Synthesis and tautomeric structure of 3,7-bis(arylazo)-2,6-dimethyl- 1Himidazo 1,2-b]pyrazoles

Article abstract of DOI:10.3184/174751913X13588723344455

Three series of 3,7-bis(arylazo)-2,6-dimethyl-1H-imidazo[1,2-b]pyrazoles were prepared starting from N-aryl-2-oxopropanehydrazonoyl chlorides. The acid dissociation constants pKa were determined and correlated with the Hammett equation. The results of suc

Full text of DOI:10.3184/174751913X13588723344455

JOURNAL OF CHEMICAL RESEARCH 2013
RESEARCH PAPER 127
MARCH, 127–130
Synthesis and tautomeric structure of 3,7-bis(arylazo)-2,6-dimethyl-1H-
imidazo[1,2-b]pyrazoles
Ahmad Sami Shawali*, Magda A. Abdallah, Mohamed R. Shehata and Mohamed Kandil
Department of Chemistry, Faculty of Science, University of Cairo, Giza, Egypt
Three series of 3,7-bis(arylazo)-2,6-dimethyl-1H-imidazo[1,2-b]pyrazoles were prepared starting from N-aryl-2-oxo-
propanehydrazonoyl chlorides. The acid dissociation constants pKa were determined and correlated with the
Hammett equation. The results of such correlations together with the spectroscopic data indicated that the title
compounds exist predominantly in the 1H-bis(arylazo) form.
Keywords: hydrazonoyl halides, azo compounds, pyrazoles, imidazo[1,2-b]pyrazoles
A number of 1H-imidazo[1,2-b]pyrazole derivatives has
been found to exhibit interesting biological activities such as
inhibition of DNA synthesis1 and fMLP-induced neutrophil
chemotaxis.2 In addition, some arylazo heterocycles have
found uses as organic second order non-linear optical (NLO)
materials suitable for applications such as harmonic genera-
tion and optical switching3 and photodynamic therapy.4 In the
light these findings, and in continuation of our studies on the
use of hydrazonoyl halides as precursors for the synthesis of
various arylazo heterocycles,5 we explored the utility of such
halides for synthesis of the title compounds which have not
been reported hitherto. Our objective is to determine their
actual tautomeric structure prior to exploring their application.
This is because such compounds can theoretically have four
possible tautomeric structures A – D (Scheme 1).
confirmed by their IR, NMR, mass spectra and elemental
analysis. Their physical constants were similar to those previ-
ously reported in the literature.10 Their IR spectra revealed the
absence of the CO and CN bands present in the spectra of their
respective precursors 2a–e and their 1H NMR spectra showed
three common singlet signals in the regions δ 2.25–2.39, 6.84–
7.24 and 12.20–12.80 assignable to the CH3, NH2 and NH
protons, respectively.
Reaction of compounds 3a–e each with the hydrazonoyl
chloride1cinrefluxingdioxaneinthepresenceoftriethylamine
afforded the respective 2,6-dimethyl-3-arylazo-7-phenylazo-
1H-imidazo[1,2-b]pyrazoles 4a–e (Scheme 2). Similarly,
reaction of 3c with each of the hydrazonoyl chlorides 1a–e
furnished the respective 7-arylazo-3-phenylazo-2,6-dimethyl-
1H-imidazo[1,2-b]pyrazoles 5a–e (Scheme 1). Furthermore,
reactions of each of the halides 1a, 1d and 1e with each of the
pyrazole derivatives 3a, 3d and 3e under similar conditions
yielded the respective 3,7-bis(arylazo)-2,6-dimethyl-1H-imid-
azo[1,2-b]pyrazoles 6a–g (Scheme 2). The structures of the
new products 4–6 were confirmed by their microanalyses and
spectral data (see Experimental). For example, the IR spectra
of such products revealed, in each case, a weak NH band near
3200 cm−1. Their mass spectra showed, in each case, the respec-
tive molecular ion peak in addition to characteristic peaks at
m/z values corresponding to C6H5, XC6H4 and 2,6-dimethyl-
imidazo[1,2-b]pyrazole ion fragments. The 1H NMR spectra in
CDCl3 exhibited, in each case, in addition to the aromatic
proton signals of the XC6H4 groups, three common signals in
the regions δ 10.20–11.80, 2.31–2.38 and 2.40–2.46 due to the
NH and the two CH3 proton resonances, respectively. Although
these data are consistent with the assigned structures 4–6, they
do not distinguish between the four possible tautomeric forms
A-D (Scheme 1).
Results and discussion
The synthetic strategy adopted for synthesis of the target com-
pounds 4–6 is depicted in Scheme 2. The required precursors
5-amino-4-arylazo-3-methyl-1H-pyrazoles 3 were reported to
be prepared by coupling of 3-amino-2-butenonitrile A with
appropriate diazonium salts and hydrazinolysis of the resulting
2-arylhydrazono-3-iminobutyronitriles B.6–9 In this study,
we developed a new alternative synthetic strategy for such
precursors via reaction of the hydrazonoyl chlorides 1a–e
with potassium cyanide in ethanol to give the corresponding
2-arylhydrazono-3-oxobutanonitriles 2a–e and the treatment
of the latter with hydrazine hydrate in refluxing ethanol to
yield the respective 5-amino-4-arylazo-3-methylpyrazole 3
(Scheme 2). The structures of the products 3a–e prepared were
To shed some light on the actual tautomeric structure of
such compounds, the electronic absorption spectra were exam-
ined. The results are given in Table 1. As shown, the electronic
absorption spectra of compounds 4–6 in dioxane showed, in
each case, two absorption bands in the regions 420–495 and
329–360 nm. This absorption pattern is analogous to that
reported for the azo chromophore.12–14 Also, the electronic
absorption spectra of compound 4c, taken as a typical example
of the three series prepared, in different solvents showed little,
if any, shift (Table 1). This result indicates that the studied
compounds exist only in one tautomeric bis-azo form.
To provide an unambiguous evidence for the actual tauto-
meric structure of compounds 4–6, their acid dissociation con-
stants (pKa) were determined potentiometrically in an 80%
dioxane–water mixture at ionic strength (KNO3) of 0.1 M and
25 0.1 °C, and their correlations with the Hammett equation
were examined. The pKa values are summarised in Table 2.
As shown, the data indicate that the acidity constants of each
series of compounds 4–6 are influenced by the ring substitu-
ents, being increased by electron-withdrawing substituents and
Scheme 1
* Correspondent. E-mail: as_shawali@mail.com

128 JOURNAL OF CHEMICAL RESEARCH 2013
Scheme 2
that all of the studied compounds exist in the bis(arylazo)
tautomeric form A (Scheme 1). This is because the ρ values
(1.143 and 1.218) for the two series 4 and 5 are very similar.
This similarity provides evidence that the bridges between the
substituent and the acidic site (NH) in both series are of the
same length and this is fulfilled by structure A. This conclu-
sion is further supported by our finding that correlation of the
acidity constants (pKa) of the third series 6 with ∑σX resulted
in Eqn (3) with a ρ value (1.029) similar to that found for the
two series 4 and 5.
On the basis of these findings, the other possible tautomeric
structures B–D were discarded. This exclusion is based on the
following. If structure B was predominant, it would be expected
that the ρ values for the two series 4 and 5 will be different
since in such a structure the bridges between the substituent
decreased by electron-donating substituents. Correlation of the
pKa data of the three series 4–6 each with Hammett substituent
constants σX using the least squares method resulted in the
following equations, respectively:
pKa(4) = 5.920 – 1.143 σX;
pKa(5) = 5.910 – 1.218 σX;
r = 0.991; s = 0.050
r = 0.973; s = 0.089
(1)
(2)
(3)
pKa(6) = 6.010 – 1.029 ∑σX; r = 0.973; s = 0.089
where r and s are the correlation coefficient and standard
deviation, respectively. These excellent correlations indicate
Table 1 Electronic absorption spectra of compounds 4 and 5
in dioxane
Compound no.
λmax/nm (log ε)
Table 2 Acid dissociation constants pKa of compounds 4
and 5
4a
4b
4ca
4d
4e
5a
5b
5d
5e
5f
465 (4.951), 329 (4.721)
455 (4.623), 335 (4.593)
453 (4.635), 336 (4.599)
467 (4.813), 332 (4.916)
472 (4.793), 331 (4.622)
420 (4.761), 331 (4.916)
433 (4.645), 340 (4.696)
445 (4.631), 342 (4.602)
450 (4.851), 340 (4.656)
461 (4.756), 330 (4.788)
475 (4.850), 355 (4.740)
485 (4.817), 350 (4.790)
477 (4.790), 347 (4.789)
495 (4.791), 360 (4.849)
480 (4.645), 349 (4.783)
477 (4.814), 352 (4.716)
487 (4.745), 358 (4.992)
Compound no.
pKa
σX
4a
4b
4c
4d
4e
5a
5b
5d
5e
5f
6.23
6.07
5.81
5.62
5.03
6.25
6.08
5.61
5.05
5.16
6.65
6.09
6.05
5.45
4.49
5.47
5.45
–0.27
–0.17
0.00
0.23
0.78
–0.27
–0.17
0.23
6a
6b
6c
6d
6e
6f
0.78
0.50
6a
6b
6c
6d
6e
6f
–0.54
–0.04
–0.04
0.46
6g
1.56
Solvent λmax/nm (log ε): ethanol,450 (4.63), methanol: 456 (4.73),
acetic acid: 451 (4.70), acetonitrile: 449 (4.74), ether: 450 (4.72),
cyclohexane: 453 (4.72).
0.51
6g
0.51

JOURNAL OF CHEMICAL RESEARCH 2013 129
2,6-Dimethyl-7-(4-methoxyphenylazo)-3-phenylazo-1H-imid-
azo[1,2-b]-pyrazole (4a): Brown crystals (1.4 g, 80%), m.p. 108–
110 °C (dioxane/water), IR: ν (KBr) 3244 (NH) cm−1. 1H NMR
(DMSO-d6) δ 2.38 (s, 3H, CH3), 2.43 (s, 3H, CH3), 3.76 (s, 3H, CH3O),
6.97–7.05 (m,5H, ArH), 7.31 (d, 2H, ArH), 7.47 (d, 2H, ArH), 10.65
(s, 1H, NH). MS, m/z (%): 375 (M++2,11), 374 (M++1,29), 373 (M+,
33), 353 (12), 315 (10), 256 (18), 244 (11), 231 (41), 196 (10), 148
(20), 135 (20), 122 (35), 121 (56), 107 (49), 92 (47), 80 (100), 77 (72),
64 (98), 55 (25). Anal. Calcd for C20H19N7O (373.17): C, 64.33; H,
5.13; N, 26.26. Found: C, 64.40; H, 5.20; N, 26.20%.
and the acidic site (NH) are different and this was found not to
be the case. Also, if the compounds 4–6 exist in one of tauto-
meric forms C or D, their pKa values will be better correlated
−
with the enhanced Hammett substituent constants σX as in
such structures the substituent is in a direct interaction with the
negative charge on the nitrogen atom of the respective conju-
gate base. In addition, the pKa values of series 6 will be better
−
correlated with ∑(σX + σX ) and this was also found not to be
the case.
2,6-Dimethyl-7-(4-methylphenylazo)-3-phenylazo-1H-imid-
azo[1,2-b]-pyrazole (4b): Pale brown solid (1.38 g, 77%), m.p. 150–
152 °C (dioxane/water), IR: ν (KBr) 3248 (NH) cm−1. 1H NMR
(DMSO-d6) δ 2.36 (s, 3H, CH3), 2.45 (s, 3H, CH3), 2.54 (s, 3H, CH3),
6.91–6.95 (m, 4H, ArH), 7.27–7.43 (m, 5H, ArH), 10.2 (s, 1H, NH).
MS, m/z (%): 358 (M++1, 6), 357 (M+, 23), 329 (11), 322 (11), 308
(55), 281 (24), 271 (14), 267 (34), 255 (57), 240 (71), 213 (100), 141
(14), 118 (39), 96 (15), 55 (11). Anal. Calcd for C20H19N7 (357.17): C,
67.21; H, 5.36; N, 27.43. Found: C, 67.12 ; H, 5.40; N,27.41%.
2,6-Dimethyl-3,7-bis(phenylazo)-1H-imidazo[1,2-b]pyrazole (4c):
Pale red needles (1.5 g, 87%), m.p. 180–181 °C (dioxane/water), IR:
Finally, note that the foregoing results are consistent with
ourpreviousreportsonother2,6-disubstituted-3,7-bis(arylazo)-
1H-imidazo[1,2-b]pyrazoles which were found to exist in both
their ground and excited states exclusively in the bis(arylazo)
tautomeric form of type A (Scheme 1).7–8 Furthermore, the
results of the present study together with those of our previous
reports7–8 indicate collectively that the tautomeric structure of
3,7-bis(arylazo)-1H-imidazo[1,2-b]pyrazoles is independent
of the nature of the substituents at C-2 and C-6 of this ring
system.
1
ν (KBr) 3248 (NH) cm−1. H NMR (DMSO-d6) δ 2.33 (s, 3H, CH3),
2.37 (s, 3H, CH3), 6.91–6.95 (m, 5H, ArH), 7.27–7.67 (m, 5H, ArH),
10.31 (s, 1H, NH). MS, m/z (%): 344 (M++1, 21), 343 (M+, 34), 331
(20), 328 (29), 303 (20), 282 (37), 276 (35), 267 (26), 253 (27), 246
(27), 241 (100), 223 (37), 209 (43), 111 (19), 96 (50), 87 (30), 83 (17),
57 (39). Anal. Calcd for C19H17N7 (343.39): C, 66.46; H, 4.99; N,
28.55. Found: C, 66.36 ; H, 4.92; N, 28.35%.
Conclusion
Hydrazonoyl halides proved to be useful synthons for
3,7-bis(arylazo)-2,6-dimethyl-1H-imidazo[1,2-b]pyrazoles. In
addition, the results of correlations of the acidity constants
with the Hammett equation provided unambiguous evidence
that the actual tautomeric structure of such compounds is the
bis(arylazo) tautomeric form.
7-(4-Chlorophenylazo)-2,6-dimethyl-3-phenylazo-1H-imid-
azo[1,2-b]-pyrazole (4d): Dark red needles (1.65 g, 88%), m.p. 140–
1
141 °C (EtOH), IR: ν (KBr) 3256 (NH) cm−1. H NMR (DMSO-d6)
δ 2.33 (s, 3H, CH3), 2.46 (s, 3H, CH3), 7.12–7.27 (m, 4H, ArH), 7.28–
7.43 (m, 5H, ArH), 10.85 (s,1H, NH). MS, m/z (%): 379 (M++1, 6.0),
377.5 (M++5.0), 348 (26.1), 296 (25.1), 258 (31.1), 177 (21.1), 149
(100), 117 (27.1), 77 (41.1), 51 (25.8). Anal. Calcd for C19H16 ClN7
(377.80): C, 60.40; H, 4.27; N, 25.95. Found: C, 60.18; H, 4.40; N,
25.75%.
Experimental
All melting points were determined on a Gallenkamp apparatus and
are uncorrected. Solvents were generally distilled and dried by stan-
dard literature procedures prior to use. The IR spectra were measured
1
in potassium bromide using Pye-Unicam SP300 instrument. The H
2,6-Dimethyl-7-(4-nitrophenylazo)-3-phenylazo-1H-imidazo[1,2-
b]-pyrazole (4e): Red needles (1.71 g, 88%), m.p. 170–172 °C (diox-
ane/water), IR: ν (KBr) 3248 (NH) cm−1. 1H NMR (DMSO-d6) δ 2.31
(s, 3H, CH3), 2.36 (s, 3H, CH3), 6.91–6.95 (m, 4H, ArH), 7.27–7.37
(m, 5H, ArH), 10.29 (s, 1H, NH). MS, m/z (%): 388 (M+,17), 387.5
(20), 310 (15), 293 (19), 288 (19), 254 (21), 234 (24), 232 (88), 172
(13), 150 (48), 142 (17), 122 (100), 104 (49), 97 (31), 89 (65), 71 (40),
57 (61), 55 (29). Anal. Calcd for C19H16 N8O2 (388.14): C, 58.76; H,
4.15; N, 28.85 Found: C, 58.9; H, 4.20; N, 28.70%.
NMR spectra were recorded for solutions in CDCl3 using a Varian
Mercury VXR-300 MHz spectrometer and the chemical shifts δ are
downfield from TMS as internal standard. Mass spectra were recorded
on a GCMS-Q1000-EX Shimadzu and GCMS 5988-A HP spectrom-
eters, the ionizing voltage was 70 eV. Electronic absorption spectra
were recorded on Perkin-Elmer Lambda 40 spectrophotometer.
Elemental analyses were carried out at the Microanalytical Centre of
Cairo University, Giza, Egypt. 2-Oxopropanehydrazonoyl chlorides
1a–e were prepared as previously described.15–17
2,6-Dimethyl-3-(4-methoxyphenylazo)-7-phenylazo-1H-imid-
azo[1,2-b]-pyrazole (5a): Dark red solid (1.56 g, 85%), m.p. 175 °C
(EtOH), IR: ν (KBr) 3238 (NH) cm−1. 1H NMR (DMSO-d6) δ 2.37 (s,
3H, CH3), 2.47 (s, 3H, CH3), 3.77 (s, 3H, CH3O), 6.87–7.05 (m, 5H,
ArH), 7.21 (d, 2H, ArH), 7.57 (d, 2H, ArH), 10.25 (s,1H, NH). MS,
m/z (%): 374 (M++1, 14), 373 (M+, 40), 348 (29), 280 (23), 257 (26),
193 (20), 135 (32), 104 (33), 91 (29), 77 (100), 64 (21), 51 (59). Anal.
Calcd for C20H19N7O (373.17): C, 64.33; H, 5.13; N, 26.26. Found: C,
64.20; H, 5.25; N, 26.40%.
Synthesis of 2-Arylhydrazono-3-oxobutanonitriles (2); general
procedure
Equimolar quantities of the appropriate hydrazonoyle chloride 1 and
potassium cyanide (0.02 mol each) in ethanol (40 mL) were stirred
for 15 min and left overnight at room temperature. The crude product
was filtered off, washed with water and crystallised from aqueous
methanol to give the respective product 2. The physical constants of
the products 2a–e were identical to those previously reported.18–20
2,6-Dimethyl-3-(4-methylphenylazo)-7-phenylazo-1H-imid-
azo[1,2-b]-pyrazole (5b): Dark red solid (1.55 g, 87%), m.p. 167–
Synthesis of 4-arylazo-5-amino-3-methylpyrazoles (3); general
procedure
1
169 °C (EtOH), IR: ν (KBr) 3248 (NH) cm−1. H NMR (DMSO-d6)
δ 2.26 (s, 3H, CH3), 2.35 (s, 3H, CH3), 2.47 (s, 3H, CH3), 7.05–7.54
(m, 9H, ArH), 10.55 (s,1H, NH). MS, m/z (%): 358 (M++1, 32), 357
(M+, 19), 332 (54), 310 (40), 281 (21), 267 (45), 255 (38), 245 (47),
240 (42), 225 (25), 206 (42), 184 (48), 117 (100), 86 (39), 74 (19), 50
(12). Anal. Calcd for C20H19N7 (357.17): C, 67.21; H, 5.36; N, 27.43.
Found: C, 67.42; H, 5.48; N, 27.22%.
A mixture of hydrazine hydrate and the appropriate compound 2
(0.01 mole) in absolute ethanol (10 mL) was refluxed for 9 h then the
solvent was evaporated to half its volume and the mixture was left to
cool. The solid precipitate that formed was filtered off and crystallised
from the appropriate solvent to give the respective pyrazole derivative
3. The physical constants of the latter products 3a–e were identical to
those previously reported.7–9
2,6-Dimethyl-3-(4-chlorophenylazo)-7-phenylazo-1H-imid-
azo[1,2-b]-pyrazole (5d): Dark red needles (1.66 g, 88%), m.p. 120–
1
3,7-Bis(arylazo)-2,6-dimethyl-1H-imidazo[1,2-b]pyrazoles (4–6);
general procedure:
122 °C (EtOH), IR: ν (KBr) 3256 (NH) cm−1. H NMR (DMSO-d6)
δ 2.33 (s, 3H, CH3), 2.46 (s, 3H, CH3), 7.12–7.27 (m, 4H, ArH), 7.28–
7.43 (m, 5H, ArH), 10.95 (s, 1H, NH). MS, m/z (%): 380 (M++2, 2.3),
379 (M++1, 4.0), 378 (21), 347 (25.1), 298 (24.1), 258 (30.1), 178
(21.1), 149 (100), 119 (29), 77 (36.1), 51 (28.8). Anal. Calcd for
C19H16ClN7 (377.8): C, 60.40; H, 4.27; N, 25.95. Found: C, 60.32; H,
4.50; N, 25.80%.
2,6-Dimethyl-3-(4-nitrophenylazo)-7-phenylazo-1H-imidazo[1,2-
b]-pyrazole (5e): Dark red solid (1.71 g, 88%), m.p. 152–155 °C
(EtOH), IR: ν (KBr) 3248 (NH) cm−1. 1H NMR (DMSO-d6) δ 2.37 (s,
Triethylamine (0.7 mL) was added to a stirred mixture of the appropri-
ate pyrazole derivative 3 (0.05 mole) and hydrazonoyl chloride 1
(0.05 mole) in dioxane. The reaction mixture was refluxed for 5 h and
then cooled to room temperature. The reaction mixture was poured
onto cold water while being stirred. The solid that precipitated was
filtered off, dried and finally crystallised from the appropriate solvent
to give the respective 3,7-bis(arylazo)-2,6-dimethyl-1H-imidazo[1,2-b]
pyrazole.

130 JOURNAL OF CHEMICAL RESEARCH 2013
3H, CH3), 2.39 (s, 3H, CH3), 7.43–8.27 (m, 9H, ArH), 11.36 (s, 1H,
NH). MS, m/z (%): 388 (M+, 1.4), 352 (14), 153 (4), 123 (100), 106
(5), 93 (12), 65 (25). Anal. Calcd for C19H16N8O2 (388.14): C, 58.76;
H, 4.15; N, 28.85. Found: C, 58.50; H, 4.28; N, 28.63%.
73 (39). Anal. Calcd for C20H19N7O3 (418.12): C, 57.41; H, 4.34; N,
26.78. Found: C, 57.19; H, 4.62; N, 26.90%.
pKa Determination
The acid dissociation constants pKa of the compounds 4–6 were
determined potentiometrically in 80% (v/v) dioxane–water mixture at
25 °C and ionic strength of 0.01 M (KNO3). A Metrohm 686 titropro-
cessor equipped with a 665 dosimat fitted with combined glass elec-
trode type 518635 was employed for measurement of pH values. The
instrument was accurate to 0.01 pH unit. It was calibrated using two
standard Beckman buffer solutions of pH 4.01 and 7.00. The pH meter
readings (B) recorded in dioxane–water solutions were converted to
hydrogen ion concentration [H+] by means of the widely used relation
of Van Uitert and Hass21 namely: –log [H+] = B + log UH, where log
UH is the correction factor for the solvent composition and ionic
strength used for which B is read. The value of log UH was determined
by recording the pH values for a series of hydrochloric acid and
sodium chloride such that the ionic strength is 0.1 M in 80% (v/v)
dioxane–water at 27 °C. The value of log UH was found to be 0.48.
The experimental procedure followed in the determination of pK con-
stants and their calculations, by the method of least squares, from the
titrant volume-pH data using the relation:
2,6-Dimethyl-3-(4-ethoxycarbonylphenylazo)-7-phenylazo-1H-
imidazo[1,2-b]pyrazole (5f): Brown solid (1.82 g, 88%), m.p. 183–
185 °C (dioxane–water), IR: ν (KBr) 3248 (NH) cm−1. 1H NMR
(DMSO-d6) δ 1.18 (t, 3H, CH3), 2.35 (s, 3H, CH3), 2.40 (s, 3H, CH3),
4.24 (q, 2H, CH2), 7.16–7.42 (m, 4H, ArH), 7.57–7.95 (m, 5H, ArH)
11.39 (s, 1H, NH). MS, m/z (%): 416 (M++1, 16), 415 (M+,19), 400
(19), 372 (26), 312 (27), 273 (32), 207 (23), 185 (24), 163 (25), 137
(53), 120 (100), 93 (59), 81 (29), 64 (35).Anal. Calcd for C22H21N7O2
(415.45): C, 63.60; H, 5.09; N, 23.60. Found: C, 63.60; H, 5.12; N,
23.40%.
2,6-Dimethyl-3,7-bis(4-methoxyphenylazo)-1H-imidazo[1,2-
b]pyrazole (6a): red solid (1.41 g, 70%), m.p. 160 °C (dioxane–water),
1
IR: ν (KBr) 3217 (NH) cm−1. H NMR (DMSO-d6) δ 2.27 (s, 3H,
CH3), 2.4 (s, 3H, CH3), 3.72 (s, 6H, OCH3), 7.37–8.32 (m, 8H, ArH),
10.97 (s, 1H, NH). MS, m/z (%): 404 (M++1, 51), 403 (M+, 15), 380
(25), 365 (18), 352 (16), 238 (34), 322 (35), 298 (50), 268 (37), 241
(84), 213 (47), 173 (29), 132 (54), 92 (41), 77 (49). Anal. Calcd for
C21H21N7O2 (403.44): C, 62.52; H, 5.25; N, 24.30. Found: C, 62.29; H,
5.30; N, 24.33%.
pKa = pHi – log Vi/(Ve – Vi)
7-(4-Chlorophenylazo)-2,6-dimethyl-3-(4-methoxyphenylazo)-1H-
imidazo[1,2-b]pyrazole (6b): Reddish brown solid (1.45 g, 71%),
where pHi is the corrected pH value of the solution when the volume
of the added titrant is Vi and Ve is the volume of the titrant at the
equivalent point as previously described.21 The calculations of the pKa
values were carried out using the computer program MINIQUAD-
75.22 The pKa values obtained were reproducible to within 0.02 pKa
unit. The results are given in Table 2.
1
m.p. 143–145 °C (ethanol), IR: ν (KBr) 3248 (NH) cm−1. H NMR
(DMSO-d6) δ 2.25 (s, 3H, CH3), 2.38 (s, 3H, CH3), 3.72 (s, 3H, OCH3),
7.37–8.32 (m, 8H, ArH), 11.17 (s, 1H, NH). MS, m/z (%): 407 (M+,
20), 288 (24), 248 (42), 180 (13), 163 (37), 138 (37), 108 (58), 92
(79), 76 (71), 50 (100). Anal. Calcd for C20H18ClN7O (407.13): C,
58.90; H, 4.45; N, 24.04. Found: C, 58.81; H, 4.32; N, 24.00%.
3-(4-Chlorophenylazo)-2,6-dimethyl-7-(4-methoxyphenylazo)-1H-
imidazo[1,2-b]pyrazole (6c): Brown solid (1.5 g, 77%), m.p. 173–
175 °C (ethanol), IR: ν (KBr) 3248 (NH) cm−1. 1H NMR (DMSO-d6)
δ 2.28 (s, 3H, CH3), 2.40 (s, 3H, CH3), 3.79 (s, 3H, OCH3), 7.45–8.52
(m, 8H, ArH), 11.2 (s, 1H, NH). MS, m/z (%): 407 (M+, 40), 288 (24),
240 (42), 190 (19), 160 (37), 135 (37), 106 (60), 92 (79), 76 (78), 50
(100). Anal. Calcd for C20H18ClN7O (407.13): C, 58.90; H, 4.45; N,
24.04. Found: C, 58.81; H, 4.52; N, 24.20%.
Received 7 October 2012; accepted 1 January 2013
Paper 1201559 doi: 10.3184/174751913X13588723344455
Published online: 12 March 2013
References
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3,7-Bis(4-chlorophenylazo)-2,6-dimethyl-1H-imidazo[1,2-b]pyr-
azole (6d): Red solid (1.62 g, 79%), m.p. 150–152 °C (dioxane), IR:
1
ν (KBr) 3232 (NH) cm−1. H NMR (DMSO-d6) δ 2.38 (s, 3H, CH3),
2.41 (s, 3H, CH3), 7.31–7.57 (m, 8H, ArH), 11.38 (s, 1H, NH). MS,
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(34), 266 (34), 187 (22), 160 (36), 135 (28), 98 (37), 89 (100), 78 (30).
Anal. Calcd for C19H15Cl2N7 (412.28): C, 55.35; H, 3.67; N, 23.78.
Found: C, 55.09; H, 3.49; N, 23.58%.
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A.S. Shawali and M.A.N. Mosselhi, J. Heterocycl. Chem. 2003, 40, 725.
R. Aggarwal, V. Kumar, R. Kumar and S.P. Singh, Beil. J. Org. Chem.,
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2,6-Dimethyl-3,7-bis(4-nitrophenylazo)-1H-imidazo[1,2-b]pyraz-
ole (6e): Dark red solid (1.7 g, 82%), m.p. 175–178 °C (dioxane), IR:
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A.S. Shawali, M.A.N. Mosselhi, F.M.A. Altablawy, T.A. Farghaly and
N.M. Tawfik, Tetrahedron, 2008, 64, 5524.
A.S. Shawali, M.H. Abdelkader and F.M.A. Altablawy, Tetrahedron, 2002,
58, 2875.
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1
ν (KBr) 3224 (NH) cm−1. H NMR (DMSO-d6) δ 2.39 (s, 3H, CH3),
2.55 (s, 3H, CH3), 7.37–8.32 (m, 8H, ArH), 11.6 (s, 1H, NH). MS,
m/z (%): 433 (M+, 30), 390 (22), 355 (39), 315 (26), 300 (38), 268
(39), 212 (22), 166 (38), 155 (29), 135 (30), 99 (39), 89 (100), 77 (30).
Anal. Calcd for C20H19N7O4 (433.12): C, 52.66; H, 3.49; N, 29.09.
Found: C, 52.39; H, 3.39; N, 28.89%.
2,6-Dimethyl-3-(4-methoxyphenylazo)-7-(4-nitrophenylazo)-1H-
imidazo[1,2-b]pyrazole (6f): Red solid (1.6 g, 79%), m.p. 155–157 °C
(ethanol), IR: ν (KBr) 3226 (NH) cm−1. 1H NMR (DMSO-d6) δ 2.38 (s,
3H, CH3), 2.53 (s, 3H, CH3), 3.92 (s, 3H, OCH3), 7.37–8.32 (m, 8H,
ArH), 11.2 (s, 1H, NH). MS, m/z (%): 418 (M+, 30), 395 (23), 350
(40), 300 (38), 200 (53), 149 (100), 137 (40), 112 (73), 92 (80), 77
(41). Anal. Calcd for C20H19N7O3 (418.12): C, 57.41; H, 4.34; N,
26.78. Found: C, 57.62; H, 4.20; N, 26.68%.
2,6-Dimethyl-3-(4-nitrophenylazo)-7-(4-methoxyphenylazo)-1H-
imidazo[1,2-b]pyrazole (6g): Brown solid (1.5 g, 73%), m.p. 166–
168 °C (ethanol), IR: ν (KBr) 3230 (NH) cm−1. 1H NMR (DMSO-d6)
δ 2.35 (s, 3H, CH3), 2.40 (s, 3H, CH3), 4.00 (s, 3H, OCH3), 7.4–8.42
(m, 8H, ArH), 11.0 (s, 1H, NH). MS, m/z (%): 418 (M+, 30), 400 (35),
359 (54), 319 (29), 273 (45), 248 (100), 177 (30), 156 (35), 99 (45),
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