Mono-a-oxidation

It is useful to compare the spectroscopic data of 1,2,4-triazine mono-A-oxides with the data for the corresponding 1,2,4-triazines. Introduction of an A-oxide group in the 1,2,4-triazine ring changes its physicochemical properties dramatically, and the analysis of these changes allows one to determine which of three nitrogens is oxidized. The most useful method in this case is NMR spectroscopy, including H, C, and N NMR. 

Cycloaddition of 2-nitrosopyridine 48 with nitrile oxides can give either di-A -oxides such as 49 or 3-mono-A -oxides such as 50 (93JHC287). In general, greater electron withdrawing character in the aromatic substituent appears to favor formation of the di-A -oxides. Sulfur ylides such as compound 51 are obtained from aryl isothiocyanates and l-amino-2-methylthiopyridinium iodides (84JCS(P1)1891) nitrogen ylides can be obtained from a similar reaction (86H(24)3363). 

Substituted quinoxalines afford mono-A -oxides, presumably the 1-oxides, and are resistant to further oxidation, though 5-methoxyquinoxaline is exceptional in forming a 1,4-dioxide. In the case of 6-substituted quinoxalines, as the substituent becomes more electron attracting, the yields of 1,4-dioxide decrease but more of the corresponding 2,3-dioxo compound (41) is formed. ... 

There is an extensive literature on the use of 2,1,3-benzoxadiazole 1-oxide [often called benzofuroxanie) (BFO) (462)] as a substrate for the primary synthesis of quinoxaline 1,4-dioxides and occasionally quinoxaline mono-A -oxides or even simple quinoxalines. Very few substituted derivatives of the parent substrate (462) have been employed in recent years. The general mechanism clearly involves a fission (usually amine-catalyzed) of the oxadiazole ring followed by reaction with an ancillary synthon. The following examples are divided according to the type of synthon employed. 

Oxybis(iminomethylfuran) mono-A-oxide (Dehydrofurfural oxime)... 

A-Nitroamino)pyridine A-oxide, 1852 2,2 -bipyridyl 1-oxide, 3258 4-Nitropyridine A-oxide, 1833 2,2 -Oxybis(iminomethylfiu an) mono-A-oxide, 3260 Pyridine A-oxide, 1849... 

Finally, in this section, the reaction of l,2-bis(4-methylbenzylthio)benzene mono-A-oxide 200 with Tf20 in the presence of alkynes and alkenes produces 1,4-benzodithiins 201 and 2,3-dihydro-1,4-benzodithiins 202, respectively (Scheme 17) <2000CC1667>. 

Application of this concept to the metalation with LDA of pyrazine-mono-A-oxides 505 and subsequent quenching with electrophiles led to the formation of substituted products 506 (Scheme 153) [83H(20)154]. 

The reaction of 142 with hydrogen peroxide and acetic acid afforded a mono-A-oxide. However, the position of the A-oxide function was not established.70 The l,6-dimethyl-2-naphthyridinone (143) on similar treatment gave the 5-oxide (144).70... 

During isolation of the di-A-oxide of 2,5-dimethylpyrazine [1] and of the mono-A-oxide of 2,2-bipyridyl [1], prepared by action of hydrogen peroxide in acetic acid on the heterocycles, violent explosions occurred on evaporation of the excess peroxy-acetic acid. In the preparation of 3-bromopyridine A-oxide, the necessity to take adequate precautions against the possibility of explosion while vacuum distilling off excess reagents from a water bath maintained at 50°C is stressed [3]. For a method not involving this considerable explosion risk,... 

Cyclic sulfimidates can be easily oxidized to the corresponding sulfamidates. The preparation of sulfamidates from tvV-aminoalcohols can be achieved in one step without isolation of intermediate mono-A-oxides (Equation 37) <20010L405, 2002TL1915, 2005TA1583>. Yields are from moderate to high. 

Thin-layer chromatography indicates that prolonged reaction of pyrazine 1,4-dioxide with acetic anhydride gives the mono-iV-oxide, together with other unidentified products.406 Pyrazine mono-A-oxide is also formed on reaction of pyrazine-2-carboxylic acid 4-oxide with acetic anhydride.408... 

Many pyrazine and quinoxaline syntheses yield mono- or di-AT-oxides (76H(4)769). The condensation of a-aminooximes with 1,2-diketones results in the direct formation of pyrazine mono-A/ -oxides. The a-aminooximes themselves are not easily prepared but 2-amino-2-deoxy sugars readily form the oximes, which have been condensed with glyoxal to yield the pyrazine 4-oxides (Scheme 18) (72JOC2635, 80JOC1693). 

Phenazine mono-A/-oxides have also been prepared from nitrobenzene derivatives. Condensation of nitrobenzene with aniline using dry NaOH at 120-130 °C results in modest yields of phenazine 5-oxide, although the precise mechanism of this reaction is not well understood <57HC(ll)l) with unsymmetrical substrates it is not possible to predict which of the isomeric N-oxides will be produced. Nitrosobenzene derivatives also function as a source of phenazine mono-Af-oxides thus, if 4-chloronitrosobenzene is treated with sulfuric acid in acetic acid at 20 °C the AT-oxide is formed (Scheme 21). 

Cyclization of amidines 1 to the corresponding quinoxalin-3-amine 1-oxides 2 can be readily achieved by reaction with bases. This ring closure occurs via deprotonation of the benzyl group and intramolecular nucleophilic addition to the nitro group giving structurally definite compounds, in contrast to the mono-A -oxidation reaction of the parent hcterocycles (sec Section6.3.2.1.4.1.). ... 

Irradiation of phenazine mono-A -oxide with ultraviolet light in different solvents (e.g., acetonitrile, benzene) affords a mixture of products 1 and... 

Whereas pyrazine and alkylpyrazines exhibit an absorption at about 260-270 nm in water, their mono A -oxides show two peaks, one about 215 nm, and the other about 260 nm, which are characteristic of the presence of an A -oxide function (838). The u.v. absorption maxima of pyrazine A -oxide moved to shorter wavelengths from that in heptane as the polarity was increased in ethanol and water (1481). Band analyses of pyrazine mono- and di-A -oxides have been carried out (627). 

A study of the a-arylation of diazine mono A-oxides, under Heck-like conditions, also gave emphasis to pyrazines but a number of examples using pyrimidines and pyridazines were also described (Scheme 1). A wide range of aryl chlorides, bromides and iodides was used and the products were easily deoxygenated by catalytic reduction. An interesting feature was the use of a copper additive, which was only required for the pyrimidine reactions, to give a very substantial improvement in yield <06AG(I)7781>. 

Dming isolation of the di-A-oxide of 2,5-dimethyIpyrazine [1] and of the mono-A-oxide of 2,2-bipyridyl [1], prepared by action of hydrogen peroxide in acetic... 

Dinitrobiphenyl. on mild reduction in the presence of an aged Raney nickel catalyst, is converted into a benzocinnoline dioxide. The mono-A -oxide is formed as a minor product from some dinitrobipyridyis. 

The parent pyrido[3,4-c/]pyridazine upon oxidation by 3-chloroperoxybenzoic acid in chloroform at room temperature gives the three mono-A-oxides.163... 

A route in which a synthon for such a dialdehyde is central depends on ortho lithiation of an aryl bromide for conversion to ortho bromoaryl aldehyde, then palladium-catalysed replacement of the halide with an alkyne, subsequent reaction with ammonia producing the isoquinoline. The sequence below shows how this type of approach can be used to produce naphthyridine mono-A-oxides by reaction of the alkynyl-aldehyde with hydroxylamine instead of ammonia. 

The reaction conditions are generally milder for the Pd-catalyzed hydrogenation of heterocycles. In many instances the use of Pt or Rh catalyst is not as selective as with Pd catalyst. For the bipyridyl mono A -oxide system, hydrogenation of the pyridine A -oxide ring is preferred over the pyridine ring (Scheme 47). ° ... 

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