Mannitol, acetylation derivatives

J The hexa.acetyl derivative, m.p. 121°, may be prepared as follows. Boil under reflux 1 part of mannitol with 5 parts by weight of acetic anhydride and 1 part of anhydrous sodium acetate or with a little anhydrous zinc chloride for 15-20 minutes, pour into excess of water, stir the mixture until the oil has solidifled, and then recrystallise from methylated spirit. 

Mannitol hexanitrate is obtained by nitration of mannitol with mixed nitric and sulfuric acids. Similarly, nitration of sorbitol using mixed acid produces the hexanitrate when the reaction is conducted at 0—3°C and at —10 to —75°C, the main product is sorbitol pentanitrate (117). Xylitol, ribitol, and L-arabinitol are converted to the pentanitrates by fuming nitric acid and acetic anhydride (118). Phosphate esters of sugar alcohols are obtained by the action of phosphorus oxychloride (119) and by alcoholysis of organic phosphates (120). The 1,6-dibenzene sulfonate of D-mannitol is obtained by the action of benzene sulfonyl chloride in pyridine at 0°C (121). To obtain 1,6-dimethanesulfonyl-D-mannitol free from anhydrides and other by-products, after similar sulfonation with methane sulfonyl chloride and pyridine the remaining hydroxyl groups are acetylated with acetic anhydride and the insoluble acetyl derivative is separated, followed by deacetylation with hydrogen chloride in methanol (122). Alkyl sulfate esters of polyhydric alcohols result from the action of sulfur trioxide—trialkyl phosphates as in the reaction of sorbitol at 34—40°C with sulfur trioxide—triethyl phosphate to form sorbitol hexa(ethylsulfate) (123). 

Example.—Mannitol.—The hexa-acetyl derivative (p. 259) is prepared and purified, and a quantity of it—about 0-2 gm.—along with 100 c.cs. of 10% benzene sulphonic acid solution placed in a steam distillation flask. The flask is connected to a condenser on one side and to an apparatus for the generation of pure steam on the other. A suction flask to serve as receiver is attached by a cork to the condenser, and to the side tube of the suction flask a soda-lime tube to prevent the entrance of carbon dioxide is attached. Steam is blown through the flask until (1-5—3 hours) the distillate passing over is neutral. The whole distillate is then titrated with standard baryta, using phenolphthalein as indicator. 

In our laboratory we routinely use columns (3 m x 2.2 mm) containing 3% w/w OV-225 at 200°C to obtain baseline resolution of the acetylated derivatives of rhamnitol, arabinitol, xylitol, mannitol, galacti-tol, and glucitol in approximately 45 min (Selvendran et al., 1979). With high quality columns containing OV-225, it may also be possible to achieve partial resolution of the acetylated derivatives of rhamnitol and fucitol. 

Mannitol, CH,0H(CH0Hi4CH40H, is a hexahydric alcohol obtained by the reduction of mannose. Since ring formation does not occur in mannitol, the hexacetyl derivative can exist in only one form, and therefore either zinc chloride or sodium acetate can be used as a catalyst for the acetylation. 

Oxidation of PI with chromium trioxide. Fraction PI was twice acetylated as described above. The peracetylated polysaccharide (75 mg), together with 20 mg of mannitol hexacetate as internal standard was dissolved in 1.5 mL of HCCI3, and treated with 1.89 mL of glacial acetic acid and 189 mg of chromium trioxide, at 50°C. Aliquots were removed at zero, 30, 60 and 120 min, water then added, and the material recovered by extraction with chloroform, hydrolyzed and analysed by GLC of derived alditol acetates. 

Intramolecular cyclization can also be effected with acyclic intermediates derived from such readily available alditols as D-mannitol. Kuszmann and Vargha63 reported the formation of 2,5-anhydro-l,6-dibromo-l,6-dideoxy-4-0-(methylsulfonyl)-D-glucitol (63), in 73% yield, by boiling 3,5-di-0-acetyl-l,6-dibromo-l,6-dideoxy-2,4-di-0-... 

Tri-0-acetyl-l,5-anhydro-2-deoxy-D-arabino-hex-l-enitol (tri-O-acetyl-D-glucal) was the starting point for the synthesis of 1,5-anhy-dro-2-chloro-2-deoxy-D-glucitol or -D-mannitol by way of the 1,2-dichloride (22), which was reduced32 by means of lithium aluminum hydride to the 2-chloro-2-deoxy derivative (23). That the chlorine... 

Various protected bicyclic 2,5-anhydro derivatives of 5-thio-D-mannitol were obtained from methyl 2,3,4-tri-(9-acetyl-6-(9-mesyl-5-thio-a-D-glucopyranoside by transannular participation of the ring sulfur atom and ring opening of the thiiranium ion [35]. Similar reactions were earlier observed with, for example, a 4-(9-methanesulfony 1-5-thio-D-xylopyranose [36]. 

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