Oxidation and Reduction of Substituted Benzenes

Oxidation and reduction reactions are valuable tools for preparing many other benzene derivatives. Because the mechanisms are complex and do not have general applicability, reagents and reactions are presented only, without reference to the detailed mechanism. 

Arenes containing at least one benzylic C-H bond are oxidized with KMn04 to benzoic acid, a carboxylic acid with the carboxy group (COOH) bonded directly to the benzene ring. With some alkyl benzenes, this also results in the cleavage of carbon-carbon bonds, so the product has fewer carbon atoms than the starting material. 

Substrates with more than one alkyl group are oxidized to dicarboxylic acids. Compounds without a benzylic C-H bond are inert to oxidation. 

Ketones formed as products in Friedel-Crafts acylation can be reduced to alkyl benzenes by two different methods. 

Because both C—O bonds in the starting material are converted to C—H bonds in the product, the reduction is difficult and the reaction conditions must be harsh. 

Problem 18.27 Explain why C6H5CH2CH2Br is not formed during the radical bromination of C6H5CH2CH3. 

Problem 18.28 Draw the products formed when isopropylbenzene [C6H5CH(CH3)2] is treated with each reagent (a) Br2, FeBrsi (b) Br2, hv (c) CI2, FeCIg. 

The radical bromination of alkyl benzenes is a useful reaction because the resulting benzylic halide can serve as starting material for a variety of substitution and elimination reactions, thus making it possible to form many new substituted benzenes. Sample Problem 18.7 illustrates one possibility. 

Sample Problem 18.7 Design a synthesis of styrene from ethylbenzene. 

The double bond can be introduced by a two-step reaction sequence bromination at the benzylic position under radical conditions, followed by elimination of HBr with strong base to fomi the jc bond. 

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The first chapter discusses the concept of aromaticity, after which there is a description of aromatic substitution reactions. Chapters covering the chemistry of the major functionalized derivatives of benzene follow. A chapter on the use of metals in aromatic chemistry discusses not only the chemistry of Grignard reagents and aryllithium compounds but also the more recent uses of transition metals in the synthesis of aromatic compounds. The penultimate chapter discusses the oxidation and reduction of the benzene ring and the text concludes with the chemistry of some polycyclic compounds. 

Secondly, the rates and modes of reaction of the intermediates are dependent on their detailed structure. For example, the stability of the cation radical formed by the oxidation of tertiary aromatic amines is markedly dependent on the type and degree of substitution in the p-position (Adams, 1969b Nelson and Adams, 1968 Seo et al., 1966), and the rate of loss of halogen from the anion radical formed during the reduction of haloalkyl-nitrobenzenes is dependent on the size and position of alkyl substituent and the increase in the rate of this reaction may be correlated with the degree to which the nitro group is twisted out of the plane of the benzene ring (Danen et al., 1969). 

Table 12.4 summarizes the voltammetric oxidation potentials and peak currents for l,4-(MeO)2Ph and other alkoxy-substituted benzenes, phenols, and benzyl alcohols. Only the 1,4-(MeO)2PhX members of the series exhibit an initial irreversible anodic cyclic voltammogram via the sequence of Eq. (12.37). These plus the l,2-(MeO)2Ph isomer yield a metastable product from the second oxidation [species A, Eq. (12.37)] that undergoes a reversible reduction. Thus, the two-electron oxidation of dimethoxy benzenes yields the corresponding quinone. 

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. 

Because of Us high polarity and low nucleophilicity, a trifluoroacetic acid medium is usually used for the investigation of such carbocationic processes as solvolysis, protonation of alkenes, skeletal rearrangements, and hydride shifts [22-24] It also has been used for several synthetically useful reachons, such as electrophilic aromatic substitution [25], reductions [26, 27], and oxidations [28] Trifluoroacetic acid is a good medium for the nitration of aromatic compounds Nitration of benzene or toluene with sodium nitrate in trifluoroacetic acid is almost quantitative after 4 h at room temperature [25] Under these conditions, toluene gives the usual mixture of mononitrotoluenes in an o m p ratio of 61 6 2 6 35 8 A trifluoroacetic acid medium can be used for the reduction of acids, ketones, and alcohols with sodium borohydnde [26] or triethylsilane [27] Diary Iketones are smoothly reduced by sodium borohydnde in trifluoroacetic acid to diarylmethanes (equation 13)... 

Methods of synthesis for carboxylic acids include (1) oxidation of alkyl-benzenes, (2) oxidative cleavage of alkenes, (3) oxidation of primary alcohols or aldehydes, (4) hydrolysis of nitriles, and (5) reaction of Grignard reagents with CO2 (carboxylation). General reactions of carboxylic acids include (1) loss of the acidic proton, (2) nucleophilic acyl substitution at the carbonyl group, (3) substitution on the a carbon, and (4) reduction. 

Regioselective syntheses of 1,3,5-unsymmetrically substituted benzenes (309) are catalyzed by Pd(dba)2/PPh3 mixed alkyne/diyne reactants give mixtures containing homocoupled and mixed products (24 21 from HC CPh + HC=CC= CC Hn). The probable mechanism involves oxidative addition to the Pd(0) center, insertion of the second diyne into the Pd—H bond, reductive coupling and subsequent jr-complexation of this product to Pd(0), followed by Diels-Alder cycloaddition of the third diyne and elimination of product. 

Quinolines have also been prepared on insoluble supports by cyclocondensation reactions and by intramolecular aromatic nucleophilic substitution (Table 15.26). Entry 10 in Table 15.26 is an example of a remarkable palladium-mediated cycloaddition of support-bound 2-iodoanilines to 1,4-dienes. Reduction of the nitro group of polystyrene-bound 2-nitro-l-(3-oxoalkyl)benzenes with SnCl2 (Entry 11, Table 15.26) leads to the formation of quinoline /Y-oxides. These intermediates can be reduced to the quinolines on solid phase by treatment with TiCl3. 4-Quinolones have been prepared by thermolysis of resin-bound 2-(arylamino)methylenemalonic esters [311]. 

Aniline may be made (I) hy Ihe reduction, with iron or tin in HOI, of nitrobenzene, and (2) by the amination of chlorobenzene by healing with ammonia to a high temperature corresponding to a pressure of over 200 atmospheres in the presence of a catalyst (a mixture of cuprous chloride and oxide). Aniline is the end-point of reduction of most mono-nitrogen substituted benzene nuclei, as nitrosobenzene, beta-phenylhydroxylamine. azoxybenzene, azobenzene, hydrazobenzene. Aniline is detected by the violet coloration produced by a small amount of sodium hypochlorite. 

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