Catalysis of the deprotonation of β-keto esters by cyclodextrins

Abstract

. Can. J. Chem. 71, 2139 (1993). The rates of deprotonation of several P-keto esters in basic aqueous solution are elevated by a -and P-cyclodextrin (a-and P-CD). In most cases saturation kinetics are observed that indicate fairly strong binding of the esters to the CDs (K, = 0.22-1 1 mM); catalytic ratios (k,/k,) are in the range 1.9-17. For esters of the form RCO-CH,COOEt with both a-and P-CD the values of Kd and k,/k, show little sensitivity to the acyl group, RCO (R = Me, Et, Pr, i-Pr), and for 2-carboethoxycyclopentanone, a cyclic analogue, these parameters are similar. In contrast, for R-COCH,CO-OR' (R = Me or Et; R' = Me, Et, allyl) there is a marked dependence of the parameters on the alkoxyl group, OR'. These results suggest that the P-keto esters studied bind to the CDs with their alkoxyl groups in the CD cavity and that the catalysis ensues from the complexes thus formed. Variations in two other kinetic parameters, k, = k,/K, (substrate selectivity) and KT, = k,/k, (apparent constant for dissociation of CD from the transition state) support this interpretation. Apparent second-order rate constants for the reaction of the esters with neutral CD (k, = k,/K,) are 1900-360 000 M-' s-I (at pH ; = lo), whereas for hydroxide ion attack on ethyl acetoacetate koH = 5500 M-' s-I. Assuming the pK,s of the CDs are 12.2 and 12.3, deprotonation of the esters by the CD anions has rate constants of lo5 to 5 x lo7 M-' s-'. Thus, binding of the P-keto esters in the CD cavities, adjacent to a basic oxyanion site, enhances the reactivity of the CD anions towards these weak carbon acids by at least 2-4 orders of magnitude.OSWALD S. TEE, N. RANI IYENGAR et BRYAN K. TAKASAKI. Can. J. Chem. 71, 2 139 (1993). U s vitesses de dkprotonation de plusieurs p-cktoesters en solutions aqueuses basiques sont augmentkes par la prksence d'a-ou de P-cyclodextrine (a-et P-CD). Dans la plupart des cas, on observe des cinktiques de saturation qui indiquent la prksence d'une forte liaison des esters sur les CD (K, = 0,022-1 1 mM); les rapports catalytiques (k,/k,) sont de l'ordre de 1,9 2 1 17. Pour des esters de la forme RCO-CH,COOEt avec des CD tant a que P, les valeurs de Kd et de k,/k, ne prksentent qu'une faible sensibilitk i la nature du groupe acyle, RCO (R = Me, Et, Pr, i-Pr); pour le 2-carbokthoxycyclopentanone, un analogue cyclique, ces paramktres sont semblables. Par ailleurs, pour les esters du type R-COCH,CO-OR' (R = Me ou Et; R' = Me, Et ou allyle), il existe une dkpendance marquke des paramktres sur la nature du groupe alcoxyle, OR'. Ces rksultats suggkrent que les p-cktoesters se lient par leurs groupes alcoxyles ?I la cavitk des CD et que la catalyse dkcoule de la formation de ces complexes. Les variations dans deux autres paramktres cinktiques, k, = k,/K, (sklectivitk du substrat) et KT, = k,/k, (constante apparente de la dissociation de la CD de l'ktat de transition) sont en accord avec cette interpretation. Les constantes apparentes de vitesse du deuxikme ordre pour la rkaction des esters avec de la CD neutre (k, = kc/Kd)...

Biomimetic Reactions Catalyzed by Cyclodextrins and Their Derivatives

“…Enolizations are catalyzed, , as well as aldol condensations , and decarboxylations . Some reports have appeared dealing with free radical reactions within cyclodextrin complexes. , …”

Organic Reactions Mediated by Cyclodextrins

“…From the kinetic studies, it was suggested that the binding of the β-keto esters in the CD cavities, adjacent to a basic oxyanion site, enhances the reactivity of the CD anions toward these weak carbon acids by an order of magnitude of at least 2-4 (Figure 30). 108 Pyrolysis of O-furfuryl S-alkyl dithiocarbamate (xanthates) gave furfuryl alkyl sulfides together with S-alkyl dithocarbamates. This reaction was affected by the polarity of the solvent.…”

“…The rate of deprotonation of several β-keto esters in alkaline aqueous solution was increased by using α- and β-CDs. From the kinetic studies, it was suggested that the binding of the β-keto esters in the CD cavities, adjacent to a basic oxyanion site, enhances the reactivity of the CD anions toward these weak carbon acids by an order of magnitude of at least 2−4 (Figure ) 30 The effect of CD on the deprotonation …”

Catalysis of Ester Aminolysis by Cyclodextrins. The Reaction of Alkylamines with p-Nitrophenyl Alkanoates

“…To distinguish between the modes 1 and 2 , we studied the attack of the anions of TFE and 2-ME on a series of p -nitrophenyl alkanoates (C 2 to C 10 ) in the presence of α-CD, β-CD, and hp-β-CD. 10b, On the basis of previous studies of reactions of alkyl derivatives in the presence of CDs, ,,,, and on the binding of aliphatics to CDs, ,,, we used the sensitivity of kinetic parameters for the CD-mediated reactions to ester chain length to probe for acyl group binding in the transition state. It was found that for short esters (C 2 to C 6 ) the parameters are not sensitive to the acyl chain, but for longer esters they increase strongly with the chain length 10b.…”

“…Differences arising from the CD cavity sizes 11 were also of interest since a larger CD cavity might permit partial inclusion of both reactants in the transition state. As previously, the sensitivity of kinetic parameters to chain length would serve as the main criterion of transition state binding, ,,,10b,, along with appropriate comparisons to initial state binding parameters.…”