Bistetracene is a biradical singlet

Aromaticity &diradicals Steven Bachrach 16 Nov 2015 No Comments

Feng, Müller and co-workers have prepared a bistetracene analogue 1.1 This molecule displays some interesting features. While a closed shell Kekule structure can be written, a biradical structure results in more closed Clar rings, suggesting that perhaps the molecule is a ground state singlet biradical. The loss of NMR signals with increasing temperature along with an EPR signal that increases with temperature both support the notion of a ground state singlet biradical with a triplet excited state. The EPR measurement suggest as singlet-triplet gap of 3.4 kcal mol-1.

The optimized B3LYP/6-31G(d,p) geometries of the biradical singlet and triplet states are shown in Figure 1. The singlet is lower in energy by 6.7 kcal mol-1. The largest spin densities are on the carbons that carry the lone electron within the diradical-type Kekule structures.

singlet 1

triplet 1

Figure 1. B3LYP/6-31G(d,p) optimized geometries of the biradical singlet and triplet states of 1.


(1) Liu, J.; Ravat, P.; Wagner, M.; Baumgarten, M.; Feng, X.; Müllen, K. "Tetrabenzo[a,f,j,o]perylene: A Polycyclic Aromatic Hydrocarbon With An Open-Shell Singlet Biradical Ground State," Angew. Chem. Int. Ed. 2015, 54, 12442-12446, DOI: 10.1002/anie.201502657.


1: InChI=1S/C62H56/c1-33-25-35(3)51(36(4)26-33)53-45-17-13-15-19-47(45)57-56-44-24-22-42(62(10,11)12)30-40(44)32-50-54(52-37(5)27-34(2)28-38(52)6)46-18-14-16-20-48(46)58(60(50)56)55-43-23-21-41(61(7,8)9)29-39(43)31-49(53)59(55)57/h13-32H,1-12H3

Dynamics in the reaction of tetrazine with cyclopropene

Diels-Alder &Dynamics &Houk Steven Bachrach 09 Nov 2015 No Comments

Houk and Doubleday report yet another example of dynamic effects in reactions that appear to be simple, ordinary organic reactions.1 Here they look at the Diels-Alder reaction of tetrazine 1 with cyclopropene 2. The reaction proceeds by first crossing the Diels-Alder transition state 3 to form the intermediate 4. This intermediate can then lose the anti or syn N2, through 5a or 5s, to form the product 6. The structures and relative energies, computed at M06-2X/6-31G(d), of these species are shown in Figure 1.






Figure 1. M06-2X/6-31G(d) optimized geometries and energies (relative to 1 + 2) of the critical points along the reaction of tetrazine with cyclopropene.

The large difference in the activation barriers between crossing 5a and 5s (nearly 9 kcal mol-1) suggests, by transition state theory, a preference of more than a million for loss of the anti N2 over the syn N2. However, quasiclassical trajectory studies, using B3LYP/6-31G(d), finds a different situation. The anti pathway is preferred, but only by a 4:1 ratio! This dynamic effect arises from a coupling of the v3 mode which involves a rocking of the cyclopropane ring that brings a proton near the syn N2 functionality, promoting its ejection. In addition, the trajectory studies find short residence times within the intermediate neighborhood for the trajectories that lead to the anti product and longer residence times for the trajectories that lead to the syn product. All together, a very nice example of dynamic effects playing a significant role in a seemingly straightforward organic reaction.


(1) Törk, L.; Jiménez-Osés, G.; Doubleday, C.; Liu, F.; Houk, K. N. "Molecular Dynamics of the Diels–Alder Reactions of Tetrazines with Alkenes and N2 Extrusions from Adducts," J. Am. Chem. Soc. 2015, 137, 4749-4758, DOI: 10.1021/jacs.5b00014.


1: InChI=1S/C2H2N4/c1-3-5-2-6-4-1/h1-2H

2: InChI=1S/C3H4/c1-2-3-1/h1-2H,3H2

4: InChI=1S/C5H6N4/c1-2-3(1)5-8-6-4(2)7-9-5/h2-5H,1H2

6: InChI=1S/C5H6N2/c1-4-2-6-7-3-5(1)4/h2-5H,1H2

A novel host with two cups that work against each other

host-guest Steven Bachrach 02 Nov 2015 No Comments

Badjic, Hadad, and coworkers have prepared 1 an interesting host molecule that appears like two cups joined at the base, with one cup pointed up and the other pointed down. A slightly simplified analogue 1 of the synthesized host is shown in Figure 1. The actual host is found to bind one molecule of 2, but does not appear to bind a second molecule. Seemingly, only one of the cups can bind a guest, and that this somehow deters a second guest from being bound into the other cup.

Figure 1. B3LYP/6-31G* optimized geometry of host molecule 1. (Visualization of this molecules and the structures below are greatly enhanced by clicking on each image which will invoke the molecular viewer Jmol.)

To address negative allosterism, the authors optimized the structure of 1 at B3LYP/6-31G* (shown in Figure 1). They then optimized the geometry with the constraint that the three arms in the top cup were ever more slightly moved inward. This had the consequential effect of moving the three arms of the bottom cup farther apart. They next optimized (at M06-2x/6-31G(d)) the structures of 1 holding one molecule of guest 2 and with two molecules of guest 2. These structures are shown in Figure 2. In the structure with one guest, the arms are brought in towards the guest for the cup where the guest is bound, and this consequently draws the arms in the other cup to be farther apart, and thereby less capable of binding a second guest. The structure with two guest shows that the arms are not able to get sufficiently close to either guest to form strong non-covalent interactions.

Figure 2. M06-2x/6-31G(d) optimized structures of 1 with one or two molecules of 2.

Thus, the negative allosterism results from a geometric change created by the induced fit of the first guest that results in an unfavorable environment for a second guest.


(1) Chen, S.; Yamasaki, M.; Polen, S.; Gallucci, J.; Hadad, C. M.; Badjić, J. D. "Dual-Cavity Basket Promotes Encapsulation in Water in an Allosteric Fashion," J. Am. Chem. Soc. 2015, 137, 12276-12281, DOI: 10.1021/jacs.5b06041.

Ground and excited state (anti)aromaticity

Aromaticity Steven Bachrach 26 Oct 2015 3 Comments

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+

Structure of the 2-fluoroethanol trimer

Hydrogen bond &MP Steven Bachrach 20 Oct 2015 1 Comment

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

Keto-enol Benchmark Study

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

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.

Diels-Alder of yne-diyne species

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

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

Triprotonated rosarin: singlet or triplet?

Aromaticity &Borden Steven Bachrach 22 Sep 2015 No Comments

What is the spin state of the ground state of an aromatic species? Can this be spin state be manipulated by charge? These questions are addressed by Borden, Kim, Sessler and coworkers1 for the hexaphyrin 1. B3LYP/6-31G(d) optimization of 1 shows it to be a ground state singlet. This structure is shown in Figure 1.



Protonation of the three pyrrole nitrogens creates 13+, which has interesting frontier orbitals. The HOMO of 13+, of a1” symmetry, has nodes running through all six nitrogens. The next higher energy orbital, of a2” symmetry, has a small π-contribution on each nitrogen. Protonation will therefore have no effect on the energy of the a1” orbital, but the charge will stabilize the a2” orbital. This will lower the energy gap between the two orbitals, suggesting that a ground state triplet might be possible. The lowest singlet and triplet states of 13+ are also shown in Figure 1.


Singlet 13+

Triplet 13+

Figure 1. (U)B3LYP/6-31G(d) optimized structures of 1 and singlet and triplet 13+.

This spin state change upon protonation was experimentally verified by synthesis of two analogues of 1, shown below. The triprotonated versions of both are observed to have triplet character in their EPR spectrum.


(1) Fukuzumi, S.; Ohkubo, K.; Ishida, M.; Preihs, C.; Chen, B.; Borden, W. T.; Kim, D.; Sessler, J. L. "Formation of Ground State Triplet Diradicals from Annulated Rosarin Derivatives by Triprotonation," J. Am. Chem. Soc. 2015, 137, 9780-9783, DOI: 10.1021/jacs.5b05309.


1: InChI=1S/C45H24N6/c1-2-8-29-28(7-1)34-16-22-13-24-18-36-30-9-3-4-10-31(30)38-20-26(50-43(38)42(36)48-24)15-27-21-39-33-12-6-5-11-32(33)37-19-25(49-44(37)45(39)51-27)14-23-17-35(29)41(47-23)40(34)46-22/h1-21,46,49-50H/b22-13-,23-14-,24-13-,25-14-,26-15-,27-15-

Sumanene anions

Aromaticity Steven Bachrach 14 Sep 2015 1 Comment

Spisak, et al. treated sumanene 1 with excess potassium in THF.1

They obtained an interesting structure, characterized by x-ray crystallography: a mixture of the dianion and trianion of 1 (well these are really conjugate di- and tribases of 1, but we’ll call them di- and trianions for simplicity’s sake). A fragment of the x-ray structure is shown in Figure 1, showing that there is one potassium cation on the concave face and six potassium ions on the convex face.

Figure 1. X-ray structure of 1 surrounded by six K+ ions on the convex face and one K+ on the concave face.

To help understand this structure, they performed RIJCOSX-PBE0/cc-pVTZ computations on the mono-, di-, and trianion of 1. The structure of 1 (which I optimized at ωB97X-D/6-311G(d)) and the trianion are displayed in Figure 2. The molecular electrostatic potential of the trianion shows highly negative regions in the 5-member ring regions, symmetrically distributed and prime for coordination with 6 cations.


trianion of 1

Figure 2. Optimized structure of 1 and its trianion.


(1) Spisak, S. N.; Wei, Z.; O’Neil, N. J.; Rogachev, A. Y.; Amaya, T.; Hirao, T.; Petrukhina, M. A. "Convex and Concave Encapsulation of Multiple Potassium Ions by Sumanenyl Anions," J. Am. Chem. Soc. 2015, 137, 9768-9771, DOI: 10.1021/jacs.5b06662.


1: InChI=1S/C21H12/c1-2-11-8-13-5-6-15-9-14-4-3-12-7-10(1)16-17(11)19(13)21(15)20(14)18(12)16/h1-6H,7-9H2

Trianion of 1: InChI=1S/C21H9/c1-2-11-8-13-5-6-15-9-14-4-3-12-7-10(1)16-17(11)19(13)21(15)20(14)18(12)16/h1-5,7-8H,9H2/q-3

Review of planar hypercoordinate atoms

Schleyer Steven Bachrach 26 Aug 2015 6 Comments

Yang, Ganz, Chen, Wang, and Schleyer have published a very interesting and comprehensive review of planar hypercoordinate compounds, with a particular emphasis on planar tetracoordinate carbon compounds.1 A good deal of this review covers computational results.

There are two major motifs for constructing planar tetracoordinate carbon compounds. The first involves some structural constraints that hold (or force) the carbon into planarity. A fascinating example is 1 computed by Rasmussen and Radom in 1999.2 This molecule taxed their computational resources, and as was probably quite typical for that time, there is no supplementary materials. But since this compound has high symmetry (D2h) I reoptimized its structure at ω-B97X-D/6-311+G(d) and computed its frequencies in just a few hours. This structure is shown in Figure 1. However, it should be noted that at this computational level, 1 possesses a single imaginary frequency corresponding to breaking the planarity of the central carbon atom. Rasmussen and Radom computed the structure of 1 at MP2/6-31G(d) with numerical frequencies all being positive. They also note that the B3LYP/6-311+G(3df,2p) structure also has a single imaginary frequency.

A second approach toward planar tetracoordinate carbon compounds is electronic: having π-acceptor ligands to stabilize the p-lone pair on carbon and σ-donating ligands to help supply sufficient electrons to cover the four bonds. Perhaps the premier simple example of this is the dication 2¸ whose ω-B97X-D/6-311+G(d,p) structure is also shown in Figure 1.

The review covers heteroatom planar hypercoordinate species as well. It also provides brief coverage of some synthesized examples.



Figure 1. Optimized structures of 1 and 2.


(1) Yang, L.-M.; Ganz, E.; Chen, Z.; Wang, Z.-X.; Schleyer, P. v. R. "Four Decades of the Chemistry of Planar Hypercoordinate Compounds," Angew. Chem. Int. Ed. 2015, 54, 9468-9501, DOI: 10.1002/anie.201410407.

(2) Rasmussen, D. R.; Radom, L. "Planar-Tetracoordinate Carbon in a Neutral Saturated Hydrocarbon: Theoretical Design and Characterization," Angew. Chem. Int. Ed. 1999, 38, 2875-2878, DOI: 10.1002/(SICI)1521-3773(19991004)38:19<2875::AID-ANIE2875>3.0.CO;2-D.


1: InChI=1S/C23H24/c1-7-11-3-15-9-2-10-17-5-13-8(1)14-6-18(10)22-16(9)4-12(7)20(14,22)23(22)19(11,13)21(15,17)23/h7-18H,1-6H2

2: InChI=1S/C5H4/c1-2-5(1)3-4-5/h1-4H/q+2

Next Page »