Medium effect on the acid dissociation constants of some heterocyclic azo compounds

Article abstract of DOI:10.1021/je9802165

The effect of different organic solvent + water mixtures on the acid dissociation constants of protonated 5-amino-4-(arylazo)-3-methyl-1-phenylpyrazole derivatives were studied. The organic solvents used are methanol, ethanol, acetone, and dimethylformami

Full text of DOI:10.1021/je9802165

J . Chem. Eng. Data 1999, 44, 451-455
451
Med iu m Effect on th e Acid Dissocia tion Con sta n ts of Som e
Heter ocyclic Azo Com p ou n d s
Sa id A. Ibr a h im ,† Na sr M. Ra geh ,*,‡ Ah m ed A. Moh a m a d ,‡ a n d You ssif H. Ebea d ‡
Department of Chemistry, Faculty of Science, Assuit University, Egypt, and Department of Chemistry,
Faculty of Science, South Valley University, Qena, Egypt
The effect of different organic solvent + water mixtures on the acid dissociation constants of protonated
5-amino-4-(arylazo)-3-methyl-1-phenylpyrazole derivatives were studied. The organic solvents used are
methanol, ethanol, acetone, and dimethylformamide. The results obtained were discussed in terms of
+
the solvent characteristics.The pKBH values of the dyes in question were determined and found to depend
+
on both the amount and nature of the organic cosolvent. The decrease of the pKBH values as the amount
of organic solvent in the medium is increased can be accounted for in terms of the high stabilization of
the protonated form of the compounds by dispersion forces rather than by hydrogen bonding. Also the
+
effect of solvent polarizability and hydrogen-bonding interaction on the pKBH values and thus on the
+
spectra of the charge-transfer band observed have been discussed. The absolute pKBH value for each
compound despite the presence of more than one basicity center has also been discussed.
In tr od u ction
(1905). 5-Amino-4-(arylazo)-3-methyl-1-phenylpyrazole
derivatives were prepared according to the following pro-
cedure: The appropriate amine (aniline, p-anisidine, p-
acetylaniline, or p-nitroaniline, 0.054 mol) was dissolved
in diluted HCl (32 mL; 5.49 mol), and the resulting solution
was cooled in an ice bath to 5 °C. This solution was added
dropwise with stirring to a cold solution of sodium nitrite
(4 g; 0.058 mol/(20 mL of H2O)).
The widespread applications of the azo compounds in
various fields have attracted the attention of many re-
searchers, prompting them to study their spectral and
acid-base properties (Issa et al.,1972; Hammam et al.,
1979; El-Haty et al., 1991). Aminopyrazoles are of consid-
erable interest as intermediates in many useful biochemical
reactions (El-Nagdi et al., 1983). Skipper et al. (1957) have
shown that aminopyrazole derivatives are potential drugs
for schistosomiasis. The literature reveals that few studies
have been made on the medium effects on the basicity of
such compounds. In continuation of our studies on the
acid-base properties of azo compounds (Mahmoud et al.,
1983; Hammam et al.,1993; Rageh, 1998) we investigate
the medium effect on the basicity of the NH2 group
belonging to the 1-phenylpyrazole moiety by the study of
the electronic spectra of the compounds in aqueous acetate
buffer solutions containing varying proportions of organic
solvents of different polarities, such as methanol, ethanol,
The resulting diazonium salt was added slowly with
stirring to a cold solution (9.3 g; 0.05 mol) of 5-amino-3-
methyl-1-phenylpyrazole in 20 mL of diluted HCl (this
compound was prepared by the reaction of aminocrotoni-
trile with phenylhydrazine). After the completion of the
addition, stirring was continued for 15 min and then a
solution of sodium acetate (20 g/(60 mL of H2O)) was added
until complete precipitation of the dye was achieved. The
solid precipitate was filtered, washed with cold water, and
recrystallized from ethanol to give the corresponding azo
derivatives. The purity of these compounds was checked
by microanalysis and by IR spectroscopy. Stock solutions
(10-3 mol dm-3) of the compounds were prepared by
dissolving a known mass of the solid in the required volume
of the solvent. The pH control was achieved by using the
modified acetate buffer solution (Britton, 1952). To account
for the difference in acidity, basicity, relative permittivity,
and ion activities in partially aqueous media relative to
pure aqueous solutions, where the pH meter is standard-
ized using aqueous buffers at 25 °C, the pH values in the
former media were corrected by using the procedure
described by Douheret (1967).
+
acetone, and dimethylformamide (DMF). The pKBH values
have been determined and discussed in terms of solvent
characteristics. The studied compounds have the following
structure.
pH* ) pH(R) - δ
(1)
where pH* is the corrected reading and pH(R) is the meter
reading obtained in water-organic solvent mixtures.
The values of δ of the aqueous buffer solutions containing
varying proportions of each of the organic solvents used
were determined by Douheret (1967, 1968). The solutions
were thermostated at (25 ( 0.2) °C before their spectra
were measured. The absorption spectra were recorded on
a Shimadzu 2401PC spectrophotometer, containing a ther-
Exp er im en ta l Section
5-Amino-3-methyl-1-phenylpyrazole prepared according
to the procedure previously described by Vergl Michaelis
† Assuit University.
‡ South Valley University.
10.1021/je9802165 CCC: $18.00 © 1999 American Chemical Society
Published on Web 03/16/1999

452 J ournal of Chemical and Engineering Data, Vol. 44, No. 3, 1999
F igu r e 1. Absorption spectra of 2.0 × 10-5 M compound II (MAP) in water (1) + methanol (2) at different pH’s: (A) w2 ) 0.1653 methanol;
pH* (1) 0.60, (2) 1.02, (3) 1.24, (4) 1.35, (5) 1.55, (6) 1.85, (7) 2.11, (8) 2.39, (9) 3.00, and (10) 3.5. (B) w2 ) 0.2535 methanol; pH* (1) 0.58,
(2) 0.71, (3) 0.93, (4) 1.12, (5) 1.3, (6) 1.56, (7) 1.84, (8) 2.07, (9) 2.58, and (10) 3.85. (C) w2 ) 0.3456 methanol; pH* (1) 0.65, (2) 0.77, (3)
0.95, (4) 1.17, (5) 1.45, (6) 1.81, (7) 2.06, (8) 2.39, (9) 2.96, and (10) 3.65. (D) w2 ) 0.4421 methanol; pH* (1) 0.69, (2) 0.82, (3) 1.09, (4) 1.3,
(5) 1.48, (6) 1.72, (7) 2.01, (8) 2.25, (9) 2.42, and (10) 3.4.
tions containing different proportions of an organic solvent
(methanol, ethanol, acetone and DMF) show mainly two
bands (Figure 1). The shorter wavelength band, appearing
at low pH* values (pH* < 1.0), is mainly due to absorption
by protonated species, whereas the longer wavelength
band, observed at higher pH* values (pH*s > 1.5), is due
to the absorption by neutral molecule. On increasing the
pH of the medium, the absorbance of the former band
decreases while that of the latter band increases, where a
fine isosbestic point is achieved denoting the existence of
an equilibrium of the type
F igu r e 2. Absorption-pH* curves for compound I (PAP) in water
(1) + acetone (2), w2 ) (a) 16.53, (b) 25.42, (c) 34.56, and (d) 44.21.
moelectrically temperature-controlled cell holder, within
the wavelength range of 240-580 nm using 1-cm matched
silica cells. The pH measurements were carried out using
an Orion 501 digital ionalyzer accurate to (0.01 pH unit.
All measurements were carried out at (25 ( 0.2) °C, and
temperature control was achieved using an ultrathermostat
of accuracy (0.2 °C.
Resu lts a n d Discu ssion
The visible absorption spectra of 5-amino-4-(arylazo)-3-
methyl-1-phenylpyrazole derivatives in acetate buffer solu-
The absorbance-pH* curves obtained in all cases, as shown

J ournal of Chemical and Engineering Data, Vol. 44, No. 3, 1999 453
Ta ble 1. p KBH Va lu es for 2 × 10-5 M of P AP in Va r iou s Ma ss F r a ction s w2 of Wa ter (1) + Or ga n ic Solven t (2) Mixtu r es
a t 25 °C
+
+
pKBH
mole fraction
100w2
ꢀ
of organic solvent
method 1
method 2
method 3
mean value
SD
Water (1) + Methanol (2)
0.1653
0.2535
0.3456
0.4421
73.7 2
71.03
67.88
64.26
0.1000
0.1602
0.2288
0.3080
1.85
1.75
1.57
1.40
1.84
1.73
1.57
1.43
1.81
1.65
1.52
1.40
1.83
1.71
1.55
1.41
(0.017
(0.043
(0.42
(0.014
Water (1) + Ethanol (2)
0.1659
0.2542
0.3465
0.4430
74.46
72.00
69.08
65.54
0.0720
0.1175
0.176
1.67
1.30
1.10
1.07
1.67
1.30
1.10
1.10
1.65
1.32
1.10
1.10
1.66
1.31
1.10
1.09
(0.009
(0.009
(0.000
(0.014
0.2371
Water (1) + Acetone (2)
0.1653
0.2535
0.3456
0.4421
74.92
72.87
70.25
66.99
0.0525
0.0952
0.1407
0.1972
1.65
1.55
1.40
1.35
1.70
1.55
1.42
1.40
1.67
1.45
1.42
1.40
1.67
1.52
1.41
1.38
(0.021
(0.047
(0.009
(0.024
Water (1) + DMF (2)
0.1921
0.2896
0.3881
0.4875
76.06
74.56
72.73
70.45
0.0553
0.09123
0.1351
0.1898
1.28
1.10
0.92
0.88
1.30
1.24
1.04
1.06
0.92
1.27
1.07
0.99
0.90
(0.025
(0.025
(0.057
(0.016
1.07
1.00
0.90
Ta ble 2. p KBH Va lu es for 2.0 × 10-5 M of MAP in Va r iou s Ma ss F r a ction s w2 of Wa ter (1) + Or ga n ic Solven t (2) Mixtu r es
+
a t 25 °C
+
pKBH
mole fraction
100w2
ꢀ
of organic solvent
method 1
method 2
method 3
mean value
SD
Water (1) + Methanol (2)
0.1653
0.2535
0.3456
0.4421
73.72
71.03
67.88
64.26
0.1000
0.1602
0.2288
0.3080
1.70
1.50
1.45
1.40
1.73
1.50
1.48
1.42
1.70
1.65
1.48
1.45
1.71
1.55
1.47
1.42
(0.014
(0.071
(0.014
(0.021
Water (1) + Ethanol (2)
0.1659
0.2542
0.3465
0.4430
74.46
72.00
69.08
65.54
0.0720
0.1175
0.176
1.54
1.48
1.24
1.28
1.50
1.46
1.30
1.25
1.52
1.46
1.32
1.28
1.52
1.47
1.29
1.27
(0.016
(0.010
(0.034
(0.014
0.2371
Water (1) + Acetone (2)
0.1653
0.2535
0.3456
0.4421
74.92
72.87
70.25
66.99
0.0525
0.0952
0.1407
0.1972
1.50
1.40
1.20
1.15
1.51
1.40
1.23
1.18
1.52
1.40
1.20
1.18
1.51
1.40
1.21
1.17
(0.008
(0.000
(0.014
(0.014
Water (1) + DMF (2)
0.1921
0.2896
0.3881
0.4875
76.06
74.56
72.73
70.45
0.0553
0.09123
0.1351
0.1898
1.40
1.15
1.07
0.88
1.37
1.15
1.10
0.90
1.40
1.15
1.05
0.98
1.39
1.15
1.07
0.92
(0.014
(0.000
(0.021
(0.043
in Figure 2, are sigmoidal curves, confirming the establish-
ment of an acid-base equilibrium in each case.
(H2A+) by dispersion force in the different solvent-water
mixtures.
The acid dissociation constant of the protonated form of
the compounds were determined from the variations of the
absorbance with pH*, making use of three different spec-
trophotometric methods, namely, the half-curve height,
isosbestic point, and limting absorbance (Issa et al., 1971,
1972). The values were calculated by using a simple
program. The experimental error in detrmined pKBH
values was checked by using the least-squares method. The
obtained results are given in Tables 1-4.
On the other hand, methanol and DMF have approxi-
mately similar relative permittivity constants (32.6
and 36.7, respectively, at 25 °C), so that the electrostatic
effects in aqueous solutions containing the same mole
fraction of these two solvents are expected to be virtually
+
identical (i.e, pKBH values of a compound in such solu-
+
tions should be the same). The general trend observed is
that these values in all compounds are higher in the
presence of methanol than with DMF. (cf. Tables 1-4 and
Figure 2).
Examination of the results cited in Tables 1-4 reveals
+
that pKBH values of all compounds are largely dependent
Moreover, though ethanol and acetone have comparable
relative permittivity constants too (24.3 and 20.7, respec-
upon both the nature and the proportion of the organic
+
+
cosolvent. Generally, pKBH values decrease with an in-
tively, at 25 °C), NAP and MAP have pKBH values in the
crease of the organic cosolvent content in the medium.
This can be interpreted on the principle of the expected
relatively high stabilization of the protonated form
water + ethanol mixture more than in the water + acetone
mixture, where the same mole fraction of each is used. This
trend is the converse for PAP and AAP. This behavior

454 J ournal of Chemical and Engineering Data, Vol. 44, No. 3, 1999
F igu r e 3. (a, left) Variation of pKBH of compound IV (NAP) in water (1) + organic solvent (2) with 1/ꢀ × 102 of the medium at 25 °C:
+
+
(A) methanol, (B) ethanol, (C) acetone, and (D) DMF. (b, right) Variation of pKBH of compound III (AAP) with the mole fraction of the
organic solvent present in the aquous medium: (A) methanol, (B) ethanol, (C) acetone, and (D) DMF.
Ta ble 3. p KBH Va lu es for 2.0 × 10-5 M of AAP in Va r iou s Ma ss F r a ction s w2 of Wa ter (1) + Or ga n ic Solven t (2) Mixtu r es
+
a t 25 °C
+
pKBH
mole fraction
100w2
ꢀ
of organic solvent
method 1
method 2
method 3
mean value
SD
Water (1) + Methanol (2)
0.1653
0.2535
0.3456
0.4421
73.72
71.03
67.88
64.27
0.1000
0.1602
0.2288
0.3080
1.40
1.20
1.03
0.92
1.45
1.25
0.97
0.95
1.40
1.15
1.00
0.92
1.42
1.20
1.00
0.93
(0.024
(0.041
(0.025
(0.014
Water (1) + Ethanol (2
0.1659
0.2542
0.3465
0.4430
74.46
72.00
69.08
65.54
0.0720
0.1175
0.176
1.40
1.00
0.95
0.92
1.45
1.02
0.95
0.92
1.40
1.02
1.02
1.42
1.01
0.97
0.92
(0.024
(0.009
(0.033
(0.000
0.2371
Water (1) + Acetone (2)
0.1653
0.2535
0.3456
0.4421
74.92
72.87
70.25
66.99
0.0525
0.0952
0.1407
0.1972
1.22
1.05
1.00
0.97
1.25
1.10
1.05
1.01
1.20
1.10
1.04
1.22
1.08
1.03
0.99
(0.021
(0.024
(0.022
(0.020
Water (1) + DMF (2)
0.1921
0.2896
0.3881
0.4875
76.06
74.56
72.73
70.45
0.0553
0.09123
0.1351
0.1898
1.00
0.88
0.83
0.77
1.00
0.85
0.87
0.79
0.95
0.90
0.88
0.98
0.88
0.86
0.76
(0.024
(0.021
(0.022
(0.010
Ta ble 4. p KBH Va lu es for 2.0 × 10-5 M of NAP in Va r iou s Ma ss F r a ction s w2 of Wa ter (1) + Or ga n ic Solven t (2) Mixtu r es
+
a t 25 °C
+
pKBH
mole fraction
100w2
ꢀ
of organic solvent
method 1
method 2
method 3
mean value
SD
Water (1) + Methanol (2)
0.1653
0.2535
0.3456
0.4421
73.72
71.03
67.88
64.27
0.1000
0.1602
0.2288
0.3080
1.05
0.95
0.92
0.90
1.05
0.95
0.93
0.92
1.02
0.95
1.05
1.04
0.95
0.96
0.91
(0.014
(0.000
(0.059
(0.010
Water (1) + Ethanol (2)
0.1659
0.2542
0.3465
0.4430
74.46
72.00
69.08
65.54
0.0720
0.1175
0.176
1.07
0.87
0.85
0.82
1.07
0.90
0.90
0.80
1.00
0.90
0.90
1.05
0.89
0.88
0.81
(0.033
(0.014
(0.240
(0.010
0.2371
Water (1) + Acetone (2)
0.1653
0.2535
0.3456
0.4421
74.92
72.87
70.25
66.99
0.0525
0.0952
0.1407
0.1972
0.95
0.92
0.87
0.85
0.96
0.92
0.88
0.80
0.95
0.92
0.93
0.80
0.95
0.92
0.89
0.82
(0.005
(0.000
(0.026
(0.024
Water (1) + DMF (2)
0.1921
0.2896
0.3881
0.4875
76.06
74.56
72.73
70.45
0.0553
0.09123
0.1351
0.1898
1.05
0.70
0.65
0.60
1.05
0.72
0.63
0.65
1.00
0.75
0.62
1.03
0.72
0.63
0.62
(0.024
(0.021
(0.013
(0.025
+
supports that other solvent effects beside the electrostatic
one have a contribution in the acid-base process of the
investigated compounds. This fact is further substantiated
by the nonlinear relationship obtained by plotting pKBH
against 1/ꢀ of the medium (Figure 3), according to the
equation given by Denison and Ramsey (1955), as well as

J ournal of Chemical and Engineering Data, Vol. 44, No. 3, 1999 455
Britton, H. T. S. Hydrogen ions; Champan & Hall: London, 1952; p
by Gilkerson (1956) which relates the variation of the pKa
364.
with the relative permittivity of the medium (ꢀ). The
relative permittivity of the medium, ꢀ, is obtained from the
relation
Denison, J . T.; Ramsey, J . B. Free Energy, Enthalpy, and Entropy of
Dissociation of Some Perchlorates in Ethylene Chloride and Ethy-
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and the Effect of the Medium on the Hydrogen Ion in Theses
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dardization of the Glass-Calomel Electrodes System in These
Mixtures. Dielectric Properties of These Mixtures. Bull. Soc. Chim.
Fr. 1968, 8, 3122-3131.
El-Gyar, S. A.; Hamed, M. M. A.; Abdalla, E. M.; Mahmoud, M. R.
Medium Effects on the Acid Dissociation Constants of Some Diimine
Heterocyclic Bases. Monatsh. Chem. 1993, 124, 127-133.
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on the electronic spectra of some 4-arylazo-3,5-diaminopyrazoles.
Bull. Soc. Chim. Fr. 1991, 128, 869-872.
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1972, 78, 177-182.
ꢀ ) ꢀwxf,w + ꢀsxf,s
(3)
where ꢀ and xf are the relative permittivity and mole
fraction and the subscripts w and s refer to water and
organic solvent, respectively.
+
The observed decrease in pKBH of each compound as the
proportion of the organic cosolvent in the medium is
increased can be attributed, in addition to the relative
permittivity, to the high stabilization of the free base HA
by hydrogen bonding in pure aqueous medium relative to
that in the presence of organic solvents. Since water
molecules have a higher tendency to donate hydrogen
bonds than other solvent molecules (Franks and Ives,
1966), accordingly the free base of the studied compounds
is expected to be less stabilized by hydrogen-bonding
interaction with solvent molecules as the amount of the
organic cosolvent in the medium is increased (El-Gyar et
al., 1993). In the different media studied, an increase in
+
the pKBH values of the compounds under investigation is
observed in the presence of the same percentage of the
organic cosolvent in the medium according to the following
sequence:
DMF < acetone < ethanol < methanol
This behavior is expected to occur as a result of decreas-
ing medium polarizability on going from DMF + water to
methanol + water within the above sequence (Alfenaar and
Deligny, 1967).
+
The higher pKBH values observed in methanol than in
ethanol in solutions containing the same mole fraction of
alcohol are due to the low tendency of ethanol to donate a
hydrogen bond to the free base, since the tendency of
alcohol to associate with solute through hydrogen bonding
decreases with increasing molecular weight (Skipper et al.,
J ohn, D. H.; Donald, M.; Geoffrey, H.; Richard, M. The effects of cyclic
terminal groups in 4-aminoazobenzene and related azo dyes: Part
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dine and N-phenylpiperidine. Dyes Pigm. 1985, 6, 389-396.
Mahmoud, M. R.; Hamed, M. M.; Ibrahim, S. A. Acidity Constants of
Some Azo Imidazole Derivatives in Water-Rich Aqueous Organic
Solvents. Bull. Soc. Chem. Fr. 1983, 9-10, 220-224.
Rageh, N. M. Acidity constants of some hydroxy azo pyrazolopyrim-
idines in mixed aqueous-organic solvents. J . Chem. Eng. Data 1998,
3, 373-377.
+
1957). The pKBH of the dyes under investigation show a
small dependence of the nature of the substituent (cf.
Tables 1-4). A similar behavior was observed before (J ohn
+
et al., 1985). The values of pKBH of the nitrogen atoms of
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R. W.; Schabel, E. M. Structure-activity relations observed on
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both the heterocyclic ring and azo group cannot be deter-
mined since their protonation does not show any order in
the absorbance of the charge-transfer bands. This makes
the evaluation of their pKBH values inaccurate (El-Taher
and Gabr, 1996).
+
Liter a tu r e Cited
Received for review September 7, 1998. Accepted December 4, 1998.
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