Sulfuryl chloride with sucrose

SCHEME 27. Ballard, Fairclough, Hough, and Richardson s study of the selective low-temperature chlorination of sucrose with sulfuryl chloride (1973). 

Treatment of sucrose with sulfuryl chloride in pyridine at 50° afforded443 a complex mixture of products from which were isolated, in low yields, one tetrachloro and two pentachloro derivatives. 

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. 

Finally, a valuable example of multistep modifications of sucrose is the synthesis of Sucralose (l Ab -trideoxy-l Ab -trichloro-tya/flcm-sucrose)—a compound 650 times more sweeter than sucrose,15,326,327 which was obtained by treatment of 6-O-acetylsucrose with sulfuryl chloride in pyridine. Further reaction of this derivative with triphenylphosphine and diethyl azodicarboxylate afforded an epoxide from which a tetrachloro-derivative... 

Starting with the hexa-O-benzoyl sucrose, both C-4 and C-6 can be reduced. The C-6 hydroxyl group of the hexa-O-benzoyl sucrose can be replaced with iodine by reaction with triphenylphosphine, iodine, and imidazole. The iodinated derivative can then be reacted with sulfuryl chloride to give chlorination of C-4, with inversion of the configuration, forming 2,3,l, 3, 4, 6 -hexa-0-benzoyl-4-chloro-4,6-deoxy-6-iodo-ga/actosucrose [122]. This derivative can be reduced at C-4 and C-6 with tributyltin hydride in the presence of a radical initiator to give 4,6-dideoxysucrose (reaction 4.134). 

The 6,6 -dichloro-6,6 -dideoxysucrose can be synthesized in high yields (>70%) by reaction of sucrose with triphenylphosphine in carbontetrachloride and pyridine [28] (see reaction 4.123 in Chapter 4). It, however, is not sweet at all. The 4,6,r,6 -tetrachloro-4,6,r,6 -tetradeoxygalactosucrose was first synthesized by preparing the 6,r,6 -tri-0-(methylphenylsulfonyl) sucrose, followed by reaction with lithium chloride and chlorination of the C-4 hydroxyl with sulfuryl chloride [27] (see Fig. 5.7B). This tetrachlorogalactosucrose was found to be 200 times sweeter than sucrose. 

Direct halogenation of sucrose has also been achieved using a combination of DMF—methanesulfonyl chloride (88), sulfuryl chloride—pyridine (89), carbon tetrachloride—triphenylphosphine—pyridine (90), and thionyl chloride—pyridine—1,1,2-trichloroethane (91). Treatment of sucrose with carbon tetrachloride—triphenylphosphine—pyridine at 70°C for 2 h gave 6,6 -dichloro-6,6 -dideoxysucrose in 92% yield. The greater reactivity of the 6 and 6 primary hydroxyl groups has been associated with a bulky halogenating complex formed from triphenylphosphine dihaUde ((CgH )2P=CX2) and pyridine (90). 

The first displacement reaction at C-2 position in carbohydrates was achieved during the study of sulfuryl chloride reaction with sucrose (92). Treatment of 3,4,6,3, 4, 6 -hexa-0-acetylsucrose 2,l -bis(chlorosulfate) with lithium chloride in hexamethylphosphoric triamide at 80°C for 20 h led to the corresponding 2,l -maimo derivative in 73% yield. 

The reaction of sulfuryl chloride with disaccharides is of current interest. Although chlorine-containing products were isolated earlier from this reaction with sucrose,350 their structures were not elucidated. Since then, one tetrachlorotetradeoxy- and two penta-... 

The reaction of sulfuryl chloride with furanoid derivatives has been studied [51,52], and the reaction has been applied to disaccharides, for example, methyl p-maltoside [53] and sucrose [54,55], to yield chlorodeoxy derivatives. 

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