Benzofuroxans, nitro derivatives

Nitro derivatives of 2,1,3-benzoxadiazole (benzofurazan) and 2,1,3-benzoxadi-azole-1-oxide (benzofuroxan) were studied by H, 13C, and 15N NMR spectroscopy (Table 3.29) [746-759],... 

The pioneering work of Katritzky is presented as a complete interpretation for the proton spectra of benzofuroxan and four nitro-derivatives [757], The temperature dependence of the spectra enables to calculate AG for the tautomeric change of the benzofuroxan heterocyclic ring [757],... 

Attention was recently drawn to the initiating properties of some salts of nitro derivatives of benzofuroxane. Potassium and barium salts of 4 6-dimtro-benzofuroxane as primary explosives were suggested by Piechowicz [193] ... 

The VNS is the reaction of choice for incorporation of a-sulfonylalkyl substituents into nitroarenes and their heteroanalogues. Particularly accessible and useful are nitroarylmethyl phenyl sulfones and their heteroanalogues that are efficiently produced in the VNS reactions of carbanions of chloromethyl aryl sulfones with a great variety of nitroarenes and nitroheteroarenes. Nitro derivatives of heterocycles, such as pyrrole [54,55], furan [54], thiophene [54], imidazole [106, 112, 113], pyrazole [114], pyridine [57], indole [115], indazole [116, 117], benzimidazole [118], benzotriazole [119], benzofuroxan [120], quinoline [121], and porphyrins [122, 123], have been shown to enter this reaction. 

Nitration proceeds readily in benzofuroxan, giving first the 4-nitro, then the 4,6-dinitro compound. 6-Nitrobenzofuroxan, according to Drost, is nitrated further in the adjacent 6-position. Bailey and Case reported that the major product is the 4,6-dinitro compound, but they did succeed in isolating a small amount of the 6,6-dinitro derivative from the reaction. 

Chloro- and 5-methylbenzofuroxans are readily nitrated in the 4-position the product rearranges easily to form 7-substituted 4-nitro compounds (see Section VIII), also obtained by nitration of the corresponding 4-substituted benzofuroxans. Dinitration of 5-methylbenzofuroxan is said to give a product of m.p. 133°, while the 4-methyl gives a dinitro compound m.p. 122°-123°. For other benzofuroxans to have been nitrated see refs. 19, 36, 81, 97,121. There appears to be some confusion over the site of electrophilic substitution of naphtho[l,2-c]furoxan. Early reports in the literature state that nitration gives the 5,6-dinitro derivative (47). However, sulfona-... 

Other methods can be used to prepare the furoxan system the most common are spontaneous decomposition of azidonitroolefms 26, dehydration of a-nitrooximes 25, thermolysis of o-nitro phenylazides 27 and oxidation of o-nitrosubstituted aromatic amines 28 (Scheme 6.7). All these procedures have been discussed in detail in Ref. [10]. The latter two methods are of paramount importance in the synthesis of benzofuroxan derivatives. 

Substituents on the benzene rings exert their usual influence on the orientation and ease of electrophilic substitution reactions. For example, further nitration (H2S04/S03/HN03) of 4-nitro-benzofuroxan (496) gives the 4,6-dinitro derivative, the first nitro group direct meta as expected. 

The reactions of the homocyclic ring of benzofuroxans, which are described in detail in Section 4.22.3.3, provide access to numerous derivatives. Nucleophilic displacement of halides is facile when activating nitro groups are present, allowing alkoxy, aryloxy, thio and amino groups to be introduced. Electrophilic substitutions, e.g. nitration, are also valuable. Further transformations may also be performed on benzo-ring substituents. Such modifications include acetoxy to hydroxy acetamido to amino and acyl halides to esters and amides. Some reactions of the substituents of monocyclic furoxans allow hetero-substituted analogues of benzofuroxans to be prepared. For example, pyridazinofuroxans are formed by condensation of diacylfuroxans with hydrazine. 

It should be noted that pyrolysis of either of the substituted nitro-phenylazidcs 213 and 214 yields the same single compound Thus a tautomerism must occur between the products 216 and 217, probably via the dinitroso derivative 215, to give the more stable isomer . In the case where X = Cl or Br this has been shown, by an X-ray crystallographic study, to be the 5-substituted benzofuroxan 217... 

There are general reviews on heterocyclic syntheses by cycloaddition reactions of isocyanates and on the use of heterocyclic cations in preparative organic chemistry. More specific topics are 5-hydroxymethylfuran-2-carb-aldehyde, isobenzofurans and related ort/io-quinonoid systems, the conversion of 2//-cyclohepta[Zj] furan-2-one (1) into derivatives of azulene, the synthesis of indoles from o-alkylphenyl isocyanides, and abnormal Fischer indolization reactions of o-methoxyphenylhydrazones. Two reviews on isoindoles have appeared and a lecture on highly conducting charge-transfer complexes that are based on heterocyclic selenium and tellurium donors has been reprinted.Recent advances in the chemistry of imidazole and in the use of nitro-imidazoles as radiosensitizers have been summarized. There have been reviews on benzimidazole A -oxides and on dihydrobenzimidazoles, benzimidazolones, benzimidazolethiones, and related compounds. Other topics are synthetic applications of 1,3-dithiolium and 1,3-oxathiolium salts and of isoxazoles, the chemistry of benzisoxazoles, 2-amino-oxazoles, 5-oxazolones (2), furoxans, benzofuroxans, and related systems, the synthesis of five-membered meso-ionic compounds, and tetrazoles. ... 

Hydrogen transfer from hydrazobenzene to benzofuroxan (622) results in azobenzene and o-benzoquinone dioxime (623). Compound (622) reacts with formaldehyde to yield the benzimidazolinone (624). Chlorobenzofuroxan aldehyde condenses with derivatives of hydroxylamine or hydrazine to yield oximes or hydrazones (625 R = OH, OMe, NHPh, NMe2, etc.), which rearrange thermally to indazoles (626). Treatment of 7-methoxy-4-nitro-benzofurazan 1-oxide with aqueous potassium hydroxide affords a mixture of the corresponding 7-hydroxy-compound (627) and the rearranged 5-hydroxy-4-nitrobenzofuroxan (628). ... 

---