Determination of the pKa of Benzophenones in Ethanol-Water

Abstract

The pKa of monohydroxylated benzophenones was determined by UV spectros-copy. The values obtained are coherent with the resonant forms and hydrogen bond in-tramolecular of the analyzed compounds.

Introduction

The pKa of a drug is one of the most important parameters to explain its physicochemical behavior and acid-base properties [1], to program assays of pharmaceutical preformulation [2], etc. In this work, the pKa values of monohydroxylated benzophenones (BP) were determined by UV-visible spectros-copy. These substances exhibit interesting adsorptive properties, they act as ligands in the complexa- tion of metallic ions and, also, they have biochemical applications as antimicrobial agents and in in-dustry as commercial sun blocks [3].

Experimental

The figure shows the basic structure of the analyzed aromatic ketones: 1: 4(OH)-BP (X₂=H, X₄=OH); 2: 2(OH)-BP (X₂=OH, X₄=H); 3: 2(OH),4(CH₃O)-BP (X₂=OH, X₄=CH₃O). For pKa deter-mination, a UV-vis spectroscopic procedure based on the Henderson-Hasselbalch [4] was used. The buffer solutions used were: a) HCl-KCl, pH 1.5; b) NaOH-KCl, pH 12.5; c) KH₂PO₄-Na₂HPO₄ 0.01M for a 7.2-8.0 pH interval; d) Na₂CO₃-NaHCO₃ 0.01M, pH 9.2-10.0. All buffer solutions were prepared with a 20% w/w ethanol-water mixture, keeping the ionic strength constant (0.05) with KCl.

Results and Discussion

The maximum absorption wavelengths record for the acid (λa) and ionized (λb) forms of the BP were: λa (1) 294.5nm, λb (1) 348nm; λa (2) 334nm, λb (2) 382nm; λa (3) 320nm, λb (3) 372nm. The pKa determined were the following: pKa (1)=7.83; pKa (2)=9.54 and pKa (3)=9.60. The carbonyl group of the benzophenones interacts with the adjacent aromatic rings through the σ and π bonds, fa-voring the π-electronic delocalization of the molecules. The participation of the C=O group in the conjugate molecular system is reflected in its bonding characteristics and in the influence it exerts on the acid-base properties of the hydroxyl groups. The increase of the pKa values in the order pKa (1) < pKa (2) < pKa (3) is coherent with the resonant forms and intramolecular hydrogen bonds exhibited by BPs 2 and 3. The pKa of 1 is markedly lower than that of 4(OH)-chalcone, pKa=8.17 [5]. This indi-cates that the C=O α,β-unsaturated group of the chalcone, increase the π-electronic delocalization of the molecule, decreasing the acidity of the H atom the OH group at position 4.