Toluene electrophilic substitution

If acetoxylation were a conventional electrophilic substitution it is hard to understand why it is not more generally observed in nitration in acetic anhydride. The acetoxylating species is supposed to be very much more selective than the nitrating species, and therefore compared with the situation in (say) toluene in which the ratio of acetoxylation to nitration is small, the introduction of activating substituents into the aromatic nucleus should lead to an increase in the importance of acetoxylation relative to nitration. This is, in fact, observed in the limited range of the alkylbenzenes, although the apparently severe steric requirement of the acetoxylation species is a complicating feature. The failure to observe acetoxylation in the reactions of compounds more reactive than 2-xylene has been attributed to the incursion of another mechan-104... 

TABLE 7.1 Partial rate factors for some electrophilic substitutions of toluene... 

The PMBs, when treated with electrophilic reagents, show much higher reaction rates than the five lower molecular weight homologues (benzene, toluene, (9-, m- and -xylene), because the benzene nucleus is highly activated by the attached methyl groups (Table 2). The PMBs have reaction rates for electrophilic substitution ranging from 7.6 times faster (sulfonylation of durene) to ca 607,000 times faster (nuclear chlorination of durene) than benzene. With rare exception, the PMBs react faster than toluene and the three isomeric dimethylbenzenes (xylenes). 

Toluene, an aLkylben2ene, has the chemistry typical of each example of this type of compound. However, the typical aromatic ring or alkene reactions are affected by the presence of the other group as a substituent. Except for hydrogenation and oxidation, the most important reactions involve either electrophilic substitution in the aromatic ring or free-radical substitution on the methyl group. Addition reactions to the double bonds of the ring and disproportionation of two toluene molecules to yield one molecule of benzene and one molecule of xylene also occur. 

Evidently S, is a measure of intramolecular selectivity because it involves a ratio, the contribution of the benzene substitution rate disappears, and the selectivity factor expresses the selectivity of the reagent X in Eq. (7-83) for the para position relative to the meta position. Each individual partial rate factor, on the other hand, is expressive of an inteimolecular selectivity thus p is a measure of the selectivity of the reagent for the para position in CgHsY relative to benzene. It was observed that Eq. (7-85), where Cmc is a constant, is satisfied for a large number of electrophilic substitutions of toluene. 

Equation (7-85) is a selectivity-reactivity relationship, with lower values of Sf denoting lower selectivity. Lower values ofpt correspond to greater reactivity, with the limit being a partial rate factor of unity for an infinitely reactive electrophile. This selectivity-reactivity relationship is followed for the electrophilic substitution reactions of many substituted benzenes, although toluene is the best studied of these. 

Toluene (methylbenzene) is similar to benzene as a mononuclear aromatic, but it is more active due to presence of tbe electron-donating metbyl group. However, toluene is much less useful than benzene because it produces more polysubstituted products. Most of tbe toluene extracted for cbemical use is converted to benzene via dealkylation or disproportionation. Tbe rest is used to produce a limited number of petro-cbemicals. Tbe main reactions related to tbe cbemical use of toluene (other than conversion to benzene) are the oxidation of the methyl substituent and the hydrogenation of the phenyl group. Electrophilic substitution is limited to the nitration of toluene for producing mono-nitrotoluene and dinitrotoluenes. These compounds are important synthetic intermediates. 

Nitration of toluene is the only important reaction that involves the aromatic ring rather than the aliphatic methyl group. The nitration reaction occurs with an electrophilic substitution hy the nitronium ion. The reaction conditions are milder than those for henzene due to the activation of the ring hy the methyl substituent. A mixture of nitrotoluenes results. The two important monosubstituted nitrotoluenes are o- and p-nitrotoluenes ... 

Would you expect (trifluoromethyl)benzene to be more reactive or less reactive than toluene toward electrophilic substitution Explain. 

TABLE 11.3 Relative Rates and Product Distributions in Some Electrophilic Substitutions on Toluene and Benzene... 

The Fricdel-Crafts type polyalkylation of alkyl-substituted benzenes with 3 becomes easier and faster as the number of electron-donating methyl groups on the phenyl group increases. This is consistent with the fact that the alkylation occurs in the fashion of electrophilic substitution. The tendency of starting incthylben-zenes to form reoriented products also increases in the same order from toluene to mesitylene. 

For toluene fluorination, the impact of micro-reactor processing on the ratio of ortho-, meta- and para-isomers for monofluorinated toluene could be deduced and explained by a change in the type of reaction mechanism. The ortho-, meta- and para-isomer ratio was 5 1 3 for fluorination in a falling film micro reactor and a micro bubble column at a temperature of-16 °C [164,167]. This ratio is in accordance with an electrophilic substitution pathway. In contrast, radical mechanisms are strongly favored for conventional laboratory-scale processing, resulting in much more meta-substitution accompanied by imcontroUed multi-fluorination, addition and polymerization reactions. 

OS 32] ]R 16a] ]P 23]Toluene nitration rates determined in the capillary-flow reactor were generally higher than benzene nitration rates [31, 97]. This is not surprising, as it stems from the higher reactivity of toluene towards electrophilic substitution owing to its more electron-rich aromatic core. For instance, at a reaction temperature of 60 °C, rates of 6 and 2 min were found for toluene and benzene nitration, respectively. However, care has to be taken when quantitatively comparing these results, since experimental details and tube diameters vary to a certain extent or are not even listed completely. 

GL 1] [R 4] [P 2] Variation of solvent affects also the substitution pattern to a certain extent [13], A ratio of ortho-, meta- and para-isomers for mono-fluorinated toluene amounting on average to 3.5 1 2 was found in the dual-channel micro reactor at room temperature, using acetonitrile as solvent [13]. Using methanol as solvent, the ratio was on average 5.5 1 2.4. Hence more products referring to an electrophilic substitution were formed [13]. 

The xylenes are produced in an equilibrium mixture containing 24% p-, 54% m-, and 22% o-xylene (11) This is readily understandable. The transalkylation occurs via an electrophilic substitution of toluene by a benzyl cation. In the absence of steric constraints, p- and o-xylene are expected as predominant... 

Friedel-Crafts reactions involving electrophilic substitution of aromatic compounds have been reported on solid base catalysts such as thallium oxide and MgO. The rates of benzylation of toluene by benzyl chloride over MgO nanocrystals were found to be of the order CP-MgO > CM-MgO > AP-MgO.56 An important observation in the study was that x-ray diffraction of the spent catalyst... 

General Procedure for the Hydroformylation/Electrophilic Substitution. Synthesis of 5,6-dihydroindolizines. A solution of 1-allylpyrroles (leq) and Rh4(CO)i2 (lmol%) in toluene was introduced by suction into an evacuated stainless-steel reaction vessel. CO (60 bar) was introduced, the autoclave was then rocked, heated to the desired temperature and H2 (60 bar) was introduced rapidly. When the gas absorption reached the value corresponding to the fixed conversion, the reaction mixture was siphoned out. The degree of conversion and the product distributions were determined by GC and GC-MS, by using acetophenone as an internal standard. 

The acetylation over protonic zeolites of aromatic substrates with acetic anhydride was widely investigated. Essentially HFAU, HBEA, and HMFI were used as catalysts, most of the reactions being carried out in batch reactors, often in the presence of solvent. Owing to the deactivation effect of the acetyl group, acetylation is limited to monoacetylated products. As could be expected in electrophilic substitution, the reactivity of the aromatic substrates is strongly influenced by the substituents, for example, anisole > m-xylene > toluene > fluorobenzene. Moreover, with the poorly activated substrates (m-xylene, toluene, and fluoroben-zene) there is a quasi-immediate inhibition of the reaction. It is not the case with activated substrates such as anisole and more generally aromatic ethers. It is why we have chosen the acetylation of anisole and 2-methoxynaphtalene as an example. 

Toluene, like benzene, undergoes electrophilic substitutions, where the substitutions take place in ortho and para positions. As the —CH3 group is an activating group, the reaction rate is much faster than usually observed with benzene. For example, the nitration of toluene produces ortho-nitro-toluene (61%) and para-nitrotoluene (39%). 

TABLE 11.3 Relative rates and product distributions in some electrophilic substitutions on toluene and benzene76... 

De-f-butylation during electrophilic substitution is a fairly common phenomenon in thiophene chemistry. The A1C13 catalyzed acylation of 2-methyl-5-f-butylthiophene with acetyl chloride gives 3,5-diacetyl-2-methylthiophene as the main product (69BSF991). Treatment of the acid (324) with PPA in toluene results in ring closure and de-r-butylation to form (325) (73BSF343). 

Substituents have a profound effect on the electrophilic substitution rate constants of organic compounds reacting with e (Anbar and Hart, 1964). Table 12.5 lists the rate constants for substituted benzenes, toluene, and phenols. Four orders of magnitude of rate constants may vary from 4 x 106 Mr1 s 1 for phenol to 3 x 1010 M 1 s 1 for nitrobenzene. To gain insight into the reaction mechanisms involving e, Anbar and Hart (1964) applied Hammett s equation to the rate constants and the substituent constants. T is defined as the ratio of rate constants of substituted compounds vs. nonsub-stituted reference compounds such as benzene, toluene, and phenol as follows ... 

Because the p value is positive, negatively charged carbon ions are considered to be the primary transition state complex (TSC). The TSC will dissociate to a substituted phenol radical and a stable anion. It may also be neutralized by the toluene, resulting in the addition of a proton, H+ (Arai and Dorfman, 1964) therefore, eaq is considered to interact with the ir-orbital of the ring as in electrophilic substitution rather than to affect electron distribution and polarizability of a certain substituent. 

An attempt has been made to analyse whether the electrophilicity index is a reliable descriptor of the kinetic behaviour. Relative experimental rates of Friedel-Crafts benzylation, acetylation, and benzoylation reactions were found to correlate well with the corresponding calculated electrophilicity values. In the case of chlorination of various substituted ethylenes and nitration of toluene and chlorobenzene, the correlation was generally poor but somewhat better in the case of the experimental and the calculated activation energies for selected Markovnikov and anti-Markovnikov addition reactions. Reaction electrophilicity, local electrophilicity, and activation hardness were used together to provide a transparent picture of reaction rates and also the orientation of aromatic electrophilic substitution reactions. Ambiguity in the definition of the electrophilicity was highlighted.15... 

The Selectivity Relationship was shown to be applicable for substitution in the meta and para positions of toluene (Section II). The fine adherence of the -methyl group to a linear free-energy relationship (Fig. 37) is apparently typical of the behavior of the other alkyl substituents, as illustrated for the p-ethyl, p-i-propyl, and p-t-butyl groups (Figs. 38-40). Indeed, the data for electrophilic substitution in toluene are better correlated by a linear relationship than are the data for ordinary side-chain reactions of p-tolyl derivatives (Stock and Brown, 1959a). In the Extended Selectivity Treatment (Fig. 25) the side-chain reactions show a slightly greater scatter from the correlation line than the aromatic substitution reactions. 

Stock and Brown (1959) have carried out a detailed study of reactions involving the electrophilic substitution of hydrogen in toluene, and have shown that the selectivity relationship (eqs. (11), (20-23) of article by Stock and Brown) is applicable. 

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