Reactions of Substituted Benzenes

The intrinsic stability of the aromatic n system has two major consequences for the course of reactions involving it directly. First, the aromatic ring is less susceptible to electrophilic, nucleophilic, and free-radical attack compared to molecules containing acyclic conjugated n systems. Thus, reaction conditions are usually more severe than would normally be required for parallel reactions of simple olefins. Second, there is a propensity to eject a substituent from the tetrahedral center of the intermediate in such a way as to reestablish the neutral (An + 2)-electron system. Thus, the reaction is two step, an endothermic first step resulting in a four-coordinate carbon atom and an exothermic second step, mechanistically the reverse of the first, in which a group is ejected. The dominant course is therefore a substitution reaction rather than an addition. 

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Table 10.1. Energy Changes for Isodesmic Proton-Transfer Reactions of Substituted Benzenes"...

The table below gives first-order rate constants for reaction of substituted benzenes with w-nitrobenzenesulfonyl peroxide. From these data, calculate the overall relative reactivity and partial rate factors. Does this reaction fit the pattern of an electrophilic aromatic substitution If so, does the active electrophile exhibit low, moderate, or high substrate and position selectivity ... 

We will restrict our consideration to reactions of substituted benzenes and to nitrogen heteroaromatic systems in which the reaction takes place first with the n system. The simplest example of reaction of a monosubstituted benzene with an electrophile (Lewis acid) is shown in Scheme 11.1. The electrophile may attach itself to the n system (step A) in four distinct modes, ipso, ortho, meta, and para. The reactivity of the aromatic ring and the mode of attachment of the electrophile will be influenced by the specific nature of the substituent group, which may be X , Z, or C type. Detachment of the electro-... 

The reaction mechanism for the reaction of substituted benzenes with hydroxyl radical appears to be hydroxylation. Hydroxyl radical attack on... 

Specific Rate Constants and Relative Rates of Reaction of Substituted Benzene, Toluene, and Phenols... 

Pearson et al. (1952) employed this approach to derive a series of substituent parameters for electron-deficient reactions of substituted benzenes. These constants, designated as sigmae, were based on a study of the Beckmann rearrangement of -substituted acetophenone oximes. These authors considered the rates of the rearrangement reaction of the oximes to deviate from the Hammett eq. (1). It is pertinent that, with the sole exception of the yi-OMe group, the deviations were not major. The entropy of activation, AS, for the -anisyl derivative was, however, 20 e.u. different from the essentially constant values for the other substituents. To remedy the deviations, Pearson and his associates suggested the sigmae constants. It was indicated that these constants were more suitable for the correlations of electron-deficient reactions than the conventional cr-values. 

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

First, the preparation of the substituted benzene 172 is explained. In the reaction of substituted benzene complex 175 with carbanions, the meta orientation to give 176 is observed even in the presence of ortho- and para-orienting electron-donating groups, such as methoxy and amino groups [45], Using this property, the nucleophilic substitution reaction, complementary to ordinary electrophilic substitution reaction, is... 

Among all the benzoylation reactions of substituted benzene derivatives, the phenol reaction is interesting to consider and to develop due to the fact that it may occur... 

Fig. 6.2. Variation in transition-state structure with electrophile reactivity in reactions of substituted benzenes. A, Activated benzene (e.g., anisole) B. deactivated benzene (e.g., nitrobenzene).

The second route utilizes the introduction of the chlorosulfonyl substituent directly onto the aromatic nucleus. The reaction of substituted benzenes with chlorosulfonic acid gives good yields of arylsulfonyl chlorides however, the aryl substituent dictates the position of attachment of the chlorosulfonyl function in this electrophilic aromatic substitution.7 The method described herein allows replacement of a diazotized amine function by the chlorosulfonyl group. The ready availability of substituted anilines makes this the method of choice for the preparation of arylsulfonyl chlorides. 

We learned in Section 18.6 which groups are electron donating and electron withdrawing. As a result, we know which groups increase or decrease the rate of reaction of substituted benzenes with electrophiles. 

We finish Chapter 18 by learning some additional reactions of substituted benzenes that greatly expand the ability to synthesize benzene derivatives. These reactions do not involve the benzene ring itself, so they are not further examples of electrophilic aromatic substitution. In Seaion 18.13 we return to radical halogenation, and in Section 18.14 we examine useful oxidation and reduction reactions. 

Phototransposition reactions of substituted benzenes and heteroarenes by way of valence-bond isomers and their diradical precursors, have been studied for a considerable number of years and are the subject of several reports in the review period. Such reactions within the six isomers of dimethylbenzotrifluoride are reported to be efficient, with each isomer giving rise to the others. The major product isomers observed in each case, however, allow the starting isomers to be divided into the two triads of 2,6-, 2,3- and 3,4-dimethyl- and 3,5-, 2,4- and... 

In Chapter 16, we will look at the reactions of substituted benzenes. First we will study reactions that change the nature of the substituent on the benzene ring and we will see how the nature of the substituent affects both the reactivity of the ring and the placement of any incoming substituent. Then we will look at three types of reactions that can be used to synthesize substituted benzenes other than those discussed in Chapter 15— reactions of arene diazonium salts, nucleophilic aromatic substitution reactions, and reactions that involve benzyne intermediates. You will then have the opportunity to design syntheses of compounds that contain benzene rings. 

In Chapter 15, we looked at the reactions benzene undergoes and we saw how monosubstituted benzenes are named. Now we will see how disubstituted and polysubstituted benzenes are named, and then we will look at the reactions of substituted benzenes. The physical properties of several substituted benzenes are given in Appendix I. 

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