Acetals of D-fructose

Study of this reaction has not been limited to cyclic acetals of aldoses and aldosides, and synthetic applications in the ketose series have been developed,273,276,278,278 particularly for isopropylidene acetals of D-fructose. As an illustration of these reactions, two examples are given here. The action of butyllithium on 2,3 4,5-di-0-isopropyli-dene-l-0-methyl-/3-D-fructopyranose (280) gave273 a 30% yield of the 5-enopyranose 282. Abstraction by the base of the axial hydrogen atom from the 6-methylene group, giving the anion 281, was invoked... 

Retention Times of Per(trimethylsilyl) Ethers and Other Derivatives of Some Acetals of D-Fructose and D-Psicose... 

Two crystalline diisopropylidene acetals of D-fructose were prepared by E. Fischer in 1895 by the action of acetone containing 0.2% of hydrogen chloride on the sugar at room temperature. The acetal isolated first was provisionally termed a until structural determinations had been made it was obtained in 50% yield. A small proportion of a second diacetal, arbitrarily termed p, was on one occasion isolated from the mother liquors. Fischer was unable to repeat the experiment in which he had obtained the /3 form. 

Thermolysis of D-fructose in acid solution provides 11 and 2-(2-hydrox-yacetyl)furan (44) as major products. Earlier work had established the presence of 44 in the product mixtures obtained after acid-catalyzed dehydrations of D-glucose and sucrose. Eleven other products were identified in the D-fructose reaction-mixture, including formic acid, acetic acid, 2-furaldehyde, levulinic acid, 2-acetyl-3-hydroxyfuran (isomaltol), and 4-hydroxy-2-(hydroxymethyl)-5-methyl-3(2//)-furanone (59). Acetic acid and formic acid can be formed by an acid-catalyzed decomposition of 2-acetyl-3-hydroxyfuran, whereas levulinic acid is a degradation prod-uct of 11. 2,3-Dihydro-3,5-dihydroxy-6-methyl-4//-pyran-4-one has also been isolated after acid treatment of D-fructose.The pyranone is a dehydration product of the pyranose form of l-deoxy-D-eo f o-2,3-hexodiulose. In aqueous acid seems to be the major reaction product of the pyranone. 

Conditions are slightly different during the so-called mannitol fermentation of sugars, especially of D-fructose. The process, which has been known for a long time, has recently been investigated more thoroughly by Bolcato. He found that 3 moles of D-fructose yield 2 moles of carbon dioxide, 2 moles of acetic acid and 2 moles of D-mannitol. Up to now, a maximum of 60% of the theoretically possible amount of D-mannitol has been isolated. The mechanism of the reaction may be assumed to be as follows ... 

Hudson and Brauns87 were the first to prepare crystalline /8-D-fructo-pyranose pentaacetate, m. p. 108-109°, [o]d —120.9° in chloroform. It was obtained in 20% yield by the action of acetic anhydride and sulfuric acid on D-fructose at —15°. This is still the only direct method available for making this compound. The same pentaacetate was obtained by the further acetylation of D-fructose 1,3,4,5-tetraacetate with acetic anhydride and sulfuric acid at —15°. 

Incidental reactions that have been reported include the preparation of derivatives of 5-(hydroxymethyl)-2-furaldehyde by reaction of D-fructose in acetic or propionic acid in the presence of the respective anhydride.158 The condensation of D-glucose with phenol has been effected in acetic acid in the presence of dry hydrogen chloride, prior to resinification,157 and the reaction of sucrose with thionyl chloride in acetic acid-acetic anhydride produced partially acetylated chlorodeoxysucroses.158 Sucrose has been condensed with maleic anhydride in acetic anhydride mixed with acetic acid or formic acid, to give solid products having an undetermined structure.159... 

Acylation66 of D-fructose leads67 to substantial yields of a completely esterified, acyclic derivative (6) in which the ketonic center exists as a free carbonyl group, and provides an indirect route for the synthesis of ketose dialkyl dithioacetals, as 6 reacts with two equivalents of thiol under acid catalysis to produce68 the acylated dithio-acetal 7, which can subsequently be saponified to yield the free... 

At the temperatures commonly used in mass spectroscopy, this method is only valuable for the identification of such derivatives of D-fructose as the methyl ethers and acetates, but permits differentiation of ketoses from aldoses. ... 

Condensation of D-fructose with dry acetone or benzaldehyde affords cyclic acetals. The same procedure with cyclopentanone, with concentrated sulfuric acid as the catalyst and stirring at room temperature for some 40 hours, gave a sirupy product which was characterized by its p-tolylsulfonyl derivative. Cyclohexanone yielded a crystalline product of m.p. = 142°, readily isolated and purified. For the acetal, structure... 

Structure of d-Fructose.—As d-fructose yields d-sor-bitol and d-mannitol on reduction, it must contain a straight chain of six carbon atoms. Acetic anhydride converts the carbohydrate into a penta-acetate, a fact which indicates that it contains five hydroxyl groups. On oxidation d-fructose does... 

Emil Fischer first described the condensation of D-fructose with acetone in 1895, and most of the early work on cyclic acetals of ketoses was performed with D-fructose. In 1934, Reichstein and Griissner published their classic synthesis of L-ascorbic acid (vitamin C), in which L-sorbose was converted into 2,3 4,6-di-0-isopropylidene-a-L-sorbofuranose or other di-alkylidene acetals. The emphasis of research activity then shifted to L-sorbose, and to the elucidation of an optimal procedure for preparing such diacetals. At about the same time, Levene and Tipson used isopropylidene acetals as derivatives for the purification of L-cri/thro-pentulose (as the di-isopropylidene acetal) and D-thrco-pentulose (as the monoisopropyli-dene acetal). Soon thereafter, Reichstein and coworkers used diisopropylidene acetals of D- and L-psicose, and D-tagatose, to purify the respective sugars. 

Proton magnetic resonance spectroscopy has also been used to study the conformations of several pyranoid derivatives of D-fructose and L-sorbose. Once more, data obtained in this study are limited, because of the lack of a proton at the anomeric center the only coupling constants useful in conformational studies of acetals of ketopyranoses are 73,4, 7s.b. and Js-s. and the conclusions that... 

Zervas and Sessler synthesized an isomeric mono-O-isopropylidene-D-fructose by acetonating 1,6-di-O-benzoyl-D-fructose, prepared by treatment of D-fructose cyanohydrin with two molar proportions of benzoyl chloride in the presence of pyridine. The cyclic acetal obtained after debenzoylation was named 2,3-acetone-a-D-fructo-furanose by the authors, although, quite evidently, it is 2,3-0-isopropylidene-j8-D-fructofuranose (90). 

Lobry de Bruyn and Alberda van Ekenstein obtained a di-O-meth-ylene-D-fructose by treating a mixture of D-fructose and paraformaldehyde with either 50% sulfuric acid or 75% phosphoric acid. The diacetal, which melted at 92° and had [aJi, -34.9° in water, did not reduce Fehling solution nor react with phenylhydrazine, but it did form a monoacetate, from which the parent diacetal could be recovered by saponification. By analogy with 2,3 4,5-di-0-isopropyli-dene-)8-D- ctopyranose (2) ([a]o —33.7°), the dimethylene acetal may be formulated as 2,3 4,5-di-0-methylene-j8-D-fructopyranose (95). 

---