Proc. Natl. Acad. Sci. USA Vol. 74, No. 10, pp. 4121-4125, October 1977 Electrophilic mercuration and thallation of and substituted in trifluoroacetic acid solution* (electrophilic substitution/selectivity) GEORGE A. OLAH, IWAO HASHIMOTOt, AND HENRY C. LINtt Institute of Chemistry, Department of Chemistry, University of Southern California, Los Angeles, California 90007; and the Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44101 Contributed by George A. Olah, July 18, 1977

ABSTRACT The mercuration and thallation of benzene and iments at 250 and quenched the mixtures after 5 min, whereas substituted benzenes was studied with mercuric and thallic Brown and Nelson carried out the reaction for 6.5 hr. In sub- trifluoroacetate, respectively, in trifluoroacetic acid. With the in view of the importance of both the mechanistic shortest reaction time (1 sec) at 00, the relative rate of mercu- sequent work, ration of compared to that of benzene was 17.5, with and practical implications of the orientation-rate correlation, the isomer distribution in toluene of: ortho, 17.4%; meta, 5.9%; Brown and McGary (7), carried out a more detailed study of and para, 76.7%. The isomer distribution in toluene varied with the mercuration reaction. They concluded: "A redetermination the reaction time, significantly more at 25° than at 00. The of the isomer distributions and relative rates indicates excellent competitive thallation of benzene and toluene with thallic tri- agreement with the linear relationship of orientation and rel- fluoroacetate in trifluoroacetic acid at 150 showed the relative ative however, that the isomer distri- rate, toluene/benzene, to be 33, with the isomer distribution in rate." They recognized, toluene of: ortho, 9.5%; meta, 5.5%; and para, 85.0%. With butions change with time but still claimed that the corrected increasingly higher reaction temperatures in both mercuration meta isomer distribution in the mercuration of toluene is 9.5 and thallation reactions of aromatics, (both in- + 0.5% and remarked, "there remains a relatively minor dis- tramolecular and intermolecular) within the relevant ortho- and agreement with the values reported by Klapproth and West- para-metallated intermediate ions and/or of the isomers be- heimer (6% meta) for which we are unable to account." comes more important. Competitive rates and isomer distri- In we have that, regardless of butions of mercuration and thallation of benzene and substi- preceding work (8) suggested tuted benzenes were also determined. The predominant para the substrate selectivity in electrophilic aromatic substitutions substitution in both mercuration and thallation of methylben- (which generally can be most conveniently expressed by kT/kB zenes reflects, besides some steric factors, the strong stabilizing rate ratios), the regioselectivity (positional) of the reactions effect of para methyl groups on the arenium ion intermediates. remains high, with usually predominant ortho-para substitu- Under predominantly kinetically controlled conditions, no tion, the amount of meta isomer being 2-5%. anomalous increase in the amount of meta substitution was We considered it possible that the reported relatively high observed. meta isomer ratio observed in preceding studies of mercuration The mercuration of aromatic with mercuric of toluene (as well as related alkylbenzenes) was still the result trifluoroacetate in trifluoroacetic acid at 250 has been studied, of ongoing faster isomerization and/or disproportionation of predominantly by Brown and coworkers (1-3). The rate ratio the ortho and para isomers, compared to the more stable meta of toluene to benzene (kT/kB) was found to be 9.89 and the isomer (7) or related rearrangements in the a-complex inter- isomer distribution in toluene was: ortho, 12.2%; meta, 8.6%; mediates of the reactions. These would fully explain the dis- and para, 79.2%. From these results, as well as from their pre- agreements with Klapproth and Westheimer's work. Conse- ceding studies in solution with perchloric acid cat- quently, it appeared desirable to reinvestigate in detail the alyst giving kT/kB = 3.6-7, and 12-16% meta isomer, it was mercuration of benzene and substituted benzenes under pre- concluded that the relatively high meta isomer ratio observed dominantly kinetically controlled conditions, minimizing the was due to the high electrophilic reactivity of the mercurating possibility of isomerization and disproportionation affecting agent causing the observed low selectivity substitutions. These the results. results were correlated by the so-called Brown selectivity re- The thallation of benzene and substituted benzenes with lationship (for a review, see ref. 4). thallium trifluoroacetate in trifluoroacetic acid, the mechanism It should be pointed out that, in their original paper on of which was considered to be similar to that of related mer- mercuration of toluene and benzene, Brown and Nelson, (5) curations (9-11), was also studied under similar conditions. extending the claimed quantitative selectivity relationship MATERIALS AND METHODS governing isomer distributions in aromatic substitution, com- mented on the preceding work of Klapproth and Westheimer Materials. Benzene, toluene, and alkylbenzenes were of (6) who found that, in glacial acetic acid with perchloric acid highest available purity. Trifluoroacetic acid (Cationics, Inc.) as catalyst, toluene was mercurated by mercuric acetate at 250 was obtained in sufficient purity to be used without further to give 6% of the meta isomer. Brown and Nelson claimed to purification (boiling point 730). Mercuric and thallium triflu- have observed 12% meta isomer under similar conditions and oroacetate were commercial materials (Aldrich Chemical Co., stated "we are, however, unable to account for the differences Inc.). between the values of the meta isomer." In the former case (6), a precise radiochemical technique was used in establishing Abbreviation: kT/kB, ratio of reaction rates for toluene and ben- orientation, whereas infrared analysis was utilized in the latter. zene. * Paper no. 40 in the series "Aromatic Substitution." Paper no. 39 was Comparison of the experimental sections of Brown and Nelson's Olah, G. A., Pelizza, F. Kobayashi, S. & Olah, J. A. (1976) J. Am. and Klapproth and Westheimer's papers, however, indicates Chem. Soc. 98,296. that the claim of reinvestigation "under similar conditions" is t Visiting Scientist from the Wakayama Technical College, Japan. incorrect. Klapproth and Westheimer carried out their exper- * Senior Research Associate (1974-1975). 4121 Downloaded by guest on September 24, 2021 4122 Chemistry: Olah et al. Proc. Natl. Acad. Sci. USA 74 (1977)

r - - -- 1 Table 1. Gas/liquid chromatographic parameters Conditionst of retention Bromo compound Column* Column Time, min E ~G Bromobenzene D I 5.9 Quench o-Bromotoluene D I 10.0 m-Bromotoluene D I 11.0 p -Bromotoluene D I 12.3 FIG. 1. Flow-quenching apparatus for the mercuration of o-Bromoethylbenzene D I 10.3 polymethylbenzenes. Two 50-ml syringes (A and B) are driven by a m-Bromoethylbenzene D I 12.0 syringe pump (C; Sage Instruments, model 351). The separate solu- p-Bromoethylbenzene D I 14.2 tions came together via two flexible Teflon tubes (D and E, inside o-Bromoisovronvlbenzene D I 11.7 diameter 1.4 mm; length, 60 cm), mix at F, react during passage G, and D I 13.8 are quenched at the end of G. p-Bromoisopropylbenzene D I 18.3 o-Bromo-tert- butylbenzene D I 16.2 Competitive Mercuration of Benzene and Substituted m-Bromo-tert- butylbenzene D I 19.3 Benzenes. Mercuric trifluoroacetate (25 ml of 0.2 M solution p-Bromo-tert-butylbenzene D I 22.3 in trifluoroacetic acid) was added rapidly to 25 ml of 1 M so- 4-Bromo-o- C I 2.9 lutions of the aromatics in the same solvent with vigorous stir- 4-Bromo-m-xylene C I 2.7 ring, both precooled and kept at 00. After specific time inter- 2-Bromo-p-xylene C I 3.0 vals, the reaction mixture was quenched with aqueous sodium Bromoesitylene C III 3.2 bromide, maintaining a bromide ion to mercuric ion ratio of 4-Bromo-1,2,3-trimethylben- 3:1. The precipitated arylmercuric bromides were filtered and zene C I 5.1 thoroughly dried under reduced pressure. Then, the mixture 5-Bromo-1,2,4-trimethyl- of arylmercuric bromides was slowly treated with bromine in benzene C I 4.8 chloroform at 00 until a permanent red color developed. Stir- 5-Bromo-1,2,3,4-tetramethyl- ring was continued for 5 hr at 0° and then for an additional hour benzene C II 4.5 at room temperature. Conversion of arylmercuric bromides to 4-Bromo-1,2,3,5-tetramethyl- the corresponding bromoarenes under these conditions was benzene C II 4.5 found to be quantitative for all practical purposes (the slower Bromodurene C III 6.6 conversion of the parent phenylmercuric bromide without Bromopentamethylbenzene C III 17.8 to is not o-Bromofluorobenzene B IV 12.2 raising the temperature ambient always quantitative). m-Bromofluorobenzene B IV 9.8 The reaction mixture was washed with sodium bisulfite solution p-Bromofluorobenzene B IV 10.5 and water and then dried over sodium sulfate. Bromoarenes o-Bromochlorobenzene B V 15.1 were subsequently analyzed by gas/liquid . m-Bromochlorobenzene B V 13.0 Competitive Mercuration of Polymethylbenzenes. The p-Bromochlorobenzene B V 13.2 rates of mercuration of polymethylbenzenes are so fast that it o-Dibromobenzene B V 25.8 is difficult to carry out the reactions by the usual methods. m-Dibromobenzene B V 21.9 Therefore, a modified flow-quench apparatus (12) was used p-Dibromobenzene B V 22.2 to allow short reaction times (of the order of 1 sec) (Fig. 1). o-Bromoanisole A VI 10.9 Quenching was with aqueous sodium bromide surrounded by m-Bromoanisole A VI 9.6 ice. The quenched products were worked up, brominated with p-Bromoanisole A VI 10.1 bromine in chloroform, and then analyzed by gas/liquid * A, stainless steel open tubular column, 150 ft X 0.01 inch, wall coated chromatography. with butanediol succinate; B, stainless steel open tubular col- Competitive Thallation of Benzene and Substituted umn, 150 ft X 0.01 inch, wall coated with m-bis(m-phenoxyphen- Benzenes. The thallations were carried out with exclusion of oxy)benzene modified with 20% Apiezon L grease; C, stainless steel in a manner similar to that for packed column, 12 ft X 1/8 inch, with solid support 80-100-mesh light, the mercurations. The Chromosorb W and liquid phase 1.75% butanediol succinate; D, reaction mixture was quenched in aqueous sodium chloride, stainless steel packed column, 12 ft X 1/8 inch, with solid support and the solution was evaporated under reduced pressure until 80-100-mesh Chromosorb W and liquid phase 15.0% 4,4'-di- a white solid remained. The bromination of arylthallium methoxyazoxybenzene. chlorides was performed with bromine in carbon tetrachloride t Column conditions [column temperature, °C (carrier gas, , according to the procedure described by Wright (13). Product pressure (psi) or flow rate (ml/min)]: I, 130 (20 ml/min); II, 140° (20 bromoarenes were analyzed by gas/liquid chromatography as ml/min); III, 145° (20 ml/min); IV, 950 (20 psi); V, 1300 (20 psi); VI, in the case of mercuration. 1500 (20 psi). Analytical Procedure. All products were analyzed by gas/ The apparent decrease of kT/kB with time is accompanied liquid chromatography, with a Perkin-Elmer model 900 gas by an increase in the amount of the ortho and meta isomers at chromatograph equipped with a flame ionization the corresponding expense of the para isomer. The possible detector and either open tubular capillary columns or a packed isomerization (transmercuration) in the involved reaction in- column. Peak areas were calculated with the Infortronics model termediates, although not necessarily of the arylmercury tri- CRS-100 electronic printing integrator. fluoroacetate products, was not fully recognized previously Characteristic retention times of bromo compounds along when limited product isomerization was only considered. We with type of column and conditions are listed in Table 1. Au- are forced to conclude that the higher proportions of the meta thentic samples of pure substituted bromobenzene isomers were (and ortho) isomer reported previously may be a result of the available in our laboratory from previous work. A 12-ft 4,4'- isomerization (disproportionation) of the kinetically favored azoxyanisole-packed column was utilized at 1300 to achieve initially formed para and ortho arenium ions, compared with complete separation of bromotoluene isomers (14). the thermodynamically more stable meta substituted ions. Downloaded by guest on September 24, 2021 Chemistry: Olah et al. Proc. Nati. Acad. Sci. USA 74 (1977) 4123 Table 2. Variation of kT/kB for mercuration of benzene and Table 3. Competitive mercuration of monosubstituted benzenes toluene and of isomer distribution in toluene with reaction with mercuric trifluoroacetate in trifluoroacetic acid at 00 time at room temperature (22°)* with 2-sec reaction time* Time, Isomer distribution, % Isomer distribution, % min kT/kB Ortho Meta Para ArH kArH/kB Ortho Meta Para 0.15 sec 15 21.3 6.9 71.8 Benzene 1 0.91 sec 15 23.7 7.6 68.7 Toluene 18 20.6 6.4 73.0 1 14 23.3 7.9 68.8 Ethylbenzene 15 2.3 3.5 94.2 2 13 26.6 8.7 64.7 Isopropylbenzene 14 0.6 5.4 93.9 3 11 30.0 9.1 60.9 tert-Butylbenzene 10 0 8.4 91.6 6 10 30.2 9.7 60.1 Fluorobenzene 0.24 27.6 0.2 72.2 15 10 32.5 10.1 57.4 Chlorobenzene 0.03 27.3 0.1 72.6 160 8 37.4 12.6 50.0 Bromobenzene 0.2 18.7 1.7 79.6 Anisole 860 18.8 0.2 81.1 * Concentrations: total [ArH], 1.00 M; [Hg(OCOCF3)2], 0.10 M. * Concentrations: total [ArH], 1.0 M; [Hg(OCOCF3)2], 0.1 M. RESULTS AND DISCUSSION served at 220 (kT/kB = 18; 17.4% ortho, 5.9% meta, and 76.7% Mercuration. We first restudied the competitive mercuration para). There was no significant variation of kT/kB and only a of toluene and benzene with mercuric trifluoroacetate in tri- small variation of the isomer distribution (particularly of the fluoroacetic acid at ambient room temperature (220). [The rates ortho/para ratio) with reaction times of up to 60 min, when of mercuration of monoalkyl- and polymethylbenzenes with kT/kB = 18 with an isomer distribution of 25.6% ortho, 7.7% mercuric acetate in acetic acid have been determined (15).] The meta, and 67.2% para. products were precipitated as aryl mercuric bromides, filtered Consequently, in further studies the mercuration of mono- off, and then convertedby bromination into bromobenzene and substituted benzenes with mercuric trifluoroacetate in triflu- the corresponding bromotoluenes, which were analyzed by oroacetic acid was carried out at 00 in order to minimize the gas/liquid chromatography. possible effect of isomerization (disproportionation) on the Hg(OCOCF) isomer distributions and kT/kB, and the competitive experi- ments were performed with the shortest feasible reaction times (2 sec). The data obtained are summarized in Table 3. + Hg(OCOCF3)2 riiiaq.NaBr In the mercuration of monoalkylbenzenes, a decreasing order of the relative reactivities (Me > Et > i-Pr > t-Bu) was ob- HgBr Br served, accompanied by an increase of meta substitution and a decrease of ortho/para isomer ratio. Br, The mercuration of polymethylbenzenes was also studied by the competitive method with reaction times of 2 sec at 00. min CHC1. The data were compared with the relative stabilities of Because the mercuration of benzene and alkylbenzene in the corresponding ir- and a-complexes in order to show a trifluoroacetic acid is fast, it was considered necessary to use comparable trend indicative of the rate-determining step (16). a flow-quenching apparatus (12) to allow proper mixing of the The relative mercuration rates and corresponding ir- and reagents before reaction. a-basicities of benzene and methylbenzenes are shown in Table The relative rates and isomer distributions in the competitive 4. mercuration of toluene and benzene at 220, summarized in The rate of mercuration of polymethylbenzene was so fast Table 2, show the variation of the data with reaction time, as that competitive mercuration of polymethylbenzenes and well as the difficulties one can encounter due to the lack of ki- benzene could not be directly evaluated. Therefore, the com- netic control when intermolecular and/or intramolecular petitive mercurations of 1,2-, 1,3-, and 1,4-dimethylbenzenes affect the data. were measured against toluene, those of 1,2,3-, 1,2,4-, and CH3 1,3,5-trimethylbenzenes against 1,3-dimethylbenzene, and CH3 CH3 those of 1,2,3,4-, 1,2,3,5-, and 1,2,4,5-tetramethylbenzenes and pentamethylbenzenes against 1,3,5-trimethylbenzene. From __ ~~~~~~~~Hetc. these data and the kT/kB value, the relative reactivity of each polymethylbenzene with respect to that of benzene was ob- HAHgOCCF3 X+ HgOCCF, tained. It is significant to note the low reactivity of 1,4-di- HgOCCF3 methylbenzene and particularly of 1,2,4,5-tetramethylbenzene. 0 An unsubstituted ring position para to a seems 0~~~~ to be necessary in order to achieve high substrate reactivity. The ready mercury shifts in arenemercurenium ions was The correlation coefficient between the logarithms of the previously demonstrated in our studies under stable long-lived relative mercuration rates and the logarithms of the corre- ion conditions. sponding ir- and c-basicities of methylbenzenes is 0.82 for Because of the changing isomer distributions encountered ir-complexes and 0.89 for a-complexes. in the mercuration of benzene or toluene at 220, we next studied In an attempt at more quantitative treatment of the results the reaction at 0° (the lowest practical temperature attainable) on monosubstituted benzenes, both the Hammett-Brown c++p to slow down the isomerization processes. linear relationship and the improved multiparameter Yu- The amount of meta isomer in the mercuration of toluene kawa-Tsuno relationship (17), taking into consideration both was 5.9% with the shortest reaction time (1 sec) studied at 00, conjugative and inductive effects of , were used. compared to the lowest proportion of meta isomer, 6.9% ob- The Hammett-Brown treatment gave a p value of -6.31 and Downloaded by guest on September 24, 2021 4124 Chemistry: Olah et al. Proc. Natl. Acad. Sci. USA 74 (1977)

Table 4. Relative rates of mercuration of benzene and Table 5. Variation of relative rate and isomer distribution with polymethylbenzenes at 00 with reaction time of 2 sec and temperature in thallation of benzene and toluene comparison with r and a basicities* in trifluoroacetic acid* Relative Relative Relative 7r-complext a-complex$ Temp., Time, Isomer distribution, % mercuration stability stability °C min kT/kB Ortho Meta Para ArH rates* with HCl with HF-BF3 10 2 34 8.8 5.1 86.1 Benzene 1 1.0 1 15 3 35 9.5 5.5 85.0 Toluene 18 1.5 7.9 X 102 15 60 34 9.0 5.7 85.6 1,2-Dimethylbenzene 335 1.8 7.9 X 103 33 9.1 5.9 85.0 1,3-Dimethylbenzene 362 2,0 106 25 3 33 9.7 5.8 84.6 1,4-Dimethylbenzene 41 1.6 3.2 X 103 25 60 28 9.3 6.2 84.6 1,2,3-Trimethylben- 50 3 21 10.6 7.5 81.9 zene 2 X 104 2.4 2 X 106 50 60 19 12.6 7.8 79.7 1,2,4-Trimethylben- 73 30 18 12.2 8.3 79.4 zene 1 X 103 2.2 2 X 106 73 60 14 15.0 10.7 74.3 1,3,5-Trimethylben- 73 180 8 19.6 17.0 63.4 zene 5.7 X 104 2.6 6.3 X 108 73 360 4 25.8 27.2 47.0 1,2,3,4-Tetramethyl- 73 1440 2 28.6 46.1 25.4 benzene 2.3 X 105 2.6 2 X 107 * Concentrations: total [ArH], 1.00 M; [Tl(OCOCF3)3], 0.10 M. 1,2,3,5-Tetramethyl- benzene 1.35 X 105 2.7 2 X 109 the reaction was carried out up to approximately 60% com- 1,2,4,5-Tetramethyl- pletion. There was no significant variation in the isomer dis- benzene 67 2.8 107 tributions observed, and thus there is no evidence for diar- Pentamethylbenzene 4.4 X 105 2 X 109 ylthallium compounds. * Concentrations: total [ArH], 1.0 M; [Hg(OCOCF3)2], 0.1 M. No significant variation of the relative rate and of isomer t Andrews, L. J. & Keefer, R. M. (1964) Molecular Complexes in distributions of thallation with time was observed at 15°. Organic Chemistry (Holden-Day, San Francisco, CA), and refer- Therefore, under the experimental conditions used, isomer- ences quoted therein. of the isomeric reaction Mackor, E. L., Hofstra, A. & van der Waals, J. H. (1958) Trans. ization and disproportionation products ref. 7, p. 241. in the thallation of toluene may be considered insignificant. Faraday Soc. 54, 66, 187, and references given in In order to study further the influence of reaction tempera- a correlation coefficient of 0.95. The Yukawa-Tsuno treatment ture on the isomer distribution, the competitive thallation of gave an n-value of 0.69, p = -5.82, and a correlation coefficient toluene and benzene was also carried out at higher tempera- of 0.98. These results suggest that the transition state of highest tures. The relative rates and isomer distributions are summa- in mercuration of methylbenzenes is predominantly of rized in Table 5. a-complex nature. It also should be noted that a large primary At higher reaction temperatures, specifically at 730 (the boil- kinetic hydrogen effect was observed in aromatic ing point of trifluoroacetic acid), a marked decrease in kT/kB mercuration (kH/kD = 6.0 + 0.1 at 250) (18). Consequently, was observed and the ortho and meta isomers increased at the proton elimination can at least be partially rate determining expense of the kinetically favored para isomer. These results and a relatively slow process gives rise to a significant isotope mean that aromatic thallation under the more severe reaction effect. Intramolecular rearrangements in a relatively long-lived conditions is an increasingly reversible electrophilic aromatic a-intermediate ion prior to deprotonation are thus quite fea- substitution, accompanied by rapid isomerization and trans- sible. thallation. Thallation. The competitive thallation of benzene and tol- Because no isomerization (transthallation) was apparent in uene with thallium trifluoroacetate was studied in trifluo- the thallation of toluene below 15', the thallation of substituted roacetic acid in a manner similar to the mercurations described benzenes was also carried out at 100 with reaction times of 2 above. Thallated aromatics were isolated by precipitation with min. The relative reactivities and the isomer distributions are aqueous sodium chloride, brominated in carbon tetrachloride summarized in Table 6. to form the corresponding bromoarenes, and then analyzed as The results in Table 5 show that the relative reactivities of such by gas/liquid chromatography. the thallation of halobenzenes are in the order F > Cl > Br, Tl(OCOCF3)2 TlCl2 Br Br, (~ + Tl(OCOCF3X3 [ aq. NaCIG in aq. KBr + CC14 In order to establish whether the studied thallations indeed accompanied by a decrease of the ortho substitution in the involved real competition of the substrates, variation of the above order. The thallation of monoalkylbenzenes under the concentration of toluene and benzene in the competitive thal- same experimental conditions gave the order of reactivities: Me lation experiments was carried out at 150. Varying the tolu- < Et < i-Pr < t-Bu. This order is the reverse of that of the ene/benzene concentration ratio from 1:1 to 1:8 caused no mercuration of the same monoalkylbenzenes. However, the apparent change in the kT/kB ratio, 35. The isomer distribution ortho isomer obtained in the thallation of ethylbenzene was only also remained constant (9% ortho, 5% meta, and 86% para). 0.6% and in the cases of isopropylbenzene and tert-butylben- To determine whether diarylthallium complex formation zene, no ortho isomer was formed. These results indicate that (9) had any influence on the data, the molar ratio of toluene to the thallation reaction evidently has larger steric requirements thallium trifluoroacetate was also varied from 1:1 to 10:1 and and also seems to be in accord with Arnett and Abboud's (19) Downloaded by guest on September 24, 2021 Chemistry: Olah et al. Proc. Nati. Acad. Sci. USA 74 (1977) 4125 Table 6. Competitive thallation of monosubstituted benzenes Table 7. Relative rates of thallation of benzene and with thallium trifluoroacetate in trifluoroacetic acid at 100 polymethylbenzenes at 100 with 2-min reaction time* with 2-min reaction time* ArH kApjkB Isomer distribution, % Benzene 1 Ar kAr/kB Ortho Meta Para Toluene 34 1,2-Dimethylbenzene 145 Benzene 1 1,3-Dimethylbenzene 1500 Toluene 34 8.8 5.1 86.1 1,4-Dimethylbenzene 33 Ethylbenzene 70 0.6 2.2 97.2 1,2,3-Trimethylbenzene 7200 Isopropylbenzene 90 0 2.1 97.9 1,2,4-Trimethylbenzene 1550 tert-Butylbenzene 200 0 0.5 99.5 1,3,5-Trimethylbenzene 7750 Fluorobenzene 0.14 4.5 0.1 95.3 1,2,3,4-Tetramethylbenzene 6300 Chlorobenzene 0.03 1.8 0.9 97.4 1,2,3,5-Tetramethylbenzene 6350 Bromobenzene 0.02 1.6 1.8 96.7 1,2,4,5-Tetramethylbenzene 2300 Anisole 270 8.0 0.1 91.9 Pentamethylbenzene 7500 Anisole 1900t 14.0 0.6 85.5 * Concentrations: total [ArH], 1.0 M; [Tl(OCOCF3)3], 0.1 M. * Concentrations: total [ArH], 1.0 M; [Tl(OCOCF3)3], 0.1 M. t Reaction temperature, -200. recent conclusion that the Baker-Nathan effect is substantially namically controlled intramolecular or intermolecular processes of steric origin. affecting primarily the ortho/para metallated derivatives and The thallation of polymethylbenzenes with thallium triflu- not to enhanced meta substitution. The discrepancy thus can oroacetate was also carried out in trifluoroacetic acid at 00 with be resolved by pointing out that in the latter case the necessity 2-min reaction time (Table 7). The correlation coefficients to differentiate kinetic from thermodynamically controlled between the logarithms of the relative rates of the thallation of processes, when considering substrate and regioselectivities in polymethylbenzenes and the logarithms of either the 7r- or aromatic substitution, was not fully taken into account. a-basicities of the corresponding polymethylbenzenes are 0.97 Support of our work by the National Science Foundation is gratefully for ir-complexes and 0.95 for a-complexes. The Hammett- acknowledged. Brown y+p equation gave a p value of -6.92 and a correlation coefficient of 0.96, whereas the Yukawa-Tsuno treatment gave 1. Brown, H. C. & Wirkkala, R. A., (1966) J. Am. Chem. Soc. 88, ,y = 0.44 with p = -8.34, and a correlation coefficient of 0.98. 1447-1452. The similar values of both -r- and a-correlation coefficients 2. Brown, H. C., & Wirkkala, R. A. (1966) J. Am. Chem. Soc. 88, in thallations per se would not allow differentiation of the na- 1453-1456. 3. Brown, H. C. & R. A. Am. ture of transition state energy Wirkkala, (1966) J. Chem. Soc. 88, the of highest in the thallation 1456-1458. of polymethylbenzenes. Primary kinetic hydrogen isotope ef- 4. Stock, L. M. & Brown, H. C. (1963) in Advances in Physical fects in the thallation of both heavy benzene and toluene (kH/kD Organic Chemistry, Vol. I, ed. Gold, V. (Academic Press Inc., = 3.7 for benzene and 3.6 for toluene) (20), however, seem to New York), Vol. I, pp 35-154. support the a-complex nature of the transition state of highest 5. Brown, H. C. & Nelson, K. L. (1953) J. Am. Chem. Soc. 75, energy. 6292-6299. Competitive thallation of polymethylbenzenes and benzene 6. Klapproth, W. J. & Westheimer, F. H. (1950) J. Am. Chem. Soc. could not be directly evaluated because the rates of thallations 72,4461-4465. of polymethylbenzenes were too fast compared with that of 7. Brown, H. C. & McGary, C. W., Jr. (1955) J. Am. Chem. Soc. 77, of and 2300-2306. benzene. Therefore, competitive thallation 1,2-, 1,3-, 8. Olah, G. A. (1971) Acc. Chem. Res. 4,240-248. 1,4-dimethylbenzenes with toluene, of 1,2,3-, 1,2,4-, and 9. Henry, P. M. (1970) J. Org. Chem. 35,3083-3086. 1,3,5-trimethylbenzenes with 1,3-dimethylbenzene, and of 10. McKillop, A., Hunt, J. D., Zelesko, M. J., Fowler, J. S., Taylor, E. 1,2,3,4-, 1,2,3,5-, and 1,2,4,5-tetramethylbenzenes and pen- C., McGillivray, G. & Kienzle, F. (1971) J. Am. Chem. Soc. 93, tamethylbenzenes with 1,3,5-trimethylbenzene was deter- 4841-4844. mined. From these results and the kT/kB the relative reactivities 11. McKillop, A., Swann, B. P. & Taylor, E. C. (1970) Tetrahedron of polymethylbenzenes with respect to benzene were estab- Lett., 5281-5284. lished. 12. Olah, G. A. & Lin, H. C. (1974) J. Am. Chem. Soc. 96, 549- The leveling off of the value of the relative reactivities in 553. 13. H. & thallation can be explained the fact that the activation en- Maliyandi, M., Sawatzky, Wright, G. F. (1961) Can. J. by Chem. 1827-1835. ergy of the reactions in must 39, trifluoroacetic acid be relatively 14. Dewar, M. J. S. & Schroeder, J. P. (1964) J. Am. Chem. Soc. 86, lower than that of mercuration or other electrophilic aromatic 5235-5239. substitions of higher selectivity (7). 15. Brown, H. C. & McGary, C. W., Jr. (1955) J. Am. Chem. Soc. 77, The predominant para substitution observed in the mercu- 2310-2312. ration and thallation of methylbenzenes reflects, besides some 16. Condon, F. E. (1952) J. Am. Chem. Soc. 74,2528-2529. steric factors, also the strong stabilizing effect of para-methyl 17. Yukawa, Y., Tsuno, Y. & Sawada, M. (1966) Bull Chem. Soc. Jpn. groups on the arenium ion intermediates. Isomer distributions 39,2274-2286. were somewhat affected by intramolecular rearrangements 18. Kresge, A. J. & Brennan, J. F. (1963) Proc. Chem. Soc. London 215. within the reaction intermediates or by the reversibility of the 19. Arnett, E. M. & Abboud, J. L. M. (1975) J. Am. Chem. Soc. 97, systems, but meta substitution, under predominant kinetic 3864-3865. control, stayed low (i.e., 5-6% or less), in good agreement with 20. Brody, J. M. & Moore, R. A. (1970) Chem. Ind. (London), Klapproth and Westheimer's (6) report of 6% in the mercura- 803. tion of toluene. In contrast, the higher meta values reported by 21. Brown, H. C. & McGary, C. W., Jr. (1955) J. Am. Chem. Soc. 77, Brown and McGary (21) are, in our view, due to thermody- 2300-2306. Downloaded by guest on September 24, 2021