A green and practical one-pot two-step strategy for the synthesis of symmetric 3,6-diarylpyridazines

Article abstract of DOI:10.1002/jccs.201700470

A simple, mild, and efficient synthesis of symmetric 3,6-diarylpyridazine derivatives using a green catalytic one-pot two-step reaction of aryl methyl ketones, arylglyoxal monohydrates, and hydrazine hydrate was developed. Environmentally benign nature, high atom-economy, no harmful byproduct, easy workup procedure, no column chromatography steps, and moderate to excellent yields of the products are the salient features of this new multicomponent-based methodology.

Full text of DOI:10.1002/jccs.201700470

Received: 16 January 2018
Revised: 7 May 2018
Accepted: 16 May 2018
DOI: 10.1002/jccs.201700470
A R T I C L E
A green and practical one-pot two-step strategy for the synthesis
of symmetric 3,6-diarylpyridazines
1
1
2
1
Mehdi Rimaz
| Hossein Mousavi
| Behzad Khalili | Farkhondeh Aali
1
Department of Chemistry, Payame Noor
University, Tehran, Iran
A simple, mild, and efficient synthesis of symmetric 3,6-diarylpyridazine deriva-
tives using a green catalytic one-pot two-step reaction of aryl methyl ketones,
arylglyoxal monohydrates, and hydrazine hydrate was developed. Environmentally
benign nature, high atom-economy, no harmful byproduct, easy workup procedure,
no column chromatography steps, and moderate to excellent yields of the products
are the salient features of this new multicomponent-based methodology.
2
Department of Chemistry, Faculty of Science,
University of Guilan, Rasht, Iran
Correspondence
Mehdi Rimaz, Department of Chemistry, Payame
Noor University, PO Box 19395-3697, Tehran,
Iran.
Email: rimaz.mehdi@gmail.com
Funding information
KEYWORDS
Research Council of Payame Noor University,
Grant/Award Number: 68424
3
,6-Diarylpyridazine, aryl methyl ketone, arylglyoxal monohydrate, DABCO,
one-pot, ZrOCl Á 8H O
2
2
[
4]
[5]
[6]
1
| INTRODUCTION
as antihistaminic, antibacterial, antihypertensive, anti-
[
7]
[8]
diabetic and anti-inflammatory agents. It is worth noting
that, some pyridazine derivatives have been incorporated
into semiconductor materials as well as in substances with
nonlinear optical properties. On the other hand, some pyri-
dazine scaffolds have been found as promising agrochemical
products (Figure 2).
It should be mentioned that literature survey reveals that
only a very few articles have been reported for the synthesis
of symmetric 3,6-diarylpyridazine derivatives.
reported methods suffer from one or more disadvantages
such as harsh reaction conditions, unsatisfactory yields,
multistep synthetic operation, tedious workup and, etc.
Therefore, obviation of these limitations is necessary to
develop a green, simple, and efficient strategy for the synthe-
sis of symmetric 3,6-diarylpyridazine systems.
The field of green chemistry has quickly developed during
the new century following the recognition that eco-friendly
products and processes represent economically attractive
long-term synthetic strategies. The important areas of green
chemistry include the development of novel chemical
processes that show intrinsically high atom-economies,
pronounced energy savings, use of environmentally benign
solvents and catalysts, low levels of waste production, and
[
9]
[
10]
These
[1]
facile workup procedures.
Nowadays, one-pot multicomponent reactions (MCRs)
are very useful in organic synthesis, drug, and drug-like
molecular discovery owing to their simplicity, flexibility,
and efficiency compared with a conventional multistep linear
[
2]
synthetic strategy.
Design and synthesis of symmetric heterocyclic com-
pounds are currently receiving a great deal of attention due
to their exclusive specifications and wide applications in
organic synthesis, medicinal chemistry, inorganic chemistry,
As part of our ongoing efforts toward the development
of new synthetic methods for important heterocyclic
[
11]
frameworks,
herein, we report a one-pot two-step process
for the synthesis of symmetric 3,6-diarylpyridazine deriva-
tives using a three-component reaction of aryl methyl
ketones, arylglyoxal monohydrates, and hydrazine hydrate.
This new method is green, simple, and efficient, which can
be extended to the synthesis of many other important
symmetric and asymmetric 3,6-diarylpyridazine scaffolds
(Scheme 1).
[3]
materials science and etc.
Pyridazines belong to a family of six-membered N-
heterocyclic compounds that exhibit remarkable pharmaceu-
tical activities (Figure 1). For example, several members of
this class of heterocyclic scaffolds have been utilized in the
development of therapeutic agents that have been employed
©
2018 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J Chin Chem Soc. 2018;1–9.
http://www.jccs.wiley-vch.de
1

2
RIMAZ ET AL.
FIGURE 1 Examples of pyridazine-based drugs
chemistry factors, nonhazardous solvents (water, ethanol,
and H O–EtOH) are used as the preferred solvents for all of
2
the optimization experiments. It should be noted that, all of
our efforts for one-pot single-step synthesis of 3a using dif-
ferent catalysts were unsuccessful (Table 1). Therefore, we
changed our three-component single-step strategy to a com-
binatorial one-pot two-step protocol. In the step 1, we tested
the reaction of 1a and 2a for the preparation of a suitable
intermediate in the presence of various molar ratios of
1
,4-diazabicyclo[2.2.2]octane (DABCO) as a cheap and eco-
friendly base-organocatalyst under different temperature
conditions in green solvents. In the presence of 20 mol% of
DABCO, when water was used as a solvent at room temper-
ature, the reaction proceeded well and the best mass of the
desired intermediate obtained within 11 hr. It should be
mentioned that, in the step 1, the reaction mixture gave an
adhesive material, which stuck to the magnetic stir bar and
precipitation of the obtained product (intermediate) was not
occurred. Then, material obtained from step 1 was easily fil-
tered from the reaction flask. Subsequently, we have started
our study on the step 2 with the condensation of obtained
intermediate and hydrazine hydrate in the presence of
FIGURE 2 Selected pyridazine-based agrochemical products
2
| RESULTS AND DISCUSSION
Initially, we selected acetophenone (1a), phenylglyoxal
monohydrate (2a), and hydrazine as model substrates to
establish optimum reaction conditions for the synthesis of
symmetric 3,6-diphenylpyridazine (3a). To maintain green
SCHEME 1 One-pot two-step synthesis of symmetric 3,6-diarylpyridazines

RIMAZ ET AL.
3
TABLE 1 Investigation of the reaction conditions using a one-pot single-step protocol
ꢀ
Entry
Solvent
Hydrazine
Hydrate
Catalyst (mol%)
DABCO (20)
DABCO (20)
DABCO (50)
Temp. ( C)
Time (hr)
48
Yield (%) of 3a
NR
1
2
3
4
5
6
7
8
9
H
H
H
H
H
H
2
2
2
2
2
2
O
O
O
O
O
O
rt
Hydrate
50
48
NR
Hydrate
rt
48
NR
Hydrate
ZrOCl
L-proline (20)
ZrOCl O (20)
Á8H
2
Á8H
2
O (20)
rt
24
NR
Hydrate
rt
24
NR
Dihydrochloride
Hydrate
2
2
50
24
NR
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
DABCO (20)
rt
24
NR
Hydrate
DABCO (20)
Reflux
rt
24
NR
Hydrate
ZrOCl
ZrOCl
ZrOCl
ZrOCl
2
Á8H
2
Á8H
2
Á8H
2
Á8H
2
2
2
2
O (20)
O (20)
O (20)
O (20)
48
NR
10
11
12
13
15
16
17
18
19
20
21
22
Hydrate
Reflux
rt
24
NR
Dihydrochloride
Dihydrochloride
Hydrate
24
NR
Reflux
rt
24
NR
L-proline (10)
L-proline (10)
L-proline (10)
DABCO (20)
24
NR
Dihydrochloride
Dihydrochloride
Hydrate
rt
24
NR
Reflux
rt
24
NR
H
H
H
H
H
H
2
2
2
2
2
2
O–EtOH (1:1)
O–EtOH (1:1)
O–EtOH (1:1)
O–EtOH (1:1)
O–EtOH (1:1)
O–EtOH (1:1)
24
NR
Hydrate
ZrOCl
ZrOCl
2
Á8H
Á8H
2
O (20)
O (20)
rt
24
NR
Dihydrochloride
Hydrate
2
2
Reflux
rt
24
NR
L-proline (10)
L-proline (10)
L-proline (10)
24
NR
Hydrate
Reflux
Rrefux
24
NR
Dihydrochloride
48
NR
different catalysts such as zirconium (IV) oxydichloride octa-
Based on the experimental observation, the plausible
stepwise mechanism for the one-pot two-step synthesis
of symmetric 3,6-diarylpyridazine derivatives (3a–h) is
described in Scheme 2. In the first step, aryl methyl
ketone (1a–h) was converted to the corresponding
anionic form (4a–h) by DABCO. Subsequently, the aldol
reaction of 4a–h with the formyl group of arylglyoxal (6a–
h) resulted in the intermediate 7a–h. In the presence of
ZrOCl Á 8H O, intermediate 7a–h converted the α,β-unsatu-
hydrate (ZrOCl Á 8H O), L-proline, and DABCO for the
2
2
expected symmetric 3,6-diphenylpyridazine (3a). Also, in this
step (step 2), the effects of different solvents and temperatures
were investigated (Table 2). The best result for step 2 was
obtained when we used 30 mol% of ZrOCl Á 8H O as a green
2
2
[12]
Lewis acid catalyst (LD [oral rat] = 2,950 mg/kg) in eth-
50
anol at reflux under vigorous stirring within 2 hr. It is notice-
able that, both steps (step 1 and step 2) of this one-pot reaction
were carried out in a flask without purification of the interme-
diate obtained from the step 1. With optimized reaction condi-
tions in hand, we further carried out the reaction by using
various aryl methyl ketones (1a–h) and arylglyoxal monohy-
drate derivatives (2a–h) to investigate the scope and generality
of this one-pot two-step protocol for the synthesis of symmet-
ric 3,6-diarylpyridazine derivatives (3a–h) (Table 3). Pure
products (3a–h) with moderate to excellent yields were
obtained simply by filtration and washing of the solid with hot
ethanol (no need of column chromatography stages).
2
2
rated-1,4-dicarbonyl compound (9a–h) by elimination of
water. Then, 9a–h that were activated by ZrOCl Á 8H O
2
2
facilitate a nucleophilic attack of the hydrazine hydrate (11)
followed by a dehydration reaction to give the final product
(
3a–h).
It is worthwhile to note that Saraei and coworkers reported
a simple method to synthesize 2-hydroxy-1,4-diarylbutane-
,4-diones via the DABCO-catalyzed aldol reaction of aceto-
phenone derivatives and arylglyoxal monohydrates in water at
1
[13]
The structures of all the symmetric 3,6-diarylpyridazine
derivatives (3a–i) were well characterized from their spectral
room temperature (Scheme 3).
Saraei’s work is powerful
evidence to verify our mechanism, especially the formation of
the aldol adduct in step 1.
1
13
(
IR, H NMR, and C NMR) studies and CHN analysis.

4
RIMAZ ET AL.
TABLE 2 Optimization of the reaction conditions using a one-pot two-step strategy
Step 1
Step 2
Solvent
—
Entry
Solvent
DABCO (mol%)
—
Cond.
Time (hr)
48
Catalyst (mol%)
Cond.
—
Time (hr)
—
Yield (%) of 3a
1
2
3
4
5
6
7
8
9
H
H
2
O
O
rt
—
—
—
—
—
—
—
—
NR
NR
NR
NR
NR
21
2
—
Reflux
48
—
—
—
EtOH
EtOH
—
rt
48
—
—
—
—
Reflux
48
—
—
—
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
(20%)
(50%)
(60%)
(20%)
(20%)
(20%)
(20%)
(20%)
(20%)
(20%)
(20%)
(20%)
(20%)
(20%)
(20%)
(20%)
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
11
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
rt
24
11
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
rt
24
11
24
21
11
24
19
11
ZrOCl
ZrOCl
ZrOCl
ZrOCl
ZrOCl
ZrOCl
ZrOCl
2
2
2
2
2
2
2
(5%)
24
17
10
11
12
13
14
15
16
17
18
19
20
11
(10%)
(15%)
(30%)
(30%)
(30%)
(30%)
24
18
11
24
18
11
2
62
11
48
NR
NR
NR
20
11
H
H
2
2
O
O
rt
48
11
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
48
11
EtOH
EtOH
EtOH
EtOH
EtOH
DABCO (10%)
DABCO (20%)
L-proline (10%)
L-proline (20%)
L-proline (30%)
24
11
24
21
11
24
21
11
24
21
11
24
21
3
| EXPERIMENTAL
.1 | Materials and techniques
for appropriate time as mentioned in Table 3 at room tem-
perature. After completion of the reaction (monitored by
(TLC) Thin Layer Chromatography), the intermediate
3
obtained was easily filtered from the reaction flask. Then, a
mixture of the obtained intermediate and hydrazine hydrate
Melting points were determined on an Electrothermal
1
13
9
200 apparatus. H (300 MHz) and C (75 MHz) NMR
(
3 mmol) in the presence of ZrOCl Á 8H O (30 mol%) as a
2
2
spectra were recorded on a Bruker DRX-300 AVANCE
green Lewis-acid catalyst was stirred in ethanol (7 mL) at
reflux. After completion of the reaction, the reaction mixture
was cooled to room temperature and filtered to give the
crude product, which was purified by recrystallization from
boiling ethanol.
spectrometer in CDCl with tetramethylsilane as the inter-
3
nal standard. Infrared spectra were recorded on a Perki-
nElmer Spectrum Two FT-infrared spectrophotometer,
measured using KBr disks. Microanalyses were performed
on a Leco Analyzer 932. All substrates and reagents were
commercially available and used without further
purification.
3
.3 | Physical and spectral data for compounds 3a–h
3
.3.1 | 3,6-Biphenylpyridazine (3a)
3
.2 | General procedure for the one-pot two-step
synthesis of symmetric 3,6-diarylpyridazine derivatives
3a–h)
ꢀ
1
White solid; mp 224–226 C. H NMR (300 MHz, CDCl ):
3
8
.17 (d, J = 6.9 Hz, 4H, Ar), 7.94 (s, 2H, Ar), and 7.58–7.50
(
13
(m, 6H, Ar); C NMR (75 MHz, CDCl ): 157.6, 136.1,
3
In a round-bottom flask (25 mL) equipped with a magnetic
stirrer, DABCO (20 mol%) was added to a solution of aryl
methyl ketone (1 mmol) and arylglyoxal monohydrate
130.0, 129.0, 126.9, and 124.2; FT-IR (KBr) v: 3,054, 1,582,
1,448, 1,407, 1,311, 1,154, 1,126, 1,019, 867, 757, 743, 691,
−1
and 588 cm . Anal. calcd for C H N : C, 82.73; H, 5.21;
1
6 12 2
(1 mmol) in water (5 mL). The reaction mixture was stirred
and N, 12.06. Found: C, 82.73; H, 5.21; and N, 12.06.

RIMAZ ET AL.
5
calcd for C H Br N : C, 49.27; H, 2.58; and N, 7.18.
16
10
2 2
Found: C, 49.27; H, 2.58; and N, 7.18.
3
.3.3 | 3,6-Bis(4-chlorophenyl)pyridazine (3c)
ꢀ
1
Yellow solid; mp 260–262 C. H NMR (300 MHz,
CDCl ): 8.10 (d, J = 5.4 Hz, 4H, Ar), 7.92 (s, 2H, Ar), and
3
13
7
1
.53 (d, J = 6.3 Hz, 4H, Ar); C NMR (75 MHz, CDCl3):
58.1, 136.5, 129.3, 128.4, 128.1, and 124.0; FT-IR (KBr)
v: 3,089, 3,048, 1,597, 1,489, 1,420, 1,410, 1,381, 1,306,
−1
1
,297, 1,095, 1,009, 994, 820, 797, 747, and 578 cm .
Anal. calcd for C H Cl N : C, 63.81; H, 3.35; and N,
16
10
2 2
9
.30. Found: C, 63.81; H, 3.35; and N, 9.30.
3
.3.4 | 3,6-Bis(4-methoxyphenyl)pyridazine (3d)
ꢀ
1
Yellow solid; mp 236–238 C. H NMR (300 MHz,
CDCl ): 8.10 (d, J = 5.8 Hz, 4H, Ar), 7.83 (s, 2H, Ar), 7.05
3
13
(
d, J = 5.7 Hz, 4H, Ar), and 3.89 (s, 6H, 2 × OCH3);
C
NMR (75 MHz, CDCl ): 161.1, 128.6, 128.1, 123.4, 114.3,
3
1
1
1
13.6, and 55.3; FT-IR (KBr) v: 3,068, 3,048, 2,962, 2,839,
,606, 1,574, 1,506, 1,426, 1,398, 1,301, 1,252, 1,244,
−
1
,193, 1,032, 1,024, 832, and 821 cm . Anal. calcd for
C H N O : C, 73.95; H, 5.52; and N, 9.58. Found: C,
18 16 2 2
7
3.95; H, 5.52; and N, 9.58.
3
.3.5 | 3,6-Bis(3,4-dimethoxyphenyl)pyridazine (3e)
ꢀ
1
White solid; mp 201–203 C. H NMR (300 MHz, CDCl ):
3
8.00 (s, 2H, Ar), 7.85 (s, 2H, Ar), 7.55–7.52 (m, 2H, Ar), 6.99
(
6
d, J = 8.4 Hz, 2H, Ar), 4.02 (s, 6H, 2 × OCH ), and 3.96 (s,
3
13
H, 2 × OCH3); C NMR (75 MHz, CDCl ): 156.4, 150.8,
3
149.5, 128.7, 123.5, 119.2, 111.0, 109.5, 56.0, and 55.9;
FT-IR (KBr) v: 3,003, 2,949, 2,839, 1,600, 1,591, 1,518,
1
8
6
,464, 1,424, 1,407, 1,274, 1,253, 1,224, 1,146, 1,020,
−1
43, 810, and 801 cm . Anal. calcd for C H N O : C,
20 20 2 4
8.17; H, 5.72; and N, 7.95. Found: C, 68.17; H, 5.72;
and N, 7.95.
3
.3.6 | 3,6-Bis(3,4-Methylenedioxyphenyl)pyridazine (3f)
ꢀ
1
White solid; mp 245–248 C. H NMR (300 MHz, CDCl ):
3
7.80 (s, 2H, Ar), 7.41 (s, 2H, Ar), 7.60 (d, J = 7.2 Hz, 2H,
Ar), 6.96 (d, J = 7.8 Hz, 2H, Ar), and 6.07 (s, 4H,
1
3
2
1
× OCH O); C NMR (75 MHz, CDCl ): 167.4, 164.5,
2 3
57.3, 131.3, 123.6, 121.0, 108.6, 107.1, and 101.5; FT-IR
(KBr) v: 3,080, 2,990, 2,904, 1,606, 1,501, 1,489, 1,447,
SCHEME 2 Plausible stepwise mechanism for the green one-pot two-step
1
9
6
,410, 1,373, 1,275, 1,240, 1,140, 1,111, 1,102, 1,036,
synthesis of symmetric 3,6-diarylpyridazine derivatives
−1
31, 895, 847, and 822 cm . Anal. calcd for C H N O : C,
18 12 2 4
7.50; H, 3.78; and N, 8.75. Found: C, 67.50; H, 3.78;
3
.3.2 | 3,6-Bis(4-bromophenyl)pyridazine (3b)
ꢀ
1
and N, 8.75.
Yellow solid; mp 285–287 C. H NMR (300 MHz, CDCl ):
3
8
.05 (d, J = 8.7 Hz, 4H, Ar), 7.92 (s, 2H, Ar), and 7.70 (d,
1
3
J = 8.4 Hz, 4H, Ar); C NMR (75 MHz, CDCl ): 158.0,
3
1
3
1
37.2, 132.3, 128.4, 125.1, and 124.0; FT-IR (KBr) v: 3,089,
,048, 1,588, 1,485, 1,420, 1,408, 1,379, 1,328, 1,303,
−1
,297, 1,074, 1,006, 816, 793, 731, and 577 cm . Anal.
SCHEME 3 Aldol reaction reported by Saraei and coworkers

6
RIMAZ ET AL.
3
.3.7 | 3,6-Bis(3-bromophenyl)pyridazine (3g)
Ar), 7.66 (d, J = 6.9 Hz, 2H, Ar), and 7.43 (t, J = 8.1 Hz,
1
13
ꢀ
White solid; mp 185–188 C. H NMR (300 MHz, CDCl ):
8
2H, Ar); C NMR (75 MHz, CDCl
): 156.6, 137.8, 133.1,
3
3
.33 (s, 2H, Ar), 8.10 (d, J = 7.8 Hz, 2H, Ar), 7.94 (s, 2H,
130.6, 130.0, 125.4, 124.2, and 123.3; FT-IR (KBr) v:
TABLE 3 Regioselective one-pot two-step synthesis of symmetric 3,6-diarylpyridazine derivatives
Time (hr)
Entry
Aryl methyl ketone
Arylglyoxal monohydrate
3,6-diarylpyridazine
Step 1 Step 2 Yield (%) of 3
1
11
2
62
2
3
4
10
1
90
10
1
92
9
2
79

RIMAZ ET AL.
7
TABLE 3 (Continued)
Time (hr)
Entry
Aryl methyl ketone
Arylglyoxal monohydrate
3,6-diarylpyridazine
Step 1 Step 2 Yield (%) of 3
5
9
2
86
6
9
2
96
7
12
3
60
8
12
3
65
3
1
,064, 1,581, 1,562, 1,432, 1,419, 1,391, 1,284, 1,078,
,061, 996, 847, 789, 757, 685, and 656 cm . Anal. calcd
3.3.8 | 3,6-Bis(3-methoxyphenyl)pyridazine (3h)
−
1
1
ꢀ
White solid; mp 186–189 C. H NMR (300 MHz, CDCl ):)
3
for C H Br N : C, 49.27; H, 2.58; and N, 7.18. Found: C,
7.93 (s, 2H, Ar), 7.87 (s, 2H, Ar), 7.65 (d, J = 7.5 Hz, 2H,
16
10
2 2
49.27; H, 2.58; and N, 7.18.
Ar), 7.45 (t, J = 8.1 Hz, 2H, Ar), 7.07 (dd, J = 6 Hz,

8
RIMAZ ET AL.
1
3
[
2] (a) M. Waheed, N. Ahmed, M. A. Alsharif, M. I. Alahmadi, S. Mukhtar,
ChemistrySelect 2017, 2, 7946. (b) K. A. Grice, R. Patil, A. Ghosh,
J. D. Paner, M. A. Guerrero, E. J. M. Camacho, P. S. Cao, A. H. Niyazi,
S. Zainab, R. D. Sommer, G. Waris, S. Patil, New J. Chem. 2018, 42, 1151.
(c) V. A. Palchykov, R. M. Chabanenko, V. V. Konshin, V. V. Dotsenko,
S. G. Krivokolysko, E. A. Chigorina, Y. I. Horak, R. Z. Lytvyn,
A. A. Vakhula, M. D. Obushak, A. V. Mazepa, New J. Chem. 2018, 42,
J = 2.1 Hz, 2H, Ar), and 3.93 (s, 6H, 2 × OCH3); C NMR
75 MHz, CDCl ): 160.2, 157.4, 137.4, 130.0, 124.3, 119.1,
(
3
1
1
1
16.5, and 111.6; FT-IR (KBr) v: 3,048, 2,970, 2,839, 1,592,
,549, 1,456, 1,429, 1,417, 1,324, 1,310, 1,223, 1,186, 1,038,
,026, 863, 795, 781, and 699 cm . Anal. calcd for
C H N O : C, 73.95; H, 5.52; and N, 9.58. Found: C,
−1
18 16 2 2
1403. (d) X. Gao, Z. Yang, W.-J. Hao, B. Jiang, S. J. Tu, J. Heterocyclic
73.95; H, 5.52; and N, 9.58.
Chem. 2017, 54, 2434. (e) S. J. Jadhav, R. B. Patil, D. R. Kumbhar,
A. A. Patravale, D. R. Chandam, M. B. Deshmukh, J. Heterocyclic Chem.
2
2
017, 54, 2434. (f) M. Beerappa, K. Shivashankar, J. Heterocyclic Chem.
017, 54, 2197. (g) C. Kathing, S. Kumar, S. Tumtin, N. G. Singh,
4
| CONCLUSIONS
J. W. S. Rani, R. Nongrum, R. Nongkhlaw, J. Heterocyclic Chem. 2017,
4, 1486. (h) M. Ghandi, S. Rahimi, N. Zarezadeh, J. Heterocyclic Chem.
2017, 54, 102. (i) G. M. Reddy, J. Raul Garcia, J. Heterocyclic Chem.
017, 54, 89. (j) J. Safaei-Ghomi, H. Shahbazi-Alavi, S. H. Nazemzadeh,
J. Chin. Chem. Soc. 2017, 64, 1213. (k) A. R. Moosavi-Zare,
H. Goudarziafshar, S. Dastbaz, J. Chin. Chem. Soc. 2017, 64, 727.
5
In summary, we have developed a novel, simple, and efficient
method for the synthesis of symmetric 3,6-diarylpyridazine
derivatives using a green catalytic one-pot two-step reaction
of aryl methyl ketones, arylglyoxal monohydrates, and hydra-
zine hydrate. Mild reaction conditions, operational simplicity,
clean reaction profiles, the absence of a tedious separation
procedure, high atom-economy, moderate to excellent yields,
and easy workup, as well as the use of inexpensive and envi-
ronmentally benign catalysts and solvents are the key advan-
tages of this multicomponent method.
2
(
l) H. Alinezhad, V. Alinezhad, S. Mohseni Tavakkoli, J. Chin. Chem. Soc.
2017, 64, 385. (m) E. Tabrizian, A. Amoozadeh, J. Chin. Chem. Soc. 2017,
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6
J. Chin. Chem. Soc. 2017, 64, 138. (o) M. Rimaz, H. Mousavi,
M. Behnam, L. Sarvari, B. Khalili, Curr. Chem. Lett. 2017, 6, 55.
(p) N. Azizi, M. Edrisi, Res. Chem. Intermed. 2017, 43, 379.
(
q) S. Golchin, M. H. Mosslemin, A. Yazdani-Elah-Abadi, N. Shams, Res.
Chem. Intermed. 2017, 43, 1735. (r) S. Kumari, M. Rajeswari,
J. M. Khurana, Aust. J. Chem. 2016, 43, 1735. (s) J. Sindhu, H. Singh,
J. M. Khurana, K. R. Aneja, Aust. J. Chem. 2013, 66, 717. (t) H. Singh,
J. Sindhu, J. M. Khurana, C. Sharma, K. R. Aneja, Aust. J. Chem. 2013, 66,
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ACKNOWLEDGMENTS
(
v) E. Doustkhah, S. Rostamnia, A. Hasankhani, J. Porous Mater. 2016,
3, 549. (w) H. Golchin Hosseini, E. Doustkhah, M. V. Kirillova,
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This work was partially supported by the Research Council
of Payame Noor University.
2
5
ORCID
4
Mehdi Rimaz
http://orcid.org/0000-0002-5175-0894
http://orcid.org/0000-0003-4292-3762
478, 280.
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How to cite this article: Rimaz M, Mousavi H,
Khalili B, Aali F. A green and practical one-pot two-
step strategy for the synthesis of symmetric 3,6-diaryl-
pyridazines. J Chin Chem Soc. 2018;1–9. https://doi.
org/10.1002/jccs.201700470
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(