Novel one-pot synthesis for 2,5-diaryl and 5-Aryl-pyridazin-3(2H)-ones

Article abstract of DOI:10.1080/00397911.2010.515330

A novel method for the synthesis of 2-phenyl-5-(o-hydroxyphenyl)-pyridazin- 3(2H)-ones and 5-(o-hydroxyphenyl)-pyridazin-3(2H)-ones has been found during the reaction of 4-bromomethylcoumarins with phenylhydrazine and hydrazinehydrate, respectively, under

Full text of DOI:10.1080/00397911.2010.515330

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Novel One-Pot Synthesis for 2,5-Diaryl
and 5-Aryl-pyridazin-3(2H)-ones
Mahantesha Basanagouda a & Manohar V. Kulkarni a
a P. G. Department of Chemistry, Karnatak University, Dharwad,
Karnataka, India
Version of record first published: 29 Jun 2011.
To cite this article: Mahantesha Basanagouda & Manohar V. Kulkarni (2011): Novel One-Pot Synthesis
for 2,5-Diaryl and 5-Aryl-pyridazin-3(2H)-ones, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 41:17, 2569-2582
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Synthetic Communications1, 41: 2569–2582, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.515330
NOVEL ONE-POT SYNTHESIS FOR 2,5-DIARYL AND
5-ARYL-PYRIDAZIN-3(2H)-ONES
Mahantesha Basanagouda and Manohar V. Kulkarni
P. G. Department of Chemistry, Karnatak University, Dharwad,
Karnataka, India
GRAPHICAL ABSTRACT
Abstract A novel method for the synthesis of 2-phenyl-5-(o-hydroxyphenyl)-pyridazin-
3(2H)-ones and 5-(o-hydroxyphenyl)-pyridazin-3(2H)-ones has been found during
the reaction of 4-bromomethylcoumarins with phenylhydrazine and hydrazinehydrate,
respectively, under controlled alkaline conditions.
Keywords Coumarin; diphenyl; heterocycle; hydrazinehydrate; phenylhydrazine;
pyridazinone
INTRODUCTION
Pyridazine is an electron-deficient heterocyclic system isosteric with benzene
and other six-membered heterocycles. Derivatives of pyridazine have gained con-
siderable importance in the fields of medicine and agriculture.[1,2] Among the func-
tionalized pyridazines, the pyridazin-3(2H)-one moiety has been found to be a
part of clinically accepted cardiovascular[3,4] and anti-inflammatory[5–7] drugs. The
importance of pyridazin-3(2H)-ones in agriculture is best exemplified by established
weedicidal and muticidal agents such as chloridazon and pyridaben (Fig. 1).[8,9]
Earlier approaches to the pyridazine skeleton make use of 1,4-diketonyl com-
pounds and derivatives of hydrazine[10] to obtain a variety of functionalized pyrida-
zines. Introduction of the aryl moiety on the carbon skeleton in pyridazine has been
a challenge, which has been met by a variety of coupling reactions involving the use
of arylboronic acids, palladium complexes, and organotin compounds. It has been
the subject of an extensive review.[9,11] In addition to the stringent experimental
Received February 9, 2010.
Address correspondence to Manohar V. Kulkarni, P. G. Department of Chemistry, Karnatak
University, Dharwad 580 003, Karnataka, India. E-mail: manohar274@gmail.com
2569

2570
M. BASANAGOUDA AND M. V. KULKARNI
Figure 1. Structures of chloridazon and pyridaben.
conditions, all these methods of introduction of the aryl moiety require a preformed
pyridazine, preferentially a chloro pyridazine.
Recently we have reported the formation of 5-(o-hydroxyphenyl)-pyridazin-
3(2H)-ones from 4-bromomethylcoumarins, facilitating the introduction of a func-
tionalized aryl moiety at C-5 position in a single step.[12] In the present article, we
have found that in the presence of anhydrous potassium carbonate, phenylhydrazine
also reacts with 4-bromomethylcoumarins to yield 2,5-diaryl-pyridazin-3(2H)-ones.
Our earlier methodology of using hydrazinehydrate has been extended to other func-
tionalized bromomethylcoumarins, showing that 4-bromomethylcoumarins are good
synthons to introduce aryl groups on the pyridazine ring.
RESULTS AND DISCUSSION
The required substituted 4-bromomethylcoumarins[13] 1 were prepared by the
Pechmann cyclization of substituted phenols with 4-bromoethylacetoacetate[14] using
sulfuric acid as the condensing agent.
Initially, we extended our earlier method for the synthesis of 5-(o-hydroxy
phenyl)-pyridazin-3(2H)-ones from 4-bromomethylcoumarins by synthesizing newer
compounds (Table 1).[12] It was then thought to explore this method to synthesize
diaryl-pyridazin-3(2H)-ones by modifying the procedure (Scheme 1). We examined
the optimum reaction conditions for the reaction with 6-methyl-4-bromomethylcou-
marin 1h, and the results are summarized in Table 2. With 1 equivalent of K2CO3,
conversion of starting material 1h was the best (Table 2, entry 6). As a part of
ongoing efforts to synthesize 2-phenyl-5-aryl-pyridazin-3(2H)-ones, we have
attempted the reaction with 6-methyl-4-bromomethylcoumarin 1h and phenylhydra-
zine 4 as a model system. We first envisioned reaction conditions without any addi-
tives or catalyst; however, refluxing the equimolar amounts of starting materials 1h
and 4 in ethanol did not result in the formation of desired product 5h as monitored
by thin-layer chromatography (TLC) even after 24 h and longer (Table 2, entry 1).
Then we increased the amount of 4 in 2 and 5 equivalents refluxed for 8–24 h, which
resulted in formation of product 5h in 5% and 9% respectively (Table 2, entries 2
and 3). Increasing amounts of K2CO3 (0.25 equivalent) and (0.50 equivalent) as a
base increased the yields of the product 5h to 12% and 30% respectively (Table 2,
entries 4 and 5). With 1 equivalent of K2CO3, conversion of starting material 1h
and 4 took place quantitatively within 3 h. Product 5h was isolated after workup

SYNTHESIS OF ARYL-PYRIDAZIN-3(2H)-ONES
2571
Table 1. Synthesis of 5-aryl substituted pyridazin-3(2H)-ones 3a–g
Entry
Substrate
Product
Yield (%)
Melting point (ꢀC)
1
71
244
204
2
3
4
69
72
68
255
198
5
6
7
71
65
63
191
216
206
in 75% yield (Table 2, entry 6). This result could not be improved with more K2CO3
(2 equivalents gave 74% yield). Having established the optimized reaction conditions,
a series of 2,5-diaryl-pyridazin-3(2H)-ones 5a–o were synthesized in good to excellent
yields, and the results are shown in Table 3. The electron-donating and

2572
M. BASANAGOUDA AND M. V. KULKARNI
Scheme 1. Synthesis of phenyl pyridazin-3(2H)-ones 3 and 5.
Table 2. Optimization of the reaction conditions for the synthesis of 5h
Entry
Phenylhydrazine
K2CO3
Time (h)
Yield (%)
1
2
3
4
5
6
1 equivalent
2 equivalents
5 equivalents
5 equivalents
5 equivalents
5 equivalents
—
—
24
8
—
5
—
8
9
0.25 equivalent
0.50 equivalent
1.00 equivalent
8
12
30
75
8
3
electron-withdrawing substituents on the coumarin ring did not profoundly affect
the efficiency of the reactions. In the case of strong electron-withdrawing groups,
such as a nitro group, somewhat lower yields were obtained (Table 3, entry 7).
The plausible mechanism for this conversion resembles that already reported
by our laboratory (Scheme 2).[12] The nucleophilic attack of phenyl hydrazine on
the lactone carbonyl and the C-4 methylene on 4-bromomethylcoumarins 1 is
equally probable, because excess of this reagent is employed and would produce a
hydrazino hydrazide B. The support for the initial allylic substitution product is
from our earlier observation that this reaction in acetic acid leads to the N-acetylated
product of the intermediate A, which has been isolated and characterized.[12] Hydra-
zine hydrate and other double nucleophiles such as amidines and thiourea are known
to bring about similar ring opening of coumarins, which have resulted in the forma-
tion of o-hydroxyphenyl substituted pyrazoles[15] and pyrimidines.[16] Further, an
intramolecular nucleophilic attack of the phenyl hydrazine on the carbonyl group
of the hydrazide followed by the expulsion of phenyl hydrazine results in the inter-
mediates C, which undergo in situ dehydrogenation to give pyridazinones 5.
Intramolecular expulsion of acetic acid hydrazide has been proposed in the for-
mation of 3-hydrazinopyridazinones.[17] The driving force for this nucleophilic sub-
stitution, followed by ring opening and ring closure (SNRORC), seems to be the
stability of the aromatic pyridazinones. Numbering of 3 and 5 are given in Scheme 3.
EXPERIMENTAL
Materials
All the starting materials and reagents were purchased from commercial sup-
pliers and used after further purification. Thin-layer chromatography (TLC) was

SYNTHESIS OF ARYL-PYRIDAZIN-3(2H)-ONES
2573
Table 3. Synthesis of 2,5-diaryl substituted pyridazin-3(2H)-ones 5a–o
Entry
Substrate
Product
Yield (%)
Melting point (ꢀC)
1
71
201
2
3
4
73
75
76
195
212
184
5
6
7
76
70
66
188
208
170
(Continued )

2574
M. BASANAGOUDA AND M. V. KULKARNI
Table 3. Continued
Entry
Substrate
Product
Yield (%)
Melting point (ꢀC)
8
9
75
74
78
72
226
244
224
169
10
11
12
71
270
13
14
15
70
68
71
237
192
258

SYNTHESIS OF ARYL-PYRIDAZIN-3(2H)-ONES
2575
Scheme 2. Plausible mechanism for the formation of 2,5-diaryl-pyridazin-3(2H)ones 5 from coumarins.
carried out on silica-gel plates obtained from Merck (Germany). The melting
points were determined by using a Shital melting-point apparatus and are uncor-
rected. All the compounds were analyzed satisfactorily for C, H, and N. Infrared
(IR) spectra (KBr disc) were recorded on a Nicolet-5700 Fourier transform (FT)–IR
Scheme 3. Numbering of 3 and 5.

2576
M. BASANAGOUDA AND M. V. KULKARNI
1
spectrophotometer. H and 13C NMR spectra were recorded on Bruker 300- and
400-MHz spectrometer using CDCl3 as a solvent and tetramethylsilane (TMS) as
an internal standard. The chemical shifts are expressed in d ppm scale downfield
from TMS, and proton signals are indicated as s, singlet; d, doublet; t, triplet; and
m, multiplet. Autospec electron-impact mass spectrometer (70 ev) was used to record
mass spectra.
General Procedure for Synthesis of 5-Aryl-pyridazin-3(2H)-ones
(3a–g)
A mixture of subtituted-4-bromomethylcoumarin 1 (10 mmol) was refluxed
with hydrazine hydrate 2 (99%) (50 mmol) in ethanol (10 mL) for 2 h. The reaction
mixture was cooled and poured on ice-cold water, and the separated solid 3 was fil-
tered off. It was washed several times with cold ethanol, dried, and recrystallized
from a suitable solvent.
Selected Data
5-(2-Hydroxy-phenyl)-pyridazin-3ꢁ(21H)-one (3a). Colorless solid (ethanol),
mp 244 ꢀC, yield 71%; IR (KBr, t in cm ): 3210 (br), 1655 (pyridazinone C O);
=
1H NMR (400 MHz, DMSO): d 6.25 (s, 1H, C4-H of pyridazinone), 6.74–7.96 (m,
4H, Ar-H), 8.05 (s, 1H, C6-H of pyridazinone), 10.25 (s, 1H, NH, D2O exchange-
able), 12.60 (s, 1H, OH, D2O exchangeable). Anal. calc. for C10H8N2O2: C, 63.82;
H, 4.28; N, 14.89. Found: C, 63.71; H, 4.20; N, 14.82.
5-(2,4-Dihydroxy-phenyl)-pyridazin-3(2H)-one (3b). Colorless solid (etha-
nol), mp 204 ꢀC, yield 69%; IR (KBr, t in cmꢁ1): 3232 (br), 1645 (pyridazinone
1
=
C O); H NMR (400 MHz, DMSO): d 6.49 (s, 1H, C4-H of pyridazinone), 6.80
(s, 1H, C30-H), 6.94 (d, 1H, J ¼ 7.34 Hz, C50-H), 7.42 (d, 1H, J ¼ 7.56 Hz, C60-H),
8.09 (s, 1H, C6-H of pyridazinone), 10.30 (s, 1H, OH, D2O exchangeable), 10.92
(s, 1H, OH, D2O exchangeable). Anal. calc. for C10H8N2O3: C, 58.82; H, 3.95; N,
13.72. Found: C, 58.87; H, 4.03; N, 13.81.
5-(2-Hydroxy-4-methoxy-phenyl)-pyridazin-3(2H)-one
(3c). Colorless
solid (ethanol), mp 255 ꢀC, yield 72%; IR (KBr, t in cmꢁ1): 3129 (br), 1652 (pyrida-
1
=
zinone C O); H NMR (400 MHz, DMSO): d 3.74 (s, 3H, OCH3), 6.52 (m, 2H,
C4-H of pyridazinone and C30-H), 6.91 (d, 1H, J ¼ 7.38 Hz, C50-H), 7.37 (d, 1H,
J ¼ 7.60 Hz, C60-H), 8.11 (s, 1H, C6-H of pyridazinone), 10.27 (s, 1H, NH, D2O
exchangeable), 12.84 (s, 1H, OH, D2O exchangeable). 13C NMR (100 MHz, DMSO):
55.32, 113.42, 119.34, 121.63, 128.75, 130.21, 132.29, 148.57, 155.63, 156.31, 161.14;
LCMS m=z: 219 [M þ 1]. Anal. calc. for C11H10N2O3: C, 60.55; H, 4.62; N, 12.84.
Found: C, 60.48; H, 4.70; N, 12.78.
5-(2-Hydroxy-4,6-dimethyl-phenyl)-pyridazin-3(2H)-one (3d). Colorless
solid (ethanol), mp 198 ꢀC, yield 68%; IR (KBr, t in cmꢁ1): 3188 (br), 1664 (pyrida-
1
=
zinone C O); H NMR (400 MHz, DMSO): d 2.25 (s, 3H, CH3), 2.29 (s, 3H, CH3),
6.16 (s, 1H, C4-H of pyridazinone), 6.55 (s, 1H, C30-H), 6.68 (s, 1H, C50-H), 8.00 (s,
1H, C6-H of pyridazinone), 10.22 (s, 1H, NH, D2O exchangeable), 12.36 (s, 1H, OH,

SYNTHESIS OF ARYL-PYRIDAZIN-3(2H)-ONES
2577
D2O exchangeable). Anal. calc. for C12H12N2O2: C, 66.65; H, 5.59; N, 12.96. Found:
C, 66.56; H, 5.70; N, 12.79.
5-(2-Hydroxy-3,4-dimethyl-phenyl)-pyridazin-3(2H)-one (3e). Colorless
solid (ethanol), mp 191 ꢀC, yield 71%; IR (KBr, t in cmꢁ1): 3185 (br), 1659 (pyrida-
1
=
zinone C O); H NMR (400 MHz, DMSO): d 2.35 (s, 3H, CH3), 2.40 (s, 3H, CH3),
6.31 (s, 1H, C4-H of pyridazinone), 7.18 (d, 1H, J ¼ 7.41 Hz, C50-H), 7.49 (d, 1H,
J ¼ 7.78 Hz, C60-H), 8.12 (s, 1H, C6-H of pyridazinone), 10.24 (s, 1H, NH, D2O
exchangeable), 12.94 (s, 1H, OH, D2O exchangeable). Anal. calc. for C12H12N2O2:
C, 66.65; H, 5.59; N, 12.96. Found: C, 66.52; H, 5.71; N, 12.82.
5-(3-Chloro-6-hydroxy-2,4-dimethyl-phenyl)-pyridazin-3(2H)-one
(3f).
Colorless solid (benzene), mp 216 ꢀC, yield 65%; IR (KBr, t in cmꢁ1): 3232 (br),
1
=
1645 (pyridazinone C O); H NMR (400 MHz, DMSO): d 2.24 (s, 3H, CH3), 2.28
(s, 3H, CH3), 6.14 (s, 1H, C4-H of pyridazinone), 6.51 (s, 1H, C30-H), 8.10 (s, 1H,
C6-H of pyridazinone), 10.21 (s, 1H, NH, D2O exchangeable), 12.68 (s, 1H, OH,
D2O exchangeable). Anal. calc. for C12H11ClN2O2: C, 57.49; H, 4.42; N, 11.17.
Found: C, 57.32; H, 4.34; N, 11.10.
5-(2-Hydroxy-4-methyl-3,5-dinitro-phenyl)-pyridazin-3(2H)-one
(3g).
Yellow-colored solid (ethanol), mp 206 ꢀC, yield 65%; IR (KBr, t in cmꢁ1): 3212
(br), 1651 (pyridazinone C O); 1H NMR (400 MHz, DMSO): d 2.41 (s, 3H,
=
CH3), 6.28 (s, 1H, C4-H of pyridazinone), 7.55 (s, 1H, C60-H), 8.10 (s, 1H, C6-H
of pyridazinone), 10.28 (s, 1H, NH, D2O exchangeable), 12.62 (s, 1H, OH, D2O
exchangeable). Anal. calc. for C11H8N4O6: C, 45.21; H, 2.76; N, 19.17. Found: C,
45.10; H, 2.65; N, 19.06.
General Procedure for Synthesis of 2,5-Diaryl-pyridazin-3(2H)-ones
(5a–o)
K2CO3(10 mmol) was added in ethanol (25 mL) to a mixture of subtituted-
4-bromomethylcoumarin 1 (10 mmol) and phenylhydrazine 4 (50 mmol). The
reaction mixture was refluxed for 3 h, cooled, and poured on ice-cold water, and
the separated solid 5 was filtered off. It was washed several times with aqueous
ethanol, dried, and recrystallized from suitable solvent.
Selected Data
5-(2-Hydroxy-phenyl)-2-phenyl-pyridazin-3(2H)-one (5a). Colorless solid
(benzene), mp 201 ꢀC, yield 71%; IR (KBr, t in cmꢁ1): 3260 (OH), 1664 (pyridazi-
1
=
none C O); H NMR (400 MHz, DMSO): d 6.61 (s, 1H, C4-H of pyridazinone),
6.92 (t, 1H, J ¼ 7.28 Hz, C400-H), 7.16 (d, 2H, J ¼ 7.60 Hz, C300 and C500-H),
7.28–7.33 (m, 2H, Ar-H), 7.38 (d, 1H, J ¼ 8.60 Hz, Ar-H), 7.80 (d, 1H, J ¼ 8.82 Hz,
Ar-H), 8.10 (s, 1H, C6-H of pyridazinone), 8.38 (d, 1H, J ¼ 9.50 Hz, Ar-H), 8.53 (d,
1H, J ¼ 8.90 Hz, Ar-H), 11.30 (s, 1H, OH, D2O exchangeable). Anal. calc. for
C16H12N2O2: C, 72.72; H, 4.58; N, 10.60. Found: C, 72.80; H, 4.64; N, 10.69.
5-(2,4-Dihydroxy-phenyl)-2-phenyl-pyridazin-3(2H)-one (5b). Colorless
solid (benzene), mp 195 ꢀC, yield 73%; IR (KBr, t in cmꢁ1): 3240 (OH), 1661

2578
M. BASANAGOUDA AND M. V. KULKARNI
1
=
(pyridazinone C O); H NMR (400 MHz, DMSO): d 6.64 (s, 1H, C4-H of pyrida-
zinone), 6.86 (t, 1H, J ¼ 7.30 Hz, C400-H), 7.17 (d, 2H, J ¼ 7.56 Hz, C300 and C500-H),
7.26–7.32 (m, 4H, Ar-H), 7.41 (d, 1H, J ¼ 8.20 Hz, Ar-H), 8.00 (s, 1H, C6-H of
pyridazinone), 11.12 (s, 1H, OH, D2O exchangeable), 11.31 (s, 1H, OH, D2O
exchangeable). Anal. calc. for C16H12N2O3: C, 68.56; H, 4.32; N, 9.99. Found: C,
68.51; H, 4.26; N, 9.87.
5-(2-Hydroxy-4-methoxy-phenyl)-2-phenyl-pyridazin-3(2H)-one
(5c).
Orange-colored solid (benzene), mp 212 ꢀC, yield 75%; IR (KBr, t in cmꢁ1): 3237
(OH), 1656 (pyridazinone C O); 1H NMR (400 MHz, DMSO): d 3.84 (s, 3H,
=
OCH3), 6.64 (s, 1H, C4-H of pyridazinone), 6.90 (t, 1H, J ¼ 7.28 Hz, C400-H), 7.18
(d, 2H, J ¼ 7.60 Hz, C300 and C500-H), 7.22–7.34 (m, 2H, Ar-H), 7.52 (d, 1H,
J ¼ 8.80 Hz, Ar-H), 7.62 (d, 1H, J ¼ 8.20 Hz, Ar-H), 8.01 (s, 1H, C6-H of pyridazi-
none), 8.33 (s, 1H, C30-H), 11.31 (s, 1H, OH, D2O exchangeable). Anal. calc. for
C17H14N2O3: C, 69.38; H, 4.79; N, 9.52. Found: C, 69.28; H, 4.70; N, 9.58.
5-(2-Hydroxy-4,6-dimethyl-phenyl)-2-phenyl-pyridazin-3(2H)-one (5d).
Colorless solid (benzene), mp 184 ꢀC, yield 76%; IR (KBr, t in cmꢁ1): 3236 (OH),
1
=
1667 (pyridazinone C O); H NMR (400 MHz, DMSO): d 2.30 (s, 3H, CH3), 2.41
(s, 3H, CH3), 6.62 (s, 1H, C4-H of pyridazinone), 6.94 (t, 1H, J ¼ 7.28 Hz,
C400-H), 7.16 (d, 2H, J ¼ 7.60 Hz, C300 and C500-H), 7.26–7.39 (m, 2H, Ar-H), 7.51
(s, 1H, Ar-H), 8.01 (s, 1H, C6-H of pyridazinone), 8.31 (s, 1H, Ar-H), 11.26 (s,
1H, OH, D2O exchangeable). Anal. calc. for C18H16N2O2: C, 73.95; H, 5.52; N,
9.58. Found: C, 73.84; H, 5.39; N, 9.50.
5-(2-Hydroxy-3,4-dimethyl-phenyl)-2-phenyl-pyridazin-3(2H)-one (5e).
Orange-colored solid (benzene), mp 188 ꢀC, yield 76%; IR (KBr, t in cmꢁ1): 3240
(OH), 1660 (pyridazinone C O); 1H NMR (400 MHz, DMSO): d 2.30 (s, 3H,
=
CH3), 2.38 (s, 3H, CH3), 6.59 (s, 1H, C4-H of pyridazinone), 6.89 (t, 1H, J ¼ 7.28 Hz,
C400-H), 7.16 (d, 2H, J ¼ 7.14 Hz, C300 and C500-H), 7.26–7.35 (m, 3H, Ar-H), 8.08 (s,
1H, C6-H of pyridazinone), 8.21 (d, 1H, J ¼ 8.10 Hz, Ar-H), 11.26 (s, 1H, OH, D2O
exchangeable). 13C NMR (100 MHz, DMSO): d 20.69, 21.20, 109.20, 113.24, 115.49,
117.64, 121.54, 126.48, 130.24, 131.49, 134.65, 134.99, 143.52, 147.24, 150.32, 161.18;
LCMS m=z: 293 [M þ 1]. Anal. calc. for C18H16N2O2: C, 73.95; H, 5.52; N, 9.58.
Found: C, 73.89; H, 5.50; N, 9.49.
5-(3-Chloro-6-hydroxy-2,4-dimethyl-phenyl)-2-phenyl-pyridazin-3(2H)-
one (5f). Colorless solid (benzene), mp 208 ꢀC, yield 70%; IR (KBr, t in cmꢁ1): 3231
1
=
(OH), 1650 (pyridazinone C O); H NMR (400 MHz, DMSO): d 2.32 (s, 3H, CH3),
2.42 (s, 3H, CH3), 6.65 (s, 1H, C4-H of pyridazinone), 6.97 (t, 1H, J ¼ 7.28 Hz,
C400-H), 7.19 (d, 2H, J ¼ 7.52 Hz, C300 and C500-H), 7.31–7.40 (m, 2H, Ar-H), 8.01
(s, 1H, C6-H of pyridazinone), 8.24 (s, 1H, C30-H), 11.23 (s, 1H, OH, D2O exchange-
able). Anal. calc. for C18H15ClN2O2: C, 66.16; H, 4.63; N, 8.57. Found: C, 66.05; H,
4.69; N, 8.52.
5-(2-Hydroxy-4-methyl-3,5-dinitro-phenyl)-2-phenyl-2H-pyridazin-3-one
(5g). Yellow-colored solid (benzene), mp 170 ꢀC, yield 66%; IR (KBr, t in cmꢁ1):
1
=
3230 (OH), 1656 (pyridazinone C O); H NMR (400 MHz, DMSO): d 2.42 (s,
3H, CH3), 6.67 (s, 1H, C4-H of pyridazinone), 6.98 (t, 1H, J ¼ 7.30 Hz, C400-H),

SYNTHESIS OF ARYL-PYRIDAZIN-3(2H)-ONES
2579
7.20 (d, 2H, J ¼ 7.58 Hz, C300 and C500-H), 7.12–7.40 (m, 2H, Ar-H), 8.04 (s, 1H,
C6-H of pyridazinone), 8.20 (s, 1H, C60-H), 11.31 (s, 1H, OH, D2O exchangeable).
Anal. calc. for C17H12N4O6: C, 55.44; H, 3.28; N, 15.21. Found: C, 55.39; H, 3.19;
N, 15.10.
5-(2-Hydroxy-5-methyl-phenyl)-2-phenyl-2H-pyridazin-3-one
(5h).
Yellow-colored solid (benzene), mp 226 ꢀC, yield 75%; IR (KBr, t in cmꢁ1): 3237
(OH), 1671 (pyridazinone C O); 1H NMR (400 MHz, DMSO): d 2.42 (s, 3H,
=
CH3), 6.56 (s, 1H, C4-H of pyridazinone), 6.88 (t, 1H, J ¼ 7.28 Hz, C400-H), 7.16
(d, 2H, J ¼ 7.76 Hz, C300 and C500-H), 7.26–7.35 (m, 4H, Ar-H), 8.03 (s, 1H, C6-H
of pyridazinone), 8.43 (s, 1H, C60-H), 11.23 (s, 1H, OH, D2O exchangeable); 13C
NMR (100 MHz, DMSO): d 20.69, 110.40, 112.93, 116.53, 116.63, 120.86, 125.88,
129.41, 130.99, 132.59, 133.36, 143.75, 145.57, 151.77, 160.26; LCMS m=z: 279
[M þ 1]. Anal. calc. for C17H14N2O2: C, 73.37; H, 5.07; N, 10.07. Found: C, 73.32;
H, 5.01; N, 10.05.
5-(2-Hydroxy-4-methyl-phenyl)-2-phenyl-2H-pyridazin-3-one (5i). Yellow-
colored solid (benzene), mp 244 ꢀC, yield 74%; IR (KBr, t in cmꢁ1): 3238 (OH),
1
=
1665 (pyridazinone C O); H NMR (400 MHz, DMSO): d 2.42 (s, 3H, CH3), 6.61
(s, 1H, C4-H of pyridazinone), 6.88 (t, 1H, J ¼ 7.28 Hz, C400-H), 7.16 (d, 2H,
J ¼ 7.60 Hz, C300 and C500-H), 7.29–7.35 (m, 3H, Ar-H), 7.45 (d, 1H, J ¼ 8.40 Hz,
Ar-H), 8.03 (s, 1H, C6-H of pyridazinone), 8.43 (s, 1H, C30-H), 11.23 (s, 1H, OH,
D2O exchangeable); 13C NMR (100 MHz, DMSO): d 21.21, 110.92, 113.45,
117.05, 117.15, 121.38, 126.41, 129.93, 131.51, 133.11, 133.88, 144.27, 146.09,
152.29, 160.79; LCMS m=z: 279 [M þ 1]. Anal. calc. for C17H14N2O2: C, 73.37; H,
5.07; N, 10.07. Found: C, 73.29; H, 4.99; N, 10.01.
5-(2-Hydroxy-5-methoxy-phenyl)-2-phenyl-2H-pyridazin-3-one
(5j).
Orange-colored solid (benzene), mp 224 ꢀC, yield 78%; IR (KBr, t in cmꢁ1): 3246
(OH), 1661 (pyridazinone C O); 1H NMR (400 MHz, DMSO): d 3.87 (s, 3H,
=
OCH3), 6.62 (s, 1H, C4-H of pyridazinone), 6.88 (t, 1H, J ¼ 7.28 Hz, C400-H), 7.17
(d, 2H, J ¼ 7.60 Hz, C300 and C500-H), 7.24–7.32 (m, 3H, Ar-H), 7.37 (d, 1H,
J ¼ 9.04 Hz, Ar-H), 8.04 (s, 1H, C6-H of pyridazinone), 8.20 (s, 1H, C60-H), 11.24
(s, 1H, OH, D2O exchangeable); 13C NMR (100 MHz, DMSO): d 56.09, 109.46,
112.38, 113.42, 117.57, 118.37, 119.85, 121.38, 129.89, 132.60, 144.25, 145.78,
148.55, 155.89, 160.83; LCMS m=z: 295 [M þ 1]. Anal. calc. for C17H14N2O3: C,
69.38; H, 4.79; N, 9.52. Found: C, 69.32; H, 4.75; N, 9.56.
5-(2-Hydroxy-naphthalen-1-yl)-2-phenyl-2H-pyridazin-3-one (5k). Brown-
colored solid (benzene), mp 169 ꢀC, yield 72%; IR (KBr, t in cmꢁ1): 3254 (OH),
1
=
1644 (pyridazinone C O); H NMR (400 MHz, DMSO): d 6.71 (s, 1H, C4-H of pyr-
idazinone), 6.89 (t, 1H, J ¼ 7.28 Hz, C400-H), 7.18 (d, 2H, J ¼ 7.60 Hz, C300 and
C500-H), 7.32–7.38 (m, 2H, Ar-H), 7.70–7.74 (m, 2H, Ar-H), 7.91 (d, 1H, J ¼ 8.90 Hz,
Ar-H), 8.02 (d, 1H, J ¼ 9.12 Hz, Ar-H), 8.12 (s, 1H, C6-H of pyridazinone), 8.39 (d,
1H, J ¼ 9.48 Hz, Ar-H), 8.51 (d, 1H, J ¼ 8.90 Hz, Ar-H), 11.30 (s, 1H, OH, D2O
exchangeable). Anal. calc. for C20H14N2O2: C, 76.42; H, 4.49; N, 8.91. Found: C,
76.28; H, 4.40; N, 8.82.

2580
M. BASANAGOUDA AND M. V. KULKARNI
5-(1-Hydroxy-naphthalen-2-yl)-2-phenyl-2H-pyridazin-3-one (5l). Orange-
colored solid (benzene), mp 270 ꢀC, yield 71%; IR (KBr, t in cmꢁ1): 3267
(OH), 1650 (pyridazinone C O); 1H NMR (400 MHz, DMSO): d 6.75 (s, 1H,
=
C4-H of pyridazinone), 6.90 (t, 1H, J ¼ 7.24 Hz, C400-H), 7.20 (d, 2H, J ¼ 7.60 Hz,
C300 and C500-H), 7.31–7.35 (m, 2H, Ar-H), 7.72–7.75 (m, 2H, Ar-H), 7.93 (d, 1H,
J ¼ 9.01 Hz, Ar-H), 8.04 (d, 1H, J ¼ 9.16 Hz, Ar-H), 8.17 (s, 1H, C6-H of pyrida-
zinone), 8.40 (d, 1H, J ¼ 9.52 Hz, Ar-H), 8.54 (d, 1H, J ¼ 8.92 Hz, Ar-H), 11.32 (s,
1H, OH, D2O exchangeable); 13C NMR (100 MHz, DMSO): d 110.17, 113.02,
113.57, 121.46, 122.19, 122.30, 123.01, 124.46, 127.86, 128.32, 129.33, 129.95,
131.71, 134.61, 144.22, 147.16, 151.11, 160.53; LCMS m=z: 315 [M þ 1]. Anal.
calc. for C20H14N2O2: C, 76.42; H, 4.49; N, 8.91. Found: C, 76.48; H, 4.54;
N, 8.94.
5-(2-Hydroxy-5-chloro-phenyl)-2-phenyl-2H-pyridazin-3-one
(5m).
Orange-colored solid (benzene), mp 237 ꢀC, yield 70%; IR (KBr, t in cmꢁ1):
1
=
3258 (OH), 1678 (pyridazinone C O); H NMR (400 MHz, DMSO): d 6.68 (s,
1H, C4-H of pyridazinone), 6.90 (t, 1H, J ¼ 7.32 Hz, C400-H), 7.14 (d, 2H,
J ¼ 7.64 Hz, C300 and C500-H), 7.30–7.35 (m, 2H, Ar-H), 7.45 (d, 1H, J ¼ 8.84 Hz,
Ar-H), 7.68 (d, 1H, J ¼ 8.84 Hz, Ar-H), 8.00 (s, 1H, C6-H of pyridazinone), 8.79
(s, 1H, C60-H), 11.29 (s, 1H, OH, D2O exchangeable); 13C NMR (100 MHz,
DMSO): d 112.50, 112.94, 118.02, 118.79, 121.06, 126.13, 128.16, 128.26,
129.44, 131.34, 131.72, 143.63, 144.42, 152.30, 159.73; LCMS m=z: 299 [M þ 1].
Anal. calc. for C16H11ClN2O2: C, 64.33; H, 3.71; N, 9.38. Found: C, 64.28; H,
3.75; N, 9.30.
5-(2-Hydroxy-4-chloro-phenyl)-2-phenyl-2H-pyridazin-3-one (5n). Orange-
colored solid (benzene), mp 192 ꢀC, yield 68%; IR (KBr, t in cmꢁ1): 3250 (OH),
1
=
1672 (pyridazinone C O); H NMR (400 MHz, DMSO): d 6.67 (s, 1H, C4-H of pyr-
idazinone), 6.91 (t, 1H, J ¼ 7.32 Hz, C400-H), 7.18 (d, 2H, J ¼ 7.82 Hz, C300 and
C500-H), 7.31–7.38 (m, 2H, Ar-H), 7.54 (d, 1H, J ¼ 8.80 Hz, Ar-H), 7.64 (d, 1H,
J ¼ 8.82 Hz, Ar-H), 8.03 (s, 1H, C6-H of pyridazinone), 8.66 (s, 1H, C30-H), 11.32
(s, 1H, OH, D2O exchangeable); 13C NMR (100 MHz, DMSO): d 112.46, 112.92,
118.00, 118.75, 121.01, 126.10, 128.13, 128.23, 129.42, 131.31, 131.69, 143.60,
144.41, 152.25, 159.71; LCMS m=z: 299 [M þ 1]. Anal. calc. for C16H11ClN2O2: C,
64.33; H, 3.71; N, 9.38. Found: C, 64.25; H, 3.77; N, 9.28.
5-(2-Hydroxy-5-bromo-phenyl)-2-phenyl-2H-pyridazin-3-one
(5o).
Orange-colored solid (benzene), mp 258 ꢀC, yield 71%; IR (KBr, t in cmꢁ1): 3227
(OH), 1677 (pyridazinone C O); 1H NMR (400 MHz, DMSO): d 6.67 (s, 1H,
=
C4-H of pyridazinone), 6.90 (t, 1H, J ¼ 7.24 Hz, C400-H), 7.14 (d, 2H, J ¼ 7.64 Hz,
C300 and C500-H), 7.30–7.35 (m, 2H, Ar-H), 7.40 (d, 1H, J ¼ 8.80 Hz, Ar-H), 7.80
(d, 1H, J ¼ 8.84 Hz, Ar-H), 8.00 (s, 1H, C6-H of pyridazinone), 8.96 (s, 1H,
C60-H), 11.30 (s, 1H, OH, D2O exchangeable); 13C NMR (100 MHz, DMSO): d
112.53, 112.94, 116.03, 118.49, 119.08, 121.06, 129.22, 129.43, 131.75, 134.09,
143.64, 144.34, 152.70, 159.69; LCMS m=z: 345 [M þ 1]. Anal. calc. for
C16H11BrN2O2: C, 56.00; H, 3.23; N, 8.16. Found: C, 55.88; H, 3.17; N, 8.09.

SYNTHESIS OF ARYL-PYRIDAZIN-3(2H)-ONES
2581
CONCLUSION
In conclusion, this article provides an efficient method for the synthesis of
mono- and diaryl-pyridazin-3(2H)-ones. Different substituents on coumarin and
arylhydrazine provide a plethora of substituted 2,5-diaryl-pyridazin-3(2H)-ones.
The synthetically viable yields (typically 50–80% or moderate to good isolated yield)
and straightforward procedure for the preparation make this an attractive route to
the diaryl-pyridazin-3(2H)-ones. The advantages offered by this method are readily
available starting material, simple operation, insensitivity to air and moisture, good
yields of products, and cost-effectiveness. Further, the reactivity of the phenolic
hydroxyl group of 5-aryl moiety may be extended in the synthesis of biologically
active compounds.
ACKNOWLEDGMENTS
The authors are thankful to the University Sophisticated Instrumentation
Centre (USIC), Karnatak University, Dharwad, for providing spectral and analyti-
cal data. One of us (Mahantesha Basanagouda) grateful to Karnatak University,
Dharwad, for a university research studentship.
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