Oxidation of aromatic methyl groups

Oxidation of monophenols to polyphenols or oxidation of aromatic methyl groups by persulfates (Caro s acxJ)... 

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. 

A Potthast, T Rosenau, C-L Chen, JS Gratzl. Selective enzymatic oxidation of aromatic methyl groups to aldehydes. J Org Chem 60 4320-4321,1995. 

Oxidation of aromatic alkyl groups. Aromatic methyl or ethyl groups para or ortho2 to an alkoxy function can be oxidized by DDQ in refluxing methanol to aldehydes or methyl ketones, respectively. Simultaneous dehydrogenation can also be effected. ... 

Several procedures for the synthesis of aromatic aldehydes are available which involve the selective oxidation of a methyl group attached to an aromatic ring. A useful general reagent is a solution of chromium trioxide in acetic anhydride and acetic acid. The aldehyde is converted into the gem-diacetate as it is formed and is thus protected from further oxidation. The aldehyde is liberated from the diacetate by hydrolysis under acid conditions the yields, however, are frequently only moderate (e.g. p-nitrobenzaldehyde, Expt 6.117). 

Answer Procedure X-3 which is the oxidation of a methyl group attached to an aromatic ring. A procedure Tor placing an aldehyde function ortho to an -OH group on an aromatic ring is tile Reimer-Tiemann reaction,. It proceeds as illustrated... 

The final reaction in this section provides a method to prepare aromatic rings bonded to a carboxylic acid group. Because we do not have a direct way to attach this group, this procedure is very useful. The reaction is usually accomplished by oxidation of a methyl group to the carboxylic acid employing hot potassium permanganate in basic solution ... 

An oxidizable alkyl group is not necessarily attached to an aromatic nucleus. Oxidation of a methyl group of trimethylacetic acid by heating for 7 hours with alkaline permanganate gives dimethylmaIonic acid (35%). Other examples include the a-keto acids, trimethylpyruvic acid (40%) ° from pinacolone and /3-naphthylglyoxylic acid (40%) from -acetyl-naphthalene. 

Lead dioxide (lead superoxide), PbOj, and red lead, Pb304, are used only to a limited extent. PbOj is used mainly for the oxidation of phenols to quinones [368, 430, 431] and of aromatic methyl groups to carboxyls... 

Laccase can be used to catalyze the oxidation of aromatic methyl or methylol groups to the corresponding aldehydes (where R = Cl, alkoxy, nitro) by oxygen in the presence of a benzothiazoline compound (9.12).158... 

Ring-A-aromatic steroids are formed biologically from androst-4-ene-3,17-dione. A series of enzymes, collectively named aromatases, mediate the stepwise oxidation of the methyl group at position 10 to carboxaldehyde (4-1) (Scheme 3.4). The functionality in ring A in essence consists of a vinylogous p-dicarbonyl function, an array known readily to lose one of the carbonyl carbons. The enzyme ehmination aromatase then catalyzes expulsion of the angular carbonyl function to afford estrone (1-2). 

Meclofenamate sodium is rapidly and almost completely absorbed following oral administration, reaching peak plasma levels within 2 hours. It is highly bound to plasma proteins (99%) and has a plasma half-life of 2 to 4 hours. Metabolism involves oxidation of the methyl group, aromatic hydroxylation, monodehalogenation, and conjugation. Urinary excretion accounts for approximately 75% of the administered dose. The major metabolite is the product of 3 -methyl oxidation and has been shown to possess anti-inflammatory activity (Fig. 36.21). 

Reaction of the arylamine 62 with the complex salt 52 in acetonitrile at room temperature afforded complex 64 in 87% yield (Scheme 17) [125]. Subsequent oxidative cyclization, aromatization and demetalation using iodine in pyridine provided carbazole 65 in 71% yield. Heating of compound 65 in chlorobenzene in the presence of the acidic cation exchange resin amberlyst 15 led to ring closure with formation of the furo[3,2-a]carbazole 66. Oxidation of the methyl group at C-3 to a formyl group using 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ)... 

As another example of the importance of order in electrophilic aromatic substitutions, consider the conversion of toluene to nitrobenzoic acid. The nitro group can be introduced with a nitrating mixture of nitric and sulfuric acids. The carboxyl group can be produced by oxidation of the methyl group (Section 9.4). 

Itoh, A. Kodama, T. Hashimoto, S. Masaki, Y. Oxidation of the methyl group at the aromatic nucleus with molecular oxygen in the presence of A-bromosuccinimide under photoirradiation. Synthesis 2003, 2289-2291. 

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