Osazones chelation

Chelation, in osazone formation, III, 43 Chemical constitution, physiological activity and, of ascorbic acid analogs,... 

It will be seen that the cleavage of the hypothetical hydrazo derivatives to the hypothetical imino compounds obviates the necessity of assuming direct oxidation by phenylhydrazine. Fieser and Fieser inquire why osazone formation ceases with the introduction of two phenylhydrazine residues, and seek to explain this fact by the postulation of chelate tautomeric ring structures XLIII or to the existence of a resonance... 

In order to find the reason for the failure of formazan reaction, a model experiment was set up using 2-quinolinecarboxaldehyde phenylhydrazone whose structure, if the nitrogen of the quinoline be considered, is like that of a phenylosazone, with the six-membered chelate ring in it as proposed by Fieser and Fieser for sugar osazones. 

Analogous to the formazans obtained by loosening the chelate ring in the above manner, the sugar osazones of supposedly chelate structure were found to undergo reaction in alkaline alcohol and to give n-glucose phenylosazone formazan in dark-violet needles. Mild acetylation produces the black tetraacetate of this compound. 

On the basis of these experimental facts and the above considerations concerning the structure of n-glucose phenylosazone, the chelate ring form VI of Fieser and Fieser appears to describe the finer structure of the mixed osazone A. 

Figure 6.16 Osazone formation. The hydrogen-bonded ring is that established directly by NMR spectroscopy the chelated proton appears to move in a single potential well.

The structure of inosose bis(phenylhydrazones) resembles that of saccharide osazones in that the bishydrazone residues in both are chelated that is, bridged by an imino group (the other NH group is unchelated). 

The Fiesers suggested, on theoretical grounds, that osazones exist in tautomeric, chelated forms which stabilize these unsaturated compounds and prevent the reaction of hydrazines with saccharides from proceeding... 

The osazones are yellow, crystalline compounds that melt with decomposition. They exhibit mutarotation this had previously been attributed to a variety of causes, ranging from cyclization to partial hydrolysis.The present view, however, is that mutarotation of osazones is due to chelation. This explanation was devised because it was found that mutarotation occurs only with osazones capable of forming chelated rings the disubstituted osazones, such as n-araWno-hexulose 2-methyl-2-phenylosazone, do not mutarotate. Furthermore, mutarotation takes place only in such basic solvents as pyridine, which might cause a partial breakdown of the chelated ring. 

The apparent dissociation constant of different substituted osazones has been measured in acetic acid, and shown to follow Hammett s equation. The reduction potential has been followed polarographically and used, as noted previously (see p. 159), to demonstrate the chelated nature of osazones. 

A striking feature in the reactions of osazones is the fact that the two hydrazone residues are nonidentical in their reactivity. The hydrazone residue at C-1 is readily alkylated and acylated, but that at C-2 is not. This behavior has been attributed to chelation of the imino proton of the hydrazone at C-2. Furthermore, among the hydroxyl groups of the sugar residue, the one on C-3 seems to be very reactive, readily undergoing dehydration and, in some cases, inversion this is followed in reactivity by the primary hydroxyl group (on C-6 of hexoses), which readily engages in the formation of 3,6-anhydrides. 

In similar studies on the structures of osazones, but using 100 Mc./sec. n.m.r. spectroscopy, a long-range coupling between the C-1 proton and the non-chelated imino-proton was observed, and was confirmed by double resonance and deuteration techniques. 

It should be noted that the members of the chelated pair have never been separated in the case of saccharide osazones, but this has been achieved with noncarbohydrate bis(phenylhydrazones). In at least one case they were found to be interconvertible, either by irradiation with light (pho-tochromism) or by treatment with acids or bases (see Fig. 2)316... 

Further evidence for the chelated structure of osazones was obtained by physical methods,317 such as polarography318 and ultraviolet3 7,319 327 and 1H NMR307 312326 spectroscopy, which clearly showed that the two NH groups (attached to C-l and C-2) were not in identical environments. Similarly, 5N N M R spectroscopy revealed significant differences in the chemical shifts of the two H-coupled nitrogen atoms, attributable to chelation.328,329... 

The presence of stable chelated rings in osazones is also evident from the slowing down, and sometime inhibition, of certain reactions. Thus, the for-mazan reaction223 requires potassium hydroxide to break the chelated ring of osazones and to effect coupling with the diazonium ion.319,320 Similarly, the formation of polyhydrazones is inhibited by chelation accross the C-l... 

Scheme 35. Two pairs ol tautomeric chelated osazones are possible, but only the top pair is formed.

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