Rates of rnethanolysis reactions of D-glucose, D-galactose, and D-mannose have been determined. The results confirm those found earlier for pentoses that the glycosidation reaction proceeds to equilibrium through four distinguishable competing reactions: (I) hexose -P furanosides, (2) anomerization of furanosides, (3) furanosides + pyranosides, and (4) anomerization of pyranosides. The glycoside compositions at equilibrium are interpreted in terms of conformational analysis for furanoid and pyranoid rings. The energy differences between the ground states also contribute to a n important degree in determining the relative rates of reaction.Canadian Journal o f Chemistry, 46, 3085 (1968) Earlier papers (1, 2) in this series described a study of the kinetics of methanolysis of the four D-pentoses and summarized the literature on this topic. The present paper reports the extension of these studies to the three hexoses, Dglucose, D-galactose, and D-mannose.The conditions cited for the reactions were carefully controlled and products were analyzed by gas-liquid chromatography of their fully trimethylsilylated derivatives as described previously (3). Products in one of the reactions in the D-galactose series (Table VII) were analyzed methanol. The equilibrium constants (K) in Table I were obtained from glycoside compositions after prolonged reaction periods (Table 11).Reliable rate data for reaction 1 (Table V) could only be obtained with D-glucose; Dgalactose and D-mannose were not sufficiently soluble in methanol at the concentrations used.No detailed interpretation of reaction 1 can be offered on the evidence available; the reaction was examined only t o establish the identities of the initial products. Qualitative examination c o l o r i~e t r i c a~l~ (4) after separation by paper of the products from methanolysis of galactose chromatography (5).confirmed the results obtained with D-glucose As with the pentoses, it was found that meth-that furanosides were the initial products in anolysis proceeds to equilibrium through four this reaction. For D-mannose, the initial proddistinguishable competing reactions and it was uct of methanolysis was methyl p-D-mannopossible to establish conditions under which a pyranoside. This result is similar to that found single reaction predominated. Since the observations were made at constant hydrogen ion concentrations, the bimolecular reaction could be expressed in terms of first-order rate kinetics. Compositions of reaction products at different times under specific conditions are given in Tables V-VIII (see Experimental). These results show that single reactions predominated during the early periods and were characterized earlier for the stereochemically equivalent lyxose which also gave pyranosides as initial products in methanolysis (2). Two recent reports (6,7) have discussed the role of dimethyl acetals as intermediates in the formation of furanosides from glycoses during methanolysis. The amounts of dimethyl acetals found were small and from rate studies it was concluded...

The previous paper (1) in this series described a study of the lcinetics of metl~anolysis of the four D-pentoses. As a prelude to extending this work to the hexoses it was necessary to find methods for analyzing the methyl hexosides by gas-liquid chromatography. The present communication describes the gas-liquid chromatographic separation of the four methyl glycosides of each of the three aldohexoses, D-galactose, D-glucose, and D-mannose.Unsubstituted methyl glycosides are considerably less volatile than Inany other derivatives in which some of the hydroxyl groups of the sugar ring are substituted bj, ester or ether groups. Nevertheless, gas-liquid chromatography of a number of unsubstituted methyl glycosides has been described (2, 3). However, the conditions required for these separations vrere not sufficiently selective to resolve the four isomeric glycosides of a single monosaccharide. In the previous studies in this series (1, 4) the methyl glycosides were 0-inethylated or 0-acetylated to make them sufficiently volatile for analysis by gas-liquid chromatography. In the present study it was found that the 0-trimethylsilyl derivatives of the methyl hexosides could be resolved better than either the 0-acetyl or the 0-methyl derivatives. The use of 0-trimethylsilyl derivatives has the advantage of ease of preparation and simple recovery of the original con~pound by a very mild hydrolysis ( 5 ) . The separations described here may therefore also be used on a preparative scale to provide pure sainples of individual methyl glycosides for spectroscopic examination or studies of kinetics of hydrolysis.The retention times of the methyl tetra-0-trimethylsilyl hexosides and of the trimethylsilyl tetra-0-triinethylsilyl hexosides, relative to the fastest moving componeilt in each series, are shown in Table I. Three column pacltings nrere used and each required a different column temperature for optiinuin resolution. The crystalline hexoses each gave only one peak after trimethylsilylation; it is not kno\vn whether these single pealts contained more than one anomer or ring form. However, it is likely that the hexoses underwent trimethylsilylation before equilibration in the pyridine solution. If this was so, then the single pealts for each hexose must represent the anomeric species present in the common crystalline forin of the sugar. This is in agreement with the results of S\\.eeley et al. (6), who found that "the products obtained from pure single anomers of pentoses and hexoses generally show a single peak on gas chromatography though, in some cases, small amounts of another anonleric form may be apparent. In general, anoinerizations occurring in pyridine during preparation of the trimethylsilyl derivative are remarkably minimal."The four methyl D-mannosides were well resolved on columns a or b, with the latter providing slightly better separation. Similarly, the four methyl D-glucosides were resolved on columns b or c but the separation was significantly improved on the latter column. The four methyl D-galactosides ...