Reaction mechanism of the buffer-catalyzed and substituted [beta]-cyclodextrin-catalyzed hydrolysis of catechol cyclic phosphates

Abstract

The mechanism for the imidazole-catalyzed hydrolysis of catechol cyclic phosphate has been investigated. The Bronsted β-value obtained for the buffer-catalyzed hydrolyses at a 1:1 buffer ratio was 0.41. The Hammett φ-value obtained for the 1:1-[imidazole]: [imidazolium ion] buffer-catalyzed hydrolysis of substituted catechol cyclic phosphate was 1.08. The proton inventory plots for the imidazole-catalyzed hydrolysis of catechol cyclic phosphate at buffer ratios 75:25, 50:50, and 25:75 [imidazole]: [imidazolium] were dome-shaped, linear, and bowl-shaped, respectively. These different proton inventories indicate that the rate determining step of the reaction changes with the [imidazole]: [imidazolium] ratio and, thus, supports a stepwise mechanism for this reaction. An inverse solvent isotope effect for the hydroxide catalyzed hydrolysis of catechol cyclic phosphate (k(D₂O)/k(H₂O) = 1.63) and the decrease in the normal solvent isotope effects for the imidazole-catalyzed hydrolysis of 4-chlorocatechol cyclic phosphate and 4-nitrocatechol cyclic phosphate (k(H₂O)/k(D₂O) = 1.44, 1.83, respectively) further support this stepwise mechanism. Based on the ³¹P-NMR spectra for the β-cyclodextrin and substituted β-cyclodextrin-catalyzed hydrolysis of 4-tert butyl catechol cyclic phosphate, 6, the reaction occurs with inclusion of the 4-tert butyl catechol cyclic phosphate into the cavity of the cyclodextrin followed by the formation of the product. Heptakis-(2,6-dimethoxy)-β-cyclodextrin and heptakis-(2,3,6-trimethoxy)-β-cyclodextrin were poorer catalysts for the hydrolysis of 6 and 6-mono-imidazole β-cyclodextrin was a better catalyst for the hydrolysis of 6 than β-cyclodextrin. The solvent isotope effects, k(H₂O)/k(D₂O), for the β-cyclodextrin-catalyzed and the 6-mono-imidazole β-cyclodextrin-catalyzed hydrolyses of 6 were 1.35 and 2.35, respectively. Based on the proton inventory for the 6-mono-imidazole β-cyclodextrin-catalyzed hydrolysis of 6, the reaction mechanism is similar to that for the simple model study.