Phenylhydrazones and Osazones

The recent literature on the synthesis and reactions of carbohydrate phenylhydrazones and osazones has been reviewed.  

An investigation of the structures of the D-pentose phenylhydrazones in water, methanol, and pyridine by chemical, spectroscopic, and chiroptical methods has indicated that the acyclic form is adopted in these solvents. A related study has shown that D-glucose phenylhydrazone also adopts the acyclic form in DMSO, whereas solutions of the corresponding 4-nitro- and 2,4-dinitro-phenylhydrazones in DMSO contain only 40 and 10%, respectively, of the acyclic form. An n.m.r. study of 2,5-anhydro-D-lyxose and -xylose 4-nitrophenylhydrazones is mentioned in Chapter 20. 

El Ashry s group has extended its earlier studies on the chemistry of carbohydrate hydrazones. Reaction of the 2-(phenylhydrazone) (227) derived from L-t/ireo-2,3-hexodiulosono-l,4-lactone (228) with methylhydrazine gave a rearranged product, identified as the pyrazoledione derivative (229). Methyl- 

Simon and A. Kraus, Amer. Chem. Soc. Symposium Ser 1976, No. 39, Synthetic Methods Carbohydrates Symposium, 188 (Chem. Abs., 1977,87, 136 157/c). 

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Electron Spin Resonance Studies of Chemical Changes of Phenylhydrazones and Osazones in Alkaline Solution... 

Figure 2. Electron spin resonance spectra of sugar phenylhydrazones and osazones (2.5 mM to 3.5 mM, in Me2SO-l% K-tert-BuO)...

Table I. Free Radicals from Sugar Phenylhydrazones and Osazones in Methyl Sulfoxide-1 % Potassium ferf-butoxide at 25 zt 3°C...

In order to reduce an orange dye which is formed when the diazonium salt is added to the bisulfite solution, a small amount of zinc and acetic acid is added. To prepare the base, the hydrochloride is treated with excess 30 per cent sodium hydroxide solution, and the oily base is extracted with ether. The ethereal extract is dried and, after removal of ether, is distilled under reduced pressure. Substituted phenylhydrazines, such as p-nitrophcnylhydrazine and p-bromophenylhydrazine, are prepared in the same manner. Arylhydrazines are strong bases forming characteristic salts, which are important reagents in the identification of aldehydes, ketones, and sugars (see preparation of phenylhydrazones and osazones). 

Fischer phenylhydrazone and osazone reaction. Formation of phenylhydrazones and osazones by heating sugars with phenylhydrazine in dilute acid. 

The formation of phenylhydrazones and osazones from dehydroas-corbic acid is the basis of the most commonly used method of ascorbic acid analysis. The reactions are described in the section on determinations. There is no great specificity to this reaction, which is given by most compounds containing keto groups. However, most phenylhydrazones become intensely colored only in alkaline solution, while the dehy-droascorbic acid type of compound is intensely colored in acid solution. Both dehydroascorhic acid and 2,3-diketogulonic acid are converted to the same osazone under the conditions used. 

For many years the precise structures of some of the products obtained from reaction of sugars with phenylhydrazine have been the subject of much discussion. Reaction of D-mannose phenyl-hydrazone with acetic anhydride in pyridine yields D-ara6fwo-3,4,5,6-tetraacetoxyl-l-phenylazo-1-hexene. The n.m.r. spectrum of this compound clearly establishes its structure. Acyclic structures have similarly been assigned to various phenylhydrazones and osazones. The work of Wolfrom and his co-workers perhaps best illustrates the kind of approach that has been adopted. The n.m.r. spectrum of o-lyxohexose phenylosazone was measured in dimethyl sulphoxide. The three possible structures of the osazone (44, 45, 46) were considered in terms of the spectrum. 

Nevertheless the disentangling of these closely related compounds offered practical stumbling blocks which even the finest experimental skill could hardly surmount. It was Fischer s discovery of phenylhydrazones and osazones that opened afresh the pathway toward complete understanding. The new tool supplied by phenylhydrazine was most powerful and produced a complete change in one aspect of the carbohydrate chemistry. In an almost incredibly short time, Fischer carried to a successful conclusion a vast research which ended with the deterrnination of the structures and spatial configurations of all the known pentoses and hexoses. 

Other references related to the Fischer phenylhydrazone and osazone synthesis are cited in the literature. "... 

The mechanism for the formation of hydrazone or osazone of carbohydrate with hydrazine or phenylhydrazine was described in detail for the Fischer Phenylhydrazone and Osazone Synthesis, so only a part of the mechanism for the preparation of quinoxa-line derivative is illustrated here. The presence of boric acid and acetic acid may help the formation of hydrazone. 

Identification. Phenylhydrazone and osazone octaacetate. Oxidation of hydrolysis products to give mucic acid. 

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