Furoxans monosubstituted

A new general synthesis of 3-substituted derivatives has been reported (99MC13) (Scheme 9). Thus, the nitro group of furoxan 27 underwent a facile hydride replacement on treatment with NaBH4 in EtOH to give 3-monosubstituted furoxans 23. The result of this reaction is independent of the nature of R. 

In general, furoxans are fairly stable compounds in acid solution but are sensitive to bases [6, 9]. This is true in particular for the parent ring and for the 4- and 3-monosubstituted compounds. The former undergoes extensive decomposition, while the latter two produce a-hydroxyimino substituted nitrile oxides 5 and a-nitro substituted nitriles 6, respectively. 4-Aryl-3-methylfuroxans 7, unlike their 4-methyl isomers, give Angeli s rearrangement, namely they are converted to the corresponding 3-arylisoxazolin-4-one oximes 8, by the action of concentrated alkali hydroxides or alkoxides (Scheme 6.1). 

Scheme 6.1 Decomposition in alkali solution of4- and 3-monosubstituted furoxans and 4-aryl-3-methylfuroxans.

Carbon-13 NMR spectroscopy has also been utilized to probe the structure, isomers, and conformational aspects of 1,2,5-oxadiazole chemistry. The dc values for monocyclic furazans vary from 140 to 160 ppm depending on the substituent, and C- H couplings of ca. 200 Hz are observed for the parent furazan and monosubstituted derivatives (92KGS1 lOl >. For furoxans the most noteworthy feature of their carbon spectra is the large displacement of the C(3) resonance to lower chemical shift. While the C(4) peak remains in the range 140-160 ppm that for C(3) is shifted to 100-125 ppm. At low temperatures benzofuroxan shows two peaks at 113.7 (C(3)) and 152.2 (C(4)) which coalesce on warming. The parent furoxan has C- H couplings of 211 Hz for C(3) and 202 Hz for... 

The furoxan ring is notably resistant to electrophilic attack and reaction normally takes place at the substituents. Thus aryl groups attached to monocyclic furoxans and the homocyclic ring of benzofuroxans are nitrated and halogenated without disruption of the heterocycle. Reaction with acid is also slow protonation is predicted to occur at N-5 <89KGS1261> and benzofuroxans have pKj, values of ca. 8, similar to those of benzofurazans. Monosubstituted furoxans are, as expected, less stable and can be hydrolyzed to the corresponding carboxylic acid. Treatment of the parent furoxan (3) with concentrated sulfuric acid results in rearrangement to (hydroxyimino)acetonitrile oxide (HON=CHC=N —O ) and subsequent dimerization to bis(hydroxyiminomethyl)furoxan... 

Treatment of some a-ethynyl acetates with a mixture of nitrosyl fluoride and nitrosonium tetrafluoroborate affords bis[(acetoxyalkyl)carbonyl]furoxans the presence of the a-acetoxy group appears to be essential (81JOC312). Monosubstituted furoxans have been obtained by nitrosation of unsaturated hydrocarbons thus the reaction of nitrous acid with p -hydroxycin-namic acid affords 3-(p-hydroxyphenyl)furoxan, its structure being confirmed by X-ray crystallography (80LA1557). 

Unsubstituted furoxan (1 R1 = R2 = H) is unknown. Fulminic acid (HCNO) oligomerizes readily, but the products are mainly trimers and tetramers they are summarized in part in Section V,C, and elsewhere.369,370 Monosubstituted furoxans are labile compounds, but some have been reported (not all of them reliably). The best studied are the phenylfuroxans, on which there is an extensive literature, much of it extremely confused, since Ponzio worked on the compounds for some 20 years, over which period his views on their structures changed several times, and it was only at the end that he accepted that any contained a furoxan ring. 

From the fulminic acid oligomer studies of Wieland, Grundmann et al., two 3-monosubstituted furoxans have been reported. These are the precursor (127) of prefulminuric acid,371 and, in the cyanilic acid field, the furoxan 146.372 The methylfuroxan prepared by oxidation (N204) of methyl-glyoxime190 and the corresponding propylfuroxan461 were not isolated pure and are of undetermined structure. 

Some further monosubstituted furoxans which have been reported are either of very doubtful authenticity or have been discredited. The phenacyl derivatives of Harries and Tietz,462 formed by the nitrosation of /J-aryl-oc,/ -unsaturated oximes, have been shown to be pyrazolone di-JV-oxides 463 The degradation of Holleman s peroxide (29) by hydroxylamine and alkali was reported to form structure 218, or its 3-substituted isomer, by Boyer and Chang.29 It does, however, seem unlikely that a monosubstituted furoxan could withstand such reaction conditions. Decarboxylation of furoxandi-carboxylic acid has been suggested to provide the 4-monocarboxylic acid,464 but Ponzio and De Paolini465 have assigned a nitrile oxide structure to the product. 

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