Anadolu Üniversitesi Bilim ve Teknoloji Dergisi A- Uygulamalı Bilimler ve Mühendislik Anadolu University Journal of Science and Technology A- Applied Sciences and Engineering 2016 - Volume: 17 Number: 2 Page: 263 - 272 DOI: 10.18038/btda.96904 Received: 07 January 2016 Revised: 08 April 2016
Accepted: 09 May 2016
DETERMINATION AND EVALUATION OF ACIDITY CONSTANTS OF SOME IMIDAZOLE AND THIAZOLE LINKED ACETAMIDE COMPOUNDS Funda TAY1*, Murat DURAN1, Cihan İSPİR1 , Şeref DEMİRAYAK2 1Department 2Department
of Chemistry, Faculty of Sciences, Eskişehir Osmangazi University, Eskişehir, Turkey of Pharmaceutical Chemistry, School of Pharmacy, Medipol University, 34083, İstanbul, Turkey
ABSTRACT In this work, the effect of substituents on the acidity constants of some acetamide derivatives was investigated. The acidity constants of nine acetamide derivatives were determined at 25 °C using a UV spectrophotometric method. When the molecules possessed different substituents the values of the acidity constants changed from 6.01 to 8.22 for the first protonation and from 3.07 to 4.73 for the second protonation. The first protonation under these circumstances was observed to occur on the nitrogen atom of the 2-mercaptoimidazole ring. The second protonation was observed to occur on the nitrogen atom of the thiazole ring. Keywords: Imidazole, Thiazole, Acetamide, Protonation paths, UV spectroscopy, pKa
1. INTRODUCTION During the last few years, numerous articles detailing the determination of the acid–base properties of organic molecules have been reported [1-12]. The acid dissociation constant, pKa, is defined as tendency of an acid to release a proton in an aqueous solution. The acidity constants of organic reagents play a fundamental role in numerous chemical and biological processes, such as analytical procedures, acid-base titrations, solvent extraction, ion transport, complex formation, chemical synthesis, electrochemical properties, pharmacokinetics, drug design, drug metabolism and enzymatic reactions [13-15]. Acidity constants are very important in the analysis of the mechanisms of action of drugs because they are the key parameters for predicting the extent of the ionization of a molecule in solution at different pH [16]. Spectrophotometric methods are highly sensitive and suitable for the determination of acidity constants. Different spectroscopic methods for the experimental determination of acidity constants have been developed, including UV–Vis absorption, 1H NMR, FT-IR, and Raman techniques [17-20]. Knowledge of the acidity constant of a molecule is one of the most important parameters in explaining the physicochemical behavior of drugs and in investigating pharmaceutical synthesis methods [21]. Changes in pKa values in molecules depend on intramolecular interactions [22]. Imidazole and thiazole represent an interesting class of heterocyclic compounds. Phenyl thiazole and imidazole-2-thione were observed to play important roles in biological functions, such as antimicrobial, antidiabetic, antiviral, anti-inflammatory, antituberculosis, and anticancer activities [2331]. In particular, 2-amino-4-phenyl-1,3-thiazole has pharmaceutical characteristics and it is used in industrial applications [32-34]. Thiazole compounds have also been used in electrochemical applications [35-42].
*Corresponding Author:
[email protected]
Tay et al. / Anadolu Univ. J. of Sci. and Technology – A – Appl. Sci. and Eng. 17 (2) - 2016
In this study, UV-visible spectrophotometry and a physicochemical approach are used to determine the acidity constants of nine 2-(4,5-dimethyl-1-(arylamino)-1H-imidazol-2-yl)thio)-N-(4-arylthiazol-2yl)acetamide derivatives (Figure 1).
Figure 1. Structures of 2-(4,5-dimethyl-1-(arylamino)-1H-imidazol-2-yl)thio)-N-(4-arylthiazol-2-yl) acetamide derivatives 2. MATERIAL AND METHOD The studied acetamide derivatives were synthesized according to the methods described in our previous work [31]. The buffer solutions used were prepared from: (a) HCl-KCl, pH = 1.0; (b) KH2PO4-NaOH, pH = 7.0; (c) borax-HCl, pH = 8.0 to 9.0; (d) borax-NaOH, pH = 9.3 to 10.7. All these materials and buffer solutions were from Merck and were not further purified [43]. The percentage of sulfuric acid solution [(1 to 98%) H2SO4] was determined by titration with Na2CO3 using methyl red as an indicator. An Orion model 720A+ pH/ion analyzer with a combination glass electrode was used for pH measurements after being calibrated against standard buffers of pH 4, 7 and 9. A Unicam UV2 UVVis scanning spectrophotometer was used to record the electronic absorption spectra. The UV-Vis spectra, which were obtained to determine the values of the acidity constants, were recorded at pH which are (1-14) and Ho (acidity range) which is -0.20 and -10.72. The spectrophotometer was equipped with quartz cells with a 1 cm path length and the spectra were recorded over the wavelength range of 220-400 nm. Acid solutions, CO2-free NaOH solutions, and pH solutions were prepared by using the methods described in the literature [44-46]. For bases ionization process can be described as in Eq.1. (1) A mathematical expression of the acid ionization constant can be written as in Eq.2. Ka = aH+ aB / aBH+
(2)
Where a represent the activity of each species. At a given temperature, the constants expressed above are thermodynamic quantities also known as thermodynamic ionization constants, which we can refer to Ka. These constants are independent of concentration because all terms involved are in terms of activities. Another type of constant which we can make use of is the concentration ionization constant, Kc, which is defined for bases by Eq. 3 in which the square brackets denote the concentration of each ionic species. Kc = [H+] [B] / [BH+]
(3) 264
Tay et al. / Anadolu Univ. J. of Sci. and Technology – A – Appl. Sci. and Eng. 17 (2) - 2016
Equation 3 is generally used in the following form (Eq 4), in which pKa is the negative logarithm of the ionization constant and only applicable if [H+] aH+, i.e., H+ 1, as indicated below: pKa = pH + log [BH+]/[B]
(4)
The difference between thermodynamic and concentration constants is that the activities of the ions have to be taken care in calculating the former. These activities compensate for the attraction ions which can exert on one another (ion pair) as well as for the incomplete hydration of ions in solutions that are concentrated. The lower the concentration, the less this interaction becomes, until infinite dilution, the concentration becomes numerically equal to the thermodynamic constant. Equation 3 can be used for the simplicity, provided that the constant is determined in solution not stronger than 0.01 mol/L and only univalent ions are present. For the present, it needs only to be noted that activity of neutral species does not differ appreciably from its concentration and that pH, as commonly determined, is nearer to hydrogen ion activity than that to hydrogen ion concentration, although at low ionic strength (I
