Mannitol preparation

A solution of bismuth (III) nitrate and mannitol, prepared as described above under BiONOs, is precipitated with borax solution. The finely granular crystal powder is removed by suction, washed and dried. 

A dodecitol has been isolated from the mother liquors of a mannitol preparation. Apparently it was formed by a reductive coupling of two molecules of glucose (86a). 

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. 

Etherification. The reaction of alkyl haUdes with sugar polyols in the presence of aqueous alkaline reagents generally results in partial etherification. Thus, a tetraaHyl ether is formed on reaction of D-mannitol with aHyl bromide in the presence of 20% sodium hydroxide at 75°C (124). Treatment of this partial ether with metallic sodium to form an alcoholate, followed by reaction with additional aHyl bromide, leads to hexaaHyl D-mannitol (125). Complete methylation of D-mannitol occurs, however, by the action of dimethyl sulfate and sodium hydroxide (126). A mixture of tetra- and pentabutyloxymethyl ethers of D-mannitol results from the action of butyl chloromethyl ether (127). Completely substituted trimethylsilyl derivatives of polyols, distillable in vacuo, are prepared by interaction with trim ethyl chi oro s il an e in the presence of pyridine (128). Hexavinylmannitol is obtained from D-mannitol and acetylene at 25.31 MPa (250 atm) and 160°C (129). 

In the human market, oral and parenteral dosage forms are prepared from the crystal. However, because of the extremely high potency, more dilute (0.1—10%) forms are avabable. These include dilutions with mannitol, triturations on dicalcium phosphate or resins, and spray-dried forms. Prices for these forms are driven by that of the crystal, which in early 1996 was ca 9.50/gram (95). Prices for the vitamin have risen during the first half of the 1990s. However, Htde growth in price beyond inflation is anticipated. 

Me2C(OMe)2, SnCl2, DME, 30 min, 54% yield. This reaction has been used to prepare the bisacetonide of mannitol on a 100-kg scale. 

A detailed spectroscopic and theoretical study of the conformation of dioxolanes 1 has appeared <96T8275>, and a theoretical study has shown that the anomeric effect explains the non-planarity of 1,3-dioxole <96JA9850>. The tetraalkynyldioxolanone 2 has been prepared and its structure and reactivity studied <96HCA634>. Both enantiomers of the chiral glycolic acid equivalent 3 can be prepared from D-mannitol <96HCA1696>, and lipase-mediated kinetic... 

Deoxy-4-fluoro-D-fructose (552) was prepared (59%) by fermentation of 3-deoxy-3-fluoro-D-mannitol with Gluconobacter oxydans. The structure of 552 (fi-T) form) was confirmed by the n.m.r. spectrum, which resembles that of 4-deoxy-4-fluoro-Q -D-sorbopyranose (553) 552 was identical with one of the products obtained from the oxirane-ring opening of 3,4-anhy-dro-l,2-0-isopropylidene- -D-tagatopyranose with KHFj. 

Fom- title compounds, 5-deoxy KDG Me estw, 5-epi KDG Me ester, 4-0-Me KDG Me ester and 4-deoxy KDG Me ester were prepared either from D-glucono-l,5-lactone or from 1,2 5,6 di-O-isopropylidene-D-mannitol. Biological tests perfcHined rat these molecules have shown that the compounds modified on the C-5 position (5-deoxy KDG Me ester and 5-epi KDG Me ester) are gratuitous inducers of the e>q>ression of pectinase genes in the phytopathogenic bacteria Erwinia Chrysanthemi when the C-4 modified molecules (4-0-Me KDG Me ester and 4-deoxy KDG Me ester) are not inducers. 

Both solid and liquid dosage forms may contain saccharin. Saccharin is a nonnutritive sweetening agent, which is 300 times as sweet as sucrose. In a survey of sweetener content of pediatric medications, seven out of nine chewable tablets contained saccharin (0.45-8.0 mg/tablet) and sucrose or mannitol. Seventy-four of the 150 liquid preparations investigated contained saccharin (1.25-33 mg/5 mL) [62], Saccharin is a sulfanamide derivative that should be avoided in children with sulfa allergies [54],... 

Another procedure for preparing 4-hydroxy-4,5-dihydroisoxazole 2-oxides derivatives in 86-100% yield, and published by the same group [27], is based on an oxidative cleavage of D-mannitol-derivatives furnishing 2 equiv. of identical enantiopure (2R)-2-methanesulfonyloxyaldehydes which can react with a-nitroacetate in the usual manner. 

Cobalt-on-alumina catalysts with increased dispersion and catalytic activity are prepared by addition of mannitol to the cobalt nitrate solution prior to impregnation. Thermogravimetric analysis (TGA) and in situ visible microscopy of the impregnation solution show that the organic compound reacts with cobalt nitrate, forming a foam. The foam forms because significant amounts of gas are released through a viscous liquid. The structure of the foam is retained in the final calcined product. It is this effect that is responsible for the increased dispersion. 

As described above, understanding the mechanism of the dispersion increase is a difficult task. In this work we compare a catalyst prepared by cobalt nitrate impregnation onto alumina with one modified by the addition of mannitol, and use TGA and in situ microscopy to investigate the increased dispersion. Mannitol is a sugar alcohol that is structurally similar to sorbitol [31], as shown in Figure 1.1. 

The unmodified catalyst was prepared by dissolving cobalt nitrate hexahydrate (19.76g, 68 mmol) in water (9 ml) and impregnating the solution into alumina (16.0 g). The catalyst was dried at 105°C in static air for 3 h and calcined at 400°C for 1 h. The mannitol-containing catalyst was prepared as described above, except that mannitol (2 g, 11 mmol) was dissolved in the cobalt nitrate solution prior to impregnation. The Co/mannitol ratio was 6.2. 

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