Bromine ketoses

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. 

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 ... 

The recognition of sorbose as a ketose came initially from the observation by Kiliani and Scheibler in 1888 (see reference 88) that the sugar is not oxidized readily by bromine water. 

Ruff noticed in the mother liquors of an erythrose preparation obtained by degradation of L-arabonic acid, a small amount of another sugar, apparently a keto tetrose, which was not oxidized by bromine. The ketose gave the same phenylosazone as that obtained from L-ery-throse, but was not isolated otherwise. Neuberg oxidized erythritol to form an optically inactive tetrose solution and claimed that color reactions showed the presence of a keto tetrose. 

Attempts by Smith and ToUens " to oxidize n-fructose with bromine by the method of Clowes and Tollens were unsuccessful a double compound of D-fructose and calcium bromide was obtained. No yield of this product was given. The reaction mixture of D-fructose, calcium carbonate, water and bromine was shaken until all the bromine had dissolved, after which the double compound was separated from the concentrated solution. The calcium bromide was formed from the interaction of calcium carbonate with hydrogen bromide in the reaction solution. The hydrogen bromide could be formed in two ways by the hydrolysis of bromine in water (reaction 1, page 134) or by the reduction of bromine during the oxidation of D-fructose. The former is the more probable explanation, but a blank run without the ketose was not attempted. 

In their speed of reaction with the halogens, in acid or in alkaline solutions, the simple sugars may be divided into two main classes, the aldoses and the ketoses. The oxidation of the former is very rapid compared with that of the latter. Kiliani showed that when D-glucose and D-fructose were each treated with an equal weight of bromine in water, the ketose required 350-500 hours for completion of the oxidation, in contrast to two to three hours for the aldose. The same difference exists in buffered solutions Honig and Ruzicka found that the rates were two hours and five minutes, respectively. In alkaline solution under controlled conditions, the aldoses can be quantitatively oxidized with sodium hypoiodite in the presence of D-fructose or L-sorbose without appreciable attack on the ketoses. Ochi reported a similar but less clear-cut difference with calcium hypochlorite as the oxidant. Chlorous acid attacks only the aldoses, leaving the ketoses unaltered. The same effect was noted with the keto acids Kiliani reported that 2-keto-L-rhamnonic acid was stable to the action of bromine water. A little preliminary work has been done with iodic acid by Williams and Woods who found that D-fructose was oxidized more rapidly than the aldoses. No confirmation of this work has appeared. 

Oxidation of an aldose with bromine water at neutral pH converts the aldehyde group to a carboxyl group. Hydrobromous acid formed by the reaction of water with bromine acts as an oxidizing agent. Ketoses are not readily oxidized by bromine water. Aldoses are not only oxidized by bromine water but also by the alkaline iodine solution. 

Bromine water oxidizes aldoses, but not ketoses as an acidic reagent it does not cause isomerization of the molecule. It can therefore be used to differentiate an aldose from a ketose, and is the reagent chosen to synthesize the aldonic acid (monocarboxylic acid) from an aldose. 

The best source of D-fructose for large-scale purposes is probably the inversion of sucrose by acids or invertase. The separation of the ketose from the concomitant D-glucose may then be accomplished by direct crystallization, by removal of the d-glucose after oxidation with bromine to D-gluconic acid (the ketose is not affected), or by precipitation of the calcium fructosate. Hydrolysis of the natural inulins already mentioned may also serve for the preparation of D-fructose, which may be isolated from the hydrolyzate by precipitation of the lime complex.141 D-Fructose is fermented by yeast. 

Aldoses can be distinguished from ketoses by observing what happens to the color of an aqueous solution of bromine when it is added to the sugar. Br2 is a mild oxidizing agent and easily oxidizes the aldehyde group, but it cannot oxidize ketones or alcohols. Consequently, if a small amount of an aqueous solution of Br2 is added to an unknown monosaccharide, the reddish-brown color of Br2 will disappear if the monosaccharide is an aldose, but will persist if the monosaccharide is a ketose. The product of the oxidation reaction is an aldonic acid. 

The aldoses in such mixtures may be oxidized by bromine, which has no action on the ketoses. The aldonic acids formed in this manner are conveniently separated from the ketoses by ion-exchange resins. 

With other oxidizing agents, it is possible to obtain reducing sugars. Bromine water produces a mixture of the corresponding aldoses and 2-ketoses. Before the bacterial process was perfected, oxidation of sorbitol by bromine to sorbose was widely used in the laboratory. (See 106).)... 

The keto acids show some similarity to ketoses in their behavior toward oxidizing agents 128). 5-Ketogalactonic acid is not affected by bromine... 

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. 

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