Electrophilic aromatic substitutions bromination

Complexation of bromine with iron(III) bromide makes bromine more elec trophilic and it attacks benzene to give a cyclohexadienyl intermediate as shown m step 1 of the mechanism (Figure 12 6) In step 2 as m nitration and sulfonation loss of a proton from the cyclohexadienyl cation is rapid and gives the product of electrophilic aromatic substitution... 

Electrophilic aromatic substitution (Sec tion 22 14) Arylamines are very reac tive toward electrophilic aromatic sub stitution It IS customary to protect arylamines as their N acyl derivatives before carrying out ring nitration chio rination bromination sulfonation or Friedel-Crafts reactions... 

The six-position may be functionalized by electrophilic aromatic substitution. Either bromination (Br2/CH2Cl2/-5°) acetylation (acetyl chloride, aluminum chloride, nitrobenzene) " or chloromethylation (chloromethyl methyl ether, stannic chloride, -60°) " affords the 6,6 -disubstituted product. It should also be noted that treatment of the acetyl derivative with KOBr in THF affords the carboxylic acid in 84% yield. The brominated crown may then be metallated (n-BuLi) and treated with an electrophile to form a chain-extender. To this end, Cram has utilized both ethylene oxide " and dichlorodimethyl-silane in the conversion of bis-binaphthyl crowns into polymer-bound resolving agents. The acetylation/oxidation sequence is illustrated in Eq. (3.54). 

Aryl chlorides and bromides are conveniently prepared by electrophilic aromatic substitution. The reaction is limited to chlorination and bromination. Fluorination is difficult to control iodi-nation is too slow to be useful. 

A hydroxyl group is a very powerful activating substituent, and electrophilic aromatic substitution in phenols occurs far- faster, and under milder conditions, than in benzene. The first entry in Table 24.4, for exfflnple, shows the monobromination of phenol in high yield at low temperature and in the absence of any catalyst. In this case, the reaction was carried out in the nonpolar- solvent 1,2-dichloroethane. In polar- solvents such as water it is difficult to limit the bromination of phenols to monosubstitution. In the following exfflnple, all three positions that are ortho or para to the hydroxyl undergo rapid substitution ... 

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. 

In 2011, Hartwig and coworkers reported the total synthesis of taiwaniaquinol B (55, Scheme 11.9), a member of a family of diterpenoids that are derived from the abietane skeleton [36]. A key aspect of the Hartwig synthesis of taiwaniaquinol B was the use of the iridium-catalyzed borylation reaction to accomplish the C(5) functionalization of resorcinol derivative 53. This regioselectivity for the overall bromination is complementary to that which would be obtained using a standard electrophilic aromatic substitution (EAS) reaction. In the transformation of 53 to 54, a sterically controlled borylation was first accomplished, which was then followed by treatment of the boronic ester intermediate with cupric bromide to... 

To provide an example of a reaction that is very different to electrophilic aromatic substitution, the oxidation of formic acid by bromine was also studied. This reaction, which involves electrophilic attack on the formate anion (15) (Cox and McTigue, 1964 Smith, 1972 Herbine et al., 1980 Brusa and Colussi, 1980), is catalysed by a-CD (/c /k2u = 11) (Tee et al., 1990a), and the degree of transition state stabilization (Xts = 0.18 mM) is similar to that for phenols (Table A4.2) and most of the other substrates (Table A4.4). 

Reactions similar to electrophilic aromatic substitution of 1,4-thiazine carbon atoms with electrophiles are shown below. Compounds 114 and 185 were ring-brominated (Equation 7) <1986LA1648> and 189 and 190 reacted with the electrophilic side chain to give bicyclic products (Equation 8) <1987LA551>. 

Electrophilic aromatic substitution of other benzo-fused v-deficient systems generally follows predictable pathways. Thus, benzopyrylium salts are in general resistant to electrophilic substitution even in the benzo-fused ring. Chromones behave somewhat similarly, although substitution can be effected under forcing conditions. Coumarins, on the other hand, undergo nitration readily in the 6-position while bromination results in substitution at the 3-position as a consequence of addition-elimination. 

Solutions of bromine in thionyl chloride or sulfuryl chloride may not brominate by the usual electrophilic aromatic substitution process (60JA4430). 

Electrophilic aromatic substitutions Quinoline and isoquinoline undergo electrophilic aromatic substitution on the benzene ring, because a benzene ring is more reactive than a pyridine ring towards such reaction. Substitution generally occurs at C-5 and C-8, e.g. bromination of quinoline and isoquinoline. 

Electrophilic aromatic substitution Electrophilic aromatic substitution of indole occurs on the five-membered pyrrole ring, because it is more reactive towards such reaction than a benzene ring. As an electron-rich heterocycle, indole undergoes electrophilic aromatic substitution primarily at C-3, for example bromination of indole. 

Bromination of benzene follows the same general mechanism of the electrophilic aromatic substitution. The bromine molecule reacts with FeBr3 by donating a pair of its electrons to it, which creates a more polar Br—Br bond. 

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