Benzofuroxans

Benzofuroxans are far more stable than simple furoxans and are more favourable for practical applications. There are two standard methods for the synthesis of the benzofuroxan skeleton (1) treating an ortho-nitroarylamine with a mild oxidant like sodium hypochlorite and (2) either heating or irradiating an orf/to-nitroarylazide with UV light. Benzofuroxan itself has also been prepared by treating 1,2-benzoquinone dioxime with alkaline hypochlorite or alkaline potassium ferricyanide solution.  

Benzenetrifuroxan (66) is a powerful explosive which was first synthesised by Turek in 1931 by heating 1,3,5-triazido-2,4,6-trinitrobenzene (65) to its melting point (131 °C) the latter prepared from the reaction of 1,3,5-trichloro-2,4,6-trinitrobenzene with sodium azide in aqueous ethanol. 

6-Dinitrobenzofuroxan (DNBF) (68) has been prepared from the nitration of benzofuroxan (69) with mixed acid, and by treating picryl chloride (67) with sodium azide and heating the resulting picryl azide (70) in an inert solvent.  

DNBF (68) readily forms stable Meisenheimer complexes (71) with numerous oxygen and nitrogen nucleophiles and some of these are primary explosives with useful initiating properties. 

The fused pyridine-furoxan (74) has been synthesized from 3,5-dinitro-2-chloropyridine (72) via the azide (73).  

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Perhaps one of the most exciting developments in the chemistry of quinoxalines and phenazines in recent years originates from the American University of Beirut in Lebanon, where Haddadin and Issidorides first made the observation that benzofuroxans undergo reaction with a variety of alkenic substrates to produce quinoxaline di-AT-oxides in a one-pot reaction which has subsequently become known as the Beirut reaction . Many new reactions tend to fall by the wayside by virtue of the fact that they are experimentally complex or require starting materials which are inaccessible however, in this instance the experimental conditions are straightforward and the starting benzofuroxans are conveniently prepared by hypochlorite oxidation of the corresponding o-nitroanilines or by pyrolysis of o-nitrophenyl azides. 

In spite of the usefulness of the Beirut reaction, mechanistically it is not well understood. It has been suggested that the first step involves the nucleophilic attack by the enolate or the enamine at N-3 of the benzofuroxan to yield an intermediate iV-oxide (Scheme 50) which subsequently undergoes tautomerism to an hydroxylamino derivative. This intermediate then cyclizes to the dihydroquinoxaline 1,4-dioxide. This suggestion has not been proven, and indeed there is evidence that benzofuroxan is in equilibrium with 1,2-dinitrosobenzene... 

Scheme 51), so it has been suggested that the initial reaction involves the dinitrosobenzene. It does seem, however, that this may be an over-simplification, as there are documented cases where mono-iV-oxides rather than the di-iV-oxides are formed for instance, the reaction of benzofuran-3(2//)-ones with benzofuroxan yields 3-(o-hydroxyphenyI)quinoxa-line 1-oxide (Scheme 52). Other mechanistic possibilities may also be put forward but it seems probable that more than one pathway may be operating, particularly in view of the more recent findings on the reactions of benzofuroxans (81AHC(29)251). 

Catalytic reduction of 1,2,4-oxadiazoles also breaks the N—O bond e.g. (264) gives (265). Benzofuroxan can be reduced under various conditions to benzofurazan (266), the dioxime (267) or o-phenylenediamine (268) (69AHC(10)l). Reduction by copper and hydrochloric acid produced o-nitroanilines (Scheme 30) (69AHC(lO)l). 

Enamines and enolate anions react with benzofuroxan to give quinoxaline di-A -oxides (Scheme 38) (69AHC(10)1). Sydnones (274) with phenyl isocyanate give 1,2,4-triazoles (275) (76AHC(19)l), and from (276) the intermediate adduct (277) can be isolated (73JA8452). This is one of the few instances in which such primary cycloadducts have been isolated in the oxazole series of mesoionic compounds. 

Most fused benzene rings are stable toward nucleophilic attack, but exceptions are known for highly electron-deficient benzazoles. Thus aniline and benzofuroxan at 150°C give the anil (354) <45HCA850). 

Halogen atoms on benzazole rings can be activated toward nucleophilic displacement by electron-withdrawing groups. Thus azide ion displaces chlorine from 5-chloro-4-nitro- and 4-chloro-7-nitro-benzofuroxan (65JCS5958). 

The literature on benzofuroxans is considerably complicated by uncertainties concerning their structure, which were resolved only in 1960. Thus, Beilstein s Hauptwerk includes them in Volume 7 (as derivatives of o-quinones, depicted as dioxadiazines, and named as... 

Since the earlier reviewers, and Mallory and Wood, and, for the earlier literature, Hammick el al. have summarized the history of the structure problem fairly fully, and since it cannot in any case be treated properly in isolation from that of the monocyclic furoxans, we shall present only a brief outline here. The earliest formulas to be suggested (3 and 4), in connection with 1,2-naphthofuroxan, discovered by Koreff and von Ilinski in 1886, were open to the objections that the first is a peroxide structure, whereas the benzofuroxans... 

The tautomeric structure leads to ambiguities in the nomenclature of compounds in this series. Thus, 5-methyl- and 6-methylbenzo-furoxan denote two different molecules which, because of their interconversion, cannot be isolated separately at normal temperatures. Throughout this review, when we intend to refer to the ambiguous mixture, we shall use the system employing the lowest numbers. The above methyl derivative, for example, will be described as 6-methyl-benzofuroxan regardless of the form adopted in the crystal. When a... 

No systematic investigation into the vibrations of the benzofuroxan molecule has been reported. Infrared data are available for a number of compounds, however. Boyer et al in 1963 listed four bands in the benzofuroxan spectrum at 1630, 1600, 1645, and 1500 cm . It is the present authors experience that four strong bands of comparable intensities at or near the frequencies quoted commonly occur in the spectra of substituted benzofuroxans, and are very useful for diagnostic purposes. One or more bands may be weak or absent, however for 2,3-pyridofuroxan (4-azabenzofuroxan) only two bands are reported in this region. 

Further benzofuroxan spectra are reported by Gaughran, Picard, and Kaufman, who compare them with benzofurazans, by Boyer et al., who find similarities with furoxans and nitroso compounds, and by others. Hexanitrosobenzene was shown by IR and Raman spectroscopy to exist in the benzotrifuroxan structure. ... 

Benzofuroxan is a very pale yellow crystalline solid, of melting point 72°. Its dipole moment is given by Tappi as 5.29 D, and the moments of eight other benzofuroxans, their molar refractivities, and melting points, are also recorded.It is appreciably steam-volatile, but far less so than its deoxygenated analog benzofurazan. Melting points of benzofuroxans are listed by Kaufman and Picard, and in Section X of this article. 

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