Benzofuroxans, nitro

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 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. 

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... 

Nucleophilic displacement of a nitro group by aniline in 5,6-dinitrobenzofuroxan has been reported. Rearrangements of 4-nitro-benzofuroxans are discussed in Section VIII. 

Benzofuroxan and 5-methylbenzofuroxan are oxidized by trifluoro-peracetic acid to o-dinitrobenzene and 3,4-dinitrotoluene, respectively. 4-Nitro- and 4,6-dinitrobenzofuroxan are unaffected by this reagent, whereas the 5-chloro and 5-methoxy compounds are destroyed.Milder reagents (performic, peracetic acids) do not oxidize benzofuroxans. ... 

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-... 

The 1-oxide 3-oxide tautomerism [Eq. (3), p. 4] has been discussed earlier (Sections II and III,C) in connection with the problem of the structure of benzofuroxan. A second type of rearrangement involves the furoxan ring and an adjacent substituent group, and arose out of a suggestion of Bailey and Case that 4-nitro-benzofuroxan might be a resonance hybrid of type (57)-(-> (58), rather than 57. NMR ruled out this possibility the three protons present in... 

Some toxicity studies were performed analyzing Bfx and Fx mutagenic effects [240-242], For example, Bfx and Bfz nitro-substituted were tested for mutagenicity in Salmonella typhimurium (S. typhimurium) TA 98 and TA 100 strains with and without metabolic activation (Ames test). All the Bfx (10/10) and some of the Bfz (9/15) are mutagenic without activation. Other study has demonstrated benzofuroxan (128, Fig. 20) is mutagenic in the Luria and Del-brueck s fluctuation test, with Klebsiella pneumoniae, and in the Ames test. In another study it has been found that compound 137 (Fig. 21) is not mutagenic to S. typhimurium. 

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. 

Some reagents are milder and less powerful oxidants and have been used to oxidize arylamines to the corresponding nitroso compounds. These include 30 % hydrogen peroxide in acetic acid, ° aqueous solutions of potassium permanganate, and alkaline hypochlorite amongst others. The hypochlorite oxidation of arylamines containing o-nitro substiffients is reported to yield benzofuroxans. For a discussion of the synthesis of aromatic nitroso compounds the readers are directed to a review by Boyer. ... 

The introduction of amino functionality adjacent to a nitro group in a benzofuroxan is known to reduce impact sensitivity and increase thermal stability. Accordingly,... 

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). 

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. 

At 6 DzT2it7obg7izQ(uTQX t 2 (formerly called 4,5 1 1 nitro-l,3-dinitrosobenzene ), yel ndls(from glac AcOH), mp 172° sol in most org solvs. Can be prepd either by heating 2,4,6-trinitrophenylazide at 90-100° or by nitrating benzofuroxan with a sulfuric-nitric acid mixt at 5-20°(Refs 1,2,3 9)... 

One of the first examples of azide thermolysis cyclization reactions was demonstrated in the synthesis of biologically active benzofuroxanes.49 The cyclization of aryl azides 51 based on the ortho-nitro resins 50 was achieved at ca. 70° to give the benzofuroxanes 52 (Scheme 9). 

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