Carboxylic methyl groups , oxidation

Experiments with C- and H-acetate showed that the methyl group of acetate is the major precursor of methane and the carboxyl-carbon is oxidized to CO2, providing electrons for reduction of the methyl-carbon to CH4 [7,231,232]. However, Krzyeki et al. [233] showed that 14% of the methane produced by whole cells of an acetate-adapted strain of M. barkeri originated from the carboxyl-carbon, and an equivalent amount of CO2 came from methyl-group oxidation the reduction of carboxyl-carbon to methane has also been observed in extracts [7,234]. 

This implies that only the 2-methyl group is sufficiently active to undergo oxidation to a carboxylic acid intermediate that then undergoes rapid decarboxylation. 

On account of the high degree of stability of the thiazole ring a large variety of substituted derivatives yield thiazolecarboxylic acids upon oxidation. The oxidation of a methyl group or a substituted methyl group to a carboxyl group has been accomplished in a few instances. 

Because it may be oxidized to a carboxyl group (Section 11 13) a methyl group can be used to introduce the nitro substituent m the proper position... 

Methyl groups in pyridopyrazines (64IMC240) and pyridopyrazinones (71TH21500) are oxidized to carboxylic acids with potassium permanganate. Aryl carbinol substituents are also very readily oxidized to benzoyl derivatives in alkaline conditions (76CPB238). Bromina-tion of 2,3-dimethylpyrido[3,4-f ]pyridazine gives the 2,3-bisbromomethyl derivative, whilst... 

In man, the metabolic pathways of mepirizole were distinct from those in experimental animals, since hydroxylation on each of the aromatic rings did not occur in man. Compound (752) was obtained by oxidation of the 3-methyl group to the carboxylic acid (a similar process occurs with 5-methylpyrazole-3-carboxylic acid, an active metabolite of 3,5-dimethylpyrazole). However, the carboxylic acid metabolite of mepirizole had no analgesic activity and did not decrease blood glucose. 

A number of alkyl and dialkyl (mainly methyl) benzofuroxans are known. The 4-methyl compound resisted attempts to brominate the methyl group and to oxidize it to the carboxylic acid. ... 

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 treatment of an arenediazonium salt with CuCN yields the nitrile, ArCN, which can then be further converted into other functional groups such as carboxyl, for example, Sandmeyer reaction of o-methylbenzenediazonium bisulfate with CuCN yields o-methylbenzonitrile, which can be hydrolyzed to give o-methylbenzoic acid. This product can t be prepared from o-xvlene by the usual side-chain oxidation route because both methyl groups would be oxidized. 

Another class of hydrocarbon binders used in propints are the carboxy-terminated polybutadiene polymers which are cross-linked with either tris[l-(2-methyl)aziridinyl] phosphine oxide (MAPO) or combinations with phenyl bis [l -(2-methyl)aziridinyl] phosphine oxide (Phenyl MAPO). Phenyl MAPO is a difunctional counterpart of MAPO which makes possible chain extension of polymers with two carboxylic acid groups. A typical propint formulation with ballistic properties is in Table 11 (Ref 83) Another class of composites includes those using hydroxy-terminated polybutadienes cross-linked with toluene diisocyanate as binders. The following simplified equations illustrate typical reactions involved in binder formation... 

It has been shown already that C-2 of ribose is the precursor of the methyl group, and C-l is eliminated in the biosynthesis. The following observation can be pertinent to the point. Pyrimidine (58) is very unstable and quickly decar-boxylates in aqueous solution at room temperature to give pyramine (Scheme 32).67 Thus, if a C-l -C-2 fragment of the ribose part of AIRs became attached by C-2 to C-2 of a pyrimidine, oxidation of C-l to produce a carboxylic acid function could result in its smooth elimination. 

In the absence of bromide ion the p-xylene undergoes rapid autoxidation to p-toluic acid but oxidation of the second methyl group is difficult, due to deactivation by the electron-withdrawing carboxyl group, and proceeds only in low yield at elevated temperatures. Although bromide-free processes were subsequently developed (ref. 5) they require the use of much higher amounts of cobalt catalyst and have not achieved the same importance as the Amoco-MC process. Indeed, the... 

In the oxidation of p-xylene the first methyl group undergoes rapid autoxidation to afford p-toluic acid (Fig. 8). The second methyl group is, however, deactivated by the electron-withdrawing carboxyl group, and further oxidation of p-toluic to terephthalic acid is much slower, i.e. the relative reactivities of toluene and p-toluic acid are 26 1 (Fig. 8). It is not surprising, therefore, that the autoxidation of p-xylene to terephthalic acid proved to be a difficult proposition. 

Both the (+)- and (-)- enantiomers of limonene were transformed by larvae of the cutworm Spodop-tera litura (Miyazawa et al. 1998). For both of them the reactions involved are (a) dihydroxylation between C-8 and C-9 and (b) oxidation of the C-1 methyl group to carboxyl. These transformations were not dependent on the intestinal microflora in contrast to the transformation of a-terpinene to p-mentha-l,3-dien-7-ol and p-cymene whose formation could be attributed to the intestinal flora. 

The transformation of sulfonylureas by Streptomyces griseolus grown in a complex medium containing glucose when the methyl group of the heterocyclic moieties is hydroxylated, and for some substrates, subsequently oxidized to the carboxylic acid (Romesser and O Keefe 1986 O Keefe et al. 1988). 

Althongh the degradation of naphthalene-2-carboxylate by Burkholderia sp. strain JT 1500 involves the formation of 1-hydroxy naphthalene-2-carboxylate, this is not formed from the expected (l/ ,25)-di-l,2-dihydrodiol-2-naphthoate. Possibly, therefore, the reaction is carried out by a monooxygenase, or a dehydration step is involved. Subsequent reactions produced pyruvate and o-phthalate that was degraded via 4,5-dihydroxyphthalate (Morawski et al. 1997). Degradation of naphthalene carboxylates formed by oxidation of methyl groups has already been noted. 

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

Scheme 12.22 provides some examples of the oxidation of aromatic alkyl substituents to carboxylic acid groups. Entries 1 to 3 are typical oxidations of aromatic methyl groups to carboxylic acids. Entries 4 and 5 bring the carbon adjacent to the aromatic ring to the carbonyl oxidation level. 

---