Sulfonic esters of sugars

Studies on sulfonic esters of sugar alcohols have revealed that sulfonic... 

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 purifying, and assessing the purity of, sulfonic esters of sugars, a knowledge of some of their general physical properties is helpful. 

Many sulfonic esters of monosaccharides and their derivatives crystallize with comparative ease, thereby affording a means of purification. As a consequence, little attention has been paid to application of other methods of purification. A few sulfonic esters of sugars have been purified chromatographically.148161 -3181... 

In order that full advantage may be taken of the chemical transformations that sulfonic esters of sugars can undergo, a knowledge of the conditions under which they are chemically unreactive is essential. In this connection, specific chemical reagents and the physical conditions of their application must both receive consideration. 

Sulfonic esters of sugar alcohols often react similarly with ammonia thus, l,4 3,6-dianhydro-2,5-di-0-tosyl-D-mannitol and -sorbitol give326 the corresponding 2,5-diamino-2,5-dideoxy derivatives. However, 1,4 3,6-dianhydro-L-iditol affords326 a compound thought to be 1,4 3,6-dianhydro-2,5-dideoxy-2,5-imino-D-mannitol. 

The p-toluenesulfonic esters of alditols (Tipson, 1952) have bands at 1370-1350 and 1190-1175 cm" for the asymmetrical and symmetrical stretching modes of the —SO2— group (Onodera et al, 1965 Albano et al, 1966). Sulfonic esters of sugars... 

Another deviation from the normal displacement reaction of primary tosylates occurs in nucleoside derivatives (39, 81) where cyclonucleosides and anhydronucleosides are formed by participation of a nitrogen atom (as in purine nucleosides) and oxygen atom (as in pyrimidine nucleosides ), respectively. Iodonucleosides can result from these reactions only if these cyclic compounds are prone to attack by iodide ion. Several new examples of unexpected reactions during the solvolysis of sulfonate esters in sugar derivatives have been recorded in the past few years (2, 4,5,7,15,44,62,63,94). 

The use of tetra-n-butylammonium fluoride (54) in an aprotic solvent such as acetonitrile may be more advantageous. Foster and colleagues (19, 37) have effected an SN2 type of reaction using this reagent in the conversion of l,2 5,6-di-0-isopropylidene-3-0-p-tolylsulfonyl-D-allofura-nose into the C-3 epimeric fluorodeoxy derivative. Note that whereas potassium fluoride is ineffective in displacing secondary sulfonate esters in sugars, tetra-n-butylammonium fluoride is capable of effecting a displacement with Walden inversion even in a furanose drivative. 

Mannitol hexanitrate is obtained by nitration of mannitol with mixed nitric and sulfuric acids. Similarly, nitration of sorbitol using mixed acid produces the hexanitrate when the reaction is conducted at 0—3°C and at —10 to —75°C, the main product is sorbitol pentanitrate (117). Xylitol, ribitol, and L-arabinitol are converted to the pentanitrates by fuming nitric acid and acetic anhydride (118). Phosphate esters of sugar alcohols are obtained by the action of phosphorus oxychloride (119) and by alcoholysis of organic phosphates (120). The 1,6-dibenzene sulfonate of D-mannitol is obtained by the action of benzene sulfonyl chloride in pyridine at 0°C (121). To obtain 1,6-dimethanesulfonyl-D-mannitol free from anhydrides and other by-products, after similar sulfonation with methane sulfonyl chloride and pyridine the remaining hydroxyl groups are acetylated with acetic anhydride and the insoluble acetyl derivative is separated, followed by deacetylation with hydrogen chloride in methanol (122). Alkyl sulfate esters of polyhydric alcohols result from the action of sulfur trioxide—trialkyl phosphates as in the reaction of sorbitol at 34—40°C with sulfur trioxide—triethyl phosphate to form sorbitol hexa(ethylsulfate) (123). 

It appears that the initial lack of interest in sulfonic esters of carbohydrates can be attributed to the fact that sugar chemists were so accustomed to thinking of sugar esters in terms of carboxylic esters (particularly, acetates and benzoates) that they overlooked an earlier... 

As a result of these considerations, a rejuvenescence of interest in sulfonic esters of acyclic-sugar derivatives, e.g., of sugar mercaptals, is to be expected, since they afford a route to the synthesis not only of compounds having one or more methylene groups at desired positions in the sugar chain (of which 2-deoxy-D- ribose, or 2-deoxy-D-eryother groupings, e.g., double bonds, at selected positions in the chain. 

However, reduction of primary sulfonic esters of D-galactopyrano-sides with lithium aluminum hydride in tetrahydrofmran can also result in formation of deoxy sugars. Heyns and coworkers reduced methyl 3-0-methyl-6-0-p-tolylsulfonyl- 8-D-galactopyranoside in this... 

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