Synthesis and single-crystal X-ray diffraction analysis of new heterocyclic coloured materials. 3-Arylazo-8H-imidazo[1,2-b] pyrazolo[4,3-d]pyridazines

Article abstract of DOI:10.1016/j.tet.2010.02.012

A simple synthetic strategy is described for the hitherto unreported 3-arylazo-8H-imidazo[1,2-b]pyrazolo[4,3-d]pyridazines 7 is described based on the reaction of 3-acetyl-4-cyano-1,5-diphenylpyrazole hydrazone 3 with the hydrazonoyl halides 1a-l. The structures of such dyes were confirmed by spectroscopic and X-ray crystallographic analyses. The mechanism of formation of such compounds was also discussed.

Full text of DOI:10.1016/j.tet.2010.02.012

Tetrahedron 66 (2010) 2700–2704
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Tetrahedron
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Synthesis and single-crystal X-ray diffraction analysis of new heterocyclic
coloured materials. 3-Arylazo-8H-imidazo[1,2-b] pyrazolo[4,3-d]pyridazines
*
Thoraya A. Farghaly, Ahmad Sami Shawali
Department of Chemistry, Faculty of Science, University of Cairo, Giza 12613, Egypt
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple synthetic strategy is described for the hitherto unreported 3-arylazo-8H-imidazo[1,2-b]pyr-
azolo[4,3-d]pyridazines 7 is described based on the reaction of 3-acetyl-4-cyano-1,5-diphenylpyrazole
hydrazone 3 with the hydrazonoyl halides 1a–l. The structures of such dyes were confirmed by spec-
troscopic and X-ray crystallographic analyses. The mechanism of formation of such compounds was also
discussed.
Received 24 October 2009
Received in revised form 26 December 2009
Accepted 1 February 2010
Available online 4 February 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Heterocycles
Azo dyes
Hydrazonoyl halides
Formazans
Hydrazones
1. Introduction
cyclized product, namely the pyrazolo[3,4-d]pyridazine derivative
4, failed, however (Scheme 1). This finding seems to be compatible
In continuation of our studies dealing with the utility of
hydrazonoyl halides as precursors for synthesis of various hetero-
cyclic systems1–10 and their aryl- and hetaryl-azo dyes,11 we wish to
with other literature reports,19 which indicated that hydrazinolysis
of 3-acetyl-4-cyanopyrazole derivatives afforded in such cases the
respective hydrazones.
report herein
a facile synthesis of 3-arylazo-8H-imidazo[1,2-
N-NH
b]pyrazolo[4,3-d]pyridazines that have not been reported hitherto.
Our interest in synthesis of such new azo dyes is due to the fact that
many arylazo derivatives of various heterocyclic systems were
found useful in the fields of material sciences and theoretical
chemistry.12 For example, in addition to their use as dyes in various
fields such as dyeing of textile fibres, coloured plastics, biological-
medical studies and advanced applications in organic synthesis,13
they are used in various fields such as printing, electronic photog-
raphy, colour formers, liquid crystal displays laser technology, data
storage and solar energy conversion.14
O
O
2
CN
CN
H C
3
Cl PhCOCH CN
2
H C
3
NH NH
2 2
H C
3
N
N
N
Ph
Ph
N
EtOH / EtONa
N
NH
Ph
1b
Ph
Ph
2
3 (89%)
N
N
H C
3
NH
2
N
Ph
N
4
Ph
Scheme 1. Synthesis of compound 3.
2. Results and discussion
The required hydrazonoyl halides 1a–l15–17 and 3-acetyl-4-cy-
ano-1,5-diphenylpyrazole 218 were prepared as previously repor-
Next, reactions of 3 with various hydrazonoyl halides were
examined. In our hands, it was found that the products of such
reactions depend on the structure of the hydrazonoyl halides used.
For example, when equimolar quantities of 3 and each of the
hydrazonoyl halides 1a–g were refluxed in dioxan in the presence
of triethylamine, a single product was obtained in each case as
evidenced by TLC analysis of the crude product. The results of both
ted. Hydrazinolysis of the latter pyrazole derivative
hydrazine hydrate in refluxing ethanol was found to give the re-
spective hydrazone derivative 3 (Scheme 1). All attempts to get the
2 with
* Corresponding author.
E-mail address: as_shawali@mail.com (A.S. Shawali).
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.02.012

T.A. Farghaly, A.S. Shawali / Tetrahedron 66 (2010) 2700–2704
2701
microanalyses and spectral data (MS, IR and 1H NMR) of the
isolated products indicated that the products isolated from such
reactions are the respective substitution products namely the 1,2-
dihydroformazan derivatives 5a–g (Scheme 2). On the other hand,
similar reactions of 3 with each of the hydrazonoyl halides 1h–l
were found to yield the arylazo derivatives 7h–l (Scheme 2). In such
cases, it seems that the initially formed substitution intermediates
5h–l underwent in situ cyclization to give the corresponding
arylazo derivatives 7h–l as end products.
example of the series prepared, is shown in Figure 1 with selected
bond distances and bond angles depicted in Table 2.23 This ORTEP
indicates that the products isolated from either thermal acidic cy-
clization of the hydrazone derivatives 5a–g or the reactions of 3
with 1h–l have the assigned structure 7. In addition, the foregoing
results suggest that the reactions leading to 7 are site selective and
proceed via the intermediates 5 and 6 depicted in Scheme 2.
N-NH-Ar
N-NH
2
N
N
H
COR
CN
CN
Ph
R-CO-C(X)=N-NH-Ar
1
H C
3
H C
3
Et N / dioxan
N
3
N
N
Ph
N
3
Ph
Ph
5 (52 - 66%)
AcOH
Heat
ArN=N
ArNHN
R
COR
NH
N
N
N
N
N
H C
3
H C
3
- H O
2
N
N
Ph
Ph
N
N
7 (57- 69%)
6
Ph
Ph
Ar = YC H
6
4
R / Y : a CH / 4-CH ; b,CH / H; c, CH / 4-Cl; d,CH / 3-Cl; e, CH / 3-NO ;
3
3
3
3
3
3
2
f, CH / 4-NO ; g, CH / 4-COCH ; h, CH / 4-OCH ; i, Ph / H; j, 2-thienyl / H;
3
2
3
3
3
3
k, 2-naphthyl / H; l, 2-naphthyl / 4-CH
3
Scheme 2. Reaction of compound 3 with hydrazonoyl halides.
When each of the hydrazone derivatives 5a–g was refluxed in
glacial acetic acid, it underwent dehydrative cyclization and affor-
ded the respective 3-arylazo-8H-imidazo[1,2-b]pyrazolo[4,3-
d]pyridazines 7a–g (Scheme 2).
The electronic absorption spectra of compounds 7a–l were of
typical azo chromophore12,20–22 and they are depicted in Table 1. As
shown each compound exhibits two bands in the regions 455–404
and 314–259 nm. The spectra of compound 7j, taken as a typical
example of the series studied, in different solvents of different
polarity, showed little, if any, change. These data are similar to
those of typical azo chromophore and indicate that compounds 7a–
l exist predominantly in the assigned azo structure.
Figure 1. ORTEP plot of the molecular structure of compound 7i. Notice the crystal-
lographic numbering differs from the IUPAC systematic numbering used in nomen-
clature. Selected bond distances and bond angles are shown in Table 2.
Table 2
Finally, to provide a conclusive evidence for the assigned
structure 7, we turned to X-ray crystallographic analysis. The ORTEP
drawing of 7i isolated from reaction of 3 with 1i, taken as a typical
Selected bond lengths and bond angles in the ORTEP of compound 7i in the crystal.
The crystallographic numbering does not reflect systematic numbering
Bond length, Å
Bond length, Å
Bond length, Å
N1–C21, 1.372
C21–C15, 1.377
C15–N2, 1.405
N2–N4, 1.387
N4–C10, 1.303
C10–C18, 1.457
C18–N5, 1.335
N5–N3, 1.376
N3–C16, 1.367
C16–C13, 1.389
C13–C25, 1.413
C25–N1, 1.327
C25–N2, 1.389
C18–C13, 1.403
C11–H11, 0.960
C14–H14, 0.960
N1–C25, 1.327
C22–H22, 0.960
C11–C12, 1.369
C14–C23, 1.364
C23–H23, 0.960
Table 1
Electronic absorption spectra of compounds 7a–l in dioxan
Compd. no.
lmax (log 3) nm
7a
7b
7c
7d
7e
7f
436 (5.11), 266 (5.40)
440 (3.93), 314 (4.14), 227 (4.51)
441 (4.19), 275 (4.27), 250 (4.66)
404 (4.20), 275 (4.48), 251 (4.82)
455 (4.65), 259 (5.41)
430 (4.88), 292 (4.69), 277 (4.69), 250 (5.15)
425 (4.62), 295 (4.82)
405 (4.46), 298 (5.01), 255 (4.62)
408 (4.54), 300 (4.62), 249 (4.82)
435 (4.51), 310 (4.65)
412 (4.74), 290 (5.02), 258 (5.41)
430 (4.32), 300 (4.68)
Angle (
u)
Angle (
u
)
Angle (u)
C21–N1–C25, 106.0
N4–N2–C15, 126.4
N4–N2–C25, 127.5
C15–N2–C25, 105.9
N5–N3–C16, 113.5
N5–N3–C27, 116.5
C16–N3–C27, 129.7
N2–N4–C10, 117.6
N3–N5–C18, 102.7
N9–N6–C15, 117.9
C21–C7–C24, 123.9
C21–C7–C30, 118.9
C24–C7–C30, 117.2
C17–C8–C19, 119.7
N6–N9–C12, 111.3
N4–C10–C18, 119.6
N4–C10–C28, 118.4
C18–C10–C28, 122.0
C12–C11–C35, 120.1
N9–C12–C11, 122.3
N9–C12–C36, 117.6
C11–C12–C36, 119.6
C16–C13–C18, 105
C16–C13–C25, 137.2
C18–C13–C25, 117.8
C20–C14–C23, 120.6
N2–C15–N6, 128.6
N2–C15–C21, 105.6
N6–C15–C21, 124.8
N3–C16–C13, 105.4
7g
7h
7i
7ja
7k
7l
a
Solvent: lmax (log
3
): acetic acid 441 (4.36), 309 (4.60); chloroform 436 (4.87),
313 (5.10); DMF 437 (4.78), 311 (5.01); ethanol 435 (4.44), 308 (4.66).

2702
T.A. Farghaly, A.S. Shawali / Tetrahedron 66 (2010) 2700–2704
3. Conclusion
products 5a–g and 7h–l together with their physical constants are
listed below.
In summary, a convenient synthetic strategy for the title new 3-
arylazo-8H-imidazo[1,2-b]pyrazolo[4,3-d]pyridazines was de-
scribed. Their characterization and absorption spectra were studied
and discussed.
4.4.1. 3-Acetyl-5-(4-methylphenyl)-1-[1-(4-cyano-1,5-diphenyl-pyr-
azol-3-yl)ethylidene]-1,2-dihydroformazan (5a). Dark yellow solid
(0.78 g, 66%), mp 226–228 ꢀC (ethanol). 1H NMR (DMSO-d6,
300 MHz)
d 2.45 (s, 3H, CH3), 2.49 (s, 3H, CH3), 2.57 (s, 3H, CH3),
4. Experimental
4.1. General
7.38–7.49 (m, 10H, ArH), 7.50 (d, J¼9 Hz, 2H, ArH), 8.13 (d, J¼9 Hz,
2H, ArH), 9.37 (s,1H, NH),11.31 (s,1H, NH); IR (KBr) nmax 3430, 3061,
2233, 1670, 1597, 1527, 1496 cmꢁ1. MS m/z (%), 476 (Mþþ1, 14), 475
(Mþ, 33), 105 (53), 91 (75), 77 (100). Anal. Calcd for C28H25N7O
(475.56): C, 70.72; H, 5.30; N, 20.62. Found: C, 70.60; H, 5.16; N,
20.49%.
Melting points were determined on a Gallenkamp apparatus. IR
spectra were recorded in potassium bromide using Perkin Elmer
FTIR 1650 and Pye-Unicam SP300 infrared spectrophotometers.
The 1H and 13C NMR spectra were recorded in deuterated chloro-
form or deuterated dimethyl sulfoxide on a Varian Mercury VXR-
300 spectrometer (300 MHz for 1H NMR and 75 MHz for 13C
NMR). Mass spectra were recorded on a GCMS-QP 1000 EX Shi-
madzu and GCMS 5988-A HP spectrometers. Electronic absorption
spectra were recorded on Perkin–Elmer Lambada 40 spectropho-
tometer. Elemental analyses were carried out at the Microanalytical
Laboratory of Cairo University, Giza, Egypt. The starting compounds
hydrazonoyl halides 1 and the pyrazole derivative 2 were prepared
as previously described.15–18
4.4.2. 3-Acetyl-5-phenyl-1-[1-(4-cyano-1,5-diphenyl-pyrazol-3-yl)e-
thylidene]-1,2-dihydroformazan (5b). Dark orange solid (0.71 g,
62%), mp 238–240 ꢀC (ethanol). 1H NMR (DMSO-d6, 300 MHz)
d
2.42 (s, 3H, CH3), 2.61 (s, 3H, CH3), 7.27–7.89 (m, 15H, ArH), 9.18 (s,
1H, NH), 10.84 (s, 1H, NH); IR (KBr) nmax 3425, 3271, 2229, 1674,
1624, 1596, 1496 cmꢁ1. MS m/z (%) 461 (Mþ, 31), 92 (46), 84 (34), 77
(100). Anal. Calcd for C27H23N7O (461.53): C, 70.27; H, 5.02; N,
21.24. Found: C, 70.16; H, 5.29; N, 21.03%.
4.4.3. 3-Acetyl-5-(4-chlorophenyl)-1-[1-(4-cyano-1,5-diphenyl-pyr-
azol-3-yl)ethylidene]-1,2-dihydroformazan
(0.80 g, 65%), mp 110–112 ꢀC (dioxan/ethanol). 1H NMR (DMSO-d6,
300 MHz) 2.42 (s, 3H, CH3), 2.60 (s, 3H, CH3), 7.29–7.51 (m, 10H,
(5c). Orange
solid
4.2. Crystallographic analysis
d
The crystals were mounted on a glass fibre. All measurements
were performed on an ENRAF NONIUS FR 590. The data were col-
ArH), 7.52 (d, J¼8 Hz, 2H, ArH), 7.82 (d, J¼8 Hz, 2H, ArH), 9.18 (s, 1H,
NH), 10.83 (s, 1H, NH); IR (KBr) nmax 3427, 3310, 2228, 1672, 1624,
1593, 1493 cmꢁ1. Anal. Calcd for C27H22ClN7O (495.98): C, 65.39; H,
4.47; N, 19.77. Found: C, 65.22; H, 4.19; N, 19.65%.
lected at a temperature of 25 ꢀC using the
u scanning technique to
a maximum of a 20 of 22.986ꢀ. The structure was solved by direct
method using SIR 92 and refined by full-matrix least squares. Non-
hydrogen atoms were refined anisotropically. Hydrogen atoms
were located geometrically and were refined isotropically.
4.4.4. 3-Acetyl-5-(3-chlorophenyl)-1-[1-(4-cyano-1,5-diphenyl-pyr-
azol-3-yl)ethylidene]-1,2-dihydroformazan (5d). Dark orange solid
(0.67 g, 54%), mp 200–202 ꢀC (ethanol). 1H NMR (DMSO-d6,
4.2.1. Crystal data. For compound 7i: C32H23N7, M¼505.585, tri-
clinic, a¼8.9652 (5), b¼9.5090 (5), c¼15.5928 (11) Å, v¼1258.42
300 MHz) d 2.42 (s, 3H, CH3), 2.61 (s, 3H, CH3), 7.24–7.82 (m, 14H,
ArH), 9.21 (s, 1H, NH), 10.87 (s, 1H, NH); IR (KBr) nmax 3442, 3310,
2227, 1674, 1620, 1593, 1495 cmꢁ1. MS m/z (%) 498 (Mþþ2, 5), 497
(Mþþ1, 16), 496 (Mþ, 13), 495 (40), 479 (33), 477 (49), 448 (50), 356
(13), 111 (33), 77 (100). Anal. Calcd for C27H22ClN7O (495.98): C,
65.39; H, 4.47; N, 19.77. Found: C, 65.59; H, 4.61; N, 19.50%.
(13),
a
¼72.527 (2)ꢀ,
g
¼83.827 (2)ꢀ,
b
¼84.947 (2)ꢀ, space group: P-1,
Z¼2, Dx¼1.334 Mg mꢁ3 reflection 6634 measured, qmax¼25.02ꢀ.
Figure 1 illustrates the structure as determined.23
4.3. Preparation of 3-acetyl-4-cyano-1,5-diphenylpyrazole
hydrazone (3)
4.4.5. 3-Acetyl-5-(3-nitrophenyl)-1-[1-(4-cyano-1,5-diphenyl-pyr-
azol-3-yl)ethylidene]-1,2-dihydroformazan (5e). Dark red solid
(0.66 g, 52%), mp 240–242 ꢀC (dioxan/ethanol). 1H NMR (DMSO-d6,
A mixture of 2 (1.44 g, 5 mmol) and hydrazine hydrate (5 mL) in
absolute ethanol (15 mL) was heated to reflux for 5 h, then cooled.
The solid formed was collected by filtration and recrystallized from
ethanol to give compound 3 as yellow crystals (1.33 g, 89%). Mp
300 MHz)
d 2.43 (s, 3H, CH3), 2.50 (s, 3H, CH3), 7.36–8.13 (m, 14H,
ArH), 9.25 (s 1H, NH), 11.06 (s, 1H, NH); IR (KBr) nmax 3427, 3061,
2227, 1697, 1618, 1595, 1496 cmꢁ1. Anal. Calcd for C27H22N8O3
(506.53): C, 64.02; H, 4.38; N, 22.12. Found: C, 63.79; H, 4.52; N,
22.46%.
154–156 ꢀC. 1H NMR (DMSO-d6, 300 MHz)
d 2.10 (s, 3H, CH3), 5.52
(s, 2H, NH2), 7.30–7.48 (m, 10H, Ar–H); IR (KBr) nmax 3420, 3318,
2227, 1590, 1537, 1499 cmꢁ1. MS m/z (%) 302 (Mþþ1, 4), 301 (Mþ,
22), 300 (32), 180 (7), 91 (3), 77 (100). Anal. Calcd for C18H15N5
(301.35): C, 71.74; H, 5.02; N, 23.24. Found: C, 71.65; H, 5.00; N,
23.13%.
4.4.6. 3-Acetyl-5-(4-nitrophenyl)-1-[1-(4-cyano-1,5-diphenyl-pyr-
azol-3-yl)ethylidene]-1,2-dihydroformazan (5f). Dark orange solid
(0.72 g, 57%), mp >300 ꢀC (dioxan/ethanol). 1H NMR (DMSO-d6,
300 MHz)
d
2.22 (s, 3H, CH3), 2.63 (s, 3H, CH3), 7.04 (d, J¼9 Hz, 2H,
4.4. Reaction of compound 3 with hydrazonoyl halides 1
ArH), 7.21 (d, J¼9 Hz, 2H, ArH), 7.36–7.78 (m, 10H, ArH), 9.13 (s 1H,
NH), 10.13 (s, 1H, NH); IR (KBr) nmax 3316, 3063, 2228, 1678, 1593,
1545, 1496 cmꢁ1. Anal. Calcd for C27H22N8O3 (506.53): C, 64.02; H,
4.38; N, 22.12. Found: C, 64.23; H, 4.19; N, 21.88%.
To a mixture of 3 (0.75 g, 2.5 mmol) and the appropriate
hydrazonoyl halide 1a–g (2.5 mmol of each) in dioxan (20 mL) was
added triethylamine (0.35 mL) and the mixture was heated to
reflux for 20 h, then cooled. The solution was poured onto ice and
concentrated hydrochloric acid. The solid produced was collected
by filtration and crystallized from the appropriate solvent to give
the corresponding compounds 5a–g, respectively.
4.4.7. 3-Acetyl-5-(4-acetylphenyl)-1-[1-(4-cyano-1,5-diphenyl-pyr-
azol-3-yl)ethylidene]-1,2-dihydroformazan
(0.70 g, 56%), mp 244–246 ꢀC (dioxan). 1H NMR (DMSO-d6,
300 MHz) 2.43 (s, 3H, CH3), 2.56 (s, 3H, CH3), 2.65 (s, 3H, CH3),
(5g). Orange
solid
d
When the above procedure was repeated using 1h–l in place of
1a–g, the respective 3-arylazo derivatives 7h–l were obtained. The
7.35–7.88 (m, 10H, ArH), 7.91 (d, J¼8 Hz, 2H, ArH), 8.11 (d, J¼8 Hz,
2H, ArH), 9.27 (s, 1H, NH), 11.12 (s, 1H, NH); IR (KBr) nmax 3440,

T.A. Farghaly, A.S. Shawali / Tetrahedron 66 (2010) 2700–2704
2703
3304, 2229,1685,1670,1595,1496 cmꢁ1. Anal. Calcd for C29H25N7O2
(503.57): C, 69.17; H, 5.00; N, 19.47. Found: C, 68.98; H, 4.85; N,
19.22%.
14H, ArH); IR (KBr) nmax 1594, 1526, 1484 cmꢁ1. MS m/z (%) 458
(Mþþ1, 1.3), 457 (Mþ, 3), 180 (8), 119 (6), 105 (38), 91 (39), 77 (100).
Anal. Calcd for C28H23N7 (457.54): C, 73.50; H, 5.07; N, 21.43. Found:
C, 73.26; H, 5.30; N, 21.33%.
4.4.8. 2,6-Dimethyl-3-[4-methoxyphenylazo]-8,9-diphenyl-imidazo-
[1,2-b]pyrazolo[4,3-d]pyridazine (7h). Red solid (0.71 g, 60%), mp
4.5.2. 2,6-Dimethyl-3-[phenylazo]-8,9-diphenyl-imidazo[1,2-b] pyr-
>300 ꢀC (dioxan/ethanol). 1H NMR (DMSO-d6, 300 MHz)
d
2.29 (s,
azolo [4,3-d]pyridazine (7b). Dark orange solid (0.24 g, 55%), mp
3H, CH3), 2.37 (s, 3H, CH3), 3.68 (s, 3H, OCH3), 7.12–7.44 and 7.83–
7.86 (m, 10H, ArH), 7.45 (d, J¼7 Hz, 2H, ArH), 7.55 (d, J¼8 Hz, 2H,
ArH); IR (KBr) nmax 1587, 1526, 1494 cmꢁ1. MS m/z (%) 474 (Mþþ1,
25), 473 (Mþ, 76), 444 (32), 351 (16), 338 (10), 287 (22), 180 (25),
135 (14), 107 (29), 92 (14), 77 (100). Anal. Calcd for C28H23N7O
(473.54): C, 71.02; H, 4.90; N, 20.71. Found: C, 70.93; H, 4.58; N,
20.46%.
220–222 ꢀC (dioxan). 1H NMR (DMSO-d6, 300 MHz)
d 2.32 (s, 3H,
CH3), 2.62 (s, 3H, CH3), 7.23–8.06 (m, 15H, ArH); IR (KBr) nmax 1594,
1492, 1474 cmꢁ1. MS m/z (%) 444 (Mþþ1,6), 443 (Mþ, 8), 141 (12),
129 (12),111 (36), 92 (10), 83 (15), 77 (100). Anal. Calcd for C27H21N7
(443.52): C, 73.12; H, 4.77; N, 22.11. Found: C, 73.00; H, 4.25; N,
21.93%.
4.5.3. 2,6-Dimethyl-3-[4-chlorophenylazo]-8,9-diphenyl-imi-
4.4.9. 6-Methyl-3-phenylazo-2,8,9-triphenyl-imidazo[1,2-b]pyr-
dazo[1,2-b] pyrazolo[4,3-d]pyridazine (7c). Pink solid (0.21 g, 43%),
azolo-[4,3-d]pyridazine (7i). Dark orange crystals (0.85 g, 67%), mp
mp180–182 ꢀC (ethanol). 1H NMR (CDCl3, 300 MHz)
d 2.07 (s, 3H,
230–232 ꢀC (dioxan). 1H NMR (DMSO-d6, 300 MHz)
d
2.56 (s, 3H,
CH3), 7.43–8.22 (m, 20H, ArH); IR (KBr) nmax 1595, 1537, 1492 cmꢁ1
13C NMR (DMSO-d6, 300 MHz)
17.6, 109.1, 114.0, 120.6, 120.7, 121.8,
CH3), 2.69 (s, 3H, CH3), 7.32–7.50 (m, 14H, ArH); IR (KBr) nmax 1594,
1523, 1445 cmꢁ1. MS m/z (%) 479 (Mþþ1, 16), 478 (Mþ, 51), 381 (11),
245 (15), 141 (16), 128 (11), 113 (24),111 (29), 91 (16), 77 (100). Anal.
Calcd for C27H20ClN7 (477.96): C, 67.85; H, 4.22; N, 20.51. Found: C,
67.64; H, 4.03; N, 20.29%.
.
d
125.6, 126.2, 127.0, 128.1, 128.2, 128.8, 129.1, 129.2, 129.3, 129.4,
129.5, 130.3, 133.3, 138.2, 138.9, 148.0, 150.1, 153.5. MS m/z (%) 505
(Mþ, 19), 504 (18), 476 (11), 252 (3), 180 (7), 77 (100). Anal. Calcd for
C32H23N7 (505.59): C, 76.02; H, 4.59; N, 19.39. Found: C, 76.11; H,
4.42; N, 19.25%.
4.5.4. 2,6-Dimethyl-3-[3-chlorophenylazo]-8,9-diphenyl-imi-
dazo[1,2-b] pyrazolo[4,3-d]pyridazine (7d). Dark red solid (0.25 g,
52%), mp 250–252 ꢀC (ethanol). 1H NMR (DMSO-d6, 300 MHz)
4.4.10. 6-Methyl-3-phenylazo-8,9-diphenyl-2-(2-thienyl)-imidazo-
d 2.62 (s, 3H, CH3), 2.76 (s, 3H, CH3), 7.39–8.20 (m, 14H, ArH); IR
[1,2-b]pyrazolo[4,3-d]pyridazine (7j). Red solid (0.84 g, 66%), mp
(KBr) nmax 1617, 1523, 1450 cmꢁ1. MS m/z (%) 479 (Mþþ1, 1), 478
(Mþ, 2), 476 (12), 325 (22), 272 (10), 111 (12), 77 (100). Anal. Calcd
for C27H20ClN7 (477.96): C, 67.85; H, 4.22; N, 20.51. Found: C, 67.71;
H, 4.18; N, 20.35.
128–130 ꢀC (ethanol/dioxan). 1H NMR (DMSO-d6, 300 MHz)
d 2.49
(s, 3H, CH3), 7.21–7.55 (m, 18H, ArH); IR (KBr) nmax 1597, 1495,
1480 cmꢁ1. MS m/z (%) 511 (Mþ, 1), 362 (7), 347 (12), 285 (3), 180
(6), 118 (6), 111 (28), 93 (8), 77 (100). Anal. Calcd for C30H21N7S
(511.61): C, 70.43; H, 4.14; N, 19.16. Found: C, 70.11; H, 4.32; N,
19.25%.
4.5.5. 2,6-Dimethyl-3-[3-nitrophenylazo]-8,9-diphenyl-imidazo[1,2-
b] pyrazolo[4,3-d]pyridazine (7e). Dark pink solid (0.24 g, 49%), mp
>300 ꢀC (ethanol). 1H NMR (DMSO-d6, 300 MHz)
d 1.71 (s, 3H, CH3),
4.4.11. 6-Methyl-3-phenylazo-8,9-diphenyl-2-(2-naphthyl)-imidazo-
2.49 (s, 3H, CH3), 7.40–7.62 (m, 14H, ArH); IR (KBr) nmax 1597,
1495 cmꢁ1. MS m/z (%) 489 (Mþþ1, 33), 488 (Mþ, 91), 410 (20), 414
(18), 338 (24), 270 (38), 122 (12), 104 (10), 92 (13), 77 (100). Anal.
Calcd for C27H20N8O2 (488.55): C, 66.39; H, 4.13; N, 22.94. Found: C,
66.21; H, 4.02; N, 22.56%.
[1,2-b]pyrazolo[4,3-d]pyridazine (7k). Red crystals (0.96 g, 69%), mp
260–262 ꢀC (ethanol/dioxan). 1H NMR (DMSO-d6, 300 MHz)
d 2.82
(s, 3H, CH3), 7.51–7.74 (m, 16H, ArH), 7.90 (d, J¼8 Hz, 2H, ArH), 8.32
(d, J¼8 Hz, 2H, ArH), 8.81 (s, 1H, naphthoyl-H); IR (KBr) nmax 1597,
1494, 1467 cmꢁ1. MS m/z (%) 556 (Mþþ1, 9), 555 (Mþ, 24), 526 (15),
466 (15), 180 (15), 164 (12), 93 (10), 77 (100). Anal. Calcd for
C36H25N7 (555.65): C, 77.82; H, 4.54; N, 17.65. Found: C, 77.60; H,
4.33; N, 17.42%.
4.5.6. 2,6-Dimethyl-3-[4-nitrophenylazo]-8,9-diphenyl-imidazo[1,2-
b] pyrazolo[4,3-d]pyridazine (7f). Pink solid (0.27 g, 56%), mp 120–
122 ꢀC (dioxan). 1H NMR (DMSO-d6, 300 MHz)
d 2.32 (s, 3H, CH3),
2.51 (s, 3H, CH3), 7.14 (d, J¼8 Hz, 2H, ArH), 7.22 (d, J¼8 Hz, 2H, ArH),
7.45–7.88 (m, 10H, ArH); IR (KBr) nmax 1605, 1525, 1475 cmꢁ1. MS m/
z (%) 488 (Mþ, 34), 487 (96), 486 (100), 444 (59), 368 (38), 367 (42),
341 (24), 338 (30), 106 (32), 91 (40), 77 (27). Anal. Calcd for
C27H20N8O2 (488.51): C, 66.39; H, 4.13; N, 22.94. Found: C, 66.11; H,
4.58; N, 22.56%.
4.4.12. 6-Methyl-3-(4-methylphenylazo)-8,9-diphenyl-2-(2-naph-
thyl)-imidazo[1,2-b]pyrazolo[4,3-d]pyridazine (7l). Red solid (1.02 g,
72%), mp 258–260 ꢀC (dioxan). 1H NMR (DMSO-d6, 300 MHz)
d 2.46
(s, 3H, CH3), 2.68(s, 3H, CH3), 7.37–8.17 (m, 22H, ArH), 8.93 (s, 1H,
naphthoyl-H); IR (KBr) nmax 1600, 1495, 1480 cmꢁ1. MS m/z (%) 570
(Mþþ1, 7), 569 (Mþ, 13), 555 (34), 270 (10), 180 (25), 141 (10), 114
(12), 77 (100). Anal. Calcd for C37H27N7 (569.67): C, 78.01; H, 4.78;
N, 17.21. Found: C, 77.90; H, 4.35; N, 17.00%.
4.5.7. 2,6-Dimethyl-3-[4-acetylphenylazo]-8,9-diphenyl-imi-
dazo[1,2-b] pyrazolo[4,3-d]pyridazine (7g). Brown solid (0.28 g,
57%), mp >300 ꢀC (dioxan/ethanol). 1H NMR (DMSO-d6, 300 MHz)
4.5. Cyclization of compounds 5a–g
d 2.32 (s, 3H, CH3), 2.55 (s, 3H, CH3), 2.61 (s, 3H, CH3), 7.23–8.06 (m,
14H, ArH); IR (KBr) nmax 1682, 1594, 1484 cmꢁ1. MS m/z (%) 486
(Mþþ1, 86), 485 (Mþ, 100), 255 (66), 105 (4), 76 (4). Anal. Calcd for
C29H23N7O (485.55): C, 71.74; H, 4.77; N, 20.19. Found: C, 71.52; H,
4.41; N, 19.76%.
A solution of compound 5a–g (1 mmol) in glacial acetic acid
(10 mL) was refluxed for 15 h. After cooling the solution was poured
into ice and sodium acetate, the precipitate formed was filtered off
and crystallized from the appropriate solvent to give compounds
7a–g
References and notes
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5. Shawali, A. S.; Elsheikh, S. M. J. Heterocycl. Chem. 2001, 38, 541–559.
4.5.1. 2,6-Dimethyl-3-[4-methylphenylazo]-8,9-diphenyl-imi-
dazo[1,2-b] pyrazolo[4,3-d]pyridazine (7a). Brown solid (0.23 g,
51%), mp >300 ꢀC (dioxan/ethanol). 1H NMR (DMSO-d6, 300 MHz)
d
1.69 (s, 3H, CH3), 2.49 (s, 3H, CH3), 2.61 (s, 3H, CH3), 7.02–7.48 (m,

2704
T.A. Farghaly, A.S. Shawali / Tetrahedron 66 (2010) 2700–2704
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