Hydrolysis of cholinergic anabaseine and N-methylanabaseine: Influence of cosolvents on the position of the ring-chain equilibrium—Compensatory changes

Abstract

The position of the ring-chain equilibrium established by the addition of water to the iminium ring (Im) in the title compounds and subsequent ring cleavage to give the acyclic conjugate acid amino ketones (AK) were investigated by proton NMR using D 2O, dimethyl sulfoxide (DMSO)- d 6, and CD 3OD solvents. A linear free energy relationship expressing the change in the logarithmic value of the equilibrium constant [AK] ([Im][D 2O]) for the mixed solvent with the mole fraction of water added to methanol is found for the substrates, giving the equilibrium constants for the pure solvents. Equilibrium constants for the pure solvents increase in the order water, methanol, DMSO. Although there is less water in the largely nonaqueous solvents, the increase in the magnitude of the equilibrium constants partially compensates for this decrease, thereby resulting in a moderated reduction of the value of the ratio [AK] [Im] . Replacement of the deuteron bonded to the imine nitrogen atom by a methyl group causes much more acyclic keto-ammonium ion to form in D 2O due to steric compression between this methyl group and the adjacent pyridine ring causing an increase in energy of about 1.7 kcal/mol.