Glycosylamines, mutarotation

Ellis and Honeyman80 have raised strong doubts as to the validity of the structural determinations that have been applied to glycosylamines these doubts are based on the fact that such compounds are readily isomerized, as evidenced by their mutarotation. The formation of a trityl ether cannot be considered valid evidence for the presence of a primary hydroxyl group in the compound tritylated, and periodate oxidation, which is often excessive, may lead to faulty conclusions. 

Most glycosylamine acetates are readily obtainable in crystalline condition. Their stability is excellent they can be stored indefinitely without occurrence of any decomposition. Since their melting points are sharp and reproducible, and their chloroform solutions do not mutarotate, they are derivatives suitable for identifying sugars and glycosylamines. 

The mutarotation of glycosylamines has been studied more in methanolic solutions than in water, because any intermediate from addition of this solvent to the acyclic Schilf base cannot yield aldehydo sugar. As would be expected from the mechanisms of Figure 3.23, increased acid strength results in faster mutarotation (Figure 1.24). 

Figure 1.24 Mutarotation and hydrolysis of glycosylamines, illustrated with N-aryl glucosylamines.

The surprising inertness of the glycosylamines to mutarotation by a base-catalyzed mechanism arises from the small tendency of an amino nitrogen-atom to release a proton. At high alkalinities, the base-catalyzed reaction takes place to a small degree with glycosylamines of primary and secondary amines.277 With those of tertiary amines, there is no proton to be released, and the mutarotation reaction must take place by acid catalysis (see Fig. 16). The high sensitivity of the... 

Isbel HS, Frush HL (1958) Mutarotation, hydrolysis and rearrangement reactions of glycosylamines. J Org Chem 23 1309-1319... 

Many glycosylamines exhibit mutarotation which may be due to the establishment of an equilibrium between the a- and jS-isomers and the corresponding Schiff base or possibly to a partial hydrolysis (id, 62 dP, Pa,6). The mechanism outlined necessitates the presence of a hydrogen atom attached to the nitrogen atom, i.e., the aglycon amine must be a primary amine. However, the observed mutarotation of the corresponding derivatives of secondary amines may be ascribed to the formation of an intermediate quaternary ion R2N+=CH—(CHOH)4—CH2OH. 

Isbell and Frush (9a) have proposed a mechanism for the mutarotation of the glycosylamines ... 

In comparison with the sugars, the mechanism for basic catalysis accounts for the lessened catalytic effect of the hydroxyl ion on the mutarotation of the glycosylamines. The amino nitrogen will have less tendency to donate proton (V VI) than will the hemiacetal hydroxyl of the sugars. Other mechanisms for mutarotation may also be operative simultaneously. 

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