¹ One might imagine the many difficulties in this process – the strong dependency on very minor changes in the name can mean substantially different chemicals (think of propane vs. propene vs. propyne vs. propanol vs. propanal vs. propenal, etc.) and all this needs to be carefully recognized and translated.

My interest here is that chemical names including IUPAC names are really not the lingua franca of chemistry. Yes, chemists do use names but we really rely most on chemical structure drawings – that’s the surest way of transmitting our meaning to one another. But images are not a very good way for computers to communicate meaning. And that’s where the InChI label steps in. InChIs provide a standard means for two chemists (or two computers) to exchange chemical information without introducing errors and without the need for an intervening third-party to guarantee the meaning.

Here is a simple example of the benefit of the InChI using the first example from Sayle’s article. Figure 1 in his paper has the two similarly names compounds phenylacetate 1 and phenyl acetate 2. Note the critical importance of the blank space (actually this blank space is omitted in Figure 1 of the paper indicating just how easy it is for errors to sneak in!). Sayle points out that many languages beside English do not make use of whitespace in the way that English does, so that this translation must be done with special care.

Now the InChIs of 1 and 2 are unambiguous and will be the same in all (human) languages, eliminating the need of translation concerns. And if you’re unhappy with the length of the InChI, the InChIKey provides a fixed length string that captures almost all of the information of the InChI itself.

All compounds mentioned in my blog are listed at the end with their InChIs to promote the exchange of information and to encourage search-and-retrieval through the web. The leader in this sort of technology has been the Chemspider site, and I urge you to explore it and the use of InChIs.

As an aside, for all you Star Trek nerds, the paper includes this quote

and includes a reference to the Klingon Language Institute! This just might be the first time Klingon has appeared in a chemistry journal!

References

(1) Sayle, R., "Foreign Language Translation of Chemical Nomenclature by Computer," J. Chem. Inf. Model. 2009, DOI: 10.1021/ci800243w.

I am grateful for another very nice review of my book Computational Organic Chemistry, this one appearing in Organic Process Research and Development written by Eddy M. E. Viseux: Org. Process Res. Dev., 2008, 12, 1313, DOI: 10.1021/op800178c.

I have an immediate opening in my group for a post-doctoral associate. The position involves computational approaches to a variety of problems, including nucleophilic substitution at heteroatoms, solvent effects, and host-guest chemistry. The candidate must have some experience with computational chemistry, especially with any one of the major ab initio programs (like Gaussian, or Gamess or NWChem, etc.).

If you are interested in the position, please see the description here.

Here is another review of my book Computational Organic Chemistry; DOI: 10.1002/aoc.1406. This one is by John Brazier James Platts of Cardiff University and it appears in Applied Organometallic Chemistry. I do plead guilty to the charge of the interviews being USA-centric. This was due to scheduling problems that did not allow me to travel overseas.