1.3.4- Oxadiazol-2 -one 4- nitro

One of the best-known common approaches to generate the 1,2,5-oxadiazole AT-oxide system involves cychzation of a nitro group unto a nitrene, arising... 

The iron-catalyzed [3 + 2]-cycloaddition (Huisgen reaction) of nitriles and carbonyl compounds as reported by Itoh et al. is one of the rare examples reported where an iron reagent can be utilized for the synthesis of 1,2,4-oxadiazoles (Scheme 9.35) [93]. In this reaction, methyl ketones are nitrated at the a-position by Fe(N03)3 to generate an a-nitro ketone. This intermediate rearranges to an acyl cyanate, which reacts further with the nitrile to give the heterocyclic product 48 in good to excellent yields (R1 = Ph, R2 = CH3 95% yield). 

The chemistry of cyclopentafurazans (cyclopen-ta-1,2,5-oxadiazoles) and furazans fused to five-membered heterocycles with one to four heteroatoms has been reviewed (95JHC371). Treatment of 3-amino-4-nitro-l,2,5-oxadiazole with dinitrogen pentoxide yields dinitro-1,2,5-oxadiazole 89 (95MC102). The latter reacts normally with benzenethiol to give the sulfide 90,... 

The reaction of 3-(2-nitroaryl)-2,3-dihydro[l,2,4]oxadiazol-2-ones (385) with phosphorus pentasulfide in refluxing xylene transforms the oxadiazole ring into the thiadiazole ring concomitant reduction of the nitro group and closure of the imidazole ring affords [l,3,4]thia-diazolo[3,2-a]benzimidazoles (386). The reaction of l,3-dinitro-4,6-bis[(5-(l,l-dimethylethyl)-2-oxo-2,3-dihydro[l,3,4]oxadiazol-3-yl)benzene (387) is only partially successful and gives some 2-( 1,1 -dimethyl-ethyl)-5-[5-( 1,1 -dimethylethyl)-2-thioxo-2,3-dihydro-[l,3,4]oxadiazol-3-yl]-6-nitro-5-[l,3>4]thiadiazolo[3,2-a]benzimidazole (388) (Equation (132)) <88PS(36)139>. 

Another example is the nitrosation of creatinine in meat, by which 5-oxocreatinine-5-oxime and l-methyl-5-oxohydantoin-5-oxime can arise (Figure 12.32). Some phenols also react with nitrosation reagents yielding nitroso compounds and oximes. In addition to nitroso compounds and oximes, in reactions with nitrosation agents there also arise nitro, oxynitro and nitronitroso compounds, as in the case of polycyclic aromatic hydrocarbons (PAHs). The mechanisms of their formation and other aspects of their presence in food are not yet sufficiently known. An example is the nitrosation of p-coumaric acid, which is dependent on pH. Acidic pH results in 4-hydroxybenzaldehyde (16%), l d-dihydroxybenzeneacetaldehyde oxime (59%), 4-hydroxy-l -oxobenzeneacetaldehyde oxime (26%) and 7-hydroxy-l,2(4H)-benzoxazin-4-one (6%), whereas 4-(2-oxido-l,2,5-oxadiazol-3-yl)phenol was formed at acidic (6%) and neutral and alkaline pH (both 1%) (Figure 12.38). 

Dipolar cycloadditions of nitrile oxides to the various unsaturated alditol derivatives 92 led to pairs of isoxazolidine regio-isomers, e.g. 93 and 94, each as predominantly one stereoisomer (Scheme 16). The isoxazole 95 was the major product from addition of bromoformonitrile oxide to the nitro-alkene. The nitrile moiety of D-mannononitrile pentabenzoate was transformed into either a 3-substituted 5-methyl-1,2,4-oxadiazole moiety (with NH2OH then AC2O) or a 5-substituted 2-methyl-1,3,4-oxadiazole moiety (with NH4N3 then AC2O, Py) cf. Vol.24, p.l35. The synthesis of 2-(alditol-l-yl) substituted 2-aza-3,7-dioxabicy-clo[3.3.0]octanes by intramolecular dipolar cyclization of 2-0-d y -aldehydo-sugar nitrones is covered in Chapter 24. 

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