Changes to the blog

Uncategorized Steven Bachrach 11 Jul 2016 5 Comments

I have been posting regularly on this blog for over nine years, beginning in July 2007. I have used this blog as a way to keep my book Computational Organic Chemistry current for its readers. I have also used it as a way for me to keep current with the literature.

It has been a terrific adventure for me, but an important change will be taking place in my life that will have an impact on the blog. Starting on August 1, 2016 I will become the Dean of the School of Science at Monmouth University in West Long Branch, NJ. (See the announcement.) I am extraordinarily excited to take on the challenges of leading the School. I suspect that my duties as Dean will keep me from finding the time to post as often as I have been for this past years. I will try to occasionally write a post as I intend to keep connected to the computational chemistry community. I have a few posts backlogged but expect a more infrequent posting schedule come August.

I fully intend to maintain the blog so that past posts remain accessible.

I want to thank all of the readers of this blog, those who read me through the Computational Chemistry Highlights blog, and especially those of you who have posted comments.

Redox switching

Aromaticity Steven Bachrach 06 Jul 2016 No Comments

In searching for a redox switch, Matsuda, Ishikawa and co-workers1 landed on 13,14-picenedione 1, which could, at least in principle, be reduced by reacting with H2 to form the diol 2. The back reaction could then occur via the reaction with oxygen gas.

They first optimized the geometries of both compounds at B3PW91/6-311+G(2d), and these geometries are shown in Figure 1. TD-DFT computations then predicted that 1 would be yellow (maximum absorption at 412nm) and 2 would be colorless (maximum absorption at 378nm). Furthermore, 1 should have no fluorescence while 2 should fluoresce at 464nm and be blue.



Figure 1. B3PW91/6-311+G(2d) optimized geometries of 1 and 2.

Of particular note is that the geometry of 1 is twisted, with the O-C-C-O dihedral angle being 34.9°, while there is essentially no such twisting in 2 (its O-C-C-O dihedral angle is 0.7°). The twisting in 1 manifests in antiaromatic character of the central ring, with NICS(0)=+13.2ppm, while the central ring of 2 is aromatic, with NICS(0)=-10.0. The redox properties therefore reflect the change in the aromatic character.

They next synthesized 2 and reduced it with hydrogen gas to 1. The x-ray crystal structure of 1 shows a twisted structure (O-C-C-O dihedral of 28.87°). As predicted, 1 is yellow and 2 is colorless, and 1 has no fluorescence while 2 fluoresces blue.


(1) Urakawa, K.; Sumimoto, M.; Arisawa, M.; Matsuda, M.; Ishikawa, H. "Redox Switching of Orthoquinone-Containing Aromatic Compounds with Hydrogen and Oxygen Gas," Angew. Chem. Int. Ed. 2016, 55, 7432-7436, DOI: 10.1002/anie.201601906.


1: InChI=1S/C22H12O2/c23-21-19-15-7-3-1-5-13(15)9-11-17(19)18-12-10-14-6-2-4-8-16(14)20(18)22(21)24/h1-12H

2: InChI=InChI=1S/C22H14O2/c23-21-19-15-7-3-1-5-13(15)9-11-17(19)18-12-10-14-6-2-4-8-16(14)20(18)22(21)24/h1-12,23-24H

Predicting chemical structure using DP4+

NMR Steven Bachrach 20 Jun 2016 1 Comment

Structure determination has been greatly facilitated by the use of computed NMR spectra to compare with experimental spectra. Perhaps the best method for doing this is the DP4 procedure developed by Smith and Goodman.1 (I have a previous post on their paper.) The basic idea is that if you have an experimental NMR spectrum and a number of potential structures, the computed spectra for each possibility are ranked by a statistical treatment based on the Student t-test.

Grimblat, Zanardi, and Sarotti question a couple of the assumptions embedded within the DP4 method, and offer a revision that they call DP4+.2 The two assumptions are (1) that the chemical shifts are computed at B3LYP/6-31G**//MMFF and (2) that the chemical shifts are scaled and then utilized in the analysis.

To test these assumptions, they examine a set of 72 organic compounds comprising 1219 13C shifts and 1123 1H shifts. They optimized the structures at B3LYP/6-31G* and computed the chemical shifts of these compounds using the B3LYP and mPW1PW91 functionals with 6 basis sets (6-31G*, 6-31G**, 6-31+G**, 6-311G*, 6-311G**, and 6-311+G**). With all of the combinations, the standard deviation of both the proton and carbon chemical shifts were significantly smaller than with the originally proposed method.

With regards to the second assumption, they define a new probability functions that multiplies the error using scaled chemical shifts with the error using unscaled chemical shifts, and this they call DP4+. Again with all of the computational methods, the DP4+ prediction outperforms the DP4 prediction.

As a test case, they looked at cryptomoscatone D1 and D2 (1), for which the structures were determined with traditional methods. DP4 predicts that both cryptomoscatone D1 and D2 are structure 1d. However, DP4+ correctly predicts that cryptomoscatone D1 is 1b and cryptomoscatone D2 is 1a.

Lin and Tagliatatela-Scafati have reported the use of DP4+ to aid in the structure determination of plakdiepoxide 2.3 ROESY NMR could not provide definitive judgement of the stereochemical relationship about the bond between the two epoxide rings. They computed a number of conformers of the model compounds 2a and 2b at B3LYP/6-31G(d). The computed chemical shifts were then used with the DP4+ procedure to determine that the structure has the stereochemistry of 2b.


(1) Smith, S. G.; Goodman, J. M. "Assigning Stereochemistry to Single Diastereoisomers by GIAO NMR Calculation: The DP4 Probability," J. Am. Chem. Soc. 2010, 132, 12946-12959, DOI: 10.1021/ja105035r.

(2) Grimblat, N.; Zanardi, M. M.; Sarotti, A. M. "Beyond DP4: an Improved Probability
for the Stereochemical Assignment of Isomeric Compounds using Quantum Chemical Calculations of NMR Shifts," J. Org. Chem. 2015, 80, 12526-12534, DOI: 10.1021/acs.joc.5b02396.

(3) Chianese, G.; Yu, H.-B.; Yang, F.; Sirignano, C.; Luciano, P.; Han, B.-N.; Khan, S.; Lin, H.-W.; Taglialatela-Scafati, O. "PPAR Modulating Polyketides from a Chinese Plakortis simplex and Clues on the Origin of Their Chemodiversity," J. Org. Chem. 2016, 81 (12), 5135–5143, DOI: 10.1021/acs.joc.6b00695.


Cryptomoscatone D1: InChI=1S/C17H20O4/c18-14(10-9-13-5-2-1-3-6-13)11-15(19)12-16-7-4-8-17(20)21-16/h1-6,8-10,14-16,18-19H,7,11-12H2/b10-9+/t14-,15-,16-/m1/s1

Cryptomoscatone D2: InChI=1S/C17H20O4/c18-14(10-9-13-5-2-1-3-6-13)11-15(19)12-16-7-4-8-17(20)21-16/h1-6,8-10,14-16,18-19H,7,11-12H2/b10-9+/t14-,15+,16+/m0/s1

plakdiepoxide: InChI=1S/C18H32O4/c1-6-9-10-13(4)12-17(7-2)16(22-17)18(8-3)14(21-18)11-15(19)20-5/h13-14,16H,6-12H2,1-5H3/t13?,14-,16-,17+,18-/m0/s1

Mechanism of dimethyldioxirane oxidation

Houk Steven Bachrach 06 Jun 2016 No Comments

Dimethyldioxirane can oxidize alkanes to alcohols. The mechanism for the oxidation has been controversial, ranging from concerted, to radical intermediates to an H-abstraction—O-rebound mechanism. Yang, Yu, and Houk now offer a molecular dynamics examination of the reaction of dimethyldioxirane with isobutane.1

Gas–phase (U)B3LYP/6-311++G(d,p)//(U)B3LYP/6-31G(d) computations give critical points outlined in the reaction below. The structures of the transition states and the intermediate are shown in Figure 1.




Figure 1. (U)B3LYP/6-31G(d) optimized geometries of TS1, INT, and TS2. Relative free energies (kcal mol-1) in the gas (top) and solution (bottom) phases

The PES indicates a rebound mechanism, though in acetone solution phase, there was no transition state located for the second step; it appears to be barrierless. It should be noted that the size of the barrier is very small even in the gas phase. The energy given in Figure 1 is for the gas phase structure computed in solution.

Trajectories for both gas and solution phase were computed. For the gas phase, about 90% of the trajectories lead to separated radicals, but in an acetone about 90% of the trajectories lead directly to the alcohol, with only 10% leading to radicals. Even so, the acetone trajectories divide into two types, a dynamically concerted path where the time gap between the formation of the new C-O and O-H bonds is less than 60 fs, and a dynamically stepwise path where the time gap is greater than 60 fs, though for the trajectories that lead to product the gap is typically still less than 150 fs.


(1)  Yang, Z.; Yu, P.; Houk, K. N. "Molecular Dynamics of Dimethyldioxirane C–H Oxidation," J. Am. Chem. Soc. 2016, 138, 4237-4242, DOI: 10.1021/jacs.6b01028.


Dimethyldioxirane: InChI=1S/C3H6O2/c1-3(2)4-5-3/h1-2H3

Isobutane: InChI=1S/C4H10/c1-4(2)3/h4H,1-3H3

Diels-Alder reaction of buckybowls

Diels-Alder &fullerene Steven Bachrach 23 May 2016 No Comments

Fullerenes can undergo the Diels-Alder reaction with some specificity: the diene preferentially adds across the bond shared by two fused 6-member rings over the bond shared by the fused 6- and 5-member rings. Garcia-Rodeja and colleagues have examined the analogous Diels-Alder reaction of cyclopentadiene with five curved aromatic compounds, 1-5.1

The computations were performed at BP86-D3/def2-TZVPP//RI-BP86-D3/def2-SVP. Representative transition states for the addition of cyclopentadiene with 3 over the 6,6-bond and 5,6-bond are shown in Figure 1.



Figure 1. RI-BP86-D3/def2-SVP optimized transition states for the reaction of cyclopentadiene with 3.

For the reactions of cyclopentadiene with 2-5 the reactions with the 6,6-bond is both kinetically and thermodynamically favored, while with 1 the 6,6-bond is kinetically preffered and the 5,6-adduct is the thermodynamic product. As the molecules increase in size (from 1 to 5), the activation barrier decreases, and the barrier for the reaction with 5 is only 1.4 kcal mol-1larger than the barrier with C60. The reaction energy also becomes more exothermic with increasing size. There is a very good linear relationship between activation barrier and reaction energy.

Use of the distortion/interaction model indicates that the preference for the 6,6-regioselectivity come from better interaction energy than for the 5,6-reaction, and this seems to come about by better orbital overlap between the cyclopentadiene HOMO and the 6,6-LUMO of the buckybowl.


(1) García-Rodeja, Y.; Solà, M.; Bickelhaupt , F. M.; Fernández, I. "Reactivity and Selectivity of Bowl-Shaped Polycyclic Aromatic Hydrocarbons: Relationship to C60," Chem. Eur. J. 2016, 22, 1368-1378, DOI: <10.1002/chem.201502248.


1: InChI=1S/C20H10/c1-2-12-5-6-14-9-10-15-8-7-13-4-3-11(1)16-17(12)19(14)20(15)18(13)16/h1-10H


3: InChI=1S/C26H12/c1-5-13-14-6-2-11-19-20-12-4-8-16-15-7-3-10-18-17(9-1)21(13)25(22(14)19)26(23(15)18)24(16)20/h1-12H

4: InChI=1S/C30H12/c1-2-14-6-10-18-20-12-8-16-4-3-15-7-11-19-17-9-5-13(1)21-22(14)26(18)29(25(17)21)30-27(19)23(15)24(16)28(20)30/h1-12H

5: InChI=1S/C36H12/c1-7-16-17-9-3-14-5-11-20-21-12-6-15-4-10-19-18-8-2-13(1)22-25(16)31-32(26(18)22)34-28(19)24(15)30(21)36(34)35-29(20)23(14)27(17)33(31)35/h1-12H

Benchmarking Platonic solids and related hydrocarbons

QM Method &Schreiner Steven Bachrach 10 May 2016 No Comments

Karton, Schreiner, and Martin have benchmarked the heats of formation of some Platonic Solids and related hydrocarbons.1 The molecules examined are tetrahedrane 1, cubane 2, dodecahedrane 3, trisprismane 4, pentaprismane 5, and octahedrane 6.

The optimized structures (B3LYP-D3BJ/def2-TZVPP) of these compounds are shown in Figure 1.







Figure 1. B3LYP-D3BJ/def2-TZVPP optimized geometries of 1-6.

Using the W1-F12 and W2-F12 composite methods, the estimated the heats of formation of these hydrocarbons are listed in Table 1. Experimental values are available only for 2 and 3; the computed values are off by about 2 kcal mol-1, which the authors argue is just outside the error bars of the computations. They suggest that the experiments might need to be revisited.

Table 1. Heats of formation (kcal mol-1) of 1-6.


ΔHf (comp)

ΔHf (expt)






142.7 ± 1.2



22.4 ± 1










They conclude with a comparison of strain energies computed using isogyric, isodesmic, and homodesmotic reactions with a variety of computational methods. Somewhat disappointingly, most DFT methods have appreciable errors compared with the W1-F12 results, and the errors vary depend on the chemical reaction employed. However, the double hybrid method DSD-PBEP86-D3BJ consistently reproduces the W1-F12 results.


(1)  Karton, A.; Schreiner, P. R.; Martin, J. M. L. "Heats of formation of platonic hydrocarbon cages by means of high-level thermochemical procedures," J. Comput. Chem. 2016, 37, 49-58, DOI: 10.1002/jcc.23963.


1: InChI=1S/C4H4/c1-2-3(1)4(1)2/h1-4H

2: InChI=1S/C8H8/c1-2-5-3(1)7-4(1)6(2)8(5)7/h1-8H

3: InChI=1S/C20H20/c1-2-5-7-3(1)9-10-4(1)8-6(2)12-11(5)17-13(7)15(9)19-16(10)14(8)18(12)20(17)19/h1-20H

4: InChI=1S/C6H6/c1-2-3(1)6-4(1)5(2)6/h1-6H

5: InChI=1S/C10H10/c1-2-5-3(1)7-8-4(1)6(2)10(8)9(5)7/h1-10H

6: InChI=1S/C12H12/c1-2-4-6-5(11-7(1)10(4)11)3(1)9-8(2)12(6)9/h1-12H

Diels-Alder reactions of some arenes

Aromaticity &Diels-Alder &Houk Steven Bachrach 26 Apr 2016 No Comments

Houk has examined the Diels-Alder reaction involving ethene with benzene 1 and all of its aza-substituted isomers having four or fewer nitrogen atoms 2-11.1 The reactions were computed at M06-2X/6-311+G(d,p).

All of the possible Diels-Alder reactions were examined, and they can be classified in terms of whether two new C-C bonds are formed, one new C-C and one new C-N bond are formed, or two new C-N bonds are formed. Representative transition states of these three reaction types are shown in Figure 1, using the reaction of 7 with ethene.

Figure 1. M06-2X/6-311+G(d,p) optimized transition states for the Diels-Alders reactions of 7 with ethene.

A number of interesting trends are revealed. For a given type of reaction (as defined above), as more nitrogens are introduced into the ring, the activation energy decreases. Forming two C-C bonds has a lower barrier than forming a C-C and a C-N, which has a lower barrier than forming two C-N bonds. The activation barriers are linearly related to the aromaticity of the ring defined by either NICS(0) or aromatic stabilization energy, with the barrier decreasing with decreasing aromaticity. The barrier is also linearly related to the exothermicity of the reaction.

The activation barrier is also linearly related to the distortion energy. With increasing nitrogen substitution, the ring becomes less aromatic, and therefore more readily distorted from planarity to adopt the transition state structure.


(1) Yang, Y.-F.; Liang, Y.; Liu, F.; Houk, K. N. "Diels–Alder Reactivities of Benzene, Pyridine, and Di-, Tri-, and Tetrazines: The Roles of Geometrical Distortions and Orbital Interactions," J. Am. Chem. Soc. 2016, 138, 1660-1667, DOI: 10.1021/jacs.5b12054.

Interesting chemistry of biphenalenylidene

Uncategorized Steven Bachrach 19 Apr 2016 No Comments

Uchida and co-workers reported on the preparation of biphenalenylidene 1 and its interesting electrocyclization to dihydroperopyrene 2.1 The experimental barrier they find by experiment for the conversion of 1-Z to 1-E is only 4.3 kcal mol-1. Secondly, the photochemical electrocyclization of 2-anti to 1-Z proceeds rapidly, through an (expected) allowed conrotatory pathway. However, the reverse reaction did not occur photochemically, but rather did occur thermally, even though this is formally forbidden by the Woodward-Hoffman rules.

To address these issues, they performed a number of computations, with geometries optimized at UB3LYP(BS)/6-31G**. First, CASSCF computations indicated considerable singlet diradical character for 1-Z. Both 1-Z and 1-E show significant twisting about the central double bond, consistent with the singlet diradical character. 1-Z is 1.8 kcal mol-1 lower in energy than 1-E, and the barrier for rotation interconverting these isomers is computed to be 7.0 kcal mol-1, in reasonable agreement with the experiment. These geometries are shown in Figure 1.



TS (Z→E)

Figure 1. UB3LYP(BS)/6-31G** optimized geometries of 1-Z and 1- and the transition state to interconvert these two isomers.

The conrotatory electrocyclization that takes 1-Z into 2-anti has a barrier of 26.0 kcal mol-1 and is exothermic by 3.4 kcal mol-1. The disrotatory process has a higher barrier (34.2 kcal mol-1) and is endothermic by 8.4 kcal mol-1. These transition states and products are shown in Figure 2. So, despite being orbital symmetry forbidden, the conrotatory path is preferred, and this agrees with their experiments.

TS (con)

TS (dis)



Figure 2. UB3LYP(BS)/6-31G** optimized geometries of 2-anti and 2-syn and the transition states leading to them.

The authors argue that the large diradical character of 1 leads to both its low Z→E rotational barrier, and the low barrer for electrocyclization. The Woodward-Hoffmann allowed disrotatory barrier is inhibited by its highly strained geometry, making the conrotatory path the favored route.


(1) Uchida, K.; Ito, S.; Nakano, M.; Abe, M.; Kubo, T. "Biphenalenylidene: Isolation and Characterization of the Reactive Intermediate on the Decomposition Pathway of Phenalenyl Radical," J. Am. Chem. Soc. 2016, 138, 2399-2410, DOI: 10.1021/jacs.5b13033.


1-E: InChI=1S/C26H16/c1-5-17-9-3-11-23-21(15-13-19(7-1)25(17)23)22-16-14-20-8-2-6-18-10-4-12-24(22)26(18)20/h1-16H/b22-21+

1-Z: InChI=1S/C26H16/c1-5-17-9-3-11-23-21(15-13-19(7-1)25(17)23)22-16-14-20-8-2-6-18-10-4-12-24(22)26(18)20/h1-16H/b22-21-

2-anti: InChI=1S/C26H18/c1-3-15-7-11-19-21-13-9-17-5-2-6-18-10-14-22(26(21)24(17)18)20-12-8-16(4-1)23(15)25(19)20/h1-14,19,21,25-26H/t19-,21-,25?,26?/m0/s1

2-syn: InChI=1S/C26H18/c1-3-15-7-11-19-21-13-9-17-5-2-6-18-10-14-22(26(21)24(17)18)20-12-8-16(4-1)23(15)25(19)20/h1-14,19,21,25-26H/t19-,21+,25?,26?

Cyclization reaction of 1,2-cyclohexadiene

cycloadditions &Houk Steven Bachrach 11 Apr 2016 No Comments

1,2-Cyclohexadiene 1 is a very strained and highly reactive species. Houk, Garg and co-workers report on its use as the ene component in a cyclization with a 1,3-dipole, namely nitrones.1 For example, 1 reacts with nitrone 2 to give the cycloadducts 3a and 3b in a ratio of 8.9:1.

To investigate the mechanism of this reaction, they optimized the structures of all compounds at CPCM(acetonitrile)B3LYP/6-31G(d) and single-point energies were obtained using the B3LYP-D3 functional. The structures of some pertinent critical points are shown in Figure 1. They did locate a concerted transition state (TS1) leading to 3a, with a barrier of 14.5 kcal mol-1, but could not find a concerted TS leading to 3b. (Also, the barriers leading to the other regioisomer are much higher than the ones leading to the observed products.) Rather, they identified a stepwise transition state (TS2) with a barrier of nearly the same energy (14.4 kcal mol-1) that leads to the intermediate (INT), which lies 16.5 kcal mol-1 below reactants. They located two transition states from his intermediate, TS3a and TS3b, leading to the two different products. The barrier to 3a is 1.2 kcal mol-1 lower than the barrier leading to 3b, and this corresponds nicely with the observed diastereoselectivity.









Figure 1. CPCM(acetonitrile)B3LYP/6-31G(d) optimized geometries and CPCM(acetonitrile)B3LYP-D3/6-31G(d) free energies.


(1) Barber, J. S.; Styduhar, E. D.; Pham, H. V.; McMahon, T. C.; Houk, K. N.; Garg, N. K.
"Nitrone Cycloadditions of 1,2-Cyclohexadiene," J. Am. Chem. Soc. 2016, 138, 2512-2515, DOI: 10.1021/jacs.5b13304.


1: InChI=1S/C6H8/c1-2-4-6-5-3-1/h1,5H,2,4,6H2

2: InChI=1S/C11H15NO/c1-11(2,3)12(13)9-10-7-5-4-6-8-10/h4-9H,1-3H3/b12-9-

3a: InChI=1S/C17H23NO/c1-17(2,3)18-16(13-9-5-4-6-10-13)14-11-7-8-12-15(14)19-18/h4-6,9-11,15-16H,7-8,12H2,1-3H3/t15-,16-/m0/s1

3b: InChI=1S/C17H23NO/c1-17(2,3)18-16(13-9-5-4-6-10-13)14-11-7-8-12-15(14)19-18/h4-6,9-11,15-16H,7-8,12H2,1-3H3/t15-,16+/m1/s1

A linear acene with 13 rings

Aromaticity Steven Bachrach 04 Apr 2016 No Comments

Bunz and co-workers have synthesized the novel aromatic compound 1 that contains 13 acenes in a row.1

They optimized the geometry of 1 at B3LYP/6-311G*, and its geometry is shown in Figure 1. Even though this compound has quite an extensive π-system, an unrestricted computations collapses to the closed-shell wavefunction.


Figure 1. B3LYP/6-311G* optimized geometry of 1. (As always, don’t forget to click on this image to launch JMol and visualize the molecule in 3-D.)

NICS(1)πzz values for the rings are given in Table 1. Interestingly, the aromaticity of the coronene moiety is reduced; in fact the central ring (ring A, with rings labeled sequentially working towards either end from the center) has a very small NICS value of only -3.77.

Table 1. NICS(1)πzz values for the rings of 1.






(1) Endres, A. H.; Schaffroth, M.; Paulus, F.; Reiss, H.; Wadepohl, H.; Rominger, F.; Krämer, R.; Bunz, U. H. F. "Coronene-Containing N-Heteroarenes: 13 Rings in a Row," J. Am. Chem. Soc. 2016, 138, 1792-1795, DOI: 10.1021/jacs.5b12642.


1: InChI=1S/C100H76N8O4Si4/c1-49(2)56-31-24-32-57(50(3)4)75(56)84-95(111)72-47-68-80-78-66(89-91(68)107-99-97(105-89)101-85-58(33-37-113(5,6)7)62-41-52-27-20-22-29-54(52)43-64(62)60(87(85)103-99)35-39-115(11,12)13)45-70-76-71(94(110)74(93(70)109)51-25-18-17-19-26-51)46-67-79(82(76)78)81-69(48-73(96(84)112)77(72)83(80)81)92-90(67)106-98-100(108-92)104-88-61(36-40-116(14,15)16)65-44-55-30-23-21-28-53(55)42-63(65)59(86(88)102-98)34-38-114(8,9)10/h17-32,41-50,74,84H,1-16H3

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