A simple one-pot, three component synthesis of 3-arylpyrimido[4,5-c] pyridazine-5,7(6h,8h)-diones and their sulfur analogues as potential monoamine oxidase inhibitors

Article abstract of DOI:10.1071/CH09569

Several new 3-arylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-diones and 3-aryl-5-oxo-7-thioxo-7,8-dihydropyrimido[4,5-c]pyridazin-5(6H)-ones have been synthesized by a three-component reaction of barbituric acid or thiobarbituric acid with arylglyoxals in the presence of a catalytic amount of pyridine and hydrazine hydrate at room temperature in water.

Full text of DOI:10.1071/CH09569

Full Paper
CSIRO PUBLISHING
www.publish.csiro.au/journals/ajc
Aust. J. Chem. 2010, 63, 507–510
A Simple One-Pot, Three Component Synthesis of
3-Arylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-diones
and their Sulfur Analogues as Potential Monoamine
Oxidase Inhibitors
Mehdi Rimaz,A Jabbar Khalafy,A,C Nader Noroozi Pesyan,A and Rolf H. PragerB
AChemistry Department, Urmia University, Urmia 57154, Iran.
BSchool of Chemistry, Physics and Earth Sciences, Flinders University, Adelaide, SA 5001, Australia.
CCorresponding author. Email: j.khalafi@mail.urmia.ac.ir; jkhalafi@yahoo.com
Several new 3-arylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-diones and 3-aryl-5-oxo-7-thioxo-7,8-dihydropyrimido[4,5-c]
pyridazin-5(6H)-ones have been synthesized by a three-component reaction of barbituric acid or thiobarbituric acid with
arylglyoxals in the presence of a catalytic amount of pyridine and hydrazine hydrate at room temperature in water.
Manuscript received: 27 October 2009.
Manuscript accepted: 18 January 2010.
H
Introduction
N
N
O
N
Pyridazine derivatives and heterocyclic annelated pyridazines
continue to attract attention due to their wide variety of
interesting biological activities.[1] The synthesis and utility
of many pyridazine derivatives as analgesics, insecticidals,[2]
fungicidals[3,4] cardiotonics,[5] and bacteriocides[6] have been
reported. In particular, pyrimido[4,5-c]pyridazine-5,7(6H,8H)-
diones are common sources for the development of new potential
therapeutic agents.[7–9] In addition, some derivatives of 6,8-
dimethylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-dione undergo
new heterocyclizations based on SHN methodology.[10–14]
Monoamine oxidase (MAO) is an enzyme of the outer
mitochondrial membrane that catalyzes the oxidative deamina-
tion of various neurotransmitters and dietary amines.[15] MAO
exists in two enzymatic forms, MAO-A and MAO-B, differ-
ing in their substrate specificity, sensitivity to inhibitors[16]
and amino acid sequence.[17,18] As pointed out by Carotti and
coworkers,[19] there has been a renewed interest in MAO since
the discovery that the neurotoxin 1-methyl-4-phenyl-1,2,3,6-
tetrahydropyridine (MPTP) causes the death of dopaminergic
neurons and induces symptoms very similar to Parkinson’s dis-
ease in humans.[20] In addition, the selective and reversible
inhibitors of MAO-A or MAO-B may be useful therapeu-
tic agents devoid of undesirable side-effects.[21] In humans,
MAO-B inhibitors (e.g. deprenyl) are useful in the treatment
of Parkinson’s disease,[22–24] whereas MAO-A inhibitors are
valuable antidepressant and anti-anxiety agents.[25–27] Carotti
and coworkers have demonstrated that the 3-arylpyrimido[4,5-
c]pyridazine-5,7(6H,8H)-diones 1–2 (Scheme 1) have MAO
inhibitory activity, and substituents on the diazine nucleus
modulate the inhibitory activity.[19]
NH
O
R
1 R ꢀ H
2 R ꢀ CF3
Scheme 1.
H
H
N
H
N
O
O
N
X
O
N
X
X
N
O
H
ꢁ
NH
NH
NH
Ar
Ar
Ar
O
O
OH
O
O
3 X
4 X
ꢀ
ꢀ
O
S
5 X
6 X
ꢀ
ꢀ
O
S
7
Scheme 2.
of barbituric acid 5 or thiobarbituric acid 6 with arylglyox-
als 7 (Scheme 2) in the presence of excess hydrazine hydrate,
and traces of pyridine. Previous methods of synthesis[19,28]
involve treating alloxan with acetophenones and hydrazine in
a two-step, one-pot sequence. The method reported in this paper
has the advantage of using barbituric or thiobarbituric acids
as reagents, possibly offering broader applications, offering
milder conditions for the formation of 3-arylpyrimido[4,5-c]
pyridazine-5,7(6H,8H)-diones and their sulfur analogues. Only
thesynthesisofcompounds 1–2hasbeenpreviouslyreported,[19]
and the yield of compound 1 herein reported (83%) is higher than
that (76%) reported previously.[19]
In view of the above, we report herein a novel mild
one-pot synthesis of new 3-aryl pyrimido[4,5-c]pyridazine-
5,7(6H,8H)-diones 3 and the corresponding 5-oxo-7-thioxo-6,8-
dihydropyrimido[4,5-c]pyridazin-5(6H)-ones 4 by condensation
Results and Discussion
The arylglyoxals 7a–h were prepared from commercially avail-
able acetophenones 8a–h as outlined in Scheme 3.[29]
© CSIRO 2010
10.1071/CH09569
0004-9425/10/030507

508
M. Rimaz et al.
The reactions were performed by adding arylglyoxals 7a–h
Conclusion
to the mixture of barbituric acid 5 or thiobarbituric acid 6 and a
catalytic amount of pyridine in water at room temperature in the
presence of excess hydrazine hydrate (Scheme 4). In the absence
of pyridine, yields were uniformly lower, being contaminated by
hydrazone products before purification. For example, with 4-
fluorophenylglyoxal, the yield of 11 in the absence of pyridine
was 80% (91% with pyridine) and with phenylglyoxal, the yield
of 16 in the absence of pyridine was 62% (93% with pyridine).
In the case of arylglyoxals 7e–h, in the presence of pyridine,
the desired pyrimidopyridazines 12–15 and their sulfur ana-
logues 20–23 were obtained in moderate to good yields 43–83%
(Scheme 4), whereas in the absence of pyridine, the products
were chiefly the corresponding mono-hydrazones 26–29 in high
yields and both barbituric and thiobarbituric acids were mainly
recovered (Scheme 5). We believe that the presence of pyridine
increases the proportion of the barbituric (thiobarbituric) acid
enolate, necessary for reaction with the glyoxal.
As shown in Scheme 4, most of the derivatives exist solely
as the lactam tautomers, but two of the thio compounds were
isolated as a mixture of both lactam 17–18 and lactim 24–25
tautomers. The structures of the products follow simply from
consideration of the 1H NMR data, which are consistent with that
of analogues previously published by Carotti and coworkers.[28]
In particular, the singlet around δ 8.6 in the diones, δ 8.5 in the
thione, and δ 7.6 in the enol tautomers, was diagnostic of H-4 in
the newly formed pyridazine ring.
The procedure outlined provides a very straightforward
route to various 3-aryl substituted pyrimido[4,5-c]pyridazine-
5,7(6H,8H)-diones and 7-thioxo-7,8-dihydropyrimido[4,5-c]
pyridazin-5(6H)-ones. The compounds are currently being
assessed as potential MAO inhibitors.
Experimental
General Procedures
Melting points were determined on a Philip Harris C4954718
apparatus and are uncorrected. Infrared spectra were recorded
on aThermonicolet (Nexus 670) Fourier transform (FT) infrared
spectrometer, using sodium chloride cells and measured as film
or KBr discs. 1H (300 MHz) and 13C (75.5 MHz) NMR spectra
were recorded on a Bruker 300 spectrometer in [D6]DMSO
usingTMS as the internal reference. Mass spectra were recorded
on a Varian Matt 311 spectrometer and relative abundances
of fragments are quoted in parentheses after the m/z values.
Microanalyses were performed on a Leco Analyzer 932.
General Procedure for the Synthesis of 3-Arylpyrimido
[4,5-c]pyridazine-5,7(6H,8H)-diones and their Sulfur
Analogues
To a mixture of barbituric acid or thiobarbituric acid (1 mmol)
and arylglyoxal (1 mmol) in water (10 mL), was added pyri-
dine (two drops) at room temperature. The resultant mixture was
stirred for 20 min. After the appropriate time, hydrazine hydrate
was added to the reaction mixture and it was stirred until further
precipitation of product ceased. The product was then collected,
washed with water (3 × 10 mL), and purified by recrystallization
from methanol.
The proposed mechanism of the reaction involves the initial
aldol condensation and subsequent dehydration reaction of 5
with the phenylglyoxal 7a as shown in Scheme 6, followed by
reaction of the intermediate 30 with hydrazine, leading to the
formation of the pyridazine ring after dehydration.
3-Phenylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-dione (1):
pink solid, 83%, mp 271◦C (dec.) (Found C 60.14, H 3.42, N
23.23%. C12H8N4O2 requires C 60.00, H 3.36, N 23.32%).[19]
δH 14.24 (1H, bs), 11.38 (1H, s), 8.60 (1H, s), 7.91 (2H, dt, J1
7.5, J2 1.8), 7.48–7.55 (3H, m). δC 126.3, 128.5, 129.5, 130.2,
133.2, 134.3, 145.8, 153.1, 160.7, 162.8. νmax(KBr)/cm−1 3387,
3123, 1701, 1645, 1580, 1496, 1373, 799, 621, 602. m/z [%]: 241
([M+ + 1], 100), 240 ([M+], 4), 213 (18), 199 (30), 187 (25),
172 (25), 158 (20), 115 (42), 77 (26).
3-(4-Bromophenyl)pyrimido[4,5-c]pyridazine-5,7(6H,
8H)-dione (9): white solid, 78%, mp 256◦C (dec.) (Found C
45.27, H 2.25, N 17.43%. C12H7BrN4O2 requires C 45.17, H
2.21, N 17.56%). δH 14.28 (1H, bs), 11.36 (1H, s), 8.60 (1H, s),
7.88 (2H, d, J 8.7), 7.71 (2H, d, J 8.7). δC 123.7, 128.4, 128.6,
O
SeO2
H
Ar
Ar
Dioxane/water
Reflux 3–4 h
63–85%
O
O
8a Ar ꢀ C6H5
7a Ar ꢀ C6H5
7b Ar ꢀ 4-BrC6H4
7c Ar ꢀ 4-ClC6H4
7d Ar ꢀ 4-FC6H4
7e Ar ꢀ 4-MeOC6H4
7f Ar ꢀ 4-NO2C6H4
7g Ar ꢀ 3,4-(MeO)2C6H3
7h Ar ꢀ 3,4-(OCH2O)C6H3
8b Ar ꢀ 4-BrC6H4
8c Ar ꢀ 4-ClC6H4
8d Ar ꢀ 4-FC6H4
8e Ar ꢀ 4-MeOC6H4
8f Ar ꢀ 4-NO2C6H4
8g Ar ꢀ 3,4-(MeO)2C6H3
8h Ar ꢀ 3,4-(OCH2O)C6H3
Scheme 3.
O
H
N
N
X
Pyridine/H2O
N
N
SH
N
NH
N
ꢁ
7a–h
ꢁ
NH
NH2NH2/rt
45–60 min
43–93%
N
Ar
O
N
H
X
Ar
O
OH
24–25
5 X ꢀ O
6 X ꢀ S
1, 9–23
1 X ꢀ O, Ar ꢀ C6H5 (83%)
16 X ꢀ S, Ar ꢀ C6H5 (93%)
9 X ꢀ O, Ar ꢀ 4-BrC6H4 (78%)
10 X ꢀ O, Ar ꢀ 4-ClC6H4 (80%)
11 X ꢀ O, Ar ꢀ 4-FC6H4 (91%)
12 X ꢀ O, Ar ꢀ 4-MeOC6H4 (77%)
13 X ꢀ O, Ar ꢀ 4-NO2C6H4 (43%)
14 X ꢀ O, Ar ꢀ 3,4-(MeO)2C6H3 (81%)
15 X ꢀ O, Ar ꢀ 3,4-(OCH2O)C6H3 (78%)
17 X ꢀ S, Ar ꢀ 4-BrC6H4 (total yield of 17 ꢁ 24, 74%)
18 X ꢀ S, Ar ꢀ 4-ClC6H4 (total yield of 18 ꢁ 25, 65%)
19 X ꢀ S, Ar ꢀ 4-FC6H4 (77%)
20 X ꢀ S, Ar ꢀ 4-MeOC6H4 (73%)
21 X ꢀ S, Ar ꢀ 4-NO2C6H4 (46%)
22 X ꢀ S, Ar ꢀ 3,4-(MeO)2C6H3 (83%)
23 X ꢀ S, Ar ꢀ 3,4-(OCH2O)C6H3 (70%)
Scheme 4.

Synthesis of 3-Arylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-diones
509
O
O
O
NH2NH2/H2O
rt, 10–20 min
NH
NH
NNH2
7e–h ꢁ
ꢁ
Ar
O
N
H
X
O
N
X
H
26–29 (82–92%)
5–6
5–6
26 Ar ꢀ 4-(MeO)C6H4
27 Ar ꢀ 4-(NO2)C6H4
28 Ar ꢀ 3,4-(MeO)2C6H3
29 Ar ꢀ 3,4-(OCH2O)C6H3
Scheme 5.
140.2, 143.8, 148.3, 150.7, 160.7, 162.7. νmax(KBr)/cm−1 3414,
3288, 2943, 2901, 1694, 1654, 1566, 1517, 1496, 1368, 1350,
1234, 1098, 861, 609.
O
H
N
O
O
HO
HN
O
O
HN
O
O
O
NH
O
7a
O
3-(3,4-Dimethoxyphenyl)pyrimido[4,5-c]pyridazine-5,7
(6H,8H)-dione (14): yellow solid, 81%, mp 283◦C (dec.)
(Found C 56.12, H 4.10, N 18.50%. C14H12N4O4 requires C
56.00, H 4.03, N 18.66%). δH 14.09 (1H, bs), 11.43 (1H, s),
8.59 (1H, s), 7.48 (1H, dd, J1 8.4, J2 1.5), 7.44 (1H, d, J 1.8),
7.06 (1H, d, J 8.1), 3.82 (3H, s), 3.80 (3H, s). δC 56.0, 56.1,
109.2, 112.3, 119.4, 126.8, 133.1, 145.7, 149.6, 150.8, 153.1,
160.6, 163.0. νmax(KBr)/cm−1 3388, 3226, 2998, 1717, 1697,
1633, 1578, 1504, 1422, 1363, 1296, 1258, 1216, 1158, 1022,
801, 603, 523.
NH
H
O
NH
Pyridine
ꢂH2O
5
30
H
OH
H
N
H
N
N
O
N
O
N
N
NH2NH2
NH
ꢂ2H2O
NH
OH
O
O
1
Scheme 6.
3-(Benzo[d][1,3]dioxol-5-yl)pyrimido[4,5-c]pyridazine-5,7
(6H,8H)-dione(15):yellowsolid, 78%, mp282◦C(dec.)(Found
C 55.00, H 2.87, N 19.60%. C13H8N4O4 requires C 54.93, H
2.84, N 19.71%). δH 14.11 (1H, bs), 11.40 (1H, s), 8.53 (1H,
s), 7.41–7.44 (2H, m), 7.03 (1H, d, J 8.7), 6.1 (2H, s). δC 102.1,
106.2, 109.1, 121.1, 128.3, 128.4, 133.1, 145.5, 148.6, 149.1,
153.1, 160.6, 162.9. νmax(KBr)/cm−1 3402, 3199, 2900, 1701,
1649, 1595, 1501, 1446, 1374, 1229, 1038, 617, 555.
3-Phenyl-7-thioxo-7,8-dihydropyrimido[4,5-c]pyridazin-
5(6H)-one(16):paleyellowsolid, 93%, mp240◦C(dec.)(Found
C 56.33, H 3.20, N 21.94%. C12H8N4OS requires C 56.24, H
3.15, N 21.86%). δH 13.92 (1H, bs), 10.47 (1H, s), 8.49 (1H,
s), 7.88 (2H, dt, J1 7.2, J2 1.2), 7.47–7.51 (3H, m). δC 126.2,
128.3, 129.5, 130.0, 131.0, 134.6, 145.6, 159.9, 160.6, 163.5.
νmax(KBr)/cm−1 3353, 3152, 3065, 1692, 1661, 1577, 1532,
1217, 699, 601. m/z [%]: 256 ([M+], 20), 230 (100), 199 (90),
172 (94), 143 (33), 115 (43), 100 (39), 77 (42).
Mixture of 3-(4-bromophenyl)-7-thioxo-7,8-dihydro-
pyrimido [4,5-c]pyridazin-5(6H)-one (17) and 3-(4-bromo-
phenyl)-7-mercaptopyrimido[4,5-c]pyridazin-5-ol(24):beige
solid, 74%, mp 235◦C (dec.) (Found C 43.15, H 2.20, N 16.80%.
C12H7BrN4OS requires C 43.00, H 2.11, N 16.72%). δH 13.89
(1H, bs), 10.45 (1H, s), 8.69 (1H, s), 8.48 (1H in one tautomer, s),
7.85 (2H in one tautomer, d, J 8.4), 7.78 (2H in other tautomer, d,
J 8.4), 7.69 (2H in one tautomer, d, J 8.4), 7.64 (2H in other tau-
tomer, d, J 8.4), 7.44 (1H in other tautomer, s). δC 121.6, 123.5,
125.7, 128.4, 129.6, 130.2, 130.9, 131.3, 131.7, 132.2, 132.4,
133.8, 137.2, 144.6, 159.8, 160.5, 188.9. νmax(KBr)/cm−1 3364,
3172, 3032, 1681, 1644, 1596, 1493, 1399, 1218, 1011, 830, 754,
592. m/z [%]: 337 ([M+ + 2], 1), 335 ([M+], 1), 310 (98), 308
(100), 279 (39), 277 (39), 252 (50), 250 (50), 223 (20), 221 (22),
183 (24), 142 (25), 113 (29), 57 (33), 43 (30).
132.4, 133.0, 133.5, 144.8, 153.1, 160.7, 162.8. νmax(KBr)/cm−1
3417, 3122, 1723, 1701, 1649, 1594, 1570, 1492, 1396, 1371,
1244, 823, 798, 752, 620. m/z [%]: 321 ([M+ + 2], 100), 319
([M+], 98), 295 (42), 241 (36), 227 (34), 183 (46), 115 (43), 97
(42), 83 (65), 57 (72), 43 (79).
3-(4-Chlorophenyl)pyrimido[4,5-c]pyridazine-5,7(6H,
8H)-dione (10): beige solid, 80%, mp 264◦C (dec.) (Found C
52.42, H 2.65, N 20.51%. C12H7ClN4O2 requires C 52.47, H
2.57, N 20.40%). δH 14.27 (1H, bs), 11.35 (1H, s), 8.59 (1H, s),
7.94 (2H, d, J 8.7), 7.56 (2H, d, J 8.4). δC 128.2, 128.5, 129.5,
133.0, 133.1, 135.0, 144.7, 153.1, 160.7, 162.8. νmax(KBr)/cm−1
3426, 3230, 3085, 1695, 1654, 1566, 1494, 1370, 1089, 836, 799,
606, 477. m/z [%]: 277 ([M+ + 2], 50), 275 ([M+], 100), 251
(33), 249 (100), 206 (39), 176 (18), 164 (17), 149 (50), 136 (68),
115 (65), 75 (40), 44 (47).
3-(4-Fluorophenyl)pyrimido[4,5-c]pyridazine-5,7(6H,8H)-
dione (11): white solid, 91%, mp 257◦C (dec.) (Found C 55.87,
H 2.79, N 21.59%. C12H7FN4O2 requires C 55.82, H 2.73, N
21.70%). δH 14.22 (1H, bs), 11.37, (1H, s), 8.58 (1H, s), 7.94–
7.98 (2H, m), 7.30–7.36 (2H, m). δC 116.3, 116.6, 128.5, 128.7,
128.8, 130.8, 130.9, 133.2, 145.0, 153.1, 160.6, 161.8, 162.8,
165.1. νmax(KBr)/cm−1 3422, 3122, 3044, 1696, 1654, 1566,
1508, 1371, 1232, 1162, 843, 610, 546. m/z [%]: 259 ([M+ + 1],
100), 233 (33), 217 (23), 190 (22), 133 (41), 120 (30).
3-(4-Methoxyphenyl)pyrimido[4,5-c]pyridazine-5,7(6H,
8H)-dione (12): beige solid, 77%, mp 258◦C (dec.) (Found C
57.87, H 3.77, N 20.66%. C13H10N4O3 requires C 57.78, H
3.73, N 20.73%). δH 14.08 (1H, bs), 11.44 (1H, s), 8.55 (1H, s),
7.85 (2H, d, J 9.0), 7.05 (2H, d, J 9.0), 3.80 (3H, s). δC 55.7,
114.9, 126.7, 127.8, 128.4, 132.9, 145.6, 153.1, 160.6, 161.0,
162.9. νmax(KBr)/cm−1 3403, 3155, 2837, 1691, 1648, 1600,
1580, 1501, 1461, 1382, 1259, 1180, 1099, 831, 621, 561.
3-(4-Nitrophenyl)pyrimido[4,5-c]pyridazine-5,7(6H,8H)-
dione (13): cream solid, 43%, mp 331◦C (dec.) (Found C 50.60,
H 2.51, N 24.45%. C12H7N5O4 requires C 50.53, H 2.47, N
24.55%). δH 14.45 (1H, bs), 11.27 (1H, s), 8.68 (1H, s), 8.32
(2H, d, J 8.7), 8.18 (2H, d, J 8.7). δC 124.6, 127.6, 128.2, 130.7,
Mixture of 3-(4-chlorophenyl)-7-thioxo-7,8-dihydro-
pyrimido[4,5-c]pyridazin-5(6H)-one (18) and 3-(4-chloro-
phenyl)-7-mercaptopyrimido[4,5-c]pyridazin-5-ol(25):white
solid, 65%, mp 315◦C (dec.) (Found C 49.65, H 2.50, N 19.15%.
C12H7ClN4OS requires C 49.57, H 2.43, N 19.27%). δH 13.88
(1H, bs), 10.44 (1H, s), 8.49 (1H in one tautomer, s), 8.47 (1H in

510
M. Rimaz et al.
other tautomer, s), 7.93 (2H in one tautomer, d, J 8.4), 7.90 (2H in
other tautomer, d, J 8.4), 7.56 (2H in one tautomer, d, J 8.4), 7.53
(2H in other tautomer, d, J 8.4). δC 128.1, 129.5, 129.6, 130.9,
131.5, 133.4, 134.8, 144.5, 159.8, 160.5. νmax(KBr)/cm−1 3170,
3033, 1682, 1591, 1528, 1496, 1404, 1090, 1015, 832, 593. m/z
[%]: 292 ([M+ + 2], 2), 290 ([M+], 7), 266 (71), 264 (100), 235
(28), 233 (76), 208 (32), 206 (94), 177 (33), 149 (25), 137 (31),
113 (26).
References
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1996, 127, 739. doi:10.1007/BF00817265
[2] T. Numata, T. Ogura, K. Hirat, M. Kudo, Jpn Kokai Tokyo Koho Jp
1989, 63, 159.
[3] H. Yoshioka, T. Obato, K. Fujii, Y. Fukuda, A. Ooka, Eur. Pat. Appl.
Ep. 1989, 283, 271.
[4] G. Matolesy, World Rev Pest Contr 1971, 10, 50 [Chem. Abstr. 1972,
76, 820315].
3-(4-Fluorophenyl)-7-thioxo-7,8-dihydropyrimido[4,5-c]
pyridazin-5(6H)-one (19): cream solid, 77%, mp 278◦C (dec.)
(Found C 52.65, H 2.65, N 20.31%. C12H7FN4OS requires C
52.55, H 2.57, N 20.43%). δH 13.92 (1H, bs), 10.46 (1H, s),
8.48 (1H, s), 7.93–7.98 (2H, m), 7.30–7.36 (2H, m). δC 116.2,
116.5, 128.6, 128.7, 129.6, 131.1, 131.2, 144.8, 159.8, 160.4,
161.7, 165.0. νmax(KBr)/cm−1 3224, 3105, 3055, 1701, 1601,
1514, 1460, 1244, 1159, 921, 837, 551. m/z [%]: 275 ([M+ + 1],
100), 248 (73), 233 (28), 217 (28), 190 (41), 149 (35), 121 (34),
57 (34), 43 (34).
3-(4-Methoxyphenyl)-7-thioxo-7,8-dihydropyrimido[4,5-c]
pyridazin-5(6H)-one (20): pale green solid, 73%, mp 243◦C
(dec.) (Found C 54.58, H 3.55, N 19.62%. C13H10N4O2S
requires C 54.54, H 3.52, N 19.57%). δH 13.83 (1H, bs), 10.50
(1H, s), 8.45 (1H, s), 7.84 (2H, d, J 9.0), 7.05 (2H, d, J 9.0), 3.80
(3H, s). δC 55.7, 114.9, 127.0, 127.7, 128.4, 129.4, 130.9, 145.4,
160.0, 160.4, 160.8. νmax(KBr)/cm−1 3423, 3321, 3016, 2935,
2841, 1689, 1669, 1637, 1609, 1589, 1577, 1514, 1253, 1176,
1022, 831, 566.
3-(4-Nitrophenyl)-7-thioxo-7,8-dihydropyrimido[4,5-c]
pyridazin-5(6H)-one (21): beige solid, 46%, mp 362◦C (dec.)
(Found C 47.80, H 2.37, N 23.32%. C12H7N5O3S requires C
47.84, H 2.34, N 23.25%). δH 14.13 (1H, bs), 10.41 (1H, s),
8.58 (1H, s), 8.33 (2H, d, J 8.7), 8.18 (2H, d, J 8.7). δC 124.6,
127.5, 127.6, 129.6, 131.1, 140.6, 143.7, 148.2, 159.7, 160.5.
νmax(KBr)/cm−1 3414, 3288, 2943, 2901, 1694, 1654, 1566,
1517, 1496, 1368, 1350, 1234, 1098, 861, 609.
3-(3,4-Dimethoxyphenyl)-7-thioxo-7,8-dihydropyrimido
[4,5-c]pyridazin-5(6H)-one (22): pale yellow solid, 83%, mp
254◦C (dec.) (Found C 53.26, H 3.89, N 17.58%. C14H12N4O3S
requires C 53.16, H 3.82, N 17.71%). δH 13.83 (1H, bs), 10.49
(1H, s), 8.47 (1H, s), 7.43–7.46 (2H, m), 7.05 (1H, d, J 8.4), 3.82
(3H, s), 3.80 (3H, s). δC 56.0, 56.1, 109.1, 112.2, 119.3, 127.1,
129.4, 131.0, 145.5, 149.5, 150.6, 160.0, 160.4. νmax(KBr)/cm−1
3319, 3251, 2996, 2937, 1682, 1638, 1584, 1519, 1466, 1382,
1266, 1228, 1137, 1020, 845, 597.
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3-(Benzo[d][1,3]dioxol-5-yl)-7-thioxo-7,8-dihydropyrimido
[4,5-c]pyridazin-5(6H)-one (23): pale green solid, 70%, mp
262◦C (dec.) (Found C 52.09, H 2.76, N 18.53%. C13H8N4O3S
requires C 52.00, H 2.69, N 18.66%). δH 13.82 (1H, bs), 10.46
(1H, s), 8.42 (1H, s), 7.38–7.41 (2H, m), 7.02 (1H, d, J 8.7),
6.09 (2H, s). δC 102.0, 106.2, 109.0, 120.8, 128.7, 129.4, 131.1,
145.3, 148.6, 149.0, 159.9, 160.4. νmax(KBr)/cm−1 3317, 3238,
3058, 2917, 1685, 1663, 1572, 1508, 1491, 1443, 1254, 1231,
1033, 886, 556.
2-Hydrazono-1-(4-methoxyphenyl)ethanone (26): white
solid, 92%, mp 130–131◦C. δH 8.09 (2H, d, J 9.0), 7.57 (1H,
s), 6.94 (2H, d, J 9.0), 6.35 (2H, s). δC 55.4, 113.4, 114.0, 129.5,
130.2, 138.3, 163.1, 188.2. νmax(KBr)/cm−1 3369, 3180, 1641,
1595, 1490, 1307, 1265, 1228, 1166, 1023, 834, 761, 608.
Acknowledgements
The authors express their thanks to Urmia University for financial support.