Sodium hydride carbohydrates

The value of methylation studies in structural determination of carbohydrates is well known. Methylation of sucrose has generally been achieved by the use of dimethyl sulfate-sodium hydroxide,34,35 methyl iodide-silver oxide-acetone,20 sodium hydride-methyl io-dide-N,N-dimethylformamide,35 or diazomethane-boron trifluoride etherate.36,37 The last method (already applied to monosaccharides38,39) has been found particularly useful for sucrose, because it proceeds without concomitant migration of acyl groups. The reaction of 2,3,6,T,3, 4, 6 -hepta-0-acetylsucrose (21) and 2,3,4,6,1, 3, 4 -hepta-O-acetylsucrose (22) with diazomethane in dichloromethane in the presence of a catalytic proportion of boron trifluoride etherate for 0.5 h at —5° gave the corresponding 4-methyl (23) and 6 -methyl (24)... 

Sodium hydride in THF can be used with advantage to deprotonate nitro derivatives of carbohydrates in the presence of Bu Me2SiCl (182, 183). In these cases, the yields of respective SENAs are 60% to 80%. 

The classical permanent protecting group of carbohydrate hydroxyl functions is probably the benzyl ether. It is very stable and can be readily removed under essentially neutral conditions. For this reason, numerous benzylation and 0-debenzylation procedures have been described. Benzyl ether formation is usually achieved by the reaction of alcohols and benzyl halides in the presence of a base such as sodium hydride in anhydrous DMF (O Scheme 2) [11], or a mild base (Ag20) in THF using a phase-transfer catalyst [12]. Benzylation can also be accomplished by the use of an acidic catalyst with benzyltrichloroacetimidate as the reagent [13]. A method using the reductive etherification of TMS ethers under non-basic conditions has also been reported [14]. 

Cyclic sulfates can be prepared from cyclic but not acyclic carbohydrate units by reaction with sulfuryl chloride in pyridine [98] or phenyl chlorosulfate and sodium hydride [99]. The reactivity of cyclic sulfates is quite similar to that of epoxides. Thus, they can be used to form fluoro or azido derivatives of polysaccharides by highly regiospecific approaches, usually, but not always, leading to trans-diaxial products from which the sulfate can be easily removed by mild, acid-catalyzed hydrolysis [100,101]. 

BeHtylatUm. Tale and Bishop found sodium hydride an excellent base for the hcnzylation of carbohydrates with benzyl chloride. For example, methyl a-D-glucopyranoililo wm converted into the tetrabenzyl ether in high yield and without by-product whwVN In the usual procedure, with powdered KOH ns base, the yield WBi onlv 3Mathar wax a malor nroduut. 

Benzylation of carbohydrates [1, 301, before Hydrolysis]. Carbohydrates are benzylated in good yield by benzyl chloride in DMSO in the presence of a base.30 The most satisfactory bases are sodium hydride, sodium amide, and sodium or potassium hydroxide. 

Methylation of carbohydrates. Anderson and Cree21 used the combination methyl iodide-sodium hydride—DMSO and achieved complete methylation of monosaccharides and acidic disaccharides in one step, but acidic polysaccharides were methylated only partially. Stacey et al.a used methyl bromide, sodium hydride, and DM F or N-methyl-2-pyrrolidone for methylation of glucopyranosides. 

The most important development in methylation technique is due to Hakomori, who used as the base methylsulfinyl carbanion, formed by reaction of methyl sulfoxide with sodium hydride, and thus extended to carbohydrates the reaction developed by Corey and Chaykovsky/ In certain cases, completely methylated polysaccharide may be obtained in high yield by one treatment within an hour. This method was used by Sandford and Conrad in a re-examination of the polysaccharide from Aerobacter aerogenes, and their paper should be consulted for the excellent experimental details contained therein. These authors showed that this polysaccharide has a simple, repeating structure, and previous suggestions that it is complicated and highly branched arose from interpretation based on products of incomplete methylation. 

Sodium hydride in DMF is also used to deprotonate carbohydrate derivatives, for methylation or benzylation (eq 4). ... 

Carbohydrate auxiliaries have been used for diastereocontrol in Darzens reactions. Thus, 404 reacted with p-anisaldehyde and sodium hydride to give 405 and its diastereomer in 65 35 ratio. The major isomer 405 was further elaborated via a-hydroxy acid 406 to e/if-diltiazen 407, the enantiomer of a known calcium channel blocker. 6-Chloroacetyl-l,2 3,4-diisopropylidene-D-galactose also reacted as did 404 in a Darzens reaction, generating a single isomeric glycidic ester. ... 

A non carbohydrate route to the cydopentanone diol 87 in live steps from diethjd maleate has been described. Sequential reaction of 87 with benzyl bromide-sodium hydride, methanolic... 

Benzyl ethers of carbohydrates are formed with both primary and secondary hydroxyl groups by reaction with benzyl chloride or bromide in a strong alkaline solution of the carbohydrate. The carbohydrate is dissolved directly in the benzyl halide, containing 4.5 M potassium hydroxide, and heated to 90-100 C for several hours [13] (reaction 4.17). Sometimes the carbohydrate is dissolved in dioxane or dimethylformamide (DMF), containing 4.5 M potassium hydroxide and benzyl halide, and heated for several hours. Difficult benzylations are accomplished by dissolving the carbohydrate in DMF that was treated with sodium hydride, similar to the Hakomori reagent, followed by the addition of benzyl halide [14]. 

Oxirans. - Treatment of methyl 4,6-0-benzylidene-a-D-glucopyranoside with a mixture of diethyl carbonate and potassium carbonate in DMF has afforded directly a new simple synthesis of methyl 2,3-anhydro-4,6-0-benzylidene-a-D-allopyranoside. The corresponding 2,3-cyclic carbonate is postulated as an intomediate. Some carbohydrate examples have been published of the use of sodium hydride and p-toluenesulfonyl chloride for the conversion of 1,2-diols to epoxides. Simple routes to the Cemy epoxides 6 and 7 finom D-glucal have been develc red (Scheme 1). In this scheme the flrst step involves a dehydration elimination with allylic rearrangement Syntheses of methyl 2,3-anhydro-a- and L-OTthiofuranoside have been reported. Some nitro-sugar epoxides are mentioned in Chapter 10. 

The carbonyl group of carbohydrates can be reduced to an alcohol function Typi cal procedures include catalytic hydrogenation and sodium borohydnde reduction Lithium aluminum hydride is not suitable because it is not compatible with the solvents (water alcohols) that are required to dissolve carbohydrates The products of carbohydrate reduc tion are called alditols Because these alditols lack a carbonyl group they are of course incapable of forming cyclic hemiacetals and exist exclusively m noncyclic forms... 

The importance of reactions with complex, metal hydrides in carbohydrate chemistry is well documented by a vast number of publications that deal mainly with reduction of carbonyl groups, N- and O-acyl functions, lactones, azides, and epoxides, as well as with reactions of sulfonic esters. With rare exceptions, lithium aluminum hydride and lithium, sodium, or potassium borohydride are the... 

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