Addition Reactions of Benzene Derivatives

Although substitution is more common, aromatic compounds may undergo addition if forcing conditions are used. When benzene is treated with an excess of chlorine under heat and pressure (or with irradiation by light), six chlorine atoms add to form 1,2,3,4,5,6-hexachlorocyclohexane. This product is often called benzene hexachlotide (BHC) because it is synthesized by direct chlorination of benzene. 

The addition of chlorine to benzene, believed to involve a free-radical mechanism, is normally impossible to stop at an intermediate stage. The first addition destroys the ring s aromaticity, and the next 2 moles of CI2 add very rapidly. All eight possible stereoisomers are produced in various amounts. The most important isomer for commercial purposes is the insecticide lindane, which is used in a shampoo to kill head lice. 

Catalytic hydrogenation of benzene to cyclohexane takes place at elevated temperatures and pressures, often catalyzed by ruthenium or rhodium. Substituted benzenes react to give substituted cyclohexanes disubsituted benzenes usually give mixtures of cis and trans isomers. 

Catalytic hydrogenation of benzene is the commercial method for producing cyclohexane and substituted cyclohexane derivatives. The reduction cannot be stopped at an intermediate stage (cyclohexene or cyclohexadiene) because these alkenes are reduced faster than benzene. 

In 1944, the Australian chemist A. J. Birch found that benzene derivatives are reduced to nonconjugated 1,4-cyclohexadienes by treatment with sodium or lithium in a mixture of liquid ammonia and an alcohol. The Birch reduction provides 

---

Aromatic Substitutions Using Organometallic Reagents 790 17-14 Addition Reactions of Benzene Derivatives 796 Mechanism 17-9 The Birch Reduction 797 17-15 Side-Chain Reactions of Benzene Derivatives 798... 

Benzoic acid and naphthoic acid are formed by the oxidative carbonylation by use of Pd(OAc)2 in AcOH. t-Bu02H and allyl chloride are used as reoxidants. Addition of phenanthroline gives a favorable effect[360], Furan and thiophene are also carbonylated selectively at the 2-position[361,362]. fndole-3-carboxylic acid is prepared by the carboxylation of 1-acetylindole using Pd(OAc)2 and peroxodisulfate (Na2S208)[362aj. Benzoic acid derivatives are obtained by the reaction of benzene derivatives with sodium palladium mal-onate in refluxing AcOH[363]. 

For a long time aromatic compounds were believed to be stable when exposed to ultraviolet irradiation. The interest in the photochemistry of arenes only started in the late 1950s when several groups observed both isomerization and addition reactions of benzene and its derivatives. Among the pioneers who were active at that time are the groups of Bryce-Smith and Schenck. Since then the photochemistry of aromatic compounds has become the subject of innumerable papers dealing with their conversion to other aromatic systems (by substitution or isomerization) or even to nonaromatics. 

Addition of molten sulfur to limonene in a 9 kl reactor led to a violent runaway exothermic reaction. Small scale pilot runs had not shown the possibility of this. Heating terpenes strongly with sulfur usually leads to formation of benzene derivatives with evolution of hydrogen sulfide. 

The addition reactions of zirconacyclopentadienes to carbon—carbon triple bonds can be classified into two types (a) 1,1-addition reactions, and (b) 1,2-addition reactions, which furnish benzene derivatives as shown in Eq. 2.45. 

There are several examples of the concerted mechanism. However, no report of an insertion of a carbon—carbon triple bond into a metallacyclopentadiene had appeared prior to discovery of this reaction. At low temperatures, during the reaction of zirconacyclopentadienes with DMAD, the formation of trienes (79) is observed upon hydrolysis. This clearly indicates that the benzene formation involves the insertion (addition) reaction of DMAD. As shown in Eq. 2.50, the alkenyl copper moiety adds to the carbon—carbon triple bond of DMAD and elimination of Cu metal leads to the benzene derivatives 72. Indeed, a copper mirror is observed on the wall of the reaction vessel. 

Photoadditions that arise by initial excitation of the aromatic compound are not common. Benzvalenes are readily attacked by hydroxylic compounds, and so irradiation of benzene in aqueous solutions of acetic acid, for example, results in the formation of a bicydic product (and an isomer derived from it by subsequent photoisomerizationl as a result of addition to the initially formed valence isomer (3.38). A different kind of photoaddition occurs when benzenes react photochemically with amines cyclohexa-T, 4-dienes are the major products (3.39), accompanied by cyclohexa-1.3-dienes, and unlike many of the photochemical reactions of benzene this does not suffer loss of efficiency in scaling-up. 

This process competes favorably with benzylic hydrogen abstraction in toluene, less in ethylbenzene, and least in cumene (31). Such reactions do not seem significant in the oxidation of benzene derivatives. However, naphthalene reacts about 20 times as rapidly with phenyl radical as does benzene (16), and radical addition to the naphthalene nucleus may at least partly account for the slow oxidation rate in the methylnapthalenes. Among the minor products from both methylnaphthalene oxidations were compounds of molecular weight 296 ... 

Routes to benzo-fused derivatives of 1,4-dioxanes, 1,4-oxathianes and 1,4-dithianes make use of anions or dianions of the appropriate 1,2-disubstituted benzene. An alternative approach to the synthesis of 1,4-benzodioxanes involves Diels-Alder addition reactions of alkenes across the quinone function of 1,2-benzoquinones, e.g. (352) — (353). 

Mesylates are used for Ni-catalysed reactions. Arenediazodium salts 2 are very reactive pseudohalides undergoing facile oxidative addition to Pd(0). They are more easily available than aryl iodides or triflates. Also, acyl (aroyl) halides 4 and aroyl anhydrides 5 behave as pseudohalides after decarbonylation under certain conditions. Sulfonyl chlorides 6 react with evolution of SO2. Allylic halides are reactive, but their reactions via 7t-allyl complexes are treated in Chapter 4. Based on the reactions of those pseudohalides, several benzene derivatives such as aniline, phenol, benzoic acid and benzenesulfonic acid can be used for the reaction, in addition to phenyl halides. In Scheme 3.1, reactions of benzene as a parent ring compound are summarized. Needless to say, the reactions can be extended to various aromatic compounds including heteroaromatic compounds whenever their halides and pseudohalides are available. 

There have been several papers reporting new oxidative addition reactions of [Pd(PPh3)4], Alkoxalyl compounds (1), formed by addition of C1C0C02R (R = Me or Et), decarbonylate in chloroform or benzene at room temperature to yield trans-[PdCl(C02R)(PPh3)2].7 The X-ray structure (Table 1, p. 399) of the methyl derivative... 

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. 

Since we introduced conjugate addition in Chapter 10, a number of new reactions have been covered and a number of new nucleophiles introduced. Some of these can lead to conjugate addition. One important new reaction is electrophilic aromatic substitution, which we met in the last chapter. Michael acceptors can combine with Lewis acids to provide electrophiles for reactions with benzene derivatives. 

In Chapter 1 it was stated that the principal reaction of benzene and its derivatives is subsUtmion rather than addition. Indeed, electrophilic substitution in aromatic systems is one of the most important reactions in chemistry and has many commercial applications. 

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. 

---