Chapter 3
Physico chemical properties
Section-I
Acoustical properties
Section-I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005 82
INTRODUCTION
In general waves, having frequency above the range audible to the human ear are
known as Ultrasound. The actual range of ultrasounds lies above 20 KHz.
In 21st century, ultrasonic dependant devices are a handy tool in various industries
such as cement1-3, paper4-5, glass6-9, soap10-14, petrochemicals15-17, plastic18-19, steel20,
dairy21, liquor22 etc, because of it’s non destructive nature and accurate measuring. In
industries, it could be used in various processes like dyeing23, cleaning24, repairing of
cracks25, design26, food processing27, bleaching28, deacidification29, extraction30-31,
viscosity reduction32, electroplating33, powder compression34, wastewater treatment
effluents35 etc.
Latest development in sonography is used in medical treatment36-38. Mainly, it is
used for the diagnosis of diseases in the body organs like thyroid39, abdoman40, kidneys41,
urinary tracts42 etc. Boucaud et al. have performed the skin permeation study of caffeine
across human and rat.43.Various uses of ultrasonics has been reported for diagnosis as
well as treatment of cancer44-46 and other tumours47,48
Further, in medicine, the ultrasonic method is combined with other technique to
give more elaborate diagnosis49-51. It is also useful in forensic science52,53. Zhou et al.
have used the ultrasonic waves in biomedical applications54, while Song et al. have
studied genetic transformation55 by using this techniqur55. Nowadays, in nanotechnology
also, ultrasounds waves have been used56-59. The studies in some liquid crystals have also
been done by Ayachit et al60.
In synthetic organic chemistry, a lot of interest has been generated on the use of
ultrasound radiations because of its compatible features like less reaction time, higher
percentage of yield, lower reaction temperature, avoidance of phase transfer catalysis
etc61-66. It is a pollution free green chemistry approach for synthesis of organic materials.
Sono chemistry is also useful in the isomerisation of carbon-carbon double bond67,
crystallization68,69, solvent extraction70 etc.
The ultrasonic measurements have also been used to study molecular interactions
in various pure liquids71-73, liquid mixtures74-77 and solutions of organic and inorganic
compounds78-80, polymers81, amino acids82, drugs83,84 etc. The thermodynamic parameters
calculated through ultrasonic velocity measurements can give idea about intermolecular
attraction between molecules (solute-solute or solute-solvent)85.
Section-I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005 83
In our laboratory, the ultrasonic studies of some compounds like Schiff bases86,
benzodiazepines87, dihydropyrimidines88 etc. have been studied in different solvents.
In the present section, ultrasonic studies of tetrahydropyrimidine derivatives have
been studied in N, N dimethylformamide and tetrahydrofuran solutions of various
concentrations at 303.15 K with a view to understand molecular interactions in these
solutions.
Section-I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005 84
EXPERIMENTAL
The selected solvents, DMF and THF for the present study were distilled by the
reported procedure89. The synthesized tetrahydropyrimidine derivatives (PAB 101-PAB
110) were recrystalized before use.
The densities, viscosities and ultrasonic velocities of pure solvents and solutions
of tetrahydropyrimidine derivatives of different concentrations were measured at 303.15
K by using pyknometer, an Ubbelohde suspended level viscometer and single frequency
ultrasonic interferometer operating at 2 MHz, with the uncertainties of 0.0001 g/cm3, +
0.06 % and 0.01% respectively.
Density measurements:
The weight of distilled water, pure solvents and solutions of synthesized
compounds were measured by using pyknometer. The densities (ρ) were evaluated by
using following equation:
3 wt. of solvent or solution density of waterρ g cm =
wt. of water … (3.1.1)
Viscosity Measurements:
To determine the viscosity of solution, Ubbelohde viscometer90 was used, which
obeys Stoke’s low91. The measured quantity of the distilled water / solvent / solution was
placed in the viscometer, which was suspended in a thermostat at 303.15 K. The digital
stopwatch, with an accuracy of + 0.01 sec was used to determine flow time of solutions.
Using the flow times (t) and known viscosity of standard water sample, the viscosity of
solvent (η1) and solutions (η2) were determined according to equation:
1 1 1
2 2 2
t
t
... (3.1.2)
Sound velocity measurement:
Ultrasonic interferometer, (Mittal Enterprise, New Delhi, Model No.F-81)
working at frequency of 2 MHz was used to determine sound velocity.
The solvent / solution were filled in the measuring cell with quartz crystal and
then micrometer was fixed. The circulation of water from the thermostat at 303.15 K was
started and test solvent / solution in the cell is allowed to thermally equilibrate. The
micrometer was rotated very slowly so as to obtain a maximum or minimum of anode
current (n). A number of maximum reading of anode current were counted. The total
Section-I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005 85
distance (d) travelled by the micrometer for n=10, was read. The wave length (λ) was
determined by the equation:
2d
n ... (3.1.3)
and sound velocity (U) of solvent and solutions were calculated by the equation:
U F ... (3.1.4)
where F is the frequency, which is equal to 2 x 106 Hertz.
Section-I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005 86
RESULTS AND DISCUSSION
Table 3.1.1 shows the experimental data of density (ρ), viscosity (η) and sound
velocity (U) of pure solvents and solutions of PAB compounds in DMF and THF
solutions at 303.15 K.
From these experimental data, various acoustical parameters like specific acoustical
impedance (Z), isentropic compressibility (κs), inter molecular free length (Lf), molar
compressibility (W), Rao’s molar sound function (Rm), Vander Waals constant (b),
relaxation strength (r), relative association (RA), internal pressure (π ), apparent molar
compressibility (k) etc., were evaluated using the following equations:
1. Specific acoustical impedance:
Specific acoustical impedance (Z) can be calculated as:
Z U ... (3.1.5)
2. Isentropic compressibility:
Isentropic compressibility ( s ) can be evaluated by the equation92
2
1s U
… (3.1.6)
3. Intermolecular free path length:
Jacobson93 proposed an equation to calculate the intermolecular free path length
(Lf), which is given below:1 2
f j sL K … (3.1.7)
where KJ is Jacobson constant (=2.0965 X 10-6)
4. Molar compressibility:
Molar compressibility (W) can be calculated by the following equation94
1 7s
MW
… (3.1.8)
The apparent molecular weight (M) of the solution can be calculated according to
following equation:
1 1 2 2M M W M W … (3.1.9)
where W1 and W2 are weight fractions of solvent and solute respectively. M1 and M2 are
the molecular weights of the solvent and compounds respectively.
Section-I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005 87
Table 3.1.1: The density (ρ), ultrasonic velocity (U) and viscosity (η) of PAB
compounds in DMF and THF at 303.15 K.
Conc.M
Densityρ
g.cm-3
VelocityU. 10-5
cm.s-1
Viscosityη.103
poise
Densityρ
g.cm-3
VelocityU. 10-5
cm.s-1
Viscosityη.103
poise
DMF THF
PAB-101
0.00 0.9304 1.4416 7.8072 0.8911 1.2852 5.5154
0.01 0.9323 1.4440 7.9519 0.9162 1.2868 5.7508
0.02 0.9326 1.4468 8.0492 0.9168 1.2892 5.8281
0.04 0.9331 1.4528 8.1727 0.9176 1.2916 5.9027
0.06 0.9338 1.4556 8.2948 0.9188 1.2944 5.9571
0.08 0.9342 1.4572 8.3970 0.9196 1.2976 6.0003
0.10 0.9353 1.4588 8.5466 0.9202 1.3016 6.0825PAB-102
0.01 0.9330 1.4424 8.3932 0.9164 1.2888 5.7943
0.02 0.9333 1.4436 8.4676 0.9168 1.2908 5.9093
0.04 0.9338 1.4448 8.5515 0.9179 1.2924 5.9597
0.06 0.9340 1.4464 8.6868 0.9184 1.2952 6.0174
0.08 0.9351 1.4480 8.7645 0.9188 1.2984 6.1145
0.10 0.9370 1.4488 8.8553 0.9194 1.3028 6.1293
PAB-1030.01 0.9359 1.4416 7.1965 0.9160 1.2876 5.6805
0.02 0.9365 1.4428 7.2834 0.9177 1.2896 5.7614
0.04 0.9370 1.4444 7.3801 0.9186 1.2916 5.8214
0.06 0.9376 1.4464 7.5084 0.9196 1.2936 5.8730
0.08 0.9380 1.4488 7.6104 0.9205 1.2948 5.9277
0.10 0.9384 1.4516 7.7034 0.9215 1.2960 6.0181
PAB-1040.01 0.9359 1.4428 8.3009 0.9132 1.2876 5.6329
0.02 0.9365 1.4444 8.3918 0.9147 1.2888 5.7024
0.04 0.9370 1.4464 8.4869 0.9167 1.2900 5.7623
0.06 0.9376 1.4492 8.6158 0.9186 1.2912 5.8361
0.08 0.9380 1.4524 8.7194 0.9195 1.2928 5.8985
0.10 0.9384 1.4540 8.8229 0.9206 1.2948 5.9772PAB-105
0.01 0.9330 1.4540 8.0501 0.9133 1.2864 5.6734
0.02 0.9340 1.4564 8.1538 0.9144 1.2876 5.7104
0.04 0.9341 1.4592 8.2583 0.9169 1.2896 5.7326
0.06 0.9346 1.4620 8.2917 0.9187 1.2904 5.7707
0.08 0.9355 1.4648 8.3560 0.9199 1.2924 5.8490
0.10 0.9356 1.4680 8.4511 0.9224 1.2936 5.9011
….. Continue
Section-I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005 88
….. ContinueConc.
MDensity
ρg.cm-3
VelocityU. 10-5
cm.s-1
Viscosityη.103
poise
Densityρ
g.cm-3
VelocityU. 10-5
cm.s-1
Viscosityη.103
poise
DMF THF
PAB-106
0.00 0.9304 1.4416 7.8072 0.8911 1.2852 5.5154
0.01 0.9356 1.4528 8.2097 0.9124 1.2892 5.7657
0.02 0.9372 1.4548 8.2882 0.9134 1.2904 5.7945
0.04 0.9386 1.4564 8.3225 0.9152 1.2916 5.8137
0.06 0.9388 1.4588 8.3990 0.9164 1.2932 5.8376
0.08 0.9391 1.4604 8.5292 0.9169 1.2940 5.8528
0.10 0.9395 1.4628 8.5672 0.9189 1.2956 5.8814PAB-107
0.01 0.9347 1.4468 8.1715 0.9185 1.2924 5.6602
0.02 0.9348 1.4480 8.1942 0.9187 1.2936 5.7478
0.04 0.9350 1.4496 8.2044 0.9188 1.2944 5.8028
0.06 0.9351 1.4508 8.2229 0.9198 1.2960 5.8333
0.08 0.9354 1.4524 8.2415 0.9211 1.2972 5.8969
0.10 0.9359 1.4536 8.2580 0.9223 1.2988 5.9461
PAB-108
0.01 0.9339 1.4444 8.2362 0.9134 1.2904 5.8559
0.02 0.9350 1.4476 8.2691 0.9153 1.2920 5.9171
0.04 0.9365 1.4504 8.2990 0.9156 1.2936 5.9470
0.06 0.9374 1.4552 8.3269 0.9181 1.2956 6.0038
0.08 0.9383 1.4568 8.3546 0.9197 1.2968 6.0647
0.10 0.9393 1.4604 8.3875 0.9213 1.2980 6.0899PAB-109
0.01 0.9339 1.4544 8.0771 0.9138 1.2888 5.7141
0.02 0.9349 1.4564 8.1165 0.9148 1.2900 5.7952
0.04 0.9360 1.4584 8.1850 0.9155 1.2912 5.9022
0.06 0.9366 1.4600 8.2839 0.9164 1.2928 5.9793
0.08 0.9378 1.4612 8.3498 0.9179 1.2944 6.0377
0.10 0.9387 1.4632 8.5351 0.9192 1.2960 6.1267PAB-110
0.01 0.9329 1.4468 8.1762 0.9126 1.2892 5.6894
0.02 0.9333 1.4520 8.2571 0.9128 1.2904 5.7681
0.04 0.9334 1.4544 8.3245 0.9158 1.2920 5.8487
0.06 0.9359 1.4560 8.4070 0.9178 1.2936 5.8854
0.08 0.9363 1.4580 8.4717 0.9189 1.2944 5.9362
0.10 0.9371 1.4596 8.5343 0.9214 1.2956 6.0433
Section-I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005 89
5. Rao’s molar sound function:
Rao’s molar sound function (Rm) can be evaluated by an equation given by
Bagchi et al.95
1 3m
MR U
… ... (3.1.10)
6. Van der Waals Constant:
Van der Waals constant (b) can be calculated as follows96
2
21 1 1
3
M RT MUb
MU RT
... (3.1.11)
where R is the gas constant (=8.3143 JK-1 mol-1) and T is the absolute temperature.
7. Relaxation Strength:
The relaxation strength (r) can be calculated as follows97
2
1rUU
… (3.1.12)
where U = 1.6 x 105 cm .sec-1.
8. Relative Association (RA):
1 3
0
0A
UR
U
… (3.1.13)
where U, 0U and ρ , 0ρ are ultrasonic velocities and densities of solution and solvent
respectively.
9. Apparent Molar Compressibility (k):
The apparent molar compressibility ( K ) of the solutions was calculated by the
following equation:
Section-I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005 90
0 00 2
0 0
1000s s sK
M
c
... (3.1.14)
where ρ0 and 0s are density and isentropic compressibility of pure solvent respectively, c
is the concentration of the solution and M2 is the molecular weight of the compound.
10. Solvation number:
0
2
1
1 100
s
sn
M XS
M X
… (3.1.15)
where X is the number of grams of solute in 100 gm of the solution. M1 and M2 are the
molecular weights of solvent and solute respectively.
Some of the calculated acoustical parameters are given in Tables 3.1.2 and 3.1.3
for all the compounds in DMF and THF solutions respectively. Figures 3.1.1 and 3.1.2
show the variation of ultrasound velocity (U) with concentration in DMF and THF
respectively. It is observed that overall ultrasonic velocity (U) increases non linearly with
concentration for all the compounds in both the solvents. The velocity depends on
intermolecular free length ( Lf ). Comparison of ultrasonic velocity and intermolecular
free length (Tables 3.1.2 and 3.1.3) shows these two parameters are inversely related. The
decrease in the free length causes velocity to increase or vice versa. As evident from
Tables 3.1.2 and 3.1.3, Lf decrease continuously which is due to strong interaction
between solvents and compound molecules. This causes velocity to increase.
This is further supported by isentropic compressibility ( κs ) and relaxation
strength (r). The isentropic compressibility ( κs ) of the solutions in both the solvents is
also found to decrease with increase of concentration, as shown in Figures 3.1.3 and
3.1.4.
This phenomenon can be explained by assuming that the solvated molecules fully
compressed by the electrical forces of the ions98
. The compressibility of the solution is
mainly due to the free solvent molecules. Due to solute-solvent interactions in the system,
compressibility of the solution decreases with the increase in solute concentration. This is
further confirmed by decrease of relaxation strength (r) and increase in specific
impedance (Z) values (as reported in Tables 3.1.2 and 3.1.3).
Section-I
Department of Chemistry, Saurashtra University, Rajkot
Figure 3.1.1: The variation of
concentration in
1.440
1.445
1.450
1.455
1.460
1.465
1.470
0
U.1
0-5
(cm
.s-1
)
PAB-101
1.440
1.445
1.450
1.455
1.460
1.465
0
U.1
0-5
(cm
.s-1
)
PAB-
I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005
ariation of ultrasonic velocity (U) of PAB compounds
concentration in DMF at 303.15 K.
0.02 0.04 0.06 0.08
Concentration (M)
101 PAB-102 PAB-103 PAB-104
0.02 0.04 0.06 0.08
Concentration (M)
-106 PAB-107 PAB-108 PAB-109
Acoustical properties
91
) of PAB compounds with
0.1
PAB-105
0.1
PAB-110
Section-I
Department of Chemistry, Saurashtra University, Rajkot
Figure 3.1.2: The variation of
concentration
1.284
1.288
1.292
1.296
1.300
1.304
0
U.1
0-5
(cm
.s)-1
PAB-101
1.288
1.290
1.292
1.294
1.296
1.298
1.300
0
U.1
0-5
(cm
.s-1
)
PAB-106
I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005
ariation of ultrasonic velocity (U) of PAB compounds
concentration in THF at 303.15 K.
0.02 0.04 0.06 0.08
Concentration (M)
101 PAB-102 PAB-103 PAB-104
0.02 0.04 0.06 0.08
Concentration (M)
106 PAB-107 PAB-108 PAB-109
Acoustical properties
92
compounds with
0.1
PAB-105
0.1
PAB-110
Section-I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005 93
Table 3.1.2: Some acoustical parameters of PAB compounds in DMF at 303.15 K.
Conc.M
Z .10-5
g.cm-2
Lf
Ao
Rm.10-3
cm-8/3.s-1/3
bcm3.mol-1 r RA
PAB-101
0.00 1.3413 1.5077 4.1191 78.5558 0.1882 1.00000.01 1.3462 1.5037 4.1314 78.7470 0.1855 1.00150.02 1.3493 1.5005 4.1512 79.0724 0.1823 1.00120.04 1.3556 1.4939 4.1914 79.7287 0.1755 1.00030.06 1.3593 1.4905 4.2277 80.3668 0.1724 1.00050.08 1.3613 1.4886 4.2645 81.0369 0.1705 1.00040.10 1.3644 1.4860 4.2973 81.6305 0.1687 1.0013
PAB-102
0.01 1.3458 1.5048 4.1328 78.8017 0.1873 1.00260.02 1.3473 1.5033 4.1569 79.2408 0.1859 1.00270.04 1.3492 1.5016 4.2045 80.1260 0.1846 1.00290.06 1.3509 1.4998 4.2539 81.0362 0.1828 1.00280.08 1.3540 1.4973 4.2989 81.8632 0.1810 1.00360.10 1.3575 1.4949 4.3390 82.6115 0.1801 1.0054
PAB-103
0.01 1.3492 1.5033 4.1213 78.5982 0.1882 1.00590.02 1.3512 1.5015 4.1459 79.0451 0.1868 1.00630.04 1.3534 1.4995 4.1979 80.0059 0.1850 1.00650.06 1.3561 1.4970 4.2499 80.9609 0.1828 1.00660.08 1.3589 1.4941 4.3028 81.9230 0.1801 1.00650.10 1.3622 1.4909 4.3562 82.8860 0.1769 1.0063
PAB-104
0.01 1.3503 1.5020 4.1225 78.7303 0.1868 1.00390.02 1.3527 1.4998 4.1474 79.1701 0.1850 1.00440.04 1.3553 1.4974 4.1998 80.1523 0.1828 1.00420.06 1.3587 1.4941 4.2527 81.1342 0.1796 1.00390.08 1.3623 1.4904 4.3064 82.1305 0.1760 1.00320.10 1.3644 1.4885 4.3586 82.9592 0.1742 1.0049
PAB-105
0.01 1.3565 1.4928 4.1418 78.7637 0.1742 0.99990.02 1.3603 1.4895 4.1618 79.0998 0.1714 1.00040.04 1.3630 1.4866 4.2085 79.9372 0.1683 0.99990.06 1.3664 1.4833 4.2533 80.7351 0.1651 0.99980.08 1.3703 1.4798 4.2962 81.4975 0.1619 1.00010.10 1.3735 1.4765 4.3431 82.3289 0.1582 0.9995
Continue…..
Section-I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005 94
….. Continue
Conc.M
Z .10-5
g.cm-2
Lf
Ao
Rm.10-3
cm-8/3.s-1/3
bcm3.mol-1 r RA
PAB-106
0.00 1.3413 1.5077 4.1322 78.5558 0.1882 1.00000.01 1.3592 1.4919 4.1521 78.6023 0.1755 1.00300.02 1.3634 1.4886 4.1978 78.9452 0.1733 1.00420.04 1.3669 1.4859 4.2493 79.7839 0.1714 1.00540.06 1.3695 1.4832 4.2997 80.7187 0.1687 1.00510.08 1.3715 1.4814 4.3505 81.6472 0.1669 1.00500.10 1.3743 1.4786 4.1322 82.5651 0.1641 1.0049
PAB-107
0.01 1.3524 1.4988 4.1341 78.7475 0.1823 1.00350.02 1.3536 1.4975 4.1641 79.2968 0.1810 1.00330.04 1.3553 1.4957 4.2234 80.3958 0.1792 1.00310.06 1.3566 1.4944 4.2825 81.4985 0.1778 1.00290.08 1.3586 1.4925 4.3408 82.5776 0.1760 1.00290.10 1.3604 1.4908 4.3979 83.6416 0.1746 1.0031
PAB-108
0.01 1.3490 1.5019 4.1357 78.8206 0.1850 1.00320.02 1.3536 1.4977 4.1633 79.2882 0.1814 1.00360.04 1.3584 1.4936 4.2179 80.2768 0.1783 1.00460.06 1.3642 1.4880 4.2771 81.3138 0.1728 1.00440.08 1.3669 1.4857 4.3331 82.3494 0.1710 1.00500.10 1.3717 1.4812 4.3906 83.3725 0.1669 1.0052
PAB-109
0.01 1.3583 1.4916 4.1321 78.5709 0.1737 1.00080.02 1.3616 1.4888 4.1458 78.7968 0.1714 1.00140.04 1.3651 1.4858 4.1751 79.3173 0.1692 1.00220.06 1.3674 1.4838 4.2066 79.8866 0.1673 1.00240.08 1.3703 1.4816 4.2347 80.3978 0.1660 1.00340.10 1.3735 1.4789 4.2649 80.9331 0.1637 1.0039
PAB-110
0.01 1.3497 1.5003 4.1351 78.7655 0.1823 1.00150.02 1.3552 1.4946 4.1602 79.1487 0.1764 1.00070.04 1.3576 1.4920 4.2058 79.9740 0.1737 1.00030.06 1.3627 1.4884 4.2400 80.5940 0.1719 1.00260.08 1.3651 1.4860 4.2837 81.3880 0.1696 1.00260.10 1.3678 1.4838 4.3252 82.1465 0.1678 1.0031
Section-I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005 95
Table 3.1.3: Some acoustical parameters of PAB compounds in THF at 303.15 K.
Conc.M
Z .10-5
g.cm-2
Lf
Ao
Rm.10-3
cm-8/3.s-1/3
bcm3.mol-1 r RA
PAB-101
0.00 1.1452 1.7281 4.0775 80.7969 0.3548 1.00000.01 1.1790 1.7021 3.9860 78.9496 0.3532 1.02770.02 1.1819 1.6984 4.0044 79.2653 0.3508 1.02780.04 1.1852 1.6945 4.0402 79.9241 0.3483 1.02800.06 1.1893 1.6897 4.0745 80.5461 0.3455 1.02860.08 1.1933 1.6848 4.1111 81.2013 0.3423 1.02870.10 1.1977 1.6791 4.1493 81.8726 0.3382 1.0283
PAB-102
0.01 1.1810 1.6993 3.9932 79.0521 0.3512 1.02740.02 1.1834 1.6963 4.0180 79.5028 0.3492 1.02730.04 1.1863 1.6932 4.0637 80.3741 0.3475 1.02810.06 1.1895 1.6891 4.1132 81.2933 0.3447 1.02800.08 1.1930 1.6845 4.1635 82.2207 0.3415 1.02760.10 1.1978 1.6783 4.2142 83.1281 0.3370 1.0271
PAB-103
0.01 1.1795 1.7012 3.9957 79.1257 0.3524 1.02730.02 1.1835 1.6970 4.0169 79.5058 0.3504 1.02870.04 1.1865 1.6936 4.0680 80.4756 0.3483 1.02920.06 1.1896 1.6901 4.1188 81.4377 0.3463 1.02970.08 1.1918 1.6877 4.1688 82.4004 0.3451 1.03040.10 1.1943 1.6852 4.2179 83.3466 0.3439 1.0312
PAB-104
0.01 1.1759 1.7038 4.0080 79.3708 0.3524 1.02420.02 1.1788 1.7009 4.0296 79.7726 0.3512 1.02550.04 1.1825 1.6975 4.0753 80.6530 0.3500 1.02740.06 1.1860 1.6941 4.1210 81.5316 0.3488 1.02920.08 1.1887 1.6912 4.1713 82.4936 0.3471 1.02980.10 1.1919 1.6876 4.2212 83.4371 0.3451 1.0305
PAB-105
0.01 1.1749 1.7053 4.0020 79.2762 0.3536 1.02460.02 1.1774 1.7027 4.0209 79.6251 0.3524 1.02550.04 1.1824 1.6978 4.0565 80.2886 0.3504 1.02780.06 1.1855 1.6951 4.0938 81.0111 0.3496 1.02960.08 1.1889 1.6913 4.1347 81.7775 0.3475 1.03040.10 1.1933 1.6874 4.1682 82.4151 0.3463 1.0329
Continue…..
Section-I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005 96
….. Continue
Conc.M
Z .10-5
g.cm-2
Lf
Ao
Rm.10-3
cm-8/3.s-1/3
bcm3.mol-1 r RA
PAB-106
0.00 1.1452 1.7281 4.0775 80.7969 0.3548 1.00000.01 1.1762 1.7025 4.0123 79.4216 0.3508 1.02280.02 1.1786 1.7000 4.0349 79.8448 0.3496 1.02360.04 1.1821 1.6967 4.0791 80.6943 0.3483 1.02530.06 1.1851 1.6935 4.1263 81.5945 0.3467 1.02630.08 1.1865 1.6920 4.1758 82.5557 0.3459 1.02660.10 1.1905 1.6881 4.2190 83.3769 0.3443 1.0284
PAB-107
0.01 1.1871 1.6926 3.9925 78.9643 0.3475 1.02890.02 1.1884 1.6909 4.0224 79.5322 0.3463 1.02870.04 1.1893 1.6898 4.0813 80.6798 0.3455 1.02860.06 1.1921 1.6867 4.1367 81.7414 0.3439 1.02930.08 1.1948 1.6840 4.1903 82.7752 0.3427 1.03050.10 1.1979 1.6808 4.2444 83.8089 0.3411 1.0314
PAB-108
0.01 1.1786 1.7000 4.0134 79.4199 0.3496 1.02360.02 1.1826 1.6961 4.0362 79.8383 0.3479 1.02540.04 1.1844 1.6937 4.0962 80.9904 0.3463 1.02520.06 1.1895 1.6888 4.1457 81.9283 0.3443 1.02760.08 1.1926 1.6858 4.1990 82.9546 0.3431 1.02900.10 1.1959 1.6827 4.2510 83.9570 0.3419 1.0305
PAB-109
0.01 1.1777 1.7017 3.9965 79.1180 0.3512 1.02450.02 1.1801 1.6992 4.0096 79.3526 0.3500 1.02540.04 1.1821 1.6970 4.0407 79.9438 0.3488 1.02580.06 1.1847 1.6940 4.0713 80.5160 0.3471 1.02640.08 1.1881 1.6906 4.0990 81.0303 0.3455 1.02760.10 1.1912 1.6873 4.1274 81.5565 0.3439 1.0286
PAB-110
0.01 1.1765 1.7023 4.0079 79.3344 0.3508 1.02310.02 1.1778 1.7006 4.0307 79.7612 0.3496 1.02290.04 1.1832 1.6957 4.0632 80.3721 0.3479 1.02590.06 1.1872 1.6917 4.0999 81.0643 0.3463 1.02770.08 1.1895 1.6896 4.1395 81.8295 0.3455 1.02880.10 1.1937 1.6858 4.1731 82.4699 0.3443 1.0312
Section-I
Department of Chemistry, Saurashtra University, Rajkot
Figure 3.1.3: The variation of
with concentration in
4.95
5.00
5.05
5.10
5.15
5.20
0
ks.1
011
(cm
2 .d
yn-1
)
PAB-101
4.95
5.00
5.05
5.10
5.15
5.20
0
ks.1
011
(cm
2 .d
yn-1
)
PAB-106
I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005
ariation of isentropic compressibility (κs) of PAB compounds
with concentration in DMF at 303.15 K.
0.02 0.04 0.06 0.08
Concentration (M)
101 PAB-102 PAB-103 PAB-104
0.02 0.04 0.06 0.08
Concentration (M)
106 PAB-107 PAB-108 PAB-109
Acoustical properties
97
PAB compounds
0.1
PAB-105
0.1
PAB-110
Section-I
Department of Chemistry, Saurashtra University, Rajkot
Figure 3.1.4: The variation of
with concentration in THF
6.35
6.40
6.45
6.50
6.55
6.60
6.65
0
ks.1
011
(cm
2.d
yn-1
)
PAB-101
6.40
6.45
6.50
6.55
6.60
6.65
0
ks.1
011
(cm
2 .d
yn-1
)
PAB-106
I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005
ariation of isentropic compressibility (κs) of PAB compounds
with concentration in THF at 303.15 K.
0.02 0.04 0.06 0.08
Concentration (M)
101 PAB-102 PAB-103 PAB-104 PAB
0.02 0.04 0.06 0.08
Concentration (M)
106 PAB-107 PAB-108 PAB-109
Acoustical properties
98
compounds
0.1
PAB-105
0.1
PAB-110
Section-I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005 99
Further, molar compressibility (W) is observed to increase linearly in both the
solvents for all the studied compounds as shown in Figures 3.1.5 and 3.1.6. The Rao’s
molar sound function (Rm) and Vander Waal’s constant (b) are also observed to increase
linearly (correlation coefficient 0.9920-0.9998) with concentration for all the compounds
in both the solvents. The linear increase of these parameters shows absence of complex
formation in these systems.
From the Tables 3.1.2 and 3.1.3, it is also observed that the relative association
also increases with concentration almost for all the compounds in both the solvents
suggesting thereby predominance of solute-solvent interactions in the studied systems.
The type of interactions in a solution can also be confirmed by the solvation
number, which is a measure of structure forming or structure breaking tendency of a
solute in a solution. Figures 3.1.7 and 3.1.8 show that for all the compounds, solvation
number (Sn) increases with concentration. Further, these Sn values are positive for all the
compounds in both the solvents. The positive Sn values suggest structure forming
tendency of compounds in solution. This further confirms that there exist strong solute-
solvent interactions in the studied solutions.
The isentropic compressibility of all the solutions was also fitted to the following
Bachem’s relation99:
0 3 2s s AC BC … (3.1.16)
From the plot of 0 /s s C verses √C, values of A and B were evaluated from
the intercept and slope respectively. 0s is the isentropic compressibility of pure solvent.
Further, the apparent molar compressibility (k) of the solutions is fitted to Gucker’s
relation100:
k = ok + Sk √C … (3.1.17)
From the plot of k verses √C, ok and Sk values are evaluated from the intercept
and slope. Sk is known as interaction parameter.
The apparent molar volumes ΦV of the solutions were calculated by the following
equation:
Φv = M/ρ-[1000(ρ-ρ0)/ρc]
... (3.1.18)
Section-I
Department of Chemistry, Saurashtra University, Rajkot
Figure 3.1.5: The variation of
with concentration in DMF
2.30
2.35
2.40
2.45
2.50
0 0.01
W.1
0-3
(cm
-1.d
yn-1
)
PAB
2.30
2.35
2.40
2.45
2.50
0
W.1
0-3
(cm
-1.d
yn-1
)
PAB-
I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005
ariation of molar compressibility (W) of PAB compounds
with concentration in DMF at 303.15 K.
0.02 0.03 0.04 0.05 0.06 0.07 0.08
Concentration (M)
PAB-101 PAB-102 PAB-103 PAB-104
0.02 0.04 0.06 0.08
Concentration (M)
-106 PAB-107 PAB-108 PAB-109
Acoustical properties
100
PAB compounds
0.08 0.09 0.1
PAB-105
0.1
PAB-110
Section-I
Department of Chemistry, Saurashtra University, Rajkot
Figure 3.1.6: The variation of
with concentration in THF
2.20
2.25
2.30
2.35
2.40
0
W.1
0-3
(cm
-1.d
yn-1
)
PAB-
2.20
2.25
2.30
2.35
2.40
0
W.1
0-3
(cm
-1.d
yn-1
)
PAB
I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005
ariation of molar compressibility (W) of PAB compounds
with concentration in THF at 303.15 K.
0.02 0.04 0.06 0.08
Concentration (M)
-101 PAB-102 PAB-103 PAB-104
0.02 0.04 0.06 0.08
Concentration (M)
PAB-106 PAB-107 PAB-108 PAB-109
Acoustical properties
101
PAB compounds
0.1
PAB-105
0.1
PAB-110
Section-I
Department of Chemistry, Saurashtra University, Rajkot
Figure 3.1.7: The Variation of
concentration in DMF
0.00
1.00
2.00
3.00
4.00
5.00
6.00
0
Sn
PAB-101
0.00
1.00
2.00
3.00
4.00
5.00
0
Sn
PAB-106
I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005
Variation of solvation number (Sn) of PAB compounds
concentration in DMF at 303.15 K.
0.02 0.04 0.06 0.08
Concentration (M)
101 PAB-102 PAB-103 PAB-104
0.02 0.04 0.06 0.08
Concentrtaion (M)
106 PAB-107 PAB-108 PAB-109
Acoustical properties
102
PAB compounds with
0.1
PAB-105
0.1
PAB-110
Section-I
Department of Chemistry, Saurashtra University, Rajkot
Figure 3.1.8: The Variation of
concentration in THF
0.00
0.50
1.00
1.50
2.00
2.50
0
Sn
PAB-
0.00
0.50
1.00
1.50
2.00
2.50
0
Sn
PAB-106
I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005
Variation of solvation number (Sn) of PAB compounds
concentration in THF at 303.15 K.
0.02 0.04 0.06 0.08
Concentration (M)
101 PAB-102 PAB-103 PAB-104
0.02 0.04 0.06 0.08
Concentration (M)
106 PAB-107 PAB-108 PAB-109
Acoustical properties
103
of PAB compounds with
0.1
PAB-105
0.1
PAB-110
Section-I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005 104
and were fitted in the relation:
ΦV = ΦVo +Sv C ... (3.1.19)
From the plot of ΦV verses C, ΦVo and Sv values were calculated from the
intercept and slope respectively. Sv is the measure of solute-solvent interactions. All these
values are given in Table 3.1.4.
It is evident from Table 3.1.4 that in both DMF and THF solutions, A, ok, and Φ
V
o
values are negative whereas B, Sk and Sv values are positive. The lower or negative A, B,
ok confirms interaction between solvent and compound molecules. Further, negative
values of ΦV
oimplies electrostrictive solvation of ions(101,102) i.e., more compressibility in
solution. Table 3.1.4 shows that in comparison to DMF, for THF solutions, A, ok and Φ
V
o
are more negative whereas B, Sk and Sv values are more positive. This suggests that
compressibility is higher in THF than that in DMF solutions. Further, the positive and
higher values of interaction parameters Sk and Sv confirms the predominance of solute-
solvent interactions in studied systems.
Thus, it is concluded that in the studied systems, solute-solvent interactions
dominate in both DMF and THF solutions.
Section-I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005 105
Table 3.1.4: The Bachem’s constants A and B, ok and Sk, ΦV
o and Sv of PAB
compounds in DMF and THF at 303.15 K.
Comp.
A X 1011
dyn-1. cm3
mol-1
B X 1011
dyn-1.cm-1/2
mol-3/2
ok X 108
dyn-1.mol-1
Sk X 108
dyn-1cm-3/2
mol-3/2
ΦVo
cm2 . mol-1
Sv
cm2.dm1/2
.mol-3/2
DMFPAB-101 -3.38 5.94 -3.38 9.26 -4.995 351.1
PAB-102 -2.69 7.70 -2.93 11.99 -116.3 2323
PAB-103 -2.01 3.08 -5.66 19.36 -170.2 1938
PAB-104 -1.96 2.26 -5.18 18.86 -236.9 3968
PAB-105 -6.01 12.62 -12.44 39.81 -42.87 710.2
PAB-106 -5.50 11.28 -10.94 33.21 -335.4 4085
PAB-107 -3.49 7.64 -9.31 35.37 -185.5 2787
PAB-108 -4.99 11.46 -5.26 15.64 -124.0 1194
PAB-109 -6.62 15.20 -11.08 35.28 -64.54 576.7
PAB-110 -7.82 27.49 -6.84 20.97 -93.23 1123
THF
PAB-101 -11.03 23.61 -19.13 47.96 -869.7 6694
PAB-102 -11.58 25.28 -19.69 50.61 -689.6 4731
PAB-103 -12.34 29.20 -20.51 54.37 -900.8 6919
PAB-104 -10.61 24.28 -17.94 46.93 -678.7 4498
PAB-105 -10.37 23.53 -17.71 45.45 -652.4 4048
PAB-106 -11.12 26.16 -17.96 47.63 -608.6 3997
PAB-107 -13.68 32.57 -21.73 57.42 -706.8 4597
PAB-108 -11.99 27.37 -18.61 47.47 -648.9 4119
PAB-109 -10.79 24.80 -17.98 46.32 -606.3 3885
PAB-110 -11.39 26.35 -18.31 47.13 -630.3 3937
Section-I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005 106
REFERENCES
1. Niyogi, S.; Roy, P. and Roychaudhuri, M.; “Acousto-ultrasonic study on
hydration of portland cement.” Cera. Trans. (Adv. Cem. Mater.) 1991, 37-45.
2. Ranachowski, J. and Rejmund, F.; “Acoustic emission in thermomechanical
studies of Ceramics and cement Material.” Prace. Komi. Nau. Cera. 1994, 177-
186.
3. Ohtsu, M.; Shigeishi, M. and Munwam, M.; “Damage mechanics and fracture
mechanics of concrete by SiGMA.” J. Acou. Emis. 1998, 16(1-4), S 65-74.
4. Craver, J.; “Ultrasonic impedometric studies in the cellulose pulp water system.”
Trans. Symp. 1966, 1, 445-472.
5. Dion, J.; Garceau, J. and Morissette, J.; “Acousto-optical evaluation of fiber size
in wood pulp.” Proc. SPIE Int. Soc. Opt. Eng. 1986, 665, 361-365.
6. Moran, T.; Batra, N.; Bucholtz, F. and Thomas, R.; “Elastic properties of
manganese (II) oxide-alumina-silica glasses.” J. Ultra. Symp. Proc. 1974, 506-
508.
7. Berret, J.; Pelous, J.; Vacher, R.; Raychaudhuri, A. and Schmidt, M.; “Acoustic
properties and relationship with the low frequency light scattering in an optical
glass.” J. Non-Cryst. Solids. 1986, 87(1-2), 70-85.
8. Kezionis, A.; Orliukas, A.; Samulionis, V.; Jakubowski, W.; Bogusz, W. and B.
Wnetrzewski; “Electrical and ultrasonic properties of AgI, AgPO3 glasses.”
Lietuvos Fizikos Zurnalas. 1995, 35(3), 202-205.
9. Vasantharani, P.; Karthikeyani, K. and Vijayakumari; “Thermal expansion and
acoustical properties of zinc bismuth borate glasses.” Bull. Pure & App. Sci. 2007,
26D(2), 67-72.
10. Mehrotra, K. and Upadhyaya S.; “Acoustical studies of calcium soaps.” Acou.
Lett. 1987, 11(4), 66-71.
11. Mehrotra, K.; Shukla, R. and Chauhan M.; “Ultrasonic studies on neodymium
soap solutions.” Acustica. 1991, 75(1), 82-85.
12. Mehrotra, K. and Jain M.; “Ultrasonic measurements of chromium(III) soaps in
chloroform.” Acous. Lett. 1994, 18(3), 50-54.
13. Mehrotra, K. and Anis, M.; “Apparent molar volume and acoustic behaviour of
zirconyl soap solutions in benzene-chloroform mixture.” J. Ind. Chem. Soc. 1997,
74(9), 720-722.
Section-I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005 107
14. Upadhyay, S.; Shukla, R. and Sharma, G.; “Acoustic behaviour of dysprosium
soaps in methanol.” Asi. J. Chem. 2007, 19(4), 2993-2998.
15. Botto, R.; “Applications of ultrasonic nebulization in the analysis of petroleum
and petrochemicals by inductively coupled plasma atomic emission spectrometry”
J. Anal. Atom. Spectro.1993, 8, 51-57.
16. Amani, M.; Najafi I. and Makarem, M.; “Application of ultrasound waves to
increase the efficiency of oxidative desulfurization process” Adv. Petro. Exp. Dev.
2011, 2(2) 63-69.
17. Pena, P.; Ivascan, L.; Georgescu, V. and Iacob.; “Investigations reffering to
Utilization of the ultrasonic devices to prevent depositions in oil refining plants.”
Chimie. 2005, 13, 113-120.
18. Anderson, B.; “Technical plan for nondestructive examination technology
development.” Avail. NTIS. Rep. 1982, 33.
19. Yan, J.; Li, D.; Dong, Z. and Zhen, Y.; “Analysis and measurement of acoustic
power in plastics ultrasonic welding process.” China Welding 1998, 7(2), 106-
111.
20. Meysam, A. and Mehdi, A.; “The application of Acoustic Emission technique to
plastic deformation of low carbon steel” Physics Procedia. 2010, 3(1), 795-801.
21. Kun, Y.; Jiaping, Lu.; Yuejie, Xie. and Jie, Sun.; “Application of ultrasound
technology in the dairy processing” Zhongguo Rupin Gongye. 2009, 37(11), 29-
32.
22. Zhanjun, Z. and Fuhua, W.; “Application of ultrasound techniques in traditional
liquor-making industry” Niangjiu. 2009, 36(4), 27-29.
23. McNeil, S. J. and McCall, R. A.; “Ultrasound for wooldyeing and finishing”
Ultra. Sonochem. 2011, 18(1), 401-406.
24. Foguel, M.; Uliana, C.; Tomaz, U.; Marques, O.; Yamanaka, H. and Ferreira, A.;
“Evaluation of the CDtrode cleaning constructed from gold recordable
CD/galvanoplasty tape” Ecletica Quimica. 2009, 34(2), 59-66.
25. Qian J.; “Method for cleaning parts of equipment in semiconductor device
fabrication” Chinese Pat. Appl. Patent No. CN 101439341, 2009, 9
26. Nanda, S.; Rao, R. and Anand, S.; “Use of factorial design in sonophoretic
transdermal delivery of propranolol HCL” Ind. Pharm. 2010, 9(98), 49-54.
Section-I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005 108
27. Buyukkamaci, N.; Filibeli, A. and Erden, G.; “Effect of low frequency ultrasound
on anaerobic biodegradability of meat processing effluent”
Desalination. 2010, 259(13), 223-227.
28. Hong-xia, G.; Xiu-qiong, Guan.; Hong-ru, B. and Kui, Wang.; “Application of
ultrasound wave in bamboo pulp bleaching” Yinran Zhuji 2010, 27(2), 34-35.
29. Li, Xie.; Wei, Z.; Zifeng, L. and Xuhong, M.; “Study on the application of
ultrasonic in the esterification deacidification of high-acid crude oil” Shiyou
Lianzhi Yu Huagong 2010, 41(1), 6-10.
30. Juan, C.; Jose, G.; Antonio, Mulet.; Ligia, R. and Enrique, R.; “Ultrasonically
assisted antioxidant extraction from grape stalks and olive leaves” Procedia.
2010, 3(1), 147-152.
31. Mason, T.; Chemat, F. and Vinatoru, M.; “The Extraction of Natural Products
using Ultrasound or Microwaves” Curr. Org. Chem. 2011, 15(2), 237-247.
32. Weihua, Z.; Aixiang, W.; Chunfang, Zhang.; Xiaoping, L. and Pingfang, H.;
“Application of ultrasound in the viscosity reduction of vacuum residuum”
Huagong Jinzhan 2009, 28(11),1896-1900.
33. Chaowu, Z.; Fangyuan, Z.; Fen W.; Jun,Y. and Ling, X.; “Ultrasonic co-deposit
fabrication of Si-Ha nanopowder and mechanical performance of its Bio-cement”
Zhongguo Taoci Gongye 2010, 17(4), 23-27.
34. Levina, M.; Michael, H.; Rubinstein.; Ali, R. and Siahboomi, R.; “Principles and
application of ultrasound in pharmaceutical powder compression” Pharma. Res.
2000, 17(3), 257-265.
35. Isariebel, Q; Carine, J.; Ulises-Javier, J.; Anne-Marie, W. and Henri, D.;
“Sonolysis of levodopa and paracetamol in aqueous solutions” Ultra. Sonochem.
2009, 16(5), 610-616.
36. Hong, Y.; Xuemian, L.; Jiguang, L.; Yuantong, G. and Min, X.; “Application
value of ultrasonic measurement of intra-abdominal fat in assessment of
abdominal obesity” Hebei Yike Daxue Xuebao 2010, 31(1), 71-73.
37. Patil, M. and Onuora V.; “The value of ultrasound in the evaluation of patients
blunt scrotal trauma” Injury 1994, 25(3), 177-178.
38. Szenci, O.; Taverne, M.; Beckers, J.; Varga, J.; Börzsönyi, L.; Hanzen, C. and
Schekk, G.; “Evaluation of false ultrasonographic diagnoses in cows by
Section-I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005 109
measuring plasma levels of bovine pregnancy-associated glycoprotein” Veterinary
Record 1998, 142, 304-306.
39. Perlmutter, G.; Goldberg, B. and Charkes, N.; “Ultrasound evaluation of the
thyroid” Seminars in Nuclear Medicine 1975, 5(4), 299-305.
40. Meizne, I. and Bar-Ziv, J.; “Prenatal ultrasonic diagnosis of anterior abdominal
wall defects” Eur. J. Obst. Gyn. Repro. Bio.1986, 22(4), 217-224.
41. Lovett, I.; Doust, B. and Orr, N.; “The Role of Ultrasound in the Diagnosis of
Parenchymal Disease in Transplanted Kidneys” Aust. Radio. 1988, 32(1), 104–
106.
42. Edward, S.; Amis, J.; John, J.; Cronan, M.; Richard, C.; Pfister, M.; Isabel, C. and
Yoder, M.; “Ultrasonic inaccuracies in diagnosing renal obstruction” Urology
1982, 19(1),101-105.
43. Boucaud, A.; Machet, L.; Arbeille, B.; Machet, M. C.; Sournac, M.; Mavon, A.;
Patat, F. and Vaillant, L.; “In vitro study of low-frequency ultrasound-enhanced
transdermal transport of fentanyl and caffeine across human and hairless rat skin”
Int. J. Pharma. 2001, 228(1-2), 69-77.
44. Annema, J.; Versteegh, M.; Veseliç, M.; Welker, L.; Mauad, T.; Sont, J.; Willems,
L. and Rabe, K.; “Endoscopic Ultrasound Added to Mediastinoscopy for
Preoperative Staging of Patients with Lung Cancer” JAMA 2005, 294(8), 931-936.
45. Nehmat, H.; Stefano, C.; Turner, R.; Cody, H. and Macaskill, P.; “Preoperative
Ultrasound-Guided Needle Biopsy of Axillary Nodes in Invasive Breast Cancer:
Meta-Analysis of Its Accuracy and Utility in Staging the Axilla” Annal. Surgery
2011, 254 (2), 243–251.
46. Husseini, G. and Pitt, W.; “Ultrasonic activated micellar drug delivery for cancer
treatment” J. Pharm. Sci. 2009, 98(3), 795-811.
47. Winkler, P. and Helmke, K.; “Ultrasonic diagnosis and follow-up of malignant
brain tumors in childhood A report of 4 cases and a review of the literature”
Pediatric Radiology 1985, 15(4), 215-219.
48. Tanaka, K.; Kazufumi M.; Ito, M. and Toshio Wagai, M.; “The Localization of
Brain Tumors by Ultrasonic Techniques” J. of Neurosur. 1965, 23(2), 135-147.
49. Hernandez, A.; Goldring, D.; Alexis, F.; Hartmann, J.; Charles Crawford, B. and
Reed, G.; “Measurement of blood pressure in infants and children by Doppler
ultrasonic technique” Pediatrics 1971, 48(5), 788-794.
Section-I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005 110
50. Harvey, D.; Prince, J.; Bunton, J.; Parkinson, C. and Campbell, S.; “Abilities of
Children Who Were Small-for-Gestational-Age Babies” Pediatrics 1982, 69(3),
296-300.
51. Papanicolaou, N.; Pfister, R.; Young, H.; Yoder, I. and Herrin, J.; “Percutaneous
ultrasonic lithotripsy of symptomatic renal calculi in children” Pediatric
Radiology 1986,16(1), 13-16.
52. Uchigasaki, S.; Oesterhelweg, L.; Gehl, A.; Sperhake, J.; Püschel, K.; Oshida, S.;
Nemoto, N.; “Application of compact ultrasound imaging device to postmortem
diagnosis” For. Sci. Inter. 2004, 140(1), 33-41.
53. Uchigasaki, S.; Oesterhelweg, L.; Sperhake, J.; Püschel, K. and Oshida, S.;
“Application of ultrasonography to postmortem examination: Diagnosis of
pericardial tamponade” For. Sci. Inter. 2006, 162(1-3), 167-169.
54. Qifa Z.; Sienting, L.; Dawei, W. and Shung, K.; “Piezoelectric films for high
frequency ultrasonic transducers in biomedical applications” Prog. Mat. Sci.
2011, 56(2), 139-174.
55. Houhui, S.; Lu, Lin.; Wei, H. and Jian, Xu.; “Application of ultrasonic-mediated
genetic transformation of microorganism” Faming Zhuanli Shenging Chinese Pat.
Appl. 2010, Patent No CN 101875947 A 20101103.
56. Hong-zhi, W.; Zhi-xian, Z.; Rong-rong, Miao.; Su-wei, Y. and Wei-guo, Zhang.;
“Pulsed ultrasound enhances nanoparticle penetration into breast cancer
spheroids” Diandu Yu Jingshi 2010, 32(2),15-20.
57. Haijun, Z.; Hui, J.; Huangping, W.; Juan, Z.; Baoan, C. and Xuemei, W.;
“Ultrasound mediated drug-loaded nanoparticles crossing cell membranes as a
new strategy to reverse cancer multidrug resistance” J. Nanosci. Nanotech. 11(3)
2011, 1834-1840.
58. Yong, Li.; Xiao-ling, G. and Cha-fang, Q.; “Application of ultrasonic technology
in preparation and photocatalysis of nano-TiO2” Yinran Zhuji 2009, 26(9), 9-12.
59. Chaowu, Z.; Fangyuan, Z.; Fen, W.; Jun, Yang. and Ling, X.; “Ultrasonic co-
deposit fabrication of Si-Ha nanopowder and mechanicalperformance of its bio-
cement” Zhongguo Taoci Gongye 2010, 17(4), 23-27.
60. Ayachit, N.; Vasan, S.; Sannaningannavar, T. and Deshpande, D.;
“Thermodynamic and acoustical parameters of some nematic liquid crystals.” J.
Mol. Liq. 2007, 133(1-3), 134-138.
Section-I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005 111
61. Ming Yang, H. and Yi Peng, G.; “Ultrasound-assisted third-liquid phase-transfer
catalyzed esterification of sodium salicylate in a continuous two-phase-flow
reactor” Ultra. Sonochem. 2010, 17(1), 239-245.
62. Katoh, R.;Yokoi, H.; Usuba, S.; Kakudate, Y. and Fujiwara, S.; “Sonochemical
polymerization of benzene derivatives: the site of the reaction.” Ultra. Sonochem.
1998, 5(2), 69-72.
63. Kruger, O.; Schulze, T. and Peters, D.; “Sonochemical treatment of natural ground
water at different high frequencies: preliminary results.” Ultra. Sonochem. 1999,
6(1-2), 123-128.
64. Zhao, Y.; Liao, X.; Hong, J. and Zhu, J.; “Synthesis of lead sulphide nanocrystals
via microwave and sonochemical methods” Mat. Chem. Phys. 2004, 87(1), 149-
153.
65. Mexiarová, M. and Kiripolský, T.; “The sonochemical arylation of active
methylene compounds.” Ultra. Sonochem. 2005, 12(5), 401-403.
66. Ming Yang, H. and Cheng Chiu, C.; “Ultrasound-assisted phase-transfer catalysis:
Benzoylation of sodium 4-acetylphenoxide by dual-site phase-transfer catalyst in
a tri-liquid system” Ultra. Sonochem. 2011, 18(1), 363-369.
67. Jun Hong, Y.; Yusheng, C. and Yi, P.; “Application of sonochemistry in the
isomerization of carbon-carbon double bonds” J. Poly. Sci. Part A
2010, 48(22), 5254-5257.
68. Suyog, A.; Ravindra, D.; Kakasaheb, M.; Anant, P. and Peter,Y.; “Ultrasound
assisted cocrystallization from solution (USSC) containing a non-congruently
soluble cocrystal component pair: Caffeine/maleic acid” Eur. J. Pharm. Sci.
2010, 41(5), 597-602.
69. Park, M. and Do Yeo, S.; “Antisolvent Crystallization of Roxithromycin and the
Effect of Ultrasound” Sep. Sci. Tech. 2010, 45, 1402–1410.
70. Shengdan, Y. and Dayou, F.; “Application of ultrasonic wave, microwave-assisted
extraction and their combined extraction technology for extracting effective
constituents from Chinese herbal medicine” Guangdong Huagong 2010,
37(2), 120-122.
71. Kim, M.; Kemp K. and Letcher, S.; “Ultrasonic measurement in liquid alkali
metals.” J. Acous. Soc. Am. 1971, 49(3), 706-712.
Section-I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005 112
72. Raman, S. and Tipnis, C.; “Ultrasonic studies in camphene solutions.” Ind. J. Pure
App. Phys. 1982, 20(1), 79-80.
73. Inoue, N.; Hasegawa, T. and Matsuzawa, K.; “Ultrasonic velocity measurement of
liquids in the frequency range 0.2-7 MHz using an improved ultrasonic
interferometer.” Acustica 1991, 74(2), 128-133.
74. Takagi, T.; “Ultrasonic velocity in binary mixtures under high pressures and their
thermodynamic properties.-Binary mixture for nitrobenzene-aniline.” Review
Phys. Chem. 1978, 48(1), 10-16.
75. Nath, J. and Dixit, A.; “Ultrasonic velocities in, and adiabatic compressibilities
for, binary liquid mixtures of acetone with benzene, toluene, p-xylene, and
mesitylene at 308.15 K.” J. Chem. Eng. Data. 1984 29(3), 320-321.
76. Ali, A.; Nain, A. and Kamil, M.; “Physical-chemical studies of non-aqueous
binary liquid mixtures at various temperatures.” Thermo. Chim. Acta, 1996, 274,
209-221.
77. Ezhil Raj, A.; Resmi, L.; Bena Jothy, V.; Jayachandran, M. and Sanjeeviraja, C.;
“Ultrasonic study on binary mixture containing dimethylformamide and methanol
over the entire miscibility range (0 < x < 1) at temperatures 303–323 K” Fluid
Phase Equi. 2009, 281(1), 78-86.
78. Pancholy, M. and Singal S.; “Ultrasonic studies in aqueous solutions of
electrolytes.” J. Sci. Ind. Res. 1962, 21B (2), 70-73.
79. Kim, W.; Yu, M.; Choi, I. and Kim, M.; “Measurement of ultrasonic relaxational
characteristics in aqueous solution of ZnCl2-DMF.” Ungyong Mulli 1998, 11(6),
675-682.
80. Laux, D.; Leveque, G. and Cereser, C.; “Ultrasonic properties of water/sorbitol
solutions.” Ultrasonics 2009, 49(2), 159-161.
81. Hassun, S.; Shihab, A. and Jassim, F.; “Studies on ultrasonic absorption and
visco-relaxation of poly (ethylene glycol) aqueous solutions.” Chin. J. Poly. Sci.
1989, 7(3), 270-279.
82. Srivastava, S. and Laxmi, S.; “Ultrasonic studies of amino acids” Z. Phys. Chem.
1970, 70, 219-223.
83. Sharma, P.; Chauhan, S.; Chauhan, M. and Syal, V.; “Ultrasonic velocity and
viscosity studies of tramacip and parvodex in binary mixtures of alcohol + water”
Ind. J. Pure Appl. Phys. 2008, 46 (12), 839-843.
Section-I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005 113
84. Baluja, S.; Solanki, A. and Kachhadia, N.; “An ultrasonic study of some drugs in
solutions.” Russ. J. Phys. Chem. 2007, 81, 859-863.
85. Sasaki, K. and Arakawa, K.; “Ultrasonic and thermodynamic studies on the
aqueous solutions of tetramethylurea.” Bull. Chem. Soc. Jpn. 1973, 46(9), 2738-
2741.
86. S. Baluja; “Acoustical studies of some Schiff bases in 1,4-dioxane and
dimethylformamide at 318.15 K.” Chin. J. Chem. 2006, 24(10), 1327-1331.
87. Godvani, N.; Movaliya J. and Baluja, S.; “Acoustical studies of some derivatives
of 1,5-benzodiazepines at 298.15 K.” Russ. J. Phys. Chem. 2009, 83(13), 2223-
2229.
88. Gajera, R.; Bhalodia, R. and S. Baluja; “Synthesis and ultrasonic studies of some
dihydropyrimidines in different solvent at 298.15 K.” Int. J. Appl. Chem. 2009,
5(1), 47-55.
89. Riddick, J.; Bunger, W. and Sakano T.; “Organic solvents-Physical properties and
Methods for purification” 4th Edition, Techniques of Chemistry, Vol.II, Wiely,
New York 1986.
90. Ubbelhode, L.; “The simplest and most accurate viscometer and other apparatus
employing the hanging level.” J. Inst. Pet. 1933, 19, 376-420.
91. Robinson, R. and Stokes, R.; "Electrolyte Solutions", Butterworths Scientific
Publications, London; 1955.
92. Sastry, G.; Sastry, V. and Krishnamurty, B.; “Ultrasonic parameters in mixed salt
solutions.” Ind. J. Pure Appl. Phy. 1968, 6, 637-638.
93. Jacobson, B.; Nature (London), 1954, 173, 772-773.
94. Wada; Y.; “The relation between compressibility and molal volume of
organicliquids” J. Phy. Soc. Jpn. 1949, 4, 280-283.
95. Sendhilnathan, S.; Bagchi, S.; Nema, S. and Singh R.; “Ultrasonic and rheological
investigations of solid propellant binders” Euro. Poly. J. 1989, 25, 441-444.
96. Vigoureux, P.; “Ultrasonics”, Chapman and Hall, London 1952.
97. Johri G. K. and Misra R. C.; “Phase-transition study and ultrasonic investigations
in tert-butyl alcohol (TBA)” Ind. J. Phy. 1985, 59, 482-488.
98. Yawale, S.; Pakade, S. and Adagonkar, S.; “Solid state variable frequency pulser-
receiver system for ultrasonic measurements.” I. J. pure. App. Phy. 1995, 33, 638-
642.
Section-I Acoustical properties
Department of Chemistry, Saurashtra University, Rajkot-360005 114
99. Bachem, C.; Electrochem. 1935, 41,570.
100. F.T. Gucker (Jr.), Chem. Rev.1993, 64, 111.
101. Korey, V. B.; “Adiabatic compressibilities of some aqueous ionic solutions and
their variation with indicated liquid structure of the water” Phys. Rev. 1993, 64,
350-357.
102. Nikam, P. S and Hiray, R. A.; “Temperature and concentration dependence of
ultrasonic velocity and allied parameters of monochloro acetic acid in ethanol-
nitrobenzene mixtures” Ind. J. Pure appl. Phys. 1991, 29, 601-605.
Section-II
Solubility
Section-II Solubility
Department of Chemistry, Saurashtra University, Rajkot-360005 115
INTRODUCTION
The solubility of pharmaceuticals compounds is an important aspect of drug
development. The knowledge of an accurate solubility is needed for the design of
separation processes such as extractive crystallization or for the safe operation of different
processing units such as distillation columns, absorption units and extraction plants.
The extensive information on the thermodynamic properties of organic
compounds is needed not only their use in many industrial processes but also for the
advancement of theoretical developments through an understanding of the intermolecular
forces-solution structure-property relationship. Literature survey shows that many
researchers have studied the solubility of gases1, organic compounds2-4, amino acids5,6,
polymers7-9, ionic liquids10,11, inorganic compounds12-15, drugs16-19 etc.
In the field of pharmaceutical research, solubility is a key factor to concentrate20
as it is pivotal to determine the bio availability of drugs21. So, many researchers have
studied the solubility of various drugs like difloxacin22, clopidogril23, oxaprozin24,
bupivacaine25, aciclovir26, ibuprofen27 etc.
To study the solubility, various methods have been used such as HPLC28,
Differential Scanning Calorimetry29, 1H and 13P NMR30, laser monitoring observation
technique31 etc. Solubility of drugs can also be predicted by various theoretical methods32
like multiple linear regression33, general solubility equation34, group contribution
approach35 etc.
The dissolution of a solute in a solvent is accompanied by the heat change. If the
heat is absorbed, i.e., the solution is cooler, the enthalpy change (∆H) would be positive.
If the heat is evolved, solution is warmer and so enthalpy change would be negative.
Thus, the heat of solution is defined as the change in enthalpy, when one mole of
substance is dissolved in specified quantity of solvent at a given temperature. By using
the computation of solubility data, thermodynamics parameters of solution can also be
deduced36.
Our research group has actively engaged to study the solubility of various drug
APIs (Active Pharmaceutical Ingredients)37,38 and other bio active heterocyclic molecules 39,40.
Section-II Solubility
Department of Chemistry, Saurashtra University, Rajkot-360005 116
In this chapter, solubility study of some tetrahydropyrimidine derivatives (PAB-
101 to PAB-110) have been done in various solvents such as methanol, ethanol, isopropyl
alcohol and tetrahydrofuran, at various temperatures (293.15 to 313.15K). Further, some
thermodynamic parameters such as dissolution enthalpy, Gibb’s energy of dissolution and
entropy have also been evaluated from the solubility data.
Section-II Solubility
Department of Chemistry, Saurashtra University, Rajkot-360005 117
EXPERIMENTAL
All the synthesized compounds were recrystallized in chloroform. The solubility
of these synthesized compounds (PAB-101 to PAB-110) is determined in methanol,
ethanol, isopropyl alcohol and tetrahydrofuran. The choice of these solvents is due to
their different dielectric constants and solubility of compounds.
All these selected solvents were purified by fractional distillation and its purity
was checked by HPLC.
The gravimetric method41 was used to study the solubility. An excess mass of
compound was added to a known mass of solvent. The solution was warmed to a constant
temperature with continuous stirring. After, at least 3 hr the stirring was stopped and the
solution was kept at a constant temperature for 2 hr. A portion of this solution was filtered
and by a preheated injector, 5 ml of this clear solution was taken to pre weighted
measuring vial (m0). The vial was quickly and tightly closed and weighted (m1) to
determine the mass of the sample (m1- m0). To prevent dust contamination, the vial was
covered with a piece of filter paper. After completely dryness of vial mass, the vial was
reweighed (m2) to determine the mass of the constant residue solid (m2- m0). All the
weights were taken using electronic balance ( Mettler Toledo AB204-S, Switzerland)
with uncertainty of 0.0001 g. The procedure was repeated three times at each
temperature.
Section-II Solubility
Department of Chemistry, Saurashtra University, Rajkot-360005 118
RESULTS AND DISCUSSION
Using the weights of residues and solvents, the mole fraction solubility (x) of the
compound in the solution is determined by the equation:
2 0 1
2 0 1 1 2 2
( ) /
( ) / ( ) /
m m Mx
m m M m m M
… (3.2.1)
where M1 and M2 are the molar mass of compound and solvent respectively. For each
solvent, the experiment was repeated three times at each temperatures and an average
value is given in Tables 3.2.1 to 3.2.4 for all the selected solvents.
It is obvious from these tables that the solubility is much higher in THF in
comparison to alcohols. In the studied alcohols, maximum solubility is observed for
compound PAB-103 and minimum for PAB-104. However, in THF, maximum solubility
is observed for PAB-102 and minimum is observed for PAB-108.
The variation of solubility with temperature is also shown in Figures 3.2.1 to 3.2.4
for all the compounds in the studied solvents. It is evident from these figures that
solubility increases with temperature for all the compounds in the studied solvents.
Further, the temperature dependence of solubility in solvents is studied by the following
modified Apelblat equation42,43:
ln x = A + B/T + C lnT ... (3.2.2)
where x is the mass fraction solubility of compound, T is the absolute temperature and A,
B and C are the parameters. The values of these parameters are also given in Table 3.2.5.
Using these parameters, values of solubility (xc) were evaluated and are given in
Tables 3.2.1 to 3.2.4. Further, root-mean-square deviations (RMSD) were calculated by
equations (3.2.3) and are listed in Table 3.2.5.
1/ 22
1
( )
1
Nci i
i
x xRMSD
N
… (3.2.3)
where N is the number of experimental points and xci is the calculated solubility.
Using experimental data of solubility in different solvents, some thermodynamic
parameters such as dissolution enthalpy, Gibb’s energy of dissolution and entropy have
also been evaluated.
Section-II Solubility
Department of Chemistry, Saurashtra University, Rajkot-360005 119
Table 3.2.1: The experimental mole fraction solubility (x) and calculated solubility
(xc) of tetrahydropyrimidine derivatives (PAB) in methanol at different
temperatures.
Temp.K
x. 103 xc.103 x. 103 xc.103
PAB-101 PAB-106
293.15 2.3355 2.4577 0.7946 0.7973
298.15 2.7406 2.8905 0.9063 0.9104
303.15 3.1486 3.2921 1.0281 1.0363
308.15 3.4323 3.6382 1.1783 1.1762
313.15 3.7212 3.9087 1.3229 1.3311
PAB-102 PAB-107
293.15 2.4890 2.5186 0.9903 0.9937
298.15 2.8392 2.8875 1.2376 1.2248
303.15 3.1960 3.2090 1.4849 1.5180
308.15 3.3958 3.4636 1.9204 1.8910
313.15 3.5996 3.6376 2.3533 2.3668
PAB-103 PAB-108
293.15 3.4381 3.2917 2.0302 2.1090
298.15 3.5237 3.3757 2.0928 2.1698
303.15 3.6168 3.4630 2.1296 2.2293
308.15 3.7144 3.5536 2.2177 2.2874
313.15 3.8097 3.6476 2.2491 2.3440
PAB-104 PAB-109
293.15 0.5055 0.5031 1.5909 1.5793
298.15 0.5303 0.5273 1.8949 1.8458
303.15 0.5517 0.5480 2.2075 2.2584
308.15 0.5666 0.5648 2.9960 2.8837
313.15 0.5814 0.5778 3.8391 3.8322
PAB-105 PAB-110
293.15 1.0337 1.0665 1.9735 2.0592
298.15 1.3007 1.3287 1.9931 2.0815
303.15 1.5713 1.6386 2.0126 2.0981
308.15 1.9606 2.0014 2.0180 2.1091
313.15 2.3465 2.4222 2.0262 2.1148
Section-II
Department of Chemistry, Saurashtra University, Rajkot
Figure 3.2.1: The variation
compounds
0.000
0.001
0.002
0.003
0.004
0.005
290 295
X
0.000
0.001
0.002
0.003
0.004
0.005
290 295
x
II
Department of Chemistry, Saurashtra University, Rajkot-360005
The variation of mole fraction solubility x with temperature
in methanol.
295 300 305 310
Temperature (K)PAB-101 PAB-101PAB-102 PAB-102 PAB-103 PAB-103 PAB-104 PAB-104PAB-105 PAB-105
295 300 305 310Temperature (K)
PAB-106 PAB-106 PAB-107 PAB-107 PAB-108 PAB-108 PAB-109 PAB-109 PAB-110 PAB-110
Solubility
120
with temperature for PAB
315
315
Section-II Solubility
Department of Chemistry, Saurashtra University, Rajkot-360005 121
Table 3.2.2: The experimental mole fraction solubility (x) and calculated solubility
(xc) of PAB compounds in ethanol at different temperatures.
Temp.K
x. 103 xc.103 x. 103 xc.103
PAB-101 PAB-106
293.15 1.3072 1.3675 1.7157 1.7662
298.15 1.7253 1.7821 1.7743 1.8425
303.15 2.1403 2.2514 1.8616 1.9161
308.15 2.6533 2.7623 1.9291 1.9868
313.15 3.1631 3.2974 1.9864 2.0544
PAB-102 PAB-107
293.15 1.3191 1.3927 1.0706 1.0732
298.15 1.6316 1.7115 1.1833 1.1824
303.15 1.9492 2.0714 1.2898 1.2944
308.15 2.3545 2.4713 1.4071 1.4088
313.15 2.7542 2.9088 1.5225 1.5246
PAB-103 PAB-108
293.15 3.5601 3.6655 2.6090 2.6237
298.15 3.6772 3.7842 2.6994 2.7162
303.15 3.7829 3.8939 2.7894 2.8019
308.15 3.8768 3.9943 2.8609 2.8806
313.15 3.9688 4.0855 2.9366 2.9523
PAB-104 PAB-109
293.15 0.5222 0.5126 3.8183 3.7898
298.15 0.5503 0.5377 3.8222 3.7936
303.15 0.5783 0.5727 3.8263 3.7975
308.15 0.6365 0.6189 3.8305 3.8015
313.15 0.6892 0.6779 3.8345 3.8055
PAB-105 PAB-110
293.15 1.8953 1.8748 2.6738 2.7602
298.15 2.0290 1.9972 2.9140 3.0049
303.15 2.1626 2.1501 3.1545 3.2617
308.15 2.3760 2.3375 3.4243 3.5307
313.15 2.5930 2.5647 3.6908 3.8118
Section-II
Department of Chemistry, Saurashtra University, Rajkot
Figure 3.2.2: The variation
compounds in
0
0.001
0.002
0.003
0.004
0.005
290 295
X
0.0000
0.0010
0.0020
0.0030
0.0040
0.0050
290 295
X
II
Department of Chemistry, Saurashtra University, Rajkot-360005
of mole fraction solubility x with temperature
in ethanol.
295 300 305 310
Temperature (K)PAB-101 PAB-101PAB-102 PAB-102PAB-103 PAB-103 PAB-104 PAB-104 PAB-105 PAB-105
295 300 305 310Temperature (K)
PAB-106 PAB-106 PAB-107 PAB-107 PAB-108 PAB-108 PAB-109 PAB-109 PAB-110 PAB-110
Solubility
122
with temperature for PAB
315
315
Section-II Solubility
Department of Chemistry, Saurashtra University, Rajkot-360005 123
Table 3.2.3: The experimental mole fraction solubility (x), calculated solubility (xc)
of PAB compounds in isopropyl alcohol at different temperatures.
Temp.K
x. 103 xc.103 x. 103 xc.103
PAB-101 PAB-106
293.15 1.7325 1.7150 0.8418 0.86832
298.15 1.9229 1.8878 0.8843 0.91518
303.15 2.1056 2.1047 0.9330 0.96217
308.15 2.4231 2.3745 0.9778 1.00919
313.15 2.7347 2.7086 1.0220 1.05614
PAB-102 PAB-107
293.15 4.0837 3.9834 0.4842 0.4755
298.15 4.1653 4.0677 0.5022 0.4877
303.15 4.2664 4.1609 0.5082 0.5022
308.15 4.3717 4.2633 0.5319 0.5190
313.15 4.4834 4.3747 0.5495 0.5381
PAB-103 PAB-108
293.15 5.6778 5.5748 2.3497 2.4000
298.15 5.7814 5.6824 2.4980 2.5408
303.15 5.8845 5.7716 2.6398 2.7074
308.15 5.9458 5.8431 2.8527 2.9024
313.15 6.0066 5.8971 3.0632 3.1289
PAB-104 PAB-109
293.15 0.4671 0.4867 3.6885 3.5707
298.15 0.5047 0.531 3.7480 3.6336
303.15 0.5485 0.5658 3.8282 3.7076
308.15 0.5599 0.5897 3.9217 3.7925
313.15 0.5777 0.6020 4.0137 3.8884
PAB-105 PAB-110
293.15 0.8224 0.7842 2.8864 2.8319
298.15 0.9502 0.8969 3.2916 3.2116
303.15 1.0775 1.0422 3.7028 3.6718
308.15 1.3089 1.2290 4.3595 4.2294
313.15 1.5383 1.4693 4.9881 4.9058
Section-II
Department of Chemistry, Saurashtra University, Rajkot
Figure 3.2.3: The variation
compounds
0
0.001
0.002
0.003
0.004
0.005
0.006
0.007
290 295
X
0
0.001
0.002
0.003
0.004
0.005
0.006
290 295
X
II
Department of Chemistry, Saurashtra University, Rajkot-360005
The variation of mole fraction solubility x with temperature
compounds in isopropyl alcohol.
295 300 305 310Temperature (K)
PAB-101 PAB-101PAB-102 PAB-102PAB-103 PAB-103 PAB-104 PAB-104 PAB-105 PAB-105
295 300 305 310Temperature (K)
PAB-106 PAB-106 PAB-107 PAB-107 PAB-108 PAB-108 PAB-109 PAB-109 PAB-110 PAB-110
Solubility
124
with temperature for PAB
315
315
Section-II Solubility
Department of Chemistry, Saurashtra University, Rajkot-360005 125
Table 3.2.4: The experimental mole fraction solubility (x) and calculated solubility
(xc) PAB compounds in THF at different temperatures.
Temp.K
x. 103 xc.103 x. 103 xc.103
PAB-101 PAB-106
293.15 8.3590 8.7955 9.1415 9.4364
298.15 8.5903 9.0499 9.6052 9.9275
303.15 8.8212 9.2752 10.0701 10.3933
308.15 8.9873 9.4709 10.4860 10.8310
313.15 9.1530 9.6372 10.8784 11.2384
PAB-102 PAB-107
293.15 21.0426 21.9747 16.4174 16.5920
298.15 21.6805 22.6781 16.5749 16.7635
303.15 22.3133 23.2710 16.7336 16.9035
308.15 22.6998 23.7520 16.8228 17.0132
313.15 23.0872 24.1215 16.9100 17.0939
PAB-103 PAB-108
293.15 11.5150 12.1014 6.9170 7.1175
298.15 12.0429 12.6292 7.0822 7.2958
303.15 12.4813 13.1149 7.2556 7.4625
308.15 12.8859 13.5559 7.3964 7.6173
313.15 13.2852 13.9505 7.5377 7.7605
PAB-104 PAB-109
293.15 11.2591 10.9118 8.2134 8.1346
298.15 12.0687 11.5944 8.3264 8.2351
303.15 12.8938 12.6383 8.4152 8.3354
308.15 14.7346 14.1087 8.5199 8.4356
313.15 16.6013 6.1050 8.6250 8.5357
PAB-105 PAB-110
293.15 15.4735 14.7188 8.2966 8.5012
298.15 15.5848 14.8336 8.3941 8.6027
303.15 15.7250 14.9523 8.4921 8.6995
308.15 15.8547 15.0748 8.5743 8.7917
313.15 15.9845 15.2009 8.6642 8.8794
Section-II
Department of Chemistry, Saurashtra University, Rajkot
Figure 3.2.4: The variation
compounds
0.000
0.005
0.010
0.015
0.020
0.025
0.030
290 295
x
0.004
0.006
0.008
0.010
0.012
0.014
0.016
0.018
290 295
X
II
Department of Chemistry, Saurashtra University, Rajkot-360005
The variation of mole fraction solubility x with temperature
compounds in tetrahydrofuran.
295 300 305 310Temperature (K)
PAB-101 PAB-101PAB-102 PAB-102 PAB-103 PAB-103 PAB-104 PAB-104 PAB-105 PAB-105
295 300 305 310Temperature (K)
PAB-106 PAB-106 PAB-107 PAB-107 PAB-108 PAB-108 PAB-109 PAB-109 PAB-110 PAB-110
Solubility
126
with temperature for PAB
315
315
Section-II Solubility
Department of Chemistry, Saurashtra University, Rajkot-360005 127
Table 3.2.5: Coefficient A, B and C of equation 3.2.2 and Root Mean Square Deviation (RMSD) of PAB compounds in different solvents.
Compounds A B C104
RMSDA B C
104
RMSD
Methanol Ethanol
PAB -101 650.84 -31438.39 -96.75 1.8415 549.75 -28520.52 -80.81 1.1085
PAB -102 646.2 -30853.69 -96.28 0.4859 209.6 -12614.36 -30.48 1.2683
PAB -103 -32.51 810.07 4.23 1.7254 50.54 -2954.79 -8.11 1.2482
PAB -104 167.46 -8436.42 -25.75 0.03281 -416.72 17374.83 61.59 0.1336
PAB -105 77.91 -7010.54 -10.71 0.58747 -307.87 12390.4 45.65 0.3104
PAB -106 -30.06 -956.71 4.61 0.0642 37.52 -2566.06 -6.18 0.6736
PAB -107 -296.33 9687.27 45.13 0.2404 74.26 -5022.78 -11.26 0.03062
PAB -108 6.57 -984.84 -1.65 0.9481 54.45 -3183.21 -8.72 0.1801
PAB -109 -1228.76 51705.93 184.12 0.6665 -6.72 35.48 0.18 0.32153
PAB -110 55.06 -2866.87 -9.06 0.9829 1.78 -1600.02 -0.39 1.1537
Isopropyl alcohol THF
PAB -101 -385.27 15320.36 57.5 0.3382 69.41 -3700.3 -10.83 5.1876
PAB -102 -63.21 2238.66 8.81 1.1646 110.84 -5535.32 -16.86 11.1337
PAB -103 65.65 -3414.52 -10.42 1.1795 84.02 -4542.43 -12.84 7.0374
PAB -104 498.18 -23647.46 -74.84 0.2674 -666.94 28375.61 99.57 5.1204
PAB -105 -488.72 19288.85 73.19 0.6454 -14.86 354.91 1.66 8.5917
PAB -106 14.48 -1732.03 -2.75 0.3414 76.09 -4322.34 -11.62 3.6875
PAB -107 -119.92 4584.6 17.01 0.1234 35.98 -1924.1 -5.9 2.0313
PAB -108 -204.98 7946.11 30.25 0.6277 29.24 -1878.37 -4.89 2.3829
PAB -109 -83.46 3180.31 11.79 1.3587 -9.9 42.6 0.87 0.9477
PAB -110 -294.36 10882.28 44.25 0.9219 3.03 -520.89 -1.06 2.3562
Section-II Solubility
Department of Chemistry, Saurashtra University, Rajkot-360005 128
According to van’t Hoff analysis, the standard enthalpy change of solution is
obtained from the slope the ln x versus 1/T plot. However, in recent thermodynamic
treatments, some modifications have been introduced in the van’t Hoff equation to
diminish the propagation of errors and consequently to separate the chemical effects from
those due to statistical treatment used when enthalpy-entropy compensation plots are
developed42. For this reason, the mean harmonic temperature (Thm) is used in the van’t
Hoff analysis, which is calculated by modified van’t Hoff equation.
The enthalpy of solution (Hsol) was calculated by modified Van’t Hoff equation44
ln
1 1Sol
hm P
Hx
RT T
... (3.2.6)
where T is the experimental temperature and R is gas constant. Thm is the mean harmonic
temperature which is given as
1hm n
i
nT
T
... (3.2.7)
where n is the number of experimental temperatures. In the present case, the Thm value
obtained is only 302.99 K. The slope of the plot of ln x versus (1/T-1/Thm) gives the value
of Hsol.
The Gibbs energy change (Gsol) for the solubility process was then evaluated
from intercept of the above plot using following relation45:
ΔGsol = -RT. intercept ... (3.2.8)
Using these evaluated Hsol and Gsol values, the entropies of solutions Ssol were
obtained from equation
solsol
sol
hm
H - GS =
T ... (3.2.9)
All these thermodynamic parameters are given in Table 3.2.6.
It is evident from Table 3.2.6 that for all the compounds Hsol are Gsol values are
positive in all the studied solvents. However, Ssol values are negative for some
Section-II Solubility
Department of Chemistry, Saurashtra University, Rajkot-360005 129
compounds. When stronger bonds are broken and weaker bonds are formed, energy is
consumed. So, Hsol becomes positive49. This indicates endothermic dissolution of
Table 3.2.6: The thermodynamic parameters of PAB compounds in different
solvents.
Comp.
code
ΔHsol
kcal.mol-1ΔGsol
kcal.mol-1ΔSsol
cal.mol-1.K-1
ΔHsol
kcal.mol-1ΔGsol
kcal.mol-1ΔSsol
cal.mol-1.K-1
Methanol Ethanol
PAB-101 17.7067 14.6103 10.2195 33.5886 15.5348 59.5864
PAB-102 14.0451 14.5599 -1.6992 28.0847 15.7363 40.7558
PAB-103 3.9370 14.1614 -33.7456 4.1288 14.0576 -32.7701
PAB-104 5.2536 18.9229 -45.1152 10.6622 18.7188 -26.5908
PAB-105 31.3184 16.2477 49.7409 11.9588 15.4164 -11.4118
PAB-106 19.5667 17.3308 7.3796 5.7525 15.8497 -33.3257
PAB-107 33.1166 16.3484 55.3432 13.4022 16.7691 -11.1125
PAB-108 4.0115 15.4794 -37.8496 4.5029 14.8269 -34.0745
PAB-109 33.8046 15.2149 61.3554 0.1621 14.0183 -45.7323
PAB-110 0.9562 15.6431 -48.4740 12.3061 14.5095 -7.2726
Isopropyl alcohol Tetrahydrofuran
PAB-101 14.5079 15.9555 -4.7775 3.4653 11.9275 -27.9297
PAB-102 9.6276 16.8749 -23.9196 3.5401 9.5949 -19.9839
PAB-103 3.3762 15.1796 -38.9569 5.4055 11.0532 -18.6401
PAB-104 5.7225 14.7992 -29.9576 14.8559 10.8570 13.1984
PAB-105 0.8234 14.5624 -45.3455 1.2529 10.4590 -30.3845
PAB-106 5.0308 14.1871 -30.2203 6.6562 11.5950 -16.3006
PAB-107 7.8177 14.3760 -21.6459 0.9869 10.3129 -30.7804
PAB-108 0.2333 13.8470 -44.9321 3.3846 12.4137 -29.8004
PAB-109 26.1558 12.0031 46.7110 1.4832 12.0258 -34.7957
PAB-110 32.1004 11.8142 66.9543 1.6478 12.0132 -34.2108
Section-II Solubility
Department of Chemistry, Saurashtra University, Rajkot-360005 130
compounds. The endothermic effect in the dissolving process is perhaps because the
interactions between compound molecules and solvent molecules are more powerful than
those between the solvent molecules50. The positive value of Gsol indicates that the
dissolution process is not spontaneous49, 37. The entropy values are positive for some
compounds in some solvents whereas these values are negative in other solvents for few
compounds. The positive entropy indicates that dissolution process increases the
randomness in solution whereas negative entropy is due to more order in solutions51. This
depends on the functional groups present in the compound as well as on the solvent.
Different functional groups interact differently with the solvent, so randomness will be
different. It is observed that in tetrahydrofuran, entropy is negative for all the compounds
indicating thereby less randomness in this solvent. In alcohols, for some compounds,
randomness is more in methanol than in ethanol and isopropyl alcohol. So, entropy values
are positive for most of the compounds in methanol than other two alcohols.
Thus, it is concluded that for the studied compounds, dissolution process is not
completely enthalpy or entropy driven in the selected solvents.
Section-II Solubility
Department of Chemistry, Saurashtra University, Rajkot-360005 131
REFERENCES
1. Weiss, R.; “Solubility of nitrogen, oxygen, and argon in water and seawater”
Deep-Sea Res. Oceano. Abs. 1970, 17, 721-735.
2. Buchowski, H.; Ufnalski, W. and Jodzewicz, W.; “Solubility and hydrogen
bonding, part III solubility of 4-nitro-5-methylphenol in binary solvents” Roczniki
Chemii, 1977, 51, 2223-2232.
3. Regosz, A.; Krzykowska, Z.; Weclawska, K. and Chmielewska, A.; “Solubility
and thermo-dynamics of aqueous solutions of benzodiazepines” Pharmazie 1990,
45, 867-868.
4. Zhou, X.; Wang, Z. and Gao, J.; “Solubility of anthracene in butanol/alkane
binary solvent” Meitan Zhuanhua, 1995, 18, 84-89.
5. Amend, J. and Helgeson, H.; “Solubilities of the common L-α -amino acids as a
function of temperature and solution pH” Pure Appl. Chem. 1997, 69, 935-942.
6. Gao, L.; Liu, H.; Cai, S.; Chai, Y.; Liu, L. and Wu Y.; “Solubility behavior of four
diastereo-meric salts and two amino acids in near-critical CO2” Yao. Xue. 2002,
37, 355-358.
7. Tuminello, W.; “Solubility of polyand its copolymers” Fluoropolymers 1999, 2,
137-143.
8. Nagarajan, R.; “Solubilization vs. microemulsification in block copolymer-oil-
water systems” Abstracts of Papers, 224th ACS National Meeting, Boston, August
2002, 18-22.
9. Minati, L. and Biffis, A.; “A polymer support with controllable solubility in
mutually immiscible solvents” Chemi. Comm. 2005, 8, 1034-1036.
10. Freire, M.; Neves, C.; Carvalho, P.; Gardas, R.; Fernandes, A.; Marrucho, I.;
Santos, L. and Coutinho; J.; “Mutual Solubilities of Water and Hydrophobic Ionic
Liquids” J. Phy. Chem. 2007, 111, 13082-13089.
11. Kerle, D.; Ludwig, R.; Geiger, A. and Paschek, D.; “Temperature dependence of
the solubility of carbon dioxide in imidazolium-based ionic liquids” J. Phy.
Chemi. 2009, 113, 12727-12735.
12. Kruchenko, V.; “Solubility of gypsum in aqueous solutions of lithium salts” Khim.
Reaktsii, Alma-Ata. 1983, 29, 8-14.
Section-II Solubility
Department of Chemistry, Saurashtra University, Rajkot-360005 132
13. Zaitseva, I.; Sytnik, O.; Krasnoperova, A. and Bondarev N.; “Influence of
properties of nonaqueous solvents on the solubility of NH4Cl and thermody
namics of its solution” Russ. J. Gen. Chem. 2005, 75, 25-30.
14. Skriptun, I. and Zarubitski, O.; “Solubility of CrO3, MoO3 and WO3 oxides in
molten alkali” Ukra. Khimiche. Z. 2007, 73, 37-39.
15. Benezeth, P.; Dandurand, J. and Harrichoury, J.; “Solubility product of siderite
(FeCO3) as a function of temperature (25-250 oC)” Chemi. Geology 2009, 265, 3-
12.
16. Kim, C.; “Effects of drug solubility, drug loading, and polymer molecular weight
on drug release from polyox tablets” Drug Dev. Indu. Phar. 1998, 24, 645-651.
17. Li, J.; Masso, J. and Guertin, J.; “Prediction of drug solubility in an acrylate
adhesive based on the drug-polymer interaction parameter and drug solubility in
acetonitrile” J. Controlled Release. 2002, 83, 211-221.
18. Nti-Gyabaah, J. and Chiew, Y.; “Solubility of Lovastatin in ethyl acetate, propyl
acetate, isopropyl acetate, butyl acetate, sec-butyl acetate, isobutyl acetate, tert-
butyl acetate, and 2-butanone, between (285 and 313) K” J. Chem. Eng. Data.
2008, 53, 2060-2065.
19. Ali, S.; Mohammad, A.; William, E. and Abolghasem, J.; “Solubility if
Lamotrigine, Diazepam and Clonazepam in ethanol+water mixture at 298.15K” J.
Chem. Eng. Data. 2009, 54, 1107-1109.
20. Hughes, L.; Palmer, D.; Nigsch F. And Mitchell, J.; “Why Are Some Properties
More Difficult To Predict than Others? A Study of QSPR Models of Solubility,
Melting Point, and Log P” J. Chem. Inf. Model. 2008, 48, 220-232.
21. Muenster, U.; Pelzetter, C.; Backensfeld, T.; Ohm, A.; Kuhlmann, T.; Mueller, H.;
Lustig, K.; Keldenich, J.; Greschat, S.; Andreas, H.; Mark, G. and Gnoth, J.;
“Volume to dissolve applied dose (VDAD) and apparent dissolution rate (ADR):
Tools to predict in vivo bioavailability from orally applied drug suspensions” Eur.
J. Pharm. Bio. 2011, 78, 522–530.
22. Baluja, S.; Bhalodia, R.; Gajera, R.; Vekariya, N. and Bhatt, M.; “Solubility of
Difloxacin in Acetone, Methanol, and Ethanol from (293.15 to 313.15) K” J.
Chem. Eng. Data. 2009, 54, 1091–1093.
23. Song, L.; Minxu, Li. and Gong, J.; “Solubility of Clopidogrel Hydrogen Sulfate
(Form II) in Different Solvents” J. Chem. Eng. Data. 2010, 55, 4016–4018.
Section-II Solubility
Department of Chemistry, Saurashtra University, Rajkot-360005 133
24. Maestrelli, F.; Cirri, M.; Mennini, N.; Zerrouk, N.; Mura, P.; “Improvement of
oxaprozin solubility and permeability by the combined use of cyclodextrin,
chitosan, and bile components” Eur. J. Pharm. Bio. 2011, 78, 385–393.
25. Jug, M.; Mennini, N.; Melani, F.; Maestrelli, F. and Mura, P.; “Phase solubility,
1H NMR and molecular modelling studies of bupivacaine hydrochloride
complexation with different cyclodextrin derivates” Chem.Phy.Lett. 2010, 500,
347–354.
26. Brandi,G.; Rossi, L.; Giuditta, F.; Schiavano, M. and Magnani, M.; “A new
homodimer of aciclovir as a prodrug with increased solubility and antiviral
activity” Int. J. Anti. Age. 2009, 34,177–180.
27. Avdeef, A.; “Solubility of sparingly-soluble ionizable drugs” Adv.Drug Del.Rev.
2007, 59, 568–590.
28. Hua Mu, T.; SzeTan, S. and Lin Xue, Y.; “The amino acid composition, solubility
and emulsifying properties of sweet potato protein” Food Chemistry 2009, 112,
1002–1005
29. Bala, I.; Bhardwaj, V.; Hariharan, S. and Ravi Kumar, M.; “Analytical methods
for assay of ellagic acid and its solubility studies” J. Pharm. Bio. Ana. 2006, 40
(1) 206–210.
30. Bustamanate, P.; Romero, S.; Pen, A.; Escalera, B. and Reillo, A.; “Enthalpy-
Entropy Compensation for the Solubility of Drugs in SolventMixtures:
Paracetamol, Acetanilide, and Nalidixic Acid in Dioxane–Water” J. Pharm. Sci.
1998, 87(12), 1590-1596.
31. Zhi, X.; Guo. and Sheng Wang, L.; “Solubilities of Phosphorus-Containing
Compounds in Selected Solvents” J. Chem. Eng. Data. 2010, 55, 4709–4720.
32. Qiang Liu, J.; Qian, C. and Zhi Chen, X.; “Solubilities of 2,4-Dinitro-L-
phenylalanine in Monosolvents at (273.15 to 368.15) K” J. Chem. Eng. Data.
2010, 55, 5302–5304.
33. Jorgensena, W. and Duffyb, E.; “Prediction of drug solubility from structure” Adv.
Drug Del. Rev. 2002, 54, 355–366.
34. Mitchell, B. and Jurs, Peter.; “Prediction of Aqueous Solubility of Organic
Compounds from Molecular Structure” J. Chem. Inf. Comput. Sci. 1998, 38, 489-
496.
Section-II Solubility
Department of Chemistry, Saurashtra University, Rajkot-360005 134
35. Ran,Y. and Yalkowsky, S.; “Prediction of Drug Solubility by the General
Solubility Equation (GSE)” J. Chem. Inf. Comput. Sci. 2001, 41, 354-357.
36. Klopman, G. and Zhu, H.; “Estimation of the Aqueous Solubility of Organic
Molecules by the Group Contribution Approach” J. Chem. Inf. Comput. Sci. 2001,
41, 439-445.
37. Liang Zhang, C.; Zhao, F. and Wang, Y.; “Thermodynamics of the solubility of
sulfamethazine in methanol, ethanol,1-propanol, acetone, and chloroform from
293.15 to 333.15 K” J. Mol. Liq. 2011, 159, 170–172.
38. Baluja, S.; Bhalodia, R.; Bhatt, M.; Vekariya, N. and Gajera, R.; “Solubility of
Enrofloxacin Sodium in Various Solvents at Various Temperatures” J. Chem.
Eng. Data. 2008, 53, 2897–2899.
39. Baluja, S.; Gajera, R.; Bhalodia, R.; Vekariya, N. and Bhatt, M.; “Solubility of
Difloxacin in Acetone, Methanol and Ethanol from (293.15 to 313.15) K”. J.
Chem. Eng. Data. 2009, 54, 1091-1093.
40. Baluja, S.; Gajera, R. and Kulshreshtha, A.; “Solubility of biologically active
chalcones in 1, 4 - dioxane and N, N dimethyl formamide from (298.15 to 318.15)
K” J. Chem. Eng. Data. 2010, 55, 574–577.
41. Patel, A.; Vaghasiya, A.; Gajera, R.; and Baluja, S.; “Solubility of 5-amino
salicylic acid in different solvents at various temperatures” J. Chem. Eng. Data.
2010, 55, 1453-1455.
42. Zhu, M.; “Solubility and Density of the Disodium Salt Hemiheptahydrate of
Ceftriaxone in Water + Ethanol Mixtures” J. Chem. Eng. Data 2001, 46, 175-
176.
43. Apelblat, A. and Manzurola, E.; “Solubilities of o-acetylsalicylic, 4-aminosalic, 3,
5-di nitrosalicylic, and p-toluic acid, and magnesium DL-aspartate in water from
T= (278 to 348) K” J. Chem. Therm. 1999, 31, 85-91.
44. Gao, J.; Wang, Z.; Xu, D. and Zhang, R.; “Solubilities of triphenylphosphine in
ethanol, 2-propanol, acetone, benzene and toluene” J. Chem. Eng. Data. 2007,
52, 189-191.
45. Shalmashi, A. and Eliassi, A.; “Solubility of salicylic acid in water,ethanol,carbon
tetrachloride, ethyl acetate and xylene” J. Chem. Eng. Data. 2008, 53,199- 200.
46. Kong, M.; Shi, X.; Cao, Y. and Zhou, C.; “Solubility of imidacloprid in different
solvents.” J. Chem. Eng. Data 2008, 53, 199-200.
Section-II Solubility
Department of Chemistry, Saurashtra University, Rajkot-360005 135
47. Glasstone, S.; “Thermodynamics for Chemist”, Litton Edu.Pub.,Inc.New York.
48. Krug, R.; Hunter, W. and Grieger, R.; “Enthalpy-entropy compensation. 2.
Separation of the chemical from the statistical effects” J. Phys. Chem. 1976, 80,
2341-2351.
49. Kalsi, P.; “Organic reactions and their mechanisms.”(2nd Edition), New Age
International (P) Limited 2004, 119.
50. Triana, M. T.; Reyes, A. C.; Jimenez-Kairuz, A. F.; Manzo, R. H.; Martinez, F.;
“Solution and mixing thermodynamics of propranolol and atenolol in aqueous
media”, J. Sol. Chem., 2009, 38, 73-81.
51. El-Bindary, A.; El-Sonbati, A.; El-Mosalamy, E. and Ahmed, R.; “Potentiometric
and thermodynamic studies of Azosulfonamide drugs X” Chem. Pap. 2003, 57,
255-258.
Section-III
Density and refractive index
Section-III Density and refractive index
Department of Chemistry, Saurashtra University, Rajkot-360005 136
INTRODUCTION
The ratio of the velocity of light in vacuum to its velocity in the given medium is
known as refractive index. The refractive index of a material is the most important
property of any optical system that uses refraction.
The refractive index is a characteristic property of a substance, which depends
upon temperature and the wavelength of the light used. It decreases with increasing
temperature and wavelength. So, it is used to determine the structure and identity of
unknown compounds. It also determines isotropic and anisotropic behaviour of the crystal
by the arrangement of atoms1. The number of atoms, groups, radicals and bonds present
in the compound can also be calculated by refractive index measurement. Generally,
refractive index is a unit less number. Most compounds have refractive index values
between 1.3000 and 1.7000, but some materials give negative refractive index values and
are known as meta materials. These materials were first demonstrated for microwave
frequencies2.
The refractive index of a material medium is an important optical parameter since
it exhibits the optical properties of the material. It is important parameter in the design of
a solid state laser3.
Properties like refractive index, viscosity and density of binary liquid mixtures
over the whole composition range are useful for a full understanding of their
thermodynamic as well as for practical chemical engineering purposes and is also useful
for the adequate design of industrial processes4,5 and for theoretical purposes6. Various
applications of refractive index in optical fibers and other fields have also been reported7-
15. It is used in various industries to control manufacturing processes such as
fermentation16, dyes17, canning and preservation of food18,19 and for the identification or
assaying of some solids, liquids or constituents of a solution. A very well known
application is to determine the thickness of film20-24. Thus, this property has been used to
study various substances.
Nowadays refractive index also found useful in research related to medical
science and biotechnology25,26. Recent years have seen a rapid increase of research
interests in determining the cell physical parameters such as size, shape and refractive
index of living cells as demanded by biological studies and cell-based drug screening27,28.
Section-III Density and refractive index
Department of Chemistry, Saurashtra University, Rajkot-360005 137
The refractive index method also permits the determination of the concentration
distribution of solutes under non-destructive circumstances29.
Literature survey shows that refractive index of various types of materials such as
ionic liquids30-35, oils36,37, amino acids38, proteins39, sugar40,41, liquid crystals42,43, optical
fibres44-46, detergent47, photo sensitive materials48, nanomaterials49,50, holographic
materials51, various gases52, other materials53,54 etc has been reported.
The refractive index plays a vital role in various branches of science. It plays a
crucial role in instruments related to chemistry. Refractive index (RI) detection has been
successfully applied to many analytical techniques including HPLC55,56 size exclusion
chromatography57 and CE58,59. RI based detectors60 are more attractive alternatives to
fluorescence and absorption methods.
Further, various workers studied refractive index in liquid mixtures60-75, but scanty
work has been reported for the solutions of organic76-78, inorganic79-84 and polymeric
materials85-89. Study of solutions for solute-solute and solute-solvent interactions is found
to be attractive for researchers90-94 and have been studied by the knowledge of refractive
index. Refractive index of some aliphatic alcohols with dioxane has also been reported by
Sherstneva and Koleboshin95. Refractive index of methyl isobutyl ketone + pentanols has
also been measured by Riggio et al.96. Aal-Wahaibi et al. have reported refractive index
of ternary system: isopropyl alcohol + cyclohexane + water97. Campos et al. 98 have
determined the refractive index of formamide + water system. Aminabhavi99 has
predicted refractive index of some binary solvent mixtures. Govindan et al100 have
measured of refractive index of liquids using fiber optic displacement sensors.
Iulian, et al101 have studied Refractive index for water-organic component
homogeneous liquid mixtures. The characterization of an organic nonlinear optical crystal
urea ninhydrin monohydrate was also studied by refractive index measurement102.
In the present section, the density and refractive index of synthesized
tetrahydropyrimidine were measured in N, N-dimethylformamide and tetrahydrofuran
solutions of different concentrations. Further, molar refraction have been evaluated. From
these data, the refractive index and density of compounds were determined
Section-III Density and refractive index
Department of Chemistry, Saurashtra University, Rajkot-360005 138
EXPERIMENTAL
The solvents N. N-dimethyformamide (DMF) and tetrahydrofuran (THF) were of
LR grade and are fractionally distilled by the reported method103
. All the studied
synthesized tetrahydropyrimidine derivatives were recrystalized from chloroform. For
each compound, a series of solutions of different concentrations were prepared in DMF
and THF solvents.
The density and refractive index of solutions were measured by using pyknometer
and Abbe refractometer respectively at constant temperature 303.15 K. The temperature
was maintained by circulating water through jacket around the prisms of refractometer
from an electronically controlled thermostatic water bath (NOVA NV-8550 E). The
uncertainty of temperature was ±0.1o C. Mettler Toledo AB204-S, Switzerland electronic
balance with uncertainty of 0.0001 g, was used for all the weights taken for density
measurements.
The experimental data of density and refractive index of solutions are given in
Table 3.3.1.
Section-III Density and refractive index
Department of Chemistry, Saurashtra University, Rajkot-360005 139
RESULTS AND DISCUSSION
The density of solution (ρ12) is related to densities of the solvent, solute and their
weight fractions g1 and g2 according to the equation:
1 2
12 1 2
1 g g
… (3.3.1)
where ρ12 is the density of solution and ρ1 and ρ2 are the densities of solvent and solute
respectively. Table 3.3.1 shows the experimental values of densities and refractive index
for all the ten synthesized tetrahydropyrimidine in different solutions.
The slope of the plot of 1 121 g verses 2 1g g gives the density of these
compounds. The plot of 1 121 g verses 2 1g g is given in Figure 3.3.1 for PAB-101 in
DMF and THF respectively. The densities of all the synthesized compounds were
evaluated from the slope of such plots. The inverse of slope gives density of compound
(ρ2). Table 3.3.2 shows these calculated densities for all the compounds. Further, the
density of compounds were calculated by using the following equation (3.3.2),
A iKM N V … (3.3.2)
ρ indicates the density of the compound, K is packing fraction which is equal to 0.599 for
organic compounds, M is for molecular weight of the compound, NA is the Avogadro’s
number and ΔVi is the volume increment of the atoms and atomic groups present in the
compound. The density of all the studied compounds have been evaluated and reported in
Table 3.3.2. The calculated volume increment ΔVi for different atomic groups are given
in Table 3.3.3.
Comparison of densities evaluated from graphs and those calculated from eq.
(3.3.2) showed that calculated values are different from those evaluated graphically. For
the same compound, density in the two different solvents is different. This suggests that
one has to consider the role of solvent in the measurement of the physical parameters of
any solutions. It is because of the fact that, in every solution molecular interactions exists
which differs with different solvents. This is further confirmed by acoustical parameter
which is already discussed in Section I. Generally, intermolecular interactions do not
affect the density but due to the presence of different substituted groups in solutes,
interactions differ in different solvents which may cause change in volume thereby
affecting the density of solute in a particular solvent.
Section-III Density and refractive index
Department of Chemistry, Saurashtra University, Rajkot-360005 140
Table 3.3.1: The density (ρ12) and refractive index (n) of tetrrahydropyrimidine
derivatives in DMF and THF at 303.15 K.
Conc.(M)
DMF THF DMF THFρ12
(g.cm-3)n
ρ12
(g.cm-3)n
ρ12
(g.cm-3)n
ρ12
(g.cm-3)n
PAB-101 PAB-1060.00 0.9304 1.4171 0.8779 1.4032 0.9304 1.4171 0.8779 1.40320.01 0.9323 1.4237 0.8776 1.4038 0.9356 1.4260 0.8760 1.40410.02 0.9326 1.4246 0.8790 1.4047 0.9372 1.4262 0.8770 1.40580.04 0.9331 1.4260 0.8794 1.4056 0.9386 1.4268 0.8788 1.40790.06 0.9338 1.4275 0.8800 1.4069 0.9388 1.4272 0.8800 1.40940.08 0.9342 1.4289 0.8816 1.4081 0.9391 1.4280 0.8806 1.41000.10 0.9353 1.4304 0.8846 1.4093 0.9395 1.4288 0.8825 1.4114
PAB-102 PAB-1070.01 0.9330 1.4239 0.8790 1.4053 0.9347 1.4259 0.8820 1.40580.02 0.9333 1.4248 0.8804 1.4070 0.9348 1.4267 0.8823 1.40620.04 0.9338 1.4259 0.8815 1.4082 0.9350 1.4281 0.8829 1.40700.06 0.9340 1.4271 0.8820 1.4089 0.9351 1.4291 0.8835 1.40780.08 0.9351 1.4291 0.8824 1.4102 0.9354 1.4301 0.8847 1.40910.10 0.9370 1.4309 0.8830 1.4109 0.9359 1.4313 0.8860 1.4101
PAB-103 PAB-1080.01 0.9359 1.4243 0.8797 1.4045 0.9339 1.4268 0.8770 1.40420.02 0.9365 1.4248 0.8814 1.4049 0.9350 1.4272 0.8789 1.40620.04 0.9370 1.4255 0.8823 1.4052 0.9365 1.4279 0.8792 1.40760.06 0.9376 1.4269 0.8832 1.4057 0.9374 1.4287 0.8818 1.40970.08 0.9380 1.4281 0.8841 1.4063 0.9383 1.4291 0.8833 1.41120.10 0.9384 1.4289 0.8851 1.4077 0.9393 1.4298 0.8850 1.4128
PAB-104 PAB-1090.01 0.9343 1.4255 0.8769 1.4045 0.9339 1.4257 0.8774 1.40460.02 0.9351 1.4258 0.8783 1.4062 0.9349 1.4265 0.8785 1.40520.04 0.9354 1.4262 0.8803 1.4071 0.9360 1.4274 0.8792 1.40630.06 0.9356 1.4271 0.8822 1.4089 0.9366 1.4279 0.8800 1.40730.08 0.9357 1.4288 0.8831 1.4093 0.9378 1.4289 0.8815 1.40860.10 0.9376 1.4302 0.8842 1.4099 0.9387 1.4296 0.8828 1.4096
PAB-105 PAB-1100.01 0.9330 1.4251 0.8770 1.4048 0.9329 1.4259 0.8780 1.40490.02 0.9340 1.4249 0.8781 1.4052 0.9333 1.4265 0.8774 1.40590.04 0.9341 1.4251 0.8806 1.4062 0.9334 1.4272 0.8794 1.40790.06 0.9346 1.4262 0.8823 1.4073 0.9359 1.4292 0.8814 1.40980.08 0.9355 1.4279 0.8851 1.4092 0.9363 1.4301 0.8826 1.41080.10 0.9356 1.4290 0.8861 1.4094 0.9371 1.4314 0.8850 1.4122
Section-III
Department of Chemistry, Saurashtra University, Rajkot
Figure 3.3.1: The variation of 1/g
THF at 303.15 K.
1.06
1.07
1.08
1.09
1.10
0.00
1/ρ
12g
1
1.12
1.14
1.16
1.18
0.00
1/ρ
12g
1
III Density and refractive index
Department of Chemistry, Saurashtra University, Rajkot-360005
1: The variation of 1/g1ρ12 with g2/g1 for PAB-101 in [A] DMF and [B]
at 303.15 K.
0.01 0.02
g2/g1
[A]
0.01 0.02
g2/g1
[B]
Density and refractive index
141
in [A] DMF and [B]
0.03
0.03
Section-III Density and refractive index
Department of Chemistry, Saurashtra University, Rajkot-360005 142
Table 3.3.2: Experimental and calculated densities of tetrahydropyrimidine
derivatives in DMF and THF solutions at 303.15 K.
Compound CodeDensity (g.cm-3) calculated from Fig. 3.5.1 Density (g.cm-3)
calculated fromEqn. 3.5.2DMF THF
PAB-101 1.1405 1.2143 1.3048PAB-102 1.1756 1.0845 1.2404
PAB-103 1.1962 1.1716 1.3865PAB-104 1.1545 1.2259 1.3865
PAB-105 1.1339 1.4478 1.3648
PAB-106 1.2918 1.1217 1.2840
PAB-107 1.0711 1.1360 1.5496
PAB-108 1.3046 1.2261 1.3191
PAB-109 1.3891 1.1574 1.5199PAB-110 1.2563 1.2663 1.3444
Section-III Density and refractive index
Department of Chemistry, Saurashtra University, Rajkot-360005 143
Table 3.3.3: Volume increments of some atoms and groups of atoms.
Atoms orAtomic group
VolumeIncrements (Ao)3
Atoms orAtomic group
VolumeIncrements (Ao)3
C
C
C
N1 37. 1 4. 10.2 N
C
C
C 1 37.1 37.
0.9
C
C
C
C. 1 54.
1 349.0
C N C1 28.1 37. 5.62
C
C
N
H1 00. 1 28.
1 48.
3.61C
O
H
HH
1 091 09. .
1 5.
26.3
C
C
C
F 11.40 C
C
C
O 11.65
C Cl
C
C
10.39 C Cl1 77.
19.35
C C N 15.9 O H 4.7
C F1 34.
9.2 Car O Cal1 37.1 5. 2.67
CH
C
C
1 4. 14.7 C O H1 37.
5.36
N
O
O
C 1 21.1 57.
7.46 C N 10.0
N
C
C
H 1.36.1.08
.8.3 N
H
H
C ..
6.38
Section-III Density and refractive index
Department of Chemistry, Saurashtra University, Rajkot-360005 144
Further, the molar refraction of a pure liquid (MRD) 1 can be calculated using the
Lorentz-Lorenz equation104:
2
21
1
1
n MMRD
n
… (3.3.3)
where n, M and ρ are refractive index , molecular weight and density of pure liquid
respectively.
For solutions, the following eq. (3.3.4) was used to determine molar refraction.
212 1 1 2 221212 12
1
1
n X M X MMRD
n
... (3.3.4)
where n12 and ρ12 are refractive index and density of solution respectively. X1 and X2 are
the mole fractions and M1 and M2 are the molecular weight of the solvent and solute
respectively.
The plots of (MRD) 12 verses concentration for all the studied compounds in DMF
and THF are given in Figures 3.3.2 and 3.3.3. It is evident from these figures that (MRD)
12 increases with the increase in concentration. From the values of the molar refraction of
solution and pure solvent, molar refraction of solid compounds were determined by
following equation:
1 212 1 2MRD X MRD X MRD … (3.3.5)
From the density and molar refraction data, the refractive indexes of all the
compounds were calculated from eq. (3.3.3). The molar refraction (MRD)2 and refractive
index of all the compounds are reported in Table 3.3.4 for 0.1 M solution.
Each solvent interacts differently with different functional groups, so that (MRD)2
and refractive index of compounds is different in each solvent, as shown in Table 3.3.4.
As discussed above, in different solvents intermolecular interactions are different, which
affect these parameters. In some solvents, aggregation or hydrogen bonding takes place
whereas in others, breakage of bonds takes place. The refractive index and molar
refraction depends not only upon atomic refraction but also upon single, double or triple
bonds. However, it is reported that bond refraction is more effective than atomic
refraction. Further, bond polarity also causes change in molar refraction. Thus, type of
solvent affects the refractive index and molar refraction of a solute.
Section-III
Department of Chemistry, Saurashtra University, Rajkot
Figure 3.3.2: The plots of molar refraction (MRD)
tetrahydropyrimidine derivatives
19.50
20.00
20.50
21.00
0.00
(MRD
) 12
PAB
19.50
20.00
20.50
21.00
0.00
(MRD
) 12
PAB 106
III Density and refractive index
Department of Chemistry, Saurashtra University, Rajkot-360005
2: The plots of molar refraction (MRD)12 against concentration of
tetrahydropyrimidine derivatives in DMF solutions at 303.15 K.
0.02 0.04 0.06 0.08
Concentration (M)
PAB-101 PAB-102 PAB-103 PAB-104
0.02 0.04 0.06 0.08Concentration (M)
PAB 106 PAB 107 PAB 108 PAB 109
Density and refractive index
145
against concentration of
in DMF solutions at 303.15 K.
0.08 0.10
PAB-105
0.10
PAB 110
Section-III
Department of Chemistry, Saurashtra University, Rajkot
Figure 3.3.3: The plots of molar refraction (MRD)
tetrahydropyrimidine
20.00
20.50
21.00
0.00
(MRD
) 12
PAB-101
20.00
20.50
21.00
0
(MRD
) 12
PAB-106
III Density and refractive index
Department of Chemistry, Saurashtra University, Rajkot-360005
3: The plots of molar refraction (MRD)12 against concentration of
tetrahydropyrimidine derivatives in THF solutions at 303.15 K.
0.02 0.04 0.06 0.08
Concentration (M)
101 PAB-102 PAB-103 PAB-104
0.02 0.04 0.06 0.08
Concentration (M)
106 PAB-107 PAB-108 PAB-109
Density and refractive index
146
against concentration of
solutions at 303.15 K.
0.10
PAB-105
0.1
PAB-110
Section-III Density and refractive index
Department of Chemistry, Saurashtra University, Rajkot-360005 147
Table 3.3.4: Calculated molar refraction and refractive index of 0.1 M solution of
tetrahydropyrimidine derivatives in DMF and THF at 303.15 K.
Compounds
SolventsDMF THF
(MRD)2 n (MRD)2 nPAB-101 114.6601 2.3786 73.0112 1.7662PAB-102 119.6821 2.2822 92.6678 1.7736PAB-103 107.8992 2.0531 73.1031 1.6026PAB-104 116.7910 2.1278 86.8397 1.7980PAB-105 115.3017 2.2076 74.4360 1.8980PAB-106 103.1046 2.1386 97.7948 1.8526PAB-107 129.9348 2.1108 86.1133 1.6762PAB-108 113.3016 2.2177 102.7612 1.9493PAB-109 98.7597 2.6587 76.6407 1.8134PAB-110 119.3591 2.5593 91.2837 2.0012
Section-III Density and refractive index
Department of Chemistry, Saurashtra University, Rajkot-360005 148
REFERENCES
1. Twieg, R.; He, M.; Sukhomlinova, F.; You, W.; Moerner, E.; Diaz-Garcia, M.;
Wright, D.; Casperson, J.; Wortmann, R.; Glania, C.; Kramer, P.; Lukaszuk, K.;
Matschiner, R.; Singer, K.; Ostoverkhov, V. and Petschek, R.; “Design and
optimization of chromophores for liquid crystal and photorefractive applications.”
Mat. Res. Soc. Symp. Proc. 1999, 561, 119-130.
2. Valentine, J.; Zhang, S.; Zentgraf, T.; Ulin-Avila, E.; Genov, D.; Bartal, G. and
Zhang, X.; “Three-dimensional optical metamaterial with a negative refractive
index” Nature 2008, 455, 376-379.
3. Singh, S.; “Refractive index measurement and its applications”, Phys. Scripta,
2002, 65, 167-180.
4. Heavens, O. S. and Ditchburn, R. W.;”Interferometry in Insight into optics”, John
Wiley and Sons Ltd. Chichester West Sussex UK, 1991, 193-202.
5. Angelis, D. M.; Nicole, D. S.;Ferraro, P.; Finizio, A. and Pierattini, G.;”Liquid
refractometer based on interferometric fringe projection” Optics Commu. 2000,
175, 315-321.
6. Frederick, W.; “Optical Properties of Solids”. Academic Press, New York, 1972,
49.
7. Meriaudeau, F.; Wig, A. G.; Passian, A. and Ferrell, T. L.; “New fiber optic
sensor: application to refractive index sensing” Proc. SPIE 1986, 4074, 354-364.
8. Banerjee, A.; Mukherjee, S.; Verma, R. K.; Jana, B.; Khan, T. K.; Chakroborty,
M.; Das, R.; Biswas, S.; Saxena, A.; Singh, V.; Hallen, R. M.; Rajput, R. S.;
Tewari, P.; Kumar, S.; Saxena, V.; Ghosh, A. K.; John, J. and Gupta, B. P.; “Fiber
optic sensing of liquid refractive index” Sensors and Actuators B-Chemical,
2007, 123, 594-605.
9. Buck J. A.; “Fundamentals of optical fibers” John Wiley and Sons Inc. New
Jersey, USA. 2004.
10. Chiu, M. H. and Wang, S. F.; “New-type fiber optical liquid refractometer,
Novel Optical Systems Design and Optimization VII.” Proc. SPIE 2004, 5524,
169-175.
Section-III Density and refractive index
Department of Chemistry, Saurashtra University, Rajkot-360005 149
11. Huang, X. F.; Chen, Z. M.; Shao, L. Y.; Cen, K. F.; Sheng, D. R.; Chen, J. and
Zhou, H.; “Design and characteristics of refractive index sensor based on
thinned and microstructure fiber Bragg grating” Appl. Optics 2008, 47, 504-511.
12. Kaur, H.; “Optical Fibre Refractive in Voltage and Strain Sensor Fabrication and
Application” Ph. D thesis, Victoria University, Australia. 2011.
13. Flavell, R. G. and Lane, J. A.; “The application of potential refractive index in
tropospheric wave propagation” J. Atmos. Terr. Phys.1962, 24, 47-56.
14. Petrin, A.; “Application of Media with Negative Refraction Index to
Electromagnetic Imaging. Fundamental Aspects”, Wave Propagation in Materials
for Modern Applications, ISBN: 978-953-7619-65-7.
15. Yang, S. Y.; Chieh, J. J.; Horng, H. E.; Hong, C. Y. and Yang, H. C.; “Origin and
applications of magnetically tunable refractive index of magnetic fluid films”
Appl. Phys. Lett. 2004, 84, 5204-5206.
16. Yuan, W.; Kong, L. and Bai, Z.; “Simultaneous determination of ethanol, sugar
and organic acids in Kluveromyces marxious broth by high performance liquid
chromatography-ultraviolet/refractive index detector” Fenxi Huaxue 2009, 37(6),
850-854.
17. Rekha, R. and Ramalingam, A.; “Nonlinear characteristic and optical limiting
effect of oil red azo dye in liquid and solid media” J. Modern Optics. 2009, 56(9),
1096-1102.
18. Kirchner, J. and Miller, J.; “Volatile water-soluble and oil constituents of valencia
orange juice” Canning and Storage Effects. 1957, 5(4), 283-291.
19. Patindol, J.; Gonzalez, B.; Wang, Y. and McClung, A.; “Starch fine structure and
physicochemical properties of specialty rice for canning” J Cereal Sci. 2007,
45(2), 209-218.
20. Diao, J. and Hess, D.; “Refractive index measurements of films with biaxial
symmetry-Determination of film thickness and refractive indices using polarized
transmission spectra in the transparent wavelength range” J. Phys. Chem. 2005,
109(26), 12819-12825.
21. Shabana, H.; “Determination of film thickness and refractive index by
interferometry” Polym. Testing 2004, 23(6), 695-702.
Section-III Density and refractive index
Department of Chemistry, Saurashtra University, Rajkot-360005 150
22. Nordman, O.; Nordman, N. and Peyghambarian, N.; “Electron beam induced
changes in the refractive index and film thickness of amorphous AsxS100 – x and
AsxSe100 – x films” J. Appl. Phy. 1998, 84(11), 6055-6058.
23. Nair, S. and Tsapatsis, M.; “Infrared reflectance measurements of zeolite film
thickness, refractive index and other characteristics” Micro. Meso. Mat. 2003,
58(2), 81-89.
24. Kensuke, M. and Akira, A.; “Silicone coated films with good heat resistance, and
high transparency and refractivity, and their manufacture.” Jap. Pat. Appl. 2009,
Patent no.: JP-2009148670
25. Zillies, J.; Zwiorek, K.; Winter, G. and Coester, C.; “Method for Quantifying the
PEGylation of Gelatin Nanoparticle Drug Carrier Systems Using Asymmetrical
Flow Field-Flow Fractionation and Refractive Index Detection” Anal. Chem.
2007, 79, 4574-4580.
26. Park, Y.; Diez-Silva, M.; Popescu, G.; Lykotrafitis, G.; Choi, W.; Feld, M. and
Suresh, S.; “Refractive index maps and membrane dynamics of human red blood
cells parasitized by Plasmodium falciparum” PNAS 2008, 105(37), 13730–13735.
27. Song, W.; Zhang, X.; Liu, A. and Lim, C.; “Refractive index measurement of
single living cells using on-chip Fabry-Perot cavity” App. Phys. Lett. 2006, 89,
203901-203903.
28. Kemper, D.; Carl, J.; Schnekenburger, I.; Bredebusch, M.; Schäfer, W.
Domschke. and von Bally, G.; “Self-interference digital holographic microscopy
for live cell imaging” J. Biomed. Opt. 2006, 11, 34005-34011.
29. Weng, L.; Lu, Y.; Shi, L.; Zhang, X.; Zhang, L.; Guo, X. and Xu, J.; “In Situ
Investigation of Drug Diffusion in Hydrogels by the Refractive Index Method”
Anal. Chem. 2004, 76, 2807-2812
30. Soriano, A.; Doma, B. and Hui Li, M.; “Measurements of the density and
refractive index for 1-n-butyl-3-methylimidazolium-based ionic liquids” J. Chem.
Thermo. 2009, 41, 301–307.
31. Mokhtarani, B.; Mojtahedi, M. M.; Mortaheb, H. R.; Mafi, M.; Yazdani, F. and
Sadeghian, F.; “Densities, refractive indices, and viscosities of the ionic liquids 1-
methyl-3-octylimidazolium tetrafluoroborate and 1-methyl-3-butyl imidazolium
perchlorate and their binary mixtures with ethanol at several temperatures” J.
Chem. Eng. Data. 2008, 53, 677−682.
Section-III Density and refractive index
Department of Chemistry, Saurashtra University, Rajkot-360005 151
32. Tariq, M.; Forte, P. A. S.; Gomes, M. F. C.; Lopes, J. N. C. and Rebelo, L. P. N.;
“Densities and refractive indices of imidazolium- and phosphonium-based ionic
liquids: Effect of temperature, alkyl chain length, and anion” J. Chem. Thermo.
2009, 41,790 −798.
33. Anouti, M.; Vigeant, A.; Jacquemin, J.; Brigouleix, C. and Lemordant, D.
“Volumetric properties, viscosity and refractive index of the protic ionic liquid,
pyrrolidinium octanoate, in molecular solvents” J. Chem. Thermo. 2010, 42, 834
−845.
34. Yu, Z.; Gao, H.; Wang, H. and Chen, L. “Densities, viscosities, and refractive
properties of the binary mixtures of the amino acid ionic liquid [bmim][Ala] with
methanol or benzylalcohol at T = (298.15 to 313.15) K. J. Chem. Eng. Data.
2011, 56, 2877 −2883.
35. Xu, Y.; Yao, J.; Wang, C. and Li, H.; “Density, Viscosity, and Refractive Index
Properties for the Binary Mixtures of n -Butylammonium Acetate Ionic Liquid +
Alkanols at Several Temperatures” J. Chem. Eng. Data. 2012, 57, 298-308.
36. Rhodes, F. and Goldsmith, H.; “Variation of Refractive Index of China Wood Oil
with Temperature.” Ind. Eng. Chem. 1923, 15, 786-795.
37. Mitsuhiro, F.; Tadashi, Y.; Satoshi, M. and Yasuhiro, O.; “Concentration
measurement of refrigerant/refrigeration oil mixture by refractive index.” Int. J.
Refrig. 2004, 27, 346-352.
38. Yu, Z.; Gao, H.; Wang, H. and Chen, L.; “Densities, Viscosities, and Refractive
Properties of the Binary Mixtures of the Amino Acid Ionic Liquid [bmim][Ala]
with Methanol or Benzylalcohol at T = (298.15 to 313.15) K” J. Chem. Eng. Data
2011, 56, 2877–2883.
39. Husband, F.; Garrood, M.; Mackie, A.; Burnett, G. and Wilde, P.; “Adsorbed
Protein Secondary and Tertiary Structures by Circular Dichroism and Infrared
Spectroscopy with Refractive Index Matched Emulsions” J. Agric. Food Chem.
2001, 49, 859-866.
40. Barroso, M.; Pineiro, M.; Silva, S. and Seixas d.; “Refractometry in determination
of sugar and Aspartame contents in commercial beverages.” Quimica 2003, 91,
61-65.
41. Riyazuddeen and Usmani M.; “Densities, Speeds of Sound, and Viscosities of (L-
Proline + Aqueous Glucose) and (L-Proline + Aqueous Sucrose) Solutions in the
Section-III Density and refractive index
Department of Chemistry, Saurashtra University, Rajkot-360005 152
Temperature Range (298.15 to 323.15) K” J. Chem. Eng. Data. 2011, 56, 3504–
3509.
42. Murakami, N. and Yoshimi, H.; “Liquid crystal cell substrate for liquid crystal
display device and refractive indices thereof.” Jpn. Kokai Tokkyo Koho. 2009, 26,
31-38.
43. Sim, J.; Baek, G.; Won, Y.; Park, Y.; Park, I. and Jeon, S.; “Optically anisotropic
films with controlled refractive index in the thickness direction for liquid crystal
displays.” Repub. Korean Kongkae Taeho Kongbo. 2009, 6, 26-31.
44. Abe, I.; De Goes, R.; Fabris, J.; Kalinowski, H.; Müller, M.; Fugihara, M.; Falate,
R.; Diesel, B.; Kamikawachi R. and Barbosa, C.; “Production and characterization
of refractive index gratings in high- birefringence fibre optics.“ Optics and
Lasers in Eng. 2003, 39(5-6), 537-548.
45. Michael, R.; Marle, J.; Vrensen, G. and Van den Berg, T.; “Changes in the
refractive index of lens fibre membranes during maturation – impact on lens
transparency” Exper. Eye Res. 2003, 77(1), 93-99.
46. Martincek, I.; Kacik, D.; Turek, I. and Peterka, P.; “The determination of the
refractive index profile in α-profile optical fibres by intermodal interference
investigation” Optik. Int. J. Light and Electron Optics 2004, 115(2), 86-88.
47. Strop P. and Brunger, A. T.; “Refractive index-based determination of detergent
concentration and its application to the study of membrane proteins” Protein Sci.
2005, 14(8), 2207–2211.
48. Lee, B.; Choi, J.; Choi, K.; Kang, D. and Lim, M.; “Photosensitive paste
composition, barrier ribs prepared using the composition and plasma display panel
comprising the barrier ribs.” Korean Pat. Appl. 2009, Patent no. KR 2009080756
49. Oosterbaan, D.; Vrindts, V.; Berson, S.; Guillerez, S.; Douheret, O.; Ruttens, B.;
D'Haen, J.; Adriaensens, P.; Manca, J.; Lutsen, L. and Vanderzande, D.; “Efficient
formation, isolation and characterization of poly(3-alkylthiophene) nanofibres:
probing order as a function of side-chain length.” J. Mat. Chem. 2009, 19(30),
5424-5435.
50. Yakuphanoglu, F.; Mehrotra, R.; Gupta, A. and Munoz, M.; “Nanofiber organic
semiconductors: The effects of nanosize on the electrical charge transport and
optical properties of bulk polyanilines.” J. Appl. Poly. Sci. 2009, 114(2), 794-799.
Section-III Density and refractive index
Department of Chemistry, Saurashtra University, Rajkot-360005 153
51. Belendez, A.; Belendez, T.; Neipp, C. and Pascual, I.; “Determination of the
refractive index and thickness of holographic silver halide materials by use of
polarized reflectances.” Appl Opt. 2002, 41(32), 6802-6808.
52. Clergent, Y.; Durou, C. and Laurens, M.; “Refractive Index Variations for Argon,
Nitrogen, and Carbon Dioxide at = 632.8 nm (He-Ne Laser Light) in the Range
288.15 K, T 323.15 K, 0 < p < 110 kPa.” J. Chem. Eng. Data. 1999, 44, 197-199.
53. Burokur, S.; Sellier, N.; Kante, A.; Lustrac, B. and De, A.; “Symmetry breaking in
metallic cut wire pairs metamaterials for negative refractive index” Appl. Phys.
Let. 2009, 94(20), 2011111-2011113.
54. Wang, J.; Hutchins, M.; Woo, K.; Matayabas, C. and Konish, T.; “Halogen-free,
radiation-curable, high refractive index materials” JCT Coatings Tech. 2009, 6,
44-49.
55. Bornhop, D. J. and Dovichi, N. J.; “Simple nanoliter refractive index detector”
Anal. Chem. 1986, 58, 504-505.
56. Peepliwal, A.; Bonde, C. and Bothara, K.; “A validated RP-HPLC method for
quantitative determination of related impurities of ursodeoxycholic acid (API) by
refractive index detection” J. Pharm. Bio. Ana. 2011, 54, 845–849.
57. Turner, C. E.; Williamson, D. A.; Stroud, P. A. and Talley, D. J.; “Evaluation and
comparison of commercially available Aloe vera L. products using size exclusion
chromatography with refractive index and multi-angle laser light scattering
detection” Inter. Immuno. 2004, 4, 1727–1737.
58. Bornhop, D. J. and Dovichi, N. J.; “Simultaneous laser-based refractive index and
absorbance determinations within micrometer diameter capillary tubes” Anal.
Chem.1987, 59, 1632-1636.
59. Bruno, A. E.; Krattiger, B.; Maystre, F. and Widmer, H. M.; “On-column laser-
based refractive index detector for capillary electrophoresis” Anal. Chem. 1991,
63, 2689-2697.
60. Burggraf, N.; Krattiger, B.; De Mello, A.; De Rooij, N. and Manz, A.;
“Holographic refractive index detector for application in microchip-based
separation systems” Analyst 1998, 123, 1443–1447.
61. Heric, E. L. and Brewer, J. G.; “Refraction in some ternary and Quaternary liquid
nonelectrolyte systems” J. Chem. Eng. Data. 1971, 16, 317-321.
Section-III Density and refractive index
Department of Chemistry, Saurashtra University, Rajkot-360005 154
62. Gee, N. and Freeman, G. R.; “Relative permittivities of 10 organic liquids as
function of temperature” J. Chem. Thermodyn. 1993, 25, 549-554.
63. Proutiere, A.; Megnassan, E. and Hucteau, H.; “Reply to Comment on "Refractive
Index and Density Variations in Pure Liquids. A New Theoretical Relation” J.
Phys. Chem. 1994, 98, 4769-4769.
64. Fornefeld-Schwarz, U. M. and Svejda, P.” Refractive index and relative
permittivities of liquid mixtures of γ-butyrolactone, γ-valerolactone, δ-
valerolactone, or ε-Caprolactone+benzene, toluene, or +ethylbenzene at 293.15 K
and 313.15 K and atmospheric pressure” J. Chem. Eng. Data. 1999, 44, 597-604.
65. Toti, U.; Kariduraganavar, M.; Aralaguppi, M. and Aminabhavi, T.; “Density,
Viscosity, Refractive Index, and Speed of Sound of Ternary Systems: Polystyrene
in 1,4-Dioxane + Tetrahydrofuran Mixtures at (298.15, 303.15, and 308.15) K.” J.
Chem. Eng. Data. 2000, 45, 920-925.
66. Gomez-Diaz, D.; Mejuto, J. and Navaza, J.; “Physicochemical Properties of
Liquid Mixtures. 1. Viscosity, Density, Surface Tension and Refractive Index of
Cyclohexane + 2,2,4-Trimethylpentane Binary Liquid Systems from 25 C to 50
C” J. Chem. Eng. Data. 2001, 46, 720-724.
67. Chen, S.; Lei, Q. and Fang, W.; “Density and Refractive Index at 298.15 K and
Vapor-Liquid Equilibria at 101.3 kPa for Four Binary Systems of Methanol, n-
Propanol, n-Butanol, or Isobutanol with N-Methylpiperazine” J. Chem. Eng. Data.
2002, 47, 811-815.
68. Pandey, J.; Jain, P. and Vyas, V.; “Speed of sound, viscosity, and refractive index
of multicomponent systems: analysis of experimental data from the Bertrand-
Acree-Burchfield equation” Can. J. Chem. 1994, 72, 2486-2492.
69. Gomez-Diaz, D.; Mejuto, J.; Navaza, J. and Rodriguez-Alvarez, A.; “Effect of
Composition and Temperature upon Density, Viscosity, Surface Tension, and
Refractive Index of 2,2,4- Trimethylpentane + Cyclohexane + Decane Ternary
Liquid Systems.” J. Chem. Eng. Data. 2003, 48, 231-235.
70. Resa, J.; Gonzalez, C. and Juez, M.; “Density, refractive index and speed of sound
for mixtures of ethyl acetate with 2-butanol and 3-methyl-1-butanol. Vapor-liquid
equilibrium of the ethyl acetate + 3-methyl-1-butanol system.” Fluid Phase Equi.
2004, 217, 175-180.
Section-III Density and refractive index
Department of Chemistry, Saurashtra University, Rajkot-360005 155
71. Baluja, S.; Pandaya, N.; Kachhadia, N. and Solanki, A.; “Refractive index:
theoretical evaluation in binary liquid mixtures.” J. Ultra Sci. Phys. Sci. 2006, 18,
247-250.
72. Resa, J.; Gonzalez, C.; Diez, E.; Concha, R. and Iglesias, M.; “Mixing properties
of isopropyl acetate + aromatic hydrocarbons at 298.15 K: Density, refractive
index and isentropic compressibility.” Korean J. Chem. Eng. 2009, 21, 1015-
1025.
73. Mirjana, L.; Kijevcanin, I.; Radovic, B.; Djordjevi, C.; Aleksandat, Z.; Tasi, C.;
Slobodan, P. and Serbanovi, C.; “Experimental determination and modeling of
densities and refractive indices of the binary systems alcohol + dicyclohexylamine
at T = (288.15–323.15) K” Thermochim. Acta 2011, 525, 114– 128.
74. Berm C.; Salguero, U. and Gracia-Fadrique, J.; “Densities, Refractive Indices,
Speeds of Sound and Surface Tensions for Dilute Aqueous Solutions of 2-Methyl-
1-propanol, Cyclopentanone, Cyclohexanone, Cyclohexanol and Ethyl
Acetoacetate at 298.15 K” J. Chem. Eng. Data. 2011, 56, 3823–3829.
75. Taib, M. M.; Ziyada, A. K.; Wilfred, C. D. and Murugesan, T.; “Volumetric
properties and refractive indeces for binary mixtures of 1-propyronitrile-3-
hexylimidazolium bromide+ethanol at temperatures from 293.15 to 323.15 K” J.
Sol. Chem. 2012, 41, 100-111.
76. Benjamin, J. and Ernest, G.; “Molar refraction as an index of proton transfer: An
estimate of the acid strength of p-toluenesulfonic acid” J. Am. Chem. Soc. 1961,
83, 2956-2956.
77. Tanio, N. and Irie, M.; “Refractive index of organic photochromic dye-amorphous
polymer composites” Jap. J. Appl. Phys. 1994, 33, 3942-3946.
78. Liu, J.; Nakamura, Y.; Shibasaki, Y.; Ando, S. and Ueda, M.; “High Refractive
Index Polyimides Derived from 2,7-Bis(4-amino phenylenesulfanyl) thianthrene
and Aromatic Dianhydrides” Macromol. 2007, 40, 4614-4620.
79. Yakowitz, M. and Jorgensen, P.; “Refractive Index of Strontium Nitrate” Ind.
Eng. Chem. Anal. 1937, 9, 204-204.
80. Koutnik, V.; “Refractive index of inorganic pigments” Chem. Prumysl. 1964, 14,
604-606.
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Department of Chemistry, Saurashtra University, Rajkot-360005 156
81. Upadhyay, R. K. and Bansal, R. R.; “Refractometry determination of formation
constant of gold, platinum, osmium and iridium complexes”, Ind. J. Chem., 1977,
15A, 756-757.
82. Sahai, R.; Singh, V. and verma, R.; “Differential refractometric and
conductometric studies on the charge transfer interactions of some metal β-
diketonates with iodine” J. Ind. Chem. Soc. 1982, 59(1), 46-51.
83. Sangwal, K. and Kucharczyk, W.; “Relationship between density and refractive
index of inorganic solids” J. Phys. D. Appl. Phys. 1987, 20, 522-525.
84. Taboada, M. E.; Veacuteliz, D. M.; Gallequillos, H. R. and Teoacutefilo, A.;
“Solubility, densities, viscosities, electrical conductivities and refractive index of
saturated solutions of potassium sulfate in water+1-propanol at 298.15, 308.15
and 318.15K” J. Chem. Eng. Data. 2002, 47(5), 1193-1196
85. Kalyanasundaram, S.; Stephan, A. M. and Gopalan, A.; “The Rao formulism and
refractometric studies on poly (methylmethacrylate) in dimethyl formamide”
Acustica 1999, 85, 136-138.
86. Ottani, S.; Vitalini, D.; Camelli, F. and Castellari, C.;”Densities, viscosities and
refractive index of poly(ethylene glycol) 200 and 400+cyclic ethers at 303.15K” J.
Chem. Eng. Data. 2002, 47(5), 1197-1204.
87. Assaid, I.; Bosc, D. and Hardy, I.; “Improvements of the Poly(vinyl cinnamate)
Photoresponse in Order to Induce High Refractive Index Variations” J. Phys.
Chem. B. 2004, 108, 2801-2806.
88. Lu, C.; Guan, C.; Liu, Y.; Cheng, Y. and Yang, B.; “PbS/Polymer Optical
Materials with High Refractive Index” Chem. Mater. 2005, 17, 2448-2454.
89. Mohsen, N.; Modarress, H. and Rasa, H.; “Measurement and Modeling of
Density, Kinematic Viscosity, and Refractive Index for Poly(ethylene Glycol)
Aqueous Solution at Different Temperatures” J. Chem. Eng. Data. 2005, 50,
1662-1666.
90. Aminabhavi, T. M.; Phayde, H. T. S.; Khinnavar, R. S. and Bindu, G.; “Density,
refractive index, speed of sound and viscosities of diethylene glycol dimethyl
ether + butyl acetate at 298.15, 303.15, 308.15, 313.15 and 218.15 K” J. Chem.
Eng. Data.1993, 38, 542-545.
91. Iglesias, M, Orge, B. And Tojoq, J.; “Refractive index, density and excess
property on mixing of the system acetone+methanol+water and
Section-III Density and refractive index
Department of Chemistry, Saurashtra University, Rajkot-360005 157
acetone+methanol+1-butanol at 298.15K” Fluid Phase Equi. 1996, 126(2), 203-
223.
92. Mariano, A.; Postigo, M.; Gonzalez-Salgado, D. and Roman, L.; “Densities,
speeds of sound, and refractive indices of the ternary mixtures (toluene + methyl
acetate + butyl acetate) and (toluene + methyl acetate + methyl heptanoate) at
298.15 K” J. Chem. Thermodyn. 2007, 39, 218–224.
93. Shyam, S.; Pradhan, P. and Roy, M.; “Solute–solvent and solvent–solvent
interactions of menthol in isopropyl alcohol and its binary mixtures with methyl
salicylate by volumetric, viscometric, interferometric and refractive index
techniques” Thermochim. Acta 2010, 499, 149–154.
94. Kurnia Kiki, A.; Taib, M.; Abdul Mutalib, M. and Murugesan, T.; “Densities,
refractive indices and excess molar volumes for binary mixtures of protic ionic
liquids with methanol at T=293.15 to 313.15 K” J. Mol. Liq. 2011, 159, 211–219.
95. Sherstneva, T. and Koleboshin, G.; “Physicochemical study of binary systems
containing dioxane and aliphatic alcohol” Zhu. Prikli Khimii 1972, 28(13), 53-56.
96. Riggio, R.; Martinez, H. and Solimo, H.; “Densities, viscosities, and refractive
indexes for the methyl isobutyl ketone + pentanols systems. Measurements and
correlations.” J. Chem. Eng. Data 1986, 31(2), 235-238.
97. Al-Wahaibi, Y.; Grattoni, C. and Muggeridge, A.; “Physical Properties (Density,
Viscosity, Surface Tension, Interfacial Tension, and Contact Angle) of the System
Isopropyl Alcohol + Cyclohexene + Water.” J. Chem. Eng. Data. 2007, 52(2),
548-552.
98. Campos, V.; Gomez, M. and Solimo, H.; “Density, viscosity, refractive index,
excess molar volume, viscosity, and refractive index deviations and their
correlations for the (formamide + water) system. Isobaric (vapour + liquid)
equilibrium at 2.5 kPa.” J. Chem. Eng. Data. 2008, 53(1), 211-216.
99. Aminabhavi, T. M.; “Predicting refractive index and density increment of binary
solvent mixtures”, J. Chem. Eng. Data. 1987, 32, 406-409.
100. Govindan G.; Gokul R. S. and Sastikumar D.; “Measurement of refractive index
of liquids using fiber optic displacement sensors” J. Am. Sci. 2009, 5(2), 13-17.
101. Iulian, O.; Iliuta, M.; Hamplea, L. and Lintes, G.; “Refractive index composition
calibration curves for water-organic component homogeneous liquid mixtures.”
Revista de Chim, 1995, 46(6), 591-593.
Section-III Density and refractive index
Department of Chemistry, Saurashtra University, Rajkot-360005 158
102. Uma Devi, T.; Lawrence, N.; R. Ramesh Babu, S.; Selvanayagam, H.; Stoeckli-
Evans and Ramamurthi, K.; “Characterization of a newly synthesized organic
nonlinear optical crystal: Urea ninhydrin monohydrate.” J. Crystal Growth 2009,
311(13), 3485-3490.
103. Riddick, J. A.; Bunger, W. B. and Sakano, T.; Organic Solvents: Physical
Properties and methods of purification, Fourth Edition., Techniques of Chemistry,
II, A Wiley-Interscience Publication, John Wiley, New York 1986.
104. Lorentz, H. A. And Lorentz,” Theory of Electronics”, Leipzig 1906.
Section-IV
Dissociation constants
Section-IV Dissociation constants
Department of Chemistry, Saurashtra University, Rajkot-360005 159
INTRODUCTION
In general, the term ionization constant means a constant, which is used to
measure the strength of acids and bases. It is often known as dissociation constant. The
knowledge of dissociation constant is a key parameter for understanding the chemical
interactions between the compounds of interest. It also provides useful information in
drug design studies, in explaining the biopharmaceutical properties of substances1,2, to
understand the absorption site of drug, distribution to various organs and excretion3-5 etc.
Further, it is also helpful in developing analytical methods, like HPLC6, in screening
salts, developing pre-clinical and clinical formulation7-9 .
In literature, various researchers have used several methods to determine the
dissociation constant like potentiometer10, pH metry11-14, capillary electrophoresis15,
kinetic exclusion assay16 , NMR methods17, polarography18, conductometry19-21,
ratiometry22-23, spectrophotometric24-25, interfacial FT-IR spectroscopy26, separation
methods (RP-HPLC)27, UV-visible spectroscopy28-29 etc . Krebs and Speakman30 have
reported the dissociation constant of some solvents. Danish et al. have determined the
dissociation constant of Zn2+ ions in live cells and tissues by using a photon microscopic
method31. Potentiometry is mostly used for the determination of dissociation constants of
acids32-33 because it is economical in time. Further, it can be used for acids of pKa range
from 2 to 11 units34. Kodo et al. have studied the ion-pair formation constants of some
salts and ether derivatives by potentiometry35. Jano et al36 have used potentiometric
titration to determine dissociation constants of polyprotic acids and bases. However, for
very low pKa values, this method does not give accurate results. In such cases, more
sensitive instruments should be used. Spectrophotometer method is considered to be an
ideal method. The determination of the dissociation constant of different systems by
spectrophotometric technique has been reported by various workers37-40. However, this
method is also found to be more time consuming. A number of workers41-44 has thus used
pH metry for the determination of dissociation constants of various compounds in various
solvents, to get the reliable results. However, there are certain difficulties in mixed
aqueous media and non aqueous media.
The dissociation constant of various types of substance such as complexes45-50,
amino acids51-52, various acids and their derivatives53-57, drugs58,-59, indicators60-61 etc.,
have been reported using different methods. Fedorov et al62 reported the dissociation
constants of micelle-solubilized compounds. Hayman and Tapuhi63 have determined the
Section-IV Dissociation constants
Department of Chemistry, Saurashtra University, Rajkot-360005 160
dissociation constant of tri chloro acetic acids using distribution method. Meloun et al64-65
have determined dissociation constant of various drugs using spectroscopic and
potentiometric method.
Further, in last few years dissociation constant of various organic compounds66-73
have been studied by various workers. Azimi et al.74 have reported dissociation constant
of some newly Synthesized 1,2,4-Triazole Derivatives in Ethanol-Water Mixtures.
Bhagwatkar et al.75 have been reported pH metric studies of some synthesized ligands.
In this chapter, the dissociation constant of all synthesized tetrahydropyrimidine
derivatives (PAB101-110) are studied in dimethyl formamide-water mixture at 303.15 K
by Calvin Bjerrum pH titration technique.
Section-IV Dissociation constants
Department of Chemistry, Saurashtra University, Rajkot-360005 161
EXPERIMENTAL
All solutions used for the titration are prepared using distilled water. Following
are the concentrations of the solutions used for the titration. The chemicals used were of
B.D.H Analar grade.
Solutions Concentration (M)
Nitric acid 1.0
Sodium hydroxide 0.5
Sodium nitrate 1.0
Ligand (in DMF) 0.1
Nitric acid and sodium hydroxide were standardized by titrating with 0.1 N
NaOH and 0.05 M succinic acid solution respectively.
The buffer solutions used for the calibration of pH meter were 0.05 M potassium
hydrogen phthalate and 0.01 M Borax buffer.
A Elico pH meter (Model No. Li 610) with combined electrode was used for the
pH determination. Before measurement, the pH meter was calibrated with buffer solution
of known pH.
Section-IV Dissociation constants
Department of Chemistry, Saurashtra University, Rajkot-360005 162
Calvin Bjerrum pH titration:
The following sets of mixtures were prepared for titration:
(I) 2 ml HNO3 (1.0M) + 4 ml water + 30 ml DMF + 4.0 ml NaNO3 (1.0 M).
(ii) 2 ml HNO3 (0.1M) + 4 ml water + 28 ml DMF + 2.0 ml ligand solution (0.1M) +
4.0 ml NaNO3 (1.0 M).
Thus, total volumes (V0) in each set = 40.0 ml and DMF: Water ratio 60:40 (v/v).
The above mentioned solutions were allowed to attain a constant temperature (303.15 K)
and then titrated against standard NaOH solution (0.5 M) under an inert atmosphere of
nitrogen.
Section-IV Dissociation constants
Department of Chemistry, Saurashtra University, Rajkot-360005 163
THEORY
In the present work out of ten synthesized compounds i.e., tetrahydropyrimidines,
eight are of HL type whereas two are of H2L type. For these, the equilibria are,
L H HL
In general, the synthesized tetrahydropyrimidines, are represented by LH j-1. The
equilibrium can be written as:
1j jLH H LH
The thermodynamic proton-ligand stability constant ( HjTK ) is given by:
1
jHj
j
LHTK
LH H
.... (3.4.1)
TKjH is reciprocal of the thermodynamic dissociation constant of the acid LHj
dissociating as:
1i iLH LH H
The overall thermodynamic proton-ligand stability constant jH is given by:
jH
j j
LHT
L H
… (3.4.2)
and it refers to the reaction:
jL JH LH
The stoichiometric proton-ligand stability constant is given by:
1
jHj
j
LHK
LH H
… (3.4.3)
and
jHj j
LH
L H
… (3.4.4)
Section-IV Dissociation constants
Department of Chemistry, Saurashtra University, Rajkot-360005 164
These thermodynamic constants are difficult to determine because of the
existence of several complexes. So, an inert electrolyte is used to determine the stability
constant in a particular salt medium. Sodium nitrate is mostly preferred as supporting
electrolyte, because of very slight complexing tendency of nitrate ion. Generally, the
competition between nitrate ion and the ligand under study is minor importance. The
molar concentrations are used in place of activities.
For the determination of dissociation constants, Bjerrum76 introduced a relation for
the determination of Hn , which is defined as average number of hydrogen bound to each
ligand.
Hn = {K1H [H] + 2K1
H K2H [H]2 + .....JK1
H K2H [H] ... Kj
H [H]j} / {1 + K1H [H] + K1
H
K2H [H]2.....K1
HK2H.....Kj
H [H]j .... (3.4.5)
From equation (3.4.4), we can write
1
1
jHj
jH
jHj
j
j H
nH
: 0 1H … (3.4.6)
Equation (3.4.6) is called Bjerrum formation function of the system.
The determination of dissociation or formation constants from experimental data
comprises the following three steps: (i) evaluation of formation curve of the system (ii)
calculation of stoichiometric K`s of the system by direct solution of the formation
function and (iii) conversion of stoichiometric constants into thermodynamic constants.
When the system consists of a ligand, which is a conjugated base of a weak acid,
the pH-metric method introduced by Bjerrum has been widely used. This method is
known as "Bjerrum-Calvin pH titration technique". In this technique, by pH-meter, the
concentration of H+ ions is measured. Thus, a large amount of data can be obtained in a
short period of time. However, the Irving and Rossotti method77 is more popular because
it has some advantages. This method is valid for both pure water and for the mixed
solvents. In this method, the conversion of pH-meter reading in to stoichiometric
hydrogen ion concentration is not necessary and it is not necessary to know the
stoichiometric concentration of neutral salt added to maintain the ionic strength constant.
Section-IV Dissociation constants
Department of Chemistry, Saurashtra University, Rajkot-360005 165
Due to these advantages, this method is used in the present work. In this method,
the pH-meter is standardized using an aqueous buffer. The pH (B) is measured for two
solutions: (1) A mixture containing a mineral acid, a chelating agent and a neutral
electrolyte to keep ionic strength constant and (2) A mixture same as above but without
the chelating agent, when titrated against an alkali solution.
After each addition of standard alkali, the pH meter reading (B) is noted using a
glass electrode-saturated calomel electrode combination. For both the titrations, same
initial volume of the mixture and same standard alkali is used. The titration curves
obtained in the above two titrations are designated as the reagent or ligand titration curve
and the acid titration curve respectively.
The possible hydrolysis reactions are ignored because (i) fresh reagent solutions
were used in pH titrations, (ii) titration times were within one hour, (iii) there were no
observable drifts with time in the meter readings and (iv)the concentrations of the mineral
acid or alkali in the solutions were small.
Usually, a pH-meter calibrated with an aqueous buffer is used for aqueous solutions
only. However, for the mixed aqueous media, especially aqueous dioxane solutions, van
Uitert and Haas78 gave a relation between the glass electrode reading B in dioxane-water
medium and the stoichiometric hydrogen ion concentration of the same in mixture of
varied composition and ionic strength. They reported the relation:
0log log log HH pH f U … (3.4.7)
where f is the activity coefficient of the hydrogen ions in the solvent mixture under
consideration at the same temperature and ionic strength, and 0HU is a correction factor
at zero ionic strength, which depends only on the solvent composition and temperature.
0HU is taken as unity in aqueous media. The meter reading in any aqueous dioxane
solution can, therefore, be converted into hydrogen ion concentration using equation
(3.4.7), provided that correction factor for the appropriate solvent, salt medium, and
temperature, has been determined.
Equation (3.4.7) can be written as:
01 log [ ] Hanti pH H fU ... (3.4.8)
Section-IV Dissociation constants
Department of Chemistry, Saurashtra University, Rajkot-360005 166
0
1
log H
Hanti pH fU
... (3.4.9)
Substituting for [H+] in equation (3.4.5) we get,
Hn = (K1H/f U0
H)[1/antilog B] +....+ ((JK1H K2
H...KJH) /(f U0
H)J)[1/antilog pH]J
/(1+K1H/f U0
H))[1/antilog B]+..+ ((K1HK2
H...KJH)/(f U0
H)J)[1/antilogpH] ... (3.4.10)
0 .H Hj H jK fU pK ... (3.4.11)
0 .H Hj H jfU p ... (3.4.12)
The proton-ligand constant, pKjH can be obtained by the following methods:
1. Interpolation at half Hn values:
At the following Hn values, log K1 and log K2 can be determined:
10.5
log HK n … (3.4.13)
21.5
log HK n ... (3.4.14)
2. Midpoint slope method:
For H2L type ligands:
21 2[ ] 1K K L
or 1 2 1log 2K K pL …(3.4.15)
From the measured mid-point slope, D, the ratio K1/K2 can be calculated by eq.
(3.4.16):
1
2
4.606
2
DK
K
... (3.4.16)
The individual values of K1 and K2 were obtained by using K1/K2 values and
relation (3.4.15). This method is applicable only where K1/K2 lies between 103 and 10-2
and it uses only a very small portion of the formation curve in the region of mid point.
Section-IV Dissociation constants
Department of Chemistry, Saurashtra University, Rajkot-360005 167
RESULTS AND DISCUSSION
The titration curves obtained in the above two titrations are designated as the acid
titration curve and ligand or reagent titration curve respectively. The titration curves for
PAB-101 and PAB-110 are shown in Figure 3.4.1.
From these curves, the average number of protons associated with ligand ( Hn ) can
be calculated by Irving and Rossotti equation.
= − // /{( /) } … (3.4.17)
where Y is the number of displaceable protons per ligand molecule. V/ and V// are the
volume of alkali required at the same pH for both acid and ligand titration curves
respectively. V0 is the initial volume of the test solution. N0, E0 and T0L are the initial
concentration of the alkali, acid and ligand respectively. For PAB-108 and PAB-110,
value of Y is 2. Whereas for other compounds, Y is equal to one.
The calculated values of Hn for all the studied compounds are given in Table
3.4.1. It is evident from table that Hn values are in between zero and one for all the
system except PAB-108 and PAB-110 for which, the values of Hn extend over the range
from 0 to 2 indicating two dissociation steps. The 1HpK values at Hn = 0.5 were evaluated
for each systems except PAB-108 and PAB-110. For these two compounds, the 1HpK and
2HpK were calculated at Hn = 0.5 and Hn = 1.5 respectively. The general plots for the
variation of Hn with B of PAB-101 and PAB-110 are given in Figure 3.4.2.
Further, the log 1H Hn n values are plotted against B as shown in Figure 3.4.3.
The plots are straight lines from which 1log HpK values were calculated at several B
values, by the following equation.
log = + log … (3.4.18)
Section-IV
Department of Chemistry, Saurashtra University, Rajkot
Figure 3.4.1: The plot of pH
[B] PAB-110
IV Dissociation constants
Department of Chemistry, Saurashtra University, Rajkot-360005
pH (B) against volume of NaOH for for [A] PAB
110 at 303.15 K.
Dissociation constants
168
[A] PAB-101 and
Section-IV Dissociation constants
Department of Chemistry, Saurashtra University, Rajkot-360005 169
Table 3.4.1: The pH (B), pK1H and other terms for Tetrahydropyrimidine derivatives
at 303.15 K.
pH V/ V// V//-V/ log( / − ) pK1H/ pK2
H
PAB-1019.60 4.3577 5.2940 0.5463 0.3547 -0.3322 9.01819.70 4.3599 5.3122 0.5623 0.3944 -0.2898 9.15159.80 4.3610 5.3366 0.5856 0.4521 -0.2374 9.29329.90 4.3644 5.3610 0.6066 0.5040 -0.1978 9.4252
10.00 4.3682 5.3854 0.6272 0.5550 -0.1644 9.552610.10 4.3735 5.4103 0.6468 0.6034 -0.1368 9.675610.20 4.3785 5.4359 0.6674 0.6543 -0.1114 9.797210.30 4.3834 5.0715 0.6881 0.7054 -0.0889 9.916610.40 4.3892 5.0903 0.7011 0.7374 -0.0762 10.0278
Ave. pK1H =9.5397
PAB-10212.50 4.6677 5.3097 0.642 0.5810 -0.1492 12.065212.60 4.6925 5.3234 0.6309 0.5528 -0.1658 12.151512.70 4.7186 5.3372 0.6186 0.5216 -0.1857 12.235112.80 4.7415 5.3510 0.6095 0.4985 -0.2018 12.322012.90 4.7627 5.3648 0.6021 0.4796 -0.2157 12.410713.00 4.7751 5.3786 0.6035 0.4826 -0.2134 12.512613.10 4.7859 5.3924 0.6065 0.4896 -0.2082 12.6168
Ave. pK1H = 12.3306
PAB-1039.10 4.3399 4.5001 0.1602 0.6026 -0.5535 9.28079.20 4.3427 4.5161 0.1734 0.5699 -0.5678 9.32219.30 4.3449 4.5321 0.1872 0.5356 -0.5839 9.36209.40 4.3468 4.5481 0.2013 0.5007 -0.6017 9.40129.50 4.3544 4.5641 0.2097 0.4799 -0.6130 9.46519.60 4.3577 4.5801 0.2224 0.4485 -0.6314 9.51029.70 4.3599 4.5961 0.2362 0.4143 -0.6534 9.5496
Ave. pK1H = 9.4130
PAB 1049.20 4.3427 4.9230 0.5803 0.5605 -0.5721 9.30559.30 4.3449 4.9345 0.5896 0.5375 -0.5830 9.36529.40 4.3468 4.9460 0.5992 0.5137 -0.5949 9.42389.50 4.3544 4.9575 0.6031 0.5043 -0.5998 9.50759.60 4.3577 4.9690 0.6113 0.4841 -0.6107 9.57239.70 4.3599 4.9805 0.6206 0.4611 -0.6239 9.63239.80 4.3610 4.9920 0.631 0.4353 -0.6396 9.6870
Ave. pK1H = 9.4991
Section-IV Dissociation constants
Department of Chemistry, Saurashtra University, Rajkot-360005 170
pH V/ V// V//-V/ log( / − ) pK1H/ pK2
H
PAB 1059.70 4.3599 4.5089 0.1490 0.6305 -0.5421 9.83219.80 4.3610 4.5268 0.1658 0.5889 -0.5594 9.85609.90 4.3644 4.5446 0.1802 0.5532 -0.5755 9.892810.00 4.3682 4.5625 0.1943 0.5183 -0.5925 9.931810.10 4.3735 4.5804 0.2069 0.4871 -0.6090 9.977610.20 4.3785 4.5982 0.2197 0.4554 -0.6272 10.022410.30 4.3834 4.6265 0.2431 0.3975 -0.6650 10.0194
Ave. pK1H = 9.9331
PAB-1069.60 4.3577 4.5165 0.1588 0.6062 -0.5520 9.78739.70 4.3599 4.5332 0.1733 0.5703 -0.5676 9.82299.80 4.3610 4.5501 0.1891 0.5311 -0.5861 9.85419.90 4.3644 4.5645 0.2001 0.5039 -0.6000 9.906710.00 4.3682 4.5900 0.2218 0.4501 -0.6305 9.913010.10 4.3735 4.6256 0.2521 0.3751 -0.6815 9.878310.20 4.3785 4.6513 0.2728 0.3238 -0.7242 9.8802
Ave. pK1H = 9.8632
PAB-10710.60 4.4062 4.9780 0.5718 0.4164 -0.6520 10.453410.70 4.4144 4.9980 0.5836 0.4454 -0.6333 10.604710.80 4.4234 5.0196 0.5962 0.4763 -0.6151 10.758810.90 4.4331 5.0413 0.6082 0.5057 -0.5991 10.909911.00 4.4439 5.0630 0.6191 0.5323 -0.5855 11.056211.10 4.4555 5.0848 0.6293 0.5571 -0.5736 11.199711.20 4.4667 5.1065 0.6398 0.5827 -0.5621 11.3450
Ave. pK1H = 10.9040
PAB-1083.30 3.7458 3.9046 0.1588 1.6007 0.5117 3.50433.40 3.7875 3.9316 0.1441 1.6380 0.5920 3.61433.50 3.8112 3.9586 0.1474 1.6299 0.5733 3.71223.60 3.8272 3.9857 0.1585 1.6022 0.5146 3.80473.70 3.8432 4.0136 0.1704 1.5725 0.4598 3.89663.80 3.8592 4.0560 0.1968 1.5064 0.3605 3.97793.90 3.8752 4.0864 0.2112 1.4705 0.3163 4.06754.00 3.8912 4.1227 0.2315 1.4198 0.2624 4.15224.10 3.9072 4.1591 0.2519 1.3689 0.2161 4.2364
Ave. pK1H = 3.8851
9.90 4.3644 4.9284 0.5640 0.6016 -0.1578 9.533710.00 4.3682 4.9468 0.5786 0.5655 -0.1726 9.595710.10 4.3735 4.9651 0.5916 0.5334 -0.1861 9.660810.20 4.3785 4.9835 0.6050 0.5004 -0.2005 9.723310.30 4.3834 5.0014 0.6180 0.4683 -0.2151 9.785410.40 4.3892 5.0157 0.6265 0.4475 -0.2249 9.859710.50 4.3972 5.0300 0.6328 0.4322 -0.2324 9.9403
Ave. pK2H = 9.7284
Section-IV Dissociation constants
Department of Chemistry, Saurashtra University, Rajkot-360005 171
pH V/ V// V//-V/ log( / − ) pK1H/ pK2
H
PAB-10910.60 4.4062 4.5670 0.1608 0.6017 -0.5539 10.779110.70 4.4144 4.5853 0.1709 0.5767 -0.5647 10.834410.80 4.4234 4.6046 0.1812 0.5513 -0.5764 10.889510.90 4.4331 4.6276 0.1945 0.5185 -0.5924 10.932111.00 4.4439 4.6506 0.2067 0.4884 -0.6083 10.979911.10 4.4555 4.6736 0.2181 0.4603 -0.6243 11.031011.20 4.4667 4.6966 0.2299 0.4313 -0.6422 11.0799
Ave. pK1H = 10.9323
PAB-1103.40 3.7875 4.0363 0.2488 1.3750 0.2213 3.74243.50 3.8112 4.0452 0.2340 1.4125 0.2553 3.88103.60 3.8272 4.0532 0.2260 1.4328 0.2753 4.00243.70 3.8432 4.0607 0.2175 1.4543 0.2981 4.12573.80 3.8592 4.0695 0.2103 1.4726 0.3187 4.24593.90 3.8752 4.0757 0.2005 1.4973 0.3488 4.37404.00 3.8912 4.0832 0.1920 1.5188 0.3772 4.4992
Ave. pK1H = 4.1244
9.50 4.3544 4.9478 0.5934 0.5284 -0.4449 9.05519.60 4.3577 4.9545 0.5968 0.5200 -0.4542 9.14589.70 4.3599 4.9608 0.6009 0.5099 -0.4657 9.23439.80 4.3610 4.9651 0.6041 0.5020 -0.4748 9.32529.90 4.3644 4.9723 0.6079 0.4927 -0.4856 9.4144
10.00 4.3682 4.9815 0.6133 0.4795 -0.5012 9.498810.10 4.3735 4.9905 0.6170 0.4705 -0.5120 9.5880
Ave. pK2H = 9.3231
Section-IV
Department of Chemistry, Saurashtra University, Rajkot
Figure 3.4.2: The plot of
0.3
0.4
0.5
0.6
0.7
0.8
9.4 9.6
nH
IV Dissociation constants
Department of Chemistry, Saurashtra University, Rajkot-360005
against B for PAB-101 and PAB-110 at 303.15 K.
9.8 10.0 10.2 10.4
B
[A]
Dissociation constants
172
at 303.15 K.
10.6
Section-IV Dissociation constants
Department of Chemistry, Saurashtra University, Rajkot-360005 173
The average pK1H values are evaluated and given in Table 3.4.1 for all compounds.
Further, from Figure 3.4.2 (A), at Hn = 0.5, the pK1H values were evaluated for
PAB-1 –PAB-107 and PAB-109 and are given in Table 3.4.2. It is evident from Table
3.4.2 that for most of the compounds, the pK1H values calculated by average method and
half-integral method are in good agreement.
For PAB-108 and PAB-110, the proton-ligand constants were calculated by
solving equation 3.4.1. For all the points below Hn =1, the following equation was used
HH H1log pK = pH +log n n -1
… (3.4.19)
Whereas for the points above Hn =1, the equation used was:
Hlogp K = pH +log n -1 2 - n2 H H … (3.4.20)
From the various values of log pK1H (or log pK2
H), the average value was
calculated. The values of log pK1H and log pK2
H calculated by the two methods i.e., half-
integral method and average method are given in Table 3.4.2.
Comparison of pK1H values of studied compounds (except PAB-108 and PAB-
110, which are of H2L type) shows that, PAB-102 which is most basic which is followed
by PAB-109. PAB-103 is found to be most acidic. All the compounds have the same
central moiety but different side chains which affects the dissociation constant. PAB-102
contains cinnamaldehyde side chain which is found to increase the basic character of this
compound whereas in PAB-109, due to furfuladehyde side chain, basic character is
greater than other studied compounds but less than that of PAB-102. PAB-103 contains
chloro group at meta position and its acidic character is higher. However, PAB-104 also
contains chloro group but at para position and acidic character of this compound is
slightly decreased. This suggests that the position of groups also affects the dissociation.
In case of PAB-105, fluoro group is at para position which further decreases the acidic
character in comparison to p-chloro group (as in PAB-104). Other compounds show
intermediate acidic character.
PAB-108 and PAB-110 are of H2L type and both contain hydroxyl groups at para
positions. Comparison of pK1 and pK2 values of these two compounds shows slight
difference. However, significant variations in these pK1 values evaluated by average and
Section-IV Dissociation constants
Department of Chemistry, Saurashtra University, Rajkot-360005 174
half-integral methods are also observed. Thus, it is difficult to compare the acidic
character of these two compounds. However, considering the pK2 values of these two
indicates the higher acidity of PAB-108, which may be due to presence of methoxy
group. Same characteristic behavior was also reported earlier79. Alteration of hydroxy
group with any other functional group can also change the dissociation of rate of the
compounds80.
From these results, it is concluded that different compounds exhibit different
dissociation constant which also depends upon the type of substituent group81. This is due
to inductive or mesomeric effect of functional groups.
Section-IV
Department of Chemistry, Saurashtra University, Rajkot
Figure 3.4.3: The plot of log
against B for PAB
-0.40
-0.35
-0.30
-0.25
-0.20
-0.15
-0.10
-0.05
0.00
9.4 9.5lo
g(
nH/(
1-n
H)
-0.22
-0.21
-0.20
-0.19
-0.18
9.4 9.5
log
( n
H/(
2-n
H)
IV Dissociation constants
Department of Chemistry, Saurashtra University, Rajkot-360005
log (nH/(1-nH) against B for PAB-101 and log (
PAB-110
9.6 9.7 9.8 9.9 10.0 10.1 10.2
B
9.6 9.7 9.8 9.9 10.0 10.1
B
Dissociation constants
175
(nH /(2-nH) in
10.2 10.3
10.2
Section-IV Dissociation constants
Department of Chemistry, Saurashtra University, Rajkot-360005 176
Table 3.4.2: The log pK1H and log pK2
H values for all the studied compounds
calculated by different methods.
Compounds
log pK1H log pK1
H / log pK2H
Half-
integral
method
Average
method
Half-integral
method
Average
method
PAB-101 9.88 9.54 PAB-107 10.90 10.90
PAB-102 12.78 12.33PAB-108
3.86 (nH=1.5)
10.2 (nH=0.5)
3.88 (nH=1.5)
9.73 (nH=0.5)PAB-103 9.40 9.41
PAB-104 9.50 9.50 PAB-109 10.96 10.93
PAB-105 9.94 9.93PAB-110
4.00 (nH=1.5)
9.8 (nH=0.5)
4.12 (nH=1.5)
9.32 (nH=0.5)PAB-106 9.84 9.86
Section-IV Dissociation constants
Department of Chemistry, Saurashtra University, Rajkot-360005 177
References
1. Foulon, C.; Danel, C.; Vaccher, C.; Yous, S.; Bonte, J.; Goossens, J.;
“Determination of ionization constants of N-imidazole derivatives, aromatase
inhibitors, using capillary electrophoresis and influence of substituents on pKa
shifts” J. Chroma. A 2004, 1035, (1)131–136.
2. Poupaert, J.; Carato, P.; Colacino, E; “2(3H)-Benzoxazolone and bioisosters as
privileged scaffold in the design of pharmacological probes” Curr. Med. Chem
2005, 12 877–885.
3. Avdeef, A.; Box, K. J.; Comer, J. E. A.; Gilges, E.; Hadley, M.; Hibbert, C.;
Patterson, W.; Tam K.Y.; “pKa determination of water-insoluble drugs in organic
solvent-water mixtures” J. Pharm. Biomed. Anal. 1999, 20, 631-641.
4. Shargel, L.; Andrew BC, Y.; “Applied Biopharmaceutics and Pharmacokinetics,
4th Edition, Appleton and Lange, 1999.
5. Poole, S. K.; Patel S.; Dehring, K.; Workman, H. and Poole, Colin F.;
“Determination of acid dissociation constants by capillary electrophoresis” J.
Chrom. A, 2004, 1037, 445–454.
6. Venkatesh, G.; Ramanathan, S.; Mansor, S. M.; Nair, N. K.; Abdul Sattar, M.;
Croft, S. L. and Navaratnam, L.; “Development and validation of RP-HPLC-UV
method for simultaneous determination of buparvaquone, atenolol, propranolol,
quinidine and verapamil: A tool for the standardization of rat in situ intestinal
permeability studies” J. Pharm. Bio. Ana. 2007, 43(4), 1546-1551.
7. TonyTong, W. Q. and Whitesell, G.; “In Situ Salt Screening-A Useful Technique
for Discovery Support and Preformulation Studies” Pharm. Dev. Technol., 1998,
3, 215-223.
8. Lee, Y.; Zocharski, P. and Samas, B.; “An intravenous formulation decision tree for
discovery compound formulation development” Int. J. Pharm. 2003, 253, 111-119.
9. Basavaraj, S.; Sihorkar, V.; Shantha Kumar, T. R.; Sundaramurthi, P.; Srinivas, N.
R.; Venkatesh, P.; Ramesh, M. and Kumar Singh, S.; “Bioavailability
Enhancement of Poorly Water Soluble and Weakly Acidic New Chemical Entity
with 2-Hydroxy Propyl-β-Cyclodextrin: Selection of Meglumine, a Polyhydroxy
Base, as a Novel Ternary Component” Pharm. Dev. Technol., 2006, 11, 443-451.
10. Dawsan, H. M.; Hall, G. V. and Key, A.; “Acid and salt effects in catalysed
reactions. Part XVII. The variation of the catalytic activity of an acid with its
Section-IV Dissociation constants
Department of Chemistry, Saurashtra University, Rajkot-360005 178
concentration, and the determination of ionisation constants” J. Chem. Soc. 1928,
2844-2853.
11. Dey, B.; Coates, J.; Duckworth, P.; Lincoln, S. and Wainwright, K.; “pH-metric
studies on the acid dissociation constants of a macrocyclic ligand and the apparent
formation constants of some transition metal complexes of the ligand” Science
1993, 17(2), 57-65.
12. Fan, J.; Shen, X. and Jianji, W.; “Determination of acids-base dissociation
constants of glycine in ethanol-water mixed” Fenxi. Shiyanshi 1997, 16(2), 66-70.
13. Saraswathi, K.; Babu, S. S. and Sunandamma, Y.; “pH-metric method for ligand
dissociation constants of mercaptotriazoles and their reactions” Asian. J. Chem.
2000, 12(1), 313-314.
14. Maharramov, A.; Babayeva, G.; Gasanov, V.; Chyraqov, F.; Sadikhova, N. and
Allakhverdiyev, M.; “Determination of dissociation constants of (2-imino-4-
oxothiazolidin-5-yl) acetic acid and stability constnants of its complexes with
some metals” Sakartvelos Mec. 2008, 34(2), 175-178.
15. Mercier, J. P.; Morin, Ph. and Tambute, D.; “Determination of weak (2.0-2.5)
dissociation constants of non-UV absorbing solutes by capillary electrophoresis”
Chromatographia 1998, 48, 529-534.
16. Winzor, D.; “Specific allowance for antibody bivalence in the determination of
dissociation constants by kinetic exclusion assay” Anal. Bio. 2011, 414, 273–277.
17. Fielding, L.; “NMR methods for the determination of protein-ligand dissociation
constants” Prog. In NMR Spect. 2007, 51, 219-242.
18. Delahay, P. and Vielstich, W.; “Kinetics of the dissociation of weak acids and
bases. Application of polarography and voltammetry at constant current” J. Am.
Chem. Soc. 1955, 77, 4955-4958.
19. Dauphin, J.; Chatonier, D.; Couquelet, J.; Payard, M. and Picard, M.; “Application
of conductimetry to the study of dissociation constants of 2-chromo Necarboxylic
acid and its sodium salt” Labo-Pharma – Prob. Tech. 1970, 18, 58-59.
20. Funasaki, N.; “The dissociation constants of acid-base indicators on the micellar
surface of dodecyldimethylamine oxide” J. Colloid Inter. Sci. 1977, 60, 54-59.
21. Levitt, L.; “Determination of the dissociation constant and limiting equivalent
conductance of a weak electrolyte from conductance measurements on the weak
electrolyte” Anal. Chim. Acta. 1981, 125, 219-220.
Section-IV Dissociation constants
Department of Chemistry, Saurashtra University, Rajkot-360005 179
22. Tanaka, H.; Aritsuka, K.; Tachibana, T.; Chuman, H. and Dasgupta, P. K.;
“Determination of dissociation constants of weak acids by feedback-based flow
ratiometry,” Anal. Chim. Acta. 2003, 499, 199-204.
23. Tanaka, H.; Tachibana, T.; Oda, R. and Dasgupta, P.; “Determination of acid
dissociation constants based on continuous titration by feedback-based flow
ratiometry,” Talanta 2004, 64, 1169-1174.
24. Sıdır, Y. G.; Sıdır, I. and Berber, H.; “Spectroscopic Determination of Acid
Dissociation Constants of N-Substituted-6-acylbenzothiazolone Derivatives” J.
Phys. Chem. A 2011, 115, 5112–5117.
25. Ogretir, C.; Demirayak, S. and Duran, M.; “Spectroscopic Determination and
Evaluation of Acidity Constants for Some Drug Precursor 2-Amino-4-(3- or 4-
substituted phenyl) Thiazole Derivatives” J. Chem. Eng. Data. 2010, 55, 1137–
1142.
26. Lachenwitzer, A.; Li, N. and Lipkowski, J.; “Determination of the acid
dissociation constant for bisulfate adsorbed at the Pt(111) electrode by
subtractively normalized interfacial Fourier transform infrared spectroscopy” J.
Electroanal. Chem. 2002, 532, 85-98.
27. Uhrova, M.; Miksik, Z. and Bellini, D.; “Determination of dissociation constants
by separation method (HPLC and CE). Theoretical background and guidelines for
application”, Process Control Quality, 1997, 10, 151-167.
28. Bogolitsyn, K. G.; Kosyakov, D. S.; Gorbova, N. S.; Aizenshtadt, A. M. and
Shorina, N. V.; “The acidity and salvation of ligninrelated phenols in water-1,4-
dioxane mixtures” Russ. J. Phys. Chem. A. 2008, 82, 237-241.
29. Blano, S. E.; Almandoz, M. C. and Ferretti, F. H.; “Determination of overlapping
pKa values of recorcinol using UV-visible spectroscopy and DFT methods”
Spectrochem. Acta. A 2005, 61, 93-102.
30. Krebs, H. A. and Speakman, J. C.; “Dissociation constant, Solubility and the pH
value of the solvent J. Chem. Soc. 1945, 593-595.
31. Danish, I. A.; Lim, C. S.; Shun Tian, Y. S.; Han, J. H.; Kang, M. Y. and Cho, B.
R.; “Two-Photon Probes for Zn2+ Ions with Various Dissociation Constants.
Detection of Zn2+ Ions in Live Cells and Tissues by Two-Photon Microscopy”
Chem. Asian J. 2011, 6, 1234 – 1240.
Section-IV Dissociation constants
Department of Chemistry, Saurashtra University, Rajkot-360005 180
32. Sue, K.; Morita, T.; Totsuka, K.; Takebayashi, Y.; Yoda, S.; Furuya, T. and Hiaki,
T.; “Determination of Dissociation Constants of Hexanoic, Heptanoic, and
Benzoic Acids to 673 K and 30 MPa by Potentiometric pH Measurements” J.
Chem. Eng. Data 2010, 55, 4823–4826.
33. Meloun, M.; Ferencíkova, Z.; Netolicka, L. and Pekarek, T.; “Thermodynamic
Dissociation Constants of Alendronate and Ibandronate by Regression Analysis of
Potentiometric Data” J. Chem. Eng. Data 2011, 56, 3848–3854.
34. Albert, A. and Serjeant, E. P.; “Ionization Constants of Acids and Bases”,
Methuen and Co., Ltd. 1962, 69-92.
35. Kudo, Y.; Takeuchi, S.; Kobayashi, Y.; Katsuta, S. and Takeda, Y.”
“Potentiometric determination of ion-pair formation constants for cadmium,
calcium salts, and cadmium-18-crown-6 ether derivative complexes with a
sulphate ion in water”. J. Chem. Eng. Data 2007, 52(5), 1747-1752.
36. Jano, I.; Hardcastle, J.; Jano, L.; Bates, K. and McCreary, H.; “General equation
for determining the dissociation constants of polyprotic acids and bases from
additive properties Part IV. Application to potentiometric titration” Anal. Chim.
Acta. 2001, 428, 309–321.
37. Pryszczewska, M. and Lipiec, T.; “Spectrophotometric determination of the
dissociation constant of a complex compound” Roczniki Chemii. 1955, 29, 985-
992.
38. Ernst, Z. L. and Menashi, J.; “Spectrophotometric determination of the
dissociation constants of some substituted salicylic acids” Trans. Farad. Soc.
1963, 59, 230-240.
39. Hewala, I. I.; el-Yazbi, F. A.; Awad, A. and Wahbi, A. M.; “Determination of
dissociation constants of some pharmaceutical compounds using derivative
spectrophotometry” J. Clin. Pharm. Thera. 1992, 17, 233-239.
40. Kadar, M. Biro, A.; Toth, K.; Vermes, B. and Huszthy, P.; “Spectrophotometric
determination of the dissociation constants of crown ethers with grafted acridone
unit in methanol based on Benesi-Hildebrand evaluation” Spectrochim. Acta, Part
A: Mol. Biomol. Spect. 2005, 62, 1032-1038.
41. Unal, G.; Yeloglu, I.; Anilanmert, B. and Narin, I.; “pKa Constant of Varenicline”
J. Chem. Eng. Data 2012, 57, 14 – 17.
Section-IV Dissociation constants
Department of Chemistry, Saurashtra University, Rajkot-360005 181
42. Kamps, A. P. and Maurer, G.; “Dissociation Constant of N-Methyldiethanolamine
in Aqueous Solution at Temperatures from 278 K to 368 K” J. Chem. Eng. Data
1996, 41, 1505-1513.
43. Taha, M. and Fazary, A.; “Thermodynamics of the second-stage dissociation of 2-
[N-(2-hydroxyethyl)- N -methylaminomethyl]-propenoic acid (HEMPA) in water
at different ionic strength and different solvent mixtures” J. Chem. Thermo. 2005,
37, 43–48.
44. Evagelou, V.; Tsantili-Kakoulidou A.; Koupparis, M.; “Determination of the
dissociation constants of the cephalosporins cefepime and cefpirome using UV
spectrometry and pH potentiometry” J. Pharm. Bio. Ana. 2003, 31(6), 1119-1128.
45. Hagenmuller, P.; “New method of determination of the dissociation constant of a
complex in solution” Compt. rend. 1950, 230, 2190-2192.
46. Vasil'ev, V.; “Effect of ionic strength on the dissociation constants of complex
compounds” Zhur. Neorga. Khim. 1962, 7, 1788-1794.
47. Patel, C. and Patel, R.; “Acid dissociation constants of some 3-substituted 2-
hydroxy-5-methylacetophenones and the formation constants of their metal
complexes” J. Ind. Chem. Soc. 1975, 52, 312-314.
48. Morrison, J. F. and Cleland, W. W.; “A kinetic method for determining
dissociation constants for metal complexes of adenosine 5'-triphosphate and
adenosine 5'-diphosphate” Biochem. 1980, 19, 3127-3131.
49. Piran, U. and Riordan, W. J.; “Dissociation rate constant of the biotin-streptavidin
complex” J. Immuno. Methods. 1990, 133, 141-143.
50. Rózga, M.; Kłoniecki, M.; Dadlez, M. and Bal, W.; “A Direct Determination of
dissociation Constant for the Cu(II) Complex of Amyloid β 1−40 Peptide” Chem.
Res. Toxico. 2010, 23 (2), 336–340.
51. Zuskova, I.; Novotna, A.; Vcelakova, K. and Gas, B.; “Determination of limiting
mobilities and dissociation constants of 21 amino acids by capillary zone
electrophoresis at very low pH” J. Chromato. B. 2006, 841, 129-134.
52. Nagai, H.; Kuwabara, K.; Carta, G.; “Temperature Dependence of the
Dissociation Constants of Several Amino Acids” J. Chem. Eng. Data. 2008, 53,
619–627.
Section-IV Dissociation constants
Department of Chemistry, Saurashtra University, Rajkot-360005 182
53. Leyda, J. P.; Lamb, D. J. and Harris, L. E.; “Distribution coefficients and
dissociation constants of a series of barbituric acid derivatives” J. Am. Pharm.
Asso. Sci. Edi. 1960, 49, 581-583.
54. Dang, U.; Nguyen, T. and Vuong, D.; “Determination of dissociation constant of
monoprotic acids from pH data by simplex algorithm” Tap Chi Phan Tich Hoa, Ly
Va Sinh Hoc. 2002, 7, 31-36.
55. Delphay, P. and Vielstich, W.; “Kinetics of the dissociation of weak acids and
bases-application of polarography and voltammetry at constant current” Phy.
Inorg. Chem. 1955, 77, 4955-4958.
56. Poe, M.; “Acidic dissociation constants of folic acid, dihydrofolic acid, and
methotrexate” J. Bio. Chem. 1977, 252, 3724-3728.
57. Brockman, F. G.; Kilpatrick, M.; “The Thermodynamic Dissociation Constant of
Benzoic Acid from Conductance Measurements” J. Am. Chem. Soc. 1934, 56(7),
1483–1486.
58. Oumada, F. Z.; Rafols, C.; Roses, M. and Bosch, E.; “Chromatographic
determination of aqueous dissociation constant of some water-insoluble
antiinflamatory drugs” J. Pharm. Sci. 2002, 91(4), 991-999.
59. Şanli, S.; Şanli, N. and Alsancak, G.; “Determination of Protonation Constants of
Some Tetracycline Antibiotics by Potentiometry and LC Methods in Water and
Acetonitrile-Water Binary Mixtures” J. Braz. Chem. Soc. 2009, 20(5), 939-946.
60. Srour, R. K. and McDonald, L. M.; “Determination of the Acidity Constants of
Methyl Red and Phenol Red Indicators in Binary Methanol - and Ethanol-Water
Mixtures” J. Chem. Eng. Data 2008, 53, 116–127.
61. Funasaki. N.; “The dissociation constants of acid-base indicators on the micellar
surface of dodecyldimethylamine oxide” J. Colloid Interface Sci. 1977, 60, 54-59.
62. Fedorov, S.; Kudryavtseva, L.; Bel'skii, V.; Ivanov, B.; “Determination of the
dissociation constants of micelle-solubilized compounds, Kolloidnyi Zhur” 1986,
48, 199-201.
63. Hayman, B. and Tapuhi, E.; “The Dissociation Constants of Dim and
Trichloroacetic Acids Measured by a Distribution Method” J. Chem. Eng. Data
1977, 22(1), 22-24.
Section-IV Dissociation constants
Department of Chemistry, Saurashtra University, Rajkot-360005 183
64. Melouna, M.; Ferenciková, Z. and Vrána, A.; “Determination of the
thermodynamic dissociation constant of capecitabine using spectrophotometric
and potentiometric titration data” J. Chem. Thermo. 2011, 43, 930–937.
65. Meloun, M.; Syrovy, T. and Vrana, A.; “The thermodynamic dissociation
constants of losartan, paracetamol, phenylephrine and quinine by the regression
analysis of spectrophotometric data” Anal. Chim. Acta 2005, 533, 97–110.
66. Solinova, V.; Kasicka, V.; Koval, D.; Cesnek, M. and Holy, A.; “Determination of
acid-base dissociation constants of amino- and guanidinopurine nucleotide
analogs and related compounds by capillary zone electrophoresis”
Electrophoresis. 2006, 27, 1006-1019.
67. Issam, J.; James, H.; Jano, L.; Bates, K. and McCreary, H.; “General equation for
determining the dissociation constants of polyprotic acids and bases from additive
properties Part IV. Application to potentiometric titration” Anal. Chim. Acta 2001,
428, 309–321.
68. Kulig, K.; Rybicka, K. and Malawska, B.; “Application of RP-TLC technique for
the determination of dissociation constants of 1-substituted pyrrolidin-2-one
derivatives” Biomed. Chroma. 2008, 22, 1225-1229.
69. Yagil, G.; “The protein dissociation constant of Pyrrole, Indole and related
compounds” Tetrahedron 1967, 23, 2855-2861.
70. Bartolini, M.; Bertucci, C.; Gotti, R.; Tumiatti, V.; Cavalli, A.; Recanatini, M. and
Andrisano, V.; “Determination of the dissociationconstants (pKa) of basic
acetylcholinesterase inhibitors by reversed-phase liquid chromatography” J.
Chrom. 2002, 958(1–2), 59–67.
71. Hwan Urn, I.; Ju Hong, Y.; and Sook Kwon, D.; “Acid dissociation constants of
phenols and reaction mechanism for the reactions of substituted phenyl benzoates
with phenoxide anions in absolute ethanol” Tetrahedron 1997, 53(14), 5073-5082.
72. Belikov, V.; Belokon, Y.; Dolgaya, M. and Mawtinkova, N.; “The kinetics and
mechanism of mannich base dissociation in aqueous buffers” Tetrahedron 1970,
26, 1199-1216.
73. Tamura, H. and Furuichi, R.; “Determination of the dissociation constants of
surface hydroxyl groups: application to the characterization of metal oxides”
Nipp. Kinz. Gakk. Kai. 1988, 27, 158-164.
Section-IV Dissociation constants
Department of Chemistry, Saurashtra University, Rajkot-360005 184
74. Azimi, G.; Khoobi, A.; Zamani, K. and Zolgharnein, J.; “Multiwavelength
Spectrophotometric Determination of Acidity Constants of Newly Synthesized
1,2,4-Triazole Derivatives in Ethanol-Water Mixtures” J. Chem. Eng. Data 2008,
53, 1862–1866.
75. Bhagwatkar, R.; Tayade, D.; Pund, D.; Rathod, D. and Bhagwatkar, N.; “pH
Metric Studies of Interaction of Synthesized Ligands 2-amino-4-hydroxy-6-
methylpyrimidine and 1-(4-hydroxy-6-methylpyrimidino)-3 -phenylthiocarbamide
with Cu(II), Cd(II), Cr(II), Cations At 0.1 M Ionic Strength” I. J. Chem. 3(1),
2011, 36-41.
76. Bjerrum, J. and Hease, P. “Metal Ammine Formation in aqueous solution” 1941.
77. Irving, H. M. and Rossoti, H. S.; “The calculation of formation curves of metal
complexes from pH titration curves in mixed solvents” J. Chem. Soc. 1954, 10,
2904-2910.
78. Uitert, L. and Hass, C.; “A Method for Determining Thermodynamic Equilibrium
Constants in Mixed So1vents” J. Am. Chem. Soc. 1953, 75, 451-455.
79. Ephraim, J.; Alegret, S.; Mathuthu, A.; Bicking, M.; Malcolm, R. and Marinsky,
J.; “A unified physicochemical description of the protonation and metal ion
complexation equilibria of natural organic acids (humic and fulvic acids). 2.
Influence of polyelectrolyte properties and functional group heterogeneity on the
protonation equilibria of fulvic acid.” Environ. Sci. Technol. 1986, 20(4), 354–
366.
80. Yoda, A.; “Structure-Activity Relationships of Cardiotonic Steroids for the
Inhibition of Sodium- and Potassium-Dependent Adenosine Triphosphatase I.
Dissociation Rate Constants of Various Enzyme-Cardiac Glycoside Complexes
Formed in the Presence of Magnesium and Phosphate.” Mol. Pharmacol. 1973,
9(1), 51-60.
81. El-Sonbati, A.; El-Bindary, A.; Shoair, A. and Younes, R.; “Stereochemistry of
new nitrogen containing heterocyclic aldehyde. vii. potentiometric,
conductometric and thermodynamic studies of novel quinoline azodyes and their
metal complexes with some transition metals.” Chem. Pharma. Bull. 2001, 49(10),
1308-1313.
Section-V
Thermal properties
Section-V Thermal properties
Department of Chemistry, Saurashtra University, Rajkot-360005 185
INTRODUTION
Thermal analysis has been proved to be a key method in the study and
characterization of various materials and finds wide applications in industrial and
research fields. Among the several instruments and technique, thermal analysis has grown
rapidly in recent years. This increasing importance is due to the advancement of thermal
analysis technology, relative low cost of the equipment and time required to achieve the
desired results.
For the complete development of a new drug, thermal analysis has many
applications1,2. The information obtained regarding the compounds under study is useful
for the initial chemical research phase3. In the chemical research phase, thermal analysis
plays an important role. The purity of the compound, the compound’s ability to be able to
exist in various crystalline forms as well as to characterize polymorphs and other forms of
solid state should be investigated. It also makes possible to determine optimum conditions
of storage of drugs and to define the parameters of technological processes, which can be
used without loss of specific physicochemical properties of a drug 4-5
Apart from its traditional use in investigations of chemical reactions, temperature
programmed decompositions, reaction kinetics and mechanism, determination of material
purity etc. can also be studied. This technique is also used in pharmaceutical science6,7,
forensic science8, archeology9,10 etc. Various thermal methods have been used in
analyzing and characterizing a wide variety of materials like coals, rocks and minerals11,12
petroleum coke13, hydrocarbon sludge from petrochemical plants14,15, hydrogen storage
materials16, catalysis17,18, dyes19,20, fertilizers21,22, nuclear fuel23,24, vitamin25, honey26,
tobacco27 and edible oil28 and even rocks from moon.
Literature survey shows that various workers have studied thermal properties of
various drugs29-34 and organic compounds35-37. Bei et al.38 have reported the thermal
decomposition kinetic of 5-flourouracil from thermogravimetric analysis. Vora et al39
studied thermal stability of folic acid. Quan et al40 have reported thermal data of 4-
Dimethylaminopyridine. Thermal behavior of cobalt(II) 5-chloro-piridylamides
complexes have been studied by Lima et al41. Thermal decomposition studies of triazole
and 1-methyl-3,4,5-trinitropyrazole have been reported by Sasidharan et al42 and Ravi et
al43 respectively.
Section-V Thermal properties
Department of Chemistry, Saurashtra University, Rajkot-360005 186
Differential scanning calorimetry (DSC) has been extensively used for material
characterization in a wide variety of research areas, including food science,
pharmaceutics, material science, biochemistry, and physics, due to a number of
significant advantages, such as ease of sample preparation, applicability to solid and
liquid samples, fast analysis time, and a broad temperature range44. DSC provides both
quantitative and qualitative thermal and physical material property information (e.g.,
phase transition, glass transition, cold crystallization, polymorphism, and purity) as a
function of time and temperature. Because every change in structure (transition) either
absorbs or releases heat, DSC is the universal detector for measuring structural changes45.
Various researchers have reported the calorimetric study of drugs46-48. Lee et al.49,50 have
shown that the loss of crystalline structure in sucrose, glucose, and fructose is due to the
kinetic process of thermal decomposition, dehydration, and chemical reactions. Thermo
physical study of several barbituric acid derivatives was done by differential scanning
calorimetry51.
Both calorimetry and thermogravimetry can also be used in the evaluation of
compound stability52-56 Predicting stability or instability at a very early stage of product
development, such as immediately after the initial synthesis process, provides valuable
information.
In the present study, thermal analysis of some new synthesized
tetrahydropyrimidine derivatives has been done by DSC and TGA techniques.
Section-V Thermal properties
Department of Chemistry, Saurashtra University, Rajkot-360005 187
THEORY
From TGA curves, various kinetic parameters can be evaluated by several
methods. In all these methods, it is assumed that thermal and diffusion barriers are
negligible because small quantity of material is used. The shape of any TGA curve
depends on the nature of apparatus and the way in which it is used. Further, Arrhenius
equation is valid in all these methods.
The kinetic treatments are generally based on the relationship of the type:
dC/dt = K f (C) ... (3.5.1)
where C is the degree of conversion, t is time and K is rate constant. f(C) is a temperature
independent function of C.
The constant K is assumed to have the Arrhenius form:
K = A e -E/RT ... (3.5.2)
C can also be defined as:
C = 1-(W/ W0) ... (3.5.3)
where W0 and W are the initial weight at t=0 and weight at any time t of the material.
Equation (3.5.3) can be written as:
(W/W0) = (1-C) ... (3.5.4)
W/ W0 is known as residual weight fraction.
Thus, the rate of conversion is,
dC/dt = - (1/ W0) (dW/dt) ... (3.5.5)
For homogeneous kinetics, the conversion is assumed to be of the form:
f (C) = (1-C)n ... (3.5.6)
where n is the order of the reaction.
Substituting the values from equation (3.5.2) and (3.5.6) in equation (3.5.1) gives:
dC/ dt = A e -E/RT (1-C)n
or dC/dt = (A/β) e -E/RT (1-C)n ... (3.5.7)
where A is the frequency factor, β is the rate of heating and E is the energy of activation.
Section-V Thermal properties
Department of Chemistry, Saurashtra University, Rajkot-360005 188
Various methods for single and multiple heating rates have been reported. The
methods of single heating rate are as follows:
1. Freeman-Carroll57 and Anderson-Freeman Method58:
At a single heating rate, Freeman and Carroll gave the following relation to
analysis TGA data :
ln (dC/dt)/ln (1-C) = n-E/R [(1/T/(△ln(1-C)] ... (3.5.8)
A plot of left hand side against (1/T)/( △ln(1-C)) gives a straight line with a slope
equal to -E/R and the intercept is equal to n.
Above equation (3.5.8) is modified by Anderson and Freeman in the following
form:
(△ln[dC/dt]) = n (△ln(1-C)) - E/R△(1/T) ... (3.5.9)
The plot of (△ln[dC/dt]) against (△ln(1-C)) for equal intervals of △(1/T) gives a
straight line with slope equal to n and intercept -E/R△(1/T).
2. Horowitz and Metzger method59 :
In this method, the value of energy of activation E can be determined from a
single TG curve by the relation:
ln [ln(1-C)-1] = (E/RTs
2) θ ... (3.5.10)
where θ = T-Ts. Ts is the temperature at which the rate of decomposition is maximum.
The frequency factor A and entropy change △S can be determined by the following equations:
ln E - ln (RTs2) = ln A - ln β - E/RTs ... (3.5.11)
A = (kbT / h) e△S/R ... (3.5.12)
where kb is Boltzmann constant and h is Planck’s constant.
Section-V Thermal properties
Department of Chemistry, Saurashtra University, Rajkot-360005 189
EXPERIMENTAL
Thermo gravimetric analysis (TGA) and Differential Scanning Calorimetry (DSC)
measurements were made on the instrument “Pyris-1, Perkin Elmer Thermal Analysis” at
the heating rate of 10C /min in nitrogen atmosphere for all the tetrahydropyrimidine
derivatives.
Section-V Thermal properties
Department of Chemistry, Saurashtra University, Rajkot-360005 190
RESULTS AND DISCUSSION
The TGA thermo grams of PAB-101 and PAB-109 are given in Figure 3.5.1.
Various thermal properties such as initial decomposition temperature (IDT), the
decomposition temperature range and the maximum degradation along with the
percentage weight loss are reported in Table 3.5.1.
For all the compounds, degradation is single step process. Out of ten compounds,
PAB-102 is most unstable which is followed by PAB-103. PAB-107 is the most stable
compound which is followed by PAB-106. All the studied compounds have the same
central moiety but substitution groups are different. Thus, substitution affects the thermal
stability of a compound. PAB-102 contains cinnamaldehyde as substitution to aromatic
ring. Thus, cinnamaldehyde makes the compound unstable whereas chloro group at meta
position (as in PAB-103) makes it a little bit less stable. However, the presence of nitro
group at meta position increases the stability as is the case for PAB-107. Whereas
presence of methoxy group at para position decreases the stability slightly. Further, it is
observed that the position of group affect the stability as observed in case of PAB-103
and PAB-104. Both these compounds contain chloro group. In PAB-103, it is at meta
position whereas in PAB-104, it is at para position. It is observed that when chloro group
is at meta position, it decreases the stability in comparison to that at para position. Both
methoxy and hydroxyl groups when present alone at para position increases the stability
as observed in PAB-106 and PAB-110. However, when both groups are present together
as in PAB-108, stability is reduced. Further, it is observed that although PAB-102 is most
unstable, weight loss is minimum for this compound whereas for PAB-1-1, it is
maximum. The variation in thermal decomposition may also be due to some
intermolecular interactions (structural as well as electronic).
Further, various kinetic parameters, such as order of the degradation (n), energy of
activation (E), frequency factor (A) and entropy change (ΔS) have also been calculated
from the thermograms and are reported in Table 3.5.2. The order of reaction (n) varies
from 0.64 to 8.09. The value of n is minimum for PAB-104 and maximum for PAB-103.
The energy of activation (E) is highest for PAB-105 containing fluoro group at
para position and minimum for PAB-103 which is containing chloro group at meta
position. The frequency factor (A) is also highest for PAB-105 but minimum for PAB-
107. Further, change in entropy (ΔS0) for all these reactions were also calculated by
Section-V
Department of Chemistry, Saurashtra University, Rajkot
Figure 3.5.1: The TGA graphs of PAB
V Thermal properties
Department of Chemistry, Saurashtra University, Rajkot-360005
The TGA graphs of PAB-101 and PAB-109
Thermal properties
191
Section-V Thermal properties
Department of Chemistry, Saurashtra University, Rajkot-360005 192
Table 3.5.1: TGA data for synthesized tetrahydropyrimidine derivatives.
Comp. Code
Amount(mg.)
InitialDecomp.Temp.(°C)
Decomp.Range (°C)
% Wt.loss
Residual wt.loss
(mg.)
Max.Degrad.Temp. (°C)
Transition
PAB-101 2.297 110.00 110-250 99.02 2.275 168.08 EndoPAB-102 5.104 70.00 70-296.50 49.72 2.538 191.49 EndoPAB-103 2.497 80.00 80-190 88.76 2.217 164.67 EndoPAB-104 1.741 140.00 140-230 93.72 1.632 181.74 EndoPAB-105 2.160 110.00 110-230 99.85 2.157 172.27 EndoPAB-106 2.938 150.00 150-246.20 71.26 2.094 209.00 EndoPAB-107 3.127 153.51 153-296.30 88.43 2.766 247.22 EndoPAB-108 1.071 90.00 90-246.80 81.37 0.872 210.00 EndoPAB-109 2.969 100.00 100-240 92.72 2.753 166.72 EndoPAB-110 1.903 145.45 145.45-246.70 87.17 1.659 213.18 Endo
Table 3.5.2: The kinetic parameters of tetrahydropyrimidine derivatives
Comp.code
n E(kJ)
A(Sec-1)
ΔSo
(J-1)
PAB-101 2.89 418.46 4.47X1049 855.48PAB-102 2.79 434.24 7.52X1048 840.22PAB-103 8.09 251.64 7.88X1029 477.38PAB-104 0.64 529.69 9.75X1060 1072.28PAB-105 1.78 535.92 1.09X1063 1111.64PAB-106 5.14 460.97 9.85X1049 861.30PAB-107 3.29 253.15 1.34X1025 384.64PAB-108 1.32 480.17 9.59X1051 899.36PAB-109 4.44 401.11 5.06X1047 818.24PAB-110 2.44 490.65 5.91X1052 914.42
Section-V
Department of Chemistry, Saurashtra University, Rajkot
Figure 3.5.2: The DSC graphs of PAB
V Thermal properties
Department of Chemistry, Saurashtra University, Rajkot-360005
igure 3.5.2: The DSC graphs of PAB-101 and PAB-109
Thermal properties
193
Section-V Thermal properties
Department of Chemistry, Saurashtra University, Rajkot-360005 194
Table 3.5.3: The melting temperature (0C) of tetrahydropyrimidine derivatives by
DSC and open capillary methods.
Comp. Code
PAB-101
PAB-102
PAB-103
PAB-104
PAB-105
PAB-106
PAB-107
PAB-108
PAB-109
PAB-110
DSC 140.00 113.29 153.75 163.51 129.04 116.48 105.77 132.94 71.60 177.94
Opencapillary 142 114 154 164 129 116 106 132 72 178
equation (3.5.12) and are reported in Tables 3.5.2. The entropy change (ΔS0) is found to
be positive for all ten compounds which indicate that the transition state is less ordered
than the original compound60.
Figure 3.5.2 shows DSC of PAB-101 and PAB-109. From DSC, melting points of
all the compounds are determined and are given in Table 3.5.3 along with melting points
determined by open capillary method. There is good agreement between the values
evaluated from DSC and those determined by open capillary method.
Thus, it is concluded that for the studied compounds, degradation is single step
process with different order of reaction. The thermal stability depends upon the type of
substituent present.
Section-V Thermal properties
Department of Chemistry, Saurashtra University, Rajkot-360005 195
REFERENCES
1. D. Giron, “Application of thermal analysis in the pharmaceutical industry” J.
Pharm. Biomed. Anal. 1986, 4(6), 755-770.
2. D. Giron, “Thermal Analysis of Drugs and Drug Products” Encyclopedia of
Pharmaceutical Technology, Third Edition, 2006.
3. Hardy, M. J.; Charsley E. L. and Warrington, S. B.; Thermal analysis-techniques
and applications, The Royal Society of Chemistry, Cambridge 1992, 180–197.
4. Rubinstein M. H.; “Pharmaceutical technology: drug stability.” Chichester: Ellis
Horwood; 1989.
5. Brittain H G.; “Physical characterization of pharmaceutical solids.” New York:
Marcel Dekker, Inc.; 1995.
6. Neill, O.; Michael, A. and Gaisford, S.; “Application and use of isothermal
calorimetry in pharmaceutical development” Inter. J. Pharm. 2011, 417(1-2), 83-
93.
7. Lizarraga, E.; Zabaleta, C. and Palop, J.; “Thermal stability and decomposition of
pharmaceutical compounds” J. Therm. Anal. Calori. 2007, 89(3) 783–792.
8. Raja, S., Thomas, P.; Stuart, B.; Guerbois, J. and O'Brien, C.; “The estimation of
pig bone age for forensic application using thermogravimetric analysis.” J. Therm.
Anal. Calori. 2009, 98(1), 173-176.
9. Cavallaro G.; Donato, I.; Lazzara G. and Milioto S.; “A comparative
thermogravimetric study of waterlogged archaeological and sound woods” J
Therm. Anal. Calori. 2011, 104, 451-457.
10. Deviese, T.; Colombini, M.; Regert, M.; Stuart, B. and Guerbois, J.; “TGMS
analysis of archaeological bone from burials of the late Roman period” J. Therm.
Anal. Calori. 2010, 99, 811–813.
11. Kodle, K.; Andrade, P.; Valenca, J. and Souza, D.; “Study on the composition of
mineral scales in oil wells” J. Petro. Sci. Eng. 2012, 81, 1-6.
12. Srivastava, Y.; Neloy, K. and Ingle, S.; “Characterization of clay minerals in the
sediments of Schirmacher Oasis, East Antarctica: their origin and climatological
implications.” Curr. Sci., 2011, 100(3), 363-372.
13. Jess, A. and Andresen, A.; “Influence of mass transfer on thermogravimetric
analysis of combustionand gasification reactivity of coke” Fuel 2010, 89 1541–
1548.
Section-V Thermal properties
Department of Chemistry, Saurashtra University, Rajkot-360005 196
14. Remmler, M.; Kopinke, F. and Stottm, E.; “Thermoanalytical methods for
characterizing hydrocarbon-sludge-soil mixtures.” Thermochim. Acta. 1995, 263,
101-112.
15. Lapuerta, M.; Ballesteros, R. and Rodriguez-Fernandez, J; “Thermogravimetric
analysis of diesel particulate matter.” Meas. Sci. Technol. 2007, 18, 650–658.
16. Kamruddin, M.; Dash, A.; Tyagi, S. and Baldev, A.; “Thermogravimetry-evolved
gas analysis–mass spectrometry system for materials research.” Bull. Mater. Sci.
2003, 26(4), 449–460.
17. Youssef, T. and Mekewi, M.; “Thermal stability eminence of PMMA prepared in
presence of photosynthesized ruthenium carbonyl Schiff base as a catalyst.” J.
Appl. Poly. Sci. 2009, 114(3), 1503-1510.
18. Babenko, V.; Pakhomov, N. and Buyanov, R.; “Study of thermal stability of
aluminum-chromium catalysts for a single-stage process of butane
dehydrogenation.” Kataliz v Promyshlennosti 2009, 1, 13-19.
19. Bindhu, C. and Harilal, S.; “Effect of the excitation source on the quantum-yield
measurements of Rhodamine B laser dye studied using thermal technique”.Anal.
Sci. 2001, 17, 141-144.
20. Long, J.; Wang, H. and Chen, X.; “Study of the inclusion action of cyclodextrin
on cationic dyes” Fan. Xue. 2002, 23, 33-35.
21. Chen, J.; Tsai, H. and Lin, Y.; “Evaluation of the suitability of three analysis
methods for determining organic matter contents in fertilizers” Nongye Huaxue Yu
Shipin Kexue, 2004, 42,116-124.
22. Kolesnikov, V. and Moskalenko, L.; “Thermal analysis studies of modification
transformations of a fertilizer obtained from ammonium nitrate” Khimiche.
Promy. Sego. 2006, 7, 18-21.
23. Sugama, H.; Okamoto, M. and Wakatani, M.; “Transport analysis based on K-β
anomalous transport model,” AIP Conf. Proc. 1994, 284, 509-525.
24. De Luca, F.; Galli, P.; Gorini, G.; Jacchia, A.; Mantica, P.; Deliyanakis, N.; Erba,
M. and L. Porte; “Sawtooth heat pulse propagation in tokamaks. Ballistic response
and Fourier analysis” Nucl. Fus. 1996, 36, 909-916.
25. Moura, T.; Gaudy, D.; Jacob, M. and Terol, A.; Pauvert, B. and Chauvet, A.;
“Vitamin C spray drying: study of the thermal constraint” Drug Develop. Ind.
Pharm. 1996, 22, 393 – 400.
Section-V Thermal properties
Department of Chemistry, Saurashtra University, Rajkot-360005 197
26. Maria, L.; Cristiane, B.; Jivaldo, R.; Lígia, B. and Roy, E.; “Optimization of
Thermogravimetric Analysis of Ash Content in Honey” J. Brazil. Chem. Soc.
2004, 15(6), 797-802.
27. Li, G.; Lv, Y.; Ma, G.; Jian, S. and Tan, H.; “Thermogravimetric investigation on
co-combustion characteristics of tobacco residue and high-ash anthracite coal”
Bio. Tech. 2011, 102(20), 9783-9787.
28. Heda, L.; Sharma, R.; Tank, P. and Sherwani, M.; “Thermogravimetric analysis of
copper (II) soaps derived from edible oils.” J. Lipid Sci. Tech. 2008, 40(1), 6-9.
29. Refat, M. and Mohamed G.; “Ti(IV), Cr(III), Mn(II), and Ni(II) Complexes of the
Norfloxacin Antibiotic Drug: Spectroscopic and Thermal Characterizations” J.
Chem. Eng. Data. 2010, 55, 3239–3246.
30. Szynkaruk, P.; Wesolowski, M. and Malgorzata, S.; “Principal component
analysis of thermal decomposition of magnesium salts used as drugs” J. Therm.
Anal. Calori. 2010, 101, 505–512.
31. Oliveira, A.; Maria Irene, Y.; Gomes, E.; Wagner da Nova, M.; Cristina Duarte,
V. and Gerson Antonio, P.; “Thermal analysis applied to simvastatin
characterization in pharmaceutical formulations” Quimica Nova 2010, 33(8),
1653-1657.
32. Seiman, C.; Vlase, T.; Vlase, G.; Seiman, D.; Albu, P. and Doca, N.; “Thermal
analysis study of amlodipine as pure compound and in binary mixture” J. Therm.
Anal. Calori. 2011, 105, 677-683.
33. Rocasoares, M.; Sobrinho, J.; Ramos, K.; Alves,L.; Lopes, P.; Corriea, L.; Souza,
F.; Macedo, O. and Neto, P.; “Thermal characterization of antimicrobial drug
ornidazole and is compatibility in a solid pharmaceutical product” J. Therm. Anal.
Calori. 2011, 104(1), 307-313.
34. Duda-Seiman, C.; Vlase, T.; Vlase, G.; Duda-Seiman, D.; Albu, P. and Doca, N.;
“Thermal analysis study of amlodipine as pure compound and in binary mixture”
J. Therm. Anal. Calori. 2011, 105, 677–683.
35. Sun, Y.; “Determination of purity of crystallized organic compounds by thermal
analysis technology” Guan. Huag. 2002, 31, 29-31.
36. Chafik, T.; Zaitan, H.; Harti, S.; Darir, A. and Achak, O.; “Determination of the
heat of adsorption and desorption of a volatile organic compound under dynamic
Section-V Thermal properties
Department of Chemistry, Saurashtra University, Rajkot-360005 198
conditions using Fourier-transform infrared spectroscopy” Spectro. Lett. 2007, 40,
763-775.
37. Leboeuf, E. and Zhang, L.; “Thermal analysis for advanced characterization of
natural nonliving organic materials” Biophys. Chem. Pro. Environ. Sys. 2009, 2,
783-836.
38. Bei, Y.; Qing-yang, L.; Gui-bin, Q. and Yuan-jun, D.; “Thermal decomposition
kinetics of 5-fluorouracil from thermogravimetric analysis” Korean J. Chem. Eng.
2008, 25(5), 980-981.
39. Vora, A.; Riga, A.; Dollimore, D. and Alexander, K. S.; “Thermal stability of folic
acid” Thermochim. Acta 2002, 392–393, 209–220.
40. Quan, S.; Zhi-Cheng, T.; You-Ying, D.; Tong, B.; Yan-Sheng, L. and Shao-Xu,
W.; “Thermal Analysis and Calorimetric Study of 4-Dimethylaminopyridine” J.
Chem. Eng. Data 2007, 52 (3), 941–947.
41. Lima, Cicero B. A.; José, G. P.; De Oliveira, S, F.; Arakaki, Luiza N. H.; Fonseca,
M, G.; Airoldi, C.; “Synthesis, characterization and thermal behavior of cobalt(II)
5-chloro-piridylamides complexes” Thermochim. Acta 2003, 407, 117–120.
42. Sasidharan, N.; Hariharanath, B. Rajendran, A. G.; “Thermal decomposition
studies on energetic triazole derivatives” Thermochim. Acta 2011, 520, 139–144
43. Ravi, P. Gore, G, M.; Sikder, A, K. and Tewari, S, P.; “Thermal decomposition
kinetics of 1-methyl-3,4,5-trinitropyrazole” Thermochim. Acta 2012, 528, 53–57.
44. Verdonck, E. and Schaap, K.; “L. C. A discussion of the principles and
application of modulated temperature DSC (MTDSC)”. Int. J. Pharm. 1999, 192,
3–20.
45. Danley, R.; Caulfield, P. and Aubuchon, S.; “A rapid-scanning differential
scanning calorimeter. Am. Lab. 2008, 40, 9–11.
46. Carvalho, T.; Matias, A.; Braga, L.; Evangelista, S. and Prado, A.; “Calorimetric
studies of removal of nonsteroidal anti-inflammatory drugs diclofenac and
dipyrone from water” J. Therm. Anal. Calori. 2011, 106(2), 475-481.
47. Raut, D.; Sakharkar, D.; Bodke, P. and Mahajan, D.; “Determination of traces of
amorphous carvidilol content in carvedilol drug substance and drug product using
modulated differential scanning calorimetry” Pharma. Lett. 2011, 3(4), 1-12.
Section-V Thermal properties
Department of Chemistry, Saurashtra University, Rajkot-360005 199
48. Keswani, N. and Kishore, N.; “Calorimetric and spectroscopic studies on
theinteraction of anticancer drug mitoxantrone with human serum albumin” J.
Chem. Thermo. 2011, 43(9), 1406-1413.
49. Lee, J.; Thomas, L. and Schmidt, S.; “Investigation of the heating rate dependency
associated with the loss of crystalline structure in sucrose, glucose, and fructose
using a thermal analysis approach (part I)” J. Agric. Food Chem. 2011, 59, 684–
701.
50. Lee, J.; Thomas, L.; Jerrell, J.; Feng, H.; Cadwallader, K. and Schmidt, S.;
“Investigation of thermal decomposition as the kinetic process that causes the loss
of crystalline structure in sucrose using a chemical analysis approach (part II).” J.
Agri. Food Chem. 2011, 59, 702–712.
51. Temprado, M.; Roux, M. V.; Ros, F.; Notario, R.; Segura, M. and Chickos, J. S.;
“Thermophysical Study of Several Barbituric Acid Derivatives by Differential
Scanning Calorimetry (DSC)” J. Chem. Eng. Data 2011, 56 (2), 263–268.
52. Ford, L. and Timmins, P.; “Pharmaceutical Thermal Analysis. Techniques and
applications. Ellis Horwood, Chichester 1989. 180-200.
53. Wesolowski, M.; and Konarski, T.; General remarks on the thermal
decomposition of some drugs. J. Thermal Anal. 43 (1995) 279-289.
54. Cheng, Y.; Huang, Y.; Alexander, K.; Dollimore, D.; “A thermal analysis study of
methyl salicylate”, Thermochim. Acta, 367–368 (2001) 23.-28
55. Thompson, K.; “Pharmaceutical applications of calorimetric measurements in the
new millennium”, Thermochim. Acta, 355 (2000) 83-87.
56. Lizarraga, E.; Zabaleta, C.; Palop, J.; “Thermal decomposition and stability of
quinoline compounds using thermogravimetry and differential scanning
calorimetry”, Thermochim. Acta. 2005, 427(1-2), 171-174.
57. Freeman, E. S. and Carroll, B.; “The application of thermoanalytical techniques to
reaction kinetics.The thermogravimetric evaluation of the kinetics of the
decomposition of calcium oxalate monohydrate” J. Phys. Chem. 1958, 62, 394-
397.
58. Anderson, D. A. and Freeman, E. S.; “Kinetics of the thermal degradation of
polystyrene and polyethylene” J. Poly. Sci. 1961, 54, 253-260.
59. Horowitz H. H. and Metzger, G.; “A New Analysis of Thermogravimetric Traces”
Anal. Chem.1963, 35(10), 1464-1468.
Section-V Thermal properties
Department of Chemistry, Saurashtra University, Rajkot-360005 200
60. Mishra, A. P.; Tiwari, V.; Singhal, R. and Gautam, S. K.; “Synthesis,
characterization, thermal decomposition and kinetic parameters of Ni (II) and
Cu(II) terephthalate-8Hg complexes.” Ind. J. Chem. 2002, 41A(10), 2092-2095.
Section-VI
Conductance
Section-VI Conductance
Department of Chemistry, Saurashtra University, Rajkot-360005 201
INTRODUCTION
The ability of a material to conduct electric current is known as conductivity.
Conductivity is the inverse of resistivity which is determined from the voltage and current
values according to Ohm's law1. In electrolytic solutions, concentration of solution,
charge on ions, mobility of ions etc., plays vital role to determine its conductance. Thus
the conductance behavior alters with concentration of strong or weak electrolytes.
By taking the importance of synthesized organic compounds in view, it is quiet
necessary to give the conductance profile of solutions of these compounds, because
conductivity measurement has widespread use in industrial applications that involve the
detection of contaminants in water and concentration measurements 2. It is also used to
determine the dissociation constant and limiting equivalent conductance of weak
electrolytes3, electro osmotic flow4, for studying conformational changes in poly
electrolytes in aqueous solutions5, etc. Baghalha and Papangelakis6, have developed
conductivity meter which is useful at high temperature and high concentration, which
found too useful in industrial process. Conductance determination is also a handed tool
for determination of nutrients in food stuffs7.
Further, knowledge of conductivity is useful to various biological processes8-11
such as determination of ascorbic acid in vitamin C tablet12, carbon in uranium carbide
and its solution in nitric acid13, enzymatic degradation of microbial biofilm14, dye-
surfactant ion pair formation in aqueous solutions15 etc. The antibiotic residues in bovin
kidneys have also been detected by conductometry16. Literature survey shows that
conductance of various inorganic and organic compounds have been measured in
aqueous17-25 and non aqueous solvents26-31. Liu et al32 have measured conductance of
macro cyclic Schiff base metal complexes in methanol. Morita et al reported ionic
conductance of polymeric electrolytes and of polymeric composite solid electrolytes33. In
aqueous solutions, conductance of antidepressant drug and surfactant was reported by
Kabir-ud-Din et al and coworkers34. The conductance measurement of pyrazinamide in
aqueous solution in presence and absence of additives at 308.15 K have also been
reported35. Some workers36-38 have studied conductance of chloro acetic acid and tartaric
acid. Yecid et al reported conductance of potassium sulphate in water-1-propanol systems
at different temperatures39. The conductance of binary mixtures of some ionic liquids
Section-VI Conductance
Department of Chemistry, Saurashtra University, Rajkot-360005 202
have also been studied40,41. Bester-Rogac42 has reported conductometric data of salicylate,
naproxen, diclofenac and ibuprofen in dilute aqueous solutions.
In our laboratory, conductance of some synthetic compounds43-45 has also been
studied.
Thus, in the present section conductance of all the synthesized tetrahydro
pyrimidine was measured in DMF and THF solutions at 303.15 K, over a wide range of
concentration.
Section-VI Conductance
Department of Chemistry, Saurashtra University, Rajkot-360005 203
EXPERIMENTAL
The solvents DMF and THF were purified by fractionally distillation by the
method reported in the literature46
.
The solutions of different concentrations were prepared for each compound in
DMF and THF and the conductance of each solution was measured by using Elico
Conductivity Meter (Model No.CM 180) at 303.15 K.
At 303.15 K, the cell constant was determined by measuring the conductance of
0.01N KCl solution and its value was found to be 0.89 cm-1.
The measured conductance was corrected by subtracting the conductance of pure
solvent.
Section-VI Conductance
Department of Chemistry, Saurashtra University, Rajkot-360005 204
RESULTS AND DISCUSSION
The measured conductance (k) of each solution after correction was used to
determine the specific conductance (κ), which is then used for the calculation of
equivalent conductance (λc).
The equations used for calculating specific conductance (κ) and equivalent
conductance (λc) are:
k … (3.6.1)
1000c C
… (3.6.2)
where θ is the cell constant and c is the concentration (g.equi./lit.) of solution. The cell
constant θ was 0.89 cm-1.
The equivalent conductance values of tetrahydropyrimidine derivatives in both
DMF and THF solutions are reported in Tables 3.6.1 and 3.6.2 along with measured
conductance (k).
It is observed that conductance is lower in THF solutions than that in DMF
solutions. The lower conductivities of THF solutions may be due to greater electro
relaxation effect owing to the higher permittivity of THF, which contributes inter ionic
repulsions to a larger extent.
Figures 3.6.1 and 3.6.2 show the variation of conductance with concentration for
all the compounds in DMF and THF solutions respectively. It is observed that for all the
compounds, conductance increases nonlinearly with concentration. However, at lower
concentrations, variation is linear.
The equivalent conductance (λc) is plotted against √C for all compounds in both
the solvents as shown in Figures 3.6.3 and 3.6.4. In DMF solutions (as shown in Figure
3.6.3), equivalent conductance increases with dilution. For most of the compounds,
compounds, the nature of graph shows weak electrolytic behavior in DMF solutions.
For weak electrolytes, it is difficult to determine λ0. However, in some solutions,
λ0 values are evaluated by extrapolation method. For compounds PAB-101, PAB-102 and
PAB-104, λ0 value cannot be evaluated by extrapolation.
Section-VI Conductance
Department of Chemistry, Saurashtra University, Rajkot-360005 205
Figure 3.6.4 shows that in THF solutions, for PAB-103 and PAB-109, equivalent
conductance increases with dilution in the beginning but after √C =0.15, it starts
decreasing. Similar behavior was observed by other workers47 in DMSO solutions. The
reason is not clear. For other compounds, equivalent conductance increases with dilution
In this case also; most of the compounds, exhibit weak electrolytic nature. The λ0 value
was evaluated by extrapolation except for compounds PAB-103, PAB-105, PAB-108 and
PAB-109.
These λ0 values are compared with those determined by an alternate procedure
using the following equation47:
0 0 ck k c c … (3.6.3)
where k and k0 are the electrolytic conductivity of the solutions and solvent respectively.
c is the equivalent concentration and the function Φ(c) denotes the effect of interionic
interactions.
The limiting conductivity can be evaluated accurately from the limiting slope of
smaller linear portions of the curve of k verses c, provided other derivatives (dk0/dc) and
d[cΦ(c)]/dc in differential form of equation (3.6.3) are neglected as compared to λ0, which
can be determined from differential form of equation (3.6.3) is
0
0
cd cdkdk
dc dc dc
… (3.6.4)
These λ0 values are reported in Table 3.6.3 along with those determined by
extrapolation.
From Table 3.6.3.it is observed that in both the solvents, calculated values of
limiting equivalent conductance (λ0) are in fair agreement with those evaluated
graphically suggesting thereby that equation 3.6.3 can be used for the studied systems.
Section-VI Conductance
Department of Chemistry, Saurashtra University, Rajkot-360005 206
Table 3.6.1: The conductance (k) and equivalent conductance (C) of tetrahydropyrimidine derivatives in DMF at 303.15 K.
Conc. (gm/lit)
k.105
()-1C
(cm2/.equiv.)k.105
()-1C
(cm2/.equiv.)k.105
()-1C
(cm2/.equiv.)k.105
()-1C
(cm2/.equiv.)k.105
()-1C
(cm2/.equiv.)PAB-101 PAB-102 PAB-103 PAB-104 PAB-105
0.000 0.50 - 0.50 - 0.50 - 0.50 - 0.50 -
0.001 1.00 4.6000 1.10 5.5200 0.98 4.4160 1.19 6.3480 0.84 3.15560.002 1.36 3.9560 1.50 4.6000 1.39 4.0940 1.69 5.4740 1.02 2.39200.004 1.88 3.1740 1.90 3.2200 1.91 3.2430 2.05 3.5650 1.47 2.23100.006 2.42 2.9440 2.50 3.0667 2.47 3.0207 2.56 3.1587 1.84 2.05470.008 2.89 2.7485 3.00 2.8750 3.06 2.9440 3.09 2.9785 2.34 2.11600.010 3.38 2.6496 3.50 2.7600 3.32 2.5944 3.72 2.9624 2.63 1.95960.020 5.52 2.3092 5.60 2.3460 5.50 2.3000 6.32 2.6772 4.08 1.64680.040 9.64 2.1022 9.70 2.1160 9.50 2.0700 10.60 2.3230 8.30 1.79400.060 12.30 1.8093 13.00 1.9167 12.70 1.8707 15.80 2.3460 9.94 1.44750.080 15.80 1.7595 16.50 1.8400 16.80 1.8745 18.60 2.0815 12.20 1.34550.100 17.30 1.5456 18.90 1.6928 18.80 1.6836 20.30 1.8216 14.10 1.2512
PAB-106 PAB-107 PAB-108 PAB-109 PAB-110
0.001 0.69 3.8364 0.95 4.2136 0.96 4.2412 0.98 4.4712 0.78 2.63120.002 0.97 3.2154 1.31 3.7260 1.39 4.0940 1.41 4.1860 0.98 2.24020.004 1.51 2.8405 1.90 3.2200 2.10 3.6800 2.19 3.8870 1.39 2.04700.006 2.01 2.6603 2.37 2.8673 2.69 3.3580 2.79 3.5113 1.81 2.00870.008 2.44 2.4898 2.81 2.6565 3.29 3.2085 3.20 3.1050 2.20 1.94930.010 2.95 2.4610 3.19 2.4748 3.68 2.9256 3.89 3.1188 2.57 1.90440.020 5.09 2.2149 5.23 2.1758 6.69 2.8474 6.54 2.7784 4.20 1.70200.040 9.60 2.1448 9.61 2.0953 12.30 2.7140 12.40 2.7370 6.82 1.45360.060 14.10 2.1198 14.10 2.0853 16.20 2.4073 16.70 2.4840 9.11 1.38000.080 16.80 1.9027 17.50 1.9550 18.70 2.0930 19.50 2.1850 13.10 1.4490
0.100 20.40 1.8515 20.30 1.8188 20.80 1.8685 21.40 1.9228 16.40 1.4628
Section-VI Conductance
Department of Chemistry, Saurashtra University, Rajkot-360005 207
Table 3.6.2: The conductance (k) and equivalent conductance (C) of tetrahydropyrimidine derivatives in THF at 303.15 K.
Conc.(gm/lit)
k.106
()-1C
(cm2/.equiv.)k.106
()-1C
(cm2/.equiv.)k.106
()-1C
(cm2/.equiv.)k.106
()-1C
(cm2/.equiv.)k.106
()-1C
(cm2/.equiv.)PAB-101 PAB-102 PAB-103 PAB-104 PAB-105
0.000 0.17 - 0.17 - 0.17 - 0.17 - 0.17 -
0.001 0.37 0.1780 0.37 0.1780 0.24 0.0623 0.38 0.1869 0.31 0.1246
0.002 0.55 0.1691 0.53 0.1602 0.31 0.0623 0.59 0.1856 0.45 0.1233
0.004 0.91 0.1647 0.86 0.1535 0.42 0.0556 0.97 0.1769 0.72 0.12170.006 1.26 0.1617 1.18 0.1498 0.50 0.0490 1.23 0.1577 0.83 0.09790.008 1.58 0.1569 1.48 0.1457 0.64 0.0523 1.51 0.1491 0.94 0.08540.010 1.82 0.1469 1.79 0.1442 0.80 0.0561 1.66 0.1329 1.03 0.07680.020 3.01 0.1264 2.99 0.1255 1.80 0.0725 2.64 0.1100 1.51 0.05980.040 3.99 0.0850 4.55 0.0975 2.78 0.0581 3.93 0.0837 2.69 0.05610.060 4.21 0.0599 5.47 0.0786 3.40 0.0479 4.25 0.0605 3.41 0.04810.080 4.38 0.0468 6.71 0.0728 4.20 0.0448 4.96 0.0533 4.28 0.04570.100 4.66 0.0400 7.57 0.0659 5.42 0.0467 5.54 0.0478 5.06 0.0435
PAB-106 PAB-107 PAB-108 PAB-109 PAB-110
0.001 0.24 0.0623 0.31 0.1246 0.23 0.0534 0.22 0.0445 0.24 0.0623
0.002 0.30 0.0579 0.44 0.1215 0.30 0.0579 0.30 0.0579 0.30 0.0579
0.004 0.42 0.0556 0.68 0.1128 0.34 0.0378 0.52 0.0779 0.42 0.05560.006 0.50 0.0490 0.85 0.1003 0.40 0.0341 0.80 0.0935 0.50 0.04900.008 0.60 0.0478 0.97 0.0884 0.43 0.0289 1.14 0.1079 0.62 0.05010.010 0.64 0.0418 1.10 0.0828 0.50 0.0294 1.40 0.1095 0.70 0.04720.020 1.10 0.0414 1.61 0.0641 0.72 0.0245 3.10 0.1304 1.02 0.03780.040 1.62 0.0323 2.21 0.0455 1.10 0.0207 4.90 0.1052 1.72 0.03450.060 2.10 0.0286 2.85 0.0398 1.50 0.0197 6.50 0.0939 2.30 0.03160.080 2.44 0.0253 3.43 0.0363 1.74 0.0175 7.29 0.0792 2.72 0.02840.100 2.80 0.0234 3.53 0.0299 2.02 0.0165 8.40 0.0732 3.02 0.0254
Section-VI
Department of Chemistry, Saurashtra University,
Figure 3.6.1: The variation of conductance with concentration for
tetrahydropyri
0.0
5.0
10.0
15.0
20.0
25.0
0
co
nd
uc
tan
ce10
5(m
ho
)
PAB-
0.0
5.0
10.0
15.0
20.0
25.0
0
con
du
ctan
ce10
5(m
ho
)
PAB
VI Conductance
Department of Chemistry, Saurashtra University, Rajkot-360005
The variation of conductance with concentration for
tetrahydropyrimidine derivatives in DMF at 303.15 K.
0.02 0.04 0.06 0.08
Concentration (M)
[A]
-101 PAB-102 PAB-103 PAB-104
0.02 0.04 0.06 0.08
Concentration (M)
[B]
PAB-106 PAB-107 PAB-108 PAB-109
Conductance
208
The variation of conductance with concentration for
.15 K.
0.1
PAB-105
0.1
PAB-110
Section-VI
Department of Chemistry, Saurashtra University,
Figure 3.6.2: The variation of
tetrahydropyrimidine derivatives
0.0
0.2
0.4
0.6
0.8
1.0
-1.53E-1
con
du
cta
nce
105
(mh
o)
PAB-101
0.0
0.2
0.4
0.6
0.8
1.0
0
Co
nd
uct
ance
105 m
ho
PAB 106
VI Conductance
Department of Chemistry, Saurashtra University, Rajkot-360005
The variation of conductance with concentration
tetrahydropyrimidine derivatives in THF at 303.15 K.
0.02 0.04 0.06 0.08
Concentraction (M)
[A]
101 PAB-102 PAB-103 PAB-104
0.02 0.04 0.06 0.08
Concentration (M)
[B]
PAB 106 PAB 107 PAB 108 PAB 109
Conductance
209
conductance with concentration for
.15 K.
0.1
PAB-105
0.1
PAB 110
Section-VI
Department of Chemistry, Saurashtra University,
Figure 3.6.3: The variation of equivalent conductance tetrahydropyrimidine derivatives
VI Conductance
Department of Chemistry, Saurashtra University, Rajkot-360005
The variation of equivalent conductance with √C for etrahydropyrimidine derivatives in DMF at 303.15 K.
Conductance
210
for
Section-VI Conductance
Department of Chemistry, Saurashtra University, Rajkot-360005 211
Figure 3.6.4: The variation of equivalent conductance with √C for tetrahydropyrimidine derivatives in THF at 303.15 K.
Section-VI Conductance
Department of Chemistry, Saurashtra University, Rajkot-360005 212
Table 3.6.3: The limiting equivalent conductance (λ0) of tetrahydropyrimidine derivatives in DMF and THF at 303.15 K.
CompoundCode
λ0
mho.cm2.equi.-1
from graph
λ0103
mho.cm2.equi.-1
from eq. (3.4.4)
λ0
mho.cm2.equi.-1
from graph
λ0103
mho.cm2.equi.-1
from eq. (3.4.4)DMF THF
PAB-101 - 4.874 0.205 0.197PAB-102 - 5.811 0.200 0.190PAB-103 5.950 4.904 - 0.050PAB-104 - 6.648 0.184 0.220PAB-105 4.250 3.081 - 0.198PAB-106 5.550 3.918 0.049 0.072PAB-107 5.650 4.575 0.158 0.161PAB-108 4.950 4.520 - 0.063PAB-109 5.550 4.789 - 0.075PAB-110 3.250 2.792 0.070 0.069
Section-VI Conductance
Department of Chemistry, Saurashtra University, Rajkot-360005 213
REFERENCES
1. Eutech Instruments - A leader in the field of electrochemical instrumentation,
1997
2. Application data sheet, “Theory and application of conductivity” ADS43
018/rev. B, August 2004
3. Levitt, L. S.; “Determination of the dissociation constant and limiting equivalent
conductance of a weak electrolyte from conductance measurements on the weak
electrolyte” Anal. Chim. Acta. 1981, 125, 219-220.
4. Tang, L. and Huber, C. O.; “Electroosmotic flow and injection: application to
conductometry” Talanta 1994, 41(10), 1791-1795.
5. Kargov, S. I. and Davydova, O. V.; “Application of conductometry for studying
conformational changes in polyelectrolytes in aqueous solutions” Russ. J. Phys.
Chem. 2005, 79, S81-S85.
6. Baghalha, M. and Papangelakis, V. G.; “High-Temperature Conductivity
Measurements for Industrial Applications” Ind. Eng. Chem. Res. 2000, 39, 3640-
3645.
7. Law, W. S.; Kubán, P.; Zhao, J. H.; Yau Li, S. F. and Hauser, P. C.;
“Determination of vitamin C and preservatives in beverages by conventional
capillary electrophoresis and microchip electrophoresis with capacitively coupled
contactless conductivity detection” Electrophoresis 2005, 26, 4648–4655.
8. Berezovskaia, G. E. and Korytnyi, V. S.; “Role of polarization processes near
electrodes during the measurement of the electrical conductivity of biological
objects.” Biofizika 1968, 13(3), 524-528.
9. De, L. J.; Berard, A. and Grabowski, B.; “Hybrid paraconductors: a new class of
components obtained by bionic synthesis, Application to analog memories and to
conductors of biological processes” Elec. Ther. 1977, 14(1), 19-25.
10. Vybornova, I. I.; Goltsov, A. N.; Yepifanov, S. Y.; Kadantsev, V. N. and
Krasilnikov, P. M.; “Modeling of mechanisms of influence of thermal and
anthropogenic chemical factors on the functioning of biological membranes.” Fiz.
Cheloveka 1994, 20(6), 124-136.
11. Canizares, P.; Beteta, A.; Saez, C.; Rodriguez, L. and Rodrigo, M. A.; “Use of
electrochemical technology to increase the quality of the effluents of bio-oxidation
processes. A case studied” Chemosphere 2008, 72(7), 1080-1085.
Section-VI Conductance
Department of Chemistry, Saurashtra University, Rajkot-360005 214
12. Grudpan, K.; Kamfoo, K. and Jakmunee, J.; “Flow injection spectrophotometric
orconductometric determination of ascorbic acid in a vitamin C tablet using
permanganate or ammonia” Talanta 1999, 49(5),1023-1026.
13. Ahmed, M. K.; Geetha, R.; Pandey, N. K.; Murugesan, S.; Koganti, S. B.; Saha,
B.; Sahoo, P. and Sundararajan, M. K.; “Conductometric determination of carbon
in uranium carbide and its solution in nitric acid” Talanta 2000, 52(5), 885-892.
14. Johansen, C.; Bredtved, B. K. and Moller, S.; “Use of conductance measurements
for determination of enzymatic degradation of microbial biofilm” Methods in
Enzymology 1999, 310, 353-361.
15. Bracko, S. and Span, J.; “Conductometric investigation of dyesurfactant ion pair
formation in aqueous solution” Dyes and Pigments 2000, 45(2), 97-102.
16. Myllyniemi, A. L.; Sipila, H.; Nuotio, L.; Niemi, A. A. and Honkanen, B. T.; “An
indirect conductimetric screening method for the detection of antibiotic residues in
bovine kidneys” Analyst 2002, 127(9), 1247-1251.
17. Apelblat, A.; “An analysis of the conductances of aqueous malonic acid.” J. Mol.
Liq. 1997, 73-74, 49-59.
18. Syal, V. K.; Chauhan, S. and Gupta, P. K.; “Conductance and viscosity studies of
some univalent electrolytes in water, dimethyl sulfoxide and water + dimethyl
sulfoxide mixtures at different temperatures.” J. Ind. Chem. Soc. 2002, 79(11),
860-865.
19. Naderi, A.; Claesson, P. M.; Bergstroem, M.; and Dedinaite, A.; “Trapped
nonequilibrium states in aqueous solutions of oppositely charged polyelectrolytes
and surfactants: effects of mixing protocol and salt concentration.” Phy. Eng. Asp.
2005, 253(1-3), 83-93.
20. Stasiewicz, W. A.; Szejgis, A.; Chmielewska, A. and Bald, A.; “Conductance
studies of NaBPh4, NBu4I, NaI, NaCl, NaBr, NaClO4 and the limiting ionic
conductance in water + propan-1-ol mixtures at 298.15 K” J. Mol. Liq. 2007,
130(1–3), 34-37.
21. Shcherbakov, V. V.; Artemkina, Y. M. and Ponamareva, T. N.; “Electric
conductivity of concentrated aqueous solutions of propionic acid, sodium
propionate and their mixtures.” Russ. J. Elec. 2008, 44(10), 1185-1190.
Section-VI Conductance
Department of Chemistry, Saurashtra University, Rajkot-360005 215
22. Shekaari, H. and Mousavi, S. S.; “Conductometric studies of aqueous ionic
liquids, 1-alkyl-3-methylimidazolium halide, solutions at T = 298.15–328.15 K”
Fluid. Phase Equi. 2009, 2862, 120-126.
23. Shekaari, H. and Jebali, F.;”Densities and electrical conductances of amino
acids + ionic liquid ([HMIm]Br) + H2O mixtures at 298.15 K” Fluid. Phase Equi.
2010, 295(1), 68-75.
24. Yan, Z.; Li, W.; Zhang, Q.; Wang, X. and Wang, J.; “Effect of sodium caproate
on the volumetric and conductometric properties of glycyl-L-glutamine and L-
alanyl-L-glutamine in aqueous solution at 298.15 K” Fluid. Phase Equi. 2011,
301(2), 156-162.
25. Chen, Y. J.; Xuan, X. P.; Zhang, H. H. and Zhuo K. L.; “Conductivities of 1-
alkyl-3-methylimidazolium chloride ionic liquids in monosaccharide + water
solutions at 298.15 K” Fluid Phase Equi. 2012, 316, 164-171.
26. Ghasemi, J. and Shamsipur, M.; “Conductance study of some transition and heavy
metal complexes with 1,10-diaza-18-crown-6 in binary acetonitrile dimethyl
sulfoxide mixtures.” J. Sol. Chem. 1996, 25(5), 485-504.
27. Jauhar, S. P. and Sandhu, S.; “Conductance and viscosity measurements of some
1:1 electrolytes in dimethylformamide + methanol mixtures at 25, 30 and 40°C.”
Ind. J. Chem. 2000, 39(4), 392-399.
28. Ozeroglu, C. and Sarac, A.; “Potentiometric and conductometric measurements of
dicarboxylic acids in non-aqueous solvents.”Asian J. Chem. 2006, 18(3), 1808-
1814.
29. Arjomandi, J. and Holze, R.; “In situ characterization of N-methylpyrrole and
(Nmethylpyrrole-cyclodextrin) polymers on gold electrodes in aqueous and non
aqueous solution.” Syn. Met. 2007, 157(24), 1021-1028.
30. Rounaghi, G. H.; Mohajeri, M.; Soruri, F. and Mohamadzadeh Kakhki, R.;
“Solvent Influence upon Complex Formation between Dibenzo-18-crown-6 with
the Y3+ Metal Cation in Pure and Binary Mixed Organic Solvents” J. Chem. Eng.
Data. 2011, 56 (6), 2836–2840.
31. Boruń, A. and Bald, A.; “Conductometric Studies of 1-Ethyl-3-
methylimidazolium Tetrafluoroborate and 1-Butyl-3-methylimidazolium
Tetrafluoroborate in N,N-Dimethylformamide at Temperatures from (283.15 to
318.15) K” J. Chem. Eng. Data. 2012, 57(2), 475–481.
Section-VI Conductance
Department of Chemistry, Saurashtra University, Rajkot-360005 216
32. Liu, J.; Masuda, Y. and Sekido, E. “A conductance study of macrocyclic Schiff
base metal (II) complexes in methanol.” Bull. Chem. Soc. Jap. 1990, 63, 2516-
2520.
33. Morita, M.; Fujisaki, T.; Yoshimoto, N. and Ishikawa, M.; “Ionic conductance
behavior of polymeric composite solid electrolytes containing lithium aluminate”
Electrochim. Acta 2001, 46, 1565-1569.
34. Kabir-ud-Din, A. A.; Mohammed, D. A.; Naqvi, A. Z. and Akram, M.;
“Conductometric study of antidepre ssant drug-cationic surfactant mixed micelles
in aqueous solution, Colloids and Surfaces.” Biointerfaces 2008, 64, 65-69.
35. Taher, A.; Mohsin, M. and Farooqui , M.;“Density, viscosity and conductance
measurement of pyrazinamide in aqueous solution in presence and absence of
additives at 308.15 K.” J. Ind. Chem. Soc. 2011, 88 (7), 959-962.
36. Niazi, M. S. K.; “Conductivities and Thermodynamic Dissociation Constants for
Chloroacetic Acid in Binary Mixed Solvent Systems at 298.15 K.” J. Chem. Eng.
Data 1993, 38, 527-530.
37. Bhat, I, J. and Shetty, K. M.; “Ion Association and Solvation of Sulfathiazole
Sodium in Aqueous and Partial Aqueous Media J. Chem. Eng. Data 2010, 55,
4721–4724.
38. Bhat, I, J. and Shivakumar, H. R.; “Conductometric studies on the solvation
bahaviour of tartaric acid in various solvent mixtures” J. Mol. Liq. 2004, 111,
101–108.
39. Yecid, P. J.; Taboada, M. E.; Flores, E. K. and Galleguillos, H. R.; “Density,
Viscosity, and Electrical Conductivity in the Potassium Sulfate + Water + 1-
Propanol System at Different Temperatures.” J. Chem. Eng. Data 2009, 54,
1932-1934.
40. Ren, R.; Zuo, Y.; Zhou, Q.; Zhang, H. and Zhang, S.; “Density, Excess Molar
Volume and Conductivity of Binary Mixtures of the Ionic Liquid 1,2-Dimethyl-3-
hexylimidazolium Bis(trifluoromethylsulfonyl)imide and Di methyl Carbonate” J.
Chem. Eng. Data 2011, 56(1), 27–30.
41. Fox, E. T.; Weaver, J. E. and Henderson, W. A.; “Tuning Binary Ionic Liquid
Mixtures: Linking Alkyl Chain Length to Phase Behavior and Ionic Conductivity”
J. Phys. Chem. C, 2012, 116 (8), 5270–5274.
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Department of Chemistry, Saurashtra University, Rajkot-360005 217
42. Bester-Rogac, M.; “Nonsteriodal Anti-Inflammatory Drugs Ion Mobility: A
Conductometric Study of Salicylate, Naproxen, Diclofenac and Ibuprofen Dilute
Aqueous Solutions. Acta Chim. Slov., 2009, 56, 70–77.
43. Baluja, S.; “Physicochemical studies of some Schiff bases derived from 6
ethylbenzene-1,3-diol.” E- J. Chem. 2004, 1, 199-205.
44. Baluja, S.; Kasundra, P. and Vekariya, N.; “Physicochemical studies of some
azomethines of 5-amino isophthalic acid in solutions of DMF and DMSO at
308.15 K.” Int. J. Chem. Sci. 2009, 7, 533-538.
45. Baluja, S.; Patel, A. and Movalia, J.; “A study of physicochemical properties of
some azomethines of vanillin”, Ife J. Sci., 2011, IV, 46-53.
46. Riddick, J. A., Bunger, W. B. and Sakano, T.; Organic Solvents-Physical
Properties and Methods of Purification, Fourth Edition., Techniques of
Chemistry, II, A Wiley-Interscience Publication, John Wiley, New York (1986).
47. Singh, M. and Prasad, B. B.; Electrolytic conductivity of the N-chloranil- and N-
xylylene-based polyelectrolytes in dimethylformamide and dimethyl sulfoxide, J.
Chem. Eng. Data, 1996, 41, 409.
Section-VII
Partition coefficient
Section-VII Partition coefficient
Department of Chemistry, Saurashtra University, Rajkot-360005 218
INTRODUCTION
General explanation of the partition coefficient or distribution coefficient is the
ratio of concentrations of a substance in the two phases of a mixture of two immiscible
solvents at equilibrium1. These coefficients have been a measure of differential solubility
of the substance between two solvents of different polarity. Partition coefficient finds
enormous applications in the various fields of general science research2, medical science3,
research related to environment4, 5 as well as industry6. Klooster et al have made very
delicious research by checking air-liquid partition coefficient of aroma volatiles in
different ice cream flavors7. So, partition coefficient also a matter of interest in food
industries too.
Literature survey shows that partition study of compound creates high interest in
medicinal or pharmaceutical chemistry research because in pharmacokinetics, the
distribution coefficient has a strong influence on ADME properties (Absorption,
Distribution, Metabolism, and Excretion) of the drug8. Whereas in Pharmacodynamics,
the hydrophobic effect is the major driving force for the binding drugs to their receptor
targets9, 10. Partition coefficient is a most crucial parameter of QSAR and QSPR study11-
13.
The knowledge of solubility and the octanol-water partition coefficient of a drug
is important in drug discovery, development, and manufacturing14-17. Latest technology
has made this study easy and versatile. Specifically UV-visible spectroscopy18-22 and gas
chromatography are sophisticated tools to study partition function23-25. Reiner et al. have
used HPLC for determination of partition coefficient26 in phenols. Leithner et al. have
studied the brain-blood partition phenomenon by using MRI27. Ward et al. have compared
different chromatographic methods for estimating octanol-water partition coefficient28.
The distribution between water and an immiscible nonpolar solvent is
acknowledged as a useful measure for the hydrophobicity of a substance. Hydrophobicity
is the association of non-polar groups or molecules in an aqueous environment which
arises from the tendency of water to exclude non-polar molecules. n-Octanol and water
are widely accepted as the best two-phase system to study partition coefficient between
biomass and water. Relationships between the partition coefficient of this system and
bioconcentration29-32, soil sorption33-35 and toxicity36-38 for fish have also been found.
Literature survey shows that various workers have studied partition coefficient of drugs39,
organic compounds40-42, aminoacids43, and flavanoids44.
Section-VII Partition coefficient
Department of Chemistry, Saurashtra University, Rajkot-360005 219
In the present study, partition coefficients of synthesized tetrahydropyrimidine
derivatives (PAB-101-PAB-110) have been studied in n-Octanol-water system by UV
spectroscopy at different pH.
Section-VII Partition coefficient
Department of Chemistry, Saurashtra University, Rajkot-360005 220
EXPERIMENTAL
n-Octanol is of analytical grade. The purity of solvent was checked by GC and
found to be 99.8%. Distilled water was used throughout for all experiments.
Preparation of standard solution:-
10 mg sample was dissolved in n-octanol to give 100 ml solution of 100
ppm. This solution was known as standard solution. Suitable dilutions were made from
this standard solution (2 g to 20 g).
Measurement:-
For the solution of each compound in octanol, absorbance (OD) was
measured at different wavelengths (λ) using UV spectrophotometer (Shimadzu, UV-1700,
Pharmaspec) to determine λmax. Solutions of different concentrations were prepared in
octanol for each compound and absorbance was measured at respective λmax to get
calibration curve.
A known amount of the compound under investigation was dissolved in n-octanol
at a concentration not higher than 20 g. Equal volumes of this solution and water is
mixed in oven dried stoppered flask and the mixture was stirred for 24 hrs. at room
temperature. After 24 hrs, the solution was transferred into 60 ml of separating funnel and
allowed to stand in order to separate the aqueous and organic layers. The organic layer
will be upper one while lower will be aqueous. The organic layer was then analyzed by
UV spectrophotometer. Using calibration curve, the concentration of compounds in
organic layer was then evaluated.
In the present study, partition coefficients of tetra hydropyrimidines have been
studied in n-octanol-water system by UV spectroscopy at different pH. The partition
coefficient is highly influenced by pH. So, in the present study, a wide range of pH (0.84
to 8.0) is selected. For 0.84 pH, 0.1 N HCl was taken whereas for 6.0, 7.4 and 8.0,
phosphate buffer was used. These values of pH are selected due to their existence in
human body. As HCl exists in gastric juice in stomach45, 0.1 N HCl is taken. Blood46 has
7.4 pH, so the study is done at pH 7.4. Further, the middle and upper range of body pH is
6.0 and 8.0 respectively, so study was done at these all pH also.
Section-VII Partition coefficient
Department of Chemistry, Saurashtra University, Rajkot-360005 221
THEORY
Partition coefficient (P) is defined as the ratio of the compounds in organic phase
to that present in the aqueous phase. i.e.,47
org
aq
CP
C …(3.7.1)
where Corg and Caq are concentration of solute in organic and aqueous phases respectively.
In the present case, concentrations were determined by UV measurement so,
equation (3.5.1) written as48:
E
E E
BP
B A
… (3.7.2)
where BE= Absorbance before extraction and AE=Absorbance after extraction.
From equation (3.5.2) log P were calculated for each set of experiment.
Section-VII Partition coefficient
Department of Chemistry, Saurashtra University, Rajkot-360005 222
RESULTS AND DISCUSSION
The log P values for the studied compounds at different pH are given in Table
3.7.2. The log P value depends upon the hydrophilic and hydrophobic character of
compounds and has inverse relation with hydrophilicity of compounds.
Table 3.7.2 shows that log P varies with pH. However, no regular pattern
is observed. The variation of log P with pH for all the studied compounds is also shown in
Figure 3.7.2. It is clear from Figure 3.7.2 that PAB-110 shows maximum hydrophobicity
almost in all pH. It is followed by PAB-106. PAB-107 is found to have minimum log P
for almost all pH range in comparison to other compounds suggesting thereby its highly
hydrophilic character. Further, for all the compounds, log P values are higher for 0.1 N
HCl i.e., at minimum pH.
All the studied compounds have the same central moiety but different side chains
i.e, substituents, as shown in Table 3.7.1. Thus the hydrophobic or hydrophilic character
of a compound depends not only on pH but also on substituent. As reported in Table
3.7.1, PAB-110 has hydroxy group at para position whereas PAB-108 has methoxy group
at para position. Thus, the presence of hydroxy group increases the hydrophobicity (as in
PAB-110) in comparison to methoxy (as in PAB-106). However, when both methoxy
and hydroxyl groups are present (as in the case of PAB-108), hydrophobic character is in
between PAB-106 and PAB-110). It means lower hydrophobicity. From this observation
one can assumes that if -OCH3 and –OH both are present in the same compound, it
increases the polar (hydrophilic) character in the solution due to presence of two
electronegative oxygen atoms. Thus, the substitution in compound plays a major role in
the nature of solution.
Further, the position of functional group is also important in the hydrophobic-
hydrophilic character of the compound. In PAB-104, chloro group is present at the para
position which gives least log P while for PAB-103, log P values are quite high in
comparison to PAB-104 although it also has chloro group but at meta position. Other
noticeable matter in this study is that PAB-104 and PAB-105 shows almost same
behavior. PAB-104 contains chloro group at para position whereas PAB-105 contains
fluoro group at para position. This suggests that at the same position, effect due to the
presence of difference halogens is negligible.
Section-VII Partition coefficient
Department of Chemistry, Saurashtra University, Rajkot-360005 223
Overall observation shows that all compounds exhibit higher hydrophobic
character in acidic pH. In some compounds, higher hydrophobic character is also
observed in water. At higher basic solutions, almost all compounds show higher
hydrophilic character.
Figure 3.7.1: General structure of tetrahydropyrimidine derivatives
Where R=side chain
Table 3.7.1: Different side chains present in tetrahydropyrimidine derivatives
Table 3.7.2: log P values for tetrahydropyrimidine derivatives
CompoundsCode
Max absorptionWavelength (nm)
log PWater 0.1N HCl 6.0 pH 7.4 pH 8.0 pH
PAB-101 308 0.1636 0.4223 0.1741 0.1415 0.1153
PAB-102 350 0.4658 0.8044 0.6443 0.5445 0.2190
PAB-103 230 0.1504 1.1841 0.9550 0.5790 0.0989
PAB-104 318 0.1320 0.5506 0.1699 0.1818 0.0647
PAB-105 314 0.1135 0.5509 0.2452 0.1341 0.1722
PAB-106 350 0.8314 1.2556 0.9315 0.8771 0.7994
PAB-107 292 0.1449 0.2152 0.1063 0.1388 0.1637
PAB-108 382 0.7814 0.9327 0.8402 0.7244 0.5553
PAB-109 342 0.6210 0.6617 0.5689 0.5607 0.4537
PAB-110 360 1.0009 1.0283 0.9333 0.8618 0.7948
Code R Code RPAB-101 C6H5- PAB-106 4-OCH3-C6H4-PAB-102 C6H4-CH=CH- PAB-107 3-NO2-C6H4-
PAB-103 3-Cl-C6H4- PAB-108 4-OH-3-OCH3-C6H4-PAB-104 4-Cl-C6H4- PAB-109 4(α-C4H3O)-PAB-105 4-F-C6H4- PAB-110 4-OH-C6H4-
N
HN
R
NH2
CN
H2N
Section-VII
Department of Chemistry, Saurashtra University, Rajkot
Figure 3.7.2: log P values for tetrahydropyrimidine
0.00
0.20
0.40
0.60
0.80
1.00
1.20
1.40
PAB 101 PAB 102 PAB 103
log
P
VII Partition coefficient
y, Saurashtra University, Rajkot-360005 224
etrahydropyrimidine derivatives.
PAB 103 PAB 104 PAB 105 PAB 106 PAB 107 PAB 108
Compounds
Water 0.1N HCl 6.0 pH 7.4 pH 8.0 pH
PAB 108 PAB 109 PAB 110
8.0 pH
Section-VII Partition coefficient
Department of Chemistry, Saurashtra University, Rajkot-360005 225
REFERENCES
1. Leo, A.; Hansch, C. and Elkins, D.; “Partition coefficients and their uses” Chem.
Rev. 1971, 71 (6), 525–616.
2. Wolf, E.; Riccomagno, E.; De Pater, J.; Deelman, B. and Koten, G.; “Parallel
Synthesis and Study of Fluorous Biphasic Partition Coefficients of 1H,1H,2H,2H-
Perfluoroalkylsilyl Derivatives of Triphenylphosphine: A Statistical Approach” J.
Comb. Chem. 2004, 6, 363-374.
3. Engel, L.; Alexander, J.; Carter, P.; Elliott, J. and Weester, M.; “Relations
between Phase Composition and Partition Coefficients for Some Neutral Steroids
A Nomographic Approach” Anal.Chem. 1954, 26(4), 639-641.
4. Miller, M.; and Waslk, S.; Huang, G.; Shlu, T. and Mackay, D.; “Relationships
between Octanol-Water Partition Coefficient and Aqueous Solubility” Environ.
Sci. Technol. 1985, 19(6), 522-529.
5. Wenhung, H.; Fuhlin, T. and Chiou, C.; “Partition Coefficients of Organic
Contaminants with Carbohydrates” Environ. Sci. Technol. 2010, 44, 5430–5436.
6. Lidgate, D.; Brandl, M,; holper, M.; Abubakari, A. and Wu, X.; “Influence of
Ferrous Sulfate on the Solubility, Partition Coefficient, and Stability of
Mycophenolic Acid and the Ester Mycophenolate Mofetil” Drug. Dev. Ind.
Pharm. 2002, 28(10), 1275-1283.
7. Klooster J.; Ciledruaux, C. and Vreeker, R.; “AirLiquid Partition Coefficients of
Aroma Volatiles in Frozen Sugar Solutions” J. Agri. Food Chem. 2005, 53, 4503-
4509.
8. Kubinyi, H.; “Nonlinear dependence of biological activity on hydrophobic
character: the bilinear model” Farmaco Sci. 1979, 34 (3), 248–276.
9. Eisenberg, D. and McLachlan, A.; “Solvation energy in protein folding and
binding” Nature 1986, 319, 199–203.
10. Miyamoto, S. and Kollman, P.; “What determines the strength of noncovalent
association of ligands to proteins in aqueous solution?” Proc. Natl. Acad. Sci.
1993, 90(18), 8402–8406.
11. Dashtbozorgi , Z. and Golmohammadi, H.; “Prediction of air to liver partition
coefficient for volatile organic compounds using QSAR approaches” Eur J. Med.
Chem. 2010, 45, 2182–2190.
Section-VII Partition coefficient
Department of Chemistry, Saurashtra University, Rajkot-360005 226
12. Posa, M.; Pilipovi, A.; Lali, M. and Popovi, J.; “Determination and importance of
temperature dependence of retention coefficient (RPHPLC) in QSAR model of
nitrazepams partition coefficient in bile acid micelles” Talanta 2011, 83, 1634–
1642.
13. Toropov, A.; Toropova, A.; Raska, I. and Benfenati, E.; “QSPR modeling of
octanol/water partition coefficient of antineoplastic agents by balance of
correlations” Eur. J. Med. Chem. 2010, 45,1639–1647.
14. Modarresi, H.; Conte, E.; Abildskov, J.; Gani, R. and Crafts, P.; “Model-based
calculation of solid solubility for solvent selection” A review. Ind. Eng. Chem.
Res. 2008, 47, 5234–5242.
15. Constable, D.;Jimenez-Gonzalez, C. and Henderson, R.; “Perspective on solvent
use in the pharmaceutical industry” Org. Process; Res. Dev. 2007, 11, 133–137.
16. Chieh-Ming, H.; Shu, Wang.; Shiang-Tai, L. and Stanley S,; “A Predictive Model
for the Solubility and Octanol-Water Partition Coefficient of Pharmaceuticals” J.
Chem. Eng. Data. 2011, 56(4), 936-945.
17. Jorgensen, W.; “The many roles of computation in drug discovery” Science 2004,
303, 1813–1818.
18. Lin H.; Xiaoying, L.; Mugan, Ding.; Xiaofen,Ye.; Jingmin, L.; Jiahui, G.;
Zhitang, L. and Guohui, L.; “Determination of equilibrium solubility and apparent
oil/water partition coefficient of silymarin” Guangdong Yaoxueyuan Xuebao
2011, 27(5), 445-449.
19. Xiuxia, L.; Lin, H.; Li, Chen.; Weiang, W.; Ruibiao, S. and Xiaoying, L.;
“Determination of equilibrium solubility and oil-water partition coefficient of
scutellarin” Guangdong Yaoxueyuan Xuebao 2011, 27(1), 1-4.
20. Ming-ming, W.; “Determination of the oil-water partition coefficient of
hymecromone by UV spectrophotometry” Anhui Nongye Kexue 2010, 38(22),
11985-11986.
21. Song, G.; Han, L.; Fang, F.; Zhiqiang, H.; Guifeng D. and Xiang, L,;
“Determination of the partition coefficient and its significance of telmisartan”
Yaowu Fenxi Zazhi 2007, 27(11), 1704-1706.
22. Lavinia, U.; Szabadai, Z.; Vlaia, V. and Miclea, L.; “Spectrophotometric
determination of piroxicam partitioning coefficient in paraffin oil/water binary
Section-VII Partition coefficient
Department of Chemistry, Saurashtra University, Rajkot-360005 227
system for different pH values of the aqueous phase” Farmacia 2005, 53(1), 112-
119.
23. Acree, W.; Baker, G.; Mutelet, F.; and Moise, J.; “Partition Coefficients of
Organic Compounds in Four New Tetraalkylammonium
Bis(trifluoromethylsulfonyl)imide Ionic Liquids Using Inverse Gas
Chromatography” J. Chem. Eng. Data. 2011, 56, 3688–3697.
24. Mutelet, F.; Laure Revelli, A.; Jaubert, J.; Sprunger, L.; Acree, W. and Baker, G.;
“Partition Coefficients of Organic Compounds in New Imidazolium and
Tetralkylammonium Based Ionic Liquids Using Inverse Gas Chromatography” J.
Chem. Eng. Data. 2010, 55, 234–242.
25. Revelli, A.; Mutelet, F. and Jaubert, J.; “Partition coefficients of organic
compounds in new imidazolium based ionic liquids using inverse gas
chromatography” J. Chrom. A, 2009, 1216, 4775–4786.
26. Reiner, G.; Labuckas, D. and Garcia, D.; “Lipophilicity of some GABAergic
phenols and related compounds determined by HPLC and partition coefficients in
different systems” J. Pharma. Biomed. Ana. 2009, 49, 686–691.
27. Leithner C.; Muller, S.; Fuchtemeier, M.; Lindauer, U.; Dirnagl U. and Royl, G.;
“Determination of the brain–blood partition coefficient for water in mice using
MRI” J. Cerebral. Meta. 2010, 30, 1821–1824.
28. Ward, R.; Davies, J.; Hodges, G. and Roberts, D.; “Applications of immobilised
artificial membrane chromatography to quaternary alkylammonium sulfobetaines
and comparison of chromatographic methods for estimating the octanol–water
partition coefficient” J. Chrom. A, 2003, 1007, 67–75.
29. Zaroogian, G.; Heltshe, J. and Johnson, M.; “Estimation of bioconcentration in
marine species using structure-activity models” Environ. Toxi. Chem. 1985, 4(1),
3-12.
30. Nishihara, T.; Saito, S. and Matsuo, M.; “Mechanism in bioconcentration of
organic chemicals in fish and its structure-activity relationship” Japan. J. Toxi.
Enviro. Health 1993, 39(6), 494-508.
31. Dimitrov, S.; Mekenyan, O. and Walker, J.; “Non-linear modeling of
bioconcentration using partition coefficients for narcotic chemicals” SAR and
QSAR Enviro. Res. 2002, 13(1), 177-184.
Section-VII Partition coefficient
Department of Chemistry, Saurashtra University, Rajkot-360005 228
32. Yang, Z. and Zeng, E.; “Comment on Bioconcentration Factor Hydrophobicity
Cutoff: An Artificial Phenomenon Reconstructed” Enviro. Sci. Tech. 2008,
42(24), 9449-9450.
33. Wallace, A. and Procopiou, J.; “A statistical analysis of crop responses to nitrogen
and phosphorus fertilizers in Greece.” Comm. Soil Sci. Plant Anal. 1982, 13(1), 7-
19.
34. Girvin, D. and Scott, A.; “Polychlorinated biphenyl sorption by soils:
measurement of soil-water partition coefficients at equilibrium” Chemosphere,
1997, 35(9), 2007-2025.
35. Franco, A. and Trapp, S.; “Estimation of the soil-water partition coefficient
normalized to organic carbon for ionizable organic chemicals” Enviro. Toxi.
Chem. 2008, 27(10), 1995-2004.
36. Zaroogian, G.; Heltshe, J. and Johnson, M.; “Estimation of toxicity to marine
species with structure-activity models developed to estimate toxicity to freshwater
fish” Aquatic Toxicol. 1985, 6(4), 251-270,
37. Saito, H.; Koyasu, J.; Shigeoka, T. and Tomita, I.; “Cytotoxicity of chlorophenols
to goldfish GFS cells with the MTT and LDH assays” Toxicology in Vitro, 1994,
8(5), 1107-1112.
38. Hay et al.; Jones, R.; Beaumont, K. and Kemp, M. “Modulation of the Partition
Coefficient between Octanol and Buffer at pH 7.4” Drug Metab Dispos. 2009, 37,
1864-1870.
39. Perillo, M.; “Determination of the membrane-buffer partition coefficient of
flunitrazepam, a lipophilic drug” J. Neuro. Meth. 1991, 36(2–3), 203–208.
40. Hilal, S.; Karickhoff, S. and Carreira, L.; “Prediction of the Solubility, Activity
Coefficient and Liquid/Liquid Partition Coefficient of Organic Compounds”
QSAR & Combi. 2004, 23(9),709–720.
41. Rich, P. and Harper, R.; “Partition coefficients of quinones and hydroquinones
and their relation to biochemical reactivity” Febs Lett. 1990, 269(1), 139–144.
42. Yamagami, C.; Takao, N. and Fujita, T.; “Partition coefficients of diazines” Prog.
Clin. Bio.Res. 1989, 291, 83-86
43. Libby, M. and Richard, D.; “Measurement and Correlation of Partition
Coefficients of Polar Amino Acids” Mole. Pharma.1981, 20 (3) 602-608.
Section-VII Partition coefficient
Department of Chemistry, Saurashtra University, Rajkot-360005 229
44. Joseph, A.; Rothwell, A.; Day, J. and Michael R.; “Experimental Determination of
Octanol−Water Partition Coefficients of Quercetin and Related Flavonoids” J.
Agric. Food Chem., 2005, 53(11), 4355–4360.
45. Pelfrêne, A.; Waterlot, C. and Douay, F.; “In vitro digestion and DGT techniques
for estimating cadmium and lead bioavailability in contaminated soils: Influence
of gastric juice pH” Sci. Enviro. 2011, 409, 5076– 5085.
46. Janjuaa, N.; Siddiqa, A.; Yaquba, A.; Sabahat,S.; Qureshi, R. and Haque S.;
“Spectrophotometric analysis of flavonoid–DNA binding interactions at
physiological conditions” Spectrochim. Acta Part A 2009, 74, 1135–1137.
47. Sawyer, Heniman and Beebe.; “Chemistry Experiments for Instrumental
Analysis” Willy 1984.
48. Jayshree, B.; Sahu, R.; Murthy.; M. and Venugopala, K.; “Synthesis determination
of partition coefficient and antimicrobial activity of triazole thiadiazinyl
bromocoumarin derivatives” Mat. Sci. Res. Ind. 2005, 3(2), 187-190.
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