Nitrile Oxides from furoxans

Phototransformation of pyridazine 1,2-dioxides sharply contrasts with that of pyridazine 1-oxides. Pyridazine 1,2-dioxide derivatives give 3a,6a-dihydroisoxazolo[5,4- f]isoxazoles (53) through postulated bisiminoxyl radicals. 3,6-Diphenylpyridazine 1,2-dioxide gives, besides the corresponding bicyclic derivative (53), 3-phenylisoxazole (54) and 4,5-diphenyl-furoxan (55). The last two products can be explained by generation of the nitrile oxide from the intermediate (53) with subsequent dimerization to the furoxan (55 Scheme 18) (79T1267). 

Aroylnitrile oxides can also be generated from diaroyl furoxans 183 under micro-wave irradiation [33]. Formation of the nitrile oxide intermediate 184 and its cycloaddition with dipolarophiles proceeds at atmospheric pressure within minutes in the absence of solvent and in good yields (Scheme 9.56). The reaction occurs by the rear-... 

Dimerization of nitrile oxides derived from 4-amino- and 4-R-substituted l,2,5-oxadiazole-3-carbohydroximoyl chlorides 201 leads to the formation of tricyclic furoxans 200 or compound 202 (Scheme 45) <2001RJ01355>. 

Some routes of chemical transformations of nitrile oxides connected with the problem of their stability were briefly discussed in Section 1.2. Here only two types of such reactions, proceeding in the absence of other reagents, viz., dimerization to furoxans and isomerization to isocyanates, will be considered. All other reactions of nitrile oxides demand a second reagent (in some cases the component is present in the same molecule, and the reaction takes place intramolecularly) namely, deoxygenation, addition of nucleophiles, and 1,3-dipolar cycloaddition reactions. Also, some other reactions are presented, which differ from those mentioned above. 

The stability of o-sulfonylbenzonitrile oxides and their thiophene analogs probably depends on electronic factors. The same factors do not prevent dimerization, as can be seen from data concerning several differently substituted nitrile oxides of the thiophene series (103). Sterically stabilized 3-thiophenecarbonitrile oxides 18 (R = R1 = R2 = Me R = R2 = Me, R1 = i -Pr), when boiled in benzene or toluene, isomerized to isocyanates (isolated as ureas on reaction with aniline) while nitrile oxides 18 with electron-withdrawing substituents (R1 and/or R2 = SOiMe, Br) dimerized to form furoxans 19. 

Several other heterocyclic systems are accessible from monocyclic furoxans. In addition to providing a source of nitrile oxides and cycloadducts derived therefrom (Section 4.05.5.2.2), they... 

The first examples of furazan and furoxan nitrile oxides have been reported in the early 1990s. 4-Aminofurazan-3-carbonitrile oxide (65) was generated from the hydroximoyl chloride with base and its cycloaddition reactions investigated <92KGS687>, and the 4-phenyl analogue (66) is formed via the nitrolic acid derivative by treatment of the aldoxime with dinitrogen tetroxide <93LA44i>. Furazan-3-amidoximes react in the usual way with nitriles to yield 3-(furazan-3-yl)-1,2,4-oxadiazoles <9013941 >. 

Interestingly, furoxanes (274) have also been shown to be competent dipoles for the [3 + 2] cycloaddition. These compounds result from a dimerization of the corresponding nitrile oxide (Eq. 2.26) (237-241). Under elevated temperatures, the addition of a dipolarophile results in the cycloadduct 275. This intermediate is unstable under the reaction conditions and undergoes a retro-[3 + 2] cycloaddition to reveal a nitronate. In the presence of excess dipolarophile, the reaction proceeds to provide bicyclic isoxazolidines in moderate yield. 

Trifluoromethyl substituted 1 -oxadiazoles 113 were prepared by heating the bis(oximes) 112 with dry silica <99H(51)627>. l -Oxadiazole-2-oxides(furoxans)are often produced by dimerisation of nitrile oxides and some novel examples of the method, which produces 3,4-disubstituted derivatives bearing medium and large rings, have been described <99JOC8428>. Two examples of compounds prepared in this way from bis(nitrile oxides) are the ftiroxans 114 (84%) and 115 (86%). 

Direct dehydrogenation of oximes is also possible, particularly for sterically hindered nitrile oxides. The most successful oxidizing agents are alkaline hypobromite and NBS in the presence of base, the latter being valuable when basic groups are present. Lead tetraacetate and alkaline hypochlorite have also been employed, but the yields are lower. The formation of furoxans from the reaction of alkoximes with nitrogen oxides is believed to proceed via the corresponding nitrolic acids. 

Nitrile oxides are generated from nitrolic acids [RC(N02)=N0H] by elimination of the elements of nitrous acid. This can occur spontaneously, on heating, or by the action of sodium bicarbonate, and it thereby provides access to symmetrically substituted dialkyl-, diaryl-, and diacyl-furoxans. 

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