1,6-dichloro-1,6-dideoxy

Then, selective halogenation has been carried out at mild conditions under which only the halogenation of the two primary hydroxyl groups occurs. The secondary hydroxyl groups remain intact under these conditions. The reaction proceeds smoothly with carbon tetrachloride and triphenylphosphine in anhydrous pyridine at 5°C for 18 hours (22). 1,6-Dichloro-1,6-dideoxy-3,4-0-isopropyli-... 

The NMR and IR spectra confirm the structure of 1,6-dichloro-1,6-dideoxy-3,4-0-isopropylidene-D-mannitol... 

Other renewable resources sorbitol (I), cellobiose (XXV), etc. can be used in similar ways as starting materials in the preparation of epoxy resins. We are now working on a direct two-step preparation of diepoxy sorbitol derivatives by direct halogenation of the two primary hydroxyl groups with the formation of 1,6-dichloro-1,6-dideoxy-sorbitol, (XXIII), followed by epoxy ring formation (1,2 5,6-dianhydrosorbitol (XXIV) ... 

Sucralose, 1,6-dichloro-1,6-dideoxy-/3-o-fructofuranosyl 4-chloro-4-deoxy-o -D-galacto-pyra-noside or 4,1, 6 -trichloro-4,l, 6 -trideoxy-ga/acfo-sucrose (Fig. 1), is a chlorinated derivative of sucrose discovered in 1976 and marketed under the brand name Splenda . Its chemical formula is C 2H 908C13 (MW 397.35). It is a white, odorless, crystalline powder that is soluble in water (280 g/L at 20°C), methanol, and ethanol. Sucralose is 400-800 times sweeter than sucrose (Table 1). It has a clean, sugarlike taste and a time-intensity profile much like that of sucrose, although more persistent. It has no bitter or any other objectionable aftertaste. It is a flavor enhancer. It shows sweetness synergism with cyclamate, acesulfame-K, and neohesperidin dihy-drochalcone (8,25,57,86). 

Under mild conditions, isosorbide (3) is converted into 1,6-dichloro-1,6-dideoxy-D-glucitol (147) by reaction with boron trichloride (Scheme 41). Compound 147, which was not isolated in pure form, was allowed to react with benzaldehyde to afford 2,4-(3-benzylidene-1,6-dichloro-1,6-dideoxy-D-glucitol (148) and 2,4 3,5-di-O-benzylidene-1,6-dichloro-1,6-dideoxy-D-glucitol (149). By this method, the two tetrahydrofuran rings are cleaved in a very mild manner.218... 

Dichloro-1, 6-dideoxy-a-D-fructofuranosyl-4-chloro-4-deoxy-ot-D-galactopyranoside, 398, (S2)33... 

Dichloro-1,6-dideoxy-P-D-fructofuranosyl-4-chloro-4-deoxy-a-D-galactopyranoside. See Sucralose... 

Enzymic methods were used to link a-D-glucopyranose to the anomeric positions of a-D-lyxopyranose and P-D-xylulose. Various dichloro-dideoxy sucroses and products derived by selective nucleophilic displacement of single chlorine atoms are referred to in Chapter 8. Trehalose derivatives carrying long-chain branched fatty acid residues are referred to in Chapter 19. 

Sucralose is quite stable to heat over a wide range of pH. However, the pure white dry powder, when stored at high temperature, can discolor owing to release of small quantities of HCl. This can be remedied by blending it with maltodextrin (93) and other diluents. The commercial product can be a powder or a 25% concentrate in water, buffered at pH 4.4. The latter solution may be stored for up to one year at 40°C. At lower pH, there is minimal decomposition. For example, in a pH 3.0 cola carbonated soft drink stored at 40°C, there is less than 10% decomposition after six months. The degradation products are reported to be the respective chlorinated monosaccharides, 4-chloro-4-deoxy-galactose (13) and l,6-dichloro-l,6-dideoxy-fmctose (14) (94). 

An attractive feature in this reaction is the possibility of direct substitution and formation of unblocked sugar derivatives containing one or more chlorodeoxy function in essentially two steps. Another facet is the formation of methyl 4,6-dichloro-4,6-dideoxy-hexosides from certain methyl glycosides in one step. Such compounds could be valuable intermediates in the synthesis of dideoxy and diamino sugars of biological importance. 

Treatment of l,4 3,6-dianhydro-D-glucitol with boron trichloride gives l,6-dichloro-l,6-dideoxy-D-glucitol (20). Although methyl 6-chloro-6-deoxy-a-D-glucopyranoside (isolated as the tribenzoate) could be isolated from the reaction of methyl 3,6-anhydro-a-D-glucopyranoside with boron trichloride (21), the application to the isomeric furanoside derivative led to complex results. 

Trichloro-4,6,6 -trideoxygalactosucrose or6-chloro-6-deoxy-p-D-fructofuranosyl 4,6-dichloro-4,6-dideoxy-a-D-galactopyranoside ( galactosucrose is a trivial name for the 4-epimer of sucrose)... 

C7H12C1204 Methyl 4,6-dichloro-4,6-dideoxy-a-D-galactopyranoside MCDGAL 31 366... 

CioHi6C1204 Methyl 2,6-dichloro-2,6-dideoxy-3,4-0-isopropylidene-a-D- CDIALT 31 350... 

Reactivity at 0-3, in addition to that at 0-4 and 0-6, was observed with methyl )3-D-galactopyranoside, which, when treated with sulfuryl chloride, yielded methyl 3,4,6-trichloro-3,4,6-trideoxy-/J-D-allopyranoside 2-(chlorosulfate) in 56% yield.352 In contrast, under similar conditions, methyl a-D-galactopyranoside gave352 methyl 4,6-dichloro-4,6-dideoxy-a-D-glucopyranoside 2,3-di(chlorosulfate). Further examples of the dependence of the reactivity on the configuration of C-l are the conversion of methyl 4,6-0-benzylidene-/3-D-glucopyranoside into methyl 4,6-0-benzylidene-3-chloro-3-deoxy-/3-i>allopyranoside by sulfuryl chloride,352 and of methyl 4,6-0-benzylidene-a-D-glucopyranoside, under similar conditions, into the 2,3-di(chlorosulfate).355... 

Many other glycosides have been subjected to selective chlorination with sulfuryl chloride. Methyl /3-L-arabinopyranoside afforded methyl 4-chloro-4-deoxy-a-D-xylopyranoside 2,3-di(chlorosulfate) in 29% yield, whereas the a-L anomer gave357 methyl 3,4-dichloro-3,4-dideoxy-/3-i)-ribopyranoside 2-(chlorosulfate) (30%). Methyl /3-d-ribopyranoside was converted into methyl 3,4-dichloro-3,4-dideoxy-a-L-arabinopyranoside through the action of pyridine hydrochloride on its 2,3,4-tri(chlorosulfate).358 Methyl a-D-lyxopyranoside gave only the 2,3,4-tri(chlorosulfate),353 as would be expected from the disposition of its hydroxyl groups, similar to that in the rhamno- and manno-pyranosides. Methyl a-D-altropyranoside was transformed into the 6-chloro-6-deoxy 2,3,4-tri(chlorosulfate) derivative in 80% yield.353... 

An important step in the synthesis of paratose (3,6-dideoxy-n-rtfoo-hexose) involved the conversion of methyl 3-chloro-3-deoxy-/8-D-allopyranoside into methyl 3,6-dichloro-3,6-dideoxy-/8-D-allo-pyranoside in 33% yield.359... 

D-Lyxose yielded a D-lyxosyl chloride 2,3,4-tri(chlorosulfate) which, on treatment with chloride ion, led to a dichlorodideoxy compound, most probably 2,4-dichloro-2,4-dideoxy-L-arabinose.353 D-Glucose gave a compound presumed to be 4,6-dichloro-4,6-dideoxy-a,/3-D-galactosyl chloride 2,3-di(chlorosulfate),360 and D-xylose afforded a monochloromonodeoxy derivative formulated, on indirect evidence, as 4-chloro-4-deoxy-L-arabinopyranosyl chloride 2,3-di(chlorosulfate).360 3,4-Dichloro-3,4-dideoxy-/3-D-ribopyranosyl chloride 2-(chlorosulfate) was the major, and 4-chloro-4-deoxy-a-D-xylopyranosyl chloride 2,3-di(chlorosulfate) the minor, product from the reaction of L-arabinose with sulfuryl chloride at room temperature for 24 hours.357,361 It has been established that, on reaction with sulfuryl chloride at low temperature, crystalline a-D-xylopyranose and /3-D-lyxopyranose afford, respectively, the 2,4,6-tri(chlorosul-fate)s of /3-D-xylopyranosyl chloride and a-D-lyxopyranosyl chloride,362 363 confirming that substitution at C-l occurs by an Sn2 process on a l-(chlorosulfuric) ester intermediate. 

Dichloro-4,6-dideoxy-a-D-galactopyranosyl 4,6-dichloro-4,6-dideoxy-a-D-galactopyranoside was obtained in 72% yield by the reaction of a,a-trehalose with sulfuryl chloride.367... 

On treatment with 30 equivalents of methanesulfonyl chloride in N,N-dimethylformamide for 8 days at 65°, methyl /3-maltoside gave a mixture of methyl 3,6-dichloro-4-0-(6-chloro-6-deoxy-a-D-glucopyranosyl)-3,6-dideoxy-/3-D-allopyranoside, isolated in 46%... 

On treatment with concentrated halogen acids, certain hexitols yield 1,6-dideoxy-l,6-dihalo compounds. The structure of the compound so obtained from galactitol, first reported by Bouchardat,404 was later verified by synthesis.405 Allitol is transformed406 into 1,4-anhydro-6-chloro-6-deoxy-DL-allitol and l,4-anhydro-5,6-dichloro-5,6-dideoxy-DL-talitol on treatment with fuming hydrochloric acid at 100°. 

The reaction of sulfuryl chloride with carbohydrates to give chloro-deoxy derivatives has been reviewed briefly in this Series.98 The reaction of sulfuryl chloride with monosaccharides has been shown to afford products in which the secondary hydroxyl groups are replaced by chlorine with inversion of configuration.68-75 Jones and coworkers reported that the reaction of methyl a-D-glucopyranoside with sulfuryl chloride and pyridine in chloroform at room temperature proceeds by way of the 4,6-bis(chlorosulfate) by an Sn2 process, with chloride as the nucleophile, to give methyl 4,6-dichloro-4,6-dideoxy-a-D-galactopyranoside 2,3-bis(chlorosulfate).74... 

However, based on the following evidence, a question has been raised about the assumed Sn2 character of the displacement reaction.78 The reaction of 2,3,4,l, 3, 4 -hexa-0-benzoylsucrose 6,6 -bis(chlorosulfate) (44) with pyridinium chloride in chloroform for 4 h at 55° gave 2,3,4,l, 3, 4 -hexa-0-benzoyl-6,6 -dichloro-6,6 -dideoxy-sucrose (54) in 96% yield. When compound 44 was heated under reflux with butanone alone, compound 54 (35%) was the only iso-... 

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