4-Nitrobenzofuroxans

Nitrobenzofuroxan (355) undergoes a rearrangement (recognizable as an isomerization in unsymmetrically substituted derivatives) which is an example of this general rearrangement (Scheme 45) (64AG(E)693) see Table 10. 

Electronic spectral considerations were invoked by Boyer et in favor of the i/i-o-dinitroso- structure and by Mallory and Wood against an oxaziridine formulation for the jV-oxide structure. The spectra of some nitrobenzofuroxans have been reported. 

Fig. 2. The proton magnetic resonance spectrum of 5-nitrobenzofuroxan, in acetone at — Sl C. The bands marked by arrows arise from the 5-nitro tautomer.

Alkoxybenzofuroxans are weU-known, and the hypochlorite oxidation method is usually used for their preparation. For the formation of haloalkoxybenzofuroxans from nitrobenzofuroxans, see Section VII, B. 

Nitration of benzofuroxans (Section VII, A) and decomposition of polynitrophenyl azides, provide generally satisfactory routes to nitrobenzofuroxans. The nitro groups render the ring susceptible to nucleophilic attack (see Section VII,B). 4,6-Dinitrobenzofuroxan, 5,6-dinitrobenzofuroxan, and nitrobenzodifuroxan (34) act as acceptors in change-transfer complex formation with aromatic hydrocarbons. Nitrobenzofuroxans have not been reduced to the... 

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. 

Several examples of nucleophilic displacement of nitro-activated leaving groups have been recorded. 5,6-Dinitrobenzofuroxan with aniline and p-bromoandine gives the corresponding substitution product (50). Azide ion displaces chloride from both 5-chloro-4-nitro- and 4-chloro-7-nitrobenzofuroxan (51 and 52) the product from the former loses nitrogen spontaneously to give furoxanobenzo-furoxan (benzobisfuroxan, 17), which is also formed, although in poor... 

Reduction of benzofuroxans is usually the most convenient route to benzofurazans and o-quinone dioximes (see Section VI, C). Reduction of 4-nitrobenzofuroxan would seem to be a method of synthesis of 1,2,3-triaminobenzene, while the haloalkoxy-substitution reaction (Section VTT,B) and the rearrangements of Section VIII provide compounds accessible only with difficulty by other methods. Apart from these reactions, the benzofuroxans appear to be of limited synthetic utility. 

Spectroscopic and kinetic investigations of the reactions between 4,6-dinitrobenzofuroxan, 4-nitrobenzofuroxan, and tertiary and secondary amines (i.e., l,4-diazabicyclo[2.2.2]octane, quinuclidine, l,8-diazabicyclo[5.4.0]undec-7-ene, and piperidine) indicate the formation of zwitterionic or anionic complexes (Equation 2). The equilibrium between zwitterionic and anionic complexes is discussed (for reaction with piperidine) on the basis of H NMR spectral data, which indicate the presence of anionic complexes arising from the zwitterionic complex by a fast proton departure. The stability and the rate of formation of title complexes are discussed and compared to similar reactions of 1,3,5-trinitrobenzene <2001J(P2)1408>. 

Diels-Alder reactivity of 4-aza-6-nitrobenzofuroxan 235 has been studied via reactions with cyclopentadiene, cyclohexadiene, and 2,3-dimethylbutadiene this has led to three types of Diels-Alder adducts, namely the normal Diels-Alder adducts 234, 236, a Diels-Alder hetero-adduct 238, and the di-adducts 237, 239 arising from a minor dinitroso tautomer of compound 235 (Scheme 59) <1999CC1009, 2000JOC7391>. 

A theoretical study of degenerate Boulton-Katritzky rearrangements concerning the anions of 3-formylamino-l,2,4-oxadiazole and 3-hydroxy-iminomethyl-1,2,5-oxadiazole has been carried out7 The treatment has shown the participation of asymmetric transition states and non-concerted processes via symmetrical intermediates. A detailed ab initio and density functional study of the Boulton-Katritzky rearrangement of 4-nitrobenzofuroxan has indicated a one-step mechanism for the process. 

One of the nitro groups in furazan (78) can be substituted by chloride and azide, and displacement of sulfonyl groups has also been reported. Nucleophilic reactions in the homocyclic ring of benzofuroxans may be accompanied by deoxygenation of the A-oxide 4-nitrobenzofuroxan with dialkyl-amines affords 4-dialkylamino-7-nitrobenzofurazans as the major product. Substitution reactions... 

The principal methods for forming the heterocyclic ring of benzofuroxans involve oxidation of o-quinone dioximes, thermolysis of o-nitroaryl azides, and oxidation of o-nitroanilines (Scheme 25). Ring chain tautomerism (Section 4.05.5.2.1) for the A -oxides of asymmetrically substituted benzofuroxans is more facile than for monocyclic analogues and mixtures of isomers may result. Benzofuroxans are also formed by Boulton-Katritzky rearrangement of 7-nitro-2,l-benzisoxazoles and 4(7)-nitrobenzofuroxans (Section 4.05.5.2.5). 

Structural assignments of the species formed by the reaction of the methoxide ion with 4-nitrobenzofurazan benefited from the analogous behavior of 4-nitrobenzofuroxan.203,204... 

By addition of one equivalent of base to solutions of 7-(2-hydroxyethoxy)-4-nitrobenzofurazan and 7-(2-hydroxyethoxy)-4-nitrobenzofuroxan in either water or a dipolar aprotic solvent, the spiro adducts 169 and 170 are completely formed212 and can be characterized by their UV-visible and H-NMR spectra. They display substantial upfield chemical shifts relative to the ring signals for the starting substrate and a complex multiplet centered at 8 4.16 for the nonequivalent dioxolane methylene protons. Isolation of the adducts as the potassium salts from acetonitrile solution was accomplished by removal of the solvent. 

Terrier etal.203 have investigated the reaction of 4-nitrobenzofuroxan with MeOK in several MeOD-DMSO-e 6 mixtures. At 20°C in 3 7 (v/v) MeOD-DMSO-c 6, only one adduct (173) is formed, by attachment to position 7, which is characterized by an ABX pattern. With 7 3 (v/v)... 

Nitrobenzofuroxan has been recently investigated in the isopro-poxide-isopropanol and cyanide-isopropanol systems.230 In both cases a reversible formation of a 7-adduct is followed by the stopped-flow method using similar spectral changes from substrate to adduct. The structure of the adduct is identified by analogy with the NMR and UV-visible properties of the product of the reaction as carried out with the MeO -MeOH system. There is no evidence that the formation of the 7-adduct is preceded by that of the 5-adduct under the conditions of the experiments. Any formation of the... 

Kinetic and Thermodynamic Data for the Formation of 7-Adducts by the Reaction of 4-Nitrobenzofuroxan (203) with Me2CHO" and CN in Isopropanol at 25°C. Comparison with Related Data for 1,3,5-Trinitrobenzene (204) ... 

The finding that adduct 173 as formed from 4-nitrobenzofuroxan, undergoes a decomposition reaction according to a complex pattern has also suggested that the biological activity might be related to some of the decomposition products.215... 

Benzofuroxan and derivs 2 B68—B69 6-Azido-5-nitrobenzofuroxan 2 B68 dinitrobenzofiiroxans 2 B68—B69 mononitrobenzofuroxan 2 B68... 

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