4- Nitrobenzofuroxan, rearrangement

Nitro groups in the 4-position may also participate in the rearrangement. For example, 5-chloro- and 5-methyl-4-nitrobenzofuroxans rearrange to their 7-chloro- and 7-methyl-4-nitro isomers, the ease of the process being attributed to steric inhibition of resonance for the nitro group in the starting materials. Similarly, 4-ethoxycarbonylamino-5,7-dinitroben-zofuroxan equilibrates with its 4,6-dinitro-5-urethane isomer. 

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. 

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. 

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. 

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). 

The tautomerism of nitrated 5(6)-fruorobenzofuroxans has been studied by Charushin and colleagues using dynamic H, 13C, 19F NMR spectroscopy [758], It has been discovered that 4-nitro-5-hydroxy-6-fluorobenzofuroxan, on dissolving in DMSO, transforms to 4-hydroxy-5-fluoro-7-nitrobenzofuroxan in a result of the Boulton-Katritzky rearrangement [758],... 

Compounds with activated halogen atoms, e.g., 7-chloro-4-nitrobenzo-furoxan (234), undergo displacement reactions with a variety of nucleophiles, including sulfides,300 443,444 amines,300,443,491 phenoxides,300 and others mentioned earlier.6 Sometimes rearrangements of the type discussed in Section V,C,4 occur, leading to products other than those of simple displacement.300,443 When 7-chloro-4-nitrobenzofuroxan is treated with an aryl-sulfinate, both substituents are replaced, and the 4,7-bisarylsulfonyl compound is formed. One of the arylsulfonyl groups is, in its turn, susceptible to replacement by other nucleophiles.444... 

Hydroxide ion replaces the methoxide of 7-methoxy-4-nitrobenzofuroxan to form the 7-hydroxy-4-nitro compound, which rearranges to the 5-hydroxy-4-nitro derivative, under certain conditions.418 Buncel et al.501 have also described the demethylation of 7-methoxy-4,6-dinitrobenzofuroxan by methoxide ion. 

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). ... 

This reaction has been widely used in heterocyclic chemistry for preparing certain types of nitrogeneous heterocycles, such as nitrobenzofuroxans, which have been used for the inhibition of nucleic acid and protein biosyntheses. Some interesting rearrangements are listed in experimental examples. 

Although the mechanism above is generally accepted, several research groups have worked to gain a better understanding of the subtleties involved in the transformation. As an example, Eckert and Rauhut have examined the well-studied rearrangement of 4-nitrobenzofuroxan (5). Their computational study examined the hypothesis that the reaction proceeded in a single step via a symmetric transition state TS. 

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