Determination of pKa values of some benzimidazole derivatives

Benzimidazoles and their derivatives including imidazole functional group are studied widely due to the fact that they exist in the structure of natural products and various drugs. Physicochemical features are determiner in the transformation of benzimidazoles into pharmaceutical products. Acids and protonated bases' pKa values have a significant place in organic synthesis, medicinal chemistry, and material and food sciences. pKa values are extremely important for drug discovery and improvement in order to determine pharmacokinetic and pharmacodynamic features such as permeation through biological barriers, interactions with the target area or side effects. Acid- base (pKa) features have great importance for physiological characteristics of prodrug compounds like benzimidazoles being used as a ligand or changing physico-chemical features by turning into salt structure. In this dissertation, a variety of benzimidazole salts as given at below scheme were synthesized. The structure of the synthesized new compounds were identified by 1H-NMR, 13C-NMR, C13DEPT, HSQC spectroscopy, FT-IR spectroscopy and element analysis techniques. The pKa values of synthesized benzimidazole salts were determined by using a new approach at 1H-NMR spectroscopy. Some benzimidazole salts pKa values were also determined by potentiometric methods in order to compare with those of the NMR results The pKa results obtained by NMR spectroscopy and potentiometric titration method were given as charts and graphics. The acidity constants of the compounds (pKa) were calculated by data and graphics obtained through both methods. The pKa values of the new synthesized benzimidazole salts were found to be 10.15 ‒ 13.48 interval by NMR spectroscopic pKa determination method using the inflection point approach, 10.10 ‒ 13.03 interval by Henderson- Hassellbalch analysis and 9.32 ‒ 12.43 interval by potentiometric titration method.