Mannitol, reaction with

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). 

The alcoholysis of the cyclic phosphate of catechol by alditols can lead, after acid hydrolysis of intermediate, cyclic phosphates, to the selective formation of phosphoric esters of the primary hydroxyl groups in the alditols. Thus, erythritol and D-mannitol afford, after chromatographic purification of the reaction products, their 1-phosphates in yields of 31 and 38%, respectively.217 The method was used to convert riboflavine into riboflavine 5 -phosphate.218 1-Deoxy-1-fluoro-L-glycerol has been converted into the 3-(dibenzyl phosphate) in 54% yield by selective reaction with dibenzyl phosphorochloridate. 219... 

Different preparative procedures have been shown to yield protein fractions which are able to catalyze different types of reactions with respect to their requirement of either NAD or NADP as coenzymes [cf. Eqs. (19), (20), and (21)]. In sera of mice poisoned by carbon tetrachloride we found polyol dehydrogenases catalyzing the oxidation of the following polyols (a) with NAD sorbitol, ribitol, mannitol (b) with NADP sorbitol, ribitol. Erythritol and mt/o-inositol were not attacked at all. Figures 8 and 9 show the results of these determinations performed at pH 9.6. In the NAD system sorbitol and ribitol are oxidized at exactly the same rate, while in the NADP system ribitol does not reach the rate of sorbitol. The ratio NAD NADP for sorbitol is calculated to be 4.20 and for ribitol 5.50. Mannitol is oxidized at 23% of the rate of sorbitol. 

There are several examples of one-pot reactions with bifunctional catalysts. Thus, using a bifunctional Ru/HY catalyst, water solutions of corn starch (25 wt.%) have been hydrolyzed on acidic sites of the Y-type zeolite, and glucose formed transiently was hydrogenated on ruthenium to a mixture of sorbitol (96%), mannitol (1%), and xylitol (2%) [68]. Similarly a one-pot process for the hydrolysis and hydrogenation of inulin to sorbitol and mannitol has been achieved with Ru/C catalysts where the carbon support was preoxidized to generate acidic sites [69]. Ribeiro and Schuchardt [70] have succeeded in converting fructose into furan-2,5-dicarboxylic acid with 99% selectivity at 72% conversion in a one-pot reaction... 

The use of tartrate esters was an obvious place to start, especially since both enantiomers are readily available commercially and had already found widespread application in asymmetric synthesis (Figure 11) (e.g.. Sharpless asymmetric epoxidation).23.24 Reagents 36-38 are easily prepared and are reasonably enantioselective in reactions with achiral, unhindered aliphatic aldehydes (82-86% ee) typical results are given in Figure 12.3c,h Aromatic and a,p-unsaturated aldehydes, unfortunately, give lower levels of enantioselection (55-70% e.e.). It is also interesting to note that all other C2 symmetric diols that we have examined (2,3-butanediol, 2,4-pentanediol, 1,2-diisopropylethanediol, hydrobenzoin, and mannitol diacetonide, among others) are relatively ineffective in comparison to the tartrate esters (see Table ll).25... 

The reaction of a, -unsaturated ketones 93, obtained from j -ketoesters 36 and chiral aldehydes 94 [derivatives of D-glyceral (92TL3809,93T7133), and D-mannitol (93T7133)], with MN have been used for the first time in the synthesis of optically pure 2-aminopyrans 95. Yields and diastereos-electivity were low however, recrystallization afforded one of the stereoisomers in a nearly pure state (d.e. 80-100%) (Scheme 27). 

Dinitroanisole (3,5-DNAns), col crysts, mp 105-105.8°, bp - sublimes, d 1.558 at 20°/4°. Chemical reactions are described in Refs 12,13 29, Urbanski (Ref 14) studied eutectic mixts of 3,5-DNAns with hexanitro-mannitol and with nitroerythritol. Methods of prepn are discussed in Refs 2b,8,9,22,31 34. The method of prepn from 1,3,5-trinitrobenzene and Na methylate in anhyd methanol is described in detail in Ref 8... 

Several D-mannitol-derived phosphines have also been examined in the asymmetric MBH reaction (Scheme 5.18) [86, 87]. Phospholane 89a catalyzed this reaction with low conversion and low ee (19%). In the presence of the hydroxyl phospholane 89b as catalyst, the reaction was accelerated significantly (83% in 9 h versus 29% in 70 h), while the enantioselectivity could not be ameliorated (Scheme 5.18). 

D-Mannitol was also used as a precursor for trehazolamine via its conversion into the (/ )-(—)-epichlorohydrin (162),91,92 which gave the optically active l-(hydroxy-methyl)spiro[2,4]cyclohepta-4,6-diene (163) in 60% yield upon treatment with lithium cyclopentadienide (Scheme 21).49 Conversion of 163 into the corresponding trichloroacetimidate 164,93 followed by reaction with I(,yy/w-collidine)2CI04, afforded... 

Howwjanz discovered that a large number of carbohydrates and poly-hydric alcohols can combine with carbon dioxide in the presence of excess milk of lime to form unstable acid carbonate salts, R—0—CO—0 M . Stable, neutral esters of carbonic acid with carbohydrates were first prepared in 1912 by Hochstetter, who patented a process involving reaction with diphenyl carbonate at about 130°. However, not one of the examples cited—derivatives of D-glucose, sucrose, D-mannitol, and starch—was completely characterized and, possibly on account of the rather drastic conditions used, Hochstetter s method has not received attention from later workers. 

The extension of the reaction with sodium iodide to tosyl derivatives of other acetals of iditol, glucitol, and mannitol could provide evidence for the conformation of 2,4 3,5-diacetals of mannitol and, more important, lead to a clarification of the steric requirements of this reaction. The importance of 2,4 3,5-diacetals of talitol, at present unknown, is now clear they will have one axial and one equatorial terminal group (see LIU), and the trans ring junction imposes a rigidity of conformation greater than that of any of the diacetals with cis junctions. 

Recently a series of compounds resulting from the reaction of mannitol esters with a varying number of moles of ethylene oxide have been made available commercially. These compositions serve as dispersion agents. One of these, mannitan monolaurate which is combined with 20 moles of ethylene oxide is employed as a dispersing agent for volatile oils, oil-soluble vitamins and many other edible and drug products. This product is an oily liquid, miscible in all proportions with water and alcohol it is soluble in cotton seed oil and insoluble in ether. 

Other than those of the carboxylic type for example, a mixture of p-toluene-sulfonic acid and triduoroacetic anhydride forms sulfones by reaction with suitably activated aromatic compounds. By the same technique, the hexa-nitrate esters of o-mannitol and D-glucitol were obtained by use of solutions of fuming nitric acid in trifluoroacetic anhydride at 0°. The probable reaction mechanisms of these and other examples of the conversion of oxy acids into reactive entities have been briefly considered. ... 

Depazay and co-workers have described the synthesis of a series of polyhydroxylated pyrrolidine, piperidine and azepanes derived from D-mannitol as novel mimetics of somatostatin [8]. The synthesis of one piperidine 116 is shown in O Scheme 9. The authors used reaction of tr) tamine with the D-mannitol derived bis-epoxide 112 followed by protection of the indole nitrogen with a Boc group to prepare the L-gulo-piperidine 113, the azepane 114 also being formed. Selective protection of the primary alcohol followed by reaction with hydrazoic acid... 

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