Electrophilic Aromatic Substitution: Enthalpies of Hydrogenation of the

Dec 3, 2013 - Wayne F. K. Schnatter, Donald W. Rogers, and Andreas A. Zavitsas*. Department of Chemistry and Biochemistry, Long Island University, ...
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Electrophilic Aromatic Substitution: Enthalpies of Hydrogenation of the Ring Determine Reactivities of C6H5X. The Direction of the C6H5− X Bond Dipole Determines Orientation of the Substitution Wayne F. K. Schnatter, Donald W. Rogers, and Andreas A. Zavitsas* Department of Chemistry and Biochemistry, Long Island University, 1 University Plaza, Brooklyn, New York 11201, United States S Supporting Information *

ABSTRACT: There are still some secrets left to this well-studied reaction. Previously unreported relationships discovered are as follows. The ordering of reactivities of C6H5X is the same as that of enthalpies of hydrogenation of the ring to the correspondingly substituted cyclohexane. The orientation of substitution (meta or ortho/para) is controlled by the dipole direction of the ipso-C−X bond, like an ON/OFF switch. The difference between the halogens and other deactivating groups is that the bond between the atom bonded to the ipso carbon has the positive end of the dipole on the ipso carbon for the halogens (Cδ+−Xδ−) but in the opposite direction (Cδ−−Xδ+) for other deactivating groups. This reverses the directing effect. For all X, including the halogens, ipso-Cδ+−Xδ− results in ortho/para substitution. p-13C NMR shifts of C6H5X greater than that of benzene predict meta substitution. A linear relationship exists between p-13C NMR shift and ΔHhyd, except for X = halogen. With halobenzenes, the ortho/para ratios of the products are linearly related to the ipso/ortho ratios of the 13C shifts of C6H5X for chlorinations, brominations, nitrations, and protonations. The relative reactivities of the halobenzenes are linearly related to the p-13C NMR shifts. The electronegativities of X are linearly related to the 13C NMR shifts of the ipso carbon.

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INTRODUCTION Electrophilic aromatic substitution has been studied extensively, and there is a large set of experimental data on relative reaction rates, product distributions, and the effects of solvent, catalyst, and temperature. Whether the mechanism involves σ or π complexes of the electrophile with the ring or single electron transfer to the electrophile to form an aromatic radical cation has been debated in the past, but the current general consensus for the large majority of cases studied is that they all lead to the formation of a carbocation intermediate, an arenium ion,1−4 as proposed by Wheland.5 Standard textbooks of organic chemistry describe the reaction mechanism as proceeding through this intermediate.6−10 Despite the voluminous knowledge accumulated for such reactions, there are some aspects that appear not to have been examined previously and that lead to some new insights. This work examines experimentally based enthalpies of complete hydrogenation of the rings of monosubstituted benzenes as they relate to their reactivities in electrophilic aromatic substitutions. This is similar to the common use of enthalpies of hydrogenation and of the stability of the carbocations formed to rationalize the results of electrophilic additions to alkenes. To the best of our knowledge, examination of enthalpies of hydrogenation, although simple and based only on experimental measurements, has not been undertaken previously. Possible relations with 13C NMR chemical shifts also do not appear to have been examined in the broad context of the many electrophilic aromatic substitutions that have been studied, even though shielding and deshielding effects of the ring carbons of C6H5X are due to © XXXX American Chemical Society

electron donation or withdrawal by the X substituent. Such spectroscopic data are examined in this work, as well as those with the direction of the dipole of the ipso-C−X bond and with electronegativities of X. In monosubstituted benzenes, the substituent is described as activating or electron-donating when the reaction rate is greater than that for the reaction of benzene and deactivating or electron-withdrawing for the reverse. Resonance (or mesomeric) effects of X are also invoked as stabilizing or destabilizing the carbocation intermediate formed and affecting the orientation of the substitution. All activating groups lead to preponderant substitution at the ortho and para positions. All electron-withdrawing groups, except for the halogens, are deactivating, with the resonance effect destabilizing the carbocation formed by ortho and para substitution, leading to meta products. The greater electronegativity of the halogens relative to carbon has been rationalized as decreasing the rate, with the resonance effect stabilizing the carbocation intermediate formed by para and ortho substitution. Thus, the set of halogens appears to be unique in decreasing the rates but leading mostly to para and ortho products. The rates of electrophilic aromatic substitutions for typical benzene substituents are in the order X = NH2 > OH > CH3 ≈ CH3CH2 > H > F > Cl > CN > NO2.3,4,8,10 Reaction rates were reported to adhere fairly well11 to the linear free energy relationship of Hammett’s equation. Received: September 26, 2013 Revised: November 14, 2013

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The Hammett substituent constants, σ, were derived from the effect of the X substituent on the pKa of substituted benzoic acids. Significant improvement of the fit of relative rate constants of electrophilic aromatic substitutions was obtained with σ+ substituent constants, which were derived from the relative rates of solvolysis of phenyl-X-substituted cumyl chlorides (2-chloro-2-phenylpropanes), which proceed via a carbocation intermediate.12,13 Evidently, σ+ values derived from reactions forming carbocations in the solvolyses are more closely related to the carbocation intermediates formed in electrophilic aromatic substitutions.

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RESULTS AND DISCUSSION

Enthalpies of Complete Hydrogenation. The enthalpy of complete hydrogenation of the benzene ring of an Xsubstituted benzene is given by the difference in the experimental standard enthalpy of formation of the substituted benzene and the enthalpy of formation of the correspondingly substituted cyclohexane (eq 1): ΔHhyd = Δf H °[C6H11X] − Δf H °[C6H5X]

Figure 1. Plot of experimentally based enthalpies of hydrogenation of the aromatic ring with the indicated X substituents to give the correspondingly substituted cyclohexanes vs the ordering of reactivities.

(1)

Direct measurements of such enthalpies of hydrogenation either are not available or cannot be obtained for all substituents. For example, nitrobenzene is hydrogenated to cyclohexylamine, not to nitrocyclohexane. Equation 1 is valid for the purpose at hand only when the X substituent does not cause steric effects that are different in the benzene and the hydrogenated product (e.g., tert-butylbenzene and tertbutylcyclohexane) or when conjugation stabilization is present in the aromatic molecule (e.g., in styrene but not in vinylcyclohexane). The experimental ΔfH° values used here with eq 1 are from a single extensive database (NIST database no. 69),14 to avoid arbitrary selection from different values that exist in the literature. The single exception is the experimental value of ΔfH°[nitrocyclohexane] (given as −38.07 ± 0.16 kcal mol−1 in ref 15), for which the NIST database provides no value. By eq 1, the experimentally based enthalpies of complete hydrogenation of the aromatic ring of the X-substituted benzenes to give X-substituted cyclohexanes are as follows: X = NH2, −44.38 ± 0.21 kcal mol−1; OH, −46.03 ± 0.14; CH3, −48.97 ± 0.36; CH2CH2, −48.37 ± 0.20; H, −49.80 ± 0.04; F, −52.68 ± 0.43; Cl, −52.77 ± 0.46; CN, −53.19 ± 0.40; NO2, −54.45 ± 0.23. For ΔHhyd[benzene], the highly accurate value experimentally obtained by direct complete hydrogenation of benzene by Kistiakowsky et al.16 was employed. The relationship between ΔHhyd and the known ordering of reactivities is shown in Figure 1. While the electron-donating or -withdrawing abilities of various X substituents are usually deduced from their effect on reaction rates relative to benzene, they are not quantified in terms of physical properties of C6H5X. The ΔHhyd values do so. Surprisingly, or perhaps not so, the ordering of the ΔHhyd values is the same as the ordering of the reactivities of the Xsubstituted benzenes. The above X substituents constitute all but one of the 18 species for which the NIST database14 provides experimental ΔfH° values for both the benzene and the corresponding cyclohexane for X that are not expected to cause different steric or conjugation effects in the benzene and the corresponding cyclohexane. It is worth noting that the deactivating effect of fluorine is known to be smaller than that of chlorine17,18 and that the ΔHhyd values are consistent with this. The inclusion of CN in the above set of substituents

may be questioned because benzonitrile may be stabilized by conjugation. However, it is included because the closely related conjugation of acrylonitrile, CH2CH−CN, is known to result in a thermodynamically measurable conjugation stabilization of zero.19,20 In addition, the CN stretching frequencies of benzonitrile and acrylonitrile are nearly the same (2235 and 2236 cm −1 , respectively 14 ), which confirms the same thermodynamic conjugative stabilization (i.e., zero) in the two compounds. As routinely done for the relative stabilities of the double bonds of alkenes,3−10 the above ΔHhyd values indicate that the ring of aniline is 5.42 kcal mol−1 more stable than that of benzene and the ring of nitrobenzene is 4.64 less stable. We are not aware of any relative stability values of monosubstituted aromatic rings having been suggested previously. The relation between reactivity and ΔHhyd in electrophilic aromatic substitutions is exactly equivalent to that reported for the reactivities of electrophilic additions to alkenes, which also proceed through a carbocation-like intermediate, which may be nonclassical, such as an H+-bridged structure for C2H5+ or a protonated cyclopropane (i.e., H3C+-bridged ethylene) for C 3 H 7 +. The rate constants for gas-phase electrophilic (Markovnikov) additions of HI to ethene (ΔHhyd = −32.54 ± 0.10 kcal mol−1), propene (ΔHhyd = −29.90 ± 0.15), and 2methylpropene (ΔHhyd = −27.78 ± 0.29) are in the ratio of 1:90:7000, respectively, and additions of HCl and HBr follow similar relative reactivity patterns.21,22 The three enthalpies of reaction for addition of HI are essentially the same (−20 ± 1 kcal mol−1). The reactivities are in the reverse order of the stabilities of the double bonds, as quantified by their ΔHhyd values. We found that a plot of the logarithm of the relative reactivity for addition of HI versus the enthalpy of hydrogenation of the alkene is linear, as shown in Figure 2: ln(k/k0) = 60.13 + 1.852(ΔHhyd). The square of the correlation coefficient, r2, is 0.997 (or r = 0.998). The error bars in Figure 2 were calculated from the reported14 uncertainties of the experimental ΔfH° of the substituted benzene and of the correspondingly substituted cyclohexane. The linearity is remarkable, even though Figure 2 does not include any B

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(Tables S2 and S3 and Figures S1 and S2). The dependence of the reactivity on ΔHhyd is common to electrophilic substitutions of alkenes and aromatics. The relative reactivities of electrophilic aromatic substitutions cannot be achieved under the same reaction conditions. For example, mononitration of aniline and of nitrobenzene cannot be achieved experimentally under the same conditions of nitrating agent, catalyst, solvent, and temperature. Electron-donating G groups in alkenes CH2CHG were reported to enhance the rate of addition of electrophiles and electron-withdrawing groups to retard it,25 generally as is the case with the same G groups in electrophilic aromatic substitutions. Gas-phase enthalpies of reaction, ΔHrxn, for the addition of H+ to three alkenes can be calculated from the known enthalpies of formation of the reactants and products.14 For CH2CH2 + H+ → CH3CH2+, CH2CHCH3 + H+ → (CH3)2CH+, and CH2C(CH3)2 + H+ → (CH3)3C+, linear regression of the data yields ΔHrxn = −378.3 − 6.643(ΔHhyd); r2 = 0.996 (r = 0.998). The plot is given in the Supporting Information (Figure S3). The enthalpies of reaction are linearly related to the enthalpies of hydrogenation. The enthalpies of reaction of gas-phase additions of H3C+ to ethene, propene, and 2-methylpropene to yield 1-propyl, 2-butyl, and 2-methylbut-2yl carbocations also can be calculated from the known enthalpies of formation of reactants and products.14 Linear regression of the data yields ΔHrxn = −292.9 − 7.041(ΔHhyd); r2 = 0.999 (or r = 1.000). The plot is given in the Supporting Information (Figure S4). As with the additions of H+, the enthalpies of reaction are in the reverse order of the enthalpies of hydrogenation, and the two are linearly related. Enthalpies of hydrogenation provide an accurate description of the ordering of electron densities of the aromatic rings and thus their susceptibility to reaction with an electrophile and their ability to stabilize the positive charge of the carbocation intermediate. The formation of this intermediate is an endothermic process because of loss of aromaticity. The difference Δ[ΔHhyd] = ΔHhyd[aniline] − ΔHhyd[benzene] is 5.42 kcal mol−1, and this will contribute to an increase in the energy of activation (Ea) for the reaction of benzene relative to aniline because of the lesser ability of benzene to stabilize the carbocation intermediate. Values of Δ[ΔHhyd] determine the ordering of the reactivities of C6H5X but not of the relative reactivities, kX/kH. Using the Arrhenius equation for rate constants and assuming approximately equal pre-exponential factors A would lead to kaniline/kbenzene = exp(5240/RT) = 9530 at 298 K, which is consistent with the high reactivity of aniline. Similarly, knitrobenzene/kbenzene = exp(−4640/RT) = 0.000399, consistent with the low reactivity of nitrobenzene. However, Δ[ΔHhyd] is not equal to Ea. Only the ordering of reactivities is correctly calculated via Δ[ΔHhyd]. No properties of the substrate C6H5X can produce kX/kH because relative reactivities are also functions of the reaction conditions. For example, the relative reactivities of toluene to benzene, kT/kB, vary with different electrophiles, catalysts, and solvents because of different sensitivities of the reactions to changes in electron density: in benzoylation by C6H5COCl, AlCl3, CH3NO2, kT/kB = 153;3 in chlorination by Cl2, AlCl3, CH3NO2, kT/kB = 18;3 in nitration by HNO3, H2SO4, H2O, kT/kB = 17;3 in benzylation by C 6 H 5 CH 2 Cl, AlCl 3 , CH 3 NO 2 , k T /k B = 5.4; 26 in isopropylation by (CH3)2CHCl, AlCl3, CH3NO2, kT/kB = 2.0;27 and in nitration with nitronium tetrafluoroborate in sulfolane (1,1-dioxidetetrahydrothiophene), kT/kB = 1.7.28 Calculation using the Δ[ΔHhyd] values as above yields kT/kB

Figure 2. Gas-phase electrophilic additions of HI to alkenes. Plot of ln(k/k0) vs ΔHhyd of the indicated alkene.

experimental uncertainty in the reported relative reactivities.21,22 Electrophilic additions of bromine to various alkenes under the same reaction conditions have also been studied:23 1hexene (k0, ΔHhyd = −29.74 ± 0.60 kcal mol−1), 2-methyl-1pentene (ΔHhyd = −29.10 ± 0.35), trans-3-hexene (ΔHhyd = −28.14 ± 0.24), 2-methyl-2-butene (ΔHhyd = −26.81 ± 0.25), 2,3-dimethyl-2-butene (−25.78 + 0.43), and other heteroatomsubstituted and cis-alkenes. We found that that the reactivities of the alkenes specifically named above again show an excellent linear dependence on their respective enthalpies of hydrogenation, as shown in Figure 3: ln(k/k0) = 69.39 + 2.326(ΔHhyd); r2 = 0.992 (r = 0.996). The results for other brominations and chlorinations of simple alkenes under different reaction conditions24 also show linear plots with high r2 values of 0.999 and 0.985, respectively. The data and plots are given in the Supporting Information

Figure 3. Liquid-phase electrophilic additions of Br2 to alkenes. Plot of ln(k/k0) vs ΔHhyd of the indicated alkene. The error bars are the experimental uncertainties. C

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= 4.5. Δ[ΔHhyd] values correctly predict the ordering of reactivities with the same electrophile, catalyst, and solvent in all cases, but not the kX/kH values, which vary. Among many others, the results of sets of measurements leading to good linear Hammett-type plots of log10(kX/kH) versus σp+ are available for eight different electrophilic aromatic substitutions, with each set of reactions carried out under different conditions for brominations in acetic acid; chlorinations in nitromethane; chlorinations in acetic acid, H2O; proton exchanges in H2SO4, CF3CO2H, H2O; acetylations in C2H4Cl2, AlCl3; nitrations in H2SO4, HNO3; chlorinations in HOCl, H+; and alkylations with ethyl bromide and GaBr3. The reported values of the slope, ρ, are all negative: −13.1, −13.0, −8.8, −8.6, −8.6, −6.4, −6.1, and −2.4, respectively.29 This shows that the ordering of the experimental relative reactivities of all Xsubstituted benzenes remains the same with all electrophiles used and with all solvents, despite the large differences in the sensitivity of each set of reactions to changes in electron donation or withdrawal, and consistent with the ordering required by the ΔHhyd values. 13 C NMR Chemical Shifts. There are available several Hammett-type correlations of relative reactivities of C6H5X with σ+, which relates to the carbocation intermediate. We have not found correlations of relative rates of the many electrophilic substitutions studied with 13C NMR chemical shifts, which are properties of the neutral C6H5X reactant. The 13C NMR shift is a good measure of the shielding, or electron density, at the particular carbon atom. Figure 4 shows a plot of p-13C NMR

The crucial difference between the deactivating halogens and other deactivating groups, such as −NO2, −CN, −CCl3, −CF3, and various −C(O)R, is in the direction of the dipole of the bond between the ipso carbon and the X substituent. The carbonyl carbons of various −C(O)R groups and the carbons of −CN, −CCl3, and −CF3 are all known to be electrondeficient; the nitrogen of the electron-withdrawing NO2 group bears a full positive formal charge. For these deactivating groups, the bond dipole has the negative end on the ipso carbon, Cδ−−Xδ+, but with the halogens the dipole is in the opposite direction, Cδ+−Xδ−. This should and does cause a reversal in the favored orientation of their substitutions (meta vs ortho/para), even though they all are deactivating groups. The effect of the orientation of the dipole of the ipso-C−X bond was examined for 13 deactivating substituents, benzene, and eight activating substituents with known directive effects and experimental 13C NMR chemical shifts available in the SDBS database.30 Table 1 lists for each X the p-13C NMR shift, Table 1. X Substituents on C6H5X, p-13C NMR Shifts in CDCl3 Solvent (ppm), Predominant Directing Effects of the Substituents, and Directions of the ipso-C−X Bond Dipoles X NO2a a

CHO CO2Ha COCH3a CO2CH3a CNa CF3a S(O)CH3a CCl3a H Ia Bra Cla CH3CH2b CH3b NHCOCH3b Fa OHb CH3Ob NH2b NHCH3b N(CH3)2b a

Figure 4. Chemical shifts of p-13C of C6H5X with the indicated X substituents vs experimentally based enthalpies of hydrogenation of the aromatic ring.

p-13C NMR shift

directing effect

ipso-C−X dipole

134.71 134.43 133.83 133.04 132.90 132.84 131.82 131.00 130.24 128.36 127.28 126.82 126.43 125.65 125.38 124.23 124.16 121.09 120.72 118.39 117.12 116.65

meta meta meta meta meta meta meta meta meta − ortho/para ortho/para ortho/para ortho/para ortho/para ortho/para ortho/para ortho/para ortho/para ortho/para ortho/para ortho/para

Cδ−−Xδ+ Cδ−−Xδ+ Cδ−−Xδ+ Cδ−−Xδ+ Cδ−−Xδ+ Cδ−−Xδ+ Cδ−−Xδ+ Cδ−−Xδ+ Cδ−−Xδ+ − Cδ+−Xδ− Cδ+−Xδ− Cδ+−Xδ− Cδ+−Xδ− Cδ+−Xδ− Cδ+−Xδ− Cδ+−Xδ− Cδ+−Xδ− Cδ+−Xδ− Cδ+−Xδ− Cδ+−Xδ− Cδ+−Xδ−

Deactivating substituent. bActivating substituent.

the experimentally established directing effect of the substituent, and the direction of the ipso-C−X bond dipole. The dipole effect is clearly reflected in the p-13C NMR shifts. All C6H5X with ipso-Cδ−−Xδ+ dipoles have para carbon NMR shifts greater than that of benzene, and substitution results predominantly in meta products. When the bond dipole is ipso-Cδ+−Xδ−, the p-13C NMR shift is smaller than that of benzene and predominantly ortho and para products are obtained. p-13C NMR shifts near the 128.36 ppm value for benzene would indicate that some significant amount of the nonpredominant product(s) will be present. When the polarity of the C6H5−X bond is ipso-Cδ−−Xδ+, the partial negative charge of the ipso carbon is delocalized to some extent to its allylic meta positions, resulting in preferred attack by the electrophile at those positions (see the structure on the

chemical shifts versus the experimentally based ΔHhyd values. Linear regression of the data represented by the filled circles yields δp‑13C = 46.48 − 1.625(ΔHhyd); r2 = 0.991 (r = 0.995). The halogen set is unique in not adhering to the regression line. The shifts for all of the ring carbons are from a single database, the extensive SDBS compilation,30 and they are provided in the Supporting Information (Table S1). The error bars in Figure 4 were calculated from the reported14 uncertainties of the experimental ΔfH° values for the substituted benzenes and the correspondingly substituted cyclohexanes. D

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reactivities kX/kH. The four plots are given in the Supporting Information (Figures S5−S8). Ratios of Ortho to Para Products. Ortho to para product ratios are often reported without quantitative explanations, except for obvious steric effects such as the absence of large amounts of the sterically congested ortho product in some reactions of tert-butylbenzene, etc. Product distributions of some electrophilic aromatic substitutions have been determined for nitration,32 chlorination,35 and bromination36 of halobenzenes, with each set of reactions performed under similar conditions in the same solvent. We found that the ratios of ortho to para substitution products are linearly related to the ratios of the ipso to ortho 13C NMR shifts of C6H5X, as shown in Figure 5.

left in the Abstract graphic). The direction of the dipole acts like a switch that turns ON predominant meta substitution. The opposite direction of the dipole, ipso-Cδ+−Xδ−, turns OFF meta substitution, and mostly ortho/para products are obtained (see the structure on the right in the Abstract graphic). All ortho/ para-directing substituents, including the halogens, have p-13C NMR shifts smaller than that of benzene and the same direction of the bond dipole. The direction of the dipole is a property of the aromatic substrate, not of the carbocation intermediate, but it clearly controls the directive effect. For phenylboron dichloride, C6H5BCl2, the ipso-C−X bond dipole of the organometallic would be as shown by the left structure in the Abstract graphic, and 68% of the nitrated product is the meta isomer.31,32 The lower overall reactivity of the halobenzenes relative to benzene has been rationalized in terms of the electronwithdrawing abilities, or electronegativities, of the halogens,3−10 which reduce the electron density of the ring. The ordering of reactivities of the halobenzenes is C6H5F > C6H5Cl > C6H5Br.17,18,34,35 Fluorobenzene is the most reactive, even though F has the highest electronegativity and electronwithdrawing ability. Textbooks often do not comment about this apparent anomaly. One reason for this ordering can be attributed to the fact that the ipso-C−F bond is the shortest. This would allow greater overlap of the unshared electrons of F with the p orbitals of the ring and stronger resonance stabilization. Accordingly, better stabilization has been attributed to better overlap and resonance stabilization between the 2p orbitals of carbon and of fluorine, the orbitals being of similar size. With chlorobenzene, overlap between the carbon 2p and the more distant 3p orbitals of chlorine would be less effective in stabilizing the carbocation.10 Such resonance structures, however, must place some positive charge on the most electronegative element, F, and this may be questionable. Politzer and Timberlake have reported that values of the overlap integrals of halogen substituents with the π electrons of the ring are smaller for the C−F bond than those of the C−Cl and C−Br bonds. It has been suggested that a repulsive interaction between the outer pπ electrons of the halogen and the π electrons of the ring has the effect of pushing the aromatic π electrons away from the substituted position, building up some π charge at the ortho and para positions.33 Consistent with this, we found that the ordering of the reactivities of fluorobenzene, chlorobenzene, and bromobenzene is related to the sum of the 13C NMR shifts of the five available ortho, meta, and para positions: 615.38 ppm for X = F, 643.15 for Cl, and 649.80 for Br; the sums of the two ortho and the para positions follow the same trend: 355.14, 383.69, and 389.82, respectively. This ordering of increasing deshielding, or decreasing electron densities, of the ring positions is the same as the ordering of their reactivities, with the least-deshielded substrate, fluorobenzene, being the most reactive: C6H5F > C6H5Cl > C6H5Br. Not only the ordering of reactivities but also the experimental relative reactivities, khalobenzene/kbenzene, are related to the above sums of the NMR shifts. Plots of the experimental relative reactivities for nitrations,32 chlorinations,35 and brominations36 versus the sums of 13C NMR shifts are linear with r2 values of 0.981, 0.997, and 0.996, respectively. Also, plots of khalobenzene/ kbenzene versus p-13C NMR shifts yield r2 = 0.975, 0.999, and 0.999, respectively. Benzylations34 yield r2 = 0.995. The experimental data indicate that the spectroscopic properties of the halobenzene reactants are linearly related to the relative

Figure 5. Plot of the ratios of ortho to para products for chlorinations, nitrations, and brominations of halobenzenes in nitromethane vs the ratios of ipso to ortho 13C NMR shifts of the halobenzenes (indicated by vertical lettering).

The three lines in Figure 5 have very high values of r2. For chlorinations (Cl2, FeCl3 or AlCl3 in nitromethane), (ortho/ para ratio) = 1.83 − 1.05 × (ipso/ortho 13C shift ratio), r2 = 0.991. For nitrations (NO2+ PF6− in nitromethane), (ortho/ para ratio) = 1.29 − 0.817 × (ipso/ortho 13C shift ratio), r2 = 0.999. For brominations (FeCl3 in nitromethane solvent with Br2 in nitromethane added), (ortho/para ratio) = 0.791 − 0.478 × (ipso/ortho 13C shift ratio), r2 = 0.996. In these three sets of reactions, not only the reactivity and the directing effect but also the ortho/para ratio are directly related to properties of the C6H5X substrate, namely, the 13C NMR shifts. The ortho/ para product ratios of nitrations,32 chlorinations,35 and brominations36 are also linearly related to the ratios of the halobenzene ortho/para 13C NMR shifts. The data and plot are given in the Supporting Information (Table S4 and Figure S9). Chlorinations of halobenzenes by Cl2 in 60% CH3CO2H/ H2O and 1.2 M HCl37 gave ortho/para product ratios different from those in Figure 5 because of the different reaction conditions. The relationship was found: (ortho/para ratio) = 1.58 − 1.03 × (ipso/ortho 13C shift ratio), r2 = 0.996. The data and plot are given in the Supporting Information (Table S5 and Figure S10). The few available data for reactions of iodobenzene with various other larger electrophiles do not fit well on the straight E

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line obtained with the other halobenzenes. This likely is due to protection of the ortho position by the large size of the iodine atom as a result of a steric effect. Data for protonations of iodobenzene,38 however, fall on the same line as the other halobenzenes with r2 = 0.995. Evidently, the small size of the electrophile in this case allows entry at the ortho position. The data and plot are given in the Supporting Information (Table S6 and Figure S11). Ortho/para product ratios for alkylations must be interpreted with care. Benzylations of toluene with benzyl bromide and gallium bromide catalyst with excess toluene as the solvent gave ratios of ortho to para benzylated toluenes that were dependent on the reaction time.39 This is due to isomerization of the initially formed products by GaBr3, which causes the metasubstituted product to be the prevalent isomer found at long reaction times. GaBr3 was used to avoid complications encountered with AlBr3 and to minimize the extent of resulting product isomerization and disproportionation.36 Isomerization of dialkylbenzenes and intermolecular transfers of alkyl groups by AlCl3 have also been demonstrated and, at long reaction times, produce distributions favoring the thermodynamically more stable meta isomers of dialkylbenzenes.40 By extrapolation of the distribution of products to zero reaction time with GaBr3, the kinetically controlled ratio of ortho to para benzylated product of toluene was found to be 1.04.36 Nitration of toluene by the oleum salt NO2+HS2O7−, also in excess toluene as the solvent as in the above benzylation, again gave a 1.04 ratio of ortho to para products.41 However, with the same oleum salt, a change in the nitration solvent from excess toluene to sulfolane gave an ortho/para ratio of 1.79.41 Therefore, the type of correlation shown in Figure 5 is not general. Ratios of ortho/para products of various nitrations of toluene change significantly depending on the solvent and any catalyst used.41 Electronegativities. The ortho/para-directing effect of the halobenzenes has been rationalized by resonance structures involving their unshared electrons, with the halogen stabilizing the carbocation formed by ortho and para substitution. These rationalizations appear in undergraduate as well as advanced texts.3−10 However, there is a problem with the attribution of the observed orientations of substitution simply to resonance stabilization of the carbocation intermediate. Were this the case, fluorobenzene would yield significant amounts of both ortho and para products, but this is not the case with several electrophiles, which are found to yield 85 to 100% para substitution in chlorinations,37 brominations,36 and benzylations.34 This apparently anomalous behavior of fluorobenzene has been noted and discussed previously,42,43 and additional similar examples of reactions are available, including acetylation and proton−tritium exchange42 and reversal of the polarity of the dipole.43 Figure 6 shows the effect of the group electronegativity of the substituent, χ,44,45 on the NMR chemical shift of the ipso carbon for four simple X substituents bonded to the ring with an atom of an element in the second row of the periodic table: F, OH, NH2, and CH3. Linear regression yielded δipso‑13C = 92.48 + 17.82χ; r2 = 0.9981. Other more complex substituents do not adhere as well to the same line, but the excellent linearity of the plot with these four simple substituents is unlikely to be fortuitous, as shown by additional similar examples below. As expected, the strong inductive effect of the fluorine causes the greatest deshielding of the ipso carbon, 163.1 ppm compared with 155.0 for OH, 146.5 for NH2, and 137.8 for

Figure 6. Plot of ipso-13C NMR shifts vs group electronegativities of the indicated benzene substituents; r2 = 0.9981.

CH3. The resonance effect of the hydroxy and amino groups is large and overwhelms the electron-withdrawing inductive effect, but the resonance effect of fluorine could be weaker compared with HO, NH2, and the other halogens because it requires a positive charge on the highly electronegative F. Inductive effects are attenuated by distance, and a reasonable proposal has been made that the resonance effect would overcome the inductive effect to a greater extent at the more remote para position than at the ortho position.35 This is supported by the fact that the partial rate factor for substitution at the para position of fluorobenzene, f p, is 1.8 to 4 times greater than that of one of the six positions of benzene.35−37,42 Therefore, fluorine would activate the para position by resonance, but the ortho position would be less activated because of the strong nearby and opposing inductive effect. The other halogens are less electronegative and better in sustaining a positive charge and therefore yield greater amounts of ortho products. However, this rationalization36 is not supported by 13C NMR shifts, as discussed below. An alternative rationalization is based on inductive effects due to the “superelectronegativity” of fluorine and considerations of stabilizing and destabilizing inductive interactions and high Coulombic stabilization between the electron-poor ipso carbon and the postulated electron-rich ortho carbon, causing in the strongest carbon− carbon bond to lose some of its double-bond character upon ortho substitution.43 The 13C NMR shifts of fluorobenzene shed light on this question. If the inductive effect of the fluorine in the fluorobenzene reactant overcomes the resonance effect at the ortho position,36 the electron density would be lower at the ortho carbon than at the para carbon. This is not supported by the 13C NMR data: the ipso, ortho, meta, and para carbons have chemical shifts of 163.13, 115.49, 130.12, and 124.16 ppm, respectively. The ortho carbon is the most shielded and electron-rich and would be expected to be the most susceptible to attack by electrophiles, but this is not the case. Substitution at the ortho position involves direct loss in some bonding between the ipso and ortho carbons, which is the strongest carbon−carbon bond of the ring. The higher strength of this bond is due to its greater polarity, as it involves the most electron-poor carbon (ipso-C, 163.1 ppm) and the most F

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electron-rich carbon (o-C, 115.5 ppm), as shown in Scheme 1. The difference of 47.6 ppm is by far the highest of any of the Scheme 1. 13C NMR Shifts of Fluorobenzene (Numerals) and Necessary Partial Charges upon Ortho and Para Substitution

corresponding differences of the other substituents of Table 1 and results in the most polar and strongest C−C bond. Substitution at the para position results in direct loss of some double bond character involving a less polar and weaker bond, that between the meta carbon and the para carbon, with a shift difference of only 5.9 ppm. The same effect is shown by the fact that fluorobenzene has the highest ipso to ortho 13C NMR shift ratio of the halobenzenes in Figure 5 and, therefore, the highest ring C−C bond dipole and the strongest bond. As a result, ortho substitution requires a higher energy of activation for weakening of this bond, in general agreement with the previously proposed alternative rationalization.43 There is an additional significant factor in favor of para substitutions in fluorobenzene. Substitution at the ortho position forces a partial positive charge directly onto the ipso carbon, which already bears the highest partial positive charge (i.e., is most deshielded) relative to those of the other halobenzenes (second structure in Scheme 1). Substitution at the para position of fluorobenzene does not force a destabilizing positive charge directly on the ipso carbon (third structure in Scheme 1). The ΔHhyd values show that the ring of fluorobenzene is destabilized: ΔHhyd[fluorobenzene] − ΔHhyd[benzene] = −2.89 kcal mol−1. However, the 13C chemical shift of the para carbon of fluorobenzene is smaller than that of benzene (124.16 vs 128.36 ppm, respectively; Figure 4), indicating greater shielding and higher electron density at the para position, resulting in values of f p greater than 1.0. In summary, there is nothing surprising or unusual about the halogens being deactivating but ortho/para-directing. The orientation of the ipso-C−X dipole of the halobenzenes is the same as that of all other ortho/para directing groups. Halobenzenes have p-13C NMR shifts smaller than that of benzene, as are those of all other ortho/para-directing groups in Table 1. Resonance effects of halogen substituents on the stability of the carbocation intermediate being formed need not necessarily be invoked to predict the directing effect of substitution (meta vs ortho/para). The stability of the carbocation intermediates being formed is clearly relevant to reactivities and directing effects, but these effects are also predictable from physical properties of the halobenzene reactants, namely, their ΔHhyd and p-13C NMR shifts (Table 1). In addition to Figure 6, there are other excellent linear relationships of 13C NMR shifts of the aromatic carbons with the electronegativities of the substituents. Figure 7 shows a plot of the 13C NMR shifts of the ipso carbon of C6H5X versus the group electronegativities of the X substituents.45 Linear regression for the simple substituents of the homologous group X = OH, SH, and SeH46 yields δipso‑13C = 56.56 + 28.10χ, r2 = 0.9991. Linear regression for the homologous group X = F,

Figure 7. Plot of the 13C NMR shifts of the ipso carbon vs the group electronegativities of the indicated benzene substituents for the two homologous groups. For OH, SH and SeH, r2 = 0.9991; for F, Cl, and Br, r2 = 0.9997.

Cl, and Br yields δipso‑13C = 13.65 + 37.90χ, r2 = 0.9997. While the trends shown in Figures 6 and 7 would be expected, the relation and the excellent linearities found have not been noted previously. Applications. There is an interesting apparent anomaly in the reactions of nitrosobenzene. Very careful experimental work by Ingold in 1925 showed unequivocally that brominations of nitrosobenzene in dry CS2 produce variable amounts of pbromonitrosobenzene in yields of up to 40%.47 Nitrations and chlorinations also were found to result in para substitution.47 The ipso-13C NMR shift of nitrosobenzene is 165.89 ppm, a value greater than that of any of the 26 substituents listed in Table S1 in the Supporting Information. This indicates a stronger electron-withdrawing inductive effect than for fluorine (163.13 ppm) or −NO2 (148.30 ppm) and indicates a greater deactivating effect than for any of the other substituents treated. The p-13C NMR shift of 135.57 ppm is larger than any of the values for meta-directing substituents in Table 1. The σp Hammett constant of −NO is 0.91,48 which is greater than the value of 0.79 for the strongly electron-withdrawing −NO2. By the criteria established in the present work, the −NO group should be strongly electron-withdrawing and meta-directing, in disagreement with the above experimental results. What was found subsequent to Ingold’s work is that nitrosobenzene can dimerize and that there is an equilibrium between the monomer and dimer in many solvents. The solid is in the cis dimer form.49 The experiments of Ingold were repeated and the results confirmed by Hammick and Illingworth in CS2 and in CCl4 solutions.50 p-Bromonitrosobenzene was obtained rapidly even at −5 °C. However, measurements of colligative properties of nitrosobenzene, including the boiling point elevation in CS2 solvent (bp 46.3 °C), resulted in a molecular weight of 116.4, not the expected 107.1, indicating a reported 16% dimerization.50 In acetic acid solution, the bp elevation gave a correct molecular weight of 107.50 A search for complexes between nitrosobenzene and acetic acid or for salt formation found neither, thus confirming that nitrosobenzene is in the monomeric form in this solvent. Bromination of nitrosobenzene in acetic acid solution gave no ortho or para G

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products and bromine was still present after 4 h. No mbromonitrosobenzene was formed either. Very high temperatures to effect meta substitution were not feasible because of the fragility of the nitrosobenzene molecule.50 These results confirm the prediction from 13C NMR shifts that the NO group is not ortho/para-directing and that it is so strongly deactivating that no meta substitution occurs. It is the dimer that undergoes para substitution, not the monomer. The 15N NMR shifts (relative to nitromethane) of the monomer (518.7 ppm) and the dimer (−77.1 ppm) show a surprisingly large difference of 595.8 ppm.51 The nitrogen of the monomer is considerably more deshielded, clearly indicating quite different electronic structures in the two. In chloroform solution at 20 °C, about 11% of nitrosobenzene is in the dimer form,51 which would react rapidly to form the para-substituted product. One way of rationalizing reactivities and such experimental results is by writing various Lewis resonance structures. Scheme 2 is one

benzene (125.48 vs 128.36 ppm, respectively), confirming the ortho/para-directing effect. Thioanisole is similar to thiophenol, with a p-13C NMR shift of 124.92 ppm. The −SCH3 group should be ortho/para-directing and more activating than SH. Both predictions are consistent with experimental determinations.54 For a benzene derivative that may not have been studied, comparison of its p-13C NMR shift to that of benzene (128.36 ppm) should be a reliable predictor of meta or ortho/para orientation in substitutions, as demonstrated in Table 1. The 13 C NMR shifts in this paragraph are from ref 46. For phenyl isocyanide, C6H5NC, the p-13C shift is 129.4 ppm, so −NC should be weakly meta-directing. For phenyl acetate, the p-13C shift is 126.4 ppm, so the −OC(O)CH3 group should be weakly ortho/para-directing. For phenylhydrazine, the p-13C shift is 119.9 ppm, so −HNNH2 should be ortho/paradirecting. For benzamide, the p-13C shift is 131.9 ppm, so −C(O)NH2 should be meta-directing. For N,N-dimethylbenzamide, the p-13C shift is 129.5 ppm, so −C(O)N(CH3)2 should be meta-directing, but less strongly than −C(O)NH2, as would be expected. For isocyanatobenzene, C6H5NCO, the p-13C shift is 125.9 ppm, so the −NCO group should be ortho/ para-directing. For phenyl thiocyanate, the p-13C shift is 127.1 ppm, so the −SCN group should be ortho/para-directing, and there is one report that nitration yields ortho/para products.55 For triphenylboron, the p-13C shift is 131.5 ppm, so the −B(C6H5)2 group should be predominantly meta-directing. For triphenylphosphine, the p-13C shift is 129.3 ppm, so −P(C6H5)2 should be weakly meta-directing. Small p-13C shift variances from benzene are predicted to result in significant amounts of product from the nonpredominant orientation. For benzene substituent X = −CH2OCH3, the p-13C shift is 128.0 ppm (nitration products contain 12% meta isomer56); for X = −CH2F, the p-13C shift is 128.7 ppm (nitration products contain 18% meta isomer56); for X = −SiMe3, the p-13C shift is 128.8 ppm (nitration products contain 40% meta isomer56); and for X = −CCl3, the p-13C shift is 130.2 ppm (nitration products contain only 64% meta isomer3). The same type of regioselectivity should be true for X = −AsPh2 (129.0), −SbPh2 (129.2), −GeMe3 (128.3), and −SnMe3 (128.3). Under some reaction conditions, organometallics (e.g., X = −SnMe3 and −SiMe3) give ipso substitutions.52 Desulfonations of aromatic rings can also proceed by electrophilic attack at the ipso position depending on the reaction conditions.57 Dealkylations of aromatic rings can also be catalyzed by AlCl3.40 This work has focused on enthalpies of hydrogenation and 13 C NMR shifts, which are experimentally observable quantities, and their relationships with experimental reactivities and orientations of substitution. The thermodynamic effects (ordering of ΔHhyd) appear to relate well with the kinetic effects obtained by relative reactivity measurements.29 Various features of electrophilic aromatic substitutions have been studied by a large variety of theoretical calculations, which span the entire period from the early days of reliable quantummechanical calculations for reasonably large molecules58 to the presenttoo many to cite all. The accuracy with which theoretical results match experimentally established facts has improved greatly over time, as demonstrated in three relatively recent articles that report new pertinent correlations, provide some short reviews of previous theoretical results, and are sources of leading references.59−61

Scheme 2. Resonance Structures of Nitrosobenzene and Its Dimer

such way. In Scheme 2, the middle structure for the nitrosobenzene monomer places a positive charge on the nitrogen (formal charge +1), which is consistent with the strong deshielding observed by 15N NMR.51 The ipso-C−X dipole has the negative end on the ipso carbon and this turns ON meta substitution (see the Abstract graphic). The double bond of the nitroso group of nitrosobenzene often reacts in the same way as the polar double bond of carbonyl groups: −SR nucleophiles add to the nitrogen; carbon nucleophiles (−CHR1R2) and Grignard reagents also add to the nitrogen; and the kinetics of reactions of weakly basic amines with nitrosobenzene are very similar to those of reaction with benzaldehyde.52 All of these observations indicate a partial positive charge on nitrogen. The structure on the right in Scheme 2 places a partial positive charge on the ortho carbon (and its allylic para carbon), and this also would direct any substitution to the meta position. The nitrosobenzene dimer is sometimes depicted by the structure on the left in Scheme 2.50,51 However, such a structure places destabilizing full positive charges on adjacent atoms and would also result in deactivation of both rings and meta substitution for the dimer, which do not occur. A more likely resonance structure is the one on the right, where there is no destabilization by adjacent positive charges. Ring A would be deactivated but ring B would be activated, leading to the observed fast para substitution. The equilibrium between the dimer and monomer would then form some monomeric parasubstituted nitrosobenzene, as found by Ingold.47 There is a dearth of information about electrophilic aromatic substitutions of thiophenol. Reactions with electrophiles often occur at the sulfur, but some alkylations have been reported to also yield some ortho- and para-alkylated thiophenols,53 consistent with a report that −SH is an activating group.54 The p-13C NMR shift of thiophenol is smaller than that of H

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(4) Smith, M. B.; March, J. March’s Advanced Organic Chemistry, 5th ed.; Wiley: New York, 2001; pp 675−714. (5) Wheland, G. W. A Quantum Mechanical Investigation of the Orientation of Substituents in Aromatic Molecules. J. Am. Chem. Soc. 1942, 64, 900−908. (6) Carey, F. A.; Giuliano, R. M. Organic Chemistry, 8th ed.; McGrawHill: New York, 2011; pp 478−512. (7) Vollhardt, P.; Schore, N. Organic Chemistry: Structure and Function, 6th ed.; W. H. Freeman: New York, 1999; pp 731−754. (8) Wade, L. G. Organic Chemistry, 8th ed.; Pearson: Glenview, IL, 2013; pp 756−774. (9) Brown, W. H.; Foote, C. S.; Iverson, B. L.; Anslyn, E. V. Organic Chemistry, 6th ed.; Brooks/Cole: Belmont, CA, 2012; pp 906−923. (10) Solomons, T. W. G.; Fryhle, C. B.; Snyder, S. A. Organic Chemistry, 11th ed.; Wiley: New York, 2014; pp 670−699. (11) Roberts, J. D.; Sanford, J. K.; Sixma, F. L. J.; Cerfontain, H.; Zagt, R. Orientation in Aromatic Nitration Reactions. J. Am. Chem. Soc. 1954, 76, 4525−4534. (12) Brown, H. C.; Okamoto, Y. Substituent Constants for Aromatic Substitution. J. Am. Chem. Soc. 1957, 79, 1913−1917. (13) Brown, H. C.; Okamoto, Y. Electrophilic Substituent Constants. J. Am. Chem. Soc. 1958, 80, 4979−4987. (14) Afeefy, H. Y.; Liebman, J. F.; Stein, S. E. Neutral Thermochemical Data. In NIST Chemistry WebBook; Linstrom, P. J., Mallard, W. G., Eds.; NIST Standard Reference Database Number 69; National Institute of Standards and Technology: Gaithersburg, MD; http://webbook.nist.gov. Vibrational frequency data were compiled by T. Shimanouchi. ΔfH°[R+] values were obtained as ΔfH°[R·] + IE[R·]. (15) Verevkin, S. P. Thermochim. Acta 1997, 307, 17−25. ΔfH° was obtained from the enthalpy of combustion of the liquid and its enthalpy of vaporization. (16) Kistiakowsky, G. B.; Ruhoff, J. R.; Smith, H. A.; Vaughan, W. E. Heats of Organic Reactions. IV. Hydrogenation of Some Dienes and of Benzene. J. Am. Chem. Soc. 1936, 58, 146−153. The value of ΔHhyd of benzene from the NIST database obtainable by eq 1 is −49.69 ± 0.21 kcal mol−1. (17) Bird, M. L.; Ingold, C. K. Influences of Directing Groups on Nuclear Reactivity in Oriented Substitutions. Part IV. Nitration of the Halobenzenes. J. Chem. Soc. 1938, 918−929. (18) Stock, L. M.; Brown, H. C. An Examination of the Applicability of the Selectivity Relationship in the Electrophilic Substitution Reactions of the Halobenzenes. J. Am. Chem. Soc. 1962, 84, 1668− 1673. (19) Zavitsas, A. A.; Rogers, D. W.; Matsunaga, N. Heats of Formation of Organic Compounds by a Simple Calculation. J. Org. Chem. 2010, 75, 6502−6515. (20) Notario, R.; Roux, M. V.; Liebman, J. F. What is the Enthalpy of Formation of Acrylonitrile? Struct. Chem. 2010, 21, 481−484. (21) Bose, A. N.; Benson, S. W. Kinetics of Addition of HI to Isobutene and Vinyl Chloride. J. Chem. Phys. 1963, 38, 878−881. (22) Benson, S. W.; Bose, A. N. Structural Aspects of the Kinetics of Four-Center Reactions in the Vapor Phase. J. Chem. Phys. 1963, 39, 3463−3473. (23) Nelson, D. J.; Cooper, P. J.; Soundararajan, R. Simplified Method of Ascertaining Steric Effects in Electrophilic Addition Reactions. A Comparison of Bromination, Oxymercuration, and Hydroboration. J. Am. Chem. Soc. 1989, 111, 1414−1418. (24) Freeman, F. Possible Criteria for Distinguishing between Cyclic and Acyclic Activated Complexes and Among Cyclic Activated Complexes in Addition Reactions. Chem. Rev. 1975, 75, 439−490. (25) Suresh, C. H.; Koga, N.; Gadre, S. R. Revisiting Markovnikov Addition to Alkenes via Molecular Electrostatic Potential. J. Org. Chem. 2001, 66, 6883−6890. (26) Olah, G. A.; Kobayashi, S.; Tashiro, M. Aromatic Substitution. XXX. Friedel−Crafts Benzylation of Benzene and Toluene with Benzyl and Substituted Benzyl Halides. J. Am. Chem. Soc. 1972, 94, 7448− 7461.

CONCLUSIONS The ordering of reactivities of various monosubstituted benzenes, C6H5X, in electrophilic aromatic substitutions is controlled by the stability of their aromatic rings, as measured by their enthalpies of hydrogenation to give the corresponding X-substituted cyclohexanes. The more stable (electron-rich) the ring, the more reactive it is because of its ability to stabilize the carbocation intermediate formed. The orientation of the substitution in all cases is controlled by the direction of the ipso-C−X bond dipole of C6H5−X, much like an ON/OFF switch. The switch is ON for predominant meta substitution when the negative end of the dipole is on the ipso carbon. It is OFF otherwise, leading to predominant ortho/para substitution. p-13C NMR shifts greater than that of benzene (128.36 ppm) also correctly predict predominant meta orientation of substitutions. These controlling effects in electrophilic aromatic substitutions are functions of properties of the C6H5X substrate for the many X substituents treated. In chlorinations, nitrations, brominations, and protonations of the halobenzenes, the ratio of ortho to para products is linearly related to the ratio of the 13 C NMR shifts of the ipso and ortho carbons of each halobenzene. The group electronegativities of substituents X are linearly related to the ipso carbon 13C NMR chemical shifts of several simple typical substituents.

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ASSOCIATED CONTENT

S Supporting Information *

Table of 13C NMR chemical shifts of all ring positions of the monosubstituted benzenes mentioned. Brominations of alkenes: data and plot of ln(k/k0) vs ΔHhyd. Chlorinations of alkenes: data and plot of ln(k/k0) vs ΔHhyd. Additions of H+ and of H3C+ to alkenes: plots of ΔHrxn vs ΔHhyd. Nitrations, chlorinations, and brominations of halobenzenes: data and plots of ortho/para product ratios vs ortho/para ratios of 13C NMR shifts of the halobenzenes. Chlorinations of halobenzenes: data and plot of ortho/para product ratios vs ipso/ortho 13 C NMR shifts of the halobenzenes. Protonations of halobenzenes: data and plot of ortho/para ratios of products vs ipso/ortho ratios of 13C NMR shifts of the halobenzenes. Nitrations, chlorinations, brominations, and benzylations of halobenzenes: plots of kPhX/kPhH vs p-13C NMR shifts of the halobenzenes. This material is available free of charge via the Internet at http://pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Notes

The authors declare no competing financial interest.

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REFERENCES

(1) Esteves, P. M.; Carneiro, J. W. de M.; Cardoso, S. P.; Barbosa, A. G. J.; Laali, K. K.; Rasul, G.; Prakash, G. K. S.; Olah, G. A. Unified Mechanistic Concept of Electrophilic Aromatic Nitration: Convergence of Computational Results and Experimental Data. J. Am. Chem. Soc. 2003, 125, 4836−4849. (2) Gwaltney, S. R.; Rosokha, S. V.; Head-Gordon, M.; Kochi, J. K. Charge Transfer Mechanism for Electrophilic Aromatic Nitration and Nitrosation via the Convergence of (ab initio) Molecular-Orbital and Marcus−Hush Theories with Experiments. J. Am. Chem. Soc. 2003, 125, 3273−3283. (3) Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry, 5th ed.; Springer: New York, 2007; Part A, Chapter 9. I

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dx.doi.org/10.1021/jp409623j | J. Phys. Chem. A XXXX, XXX, XXX−XXX