Aldoses osazone formation

Alternatively, a procedure that specifically removes the tritium by ionization, or oxidation to water-t, can be used. Thus, the presence of isotopic hydrogen at C-l of aldoses was confirmed by oxidation, either by re-isolation of the aldonic acid,7 or by measurement of the isotope appearing in the water.26 Other oxidative procedures have involved oxidation to D-glucaric acid,75 the platinum-catalyzed oxidation19 of mt/o-inositol-2-f, bacterial oxidation75 of D-glucitol-5-t, and osazone formation.76... 

According to Micheel, osazone formation starts from an aldose and requires an Amadori rearrangement, so that his scheme may not account for the reaction in the ketose series. It may be concluded that the Fischer mechanism is not valid, and that further studies are needed in order to solve the problem of interaction between ketoses and substituted phenyl-hydrazines. 

In the year 1884, Emil Fi8cheri prepared the first sugar osazones and suggested their use for identification purposes. He later used the fact that D-glucose and n-mannose give the same osazone in his determination of the structure of these two monosaccharides, and he accomplished, through osazone formation, the conversion of aldoses into ketoses. Since then, osazone formation has been used in a multitude of syntheses in the carbo-... 

Fig. 3.12. Osazone formation mechanism by the addition of three phenylhydrazine molecules to one aldose molecule...

Other reactions of carbohydrates include those of alcohols, carboxylic acids, and their derivatives. Alkylation of carbohydrate hydroxyl groups leads to ethers. Acylation of their hydroxyl groups produces esters. Alkylation and acylation reactions are sometimes used to protect carbohydrate hydroxyl groups from reaction while a transformation occurs elsewhere. Hydrolysis reactions are involved in converting ester and lactone derivatives of carbohydrates back to their polyhydroxy form. Enolization of aldehydes and ketones leads to epimerization and interconversion of aldoses and ketoses. Addition reactions of aldehydes and ketones are useful, too, such as the addition of ammonia derivatives in osazone formation, and of cyanide in the Kiliani-Fischer synthesis. Hydrolysis of nitriles from the Kiliani-Fischer synthesis leads to carboxylic acids. 

The Amadori rearrangement of aldosyl amines to aminodeoxyketoses (Chapter VIII), which is an intermediate reaction during osazone formation, also provides a means of passing from aldose to ketose structures. 

FIGURE 22.31 Osazone formation from an aldose involves conversion of both C(l) and C(2) into phenylhydrazones. 

Many years later, several groups conducted investigations into the mechanism of the osazone formation steps and concluded that an Amadori rearrangement is involved in this reaction cascade [18] (Scheme 5,14 to 16). Aldoses 14... 

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... 

In the formation of an osazone, both Cl and C2 are converted to phenylhydrazones. Therefore, a ketose gives the same osazone as its related aldose. Also notice that the stereochemistry at C2 is lost in the phenylhydrazone. Thus, C2 epimers give the same osazone. 

The pair of aldoses obtained from the sequence differ only in configuration about C 2, and hence are epimers. A pair of aldoses can be recognized as epimers not only by tbeir conversion into the same osazone (Sec. 34.7), but also by their formation in the same Kiliani-Fischer synthesis. 

Aldehydes and ketones react with one equivalent of phenylhydrazine, forming phenylhydrazones (Section 18.6). Aldoses and ketoses, in contrast, react with three equivalents of phenylhydrazine, forming osazones. One equivalent functions as an oxidizing agent and is reduced to aniline and ammonia. Two equivalents form imines with carbonyl groups. The reaction stops at this point, regardless of how much phenylhydrazine is present. (Recall that the pH at which imine formation is carried out must be carefully controlled Section 18.6.)... 

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. 

In a study of the deacetylation of acetylated sugar osazones it has been shown that under alkaline conditions and depending upon the substrate, either an external nucleophile fe.a.. Na, MeO , NH3) can be incorporated at C-3 or a 3,6-anhydride can be formed. The 3-methoxy-epimers (49) were thus formed from the L-ervthro-pentose osazone triacetate presumably by formation and 1,4-addition to a phenylazo-ene intermediate." The 2-acetoxy group of aldose diphenylformazan peracetates is also readily displaced. 2-Deoxy-D-arabino-hexose diphenylformazan (50) was thus formed when penta-Q-acetyl-D-glucose or -D-mannose H H diphenylformazan was treated with sodium borohydride." ... 

Oxidation and Optical Activity Formation of Osazones Chain Extension of Aldoses Chain Shortening of Aldoses... 

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