Mutarotation in pyridine

In analyzing polysaccharide hydrolyzates, some workers have assumed that, because mutarotation in pyridine is slow and the tri-methylsilylation reaction is fast, no change in the composition occurs during trimethylsilylation. Others have equilibrated the monosaccharides in pyridine, before trimethylsilylation.172,255 In nonaqueous solvents, the mutarotation may be catalyzed by lithium perchlorate172 or, more conveniently, by 2-pyridinol,256,257 which is volatile, but does not interfere with subsequent analyses. 

The Michaelis-Arbuzov reaction of methyl 5-deoxy-5-iodo-2,3-0-isopropylidene-/ -D-ribofuranoside38 (43) with diethyl ethylphosphonite gave,35 in 80% yield, the 5-C-[(ethoxy)ethylphosphinyl] derivative which, on treatment with SDMA and then mineral acid, yielded (30%) 5-deoxy-5-C-[(RS)-ethylphosphinyl]-D-ribopyranose (44) as a mixture of diastereoisomers. These compounds showed no mutarotation in methanol during 24 h. Upon treatment with acetic anhydride-pyridine, the product, 44, was converted (90% yield) into a syrup, presumably consisting of four diastereoisomers of the peracetate 45, separation of which was not attempted. Treatment of 45 with sodium methoxide in methanol regenerated 44 quantitatively. 

Fig. 6.—Mutarotation of 2-Desoxy-D-galactose p-Toluidide (a) In Pyridine (c, 1.0) (6) As (a) with 1 N H2SO4 (one drop) added (e) In Methanol (c, 1.0) (d) As (c) with 0.1 N H2SO4 (one drop) added.

The mutarotation of ribose was first observed by Phelps, Isbell and Pigman47 48 who studied both the d- and L-isomers in aqueous solution at 1°. The mutarotation of L-ribose in water at 0°, shown in Fig. 1, is a complex one, due probably to the existence of equilibria involving both furanose and pyranose forms. There is considerable evidence to support this view. Bredereck, Kothnig and Berger26 found that, while the mutarotation of D-ribose in pyridine at 20° is complex, the mutarotation of 5-trityl-D-ribose (which can exist only in the furanose form) in pyridine at 3° is of the normal, first order type. Isbell and Pigman48... 

Phosphorylation of XLVII with phosphorus oxychloride in pyridine solution, followed by hydrolysis to remove the methyl and isopropylidene residues, gave D-ribose 5-phosphate (XLVIII) which, as its barium salt, was found to be identical with the barium salt of the D-ribose phosphate from inosinic acid. By way of further confirmation of the structure of D-ribose 5-phosphate, Levene, Harris and Stiller129 showed that in methanolic hydrogen chloride solution both the natural and synthetic material mutarotated in a manner characteristic of a sugar which can form only a furanoside. 

This possible mechanism is applicable only to compounds having a hydrogen atom attached to the nitrogen atom, yet Kuhn and Birkofer found that mutarotation occurs in pyridine solutions of derivatives of secondary amines, namely, n-glucosylpiperidine and iVjiV -dibenzyl-D-glucosylamine, where no such hydrogen atom is available. To explain mutarotation in such cases they postulated the formation of an acyclic imonium ion by expulsion of a proton from a substituted ammonium ion. 

Hodge and Rist have found that carefully purified o-glucosylpiperidine does not mutarotate in dry pyridine, and that the compound believed by Kuhn and Birkofer to be A, iV-dibenzyl-D-glucosylamine had un-... 

Fig. 14.—Upper Curves Mutarotation of n-Glucose Phenylosazone in Pyridine-alcohol (1 1 by vol.) Lower Curves Mutarotation of n-Glucose l-(JV -Methyl-JV -...

Orthorhombic, bisphenoidal prisms from ale, dec 103-105. Sweetest of the sugars. Shows mutarotation. Mg — 132 — —92 (c = 2). Rapid and anomalous mutarota tion involves pyranose-furanose interconversion. The final value is obtained instantly in the presence of hydroxyl ions. Ka at 18" 8.8 x l0-u. Freely sol in water. One gram dissolves in 15 ml ale, in 14 ml methanol. Slightly sol in cold, freely in hot acetone sol in pyridine, ethylamine, methyl-amine. 

The catalysis of mutarotation in organic solvents can be accomplished using simple compounds that are capable of tautomerization reactions. As shown below, simultaneous deprotonation and protonation of a hemiacetal with 2-pyridone leads to ring-opiening. Bond rotation and closing of the ring interconverts the anomers. The 2-pyridone catalyzes this interconversion 7000 times faster than a mixture of phenol and pyridine. 

Hodge and Rist (70) found that the D-glucosyl derivatives of piperidine and diethanolamine do not mutarotate in dry pyridine, whereas the D-galactosyl and D-mannosyl derivatives of piperidine do mutarotate. 

Since the sugar osazones mutarotate in alcoholic pyridine solution (231) the classical formula for these substances may be questioned, and there is much evidence that they exist in cyclic as well as acyclic forms. The mutaro-tation has been ascribed to a partial hydrolysis of the osazones, and appreciable quantities of the sugar and hydrazine exist in the equilibrium solution (232). This explanation is also supported by the ease with which the hydrazine radicals of the osazones are exchanged with hydrazine molecules in the solvent (233). When the second hydrazine is different from that used in making the osazone, mixed osazones are formed (232, 234) ... 

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