Deoxygenation of benzofuroxans

Benzofurazans can be obtained by several methods (1) by dehydration of o-quinone dioxime (2) from o-substituted nitrosoarenes and (3) deoxygenation of benzofuroxans <1984CHEC(6)393, 1996CHEC-II(4)229>. For example, trihydroxyimino derivative 280 treated with sodium hypobromite, or when boiled in aqueous ammonia, affords the corresponding substituted tetrahydrobenzofurazan 281 (Equation 54) <2000CHE996>. 

The principal approaches to benzofurazans comprise the dehydration of o-quinone dioximes, the cyclization of o-disubstituted arenes, and the deoxygenation of benzofuroxans (Scheme 21). As for the monocyclic furazans these are long-established routes and have been covered in previous reviews <84CHEC-I(6)393, 84H(22)1571>. 

Sodium azide in ethylene glycol441 or acetic or isobutyric acid442 is reported to deoxygenate benzofuroxans to the furazans. Thermal deoxygenations of benzofuroxans has also been observed, in a few special cases.310... 

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 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... 

The reduction of furoxans and benzofuroxans has been reviewed in detail in CHEC(1984) and CHEC-II(1996). The main reducing agents to remove oxygen atoms from nitrogen without cleavage of the heterocyclic ring are phosphines and phosphites. These reactions, namely deoxygenation of furoxans and benzofuroxans, are discussed in Section 5.05.4.2.2. 

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... 

As for the monocyclic furazans, most of the synthetic approaches have been covered in previous reviews (B-61MI42200, 62HC(17)283, 75H(3)65l). The principal routes comprise the formation of the oxadiazole ring by cyclization of o-quinone dioximes or o-disubstituted arenes and the deoxygenation of the appropriate benzofuroxan. 

A valuable route to benzofurazans is provided by deoxygenation of the corresponding benzofuroxan. This may be accomplished either directly using trialkyl phosphites, tributyl-or triphe nyl-phosphine, or indirectly via the quinone dioxime using, for example, methanol and potassium hydroxide, hydroxylamine and alkali, sodium azide in DMSO or ethylene glycol, sodium borohydride, and occasionally thermolysis alone. More detailed discussion of these reactions is included in Section 4.22.3.2.4. 

Tervalent phosphorus compounds (phosphorous derivatives) are weil-established reagents for the deoxygenation of amine oxides and nitrones, and they provide a clean and convenient method for the preparation of furazans from furoxans. Mukaiyama et al.425 and Grundmann426 used trialkylphosphites, and they have been widely employed since that time, both with and without solvents.80,85,93,95,97,352 The simple dialkyl- and diarylfuroxans usually require more vigorous conditions (e.g., refluxing triethyl phosphite) than do strained derivatives or the benzofuroxans.85,97... 

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