Mannitol benzoylation

Brigl and Griiner45 reported the isolation of three products when 1,6-di-O-benzoyl-D-mannitol (29) was heated in boiling 1,1,2,2-tet-rachloroethane in the presence of p-toluenesulfonic acid as the catalyst. These compounds were assigned mono- and di-anhydro structures, and were later shown by Hockett and coworkers46,47 to be 1,4-anhydro-D-mannitol dibenzoate (30), l,4 3,6-dianhydro-D-man-nitol dibenzoate (31), and 2,5-anhydro-l,6-di-0-benzoyl-D-glucitol (32). The latter compound, which can be readily isolated from the... 

Miiller and Vargha65 reported that treatment of 1,6-di-O-benzoyl-D-mannitol (29) with p-toluenesulfonyl chloride gave 2,5-anhydro-l,6-di-0-benzoyl-3,4-di-0-p-tolylsulfonyl-D-glucitol (67). The formation of this compound may be the result of a favored p-toluenesulfonyla-tion at the 2(5)-hydroxyl group, followed by intramolecular cycliza-tion and subsequent esterification by the excess of the reagent. This... 

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. 

Anhydro-D-mannitol is also obtained by a novel route from 1,6-dibenzoyl-D-mannitol. When this compound is heated with p-tolu-enesulfonic acid in acetylene tetrachloride, it suffers partial dehydration and one of the products is a dibenzoyl derivative of mannitan. On debenzoylation of this substance it yields crystalline 1,4-anhydro-D-mannitol.67 The formation of dibenzoyl-1,4-anhydro-D-mannitol has involved the migration of at least one benzoyl group and Hockett and coworkers6 believe that the initial product is either 2,6- or 3,6-dibenzoyl-1,4-anhydro-D-mannitol. 

A-(4-Dimethylamino)benzoyl-1 -amino-1,2,5-trideoxy-2,5-imino-D-mannitol (156)... 

By-products of the above reactions are 1,2,6-tribenzoyl-D-mannitol and 1,2,6-tribenzoylsorbitol. The structure of the first was shown in two ways. Brigl and Griiner converted it to the known 1,2,5,6-tetra-benzoyl-3,4-isopropylidene-D-mannitol. Hockett and Fletcher oxidized it to dibenzoyl-D-glyceraldehyde with lead tetraacetate. This, and the fact that the rate of oxidation was like that of glycerol, not of ethylene glycol, established the structure. 1,2,6-Tribenzoylsorbitol consumed... 

A different reductive approach was employed by Zervas and Zioudrou,29 who catalytically reduced tetra-O-acetyl-a-D-glucopy-ranosyl bromide in the presence of palladium to obtain 1,5-anhydro-D-glucitol. It would be of interest to determine whether this or a similar reduction of tetra-0-benzoyl-/3-D-fructopyranosyl bromide would give the D-mannitol anhydride. 

As the acetal group in 2,5-O-methylene-D-mannitol is relatively resistant to hydrolysis, S. B. Baker" studied the stabilities of 1,4 3,6-dianhydro-2,5-0-methylene-D-mannitol and -D-iditol relative to that of the D-mannitol acetal. He synthesized l,4 3,6-dianhydro-2,5-0-methylene-D-mannitol by cyclizing 2,5-0-methylene-l,6-di-0-p-tolyl-sulfonyl-D-mannitol or by methylenation of l,4 3,6-dianhydro-D-man-nitol. The D-iditol isomer was prepared by cyclizing 1,6-di-O-benzoyl-... 

The same compounds isolated by Brigl and coworkers,9 who started from 2,3,4,5,6,7-hexa-O-benzoyl-D-gZt/cero-D-gaZacto-heptononitriIe, were obtained from the ammonolysis of 1,2,3,4,6-penta-O-benzoyl-a-D-mannose,19 namely, a mixture of l,l-bis(benzamido)-l-deoxy-D-mannitol (12) and N-benzoyl-D-mannopyranosylamine (13). Likewise, 1,2,3,4-tetra-O-benzoyl-L-rhamnopyranose,10 having the same steric relationship at the asymmetric carbon atoms as the perbenzoate of D-mannose, also afforded an N-benzoyl-L-rhamnopyranosylamine directly. 

To 10 gms. (1 mol.) of mannitol dissolved in 500 c.cs. of pyridine, 50 gms. (excess) of benzoyl chloride are slowly added in the warm, the whole allowed to stand overnight and poured into 1 litre of cold 10% sulphuric acid. The ester is filtered off at the pump, washed with cold water and recrystallised from alcohol. 

Borate complexes have been utilized by Brigl and Griiner47 to effect partial esterification. Anhydrous D-glucose and metaboric acid dissolved in acetone give a complex which exhibits the analysis of a diborate. Reaction of the latter with an excess of benzoyl chloride gives 2,6-di-O-benzoyl-D-glucose (XL). D-Mannitol likewise forms a diborate, which produces the 1,6-di-O-benzoyl derivative (XLI) upon benzoylation. In the presence of boric acid, D-glucose diethyl thioacetal yields the 6-benzoate (XLII). In the non-aqueous medium the formation of complexes... 

Glacial acetic acid plus concentrated hydrochloric acid was used196 for deacetonation of a di-O-benzoyl- mono-O-isopropylidene-di-O-tosyl-D-mannitol (during 5 hours at 15-20°), and for hydrolysis236 of the diethyl acetal of 2,3-di-0-tosyl-D,L-glycerose by treatment during one hour at 100-105°. 

The readily available [77, 78] l,6-di-0-benzoyl-3,4-0-benzylidene-2,5-0-methy-lene-D-mannitol has been converted [79] into the benzyl ether (60), which on periodate oxidation and borohydride reduction gives the methylene acetal (61) which readily gives 1 -O-benzyl-L-glycerol for use in lipid synthesis. The acyl derivative (62) has been used [80] in glycolipid synthesis by glycosidation of the hydroxyl group. 

A different monoanhydro-di-O-benzoyl-D-hexitol prepared from D-mannitol, designated 2,5-anhydro-l,6-di-0-benzoyl-D-mannitol (XXXIV, R = benzoyl),100 was reported to consume no lead tetraacetate, presumably... 

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