Nitrosopyridines

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). 

Reactions of 2-nitrosopyridine with nitrile oxides afford, depending on structure of the latter, either l,2,4-triazolo[l,5-a]pyridine 1,3-di-N-oxides (370) or the corresponding 1.2.4-triazolo, 5-a Ipyridine 3-oxides (371) (419). 

A reversible reduction of nitropyridines,429,430 e.g., 280 in acidic, aqueous ethanol at -TC leads [Eq. (145)] to the corresponding dihydroxylamine (281), which produces the corresponding nitrosopyridine (282) by elimination... 

Ready addition of 2-nitrosopyridine to 1,3-dienes gives 3,6-dihydro-1,2-oxazines, e.g. (774) — (773), and condensation with aromatic amines gives azo compounds, e.g. (774) — (775). Nitroso compounds are oxidized by ozone or sodium hypochlorite to the corresponding nitro compounds. 5-Nitrosopyrimidines can be reduced to the 5-amino derivatives or condensed with activated methylene groups. 

Diels-Alder reaction of onitrosobenzamide and 1,3-DIBF (no mp and spectral data given, only HRMS 93BSF101). Taylor and co-workers reported Diels-Alder type reactions of 1,3-DIBF and nitrosopyridines [82JOC552]. A Diels-Alder adduct of 1,3-DIBF and an azetidinone rearranges thermally to a ring opened product (92CJC2792). Whereas... 

The 4 + 2-cycloaddition of 2-substituted 1,2-dihydropyridines with nitrosoben-zene produces [2.2.2]bicycloadducts, which are readily reduced by alane to trans-2-substituted 3-amino-l,2,3,6-tetrahydropyridines stereospeciflcally.123 The intramolec- (g) ular nitroso-Diels-Alder reaction of a-acetoxynitroso derivatives in aqueous medium produces 3,6-dihydro-l,2-oxazines in high yield.124 The nitroso-Diels-Alder reaction of acyclic OTIPS-dienes (115) and 6-methyl-2-nitrosopyridine (114) in the presence of (g) [Cu(MeCN)4(difluorosegphos)]PF6 yielded the dihydro 1,2-oxazine cycloadduct (116) with high yield and enantioselectivity (Scheme 33). 125 (Fe)... 

Methyl-2-nitrosopyridine reacted with (lZ,3Z)-cycloocta-l,3-diene to give the iV-pyridyl-l,2-oxazocine 132. Such a Diels-Alder reaction was conducted in the presence of a catalytic amount of an asymmetric bidentate ligand and a metal to provide an enantiomerically enriched cycloadduct however, the ee observed was only 4% (Equation 11) <2005WO068457>. 

Many other examples exist for this form of reaction such as the reduction of 4-nitropyridine to hydroxylamine via 4-nitrosopyridine in aqueous media (Laviron et al., 1992) which has been described as proceeding via an overall ECE mechanism (Nadjo and Saveant, 1973). 

Reactions which formally involve the oxidation of azides have been reviewed by Boyer. Other oxidations with useful synthetic applications include two which start from nitrogen ylides. Sulfimides (50) derived from electron-deficient aromatic and heterocyclic amines are oxidized to the corresponding nitroso compounds by MCPBA. - This is a very useful method of preparation of some otherwise inaccessible nitroso compounds such as 2-nitrosopyridine and 1-nitrosoisoquinoline. They can be further oxidized, for example by ozone, to the nitro compounds. Phosphimides (51) are oxidized directly by ozone to the nitro compounds, although the nitroso compounds are intermediates. Isocyanates can also be oxidized to the corresponding nitro compounds, by dimediyldioxiraiK (1). ... 

Nitrosopyridine-2,6-diamine (5 g, 36.2 mmol), benzyl phenyl ketone (6.5 g, 33 mmol) and ethanolic NaOEt (from Na, 0.8 g, and EtOH, 150 mL), were refluxed together for 24 h. Recrystallization (EtOH) gave bright-yellow needles yield 4.1 g (38%) mp271 °C. 

The major route to these compounds involves condensation of 2,3-diaminopyridines with a-dicarbonyl compounds. Other methods of forming the pyrazine ring have occasionally been employed. These are particularly useful when the products from the standard condensation are of uncertain orientation. Such approaches have made use of the condensation of 2-amino-3-nitrosopyridines with compounds containing active... 

The reaction of 2-amino-3-nitrosopyridines with compounds containing an activated methylene group permits unambiguous synthesis of various derivatives of pyrido[2,3-b]pyrazine. For example, the pyridine 58 reacts in the presence of sodium ethoxide with a variety of arylacetonitriles and cyanoacetic acid derivatives to provide various 2-substituted 3-amino compounds (59). " " Diethyl malonate reacts similarly to give the 2-carboxylic acid 60, its ester being presumably hydrolyzed in the alkaline reaction conditions. Ethyl acetoacetate yields the 2-acetyl-3-oxo compound 61, and acetylacetone ° provides the 2-acetyl-3-methyl compound 62. The latter condensation proceeds poorly in ethanolic sodium ethoxide, but heating the nitroso compound with acetylacetone under reflux in pyridine gives a 59% yield of the product 62. °... 

Andersen, R.A., P.D. Fleming, H.R. Burton, T.R. Hamilton-Kemp, and T.G. Sutton V-Acyl and V-nitrosopyridine alkaloids in alkaloid lines of burley tobacco during growth and air-curing J. Agr. Food Chem. 37 (1989)44-50. 

Aq. SO -HaOa added dropwise below 35° during 1.5 hrs. to a stirred soln. of 2,6 diamino-3 nitrosopyridine in trifluoroacetic acid, and stirred 6-11 hrs. at room temp. -> 2,6 diamino-3-nitropyridine. Y 96%. — Similarly with simultaneous C - hydroxy la tion 4,6-Diamino - 5 - nitrosopyrimidine 4,6 - diamino - 2-... 

The second example of enantiodiveregent hetero-Diels-Alder reaction is shown in Scheme 6.28. Thus, racemic cyclohexadiene 132 was reacted with 2-nitrosopyridine 133 in the presence of a copper(I) source and the chiral phosphine ligand 134 to afford regioisomeric hetero-Diels-Alder products 135 (48% and 97% ee) and 136 (52% and 92% ee) [49b]. The Cu(I) complex of 134 functions as a chiral Lewis acid that catalyses the 2-1-4 cycloaddition. 

Nitropyridine-l-oxide undergoes reduction with phenylhydrazine to give 4-hydroxylaminopyridine-l-oxide in nearly quantitative yield This product is very reactive it undergoes oxidation in aqueous ammonia to form 4,4 -azopyiidine-l,l -dioxide, and with potassium permanganate in acid solution to give 4-nitrosopyridine-l-oxide. 

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