Synthesis of 3-arylazo-6-oxopyridazin-5-carbonitriles: A versatile precursor for condensed arylazopyridazin-6-ones

Article abstract of DOI:10.1002/jhet.5570450210

(Chemical Equation Presented) 1-[2-Phenyl-1-diazenyl]-1-[2-phenylhydrazono] acetone or 1-[-2-(4-methylphenyl)-1-diazenyl]-1-[-2-(4-methylphenyl)hydrazono]- butan-2-one were produced via coupling the (E) 2-oxopropanal-1-phenyl-hydrazone or (E) 2-oxobutanal

Full text of DOI:10.1002/jhet.5570450210

Mar-Apr 2008
359
Synthesis of 3-Arylazo-6-oxopyridazin-5-carbonitriles: A Versatile
Precursor for Condensed Arylazopyridazin-6-ones
Saleh M. Al-Mousawi,* Morsy A. El-Apasery, Najat Al-Kandery,
and Mohamed H. Elnagdi.
Department of Chemistry, Faculty of Science, University of Kuwait, P. O. Box 5969, 13060 Safat, Kuwait
E-mail: salehalmousawi@hotmail.com
Received March 27, 2007
R
S
O
R
N
Ar
R1
CN
S / piperidine
R1
NH2
R
N
N
N
N
N
O
N
O
NH
Ar
Ar
Ar
Ph
CN
CN
X
O
O
O
Ph
X
R
CN
R=H, CH3
R1=C6H5N2,
4-MeC6H4,
4-MeC6H4N2
X=NH, NCH3
R
O
R1
H2N
NH2
NH2
N
N
N
O
N
O
Ar
Ar
1-[2-Phenyl-1-diazenyl]-1-[2-phenylhydrazono]acetone or 1-[-2-(4-methylphenyl)-1-diazenyl]-1-[-2-(4-
methylphenyl)hydrazono]-butan-2-one were produced via coupling the (E) 2-oxopropanal-1-phenyl-
hydrazone or (E) 2-oxobutanal-1-(4-methylphenyl)hydrazone with aromatic diazonium salts. These
formazanes condensed readily with ethyl cyanoacetate to yield 5-methyl-3-oxo-2-phenyl-6-phenylazo-2,3-
dihydropyridazine-4-carbonitrile compound (9a), 5-ethyl-3-oxo-2-p-tolyl-6-p-tolylazo-2,3-dihydro-
pyridazine-4-carbonitrile and/or 5-ethyl-3-oxo-2,6-di-p-tolyl-2,3-dihydropyridazine-4-carbonitrile that
reacted with sulphur in presence of piperidine to yield the aminothienopyridazinones. The latter reacted
with electron poor olefins and acetylenes to yield aminophthalazines. Compound (9a) reacted also with
benzylidenemalononitrile to yield the arylazophthalazinone.
J. Heterocyclic Chem., 45, 359 (2008).
utilized by other groups, thus established their general
nature [12-14] (Scheme 1).
INTRODUCTION
Synthesis of arylazoazoles and arylazoazines is now
receiving considerable interest [1-4]. For example
arylazopyridones (1) are extensively utilized as dyes
for D2T2 printing [5,6]. However, to our knowledge,
neither arylazopyridazinones nor their benzofused
derivatives have yet been synthesized. In conjunction
to our interest in chemistry of arylazoazoles and
arylazoazines as potential dyes for D2T2 printing, we
report here results of our investigations aimed at
developing routes to these new classes of arylazo
derivatives. In the past fifteen years, Elnagdi et.al [7-
11] have established efficient routes to benzofused
phthalazines utilizing alkyl-pyridazinyl carbonitriles
as starting materials. It was reported that reacting 2
with elemental sulphur affords 3 in good yield. These
thienoazenes 3 added electron poor olefins and
acetylenes to yield 4. Alternately reacting 3 with 5 has
afforded 6. Reactions of this type has been recently
RESULTS AND DISCUSSION
1-[2-Phenyl-1-diazenyl]-1-[2-phenylhydrazono]acetone
or 1-[-2-(4-methylphenyl)-1-diazenyl]-1-[-2-(4-methyl-
phenyl)hydrazono]butan-2-one (8a,b) could be readily
obtained via coupling (E) 2-oxopropanal-1-phenyl-hy-
drazone or (E) 2-oxobutanal-1-(4-methylphenyl)hydraz-
one (7a,b) with aromatic diazonium salts. These could be
utilized as starting materials for targeted arylazo
pyridazinones. As we have placed emphasis in the last
few years on adopting microwave heating as a suitable
substitute to conventional heating in an oil bath [15-17],
we have utilized heating in a direct beam microwave
oven, in this work whenever it looked feasible heating
(8a) with ethyl cyanoacetate at 200 ºC for 15 min. in
presence of ammonium acetate has afforded (9a) in 79%
yields. However and quite unexpectedly reacting (8b)
with the same reagent afforded (9b) in addition another

360
S. M. Al-Mousawi, M. A. El-Apasery, N. Al-Kandery, and M. H. Elnagdi
Vol 45
side product for which structure (10) was established
based on X-ray crystal structure determination [18]
(Scheme 2) (cf. Figure 1). Compound 10 is considered a
side product as (9) could never yield (10) upon heating
with ammonium acetate.
To our knowledge this is first example of nitrogen
excision from aryldiazenyl derivatives in such system.
The arylazopyridazinone (9b) readily reacted with
elemental sulphur in presence of piperidine on heating in
focused microwave at 190 ºC for 10 min in dioxane as
reaction medium to yield arylazoamino thienopyridazine
(11) in good yield. Similarly (10) afforded (12) when
reacted with sulphur under the same reaction conditions.
X-ray crystal structure determination of (12) confirm with
certainly its structure [18] (Scheme 3) (cf. Figure 2).
Scheme 1
R
R
S
Me
ArHN-N
O
CN
O
X
X
CN
O
NH2
S / piperidine
N
N
N
Ar
1
N
O
N
Ar
Ar
2
Scheme 3
3
Ar
CN
CN
Y
z
S / piperidine
in dioxane for
10 min using
microwave
10
9b
R = H, Me
X = H, CO2Me, CO2Et
Y = H, CO2Me
5
Y
Ar
CN
Z = CN, CO2Et
z
R
N
R
N
Me
Me
S
S
X
X
NH2
NH2
Ar
ArN=N
NH2
NH2
N
Ar
4
O
N
O
N
N
N
O
N
O
Ar
6
Ar
Ar
11
Ar=4-MeC6H4
12
Scheme 2
O
O
N
Ar
R
R
N
R
_
N
CN
O
ArN=N
+
NH
Ar
8
CN
CO2Et
N
ArN N Cl
NH
Ar
N
N
EtOH, NaOAc
CH3COONH4
for 15 min
Ar
7,8a, R=Me, Ar=C6H5
b, R=Et, Ar=4-MeC6H4
8b
9a,Ar= C6H5, R=H
b,Ar=4-MeC6H4, R=Me
R
Ar
CN
O
N
N
Ar
10 Ar=4-MeC6H4, R=Me
Figure 2. X-Ray crystal structure of 12.
It can be noted from bond lengths and bond angles that
all nitrogens are SP2 in character. These points to
extensive delocalization of nitrogen lone pair both on ring
carbon as well as C-3 (C-4 in the Figure 1). Of interest is
observed elongation of C-C bonds in ethyl moiety perhaps
to minimize steric interaction with p-tolyl at C-3, Table 1.
Inspection of bond lengths and bond angles in Table 2
may lead to conclusion that the system is not much
aromatic although N1 lone pair is delocalized to some
extent on ring carbonyl resulting in shorter N6—C26 and
longer O4—C26 bonds while C19—C26 is typical for
Figure 1. X-Ray crystal structure of 10.

Mar-Apr 2008
Synthesis of 3-Arylazo-6-oxopyridazin-5-carbonitriles
361
single bond. The thiophene moiety is also least aromatic
as indicated from single bond character between C19 and
C20 and double bond character between C19 and C32.
important in this case than ease of reduction. Reduction of
arylazo derivatives by sodium hydrosulphide has been
observed earlier [20,21] (Scheme 5).
Scheme 5
Table 1
Selected bond lengths (Å) and bond angles (°) of compound (10).
X
S
O
O
Me
O
N1—N3
N1—C4
O2—C5
N3—C5
N3—C6
C4—C7
C5—C8
C17—C18
C17—C25
1.363 (4)
1.314 (4)
1.225 (4)
1.384 (4)
1.452 (4)
1.469 (5)
1.439 (5)
1.499 (5)
1.521 (6)
N3—N1—C4
N1—N3—C5
N1—N3—C6
C5—N3—C6
N1—C4—C7
N1—C4—C18
119.3 (3)
124.9 (3)
114.1 (3)
121.0 (3)
114.1 (3)
122.2 (4)
X=NH
ArN=N
X
X=NMe
NH2
11
N
O
in dioxane for
20 min using
microwave
N
O
Ar
15
-H2S
O
X
Table 2
Selected bond lengths (Å) and bond angles (°) of compound (12).
O
X
Me
N
O
Me
O
S1—C30
S1—C32
N3—N6
N3—C11
O4—C26
N6—C9
N6—C26
N10—C32
C19—C20
C19—C26
C19—C32
C20—C30
C30—C43
1.750 (3)
1.716 (4)
1.397 (3)
1.302 (3)
1.233 (4)
1.426 (4)
1.388 (4)
1.336 (4)
1.440 (4)
1.432 (4)
1.388 (4)
1.361 (4)
1.488 (5)
C30—S1—C32
N6—N3—C11
N3—N6—C9
N3—N6—C26
N6—C9—C12
S1—C30—C20
S1—C30—C43
93.9 (2)
118.7 (2)
113.0 (2)
125.9 (3)
119.9 (3)
109.4 (3)
117.3 (2)
H
H2N
ArN=N
N
H
+H2S
NH2
N
N
O
N
O
Ar
Ar
17a, X=NH
b, X=NMe
16
Ar=4-MeC6H4
We traced H2S elimination during reaction by lead
acetate paper. We have also investigated possible
adoption of other route, also explored by Elnagdi et al
[10], for synthesis of phthalazines. Typical to earlier
reports, arylazopyridazinones (9a) reacted with benzyl-
idenemalononitrile to yield arylazophthalazinone (21).
This is a further extension to our established phthalazine
synthesis, which is believed to proceed via intermediacy
of (19) and (20) (Scheme 6).
Typical to established behaviour of thienopyridazines
compounds (12) reacted with N-methylmaleimide in a
mixture of acetic acid and dioxane to yield (14) via
intermediary of 4+2 cycloadducts (13) that could not be
isolated but is a well accepted intermediate in this type of
reactions [19] (Scheme 4).
Scheme 4
Scheme 6
Me
O
Ph
CN
CN
S
Me
N
Me
N
N
O
Ph
CN
CN
O
O
O
H
Me
N
-H2S
Ar
N
18
CH3
PhN=N
CN
12
Ar
NH2
N
H
9a
Reflux in
dioxane
for 6h
O
Reflux in
pyridine
for 6h
N
O
N
N
O
N
O
Ar
Ph
Ar
13, Ar=4-MeC6H4
14, Ar=4-MeC6H4
19
In contrast to this straightforward application of
Elnagdi’s synthesis of fused pyridazinones from
aminothienopyridazinones [10], compound 11 reacted
with maleimide and N-methylmaleimide in a mixture of
acetic acid and dioxane, in focused microwave at 170 ºC
for 20 min to yield diamino compounds 17a,b. It is
believed that hydrogen sulphide eliminated during the
reaction reduced the arylazo function leading to the
formation of 16. Relieve of steric strain is perhaps more
Ph
Ph
CN
CN
NH
CN
PhN=N
PhN=N
NH2
N
-HCN
N
N
O
N
O
Ph
Ph
21
21
20

362
S. M. Al-Mousawi, M. A. El-Apasery, N. Al-Kandery, and M. H. Elnagdi
Vol 45
H), 11.33 (s, 1H, NH). ms (EI) m/z = 162 (M+, 100), 92 (10), 64
(10), Anal. Calcd for C9H10N2O: C, 66.65; H, 6.21; N, 17.27.
Found: C, 66.63; H, 6.07; N, 17.27.
In summary, arylazopyridazines and condensed phthal-
azines could be prepared via procedures similar to our
previously described ones. A novel nitrogen molecule
excision during the pyridazinones synthesis and a novel
ready arylazo group reduction are reported.
(E) 2-Oxobutanal-1-(4-methylphenyl)hydrazone (7b).
Compound (7b) was obtained as orange crystals. Yield (1.26 g,
66%), mp 134-136 ºC, ir (KBr) ν 3236, 1651 cm-1; UV/Vis at
λmax (CHCl3) = 347 nm,1H nmr (DMSO-d6): δ 1.01 (t, 3H, J =
7.4 Hz, CH3), 2.24 (s, 3H, CH3), 2.75 (q, 2H, J = 7.4 Hz, CH2),
7.05 (d, 2H, J = 8.4 Hz, [4-methylphenyl]-H), 7.10 (d, 2H, J =
8.4 Hz, [4-methylphenyl]-H), 7.21 (s, 1H, imine-H), 11.21 (s,
1H, NH), 13C nmr (DMSO-d6): δ 200.0, 142.0, 134.3, 131.4,
130.4, 114.4, 30.0 (CH2), 21.3 (CH3), 9.5 (CH3). ms (EI) m/z =
190 (M+, 100), 106 (60), 79 (15), 57 (22), Anal. Calcd for
C11H14N2O: C, 69.45; H, 7.42; N, 14.73. Found: C, 69.56; H,
7.34; N, 14.73.
General procedure for the preparation of compounds
(8a,b). A solution of aryldiazonium chloride (prepared from the
corresponding aromatic amine (0.01 mol) and the appropriate
quantities of both hydrochloric acid and NaNO2) (0.01 mol) at 0
0C was added to a solution of compound (7a) or (7b) (0.01 mol)
in EtOH (50 mL) containing NaOAc (2 g). The reaction mixture
was stirred at rt for 1 h and the solid product, so formed, was
collected by filtration and crystallized from EtOH.
EXPERIMENTAL
Melting points are uncorrected. All of the reactions under
microwave irradiation were conducted in heavy-walled Pyrex
tubes (capacity 10 ml) fitted with PCS cap. Microwave heating
was carried out with a single mode cavity Explorer Microwave
Synthesizer (CEM Corporation, NC, USA), producing
continuous irradiation and equipped with simultaneous external
air-cooling system. IR spectra were recorded in KBr disks using
a Perkin-Elmer System 2000 FT-IR spectrophotometer. UV/Vis
spectral data were recorded on UV/Vis spectrophotometer
(Carry-Varian 5). 1H NMR (400 MHz) and 13C NMR (100 MHz)
spectra were recorded on a Bruker DPX 400, super-conducting
NMR spectrometer in CDCl3 or DMSO as solvent and TMS as
internal standard; chemical shifts are reported in δ units (ppm).
Mass spectra were measured on MS 30 and MS 9 (AEI), 70 eV.
1-[2-Phenyl-1-diazenyl]-1-[2-phenylhydrazono]acetone (8a).
Compound (8a) was obtained as red crystals. Yield (1.54 g,
58%), mp 136-138 ºC, ir (KBr) ν 3398, 1679 cm-1; UV/Vis at
Microanalyses were performed on
Elemental Analyzer.
Compounds 7a and 8a were prepared following general
procedures [22,23].
a LECO CHNS-932
1
λmax (CHCl3) = 443 nm, H nmr (DMSO-d6): δ 2.57 (s, 3H,
CH3), 7.38 (t, 2H, J = 7.2 Hz, phenyl-H), 7.52 (t, 4H, J = 7.7 Hz,
phenyl-H), 7.84 (d, 4H, J = 7.8 phenyl-H), 14.67 (s, 1H, NH),
13C nmr (DMSO-d6): δ 193.6, 147.9, 142.0, 130.8, 129.7, 120.5,
27.4 (CH3). ms (EI) m/z =266 (M+, 78), 160 (25), 105 (26), 92
(100), 77 (75), 65 (52); Anal. Calcd for C15H14N4O: C, 67.65; H,
5.30; N, 21.04. Found: C, 67.65; H, 5.38; N, 20.80.
Crystallographic analysis. The crystals were mounted on a
glass fiber. All measurements were performed on an Enraf
Nonius FR 590 diffractometer. The data were collected at a
temperature of 20±1 ºC using the ω scanning technique to a
maximum of a 2 θmax = 24.09º. The structure was solved by
direct Methods using SIR 92 and refined by full-materix least
squares [24] Non-hydrogen atoms were refined anisotropically.
Hydrogen atoms were located geometrically and were refined
isotropically.
Crystal Data. C21H19N3O (10) Mr = 329.403, Triclinic, a =
9.3892 (5), b = 10.1999 (6), c = 11.1372 (8)Å, α = 104.983(2)°,
β = 107.878 (2)°, γ = 108.011 (3)°, Z = 2, Dx = 1.231 Mg m-3,
θmax = 24.09°. Full data can be obtained on request from CCDC
[18]. C21H19N3OS (17) Mr = 361.467, Triclinic, a = 10.6131 (6),
b = 11.8255 (7), c = 15.7381 (12)Å, α = 76.889 (2)°, β = 75.684
(3)°, γ = 79.835 (5)°, Z = 4, Dx = 1.299 Mg m-3, θmax = 24.15°.
Full data can be obtained on request from CCDC [18].
1-[-2-(4-Methylphenyl)-1-diazenyl]-1-[-2-(4-methylphenyl)-
hydrazono]butan-2-one (8b). Compound (8b) was obtained as
wine red crystals. Yield (1.84 g, 60%), mp 142-144 ºC, ir (KBr)
1
ν 3423, 1681 cm-1; UV/Vis at λmax (CHCl3) = 455 nm, H nmr
(DMSO-d6): δ 1.09 (t, 3H, J = 7.2 Hz, CH3), 2.36 (s, 6H, [4-
methylphenyl]-CH3), 2.99 (q, 2H, J = 7.2 Hz, CH2), 7.32 (d, 4H,
J = 7.8 Hz, [4-methylphenyl]-H), 7.72 (d, 4H, J = 7.8 Hz, [4-
methylphenyl]-H), 14.93 (s, 1H, NH, D2O exchangeable), 13C
nmr (DMSO-d6): δ 196.5, 145.7, 141.2, 139.5, 131.0, 120.4,
31.9 (CH2), 21.9 ([4-methylphenyl]-CH3), 9.5 (CH3). ms (EI)
m/z= 308 (M+, 36), 132 (20), 106 (100), 91 (42), Anal. Calcd for
C18H20N4O: C, 70.11; H, 6.54; N, 18.17. Found: C, 70.10; H,
6.54; N, 18.12.
General procedure for the preparation of compounds (9a).
A mixture of each of compounds (8a) (0.01mol), ethyl
cyanoacetate (1.13 g, 0.01 mol), ammonium acetate (2 g) was
heated with stirring at 200 ºC for 15 min, then left to cool and
triturated with EtOH. The solid product, so formed, was
collected by filtration and crystallized from dioxane.
5-Methyl-3-oxo-2-phenyl-6-phenylazo-2,3-dihydropyridaz-
ine-4-carbonitrile (9a). Compound (9a) was obtained as buff
crystals. Yield (2.60 g, 79%), mp. 216 ºC, ir (KBr) ν 2229, 1676
cm-1; 1H nmr (DMSO-d6): δ 2.75 (s, 3H, CH3), 7.52-7.68 (m, 8H,
phenyl-H), 7.96 (d, 2H, J = 7.8 Hz, phenyl-H), ms (EI) m/z =
315 (M+, 43), 105 (30), 77 (100), Anal. Calcd for C18H13N5O: C,
68.56; H, 4.16; N, 22.21. Found: C, 68.15; H, 4.28; N, 21.93.
General Procedure for the Reaction of Compound 8b with
Ethyl cyanoacetate. A mixture of compound (8b) (3.08 g,
0.01mol), ethyl cyanoacetate (1.13 g, 0.01 mol), ammonium
General procedure for the preparation of compounds
(7a,b). The mixture of KOH (3.5 g, 0.053 mol) in water (100
mL), ethyl acetoacetate or methyl propionyl acetate (6.5 g, 0.05
mol) was allowed to stir at rt for 24 h. The solution of KOAc
was cooled to 0 ºC and concentrated hydrochloric acid (4.5 mL)
in ice-water (15 mL) was added slowly with stirring, then
gradually treated under stirring with a solution of aryldiazonium
chloride (prepared from the corresponding aromatic amine (0.01
mol) and the appropriate quantities of both hydrochloric acid
and NaNO2. The mixture is made basic by addition of NaOAc
(8.2 g) dissolved in water (30 mL). The solid product, so
formed, was collected by filtration and crystallized from toluene.
(E) 2-Oxopropanal-1-phenylhydrazone (7a). Compound
(7a) was obtained as orange crystals. Yield (1.44 g, 89%), mp
152 ºC (Lit [22], 150 ºC), ir (KBr) ν 3249, 1649 cm-1; UV/Vis at
1
λmax (CHCl3) = 341 nm, H nmr (DMSO-d6): δ 2.31 (s, 3H,
CH3), 6.93 (t, 1H, J = 7.4 Hz, phenyl-H), 7.17 (t, 2H, J = 7.7 Hz,
phenyl-H), 7.24 (s, 1H, imine-H), 7.29 (d, 2H, J = 8 Hz, phenyl-

Mar-Apr 2008
Synthesis of 3-Arylazo-6-oxopyridazin-5-carbonitriles
363
acetate (2 g) was heated with stirring at 200 ºC for 15 min. After
cooling to room temperature, the formed precipitate was washed
with EtOH, collected by filtration, and crystallized from dioxane
to afford product (9b), the filtrate was poured onto crushed ice,
the solid product, so formed, was collected by filtration and
crystallized from EtOH to furnish product (10).
64.76; H, 4.92; N, 17.98; S, 8.23. Found: C, 65.08; H, 5.06; N,
17.91; S, 8.22.
7-Amino-5-methyl-2,4-di-p-tolyl-2H-thieno[3,4-d]pyridazin-
1-one (12). Compound (12) was obtained as buff crystals. Yield
(3.25 g, 90%), mp 202-204 ºC, ir (KBr) ν 3421, 3276, 1631
1
cm-1; UV/Vis at λmax (CHCl3) = 372 nm, H nmr (DMSO-d6): δ
5-Ethyl-3-oxo-2-p-tolyl-6-p-tolylazo-2,3-dihydropyridazine-
4-carbonitrile (9b). Compound (9b) was obtained as buff
crystals. Yield (2.28 g, 64%), mp 194-196 ºC, ir (KBr) ν 2234,
1.82 (s, 3H, CH3), 2.32 (s, 3H, [4-methylphenyl]-CH3), 2.37 (s,
3H, [4-methylphenyl]-CH3), 7.19 (d, 2H, J = 8.0 Hz, [4-
methylphenyl]-H), 7.27 (d, 2H, J = 7.7 Hz, [4-methylphenyl]-
H), 7.33 (d, 2H, J = 7.7 Hz, [4-methylphenyl]-H), 7.40-7.42 (m,
4H, [4-methylphenyl]-H, NH2, D2O exchangeable), 13C nmr
(DMSO-d6): δ 160.2, 159.5, 145.7, 139.7, 139.2, 136.5, 134.6,
130.2, 129.7, 129.6, 126.4, 125.4, 116.5, 105.4, 21.9 ([4-
methylphenyl]-CH3), 21.6 ([4-methylphenyl]-CH3), 13.8 (CH3).
ms (EI) m/z= 361 (M+, 100), 329 (22), 91 (20), Anal. Calcd for
C21H19N3OS: C, 69.78; H, 5.30; N, 11.63; S, 8.87. Found: C,
69.28; H, 5.48; N, 11.83; S, 8.94.
1
1675 cm-1; UV/Vis at λmax (CHCl3) = 325 nm, H nmr (DMSO-
d6): δ 1.26 (t, 3H, J = 7.3 Hz, CH3), 2.38 (s, 3H, [4-
methylphenyl]-CH3), 2.42 (s, 3H, [4-methylphenyl]-CH3), 3.02
(q, 2H, J = 7.0 Hz, CH2), 7.34 (d, 2H, J = 8.0 Hz, p-tolyl-H),
7.43-7.49 (m, 4H, [4-methylphenyl]-H), 7.84 (d, 2H, J = 8.0 Hz,
[4-methylphenyl]-H), 13C nmr (DMSO-d6): δ 157.6, 155.7,
151.3, 150.1, 145.2, 139.8, 138.9, 131.3, 130.3, 126.6, 124.5,
114.8, 114.3, 25.3 (CH2), 22.2 ([4-methylphenyl]-CH3), 14.4
([4-methylphenyl]-CH3), 9.0 (CH3). ms (EI) m/z = 357 (M+, 33),
342 (15), 91 (100), 65 (17); Anal. Calcd for C21H19N5O: C,
70.57; H, 5.36; N, 19.59. Found: C, 70.57; H, 5.38; N, 19.59.
5-Ethyl-3-oxo-2,6-di-p-tolyl-2,3-dihydropyridazine-4-carb-
onitrile (10). Compound (10) was obtained as buff crystals.
Yield (0.71 g, 20%), mp 201 ºC, ir (KBr) ν 2229, 1666 cm-1;
9-Amino-5,7-dimethyl-2,4-di-p-tolyl-2H-pyrrolo[3,4-g]-
phthalazine-1,6,8-trione (14). A solution of compound (12)
(3.61 g, 0.01mol), N-methylmaleimide (1.11 g, 0.01mol), in
dioxane (10 mL) and few drops of acetic acid was refluxed for 6
h. The solvent was evaporated then washed with EtOH. The
solid products, so formed, were collected by filtration and
crystallized from dioxane. Compound (14) was obtained as
bright yellow crystals. Yield (3.42 g, 78%), mp 265-267 ºC, ir
(KBr) ν 3305, 1749, 1691 cm-1; UV/Vis at λmax (CHCl3) = 470
1
UV/Vis at λmax (CHCl3) = 372 nm, H nmr (DMSO-d6): δ 1.01
(t, 3H, J = 7.5 Hz, CH3), 2.36 (s, 3H, [4-methylphenyl]-CH3),
2.37 (s, 3H, [4-methylphenyl]-CH3), 2.67 (q, 2H, J = 7.5 Hz,
CH2), 7.31 (d, 4H, J = 7.9 Hz, [4-methylphenyl]-H), 7.43 (d, 2H,
J = 7.8 Hz, [4-methylphenyl]-H), 7.49 (d, 2H, J = 8.2 Hz, [4-
methylphenyl]-H), 13C nmr (DMSO-d6): δ 156.9, 156.5, 147.9,
139.8, 139.2, 139.0, 132.3, 130.2, 130.0, 129.6, 126.1, 114.5,
114.0, 26.3 (CH2), 21.7 ([4-methylphenyl]-CH3), 21.5 ([4-
methylphenyl]-CH3), 13.6 (CH3). ms (EI) m/z = 329 (M+, 100),
182 (18), 106 (22), 91 (56), Anal. Calcd for C21H19N3O: C,
76.57; H, 5.81; N, 12.76. Found: C, 76.16; H, 5.83; N, 13.14.
General Procedure for the Reaction of Compounds 9b and
10 with Sulphur. A dried heavy-walled Pyrex tube containing a
small stir bar was charged with compounds (9b) or (10) (0.01
mol), elemental sulphur (0.32 g, 0.01 mol)) in dioxane (2 mL)
and few drops of piperidine were added. The tube containing the
reaction mixture was fitted with PCS cap and then it was
exposed to automated microwave irradiation at 190 ºC for 10
min. The build-up of pressure in the closed reaction vessel was
carefully monitored and was found to be typically in the range
170-180 psi. After the irradiation, the reaction tube was cooled
with high-pressure air through a built in system in the instrument
until the temperature had fallen below 50 °C. The crude product
was poured onto water, the solid product, so formed, was
collected by filtration and crystallized from EtOH.
1
nm, H nmr (DMSO-d6): δ 2.11 (s, 3H, CH3), 2.42 (s, 3H, [4-
methylphenyl]-CH3), 2.44 (s, 3H, [4-methylphenyl]-CH3), 3.17
(s, 3H, NCH3), 7.06 (brs, 1H, NH, D2O exchangeable), 7.26-7.30
(m, 6H, [4-methylphenyl]-H), 7.52 (d, 2H, J = 8.0 Hz, [4-
methylphenyl]-H), 9.09 (brs, 1H, NH, D2O exchangeable), ms
(EI) m/z= 438 (M+, 100), 291 (16), 91 (17), Anal. Calcd for
C26H22N4O3: C, 71.22; H, 5.06; N, 12.78. Found: C, 71.21; H,
5.06; N, 12.80.
General Procedure for The Preparation of Compounds
(17a,b). A dried heavy-walled Pyrex tube containing a small stir
bar was charged with each of maleimide, or N-methylmaleimide
(0.01 mol), compounds (11) (3.89 g, 0.01 mol), in dioxane (2
mL) and few drops of acetic acid were added. The tube
containing the reaction mixture was fitted with PCS cap and
then it was exposed to automated microwave irradiation at 170
ºC for 20 min. The build-up of pressure in the closed reaction
vessel was carefully monitored and was found to be typically in
the range 80-85 psi. After the irradiation, the reaction tube was
cooled with high-pressure air through an inbuilt system in the
instrument until the temperature had fallen below 50 ºC. The
solvent was evaporated then washed with ethanol. The solid
products, so formed, were collected by filtration and crystallized
from dioxane.
7-Amino-5-methyl-2-p-tolyl-4-p-tolylazo-2H-thieno[3,4-d]-
pyridazin-1-one (11). Compound (11) was obtained as wine red
crystals. Yield (3.43 g, 88%), mp 208 ºC, ir (KBr) ν 3322, 3278,
4,9-Diamino-5-methyl-2-p-tolyl-2H-pyrrolo[3,4-g]phthal-
azine-1,6,8-trione (17a). Compound (17a) was obtained as
orange crystals. Yield (3.04 g, 87%), mp 307-309 ºC, ir (KBr) ν
3442, 3310, 3210, 1752, 1705, 1645 cm-1; UV/Vis at λmax
1
1642 cm-1; UV/Vis at λmax (CHCl3) = 453 nm, H nmr (DMSO-
d6): δ 2.33 (s, 3H, CH3), 2.41 (s, 3H, [4-methylphenyl]-CH3),
2.45 (s, 3H, [4-methylphenyl]-CH3), 7.22 (d, 2H, J = 7.6 Hz, [4-
methylphenyl]-H), 7.37 (d, 2H, J = 7.7 Hz, [4-methylphenyl]-
H), 7.41 (d, 2H, J = 7.9 Hz, [4-methylphenyl]-H), 7.51 (s, 2H,
NH2, D2O exchangeable), 7.81 (d, 2H, J = 7.7 Hz, [4-
methylphenyl]-H), 13C nmr (DMSO-d6): δ 161.2, 159.5, 150.9,
150.4, 144.2, 139.1, 137.1, 131.0, 129.6, 126.7, 124.1, 122.5,
116.6, 105.0, 22.0 ([4-methylphenyl]-CH3), 21.5 ([4-
methylphenyl]-CH3), 15.2 (CH3). ms (EI) m/z= 389 (M+, 100),
270 (30), 106 (60), 91 (80); Anal. Calcd for C21H19N5OS: C,
1
(CHCl3) = 473 nm, H nmr (DMSO-d6): δ 2.35 (s, 3H, CH3),
2.93 (s, 3H, [4-methylphenyl]-CH3), 5.71 (s, 2H, NH2, D2O
exchangeable), 7.05 (brs, 1H, NH, D2O exchangeable), 7.25 (d,
2H, J = 8.0 Hz, [4-methylphenyl]-H), 7.47 (d, 2H, J = 8.0 Hz,
[4-methylphenyl]-H), 9.08 (brs, 1H, NH, D2O exchangeable),
11.33 (brs, 1H, NH, D2O exchangeable), 13C nmr (DMSO-d6): δ
170.7, 170.3, 160.1, 148.6, 147.2, 139.7, 137.6, 134.9, 132.9,
129.8, 126.5, 122.0, 118.7, 111.5, 21.7 (p-tolyl-CH3), 15.8
(CH3). ms (EI) m/z= 349 (M+, 100), 242 (40), 106 (22), Anal.

364
S. M. Al-Mousawi, M. A. El-Apasery, N. Al-Kandery, and M. H. Elnagdi
Vol 45
[2] Al-Shiekh, M. A.; Salah El-Din, A. M.; Hafez, E. A.;
Elnagdi, M. H. J. Heterocycl. Chem. 2004, 41, 647.
[3] Hunger, K. Industrial Dyes: Chemistry, Properties,
Applications, Wiley-VCH, 2003, p 34.
[4] Soliman, S. H.; Abdelhamid, I. A.; Elnagdi, M. H.
ARKIVOC, 2006, (XIII), 147.
[5] Bradbury, R. Thermal Printing in the Chemistry and
Calcd for C18H15N5O3: C, 61.89; H, 4.33; N, 20.05. Found: C,
61.86; H, 4.44; N, 20.30.
4,9-Diamino-5,7-dimethyl-2-p-tolyl-2H-pyrrolo[3,4-g]-
phthalazine-1,6,8-trione (17b). Compound (17b) was obtained
as orange crystals. Yield (3.06 g, 84%), mp 308-310 ºC, ir (KBr)
ν 3434, 3294, 3193, 1748, 1698, 1646 cm-1; UV/Vis at λmax
1
(CHCl3) = 470 nm, H nmr (CDCl3): δ 2.42 (s, 3H, CH3), 3.10
Technology of Printing and Imaging Systems, Academic
Professionals, London, 1996, pp 139-167.
&
(s, 3H, [4-methylphenyl]-CH3), 3.17 (s, 3H, NCH3), 4.59 (s, 2H,
NH2, D2O exchangeable), 7.04 (s, 1H, NH, D2O exchangeable),
7.29 (d, 2H, J = 7.9 Hz, [4-methylphenyl]-H), 7.48 (d, 2H, J =
7.8 Hz, [4-methylphenyl]-H), 9.35 (s, 1H, NH, D2O
exchangeable), 13C nmr (CDCl3): δ 169.3, 169.0, 160.1, 148.5,
146.9, 139.7, 137.6, 134.2, 132.8, 129.8, 126.5, 122.1, 118.9,
110.7, 24.6 (NCH3), 21.7 ([4-methylphenyl]-CH3), 16.0 (CH3).
ms (EI) m/z= 363 (M+, 100), 259 (56), 107 (15), Anal. Calcd for
C19H17N5O3: C, 62.80; H, 4.72; N, 19.27. Found: C, 62.79; H,
4.76; N, 19.13.
[6] Gregory, P. Dye Stuff in the Chemical Industry, Academic &
Professionals, London, 1994, pp 185-187.
[7] Elnagdi, M. H.; Ibraheim, N. S.; Abdelrazek, F. M.; Erian, A.
W. Liebigs Ann. Chem., 1988, 909.
[8] Al-Etaibi, A.; Al-Awadi, N.; Al-Omran, F.; Abdelkhalik, M.
M.; Elnagdi, M. H. J. Chem. Res., (M), 1999, 151.
[9] Elnagdi, M. H.; Abdelrazek, F. M.; Ibrahim, N. S.; Erian,
A. W. Tetrahedron, 1989, 45, 3597.
[10] Elnagdi, M. H.; Negm, A. M.; Sadek, K. U. Synlett, 1994,
27.
[11] Al-Awadi, H.; Al-Omran, F.; Elnagdi, M. H.; Infantes, L.;
Foces-Foces, C.; Iagerovic, N.; Elguero, J. Tetrahedron, 1995, 51,
12745.
[12] Al-Omran, F.; Abdelkhalik, M. M.; Al-Awadi, H.; Elnagdi,
M. H. Tetrahedron, 1996, 52, 11915.
[13] Al-Omran, F.; Al-Awadi, N.; Elassar, A.; El-Khair, A. J.
Chem. Res., (M). 2000, 237.
[14] Sopbue Fondjo, E.; Döpp, D. ARKIVOC, 2006, (XV), 37.
[15] Al-Saleh, B.; Abdelkhalik, M. M.; El-Apasery, M. A.;
Elnagdi, M. H. J. Chem. Res., 2005, 23.
[16] Al-Saleh, B.; El-Apasery, M. A. J. Heterocyclic Chem.,
2006, 43, 559.
[17] Al-Mousawi, S.; Elassar, A.; El-Apasery, M. A.
Phosphorus Sulfur Silicon, 2006, 181, 1755.
[18] The X-ray crystallographic structures of compounds 10 and
12 have been submitted to the Cambridge Crystallographic Data Center.
The CCDC # of compounds 10 and 12 is CCDC 616664.
[19] Nyiondi-Bonguen, E.; Sopbue Fondjo, E.; Tanee Fomum, Z.;
Döpp, D. J. Chem. Soc., Perkin Trans. 1 1994, 2191.
[20] Fieres, F. Organic Synthesis Collect. Vol II, John Wiley &
Sons, New York, NY, 1943, p 633.
5-Amino-4-oxo-3,7-diphenyl-1-phenylazo-3,4-dihydro-
phthalazine-6-carbonitrile (21). A solution of compound (9a)
(3.16 g, 0.01 mol) in pyridine (3 mL) was treated with
benzylidenemalononitrile (1.54 g, 0.01mol). The reaction
mixture was refluxed for 6 h, then poured onto water and
acidified with dilute hydrochloric acid. The solid product
obtained was crystallized from dioxane. Compound (21) was
obtained as brown crystals. Yield (3.10 g, 70%), mp 293-295 ºC,
ir (KBr) ν 3418, 3340, 2206, 1659 cm-1; UV/Vis at λmax (CHCl3)
= 394 nm, 1H nmr (CDCl3): δ 7.22-7.73 (m, 15H, phenyl-H and
NH2), 7.85 (d, 1H, J = 8 Hz, phenyl-H), 7.98- 8.02 (m, 2H,
phenyl-H). ms (EI) m/z= 442 (M+, 20), 403 (80), 361 (32), 312
(30), 119 (62), 93 (100), 77 (40), Anal. Calcd for C27H18N6O: C,
73.29; H, 4.10; N, 18.99. Found: C, 72.97; H, 4.65; N, 18.73.
Acknowledgement. The authors are grateful to University of
Kuwait, Research Administration for financial support through
project SC 02/02. Financial support of Mrs. Najat AL-Kandery
by College of Graduate Studies is highly appreciated.
Analytical facilities provided by SAF projects No. GS 01/01 &
GS 03/01 are greatly appreciated.
[21] Gibbson, M. S. The Introduction of Amino Group, John
Wiley & Sons, New York, NY, 1968, p 67.
[22] Rabjohn, N. Organic Synthesis Collect. Vol IV, John Wiley
& Sons, New York, NY, 1963, p 633.
[23] Yao, H. C. J. Org. Chem., 1964, 29, 2959.
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