Hydrolysis of 2‐(p‐nitrophenoxy)tetrahydropyran: solvent and α‐deuterium secondary kinetic isotope effects and relationships with the solvolysis of simple secondary alkyl arenesulfonates and the enzyme‐catalyzed hydrolysis of glycosides

Abstract

The effect of solvent composition in aqueous ethanol, trifluoroethanol and hexafluoropropan‐2‐ol on the rate constant and activation parameters for the uncatalysed hydrolysis of 2‐(p‐nitrophenoxy)tetrahydropyran (1) was investigated, and the m(YOTs) value is 0.60. This appreciable but less than maximal value is in accordance with an SN1 mechanism with rate‐limiting ionization. The α‐deuterium secondary kinetic isotope effect (α‐kie) for the uncatalysed hydrolysis of 1 is 1.17 in water (46°C), 1.15 in aqueous trifluoroethanol (50% mole fraction, 70.6°C) and 1.13 in aqueous ethanol (50% mole fraction, 70.6°C). These values correspond to about 1.19 at 25°C, which is characteristic of rate‐limiting ionization in an SN1 reaction and appreciably higher than values for enzyme‐catalysed glycolysis. The α‐kie is smaller under aqueous acidic conditions (1.07, 0.1 mol dm−3 hydrochloric acid, 20.2°C) when 1 hydrolyses with acid catalysis. The previously reported α‐kie for the hydrolysis of 1 in buffered aqueous dioxan (1.063, 25°C) is now seen to correspond to acid‐catalysed hydrolysis. These new results for 1 indicate that transition structures in enzyme‐catalysed glycolyses with α‐kie values of less than about 1.15 at 25°C involve a lower degree of carbenium ion character than has hitherto been assumed. Copyright © 2004 John Wiley & Sons, Ltd.

C2-Oxyanion Neighboring Group Participation: Transition State Structure for the Hydroxide-Promoted Hydrolysis of 4-Nitrophenyl α-d-Mannopyranoside

“…α-SDKIEs for substitution reactions resulting in glycosidic bond cleavage originate predominantly from changes in bending vibrations as the sp 3 anomeric carbon undergoes rehybridization to an sp 2 -like center as the reaction coordinate passes over either a dissociative S N 1 or an ‘exploded’ S N 2 transition state. α-SDKIEs for reactions involving α-glycosides include the spontaneous hydrolyses of 4-nitrophenyl tetrahydropyran ( k H / k D = 1.17) , and α- d -glucopyranosyl 4-bromo­isoquinolinium bromide ( k H / k D = 1.19), the acid-catalyzed hydrolysis of methyl α- d -glucopyranoside ( k H / k D = 1.14), and the S N 2 reaction of α- d -glucopyranosyl fluoride with an azide ion ( k H / k D = 1.19) . In the current study, the anomeric carbon atom undergoes conversion into an oxirane carbon and the bending C–H vibration changes are expected to govern the magnitude of the α-SDKIE.…”

Influence of Dielectric Environment upon Isotope Effects on Glycoside Heterolysis: Computational Evaluation and Atomic Hessian Analysis

“…The calculated B3LYP/aug-cc-pVDZ/PCM EIE (α-D, 298 K) for this heterolysis in water is 1.235. The corresponding KIE ( k H / k αD = 1.19) for this reaction was measured by Maskill and co-workers in order to shed mechanistic light on enzyme-catalyzed glycoside hydrolysis . It is of interest to consider how the EIE for heterolysis of the acetal in water (a simple model for a glycoside) depends on the relative permittivity of the dielectric continuum surrounding the THP cation, mimicking an oxacarbenium intermediate in the active site of a glycosidase.…”

“…The corresponding KIE (k H /k αD = 1.19) for this reaction was measured by Maskill and co-workers in order to shed mechanistic light on enzyme-catalyzed glycoside hydrolysis. 36 It is of interest to consider how the EIE for heterolysis of the acetal in water (a simple model for a glycoside) depends on the relative permittivity of the dielectric continuum surrounding the THP cation, mimicking an oxacarbenium intermediate in the active site of a glycosidase. Our calculations have shown that the EIE varies significantly, particularly for 2 ≤ ε ≤ 10, giving K H /K D = 1.258 at ε = 2.…”

“…1.251 at ε = 2. The reaction was studied experimentally in 50% aqueous trifluoroethanol and in 50% aqueous ethanol, 36 but as these are both polar media, any variation in the KIE might be more indicative of nucleophilic solvent participation than of any influence of a dielectric effect that might be manifest only in very nonpolar media. Atomic Hessian Analysis.…”

11 Reaction mechanisms : Part (ii) Polar reactions

“…The effect of solvent composition in aqueous ethanol, trifluoroethanol and hexafluoropropan-2-ol on the rate constant and activation parameters for the uncatalyzed hydrolysis of 2-(p-nitrophenoxy)tetrahydropyran 51 was investigated and an S N 1 mechanism with rate-limiting ionization proposed. 23 It is noted that the a-deuterium secondary kinetic isotope effect (a-KIE = 1.17) for the uncatalyzed hydrolysis of 51 is characteristic of rate-limiting ionization in an S N 1 reaction.…”