Acidity constant and solvatochromic behavior of some pyrazolo[1,5-a] pyrimidin-2-amine derivatives

Article abstract of DOI:10.1016/j.saa.2014.03.029

The UV-visible electronic spectra of some azo compounds of pyrazolo[1,5-a]pyrimidin-2-amine have been studied. The solvatochromic behavior of these compounds was investigated by studying their spectra in pure organic solvents of different polarities such as cyclohexane carbon tetrachloride, chloroform, ethanol and DMF. These exhibits a red shift in its λ_max with increase relative permittivity of medium changing from cyclohexane → carbon tetrachloride → chloroform → ethanol → DMF. The acid dissociation constants of these compounds were determined in aqueous-organic solvent mixtures such as acetone, methanol, ethanol and DMF. The ionization constants of the dyes in question depend largely on both the proportion and the nature of the organic solvent basicity contribute the major effects on the ionization process. In general, pKa values in all compounds decrease with increase relative permittivity of the medium. The acidity of studied azo compounds increases in the following order: p-NO₂ < m-CF₃ < p-F < p-Cl < p-H < p-CH₃.

Full text of DOI:10.1016/j.saa.2014.03.029

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 129 (2014) 209–218
Contents lists available at ScienceDirect
Spectrochimica Acta Part A: Molecular and
Biomolecular Spectroscopy
journal homepage: www.elsevier.com/locate/saa
Acidity constant and solvatochromic behavior of some
pyrazolo[1,5-a]pyrimidin-2-amine derivatives
Mohamed A. El-Gahami a,b, , Ahmed E.M. Mekky a,c, Tamer S. Saleh a,d, Abdullah S. Al-Bogami a
⇑
a Chemistry Department, Faculty of Science, King Abdulaziz University, North Jeddah, P.O. Box 80203, Jeddah 21589, Saudi Arabia
b Chemistry Department, Faculty of Science, Assiut University, Assiut, Egypt
c Chemistry Department, Faculty of Science, Cairo University, Giza 12613, Egypt
d Green Chemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt
h i g h l i g h t s
g r a p h i c a l a b s t r a c t
Electronic spectra, solvatochromic behavior and pKa values of some [1,5-a] pyrimidin-2-amine deriva-
tives have been studied. Absorption spectra of 1.0 ꢁ 10ꢂ5 M compound VI in water (1) + methanol (2)
at different pH’s.
ꢀ
ꢀ
ꢀ
Novel pyrazolo[1,5-a]pyrimidin-2-
amine derivatives have been
synthesis and characterized.
pKa values depended largely on both
the amount and basicity of organic
solvent.
N
R
N
R
N
N
N
N
N
N
N
HN
NH2
NH
(Form B)
(Form A)
The kmax exhibits a red shift in order
-H+
+H+
N
cyclohexane ? CCl4 ? CHCl3
C2H5OH ? DMF.
?
R
N
N
N
N
NH
Anionic Form
(
Form C)
p-NO2; m-CF3; p-F; p-Cl; p-H; p-CH3
Tautomerism Forms
.
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 27 November 2013
Received in revised form 5 March 2014
Accepted 18 March 2014
Available online 28 March 2014
The UV–visible electronic spectra of some azo compounds of pyrazolo[1,5-a]pyrimidin-2-amine have
been studied. The solvatochromic behavior of these compounds was investigated by studying their
spectra in pure organic solvents of different polarities such as cyclohexane carbon tetrachloride,
chloroform, ethanol and DMF. These exhibits a red shift in its kmax with increase relative permittivity
of medium changing from cyclohexane ? carbon tetrachloride ? chloroform ? ethanol ? DMF. The acid
dissociation constants of these compounds were determined in aqueous–organic solvent mixtures such
as acetone, methanol, ethanol and DMF. The ionization constants of the dyes in question depend largely
on both the proportion and the nature of the organic solvent basicity contribute the major effects on the
ionization process. In general, pKa values in all compounds decrease with increase relative permittivity of
the medium. The acidity of studied azo compounds increases in the following order:
p-NO2 < m-CF3 < p-F < p-Cl < p-H < p-CH3.
Keywords:
Pyrazolo[1,5-a]pyrimidin-2-amine
Solvatochromic behavior
pKa determined
Ó 2014 Elsevier B.V. All rights reserved.
⇑
Corresponding author at: Chemistry Department, Faculty of Science, King Abdulaziz University, North Jeddah, P.O. Box 80203, Jeddah 21589, Saudi Arabia. Tel.: +966
564602431; fax: +966 2600376.
E-mail address: malgahami@yahoo.com (M.A. El-Gahami).
http://dx.doi.org/10.1016/j.saa.2014.03.029
1386-1425/Ó 2014 Elsevier B.V. All rights reserved.

210
M.A. El-Gahami et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 129 (2014) 209–218
GCeMS. Elemental analyses were carried out on a Euro Vector
Introduction
instrument C, H, N, S analyzer EA3000 Series.
Microwave experiments were performed using CEM Discover &
Explorer SP microwave apparatus (300 W), utilizing 35 ml capped
glass reaction vessels automated power control based on tempera-
ture feedback.
The widespread application of azo compounds as dyes, acid–
base, redox, and metallochrome indicators, or histological stains
has attracted the attention of many researchers to study their
acid–base properties [1–4].
The absorption spectra were recorded on a Shimatzu 2401PC
spectrophotometer at 25 °C using 1 cm matched silica cells. The
pH measurements were carried out using an Orion 501 digital ana-
lyzer accurate to 0.01 pH units. All measurements were carried
out at 25 °C, and temperature control was achieved using an ultra
thermostat of accuracy 0.05 °C.
Innovations in azo dye based on heterocyclic systems have been
made as a result of intensive studies stimulated by the mounting
need for bright dyes. Generally, many of heterocyclic azo dyes
shows dramatic bathochromic shifts combined with brilliance of
shade and high tinctorial strength compared with conventional
anthraquinone dyes and amino benzene azo dyes [5–8]. One of
the most important azo dye series are arylazopyrazolopyrimidines
derivatives that used in silk screen and heat transfer printing tech-
niques on polyester and polyamide fabrics [9]. These dyes were
also used in manufacture of clothing and products with antibacte-
rial properties [9].
On the other hand, the knowledge of pKa is considered to be of
great interest in organic and inorganic compounds, because it has a
significant role in many chemical reactions; therefore, numerous
works has been devoted to the determination of pKa values of dif-
ferent azo compounds [10–13]. However, some azo dyes have tox-
icological properties and therefore require sensitive and selective
methods to determine their physicochemical characteristics [14].
The literature lacks studies on the acid–base properties or
medium effects on the acid dissociation constants of azo com-
pounds containing the pyrazolo[1,5-a]pyrimidines moiety, which
are thought to be special interest owing to their biological and
therapeutical importance [15,16].
This paper presents an investigation of the electronic spectra of
some azopyrazolo[1,5-a]pyrimidine-2-amine derivatives in pure
organic solvents of different polarities such as cyclohexane carbon
tetrachloride, chloroform, ethanol and DMF.
We have investigated the medium effect on the ionization con-
stants of azo compounds by the study of the electronic spectra of
the compounds in aqueous buffer solutions containing varying
proportions of organic solvents of different polarities, such as ace-
tone, methanol, ethanol, and N,N-dimethyl formamide (DMF). The
pKa values have been determined and discussed in terms of solvent
characteristics.
Synthesis of pyrazolo[1,5-a]pyrimidin-2-amine derivatives
Method A: To a mixture of E-3-dimethylamino-1-phenylprop-2-
en-1-one (1) (2 mmol) and the appropriate 4-(Aryldiazenyl)-1H-
pyrazole-3,5-diamine 2a–f (2 mmol) in glacial acetic acid
(25 mL), concentrated sulfuric acid is added (0.5 ml); the reaction
mixture was refluxed for about 9 h (as examined by TLC) and then
left to cool. The solid product was filtered off, washed with ethanol,
dried, and finally recrystallized from DMF/H2O to afford the corre-
sponding pyrazolo[1,5-a]pyrimidine derivatives I–VI.
Method B: This process was performed using microwave irradi-
ation (300 W, 120 °C) on the same scale described above. Here the
reactants were dissolved in acetic acid; concentrated sulfuric acid
also was added (0.5 ml) and subjected to microwave irradiation
for about 15–20 min until the starting materials were no longer
detectable by TLC. The products were obtained and purified as
described above in conventional reaction.
7-Phenyl-3-(phenyldiazenyl)pyrazolo[1,5-a]pyrimidin-2-amine (I)
m.p.: 296–298 °C; FT-IR vmax [cmꢂ1]:3321, 3154 (NH2),
1592(C@N); 1H NMR (DMSO-d6) d [ppm]: 7.25–8.05 (m, 10H,
ArAH), 7.31 (d, 1H, J = 4.2 Hz, pyrimidine), 8.19 (d, 1H, J = 4.2 Hz,
pyrimidine), 10.75 (br. S, 2H, NH2, D2O-exchangeable); MS m/z
[%]:314 [M+], Anal. Calced. For C18H14N6: C, 68.78; H, 4.49; N,
26.74. Found: C, 69.06; H, 4.36; N, 26.59.
7-Phenyl-3-(4-tolyldiazenyl)pyrazolo[1,5-a]pyrimidin-2-amine (II)
Experimental
m.p.: >300 °C; FT-IR v
max [cmꢂ1]:3316, 3149 (NH2), 1599(C@N);
1H NMR (DMSO-d6) d [ppm]: 2.11 (s, 3H, CH3), 7.19–8.02 (m, 9H,
ArAH), 7.37 (d, 1H, J = 4.5 Hz, pyrimidine), 8.63 (d, 1H, J = 4.5 Hz,
pyrimidine); 10.63 (br. s, 2H, NH2, D2O-exchangeable), MS m/z
[%]:328 [M+], Anal. Calced. For C19H16N6: C, 69.50; H, 4.91; N,
25.59. Found: C, 69.73; H, 4.83; N, 25.44.
Materials
All spectrograde organic solvents were purchased from Aldrich
and used as received unless otherwise stated. E-3-dimethylamino-
1-phenylprop-2-en-1-one (1) [17] and 4-(Aryldiazenyl)-1H-pyra-
zole-3,5-diamine derivatives 2a–f [18] were prepared according
to the reported literature.
7-Phenyl-3-((4-chlorophenyl)diazenyl)pyrazolo[1,5-a]pyrimidin-2-
amine (III)
Instruments
m.p.: 252–254 °C; FT-IR vmax [cmꢂ1]:3333, 3169 (NH2),
1591(C@N); 1H NMR (DMSO-d6) d [ppm]: 6.23 (br. s, H, NH, D2O-
exchangeable), 7.21–8.09 (m, 9H, ArAH), 7.42 (d, 1H, J = 4.2 Hz,
pyrimidine), 8.68 (d, 1H, J = 4.2 Hz, pyrimidine), 10.61 (br. s, 2H,
NH2, D2O-exchangeable); MS m/z [%]:348 [M+], Anal. Calced. For
Thin-layer chromatography (TLC) was performed on percolated
Merck 60 GF254 silica gel plates with a fluorescent indicator, and
detection by means of UV light at 254 and 360 nm. The melting
points were measured with a Stuart melting point apparatus and
are uncorrected. IR spectra were recorded on a Smart TR, which
is an ultra-high-performance, versatile Attenuated Total Reflec-
tance (ATR) sampling accessory on the Nicolet IS10 FT-IR spectro-
photometer. The NMR spectra were recorded on a Bruker Avance III
400 (9.4 T, 400.13 MHz for 1H) spectrometer with a 5-mm BBFO
probe, at 298 K. Chemical shifts (d in ppm) are given relative to
internal solvent, DMSO-d6 2.50 for 1H. Software (Topspin 3.2).
Mass spectra were recorded on a Thermo ISQ Single Quadruple
C18H13ClN6: C, 61.98; H, 3.76; N, 24.09. Found: C, 62.23; H, 3.65;
N, 23.97.
7-Phenyl-3-((4-flurophenyl)diazenyl)pyrazolo[1,5-a]pyrimidin-2-
amine (IV)
m.p.: 290–292 °C; FT-IR vmax [cmꢂ1]:3314, 3148 (NH2),
1600(C@N); 1H NMR (DMSO-d6) d [ppm]: 5.78 (br. s, H, NH, D2O-
exchangeable), 7.14–8.09 (m, 9H, ArAH), 7.54 (d, 1H, J = 4.2 Hz,

M.A. El-Gahami et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 129 (2014) 209–218
211
pyrimidine), 8.33 (d, 1H, J = 4.2 Hz, pyrimidine), 10.78 (br. S, 2H,
NH2, D2O-exchangeable); MS m/z [%]:332 [M+], Anal. Calced. For
18H13FN6: C, 65.05; H, 3.94; N, 25.29. Found: C, 65.28; H, 3.86;
Results and discussion
C
Synthesis and characterization
N, 25.14.
The enaminone 1 was treated with 4-(Aryldiazenyl)-1H-pyra-
zole-3,5-diamine derivatives 2a–f in glacial acetic acid, and pres-
ence of 2 drops of concentrated sulfuric acid under microwave
irradiation, it afforded in each case, the corresponding pyrazol-
o[1,5-a]pyrimidine derivatives I–VI in almost quantitative yield
(Scheme 1).
The mass spectrum of compound I have taken as an example of
the prepared series, revealed a molecular ion peak at m/z 314. Its
1H NMR spectrum revealed a single signal at d 7.06 (CH-3) and
two doublet signals at d 7.21, 8.61 (J = 4.2 Hz) due to pyrimidine
protons (CH-6, CH-5), respectively, in addition to aromatic protons
as a multiple at d 7.26–7.75. The IR spectrum of I revealed the
absence of any band due to carbonyl function.
7-Phenyl-3-((3-trifluromethylphenyl)diazenyl)pyrazolo[1,5-
a]pyrimidin-2-amine (V)
m.p.: >300 °C; FT-IR v
max [cmꢂ1]:3328, 3161 (NH2), 1591(C@N);
1H NMR (DMSO-d6) d [ppm]: 7.15 –8.13 (m, 9H, ArAH), 7.39 (d, 1H,
J = 4.2 Hz, pyrimidine), 8.41 (d, 1H, J = 4.2 Hz, pyrimidine), 10.68
(br. S, 2H, NH2, D2O-exchangeable); MS m/z [%]:382 [M+], Anal.
Calced. For C19H13F3N6: C, 59.69; H, 3.43; N, 21.98. Found: C,
59.91; H, 3.36; N, 21.83.
7-Phenyl-3-((4-nitrophenyl)diazenyl)pyrazolo[1,5-a]pyrimidin-2-
amine (VI)
The formation of the products I–VI is assumed to take place via
an initial addition of the exocyclic amino group in the aminopyraz-
oles 2 to the a,b-unsaturated moiety in the enaminone 1 to yield
m.p.: >300 °C; FT-IR v
max [cmꢂ1]:3312, 3154 (NH2), 1600(C@N);
1H NMR (DMSO-d6) d [ppm]: 6.15 (br. s, H, NH, D2O-exchangeable),
7.08–7.95 (m, 9H, ArAH), 7.25 (d, 1H, J = 4.2 Hz, pyrimidine), 8.51
(d, 1H, J = 4.2 Hz, pyrimidine), 11.01 (br. s, 2H, NH2, D2O-exchange-
able); MS m/z [%]:359 [M+], Anal. Calced. For C18H13N7O2: C, 60.16;
H, 3.65; N, 27.29. Found: C, 60.42; H, 3.58; N, 27.10.
the corresponding acyclic non-isolable intermediates 3a–f which
undergo intramolecular cyclization and aromatization to give the
final products I–VI (Scheme 1).
To find the specific effect of microwave on this reaction, the
mentioned reaction was carried out under the same conditions in
the absence of microwave irradiation (Table 1), and it was
observed that the reaction time increased considerably and yield
of the products decreased.
Solutions
Thus, microwave was found to have a beneficial effect on the
synthesis of pyrazolopyrimidine derivatives in which decrease
time of the above reactions from 9 h in the conventional procedure
to less than 30 min, also, a noticeable improvement in yields of
reactions under microwave irradiations.
It is noteworthy to mention here that, the azo-hydrazo tautom-
erism is not only of importance to the dyestuff manufacturer but
also another area of chemistry. Azo-hydrazo tautomerism not only
have different colors, but also have different tinctorial strengths
(and hence economics) and different properties, e.g. light fastness.
Azo dyes (I–VI) exist in two possible tautomerism forms, namely
the azo-enamine from A and the hydrazo-online form B as shown
in Scheme 2.
Stock solutions (10ꢂ3 mol dmꢂ3) of the compounds were pre-
pared by dissolving a known mass of the azo dyes solid in the
required volume of the solvent. The pH control was achieved by
using the modified universal buffer solution [19]. To account for
the difference in acidity, basicity, dielectric constant, and ion activ-
ities in partially aqueous media relative to pure aqueous solutions,
where the pH meter is standardized using aqueous buffers at 25 °C.
The pH values of the former media were corrected by using the
procedure described by Douheret [20], where:
pHꢃ ¼ pHðRÞ ꢂ d
ð1Þ
pH⁄ is the corrected value and pH(R) is the pH meter reading
obtained in water–organic solvent mixtures. Values of d for various
aqueous–organic solvent mixtures were determined as recom-
mended by Douheret [20,21]. The solutions were thermostated at
25 °C before measuring their spectra.
The FT-IR spectra of dyes I–VI showed intense amino (NH2)
bands in region 3312–3148 cmꢂ1. This suggests that these dyes
are predominantly in the azo – enamine form, as opposed to the
hydrazo imine form, in the solid state.
Scheme 1. Synthesis of pyrazolo[1,5-a]pyrimidin-2-amine derivatives.

212
M.A. El-Gahami et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 129 (2014) 209–218
Table 1
Synthesis of pyrazolo[1,5-a]pyrimidin-2-amine derivatives I–VI under both microwave irradiation and conventional method.
Entry
Product
Microwave irradiation
Conventional condition
Time (min)
17
Yield %
Time (h)
Yield %
1
93
9
72
2
3
4
15
20
15
93
93
95
9
9
9
70
71
82
5
15
90
9
75
6
20
95
9
82
The 1H NMR spectra of dyes I, II and V showed a broad signal of
amino group in the region 10–11.01 ppm. This result suggests that
dyes I, II and V are present as a single tautomerism form in DMSO,
namely azo-enamine form A as shown in Scheme 2.
The electronic absorption spectral characteristics
kmax and max values of the investigated compounds I–VI in eth-
anol, in the wavelength range 200–500 nm, are reported in Table 2.
The results show that the solvent effect on UV absorption spectra
of investigate azo compounds in very complex and strongly
depend on the nature of the substituent on phenyl ring. This phe-
nomenon is caused by the difference in the conjugational or
migrating ability of electron lone pair on nitrogen atoms and
azo-enamine; hydrazo-imine tautamerism of azo compounds.
e
On the other hand, 1H NMR spectra of dyes III, IV and VI showed
a broad signal of amino group at 10–11 ppm and a broad signal due
to the NH group at 5–6.5 ppm. These results suggest that dyes III,
IV and VI are present as a mixture of two tautomerism forms in
DMSO, namely the azo-enamine (Form A) and hydrazo-imine
(Form B) as shown in Scheme 2.

M.A. El-Gahami et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 129 (2014) 209–218
213
Scheme 2. Tautomerism forms.
can be assigned to a n–pꢃ transition involving the lone pairs of
electrons localized on the azo group nitrogen.
1.5
1.2
0.9
0.6
0.3
0.0
I
II
III
VI
IV
V
Solvatochromic behavior
The Solvatochromic behavior of the azo compounds used is
investigated by studying their electronic absorption spectra in dif-
ferent organic solvents (viz. cyclohexane, carbon tetrachloride,
chloroform, ethanol and DMF). The kmax and emax bands observed
are listed in Table 2. It is evident from this table that the visible
bands appeared in the range 405–460 nm are very sensitive to
the nature of the solvent used. This band exhibits a red shift in
its kmax with increase relative permittivity of the medium changing
from cyclohexane (2.02) ? carbon tetrachloride (2.24) ? chloro-
form (4.81) ? ethanol (24.50) ? DMF (36.70), this trend is in
harmony with the increasing polarity of the solvent. This behavior
can be explained on the principle that the excited state of such a
type of transitions is polar and consequently it is expected to be
more stabilized in higher polar solvent (viz. ethanol or DMF relative
to cyclohexane) and thus low excitation energy required for this
band with the former solvent relative to the latter one. From ideal-
ized theories, the solvent dielectric constant (i.e. The relative
300
400
500
600
wavelength (nm)
Fig. 1. Electronic spectra of compounds I–VI in ethanol.
These results are in accordance with structure of these dyes
(Table 1). This also indicates that the electronic behavior of nitro-
gen atoms of azo group in some what different between derivatives
with electron donating substituent’s.
permittivity
er) is often predicted to serve as a quantitative
The compounds comprise mainly three bands in ethanol (Fig. 1).
The shortest wavelength absorption appearing in the range 230–
260 nm is assignable to a
p–
pꢃ transition of the benzoid system
of the compounds. This assignment is quite reasonable since kmax
of this band is slightly altered on transfer from on derivative to
another indicating the local nature of such a transition.
The bands in spectra observed, in region 356–395 nm can be
assigned to p–
pꢃ transition involving to a whole electronic system
of the compounds with consider charge transfer nature of this
band is achieved from its broadness as well as the sensitivity of
its kmax to the type of substitute (R) to azo group. Examination of
the data reported in Table 2 reveals that this band acquires an
appreciable shift toward lower energy (red shift) where R is an
electron acceptor (compounds III–VI), relative to its position in
case of R is an electron donor (compound II). This behavior can
be interpreted on the basis of the expected high delocalization of
the electrons in the former compounds due to the antagonizing
effect of the electron accepting (R) groups.
Fig. 2. Absorption spectra of 1.0 ꢁ 10ꢂ5 M compound VI in water (1) + methanol (2)
at different pH’s.
x
2 = 16.53 methanol, pH⁄ (1) 4.53, (2) 5.13, (3)5.90, (4) 6.50, (5)
The band appeared as a shoulder in the spectra of the com-
pounds except compounds VI in the visible region 415–430 nm
6.92, (6) 7.21, (7) 7.45, (8) 7.7, (9) 7.92, (10) 8.3, (11) 8.45, (12) 8.60, (13) 9.50, (14)
10.53.

214
M.A. El-Gahami et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 129 (2014) 209–218
Table 2
Electronic spectral data of the pyrazolo[1,5-a]pyrimidin-2-amine derivatives in various organic solvents.
Compound
I
Cyclohexane
CCl4
CHCl3
EtOH
DMF
(kmax) nm
ð
eamaxÞ ꢁ10ꢂ3
(kmax) nm
ð
eamaxÞ ꢁ10ꢂ3
(kmax) nm
ð
eamaxÞ ꢁ10ꢂ3
(kmax) nm
ð
eamaxÞ ꢁ10ꢂ3
(kmax) nm
ð
eamaxÞ ꢁ10ꢂ3
235
360
430sh
12.00
14.00
11.00
250
375
435sh
11.00
12.00
14.00
240
365
435sh
15.00
16.50
14.00
250
365
430sh
15.60
17.00
15.30
245
375
440sh
11.30
14.60
12.00
II
250
395
420sh
11.50
12.00
11.00
225
375
420sh
11.30
14.00
4.50
245
385
425sh
12.50
14.00
6.00
260
375
430sh
12.00
15.60
5.30
235
390
460sh
13.00
15.30
10.00
III
265
375
410sh
12.20
13.30
01.50
260
370
415sh
10.00
13.00
4.00
275
380
415sh
12.20
14.00
5.00
255
360
415sh
13.50
14.00
6.20
270
385
425sh
12.10
14.00
10.30
IV
V
230
410
16.00
13.20
225
415
15.30
17.50
225
420
15.10
16.50
230
420
15.00
17.20
240
460
16.30
17.50
245
350
390
400sh
14.00
11.50
11.70
3.00
255
350
390
–
12.00
15.60
3.00
–
270
355
370
410sh
14.00
16.30
16.00
4.60
250
355
390
430sh
16.10
16.60
17.00
6.00
275
360
395
425sh
15.30
16.00
16.30
11.00
VI
255
360
415sh
13.00
12.00
3.20
265
370
415
14.00
16.70
5.20
250
360
420sh
14.20
16.00
6.20
245
360
425sh
14.60
16.10
5.30
260
365
425sh
13.10
14.00
10.00
a, cm2 molꢂ1
.
measure of solvents as a non-structured isotropic continuum, not
composed of individual solvent molecules with their own
solvent–solvent interactions and they do not into account specific
solute–solvent interaction which often play a dominant role in
solute–solvent interactions.
(460 nm) when compared with those in other solvents. These
results suggest that this dye is present as an anionic form (C) in
DMF [22], as a tautomerism form azo-enamine (A) in ethanol or
chloroform and as a different tautomerism form hydrazo-imine
(B) in carbon tetrachloride and cyclohexane [18].
On changing the medium from cyclohexane to ethanol and DMF
(Table 2), the splitting of the CT band becomes more pronounced.
These dramatic spectral changes on changing the dielectric
constant of the medium can be attributed to the existence of com-
pounds in a tautomerism equilibrium [22] of the type as stated in
Scheme 2.
The electronic absorption spectra of the 3-arylazo-7-phenylpy-
razolo[1,5-a]pyrimidin-2-amine derivatives in buffer solutions
containing different proportions of an organic solvent (ethanol,
methanol, acetone and DMF) show mainly two bands (Fig. 1).
The shorter wavelength band appearing at low pH values repre-
sents the absorption of the non-ionized species, whereas the longer
wavelength band, observed at higher pH’s, is due to the absorption
by ionized species. With increase in the pH of the medium, the
absorbance of the former band decrease which that of the latter
band increases where a fine isobestic point is achieved, denoting
the existence of and equilibrium of the type.
Azo-enamine ꢀ Hydrazo-imine ꢀ Anionic from
A compound (IV) gave a single dominate absorption peak
without a shoulder in all used solvents at 405–460 nm. It was also
observed that the kmax value of this dye was the largest in DMF
Table 3
pKa values for 1 ꢁ 10ꢂ5 M of 7-phenyl-3-(phenyldiazenyl)pyrazolo[1,5-a]pyrimidin-2-amine (I) in different water (1) + organic solvent (2) mixtures at 25 °C.
a
Mass% 100 W2
E
pKa
Mean value SD
Method 1
Method 2
Method 3
Water (1) + acetone (2)
16.53
25.35
34.56
44.21
74.92
72.87
70.25
66.99
7.40
7.50
7.55
7.75
7.40
7.50
7.70
7.80
7.40
7.55
7.60
7.75
7.40 0.02
7.51 0.02
7.61 0.02
7.76 0.02
Water (1) + methanol (2)
16.53
25.35
34.56
44.21
73.72
71.03
67.88
64.27
7.25
7.35
7.30
7.50
7.25
7.30
7.50
7.50
7.20
7.35
7.40
7.60
7.23 0.02
7.33 0.02
7.40 0.02
7.53 0.02
Water (1) + ethanol (2)
16.59
25.42
34.65
44.30
74.46
72.00
69.08
65.54
7.35
7.30
7.40
7.55
7.35
7.40
7.40
7.50
7.30
7.40
7.55
7.60
7.33 0.02
7.36 0.02
7.45 0.02
7.55 0.02
Water (1) + DMF (2)
19.21
28.96
38.81
48.75
76.06
74.56
72.73
70.45
7.20
7.30
7.25
7.30
7.15
7.22
7.32
7.35
7.15
7.30
7.35
7.40
7.16 0.02
7.27 0.02
7.31 0.02
7.35 0.02
a
Mass fraction of component I.

M.A. El-Gahami et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 129 (2014) 209–218
215
Table 4
pKa values for 1 ꢁ 10ꢂ5 M of 7-phenyl-3-((4-methylphenyl)diazenyl)pyrazolo[1,5-a]pyrimidin-2-amine in different water (1) + organic solvent (2) mixtures at 25 °C.
a
Mass% 100 W2
E
pKa
Mean value SD
Method 1
Method 2
Method 3
Water (1) + acetone (2)
16.53
25.35
34.56
44.21
74.92
72.87
70.25
66.99
7.50
7.60
7.70
7.80
7.50
7.62
7.78
7.82
7.55
7.50
7.75
7.77
7.51 0.02
7.57 0.02
7.74 0.02
7.80 0.02
Water (1) + methanol (2)
16.53
25.35
34.56
44.21
73.72
71.03
67.88
64.27
7.20
7.35
7.35
7.45
7.35
7.35
7.35
7.45
7.30
7.30
7.40
7.40
7.28 0.02
7.33 0.02
7.37 0.02
7.43 0.02
Water (1) + ethanol (2)
16.59
25.42
34.65
44.30
74.46
72.00
69.08
65.54
7.25
7.40
7.45
7.45
7.35
7.35
7.40
7.53
7.26
7.30
7.45
7.50
7.29 0.02
7.35 0.02
7.43 0.02
7.49 0.02
Water (1) + DMF (2)
19.21
28.96
38.81
48.75
76.06
74.56
72.73
70.45
7.10
7.20
7.12
7.17
7.20
7.15
7.21
7.32
7.00
7.07
7.13
7.22
7.10 0.02
7.14 0.02
7.15 0.02
7.23 0.02
a
Mass fraction of component II.
Azo-enamine ꢀ Hydrazo-imine
In the limiting absorbance method [24], thus, pKa can be deter-
mined from the plot of log (A ꢂ Amin)/(Amax ꢂ A) against the pH,
where a straight line is obtained Eq. (3).
The acid dissociation constants, pKa, of the compounds are
determined from the variation of the absorbance with pH⁄, making
use of three different spectrophotometric methods, namely: the
half-curve height [23,24], plot the absorbance–pH curve, pKa = pH
pH ¼ pKa þ logðA ꢂ AminÞ=ðAmax ꢂ AÞ
ð3Þ
at A1/2
;
The pH value where (A ꢂ Amin) equals (Amax ꢂ A) gives the
values of pKa. The pKa values were calculated by using a simple
program. The experimental error in determining pKa values was
checked by using the least-squares method. The obtained results
are given in Tables 3–8. The results listed in tables show that the
pKa values of all the compounds are dependent upon both the nat-
ure and the proportion of the organic co-solvent. In general,
increasing the organic co-solvent content in the medium results
in an increase in the pKa value. This can be explained as follows.
A1=2 ¼ ðAmax ꢂ AminÞ=2 þ Amin
ð2Þ
where Amin and Amax are the maximum and minimum absorbance
on the absorbance–pH curve (Fig. 2).
In the isobestic point method [24], the isobestic point repre-
sents the equilibrium between the (B) and (C) specie. By plotting
pH against absorbance for anion form and hydrazo-imine form,
the pH corresponding to the isobestic point equals the pKa value.
Table 5
pKa values for 1 ꢁ 10ꢂ5 M of 7-phenyl-3-((4-chlorophenyl)diazenyl)pyrazolo[1,5-a]pyrimidin-2-amine (III) in different water (1) + organic solvent (2) mixtures at 25 °C.
a
Mass% 100 W2
E
pKa
Mean value SD
Method 1
Method 2
Method 3
Water (1) + acetone (2)
16.53
25.35
34.56
44.21
74.92
72.87
70.25
66.99
7.38
7.45
7.54
7.74
7.37
7.50
7.70
7.85
7.40
7.54
7.60
7.70
7.35 0.02
7.45 0.02
7.60 0.02
7.75 0.02
Water (1) + methanol (2)
16.53
25.35
34.56
44.21
73.72
71.03
67.88
64.27
7.20
7.32
7.25
7.45
7.27
7.30
7.45
7.52
7.20
7.35
7.45
7.60
7.20 0.02
7.30 0.02
7.35 0.02
7.50 0.02
Water (1) + ethanol (2)
16.59
25.42
34.65
44.30
74.46
72.00
69.08
65.54
7.32
7.35
7.55
7.50
7.30
7.35
7.44
7.45
7.35
7.39
7.44
7.65
7.30 0.02
7.35 0.02
7.45 0.02
7.50 0.02
Water (1) + DMF (2)
19.21
28.96
38.81
48.75
76.06
74.56
72.73
70.45
7.19
7.26
7.24
7.28
7.20
7.20
7.30
7.40
7.10
7.32
7.37
7.35
7.15 0.02
7.23 0.02
7.30 0.02
7.33 0.02
a
Mass fraction of component III.

216
M.A. El-Gahami et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 129 (2014) 209–218
Table 6
pKa values for 1 ꢁ 10ꢂ5 M of 7-phenyl-3-((4-flurolphenyl)diazenyl)pyrazolo[1,5-a]pyrimidin-2-amine (IV) in different water (1) + organic solvent (2) mixtures at 25 °C.
a
Mass% 100 W2
E
pKa
Mean value SD
Method 1
Method 2
Method 3
Water (1) + acetone (2)
16.53
25.35
34.56
44.21
74.92
72.87
70.25
66.99
7.35
7.40
7.70
7.74
7.35
7.52
7.54
7.70
7.42
7.52
7.60
7.80
7.32 0.02
7.40 0.02
7.60 0.02
7.70 0.02
Water (1) + methanol (2)
16.53
25.35
34.56
44.21
73.72
71.03
67.88
64.27
7.20
7.30
7.25
7.42
7.25
7.32
7.40
7.55
7.20
7.30
7.45
7.60
7.18 0.02
7.25 0.02
7.30 0.02
7.50 0.02
Water (1) + ethanol (2)
16.59
25.42
34.65
44.30
74.46
72.00
69.08
65.54
7.30
7.40
7.50
7.46
7.32
7.30
7.45
7.50
7.35
7.40
7.45
7.40
7.30 0.02
7.35 0.02
7.42 0.02
7.46 0.02
Water (1) + DMF (2)
19.21
28.96
38.81
48.75
76.06
74.56
72.73
70.45
7.10
7.23
7.20
7.25
7.20
7.20
7.35
7.45
7.20
7.32
7.31
7.30
7.15 0.02
7.20 0.02
7.25 0.02
7.30 0.02
a
Mass fraction of component IV.
According to Coetzee and Richie [25], the acid dissociation
constant in aqueous medium (Ka) is related to that in partially
aqueous ðK0aÞ by Eq. (4):
However, methanol and DMF have similar relative permittivity
(32.6 and 36.7 respectively, at 25 °C) and all the compounds are
more acidic in water + DMF than in water + methanol, despite that
the same mole fraction of each is used (Tables 3–8). Moreover,
although ethanol and acetone have comparable relative permittiv-
ity also (24.3 and 20.7 respectively, at 25 °C), all the compounds
are more acidic in water + ethanol than in water + acetone, where
the same mole fraction of each is used. In general, pKa values in
all compounds decrease with increase relative permittivity of the
medium (i.e. the pKa values of a compound in water + organic sol-
vent are arranged according to the following sequence:
DMF < methanol < ethanol < acetone (see Fig. 3).
Ka ¼ K0aðcH
þ
cA Þ=cHA
ð4Þ
ꢂ
where
c is the activity coefficient of the subscripted species in a
partially aqueous medium relative to that in a pure aqueous one.
It is known that the electronic effect resulting from the change in
relative permittivity of the medium operates on the activity coeffi-
cients of a charged species [25] and one can expect that the increase
in the amount of the organic co-solvent in the medium will increase
the activity coefficient of both hydrazo-imine and anionic form.
According to Eq. (4), this will result in a decrease in the acid disso-
ciation constant Ka (high pKa value), which is consistent with the
results reported in Tables 3–8.
This behavior indicates that other solvent effects beside the
electrostatic one have a contribution to the ionization process of
the investigated compounds. This fact is further substantiated by
Table 7
pKa values for 1 ꢁ 10ꢂ5 M of 7-phenyl-3-((3-trifluromethylphenyl)diazenyl)pyrazolo[1,5-a]pyrimidin-2-amine (V) in different water (1) + organic solvent (2) mixtures at 25 °C.
a
Mass% 100 W2
E
pKa
Mean value SD
Method 1
Method 2
Method 3
Water (1) + acetone (2)
16.53
25.35
34.56
44.21
74.92
72.87
70.25
66.99
7.10
7.30
7.32
7.45
7.15
7.25
7.25
7.55
7.15
7.30
7.35
7.45
7.17 0.02
7.28 0.02
7.30 0.02
7.45 0.02
Water (1) + methanol (2)
16.53
25.35
34.56
44.21
73.72
71.03
67.88
64.27
7.60
7.15
7.25
7.25
7.15
7.18
7.27
7.30
7.15
7.18
7.25
7.32
7.13 0.02
7.17 0.02
7.26 0.02
7.29 0.02
Water (1) + ethanol (2)
16.59
25.42
34.65
44.30
74.46
72.00
69.08
65.54
7.06
7.10
7.30
7.25
7.15
7.16
7.20
7.30
7.09
7.20
7.25
7.30
7.10 0.02
7.15 0.02
7.25 0.02
7.28 0.02
Water (1) + DMF (2)
19.21
28.96
38.81
48.75
76.06
74.56
72.73
70.45
7.05
7.00
6.90
7.00
7.00
6.93
7.08
6.95
6.90
6.95
7.00
7.05
6.98 0.02
6.96 0.02
6.99 0.02
7.00 0.02
a
Mass fraction of component V.

M.A. El-Gahami et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 129 (2014) 209–218
217
Table 8
pKa values for 1 ꢁ 10ꢂ5 Mass% M of 7-phenyl-3-((4-nitrophenyl)diazenyl)pyrazolo[1,5-a]pyrimidin-2-amine (VI) in different water (1) + organic solvent (2) mixtures at 25 °C.
a
Mass% 100 W2
E
pKa
Mean value SD
Method 1
Method 2
Method 3
Water (1) + acetone (2)
16.53
25.35
34.56
44.21
74.92
72.87
70.25
66.99
7.25
7.30
7.45
7.60
7.28
7.40
7.53
7.50
7.15
7.45
7.20
7.60
7.22 0.02
7.38 0.02
7.46 0.02
7.57 0.02
Water (1) + methanol (2)
16.53
25.35
34.56
44.21
73.72
71.03
67.88
64.27
7.05
7.15
7.20
7.25
7.10
7.20
7.25
7.25
7.10
7.20
7.20
7.25
7.08 0.02
7.15 0.02
7.18 0.02
7.22 0.02
Water (1) + ethanol (2)
16.59
25.42
34.65
44.30
74.46
72.00
69.08
65.54
7.13
7.10
7.20
7.25
7.23
7.30
7.30
7.35
7.20
7.30
7.35
7.25
7.18 0.02
7.23 0.02
7.26 0.02
7.28 0.02
Water (1) + DMF (2)
19.21
28.96
38.81
48.75
76.06
74.56
72.73
70.45
6.90
6.90
6.95
7.00
7.05
7.07
7.05
7.10
6.90
6.95
7.00
7.00
6.95 0.02
6.97 0.02
6.99 0.02
7.03 0.02
a
Mass fraction of component (VI).
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
Acetone
Methanol
Ethanol
DMF
7.5
7.4
7.3
7.2
7.1
7.0
6.9
b
c
a
d
3
4
3
5
6
7
8
9
10
11
4
3
5
4
3
6
5
4
7
6
5
8
7
6
9
8
7
10
9
8
11
10
9
11
10 11
6.8
1.30
1.35
1.40
1.45
1.50
102/ ε
1.55
1.60
1.65
pH*
Fig. 3. Absorbance–pH⁄ curves of 2 ꢁ 10ꢂ5
M compound VI in water + DMF;
Fig. 4. Variation of pKa (compound V) in water + organic solvent with 102/
medium at 25 °C.
e
of the
x
2 = 19.21 (a); 28.96 (b); 38.81 (c); 48.75 (d).
the nonlinear relations obtained by plotting pKa against 1/
medium (Fig. 4) according to Eq. (5), which relates the variation of
pKa of the acid with the relative permittivity of the medium,
obtained from the relation [26] respectively:
em of the
to be less stabilized by hydrogen-bonding interaction with solvent
molecules as the amount of the organic co-solvent in the medium
is increased (i.e. cꢂA increase). This will tend to increase the pKa
value of the compound as Eq. (5) implies. It indicates also that
the difference in the stabilization of the ionic form by hydrogen-
bond donor solvent molecules plays an important role in the
increase in the pKa value as the amount of the organic co-solvent
in the medium increases.
e
m, is
em
¼
e
xmfð Þ þ eðsÞmfðsÞ
ð5Þ
x
e
and mf are the relative permittivity and mole fraction and the sub-
scripts and s refer to water and organic solvent.
x
In general, effects such as hydrogen bonding, solvent basicity,
dispersive forces, and proton solvent interactions play vital roles
in the ionization process of acids in the presence of organic
solvents [27]. Thus, the observed increase in the pKa of the com-
pounds as the proportion of the organic co-solvent in the medium
is increased can be ascribed, in addition to the electrostatic effect,
to the hydrogen-bonding interaction between the conjugate base
(anionic form C) and solvent molecules since water molecules have
a higher tendency to donate a hydrogen bond than other solvent
molecules [27]. The conjugate base anionic form (C) is expected
Examination of the results in Tables 3–8 reveals that the pKa
values in the presence of the poorer hydrogen bond donor DMF
are less than those obtained in the presence of corresponding
amounts of the other solvents. This behavior can be ascribed to
the high basic character of DMF [27].
There are dispersive forces, which possibly exist in the medium
used, between the delocalized charge on the conjugate base of the
dye (Aꢂ) and the localized dispersion center in near solvent mole-
cules. The proton-solvent interactions have important effects on
the ionization process the compounds studied, one should expect

218
M.A. El-Gahami et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 129 (2014) 209–218
that by increasing the amount of the organic co-solvent both Aꢂ
and H+ will be highly stabilized by DMF molecules (i.e. cAꢂ and c+H
decrease), since the effective density of dispersion centers in each
of the organic solvents used is higher that of water [28]. Thus, in
light of Eq. (4), the acid dissociation constant of the dyes studied
would increase (pKa decrease) with the increase in the amount
of the organic co-solvent in the medium. This is not the case
obtained from the results (cf. Tables 3–8).
References
[1] I.M. Issa, R.M. Issa, M.R. Mohamoud, Y.M. Temerk, Z. Phys. Chem. (Leipzig)
(1973) 253–289.
[2] A.M. Hammam, R.M. Issa, S.A. Amin, H. Dissoki, Gazz. Chem. Ital. 109 (1979)
351–355.
[3] S.H. Etaiw, N. El-Morsi, Kolor. Ert. 21 (1980) 208–218.
[4] M.T. EL-Hatu, A.H. Amrallah, M.A. Selim, Bull. Soc. Shem. Fr. 128 (1991) 869–
872.
[5] K.A. Ahmed, H.M. El-Hennawi, H.A. Abdel-Aziz, M.A. Elkashouti, J. Int. Environ.
Appl. Sci. 5 (2010) 890–900.
Effect of molecular structure on the values of pKa reported in
Tables 3–8 shows that the acidity of studied azo compounds
increases in the following order:
[6] G.H. Elgemeie, M.H. Helal, K.A. Ahmed, Pigm. Resin Technol. 32 (2003) 10–23.
[7] G.H. Elgemeie, M.H. Helal, H.M. El-Sayed, Pigm. Resin Technol. 30 (2001) 210–
221.
[8] M.A. El kashouti, G.H. Elgemie, M.M. Elmolla, H.S. Elsayad, K.A. Ahmed, Pigm.
Resin Technol. 36 (2007) 382–391.
p-NO2 < m-CF3 < p-F < p-Cl < p-H < p-CH3
[9] D. Gupta, S.K. Khare, A. Laha, Color. Technol. 140 (2004) 15–20.
[10] S. Makita, A. Saito, M. Hayashi, S. Yamada, K. Yodo, J. Otsuki, T. Takido, M. Seno,
Bull. Chem. Soc. Jpn. 73 (2000) 1525–1533.
[11] B. Simaneic, J.A. Span, Dyes Pigm. 46 (2000) 1–8.
[12] M.A. El-Taher, A.A. Gaber, Talanta 43 (1996) 1511–1518.
[13] A.A. Boraei, F. Taha, A.H. Mohamed, S.A. Ibrahim, J. Chem. Eng. Data 46 (2001)
267–275.
This trend is in accordance with the increase in the electron’s
donor’s ability of the substituent azo compounds.
Conclusions
[14] S. Topcu, N.M. Erdal, Dyes Pigm. 50 (2000) 29–33.
[15] S.A. El-Gyar, M.M.A. Hamed, E.M. Audalla, M.R. Mohamoud, Monatsch. Chem.
124 (1993) 127–133.
[16] M.R. Mahmoud, M.M. Hamed, S.A. Ibrahim, Bull. Chem. Soc. 9 (1983) 220–224.
[17] Y. Lin, S.A. Lang, J. Org. Chem. 45 (1980) 4857–4860.
[18] J. Wrubel, R. Mayer, Z. fuer Chem. (Stuttgart, Germany) 24 (1984) 256–257.
[19] H.T.S. Britton, Hydrogen Ions, Chapman & Hali, London, 1952.
[20] G. Douheret, Bull. Soc. Chim. Fr. 4 (1967) 1412–1419.
[21] G. Douheret, Bull. Soc. Chim. Fr. 8 (1968) 3122–3131.
[22] F. Karel, Dyes Pigm. 76 (2008) 97–103.
[23] R.M. Issa, H. Sadek, I.I. Izzat, Z. Phys, Chem. Neue Folge 75 (1971) 17–25.
[24] R.M. Issa, A.M. Hammam, Z. Phys. Chem. (Leipzig) 78 (1972) 253–281.
[25] J.F. Coetzee, C.D. Richie, J. Am. Chem. Soc. 77 (1955) 2615–2621.
[26] W.R. Gikerrson, J. Chem. Phys. 25 (1956) 1199–1202.
[27] F. Franks, D.J.G. Ives, Q. Rev. 20 (1966) 1–44.
In summary, solvatochromic behavior of these compounds
exhibits a red shift in the order cyclohexane, carbon tetrachloride,
chloroform, ethanol, DMF. The pKa values of the dyes studied were
determined and found depend largely on the amount and nature of
organic solvents. pKa values in all compounds decrease with in-
crease relative permittivity of the medium and are arranged
according to the following sequence: DMF < methanol < etha-
nol < acetone. pKa values of the studied azo compounds increase
in the following order p-NO2 < m-CF3 < p-F < p-Cl < p-H < p-CH3.
Acknowledgements
[28] E. Grunwald, E. Price, J. Am. Chem. Soc. 86 (1964) 4517–4528.
This paper was funded by the Deanship of Scientific Research
(DSR), King Abdulaziz University, Jeddah, under grant No. (965-
002-D1434). The authors, therefore, thank DSR for technical and
financial support.