Oxidation of the methyl group

FIGURE 24.27 Dicarboxylic acids can be formed by oxidation of the methyl group of fatty acids in a cytochrome P-450-dependent reaction. 

Friedel-Crafts cyclization of phenoxy ether 70 leads to the corresponding xanthone TJ Exhaustive oxidation of the methyl group leads to the carboxyl lie acid, xanoxate (72). ... 

Similar experiments with 1-methyl- and 2-methylnaphthalene involved oxidation of the methyl group to hydroxymethyl and carboxyl groups (Cemiglia et al. 1984a,b). 

Under anoxic conditions, TNT can serve as a terminal electron acceptor (Esteve-Nunez et al. 2000), with utilization of the compound as a source of nitrogen. A number of products were formed by oxidation of the methyl group and loss of nitrite to 4-hydroxybenzoate (Esteve-Nunez and Ramos 1998). 

The formation enthalpies of a few acids and parent hydrocarbons are given in Table 1.6. The oxidation of the methyl group of hydrocarbon to carboxyl group is a highly exothermic reaction. The enthalpy of the reaction... 

Similar reducing effects are obtained from alkali sulfides, hydrosulfides and polysulfides [241]. A peculiar reaction believed to be due to sodium polysulfide formed in situ by refluxing sulfur in aqueous-ethanolic sodium hydroxide is a conversion of p-nitrotoluene to p-aminobenzaldehyde [242]. Oxidation of the methyl group by the polysulfide generates hydrogen sulfide which then reduces the nitro group to the amino group. 

Oxidation of the methyl group in position 2 of the l,8-dioxadibenzo[e,/z]azu-lene system proceeds smoothly resulting in aldehydes. Further LAH reduction gives alcohols 149 in 35-83% yields (Scheme 29, Section 2.2.2 (2006JHC749)). 

Microbiological oxidation of the methyl group in that last intermediate using Aspergillus sclerx>-torium affords oxamniquine (60). 

The degradation pathway of p-cresol in groundwater appears to proceed by oxidation of the methyl group to first give the corresponding benzaldehyde, then benzoic acid (Kuhn et al. 1988 Smolenski and Suflita 1987 Suflita et al. 1988, 1989). The hydroxybenzoic acid then can be either decarboxylated or dehydroxylated to phenol or benzoic acid, respectively. 

Absorption of pentazocine following oral administration is rapid. The onset of action occurs within approximately 15 minutes, and the half-life is 2 to 3 hours. Pentazocine is extensively metabolized in the liver and thus has a high first-pass effect following oral administration its half-life differs considerably from patient to patient. Oxidation of the methyl groups followed by conjugation to glucuronides in the liver terminates the effects of pentazocine. Excretion occurs through the kidney. 

The effect of the electron deficiency at the y-position may be seen in the selective oxidation of the methyl group at position 2 in l-acetylamino-2,3-dimethylquinolizinium ion (47 Scheme 38). A mixture of the aldehyde (48 33%) and acid (49 35%) was obtained <68JCS(C)1082>. 

TNT demethylation has been described previously [5, 6] and different demethylation variants are technologically acceptable the most important is a process including oxidation of the methyl group and subsequent decarboxylation of the carboxyl group formed (Scheme 4.3). 

Bourguignon and coworkers in their preparation of thieno[2,3-6]pyrazine used methyl-pyrazine (364 Scheme 107) (80JHC257) as starting material. The chlorination of (364) yields 2-chloro-3-methyl- and 2-chloro-6-methyl-pyrazine in a ratio of 80 20. Without separation this mixture is treated with ethyl mercaptoacetate in the presence of sodium ethoxide to give (365) in 91% yield (based on 2-chloro-3-methylpyrazine). Oxidation of the methyl group to an aldehyde function and subsequent base catalyzed ring closure yields (366), which is transformed to (363) by the method depicted already in Scheme 106. 

White compd is formed by oxidation of the methyl group, which (as shown above) accounts for 2—3% yield loss, A lab study (Ref 37) showed that this type of oxidation is promoted by the presence of stainless steel turnings, and is greater in two-phase systems such as is present under plant conditions. It was reduced by flushing the system with nitrogen to remove N02, which suggests that this may be the species responsible... 

Oxidation of the methyl group occurs during TNT manuf, with 2-4% of yield loss occurring in this way (Ref 62). Under certain conditions, the alcohol (as its nitrate) and the aldehyde are thus formed they react to form 2,2f-dicarboxy-3,3 f,5,5 -tetranitroazoxybenzene ( white compound ) ... 

Metabolism, Mutagenicity and Carcinogenicity (Refs 14, 33, 34, 39, 46 48). A number of metabolities of TNT were reported in the literature prior to 1974. These were apparently formed by the reduction of nitro groups or by oxidation of the methyl group, and possibly by condensation of hydroxylamine groups produced by reduction (Table 1). Moreover, an unidentified glucuronide was claimed as a major metabolite and was presumed to involve the... 

In practice, zinc chloride was used as the Lewis acid to catalyze the Friedel-Crafts reaction (64% yield). Oxidation of the methyl groups occurs preferentially because the fert-butyl group has no benzylic hydrogens. 

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