Action of bases on aldose phenylhydrazones synthesis of new hydrazono-1,4-lactones

The major accomplishment of the work presented in this thesis is the synthesis of new aldonohydrazono-1,4-lactones. This new type of compounds was formed by peroxidation of aldose phenylhydrazones in basic media. The phenylazo-hydroperoxides, first formed underwent nucleophilic substitution by O-4 to give the new products without showing any sign of epimerization. Aldose phenylhydrazone acetates do not undergo this reaction, but instead eliminate leaving groups to afford azoalkenes (see Scheme I). These two reactions differ markedly from the reactions of aldoses and glycosylamines with bases. Aldoses isomerize in bases to give epimeric aldoses and ketoses and glycosylamines are converted to 1-amino-1-deoxy-ketoses. When treated with oxygen and base the carbon chain of aldoses and glycosylamines is disrupted and two acids (a lower aldonic acid and formic acid) are formed. The difference observed in the behaviour of phenylhydrazones can be explained by their inability to tautomerize. Aldoses and aldosamines possess acidic $\alpha$-hydrogens which are responsible for their tautomerization. They form resononance stabilized enolate and enolamine anions, which afford on protonation enediols and enolamines. Enediols possess two acidic OH protons which can undergo ionization. Ionization of one OH reverses the reaction and gives two epimeric aldoses; whereas ionization of the other, yields a resonance stabilized ion which affords a ketose. Accordingly, aldoses give upon treatment with base two epimeric aldoses and a ketose. Similar treatment of glycosylamines with base yields enolamines, which possesses one OH and one NH group. Since the OH proton is much more acidic than the NH proton, it will preferentially ionize to give a ketose derivative (see Scheme II). Phenylhydrazones on the other hand, possess acidic NH protons, which are significantly more acidic than their $\alpha$ hydrogens. This is because the hydrazonate ions are more stable than the enolhydrazinate ions, formed by ionization of $\alpha$-hydrogens (the hydrazone ion is a hybrid of three resonance forms, whereas the enolhydrazine ion is stabilized by only two forms). Since enediols, enolamines and enolhydrazines are needed for epimerizations and for degradative oxidations, the inability of hydrazones to enolize to any significant extent, prevents them from undergoing these two reactions. (Abstract shortened with permission of author.).