Helferich modification

In cm empirical approach (Helferich modification) it has been demonstrated on many occasions that mercuric salts (cyanide or bromide usually) in polar solvents such as nitromethane or acetonitrile favour the formation of a-glucosides, conceivably because under these conditions the mechanism of the halide displacement is rmimolecular and the carbonium ion can be approached from either side o). 

In the early works, Hg salts were often used in place of the Ag salts to initiate the reaction. This has been called the Zemplen-Helferich modification. 

Using the Helferich modification of the Koenigs-Knorr reaction, methyl 4,6-0-benzylidene-o -D-mannopyranoside has been treated with tetra-O-acetyl-a-D-mannopyranosyl bromide, yielding methyl 3-<7-0 -D-mannopyranosyl-a -D-mannopyranoside. Benzyl 2,4-di-0-benzyl-Q -D-mannopyranoside has been... 

In the Koenigs-Knorr method and in the Helferich or Zemplen modifications thereof, a glycosyl halide (bromide or chloride iodides can be produced in situ by the addition of tetraalkylammonium iodide) is allowed to react with a hydrox-ylic compound in the presence of a heavy-metal promoter such as silver oxide, carbonate, perchlorate, or mercuric bromide and/or oxide,19-21 or by silver triflu-oromethanesulfonate22 (AgOTf). Related to this is the use of glycosyl fluoride donors,23 which normally are prepared from thioglycosides.24... 

These directions are modifications of the methods used by Helferich and Klein for the original preparation of the substance,1 although it had apparently previously been obtained by Oldham by hydrolysis of tetraacetylglucose-6-mononitrate.2... 

When 3,4-di-O-acetyl-D-xylal (5), prepared by a modification of the procedure of Helferich and coworkers, was allowed to react with a mixture of carbon monoxide and hydrogen at a pressure of about 4000 Ib./in. and at a temperature of about 130° for about 90 minutes, in the presence of preformed dicobalt octacarbonyl in benzene as the catalyst, a mixture of two inseparable, partially acetylated hexitols was obtained in over 90% yield. Deacetylation of the latter with sodium methoxide in methanol yielded, in almost equimolar proportions, the chromatographically separable hexitols, l,5-anhydro-4-deoxy-L- yio-hexitol (6) and l,5-anhydro-4-deoxy-D-arahino-hexitol (7). Whenever the mixture of products was contaminated by the precursor aldehydo compounds, a prior reduction of these with sodium borohydride greatly facilitated the isolation of (6) and (7) in pure form. 

An important modification was introduced by Helferich and coworkers, consisting in using mercury salts, particularly mercury(II) cyanide or a mixture of mercury(II) cyanide and mercury(II) bromide as promoters.15-17 Mercury(II) promoters tend to give good yields, but even in the presence of acetyl substituents at 0-2, the steric outcome, a or (3, is often unpredictable. 

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