Aldehydes mutarotation

The isolation of several pairs of geometric isomers of 4-unsaturated-5-oxazolones has been described. Generally, only one isomer is obtained when an aldehyde reacts with hippuric acid in the presence of acetic anhydride. Occasionally, mixtures have been separated in base-catalyzed reactions. In acetic anhydride-sulfuric acid or in 100% sulfuric acid, a mixture is obtained, and it has been suggested that sulfuric acid inhibits mutarotation of the intermediate addition product 53, which is a mixture of diastereomers (see, e.g., compound... 

Mutarotation occurs by a reversible ring-opening of each anomer to the open-chain aldehyde, followed by reclosure. Although equilibration is slow at neutral pH, it is catalyzed by both acid and base. 

Die Reduktion mit komplexen Metallhydriden semicyclischer Halbacetale hat ihre groBeBedeutungin der Zucker-Chemie, da nur die echten Aldehyd- und Keton-zucker reduziert werden, so daB die Reduktion parallel der Mutarotation verlauft. 

However, the pattern is complicated by several factors. The sugar molecules to be hydrogenated mutarotate in aqueous solutions thus coexisting as acyclic aldehydes and ketoses and as cyclic pyranoses and furanoses and reaction kinetics are complicated and involve side reactions, such as isomerization, hydrolysis, and oxidative dehydrogenation reactions. Moreover, catalysts deactivate and external and internal mass transfer limitations interfere with the kinetics, particularly under industrial circumstances. 

In contrast to other 2,5-anhydroaldoses (which exhibit mutarota-tion, possibly due to the formation of hemiacetals28), 2,5-anhydro-D-glucose does not show any mutarotation.27 The importance of this compound as a potentially useful precursor to C-nucleosides warrants a reinvestigation of the deamination reaction, and the definitive proof of the structure of the compound. The readily accessible 2,5-anhydro-D-mannose (11) does not possess the cis-disposed side-chains at C-2 and C-5 that would be required of a synthetic precursor to the naturally occurring C-nucleosides, with the exception of a-pyrazomycin (8). The possibility of an inversion of the orientation of the aldehyde group in 11 by equilibration under basic conditions could be considered. 

Acetals and ketals are also called glycosides. Acetals and ketals (glycosides) are not in equilibrium with any open chain form. Only hemi-acetals and hemiketal s can exist in equilibrium with an open chain form. Acetals and ketals do not undergo mutarotation or show any of the reactions specific to the aldehyde or ketone groups. For example, they cannot be oxidized easily to form sugar acids. As an acetal, the carbonyl group is effectively protected. 

The configuration around the Cj of glucose (i.e. the anomeric C) is not stable and can readily change (mutarotate) from the a- to the / -form and vice versa when the sugar is in solution as a consequence of the fact that the hemiacetal form is in equilibrium with the open chain aldehyde form which can be converted into either of the two isomeric forms (Figure 2.2). 

Formation of neither a furanose nor a pyranose form can occur for 2,5-anhydro-D-talose, and the mutarotation reported for an aqueous solution must be due to hydration of the aldehyde group, or other processes,6,75 or both (see p. 20). 

FIGURE 7-6 Formation of the two cyclic forms of D-glucose. Reaction between the aldehyde group at C-l and the hydroxyl group at C-5 forms a hemiacetal linkage, producing either of two stereoisomers, the a and fi anomers, which differ only in the stereochemistry around the hemiacetal carbon. The interconversion of a and fi anomers is called mutarotation. 

Monosaccharides commonly form internal hemiacetals or hemiketals, in which the aldehyde or ketone group joins with a hydroxyl group of the same molecule, creating a cyclic structure this can be represented as a Haworth perspective formula. The carbon atom originally found in the aldehyde or ketone group (the anomeric carbon) can assume either of two configurations, a and /3, which are interconvertible by mutarotation. In the linear form, which is in equilibrium with the cyclized forms, the anomeric carbon is easily oxidized. 

Although the crystalline forms of a- and /3-D-glucose are quite stable, in solution each form slowly changes into an equilibrium mixture of both. The process can be observed as a decrease in the optical rotation of the a anomer (+112°) or an increase for the /3 anomer (+18.7°) to the equilibrium value of 52.5°. The phenomenon is known as mutarotation and commonly is observed for reducing sugars. Both acids and bases catalyze mutarotation the mechanism, Equation 20-1, is virtually the same as described for acid- and base-catalyzed hemiacetal and hemiketal equilibria of aldehydes and ketones (see Section 15-4E) ... 

No, glycosides cannot undergo mutarotation because the anomeric carbon is not free to interconvert between < = and P configurations via the open-chain aldehyde or ketone. 

Carbon-1 of the second (right hand) glucose unit in maltose is a hemiacetal carbon. Thus, the a and p forms at this carbon atom can equilibrate via the open-chain aldehyde form. Mutarotation is, therefore, possible. Note that carbon-1 of the first (left-hand) glucose unit is an acetal carbon. Its configuration is, therefore, fixed (as... 

Carbon-1 of the glucose unit in lactose is a hemiacetal carbon and will be in equilibrium with the open-chain aldehyde form. Therefore, lactose will be oxidized by Fehling s solution and will mutarotate. 

Like cellobiose, maltose has a free hemiacetal ring (on the right). This hemiacetal is in equilibrium with its open-chain form, and it mutarotates and can exist in either the a or jS anomeric form. Because maltose exists in equilibrium with an open-chain aldehyde, it reduces Tollens reagent, and maltose is a reducing sugar. 

Yes. Although it is a glycoside, the second glucose unit possesses an anomeric carbon atom and its ring can open to give an aldehyde. For the same reason, solutions of maltose display mutarotation. 

Fig. 2-8. Mutarotation of D-glucose. 1, a-D-Glucopyranose 2, /3-D-glucopyranose 3, a-D-glucofuranose 4, /3-D-glucofuranose 5, the open-chain aldehyde form.

The situation was clarified by the isolation of a, )8, and y isomers of D-glucose by Tanret in 1895. He showed that the a and y isomers mutarotate in opposite directions and, at equilibrium, each have the same rotation as the y3 form. The isomers were also found to have the same molecular weight. Tanret s three isomers of D-glucose were considered to be ring and free aldehyde forms by Lobry de Bruyn and Alberda van Ekenstein in 1895, von Lipp-mann in 1896, and Simon in 1901. Fischer in 1893, and von Lipp-mann pointed out that ring formation would produce a new asymmetric carbon atom, and thus the existence of isomeric sugars, glycosides, and acetates was clarified. 

Studies, by means of nuclear magnetic resonance measurements with pertrimethylsilyl ethers, of the behavior in solution of glycol-aldehyde and related substances formed by periodate oxidation gave striking results. Products formed under mild conditions showed that the original material was composed of dimers having p-dioxane structures products separated after complete mutarotation showed eight dimeric forms. ... 

The mechanism for this transformation is exactly the same as the mechanism that converts a hydroxy aldehyde to a cyclic hemiacetal (Mechanism 21.11). The acyclic aldehyde and two cyclic hemiacetals are all in equilibrium. Each cyclic hemiacetal can be isolated and crystallized separately, but when any one compound is placed in solution, an equilibrium mixture of all three forms results. This process is called mutarotation. At equilibrium, the mixture has 37% of the a anomer, 63% of the P anomer, and only trace amounts of the acyclic hydroxy aldehyde, as shown in Figure 27.6. 

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