Some new pyrimidine derivatives have been synthesized and their characterization was done by IR, NMR, and mass spectral data. The solubility of these synthesized compounds has been studied in methanol, N,N dimethylformamide (DMF), and carbon tetrachloride (CCl4) by gravimetrical method from 298.15 to 328.15？K under atmospheric pressure and the solubility data were correlated against temperature. The solubility is found to increase with temperature and order of solubility is DMF > methanol > CCl4. The experimental solubility data is correlated with the modified Apelblat equation. Some thermodynamic parameters such as dissolution enthalpy, Gibbs energy of dissolution, and entropy of mixing have also been calculated. 1. Introduction The pyrimidine ring is an important structure in numerous natural products and bioactive compounds [1]. Further, the pyrimidine nucleus is present as a building block in materials science [2, 3]. Literature survey reveals that as pharmacologically active compounds, substituted pyrimidine scaffolds have become increasingly important with antimicrobial [4, 5], antimalarial [6], anticancer [7], and antimycotic activities [1]. So, it will be interesting to study their solubility in different solvents due to their various applications, which may help their uses in other fields also. Thus, in the present paper, solubility of some pyrimidine derivatives in methanol, DMF, and CCl4 from 298.15 to 328.15？K has been studied at atmospheric pressure. Some thermodynamic parameters such as dissolution enthalpy, Gibbs energy of dissolution, and entropy of mixing have also been calculated. 2. Experimental 2.1. Materials The choice of solvent depends upon solubility and relative permeability. 2,4-Dichloropyrimidine (DCP) (CAS no.: 3934-20-1) and 4-((1H-1,2,4-triazol-1-yl)methyl)aniline (TMA) (CAS no.: 119192-10-8) used in the synthesis were purchased from Sigma-Aldrich. N,N-diisopropylethylamine (DIPEA) (CAS no.: 7087-68-5), the solvents methanol, dimethylformamide (DMF), and carbon tetrachloride (CCl4) used in the present work were of AR grade supplied by Spectrochem Pvt. Ltd. (Mumbai, India) and were purified according to the standard procedure [8]. The purity of solvents was checked by GC-MS (SHIMADZU-Model no.-QP-2010) and found to be greater than 99.0%. 2.2. Synthesis A mixture of 2,4-dichloropyrimidine (DCP) (1.0 equi.), 4-((1H-1,2,4-triazol-1-yl)methyl)aniline (TMA), and N,N-diisopropylethylamine (DIPEA) (1.2 equi.) in n-Butanol was refluxed for 3？h. The completion of reaction was confirmed by analytical thin layer chromatography (TLC).
References
[1]
M. Radi, S. Schenone, and M. Botta, “Recent highlights in the synthesis of highly functionalized pyrimidines,” Organic & Biomolecular Chemistry, vol. 7, no. 14, pp. 2841–2847, 2009.
[2]
G. Hughes, C. Wang, A. S. Batsanov et al., “New pyrimidine- and fluorene-containing oligo(arylene)s: synthesis, crystal structures, optoelectronic properties and a theoretical study,” Organic & Biomolecular Chemistry, vol. 1, pp. 3069–3077, 2003.
[3]
K. Itami, D. Yamazaki, and J. Yoshida, “Pyrimidine-core extended π-systems: general synthesis and interesting fluorescent properties,” Journal of the Americal Chemical Society, vol. 126, no. 47, pp. 15396–11537, 2004.
[4]
J. Cieplik, M. Stolarczyk, J. Pluta et al., “Synthesis and antibacterial properties of pyrimidine derivatives,” Acta Poloniae Pharmaceutica Drug Research, vol. 68, no. 1, pp. 57–65, 2011.
[5]
M. S. Mohamed, S. M. Awad, and N. M. Ahmed, “Synthesis and antimicrobial activities of new indolyl-pyrimidine derivatives,” Journal of Applied Pharmaceutical Science, vol. 1, no. 5, pp. 76–80, 2011.
[6]
R. Morgan, R. J. Haritakul, and P. A. Keller, “Antimalarial activity of 2,4-diaminopyrimidines,” Letters in Drug Design & Discovery, vol. 5, no. 4, pp. 277–280, 2008.
[7]
B. Ramesh and S. V. Kulakarni, “Design, synthesis and anticancer activity of some new pyrimidine derivatives,” Journal of Global Pharma Technology, vol. 2, no. 4, pp. 110–112, 2010.
[8]
J. A. Riddick, W. B. Bunger, and T. Sakano, “Organic solvents-physical properties and methods of purification, techniques of chemistry,” New York, NY, USA, 1986.
[9]
M. Zhu, “Solubility and density of the disodium salt hemiheptahydrate of ceftriaxone in water + ethanol mixtures,” Journal of Chemical & Engineering Data, vol. 46, no. 2, pp. 175–176, 2001.
[10]
Q.-S. Li, M.-G. Su, and S. Wang, “Solubility of 2-(4-ethylbenzoyl)benzoic acid in eleven organic solvents between 279.55 K and 343.15 K,” Journal of Chemical & Engineering Data, vol. 52, no. 6, pp. 2477–2479, 2007.
[11]
A. Daneshfar, H. S. Ghaziaskar, and N. Homayoun, “Solubility of gallic acid in methanol, ethanol, water, and ethyl acetate,” Journal of Chemical & Engineering Data, vol. 53, no. 3, pp. 776–778, 2008.
[12]
R. R. Krug, W. G. Hunter, and R. A. Grieger, “Enthalpy-entropy compensation. 2. Separation of the chemical from the statistical effect,” The Journal of Physical Chemistry, vol. 80, no. 21, pp. 2341–2351, 1976.
[13]
D. M. Aragón, M. A. Ruidiaz, E. F. Vargas et al., “Solubility of the antimicrobial agent triclosan in organic solvents of different hydrogen bonding capabilities at several temperatures,” Journal of Chemical & Engineering Data, vol. 53, no. 11, pp. 2576–2580, 2008.
[14]
S. P. Bustamante, A. P. Romero, B. Escalera, and A. Reillo, “Nonlinear enthalpy-entropy compensation for the solubility of drugs in solvent mixtures: paracetamol, acetanilide and nalidixic acid in dioxane-water,” Journal of Pharmaceutical Sciences, vol. 87, no. 12, pp. 1590–1596, 1998.
[15]
E. K. Panteli and E. K. Voutsas, “Solubilities of cinnamic acid esters in ionic liquids,” Journal of Chemical & Engineering Data, vol. 54, no. 3, pp. 812–818, 2009.
[16]
A. A. El-Bindary, A. Z. El-Sonbati, E. H. El-Mosalamy, and R. M. Ahmed, “Potentiometric and thermodynamic studies of azosulfonamide drugs. X,” Chemical Papers, vol. 57, no. 4, pp. 255–258, 2003.
