Oxidative Cleavage of the Benzene Ring

The breakdown of the benzene ring to aldehydes is extremely rare and has been achieved only by ozone. A historical and classical example is the disintegration of o-xylene to a mixture of glyoxal, methyl glyoxal, and diacetyl (butanedione) in the predicted ratios [104]. From the preparative point of view, the conversion of phenanthrene into 0,0 -diformyl-biphenyl (diphenaldehyde) [1123] or o-formylbiphenyl-o -carboxylic (diphenaldehydic) acid [1124] is more important (equation 154). 

The conversion of the benzene ring in benzene homologues to carboxylic groups is encountered rarely and has hardly any preparative value. One example involves the treatment of a-truxillic acid with ozone and subsequent oxidation with hydrogen peroxide (equation 155) [109]. 

The reagent of choice for the oxidation of phenyl groups to carboxyls seems to be ruthenium tetroxide with sodium periodate [231, 941] or sodium hypochlorite [701] as reoxidants. Phenylcyclohexane is oxidized to cyclohexanecarboxylic acid (equation 156) [774, 941], and -phenylpro-pionic acid is transformed mainly into succinic acid (equation 157) [701]. 

The degradation of benzene rings to carboxyls is facilitated by the presence of electron-donating groups. m-Trifluoromethylaniline is converted into trifluoroacetic acid in 90-95% yield on heating with sodium dichromate and dilute sulfuric acid for 30-40 min at 70-170 °C [638]. 

Condensed polynuclear hydrocarbons and aromatic heterocycles are converted into dicarboxylic acids. Naphthalene is oxidized to phthalic an- 

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Oxidation affects both rings of the quinoline system. Alkaline permanganate causes oxidative cleavage of the benzene ring in quinoline and 2-substituted quinolines to give pyridine-2,3-dicarboxylic acid 39 (R = H quinolinic acid). In contrast, acidic permanganate oxidizes the pyridine ring with formation of A-acylanthranilic acid 40 ... 

Although the free phenolic structures are oxidized faster, chlorine dioxide also destroys nonphenolic phenyl propane units and double bonds present in the pulp chromophores. After cleavage of the benzene ring various di-carboxylic acids are formed, such as oxalic, muconic, maleic, and fumaric acids in addition to products substituted with chlorine (Fig. 8-10). As a result of depolymerization and formation of carboxyl groups the modified lignin is dissolved during the chlorine dioxide treatment and in the sodium hydroxide extraction stage that usually follows. 

Both these series of bicyclic compounds have been used as important starting materials for the preparation of pyrazines by the oxidative removal of the benzene ring from quinoxaline and by cleavage of the pyrimidine ring in pteridines. Both preparative procedures are discussed in detail in Sections 4 and 5. 

It will be noted that in all of the cases which have been described thus far, cleavage of the benzene ring takes place only after the six valencies of the ring carbon atoms have been saturated by the addition of chlorine or hydrogen and that for the most part such oxidations have been studied only in the liquid phase. 

Irradiation of 2-phenylbenztriazole in aerated solvents leads remarkably to cleavage of the benzene ring and formation of 2-phenyl-l,2,3-triazole-4,5-dicaiboxylic acid (Amiet et al.). Ylidions, a new class of reactive intermediates, have been generated by photo-oxidation of phenacylsulphonium ylides using 9,10-dicyanoanthracene as sensitizer (Zhang and Schuster). 

Metabolism 3,4-D. is formed from tyrosine by means of tyrosine 3-monooxygenase (EC 1.14.16.2.) and tet-rahydrobiopterin. DOPA is a biosynthetic precursor of dopamine, noradrenaline, and adrenaline. It is used for therapy of Parkinson s disease (dopamine deficiency). Oxidation and subsequent polymerization lead to the formation of melanins. Extradiol cleavage of the benzene ring gives rise to betalamic acid, " stizolobic acid, stizolobinic acid, muscaflavin, etc. 3,4-D. is toxic for the development of certain insects and for the reproduction of the duckweed Lemna minor. ... 

Cleavage of the benzene ring of the hydroxyanthranilic acid moiety and conversion of the intermediate to nicotinic acid, picolinic acid, and quinolinic acid are very important steps in the metabolism of tryptophan. In addition to the formation of the above compounds, ring cleavage is part of the probable pathway for the complete oxidation of the hydroxyanthranilic acid to CO2 in vertebrates (323). 

Mestdagh, H. and VoUhart, K. P. C., Photo-oxidation of 2,3,7,8-tetrakis(trimethylsi-lyl)benzo[3,4]cyclobuta(l,2-fo]biphenylene in the presence of oxygen. Unusual cleavage of the benzene ring to generate an alkyne unit, /. Chem. Soc., Chem. Common., 281,1986. 

This versatile solvent has good chemical stability in the absence of acids and bases which catalyse the cleavage of the lactam ring. It is most conveniently dried by initial azeotropic distillation with previously dried benzene or toluene as described for DMF, and the residual liquid is shaken with barium oxide, the desiccant is removed and the solvent is fractionally distilled under reduced pressure (c. 20 mm). The pure solvent has b.p. 94-96 °C/20 mmHg, or 202 °C/760mmHg. 

Much has already been published on the irradiation of pyridine N-oxides and related compounds consistent with many observations, 6-cyanophenanthridine IV-oxide (60) was shown some years ago to give good yields of (61) on irradiation in acetone or benzene solution. In the presence of 2,3-dimethylbut-2-ene, however, irradiation of (60) produces a very different type of reaction for which there is no precedent.Thus (62) is formed in 35% yield via a process which involves cleavage of the heterocyclic ring, shift of the oxygen atom from nitrogen to the neighbouring carbon, and addition of the ethylene. 

An additional application of l-exo Heck cyclization was found in Kelly s synthesis of maxonine (223), which was isolated from the root of a plant Simira maxonii endemic to the Costa Rican tropical forest. As shown in Scheme 39, the migratory insertion step of the intramolecular Heck cyclization of substrate 220 took place to both the pendant olefin and the benzene ring of the indole moiety simultaneously, giving rise to dihydropyridine 221 and seven-membered 222, respectively [104]. Oxidative cleavage of the stilbene double bond in 222 produced maxonine (223), which was identical to authentic maxonine. Kelly s synthesis of maxonine (223) revised the original structural assignment of the natural indole alkaloid. 

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