Archive for October, 2015

Ground and excited state (anti)aromaticity

What is the relationship between a ground state and the first excited triplet (or first excited singlet) state regarding aromaticity? Baird1 argued that there is a reversal, meaning that a ground state aromatic compound is antiaromatic in its lowest triplet state, and vice versa. It is suggested that the same reversal is also true for the second singlet (excited singlet) state.

Osuka, Sim and coworkers have examined the geometrically constrained hexphyrins 1 and 2.2 1 has 26 electrons in the annulene system and thus should be aromatic in the ground state, while 2, with 28 electrons in its annulene system should be antiaromatic. The ground state and lowest triplet structures, optimized at B3LYP/6-31G(d,p), of each of them are shown in Figure 1.







Figure 1. B3LYP/6-31G(d,p) optimized geometries of 1 and 2.

NICS computations where made in the centers of each of the two rings formed by the large macrocycle and the bridging phenyl group (sort of in the centers of the two lenses of the eyeglass). The NICS values for 1 are about -15ppm, indicative of aromatic character, while they are about +15ppm for 2, indicative of antiaromatic character. However, for the triplet states, the NICS values change sign, showing the aromatic character reversal between the ground and excited triplet state. The aromatic states are also closer to planarity than the antiaromatic states (which can be seen by clicking on the images in Figure 1, which will launch the JMol applet so that you can rotate the molecular images).

They also performed some spectroscopic studies that support the notion of aromatic character reversal in the excited singlet state.


(1) Baird, N. C. "Quantum organic photochemistry. II. Resonance and aromaticity in the lowest 3ππ* state of cyclic hydrocarbons," J. Am. Chem. Soc. 1972, 94, 4941-4948, DOI: 10.1021/ja00769a025.

(2) Sung, Y. M.; Oh, J.; Kim, W.; Mori, H.; Osuka, A.; Kim, D. quot;Switching between Aromatic and Antiaromatic 1,3-Phenylene-Strapped [26]- and [28]Hexaphyrins upon Passage to the Singlet Excited State," J. Am. Chem. Soc. 2015, 137, 11856-11859, DOI: 10.1021/jacs.5b04047.


1: InChI=1S/C60H18F20N6/c61-41-37(42(62)50(70)57(77)49(41)69)33-23-8-4-19(81-23)31-17-2-1-3-18(16-17)32(21-6-10-25(83-21)35(29-14-12-27(33)85-29)39-45(65)53(73)59(79)54(74)46(39)66)22-7-11-26(84-22)36(40-47(67)55(75)60(80)56(76)48(40)68)30-15-13-28(86-30)34(24-9-5-20(31)82-24)38-43(63)51(71)58(78)52(72)44(38)64/h1-16,85-86H/b31-19+,31-20+,32-21+,32-22+,33-23+,33-27+,34-24+,34-28+,35-25+,35-29+,36-26+,36-30+

2: InChI=1S/C60H20F20N6/c61-41-37(42(62)50(70)57(77)49(41)69)33-23-8-4-19(81-23)31-17-2-1-3-18(16-17)32(21-6-10-25(83-21)35(29-14-12-27(33)85-29)39-45(65)53(73)59(79)54(74)46(39)66)22-7-11-26(84-22)36(40-47(67)55(75)60(80)56(76)48(40)68)30-15-13-28(86-30)34(24-9-5-20(31)82-24)38-43(63)51(71)58(78)52(72)44(38)64/h1-16,81-84H/b31-19+,31-20+,32-21+,32-22+,33-23+,33-27+,34-24+,34-28+,35-25+,35-29+,36-26+,36-30+

Aromaticity Steven Bachrach 26 Oct 2015 3 Comments

Structure of the 2-fluoroethanol trimer

Here is another fine example of the power of combining experiment and computation. Xu and co-worker has applied the FT microwave technique, which has been used in conjunction with computation by the Alonso group (especially) as described in these posts, to the trimer of 2-fluoroethanol.1 They computed a number of trimer structures at MP2/6-311++G(2d,p) in an attempt to match up the computed spectroscopic constants with the experimental constants. The two lowest energy structures are shown in Figure 1. The second lowest energy structure has nice symmetry, but it does not match up well with the experimental spectra. However, the lowest energy structure is in very good agreement with the experiments.



Table 1. MP2/6-311++G(2d,p) optimized structures and relative energies (kJ mol-1) of the two lowest energy structures of the trimer of 2-fluoroethanol. The added orange lines in the lowest energy structure denote the bifurcated hydrogen bonds identified by QTAIM.

Of particular note is that topological electron density analysis (also known as quantum theoretical atoms in a molecule, QTAIM) of the wavefunction of the lowest energy structure of the trimer identifies two hydrogen bond bifurcations. The authors suggest that these additional interactions are responsible, in part, for the stability of this lowest energy structure.


(1) Thomas, J.; Liu, X.; Jäger, W.; Xu, Y. "Unusual H-Bond Topology and Bifurcated H-bonds in the 2-Fluoroethanol Trimer," Angew. Chem. Int. Ed. 2015, 54, 11711-11715, DOI: 10.1002/anie.201505934.


2-fluoroethanol: InChI=1S/C2H5FO/c3-1-2-4/h4H,1-2H2, InChIKey=GGDYAKVUZMZKRV-UHFFFAOYSA-N

Hydrogen bond &MP Steven Bachrach 20 Oct 2015 1 Comment

Keto-enol Benchmark Study

The keto-enol tautomerization is a fundamental concept in organic chemistry, taught in the introductory college course. As such, it provides an excellent test reaction to benchmark the performance computational methods. Acevedo and colleagues have reported just such a benchmark study.1

First, the compare a wide variety of methods, ranging from semi-empirical, to DFT, and to composite procedures, with experimental gas-phase free energy of tautomerization. They use seven such examples, two of which are shown in Scheme 1. The best results from each computation category are AM1, with a mean absolute error (MAE) of 1.73 kcal mol-1, M06/6-31+G(d,p), with a MAE of 0.71 kcal mol-1, and G4, with a MAE of 0.95 kcal mol-1. All of the modern functionals do a fairly good job, with MAEs less than 1.3 kcal mol-1.

Scheme 1

As might be expected, the errors were appreciably larger for predicting the free energy of tautomerization, with a good spread of errors depending on the method for handling solvent (PCM, CPCM, SMD) and the choice of cavity radius. The best results were with the G4/PCM/UA0 procedure, though M06/6-31+G(d,p)/PCM and either UA0 or UFF performed quite well, at considerably less computational expense.


(1) McCann, B. W.; McFarland, S.; Acevedo, O. "Benchmarking Continuum Solvent Models for Keto–Enol Tautomerizations," J. Phys. Chem. A 2015, 119, 8724-8733, DOI: 10.1021/acs.jpca.5b04116.

Keto-enol tautomerization &QM Method Steven Bachrach 12 Oct 2015 No Comments

Diels-Alder of yne-diyne species

Cramer, Hoye, Kuwata and coworkers have examined the intramolecular cyclization of an alkyne with a diyne.1 Their model system is 1, which can cyclize through a concerted transition state TSC togive the benzyne product 2, or it can proceed through a stepwise pathway, first going through TS1 to form the intermediate INT¸ before traversing through a second transition state TS2 and on to product 2. Using both computations and experiments, they examined a series of compounds with
differing substituents at the ends of the two yne moieties.

The experiments show almost the exact same rate of reaction regardless of the terminal substituents. This includes the parent case where the terminal substituents are hydrogens and also the case where the terminal substituents (which end up on adjacent centers on the benzyne ring) are bulky TMS groups. And though there is no real rate effect due to changes in solvent or the presence of light or triplet oxygen, which suggest a concerted reaction, these substituent effects argue for a step wise reaction.

computations help explain these observations. Shown in Figure 1 are the optimized geometries and relative energies of the critical points on the reaction surface for the conversion of 1 into 2, and these results are similar with the other substituents as well.









Figure 1. SMD(o-dichlorobenzene)/B3LYP-D3BJ/6-311+G-(d,p)//M06-2X/6-311+G(d,p) optimized geometries and relative energies (kcal mol-1).

The first thing to note is that the concerted TSC is higher in energy than the stepwise TS1. The wavefunction for TSC unstable towards moving from a restricted to unrestricted formalism. Reoptimization of some of these concerted TSs actually led to the stepwise TS.

The next item of note is that TS2 for this case is actually lower in energy than the intermediate (this is a true TS on the energy surface, but when zero-point energy and other thermal corrections are included, it becomes lower in energy than INT). For some of the cases the second TS lies above the intermediate, but typically by a small amount.

Therefore, the mechanism of this reaction is stepwise, but the second step might have such a small barrier (or even no barrier) that one might consider this to be concerted, though highly asymmetric and really bearing little resemblance to more traditional concerted pericyclic reactions.

The authors obliquely hinted at some potential interesting dynamics. I suspect that molecular dynamics calculations will show no effect of that second TS, and one might observe some interesting dynamics, which could be seen in kinetic isotope experiments.


(1)  Marell, D. J.; Furan, L. R.; Woods, B. P.; Lei, X.; Bendelsmith, A. J.; Cramer, C. J.; Hoye, T. R.; Kuwata, K. T. "Mechanism of the Intramolecular Hexadehydro-Diels–Alder Reaction," J. Org. Chem. 2015 ASAP, DOI: 10.1021/acs.joc.5b01356.


1: InChI=1S/C8H4O2/c1-3-5-6-7-10-8(9)4-2/h1-2H,7H2

2: InChI=1S/C8H4O2/c9-8-7-4-2-1-3-6(7)5-10-8/h2,4H,5H2

Cramer &Diels-Alder &diradicals Steven Bachrach 05 Oct 2015 2 Comments