Synthesis, structure, and properties of 1,3,5-triarylpyridazines

Article abstract of DOI:10.1007/s10593-009-0354-z

Treatment of γ-bromodypnone with arylhydrazines gives differently structured products, i.e. γ-bromo-dypnone hydrazones, 1-aryl-3,5-diphenyl- 1,4-dihydropyridazines, 1-aryl-3,5-diphenyl-1,6-dihydro-pyridazines, and aromatic 1,3,5-triarylpyridazinium salts.

Full text of DOI:10.1007/s10593-009-0354-z

Chemistry of Heterocyclic Compounds, Vol. 45, No. 7, 2009
SYNTHESIS, STRUCTURE,
AND PROPERTIES OF
1,3,5-TRIARYLPYRIDAZINES
L. M. Potikha1*, V. A. Kovtunenko1, and A. V. Turov1
Treatment of γ-bromodypnone with arylhydrazines gives differently structured products, i.e. γ-bromo-
dypnone hydrazones, 1-aryl-3,5-diphenyl-1,4-dihydropyridazines, 1-aryl-3,5-diphenyl-1,6-dihydro-
pyridazines, and aromatic 1,3,5-triarylpyridazinium salts. We have studied the pattern of formation of
all of the products and their properties. Heating an alcohol solution of 1,3,5-triphenyl-1,4-dihydro-
pyridazine gives N,2,4-triphenyl-1H-pyrrole-1-amine or to a 1,3,5-triphenylpyridazinium salt dependent
upon the acidity of the medium. The product of addition of HBr to the 1,6-dihydropyridazine system is
5-bromo-1-(4-nitrophenyl)-3,5-diphenyl-1,4,5,6-tetrahydropyridazine.
Keywords: γ-bromodypnone, 1,3,5-triarylpyridazinium bromide, 1,3,5-triaryl-1,4-dihydropyridazine,
1,3,5-triaryl-1,6-dihydropyridazine, N,2,4-triphenyl-1H-pyrrole-1-amine.
Pyridazine derivatives are an important class of pharmacologically interesting structures [1, 2]. A
significant stimulus for an intensive study of their properties and methods of preparation has come from the
discovery in the 70's and 80's of natural, biologically active substances containing a pyridazine ring [3, 4]. The
most popular methods for the synthesis of pyridazines are based on the use of γ-dicarbonyl compounds as
starting materials [2, 3]. Examples are known of using γ-halocarbonyl compounds [3], including those that are
unsaturated [5]. We have previously reported that 1,3,5-triarylpyridazines are readily formed by reaction of
4-bromo-1,3-diphenyl-2-buten-1-one (γ-bromodypnone) (1) with arylhydrazines [6].
The reaction of γ-bromodypnone 1 with arylhydrazines can lead to different products depending on the
conditions and the structure of the starting hydrazine [6, 7]. The simplest variant of the reaction is formation of
hydrazone 2a with an open structure by treatment of the bromodypnone 1 with 1-(2,4-dinitrophenyl)hydrazine
in alcohol [7]. Under the same conditions arylhydrazines gave the pyridazines 3a,b, 4a [6] and 1H-pyrrole-
1-amine 5 [7]. In our work we have clarified the mode of action of this reaction and broadened its scope both as
regards the arylhydrazines used and the reaction conditions.
Independently of the conditions the γ-bromodypnone 1 and tolylhydrazines gave 1,3,5-triaryl-
pyridazinium bromides 3a,b [6]. At the same time, the result of the reaction with phenylhydrazine depends on
the conditions used. The main product of the reaction of the γ-bromodypnone 1 with phenylhydrazine in alcohol
1
is 1,3,5-triphenyl-1,4-dihydropyridazine 4a [6, 7]. The H NMR spectrum of the crude product also shows
_______
* To whom correspondence should be addressed, e-mail: potikha_l@mail.ru.
1 Taras Shevchenko National University, Kiev 01033, Ukraine.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1031-1039, July, 2009. Original
article submitted April 23, 2008.
0009-3122/09/4507-0815©2009 Springer Science+Business Media, Inc.
815

signals at 4.72 ppm (2H, s) and 7.29 ppm (1H, s) which differ from those in compound 4a. It was found that the
content of this product increases at lower temperature and with shortening of the heating time of the reaction
mixture both when carrying out the reaction in alcohol and when fusing in the presence of sodium acetate. The
greatest effect (according to the content of the unknown product in the mixture) is seen when carrying the
reaction out in the presence of acetic acid (AcOH–EtOH, 2:3, 25-40ºC).
Ph
Ph
Ph
Ph
Ph
+
EtO
.
N
.
N
Ph
N
N
Me
NH
_
5
Ph
NHPh
Ph
X
8
PhNHNH2
7
EtOH,
AcOH
Ph
Ph
Ph
Ph
ArNHNH2
N
N
EtO
Br
Ph
Br
COPh
Ph
N
1
2a,b
NHAr
ArNHNH2
AcONa
∆
+
∆
∆, H
EtOH
Ph
_
Br
Ph
Ph
Ph
Ph
Ph
∆
O2, HBr
+
N
N
N
∆
N
N
Ar
N
Ar
Ar
4a–c
6a–c
3a–c
HBr
Br
Ph
Ph
N
N
Ar
9a,b
3 a Ar = 2-MeC6H4, b Ar = 3-MeC6H4, c Ar = Ph;
2 a Ar = 2,4-(O2N)2C6H3, b Ar = Ph;
4a, 6a Ar = Ph, 4b, 6b, 9a Ar = 4-O2NC6H4, 4c, 6c, 9b Ar = 4-HO2CC6H4
1
Elemental analytical data and mass spectrometric, infrared, and H NMR spectroscopic data for the
unknown material separated in a pure state showed that it is a tautomer of compound 4a and has the structure
1,3,5-triphenyl-1,6-dihydropyridazine (6a). With the aim of confirming this hypothesis we have measured the
HMQC, HMBC, and NOESY spectra of compounds 4a and 6a. Analysis of the heteronuclear correlations in the
HMBC spectra (see Table 1 and Figure 1) unambiguously prove the cyclic structure of the 1,3,5-triphenyl-
pyridazine in the molecules studied. The main differences in the spectra permit a safe assignment of the
tautomers 4a and 6a through the presence (or absence) of a correlation between the C-3 atom signal in the
region 142.2-141.1 ppm and the –CH2– and =CH– groups protons. For compound 4a a correlation is seen with
816

the signal for the methylene group protons at 3.64 ppm and for compound 6a with the methine proton signal at
7.29 ppm. Differences were also seen in the UV spectra of the tautomers 4a and 6a. In the case of compound 4a
two bands were seen above 300 nm with maxima at 318 (ε = 27×103) and 392 nm (ε = 104). In the spectrum of
compound 6a both bands (with comparable intensities) were shifted by 35-36 nm to shorter wavelength
(282 nm) or to longer wavelength (427 nm) respectively. The latter points to an increase in the conjugated chain
in the molecule and this is in agreement with the structure of the 1,6-dihydro derivative.
7.67
H
7.91 H
3.64
7.29
H
H
H
137.27
137.9
1'''
108.9
24.7
137.12
136.37
1'''
134.8
111.9
1''
142.38
1''
141.06
H 8.00
7.96
H
121.4
N
45.19
N
7.72 H
N
H
4.72
N
H
Ph
A
B
Ph
Fig. 1. Structurally significant HMBC correlations for compounds 4a (A) and 6a (B).
The dihydropyridazines 4a, 6a do not change upon prolonged storage or in solutions of different
polarity solvents in neutral medium at room temperature. In the presence of acid (EtOH–HBr, 25ºC) a solution
of the 1,6-dihydropyridazine 6a does not undergo a marked change (according to TLC). Under the same
conditions compound 4a is gradually converted to 1,3,5-triphenylpyridazinium bromide (3c). The structure of
the oxidation product 3c was proved from its spectroscopic properties which agreed with data obtained
previously for the pyridazinium bromides 3a,b [6]. Analysis of the heteromuclear correlations in the HMQC and
HMBC spectra of salts 3a, 3c (see Table 1) and 1-methyl-3,5-diphenylpyridazinium bromide [7] fully confirmed
the conclusions concerning the structure of salts 3a-c.
Heating solutions of 1,6-dihydropyridazine 6a in protonic solvents gave tautomer 4a (according to TLC
and H NMR data). However this method cannot be used preparatively since the 1,4-dihydropyridazine 4a is
1
readily aromatized or undergoes more profound changes. Hence by heating 4a in alcohol in the presence of acid
(HBr, HClO4) we separated a low yield (17-20%) of N,2,4-triphenyl-1H-pyrrole-1-amine (5), previously
obtained from the reaction mixture of γ-bromodypnone 1 with phenylhydrazine in alcohol [7]. The mechanism
of formation of pyrrole 5 includes a stage of reversible cleavage of the C(6)–N(1) bond [8, 9] which is due to
addition of EtOH to the C(5)=C(6) olefinic bond through acid catalysis [8]. Recyclization of product 7 give the
1H-pyrrole-1-amine 5.
With the aim of finding optimum conditions for the method of synthesizing compound 6a we attempted
to minimise the unwanted process of conversion of 6a to 4a. However, it was found that carrying out the
reaction of the γ-bromodypnone 1 with phenylhydrazine at room temperature (EtOH–AcOH, 2:3) gave the (Z)-
4-bromo-1,3-diphenyl-2-buten-1-one N-phenylhydrazone (2b). The spectroscopic parameters of the product
obtained were fully in agreement with those observed previously for N-(2,4-dinitrophenyl)hydrazone 2a [7]. In
contrast to the derivative 2a compound 2b proved less stable. Even with attempts to recrystallize it from alcohol
or AcOH or upon storage (over 3 weeks) it was readily converted to the 1,6-dihydropyridazine 6a.
Lowering the yield of product 6a upon heating the reaction mixture (EtOH–AcOH, 2: 3) was due both to
the indicated conversion of 6a to 4a and also to the occurrence of a side reaction involving reduction of the
bromomethyl group by the hydrazine. The material isolated from the reaction mixture in less than 15% yield
was the product of an intramolecular cyclization of the 1,3-diphenyl-2-buten-1-one N-phenylhydrazone (which
was formed by reduction of the hydrazone 2b), i.e. 5-methyl-1,3,5-triphenyl-4,5-dihydro-1H-pyrazole (8). The
1H and 13C NMR spectra and melting point of the substance obtained fully agreed with that of a sample
synthesized by a previously reported method [10] from dypnone and phenylhydrazine.
817

We further studied the reaction of γ-bromodypnone 1 with 4-nitrophenylhydrazine and with 4-hydra-
zinobenzoic acid. The reactions occur with more prolonged heating (30 min compared with 15 min in the case of
phenylhydrazine [6]) of the solution of starting materials in alcohol to give the 1-aryl-3,5-diphenyl-
1,6-dihydropyridazines 6b,c. Formation of substantial amounts of 1,4-dihydropyridazines 4b,c was observed
only when carrying out the reaction by fusion in the presence of NaOAc. The content of compounds 4b,c in the
mixtures obtained reached 20% in the case of the reaction with 4-nitrophenylhydrazine and 55% for that of
4-hydrazinobenoic acid. The overall yields of the fusion reaction products proved almost twice less than when
carryied out in alcohol. In contrast to compound 6a the 1,6-dihydropyridazines 6b,c proved more stable upon
heating in solvents, the 1H NMR spectra in DMSO-d6 showing only trace amounts of the tautomers of structure
4 (H-4 signal at 3.71 ppm for 4b and 3.69 ppm for 4c). Only prolonged heating (~ 1 h) of their solutions in
AcOH in the presence of HBr led to partial oxidation but principally to opening of the pyridazine ring and to
formation of hydrolysis products (arylhydrazines according to 1H NMR spectroscopic data).
The 1,6-dihydropyridazine structure contains a fragment of the original dypnone compound and it was
found that, just as the latter [14], can add polar molecules of the type H–X to the olefinic C(4)=C(5) bond. Hence
prolonged holding of acetic solutions of compounds 6b,c in the presence of HBr gives the 1-(4-aryl)-5-bromo-
3,5-diphenyl-1,4,5,6-tetrahydropyridazines 9a,b. The yield of the compounds is low (18% for 9a and < 8% for
9b). We were unable to prepare an analytically pure sample of the tetrahydropyridazine 9b because the material
was severely contaminated by admixtures and, evidently, has a low resistance to heating in solvents [3].
1
Characteristic features of the H NMR spectra of compounds 9a,b are the presence of signals for two methylene
groups in the region 4.8-3.5 ppm as AB type spin systems with geminal spin-spin couplings of 18.0 and 12.0 Hz.
TABLE 1. Proton-Carbon Correlations for Compounds 3a, 4a, 6a, and 9a
1Н NMR,
δ, ppm
НМВС, δ, ppm
1Н NMR,
δ, ppm
НМВС, δ, ppm
3a
4a
2.41
7.59
127.95, 133.3, 144.2
3.64
7.04
108.87, 121.42, 137.89, 142.38
116.03, 129.9
19.0, 127.05, 127.95, 132.55,
144.2
7.68
7.97
8.42
129.0, 130.2, 131.55, 132.9,
133.1, 133.53
7.24
7.38
7.45
124.74
132.3, 133.3, 144.2
116.03, 124.74, 129.1, 129.9,
137.89, 144.82
129.0, 133.1, 133.53, 147.8,
161.4
126.38
9.56
131.55, 132.9, 149.0
7.48
7.65
7.67
7.72
8.00
129.1, 137.27
10.59
130.05, 131.55, 144.2, 147.8
116.03, 122.85, 142.38
108.87, 126.38, 127.11
24.72, 108.87, 137.89
126.38, 129.9
6a
9а
4.72
7.00
7.29
7.35
7.38
7.43
7.49
111.94, 134.76, 136.37
115.33
3.55
3.99
4.61
4.75
7.08
7.34
7.40
38.58, 72.56, 141.99, 151.24
38.58, 72.56, 141.99, 151.24
45.19, 136.37, 141.06
125.47
51.83, 72.56
51.83
129.63, 147.9
129.22, 137.12
129.38, 136.37
—
126.07
72.56, 126.07, 128.85,
130.12, 141.99
7.53
7.91
7.96
115.33, 121.65, 147.09
126.11, 129.93, 134.76
125.47, 128.67, 141.06
7.46
7.79
7.99
127.02, 129.52, 131.5
127.02, 130.65, 151.24
126.12, 139.01, 148.18
818

2D HMQC, HMBC, and NOESY spectra of compound 9a were studied in order to confirm the structure of the
5-bromo-1,4,5,6-tetrahydropyridazines 9a,b (see Table 1). Analysis of the molecular model and the
proton-proton correlations in the NOESY spectrum also allows us to deduce the steric structure of compounds
9a,b. These compounds have a distorted boat structure with an equatorial orientation of all of the benzene rings.
The equatorial position of the benzene ring at C-5 points to the presence of the steric proximity of its o-protons
and the protons of the CH2 group at position 6.
Hence the reaction of γ-bromodypnone 1 with arylhydrazines is a multistage process, the result of which
is determined by two factors, i.e. the reaction conditions and the structure of the arylhydrazine. The
arylhydrazones of structure 2 formed in the first step is converted to the 1,3,5-triarylpyridazine cyclic
derivatives 3, 4 and 6. The rate of cyclization and the structure of the pyridazine depend on the nature of the
substituent in the benzene ring of the N-aryl molecular fragment. Increased acceptor properties lead to a
hindrance to the cyclization process on the one hand and to stabilization of the tautomeric form of the
1,6-dihydropyridazine 6 on the other. Increasing the donor properties of the substituent increases the rate of
cyclization and tendency to form the 1,4-dihydropyridazine 4 tautomer form which can then rearrange with the
participation of alcohol as nucleophile to the N,2,4-triaryl-1H-pyrrole-1-amine 5 or oxidize by the oxygen in the
air to give the aromatic pyridazinium salt 3. The tendency to form salt 3 strengthens with increase in the donor
properties of the substituent in the N-aryl fragment. The correctness of our conclusions relating to the observed
dependence is supported by data for the properties of the 1-substituted dihydropyridazines [3]. In particular, we
have previously [9, 11-13] noted their tendency towards oxidation by atmospheric oxygen upon heating and the
dependence of the stability towards oxidation on the nature on the substituent on the N(1) atom, in fact to the
increase in the stability of the 1,6-dihydropyridazines with increase in the electronegativity of the particular
substituent [11, 13].
Speeding up of the succession of reactions 2 → 6 → 4 is enabled by increasing temperature and the
basicity of the reaction medium. Heating in the presence of acid stimulates the rearrangement process of the
pyridazine 4 formed to the N-aminopyrrole 5 and also its conversion to salt 3.
EXPERIMENTAL
1H and 13C NMR spectra were recorded on a Varian Mercury instrument (400 and 100 MHz
respectively) using DMSO-d6 with TMS as internal standard. UV spectra were obtained on a Lambda 20
UV/VIS spectrometer using MeOH. IR spectra were taken on a Pye Unicam SP3-300 instrument for KBr tablets.
Mass spectra were obtained using HPLC on an AGILENT 1200 SL instrument (CI, acetonitrile, 0.05% formic
acid). Melting points for the synthesized compounds were measured on a Boetius type heating apparatus and
were not corrected. Monitoring of the course of the reaction and the purity of the products were carried out by
1
TLC on Silufol UV-254 plates. Elemental analytical data and H NMR spectra (DMSO-d6) for 1-(2-methyl-
phenyl)-3,5-diphenylpyridazinium bromide (3a) and 1,3,5-triphenyl-1,4-dihydropyridazine (4a) have been given
1
in the study [6] and for N,2,4-triphenyl-1H-pyrrole-1-amine (5) in [7]. Assignment of the signals in the H and
13C NMR spectra of 5-methyl-1,3,5-triphenyl-4,5-dihydro-1H-pyrazole 8 were made from the experimental
HMBC, HMQC, and NOESY data.
(Z)-4-Bromo-1,3-diphenyl-2-buten-1-one N-Phenylhydrazone (2b). γ-Bromodypnone 1 (1 g, 3.32 mmol)
was dissolved with heating in a mixture of alcohol (20 ml) and acetic acid (30 ml). Phenylhydrazine (0.33 ml,
3.32 mmol) was added to the cooled solution and held at room temperature for 36 h. The precipitate formed was
filtered off and washed with alcohol. Yield 0.52 g (40%). 1H NMR spectrum, δ, ppm (J, Hz): 10.32 (1H, s, NH);
8.10 (2H, d, 3J = 9.0, H-2',6'); 7.78 (4H, d, 3J = 7.5, H-2'',6'', H-2''',6'''); 7.49 (2H, t, 3J = 8.0, H-3',5'); 7.45-7.38
(7H, m, H-4', H-3''–H-5'', H-3'''–H-5'''); 6.80 (1H, s, H-2); 4.28 (2H, s, H-4).
819

1-(2-Methylphenyl)-3,5-diphenylpyridazinium Bromide (3a). IR spectrum, ν, cm-1: 3050, 1597
(C=N), 1390, 1260, 1155, 755, 665. 13C NMR spectrum, δ, ppm: 161.4 (C-3); 149.0 (C-6); 147.8 (C-5); 144.2
(C-1'); 133.5 (C-4''); 133.3 (C-2'); 133.1 (C-4'''); 132.9 (C-1''); 132.6 (C-6'); 132.3 (C-4'); 131.6 (C-1'''); 130.22
(C-3'',5''); 130.18 (C-3''',C-5'''); 130.05 (C-4); 129.5 (C-2'',6''); 129.0 (C-2''',C-6'''); 127.9 (C-3'); 127.0 (C-5');
19.0 (CH3). Mass spectrum, m/z (Irel, %): 323 [M-Br]+ (100), 325 (40).
1,3,5-Triphenylpyridazinium Bromide (3c). A solution of concentrated hydrobromic acid (3 ml) was
added to a solution of compound 4a (0.3 g, 1 mmol) in ethanol (20 ml) and held at room temperature for 48 h.
Solvent was evaporated in vacuo without heating. The residue was recrystallized from acetic acid. Yield 0.25 g
1
(65%); mp 165-168ºC (AcOH). IR spectrum, ν, cm-1: 3050, 1595 (C=N), 1390, 1255, 1155, 760, 670. H NMR
spectrum, δ, ppm (J, Hz): 10.59 (1H, d, 4J = 1.2, H-6); 9.47 (1H, d, 4J = 1.2, H-4); 8.45 (2H, d, 3J = 8.0, H-2',6'); 8.38
(2H, m, H-2'',6''); 8.28 (2H, m, H-2''',6'''); 7.79 (3H, m, H-3'–H-5'); 7.70-7.65 (6H, m, H-3''–H-5'', H-3'''–H-5''').
Found, %: C 67.97; H 4.51; Br 20.52; N 7.22. C22H17BrN2. Calculated, %: C 67.88; H 4.40; Br 20.53; N 7.20.
1,3,5-Triphenyl-1,4-dihydropyridazine (4a). A mixture of γ-bromodypnone 1 (1 g, 3.32 mmol),
AcONa (0.33 g, 4.0 mmol), and phenylhydrazine (0.33 ml, 3.32 mmol) was fused on an oil bath at 140ºC for
1 h. After cooling, water (10 ml) was added to the melt and thoroughly triturated. The solid was filtered off,
thoroughly washed with water and then 2-propanol, and recrystallized. Yield 0.67 g (65%); mp 131-133ºC
(EtOH) (mp 133ºC [6]); Rf 0.59 (Silufol UV-254, hexane–benzene, 2:1). IR spectrum, ν, cm-1: 3040, 1590
(C=N), 1490, 1335, 1247, 1200, 745, 680. UV spectrum, λmax, nm (ε×10-3): 202 (50.49), 240 (23.62), 318
(27.23), 392 (10.08). 13C NMR spectrum, δ, ppm: 144.82 (C-1'); 142.38 (C-3); 137.89 (C-1'''); 137.27 (C-1'');
129.88 (C-3',5',4''); 129.11 (C-3'',5''); 129.08 (C-3''',5'''); 127.11 (C-4'''); 126.38 (C-2'',6''); 124.74 (C-2''',6''');
122.85 (C-4'); 121.42 (C-6); 116.03 (C-2',6'); 108.87 (C-5); 24.72 (C-4). Mass spectrum, m/z (Irel, %): 311
[M+1]+ (20), 310 [M]+ (40), 309 [M-1]+ (100).
N,2,4-Triphenyl-1H-pyrrole-1-amine (5). 1,4-Dihydropyridazine 4a (0.3 g, 1 mmol) was dissolved in
ethanol (5 ml). A solution of HClO4 (60%, 1 ml) was added and heated to reflux. Solvent was evaporated to half
volume and left at room temperature for 3 h. The precipitate was filtered off and recrystallized. Yield 0.06 g
(20%); mp 164-165ºC (2-PrOH) (mp 165ºC [7]).
1,3,5-Triphenyl-1,6-dihydropyridazine (6a). γ-Bromodypnone 1 (1 g, 3.32 mmol) was dissolved with
heating in a mixture of alcohol (30 ml) and acetic acid (20 ml). Phenylhydrazine (0.33 ml, 3.32 mmol) was
added to the warm solution and the product was held at room temperature for 10 h. The precipitate formed was
filtered, washed with an alcoholic solution of sodium carbonate (15%), and recrystallized. Yield 0.52 g (51%);
mp 143-145ºC (EtOH–AcOH, 1:1); Rf 0.47 (Silufol UV-254, hexane–benzene, 2:1). IR spectrum, ν, cm-1: 3040,
1590 (C=N), 1485, 1335, 1273, 1190, 915, 735, 670. UV spectrum, λmax, nm (ε×10-3): 204 (45.83), 228 (17.58),
1
3
256 (27.54), 282 (33.06), 427 (10.37). H NMR spectrum, δ, ppm (J, Hz): 7.96 (2H, d, J = 8.0, H-2'',6''); 7.91
(2H, d, 3J = 8.0, H-2''',6'''); 7.53 (2H, d, 3J = 8.0, H-2',6'); 7.49 (2H, t, 3J = 8.0, H-3''',5'''); 7.43 (3H, m, H-3'',5'',
H-4'''); 7.38 (2H, t, 3J = 8.0, H-3',5'); 7.35 (1H, t, 3J = 8.0, H-4''); 7.29 (1H, s, H-4); 7.00 (1H, t, 3J = 8.0, H-4');
4.72 (2H, s, H-6). 13C NMR spectrum, δ, ppm: 147.08 (C-1'); 141.06 (C-3); 137.12 (C-1''); 136.36 (C-1''');
134.76 (C-5); 129.93 (C-4'''); 129.63 (C-3',5'); 129.38 (C-3''',5'''); 129.22 (C-3'',5''); 128.67 (C-4''); 126.11
(C-2''',6'''); 125.47 (C-2'',6''); 122.65 (C-4'); 115.33 (C-2',6'); 111.94 (C-4); 45.19 (C-6). Mass spectrum, m/z (Irel,
%): 311 [M+1]+ (100), 309 [M-1]+ (40). Found, %: C 85.40; H 5.90; N 9.09. C22H18N2. Calculated, %: C 85.13;
H 5.85; N 9.03.
1-(Aryl)-3,5-diphenyl-1,6-dihydropyridazines 6b,c (General Method). A mixture of γ-bromo-
dypnone 1 (1 g, 3.32 mmol) and 4-nitrophenylhydrazine or 4-hydrazinobenzoic acid (3.32 mmol) was refluxed
in nitromethane (50 ml) for 30 min. The solution was cooled and the precipitate was filtered off, washed with
alcohol, and recrystallized from acetic acid.
Compound 6b. Yield 0.79 g (67%); mp 190-192ºC (MeNO2). IR spectrum, ν, cm-1: 3070; 1590 (C=N);
as
s
1495 (NO2 ); 1317 (NO2 ); 1285, 1185, 1110, 915, 830, 745, 685. UV spectrum, λmax, nm (ε×10-3): 202 (37.93),
1
3
274 (27.13), 450 (24.28). H NMR spectrum, δ, ppm (J, Hz): 8.18 (2H, d, J = 9.0, H-3',5'); 7.96
820

3
3
(2H, d, J = 7.5, H-2'',6''); 7.88 (2H, d, J = 7.5, H-2''',6'''); 7.63 (2H, d, 3J = 9.0, H-2',6'); 7.50-7.37 (6H, m, H-3''–
H-5'', H-3'''–H-5'''); 7.24 (1H, s, H-4); 4.86 (2H, s, H-6). Mass spectrum, m/z (Irel, %): 355 [M-Br]+ (30), 354
[M-Br-1]+ (100). Found, %: C 74.48; H 4.93; N 11.81. C22H17N3O2. Calculated, %: C 74.35; H 4.82; N 11.82.
Compound 6c. Yield 0.58 g (68%); mp 193-195ºC (AcOH). IR spectrum, ν, cm-1: 3000 (br. CH, OH),
1593 (C=N), 1420, 1270 (br. δ OH), 1170, 910, 745, 675. UV spectrum, λmax, nm (ε×10-3): 202 (53.14), 2388
(31.52), 430 (15.64). 1H NMR spectrum, δ, ppm (J, Hz): 12.23 (1H, br. s, OH); 7.93 (4H, m, H-3',5',2'',6''); 7.85
3
3
(2H, d, J = 8.0, H-2''',6'''); 7.54 (2H, d, J = 8.8, H-2',6'); 7.49-7.41 (5H, m, H-3''–H-5'', H-3''',5'''); 7.35 (1H, t,
3J = 8.0, H-4'''); 7.21 (1H, s, H-4); 4.80 (2H, s, H-6). Found, %: C 78.00; H 5.23; N 7.92. C23H18N2O2.
Calculated, %: C 77.95; H 5.12; N 7.90.
5-Methyl-1,3,5-triphenyl-4,5-dihydro-1H-pyrazole (8). The reaction of bromodypnone 1 with
phenylhydrazine was carried out as reported in the method above for the preparation of the dihydropyridazine
6a. The filtrate formed after separation of the solid product 6a was evaporated at room temperature. The residue
was washed with a small amount of 2-propanol and recrystallized several times from 2-propanol. Yield 0.1 g
1
3
(9.5%); mp 177-179ºC (2-PrOH) (mp 180ºC [10]). H NMR spectrum, δ, ppm (J, Hz): 7.69 (2H, d, J = 8.0,
H-2'',6''); 7.48 (2H, d, 3J = 8.0, H-2''',6'''); 7.38 (4H, t, 3J = 8.0, H-3'',5'',3''',5'''); 7.30 (1H, t, 3J = 8.0, H-4'''); 7.28
(1H, t, 3J = 8.0, H-4''); 7.03 (2H, t, 3J = 8.0, H-3',5'); 6.91 (2H, d, H-2',6'); 6.69 (1H, t, 3J = 8.0, H-4'); 3.54 (1H,
2
2
d, J = 17.2, HA-4); 3.33 (1H, d, J = 17.2 HB-4); 1.79 (3H, s, CH3). 13C NMR spectrum, δ, ppm: 146.5 (C-3);
146.2 (C-1'''); 143.9 (C-1'); 133.2 (C-1''); 129.6 (C-4''); 129.3 (C-3',5',3'',5'',3''',5'''); 127.9 (C-4'''); 126.3
(C-2'',6''); 126.1 (C-2''',6'''); 119.7 (C-4'); 115.2 (C-2',6'); 70.53 (C-5); 53.5 (C-4); 22.36 (CH3).
5-Bromo-1-(4-nitrophenyl)-3,5-diphenyl-1,4,5,6-tetrahydropyridazine (9a). Using the method above
for the synthesis of compounds 6b,c from the γ-bromodypnone 1 (1 g, 3.32 mmol) and 4-nitrophenyl-hydrazine
(1.18 g, 3.32 mmol) to give the product 6b. The acetic filtrate obtained after recrystallization of compound 6b
was held for 5 days and filtered to give a precipitate of compound 9a. Yield 0.26 g (18%); mp 192-194ºC
1
(AcOH). IR spectrum, ν, cm-1: 1580 (C=N); 1480, 1295, 1100, 835, 752, 675. H NMR spectrum, δ, ppm (J,
3
Hz): 7.99 (2H, d, J = 8.0, H-3',5'); 7.79 (2H, m, H-2'',6''); 7.46 (3H, m, H-3''–H-5''); 7.40 (4H, m,
H-2''',3''',5''',6'''); 7.34 (1H, t, 3J = 7.5, H-4'''); 7.09 (2H, br. m, H-2',6'); 4.75 (1H, d, 2J = 12.0, HA-6); 4.61 (1H,
2
2
2
d, J = 12.0, HB-6); 3.99 (1H, d, J = 18.0, HA-4); 3.55 (1H, d, J = 18.0, HB-4). 13C NMR spectrum, δ, ppm:
151.24 (C-3); 148.18 (C-4'); 141.99 (C-1'''); 139.01 (C-1'); 131.50 (C-1''); 130.65 (C-4''); 130.12 (C-3''',5''');
129.52 (C-3'',5''); 128.85 (C-4'''); 127.02 (C-2'',6''); 126.12 (C-3',5'); 126.07 (C-2''',6'''); 113.51 (C-2',6'); 72.56
(C-5); 51.83 (C-4); 38.58 (C-6). Found, %: C 60.62; H 4.20; Br 18.30; N 9.65. C22H18BrN3O2. Calculated, %:
C 60.56; H 4.16; Br 18.31; N 9.63.
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