The methylation of sugar mercaptals
Creators: name: Yates, Keith
Publisher: name: University of British Columbia
Year: 2012

description: It was reported in 1934 by Lieser and Leckzyck that D-glucose diethyl mercaptal could be selectively methylated by use of methyl iodide and silver oxide at 0°C to give exclusively 2-0-methyl-D-glucose diethyl mercaptal in 52% yield. They stated that the mercaptals of D-galactose, L-arabinose, D-xylose and L-rhamnose failed to react in a similar way and isolated no products. The present investigation was undertaken to determine to what extent these statements are correct, and if methylation does occur with the mercaptals of other sugars, to determine the nature of the methylated products. It was also of interest to determine if reaction predominates at any one position as in D-glucose mercaptal. The original observations of Lieser and Leckzyck were substantially confirmed by a repetition of their experiments. The present work, however, has shown that some methylation does occur with mercaptals other than that of D-glucose but to a much smaller extent, and that this is partly due to the insolubility of these mercaptals in methyl iodide. Tetrahydrofuran was found to be a suitable methylation solvent in which the diethyl mercaptals of D-glucose, D-galactose, L-arabinose and D-mannose have comparable solubility. These mercaptals were methylated in this solvent by a modification of Lieser’s procedure. Investigation of the products by paper chromatography indicated that all four gave similar results. Further there did not appear to be any significant difference in the reactions when they were carried out at 3°, 22°, and 50°C. These experiments were all on an exploratory scale. Suitable conditions were established for larger scale methylations and separations of products. One such large scale methylation and separation was carried out on D-glucose diethyl mercaptal and the products hydrolysed and separated as the free sugars by means of column chromatography. Six distinct methylated glucoses were separated showing that the reaction is by no means as selective when tetrahydrofuran is used as reaction solvent. The largest product, but no longer dominantly so, was positively identified as the 2-0-methyl derivative, again showing that reactivity is greatest at the 2-position. This was found to be the only monomethyl ether produced. A second large scale methylation and separation was carried out in an exactly similar manner on D-mannose diethyl mercaptal. Eight distinct methylated mannoses were separated with the extent of methylation being comparable with that above. Two major monomethyl products were isolated and identified by periodate oxidation studies and their osazones as the 6-0-methyl and 5-0-methyl derivatives. The results indicate that the 6-posltion is most reactive in D-mannose diethyl mercaptal. A third similar methylation of L-arabinose diethyl mercaptal, followed by separation of products by a combination of column and paper chromatography, yielded seven distinct methylated arabinoses. There were no major monomethyl products, reaction appearing to have gone largely to the dimethyl stage. Three monomethyl arabinoses were, separated in negligible amounts and could not be identified. Reaction apparently does not predominate at any one position in L-arabinose diethyl mercaptal. Preliminary experiments on D-galactose diethyl mercaptal indicated methylation to be of a highly random nature. An exploratory separation of products showed that no one monomethyl ether predominated. The large scale methylation and separation was not repeated on this mercaptal. Of the compounds investigated, unusual reactivity of the 2-hydroxyl group is only clearly manifested by D-glucose mercaptal. No marked reactivity of this position is shown by the other mercaptals, although there is evidence that the 6- and 5-hydroxyls of D-mannose mercaptal are unusually reactive.