Sorbose oxidation, chemical

Most current industrial vitamin C production is based on the efficient second synthesis developed by Reichstein and Grbssner in 1934 (15). Various attempts to develop a superior, more economical L-ascorbic acid process have been reported since 1934. These approaches, which have met with htde success, ate summarized in Crawford s comprehensive review (46). Currently, all chemical syntheses of vitamin C involve modifications of the Reichstein and Grbssner approach (Fig. 5). In the first step, D-glucose (4) is catalytically (Ni-catalyst) hydrogenated to D-sorbitol (20). Oxidation to L-sotbose (21) occurs microhiologicaRy with The isolated L-sotbose is reacted with acetone and sulfuric acid to yield 2,3 4,6 diacetone-L-sorbose,... 

Nickel oxide anodes are another example for a relatively simple oxide electrocatalyst used rather widely in the oxidation of organic substances (alcohols, amines, etc.) in alkaline solutions at relatively low anodic potentials (about +0.6 V RHE). These processes, which occur at an oxidized nickel surface, are rather highly selective. As an example, we mention the industrial oxidation of diacetone-L-sorbose to the corresponding acid in vitamin C synthesis. This reaction occurs at nickel oxide electrodes with chemical yields close to 100%. 

The heterogeneously catalyzed Mn02-mediated oxidation of diacetone-L sorbose to diacetone-2keto-L sorbic acid, the latter being a precursor to vitamin C, at nickel anodes and based on the chemical oxidation of the substrate by NiOOH is of technical relevance. The limiting current density in 1 M KOH solution is under operation conditions only 10 A/cm2 leading to relatively poor space-time yields. Robertson and Ibl showed that acceptable space-time yields can by obtained by using thin layer cells of Swiss roll type (193, 194), which leads to an efficient compression of the cell width to fractions of a millimeter. 

Commercially available ascorbic acid still includes isolation from natural sources, such as rose hips, but large-scale production will involve the microbiological approach, i.e., Acetobacter suboxidans oxidative fermentation of calcium d-gluconate or the chemical approach, i.e.. the oxidation of /-sorbose. 

In the synthesis of vitamin C, the oxidation of diacetone L-sorbose to diacetone 2-keto-L-gulonic acid proceeds at an Ni-anode in the presence of hydroxide. Under these conditions, the nickel hydroxide surface is anodically transformed to NiOOH, the nickel peroxide, which acts as chemical oxidant via hydrogen atom abstraction. Thus, a chemically modified redox-active electrode acts as a heterogeneous redox catalyst [13] ... 

Clearly, an improved synthesis of L-ascorbic acid would result from the direct oxidation of L-sorbose (25) to L-xy/o-2-hexulosonie acid (28), thus eliminating the protecting-deprotecting steps currently required in the Reichstein-Griissner synthesis (see Scheme 4). Efforts to perform this oxidation may be divided into two categories, namely, chemical and fermentative. The results of each method will be summarized. 

It is apparent from the foregoing discussion that, at the present time, the direct chemical or fennentative oxidation of L-sorbose to h-xylo-2-hexulosonic acid is not efficient enough to compete with the Reich-stein-Griissner protection-oxidation method. 

It may be noted that l,2,3,4-tetra-0-benzoyl-5,6-0-isopropylidene-D-glucitol (52) has been oxidized with trityl tetrafluoroborate324 325 to 3,4,5,6-tetra-O-benzoyl-keto-L-sorbose (53) in 50% yield. This illustrates an interesting oxidation of acetals, and constitutes a partial, chemical synthesis of L-sorbose (25) from D-glucitol (24). 

The semi-synthetic production of vitamin C is rapidly moving to a full biotech process. Vitamin C (ascorbic acid) is an important segment in the worldwide vitamin market with a market share of approximately 20 percent. Its worldwide sales amounted to around USD 0.5 bilHon in 1999. The traditional route to vitamin C is a multistep process involving chemical and fermentative steps. It starts with the catalytic hydrogenation of D-glucose to D-sorbitol, followed by the fermentative oxidation of D-sorbitol to L-sorbose, which is then converted... 

A nickel anode is in alkaline solution protected against corrosion by a layer of nickel oxides. oxide (NiOOH) is capable of oxidizing a number of functional groups primary alcohols may be oxidized to carboxylic acids [158-161], which is of interest for the technical production of an intermediate for vitamin C production [162]. NiOOH chemically oxidizes the substrate and is regenerated electrochemically a large anode surface, which is realized in the Swiss-roll cell (Chap. 31), is thus advantageous. NiOOH electrodes in form of nickel foam electrodes has been found to be useful for the oxidation of diacetone L-sorbose to diacetone 2-keto-L-gulonic acid in the vitamin C synthesis [163]. 

Attempts to eliminate the protection-deprotection steps in the Reich-stein-Griissner synthesis by carrying out a high-yield chemical or fermentative oxidation step directly on glucitol (18) or L-sorbose (19) were unsuccessful (Scheme 13). The best result reported is the platinum (or related metals) catalyzed air oxidation of 19 to 23 (62% yield) (42). 

In 1923 the bacterium Acinetobacter suboxydans was isolated and, starting in 1930, was used for the industrial oxidation of L-sorbitol to L-sorbose in the Reichstein-Griissner synthesis of vitamin C[39]. Bayer uses the same type of reaction, but instead of Acinetobacter the bacterium Gluconobacter suboxydans is used in the oxidation of N-protected 6-amino-L-sorbitol to the corresponding 6-amino-L-sorbose, which is an intermediate in miglitol production (Fig. 19-7). 1-Desoxynojirimydn is produced by chemical intramolecular reductive amination of 6-amino-L-sorbose. In contrast, the... 

The contemporary procedure for the chemical oxidation of 2,3 4,6-di-O-isopropylidene-a-L-sorbofuranose (14) with potassium permanganate to 2,3 4,6-di-0-isopropylidene-L-xyZo-hexulosonic acid (15) can be successfully replaced by electrochemical oxidation, and the permanganate oxidant, which is relatively expensive, is thus not required this procedure has been patented by Verheyden. The electro-oxidation of 2,3 4,6-di-O-isopropylidene-L-sorbose (in 4-8% concentration) is conducted in 5% potassium hydroxide solution in the presence of 2% potassium chromate... 

Fig. 3.14 TEM image of HPS-Pt-2 after the induction period during the direct oxidation of L-sorbose in an aqueous medium. Groups of single Pt nanoparticles are highlighted by circles, whereas substantially enlarged nanoparticles are identified by arrows. Reprinted with permission from Ref. [89]. Copyright (2001) American Chemical Society.

The enzyme-catalysed oxidation of alcohols to carbonyl compounds is not as attractive as the reverse reaction discussed earlier. This is because the oxidation often removes a chiral centre from the substrate, and the recycling of oxidized co-factors NAD(P) can be problematic. However, there are some instances where the enzyme technology has an advantage over conventional chemical oxidants. For example, the polyol D-sorbitol is oxidised by the micro-organism Acetobacter suboxydans to give L-sorbose (Scheme 4.14) (see also Chapter 1, Section 1.7). 

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