Solubility of Some Pyrimidine Derivatives in Methyl-Alcohol at different Temperatures.

 

Arun Kumar¹, Vinita Gupta², Sanchita Singh², Y.K. Gupta^3*

¹Research Scholar, School of Applied Sciences Singhania University Pacheri Bari, Jhunjhunu (Raj.), India

²Department of Chemistry, Agra College, Agra, U.P, India

³Head, Department of Chemistry, B K Birla Institute of Engineering and Technology, Pilani, Rajasthan, India *Corresponding Author E-mail: ykgbkbiet123@gmail.com

The solubility of some of Pyrimidine derivatives in methyl alcohol was measured by gravimetrical method at different temperatures (293.15 to 313.15 K) under atmospheric pressure. The solubility data were comprised with temperature by Apelblat equation. Some thermodynamic parameters such as dissolution enthalpy, and Gibbs’ free energy of dissolution and entropy were evaluated from solubility data.

 

 

 

INTRODUCTION:

Pyrimidine and its derivatives are potential bioactive molecules which exhibit wide spectrum of biological activities such as antibacterial^,1,2 antitumor,³ antihistaminic,⁴ analgesic,⁵ anti-inflammatory,⁶ anticancer,⁷ anticonvulsant,⁸ anti HIV,⁹ antitubercular, ¹⁰ antiprotozoal,¹¹ antiparkinsonian,¹² antifungal¹³ etc. Further, these heterocyclic are integral part of DNA and RNA¹⁴ and are present in many natural products.^{15, 16} Pyrimidine derivatives are also component in various drugs.^17-20 Owing to their pharmacological properties, the study of solubility of some Pyrimidine derivatives would be useful because solubility data play a prominent role for the discovery and development of drugs.²¹

 

In our previous work, solubility behavior of some particular active pharmaceutical ingredients in different protic and aprotic solvents has been studied.^22-24 The study is further extended in the present paper to study the effect of functional groups on solubility of Pyrimidine derivatives in methanol at different temperatures (293.15 to 313.15 K) at atmospheric pressure.

 

EXPERIMENTAL:

MATERIALS:

The following Pyrimidine derivatives have been synthesized in the laboratory and all the synthesized Pyrimidine derivatives are recrystallized from ethyl alcohol. The purity of these synthesized Pyrimidine derivatives were checked by elemental analysis, IR, NMR and mass spectral data. The melting temperature of synthesized Pyrimidine derivatives was determined by DSC method. Fig. 1 shows the general structure of these synthesized Pyrimidine derivatives. The IUPAC names of synthesized Pyrimidine derivatives are:

 

Methyl alcohol was purified by fractional distillation and its purity was checked by SHIMADZU GC-MS (Model No QP- 2010) and was found to be greater than 99.70 %.

 

Figure 1 – General Structure of Pyrimidine derivatives

 

Where R =

1: -4- OH, 3-OCH₃ C₆H₄,

2: - 4- OCH₃ C₆H₄,

3: - 4- OH C₆H₄,

4: - 4- Cl C₆H₄,

5: - 3- Cl C₆H₄,

6: - 4- F C₆H₄,

7: - 3- NO₂ C₆H₄,

8:- C₆H_5,

9: - C₄H₃O,

10: - CH=CH, C₆H₅.

 

Solubility Measurement:

The solubility of these compounds is observed in methanol at different temperature (293.15 to 313.15 K). For each measurement, an excess mass of compound was added to a known mass of solvent. Then, the equilibrium cell was heated to a constant temperature with continuous stirring. After, at least 3 hr (the temperature of the water bath approached constant value, then the actual value of the temperature was recorded), the stirring was stopped and the solution was kept still for 2 hr. A portion of this solution was filtered and by a preheated injector, 5 ml of this clear solution was taken in another weighed measuring vial (m₀). The vial was quickly and tightly closed and weighed (m₁) to determine the mass of the sample (m₁- m₀). Then, the vial was covered with a piece of filter paper to prevent dust contamination. After the methanol in the vial had completely evaporated at room temperature, the vial was dried and reweighed (m₂) to determine the mass of the constant solid residue (m₂- m₀). All the masses were measured using an electronic balance (Mettler Toledo AB204-S, Switzerland) with an uncertainty of ± 0.0001 g. Thus, the concentration of the solid sample in the solution, mole fraction, x, could be determined from   eq 1.

 

Where M₁is the molar mass of compound and M₂ is the molar mass of the methanol. At each temperature, the measurement was repeated three times and an average value is given in Table 1.

 

Table 1: Observed Mass fraction Solubilities (x) and Calculated Mass fraction Solubilities (xci) of Pyrimidine derivatives in methyl alcohol

1: 4-amino-6-(4-hydroxy-3-methoxyphenyl)-2-sulfanyl-1,4,5,6-tetrahydro pyrimidine-5- carbonitrile.
-Temp. K	x. 103	xci.103	100 RD
293.15	5.0027	5.0309	0.0001
298.15	5.0167	5.0460	0.0002
303.15	5.0337	5.0612	0.0001
308.15	5.0474	5.0764	0.0002
313.15	5.0611	5.0916	0.0001

 

2: 4-amino-6-(4-methoxyphenyl)-2-sulfanyl- 1,4,5,6-tetrahydro pyrimidine-5-carbonitrile.
-Temp. K	x. 103	xci.103	100 RD
293.15	2.1561	1.6945	-0.0075
298.15	2.2855	1.7814	-0.0083
303.15	2.4118	1.8727	-0.0089
308.15	2.5478	1.9687	-0.0097
313.15	2.6774	2.0696	-0.0103

 

3: 4-amino-6-(4-hydroxyphenyl)-2-sulfanyl-1,4,5,6- tetrahydro pyrimidine-5-carbonitrile.
-Temp. K	x. 103	xci.103	100 RD
293.15	4.4797	3.6202	0.0005
298.15	4.6153	3.7118	0.0006
303.15	4.7537	3.8057	0.0005
308.15	4.8889	3.9021	0.0005
313.15	5.0237	4.0008	0.0006

 

4. 4-amino-6-(4-chlorophenyl)-2-sulfanyl-1,4,5,6- tetrahydro pyrimidine-5-carbonitrile.
-Temp. K	x. 103	xci.103	100 RD
293.15	1.3729	1.0733	-0.0045
298.15	1.4164	1.1005	-0.0048
303.15	1.4449	1.1283	-0.0048
308.15	1.5000	1.1569	-0.0053
313.15	1.5439	1.1862	-0.0055
5: 4-amino-6-(3-chlorophenyl)-2-sulfanyl-1,4,5,6- tetrahydro pyrimidine-5-carbonitrile.
-Temp. K	x. 103	xci.103	100 RD
293.15	3.3490	2.7182	-0.0036
298.15	3.3750	2.7318	-0.0037
303.15	3.4008	2.7455	-0.0037
308.15	3.4614	2.7593	-0.0038
313.15	3.4520	2.7731	-0.0039

 

6: 4-amino-6-(4-fluorophenyl)-2-sulfanyl-1,4,5,6- tetrahydro pyrimidine-5-carbonitrile.
-Temp. K	x. 103	xci.103	100 RD
293.15	2.9765	2.6330	-0.0159
298.15	3.3969	2.9391	-0.0168
303.15	3.8218	3.2808	-0.0177
308.15	4.2439	3.6622	-0.0185
313.15	4.6704	4.0880	-0.0193

 

7: 4-amino-6-(3-nitrophenyl)-2-sulfanyl-1,4,5,6- tetrahydro pyrimidine-5-carbonitrile.
-Temp. K	x. 103	xci.103	100 RD
293.15	2.5740	2.5814	-0.0059
298.15	2.5826	2.5918	-0.0081
303.15	2.5945	2.6022	-0.0097
308.15	2.6032	2.6126	-0.0106
313.15	2.6152	2.6231	-0.0109

 

8: 4-amino-6-phenyl-2-sulfanyl-1,4,5,6-tetrahydro pyrimidine-5-carbonitrile.
-Temp. K	x. 103	xci.103	100 RD
293.15	2.7468	2.8062	0.0010
298.15	3.0801	3.1012	0.0004
303.15	3.4193	3.7877	0.0001
308.15	3.7579	3.7877	0.0005
313.15	4.0991	4.1860	0.0016

 

9: 4-amino-6-(furan-2-yl)-2-sulfanyl-1,4,5,6-tetrahydro pyrimidine-5-carbonitrile.
-Temp. K	x. 103	xci.103	100 RD
293.15	12.722	12.567	-0.0111
298.15	12.777	12.617	-0.0113
303.15	12.829	12.668	-0.0115
308.15	12.884	12.719	-0.0124
313.15	12.941	12.770	-0.0120

 

10: 4-amino-6-[(Z)-2-phenylethenyl]-2-sulfanyl- 1,4,5,6-tetrahydro pyrimidine-5-carbonitrile.
-Temp. K	x. 103	xci.103	100 RD
293.15	5.5568	4.6902	-0.0167
298.15	5.7198	4.8089	-0.0176
303.15	5.7340	4.9306	-0.0156
308.15	6.0485	5.0554	-0.0194
313.15	6.2107	5.1834	-0.0202

 

RESULTS AND DISCUSSION:

The mass fraction solubilities x of Pyrimidine derivatives in methyl alcohol at different temperatures (293.15 to 313.15 K) are summarized in Table 1. The variation of these mole fraction solubilities for all the compounds with temperature are also shown in Fig. 2. It is observed that solubility increases linearly with increase in temperature. By the modified Apelblat equation, ^{25, 26} mole fraction solubilities are related to temperature.

 

ln xci = A + B/T                                                        ......(2)

 

Where xci is the mass fraction solubility of Pyrimidine and T is the absolute temperature. A and B are the parameters. The values of these parameters are given in Table 2. Using these parameters, solubilities xci are calculated and are given in Table 1.

 

The order of solubility is synthesized Pyrimidine derivatives No 9>synthesized Pyrimidine derivatives No 10 >synthesized Pyrimidine derivatives No 1>synthesized Pyrimidine derivatives No 3>synthesized Pyrimidine derivatives No 5>synthesized Pyrimidine derivatives No 6>synthesized Pyrimidine derivatives No 8> synthesized Pyrimidine derivatives No 2>synthesized Pyrimidine derivatives No 7>synthesized Pyrimidine derivatives No 4.

 

All the compounds have the same central moiety but different side chains. Thus, solubility is affected by the side chain. Synthesized Pyrimidine derivatives No 9 contain furan as side chain.  Thus, higher solubility in synthesized Pyrimidine derivatives No 9 among the studied compound is due to furan whereas synthesized Pyrimidine derivatives No 4 containing p-chloro alkyl group exhibited minimum solubility. The position of functional group in side chain also affects the solubility. Synthesized Pyrimidine derivatives No 5 also contains chloro alkyl group but in this compound, chloro group is at meta position which causes an increase in solubility. There may be hydrogen bond formation between methanol molecules and oxygen of furan ring. Synthesized Pyrimidine derivatives No 1 and synthesized Pyrimidine derivatives No 3 also exhibit comparatively good solubility which may also be due to hydrogen bonding of - OH group with methanol molecules. Solubility of synthesized Pyrimidine derivatives No 1 is higher than synthesized Pyrimidine derivatives No 3. From this observation, it can be assumed that the solubility of compound with vanillin is higher than compound with –OH group which may be due to positive effect of –OCH₃ group. However, synthesized Pyrimidine derivatives No 2 which possesses only –OCH³ group, exhibited less solubility.

 

Fig. 2 – Variation of mole fraction solubility of synthesized pyrimidines derivatives in methyl  alcohol with temperature.

 

Table 2: Constants A and B of eq (2), Relative Average Deviations (ARD),and Root Mean Square Deviation (RMSD) of synthesized pyrimidine derivatives in methyl alcohol.

Synthesized Pyrimidine Derivatives  No.	A	B	108 RMSD	100 ARD
1	-5.469	0.0006	0.0209	0.0006
2	-9.313	0.01	7.3130	-0.0089
3	-7.088	0.005	22.369	-0.0177
4	-8.304	0.005	2.6778	-0.0050
5	-6.202	0.001	10.975	-0.0117
6	-12.39	0.022	6.4896	-0.0090
7	-6.195	0.0008	0.0017	0.0001
8	-11.74	0.02	0.0623	0.0007
9	-4.612	0.0008	0.6629	-0.0037
10	-6.829	0.005	21.339	-0.0179

Table 3: Thermodynamic parameters of dissolution of synthesized pyrimidine derivatives in methyl alcohol.

Synthesized Pyrimidine Derivatives  No.	ΔHsol kcal.mol-1	ΔGsol kcal.mol-1	ΔSsol cal.mol-1.K-1
1	0.4470	14.8302	-47.4715
2	8.2716	11.2998	-9.9946
3	4.3782	14.9547	-34.9077
4	4.4605	15.1652	-35.3311
5	1.1565	11.7306	-34.8997
6	17.1684	11.6039	18.3658
7	0.6058	12.4475	-39.0835
8	15.2645	12.5825	8.8520
9	0.6463	12.8354	-40.2299
10	4.2493	12.4669	-27.1221

 

Further, from the solubility data, some thermodynamic parameters such as solution enthalpy (ΔHsol), Gibbs’ free energy change (ΔGsol) and entropy of solution (ΔSsol) have also been evaluated.

 

It is evident from Table 3 that for all the compounds ΔHsol and ΔGsol are positive. However, ΔSsol values are negative for most of the compounds except Synthesized Pyrimidine Derivatives No. 6 and Synthesized Pyrimidine Derivatives No.8 where it is positive. When stronger bonds are broken and weaker bonds are formed, energy is consumed. So, ΔHsol becomes positive²⁹ indicating thereby endothermic dissolution of compounds. The positive value of ΔGsol indicates spontaneous dissolution of studied compounds in methanol.³⁰thepositive entropy ΔSsol indicates more randomness in solution as observed for most of the compounds whereas negative ΔSsol suggests more order in solutions.

 

CONCLUSIONS:

The solubility of synthesized Pyrimidine derivatives in methyl alcohol increases with the rise of temperature. The modified Apelblat equation is used to correlate the solubility data with temperature. The solubility calculated by Apelblat equation is in good agreement with experimental solubility. Further, solubility in the studied compounds is affected by the function groups present in the compounds and compound containing furan exhibited maximum solubility in methanol. The positive enthalpy and Gibbs free energy values indicate the dissolution process to be endothermic and spontaneous. For most of the studied compounds, dissolution results in more ordered structure as indicated by negative entropy values whereas positive entropy suggests less ordered structure for some compounds. The more ordered structure may be due to hydrogen bonding between compound and methanol molecules.

 

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Received on 09.03.2017         Modified on 18.03.2017

Accepted on 24.04.2017         © AJRC All right reserved