1.2- Dioximes, reaction with aldehydes

The reaction of a-hydroxylaminodioximes or a-dioximes with aldehydes provides a route to the formation of 1-hydro xyimidazole-3-oxides102 (see Section II,F). 

The reactions of a-aminooximes and a-dioximes with aldehydes to form imidazole iV-oxides are discussed with related synthetic methods in Section 4.08.1.2.2. 

Reaction of a-aminooximes or a-dioximes with aldehydes leading to imidazole Al-oxides will be discussed in Section II,F since all of these reactions have a common basis. The widely employed reaction of an a-diamine with an alcohol, aldehyde, or carboxylic acid has been restricted mainly to the synthesis of benzimidazoles. " ... 

Direct IV-oxidation of these heterocycles invariably fails (see Section 3.02.7.2.8), making ring synthetic methods the only viable alternative <93CHE127>. Although there has been considerable interest in the chemistry of compounds of this type, there are no new synthetic approaches of a general nature. The most common approach is to react a-oximinoketones with aldehydes and primary amines. With formaldehyde, however, the 2-unsubstituted 1-oxides rearrange to 2-imi-dazolones. Variations on this theme allow synthesis of 1-hydroxyimidazole 3-oxides. Thus, treatment of an a-dicarbonyl compound with an aldehyde and hydroxylamine, or reaction of the aldehyde oxime or aldehyde with a 1,2-dioxime are common approaches <898773 >. Similarly, a-hydroxyamino-... 

The hydroxyl in cassaic acid is secondary because oxidation of the acid with chromic acid generates a diketo acid (m.p. 238-239°, [a] —164.5° in ethanol) which did not give positive reactions for aldehydes and which formed a methyl ester (m.p. 129-130°), a dioxime (m.p. 130-132°), and a disemicarbazone (m.p. 290°). Ruzicka and Dalma (19) have suggested that the saturated acid, free of oxygen-containing substituents, from which cassaic acid is derived, be named cassanic acid. The diketo acid obtainable... 

The extent of oxidation, when determined by the reaction of the product with phenylhydrazine, is 85%. Hydrolysis of the oxidized xylan should produce approximately equimolar quantities of D-glyceraldehyde and glyoxal. Experimental determination of glyceraldehyde indicates 67 % of the theoretical when the oxidized xylan is distilled with sulfuric acid and the evolved methylglyoxal measured as the phenylosazone. Glyoxal is isolated in 63% yield, when separated as the phenylosazone or as the dioxime. Aldehyde groups in the oxidized xylan may be further... 

The aldehyde (50 mmol) and -benzoquinone dioxime (6.90 g, 50 mmol) are dissolved in ethanolic hydrochloric acid (3.5 m, 100 ml). The reaction mixture is then refluxed for several hours until the deep red colour disappears. After cooling, the hydrochloride is filtered off, suspended in ethanol (100 ml), water (200 ml) is added, and the mixture is neutralized with aqueous ammonia. The precipitate is filtered, washed in turn with water and ethanol, and dried. Prepared in this way are the following 1-hydroxybenzimidazole 3-oxides (2-substituent, yield, m.p. listed) Ph, 72%, 223-224°C -Me2NC6H4, 91%, 180-185 C -HOC6H4, 65%, 227-228°C ... 

These heterocycles have been synthesized via (1) cyclization of 3-hydroxyisoindolone (Equation 43) (2) cyclization with Burgess reagent (Equation 44) (3) reaction between oximes and 1,2-dibromoethane (Equation 65) (4) ring expansion of benzofurandione dioxime (Equation 73) (5) cyclization of 0-allylhydroxamic acid with phenylselenenyl sulfate (Equation 45) and (6) condensation of /3-ureidoxyalcohols and aromatic aldehydes (Equation 58). The last of these methods seems to be the most convenient in terms of observed reaction yields and substrate diversity. 

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