The purpose of this work is to investigate the thermodynamic properties of the solubility of methyl 6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydro-pyrimidine-5-carboxylate, which exhibits a wide spectrum of biological activity in organic solvents of different polarity and their character of mixing. As you know, the processes of synthesis and purification of solid substances, allmost, occur with the help of individual solvents or their mixture, so optimization of these processes is impossible without determining the thermodynamic parameters of their dissolution.
Enthalpy (ΔsolH) and entropy (ΔsolS) of dissolution were determined from the temperature dependence of the solubility of methyl ester of 6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahidropirymidyn-5-carboxylic acid in: ethyl acetate (ΔsolH = 24,05±0,53 kJ/mol, ΔsolS = 27,0±1,7 J/mol K); benzene (ΔsolH = 32,76±0,42 kJ/mol, ΔsolS = 40,3±1,3 J/mol K) and their mixtures in the ratio of ethyl acetate: benzene in % by weight: 75:25 (ΔsolH) = 23.30 ± 0.62 kJ / mol, (ΔsolS) = 23.8 ± 2.0 J / mol • K; 50:50 (ΔsolH) = 26.85 ± 0.44 kJ / mol; (ΔsolS) = 31.9 ± 1.4 J / mol • K; 25:75 (ΔsolH) = 28.58 ± 0.81 kJ / mol; (ΔsolS) = 34.2 ± 2.7 J / mol • K.
Enthalpies and entropies of mixing of investigated compound were determined using enthalpies and entropies of fusion of methyl 6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydro-pyrimidine-5-carboxylate at an average temperature of experiments to determine their solubility: ΔfusН487,7 = 32,9 ± 1,7 kJ / mol; ΔfusS487.7 = 67.5 ± 2.0 J / mol. Quantitys of the enthalpy and entropy of the melting of the test substance were calculated at 298K: ΔfusH298 = 23.4 ± 1.8 kJ / mol, ΔfusS298 = 32.9 ± 2.1 J / mol. After that, thermodynamic mixing parameters for the studied systems were calculated: ethyl acetate (ΔmixH) = 0.7 ± 2.0 kJ / mol, (ΔmixS) = -15.1 ± 4.3 J / mol • K; benzene (ΔmixH) = 9.4 ± 1.9 kJ / mol, (ΔmixS) = -2.6 ± 2.5 J / mol • K; 75:25 (ΔmixH) = -0,1 ± 1,9 kJ / mol, (ΔmixS) = -19,1 ± 2,9 J / mol • K; 50:50 (ΔmixH) = 3.4 ± 1.9 kJ / mol, (ΔmixS) = -11.0 ± 2.5 J / mol • K; 25:75 (ΔmixH) = 5.2 ± 2.0 kJ / mol, (ΔmixS) = -8.7 ± 3.4 J / mol • K.
Positive or close to 0 thermodynamic parameters of solubility of the compound under study at 298K indicate that the destruction of intermolecular bonds in individual substances requires higher energy expenditure than is allocated as a result of the formation of new intermolecular bonds in the systems under study.
As a result of the studies, thermodynamic properties of solubility for methyl 6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate in organic solvents of different polarity and their mixtures were determined. The experimental and calculated data can be used to optimize the purification and separation processes, to predict the reactive behavior of the substance in the solution. It was also possible to establish the presence of the compensatory effect of the process of mixing the investigated esters with ethyl acetate, benzene and their mixtures.
1. Tianhua Huang, Dingqiang Lu, Xiuquan Ling, Xinxian Wang, Tongqi Liu, Fangfang Shen, Kefei He. (2017). Thermodynamic models for determination of the solid-liquid equilibrium of istradefylline in ethyl acetate plus (isopropanol, tetrahydrofuran, acetone) binary solvent mixtures. J. Chem. Thermodynamics. 111. 31-40. doi: 10.1016/j.jct.2017.03.015
https://doi.org/10.1016/j.jct.2017.03.015
2. Huan Shen, Songgu Wu, Yumin Liu, Kangli Li., Shijie Xu, Junbo Gong. (2017). Determination and correlation of Avermectin B1a solubility in different binary solvent mixtures at temperatures from (283.15 to 313.15) K. J. Chem Thermodynamics. 105. 253-266. doi: 10.1016/j.jct.2016.10.022
https://doi.org/10.1016/j.jct.2016.10.022
3. Jinxiu Wang, Chuang Xie, Qiuxiang Yin, Linggang Tao, Jun Lv, Yongli Wang, Hongxun Hao. (2016). Measurement and correlation of solubility of cefmenoxime hydrochloride in pure solvents and binary solvent mixtures. J. Chem Thermodynamics. 95. 63-71. doi: 10.1016/j.jct.2015.11.024
https://doi.org/10.1016/j.jct.2015.11.024
4. Zhengyang Han, Hongxun Hao, HaoWu, Qi Liu, Shuyi Zong, Xin Huang. (2019). Solubility and thermodynamic properties of dirithromycin form A and form B in pure solvents and binary solvent mixture. J. Chem Thermodynamics. 132. 240-249. doi: 10.1016/j.jct.2018.12.044
https://doi.org/10.1016/j.jct.2018.12.044
5. Yüfang Wu, Jiangwei Gao, Suyue Yan, Chenmeng Wu, Bin Hu. (2019) The dissolution behavior and apparent thermodynamic analysis of temozolomide in pure and mixed solvents. J. Chem Thermodynamics. 132. 240-249. doi: 10.1016/j.jct.2018.11.026
https://doi.org/10.1016/j.jct.2018.11.026
6. JiaxinWu, RenjieXu, XinYuan, JiaZhao JianWang. (2019). Equilibrium solubility of dinitolmide in several neat solvents and binary aqueous co-solvent mixtures: Experimental determination and thermo-dynamic analysis. J. Chem Thermodynamics. 132. 373-382. . doi: 10.1016/j.jct.2019.01.013
https://doi.org/10.1016/j.jct.2019.01.013
7. Sandhu S., Sandhu J. (2012). Past, present and fu¬tu¬re of the Biginelli reaction: a critical perspective. ARKAT-USA, 1(і), 66-130. doi: 10.3998/ark.5550190.0013.103.
https://doi.org/10.3998/ark.5550190.0013.103
8. Chemistry Web-book [Електронний ресурс]. - Режим доступу: http://webbook.nist.gov.
9. Рідка О. Р., Матійчук В.С., Собечко І. Б., Кочубей В. В., Сергеєв В. В. (2017). Термодинамічні властивості метил-6-метил-2-оксо-4-феніл-1,2,3,4-тетрагідропіримідин-5-карбоксилату в органічних розчинниках. Вісник Національного університету "Львівська політехніка". 868. 57-61.
10. Собечко И. Б., Прокоп Р. Т., Горак Ю. И. и др. Термодинамические характеристики растворения 1-метил-2-пирролкарбоновой кислоты в органических растворителях Вопросы химии и химической технологии. 2013. 4. 12-15.
11. Собечко И. Б., Ван-Чин-Сян Ю. Я., Кочубей В. В. и др. Термодинамические свойства фуран-2-карбоновой и 3-(2-фурил)-2-пропеновой кислот Журнал физической химии. 2014. Т. 88. 12. С. 1885-1892.
https://doi.org/10.7868/S0044453714120322