Phenylhydrazine, reaction with sugars

Stroh914 has reviewed the influence of substituents on the reaction of phenylhydrazines with sugars and their selectivity in reaction with sugar mixtures. The so-called diphenyl-methanedimethylhydrazine [p,p/-methylenedi(Arl-methylphenylhydrazine)], for instance, is sometimes useful for separating sugar mixtures as it condenses more easily with most aldoses than with ketoses.915 1-Methyl-1-phenylhydrazine can also be used to differentiate aldoses from ketoses with aldoses it forms the hydrazone but with ketoses the osazone.916... 

Simple sugars undergo reaction with phenylhydrazine, PhNHNH2, to yield crystalline derivatives called osazones. The reaction is a bit complex, however, as shown by the fact that glucose and fructose yield the same osazone. 

Reducing sugars can be detected by reaction with phenylhydrazine to yield a hydrazone product, except the result of the reaction is not what one might imagine giving the structure of aldoses and ketoses. Glucose, for example, can react with phenylhydrazine to yield the anticipated... 

Since the discovery of the reaction of phenylhydrazine with sugars to form osazones by Fischer,35 many investigations have utilized this reaction in the identification and separation of sugars, but the precise structures of osazones and their mode of formation are still in doubt.34 There is no doubt, however, that the initial reaction involves the formation of a hydrazone, which then reacts further to yield eventually a f)u-l,2-hydrazone or osazone. 

The structure of this sugar was established as follows (a) reaction with phenylhydrazine yielded 4-methyl-D-glucosazone 11 (b) oxidation (HOBr) yielded a methylmannonolactone, which exhibited the properties that are characteristic of 8-lactones.7... 

Fig. 9. Fischer s phenylhydrazone reaction85 and the glycoblotting method first demonstrated by using aminooxy-functionalized synthetic polymers. (A) Reaction of sugars with phenylhydrazine (B) the general concept of glycoblotting and (C) the aminooxy-functionalized synthetic polymers used in the preliminary study.84 (Original figure made by the author.)...

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. 

Many 1-phenylflavazoles derived from sugars have been characterized by chromatographic Rf values " and by x-ray diffraction patterns. " Most syntheses of pyrazolo[3,4-b]quinoxalines involve polyhydroxy-alkylquinoxalines as intermediates and, by reaction with phenylhydrazine, result in the formation of 1-phenyl substituted derivatives of the ring system. Thus the o-arabotetrahydroxybutyl compound 6, obtained from reaction of o-glucose with o-phenylenediamine, reacts with three moles... 

Due to the presence of carbonyl, aldehyde or ketone radicals, sugars are capable of addition reactions with nucleophilic reagents such as phenylhydrazine (C6H5-NH-NH2). The addition of three phenylhydrazine molecules to an aldose (Figure 3.12) leads to the formation of osazone, a crystallized product with specific physicochemical characteristics, especially its melting point. This makes it possible to identify the corresponding sugar. 

The 2,4-dichlorophenylhydrazones of a great many sugars were isolated and characterized by Mandl and Neuberg (29), The hydrazones were easy to crystallize and gave good melting points. The same authors were able to differentiate between L-arabinose and D-ribose by means of their di-phenylhydrazones. Reactions with p-bromophenylhydrazine or 1-benzyl-l-phenylhydrazine also often lead to crystalline derivatives. 

Of a number of proposed derivatives, the products of the reaction of sugars with phenylhydrazine or with substituted phenylhydrazines are the most suitable. The reaction is carried out in 50% sulfuric acid at room temperature. Phenylhydrazones are formed. 

Derivatives of the Carbonyl Group. Not many reactions of the aldehyde or keto group of sugars are observed, because the carbonyl forms of sugars comprise only a fraction of one percent in the equilibrium mixture. They can be trapped, however, in a few reactions, e.g. by oximfe formation. Important for the identification of sugars is the reaction with phenylhydrazine or with substituted phenylhydrazines (E. Fischer), which involves two carbon atoms and results in osazones ... 

Another reaction that is characteristic of a-hydroxy aldehydes or ketones, which has been found of value for the characterisation of sugars, is the formation of osazones with phenylhydrazine. This reagent reacts with either an aldose... 

Sugar lactones react readily with hydrazine to give crystalline derivatives useful for isolation and identification (127). Thus, addition of hydrazine to a reaction mixture containing an aldonolactone facilitates isolation of the product. The lactone may be regenerated from the hydrazide by treatment with nitrous acid (128). The phenylhydrazides obtained on treatment of aldonolactones with phenylhydrazine are also useful for characterization (129,130). 

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