Archive for January, 2015

Twisting a benzene ring

Here’s another cruel and unusual punishment applied to the poor benzene ring. Hashimoto,et al. have created a molecule that is a fused double helicene, where the fusion is about a single phenyl ring.1 Compound 1 has two [5]helicenes oriented in opposite directions. This should provide a twist to the central phenyl ring, and the added methyl groups help to expand that twist.

They prepared 1 and its x-ray crystal structure is reported. The compound exhibits C2 symmetry. The twist (defined as the dihedral of four consecutive carbon atoms of the central ring) is 28.17°, nearly the same twist as in [2]paraphenylene.

The B3LYP/6-31G(d) structure of 1 is shown in Figure 1. This geometry is very similar to the x-ray structure. The calculated NICS value for the central ring is -4.9 (B3LYP/6-311+G(d,p)/B3LYP/6-31G(d)) and -4.3 (B3LYP/6-311+G(d,p)/x-ray structure). This diminished value from either benzene or C6(PSH2)2(CH3)4 indicates reduced aromaticity of this central ring, presumably due to the distortion away from planarity. Nonetheless, the central ring of 1 is not oxidized when subjected to MCPBA to oxidize to the bis phosphine oxides.


Figure 1. B3LYP/6-31G(d) optimized structure of 1.


(1) Hashimoto, S.; Nakatsuka, S.; Nakamura, M.; Hatakeyama, T. "Construction of a Highly Distorted Benzene Ring in a Double Helicene," Angew. Chem. Int. Ed. 2014, 53, 14074-14076, DOI: 10.1002/anie.201408390.


1: InChI=1S/C50H32P2S2/c1-25-17-21-29-9-5-13-33-41(29)37(25)45-46-38-26(2)18-22-30-10-7-15-35(42(30)38)52(54)36-16-8-12-32-24-20-28(4)40(44(32)36)48(50(46)52)47-39-27(3)19-23-31-11-6-14-34(43(31)39)51(33,53)49(45)47/h5-24H,1-4H3

Aromaticity Steven Bachrach 26 Jan 2015 No Comments

o-Phenylene conformations

In solution ortho-phenylenes preferentially coil into a helix with the phenyl rings stacked. However, 25-50% of these chains will typically misfold. Hartley and coworkers have reported the use of substituents to increase the percentage of perfectly folded chains.1

They synthesized two isomeric o-phenylenes, differing in the substitution pattern (1 and 2), with chain length of 6 to 10 phenyl rings. Substituents included methoxy, acetoxy, nitrile, and triflate. They principally employed 1H NMR to assess the conformational distribution, and used computations to confirm the conformation.

Ideally folded conformations of 1 and 2 with eight phenyl rings are shown in Figure 1. The dihedral angle formed by two adjacent phenyl rings are typically about ±55° or ±130°.



Figure 1. Idealized folding of 1 and 2 with X=OH.
Hydrogens omitted in these images, but full structures available, through Jmol, by clicking on the image.)

Given the size of these systems, and the conformation flexibility not just of the chain but with each substituent, a full search to identify the global minimum was not undertaken. Rather, a library of conformations was generated with MM, the lowest 200 conformations were then reoptimized at PM7 and then the energies were determined at PCM/B97-D/TZV(2d,2p). The lowest energy conformer was then reoptimized at this DFT level. Three conformations of 3 and 4 are shown in Figure 2 with triflate as the substituent with six phenyl rings. The first conformer has optimal stacking (perfect folding), the second conformer as one misfold at the end, and the third conformer has no stacking at all.

– ideal fold

– one misfold

3 – all misfold

4 – ideal fold

– one misfold

– all misfold

Figure 2. Optimized geometries of conformers of 3 and 4.
(Remember that clicking on one of these images will bring up the JMol applet allowing you to rotate and visualize the molecule in 3-D – a very useful feature here!)

NMR chemical shifts were then computed using these geometries at PCM/WP04/6-31G(d). In all cases examined, the chemical shifts of the major conformation was confirmed to be the perfect folding one by comparison with the computed chemical shifts. The examined substituents enhanced the proportion of properly folded chains in all cases, often to the extent where no minor conformer was observed at all.


(1) Mathew, S.; Crandall, L. A.; Ziegler, C. J.; Hartley, C. S. "Enhanced Helical Folding of ortho-Phenylenes through the Control of Aromatic Stacking Interactions," J. Am. Chem. Soc. 2014, 136, 16666-16675, DOI:10.1021/ja509902m.


3: InChI=1S/C42H26F18O18S6/c43-37(44,45)79(61,62,63)23-5-1-21(2-6-23)29-13-9-25(81(67,68,69)39(49,50)51)17-33(29)35-19-27(83(73,74,75)41(55,56)57)11-15-31(35)32-16-12-28(84(76,77,78)42(58,59)60)20-36(32)34-18-26(82(70,71,72)40(52,53)54)10-14-30(34)22-3-7-24(8-4-22)80(64,65,66)38(46,47)48/h1-20H,(H,61,62,63)(H,64,65,66)(H,67,68,69)(H,70,71,72)(H,73,74,75)(H,76,77,78)

4: InChI=1S/C42H26F18O18S6/c43-37(44,45)79(61,62,63)23-6-4-21(5-7-23)33-17-25(81(67,68,69)39(49,50)51)9-13-30(33)35-19-27(83(73,74,75)41(55,56)57)11-15-32(35)36-20-28(84(76,77,78)42(58,59)60)10-14-31(36)34-18-26(82(70,71,72)40(52,53)54)8-12-29(34)22-2-1-3-24(16-22)80(64,65,66)38(46,47)48/h1-20H,(H,61,62,63)(H,64,65,66)(H,67,68,69)(H,70,71,72)(H,73,74,75)(H,76,77,78)

Aromaticity Steven Bachrach 21 Jan 2015 No Comments

Benchmarking π-conjugation

With the proliferation of density functionals, selecting the functional to use in your particular application requires some care. That is why there have been quite a number of benchmark studies (see these posts for some examples). Yu and Karton have now added to our benchmark catalog with a study of π-conjugation.1

They looked at a set of 60 reactions which involve a reactant with π-conjugation and a product which lacks conjugation. A few examples, showing examples involving linear and cyclic systems, are shown in Scheme 1.

Scheme 1.

The reaction energies were evaluated at W2-F12, which should have an error of a fraction of a kcal mol-1. Three of the reactions can be compared with experimental values, and difference in the experimental and computed values are well within the error bars of the experiment. It is too bad that the authors did not also examine 1,3-cyclohexadiene → 1,4-cyclohexadiene, a reaction that is both of broader interest than many of the ones included in the test set and can also be compared with experiment.

These 60 reactions were then evaluated with a slew of functionals from every rung of Jacob’s ladder. The highlights of this benchmark study are that most GGA and meta-GGA and hybrid functionals (like B3LYP) have errors that exceed chemical accuracy (about 1 kcal mol-1). However, the range-separated functionals give very good energies, including ωB97X-D. The best results are provided with double hybrid functionals. Lastly, the D3 dispersion correction does generally improve energies by 10-20%. On the wavefunction side, SCS-MPs gives excellent results, and may be one of the best choices when considering computational resources.


(1) Yu, L.-J.; Karton, A. "Assessment of theoretical procedures for a diverse set of isomerization reactions involving double-bond migration in conjugated dienes," Chem. Phys. 2014, 441, 166-177, DOI: 10.1016/j.chemphys.2014.07.015.

DFT Steven Bachrach 14 Jan 2015 2 Comments

Dynamic effects in the Garratt-Braverman/[1,5]-H migration

Schmittel has examined the thermolysis of 1, which undergoes a Garratt-Braverman rearrangement followed by a [1,5]-H migration to produce 3.1 The product 3 is formed in a 10.3:1 ratio of E to Z consistently over the temperature range of 60 – 140 °C. This non-changing ratio is unusual. The difference in the computed (UB3LYP/6-31g(d)) free energy of activation for the step 23 ranges from 2.35 to 2.56 kcal mol-1 for this temperature range, manifesting in a predicted E:Z ratio of 24.9 at 60 °C to 22.7 at 140 °C.

The computed structures of 1-3 along with the transition states are shown in Figure 1. The activation free energy for the first step (Garrat-Braverman) is 30.9 kcal mol-1. This is about 30 kcal mol-1 larger than the barrier for the second step. Schmittel suggests that a non-statistical effect is manifesting here. The molecule crosses the first TS and then follows a downhill path directly over TS2E without spending any time in the region of the intermediate 2. A few computed trajectories all indicate that it takes less than 50 fs from the time the reaction crosses TS1 until the hydrogen migrates, supporting the notion that vibrational relaxation within the intermediate 2 is not occurring. This reaction is yet another example of dynamic effects dictating product distributions.









Figure 1. UB3LYP/6-31G(d) optimized structures and relative free energies (kcal mol-1) for the reaction 13. (Note that a conformational change must first take 1a into 1b before the reaction can take place.)


1) Samanta, D.; Rana, A.; Schmittel, M. “Nonstatistical Dynamics in the Thermal Garratt−Braverman/[1,5]‑H Shift of One Ene−diallene: An Experimental and Computational Study,” J. Org. Chem. 2014, 79, 8435–8439, DOI: 10.1021/jo501324w.


1: InChI=1S/C24H34/c1-5-11-21(12-6-2)17-19-23-15-9-10-16-24(23)20-18-22(13-7-3)14-8-4/h9-10,15-16,19-20H,5-8,11-14H2,1-4H3

2: InChI=1S/C24H34/c1-5-11-19(12-6-2)23-17-21-15-9-10-16-22(21)18-24(23)20(13-7-3)14-8-4/h9-10,15-18H,5-8,11-14H2,1-4H3

3E; InChI=1S/C24H34/c1-5-11-19(12-6-2)23-17-21-15-9-10-16-22(21)18-24(23)20(13-7-3)14-8-4/h9-11,15-18,23H,5-8,12-14H2,1-4H3/b19-11-

3Z: InChI=1S/C24H34/c1-5-11-19(12-6-2)23-17-21-15-9-10-16-22(21)18-24(23)20(13-7-3)14-8-4/h9-11,15-18,23H,5-8,12-14H2,1-4H3/b19-11+

Dynamics Steven Bachrach 05 Jan 2015 2 Comments