Oxidation of the aromatic ring

Additionally, as shown in Table 6.10 (items 5 and 6), strong oxidizing agents applied under vigorous conditions can result in the destruction of the aromatic ring 

A sample of some oxidation reactions of the aromatic ring. Most of the reactions shown do not proceed in good yield. 

Finally, in this vein, oxidation by ozone (O3) followed by reductive hydrolysis (ozonolysis) (Equation 6.76) can be effected on aromatic compounds and, while it occurs less readily than with alkenes, produces results that suggest that the Kekul6 structures are real. 

Problem 6.14. Experimentally, the products of the ozonolysis of 1,2-dimethylbenzene (o-xylene)(Equation 6.76), viz. (a) 2,3-butanedione [biacetyl (CH3CO)2], (b) 2-oxopropanal (methylglyoxal CH3COCHO), and (c) ethane al [glyoxal (HCO) ] are actually formed in different quantities. What is the ratio of products (a) (b) (c) anticipated if they are in fact formed in amounts that reflect the resonance forms of 1,2-dime thylbenzene (o-xylene)  

Animals that have the digestive organ known as the liver appear to utilize the liver monooxygenases to convert benzene (CeU.) and other arenes to epoxides (Table 6.10, item 2) on the way to phenols (Table 6.10, item 2) and quinones (Table 6.10, item 4) that might then be excreted or further oxidized (ultimately to carbon 

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In the production of TNT from the reaction between toluene and mixed acids (nitric/sulfuric), TeNMe forms in amounts between 0.2—0.4% of the total wt of TNT. This TeNMe has been held responsible for several expins which have occurred in TNT plants, causing fatal injuries to personnel and severe damage to facilities. These expins were attributed to the presence of TeNMe in the acid fume lines and the acid storage tanks. Mixts of TeNMe and readily oxidizable materials are known to form very powerful and sensitive expl mixts. Since TeNMe is also isolated from the nitration of Nitrobenzene (NB), the TeNMe formed in the nitration of toluene may arise from the oxidation of the aromatic ring and/or methyl group. In an effort to gain more informa-. tion on the origin of TeNMe from TNT production, radioactive carbon-14 (14C) was used as a tracer to determine the extent to which each of the carbon atoms in the toluene skeleton of the various nitro-substituted isomers contributes to... 

The largest single contribution (54.2%) is from ring carbon-1 attached to the methyl group, and the bulk (94%) of the TeNMe formed is via oxidation of the aromatic ring... 

A solution of 30% aqueous hydrogen peroxide in trifluoroacetic acid is useful for destructive oxidation of the aromatic ring in preference to the side chains as is usual with most oxidants. During work-up operations, the excess peroxide must be catalytically decomposed with manganese dioxide before removal of solvent to prevent explosions. 

Benzylic CH bonds Benzylic CH bonds can be preferentially substituted at the anode by oxidation of the aromatic ring to a radical cation, which can undergo side-chain substitution at the benzylic carbon atom and/or nuclear substitution. Benzylic substitution preponderates, when there is an alkyl substituent at the aromatic carbon bearing the highest positive charge density in the radical cation, while a hydrogen at this position leads to a nuclear substitution [16]. Anodic benzylic substitution is used in technical processes for the conversion of alkyl aromatics into substituted benzaldehydes [17, 18]. Anodic benzylic substitution has been used for the regioselective methoxylation of estratrienone at C9 (Fig. 4) [19]. 

This cycloaddition-reduction-hydrolysis sequence was also used in an approach to butyrolactones related to ribonolactone (71). These compounds are inducing agents of hunger and satiety in mammalians. Here, a subsequent aldol 1,3-diol reduction was used, and the required carboxy function was established by oxidation of the aromatic ring with ruthenium tetroxide. Cycloaddition of benzonitrile oxide to allyl alcohol afforded an enantiomeric mixture of isoxazolines 55 and 56, which were treated with sodium hydride and methyl iodide to achieve separation by chromatography on cellulose triacetate (71). 0-Demethylation, followed by... 

A mechanism involving NO3 as the initial electrophile initiating single-electron oxidation of the aromatic ring followed by coupling between the nitrate anion and the cation radical to form the a complex has been suggested to be operative 270... 

According to our results, the formation of benzyl alcohol, generated from the photooxidation of benzyl radicals (ref.4) could be associated to the presen ce of water. It is of primary importance to be considered that in aqueous sys terns, due to solubility reasons, benzyl alcohol must be easier solved than ben zaldehyde then benzyl alcohol, in the aqueous phase could be photocatalytically destroyed by a drastic photooxidation to C02 and water. In fact, the photocata lytic oxidation of the aromatic ring to CO under UV-irradiation in aqueous emulsions of TiO, have been observed by Izumi et al. (refs. 14-15). It is worthy... 

On the basis of these observations, the NIH shift was attributed to a chemical sequence involving oxidation of the aromatic ring to an arene oxide, opening of the oxide to an ionic intermediate, and finally rearrangement to a phenol with migration of a substituent. When appropriately labeled arene oxides were prepared, shifts to the extent of about 95% were observed. 

Vigorous nitric acid oxidation of strychnine gives 5,7-dinitroindole-2,3-dicarboxylic acid (XV) (158). Its only other application as an oxidizing agent has been in the partial oxidation of the aromatic ring in brucine to give bruciquinone (CXXXV) and its 4-nitro derivative at — 5° (121) and to give cacotheline (CXCI) at 50° 60° (159). 

The values in the last column of Table 1 represent the factors by which the TeNMe concn would increase over that of the total TeNMe arising from the nitration of 2,4- and 2,6-DNT if each of these isomers constituted 96% of the DNJ mixt. Thus, the unsymmetrical Dinitro isomers of toluene, which constitute only 4% of the mixt contribute most heavily to the formation of TeNMe via oxidation of the aromatic ring... 

There are various possibilities, depending on the line you choose for the oxidation of the aromatic ring. It is known that the pathway from shikimic acid involves phenylalanine and perhaps elimination of ammonia (p. 1404) but the stage at which you put the OH groups on the ring is uncertain. 

Gibson, D.T., V. Mahadevan, and J.F. Davey. 1974. Bacterial metabolism of para- and meta-xylene oxidation of the aromatic ring. J. Bacteriol. 119 930-936. 

Results of the rat metabolism studies indicate that, as in cattle, the primary route of metabolism of flunixin is via oxidation of the aromatic ring system(s) and the methyl group on the phenyl ring. Flunixin and the two hydroxylated metabolites,... 

The mechanism of formation has been postulated to involve rapid one-electron oxidation of the aromatic ring by the heme radical cation to give a Tyr radical cation [Eq. (8) (101, 112)]. Using model phenols such species undergo rapid deprotonation to give a phenoxyl radical with rate constants ca. 1010 dm3 mol 1 s 1 (125, 126). Thus, these model studies are consistent with the formation of a radical within the globin polypeptide ... 

Figure 6.18. The NIH shift involving initial formation of an epoxide metabolite in the oxidation of the aromatic ring by cytochrome P450. The starred hydrogen shows that the hydrogen undergoes a 1,2-shift and then is partially lost in the final tautomerization step.

In some instances, particularly in hydroxyla-tions meta to a halide substituent, the hydrogen on the hydroxylated carbon is quantitatively lost (i.e., there is no NIH shift), and a small deuterium kinetic isotope effect is observed These hydroxylations could result from direct oxygen insertion into the C-H bond, as in a true hydrox-ylation mechanism, but they are more likely to result from oxidation of the aromatic ring without the formation of a discrete epoxide intermediate. Isotope effect studies with deuterated benzenes bearing a variety of substituents have shed some light on this process A small, normal isotope effect is observed for weta-hydroxylation when deuterium is located meta- to the halogen in chlorobenzene = 1.1-1.3), but a small,... 

Under similar experimental conditions, the oxidation products of unsaturated compounds with an activated double bond by aromatic substitutent results essentially in cleavage of the double bond with formation of the corresponding carbonyl compounds. However, addition of oxygen leading to epoxide as secondary minor product is observed. In all cases, no oxidation of the aromatic ring is detected (Table 3). 

Irradiation of 2-[N-(pentafluorophenyI)amino]-3-phenylcyclopropenone promotes decarbonylation to give N-(pentafluorophenyl)phenylethynamine and 2-phenyl-3-[N-(pentafluorophenyl)amino]acrylic acid by a process for which there is no known precedent,and the photoextrusion of carbon monoxide from l,3-bis(ethylenedioxy)indan-2-one has been used as the first step in a new synthesis of 1,2-dioxobenzocyclobutene. This represents an unusual example of the decarbonylation of a five-membered cyclic ketone in the preparation of a highly strained and functionalised cyclobutane derivative. The photolysis of a-naphthaleneacetic acid in aqueous solution proceeds by decarboxylation and oxidation of the aromatic ring, and has been carried out at a variety of different wavelengths. The primary step occurs by pseudo-first order kinetics and the optimum photolysis rate has been observed using Ti02 as photocatalyst. Within the cavity of P-cyclodextrin, naproxene (129) has been photodecarboxylated to... 

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