Toluene meta substitution

Synthetic phenol capacity in the United States was reported to be ca 1.6 x 10 t/yr in 1989 (206), almost completely based on the cumene process (see Cumene Phenol). Some synthetic phenol [108-95-2] is made from toluene by a process developed by The Dow Chemical Company (2,299—301). Toluene [108-88-3] is oxidized to benzoic acid in a conventional LPO process. Liquid-phase oxidative decarboxylation with a copper-containing catalyst gives phenol in high yield (2,299—304). The phenoHc hydroxyl group is located ortho to the position previously occupied by the carboxyl group of benzoic acid (2,299,301,305). This provides a means to produce meta-substituted phenols otherwise difficult to make (2,306). VPOs for the oxidative decarboxylation of benzoic acid have also been reported (2,307—309). Although the mechanism appears to be similar to the LPO scheme (309), the VPO reaction is reported not to work for toluic acids (310). 

Brown has proposed that the importance of meta substitution in the alkylation is related to the activity of the attacking species, and he utilized the relative reactivity of toluene and benzene in the reaction under consideration as a measure of this activity.It might be possible that the amounts of 3-isomer formed may similarly be related to the relative reactivity of thiophene and benzene in different reactions. 

This reaction cannot be elementary. We can hardly expect three nitric acid molecules to react at all three toluene sites (these are the ortho and para sites meta substitution is not favored) in a glorious, four-body collision. Thus, the fourth-order rate expression 01 = kab is implausible. Instead, the mechanism of the TNT reaction involves at least seven steps (two reactions leading to ortho- or /mra-nitrotoluene, three reactions leading to 2,4- or 2,6-dinitrotoluene, and two reactions leading to 2,4,6-trinitrotoluene). Each step would require only a two-body collision, could be elementary, and could be governed by a second-order rate equation. Chapter 2 shows how the component balance equations can be solved for multiple reactions so that an assumed mechanism can be tested experimentally. For the toluene nitration, even the set of seven series and parallel reactions may not constitute an adequate mechanism since an experimental study found the reaction to be 1.3 order in toluene and 1.2 order in nitric acid for an overall order of 2.5 rather than the expected value of 2. 

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. 

Figure 7 displays the data of Ito4,13 and others29 in a 3 x 3 matrix of torsional potentials for o-fluorotoluene, m-fluorotoluene, and p-fluorotoluene in the three electronic states S0, S, and D0. The matrix reveals patterns that hold for other ortho, meta, and para substituents as well.9 In S0, ortho substitution creates a large barrier, while meta substitution does not. A sensible interpretation invokes steric repulsion between methyl and the ortho substituent. Hie menz-substituted cases have very small barriers like toluene itself, apparently for lack of steric effects. However, in ort/io-substituted toluenes, V3 decreases sharply on ji — n excitation from S0 to S, while in mefa-substituted toluenes, V3 increases substantially from S0 to S,. This suggests that steric interactions are not the complete story. Most intriguing of all,... 

Probtom 11.12 (a) Draw enthalpy-reaction diagrams for the first step of electrophilic attack on benzene, toluene (meia and para) and nitrobenzene (meta and para). Assume all ground states have the same energy, (b) Where would the para and meta substitution curves for C HjCI lie on this diagram ... 

A graphical examination of the data for meta substitution in toluene is presented as Fig. 8. The deviations from a precise linear relationship are larger than for the reactions at the para position of toluene. As for para substitution, the largest discrepancies are detected for the nitration and isotopic exchange reactions, indicated in Fig. 8 by broken circles. 

Consider the nitration of toluene (Following fig.). The amount of meta substitution is very small as expected and there is a preference for the ortho and para products. The formation of more ortho substitution compared to para substitution is due to the fact that there are two ortho sites on the molecule to one para site and so there is double the chance of ortho attack to para attack. Based on pure statistics it would be expected that the ratio of ortho to para attack to be 2 1. In fact, the ratio is closer to 1.5 1. In other words, there is less ortho substitution than expected. This is because the ortho sites are immediately next door to the methyl substituents and the size of the substituent tends to inference with ortho attack— a steric effect. The significance of the steric effect will vary according... 

The sigma complex for meta substitution has its positive charge spread over three 2° carbons this intermediate is similar in energy to the intermediate for substitution of benzene. Therefore, meta substitution of toluene does not show the large rate enhancement seen with ortho and para substitution. 

Activation of aromatic compounds by transition-metal complexes was initially studied with Cr(CO)3 complexes. Nucleophilic addition of 2-lithio-l,3-dithianes to arene-chromium(O) complexes 185 followed usually by iodine-promoted decomplexation affords the corresponding 2-arylated 1,3-dithianes 186. The reaction of //-(toluene)- and (anisole)tricarbonylchromium (185) with compound 161 gave mixtures (52 46 and 10 90, respectively) of ortho and meta substituted derivatives (186) (Scheme 54)244. The meta directing effect was also observed (mainly better than 95%) with amino and fluoro substituted complexes245. 

Problem 11.12 (a) Explain in terms of the reactivity-selectivity principle (Section 4.4) the following yields of meta substitution observed with toluene Br2 in CH3COOH, 0.5% HNO3 in CH3COOH, 3.5% CH3CH2Br in GaBr3,... 

In toluene, substitution is thus faster than meta substitution because... 

Now the charge is delocalized to the three carbon atoms that do not include the ipso carbon and no o conjugation from the alkyl group is possible. The situation is no worse than that of benzene, but toluene reacts some 10 faster than benzene at the ortho and para positions. The stability of the transition states for electrophilic attack on toluene can again be modelled on these intermediates, so they follow the same pattern. The transition states for ortho and para attack have some positive charge at the ipso carbon but that for meta substitution does not. 

This reaction cannot be elementary. We can hardly expect three nitric acid molecules to react at all three toluene sites (these are primarily the ortho and para sites meta substitution is not favored) in a glorious, four-body collision. Thus the fourth-order rate expression (R = kab is implausible. Instead, the mechanism of the TNT reaction involves at least seven steps (two reactions leading to ortho- or para-nitrotoluene, three reactions leading to 2,4- or 2,6-dinitrotoluene, and two reactions leading to... 

The magnitude of these effects however is surprisingly high. For example one can compare these results with corresponding data for toluene (15) (Table I). Here a smaller dependence of isomer yield on acidity is apparent, and the % meta-substitution in toluene remains almost constant. 

Resonance stabilization of meta substituted toluene. Note that positive charge does not reside directly under the methyl group. This is, therefore, not as low in energy as the ortho and para substituted toluenes. As a result, the main products of nitration of toluene are o-nitro-toluene and p-nitrotoluene. These can be separated to give p-nitrotoluene. The synthesis of p-nitrotoluene from toluene can be summarized as ... 

Selectivity is more complicated with a methyl or chloro substituent. Again, meta substitution is always significant, but ortho substitution can account for 50-70% of the mixture in some cases [2]. More reactive anions (1,3-dithianyl) and less substituted carbanions (e.g., tert-butyl lithioacetate) tend to favor ortho substitution. Representative examples are shown in Table 3. Entries 2-4 show that variation of reaction temperatures from -100 °C to 0 °C has no significant effect in that highly selective system. The added activating effect of the Cl substituent allows addition of the pinacolone enolate anion (entry 11), whereas no addition to the anisole nor toluene ligand is observed with the same anion. 

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