Ketones isotope exchange

There are at least two mechanisms available for aziridine cis-trans isomerism. The first is base-catalyzed and proceeds via an intermediate carbanion (235). The second mechanism can be either thermally or photochemically initiated and proceeds by way of an intermediate azomethine ylide. The absence of a catalytic effect and interception of the 1,3-dipole intermediate provide support for this route. A variety of aziridinyl ketones have been found to undergo equilibration when subjected to base-catalyzed conditions (65JA1050). In most of these cases the cis isomer is more stable than the trans. Base-catalyzed isotope exchange has also been observed in at least one molecule which lacks a stabilizing carbonyl group (72TL3591). 

It is also possible to measme the rate of enolization by isotopic exchange. NMR spectroscopy provides a very convenient method for following hydrogen-deuterium exchange, and this is now the preferred method. Data for several ketones are given in... 

Althoi h the equilibrium constant for hydration is unfavorable, the equilibrium between an aldehyde or ketone and its hydrate is established rapidly and can be detected by isotopic exchange, using water labeled with 0, for example ... 

Kinetic data exist for all these oxidants and some are given in Table 12. The important features are (i) Ce(IV) perchlorate forms 1 1 complexes with ketones with spectroscopically determined formation constants in good agreement with kinetic values (ii) only Co(III) fails to give an appreciable primary kinetic isotope effect (Ir(IV) has yet to be examined in this respect) (/ ) the acidity dependence for Co(III) oxidation is characteristic of the oxidant and iv) in some cases [Co(III) Ce(IV) perchlorate , Mn(III) sulphate ] the rate of disappearance of ketone considerably exceeds the corresponding rate of enolisation however, with Mn(ril) pyrophosphate and Ir(IV) the rates of the two processes are identical and with Ce(IV) sulphate and V(V) the rate of enolisation of ketone exceeds its rate of oxidation. (The opposite has been stated for Ce(IV) sulphate , but this was based on an erroneous value for k(enolisation) for cyclohexanone The oxidation of acetophenone by Mn(III) acetate in acetic acid is a crucial step in the Mn(II)-catalysed autoxidation of this substrate. The rate of autoxidation equals that of enolisation, determined by isotopic exchange , under these conditions, and evidently Mn(III) attacks the enolic form. 

Aromatic enols, that is, phenols, are generally more stable than their ketone tautomers. The pH-rate profile for the enolization reaction of 2,4-cyclohexadienone to parent phenol is shown in Fig. V.44 The rate constant kK of the reverse reaction was determined at pH = 1 by measuring the rate of isotopic exchange and correcting for isotope effects to determine the enolization constant Kb = = 5.4 x 1012, pA E = -12.73. The dashed line in... 

It has been found that the rates of reaction of a ketone in mildly basic solution are identical for the following three reactions (a) reaction with Br2 leading to the substitution of an H on the ketone by a Br (b) conversion of the D-isomer of the ketone into a mixture of d- and L-isomers of equal concentration and (c) isotopic exchange of a hydrogen atom on the carbon next to the C=0 group of the ketone by a deuterium atom in the solvent. The rate of each of these reactions is equal to fc[ketone][OH-] and is independent of [B ]. What can be concluded about the mechanism from these observations ... 

Substituent effects on rate constants of base-promoted ionisation of ketones have led to the conclusion that an electron-withdrawing substituent increases the rate of ionisation, in agreement with the anionic character of the transition state. This is based chiefly on studies on halogenation and isotope exchange of aromatic ketones. Data on p-values observed by plotting ionisation rate constants versus Hammett -parameters (Table 3) for substituted... 

Experiments on the bromination of equilibrated ketone-acetal systems in methanol were also recently performed for substituted acetophenones (El-Alaoui, 1979 Toullec and El-Alaoui, 1979). Lyonium catalytic constants fit (57), but for most of the substituents the (fcA)m term is negligible and cannot be obtained with accuracy. However, the relative partial rates for the bromination of equilibrated ketone-acetal systems can be estimated. For a given water concentration, it was observed that the enol path is more important for 3-nitroacetophenone than for 4-methoxyacetophenone. In fact, the smaller the proportion of free ketone at equilibrium, the more the enol path is followed. From these results, it can be seen that the enol-ether path is predominant even if the acetal form is of minor importance. The proportions of the two competing routes must only depend on (i) the relative stabilities of the hydroxy-and alkyoxycarbenium ions, (ii) the relative reactivities of these two ions yielding enol and enol ether, respectively, and (iii) the ratio of alcohol and water concentrations which determines the relative concentrations of the ions at equilibrium. Since acetal formation is a dead-end in the mechanism, the amount of acetal has no bearing on the relative rates. Bromination, isotope exchange or another reaction can occur via the enol ether even in secondary and tertiary alcohols, i.e. when the acetal is not stable at all because of steric hindrance. 

Rate constants for the reverse tautomerization reaction can be measured by thermal halogenation of ketones or isotope exchange reactions. Combination of the rate constants of ketonization, A , and enolization, kK, provides accurate equilibrium constants of enolization, K k> /kK. The acidity constants of ketones, K, and of the corresponding enols, Kf, are related to the enolization constant Kti by a thermodynamic cycle, pl E = pKf—pK (Scheme 5.21). 

Exceptions apart, isotopic exchange in C-H bonds, usually effected in the presence of bases, is sufficiently rapid only if some feature of the molecular structure weakens quite considerably the bond between carbon and hydrogen, i.e.9 renders the hydrogen atom acidic (semilabile hydrogen atom). Exchange reactions of that type are often carried out in order to achieve semilabile labeling, e.g., at the -position of a ketone, the material obtained in this way being later converted into stably labeled compounds by subsequent reactions, e.g., reduction to secondary alcohols. 

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