Glucitol 1,4:3,6-dianhydro

Loss of a second molecule of water occurs on heating (1) (106,107), (2), or (3) (108) with concentrated sulfuric or hydrochloric acid forming 1,4 3,6-dianhydro-D-glucitol (isosorbide) (5). Mannitol and iditol anhydrize under similar conditions to isomannide (6) and isoidide (7), respectively. In (6), both hydroxyl groups are oriented toward each other (endo) ia (7), both are oriented away from each other (exo) and ia isosorbide (5), one hydroxyl is endo and the other exo. XyUtol loses two moles of water to form l,3 2,5-dianhydrox5litol (109). 

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. 

That steric factors alone cannot account for the reactivity of hydroxyl groups was indicated by the unimolar p-toluenesulfonylation of l,4 3,6-dianhydro-D-glucitol.23 The major product, the 5-p-toluenesulfonate (45%), is derived by reaction at the sterically hindered endo-hydroxyl group, and the exo-2-p-toluenesulfonate was isolated in only 12% yield. Although the more reactive HO-5 (es-... 

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... 

Sugihara and Schmidt49 reported the isolation of 2,5-anhydro-D-glucitol in crystalline form its preparation on a relatively large scale has been described in the patent literature,50 and consists in the thermal dehydration of D-mannitol. The process leads to the formation of 1,4-anhydro-D-mannitol, 1,5-anhydro-D-mannitol, 1,4 3,6-dianhydro-D-mannitol, and 2,5-anhydro-D-glucitol, which is isolated as the crystalline 1,3-O-isopropyIidene derivative (35). 

Jackson and Hayward59hydroxyl group in l,4 3,6-dianhydro-D-glucitol is preferentially sulfonylated prior to conversion into the mixed ester is incorrect. They based their conclusions on studies of the rate of replacement of p-tolylsulfonyloxy group by iodide in the three dianhydro stereoisomers. However, their proof of structure was questioned by Lemieux and Mclnnes59acetoxonium intermediate prior to attack by the iodide ion. 

Frequencies (cm-1) of Absorption Bands of 3,6-Anhydro-D-glucitol (1), 1,4-Anhydro-D-mannitol (2), 1,4 3,6-Dianhydro-2,5-di-0-methyl-D-mannitol (3), and l,4 3,6-Dianhydro-D-glucitol (4)... 

Circular dichroism of the nitrato (ONO) chromophore of the mono- and di-nitric esters of l,4 3,6-dianhydrohexitols was found to consist of two dichroic bands, one weak and positive, at about 265 nm, and a stronger band at —228 nm, which was positive for the endo-(R)-nitrato chromophore and negative for the exo-(S)-nitrato group.68 However, for l,4 3,6-dianhydro-D-glucitol dinitrate, which has both an endo and an exo nitrato group, both bands were positive, but [ ]ma r (+ 7,260) for the band at 225 nm was about half of the algebraic sum of this band for the di-endo (+ 18,400) and di-exo (—4,460) compounds. 

The crystal and molecular structures of l,4 3,6-dianhydro-2-0-(p-bromophenylsulfonyl)-(exo)-D-glucitol 5-nitrate(endo) were reported by Camerman, Camerman, and Trotter.69 The bond distances and valency angles were found to be normal, with an intramolecular apparent attraction between an oxygen atom of the N02 and the ring-oxygen atom of the second ring the distance was found to be 0.29 nm. 

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