6-chloro-6-deoxy

The only recorded example using this method in the sugar series is the chlorination of l,2 3,4-di-0-isopropylidene-D-galactopyranose (73) which affords in addition to the expected 6-chloro-6-deoxy derivative 74a, a 5,6-unsaturated derivative 75 as well. These products were separated by silica gel column chromatography no yields were given. 

Several other methods for the introduction of halo atoms at C-6 in hexose derivatives have been known since the late 1920s. One of the earlier methods involved the reaction of methyl 2,3,4-tri-0-acetyl-6-0-trityl-a-D-glucopyranoside with phosphorus pentachloride which resulted only in an 8% overall yield of methyl 6-chloro-6-deoxy-a-D-glucoside (57). In contrast, the reaction of methyl 2,3,4-tri-0-acetyl-6-0-trityl-a-D-altropyranoside with phosphorus tribromide and bromine afforded a 73% yield of the corresponding 6-bromo-6-deoxy derivative (91). 

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. 

Sinclair (92) has described an improved method for the preparation of methyl 6-chloro-6-deoxy- -D-glucopyranoside (137) from methyl a-D-glucopyranoside (11). The reaction was effected with sulfur monochloride S2C12 in N,N-dimethylformamide at room temperature and the... 

Deoxy-6-iodo-a-D-fructofuranose p-D-fructopyranose 1,2 2,1 -dianhydride (49) 6-Chloro-6-deoxy-a-D-fructofuranose p-D-fructopyranose 1,2 2,1 -dianhydride (50) 6-5-Heptyl-6-thio-tt-D-fructofuranose p-D-fructopyranose 1,2 2,l -dianhydride (51) 6-Azido-6-deoxy-a-D-ffuctofuranose P-D-fructopyranose 1,2 2,l -dianhydride (52) 6-Anuno-6-deoxy-a-D-fructofuranose p-D-fructopyranose 1,2 2,l -dianhydride (53) 6-Acetamido-6-deoxy-a-D-fructofuranose p-D-fructopyranose 1,2 2,l -dianhydride (54)... 

Deoxy-6-iodo-p-D-fructofuranose 6-deoxy-6-iodo-p-D-fructofuranose 1,2 2,3 -dianhydride (69) 6-Chloro-6-deoxy-P-D-fructofuranose 6-chloro-6-deoxy-p-D-ffuctofuranose 1,2 2,3 -dianhydride" (70)... 

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... 

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%... 

The reaction of methyl a-D-glucopyranoside with sulfur monochloride in N,N-dimethylformamide to give the 6-chloro-6-deoxy derivative in 30-35% yield has been described392 it is possible thatN,N-... 

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°. 

Intramolecular displacement of primary sulfonyloxy or halide groups in derivatives of D-mannitol can also be brought about under basic conditions, albeit in low yield. Treatment of l,6-di-0-(methyl-sulfonyl)-D-mannitol (78), or the corresponding dichloride derivative, with sodium methoxide gave 2,5 3,6-dianhydro-D-glucitol74 (79). Treatment of the latter with hydrochloric acid at 100° in a sealed tube gave the 6-chloro-6-deoxy derivative (80), which was converted into the known 2,5-anhydro-l,6-di-0-benzoyl-D-glucitol45 47 (32). The sequence 78-80 is of interest in the context of C-/3-D-nucleoside precursors, but it suffers from the fact that yields are low. 

Raffi nose 6-Chloro-6-deoxy-a-D-f ructof uranoside... 

The reaction of methyl a-D-mannopyranoside with sulfuryl chloride gave methyl 6-chloro-6-deoxy-a-D-mannopyranoside 2,3,4-tri(chloro-sulfate) even treatment of the product with pyridinium chloride for 12 hours at 50° did not effect further substitution.25 In this case, the lack of displacement of the chlorosulfonyloxy group at C-4 is attributed to the presence of an axial group at C-2. In the (hypothetical) transition state 13 (viewed along the C-4-C-3 bond), there would be... 

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