Aromatic substitution reversibility

Isopropoxycarbonyloxy radicals undergo facile reaction with aromatic substrates (e.g. toluene) by reversible aromatic substitution. 94 Isopropoxycarbonyloxy radicals react with S to give ring substitution (ca 1%) as well as the expected double bond addition.40 ... 

It has also been argued10,40 that the second mechanism (rapid, reversible interconversion of II and IV) cannot be general. The basis for this contention is the fact that electrophilic catalysis is rare in nucleophilic aromatic substitution of non-heterocyclic substrates, an exception being the 2000-fold acceleration by thorium ion of the rate of reaction of 2,4-dinitrofluorobenzene with thiocyanate... 

Arenediazonium ions can, of course, bring about electrophilic aromatic substitution giving aromatic azo-compounds. Using PhN=N and PhO , polarized signals have been observed in the N-spectrum (6 MHz) of the coupled product (A, A) and reactant, suggesting that the reaction proceeds, at least in part, by a mechanism involving preliminary reversible electron transfer between the reactants (Bubnov et al., 1972). 

Aromatic compounds react with mercuric salts to give arylmercury compounds.69 Mercuric acetate or mercuric trifluoroacetate are the usual reagents.70 The reaction shows substituent effects that are characteristic of electrophilic aromatic substitution.71 Mercuration is one of the few electrophilic aromatic substitutions in which proton loss from the a complex is rate determining. Mercuration of benzene shows an isotope effect kB/kD = 6,72 which indicates that the [Pg.1026]

The product of electrophilic aromatic substitution is a sulfonic acid (see Section 7.13.1). Unnsnally, sulfonation is found to be reversible it is possible... 

Four years later, we reported an improved iron-mediated total synthesis of furostifoline (224) (689). This approach features a reverse order of the two cyclization reactions by first forming the carbazole nucleus, then annulation of the furan ring. As a consequence, in this synthesis the intermediate protection of the amino function is not necessary (cf. Schemes 5.178 and 5.179). The electrophilic aromatic substitution at the arylamine 1106 by reaction with the iron complex salt 602 afforded the iron... 

Alkylation of the C(2) or C(3) carbons of the pyrrole ring can be accomplished by electrophilic aromatic substitution. Such substitution reactions may be carried out on the neutral heterocycle or on a metal salt. The magnesium salts are of most synthetic importance for the alkylation of both pyrroles and indoles. As discussed in Section 3.05.1.2.7, there is a reversal of the preferred site of electrophilic substitution between pyrroles and indoles. Thus Friedel-Crafts-type substitution of pyrroles gives 2-aIkylpyrroles while similar reaction... 

Exercise 14-14 Whereas the order of reactivity of alkyl halides toward a given nucleophile is I > Br > Cl F, the reverse order of reactivity frequently is observed with aryl hal ides (F Cl a Br = I). What does this signify regarding the relative rates of the addition and elimination steps (Equations 14-3 and 14-4) in this kind of aromatic substitution ... 

Seemingly anomalous effects of substituents are known, but such effects may be due to equilibrium control. One example is the aluminum chloride-catalyzed alkylation of benzene, which leads to the formation of a 1,3,5-trialkylbenzene in preference to the expected 1,2,4-isomer (see Section 22-4E). The preferred reaction occurs particularly readily because alkylation is reversible and because alkylation is one of the least selective of the electrophilic aromatic substitutions (considerable meta isomer is formed even under conditions where kinetic control is dominant). Equilibrium control, which favors the 1,3,5-product rather than the less stable 1,2,4-product, becomes most evident when the reaction time, the reaction temperature, and aluminum chloride concentration are increased. Another source of anomalous substituent effects is discussed in the next section. 

The procedure adopted to portray the scope and utility of a linear free-energy relationship for aromatic substitution involves first a determination of the p-values for the reactions. These parameters are evaluated by plotting the values of log (k/ka) for a series of substituted benzenes against the values based on the solvolysis studies (Section IV, B). The resultant slope of the line is p, the reaction constant. The procedure is then reversed to assess the reliability and validity of the Extended Selectivity Treatment. In this approach the log ( K/ H) observations for a single substituent are plotted against p for a variety of reactions. This method assays the linear or non-linear response of each substituent to variations in the selectivity of the reagents and conditions. Unfortunately, insufficient data are available to allow the assignment of p for many reactions. It is more practical in these cases to adopt the Selectivity Factor S as a substitute for p and revert to the more empirical Selectivity Treatment for an examination of the behavior of the substituents. 

The same workers590,591 also showed that, in the Pd(II)-catalyzed acetoxylation of substituted arenes, a complete reversal of the usual pattern of isomer distribution for electrophilic aromatic substitution or anodic oxidation of aromatics is observed. To explain these results it was suggested that acetoxylation by Pd(OAc)2 takes place via the following addition-elimination sequence ... 

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