Benzofuroxans preparation

Dinitrobenzofuroxan can be prepared by thermal decomposition of 1-azido-2,4,6-trinitrobenzene (prepared from l-chlor-2,4,6-trinitrobenzene) [13, 15] or more effectively, without isolation of l-azido-2,4,6-trinitrobenzene, directly from l-chlor-2,4,6-trinitrobenzene [31]. The other method of 4,6-dinitrobenzofuroxan synthesis is based on nitration of benzofuroxan (prepared from o-nitroanUine) [31-33]. 

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. 

The most reliable method of preparing benzofuroxans is by decomposition of o-nitrophenyl azides. Decomposition can be achieved by irradiation, or more usually by pyrolysis temperatures between 100° and 1.50° are commonly used. Refluxing in glacial acetic acid is the recommended procedure for 4- or 5-sub-stituted 2-nitrophenyl azides, but with 3- or 6-substituted compounds higher boiling solvents are usually necessary. Quantitative studies on the reaction rate have been made, and a cyclic transition state invoked, an argument which has been used to account for the greater difficulty of decomposition of the 6-substituted 2-nitrophenyl azides. Substituent effects on the reaction rate have also been correlated with Hammett a constants, ... 

The action of hydroxylamine and sodium acetate in ethanol upon picryl chloride was stated to give 4,6-dinitrobenzofuroxan, and probably some of this compound was formed, although it was later shownthat much of the original work was faulty. A report that hydroxylamine and 2,4,5-trinitrotoluene give 5-methyl-6-nitro-benzofuroxan has been found to be incorrect. Benzofuroxan has not been prepared by V-oxidation of benzofurazan, and it seems unlikely that this could be achieved, since benzofuroxan itself is oxidizable by powerful reagents to o-dinitrobenzene (Section VI, B). A report of the oxidation by nitric acid of anthraceno[l,2-c]furazan to the furoxan is incorrectlv abstracted. 

The 4,.5-benzo-fused compound, 1,2-naphthofuroxan (24) was the first compound in the benzofuroxan series to be prepared the... 

Quaternization is difficult benzofuroxan is unaffected by triethyl-oxonium fluoroborate. With methyl trifluoromethanesulfonate, an interesting rearrangement occurs, and l-hydroxybenzimidazole-3-oxide (39, R = H) is formed, probably via the N-quaternized derivative (38). Compound 39 (R = Ceils) has been prepared similarly. 

The following table lists the benzofuroxan derivatives, with their melting points, which the authors have been able to find in the published literature. No attempt has been made to provide an exhaustive reference list those quoted are intended to be selected for their preparative usefulness. Substituents in parentheses indicate that a ring CH group, rather than a H atom, is replaced. Additional references (144-149) not cited earlier in the text are to be found at the foot of this page. 

The amido-, thioamido-, sulfonamido-, and semicarbazido-benzofuroxans possessing different lateral chains (het-eroaliphatic, heterocyclic, and aromatic) were prepared by traditional methods by transformation of functional group of benzene fragment. The typical chemistry of benzofuroxanes did not take place in these cases <2002AP15>. 

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. 

Scheme 6.7 Other methods to prepare the furoxan and benzofuroxan system.

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. ... 

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." " ... 

Benzofuroxans can be prepared by oxidation of o-quinone dioximes with, for example, fer-ricyanide or hypohalite in a process which closely parallels the formation of monocychc furoxans from glyoximes. Its utility is restricted by the availability of the starting materials which are themselves often best made by reduction of the furoxan. However, it is a valuable approach when the parent quinone or its monooxime is accessible by other means. It was, for example, the route originally used for naphtho[l,2-c]furoxan, the first aromatic-fused derivative <1886CB176>, and it is the method of choice for acenaphthofuroxans (11). In other cases oxidation of o-nitroanilines or thermolysis of o-nitroaryl azides are more suitable. 

Most of the main synthetic routes (Scheme 21) have been summarized in previous reviews (69AHC(10)1, 8lAHC(29)25l). They involve oxidation of o-quinone dioximes decomposition of o-nitroaryl azides and oxidation of o-nitroanilines. The interconversion of the 2- and 5-oxides for asymmetrically substituted derivatives is more facile compared with the monocyclic analogues, and mixtures of isomers are commonly formed. In no case has a benzofuroxan been prepared by direct oxidation of the corresponding benzofurazan. 

Benzofuroxans are formed from o-quinone dioximes by oxidation with, for example, alkaline ferricyanide, nitric acid, bromine water and chlorine, While the reaction is usually straightforward and high yielding the method is not generally applicable since the dioximes themselves are not readily obtainable and are often best prepared via reduction of the furoxan (see Section 4.22.3.1.3). However it can be used when the parent quinones or their monooximes (o-nitrosophenols) are available from other sources. Thus it is the method of choice for the acenaphtho- and phenanthro-furoxans, (18) and (94 n = 1), respectively. In other cases alternative routes, such as the oxidation of o-nitroanilines or the thermolysis of o-nitroaryl azides, are more commonly utilized. 

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. 

Azine approach. Benzofurazans are conveniently prepared by oxidative cyclization of o-nitrosoanilines. Benzofuroxanes, the A-oxide derivatives of benzofurazans, are similarly... 

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