Saccharinic acids formation

Saccharinic acid formation has been studied for several years. The four-step reaction proceeds rapidly in alkaline solution because of basic catalysis, particularly in the last two steps. Initially formed is an enediol that can undergo j8-elimination of a functional group, usually a hydroxyl group. The final two steps involve tautomerization to an a,j8-dicarbonyl intermediate followed by a benzilic acid rearrangement. This sequence is shown in Scheme 6 for the formation of the a- and j8 -xylometasac-charinic acids (30) by way of 3-deoxy-D-g/ycero-pentos-2-ulose (29). 

G. Machell and G. N. Richards, Mechanism of saccharinic acid formation. Part II. The a, /3-dicarbonyl intermediate in formation of D-glucoisosaccharinic acid, J. Chem. Soc., (1960) 1932-1944. 

The general statement of the isomerization mechanism, as given in the opening paragraph of this Section, is accepted at the present time as a mechanism of saccharinic acid formation. However, Nef s concept of the mode of isomerization of the original sugar to the intermediate a-dicarbonyl compound has undergone radical revision. 

The final phase of the Nef mechanism, which involves a benzilic acid type of rearrangement of a-dicarbonyl intermediates to the saccharinic acids, is at present accepted as a feature of saccharinic acid formation. Nef s concept of the conversion of reducing sugars to the a-dicarbonyl structures required revision, however, when it became evident that the formation, in this step, of the proposed methylenic intermediates is highly improbable. A departure from the methylenic intermediates was suggested in 1926 by Evans and Benoy, who proposed that the a-dicarbonyl intermediates of the Nef mechanism might arise by successive dehydration and rehydration from the enediols. It is now recognized, however, that forma-... 

The role of substitution in determining the course of saccharinic acid formation has been critically examined recently by Kenner and coworkers. They conclude that an 0-glycosyl or 0-alkyl anion is more readily extruded from the sugar enediol anion of the Isbell mechanism than is a hydroxyl ion. In addition, substitution at certain positions in the sugar molecule may inhibit competing side-reactions. For example, a substituent at C4 of the hexose molecule inhibits cleavage (by reverse aldolization) into two three-carbon fragments and the resultant formation of lactic acid, a result that had been demonstrated earlier by the experiments of Evans and his associates. A combination of the two above effects, then, preferentially... 

Interesting differences in saccharinic acid formation by different bases... 

The formation of deoxyosones, such as, for example, the 3-deoxyosones, appears to be the most important of the dehydration reactions which may take place during Lobry de Bruyn-Alberda van Ekenstein transformations. This type of reaction, which NeP first proposed in suggesting mechanisms for saccharinic acid formation, is difficult to study because the products are seldom stable in the reaction mixtures in which they are formed. Nevertheless, several different lines of evidence now indicate that reducing sugars undergo primary dehydrations of this kind, and that deoxyosones do indeed mediate in saccharinic acid formation in basic solutions, as well as in production of 2-furaldehyde and its derivatives in acidic media. 

When an aqueous solution of a carbohydrate is treated with a base, carbohydrate substances known as saccharinic acids are produced. This perplexing and intriguing saccharinic acid formation has been studied by many workers, and its history and mechanism are the subject of a review in this series. ... 

In a later investigation comparing the influence of different alkaline media, it was found that the methyl 3-keto-/3-n-glucoside (91 A) is degraded somewhat more slowly in sodium hydroxide (0.018 N, at 23°) than in lime-water of the same concentration. Further reaction of the dicarbonyl intermediate (112 B), to give acids, was much faster with lime-water, in accordance with the established catalyzing effect of calcium on saccharinic acid formation." ... 

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