Benzofurazan

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). 

The thermal or photolytic fragmentation of furazans to nitriles and nitrile Af-oxides has been reported (73JOC1054, 75JOC2880). The irradiation of dimethylfurazan (419) in the presence of cyclopentene, and benzofurazan (420) in the presence of dimethyl acety-lenedicarboxylate, gave isoxazoline (421) and isoxazole (422), respectively, in good yields. The thermolysis of acenaphtho[l,2-c]furazan (423) in the presence of phenylacetylene gave isoxazole (424) in 55% yield. 

Benzofurazan, 7-benzenesulfonyl-4-nitro-synthesis, 6, 408 Benzofurazan, 4-chloro-synthesis, 6, 419... 

Benzofurazan, 7-chloro-4-nitro-, 6, 394 as fluorigenic agents, 6, 410, 426 Benzofurazan, 4-chloro-7-sulfo-ammonium salt properties, 6, 426 Benzofurazan, 4-nitro-synthesis, 6, 408 Benzofurazans, 6, 393-426 Beckmann fragmentation, 6, 412 biological activity, 6, 425 bond angles, 6, 396 bond lengths, 6, 396 diazo coupling, 6, 409 dipole moments, 6, 400 electrochemical reduction, 5, 73 electrophilic reactions, 6, 409-410 ESR spectroscopy, 6, 400... 

Benzofurazan [273-09-6] M 120.1, m 55. Purified by crystn from EtOH and sublimed. 

The Beirut reaction involves the condensation of benzofurazan oxide (BFO) 1 with an enamine 2 or an enolate anion 3 in an alcohol solvent to give the corresponding quinoxaline-1,4-dioxide 4. ... 

Substituted benzofurazan oxides 9 and 11 have been studied by NMR at low temperature and were observed as a mixture of tautomers, presumably interconverting via the ortho-dinitroso intermediate 10. When R = Cl, MeO, or AcO, tautomer 9 is the more stable... 

There is some debate in the literature as to the actual mechanism of the Beirut reaction. It is not clear which of the electrophilic nitrogens of BFO is the site of nucleophilic attack or if the reactive species is the dinitroso compound 10. In the case of the unsubstituted benzofurazan oxide (R = H), the product is the same regardless of which nitrogen undergoes the initial condensation step. When R 7 H, the nucleophilic addition step determines the structure of the product and, in fact, isomeric mixtures of quinoxaline-1,4-dioxides are often observed. One report suggests that N-3 of the more stable tautomer is the site of nucleophilic attack in accord with observed reaction products. However, a later study concludes that the product distribution can be best rationalized by invoking the ortho-dinitrosobenzene form 10 as the reactive intermediate. 

The benzofuroxtin [benzofurazan oxide, 3,4-benzo-l,2,6-oxa-diazole-2-oxide, or 2,1,3-benzoxadiazole-l-oxide (1)] ring system has been reviewed briefly on several occasions, notably by Kaufman and Picard,Boyer, and Behr. The mqst recent of these covers the literature until 1959, and since that date there have been many advances in the subject. This, we feel, justifies the field being covered once more, and its separation from the monocyclic 1,2,5-oxadiazole oxides—the furoxans. We consider also other furoxano-fused compounds in this chapter, subject to the limitation that the ring adjacent to the furoxan is aromatic and six-membered. 

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. 

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 reduction of benzofuroxans can lead to a variety of products, depending upon the conditions. Deoxygenation to benzofurazans (40) can be effected either directly, using trialkyl phosphites, -tributyl or triphenyl - phosphine, or indirectly, via o-quinone dioximes (41), using methanol and potassium hydroxide, or hydroxyl-amine and alkali. - - The dioximes may be isolated, but... 

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. 

The reaction of benzofurazan iV-oxide with diethylamine affords 3-methyl-1,2,4-benzotriazine 4-oxide 160 (79T681, 82T1793). 

Benzofurazan (8), on irradiation in benzene solution, undergoes a complex sequence of ring openings and rearrangements to yield, in situ, the cyanobutadienylcarbonylnitrene 9 which is trapped by the solvent to give ultimately the 1 //-azcpinc 10 as the major product.125... 

Benzofurazan (benz-1,2,5-oxadiazole) reacted with bromine by addition to give a4,5,6,7-tetrabromo adduct. Bromine in hydrobromic acid solution 4-brominated both 5-methyl- and 5-bromo-benzofurazans (74JHC8I3). When 4,7-dinitrobenzofurazan was treated with ammonium chloride in refluxing acetic acid, nucleophilic displacement gave rise to the 4-chloro-7-nitro derivative (83URP1004375). Naphtho[l, 2-c]furazans (42) are mainly 4-halogenated, but there is minor substitution in the 8-position (73CHE1331). 

Dinitroso-benzol wird durch Tributyl- oder Triphenyl-phosphan zu Benzofurazan, 1,2-Dinitroso-naphthalin (2 Stdn. Kochen unter N2) zu Naphtho-[l,2-c]-furazan (65% d.Th. F 77-78°) und 4,5-Dinitroso-3,6-diphenyl-pyridazin zu4,7-Diphenyl- furazano-[.3,4-d]-pyridaZin) (36% d.Th. F 193-195°) reduziert4 ... 

Contrary to other Af-oxide containing heterocycles, Bfx and Fx are not formed by direct oxidation of the parents systems, benzofurazan (Bfz) and furazan (Fz), respectively. Even though each kind of heterocycle possesses individual synthetic procedures, some common approaches should be mentioned, i.e., thermo or photochemical intramolecular cychzation of 1,2-azidonitro derivatives and oxidative cychzation of 1,2-dioximes. Some other synthetic procedures, such as oxidation of o-nitroanUines to Bfx or dimerization of nitrile oxides and dehydration of a-nitrooximes to Fx, have been depicted. The following sections provide the most recent descriptions. 

Prados P, Fukushima T, Santa T et al (1997) 4-/V,/V-Dimethylam inosu 1 lbnyl-7 -N-(2-aminoethyl)amino-benzofurazan as a new precolumn fluorescence derivatization reagent for carboxylic acids (fatty acids and drugs containing a carboxyl moiety) in liquid chromatography. Anal Chim Acta 344 227-232... 

Uchiyama, S., Santa, T., Okiyama, N., Azuma, K. and Imai, K. (2000). Semi-empirical PM3 calculations predict the fluorescence quantum yields (Phi) of 4-monosubstituted benzofurazan compounds. J. Chem. Soc. Perkin Trans. II 6, 1199 1207. 

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