Helferich method synthesis

The Fischer- Helferich method, as a direct anomeric-oxygen replacement reaction (Scheme 1, path A), has been very successfully applied for syntheses of simple alkyl glycosides. However, because of its reversibility, it has not gained general importance in the synthesis of complex oligosaccharides and glycoconjugates (1). 

However, another application of the Fischer-Helferich method clearly exhibits its limitations. Long chain alkyl glycosides have gained interest as nonionic surfactants. Their technical synthesis is based on acid catalysis of the reaction between glucose and alcohol. Due to the inherent solubility problems, typical drawbacks of the Fischer-Helferich method are encountered the technical product consists of a mixture of different anomers and, due to the fact that excess alcohol cannot be used for solubilization of the reaction mixture, reaction of glucose with itself is also found. 

Due to the drawbacks of the Fischer-Helferich method it was early recognized that other approaches to glycoside and saccharide synthesis had to be introduced. 

Haworth Methylation Haworth Phenanthrene Synthesis Hayashi Rearrangement Heck Reaction Helferich Method Hell-Volhard-Zelinsky Reaction Henkel Process Henkel Reaction Henry Reaction... 

The nitriles can also be employed as intermediates in the condensation of ethyl glyoxylate with aJdehydo sugars under the influence of sodium methoxide, leading to the preparation of L-ascorbic acid and similar compounds. Helferich and Peters described the synthesis of D-ascorbic acid (XXVIII) from tetraacetyl-n-xylononitrile (XXVI) presumably the nitrile underwent a type of ZempMn degradation and the n-threose (XXVII) thus formed condensed with the glyoxylic ester. The method... 

Johnson and Bergmann, as well as Helferich and Kosche, noted the possibility that the glycosyl ureides might be utilized as intermediates for an improved method of synthesis of pyrimidine nucleosides. Fischer s method was used for obtaining 1-n-glucosylurea as well as 1-n-arabinosyl-urea and 1,3-di-n-xylosylurea. 

Reinhard W. Hoffmann was bom in 1933 in Wurzburg. He studied chemistry at the Universitat Bonn and received his Dr. rer. nat. in 1958 under the direction of Prof. B. Helferich. He spent two years as postdoctoral fellow at The Pennsylvania State University with Prof. G. W. Brinkley and moved then to the Universitat Heidelberg for another postdoctoral year with Prof. G. Wittig. In 1964 he obtained his habilitation and in 1967 he moved as lecturer to the Technische Hochschule Darmstadt and in 1970 to his present position as Professor of Organic Chemistry at the Universitat Marburg. His research interests are new methods in stereoselective C-C-bond formation, their application in natural products synthesis and the stereochemistry of reactive organometallic compounds. 

Regioselective, partial protection is an important transformation in carbohydrate chemistry as it simplifies preparation of differentially substituted synthetic intermediates. One such procedure is the synthesis of tetraacetyl glucose 2. The method for obtaining 2 was originally presented by Helferich and Zimer and involved a multi-step reaction that eventually led to a mixture of hemiacetal (1-OH derivative) and 2, from which the latter could be isolated in pure form by crystallization in a modest yield of 27%. Chromatographic purification of the material in the mother liquor is impractical due to the propensity of 2 to rapidly isomerize into its more stable hemiacetal counterpart. Since 2 is an important building block, the original protocol is still in frequent use. 

---