Electrophilic Aromatic Substitution Reactions Bromination

Thomson Click Organ/c Process to view an animation of the bromination of aromatic rings. 

Thomson iO Click Organic interactive to practice your problem-solving skills on the mechanism of electrophilic aromatic substitution. 

An electrophilic aromatic substitution reaction begins in a similar way, but there are a number of differences. One difference is that aromatic rings are less reac-ti e toward electrophiles than alkenes arc. For example, Br2 in CI I2CI2 solution reacts instantlv witli most alkenes but docs not react with benzene at room tern- 

O An electron pair from the benzene ring attacks the positively polarized bromine, forming a new C-Br bond and leaving a nonaromatic carbocation intermediate. 

Why does the reaction of Br2 with benzene take a different course than its reaction with an alkene The answer is straightforw ard. If addition occurred, the 150 k /moI stalrilization energy of the aromatic ring would be lost and the 

Before seeing how electrophilic aromatic substitutions occur, let s briefly recall what we said in Chapler 6 about electrophilic alkene additions. When a reagent such as HCl adds to an alkene, the electrophilic hydrogen approaches the p orbitals of the double bond and forms a bond to one carbon, leaving a positive charge at the other carbon. This carbocation intermediate then reacts with the nucleophilic Cl- ion to yield the addition product. 

0 A base removes H+ from the carbocation intermediate, and the neutral substitution product forms as two electrons from the C-H bond move to re-form the aromatic ring. 

An electrophilic aromatic substitution reaction begins in a similar way, but there are a number of differences. One difference is that aromatic rings are less reactive toward electrophiles than alkenes are. For example, Bi in CH2CI2 solution reacts instantly with most alkenes but does not react with benzene at room temperature. For bromination of benzene to take place, a catalyst such as FeBr is needed. The catalyst makes the Br2 molecule more electrophilic by polarizing it to give an FeBi Br species that reacts as if it were Br. The polarized Br2 molecule then reacts with the nucleophilic benzene ring to yield a nonaromatic carbocation intermediate that is doubly allylic (Section 11.5) and has three resonance forms. 

Why This Chapter This chapter continues the coverage of aromatic molecules begun in the preceding chapter, but we ll shift focus to concentrate on reactions, looking at the relationship between aromatic stmcture and reactivity. This relationship is critical to an understanding of how many biological molecules and pharmaceutical agents are synthesized and why they behave as they do. 

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Like Friedel-Crafts reactions, halogenation such as bromination and iodination of aromatic compounds are classified as electrophilic aromatic substitution reactions. Bromine and iodine substituents are weakly electron-withdrawing groups, and introduction of such substituents causes a decrease in reactivity, and therefore, the first halogenation is faster than the second halogenation. However, the reactions in batch macroreactors suffer from the problem of disguised chemical selectivity, i.e, the formation of dihalogenated products. 

There are many other kinds of electrophilic aromatic substitutions besides bromination, and all are thought to occur by the same general mechanism. Let s look at some of these other reactions briefly. 

SAMPLE SOLUTION (a) The ring that bears the hydroxyl group is much more reactive than the other ring. In electrophilic aromatic substitution reactions of rings that bear several substituents, it is the most activating substituent that controls the orientation. Bromination occurs para to the hydroxyl group. 

Although aromatic compounds have multiple double bonds, these compounds do not undergo addition reactions. Their lack of reactivity toward addition reactions is due to the great stability of the ring systems that result from complete n electron delocalization (resonance). Aromatic compounds react by electrophilic aromatic substitution reactions, in which the aromaticity of the ring system is preserved. For example, benzene reacts with bromine to form bromobenzene. 

A good example of a back titration involving iodine and thiosulfate is the assay of resorcinol in Resorcinol Solution BP. Resorcinol is an antiseptic that was widely used in the past, although less so now. The assay of resorcinol involves a quantitative electrophilic aromatic substitution reaction using bromine as the reagent, as shown in Figure 6.4. 

The same groups have also examined electrophilic aromatic substitution reactions, using both 223 and 255 as substrates. Bromination of 223 gave the 6-bromo derivative (256 X = Br) or the 6,8-dibromo derivative (257 X = Y = Br) depending on the conditions.147 Under all bromination conditions examined, compound 255 (R = alkyl) afforded only a 6-mono-brominated product 258 (X = Br, Y = H). 

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