A microwave assisted diazo coupling reaction: The synthesis of alkylazines and thienopyridazines

Article abstract of DOI:10.1080/10426500500536457

Heating diazoaminobenzene with active methylene compounds 1-3 in microwave oven in acetic acid, in the presence of hydrochloric acid, afforded the corresponding arylhydrazones 5-7. These reaction products were condensed with ethyl cyanoacetate in a domestic microwave oven after 1-2 minutes heating to yield the pyridazinones 8-12. Compounds 8c and 12 reacted with sulfur in basic DMF solution, in microwave oven using MORE technology to yield the thienopyridazinone 14 and 16 respectively. While 17 was produced when 8b was treated like wise with sulfur and DMF in the presence of piperidine. Compounds 16 coupled with aromatic diazonium salts to yield arylazo derivatives 21a-c. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500500536457

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A Microwave Assisted Diazo
Coupling Reaction: The
Synthesis of Alkylazines and
Thienopyridazines
Saleh Al-Mousawi a , Abdel-Zaher Elassar a & Morsy
Ahmed El-Apasery a
a Department of Chemistry , University of Kuwait ,
Safat, Kuwait
Published online: 01 Feb 2007.
To cite this article: Saleh Al-Mousawi , Abdel-Zaher Elassar & Morsy Ahmed El-Apasery
(2006) A Microwave Assisted Diazo Coupling Reaction: The Synthesis of Alkylazines and
Thienopyridazines, Phosphorus, Sulfur, and Silicon and the Related Elements, 181:8,
1755-1771, DOI: 10.1080/10426500500536457
To link to this article: http://dx.doi.org/10.1080/10426500500536457
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Phosphorus, Sulfur, and Silicon, 181:1755–1771, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500500536457
A Microwave Assisted Diazo Coupling Reaction:
The Synthesis of Alkylazines and Thienopyridazines
Saleh Al-Mousawi
Abdel-Zaher Elassar
Morsy Ahmed El-Apasery
Department of Chemistry, University of Kuwait, Safat, Kuwait
Heating diazoaminobenzene with active methylene compounds 1–3 in microwave
oven in acetic acid, in the presence of hydrochloric acid, afforded the corresponding
arylhydrazones 5–7. These reaction products were condensed with ethyl cyanoac-
etate in a domestic microwave oven after 1–2 minutes heating to yield the pyridazi-
nones 8–12. Compounds 8c and 12 reacted with sulfur in basic DMF solution, in
microwave oven using MORE technology to yield the thienopyridazinone 14 and
16 respectively. While 17 was produced when 8b was treated like wise with sul-
fur and DMF in the presence of piperidine. Compounds 16 coupled with aromatic
diazonium salts to yield arylazo derivatives 21a–c.
Keywords Aminothiophenes; coupling reactions; Gewald reactions; pyridazines
INTRODUCTION
Since 1986, when Gedye et al.1 and Giguere et al.2 published their
first articles on microwave-assisted synthesis in a household microwave
oven, there has been enormous interest in this research filed. Several
recent publications3−10 published in more than one thousand articles
have covered technical and synthetic achievements in this area. Almost
every reaction type has been conducted in a domestic microwave oven
where generally shorter reaction times and better yields were observed.
The utility of microwave organic reaction enhancement technology
developed by Bose et al.11 or the dye technologies developed by Varma12
Received September 14, 2005; accepted November 20, 2005.
The authors are grateful to the University of Kuwait, Research Administration, for
financial support through project SC 02/02. Analytical facilities provided by Science Anal-
ysis Facilities (SAF) are highly appreciated. The authors also express deep gratitude to
Dr. Balkis Al-Saleh for her valuable supervision, useful discussion, and help.
Address correspondence to Abdel-Zaher Elassar, University of Kuwait, Department
of Chemistry, Faculty of Science, P.O. Box 5969, Safat, 13060 Kuwait. E-mail: aelassar@
yahoo.com
1755

1756
S. Al-Mousawi et al.
has substantially added green value to this technology because it saves
waist and energy. The synthesis of azo dyes using microwave irradiation
has received considerable attention in recent years.13,14 Thus, treating
equimolar amounts of aromatic amine, sodium nitrite, potassium hy-
droxide, and 2-naphthol or 2-naphthylamine in the presence of a few
drops of water as an initiator with microwave irradiation was reported
to give an azo product.13 In addition, irradiation by the microwave of
nitroarenes in the presence of bismuth metal and potassium hydroxide
could be coupled to give azo dye.14 In this article, a one-pot diazo cou-
pling reaction under microwave irradiation by using diazoaminoben-
zene has been investigated. The obtained coupling product was used
as building blocks for the synthesis of polyfunctionally substituted het-
eroaromatics. Since these reactions are two basic steps in the synthesis
of our condensed aminothienopyridazines that have in the past been ex-
tensively utilized for the synthesis of phthalazenes,15−18 we decided to
develop a way to enable conducting both reactions in a microwave oven.
In addition, such heteroaromatic amines as potential intermediates for
the preparation of dyes for thermal diffusion printing was reported.19
RESULTS AND DISCUSSION
When 1a–e, 2a,b, and 3 (Scheme 1) were left at r.t. in acetic acid solution
in the presence of hydrochloric acid with an quimolecular amount of
diazoaminobenzene 4, no coupling occurred, while a rearrangement of
4 into p-aminoazobenzene was observed.
SCHEME 1
However, when the reaction mixture was heated in a microwave oven
for 150 s in glacial acetic acid and in the presence of hydrochloric acid,
arylazo derivatives 5–7 were formed in good yields (Scheme 2). The reac-
tion product was established based on elemental analysis and spectral
data. For example, the IR of compound 5a revealed the presence of the
1
NH and CN group at 3204 and 2223 cm−1, respectively. The H NMR
showed aromatic protons at 7.20–7.48 ppm and NH at 13.02 ppm. In
addition,13C NMR data agreed with the expected one. Thus, signals

Microwave-Assisted Diazo Coupling Reaction
1757
at 142.39, 130.84, 126.89, and 117.55 referred to the aromatic carbon
atoms, while signals at 110.97 and 85.54 ppm revealed the presence of
cyano and imine carbons. Moreover, MS (EI) showed m/z at 170 (M+).
SCHEME 2
The arylhydrazones 5b,d,e condensed with ethyl cyanoacetate in
presence of ammonium acetate and acetic acid on heating in a mi-
crowave oven for 60 s to yield pyridazinones 8a–c. It is of value to
report that only 5e condensed with ethyl cyanoacetate on heating in
AcOH-AcONH4 in 2 h. Under similar classical reflux conditions, 5b
failed earlier to condense, and 5d required utilizing to produce 8b
in the absence of an azotropic water separator. The amide 8d (X =
CONH2, R CH3) was the only product (Scheme 3). The reaction prod-
uct was believed to proceed through the condensation of active methy-
lene in ethyl cyanoacetate with the carbonyl group in 5b,d,e to give
an intermediate, which readily cyclized under the reaction condition
to give the pyridazinone derivatives 8a–c. The structure of 8a was
established based on 13C NMR, which showed the carbonyl group at

1758
S. Al-Mousawi et al.
156.88, in addition to the aromatic, pyridazine, and cyano carbons at
152.04, 140.74, 132.98, 130.96, 130.89, 130.30, 130.28, 129.66, 126.56,
124.02, 114.50, 114.45, and 114.00 ppm. Moreover, the mass spectrum
showed m/z of the molecular formula C18H10N4O at 298 (M+), which
agreed with the postulated structure. Similarly, compounds 8b,c were
established.
SCHEME 3
When 8b was heated under microwave irradiation for 120 s, a dimeric
compound was produced. This was assigned structure 9 rather than 10
based on 13C NMR, which revealed only two cyano carbons, 159.31,
158.59 (2CO), 158.21, 156.98, 152.27, 145.30, 141.83, 141.48, 141.02,
130.50, 130.06, 130.01, 129.77, 128.86, 127.13, 126.77, 102.28, 98.42
(aromatic and azine carbons), 115.62, 114.72 (2CN), and 20.40 ppm
(CH3). In addition,1H NMR showed a singlet at 2.64 ppm, which rep-
resented protons of the methyl group. Signals at 7.64–7.51 ppm repre-
sented 10 aromatic protons, a pyridinic proton at 7.75 ppm, and a broad
band at 8.51 ppm for the amino group (Scheme 4).
Compounds 6a and 7 were condensed with ethyl cyanoacetate,
ammonium acetate, and acetic acid in a microwave at 840 w for 60 s to
yield the pyridazinones 11 and 12, respectively (Scheme 5). Compound
11 was established based on mass spectrum, which indicated that the
reaction happened in a 1:2 ratio (6a:ethyl cyanoacetate), where m/z
equaled 359 (M+). 1H NMR showed the ester group at 1.04 ppm (triplet,
methyl) and 4.32 ppm (quartet, methylene) in addition to the other char-
acteristic protons. While compound 12 was considered as a reaction
1
product based on H NMR, which revealed the presence of benzotria-
zole protons at 7.89 ppm (d, 1H, J = 8 Hz, benzotriazolyl-H), 8.20 ppm
(d, 1H, J = 8 Hz, benzotriazol-H). In addition, other 6 aromatic protons
at 7.33–7.71 ppm.

Microwave-Assisted Diazo Coupling Reaction
1759
SCHEME 4
Alkyl groups attached at activated positions in azines were active
toward an electrophilic reagent in acidic and basic media. In a ba-
sic medium, the carbanion was stabilized by delocalizing its negative
charge on the heteroatom. The presence of the cyano group adjacent
to the alkyl group in such system was able to undergo Gewald syn-
thesis to give the thiophene ring, whereas the carbanion formed in a
basic medium and reacted with sulfur and cyclized to give the binu-
clear product. Thus, the target ring system, thienopyridazines 14 and
16, could be obtained when 8c or 12 reacted with sulfur in DMF in the
presence of piperidine in a microwave oven for 120 s and afforded the
thienopyridazinone 14 and 16. The formation of 14 and 16 was believed
to be obtained through the formation of the nonisolated intermediates
13 and 15 that readily cyclized under the reaction condition to give the
final isolated products 14 and 16 (Scheme 6). These products were char-
acterized by the presence of the elemental analysis of sulfur in 10.01%
and 8.19%, respectively.
Depicts all possible structures proposed for the reaction of 8b with
sulfur was indicated in Scheme 7. However, among these structures, 17
was assigned to be an isolated product on the basis of elemental analy-
sis and spectral data. For example, mass spectrum, which revealed the
formation of a compound 17 with the molecular formula C26H16N8O3S
and molar mass m/z = 502 (M+). In addition, the elemental analysis

1760
S. Al-Mousawi et al.
SCHEME 5
of sulfur was found to be 6.00%, which closed to the theoretical value
6.16%. Similar behavior had been reported in previous stadies.20 It was
reported that fused thiophenees added to dienophiles in a Diels-Alder
type [4 + 2] according to a suprafacial-suprafacial mode to yield prod-
ucts of addition followed by hydrogen sulfide elimination or thiepen
formation.20−22 When compound 14 underwent investigation as a diene
for cycloaddition with the 3-diethylaminoacrylonitrile as a dienophile,
in acedic medium the unexpected product 19 was obtained. Com-
pound 19 was established based on mass spectrum, which indicated the
formation of a dimer with the molecular formula C28H20N6O5S2 with
the molar mass m/z = 584 (M+). In addition, the elemental analysis of
sulfur and nitrogen were 10.60% and 14.62%, respectively (Scheme 7).
The Reactivity of aminothienopyridazine toward nitrogen elec-
trophiles, e.g., benzenediazonium chloride, was investigated. The cou-
pling took place at the amino group rather than thienyl-H; this may
be attributed to the steric effect due to the presence of bulky group,
benzotriazolyl group, at position-4. A similar coupling product has been
obtained when benzenediazonium chloride coupled with aniline in the

Microwave-Assisted Diazo Coupling Reaction
1761
SCHEME 6

1762
S. Al-Mousawi et al.
SCHEME 7
case of decreasing mineral acids. A rearrangement was expected for
these compounds in an acidic medium at 40◦C. Thus, compound 16
reacted with benzenediazonium salt in an acidic medium to afford
the diazo compound 21. The obtained compound 21 is believed to be
formed through the nonisolated intermediate 20, which underwent re-
arrangement to give the final isolated product 21a–c. Structures 21a–c
1
were supported by H NMR spectra that displayed a singlet at δH ca.
7.4 ppm, assigning for thienyl-H with downfield aromatic protons and
NH2 signals (Scheme 8).

Microwave-Assisted Diazo Coupling Reaction
1763
SCHEME 8
CONCLUSION
1. Diazo coupling has been obtained in a good yield, short time, and
in one step, when active methylene compounds were treated with
diazoaminobenzene under microwave irradiation.
2. The target thienopyridazines could be obtained when diazo com-
pounds were treated with ethyl cyanoacetate and then with sulfur
in a microwave oven.
3. The reactivity of thienopyridazines toward dienophiles and azonium
salt had been studied. Thus, developing a way to enable conducting
all reaction steps in a microwave oven had been successful.
EXPERIMENTAL
All melting points are uncorrected. IR spectra were recorded in KBr
1
disks using a Perkin-Elmer System 2000 FTIR spectrophotometer. H
and 13C NMR spectra were recorded on a Bruker DPX 400, 400MHz
superconducting NMR spectrometer in CDCl3 or DMSO-d6 as a solvent

1764
S. Al-Mousawi et al.
and TMS as an internal standard; chemical shifts are reported in units
(ppm). Mass spectra were measured on a VG Autospec-Q (high res-
olution, high performance, trisector GC/MS/MS). Microanalyses were
performed on a LECO CHNS-932 elemental analyzer. Microwave ex-
periments were conducted in a microwave oven DAEWOO, edition II
(KOR-8667).
The General Procedure for the Preparation of Compounds 5–7
A mixture of compounds 1–3 (0.01 mol), diazoaminobenzene 4 (0.01
mol), and glacial acetic acid (20 mL) in the presence of hydrochloric
acid (2 mL) was heated in a microwave oven at 560 W for 150 s. The
mixture was left to cool at r.t. and then poured onto ice water containing
sodium carbonate (2 g). The solid product, so formed, was collected by
filtration and crystallized from the proper solvent.
(Phenylhydrazono)malononitrile (5a)
Yellow crystals (70%); m.p. 157–159◦C; IR (νmax: 3204 (NH), 2223 cm−1
(CN); 1H NMR: (DMSO-d6) δH 7.20–7.48 (m, 5H, Ar-H), 13.02 ppm (br,
1H, NH). 13C NMR: (DMSO-d6) δC: 142.39, 130.84, 126.89, 117.55 (aro-
matic carbon atoms), 110.97 (CN), 85.54 ppm (imine carbon). MS (EI):
m/z = 170 (M+). Anal. calcd. for C9H6N4: C, 63.52; H, 3.55; N, 32.92.
Found: C, 63.89; H, 3.84; N, 31.37.
3-Oxo-3-phenyl-2-(phenylhydrazono)propionitrile (5b)
Yellow crystals (90%), m.p. 138–140◦C; IR (νmax: 3221 (NH); 2217 (CN),
1652 cm−1 (CO); 1H NMR (CDCl3) (δH: 7.21–8.04 (m, 10H, Arom-
H), 9.41 ppm (br, 1H, NH). 13C NMR: (DMSO-d6) (δC: 188.53 (CO),
143.06, 137.40, 133.34, 130.84, 130.54, 129.11, 126.10, 117.38, 114.16,
112.52 ppm (aromatic, imine, and cyano carbons). MS (EI) m/z = 249
(M+). Anal. calcd. for C15H11N3O: C, 72.28; H, 4.45; N, 16.86. Found: C,
71.97; H, 4.49; N, 16.91.
2-Cyano-2-(phenylhydrazono)ethanethioamide (5c)
Orange crystals (68%), m.p. 215◦C; IR (νmax: 3234 and 3140 (NH2), 3061
(NH), 2209 cm−1 (CN); 1H NMR (DMSO-d6) δH: 7.10–7.74 (m, 5H, Arom-
H), 9.34, 9.68 (s, 2H, NH2); 11.57 ppm (s, 1H, NH). 13C NMR: (DMSO-
d6) (δC: 188.94 (CS), 143.11; 130.44, 125.36, 117.50, 113.67; 112.37 ppm
(imine, aromatic, and cyano carbons). MS (EI) m/z = 204 (M+). Anal.

Microwave-Assisted Diazo Coupling Reaction
1765
calcd. for C9H8N4S: C, 52.93; H, 3.95; N, 27.43; S, 15.70. Found: C, 53.39;
H, 4.05; N, 27.39; S, 16.04.
3-Imino-2-(phenylhydrazono)butanenitrile (5d)
Yellow crystals (86%); m.p. 174–176◦C; IR (νmax: 3227 (NH); 2213 (CN),
1
1683 cm−1 (CO); H NMR (DMSO-d6) δH: 2.41 (s, 3H, CH3); 7.16–7.56
(m, 5H, Arom-H), 12.28 ppm (s, 1H, NH). 13C NMR: (DMSO-d6) (δC:
193.76 (CO), 142.99, 130.51, 126.04, 117.26, 114.60, 112.02 (imine, aro-
matic, and cyano carbons), 25.63 ppm (CH3). MS (EI) m/z = 187 (M+).
Anal. calcd. for C10H9N3O: C, 64.16; H, 4.85; N, 22.45. Found: C, 64.16;
H, 4.78; N, 22.27.
Ethyl 3-Oxo-2-(phenylhydrazono)butanoate (5e)
Yellow crystals (78%); m.p. 77◦C; IR (νmax: 3063 (NH), 1710 cm−1 (CO);
1H NMR (DMSO-d6) δH: 11.68 (br, 1H, NH), 7.44–7.06 (m, 5H, Arom-H),
4.30 (q, 2H, CH2), 2.47 (s, 3H, CH3), 1.27 ppm (t, 3H, CH3). 13C NMR:
(DMSO-d6) δC: 194.60 (acetyl carbonyl carbon), 163.64 (ester carbonyl
carbon), 143.47, 131.80, 130.45, 126.34, 117.17 (imine and aromatic
carbons), 61.45 (CH2), 26.48, 14.92 ppm (2CH3). MS (EI) m/z = 234
(M+). Anal. calcd. for C12H14N2O3: C, 61.53; H, 6.02; N, 11.96. Found:
C, 61.52; H, 6.01; N, 12.11.
2-(Phenylhydrazono)cyclohexane-1,3-dione (6a)
Orange crystals (83%), m.p. 144◦C; IR (νmax: 3055 (NH), 1676
(CO), 1628 cm−1 (CO); 1H NMR (DMSO-d6); δH: 1.94–2.00 (m, 2H,
cyclohexanyl-H); 2.50–2.67 (m, 4H, cyclohexanyl-H), 7.20–7.81 (m, 5H,
Arom-H), 14.84 ppm (s, 1H, NH). 13C NMR: (DMSO-d6) δC: 198.63,
194.21 (2CO), 142.50, 132.31, 130.71, 127.41, 118.34 (imine and aro-
matic carbons), 39.56, 39.88, 18.90 ppm (cyclohexyl-CH2). MS (EI) m/z =
216 (M+). Anal. calcd. for C12H12N2O2: C, 66.65; H, 5.59; N, 12.96.
Found: C, 66.46; H, 5.42; N, 13.00.
5,5-Dimethyl-2-(phenylhydrazono)cyclohexane-1,3-dione (6b)
Brown crystals (89%), m.p. 149◦C; IR νmax: 3052 (NH), 1673 (CO),
1632 cm−1 (CO); 1H NMR (DMSO-d6); δH: 1.03 (s, 6H, 2CH3); 2.50–2.63
(m, 4H, cyclohexanyl-H); 7.24–7.61 (m, 5H, Arom-H), 14.88 ppm (s, 1H,
NH). 13C NMR: (DMSO-d6) δC: 197.68, 193.53 (2CO), 142.30, 130.93,
130.54, 127.31, 117.94 (aromatic and imine carbons), 52.77 (cyclohexyl-
CH2), 39.71 (cyclohexyl-t-carbon), 31.14, 28.83 ppm (2 CH3). MS (EI)

1766
S. Al-Mousawi et al.
m/z = 244 (M+). Anal. calcd. for C14H16N2O2: C, 68.83; H, 6.60; N, 11.47.
Found: C, 68.84; H, 6.49; N, 11.67.
1-(1H-1,2,3-benzotriazol-1-yl)-1-[(4-methylphenyl)hydrazono]
Acetone (7)23
Brown crystals (86%), m.p. 186◦C; IR νmax: 3186 (NH), 1671 cm−1 (CO).
1H NMR (DMSO-d6); δH: 2.26 (s, 3H, CH3), 2.63 (s, 3H, COCH3), 7.10–
7.53 (m, 6H, Arom-H), 7.89 (d, 1H, J = 8 Hz, benzotriazolyl-H), 8.12 (d,
1H, J = 8Hz, benzotriazolyl-H), 10.96 ppm (br, 1H, NH). MS (EI) m/z =
293 (M+). Anal. calcd. for C16H15N5O: C, 65.52; H, 5.15; N, 23.88. Found:
C, 65.67; H, 5.15; N, 23.86.
The General Procedure for the Preparation of Compounds
8a–c, 9, 11, and 12
A mixture of 5b or 5d,e, 6a, or 7 (0.01 mol); ethyl cyanoacetate (1.13 g,
0.01 mol); ammonium acetate (2 g), and acetic acid (0.6 mol) was heated
in a microwave at 840 w for 60 s (120 s needed for compound 9) and then
left to cool and triturated with ethanol. The solid product, so formed,
was collected by filtration and crystallized from dioxane.
6-Oxo-1,4-diphenyl-1,6-dihydropyridazine-3,5-
dicarbonitrile (8a)
Orange crystals (83%), m.p. 258–259◦C; IR νmax: 2245 (CN), 1690 cm−1
(CO); 1H NMR (DMSO-d6); δH: 7.59–7.75 ppm (m, 10H, Arom-H).
13C NMR: (DMSO-d6) δC: 156.88 (CO), 152.04, 140.74, 132.98, 130.96,
130.89, 130.30, 130.28, 129.66, 126.56, 124.02, 114.50, 114.45, 114.00
ppm (aromatic, pyridazine, and cyano carbons). MS:(EI) m/z = 298 (M+).
Anal. calcd. for C18H10N4O: C, 72.48; H, 3.38; N, 18.78. Found: C, 71.98;
H, 3.71; N, 18.73.
4-Methyl-6-oxo-1-phenyl-1,6-dihydropyridazine-
3,5-dicarbonitrile (8b)
Brown crystals (81%), m.p. 182–184◦C; IR νmax: 2238 (CN), 1685 cm−1
(CO); 1H NMR (DMSO-d6); δH: 2.60 (s, 3H, CH3), 7.55–7.57 ppm (m, 5H,
Ar-H). 13C NMR: (DMSO-d6) δC: 156.46 (CO), 152.81, 140.66, 130.81,
129.77, 127.12, 126.77, 125.28, 114.64, 113.63 (aromatic, pyridazine,
and cyano carbons), 19.46 ppm (CH3). MS: (EI) m/z = 236 (M+). Anal.

Microwave-Assisted Diazo Coupling Reaction
1767
calcd. for C13H8N4O: C, 66.10; H, 3.41; N, 23.72. Found: C, 66.11; H,
3.62; N, 23.71.
Ethyl 5-Cyano-4-methyl-6-oxo-1-phenyl-
1,6-dihydropyridazine-3-carboxylate (8c)
Green crystals (84%), m.p. 168–170◦C; IR νmax: 2234 (CN), 1719 (CO
ester), 1676 cm−1 (ring CO). 1H NMR (DMSO-d6); δH 1.30 (t, 3H, CH3);
2.64 (s, 3H, CH3); 4.30 (q, 2H, CH2); 7.20–7.57 ppm (m, 5H, Arom-H).
13C NMR: (DMSO-d6) δC: 162.82, 162.79 (2CO), 160.53, 157.02, 123.12
(pyridazine carbons), 141.17, 136.51, 130.23, 126.81 (aromatic carbons),
114.43 (CN), 62.33 (CH2), 14.95, 14.90 ppm (2CH3). MS (EI): m/z = 283
(M+). Anal. calcd. for C15H13N3O3: C, 63.60; H, 4.63; N, 14.83. Found:
C, 63.45; H, 4.63; N, 14.97.
5-Amino-7-(6-cyano-2-phenyl-5-methyl-3-oxo-2,3-
dihydropyridazin-4-yl)-4-oxo-3-phenyl-3,4-
dihydropyrido[3,4-d]pyridazine-1-carbonitrile (9)
Dark brown crystals (85%), m.p. >300; IR νmax: 3282 and 3162 (NH2),
1
2217 (CN), 1652 and 1632 cm−1 (2CO). H NMR (DMSO-d6); δH 2.64
(s, 3H, CH3); 7.64–7.51(m, 10H, Arom-H), 7.75 (s, 1H, pyridine-H),
8.51 ppm (br, 2H, NH2). 13C NMR (DMSO-d6); δC 159.31, 158.59 (2CO),
158.21, 156.98, 152.27, 145.30, 141.83, 141.48, 141.02, 130.50, 130.06,
130.01, 129.77, 128.86, 127.13, 126.77, 102.28, 98.42 (aromatic and
azine carbons), 115.62, 114.72 (2CN), 20.40 ppm (CH3). MS (EI): m/z =
472 (M+). Anal. calcd. for C26H16N8O2: C, 66.10; H, 3.41; N, 23.72.
Found: C, 65.62; H, 3.66; N, 23.04.
Ethyl Cyano(4-cyano-3-imino-2-phenyl-2,3-5,6-
tetrahydrocinnolin-8-yl)acetate (11)
Dark green crystals (79%), m.p. 206–208◦C; IR νmax: 3185 (NH), 2212
(CN), 1632 cm−1 (CO); 1H NMR (DMSO-d6) δH 1.04 (t, 3H, CH3); 2.50–
3.45 (m, 5H, cyclohexenyl and CH); 4.32 (q, 2H, CH2); 6.51 (t, 1H, CH);
6.69–7.81 ppm (m, 6H, Arom-H and NH). MS (EI): m/z = 359 (M+). Anal.
calcd. for C20H17N5O2: C, 66.84; H, 4.77; N, 19.49. Found: C, 66.99; H,
4.53; N, 19.74.

1768
S. Al-Mousawi et al.
6-(1H-1,2,3-benzotraizol-1-yl)-5-methyl-2-(4-methylphenyl)-3-
oxo-2,3-dihydropyridazine-4-carbonitrile (12)
Green crystals (91%), m.p. 210◦C; IR νmax: 2229 (CN), 1673 cm−1 (CO);
1H NMR (DMSO-d6); δH 2.35 (s, 3H, CH3); 2.51 (s, 3H, CH3); 7.33–7.71
(m, 6H, Arom-H); 7.89 (d, 1H, J = 8 Hz, benzotriazolyl-H), 8.20 ppm (d,
1H, J = 8 Hz, benzotriazol-H). 13C NMR (DMSO-d6) δC: 157.00 (CO),
150.07, 145.66, 140.02, 139.00, 138.54, 133.78, 130.58, 130.46, 126.46,
126.34, 120.70, 117.26, 114.39, 112.80 (aromatic, pyridazine, and cyano
carbons), 21.78, 18.89 ppm (2 CH3). MS (EI): m/z = 342 (M+). Anal.
calcd. for C19H14N6O: C, 66.66; H, 4.12; N, 24.55. Found: C, 66.57; H,
4.17; N, 24.26.
The General Procedure for the Preparation of Compounds 14,
16, and 17
A solution of compounds 8b, 8c, or 12 (0.01 mol) in dimethyl formamide
(5 mL) was treated with sulphur (0.01 mol) and piperidine (0.2 mol).
The reaction mixture was heated in a microwave at 840 W for 120 s and
then poured onto water. The solid product, so formed, was collected by
filtration and crystallized from dioxane/ethanol.
Ethyl 5-Amino-4-oxo-3-phenyl-3,4-dihydrothieno[3,4-
d]pyridazine-1-carboxylate (14)
Green crystals (80%), m.p. 191◦C, IR νmax: 3301 and 3148 (NH2), 1701
1
(CO ester), 1643 cm−1 (ring CO); H NMR (DMSO-d6); δH 1.45 (t, 3H,
J = 8 Hz, CH3), 4.42 (q, 2H, J = 8 Hz, CH2); 7.11(s, 1H, thienyl-H). 7.37–
7.52 (m, 5H, Arom-H). 7.64(s, 2H, NH2). MS (EI): m/z = 315 (M+). Anal.
calcd. for C15H13N3O3S: C, 57.13; H, 4.16; N, 13.33; S, 10.17. Found: C,
57.16; H, 4.29; N, 13.31; S, 10.01.
7-Amino-4-(1H-1,2,3-benzotriazol-1-yl)-2-(4-
methylphenyl)thieno[3,4-d]pyridazin-1(2H)-one (16)
Green crystals (88%), m.p. 220◦C, IR νmax: 3277 and 3149 (NH2),
1641 cm−1 (CO). 1H NMR (DMSO-d6) δH 2.38 (s, 3H, CH3), 7.31 (d, 2H,
J = 8 Hz, Arom-H), 7.37(s, 1H, thienyl-H). 7.53–7.57 (m, 3H, Arom-H).
7.67 (t, 1H, J = 8 Hz, benzotriazolyl-H), 7.77 (s, 2H, NH2), 8.12 (d, 1H,
J = 8 Hz, benzotriazolyl-H), 8.22 (d, 1H, J = 8 Hz, benzotriazolyl-H),
13C NMR (DMSO-d6) δC: 164.52 (CO), 158.93, 145.95, 139.22, 137.50,
136.62, 131.97, 130.44, 130.10, 126.67, 126.63, 123.60, 120.68, 114.63,
105.85, 105.65 (aromatic and thienopyridazine carbons), 21.71 ppm

Microwave-Assisted Diazo Coupling Reaction
1769
(CH3). MS (EI): m/z = 374 (M+). Anal. calcd. for C19H14N6OS: C, 60.95;
H, 3.77; N, 22.45; S, 8.54. Found: C, 61.26; H, 3.82; N, 22.31; S, 8.19.
{Di-4-[(3,5-dicyano-1-phenylpyridazine-6-
one)]methylsulphide}monohydrate (17)
Dark brown crystals (75%), m.p. >300◦C; IR νmax: 2213 (CN), 1650 cm−1
(CO); 1H NMR (DMSO-d6) δH 2.73 (s, 2H, CH2); 2.89 (s, 2H, CH2); 7.08–
7.96 (m, 10H, Ar-H). 13C NMR (DMSO-d6) δC: 163.44 (CO), 159.71,
158.73, 140.53, 130.38, 129.53, 127.67, 126.97, 115.92, 106.95 (aro-
matic, pyridazine, and cyano carbons), 31.80 ppm (CH2). MS (EI): m/z =
502 (M+). Anal. calcd. for C26H16N8O3S: C, 59.99; H, 3.10; N, 21.53; S,
6.16. Found: C, 59.99; H, 3.46; N, 21.17; S, 6.00.
Ethyl 5-[(5-Amino-4-oxo-3-phenyl-3,4-dihydrothieno[3,4-
d]pyridazine-1-carbonyl)amino]-4-oxo-3-phenyl-3,4-
dihydrothieno[3,4-d]pyridazine-1-carboxylate (19)
A
mixture of compound 14 (3.15 g, 10 mmol) and 3-
diethylaminoacrylonitrile (1.24 g, 10 mmol) in a mixture of acetic
acid (10 mL) and dioxane (20 mL) was refluxed for 10 h and then
allowed to cool to r.t. The solvent was removed, and the residue cooled
to deposit a solid, which was crystallized from DMF.
Buff crystals (65%), m.p. >300◦C; IR νmax: 3424, 3312 (NH2) and
3168 (NH), 1726 (CO ester), 1679 and 1659 cm−1 (ring 2CO); 1H NMR
(DMSO-d6); δH 1.33 (t, 3H, J = 8 Hz, CH3), 4.36 (q, 2H, J = 8 Hz, CH2);
6.19 (s, 2H, thienyl-H). 7.21–7.48 (m, 10H, Arom-H). 8.02 (s, 2H, NH2,
D2O exchangeable), 12.22 (s, 1H, NH2, D2O exchangeable). MS (EI):
m/z = 584 (M+). Anal. calcd. for C28H20N6O5S2. C, 57.52; H, 3.45; N,
14.38; S, 10.97. Found: C, 57.52; H, 3.75; N, 14.62; S, 10.60.
The Reaction of Compound 16 with Aromatic Diazonium Salts
A solution of aryldiazonium chloride (prepared from the corresponding
aromatic amine [0.01 mol] and the appropriate quantities of both hy-
drochloric acid and sodium nitrite) (10 mmol) at 0◦C was added to a so-
lution of 16 (10 mmol) in acetic acid (50 mL) containing sodium acetate
(0.60 g). The reaction mixture was stirred at r.t. for 1 h, and the solid
product was collected by filtration and crystallized from DMF/ethanol
(3:1).

1770
S. Al-Mousawi et al.
7-(4ꢀ-Aminophenylazo)-4-[benzotriazol-1-yl]-2-P-tolyl-2H-
thieno[3,4-d] pyridazin-1-one (21a)
Light red crystals (75%), m.p. > 300◦C; IR: (max/cm−1 3326 and 3215
(NH2), 1655 (CO); 1H NMR (DMSO-d6): δH 2.38 (s, 3H, CH3), 6.49 (d,
2H, J = 8.7 Hz, 4-tolyl-H), 7.16 (d, 2H, J = 8.7 Hz, 4-tolyl-H), 7.30–7.32
(m, 2H, benzotriazolyl-H), 7.38 (s, 1H, thienyl-H), 7.49–7.60 (m, 4H,
phenyl-H), 7.76 (br, 2H, NH2, D2O exchangeable), 7.90 (d, 1H, J = 8 Hz,
benzotriazolyl-H). 8.28 (d, 1H, J = 8 Hz, benzotriazolyl-H). Ms: m/z 478
[M+]. C25H18N8OS: C, 62.74; H, 3.79; N, 23.41; S, 6.70. Found: C, 62.63;
H, 3.79; N, 23.18; S, 6.86.
7-(4ꢀ-Amino-2ꢀ-chlorophenylazo)-4-[benzotriazol-1-yl]-2-P-
tolyl-2H-thieno[3,4-d]pyridazin-1-one (21b)
Red crystals (76%), m.p. >300◦C; IR: νmax cm−1 3325 and 3220 (NH2),
1
1655 (CO); H NMR (DMSO-d6): δH = 2.38 (s, 2H, CH3), 6.43 (d, 2H,
J = 8.8 Hz, 4-tolyl-H), 7.20 (d, 2H, J = 8.8 Hz, 4-tolyl-H), 7.30–7.32
(m, 2H, benzotriazolyl-H), 7.37 (s, 1H, thienyl-H), 7.54 (d, 2H, J =
8.6 Hz, 4-chlorophenyl-H), 7.60 (d, 2H, J = 8.6 Hz, 4-chlorophenyl-
H), 7.76 (br, 2H, NH2, D2O exchangeable), 7.89 (d, 1H, J = 8 Hz,
benzotriazolyl-H), 8.31 (d, 1H, J = 8 Hz, benzotriazolyl-H). Ms: m/z
512 [M+]. C25H17N8OSCl: C, 58.53; H, 3.34; N, 21.84; S, 6.25. Found: C,
59.10; H, 3.49; N, 21.89; S, 6.32.
7-(4ꢀ-Amino-2ꢀ-nitrophenylazo)-4-[benzotriazol-1-yl]-2-P-tolyl-
2H-thieno[3,4-d]pyridazin-1-one (21c)
Light red crystals (78%), m.p. >300◦C; IR: νmax/cm−1 3323 and 3218
1
(NH2), 1666 (CO); H NMR (DMSO-d6): δH = 2.37 (s, 3H, CH3), 6.53
(d, 2H, J = 8.8 Hz, 4-tolyl-H), 7.33 (d, 2H, J = 8.8 Hz, 4-tolyl-H), 7.36
(s, 1H, thienyl-H), 7.55–7.62 (m, 5H, benzotriazolyl-H and arom-H),
7.90 (d, 1H, J = 8 Hz, benzotriazolyl-H). 7.96 (br, 2H, NH2, D2O ex-
changeable), 8.38 (d, 1H, J = 8 Hz, benzotriazolyl-H). Ms: m/z 523 [M+].
C25H17N9O3S: C, 57.35; H, 3.27; N, 24.07; S, 6.12. Found: C, 57.33; H,
3.36; N, 23.79; S, 5.88.
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Microwave-Assisted Diazo Coupling Reaction
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