Effect of an aromatic ester conjugate base on E1cB ester hydrolysis. Alkaline hydrolysis of fluorene-9-carboxylate esters

Abstract

A series of alkyl and substituted-aryl esters of fluorene-9-carboxylic acid have been synthesised and their alkaline hydrolyses studied. The pH profiles for hydrolysis indicated substrate ionisation at higher pH values (confirmed by spectral studies) and kinetic pK values for a number of these esters were obtained at 25 °C. At high pH (pKa) the rate of hydrolysis became independent of pH with the observed rate constant in this high pH plateau region being called k′. A plot of the logarithm (to base 10) of k′versus the pKa of the conjugate acid of the appropriate leaving group consisted of two limbs, A and B, flanking a minimum. The slopes of the plots described above for regions A and B were –1.01 ± 0.05 and +0.11 ± 0.01, respectively. Region A, of high negative slope, was shown to correspond to an E1cB reaction of the title esters on the basis of linear free energy relationship arguments, the solvent deuterium kinetic isotope effect, activation parameters, and comparison with the 9-methyl-blocked analogues, as well as by the observation of saturation kinetics in aniline buffers at low pH. Region B was shown to correspond to a rate-determining step of attack of hydroxide ion on the limiting amount of ester in its neutral form. The low eliminative reactivity of fluorene ester anions was discussed along with factors considered in the literature for explaining elimination rates of ester anions.