Glucopyranoside methyl 4-chloro-4-deoxy

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... 

A soln. of 2 equivalents tris(dimethylamino)phosphine in dimethylformamide added at -50 under argon to a soln. of methyl 2,3-di-O-benzyl-a-D-glucopyrano-side and excess CCI4 in dimethylformamide, and allowed to stand at room temp. -> methyl 6-deoxy-6-chloro-5-0-formyl-2,3-di-0-benzyl-a-D-glucopyranoside. Y 80%. F. O-formylations s. S. Czernecki and C. Georgoulis, C. r. 280(C), 305 (1975) replacement of sec. hydroxyl by chlorine cf. Bl. 1975, 607. 

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... 

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... 

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-... 

Sinclair95 has described the preparation of methyl 6-chloro-6-deoxy-a-D-glucopyranoside from methyl a-D-glucopyranoside by treatment with sulfur monochloride (S2C12) in N,N-dimethylformam ide a yield of 30-35% was obtained on separation of the reaction products on a column of Darco G-60-Celite 535. 

Only relatively few displacements of chloro groups in carbohydrate derivatives have been reported. Treatment of 6-chloro-6-deoxy-l,2 3,5-di-O-isopropylidene-a-D-glucofuranose (22) with anhydrous hydrazine for 2 days at reflux temperature yielded the corresponding 6-deoxy-6-hydrazino derivative.47 The chloro group in methyl 6-chloro-6-deoxy-a-D-glucopyranoside could be displaced by a benzoate group to afford methyl 6-O-benzoyl-a-D-glucopyranoside, in 74% yield, by... 

Halogen atoms have been placed at C-6 of substituted 6-deoxy-hexoses by a variety of interesting ways, and the products provide potential routes to 6-deoxyhexoses. Helferich and coworkers 4 reported a low yield of methyl 6-chloro-6-deoxy-a-D-glucoside which they prepared by reaction of the (suitably protected) corresponding 6-trityl ether with phosphorus pentachloride. Sinclair 44 has provided a convenient procedure for the preparation of the 6-chloro derivative in yields of 30-35% by allowing methyl a-D-glucopyranoside to react with sulfur monochloride, SjClj, in N,/V-dimethylformamide. A much better yield (73%) of the 6-bromo derivative was reported1 in the reaction of methyl 2,3,4-tri-O-benzoyl-6-O-trityl-a-D-altroside with phosphorus tribromide and bromine. 

When p-toluenesulfonylation is conducted with p-toluenesulfonyl chloride in pyridine at 25-30 , some substitution of chlorine may occur in the molecule. p-Toluenesulfonylation of uridine gave 3-(5-chloro-5-deoxy-2,3-di-0-p-tolylsulfonyl- S-D-ribofuranosyl) uracil, and methyl 4-0-acetyl-6-chloro-6-deoxy-2,3-di-O-p-tolylsulfonyl-a-D-glucopyranoside was obtained from methyl 4-0-acetyl-2,3-di-O-p-tolylsulfonyl-a-D-glucopyranoside, although chlorination of the (8-d anomer did not occur. Hess and Stenzel showed that p-toluenesulfonylation occurs first, followed by displacement of the sulfonyloxy group by chloride ion. At a lower temperature (20°) for sixteen days, methyl a-D-glucopyranoside gave the 2,3,4,6-tetra-p-toluenesulfonate, whereas, at 35° for four days, or 75° for two days, the... 

An alternative, or supplementary, approach is provided by oxidation with lead tetraacetate or, preferably, periodate, and possibly by identification of the products. Caution must, however, be observed in using this method, as Buchanan has shown that the compound previously designated as methyl 3-chloro-3-deoxy-a-D-gulopyranoside consumes periodic acid extremely slowly (seven days) and is, in fact, methyl 4-chloro-4-deoxy-a-D-glucopyranoside. The products of epoxide cleavage are usually completely defined by these procedures, because irans addition can be assumed, although considerable care must be exercised when there is a possibility of epoxide migration. ... 

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