Furoxans glyoximes

The ready accessibility of 1,2-dioximes (glyoximes) and the ease with which they are dehydrated has ensured that this is the most common route to furazans. The starting materials are usually prepared by oximation of the appropriately substituted 1,2-diketone or, more often, by a-nitrosation of an alkyl ketone followed by oximation of the resulting 1,2-dione monooxime (Scheme 16). 1,2-Dioximes can also be prepared by reduction of furoxans (Section 4.05.5.2.4) and, in cases where the furoxan is more readily available than the furazan, for example, by nitrile oxide dimerization, this furoxan-> glyoxime-> furazan sequence represents a viable synthetic strategy for symmetrically substituted derivatives. 

Furazan 1 was first prepared and characterized in 1964 by melting glyoxime 2 with succinic anhydride in 57% yield (64JA1863, 65JOC1854). Its A-oxide, furoxan 3, has been in a focus of attention for chemists for more than a century, but was synthesized only in 1994 by oxidation of 2 with dinitrogen tetroxide in dichloromethane in 45% yield (94MC7) (Scheme 1). The A-oxide cannot be prepared by direct oxidation of furazan. 

This route is compatible with various functionality and by choosing the appropriate reagents amino-, halo-, and nitro-substituted furoxans can be prepared illustrative examples include the conversion of cyclopentan-l,2-dione dioxime to the thermally labile trimethylenefuroxan using aqueous sodium hypochlorite <79JCR(S)314>, and of the parent glyoxime to 3,4-dinitrofuroxan by... 

Benzofuroxans can be prepared by oxidation of o-quinone dioximes with, for example, fer-ricyanide or hypohalite in a process which closely parallels the formation of monocychc furoxans from glyoximes. Its utility is restricted by the availability of the starting materials which are themselves often best made by reduction of the furoxan. However, it is a valuable approach when the parent quinone or its monooxime is accessible by other means. It was, for example, the route originally used for naphtho[l,2-c]furoxan, the first aromatic-fused derivative <1886CB176>, and it is the method of choice for acenaphthofuroxans (11). In other cases oxidation of o-nitroanilines or thermolysis of o-nitroaryl azides are more suitable. 

In marked contrast the structure of furoxans was for many years a matter of some controversy. Among the formulations proposed, and thus frequently to be found in the early literature, were the dioxadiazine (or glyoxime peroxide) (7) and the bicyclic arrangements (8) and (9). It was not until the isomerism characteristic of asymmetrically substituted furoxans was fully appreciated (see Section 4.22.3.2.1) that the N-oxide structure (2), originally proposed by Wieland (03LA(329)225) and by Werner (B-04MI42200) some 60 years previously, finally became universally accepted. 

The most frequently used method for the synthesis of monocyclic furazans involves the dehydration of the appropriately substituted a-dioxime. Its utility stems from the ready availability of the precursor. Reduction of furoxans, which may themselves be formed from a variety of sources (Scheme 17) including glyoximes (see Section 4.22.4.2.1), oximation of 1,2-diones, and a -nitrosation-oximation of ketones are among the most favored approaches. 

NMR,108 and by Gagneux and Meier,86 who found that the a-glyoxime was conveniently oxidized to the furoxan by ceric ammonium nitrate. The products of the reactions of 210 are summarized in Scheme 10. Most of these are likely to be formed through the intermediacy of the nitrile oxide (211), or a derivative (e.g., the oximate anion) of this. 4-Phenylfuroxan is a very unstable compound, and in some solvents it decomposes, at least in part, to 211 without addition of base.362 Compound 211 was first isolated by Wieland and Semper, but they assigned to it a hydroxyfurazan structure (209).194-Phenylfuroxan was found not to be quaternized by methyl iodide or dimethyl sulfate (in common with all other simple furoxans), nor to isomerize in ultraviolet light.362... 

Similar reaction sequences have also been used to prepare symmetrical furoxan sulfides and bicyclic compound 276 (95EUP683159). Other syntheses of furoxan sulfides and almost all those of furazan sulfides are based on the displacement of nitro and chloro groups by S-nucleophiles (see above). Furazan sulfides were also prepared by the reduction of the corresponding furoxans (73JHC587). The only synthesis of furazan sulfide 277 from the corresponding glyoxime was reported by Sheremetev et al. in 1991 (Scheme 179) (9 lURP 1643546). 

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