Chlorosulfate ester

This method is also used with alcohols of the stmcture Cl(CH2) OH (114). HaloaLkyl chlorosulfates are likewise obtained from the reaction of halogenated alkanes with sulfur trioxide or from the chlorination of cycHc sulfites (115,116). Chlorosilanes form chlorosulfate esters when treated with sulfur trioxide or chlorosulfuric acid (117). Another approach to halosulfates is based on the addition of chlorosulfuric or fluorosulfuric acid to alkenes in nonpolar solvents (118). 

Benzotrithiole 2-oxide (41) was obtained in 76% yield from the reaction of benzene-1,2-dithiol with thionyl chloride <93TL673>. Similarly, 1,3,2-benzodioxathiole 2-oxide was prepared from 1,2-dihydroxybenzene and thionyl chloride <66HC(2i-i)i>, and 1,2,3-benzoxadithiole 2-oxide was obtained from 2-mercaptophenol and thionyl chloride <81AG(E)570>. Reaction of the monosodium salt of 1,2-dihydroxybenzene with sulfuryl chloride afforded an intermediate chlorosulfate ester, which was dehydrochlorinated to 1,3,2-benzodioxathiole 2,2-dioxide by the action of pyridine <66HC(21-l)l>. The substituted 1,3,2-benzodioxathiole 2,2-dioxide (121) was isolated from the photolysis of pyrenedione in the presence of sulfur dioxide <87TL2057>. 

Treatment of 1,1-disubstituted epoxides of the gibberellin family with sulfuiyl chloride results in the formation of the corresponding a,3-enal in good yield, as shown in equation (31). Four examples were reported in which alcohols, esters, lactones and sdkenes survive. The postulated mechanism involves an electrophilic opening of the epoxide with elimination, followed by oxidation of the primary chlorosulfate ester. A steroidal 3-spirooxirane also undergoes this reaction, but the yield is poor and several products are obtained, suggesting that the overall scope of this reaction may be limited. 

Other Leaving Groups (Mitsunobu Reaction, Chlorosulfate Esters, Cyclic Sulfates)... 

Other reactions where the generation of the leaving group constitutes a portion of the mechanism are noted with the use of chlorosulfate esters (Scheme 6.9) and iminoesters (Scheme 6.10). The general mechanisms for these reactions are illustrated below, and will be discussed in relation to applicability to sugars later in this chapter. 

SCHEME 6.19 Chlorosulfate ester conversion of a secondary hydroxyl group to a chloride. 

Selective chlorination of sucrose, by which three of sucrose s hydroxyl groups are substituted with chlorine atoms, produces sucralose (l,6-dichloro-l,6-dideoxy- S-D-fructofuranosyl-(24>l)-4-chloro-4-deoxy-a-galactopyranoside) sweetener sold as Splenda [49]. Sucralose is approximately 650 times sweeter than sucrose and can be used in baking. Its synthesis involves treatment of a partially acetylated sucrose with sulfuryl chloride the initially formed chlorosulfate esters act as leaving groups and undergo nucleophilic displacement by chlorine [20]. Sucralose was first approved for use in Canada in 1991 as of 2006, it has been approved in over 60 countries. 

When used on sugars in the presence of a minimal proportion of pyridine, sulfuryl chloride produces chlorosulfate esters, instead of cyclic sulfates, but Jennings and Jones i were able to rationalize this by showing that, in the presence of an excess of pyridine, these chlorosulfate esters are sometimes converted into cyclic sulfates. For instance, methyl 4,6-0-benzyli-dene-a-D-glucopyranoside 2,3-dichlorosulfate (19) is readily converted by pyridine at 0 into the 2,3-cyclic sulfate (20), whereas, with a stronger... 

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