Aldoses bromine oxidation

Jeanes and Isbell39 found that, under mild conditions, aldoses are oxidized to aldonic acids, but that nonreducing carbohydrates and ketoses are oxidized only slowly. The rate of oxidation decreases in the order pentoses > hexoses > disaccharides however, in contrast to other oxidants, chlorous acid oxidizes a-hexoses more rapidly than the ft anomers. The yields of aldonic acids are, however, less than those from bromine oxidations.40 The equation for the oxidation in acidic solution was expressed as ... 

Everett and coworkers have done extensive work on this overoxidation of aldoses with bromine at 25° for long periods of time (forty to fifty days). Under these conditions, appreciable amounts of the keto acids are obtained. Hart and Everett obtained 5-keto aldonic acids from D-glucose, D-mannose, D-galactose, D-xylose and D-gulonic lactone. The barium salts were isolated and converted to the brucine salts. The structure of the oxidation product from D-xylose was not determined. The stability of these keto acids to further bromine oxidation had been noted earlier by Kiliani. ... 

Hudson and Isbell developed the buffering action further. Calcium or barium benzoate was employed to maintain the oxidation solution at a pH of 5-6, and the reaction mixture was kept in the dark. Lactose was converted to lactobionic acid without hydrolysis, and 96 and 90% yields of calcium D-gluconate and cadmium D-xylonate-cadmium bromide were reported by the use of this method. Isbell and Pigman developed this method later into a valuable tool for the study of the mechanism of bromine oxidation and for the study of the structure of various aldoses (see pages 171, 182). 

This method was of value in that it gave an insight into the actual reaction of an aldose during bromine oxidation, and was also indicative of its ring structure. The method should be used with caution, however, especially in respect to the relative velocity of the anomeric forms of the various sugars. Formation of 5-lactones can be considered excellent... 

Both chloric and iodic acid have been used as oxidants in acidic solutions. No examples with bromic acid have been reported. Withaldonic acids the primary products are keto acids. However, an example does exist of the conversion of an aldose to an aldonic acid. This might be classed as an indirect or secondary bromine oxidation, since a mixture of sodium chlorate and hydrobromic acid was used in acid solution. 

Very extensive work was done by Isbell and Pigman "" on the rate of bromine oxidation of the anomeric forms of various aldoses in buffered solution. Except for arabinose, the /3-forms were oxidized the most readily (Table X and Fig. 1). It is interesting to note that the rates for... 

There are a number of ways in which an aldose can be converted into another aldose of one less carbon atom. One of these methods for shortening the carbon chain is the Ruff degradation. An aldose is oxidized by bromine water to the aldonic acid oxidation of the calcium salt of this acid by hydrogen peroxide in the presence of ferric salts yields carbonate ion and an aldose of one less carbon atom (see Fig. 34.3). 

In the presence of a tertiary amine, in particular pyridine (Sec. 31.6), an equilibrium is established between an aldonic acid and its epimer. This reaction is the basis of the best method for converting an aldose into its epimer, since the only configuration affected is that at C-2. The aldose is oxidized by bromine water to the aldonic acid, which is then treated with pyridine. From the equilibrium mixture thus formed, the epimeric aldonic acid is separated, and reduced (in the form of its lactone) to the epimeric aldose. See, for example, Fig. 34.4. 

The aqueous-bromine oxidation rate was determined for a number of other anomeric pairs of aldoses and it was found that, in general, the jS forms (see page 17) react faster. This phenomenon has also been observed for a-D- and /S-D-galactopyraniironic acid oxidation of these compounds provides a mixture of optically active lactones of galactaric (mucic) acid. This constitutes interesting evidence for the direct oxidation of the cyclic modifications (pyranose and furanose forms), since the oxidation of... 

Ref. 200. No mechanistic work of significance has been done on the bromine oxidation of aldoses since this review. 

Aldonic acids Carboxylic acid products of Fehling s and Tollen s tests or bromine oxidation on sugars. Aldose A sugar based on aldehydes—so that a three-carbon chain would be an aldotriose, for example. Aliphatic compound A nonaromatic compound. 

Oxidation (Section 23.19) Bromine oxidizes the aldehyde function of an aldose to a carboxylic acid. The product is an aldonic acid that normally exists as a lactone. The main path to uronic acids, carbohydrates that bear a CO2H group instead of CH2OH, is biosynthetic. Nitric acid oxidizes both the CHO and CH2OH ends of an aldose to CO2H. These compounds are called aldaric acids. 

Isbell HS, Pigman WW (1937) Bromine oxidation and mutarotation measurements of a- and p-aldoses. J Res Natl Bur Stand 18 141-194... 

Conversion of alditols to aldoses without the need to protect all hydroxy groups has been achieved by monotosylation of one primary hydroxy group, displacement with azide ion and photolysis in methanol to yield the aldimine,which was then hydrolyzed to the aldose. The procedure was illustrated using 3 4-0 isopro ylideno-D-mannitol to produce D-mannose. The synthesis of D-[U- Cjgalactose from methyl <-D-[n- Cjglucopyranoside via aqueous bromine oxidation to the 4.-uloside, reduction by sodium borohydride and hydrolysis has been described, along with the isolation of D-glucuronic acid and methyl o( D-mannopyranoside as by-products. 

An aldose is oxidized to a carboxylic acid derivative via treatment with aqueous copper sulfate, silver nitrate in ammonia, bromine, aqueous potassium permanganate, or nitric acid. 

A variation of the bromine oxidation process which seems to be particularly feasible for the commercial production of aldonic acids involves the electrolysis between carbon electrodes of solutions containing sugars, small amounts of bromides, and a buffer such as calcium carbonate 179), Presumably the reaction takes place by the formation of free bromine at the anode the bromine oxidizes the aldose to the aldonic acid and is reduced to bromide. Yields are almost theoretical in many cases. If the electrolytic method is not well controlled, saccharic acids and 2-keto and 5-keto aldonic acids may be produced 180), Whereas the normal electrolytic oxidation is conducted with direct current, a yield of 55 % of gluconic acid has been obtained with alternating current 181) and platinum electrodes a very low efficiency was observed with graphite electrodes. 

Ketoses may be separated from contaminating aldoses by oxidation of the latter with bromine and removal of the aldonic acids with an ion-ex-change resin (2), Ion-exchange resins are also useful in the recovery of sugar acids and of some nitrogen-containing derivatives of sugars. 

Under mild conditions, e. g., with bromine water in buffered neutral or alkaline media, aldoses are oxidized to aldonic acids. Oxidation involves the lactol group exclusively. 3-Pyranose is oxidized more rapidly than the a-form. Since the P-form is more acidic (cf. 4.2.1.3), it can be considered that the pyranose anion is the reactive form. The oxidation product is the 5-lactone which is in equilibrium with the y-lactone and the free form of aldonic acid. The latter form prevails at pH > 3. 

The ketonic sugars are resistant to bromine oxidation, and thus may be separated from the aldoses. On more powerful oxidation, ketoses rupture at the carbonyl group, with formation of two acids. 

Derivatives of aldoses in which the terminal aldehyde function is oxidized to a car boxylic acid are called aldonic acids Aldonic acids are named by replacing the ose ending of the aldose by omc acid Oxidation of aldoses with bromine is the most com monly used method for the preparation of aldonic acids and involves the furanose or pyranose form of the carbohydrate... 

Less activated substrates such as uorohaloben2enes also undergo nucleophilic displacement and thereby permit entry to other useful compounds. Bromine is preferentially displaced in -bromofluoroben2ene [460-00-4] by hydroxyl ion under the following conditions calcium hydroxide, water, cuprous oxide catalyst, 250°C, 3.46 MPa (500 psi), to give -fluorophenol [371-41-5] in 79% yield (162,163). This product is a key precursor to sorbinil, an en2yme inhibitor (aldose reductase). 

The oxidation of an aldose (not a ketose) with bromine and water results in an aldonic acid. An example of this reaction is shown in Figure 16-9. 

Bromine water oxidizes aldose to lactones which hydrolyze to alfonic acids. 

Aldonolactones are commercially available at low cost, when compared to most of the common monosaccharides. They are typically synthesized by selective anomeric oxidation of unprotected aldoses with bromine [6]. Usually the thermodynamically more stable five-membered lactone (y-lactone) predominates over the six-membered form, with the exception of o-gluconolactone, which crystallizes as the 1,5-pyranolactone (5-lactone) [7] (Scheme 1). Another method for the preparation of sugar lactones is the dehydrogenation of unprotected or partially... 

Hydrazones 10 derived from aldose monosaccharides (9) and 2-hydrazinopyrimidine (8) gave, upon oxidative cyclization with bromine in methanol, the corresponding 3-(alditol-l-yl)-l,2,4-triazolo[4,3-a]pyrim-idines 11 [97JHC(34)1115] (Scheme 7). 

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