Nitrobenzene electrophilic aromatic substitution

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). 

Electrophilic aromatic substitution of nitrobenzene occurs selectively at the meta position. 

Aniline is an important derivative of benzene that can be made in two steps by nitration to nitrobenzene and either catalytic hydrogenation or acidic metal reduction to aniline. Both steps occur in excellent yield. Almost all nitrobenzene manufactured (97%) is directly converted into aniline. The nitration of benzene with mixed acids is an example of an electrophilic aromatic substitution involving the nitronium ion as the attacking species. The hydrogenation of nitrobenzene has replaced the iron-... 

Exercise 22-24 Draw the structures of the intermediate cations for nitration of nitrobenzene in the 2, 3, and 4 positions. Use the structures to explain why the nitro group is meta-orienting with deactivation. Use the same kind of arguments to explain the orientation observed with —CF3, —CHO, —CH2Ci, and —NH2 groups in electrophilic aromatic substitution (Table 22-6),... 

In another example of an electrophilic aromatic substitution reaction, benzene reacts with a mixture of concentrated nitric and sulfuric acids to create nitrobenzene. 

Friedel-Crafts type reactions of strongly deactivated arenes have been the subject of several recent studies indicating involvement of superelectrophilic intermediates. Numerous electrophilic aromatic substitution reactions only work with activated or electron-rich arenes, such as phenols, alkylated arenes, or aryl ethers.5 Since these reactions involve weak electrophiles, aromatic compounds such as benzene, chlorobenzene, or nitrobenzene, either do not react, or give only low yields of products. For example, electrophilic alkylthioalkylation generally works well only with phenolic substrates.6 This can be understood by considering the resonance stabilization of the involved thioalkylcarbenium ion and the delocalization of the electrophilic center (eq 4). With the use of excess Fewis acid, however, the electrophilic reactivity of the alkylthiocarbenium ion can be... 

Pyrimidine forms 4-bromopyrimidine when the hydrochloride is heated with bromine at 160°C (or at 130°C in nitrobenzene) (73JHC153), the process being preceded by a vigorous reaction at lower temperature (57CB1837 58AG571). It is likely that N-bromo compounds and perbro-mides are implicated in these reactions, which occur (3 to the ring nitrogens, and they are not conventional electrophilic aromatic substitutions. 

Electrophilic aromatic substitution by the nitronium ion gives nitrobenzene. Step 1 Attack on the electrophile forms the sigma complex. 

Nitrobenzene is about 100,000 times less reactive than benzene toward electrophilic aromatic substitution. For example, nitration of nitrobenzene requires concentrated nitric and sulfuric acids at temperatures above 100 °C. Nitration proceeds slowly, giving the meta isomer as the major product. 

Energy profiles with a deactivating group. Nitrobenzene is deactivated toward electrophilic aromatic substitution at any position, but deactivation is strongest at the ortho and para positions. Reaction occurs at the meta position, but it is slower than the reaction with benzene. 

The aromatic nitro group is a deactivating substituent as far as electrophilic aromatic substitution is concerned. Further electrophilic substitution requires vigorous conditions and takes place at the least deactivated position. Thus the preparation of 2,4,6-trinitrotoluene (TNT) from 4-nitrotoluene requires fuming nitric acid and fuming sulfuric acids. Nitrobenzene is sufficiently unreactive towards electrophilic substitution to be used as a solvent for the Friedel-Crafts alkylation of more reactive aromatic systems. 

Nitration (Section 18.4) An electrophilic aromatic substitution reaction in which benzene reacts with N02 to give nitrobenzene, C6H5NO2. 

Electrophilic aromatic substitution. 8. A kinetic study of the Frledel-Crafts benzylatlon reaction in nitromethane, nitrobenzene, and sulfolane. Substituent effects in Friedel-Crafts benzylatlon. J. Am. Chem. Soc. 1984, 106, 7038-7046. 

Electrophilic aromatic substitution is a situation in which it is useful to discuss TS structure in terms of a reaction intermediate. The ortho, para, and meta directing effects of aromatic substituents were among the first structure-reactivity relationships to be developed in organic chemistry. Certain functional groups activate aromatic rings toward substitution and direct the entering electrophile to the ortho and para positions, whereas others are deactivating and lead to substitution in the meta position. The bromination of methoxybenzene (anisole), benzene, and nitrobenzene can serve as examples for discussion. 

All of these effects are observed when comparing the rates of various electrophilic aromatic substitution reactions. Activating substituents increase the rate of reaction relative to benzene. The rate of reaction for the nitration of anisole, for example, was 9.7 x 10 times faster than nitration of benzene. The reaction of anisole with nitric and sulfuric acids, gave 44% of o-nitroanisole, 56% of p-nitroanisole and < 1% of m-nitro-anisole.2 9 contrasts with reactions involving deactivating substituents, where selectivity for the meta -product is usually very good. Nitration of nitrobenzene, for example, gave 1,3-dinitrobenzene in 94% yield, with only 6% of the ortho product and < 1% of the para product. ... 

Nitro groups are meta-directing. Both nitro groups of m-dinitrobenzene direct an incoming substituent to the same position in an electrophilic aromatic substitution reaction. Nitration of m-nitrobenzene yields 1,3,5-trinitrobenzene. 

The answer is A. This reaction is an electrophilic aromatic substitution reaction. The product formed is nitrobenzene. In the reaction, nitronium ion acts as the electrophile which attacks the benzene to form the cyclohexadienyl intermediate, followed by the elimination of the proton to form nitrobenzene. The reaction mechanism follows ... 

Bromination of nitrobenzene is remarkably good, considering the unreactivity of nitrobenzene in electrophilic aromatic substitution. One recipe uses iron powder and bromine at 140 °C and gives 74% of the meta product. We shaU need these reactions in the next section. 

There are several lines of evidence for formation of cr complexes as intermediates in electrophilic aromatic substitution. One particularly informative approach involves measurement of isotope effects on the rate of substitution. If removal of the proton at the site of substitution were concerted with introduction of the electrophile, a primary isotope effect would be observed in reactions in which electrophilic attack on the ring is rate-determining. This is not the case for nitration nor for several other types of aromatic substitution reactions. Nitration of aromatic substrates partially labeled by tritium shows no selectivity between protium- and tritium-substituted sites. Similarly, the rate of nitration of nitrobenzene is identical to that... 

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