Selenium dioxide, oxidation methyl group

Oxidation of 6-methylphenanthridines with potassium dichromate in acetic acid results in oxidative loss of the methyl group, the product being the phenanthridone (e.g. 67 Scheme 62) (61JCS3771). If a second methyl group is present it remains unchanged. Selenium dioxide oxidizes the 6-methyl group to the aldehyde. 

Methyl groups in the 2-, 4- or 6-position of pyrimidine are also more reactive. In addition to typical reactions such as condensation with benzaldehyde, selenium dioxide oxidation and halogenation, they can be converted into oximino groups by nitrous acid, and undergo Claisen condensation with (C02Et)2. In the reaction of 2,5-dimethylpyrimidine with benzaldehyde, only the electrophilic 2-methyl group reacts preferentially to yield the 2-styryl derivative (631). In quinazolines partial double bond fixation makes a methyl group in the 4-position more reactive than that in the 2-position. 

Scheme 2 shows Rapoport s synthesis [15]. The cinnamic acid derivative 3 prepared from m-methoxy benzaldehyde [20] was ethylated by diethyl sulfate to give ethyl cinnamate derivative 4, followed by Michael addition with ethyl cyanoacetate to afford compound 5. Compound 5 was converted to lactam 6 by the reduction of the cyano group and subsequent cyclization. Selective reduction of the lactam moiety of 6 was achieved by treatment with trimethy-loxonium fluorob orate followed by sodium borohydride reduction. Amine 8 was obtained by the reductive methylation of amine 7. Amine 8 was converted to compound 9 by methylene lactam rearrangement [21], followed by selenium dioxide oxidation to provide compound 10. Allylic rearrangement of compound 10 and subsequent hydrolysis gave compound 12. The construction of the decahydroisoquinoline structure began with compound 12,... 

Two further papers report lithium-ammonia reductive cleavage of some A3-THC-related compounds374 and selenium dioxide oxidation of A -THC and A6-THC.375 In the latter, it is shown that A -THC yields oxidation products predominantly from attack at C-6, whereas A6-THC is oxidized preferentially at the exocyclic allylic C-7 methyl group, to yield, for example, (269). 

Some 16-substituted cardenolides have also been prepared.16) -Methyl-3/ -acetoxy-17a-pregnan-20-one (514) was converted into the unsaturated ester (515) by a Reformatsky reaction followed by dehydration. Selenium dioxide oxidation then gave the 16)S-methyl-17a-cardenolide (516). In the same way, 16a-cyano-3/3-acetoxy-17/l-pregnan-20-one (517) was transformed to the 16a-cyano-17)S-cardenolide (518). Failure to achieve the Reformatsky reaction on (519) was explained as a result of steric interference by the 16a-methyl group. 

Comparatively little information is available concerning purine methyl groups, but it seems ° that then-reactivity is comparable to pyridine a- and y-methyl substituents, undergoing base-catalysed condensations and selenium dioxide oxidation to aldehydes. 

Alkyl Isoquinolines. Coal tar contains small amounts of l-methylisoquinoline [1721-93-3] 3-methylisoquinoline [1125-80-0] and 1,3-dimetliylisoquinoline [1721-94-4J. The 1- and 3-methyl groups are more reactive than others in the isoquinoline nucleus and readily oxidize with selenium dioxide to form the corresponding isoquinoline aldehydes (174). These compounds can also be obtained by the hydrolysis of the dihalomethyl group. The 1- and 3-methyhsoquinolines condense with benzaldehyde in the presence of zinc chloride or acetic anhydride to produce 1- and 3-styryhsoquinolines. Radicals formed by decarboxylation of carboxyUc acids react to produce 1-aIkyhsoquinolines. 

Methylpyridazine can be oxidized with selenium dioxide to give 3-formylpyridazine, and methyl groups attached to any position in pyridazine N-oxides are transformed with pentyl nitrite in the presence of sodium amide in liquid ammonia into the corresponding... 

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)... 

The pyridine-N-oxide 245 was converted into the cyanopyridine 246 and its isomer (Scheme 80). Grignard reaction, Fischer s indole synthesis, and N-protection gave a pyridinyl indole 247. Selenium dioxide selectively oxidized the methyl group to give the isonicotinic acid. The synthesis of Flavocarpine (244) was finally accomplished by a set of standard reactions as outlined in Scheme 80 (87TL5259). 

Oxidation of 2,3-dimethylquinoxaline (from phenylenediamine and diacetyl) with either peracids or hydrogen peroxide in acetic acid gives the 1,4-dioxide (162). Treatment of this bis-N-oxide with selenium dioxide leads to oxidation of one of the methyl groups to the methyl carbinol and formation of... 

Methyl-2-vinylbenzofurans also undergo cycloaddition with acetylenic dienophiles, but ready aromatization of the products is blocked by the angular methyl group. It can, however, be achieved by oxidizing agents, such as selenium dioxide or chromium trioxide, or even by exposure to air (Scheme 35). Mechanisms for these reactions have been postulated. 

Methyl groups at positions 2 and 4 in quinoline are selectively oxidized by selenium dioxide (76BSF789). For example, 2,3,8-trimethylquinoline gives 3,8-dimethylquinoline-2-carbaldehyde (Scheme 61). 

With methyl-3-nitropyridine iV-oxides, use of selenium dioxide results in complete oxidative demethylation (80TL2433). In isoquinoline methyl groups at positions 1 and 3 are efficiently oxidized to the corresponding aldehyde with selenium dioxide. 

Oxidation of 2-Butene with Selenium Dioxide. The stoichiometry of the reaction of 2-butene with selenium dioxide shows that approximately 0.85 mole of l-acetoxy-2-butene plus 0.85 mole of bis(l-methyl-2-acetoxypropyl) selenide are produced per mole of selenium dioxide consumed. This suggests that, at least for this particular group of olefins, in the mechanism of olefin oxidation with selenium dioxide the formation of selenides should be considered as the final reduced state of the oxidant rather than elemental selenium. 

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