Green chemistry: A facile synthesis of polyfunctionally substituted thieno[3,4-c]pyridinones and thieno[3,4-d]pyridazinones under neat reaction conditions

Article abstract of DOI:10.1016/j.ultsonch.2009.12.008

A facile, solvent free, ecofriendly approach for the synthesis of pyridine-2,6-diones 4a-d, pyridazinone derivatives 8a-c and thienoazines 6 and 9 is herein described employing neat reaction conditions under both microwave and ultrasound irradiations. This solventless methodology is environmentally benign as it completely eliminates the use of solvent from the reaction procedure.

Full text of DOI:10.1016/j.ultsonch.2009.12.008

Ultrasonics Sonochemistry 17 (2010) 909–915
Contents lists available at ScienceDirect
Ultrasonics Sonochemistry
journal homepage: www.elsevier.com/locate/ultsonch
Green chemistry: A facile synthesis of polyfunctionally substituted
thieno[3,4-c]pyridinones and thieno[3,4-d]pyridazinones under
neat reaction conditions
a
a
b
Khadijah M. Al-Zaydi a, , Rita M. Borik , Ramadan A. Mekheimer , Mohamed H. Elnagdi
*
a Department of Chemistry, Girls’ College of Education, King Abduls-Aziz University, Jeddah, P.O. Box 50918, Jeddah 21533, Saudi Arabia
b Department of Chemistry, Faculty of Science, University of Kuwait, P.O. Box 5969, Safe 13060, Kuwait
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 30 October 2009
Received in revised form 4 December 2009
Accepted 4 December 2009
Available online 11 December 2009
A facile, solvent free, ecofriendly approach for the synthesis of pyridine-2,6-diones 4a–d, pyridazinone
derivatives 8a–c and thienoazines 6 and 9 is herein described employing neat reaction conditions under
both microwave and ultrasound irradiations. This solventless methodology is environmentally benign as
it completely eliminates the use of solvent from the reaction procedure.
Ó 2009 Elsevier B.V. All rights reserved.
Keywords:
Green chemistry
Microwave and ultrasound irradiations
Thienoazines
X-ray crystal structure determination
1. Introduction
and tetrahydropyridazine- and hexahydropyridazine-6-carboxylic
acid structural element containing peptides, exhibiting antibiotic,
Industrial chemistry in the new millennium is widely adopting
the concept of ‘‘Green Chemistry” [1] to meet the fundamental sci-
entific challenges of protecting the human health and environment
while maintaining commercial viability. One of the advances in
this area where substantial progress has been made is the micro-
wave assisted [2–4]. But this technique does not meet the eco-
friendly goal of clean synthesis as an appreciable amount of
solvent is required for the adsorption of reactants and elution of
products. The ‘‘neat reaction” technique is an alternative solvent
free approach in which the reaction is carried out in the absence
of solvent. Further coupling of this solventless synthesis with
microwaves and ultrasound has the associated benefits of shorter
reaction time, uniform heating and better yields in comparison to
conventional heating.
The importance of pyridines and fused pyridines as calcium
antagonists [5] and hypertensives [6] are well known. Moreover,
pyridazines belong among the most significant heterocyclic rings,
which are frequently employed for the preparation of a variety of
important products [7]. Pyridazine derivatives have only recently
been discovered among the natural products, such as pyridazinomy-
cin, antifungal antibiotic isolated from Streptomyces violacoeniger,
antitumor, and collagenase inhibition activity [7]. On the other
hand, a variety of synthetic pyridazine derivatives found use in agro-
chemical, pharmaceutical, and other applications [7–9]. Keeping in
view the biological importance of the above mentioned heterocyclic
compounds and in continuation to our endeavor towards environ-
mentally benign synthesis [10–16], we report herein the synthesis
of alkyl azinylcarbonitriles 4 and 8 as a good precursors to polyfunc-
tionally substituted thienoazines, under neat reaction conditions,
utilizing both microwave irradiation and ultrasound as ecofriendly
energy sources.
2. Results and discussion
Our initial strategy aimed to synthesize the pyridine-3-carbo-
nitriles 4 and convert them to the corresponding 5-arylhydrazono-
pyridine-3-carbonitriles 5, which assumed to be very important
synthon for the synthesis of the desired polyfunctionally substi-
tuted thieno-[3,4-c]pyridinones. Cyanoacetamides 2a–d have been
prepared in our laboratory via treatment of ethyl cyanoacetate
with primary aliphatic amines 3a–d either at room temperature
for long time or via irradiation with microwave (MW) for
1–4 min at 100 W or with ultrasound (US) for 2–10 min at 40 °C.
Reacting ethyl 3-oxohexanoate (1) with cyanoacetamides 2a–d
also either via long reflux of neat reagents or by short time micro-
wave or by US for 5–7 h at 40 °C furnished the intermediate
* Corresponding author. Tel.: +966 26914554; fax: +966 6914553.
E-mail
addresses:
Alzaydi_kh@yahoo.com,
Alzaydi_kh@hotmail.com
(K.M. Al-Zaydi).
1350-4177/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.ultsonch.2009.12.008

910
K.M. Al-Zaydi et al. / Ultrasonics Sonochemistry 17 (2010) 909–915
Fig. 1. X-ray crystal structure of 5 h.
C
N
3H7
Fig. 2. X-ray crystal structure of 6c.
NC
CONHR
CN
O
O
O
2a-d
C3H7
OEt
C
N
3
H
7
1
CO2Et
CN
O
O
O
RNH2
3a-d
or
R
NC
EtO2C
CO2Et
CN
4a-d
C
3
H7
OEt
N
AcONH4 / AcOH
N
O
ArN2Cl
NH
Ar
Ar
7a-c
8a-c
Et
S
C3H7
elemental
sulphur
Ar
N
NH2
elemental
Ar
CN
O
N
in case of
N
sulphur
N
H
ArN2Cl
H
8a,b
,
Δ
MW, US
Δ
MW, US
O
N
O
O
N
R
6a-h
1
R
5a-h
Et
S
R
Ar
H2N
CO 2Et
2,3,4
5,6
7,8,9
Ar
C6H4-CO2Me-o
R
a
b
c
d
butyl
a
b
c
d
e
f
butyl
hexyl
C6H4-CO2Me- o
C6H4-CO2Me-o
C6H4-CO2Me-o
C6H4-CO2Me-o
C6H4-Cl-p
a
b
c
N
hexyl
C6H4-NO2-p
C6H4-Me-p
O
N
cyclohexyl
benzyl
cyclohexyl
benzyl
Ar
9a,b
butyl
Scheme 2.
hexyl
C6H4-Cl-p
g
h
cyclohexyl
benzyl
C6H4-Cl-p
interesting polyfunctionally substituted thieno[3,4-c]pyridinones,
with expected significant biological activity. Thus, the reaction of
aryl hydrazones 5a–g with elemental sulphur either by heating
with microwave or by US and conventional heating gave the corre-
sponding aminothienopyridinones 6a–g. The structure of com-
pounds 6a–g was established and confirmed for the reaction
products on the basis of their elemental analyses and spectral data
(MS, IR, 1H and 13C NMR) (see Section 4). Moreover, the structure of
compounds 6a–g could be unequivocally established by single
crystal X-ray diffraction of compound 6c [18] (Fig. 2). Single crystal
X-ray diffraction of compound 6c adds a sharp evidence for the
proposed structure (Scheme 1).
As the synthesis of fused heterocyclic ring systems containing
the azine moiety is the main target of this program, we therefore
considered the possibility that this design strategy could be ex-
tended to the synthesis of new thienoazines ring systems that
incorporate a thiophene nucleus in addition to pyridazine moiety,
utilizing compound 1 as starting material. Thus, coupling com-
pound 1 with aromatic diazonium salts gave the corresponding
aryl hydrazones 7a–c, in excellent yields. When aryl hydrazones
C6H4-Cl-p
Scheme 1.
pyridine-3-carbonitriles 4a–d, as viscous oils, which were sub-
jected to reaction without further purification. Alternatively, com-
pounds 4a–d could also be obtained by reacting compound 1 with
primary aliphatic amines 3a–d and ethyl cyanoacetate in the pres-
ence of ceric ammonium nitrate by US for 5 h at 40 °C.
Thus, coupling of 4a–d with aromatic diazonium salts afforded
the corresponding 5-arylhydrazono-pyridinones 5a–h. Correct ele-
mental analyses and spectral data of 5a–h substantiated their
structures (see Section 4). Furthermore, the structure of com-
pounds 5a–h could be unambiguously confirmed by single crystal
X-ray diffraction of compound 5h [17] (Fig. 1). Single crystal X-ray
diffraction of compound 5h add a strong evidence for the proposed
structure (Scheme 1).
Next we examined the reaction of aryl hydrazones 5 with ele-
mental sulphur with a view to synthesize new derivatives of the

K.M. Al-Zaydi et al. / Ultrasonics Sonochemistry 17 (2010) 909–915
911
Table 1
compounds 11 and 12 was achieved by heating the neat reagent
with microwave irradiation for 5 min at 440 W.
All reaction times were determined by follow the reaction pro-
gress via thin layer chromatography (TLC).
Formation of compounds 4–9 under three methodologies (thermal, microwave
irradiation, and ultrasound).
No.
Time
Yield (%)
D
(h)
lx
(min)
US
D
l
x
US
4a
4b
4c
4d
6a
6b
6c
6d
6e
6f
6g
8a
8b
8c
9a
9b
8
8
8
8
3
3
3
3
3
3
3
12
12
12
3
10
10
10
10
5
5
5
5
5
5
5
20
20
20
5
5 h
5 h
5 h
5 h
30 min
30 min
30 min
30 min
30 min
30 min
30 min
–
72
73
75
69
73
78
80
70
73
76
88
50
55
54
80
83
94
95
95
92
90
96
92
93
90
90
92
70
78
80
97
98
89
91
90
88
84
88
89
87
81
85
81
–
3. Conclusion
A novel environmentally benign methodology for the synthesis
of pyridinones, pyridazinones, thieno[3,4-c]pyridines and thie-
no[3,4-d]pyridazines has been developed avoiding volatile and
toxic organic solvents. This neat reaction under MWs not only gave
excellent yield of products with lesser reaction time but is also de-
void of hazardous solvents and reagents.
–
–
1 h
1 h
–
–
78
85
4. Experimental
4.1. Materials and methods
3
5
All melting points were measured on Gallenkamp electrother-
mal melting point apparatus and are uncorrected. The IR absorp-
7a–c were reacted with ethyl cyanoacetate by heating the neat
reagents with microwave or by conventional heating, an intramo-
lecular condensation took place that led directly to the new ethyl
1-aryl-5-cyano-6-oxo-4-propyl-1,6-dihydropyridazine-3-carbox-
ylate 8a–c (Scheme 2), in good yields. The structural assignment of
8a–c was based on spectral and analytical data. The molecular for-
mula was confirmed by elemental analyses and mass spectroscopy
(M+/m/e). Under analogous experimental conditions that described
above for the synthesis of compounds 6a–g, pyridazinones 8a,b
were reacted with elemental sulphur to give the polyfunctionally
substituted thieno[3,4-d]pyridazinones 9a,b.
tion spectra were measured on a Nicollet Magna 520FT IR
Spectrophotometer. 1H and 13C NMR spectra were recorded in deu-
terated dimethylsulfoxide (DMSO-d6) or deuterated chloroform
(CDCl3) at 200 MHz on a Varian Gemini NMR spectrometer and a
Bruker DPX 400 MHz spectrometer using tetramethylsilane (TMS)
as an internal reference and results are expressed as d values. Mass
spectra were performed on a Shimadzu GCMS-QP 1000 EX mass
spectrometer at 70 eV. Microwave irradiation was carried out
using the commercial microwave oven (SGO 1000W). Ultrasonic
irradiation was carried out using Sonics and Materials device,
750 W ultrasonic processor VCX 750, solid probe with non-replace-
able tip, with processing capability: 10–250 ml, length: 53/800
(136 mm), weight: 3/4 lb (340 g), titanium alloy Ti-6Al-4V, with
integrated temperature control, allows sample temperature to be
monitored up to 100 °C. Control temperature of reaction at 40 °C
via cooling the reaction vessel in a bath of cold water to maintain
desired temperature. The shape and the size of reactor dimensions
(H ꢀ Wꢀ D) 91/400 ꢀ 71/200 ꢀ 131/200 (235 ꢀ 190 ꢀ 340 mm) weight:
15 lb (6.8 kg) with sealed converter piezoelectric lead zirconate
titanate crystals (PZT) of diameter: 21/200 (63.5 mm), length: 71/
400 (183 mm), weight: 2 lb (900 g) all reactions undergo at 300 W
power (40%).
Table 1 shows yields and reaction times by the three methodol-
ogies are compared.
In order to construct new derivatives of the interesting thieno-
azine ring systems, we investigated the reaction of compounds 8
with acrylonitrile and maleic anhydride, as electron poor dieno-
philes. Thus, the reaction of compound 8b, as example, with acry-
lonitrile gave an addition intermediate 10 which lose one molecule
of hydrogen sulphide to yield the new polyfunctionally substituted
phthalazine 11 (Scheme 3). On the other hand, the cycloaddition
reaction between compound 8b and maleic anhydride furnished
the corresponding cycloadduct 12 (Scheme 3). The synthesis of
CN
NC
S
Et
Et
O
O
OEt
- H2S
H2
N
H
2
N
OEt
CN
N
N
Mw
O
N
O
N
C
Et
C
6
H4
-NO
2-p
6H4-NO2-p
S
O
10
11
H2N
OEt
N
O
N
C
O
O
S
6H4-NO2-p
O
Et
O
8b
O
O
OEt
O
H2
N
N
Mw
O
N
C6H4-NO2-p
12
Scheme 3.

912
K.M. Al-Zaydi et al. / Ultrasonics Sonochemistry 17 (2010) 909–915
Microanalytical data were obtained from the Microanalytical
CO2CH3-o), 116.9 (CN), 143.2 (C-4), 160.3 (C-5), 160.5, 162.6
(2CO), 166.9 (CO2CH3). MS: m/z (%) = 424. Anal. Calcd. for
C23H28N4O4 (424.50): C, 65.08; H, 6.65; N, 13.20. Found: C, 65.15;
H, 6.60; N, 13.15.
Data Unit at Cairo University, Egypt. Compound 1 is commercially
available from Merck Company, Germany, and used as it is without
further purification, compounds 2a–d were prepared in our labora-
tory [15].
4.2.2.3. 2-[N-(5-Cyano-1-cyclohexyl-2,6-dioxo-4-propyl-1,6-dihydro-
2H-pyridine-3-ylidene) hydrazine]benzoic acid methyl ester
4.2. Typical procedure for reactions
(5c). Yellow crystals; m.p. 253 °C. Yield 88%. IR (KBr):
m = 3434
4.2.1. Synthesis of pyridinone derivatives 4a–d
(NH, broadened due to H-bond between O and NH), 3062 (CH aro-
4.2.1.1. Method I (D). Ethyl 3-oxohexanoate (1) (0.1 mol) was
matic), 2938 (CH aliphatic), 2223 (CN), 1698 (CO ester), 1661
added to cyanoacetamides 2a–d (0.1 mol) and then the reaction
mixture was heated to reflux for 8 h. The mixture was evaporated
to dryness in vacuo to give compounds 4a–d as clear oils.
(amide CO), 1642 (amide CO) cmꢁ1 1H NMR: d = 0.99 (t, 3H,
.
J = 7 Hz, CH3), 1.29–2.90 (m, 10H, cyclohexyl-H), 1.72 (sextet, 2H,
J = 7 Hz, CH2), 3.23 (t, 2H, J = 7 Hz, CH2), 3.95 (s, 3H, CO2CH3),
4.66 (m, 1H, cyclohexyl-H), 7.35 (t, 1H, J = 7 Hz, Ar–H), 7.77 (t,
1H, J = 7 Hz, Ar–H), 7.96 (d, 1H, J = 8 Hz, Ar–H), 8.04 (d, 1H,
J = 8 Hz, Ar–H), 15.57 (s, 1H, NH) ppm. MS: m/z (%) = 422. Anal.
Calcd. for C23H26N4O4 (422.49): C, 65.39; H, 6.20; N, 13.26. Found:
C, 65.45; H, 6.29; N, 13.40.
4.2.1.2. Method II (lx). A mixture of compound 1 (0.1 mol) and
cyanoacetamides 2a–d (0.1 mol) was placed in the microwave oven
and irradiated at 460 W for 10 min to give compounds 4a–d as clear
oils.
4.2.1.3. Method III (US). Compound 1 (0.1 mol) was added to a
mixture of primary aliphatic amines 3a–d (0.1 mol) and ethyl cya-
noacetate (0.1 mol). The reaction mixture was catalyzed by
(0.1 mol) of ceric ammonium nitrate under ultrasound irradiation
at 40 °C for 5 h. Then, compounds 4a–d were isolated as clear oils
and used in the next step without further purification.
4.2.2.4. 2-[N-(1-Benzyl-5-cyano-2,6-dioxo-4-propyl-1,6-dihydro-2H-
pyridine-3-ylidene) hydrazine]benzoic acid methyl ester (5d). Orange
crystals; m.p. 217 °C. Yield 89%. IR (KBr):
m = 3329 (NH, broadened
due to H-bond between O and NH), 3095 (CH aromatic), 2955 (CH
aliphatic), 2221 (CN), 1687 (ester CO), 1645, 1638 (amide CO)
cmꢁ1 1H NMR: d = 0.96 (t, 3H, J = 7 Hz, CH3), 1.37 (sextet, 2H,
.
J = 7 Hz, CH2), 1.96 (t, 2H, J = 7 Hz, CH2), 3.88 (s, 3H, CO2CH3),
5.05 (s, 2H, CH2ph), 6.57–7.72 (m, 9H, Ar–H), 15.50 (s, 1H, NH)
ppm. 13C NMR: d = 14.1, 19.5, 25.3 (propyl carbons), 46.1 (CH2ph),
52.3 (CO2CH3), 116.8 (CN), 115.0, 117.1, 118.4, 130.5, 133.6, 147.9
(C6H4CO2CH3), 126.5, 127.1, 128.4, 142.4 (C6H5CH2), 105.1 (C-3),
145.3 (C-4), 155.3 (C-5), 162.5, 164.1 (2CO), 167.6 (CO2CH3) ppm.
MS: m/z (%) = 430. Anal. Calcd. for C24H22N4O4 (430.47): C, 66.97;
H, 5.15; N, 13.02. Found: C, 66.85; H, 5.20; N, 13.10.
4.2.2. General procedure for the synthesis of aryl hydrazone
compounds 5a–h
A cold solution of aryldiazonium salt (10 mmol), prepared by
adding a solution of sodium nitrite (1 g into 10 ml H2O) to a cold
solution of aryl amine hydrochloride or aryl amine nitrate
(10 mmol) with stirring as described earlier [11,12]. The resulting
solution of the aryldiazonium was then added to a cold solution
of pyridine-3-carbonitriles 4a–d or compound 1 (0.1 mol) in
ethanol (50 ml) containing sodium acetate (1 g in 10 ml H2O).
The mixture was stirred at room temperature for 1 h and the solid
product so-formed was collected by filtration and recrystallized
from ethanol to give compounds 5a–h and 7a–c, respectively.
4.2.2.5. 1-Butyl-5-[(4-chlorophenyl)-hydrazono]-2,6-dioxo-4-propyl-
1,2,5,6-tetrahydro-pyridine-3-carbonitrile (5e). Dark yellow crys-
tals; m.p. 182 °C. Yield 80%. IR (KBr):
due to H-bond between O and NH), 3077 (CH aromatic), 2946
(CH aliphatic), 2216 (CN), 1641 (amid CO) cmꢁ1 1H NMR:
m = 3455 (NH, broadened
.
4.2.2.1. 2-[N-(1-Butyl-5-cyano-2,6-dioxo-4-propyl-1,6-dihydro-2H-
pyridine-3-ylidene)hydrazine]-benzoic acid methyl ester (5a). Yel-
d = 0.90 (t, 3H, J = 7 Hz, CH3), 1.0 (t, 3H, J = 7 Hz, CH3), 1.30 (sextet,
2H, J = 7 Hz, CH2), 1.52 (quintet, 2H, J = 7 Hz, CH2), 1.67 (sextet, 2H,
J = 7 Hz, CH2), 2.90 (t, 2H, J = 7 Hz, CH2), 3.82 (t, 2H, J = 7 Hz, CH2N),
7.54 (d, 2H, J = 8 Hz, Ar–H), 7.73 (d, 2H, J = 8 Hz, Ar–H), 14.41 (s, 1H,
NH) ppm. MS: m/z (%) = 374, 372. Anal. Calcd. for C19H21ClN4O2
(372.86): C, 61.21; H, 5.68; N, 15.03. Found: C, 61.30; H, 5.45; N,
15.16.
low crystals; m.p. 199 °C. Yield 82%. IR (KBr):
m = 3470 (NH,
broadened due to H-bond between O and NH), 3100 (CH aromatic),
2956 (CH aliphatic), 2223 (CN), 1680 (ester CO), 1640 (amide CO)
cmꢁ1 1H NMR: d = 0.91 (t, 3H, J = 7 Hz, CH3), 1.01 (t, 3H, J = 7 Hz,
.
CH3), 1.31 (sextet, 2H, J = 7 Hz, CH2), 1.52 (quintet, 2H, J = 7 Hz,
CH2), 1.71 (sextet, 2H, J = 7 Hz, CH2), 2.49 (t, 2H, J = 7 Hz, CH2),
3.84 (t, 2H, J = 7 Hz, CH2N), 3.96 (s, 3H, CO2CH3), 7.39 (t, 1H,
J = 7 Hz, Ar–H), 7.81 (t, 1H, J = 7 Hz, Ar–H), 7.99 (d, 1H, J = 8 Hz,
Ar–H), 8.06 (d, 1H, J = 8 Hz, Ar–H), 15.66 (s, 1H, NH) ppm. MS: m/
z (%) = 396. Anal. Calcd. for C21H24N4O4 (396.45): C, 63.62; H,
6.10; N, 14.13. Found: C, 63.60; H, 6.25; N, 14.15.
4.2.2.6. 5-[(4-Chlorophenyl)-hydrazono]-1-hexyl-2,6-dioxo-4-propyl-
1,2,5,6-tetrahydro-pyridine-3-carbonitrile (5f). Orange crystals; m.p.
152 °C. Yield 88%. IR (KBr):
m = 3414 (NH, broadened due to H-bond
between O and NH), 3089 (CH aromatic), 2954 (CH aliphatic), 2219
(CN), 1647 (amide CO) cmꢁ1. 1H NMR: d = 0.83 (t, 3H, J = 6 Hz, CH3),
0.99 (t, 3H, J = 7 Hz, CH3), 1.26 (m, 6H, 3 hexyl-CH2), 1.52 (quintet,
2H, J = 7 Hz, CH2), 1.66 (sextet, 2H, J = 7 Hz, CH2), 2.88 (t, 2H,
J = 7 Hz, CH2), 3.79 (t, 2H, J = 7 Hz, CH2N), 7.51 (d, 2H, J = 8 Hz,
Ar–H), 7.71 (d, 2H, J = 8 Hz, Ar–H), 14.50 (s, 1H, NH) ppm. MS: m/
z (%) = 402, 400. Anal. Calcd. for C21H25Cl N4O2 (400.91): C, 62.92;
H, 6.29; N, 13.97. Found: C, 62.88; H, 6.30; N, 13.89.
4.2.2.2. 2-[N-(5-Cyano-1-hexyl-2,6-dioxo-4-propyl-1,6-dihydro-2H-
pyridine-3-ylidene)hydrazine]-benzoic acid methyl ester (5b). Yel-
low crystals; m.p. 160 °C. Yield 86%. IR (KBr):
3102 (CH aromatic), 2961 (CH aliphatic), 2220 (CN), 1675 (ester
CO), 1649 (amide CO) cmꢁ1 1H NMR: d = 0.86 (t, 3H, J = 6 Hz,
m = 3390 (NH),
.
CH3), 1.08 (t, 3H, J = 7 Hz, CH3), 1.27–1.30 (m, 6H, 3 hexyl-CH2),
1.60 (quintet, 2H, J = 7 Hz, CH2), 1.76 (sextet, 2H, J = 7 Hz, CH2),
3.01 (t, 2H, J = 7 Hz, CH2), 4.0 (t, 2H, J = 7 Hz, CH2N), 4.04 (s, 3H,
CO2CH3), 7.31 (t, 1H, J = 7 Hz, Ar–H), 7.64 (t, 1H, J = 7 Hz, Ar–H),
7.93 (d, 1H, J = 8 Hz, Ar–H), 8.10 (d, 1H, J = 8 Hz, Ar–H), 15.85 (s,
1H, NH) ppm. 13C NMR: d = 14.4, 22.6, 26.7 (propyl carbons),
14.1, 23.6, 27.8, 31.5, 32.7, 40.2 (hexyl carbons), 53.0 (CO2CH3),
102.8 (C-3), 114.4, 116.3 123.8, 125.8, 131.8, 134.8 (C6H4–
4.2.2.7. 1-Benzyl-5-[(4-chlorophenyl)-hydrazono]-2,6-dioxo-4-pro-
pyl-1,2,5,6-tetrahydro-pyridine-3-carbonitrile (5g). Orange crystals;
m.p. 203 °C. Yield 79%. IR (KBr):
H-bond between O and NH), 3061 (CH aromatic), 2966 (CH
aliphatic), 2223 (CN), 1641 (amide CO) cmꢁ1 1H NMR: d = 1.01
m = 3465 (NH, broadened due to
.
(t, 3H, J = 7 Hz, CH3), 1.71 (sextet, 2H, J = 7 Hz, CH2), 2.92 (t, 2H,
J = 7 Hz, CH2), 5.03 (s, 2H, CH2ph), 7.25–7.32 (m, 5H, Ar–H), 7.52

K.M. Al-Zaydi et al. / Ultrasonics Sonochemistry 17 (2010) 909–915
913
(d, 2H, J = 8 Hz, Ar–H), 7.73 (d, 2H, J = 8 Hz, Ar–H), 14.45 (s, 1H, NH)
ppm. MS: m/z (%) = 408, 406. Anal. Calcd. for C22H19Cl N4O2
(406.88): C, 64.95; H, 4.71; N, 13.77. Found: C, 64.78; H, 4.80; N,
13.69.
4.2.3.2. Method II (
l
x
). A mixture of ethyl cyanoacetate (0.1 mol),
aryl hydrazone derivatives 7a–c (0.1 mol), ammonium acetate
(0.1 mol) and a few drops of glacial acetic acid was placed in the
microwave oven and irradiated at 440 W for 20 min. After cooling
to room temperature. The solid product so-formed was filtered off,
dried and recrystallized from ethanol.
4.2.2.8. 5-[(4-Chlorophenyl)-hydrazono]-1-cyclohexyl-2,6-dioxo-4-
propyl-1,2,5,6-tetrahydro-pyridine-3-carbonitrile (5h). Yellow crys-
4.2.3.3. 5-Cyano-1-(2-methoxycarbonylphenyl)-6-oxo-4-propyl-1,6-
dihydropyridazine-3-carboxylic acid ethyl ester (8a). Yellow crystals;
tals; m.p. 227 °C. Yield 91%. IR (KBr):
due to H-bond between O and NH), 3041 (CH aromatic), 2940 (CH
aliphatic), 2220 (CN), 1645 (amide CO) cmꢁ1 1H NMR; d = 1.07
m = 3455 (NH, broadened
m.p. 190 °C. IR (KBr):
2220 (CN), 1720 (ester CO), 1685 (ester CO), 1641 (amide CO)
cmꢁ1 1H NMR: d = 1.08 (t, 3H, J = 7 Hz, CH3), 1.34 (t, 3H, J = 7 Hz,
m = 3091 (CH aromatic), 2934 (CH aliphatic),
.
(t, 3H, J = 7 Hz, CH3), 1.24–2.38 (m, 10H, cyclohexyl-H), 1.74 (sextet,
2H, J = 7 Hz, CH2), 2.95 (t, 2H, J = 7 Hz, CH2), 4.78 (m, 1H, cyclohexyl
CH–N), 7.35–7.43 (m, 4H, Ar–H), 15.02 (s, 1H, NH) ppm. MS: m/z
(%) = 400, 398. Anal. Calcd. for C21H23ClN4O2 (398.90): C, 63.23; H,
5.81; N, 14.05. Found: C, 63.38; H, 5.75; N, 14.20.
.
CH3), 1.75 (sextet, 2H, J = 7 Hz, CH2), 3.06 (t, 2H, J = 7 Hz, CH2),
3.76 (s, 3H, CO2CH3), 4.35 (q, 2H, J = 7 Hz, CH2), 7.44 (d, 1H,
J = 8 Hz, Ar–H), 7.54 (t, 1H, J = 7 Hz, Ar–H), 7.66 (t, 1H, J = 7 Hz,
Ar–H), 8.06 (d, 1H, J = 8 Hz, Ar–H) ppm. 13C NMR: 14.1
(CO2CH2CH3), 62.8 (CO2CH2CH3), 14.2, 23.5, 34.2 (COCH2CH2CH3),
52.6 (C6H4–CO2CH3-o), 112.4 (C-5), 114.7 (CN), 127.1, 128.1,
130.2, 131.4, 133.6, 137.1 (C6H4–CO2CH3-o), 139.7 (C-3), 155.2
(C-4), 156.6 (CO ring), 162.1, 164.7 (2CO ester) ppm. MS: m/z
(%) = 369. Anal. Calcd. for C19H19N3O5 (369.38): C, 61.78; H, 5.18;
N, 11.38. Found: C, 61.70; H, 5.25; N, 11.45.
4.2.2.9.
zoic acid methyl ester (7a). Yellow crystals; m.p. 178 °C. Yield
93%. IR (KBr): = 3310 (NH), 3012 (CH aromatic), 2940 (CH ali-
phatic), 1686 (ester CO), 1669 (Ketonic CO) cmꢁ1 1H NMR:
2-[N-(1-Ethoxycarbonyl-2-oxo-pentylidene)hydrazino]ben-
m
.
d = 0.96 (t, 3H, J = 7 Hz, CH3), 1.38 (t, 3H, J = 7 Hz, CH3), 1.71 (sextet,
2H, J = 7 Hz, CH2), 2.91 (t, 2H, J = 7 Hz, CH2), 3.96 (s, 3H, OCH3), 4.35
(q, 2H, J = 7 Hz, CH2), 7.08–8.03 (m, 4H, Ar–H), 14.06, 15.50 (s, 1H,
4.2.3.4. 5-Cyano-1-(4-nitrophenyl)-6-oxo-4-propyl-1,6-dihydro-pyr-
idazine-3-carboxylic acid ethyl ester (8b). Brown crystals; m.p.
NH) ppm; Z,
E
isomers. 13C NMR; 14.1 (CO2CH2CH3), 61.2
(COOCH2CH3), 17.8, 18.1, 40.7 (COCH2CH2CH3), 52.7 (CO2CH3),
114.6, 115.3, 122.9, 123.7, 131.2, 134.5 (C6H4–CO2CH3-o), 144.5
(C@N–NH), 162.5, 167.5 (2 CO ester), 197.4 (CO) ppm. MS: m/z
(%) = 320. Anal. Calcd. for C16H20N2O5 (320.35): C, 59.99; H, 6.29;
N, 8.74. Found: C, 59.82; H, 6.18; N, 8.91.
192 °C; IR (KBr):
m
= 3010 (CH aromatic), 2985 (CH aliphatic),
2214 (CN), 1689 (ester CO), 1642 (amide CO) cmꢁ1
.
1H NMR:
d = 0.99 (t, 3H, J = 7 Hz, CH3), 1.29 (t, 3H, J = 7 Hz, CH3), 1.67 (sextet,
2H, J = 7 Hz, CH2), 2.94 (t, 2H, J = 7 Hz, CH2), 4.37 (q, 2H, J = 7 Hz,
CH2), 7.92 (d, 2H, J = 8 Hz, Ar–H), 8.43 (d, 2H, J = 8 Hz, Ar–H)
ppm. MS: m/zm/z (%) = 356. Anal. Calcd. for C17H16N4O5(356.34):
C, 57.30; H, 4.53; N, 15.72. Found: C, 57.45; H, 4.60; N, 15.59.
4.2.2.10. 2-[(4-Nitrophenyl)hydrazono]-3-oxo-hexanoic acid ethyl
ester (7b). Yellow crystals; m.p. 202 °C. Yield 90%. IR (KBr):
4.2.3.5. 5-Cyano-6-oxo-4-propyl-1-(4-methylphenyl)-1,6-dihydropy-
m
= 3325 (NH), 3010 (CH aromatic), 2953 (CH aliphatic), 1715 (es-
ter CO), 1670 (ketonic CO) cmꢁ1 1H NMR: d = 0.99 (t, 3H, J = 7 Hz,
.
ridazine-3-carboxylic acid ethyl ester
m.p. > 300 °C. IR (KBr): = 3021 (CH aromatic), 2805 (CH aliphatic),
2210 (CN), 1658 (ester CO), 1645 (amide CO) cmꢁ1 1H NMR:
(8c). Brown crystals;
m
CH3), 1.39 (t, 3H, J = 7 Hz, CH3), 1.73 (sextet, 2H, J = 7 Hz, CH2), 2.89
(t, 2H, J = 7 Hz, CH2), 4.37 (q, 2H, J = 7 Hz, CH2), 7.37 (d, 2H, J = 8 Hz,
Ar–H), 8.27 (d, 2H, J = 8 Hz, Ar–H), 12.65, 14.45 (s, 1H, NH) ppm; Z,
E isomers. 13C NMR; 14.0 (CO2CH2CH3), 62.1 (CO2CH2CH3), 14.1,
22.4, 40.7 (COCH2CH2CH3), 115.0, 125.6, 134.8, 138.2 (C6H4–NO2-
p), 146.8 (C@N–NH), 196.7 (CO ester), 220.1 (CO) ppm. MS: m/z
(%) = 307. Anal. Calcd. for C14H17N3O5 (307.31): C, 54.72; H, 5.58;
N, 13.67. Found: C, 54.59; H, 5.50; N, 13.77.
.
d = 1.04 (t, 3H, J = 7 Hz, CH3), 1.30 (t, 3H, J = 7 Hz, CH3), 1.69 (sextet,
2H, J = 7 Hz, CH2), 3.04 (t, 2H, J = 7 Hz, CH2), 3.94 (s, 3H, CH3), 4.07
(q, 2H, J = 7 Hz, CH2), 7.68 (d, 2H, J = 7 Hz, Ar–H), 7.96 (d, 2H, J
= 8 Hz, Ar–H) ppm. MS: m/z (%) = 325. Anal. Calcd. for
C18H19N3O3 (325.37): C, 66.45; H, 4.89; N, 12.91. Found: C, 66.59;
H, 5.77; N, 12.90.
4.2.4. General procedure for the reaction of 5a–h and 8a,b with
elemental sulphur
4.2.4.1. Method I (D). To a solution of arylazopyridinone derivatives
5a–g or pyridazinones 8a,b (0.1 mol) in ethanol (30 ml), elemental
sulphur (0.1 mol) and a catalytic amount of triethylamine were
added. The reaction mixture was heated to reflux for 3 h. The solid
product so-formed was collected by filtration and dried.
4.2.2.11. 3-Oxo-2-(4-tolylhydrazono)hexanoic acid ethyl ester
(7c). Brown crystals; m.p. 240 °C. Yield 94%. IR (KBr):
(NH), 3001 (CH aromatic), 2962 (CH aliphatic), 1696 (ester CO),
1667 (ketonic CO) cmꢁ1 1H NMR: d = 0.96 (t, 3H, J = 7 Hz, CH3),
m = 3325
.
1.36 (t, 3H, J = 7 Hz, CH3), 1.67 (sextet, 2H, J = 7 Hz, CH2), 2.32 (s,
3H, CH3), 2.87 (t, 2H, J = 7 Hz, CH2), 4.30 (q, 2H, J = 7 Hz, CH2),
7.14–7.29 (m, 4H, Ar–H), 12.77, 14.88 (s, 1H, NH) ppm; Z, E isomers.
13C NMR: 14.1 (COOCH2CH3), 61.3 (COOCH2CH3), 14.2, 18.2, 40.5
(COCH2CH2CH3), 21.0 C6H4–CH3-p), 115.5, 126.3, 130.2, 134.7
(C6H4–CH3-p), 139.6 (C@N–NH), 164.1 (CO ester), 196.9 (CO) ppm.
MS: m/z (%) = 276. Anal. Calcd. for C15H20N2O3 (276.34): C, 65.20;
H, 7.30; N, 10.14. Found: C, 65.32; H, 7.17; N, 10.24.
4.2.4.2. Method II (lx). A mixture of 5a–g or 8a,b (0.1 mol),
elemental sulphur (0.1 mol) and a few drops of triethylamine
was placed in the microwave oven and irradiated at 440 W for
10 min. Then, the reaction mixture was left to cool to room
temperature. The solid product so-formed was filtered off and
dried.
4.2.3. General procedure for the synthesis of pyridazinone compounds
8a–c
4.2.4.3. Method III (US). To a solution of 5a–g or 8a,b (0.1 mol) in
4.2.3.1. Method I (
D
). To a mixture of aryl hydrazone derivatives
ethanol (30 ml), elemental sulphur (0.1 mol) and a catalytic
7a–c (0.1 mol) and ethyl cyanoacetate (0.1 mol) in dry benzene
and glacial acetic acid (10 mL), ammonium acetate (4 g) was
added. Then, the reaction mixture was heated to reflux for 12 h.
After cooling to room temperature, the resulting solid product
was collected by filtration and dried.
amount of triethylamine were added. The reaction mixture
was heated under ultrasound irradiation at 40 °C for 90 min
and then left to cool to room temperature. The solid product so-
formed was collected by filtration, dried and recrystallized from
ethanol.

914
K.M. Al-Zaydi et al. / Ultrasonics Sonochemistry 17 (2010) 909–915
4.2.4.4.
2[2-(3-Amino-5-butyl-1-ethyl-4,6-dioxo-5,6-dihydrothie-
4.2.4.9. 3-Amino-7-[2-(4-chlorophenyl)-hydrazono]-1-ethyl-5-hexyl-
no[3,4-c]pyridine-7(4H)-ylidene)-hydrazinyl]benzoic acid methyl
ester (6a). Brown crystals; m.p. 113 °C. IR (KBr): = 3447, 3343,
3144 ((NH2, NH), 3049 (CH aromatic), 2952 (CH aliphatic), 1702
(ester CO), 1660, 1639 (2 amide CO) cmꢁ1 1H NMR: d = 0.93 (t,
7H-thieno[3,4-c]pyridine-4,6-dione (6f). Dark red crystals; m.p.
m
161 °C. IR (KBr):
m
= 3411, 3324, 3302 (NH2, NH), 3092 (aromatic
CH), 2926 (aliphatic CH), 1663, 1645 (2 amide CO) cmꢁ1
.
1H
.
NMR: d = 0.85 (t, 3H, J = 6 Hz, CH3), 1.23 (t, 3H, J = 7 Hz, CH3),
1.27 (m, 6H, 3 hexyl-CH2), 1.51 (quintet, 2H, J = 7 Hz, CH2), 2.95
(q, 2H, J = 7 Hz, CH2), 3.79 (t, 2H, J = 7 Hz, CH2N), 7.34 (d, 2H,
J = 8 Hz, Ar–H), 7.42 (d, 2H, J = 8 Hz, Ar–H), 7.68 (s, 2H, NH2),
13.55 (s, 1H, NH) ppm. MS: m/z (%) = 434, 432. Anal. Calcd. for
C21H25ClN4O2S (432.98): C, 58.26; H, 5.82; N, 12.94. Found: C,
58.30; H, 5.76; N, 12.85.
3H, J = 7 Hz, CH3), 1.08 (t, 3H, J = 7 Hz, CH3), 1.37 (sextet, 2H,
J = 7 Hz, CH2), 1.61 (quintet, 2H, J = 7 Hz, CH2), 1.76 (q, 2H,
J = 7 Hz, CH2), 3.01 (t, 2H, J = 7 Hz, CH2N), 4.03 (s, 3H, CO2CH3),
7.29 (t, 1H, J = 7 Hz, Ar–H), 7.66 (t, 1H, J = 7 Hz, Ar–H), 7.72 (s,
2H, NH2), 7.93 (d, 1H, J = 8 Hz, Ar–H), 8.11 (d, 1H, J = 8 Hz, Ar–H),
15.85 (s, 1H, NH) ppm. 13C NMR: d = 13.9, 23.6, 32.7, 40.0 (butyl
carbons), 14.4, 20.3 (CH3CH2), 53.1 (CO2CH3), 102.8 (C-3), 114.4,
116.3, 116.9, 123.8, 125.8, 143.2 (C6H4–COOCH3-o), 131.8, 134.7
(thienyl carbons), 145.0 (C-4), 160.3 (C-5), 160.5, 162.6 (2CO),
166.9 (CO2CH3) ppm. MS: m/z (%) = 428. Anal. Calcd. for
C21H24N4O4S (428.51): C, 58.86; H, 5.65; N, 13.07. Found: C,
58.78; H, 5.60; N, 13.33.
4.2.4.10. 3-Amino-5-benzyl-7-[2-(4-chlorophenyl)-hydrazono]-1-
ethyl-7H-thieno[3,4-c]pyridine-4,6-dione (6g). Red crystals; m.p.
244 °C. IR (KBr):
m
= 3510, 3441, 3317 (NH2, NH), 3050 (aromatic
CH), 2949 (aliphatic CH), 1658 (2 amide CO) cmꢁ1
.
1H NMR:
d = 1.24 (t, 3H, J = 7 Hz, CH3), 2.99 (q, 2H, J = 7 Hz, CH2), 5.03 (s,
2H, CH2ph), 7.35 (m, 9H, Ar–H), 7.73 (s, 2H, NH2), 13.48 (s, 1H,
NH) ppm. MS: m/z (%) = 440, 438. Anal. Calcd. for C22H19ClN4O2S
(438.94): C, 60.20; H, 4.36; N, 12.76. Found: C, 60.33; H, 4.47; N,
12.55.
4.2.4.5. 2[2-(3-Amino-1-ethyl-5-hexyl-4,6-dioxo-5,6-dihydrothie-
no[3,4-c]pyridine-7(4H)-ylidene)-hydrazinyl]benzoic acid methyl
ester (6b). Dark brown crystals; m.p. 138 °C. IR (KBr):
3344, 3300 ((NH2, NH), 3095 (CH aromatic), 2925 (CH aliphatic),
1705 (ester CO), 1662, 1641 (2 amide CO) cmꢁ1 1H NMR:
m = 3444,
4.2.4.11. 5-Amino-7-ethyl-3-(2-methoxycarbonylphenyl)-4-oxo-3,4-
.
dihydrothieno[3,4-d]-pyridazine-1-carboxylic
acid
ethyl
ester
d = 0.86 (t, 3H, J = 6 Hz, CH3), 1.24 (t, 3H, J = 7 Hz, CH3), 1.29 (m,
6H, 3 hexyl-CH2), 1.51 (quintet, 2H, J = 7 Hz, CH2), 2.66 (q, 2H,
J = 7 Hz, CH2), 3.83 (t, 2H, J = 7 Hz, CH2N), 3.92 (s, 3H, CO2CH3),
7.70 (s, 2H, NH2) 7.08 (t, 1H, J = 7 Hz, Ar–H), 7.67 (t, 1H, J = 7 Hz,
Ar–H), 7.74 (d, 1H, J = 8 Hz, Ar–H), 7.98 (d, 1H, J = 8 Hz, Ar–H),
14.87 (s, 1H, NH) ppm. MS: m/z (%) = 456. Anal. Calcd. for
C23H28N4O4S (456.57): C, 60.51; H, 6.18; N, 12.27. Found: C,
60.58; H, 6.25; N, 12.15.
(9a). Brown crystals; m.p. 122 °C. IR (KBr):
m = 3412, 3314 (NH2),
3091 (aromatic CH), 2921 (aliphatic CH), 1722 (2 ester CO), 1651
(amide CO) cmꢁ1 1H NMR: d = 1.17 (t, 3H, J = 7 Hz, CH3), 1.30 (t,
.
3H, J = 7 Hz, CH3), 2.71 (q, 2H, J = 7 Hz, CH2), 3.67 (s, 3H, CO2CH3),
4.32 (q, 2H, J = 7 Hz, CH2), 7.48–7.88 (m, 6H, 4 Ar–H + NH2) ppm.
MS: m/z (%) = 401. Anal. Calcd. for C19H19N3O5S (401.44): C,
56.85; H, 4.77; N, 10.47. Found: C, 56.80; H, 4.88; N, 10.33.
4.2.4.12. 5-Amino-7-ethyl-3-(4-nitrophenyl)-4-oxo-3,4-dihydrothie-
no[3,4-d]pyridazine-1-carboxylic acid ethyl ester (9b). Brown crys-
4.2.4.6. 2[2-(3-Amino-5-cyclohexyl-1-ethyl-4,6-dioxo-5,6-dihydrothi-
eno[3,4-c]pyridine-7(4H)-ylidene)hydrazinyl]benzoic acid methyl
tals; m.p.159 °C. IR (KBr):
m = 3452, 3343 (NH2), 3088 (aromatic
ester (6c). Brown crystals; m.p. 222 °C. IR (KBr):
3302 (NH2, NH), 3045 (aromatic CH), 2931 (aliphatic CH), 1697 (es-
ter CO), 1660, 1641 (2 amide CO) cmꢁ1 1H NMR: d = 1.01 (t, 3H,
m = 3444, 3325,
CH), 2922 (aliphatic CH), 1715 (ester CO), 1663 (amide CO) cmꢁ1
.
1H NMR: d = 1.22 (t, 3H, J = 7 Hz, CH3), 1.38 (t, 3H, J = 7 Hz, CH3),
2.79 (q, 2H, J = 7 Hz, CH2), 4.39 (q, 2H, J = 7 Hz, CH2), 6.17 (s, 2H,
NH2), 7.84 (d, 2H, J = 8 Hz, Ar–H), 8.21 (d, 2H, J = 8 Hz, Ar–H)
ppm. 13C NMR: d = 14.1 (CO2CH2CH3), 16.5, 21.7 (CH2CH3), 62.6
(CO2CH2CH3), 120.5, 123.9, 125.2, 138.2 (C6H4–NO2-p), 106.3,
127.0, 145.5 (pyridazine carbons), 145.9, 159.2 (thienyl carbons),
159.6 (CO ring), 164.2 (CO ester) ppm. MS: m/z (%) = 388. Anal.
Calcd. for C17H16N4O5S (388.40): C, 52.57; H, 4.15; N, 14.42. Found:
C, 52.43; H, 4.32; N, 14.35.
.
J = 7 Hz, CH3), 1.23–2.37 (m, 10H cyclohexyl-H), 2.99 (q, 2H,
J = 7 Hz, CH2), 3.93 (s, 3H, CO2CH3), 4.69 (m, 1H cyclohexyl-H),
7.08 (s, 2H, NH2), 7.29–7.98 (m, 4H, Ar–H), 14.80 (s, 1H, NH)
ppm. MS: m/z (%) = 454. Anal. Calcd. for C23H26N4O4S (454.55): C,
60.78; H, 5.77; N, 12.33. Found: C, 60.75; H, 5.89; N, 12.40.
4.2.4.7. 2[2-(3-Amino-5-benzyl-1-ethyl-4,6-dioxo-5,6-dihydrothi-
eno[3,4-c]pyridine-7(4H)-ylidene)-hydrazinyl]benzoic acid methyl
ester (6d). Dark brown crystals; m.p. 221 °C. IR (KBr):
3449, 3344 (NH2, NH), 3050 (aromatic CH), 2950 (aliphatic CH),
1701 (ester CO), 1666 (2 amide CO) cmꢁ1 1H NMR: d = 1.27 (t,
3H, J = 7 Hz, CH3), 3.02 (q, 2H, J = 7 Hz, CH2), 3.89 (s, 3H, CO2CH3),
5.06 (s, 2H, CH2ph), 7.07 (s, 2H, NH2), 7.23–7.96 (m, 9H, Ar–H),
14.83 (s, 1H, NH) ppm. MS: m/z (%) = 462. Anal. Calcd. for
C24H22N4O4S (462.53): C, 62.32; H, 4.79; N, 12.11. Found: C,
62.44; H, 4.65; N, 12.27.
m = 3534,
4.2.4.13. Synthesis of 5-Amino-7-cyano-8-ethyl-3-(4-nitrophenyl)-4-
oxo-3,4-dihydrophthalazine-1-carboxylic acid ethyl ester (11). A
mixture of compound 8b (0.1 mol) and acrylonitrile (0.1 mol)
was placed in the microwave oven and irradiated at 440 W for
5 min. Then, the reaction mixture left to cool to room temperature.
The solid product so-formed was filtered off and recrystallized
from ethanol to yield compound 11 as brown crystals.
.
Yield 83%; m.p. 163 °C. IR (KBr):
(aromatic CH), 2974 (aliphatic CH), 2221 (CN), 1718 (ester CO),
1657 (amide CO) cmꢁ1 1H NMR: d = 1.24 (t, 3H, J = 7 Hz, CH3),
m = 3436, 3322 (NH2), 3033
4.2.4.8. 3-Amino-5-butyl-7-[2-(4-chlorophenyl)-hydrazon-
.
o]-1-ethyl-7H-thieno[3,4-c]pyridine-4,6-dione (6e). Light brown
1.45 (t, 3H, J = 7 Hz, CH3), 2.82 (q, 2H, J = 7 Hz, CH2), 4.44 (q, 2H,
J = 7 Hz, CH2), 6.22 (s, 2H, NH2), 7.27 (s, 1H, H-6), 7.89 (d, 2H,
J = 8 Hz, Ar–H), 8.26 (d, 2H, J = 8 Hz, Ar–H) ppm. MS: m/z
(%) = 408. Anal. Calcd. for C20H17N5O5(407.39): C, 58.97; H, 4.21;
N, 17.19. Found: C, 58.82; H, 4.30; N, 17.25.
crystals; m.p. 179 °C. IR (KBr):
3090 (aromatic CH), 2957 (aliphatic CH), 1665, 1640 (2 amide
CO) cmꢁ1 1H NMR: d = 0.88 (t, 3H, J = 7 Hz, CH3), 1.20 (t, 3H,
m = 3442, 3315, 3302 (NH2, NH)
.
J = 7 Hz, CH3), 1.27 (sextet, 2H, J = 7 Hz, CH2), 1.49 (quintet, 2H,
J = 7 Hz, CH2), 2.95 (q, 2H, J = 7 Hz, CH2), 3.78 (t, 2H, J = 7 Hz,
CH2N), 7.30–7.38 (m, 4H, Ar–H), 7.62 (s, 2H, NH2), 13.52 (s, 1H,
NH) ppm. MS: m/z (%) = 406, 404. Anal. Calcd. for C19H21ClN4O2S
(404.92): C, 56.36; H, 5.23; N, 13.84. Found: C, 56.42; H, 5.15; N,
13.89.
4.2.4.14. Synthesis of 1-Amino-7-ethyl-4-oxo-10-thiatricyclo
[5.2.1.02,6]
deca-8-diene-3,5-dione;1-(4-nitro-phenyl)-6-oxo-1,6-
dihydro-pyridazine-3-carboxylic acid ethyl ester (12). A mixture of
compound 8b (0.1 mol) and maleic anhydride (0.1 mol) was placed

K.M. Al-Zaydi et al. / Ultrasonics Sonochemistry 17 (2010) 909–915
915
[7] J. Svete, J. Heterocycl. Chem. 42 (2005) 361.
in the microwave oven and irradiated at 440 W for 5 min. Then, it
left to cool to room temperature. The solid product so-formed was
filtered off and recrystallized from ethanol to give compound 12 as
brown crystals.
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Rees, E.F.V. Scriven (Eds.), Comprehensive Heterocyclic Chemistry II, vol. 3,
Elsevier Science Ltd., Oxford, 1996, pp. 1–91.
[9] B. Stanovnik, Pyridazines, in: Houben–Weyl Methods of Organic Chemistry,
vol. E9a, Georg Thieme Verlag, Stuttgart, 1997, pp. 557–682 (references cited
therein).
[10] K.M. Al-Zaydi, Molecules 8 (2003) 541.
[11] K.M. Al-Zaydi, R.M. Borik, M.H. Elnagdi, Molecules 9 (2004) 910.
[12] K.M. Al-Zaydi, R.M. Borik, Molecules 12 (2007) 2061.
Yield 70%; m.p. 103 °C. IR (KBr):
(aromatic CH), 2918 (aliphatic CH), 1728 (ester CO), 1676, 1664,
1642 (3 CO) cmꢁ1 1H NMR: d = 1.06 (t, 3H, J = 7 Hz, CH3), 1.19 (t,
m = 3422, 3331 (NH2), 3088
.
3H, J = 7 Hz, CH3), 1.28 (q, 2H, J = 7 Hz, CH2), 3.41, 3.48 (s, 2H,
maleic anhydride), 4.39 (q, 2H, J = 7 Hz, CH2), 6.17 (s, 2H, NH2),
7.86 (d, 2H, J = 8 Hz, Ar–H), 8.26 (d, 2H, J = 8 Hz, Ar–H) ppm. MS:
m/z (%) = 486. Anal. Calcd. for C21H18N4O8S (486.46): C, 51.85; H,
3.73; N, 11.52. Found: C, 51.66; H, 3.82; N, 11.39.
[13] K.M. Al-Zaydi, Heterocycles 78 (2009) 2003.
[14] R.A. Mekheimer, K.U. Sadek, J. Heterocycl. Chem. 46 (2009) 149.
[15] K.M. Al-Zaydi, R.M. Borik, M.H. Elnagdi, Ultrason. Sonochem. 16 (2009) 660.
[16] K.M. Al-Zaydi, Ultrason. Sonochem. 16 (2009) 805.
[17] Crystallographic data for the structures reported in this paper have been
deposited with the Cambridge Crystallographic Data Centre as supplementary
Publications Nos. CCDC 686. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html (or from the CCDC, 12 Union Road,
Cambridge, CB2 1EZ, UK. Fax: +44 1223 336033. E-mail: deposit@ccdc.cam.
ac.uk).
[18] Crystallographic data for the structures reported in this paper have been
deposited with the Cambridge Crystallographic Data Centre as supplementary
Publications Nos. CCDC 687579. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html (or from the CCDC, 12 Union Road,
Cambridge, CB2 1EZ, UK. Fax: +44 1223 336033. E-mail: deposit@ccdc.
cam.ac.uk)
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