Acidity measurement rate exchange

Katritzky et a/.511 have measured rate coefficients for deuteration of 3,5-dimethylphenol and heterocyclic analogues. As in all of the deuteration work of this group, rates of exchange were measured by the nmr method, which is useful for following exchanges at more than one position in the molecule but is, of course, much less accurate than detritiation techniques. In this study, the chemical shift for the ortho and para protons for the parent compound was too small to allow separate integration, but it was apparent that rates of exchange at these two positions did not differ by a factor > 4. From the rate-acidity profile (Table 149) reaction clearly occurs on the neutral species at pD < 3.5 (the log kl versus pD slope was 0.96) and upon the anion at pD > 3.5 (slope zero), and the reactivity of the anion to the neutral molecule was estimated as 107-8, close to the value of 107 noted above. 

A different approach to the problem of hydrocarbon acidity, and hence carbanion stability, is that of Shatenshtein and Shapiro, who treated hydrocarbons with deuterated potassium amide and measured the rates of hydrogen exchange. The experiments did not measure thermodynamic acidity, since rates were measured, not positions of equilibria. They measured kinetic acidity, that is, which compounds... 

Chakrabarty et al have measured the exchange in the presence of 8 - quinolinol (HQ), using a similar method. The rate law at high acidities (pH < 2) and low concentrations of Fe was found to be... 

With secondary alcohols the picture is different. By measuring rates of hydration, isomerization, dehydration, and exchange, in the system of butenes and 2-butanol, Manassen and Klein (7S) proved that the hydration-dehydration intermediate in dilute acid solution is equally bonded to two water molecules ... 

Less frequently used at present is electron spin resonance spectroscopy, which is based on the use of spin probes as model componnds or covalent spin labeling of drugs. Microviscosity and micropolarity of the molecnlar environment of the probe can be derived from electron spin resonance spectra. Moreover, the spectra allow us to differentiate isotropic and anisotropic movements, which result from the incorporation of the probe into liposomal structures. Quantitative distribution of the spin probes between the internal lipid layer, the snrfactant, and the external water phase is to be determined noninvasively. On the basis of the chemical degradation of drugs released from the lipid compartment, agents with reductive features (e.g., ascorbic acid) allow us to measure the exchange rate of the drugs between lipophilic compartments and the water phase [27,28]. 

Esters can be hydrolyzed nonenzymatically in acidic and alkahne solutions. In both cases, a tetrahedral intermediate is indicated on the basis of the measured rates of hydrolysis and the rates of oxygen isotope exchange. 

The Brensted catalysis law can be applied to the problem of determination of acidity of very weak acids in the following way. First, a suitable base is chosen the base must be sufficiently strong to remove protons from the carbon acids in question at a measurable rate. The acids to be investigated are then prepared with deuterium or tritium substituted for hydrogen, and the rate of exchange of the isotopic label out of the carbon acid in the presence of the base is measured. 

The rates of acid-catalysed medioxy exchange between methanol and the three diastereomers of 2-medioxy-4,6-dimethyl-l,3-dioxalane (37a-c) were measured in benzene and methanol-chloroform. Rate constants were evaluated in a novel way using 1D-EXSY NMR pulse sequence and a weighted least-squares analysis. The critical intermediate is (38) and rates of methanol attack on it in benzene show a 24-fold axial selectivity whereas in methanol-chloroform the selectivity difference is ninefold.34... 

Equilibrium acidities are usually determined by titration, either with indicators of known plCa [24] or by following the extent of dissociation spectroscopically (e.g. by UV-spectroscopy [35]). Kinetic acidities, i.e. the rates of deprotonation of acids, can be determined by measuring rates of racemization[36] or rates of H-D or H-T exchange [37, 38], by chemical relaxation experiments (e.g. T-jump method [35, 39]), or by H NMR (line broadening and saturation recovery [40]). 

Pyridine itself is too unreactive toward acid-catalyzed hydrogen exchange for rates to be measurable, but results have been obtained for... 

In order to test for acid catalysis, the exchange was run in the presence of CF3COOH. At —20° C. the rate was too fast to measure, showing that the exchange is acid catalyzed. 

Superficially, we would expect the high electronegativity of fluorine to stabilise a carbanion centre, but measurements of acid strengths and exchange rates for a variety... 

As previously described for aromatic carboxylic acids, measurements of the line-widths of the CH3 resonance in methanol give the rate of exchange of hydroxylic protons on methanol, and measurements of the line-widths of the OH resonance give the rate of exchange of protons on phenol. Values of ft, k2 and k3 have been determined for p-bromo-phenol and p-nitrophenol [67], and are tabulated in Table 11. 

The process of acid dissociation can be thought of as comprising two steps, namely ionisation and dissociation of the ion-pair into separate products. The first step may be studied in isolation if a solvent of low dielectric constant is employed, as the second process then occurs to a negligible extent. For example, the rates of proton exchange in acetic acid (dielectric constant, 6.27) are given [73] in Table 15. The measured rate,... 

Shatenstein and coworkers performed kinetic acidity measurements with 302, 299 and 303 by exchange with KND2/ND3 and obtained the following rate constants. 

The two keto tautomers of phenol 3, i.e. 4 and 5, were generated by flash photolysis of polycyclic precursors 6-8 in aqueous solution, and the pH-rate profiles of their 4 3 and 5 3 enolization reactions were measured. The rates of the reverse reactions, 3 4 and 3 5, were determined from the rates of acid-catalyzed hydrogen exchange at the ortho- and para-positions of phenol 3 (equation 3). 

Menon (1964) has measured the rate of acid- and base-catalysed oxygen exchange between -substituted benzophenones and water in 80% dioxan-water. The rate data for the acid-catalysed oxygen exchange are summarized in Table 3. 

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