pKa Values of the Opened Form of a Thieno-1,2,4-triazolo-1,4-diazepine in Water

Abstract

The pK a values of the freely water-soluble opened form of a thieno-1,2,4-triazolo-1,4-diazepine, namely 2-(3-aminomethyl-5-methyl-1,2,4-triazolo)-3-(2-chlorobenzoyl)-[2,3-c]thienopiperidine, were determined. pH measurements were made in the range 1 < pH < 10. Two of the three pK a values found in this range significantly overlapped; they quantify the ionization of both the aminomethyl residue and the piperidino moiety of the molecule. The third corresponds exclusively to the ionization of the triazolo nucleus. The pK a value of the thienophenone was obtained by UV spectrophotometry using acidity functions. All results were extracted from experimental data by a curve-fitting method.

Determination of the kinetic constants of the reversible opening of a triazolo-1,4-thienodiazepine in water at different pH values: A striking example of the determination of intimately intricate kinetic and equilibrium constants

“…Ka ϭ Ka ϩ Ka The acido-basic behavior of Z is described by four acidic dissociation constants [18] (Scheme 9). pKЈa ϭ Ϫ7.46 Again, microforms 12 and 13 must be considered because the closeness of the pKЈa 2 and pK Јa 1 values are close.…”