Sorbose reaction with acetone

The reaction of L-sorbose with acetone, a step in the synthesis of L-ascorbic acid (vitamin C), takes place in acetone solution [Eq. (41)] (361). 

Two process improvements are worthy of special comment. Initially when L-sorbose was treated (29) with acetone and sulfuric acid, the monoacetonide (20) and the diacetonide (21) were formed. In subsequent work researchers found that when the temperature of the reaction... 

The condensation reactions are normally performed at room temperature, because the use of higher temperatures may lead to undesirable side-products resulting from hydrolysis of acid-labile substituents, inversion, or formation of anhydrides. The condensation of L-sorbose with acetone, catalyzed by 4% of sulfuric acid, is reported to be temperature-dependent. Essentially pure 2,3 4,6-di-O-isopropylidene-a-L-sorbofuranose (3) is formed below 5°, whereas a mixture composed of equal parts of 3 and 2,3-O-isopropylidene-a-L-sorbofuranose (4) is formed at 20°, and only the monoacetal... 

The mono- and di-acetal products of a reaction of L-sorbose with acetone have been examined separately, without preliminary fractionation. When the mixture of products was developed with 3 1 (v/v) hexane-acetone, the diacetals were dispersed, but the monoacetals were practically immobile. Alternatively, irrigation of the mixture of products with 2 3 (v/v) hexane-acetone effected a good separation of the isomeric monoacetals, whereas the diacetals gave rise to a single, fast-moving spot. 

Isbell made use of this reaction to S3mthesise vitamin C from L-galactono-y-lactone. The latter was first converted into the 2-0x0 derivative (see p. 83). A commercial synthesis of ascorbic acid is also based on this isomerisation. Bertrand s sortose bacterium, Acetobacter xylinium, converts sorbitol to L-sorbose (XCI) and this on condensation with acetone yields the 2,3 4,5-di-O-isopropyhdene derivative (XCII). Oxidation and hydrolysis of this... 

In the modern industrial manufacturing proce.ss, the reduction to d-sorbitol is accomplished either electrolytically or by catalytic hydrogenation (Ha/CuCrOa). Additionally, it has been found that the reaction of sorbose with acidified acetone at low temperature (— 5 °C) gives a greatly increased yield of the di-O-isopropylidenyl (as opposed to the 2,3-mono-O-isopropylidenyl) derivative. The oxidation of this protected sorbose (2,3 4,6-di-0-isopropylidene-L-sorbofuranose or diacetone sorbose ) to the corresponding 2,3 4,6-di-0-isopropylidene-2-... 

Hoping to increase the yield of 3 by ensuring anhydrous conditions, Tokuyama and Honda turned to the reaction of L-sorbose with 2,2-diethoxypropane (acetone diethyl acetal), catalyzed by p-toluenesulfonic acid. Three main products were isolated 1-0-(2-ethoxy-2-propyl)-2,3 4,6-di-0-isopropylidene-a-L-sorbofuranose (12), the 2,3 4,6-diacetal 3, and l,2 4,6-di-0-isopropylidene-a-L-sor-... 

Ohle isolated an isomeric mono-O-isopropylidene-L-sorbose from a similar reaction. After removing diacetal 3, he acetylated the remaining mixture containing monoacetals. Fractional recrystallization of the distilled mixture of triacetates was effected from methanol-water, and, on saponification, one fraction of the crystalline material gave l,2-0-isopropylidene-o -L-sorbopyranose (11) in 3% yield from L-sorbose. Periodate oxidation of 11 showed consumption of two moles of oxidant per mole, with formation of one mole of formic acid. The monoacetal 11 was also isolated in 16% yield when a suspension of L-sorbose and copper(II) sulfate in impure acetone was shaken for seven days. Other products were 3 and an isomeric di-O-isopropylidene-L-sorbose which was obtained in 1% yield and regarded by Ohle as slightly impure. Its properties (m.p. 155-157°, [aJu -f-44.9° in acetone) closely match those of l,3 4,6-di-0-isopro-pylidene-j8-L-sorbofuranose (18) (m.p. 159-160°, [a]i)-f-43.4° in acetone), identified by Maeda in 1967. Patil and Bose later isolated, but did not identify, a diacetal which was probably 18 (m.p. 155-157°, [a]n -f-4.49° in acetone). 

A study of the oleum-catalysed acetonation of L-sorbose has shown that 71-83% of ketal mixtures containing 92-94% of 2,3 4,6-di-(9-isopropylidene-L-sorbose can be obtained. Lowering the temperature from 0 to — 10°C increased the yield by 3%, but increasing the time of reaction above 20 min had little effect on purity or yield. A continuous-flow method for production of sorbose acetonide has been optimized and yields of 11,6% obtained. Room temperature reaction of lactose with 2,2-dimethoxypropane in DMF gives mainly 4,6 -O-isopropylidene lactose, whilst at reflux the same reaction gave 45% of the... 

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