Fischer synthesis

This means that the ratio of furanosides to pyranosides obtained will depend on the conversion-contact time. If reaction of the glucosides is taken to the thermodynamic equilibrium the pyranoside to furanoside ratio is ca 95 5 and the molai ratio of aip is 65 35. The thermodynamic composition of the isomers varies from one monosaccharide to another [5]. A side-reaction is the oligopolymeriza-tion of the sugar with formation of alkyl polyglycosides. An average polymerization degree is defined APG) that influences the final hydrophilic-hydrophobic properties [6]. 

With the objective of reducing the formation of oligoglucosides and also to control the stereoselectivity, Koenigs and Knorr [8] developed another route which involves protection of the hydroxyls in the sugar [9-11]. 

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An older version of this sequence is called the Kiliani-Fischer synthesis It too proceeds through a cyanohydrin but it uses a less efficient method for converting the cyano group to the required aldehyde... 

The Kiliani-Fischer synthesis pro ceeds by nucleophilic addition of HCN to an aldose followed by con version of the cyano group to an al dehyde A mixture of stereoisomers results the two aldoses are epi meric at C 2 Section 25 20 de scribes the modern version of the Kiliani-Fischer synthesis The example at the right illus trates the classical version... 

Ketose (Section 25 1) A carbohydrate that contains a ketone carbonyl group in its open chain form Kiliam-Fischer synthesis (Section 25 20) A synthetic method for carbohydrate chain extension The new carbon-carbon bond IS formed by converting an aldose to its cyanohydnn Reduction of the cyano group to an aldehyde function com pletes the synthesis... 

In the mid-1930s Universal Oil Products reported (33,34) that gasoline of improved quaHty could be produced by cracking the high boiling fractions of Fischer Hquids, and a consortium, the Hydrocarbon Synthesis, Inc., entered into an agreement with Ruhrchemie to Hcense the Fischer synthesis outside Germany. 

Natural Gas Upgrading via Fischer-Tropsch. In the United States, as in other countries, scarcities from World War II revived interest in the synthesis of fuel substances. A study of the economics of Fischer synthesis led to the conclusion that the large-scale production of gasoline from natural gas offered hope for commercial utiHty. In the Hydrocol process (Hydrocarbon Research, Inc.) natural gas was treated with high purity oxygen to produce the synthesis gas which was converted in fluidized beds of kon catalysts (42). 

A number of instances in which application of the Fischer synthesis led to extended 3,4-dihydro-j8-carbolinium derivatives have been recorded. Typical for this approach is the ring closure of the phenyl-hydrazone 123 to the expected tetracyclic product... 

Fischer s original method for conversion of the nitrile into an aldehyde involved hydrolysis to a carboxylic acid, ring closure to a cyclic ester (lactone), and subsequent reduction. A modern improvement is to reduce the nitrile over a palladium catalyst, yielding an imine intermediate that is hydrolyzed to an aldehyde. Note that the cyanohydrin is formed as a mixture of stereoisomers at the new chirality center, so two new aldoses, differing only in their stereochemistry at C2, Tesult from Kiliani-Fischer synthesis. Chain extension of D-arabinose, for example, yields a mixture of D-glucose and o-mannose. 

Just as the Kiliani-Fischer synthesis lengthens an aldose chain by one carbon, the Wohl degradation shortens an aldose chain by one carbon. The Wohl degradation is almost the exact opposite of the Kiliani-Fischer sequence. That is, the aldose aldehyde carbonyl group is first converted into a nitrile, and the resulting cyanohydrin loses HCN under basic conditions—the reverse of a nucleophilic addition reaction. 

Much of the chemistry of monosaccharides is the familiar chemistry of alcohols and aldehydes/ketones. Thus, the hydroxyl groups of carbohydrates form esters and ethers. The carbonyl group of a monosaccharide can be reduced with NaBH4 to form an alditol, oxidized with aqueous Br2 to form an aldonic acid, oxidized with HNO3 to form an aldaric acid, oxidized enzymatically to form a uronic acid, or treated with an alcohol in the presence of acid to form a glycoside. Monosaccharides can also be chain-lengthened by the multistep Kiliani-Fischer synthesis and can be chain-shortened by the Wohl degradation. 

Kiliani-Fischer synthesis (Section 25.6) A method for lengthening the chain of an aldose sugar. 

Arabinose, configuration of. 982 Kiliani-Fischer synthesis on. 995 Arachidic acid, structure of, 1062 Arachidonic acid, eicosanoids from, 1069-1070... 

Keto-enol tautomerism, 264, 842-844 Kiliani, Heinrich, 994 Kiliani-Fischer synthesis, 994-995 Kimbail, George, 216 Kinetic control, 491 Kinetics, 362... 

Scheme 8.32 Kiliani-Fischer synthesis of higher sugars.

Alkylation of an anionic acylmetallate is the second step in the classic Fischer synthesis of carbene complexes. The same type of reaction can be performed with stable neutral acyl complexes, producing cationic carbene compounds. Compound 17 has been prepared from a ruthenium acetyl complex by direct methylation and by protonation with subsequent methylenation (45) ... 

An application to n-xylose (LXII) of the Fischer synthesis of 2-amino hexonic acids from pentoses would lead theoretically to a mixture of 2-amino-D-gulonic acid (LXIII) and 2-amino-D-idonic acid (LXIV). 

Digressing from reductive desulfurization into stereochemistry, we may use this experimental proof of the equivalent symmetry of D-mannitol as a basis for an independent proof of the configurations of D-mannitol and D-arabitol. The reduction of D-arabinose yields the optically active pentitol, D-arabitol application of the Sowden-Fischer synthesis to D-arabinose yields D-mannose86 which upon reduction gives D-mannitol. 

From Fischer synthesis. b From Koenigs-Knorr synthesis. 

A sequence known as the Kiliani-Fischer synthesis was developed primarily for extending an aldose chain by one carbon, and was one way in which configurational relationships between different sugars could be established. A major application of this sequence nowadays is to employ it for the synthesis of " C-labelled sugars, which in turn may be used to explore the role of sugars in metabolic reactions. 

Construction of the indole ring via Fischer synthesis. Starting from a variety of 3,4-dihydro-lH-benzo[l ]azepine-2,5-diones 40 and arylhydrazines Fischer syntheses of indolo benzazepinones 41 have been reported (Scheme 8 (1999JMC2909)). Usually, the reaction comprises a two-step one-pot procedure with the formation of intermediate arylhydrazones in warm acetic acid followed... 

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