Hydroxymethyl group, oxidation

The hydroxymethyl group m 3-(perfluoro-l,l-dimethylbutyl)propan-l-ol is oxidized to a carboxylic group by potassium permanganate m the presence of a phase-transfer catalyst [3d] (equation 41)... 

The methyl group m 3-methyl-4,5,6,7-tetrafluoroindoles is oxidized to an aldehydic or a hydroxymethyl group with high selectivity by selenium dioxide [90] (equation 83)... 

All of these ehimnddon reacdons contain fi-carbonyl groups in the nltro compounds Of course, masked carbonyl groups are also frequently employed for such fi-elimination of HNO, as shown in Eq 7131, Eq 7 133, and Eq 7 133In these cases, the sulfinylmethyl or hydroxymethyl group is converted into the carbonyl group by the Pummerer rearrangement or by simple oxidation... 

Another beautiful example of an early domino process is the formation of daphnilactone A (0-19), as described by Heathcock and coworkers [17]. In this process the precursor 0-17 containing two hydroxymethyl groups is oxidized to give the corresponding dialdehyde, which is condensed with methylamine leading to a 2-azabutadiene. There follow a cycloaddition and an ene reaction to give the hexacycle 0-18, which is transformed into daphnilactone A (0-19) (Scheme 0.6). 

In a similar way, a-nitroselenides are prepared via the reaction of nitronates with phenylse-lenyl bromide, which gives a new synthetic method of l-nitroalkenes from nitroalkanes.130 The sequence of a-selenation, nitro-aldol reaction, and oxidation provides a useful method for the preparation of nitroalkenes with a hydroxymethyl group (Eq. 5.81).131... 

Hydroxymethyl phosphines are susceptible to oxidation to form the phosphine oxide derivative. Therefore, avoid excess oxygen, oxidizing agents, or azide compounds, which react with phosphines in the Staudinger reaction (Chapter 17, Section 5). In addition, metallic surfaces can be modified via the phosphine group to result in hydroxymethyl group substitutions. 

Obata and Yamanishi106 employed several mild oxidizing agents, without success, in their attempts to oxidize the hydroxymethyl group of kojic acid to a formyl group. 

Early observations by Heyns established that selective oxidation of carbohydrates is possible for example, the hydroxymethyl group involving C-l in L-sorbopyranose could be converted into a carboxyl... 

Chromium trioxide in pyridine selectively oxidizes the hydroxymethyl groups in thymidine, 2 -deoxyadenosine, 2 -deoxyguano-sine, and 2 -deoxycytidine to carboxyl groups,525 but the partial liberation of the free, heterocyclic bases in the reactions suggested that oxidation at C-3 also occurs to some extent. 

The chirality of compound 16b was completely inverted, to give 2,3-0-cyclohexylidene-L-ribonolactone (19), by means of a procedure (28) that involves oxidation of the hydroxymethyl group of 16b by ruthenium te-traoxide, followed by reduction of the lactone group. The resulting intermediate 1,5-lactone (18) underwent isomerization (with cyclohexylidene migration) upon refluxing in xylene, in the presence of a catalytic amount of D-camphorsulfonic acid [in Ref. (28) the formulas for the series were erroneously depicted]. 

The synthesis of L-ribofuranose derivatives from 16a has been carried out by Walker and Hogenkamp (35). The procedure involves oxidation of the hydroxymethyl group of 16a with dimethyl sulfoxide N,N dicyclohexylcarbodiimide and acid hydrolysis of the protecting group to give L-riburonic acid, which was converted into methyl (methyl a,/ -ribofurano-sid)uronates (26). Reduction of 26 with sodium bis(2-methoxyethoxy)alu-minum hydride gave the chromatographically separable anomers of methyl L-ribofuranoside (27). 

The hydroxymethyl group in a position a to the heterocyclic nitrogen is sensitive to further oxidation and tends to form an oxidative dimer product [Eq. (45)]. 

The reaction of 3-hydroxymethyIpyridine 1-oxide with methyl fluorosulfonate and potassium cyanide provides a direct method for 2,6-dicyanation (75JOC2092). However, the generality of this method is limited by the need for a 3-substituent that can form an anhydrobase. In this example (Scheme 138) the anhydrobase is formed by methylation of the 3-hydroxymethyl group followed by elimination either during or subsequent to attack by the second mole of cyanide. The use of such a powerful methylating agent overcomes... 

Tolfenamic acid is used as an injectable formulation in cattle and swine. In rats and target animals, tolfenamic acid is metabolized by hydroxylation either of the methyl or the methylchlorophenyl group producing two metabolites further oxidation of the hydroxymethyl group to the corresponding aldehyde or carboxylic acid can produce two additional metabolites. The two hydroxylated metabolites of tolfenamic acid, N-(2-hydroxymethyl-3-chlorophenyl)-anthranilic acid and N-(2-hydroxymethyl-3-chloro-4-hydroxyphenyl)-anthranilic acid, are much less potent than the parent compound in terms of anti-inflammatory and analgesic... 

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