Kinetics of mutarotation

The differential equations describing complex mutarotations resist explicit solution, and are usually solved numerically. Much mechanistic work has been done, however, on simple mutarotations monitored polarimetrically. Such reactions are can be treated as reversible first-order reactions, with the mutarotation rate constant corresponding to the sum of the ring-opening reactions of the two pyranose forms, which are the rate determining steps in each direction (Equation 1.2). 

In general, it is found that mutarotation is catalysed by acids and bases, and also exhibits a water reaction, so that we can write equation 1.3 

for a carboxylic acid as a general acid or carboxylate as a general base p = 1 and q = 2 in the acid dissociation equilibrium there is only one OH group to lose a proton from, but two basic sites to recombine, so the OH groups of carboxylic acids are more acidic by a factor of 2 compared with phenols of the 

If the proton-catalysed reaction proceeds with kobs=l x (a typical 

Homologous changes in small molecules are generally used to probe electron demand at a reaction centre. Classic Bronsted relationships are particularly simple, since they correlate rates and equilibria for a single reaction (aqueous Kn values being necessarily proportional to equilibrium constants for proton 

---

The first attempt to express the kinetics of mutarotation was made by Mills and Hogarth, who developed an empirical relation y = a... 

By application of first-order, kinetic equations, B. Anderson and Degn claimed that an equilibrated (25°) aqueous solution of D-fructose contains 31.56% of jS-D-fructofuranose and 68.44% of -D-fructopyranose. N.m.r. studies, however, showed that, at equilibrium, a solution of D-fructose contains /3-D-fructopyranose, -D-fructofuranose, a-D-fructofuranose, and a trace of a-D-fructopyranose the distribution of these isomers was shown by gas-liquid chromatography to be 76,19.5, and 4%, respectively. Based on Anderson and Degn s result, Shallenberger reasoned that, as 0.68 X 1.8 = 1.22 (which approximates the reported sweetness of mutarotated D-fructose ), the furanose form(s) must possess very little sweetness. 

Computer Modeling of the Kinetics of Tautomerization (Mutarotation) of Aldoses Implications for the Mechanism of the Process... 

In other studies, analysis of the products of reaction between formaldehyde and guanosine at moderate pH shows a new adduct—formed by condensing two molecules of each reactant—which has implications for the mechanism of DNA cross-linking by formaldehyde,17 while the kinetics of the mutarotation of N-(/ -chlorophcnyl)-//-D-glucopyranosylamine have been measured in methanolic benzoate buffers.18 For a stereoselective aldol reaction of a ketene acetal, see the next section. 

Isbell and Pigman17 have shown that the rapid and anomalous mutarotation involves pyranose—furanose interconversion. On the basis that only D-fructofuranose (Ic) is fermented by yeast, Gottschalk18 has shown that the equilibrium mixture in aqueous solution at 0° contains 12% of D-fructofuranose. Gottschalk has calculated, from the kinetics of the mutarotation, that the aqueous solution at 20° contains about 20 % of the sugar in the furanose form. 

The kinetics of the optical rotatory changes of poly-L-proline in various solvents and at various temperatures have also been studied by Steinberg et al. (1960a). In acetic acid the course of the forward mutarotation reaction was found to be independent of concentration (over the range 0.25 to 2.0 gm/KK) ml) but, as observed by Downie and Randall, the rate constant depends on the degree of mutarotation. An activation enthalpy, AH = 21 kcal/mole, was determined for both the forward mutarotation of form I in acetic acid and the reverse mutarotation of form II in acetic acid-w-pro-panol. 

The type of mutarotation kinetics found experimentally is strongly dependent on the solvent. Forward mutarotation in acetic acid yields a plot of log d[a /dt versus log ([a]( — [ ] ) which is linear over 97% of the reaction with a slope of 1.33. On the other hand the rate is virtually invariant over two-thirds of the reaction in a solvent of 30% water-70 % acetic acid. Reverse mutarotation in acetic acid-n-propanol appears to follow first-order kinetics over 90% of the transformation. From these experiments and the fact that the enthalpies of form I and form II are essentially identical (Steinberg et al., 1960a) it seems likely that solvation is decisive not only in determining the kinetic pathway of mutarotation but also the structural pattern which is stabilized in a given solution. 

Although the rate of mutarotation of cold dilute gelatin is independent of protein concentration, kinetic analysis reveals an exponential dependence of d[a]/dl on the concentration of chain elements in the unfolded form. Thus van t Hoff plots of log (d a]/dt) versus log ([ ] —[ ]<), derived from the general equation ... 

The apparent negative temperature dependence of mutarotation is another striking aspect of the kinetics which is of signal importance in... 

Differences in the rate of mutarotation of sugars in water and in deuterium oxide provide a valuable means for studying mutarotation reactions.135,224,233 237,238 The difference in rates arises from a combination of kinetic and solvent isotope-effects, and is usually expressed as a ratio,knlkD, called the isotope effect. Kinetic isotope-effects are caused by differences in the energy required for alteration of the normal and the isotopic bonds in the corresponding transition states solvent isotope-effects can exist when the isotopic compound is used both as a reactant and as a solvent. 

For elucidation of the course of mutarotation reactions, the timing of the addition and elimination of the proton is important. If the proton transfer occurs after the rate-controlling step, it will have no primary kinetic consequence. If the proton transfer occurs during the rate-... 

---