Unimolar sulfonylation

The monoacylation of 5 -0-acylated ribonucleosides leads mainly to 3, 5 -diesters, as for example, in the acylation of 5 -0-acetyladenosine,94 5 -0-acetyluridine,95 or N6-benzoyl-5 -0-benzoyl-cytidine.96 In contrast, unimolar sulfonylation favors formation of 2, 5 -diesters, as in the p-toluenesulfonylation of 5 -O-acetyluridine95,97 and 5 -0-acetyladenosine.98 It is pertinent that... 

Despite the immediate application of unimolar sulfonylation for the preparation of many w-sulfonic esters of sugar derivatives, a kinetic study of the reaction was not made until 1942 Hockett and Downing136 then found that, with p-toluenesulfonyl chloride-pyridine at 23° 2°, the time to half-esterification for a mole of l,2 3,4-di-0-isopropylidene-D-galactose (with a primary hydroxyl group) is 0.272 hours (see Fig. 2), whereas for l,2 5,6-di-0-isopropylidene-D-glucose (with a secondary hydroxyl group) it is 20.2 hours (see Fig. 3). That is, after about 120 minutes, nearly all of the compound with the free primary hydroxyl group... 

In unimolar or dimolar sulfonylations in which the product still has free hydroxyl groups (and is usually a mixture of compounds), crystallization may not occur. Very often, separation may be accomplished after the mixture has been acetylaied. A useful procedure is to add acetic anhydride to the sulfonylation mixture24 171 172 (after sulfonylation is judged to have proceeded to completion, but before addition of water)... 

Other examples of preferential sulfonylation at 0-2 are known methanesulfonylation of 8-bromoguanosine gave 8-bromo-2, 5 -di-0-(methylsulfonyl)guanosine in 42% yield, and unimolar p-toluene-sulfonylation of 5-fluoro-5 -0-trityluridine gave 5-fluoro-2 -0-p-... 

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