Mannitol with sodium methoxide

Of all the anhydrohexitols currently known, the structure of two dianhydrohexitols (reported by Wiggins57) remain unresolved. The two dianhydrides were obtained on heating D-mannitol with hydrochloric acid one had m.p. 118° and [a]D —34°, and the second was isolated only as its dimethanesulfonate, m.p. 113-114°. The apparent enantiomorph of the first was formed on treating l,6-dichloro-l,6-dideoxy-D-mannitol with sodium methoxide. 

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. 

One of the dianhydrohexitols, B, was identified with l,5 3,6-dianhy-dro-D-mannitol (neomannide, see below), but the other two, A and C, remain of unknown structure. An interesting observation concerning the dianhydride A has been made.48 When l,6-dichloro-l,6-didesoxy-D-mannitol was treated with sodium methoxide a new crystalline dianhydrohexitol was obtained. This had m. p. 118-119° but showed la]D + 33.6°. It was therefore the enantiomorph of dianhydride A. Furthermore, when dichloro-didesoxy-D-mannitol is treated with sodium amalgam yet another dianhydride was isolated. This had m. p. 118-119° and fa]D + 93.6° and is doubtless identical with the /3-mannide of Siwoloboff.49... 

The 5,6-anhydro derivatives of D-sorbitol and D-mannitol41 69 behave in like manner to the 5,6-anhydro-l,2-isopropylidene-D-glucofuranose of Freudenberg and coworkers.70 Thus, 5,6-anhydro-l,3 2,4-diethyli-dene-D-sorbitol (LXXXV) readily suffers ring scission with ammonia to give 6-amino 6-desoxy-l,3 2,4-diethylidene-D-sorbitol (LXXXVI)69 or with sodium methoxide to form 6-methyl-l,3 2,4-diethylidene-D-sorbitol.42 l,2 3,4-Diisopropylidene-5,6-anhydro-D-mannitol gives rise... 

Finally, epoxy ring formation has been carried out in methanol at room temperature with sodium methoxide as a catalyst (24). 1,2 5,6-Dianhydro-3,4-0-isopropylidene-D-mannitol (XIX) has been obtained in near quantitative yield. 

Wiggins57" reported that the physical constants of a product that he had obtained from l,2 5,6-di-0-isopropylidene-3,4-di-0-p-tolylsul-fonyl-D-mannitol by deacetalation with 70% acetic acid followed by acetylation and saponification with sodium methoxide were those of l,4 3,6-dianhydro-D-iditol. Tipson and Cohen576 have presented evi-... 

When [this nitrile, 4,6-benzylidene-2,3,5-triacetyl-D-gluconic nitrile, was treated with sodium methoxide in methanol solution in the presence of nitromethane, there was obtained readily from the reaction mixture crystalline 4,6-benzylidene-l-nitro-l-desoxy-D-mannitol. Hydrolysis of the benzylidene acetal with dilute sulfuric acid then gave the crystalline 1 -nitro-1 -desoxy-D-mannitol. 

Primary amines also take part in this addition reaction, and, when the olefin and the bases are employed in equimolar proportions, acetylated 2-alkyl-(or aryl-)amino products are obtained. By treatment with sodium methoxide, methanol may similarly be added to the olefinic bonds and, in this way, crystalline l-deoxy-2-O-methyl-l-nitro-D-mannitol has been prepared and subsequently converted into 2-0-methyl-D-mannose. 2-0-Methyl-n-ribose was synthesized by use of a similar route. 

The dimethyl derivative of isomannide was synthesized by Wiggins as follows. l,6-Dichloro-l,6-didesoxy-3,4-isopropylidene-D-mannitol was converted i nto 1,6-dichloro-l, 6-didesoxy-2,5-dimethyl-3,4-isopr opylidene-D-mannitol (LVI). This on mild acid hydrolysis gave 1,6-dichloro-l,6-didesoxy-2,5-dimethyl-D-mannitol (LVII) which with cold sodium methoxide furnished 2,5-dimethyl-l,4 3,6-dianhydro-D-mannitol (LVIII), identical with the product of methylation of isomannide itself. Further... 

The method was used successfully initially for the preparation of 2-desoxy-D-glucose.4 D-Arabinose was treated with nitromethane in the presence of sodium methoxide and gave a mixture of 1-nitro-l-desoxy-D-mannitol (XXXV) and 1-nitro-l-desoxy-D-glucitol (XXXVI). The mixture was not separated, but was acetylated and subsequently treated with bicarbonate to convert it into D-arabo-3,4,5,6-tetraacetoxy-1 -nitro-... 

Thietanes can be prepared by reactions involving neighboring sulfur groups. For example, the D-mannitol derivative (112) is converted into the interesting tricyclic D-iditol derivative (113) with methanolic sodium methoxide. " ... 

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