Benzene electrophilic reactions

The earliest reported reference describing the synthesis of phenylene sulfide stmctures is that of Friedel and Crafts in 1888 (6). The electrophilic reactions studied were based on reactions of benzene and various sulfur sources. These electrophilic substitution reactions were characterized by low yields (50—80%) of rather poorly characterized products by the standards of 1990s. Products contained many by-products, such as thianthrene. Results of self-condensation of thiophenol, catalyzed by aluminum chloride and sulfuric acid (7), were analogous to those of Friedel and Crafts. 

Bifunctional catalysis in nucleophilic aromatic substitution was first observed by Bitter and Zollinger34, who studied the reaction of cyanuric chloride with aniline in benzene. This reaction was not accelerated by phenols or y-pyridone but was catalyzed by triethylamine and pyridine and by bifunctional catalysts such as a-pyridone and carboxylic acids. The carboxylic acids did not function as purely electrophilic reagents, since there was no relationship between catalytic efficiency and acid strength, acetic acid being more effective than chloracetic acid, which in turn was a more efficient catalyst than trichloroacetic acid. For catalysis by the carboxylic acids Bitter and Zollinger proposed the transition state depicted by H. 

Ferrocene behaves in many respects like an aromatic electron-rich organic compound which is activated toward electrophilic reactions.In Friedel-Crafts type acylation of aromatic compounds with acyl halides, ferrocene is lO times more reactive than benzene and gives yields over 80%. However, ferrocene is different from benzene in respect to reactivity and yields in the Friedel-Crafts alkylation with alkyl halides or olefins. The yields of ferrocene alkylation are often very low. and the separations of the polysubstituted byproducts are tedious. 

A novel electrophilic reaction of the 2-methoxyazepinium ion 2, formed in situ from 1 on treatment with TiCl4,was observed in the presence of benzene to give 3, 4 and 5. The kinetics of the isomerisation (ki k2, k3) of the 477-azepine 3 to 8 via 6 and 7 were also reported <06EJ03803>. 

Mixed coupling between naphthalene and alkyl benzenes has also been demonstrated (Table 10, numbers 10-13). The relative yield of mixed coupling products increases with the basicity of the alkyl benzene with mesitylene 19%, with tetramethylbenzene 42%, and with pen-tamethylbenzene 64%. This suggests an electrophilic reaction between naphthalene cation radicals and alkylbenzenes. The mixed coupling reaction of phenan-threne with anisole has been studied kinetically [163]. 

Typical electrophilic reactions, such as nitration, halogenation with a Lewis acid (as a carrier ), Friedel-Crafts C-alkylation and -acylation, that work well with benzene, cannot be applied to pyrrole, because heating with strong acids, or a Lewis acid, destroys the heterocycle. However,... 

TABLE 10.30 Reactivity Scale1 for the Electrophilic Reactions of PAHs (and Benzene) ... 

The partial rate factors af and /3f for the a- and /3-positions of thiophene have been calculated for a wide range of electrophilic reactions these have been tabulated (71 AHC(13)235, 72IJS(C)(7)6l). Some side-chain reactions in which resonance-stabilized car-benium ions are formed in the transition states have also been included in this study. A correspondence between solvolytic reactivity and reactivity in electrophilic aromatic substitution is expected because of the similar electron-deficiency developed in the aromatic system in the two types of reactions. The plot of log a or log /3f against the p-values of the respective reaction determined for benzene derivatives, under the same reaction conditions, has shown a linear relationship. Only two major deviations are observed mercuration and protodemercuration. This is understandable since the mechanism of these two reactions might differ in the thiophene series from the benzene case. 

On the other hand, the Nation resin in its acidic form (Nafion-H) shows high activity in a variety of electrophilic reactions. Gas-phase alkylation of benzene with ethylene and propylene in a flow system proceeds at temperatures as low as 110°C over Nafion-H (Table 5.10). 

The inductive parameter, aL, is the same in both the meta and para positions the resonance parameter, aR, is, of course, appreciably different in the two positions the inductive reaction constant is pv This three-parameter equation was employed to calculate reaction types of meta- and para-substituted benzene derivatives. It was shown that free radical processes yielded different values, and a common set of resonance parameters was not possible. The conclusion is, of course, identical to that of van Bekkum and his co-workers (1959). The utility of a unique set of resonance parameters for electrophilic reactions is obscured by the inclusion of both electrophilic side-chain and electrophilic substitution reactions in a single series. 

Norman and his associates (Knowles et al., 1960) attempted to account for the electrophilic reactions of substituted benzenes with three parameters. 

Although electrophilic reactions involving dications with deactivated arenes may suggest the formation of superelectrophilic intermediates, there are a number of well-known examples of monocationic electrophiles that are capable of reacting with benzene or with deactivated aromatic compounds. For example, 2,2,2-trifluoroacetophenone condenses with benzene in triflic acid (eq 12).13 A similar activation is likely involved in the H2SO4 catalyzed reaction of chloral (or its hydrate) with chlorobenzene giving DDT (eq 13). 

These structures suggest that the carbons in pyridine are partially positively charged (due to the electron-withdrawing effect of the nitrogen) and, therefore, are expected to be deactivated (relative to benzene) toward reaction with electrophiles. Note that the positive charge is distributed between carbons 2, 4, and 6. Therefore, these carbons should be less reactive toward electrophiles than carbon 3 (or 5). 

Phosphinine and its derivatives are clearly aromatic however, they are considerably more reactive than benzene. The most significant influence on the reactivity of these molecules is the presence of the lone pair on phosphorus, and two significant reactions are its complexation with a variety of metals, and nucleophilic attack to form (ultimately) A5-phosphorins. The 71-system can undergo [4+2] cycloadditions, under milder conditions than benzene. Electrophilic substitution reactions on carbon are considered to be impossible <2001CRV1229>. 

Fig. 5.4. Enthalpy profile for the electrophilic addition of Br2 (reactions proceeding towards the left) and for the electrophilic substitution by Br2 (reactions proceeding towards the right) of cyclohexene (top) and of benzene (bottom). Altogether, the facts presented here are likely to be prototypical of the chemoselectivity of all electrophilic reactions on alkenes versus benzenoid aromatic compounds. In detail, though, this need not be true both in the alkene and the aromatic compound AWSubstitution as well as AWadditio depend on the electrophile, which is why an electrophilic dependency can in principle also be expected for AAH = AWsubstitution - A//a(1(l t. ol. ...

All of the electrophilic aromatic substitution reactions follow this same general mechanism. The only difference is the structure of the electrophile and how it is generated. Let s look at a specific example, the nitration of benzene. This reaction is accomplished by reacting benzene with nitric acid in the presence of sulfuric acid ... 

It should therefore be no surprise that the nitration of methoxyben-zene is easier and faster than that of benzene and yields essentially only the 1,2- and 1,4-isomers (in almost equal amounts). Less than 1% of 3-nitroanisole is formed. Other electrophilic reactions follow this pattern. 

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