Tsuji and Nakamura have prepared the tri-p­-quinodimethane 1.¹ Quinodimethanes are of interest because of their possible diradical character. This new example is most interesting. It is stable as a solid in air and ambient light for 6 months, or 2 months in solution. Its ESR shows fine structure, with a spin-spin distance estimated to be 14.6 Å, very close to the distance between the terminal carbons. The ground state is a singlet, with the triplet lying 2.12 kcal mol^-1 higher in energy.

Ar = 4-octylphenyl

UB3LYP/6-31G** computations (lacking the aryl and phenyl sidechains) indicate a ground state singlet (with sizable spin contamination) and a gap to the triplet of 1.83 kcal mol^-1. The computed geometry is shown in Figure 1.

1

Figure 1. UB3LYP/6-31G** optimized geometry of 1.

The analog having just two quinodimethane units showed no ESR signal and the computed singlet-triplet energy gap is 5.68 kcal mol^-1.

It would have been interesting to have computed the NICS values for the 6-member rings – as a measure of aromatic vs. non aromatic character to further support the participation of the biradical resonance structure contribution to 1.

References

(1) Zhu, X.; Tsuji, H.; Nakabayashi, K.; Ohkoshi, S.-i.; Nakamura, E., "Air- and Heat-Stable Planar Tri-p-quinodimethane with Distinct Biradical Characteristics," J. Am. Chem. Soc., 2011, 133, 16342-16345, DOI: 10.1021/ja206060n

InChI

1: InChI=1/C112H112N4/c1-5-9-13-17-21-29-41-81-53-63-93(64-54-81)111(94-65-55-82(56-66-94)42-30-22-18-14-10-6-2)101-73-85(87(77-113)78-114)61-71-97(101)105-107(111)99-75-104-100(76-103(99)109(105,89-45-33-25-34-46-89)90-47-35-26-36-48-90)108-106(110(104,91-49-37-27-38-50-91)92-51-39-28-40-52-92)98-72-62-86(88(79-115)80-116)74-102(98)112(108,95-67-57-83(58-68-95)43-31-23-19-15-11-7-3)96-69-59-84(60-70-96)44-32-24-20-16-12-8-4/h25-28,33-40,45-76H,5-24,29-32,41-44H2,1-4H3
InChIKey=IDOIPCRGROEZHG-UHFFFAOYAD

1 (lacking aryl side chains): InChI=1/C32H16N4/c33-13-23(14-34)17-1-3-25-19(5-17)9-31-27-8-22-12-30-26-4-2-18(24(15-35)16-36)6-20(26)10-32(30)28(22)7-21(27)11-29(25)31/h1-8H,9-12H2
InChIKey=JRLKUOJPPWAWTD-UHFFFAOYAN

Nobilisitine A was isolated by Evidente and coworkers, who proposed the structure 1.¹ Banwell and co-workers then synthesized the enantiomer of 1, but its NMR did not correspond to that of reported for Nobilisitine A.; the largest differences are 4.7 ppm for the ¹³C NMR and 0.79 ppm for the ¹H NMR.²

1

Lodewyk and Tantillo³ examined seven diastereomers of 1, all of which have a cis fusion between the saturated 5 and six-member rings (rings C and D). Low energy conformations were computed for each of these diasteromers at B3LYP/6-31+G(d,p). NMR shielding constants were then computed in solvent (using a continuum approach) at mPW1PW91/6-311+G(2d,p). A Boltzmann weighting of the shielding contants was then computed, and these shifts were then scaled as described by Jain, Bally and Rablen⁴ (discussed in this post). The computed NMR shifts for 1 were compared with the experimental values, and the mean deviations for the ¹³C and ¹H svalues is 1.2 and 0.13 ppm, respectively. (The largest outlier is 3.4 ppm for ¹³C and 0.31 for ¹H shifts.) Comparison was then made between the computed shifts of the seven diasteomers and the reported spectrum of Nobilisitine A, and the lowest mean deviations (1.4 ppm for ¹³C and 0.21 ppm for ¹H) is for structure 2. However, the agreement is not substantially better than for a couple of the other diasteomers.

2

They next employed the DP4 analysis developed by Smith and Goodman⁵ for just such a situation – where you have an experimental spectrum and a number of potential diastereomeric structures. (See this post for a discussion of the DP4 method.)The DP4 analysis suggests that 2 is the correct structure with a probability of 99.8%.

Banwell has now synthesized the compound with structure 2 and its NMR matches that of the original natural product.⁶ Thus Nobilisitine A has the structure 2.

References

(1) Evidente, A.; Abou-Donia, A. H.; Darwish, F. A.; Amer, M. E.; Kassem, F. F.; Hammoda, H. A. m.; Motta, A., "Nobilisitine A and B, two masanane-type alkaloids from Clivia nobilis," Phytochemistry, 1999, 51, 1151-1155, DOI: 10.1016/S0031-9422(98)00714-6.

(2) Schwartz, B. D.; Jones, M. T.; Banwell, M. G.; Cade, I. A., "Synthesis of the Enantiomer of the Structure Assigned to the Natural Product Nobilisitine A," Org. Lett., 2010, 12, 5210-5213, DOI: 10.1021/ol102249q

(3) Lodewyk, M. W.; Tantillo, D. J., "Prediction of the Structure of Nobilisitine A Using Computed NMR Chemical Shifts," J. Nat. Prod., 2011, 74, 1339-1343, DOI: 10.1021/np2000446

(4) Jain, R.; Bally, T.; Rablen, P. R., "Calculating Accurate Proton Chemical Shifts of Organic Molecules with Density Functional Methods and Modest Basis Sets," J. Org. Chem., 2009, DOI: 10.1021/jo900482q.

(5) 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

(6) Schwartz, B. D.; White, L. V.; Banwell, M. G.; Willis, A. C., "Structure of the Lycorinine Alkaloid Nobilisitine A," J. Org. Chem., 2011, ASAP, DOI: 10.1021/jo2016899

InChIs

2: InChI=1/C17H19NO4/c19-12-3-8-1-2-18-17(8)16-10-6-15-14(21-7-22-15)5-9(10)13(20)4-11(12)16/h5-6,8,11-12,16-19H,1-4,7H2/t8-,11-,12-,16-,17-/m0/s1

InChIKey=JISHLXUXALHAET-PUYTVRRYBF

In a follow-up to their experimental study that found that cyclobutenone is an excellent dienophile (and which I blogged about here), Danishefsky teams up with Houk and provides an insight into the reactivity.¹ In the Diels-Alder reaction of cyclopentadiene with 2-cyclohexenone, 2-cyclopentenone and cyclobutenone, the product yield increases in the order 36%, 50% and 77%. M06-2x activation enthalpies decrease in this series 15.0, 13.3 and 10.5 kcal mol^-1.

While these activation energies do not correlate with reaction energies, the activation energies do correlate nicely with the distortion energy. (Distortion energy is the energy required to distort reactants to their geometries in the transition state, but without their interaction.) Houk and Danishefsky argue that it is much easier to distort cyclobutenone to its geometry in the TS (and this distortion is primarily moving the alkenyl hydrogens out of plane, away from the incoming diene) than for the larger rings. This is due to (a) the larger s-character of the C-H bond in the smaller ring and (b) the C-C-C angle in the smaller ring is closer to the angle in the pyramidalized TS structure.

References

(1) Paton, R. S.; Kim, S.; Ross, A. G.; Danishefsky, S. J.; Houk, K. N., "Experimental Diels–Alder Reactivities of Cycloalkenones and Cyclic Dienes Explained through Transition-State Distortion Energies," Angew. Chem. Int. Ed., 2011, 44, 10366–10368, DOI: 10.1002/anie.201103998

Novel aromatic (or at least potentially aromatic species) just keep on coming! Tobe has prepared this interesting ortho-quinodimethane derivative 1b.¹ Ortho-quinodimethane derivatives are rare, due to the high reactivity of the underlying structure 2. Known derivatives of 2 tend to undergo an electrocyclic rearrangement to the cyclobutanobenzene 3. Fusing the benzene rings should minimize this electrocyclization, and the mesityl substituents should minimize dimerization. In fact 1b is stable as a solid or in solution, even in solution exposed to air.

B3LYP/6-31G(d) computations are in nice agreement with the x-ray structure concerning the important C-C distances. The terminal rings have delocalized bonds, while the interior three rings exhibit bond alternation. The authors claim that 1 should be thought of as ortho-quinodimethane bridged by two benzene rings. There does seem to be a bit of diradical character, though temperature dependent NMR shows no broadening, so the singlet-triplet gap is large, and therefore 1 exhibits small diradical character.

The computed NICS(0) for 1a values are -3.94 for the terminal ring (indicative of an aromatic phenyl), +9.20 for the 5-member ring, and +5.42 for the middle ring. These can be compared to the NICS(0) value of +3.21 for the ring of 2 and +11.51 and +21.17 for the 6 and 5-member rings of 4, respectively. So, 1a expresses some antiaromatic character.

References

(1) Shimizu, A.; Tobe, Y., "Indeno[2,1-a]fluorene: An Air-Stable ortho-Quinodimethane Derivative," Angew. Chem. Int. Ed. 2011, 50, 6906-6910, DOI: 10.1002/anie.201101950

InChIs

1a: InChI=1/C20H12/c1-3-7-15-13(5-1)11-19-17(15)9-10-18-16-8-4-2-6-14(16)12-20(18)19/h1-12H
InChIKey=PJULCNAVAGQLAT-UHFFFAOYAS

1b: InChI=1/C38H32/c1-21-17-23(3)33(24(4)18-21)35-29-13-9-7-11-27(29)31-15-16-32-28-12-8-10-14-30(28)36(38(32)37(31)35)34-25(5)19-22(2)20-26(34)6/h7-20H,1-6H3
InChIKey=BMQDJJPSCFSAIJ-UHFFFAOYAA

2: InChI=1/C8H8/c1-7-5-3-4-6-8(7)2/h3-6H,1-2H2
InChIKey=XURVRZSODRHRNK-UHFFFAOYAV

3: InChI=1/C8H8/c1-2-4-8-6-5-7(8)3-1/h1-4H,5-6H2
InChIKey=UMIVXZPTRXBADB-UHFFFAOYAR

4: InChI=1/C12H8/c1-3-9-7-8-10-4-2-6-12(10)11(9)5-1/h1-8H
InChIKey=KNNXFYIMEYKHBZ-UHFFFAOYAI

Compounds with long C-C bonds have typically been designed by placing large, sterically bulky groups attached to the two carbons. Not only does this lead to a longer bond (like the 1.67 Å C-C bond in 1) but these bulky groups also weaken the bond. This leads to molecules that tend to be difficult to isolate.

1 R = t-But

Schreiner has taken an alternative approach: design a sterically crowded molecules that is stabilized by dispersive forces between the large groups!¹ The dimer formed from diamantane 2 was prepared and isolated. The C-C distance is quite long: 1.647 Å. The compound is stable up to at least 300 ° C.

2

Computations of 2 were performed with a variety of density functional, all of which predict a long C-C bond. The bond dissociation energy of 2 is predicted to be 43.9 kcal mol^-1 at B3LYP/6-31G(d,p), a value consistent with the long CC bond. However, B3LYP does not account for dispersion. The H^…H distances between the two diamantyl groups range from 1.94 – 2.28 Å, suggesting that there could be appreciable dispersion stabilization. In fact, computing the BDE with B3LYP+D (Grimme’s dispersion correction) or B97D or M06-2x (all of which account for dispersion to some extent), predicts a much stronger bond, with the BDE ranging from 65-71 kcal mol^-1! Here is a stable molecule with a stroing, yet long C-C bond – where a good deal of the strength results not form the interaction between the two atoms of the formal bond, but rather from the energy associated form interactions across the entire molecule. This is a true delocalization effect!

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

References

(1) Schreiner, P. R.; Chernish, L. V.; Gunchenko, P. A.; Tikhonchuk, E. Y.; Hausmann, H.; Serafin, M.; Schlecht, S.; Dahl, J. E. P.; Carlson, R. M. K.; Fokin, A. A., "Overcoming lability of extremely long alkane carbon-carbon bonds through dispersion forces," Nature, 2011, 477, 308-311, DOI: 10.1038/nature10367.

InChIs

1: InChI=1/C86H126/c1-73(2,3)55-37-56(74(4,5)6)44-67(43-55)85(68-45-57(75(7,8)9)38-58(46-68)76(10,11)12
,69-47-59(77(13,14)15)39-60(48-69)78(16,17)18)86(70-49-61(79(19,20)21)40-62(50-70)80(22,23)24,71-51
-63(81(25,26)27)41-64(52-71)82(28,29)30)72-53-65(83(31,32)33)42-66(54-72)84(34,35)36/h37-54H,1-36H3
InChIKey=SFCRGHMFOGXDMZ-UHFFFAOYAS

2: InChI=1/C28H38/c1-13-7-23-19-3-15-4-20(17(1)19)24(8-13)27(23,11-15)28-12-16-5-21-18-2-14(9-25(21)28)
10-26(28)22(18)6-16/h13-26H,1-12H2
InChIKey=MMYAZLNWLGPULP-UHFFFAOYAU

Reactions whose outcomes depend on dynamic processes is a major theme of my book and this blog. The recent study of the reaction of a nucleophile (hydroxide) with bromoacetophenones adds yet another case for post-transition state product determination.

Itoh and Yamataka have examined the reaction of hydroxide with substitutes α-bromoacetophenones 1.¹ The nucleophile can attack at the carbonyl carbon or the α-carbon, though both lead ultimately to the same product, as shown in Scheme 1.

Scheme 1

B3LYP/6-31+G* computations of the reaction surface with a variety of different substituents on the phenyl ring of 1 located in all cases a single transition state for the two different reactions (addition and substitution). This TS is shown in Figure 1 for the parent case (X=H).

Figure 1. The single transition state for the addition and substitution reaction of 1 and hydroxide.

Tracing the IRC forward leads to either the carbonyl addition product or the substitution product, and which path is traced depends to some extent on the nature of the substituent. Most intriguing is that trajectories initiated at the transition state lead to both products. So once again, we see a case where a single transition state leads to two products, and product selectivity is determine by the dynamics – the initial conditions at the TS dictate which of the two products is eventually obtained.

References

(1) Itoh, S.; Yoshimura, N.; Sato, M.; Yamataka, H., "Computational Study on the Reaction Pathway of α-Bromoacetophenones with Hydroxide Ion: Possible Path Bifurcation in the Addition/Substitution Mechanism," J. Org. Chem., 2011, 70, 8294–8299, DOI: 10.1021/jo201485y

In 1955 Mislow¹ discussed the possibility of enatiomers interchanging via a path that was entirely chiral, never passing through an achiral structure. His analogy is the inversion of a rubber glove, taking a right hand rubber glove and pulling it inside out creates a left hand glove (its mirror image) but never passing through an achiral glove. Well, now a helicene with this type of stereochemistry has been developed, with a stable chiral intermediate.²

Helicenes typically interchange (P → M → P) through an achiral saddle-like structure. But larger helicenes can have high-lying intermediates along this pathway. Helquat P-1 interchanges to M-1 through the intermediate 2, which is an achiral structure and can be isolated.

Computations at B3LYP/def2-TZVP//PBE/def2-SV(P) with dispersion corrections (and PCM simulating DMSO) of the inversion process identified a number of intermediates and transition states along the stereoinversion pathway. The intermediate 2 lies 18.4 kJ mol^-1 above 1. These structures are shown in Figure 1. The highest lying TS between 2 and P-1 (labeled TSP in Figure 1) is 119 kJ mol^-1 above 2. The highest lying TS on the path from 2 to M-1 (labeled TSM in Figure 1) is 138 kJ mol^-1 above 2. Note that going from 2 to P-1 is not the mirror image path of going from 2 to M-1.

TSP

TSM

P-1

2

M-1

Figure 1. Optimized structures of 1, 2, and the highest transition states interconverting them.

Heating racemic 2 and following the conversion to 1 with NMR gives the activation barrier of 119 kJ mol^-1, in excellent agreement with the computation.

Racemic 2 was resolved through differential crystallization and its x-ray structure indicates it is (+)-[S_a,R_a]. Heating it does give just P-1, as predicted by the computations. Then heating P-1 to 180 °C does racemize it, with an experimental barrier of 157.7 kJ mol^-1. The computations predict a barrier of 156.6 kJ mol^-1, again in fine agreement with experiment. Overall, a nice piece showing experiment and computation working together to provide an understanding of an interesting chemical system!

References

(1) Mislow, K.; Bolstad, R., "Molecular Dissymmetry and Optical Inactivity," J. Am. Chem. Soc., 1955, 77, 6712-6713, DOI: 10.1021/ja01629a131

(2) Adriaenssens, L.; Severa, L.; Koval, D.; Cisarova, I.; Belmonte, M. M.; Escudero-Adan, E. C.; Novotna, P.; Sazelova, P.; Vavra, J.; Pohl, R.; Saman, D.; Urbanova, M.; Kasicka, V.; Teply, F., "[6]Saddlequat: a [6]helquat captured on its racemization pathway," Chem. Sci. 2011, ASAP, DOI: 10.1039/C1SC00468A

InChIs

1: InChI=1/C27H26N2/c1-2-11-23-20(8-1)15-19-29-18-7-10-22-14-13-21-9-3-5-16-28-17-6-4-12-24(28)25(21)26(22)27(23)29/h1-2,4,6,8,11-15,17,19H,3,5,7,9-10,16,18H2/q+2
InChIKey=YVVUWUZXUZDMQS-UHFFFAOYAP

Bendikov and co-workers have examined the dimerization of linear acenes at M06-2x/6-31G(d).¹ They have looked at the formal forbidden [4+4] reaction that takes, for example, 2 molecules of benzene into three possible dimer products 1P_anti1-2, 1P_syn1-2, and 1P_syn1-4. The relative energies of these products increases in that order, and all three are much higher in energy than reactants; the lowest energy dimer is 1P_anti1-2, lying 47.4 kcal mol^-1 above two benzene molecules. Similarly, the dimerization of naphthalene is also endothermic, but the formation of the symmetric dimer of anthracene 3P-2,2’ is exothermic by 5.4 kcal mol^-1. This gibes nicely with the best estimate of -9 ± 3 kcal mol^-1.² Dimerization of the higher acenes are increasingly exothermic.

The transition state for the dimerization of benzene is concerted, though very asymmetric, as seen in Figure 1. Its energy is quite high (77.79 kcal mol^-1) and so this reaction can be completely discounted. The TS for the dimerization of naphthalene is also concerted and asymmetric, but the reaction pathway for the dimerization is stepwise, with a diradical intermediate. Furthermore, the highest barrier for this stepwise reaction is 33.3 kcal mol^-1. The activation energy of the back reaction (anthracene dimer to two anthrecene molecules) was measured 36.3 kcal mol^-1,³ and the computed barrier of 38.7 kcal mol^-1 is in nice agreement. The computed barriers for the dimerization of the higher acenes are predicted to be even lower than that of anthracene, consistent with the observation of dimers of these molecules.

1Panti1-2	1TSanti1-2
1P-42	1TS-42

Figure 1. M06-2x /6-31G(d) optimized structures.

I was curious that the authors did not consider the formally allowed [4+2] dimerization, leading for example to 1P-42. So, I optimized this product and the concerted transition state leading to it. These are shown in Figure 1. The barrier through this transition state is still very large (54.1 kcal mol^-1) but it is 23 kcal mol^-1 lower in energy than the barrier of the [4+4] reaction! The Product of the [4+2] is also lower in energy (by 9 kcal mol^-1) than 1P_anti1-2. It seems to me that this type of dimerization is worth examining too – though I must say I have not as yet looked to see if anyone has explored this already.

References

(1) Zade, S. S.; Zamoshchik, N.; Reddy, A. R.; Fridman-Marueli, G.; Sheberla, D.; Bendikov,
M., "Products and Mechanism of Acene Dimerization. A Computational Study," J. Am. Chem. Soc., 2011, 133, 10803-10816, DOI: 10.1021/ja106594v

(2) Grimme, S.; Diedrich, C.; Korth, M., "The Importance of Inter- and Intramolecular van der Waals Interactions in Organic Reactions: the Dimerization of Anthracene Revisited," Angew. Chem. Int. Ed., 2006, 45, 625-629, DOI: 10.1002/anie.200502440

(3) Greene, F. D., "Problems of stereochemistry in photochemical reactions in the anthracene area," Bull. Soc. Chim. Fr., 1960, 1356-1360

InChIs

Benzene: InChI=1/C6H6/c1-2-4-6-5-3-1/h1-6H
InChIKey=UHOVQNZJYSORNB-UHFFFAOYAH

1P_anti1-2: InChI=1/C12H12/c1-2-6-10-9(5-1)11-7-3-4-8-12(10)11/h1-12H
InChIKey=WMPWOGVJEXSFLI-UHFFFAOYAP

1P_syn1-2: InChI=1/C12H12/c1-2-6-10-9(5-1)11-7-3-4-8-12(10)11/h1-12H
InChIKey=WMPWOGVJEXSFLI-UHFFFAOYAP

1P_syn1-4: InChI=1/C12H12/c1-2-10-4-3-9(1)11-5-7-12(10)8-6-11/h1-12H
InChIKey=BCBHEUOKKNYIAT-UHFFFAOYAI

1P-42: InChI=1/C12H12/c1-2-4-12-10-7-5-9(6-8-10)11(12)3-1/h1-12H
InChIKey=ONVDJSCNMCYFTI-UHFFFAOYAY

Anthracene: InChI=1/C14H10/c1-2-6-12-10-14-8-4-3-7-13(14)9-11(12)5-1/h1-10H
InChIKey=MWPLVEDNUUSJAV-UHFFFAOYAK

3P-2,2’: InChI=1/C28H20/c1-2-10-18-17(9-1)25-19-11-3-4-12-20(19)26(18)28-23-15-7-5-13-21(23)27(25)22-14-6-8-16-24(22)28/h1-16,25-28H
InChIKey=JUTIJVADGQDBGY-UHFFFAOYAY

There are three generic conformations of α-amino acids in the gas phase: A-C. These are stabilized by intramolecular hydrogen bonds. While computations suggest that all three are close in energy, the very detailed laser ablation- molecular beam-Fourier transform microwave (LA-MB-FTMW) experiments of the Alonso group (mentioned in these previous posts: guanine, cysteine, ephedrine) have identified only the first two conformations. Cooling of the structures in the jet expansion appears to be the reason for the loss of the (slightly) higher energy conformer C.

Alonso now reports on the structure of 1-aminocyclopropanecarboxylic acid 1.¹ The three MP2/6-311+G(d,p) optimized conformation are shown in Figure 1. The interaction between the cyclopropyl orbitals and the carbonyl π-bond suggests that only two structures (where the carbonyl bisects thecyclopropyl plane) will exist and that rotation between them may require passage through a prohibitively high barrier. In fact, computations suggest a barrier of 2000 cm^-1 (5.7 kcal mol^-1). This is much larger than the typical rotation barrier of the amino acids that interconvert A with C, which are about 400 cm^-1 (1 kcal mol^-1).

1A

1B

1C

After careful examination of the microwave spectrum, all three conformations 1A-C were identified by comparing the experimental value of the rotational constants, and ¹⁴N nuclearquadrupole coupling constants with the computed values. Really excellent agreement is found, including in the ratio of the relative amounts of the three isomers. Once again, we have an exquisite example of the importance of computations and experiments being used in conjunction to solve interesting chemical problems.

References

(1) Jimenez, A. I.; Vaquero, V.; Cabezas, C.; Lopez, J. C.; Cativiela, C.; Alonso, J. L., "The Singular Gas-Phase Structure of 1-Aminocyclopropanecarboxylic Acid (Ac3c)," J. Am. Chem. Soc., 2011, 133, 10621-10628, DOI: 10.1021/ja2033603

InChIs

1: InChI=1/C4H7NO2/c5-4(1-2-4)3(6)7/h1-2,5H2,(H,6,7)/f/h6H
InChIKey=PAJPWUMXBYXFCZ-BRMMOCHJCR

We have all learned about aromatic substitution as proceeding via the following mechanism

(Worse yet – many of us have taught this for years!) Well, Galabov, Zou, Schaefer and Schleyer pour a whole lot of cold water on this notion in their recent Angewandte article.¹ Modeling the reaction of benzene with Br₂ and using B3LYP/6-311+G(2d,2p) for both the gas phase and PCM simulating a CCl₄ solvent, attempts to locate this standard intermediate led instead to a concerted substitution transition state TS1 (see Figure 1).

TS1

Figure 1. PCM/B3LYP/6-311+G(2d,2p) optimized transitin state along the concerted pathway

However, this is not the lowest energy pathway for substitution. Rather and addition-elimination pathway is kinetically preferred. In the first step Br₂ adds in either a 1,2 or 1,4 fashion to form an intermediate. The lower energy path is the 1,4 addition, leading to P3. This intermediate then undergoes a syn,anti-isomerization to give P5. The last step is the elimination of HBr from P5 to give the product, bromobenzene. This mechanism is shown in Scheme 2 and the critical points are shown in Figure 3.

Scheme 1

TS3	P3
TS6	P5
TS9

Figure 2. PCM/B3LYP/6-311+G(2d,2p) optimized critical points along the addition-elimination pathway

The barrier for the concerted substitution process through TS1 is 41.8 kcal mol^-1 (in CCl₄) while the highest barrier for the addition-elimination process is through TS3 of 39.4 kcal mol^-1.

Now a bit of saving grace is that in polar solvents, acidic solvents and/or with Lewis acid catalysts, the intermediate of the standard textbook mechanism may be competitive.

Textbook authors – please be aware!

References

(1) Kong, J.; Galabov, B.; Koleva, G.; Zou, J.-J.; Schaefer, H. F.; Schleyer, P. v. R., "The Inherent Competition between Addition and Substitution Reactions of Br₂ with Benzene and Arenes," Angew. Chem. Int. Ed. 2011, 50, 6809-6813, DOI: 10.1002/anie.201101852