Studies of Electrophilic Aromatic Substitution

The reactivity of pyridine relative to that of benzene has been measured using the competitive technique developed by Ingold and his schoool for corresponding studies of electrophilic aromatic substitution. The validity of the method applied to free-radical reactions has been discussed. Three sources of the phenyl radical have been used the results obtained are set out in Table II. 

See related MNDO calculations by Butler s group (Anderson et al., 1989) and the study of electrophilic aromatic substitutions by Jorgensen s group (Bures et al., 1985, Table 2 and references cited in that table). 

A review of solvent properties of, and organic reactivity in, ionic liquids demonstrates the relatively small number of quantitative studies of electrophilic aromatic substitution in these media.3 Studies mentioned in the review indicate conventional polar mechanisms. 1-Methylpyrrole reacts with acyl chlorides in the ionic liquid 1-butylpyridinium tetrafluoroborate to form the corresponding 2-acylpyrrole in the presence of a catalytic amount of ytterbium(III) trifluoromethanesulfonate.4 The ionic liquid-catalyst system is recyclable. Chloroindate(III) ionic liquids5 are catalytic media for the acylation, using acid chlorides and anhydrides, of naphthalene, benzene, and various substituted benzenes at 80-120 °C. Again the ionic liquid is recyclable. 

In our study of electrophilic aromatic substitution (Sec. 11.19 and Sec. 30.9), we found that we could account for orientation on the following basis the controlling step is the attachment of the electrophilic reagent to the aromatic ring, which takes place in .uch a way as to yield the most stable intermediate carbonium ion. Let us apply this approach to the reactions of pyrrole. 

Although the nature of the first intermediate is still disputed, in gas-phase studies of electrophilic aromatic substitution the existence of 7r-complex first intermediates has been proven experimentally. The reaction mechanisms have been reviewed by Olah et al. [6]. 

Rate and product studies of electrophilic aromatic substitution in halobenzenes reveal a fairly consistent pattern of reactivity. The partial rate factors for chlorination show that, with one exception, all the ring positions of fluoro-, chloro-, and bromoben-zene are deactivated. The exception is the para position of fluorobenzene, which is slightly more reactive than a single position of benzene. 

Resonance structures (like those used here for the arenium ion) will be important for our study of electrophilic aromatic substitution. 

There are of course many other kinetic studies of electrophilic aromatic substitution, particularly of the halogenation of activated aromatic species such as phenols and anilines. These are frequently complicated by the effect of pH and halide ion concentration upon equilibria between different halogenating species and between different forms of the aromatic substance. The role of bases in removing a proton has been rarely investigated directly, and much of the mechanistic information comes from a study of isotope effects, which will be considered in Chapter 12. 

The reason for this difference in selectivity of different electrophilic reagents between the 2- and 3-positions must be sought in the finer details of the mechanism of electrophilic aromatic substitution Melander and co-workers are studying this problem by means of isotope effects. 

Except for these studies of their protonation behavior, almost the only other aspect of the chemistry of sulfonic acids that has been investigated to any extent from a mechanistic point of view is the desulfonation of aromatic sulfonic acids or sulfonates. Since this subject has been well reviewed by Cerfontain (1968), and since the reaction is really more of interest as a type of electrophilic aromatic substitution than as sulfur chemistry, we shall not deal with it here. One should note that the mechanism of formation of aromatic sulfonic acids by sulfonation of aromatic hydrocarbons has also been intensively investigated, particularly by Cerfontain and his associates, and several... 

Despite the use of new catalys.s for manufacturing some industrial organic chemicals, many well-known classical reactions still abound. The Friedel-Crafts alkylation is one of the first reactions studied in electrophilic aromatic substitution. It is used on a large scale for making ethylbenzene. 

This chapter is concerned with reactions that introduce or replace substituent groups on aromatic rings. The most important group of reactions is electrophilic aromatic substitution. The mechanism of electrophile aromatic substitution has been studied in great detail, and much information is available about structure-reactivity relationships. There are also important reactions which occur by nucleophilic substitution, including reactions of diazonium ion intermediates and metal-catalyzed substitution. The mechanistic aspects of these reactions were discussed in Chapter 10 of Part A. In this chapter, the synthetic aspects of aromatic substitution will be emphasized. 

Cycloalkadienyl cations, particularly cyclohexadienyl cations (benzenium ions), the intermediate of electrophilic aromatic substitution, frequently show remarkable stability. Protonated arenes can be readily obtained from aromatic hydrocarbons244 251 in superacids and studied by 1H and 13C NMR spectroscopy.252,253 Olah et al.252 have even prepared and studied the parent benzenium ion (C6H7+) 88. Representative 1H NMR spectra of benzenium253 and naphthalenium ions25488 and 89 are shown in Figures 3.11 and 3.12, respectively. 

The study of the structure, synthesis, and reactivity of aromatic compounds has been one of the cornerstones of the teaching of organic chemistry. An account of the historical and sometimes disputed dream of Kekule [1] is followed by the beautiful logic of electrophilic aromatic substitution rules [2], which allows students to predict syntheses of sparsely substituted aromatics. Aside from a brief diversion into reactions of halonitrobenzenes with nucleophiles [3], this topic constitutes a large chapter in our 1st year organic education but by the time we teach upper year organic majors and graduate students, aromatic chemistry... 

Aromatic compounds undergo many reactions, but relatively few reactions that affect the bonds to the aromatic ring itself. Most of these reactions are unique to aromatic compounds. A large part of this chapter is devoted to electrophilic aromatic substitution, the most important mechanism involved in the reactions of aromatic compounds. Many reactions of benzene and its derivatives are explained by minor variations of electrophilic aromatic substitution. We will study several of these reactions and then consider how substituents on the ring influence its reactivity toward electrophilic aromatic substitution and the regiochemistry seen in the products. We will also study other reactions of aromatic compounds, including nucleophilic aromatic substitution, addition reactions, reactions of side chains, and special reactions of phenols. 

In a subsequent study regarding the a and p selectivity of electrophilic aromatic substitutions, Cai, et ai.,82>83 demonstrated that, in addition to aromatic... 

These reactions, called electrophilic aromatic substitutions (EAS), allow the direct introduction of groups onto aromatic rings such as benzene, and they provide synthetic routes to many important compounds. Figure 15.1 outlines five different types of electrophilic aromatic substitutions that we will study in this chapter, including carbon—carbon bond-forming reactions and halogenations. 

Several other classes of electrophilic aromatic substitution reactions have occasionally been investigated in microreactors. Some exemplary studies are summarized in this section. 

In this section, we study several types of electrophilic aromatic substitution reactions—that is, reactions in which a hydrogen of an aromatic ring is replaced by an electrophile, E. The mechanisms of these reactions are actually very similar. In fact, they can be broken down into three common steps ... 

Issues of regioselectivity in the Blanc chloromethylation and related Friedel-Crafts reactions have been studied extensively. As is common with a majority of electrophilic aromatic substitution reactions, substitution typically occurs ortho or para to electron-donating substituents, with issues of steric strain playing a role in the relative ratio of ortho and para products. The Blanc reaction is t3q)ically somewhat regioselective, favoring the para-isomer but accompanied by lesser amounts of the ortho product. ... 

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