Aromatization and halogenation of 3,3a,4,5-tetrahydro-3-aryl-2-phenyl-2H- benzo[g]indazole using I2/DMSO, CuCl2/DMSO, and N-bromosuccinimide

Article abstract of DOI:10.1002/jhet.1049

The treatment of 3,3a,4,5-tetrahydro-3-aryl-2-phenyl-2H-benzo[g]indazoles 4 with I₂/DMSO led to the oxidation of the five-member rings (5) as well as the iodination of N-phenyl moieties along with oxidation of the five-member rings (6). However

Full text of DOI:10.1002/jhet.1049

1398
Aromatization and Halogenation of 3,3a,4,5-Tetrahydro-3-aryl-2-
phenyl-2H-benzo[g]indazole Using I2/DMSO, CuCl2/DMSO, and
N-Bromosuccinimide
Vol 49
a
a
*
Pradeep D. Lokhande, Kamal Hasanzadeh,
Hamid Khaledi,b and Hapipah Mohd Alib
aDepartment of Chemistry, University of Pune, Pune 411007, India
bDepartment of Chemistry, University of Malaya, Kuala Lumpur 50603, Malaysia
*
E-mail: pdlokhande@chem.unipune.ac.in
Received May 10, 2011
DOI 10.1002/jhet.1049
View this article online at wileyonlinelibrary.com.
The treatment of 3,3a,4,5-tetrahydro-3-aryl-2-phenyl-2H-benzo[g]indazoles 4 with I2/DMSO led to
the oxidation of the five-member rings (5) as well as the iodination of N-phenyl moieties along with ox-
idation of the five-member rings (6). However, the reactions of 4 with CuCl2/DMSO gave only compounds
5. The reaction of N-bromosuccinimide (NBS) with compounds 4 resulted in fully aromatization along with
bromination at C-5 of the indazole rings (7). The indazole six-member rings in compounds 5 and 6 also
underwent aromatization along with bromination by using NBS (7 and 8).
J. Heterocyclic Chem., 49, 1398 (2012).
INTRODUCTION
Most of the existing methods contain synthesis of
3,4-dihydrobenzo[g]-1H-indazole. For the construction
of these compounds, usually a-tetralon is used, such as
the reaction of lithium enolate of a-tetralon with isonipecotic
acid and subsequent condensation with hydrazine [11],
condensation of hydrazone of a-tetralon with substituted
aromatic ester in the presence of LDA [12], Claisen conden-
sation of diethyloxalate with a-tetralon, followed by reaction
with hydrazine hydrochloride [13] or methylhydrazine [10],
and condensation of a-tetralon with aldehydes followed by
reaction with p-cyanophenylhydrazine [14]. On the other
hand, oxidation of hydrogenated indazole derivatives has
been less encountered in literature and mostly requires
drastic reaction conditions and expensive reagents with
long reaction times and low yields. Examples are the
reaction of tetrahydro-3-aryl-1H-indazole with 10%
Pd/C in trans-decaline at reflux for 24 h [15], dehydro-
genation of tetrahydro-2,3-diaryl-2H-indazole by DDQ
Indazole derivatives, which are bioisosteres of indoles,
are an important class of compound in the medicinal
arena [1]. They have been reported to possess a
variety of biological activities including high binding
affinity for estrogen receptor [2], inhibition of protein
kinase C-b [3], 5-HT2 and 5-HT3 receptor antagonisms
[4], HIV protease inhibition [5], and antitumor activity
[6]. Lonidamine, a derivative of indazole-3-carboxylic
acid, is an anticancer drug for the treatment of lung,
breast, prostate, and brain cancers [7]. The homologues
of 2H-indazole, namely benzo[g]-2H-indazole, are a
potential pharmacophore studied as an estrogen receptor
b ligand [8], antiproliferative agent [9] and exhibit good
affinity to the imidazoline I2 receptor with low affinity
to the a2-andrenoceptor [10]. However, compared to
1H-indazoles, benzo[g]-2H-indazoles have been much
less studied, partly due to the difficulty in their preparation.
© 2012 HeteroCorporation

November 2012
Aromatization and Halogenation of
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3,3a,4,5-Tetrahydro-3-aryl-2-phenyl-2H-benzo[g]indazole
protons at C-4 and one single proton at the C-3a positions.
These protons appear as two multiplets and a triplet of
doublet, respectively, at the d = 1.93, 2.27, and 3.24 ppm (for
4b), each integrating for one proton.
Oxidation of 3,3a,4,5-tetrahydro-3-aryl-2-phenyl-2H-benzo
[g]indazole 4 by using I2-DMSO. Initially, we attempted the
(2,3-dichloro-5,6-dicyano-1,4-benzoquinone) in benzene at
reflux for 24 h [16], and oxidation of five-member ring in
hexahydro-2,3-diaryl-2H-indazole by DDQ in dioxane at
reflux with 32% yield [17]. To the best of our knowledge,
there is no report about dehydrogenation of dihydro-
2H-indazoles. Herein, we disclose our preliminary results
using different oxidizing agents for the oxidation of
tetrahydrobenzo[g]-2H-indazoles to the corresponding
benzo[g]-2H-indazoles. We have recently reported the
use of I2/DMSO as an efficient catalytic system for the
oxidation of pyrazoline to pyrazole [18] and dehydrogena-
tion of flavanones [19]. In continuation of our research
programmed on applications of such a system, it was
found that the products of the condensation reaction of
a-tetralon with substituted aromatic aldehydes followed
by cyclization with phenyl hydrazine may undergo
oxidative dehydrogenation by I2/DMSO system to con-
struct the corresponding benzo[g]-2H-indazoles. Furthermore,
CuCl2/DMSO and N-bromosuccinimide (NBS) were investi-
gated for their oxidation behavior toward the substrates.
oxidation of 3,3a,4,5-tetrahydro-2,3-diphenyl-2H-benzo[g]
indazole 4a using iodine (10%) in DMSO at 60ꢀC as per
our known procedures for the pyrazole synthesis [18].
After 10 h, thin layer chromatography (TLC) confirmed
the absence of the reactant, and two new spots were
developed. Spectral data such as 1H-NMR, 13C-NMR, and
GC-mass spectra indicated the formation of two products,
1
5a and 6a, in a ratio of 92:8. The H-NMR spectra of the
two products showed the absence of hydrogens on C3 and
C3a when compared with the spectrum of the reactant 4a.
Surprisingly, the spectral analysis of 6a revealed that
its N-phenyl ring was iodinated at the para position. The
1H-NMR of 6a showed two doublets at d = 7.12 ppm
(2H) and 7.67 ppm (2H), with the same coupling constant
(8.7 Hz). Furthermore, its 13C-NMR spectrum exhibited a
distinct absorbance at d = 91.4 ppm, and its MS spectrum
showed 126 mass units greater than that of 5a. The
reaction was then carried out using different amounts of
iodine and at different temperatures. As shown in Table 1,
the reaction time and the products ratio were found to be
dependent on the quantity of the catalyst and the reaction
temperature. Thus, while the conversion of 4a to the
products at room temperature did not occur (entries 1
and 9), the best yield of 5a was obtained by using 10%
iodine in DMSO at 120ꢀC for 3 h (entry 4). The optimal
conditions for the preparation of 6a were found to be using
1.3 equiv iodine in DMSO at 120ꢀC for 30 min (entry 12).
The products were easily purified by recrystallization from
ethanol (the yields were 73 and 86% for 5a and 6a,
respectively). To generalize the synthetic procedure, various
3,3a,4,5-tetrahydro-3-aryl-2-phenyl-2H-benzo[g]indazoles 4
were converted to the corresponding 4,5-dihydro-2,3-diaryl-
2H-benzo[g]indazoles 5 and 4,5-dihydro-2-(4-iodophenyl)-
RESULTS AND DISCUSSION
Preparation of 3,3a,4,5-tetrahydro-3-aryl-2-phenyl-2H-
benzo[g]indazole.
The precursor chalcones 3a–e were
prepared from the reaction of a-tetralon 1 with substituted
aromatic aldehydes 2 in methanolic KOH solution
(Scheme 1). The formation of 3a–e was confirmed on the
basis of their infrared (IR) and 1H-NMR data. The
chalcones were then reacted with phenyl hydrazine in
refluxing methanol for 4–6 h to form stable 2H-benzo[g]
indazoles 4a–e in 78–86% yield (Scheme 1). This reaction
probably takes place through mediation of an appropriate
hydrazone, which immediately cyclizes to 2H-benzo[g]
indazole ring system. Compounds 4a–e show in their IR
spectra absorbances for C═N at n = 1603–1609 cmÀ1
.
The 1H-NMR spectra of these compounds generally
exhibit an AMX pattern for the presence of two diastereotopic
Scheme 1. Synthesis of 3,3a,4,5-tetrahydro-3-aryl-2-phenyl-2H-benzo[g]indazoles.
Journal of Heterocyclic Chemistry
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P. D. Lokhande, K. Hasanzadeh, H. Khaledi, and H. Mohd Ali
Vol 49
Table 1
1.3 equiv copper chloride in DMSO resulted in very low
yields of 5a (entries 1 and8), the rate and the yield of the
reaction were improved with increasing the reaction
temperature and the amount of CuCl2. The best result was
obtained with the use of 2 equiv of copper chloride at
100ꢀC, in which the reaction was accomplished within 25
min and with an excellent yield (94%). To assess the
generality of the procedure, a variety of substituted 4 were
converted to the corresponding compound 5 by the action of
CuCl2-DMSO system (Scheme 2). Similar to what was
observed in the reaction with I2/DMSO, the product 5 did
not undergo dehydrogenation–oxidation at their C4—C5
bonds, even on increasing the molar ratio of the oxidant up
to six molar and increasing the reaction temperature and time
up to 160ꢀC for 48 h. Therefore, we have developed two
methods for the preparation of compounds 5 (10% I2 or 2
equiv CuCl2 in DMSO); however, copper chloride when
compared with molecular iodine gave better yields and
exclusively one product (Table 3).
Effects of the amount of the iodine catalyst and temperature on the
conversion of 4a to 5a and 6a.
Entry
I2 (%)
Temp (ꢀC)
Time
5a:6aa
c
1
2
3
4
5
6
7
8
10%
10%
10%
10%
20%
40%
60%
1eq
1.3eq
1.3eq
1.3eq
1.3eq
rtb
60
90
120
120
120
120
120
rtb
15 h
10 h
6 h
3 h
2.5 h
2 h
100 min
70 min
10 h
3 h
80 min
30 min
–
92:08
94:06
95:05
85:15
65:35
50:50
30:70
c
9
–
10
11
12
60
90
120
25:75
10:90
5:95
Oxidation of 3,3a,4,5-tetrahydro-3-aryl-2-phenyl-2H-benzo[g]
indazole 4 by using N-bromosuccinimide. N-bromosuccinimide
aThe ratio of compounds 5a and 6a were obtained based on 1H-NMR
(NBS) is a known reagent for the oxidation of primary
and secondary alcohols [26,27], 1,4-dihydropyridine [28],
cyclohexa-1,4-dien-3-carboxylates [29], N-substituted
indoles to isatins [30], pyrazolines to pyrazoles [31],
1,2,3,4-tetrahydroquinuline to 4-bromoquinuline [32],
2,3-dihydrobenzofuran to 3-bromobenzofuran [33], and 2,
3-dihydroinden-1-one to 3-bromo-1H-inden-1-one [34]. In
addition, NBS is a preferred reagent for allylic [35] and
benzylic [36,37] bromination. Herein, we describe a new
approach for the oxidation of 3,3a,4,5-tetrahydro-3-aryl-2-
phenyl-2H-benzo[g]indazoles 4 to the corresponding
2H-benzo[g]indazole derivatives using commercially available
NBS. As a model reaction, we selected compound 4e to react
with 1 equiv of NBS in CCl4 and in the presence of a catalytic
amount of benzoylperoxide. After overnight refluxing, TLC
showed that the reaction was not completed. So, we increased
the molar ratio of NBS, slowly and at different times till 3
equiv, whereupon TLC confirmed the absence of reactant 4e.
Spectroscopic analysis of the product indicated that the
reaction led to dehydrogenation in both five and six-member
rings of the indazole system and also bromination to form
spectroscopy and GC.
bRoom temperature.
cNo reaction.
3aryl-2H-benzo[g]indazoles 6 (Scheme 2). Furthermore, it
was realized that under the same conditions as for the
conversion of 4–6, compound 5 did not undergo iodination
at the N-phenyl rings (Scheme 2). Apparently, due to the
aromatization of the five-member rings, the nitrogen (N2)
lone pair electrons are not available for the N-bound phenyl
rings. It is noteworthy that in none of the dehydrogenation–
oxidation cases of the six-member ring was observed, even
on increasing the molar ratio of the reagent up to six molar
and conducting the reaction for 48 h at 120ꢀC.
Oxidation of 3,3a,4,5-tetrahydro-3-aryl-2-phenyl-2H-benzo
[g]indazole 4 by using CuCl2-DMSO. Copper (II) chloride
has low cost, readily available, and easy to work-up due to
its solubility in water. Literature survey revealed that
CuCl2-TBHP (tert-butyl hydroperoxide) applied for the
oxidation of alcohols [20,21] to aldehydes or ketones and
oxidation of alkynes [22] to a,b-acetylenic ketones.
CuCl2–O2 was used for oxidative cleavage of carbon–
carbon double bond of enol ethers to corresponding
ketones [23]. Anhydrous copper chloride in pyridine was
applied for dehydrogenation of indolines to indoles [24],
and CuCl2-DMSO showed oxidative amidation activity
toward terminal alkynes [25]. On account of these reports,
we used copper chloride in dimethylsulfoxide for the
oxidation of tetrahydro-2H-benzo[g]indazoles 4. Compound
4a was chosen as a model substrate to optimize the reaction
conditions such as the amount of CuCl2, the reaction
temperature, and the reaction time. As shown in Table 2,
while at room temperature the treatment of 4a with 10% or
1
compound 7e (Scheme 2). The H-NMR spectrum of 7e,
when compared with that of the reactant, showed the absence
of the aliphatic hydrogens and also the singlet peak at d = 7.84
ppm (1H) in the spectrum of 4e. Furthermore, the mass
spectrum of 7e showed a peak at m/z = M+-79. Under the
same reaction conditions, the other derivatives of 4 were also
converted to the corresponding 5-bromo-2,3-diaryl-2H-benzo
[g] indazoles 7a–e with high yields (Scheme 2).
In an extension of this procedure, the oxidation of the
six-member rings of compounds 5a–e and 6a–e by NBS
(2.1 equiv) was studied. In these cases also, the six-member
rings of the reactants underwent aromatization and also
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Aromatization and Halogenation of
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3,3a,4,5-Tetrahydro-3-aryl-2-phenyl-2H-benzo[g]indazole
Scheme 2. Aromatization of 3,3a,4,5-tetrahydro-3-aryl-2-phenyl-2H-benzo[g]indazoles 4 by using I2/DMSO, CuCl2/DMSO, and NBS.
Table 3
Table 2
Comparison of yields of 5a–e obtained by I2(10%) and CuCl2(2 equiv) in
Effects of the CuCl2 catalyst and temperature on the synthesis of 5a.
dimethylsulfoxide solvent.
Yield (%)
Entry
I2(10%)
CuCl2(2 equiv)
5a
5b
5c
5d
5d
73
71
75
75
72
94
90
93
94
91
Entry
CuCl2 (%)
Temp (ꢀC)
Time
Yield (%)
1
2
3
4
5
6
7
8
9
10
10%
10%
20%
20%
40%
60%
1eq
1.3eq
1.5eq
2eq
r.t.
60
60
100
60
100
100
r.t.
25 h
15 h
11 h
7 h
5.5 h
3 h
1.5 h
21 h
70 min
25 min
5
35
40
55
75
75
85
8
bromination at C5, with high yields (Scheme 3). The structures
of the products were determined by spectroscopic methods.
Among all, the structure of compound 8b was further con-
firmed by X-ray crystallographic analysis. The molecular
structure of 8b is depicted in Figure 1, and the selected inter-
atomic distances and angles are listed in Table 4. The benzo
60
100
88
94
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P. D. Lokhande, K. Hasanzadeh, H. Khaledi, and H. Mohd Ali
Vol 49
Table 4
Scheme 3. Synthesis of 5-bromo-2,3-diaryl-2H-benzo[g]indazoles.
Selected geometric parameters for 8b.
Interatomic distances (Å)
I(1)–C(22)
2.111(8)
Br(1)–C(8)
Br(1)–Br(1)#1
N(1)–N(2)
1.895(8)
3.2538(18)
1.372(9)
N(1)–C(19)
C(8)–C(9)
C(11)–C(12)
Bond angles (ꢀ)
C(11)–N(1)–C(19)
N(1)–C(11)–C(12)
1.420(10)
1.345(11)
1.466(11)
128.1(7)
126.4(7)
Symmetry transformations used to generate equivalent atoms: #1 À x + 1,
Ày + 3, Àz + 1.
rings of the reactants remained intact, aromatization of five and
six-member rings, and also bromination at C5 of compounds
4a–e took place by NBS.
[g]indazole moiety is essentially planar and makes dihedral
angles of 27.1(3)ꢀ with the N-bound aromatic ring and 57.6
(2)ꢀ with the C-bound aromatic ring. An interesting future of
the structure is a Br...Br interaction between the adjacent
molecules, related by the symmetry of Àx + 1, Ày + 3, Àz
+ 1, with the interatomic distance of 3.2538(18) Å, which is
significantly shorter than the sum of the Van der Waals radii
of the relevant atoms (3.70 Å).
EXPERIMENTAL
1H-NMR and 13C-NMR spectra were recorded on 300 and 75
MHz, respectively, and chemical shift values were recorded in
d units (ppm) relative to Me4Si as internal standard. Melting
points were determined by using a Buchi melting point apparatus.
IR spectra were recorded using KBr pellets on a Perkin-Elmer
240C analyzer. Mass spectra were recorded in an AE-IMS-30
spectrometer. TLC was performed on silica gel 60 PF254 plates
or aluminum oxide plates from Merck. Elemental analyses were
performed on a Thermo Flash EA 1112 analyzer.
CONCLUSION
We described the action of I2/DMSO, CuCl2/DMSO, and
NBS on 3,3a,4,5-tetrahydro-3-aryl-2-phenyl-2H-benzo[g]
indazoles 4a–e toward oxidation and halogenation. The
five-member rings of compounds 4a–e were aromatized by
using I2 (10%) and CuCl2 (2 equiv) in dimethylsulfoxide
as solvent, whereas by using 1.3 equiv I2, aromatization
along with iodination at the para position of N-phenyl moiety
occurred. Although within these procedures, the six-member
General procedure for synthesis of 2-arylidene-3,4-
dihydronaphthalen-1(2H)-one (3a-e). To a mixture of a-tetralone
(3.5 mmol) and appropriate benzaldehyde (3.5 mmol) in 50 mL
methanol, KOH (4 mmol) was added. The reaction mixture was
stirred at room temperature until the formation of a precipitate. The
solid obtained was isolated by filtration, washed, and recrystallized by
methanol.
2-Benzylidene-3,4-dihydronaphthalen-1(2H)-one (3a).
Yield: 78%; mp: 98ꢀC; IR (KBr) n = 1661, 1598 cmÀ1; 1H-NMR
(CDCl3) d: 2.96 (t, 2H, J = 6 Hz), 3.15 (t, 2H, J = 6 Hz),
7.25–7.28 (m, 2H), 7.34–7.43 (m, 6H), 7.89 (s, 1H), and 8.15
(d, 1H, J = 7.2 Hz); 13C-NMR (CDCl3) d: 27.5, 28.9, 125.1,
127.8, 129.1, 129.2, 129.4, 129.7, 133.6, 133.7, 134.1, 135.3,
139.5, 143.8, and 187.7; ms: m/z 234(M+). Anal. Calcd. for
C17H14O: C, 87.15; H, 6.02. Found: C, 87.17; H, 5.98.
2-(4-Methoxybenzylidene)-3,4-dihydronaphthalen-1(2H)-
one (3b).
Yield: 78%; mp: 90ꢀC; IR (KBr) n = 1670,
1601 cmÀ1; H-NMR (CDCl3) d: 2.95 (t, 2H, J = 6.6 Hz), 3.15
(t, 2H, J = 6.6 Hz), 3.85 (s, 3H), 6.95 (d, 2H, J = 9 Hz), 7.34–7.51
(m, 5H), 7.85 (s, 1H), and 8.12 (d, 1H, J = 6.3 Hz); 13C-NMR
(CDCl3) d: 28.1, 28.7, 59.3, 112.2, 125.7, 125.8, 126.1, 127.5,
128.8, 131.8, 134.3, 134.7, 134.9, 144.1, 158.5, and 187.8; ms:
m/z 264(M+). Anal. Calcd. for C18H16O2: C, 81.79; H, 6.10.
Found: C, 81.82; H, 6.07.
1
2-(3,4-Dimethoxybenzylidene)-3,4-dihydronaphthalen-1(2H)-
Figure 1. 5-Bromo-2-(4-iodophenyl)-3-(4-methoxyphenyl)-2H-benzo[g]
indazole (8b).
one (3c). Yield: 78%; mp: 95ꢀC; IR (KBr) n = 1670, 1595 cmÀ1
;
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November 2012
Aromatization and Halogenation of
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3,3a,4,5-Tetrahydro-3-aryl-2-phenyl-2H-benzo[g]indazole
1H-NMR (CDCl3) d: 2.98 (t, 2H, J = 6 Hz), 3.17 (t, 2H,
J = 6 Hz), 3.87 (s, 3H), 3.89 (s, 3H), 6.73 (s, 1H), 7.12 (d, 1H, J = 7.8 Hz),
7.22–7.51 (m, 4H), 7.82 (s, 1H), and 8.10 (d, 1H, J = 6.9 Hz);
13C-NMR (CDCl3) d: 27.5, 28.7, 58.4, 59.0, 109.6, 113.2,
117.7, 128.6, 128.7, 128.9, 129.7, 131.2, 131.8, 133.0, 133.2,
142.8, 151.4, 152.7, and 188.3; ms: m/z 294(M+).
J = 7.2 Hz), 6.89 (d, 1H, J = 8.7 Hz), 6.98–7.01 (m, 2H),
7.09–7.20 (m, 5H), 7.24–7.27 (m, 2H), and 8.05–8.08 (m, 1H);
13C-NMR (CDCl3) d: 25.7, 28.9, 55.4, 55.8, 55.9, 57.1, 112.4,
115.5, 116.1, 116.3, 122.7, 127.3, 128.6, 129.0, 129.3, 129.9,
132.1, 134.8, 141.3, 144.1, 149.2, 151.6, and 154.5; ms: m/z
384(M+), 369, 247, 199, 56, and 44. Anal. Calcd. for
C25H24N2O2: C, 78.10; H, 6.29; N, 7.29. Found: C, 78.08; H,
6.28; N, 7.28.
3,3a,4,5-Tetrahydro-3-(3,4,5-trimethoxyphenyl)-2-phenyl-
2H-benzo[g]indazole (4d). Yield: 84%; mp: 182ꢀC; IR (KBr)
n = 3056, 2931, 1609, 1588, and 1491 cmÀ1; 1H-NMR (CDCl3) d:
1.96 (m, 1H), 2.30 (m, 1H), 2.94 (m, 2H), 3.28 (td, 1H, J1 = 24.75,
J2 = 4.8 Hz), 3.85 (s, 6H), 3.86 (s, 3H), 4.51 (d, 1H, J = 11.7 Hz),
6.68 (s, 2H), 6.85 (t, 1H, J = 7.2 Hz), 7.10–7.28 (m, 7H), and 8.06
(dd, 1H, J1 = 6 Hz, J2 = 3.6 Hz); 13C-NMR (CDCl3) d: 27.4, 31.0,
55.8, 56.0, 56.1, 56.2, 109.3, 112.3, 117.0, 127.1, 128.8, 129.1,
129.2, 129.8, 129.9, 138.2, 138.4, 141.3, 144.8, 149.1, and
153.9; ms: m/z 414(M+), 399, 381, and 247. Anal. Calcd. for
C26H26N2O3: C, 75.34; H, 6.32; N, 6.76. Found: C, 75.35; H,
6.33; N, 6.77.
2-(3,4,5-Trimethoxybenzylidene)-3,4-dihydronaphthalen-1(2H)-
one (3d).
Yield: 78%; mp: 117ꢀC; IR (KBr) n = 1667 and
1
1599 cmÀ1; H-NMR (CDCl3) d: 2.97 (t, 2H, J = 6 Hz), 3.17
(t, 2H, J = 6 Hz), 3.89 (s, 6H), 3.90 (s, 3H), 6.68 (s, 2H), 7.26 (d,
1H, J = 7.2 Hz), 7.37 (t, 1H, J = 7.2 Hz), 7.50 (t, 1H, J = 7.2 Hz),
7.81 (s, 1H), and 8.12 (d, 1H, J = 7.2 Hz); 13C-NMR (CDCl3) d:
27.8, 29.1, 59.3, 60.3, 101.3, 124.3, 125.1, 125.8, 127.1, 130.3,
130.5, 133.9, 134.3, 139.4, 143.4, 155.9, and 188.6; ms: m/z 324(M+).
2-(4-Chlorobenzylidene)-3,4-dihydronaphthalen-1(2H)-one
(3e). Yield: 78%; mp: 79ꢀC; IR (KBr) n = 1673, 1595 cmÀ1
;
1H-NMR (CDCl3) d: 2.95 (t, 2H, J = 6.3 Hz), 3.09 (t, 2H, J = 6.3 Hz),
7.25 (d, 2H, J = 7.2 Hz), 7.27–7.41 (m, 4H), 7.50 (t, 1H,
J = 7.2 Hz), 7.80 (s, 1H), and 8.12 (d, 1H, J = 7.2 Hz);
13C-NMR (CDCl3) d: 27.3, 28.8, 125.1, 126.8, 126.9,
128.3, 129.7, 130.1, 130.5, 132.4, 132.6, 133.1, 135.1,
143.3, and 187.1; ms: m/z 268 (M+).
3-(4-Chlorophenyl)-3,3a,4,5-tetrahydro-2-phenyl-2H-benzo[g]
indazole (4e).
Yield: 80%; mp: 146ꢀC; IR (KBr) n = 3030,
2951, 1604, 1591, and 1485 cmÀ1
;
1H-NMR (CDCl3) d: 1.96
General procedure for preparation of 3,3a,4,5-tetrahydro-
2,3-diphenyl-2H-benzo[g]indazole (4a-e). To solution of 2-
arylidene-3,4-dihydronaphthalen-1(2H)-one 3a–e (0.03 mol) in
25 mL methanol, phenylhydrazin (3.24 g, 0.03 mol) was added.
The resulting mixture was refluxed for 5–7 h (monitored by
TLC). The mixture of reaction was cooled at room temperature,
(m, 1H), 2.29 (m, 1H), 2.92 (dd, 2H, J1 = 8.7 Hz, J2 = 2.7 Hz),
3.22 (td, 1H, J1 = 24.9 Hz, J2 = 4.8 Hz), 4.60 (d, 1H, J = 11.7
Hz), 6.83 (t, 1H, J = 7.2 Hz), 7.04 (d, 2H, J = 7.5 Hz) 7.15–7.20
(m, 3H), 7.23–7.27 (m, 2H), 7.35–7.42 (m, 4H), and 8.03–8.06
(m, 1H); 13C-NMR (CDCl3) d: 26.0, 28.9, 54.9, 55.3, 112.5,
117.3, 125.8, 128.0, 128.7, 128.8, 129.2, 129.9, 130.0, 131.3,
131.9, 140.1, 140.3, 144.8, and 153.2; ms: m/z 358(M+), 323,
and 247. Anal. Calcd. for C23H19ClN2: C, 76.98; H, 5.34; N,
7.81. Found: C, 77.01; H, 5.35; N, 7.78.
and 3,3a,4,5-tetrahydro-3aryl-2-phenyl-2H-benzo[g]indazole
4
was precipitated. The mixture was filtered and recrystallized
by methanol.
3,3a,4,5-Tetrahydro-2,3-diphenyl-2H-benzo[g]indazole (4a).
Yield: 78%; mp: 169ꢀC; IR (KBr) n = 3027, 2932, 1603, 1583,
and 1486 cmÀ1; 1H-NMR (CDCl3) d: 1.95 (m, 1H), 2.31 (m, 1H),
2.90 (m, 2H), 3.28 (td, 1H, J1 = 24.9 Hz, J2 = 4.8 Hz), 4.63
(d, 1H, J = 12.3 Hz), 6.81 (t, 1H, J = 7.2 Hz), 7.06–7.19 (m, 5H),
7.22–7.29 (m, 2H), 7.31–7.48 (m, 5H), and 8.06–8.07 (m, 1H);
13C-NMR (CDCl3) d: 26.3, 30.0, 54.8, 57.2, 112.8, 116.7, 125.2,
125.6, 128.7, 128.9, 128.9, 129.3, 130.1, 131.1, 132.8, 141.4,
143.5, 145.3, and 153.6; ms: m/z 324(M+), 280, 247, 196, 146,
and 77. Anal. Calcd. for C23H20N2: C, 85.15; H, 6.21; N, 8.63.
Found: C, 85.11; H, 6.19; N, 8.65.
General procedure for preparation of 4,5-dihydro-2,3-
diaryl-2H-benzo[g]indazole (5a–e). Method a: To solution of 4
(0.024 mol) in 15 mL dimethylsulfoxide, iodine (0.0024 mmol)
was added. The resulting mixture was heated at 120ꢀC for 3 h.
After completion, the mixture of reaction was cooled at room
temperature. The reaction mixture was diluted with water, and the
untreated iodine was removed by washing with a saturated
solution of sodium thiosulfate. The product was isolated by
filtration and recrystallized by ethanol. Method b: To solution of 4
(0.024 mol) in 20 mL dimethylsulfoxide, 2 equiv copper chloride
was added. The resulting mixture was heated at 100ꢀC for 25
min. After completion, the mixture of reaction was cooled at room
temperature. Then, the mixture was poured in crushed ice. The
precipitate compound was filtered and recrystallized by ethanol.
3,3a,4,5-Tetrahydro-3-(4-methoxyphenyl)-2-phenyl-2H-benzo[g]
indazole (4b).
Yield: 77%; mp: 158ꢀC; IR (KBr) n = 3055,
2929, 1603, 1610, 1584, 1510, and 1486 cmÀ1
;
1H-NMR
(CDCl3) d: 1.93 (m, 1H), 2.27 (m, 1H), 2.90 (m, 2H), 3.24
(td, 1H, J1 = 24.9 Hz, J2 = 4.5 Hz), 3.81 (s, 3H), 4.58 (d, 1H,
J = 12 Hz), 6.81 (t, 1H, J = 7.5 Hz), 6.93 (d, 2H, J = 8.7 Hz),
7.07–7.22 (m, 5H), 7.23–7.25 (m, 2H), 7.38 (d, 2H, J = 8.4 Hz),
and 8.05 (m, 1H); 13C-NMR (CDCl3) d: 27.0, 30.1, 55.1, 55.9, 56.4,
113.1, 116.8, 118.3, 125.4, 128.5, 129.5, 129.7, 129.8, 130.3, 132.3,
132.6, 141.2, 144.9, 154.3, and 159.1; ms: m/z 354(M+), 339, 323,
247, 218, 207, 188, 91, 77, and 51. Anal. Calcd. for C24H22N2O: C,
81.33; H, 6.26; N, 7.90. Found: C, 81.34; H, 6.26; N, 7.88.
4,5-Dihydro-2,3-diphenyl-2H-benzo[g]indazole (5a). mp:
148ꢀC; IR (KBr) n = 3051, 2928, 1594, 1494, 1436, 1366, 1032,
and 969 cmÀ1; 1H-NMR (CDCl3) d: 2.85 (t, 2H, J = 6.6 Hz), 2.99
(t, J = 6.9 Hz), 7.18–7.35 (m, 13H), and 8.07 (m, 1H); 13C-NMR
(CDCl3) d: 17.4, 31.1, 118.4, 122.3, 126.1, 127.3, 127.4, 127.6,
127.7, 128.6, 129.6, 130.1, 131.3, 131.5, 134.5, 135.5, 141.2,
152.8, and 153.4; ms: m/z 322(M+), 280, 245, 230, 218, 204, 189,
180, 153, and 77. Anal. Calcd. for C23H18N2: C, 85.68; H, 5.63;
N, 8.69. Found: C, 85.65; H, 5.63; N, 8.68.
3,3a,4,5-Tetrahydro-3-(3,4-dimethoxyphenyl)-2-phenyl-2H-
benzo[g]indazole (4c). Yield: 86%; mp: 174ꢀC; IR (KBr) n = 3045,
4,5-Dihydro-3-(4-methoxyphenyl)-2-phenyl-2H-benzo[g]
indazole (5b). mp: 126ꢀC; IR (KBr) n = 3043, 2939, 1583, 1479,
and 1375 cmÀ1; 1H-NMR (CDCl3) d: 2.82 (t, 2H, J = 7.18 Hz), 2.98
(t, 2H, J = 7.2 Hz), 3.82 (s, 3H), 6.87 (d, 2H, J = 8.4 Hz), 7.12
(d, 2H, J = 9 Hz), 7.26–7.34 (m, 8H), and 8.00 (d, 1H, J = 6.6 Hz);
1
2938, 1605, 1581, 1504, and 1488 cmÀ1; H-NMR (CDCl3) d:
1.97 (m, 1H), 2.30 (m, 1H), 2.93 (dd, 2H, J1 = 10.35 Hz,
J2 = 3.3 Hz), 3.27 (td, 1H, J1 = 24.9 Hz, J2 = 5.4 Hz), 3.85
(s, 3H), 3.90 (s, 3H), 4.55 (d, 1H, J = 12.3 Hz), 6.83 (t, 1H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1404
P. D. Lokhande, K. Hasanzadeh, H. Khaledi, and H. Mohd Ali
Vol 49
13C-NMR (CDCl3) d: 17.1, 30.9, 56.7, 117.5, 118.3, 119.5, 126.6,
126.8, 126.9, 127.3, 127.4, 128.5, 130.1, 131.2, 131.4, 138.2, 140.0,
152.7, 152.9, and 158.9; ms: m/z 352 (M+), 335, 307, 275, 261,
248, 218, 202, 168, 153, 115, and 77. Anal. Calcd. for C24H20N2O:
C, 81.79; H, 5.72; N, 7.95. Found: C, 81.77; H, 5.73; N, 7.99.
4,5-Dihydro-3-(3,4-dimethoxyphenyl)-2-phenyl-2H-benzo[g]
J = 8.7 Hz), 7.12 (m, 4H), 7.27–7.32 (m, 3H), 7.64 (d, 2H, J = 8.1
Hz), and 7.97 (d, 1H, J = 6.9 Hz); 13C-NMR (CDCl3) d: 17.6, 30.3,
53.2, 91.9, 116.7, 118.3, 122.5, 124.2, 127.3, 127.8, 127.9, 129.8,
136.8, 137.8, 138.3, 138.4, 139.3, 151.2, 154.1, and 160.1; ms: m/z
478 (M+), 461, 433, 371, 350, 349, 292, 275, 217, 175, 153, and 76.
Anal. Calcd. for C24H19IN2O: C, 60.26; H, 4.00; N, 5.86. Found: C,
60.22; H, 3.98; N, 5.89.
indazole (5c).
mp: 118ꢀC; IR (KBr) n = 3051, 2944, 1601,
1
1493, and 1377 cmÀ1; H-NMR (CDCl3) d: 2.83 (t, 2H, 6.8 Hz),
2.96 (t, 2H, 6.8 Hz), 3.77 (s, 3H), 3.89 (s, 3H), 6.59 (s, 1H),
6.83 (d, 1H, J = 8.4 Hz), 6.89 (d, 1H, J = 8.4 Hz), 7.25–7.36
(m, 8H), and 8.01 (d, 1H, J = 6.9 Hz); 13C-NMR (CDCl3) d:
17.1, 30.6, 55.8, 56.1, 111.8, 116.8, 118.6, 121.3, 122.3, 125.1,
126.6, 128.2, 128.4, 128.5, 130.1, 131.7, 131.8, 138.5, 142.2,
147.3, 149.1, 151.3, and 153.2; ms: m/z 382(M+), 367, 352, 335,
321, 305, 278, 218, 204, 191, 168, 153, 115, and 77. Anal.
Calcd. for C25H22N2O2: C, 78.51; H, 5.80; N, 7.32. Found: C,
78.49; H, 5.78; N, 7.35.
4,5-Dihydro-2-(4-iodophenyl)-3-(3,4-dimethoxyphenyl)-2H-
benzo[g]indazole (6c). Yield: 90%; mp: 165ꢀC; IR (KBr) n = 3065,
2998, 1619, 1580, 1514, 1474, 1239, 1142, 1022, 997, and 825 cmÀ1
;
1H-NMR (CDCl3) d: 2.82 (t, 2H, J = 6.9 Hz), 3.01 (t, 2H, J = 6.6 Hz),
3.71 (s, 3H), 3.92 (s, 3H), 6.64 (s, 1H), 6.80 (d, 1H, J = 8.7 Hz), 6.88
(d, 1H, J = 8.4 Hz), 7.01 (d, 2H, J = 8.7 Hz), 7.12–7.35 (m, 3H), 7.64
(d, 2H, J = 8.4 Hz), and 7.97 (d, 1H, J = 7.5 Hz); 13C-NMR (CDCl3)
d: 17.1, 29.9, 50.9, 51.3, 92.9, 114.8, 116.4, 116.8, 122.1, 122.2,
127.5, 127.7, 127.8, 128.9, 131.2, 131.3, 137.5, 137.9, 139.3, 150.8,
152.1, 151.3, and 153.8; ms: m/z 508(M+), 493, 463, 381, 338, 245,
193, 56, and 44. Anal. Calcd. for C25H21IN2O2: C, 59.07; H, 4.16;
N, 5.51. Found: C, 59.10; H, 4.14; N, 5.54.
4,5-Dihydro-3-(3,4,5-trimethoxyphenyl)-2-phenyl-2H-benzo[g]
indazole (5d). mp: 153ꢀC; IR (KBr) n = 3052, 2948, 1596, 1489,
and 1376 cmÀ1; 1H-NMR (CDCl3) d: 2.90 (t, 2H, J = 6.6 Hz), 2.99
(t, 2H, J = 6.3 Hz), 3.67 (s, 6H), 3.87 (s, 3H), 6.38 (s, 2H),
7.26–7.38 (m, 8H), and 8.02 (d, 1H, J = 6.6 Hz); 13C-NMR
(CDCl3) d: 16.9, 29.8, 55.3, 56.1, 109.4, 117.1, 119.1, 127.2,
128.1, 128.3, 128.5, 128.6, 130.0, 130.6, 130.8, 138.4, 139.3,
141.9, 150.1, 152.0, and 152.4; ms: m/z 412(M+), 397, 381, 368, 351,
335, 307, 248, 199, 145, 77, and 56. Anal. Calcd. for C26H24N2O3:
C, 75.71; H, 5.86; N, 6.79. Found: C, 75.74; H, 5.88; N, 7.81.
4,5-Dihydro-2-(4-iodophenyl)-3-(3,4,5-trimethoxyphenyl)-
2H-benzo[g]indazole (6d). Yield: 91%; mp: 173ꢀC; IR (KBr)
n = 3055, 2983, 1625, and 1591 cmÀ1 1H-NMR (CDCl3) d:
;
2.85 (t, 2H, J = 7.5 Hz), 2.99 (t, 2H, J = 7.2 Hz), 3.71 (s, 6H),
3.89 (s, 3H), 6.38 (s, 2H), 7.12 (d, 2H, J = 9 Hz), 7.26–7.32
(m, 3H), 7.67 (d, 2H, J = 8.7 Hz), and 7.96 (d, 1H, J = 6.9
Hz); 13C-NMR (CDCl3) d: 19.5, 29.5, 56.0, 60.9, 91.4, 106.5,
117.3, 122.6, 125.2, 126.5, 126.8, 127.9, 128.2, 129.2, 136.8,
137.7, 137.9, 138.3, 139.9, 149.2, and 153.1; ms: m/z 538
(M+), 523, 480, 411, 396, 305, 279, 205, 190, 160, 133, 89,
and 45. Anal. Calcd. for C26H23IN2O3: C, 58.00; H, 4.31;
N, 5.20. Found: C, 57.97; H, 4.33; N, 5.23.
3-(4-Chlorophenyl)-4,5-dihydro-2-phenyl-2H-benzo[g]indazole
(5e). mp: 135ꢀC; IR (KBr) n = 3058, 2944, 1595, 1474, 1433,
1363, 1162, 1040, 927, and 838 cmÀ1; 1H-NMR (CDCl3) d: 2.82 (t,
2H, J = 7.2 Hz), 2.99 (t, 2H, J = 7.5 Hz), 7.12 (d, 2H, J = 8.1 Hz),
7.26–7.35 (m, 10H), and 7.01 (d, 1H, J = 7.2 Hz); 13C-NMR
(CDCl3) d: 16.9, 30.4, 118.3, 119.8, 125.9, 127.4, 128.3, 128.9,
129.1, 129.4, 129.5, 130.3, 130.4, 132.3, 135.5, 140.1, 141.2, 152.8,
and 153.7; ms: m/z 356(M+), 215, 201, 161, 115, 102, 77, 63, and
41. Anal. Calcd. for C23H17ClN2: C, 77.41; H, 4.80; N, 7.85. Found:
C, 77.40; H, 4.81; N, 7.85.
General procedure for preparation of 4,5-dihydro-2-(4-
iodophenyl)-3aryl-2H-benzo[g]indazole (6a–e). To solution of
4 (0.024 mol) in 15 mL dimethylsulfoxide, 1.3 equiv iodine was
added. The resulting mixture was heated at 120ꢀC for 30 min.
After completion, the mixture of reaction was cooled at room
temperature. The reaction mixture was diluted with water, and
the untreated iodine was removed by washing with a saturated
solution of sodium thiosulfate. The product was isolated by
filtration and recrystallized by ethanol.
3-(4-Chlorophenyl)-4,5-dihydro-2-(4-iodophenyl)-2H-benzo[g]
indazole (6e). Yield: 90%; mp: 160ꢀC; IR (KBr) n = 3045, 2985,
1
1609, 1589, and 1482 cmÀ1; H-NMR (CDCl3) d: 2.79 (t, 2H,
J = 6.6 Hz), 2.98 (t, 2H, J = 7.2 Hz), 7.07 (d, 2H, J = 8.7
Hz), 7.14 (d, 2H, J = 8.4 Hz), 7.27–7.30 (m, 3H), 7.36
(d, 2H, J = 8.7 Hz), 7.65 (d, 2H, J = 8.7 Hz), and 7.95
(d, 1H, J = 6.6 Hz); 13C-NMR (CDCl3) d: 19.3, 29.4, 91.8,
117.8, 122.6, 126.4, 126.9, 128.0, 128.3, 128.4, 128.9,
129.1, 130.5, 134.3, 136.8, 137.2, 137.9, 139.7, and 149.4;
ms: m/z 482(M+), 354, 344, 279, 217, 203, 178, 160, 76
(100), and 50. Anal. Calcd. for C23H16ClIN2: C, 57.22;
H, 3.34; N, 5.80. Found: C, 57.25; H, 3.32; N, 5.77.
General procedure for preparation 5-bromo-2,3-diaryl-
2H-benzo[g]indazole (7a-e). To a solution of 4 (1.54 mmol) in
CCl4 (100 mL) were added NBS (0.81 g, 4.62 mmol) and a
catalytic amount of benzoyl peroxide, and the mixture was
refluxed for 3 h. The mixture was cold-filtered and evaporated
to dryness. The crud product was crystallized from methanol.
4,5-Dihydro-2-(4-iodophenyl)-3-phenyl-2H-benzo[g]indazole
(6a). Yield: 88%; mp: 120ꢀC; IR (KBr) n = 3038, 3012, 2931,
1
1610, 1584, and 1485 cmÀ1; H-NMR (CDCl3) d: 2.79 (t, 2H,
5-Bromo-2, 3-diphenyl-2H-benzo[g]indazole (7a). Yield:
91%; mp: 194ꢀC; IR (KBr) n = 3062, 1592, 1500, 1452, 1349,
J = 6.9 Hz), 2.95 (t, 2H, J = 6.9 Hz), 7.06 (d, 2H, J = 8.4 Hz),
7.17–7.20 (m, 2H), 7.23–7.37 (m, 6H), 7.60 (d, 2H, J = 8.7 Hz),
and 7.94 (d, 1H, J = 7.2 Hz); 13C-NMR (CDCl3) d: 17.3, 30.1,
92.8, 116.3, 123.1, 125.3, 127.9, 128.1, 128.3, 128.5, 128.8,
131.3, 131.4, 135.2, 135.4, 139.2, 141.2, 152.3, and 153.3; ms:
m/z 448(M+), 371, 320, 256, 228, 218, 160, 128, 89, and 44.
Anal. Calcd. for C23H17IN2: C, 61.62; H, 3.82; N, 6.25. Found:
C, 61.61; H, 3.82; N, 6.24.
1
1256, 1187, 1149, 1100, 1033, 920, and 854 cmÀ1; H-NMR
(CDCl3) d: 7.35–7.49 (m, 10H), 7.65–7.68 (m, 2H), 7.92
(s, 1H), 8.28 (m, 1H), and 8.71 (m, 1H); 13C-NMR (CDCl3)
d: 113.9, 119.3, 122.8, 124.6, 124.9, 125.1, 126.5, 127.3,
127.6, 127.8, 128.1, 128.7, 129.1, 130.3, 130.5, 134.6,
141.2, 144.5, and 145.1; ms: m/z 398 (M+), 318, 298, 214,
159, 145, 77, and 55. Anal. Calcd. for C23H15BrN2:
C, 69.19; H, 3.79; N, 7.02. Found: C, 69.22; H, 3.81; N, 7.04.
4,5-Dihydro-2-(4-iodophenyl)-3-(4-methoxyphenyl)-2H-
benzo[g]indazole (6b). Yield: 86%; mp: 130ꢀC; IR (KBr) n = 3044,
1
2971, 1621, 1573, and 1495 cmÀ1; H-NMR (CDCl3) d: 2.81 (t,
5-Bromo-3-(4-methoxyphenyl)-2-phenyl-2H-benzo[g]indazole
(7b). Yield: 89%; mp: 182ꢀC; IR (KBr) n = 3052, 2954, 1606,
2H, J = 7.5 Hz), 2.99 (t, 2H, J = 7.5 Hz), 3.85 (s, 3H), 6.92 (d, 2H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2012
Aromatization and Halogenation of
1405
3,3a,4,5-Tetrahydro-3-aryl-2-phenyl-2H-benzo[g]indazole
1505, 1460, 1378, 1351, 1291, 1250, 1181, 1108, 1027, 969, 840,
5-Bromo-2-(4-iodophenyl)-3-(4-methoxyphenyl)-2H-benzo
[g]indazole (8b). Yield: 92%; mp: 208ꢀC; IR (KBr) n = 3060,
2935, 1609, 1575, 1492, 1250, 1177, 1029, 966, 831, and 763
1
and 767 cmÀ1; H-NMR (CDCl3) d: 3.85 (s, 3H), 6.95 (d, 2H,
J = 8.7 Hz), 7.28 (d, 2H, J = 8.7 Hz), 7.37–7.49 (m, 5H), 7.63–7.69
(m, 2H), 7.90 (s, 1H), 8.27,(m, 1H), and 8.70 (m, 1H); 13C-NMR
(CDCl3) d: 55.2, 114.3, 118.0, 118.6, 121.4, 122.3, 122.7, 125.8,
126.1, 126.2, 127.5, 127.7, 128.0, 128.1, 128.9, 130.8, 135.9, 139.9,
145.9, and 159.7; ms: m/z 428 (M+), 397, 347, 321, 254, 158, and
44. Anal. Calcd. for C24H17BrN2O: C, 67.14; H, 3.99; N, 6.53.
Found: C, 67.15; H, 3.99; N, 6.51.
5-Bromo-3-(3,4-dimethoxyphenyl)-2-phenyl-2H-benzo[g]
indazole (7c). Yield: 88%; mp: 161ꢀC; IR (KBr) n = 3049, 2932,
1603, 1505, 1466, 1374, 1288, and 1103 cmÀ1; 1H-NMR (CDCl3)
d: 3.73 (s, 3H), 3.85 (s, 3H), 6.71 (s, 1H), 6.77 (d, 1H, J = 8.1 Hz),
6.81 (d, 1H, J = 8.1 Hz), 7.22–7.33 (m, 5H), 7.64 (d, 2H, J = 7.8
Hz), 7.97 (s, 1H), 8.18–8.21 (m, 1H), and 8.66–8.69 (m, 1H);
13C-NMR (CDCl3) d: 55.3, 55.6, 112.8, 114.3, 116.2, 118.3,
119.4, 121.3, 122.9, 124.3, 124.8, 126.1, 126.2, 127.1, 128.2,
130.1, 131.2, 131.3, 138.6, 141.5, 147.2, 153.6, and 154.3;
ms: m/z 458(M+), 427, 377, 245, 159, and 44. Anal. Calcd. for
C25H19BrN2O2: C, 65.37; H, 4.17; N, 6.10. Found: C, 65.40;
H, 4.15; N, 6.07.
cmÀ1 1H-NMR (CDCl3) d: 3.87 (s, 3H), 6.98 (d, 2H, J = 9
;
Hz), 7.22–7.30 (m, 4H), 7.65–7.70 (m, 2H), 7.73 (d, 2H, J = 9
Hz), 7.86 (s, 1H), 8.27 (m, 1H), and 8.67 (m, 1H); 13C-NMR
(CDCl3) d: 55.3, 93.1, 114.5, 118.4, 118.9, 121.2, 122.2, 122.7,
126.1, 126.4, 127.3, 127.6, 127.9, 128.1, 130.8, 135.9, 138.1,
139.7, 146.2, 160.0; ms: m/z 554(M+), 539, 473, 426, 335, 267,
205, 183, 159, and 44. Anal. Calcd. for C24H16BrIN2O:
C, 51.92; H, 2.90; N, 5.05. Found: C, 51.90; H, 2.89; N, 5.07.
5-Bromo-2-(4-iodophenyl)-3-(3,4-dimethoxyphenyl)-2H-
benzo[g]indazole (8c). Yield: 87%; mp: 170ꢀC; IR (KBr) n = 3058,
3002, 2959, 2930, 1607, 1583, 1510, 1253, 1238, 1144, 864, 824,
and 763 cmÀ1; 1H-NMR (CDCl3) d: 3.74 (s, 3H), 3.96 (s, 3H), 6.75
(s, 1H), 6.95–6.99,(m, 2H), 7.25 (d, 2H, J = 8.7 Hz), 7.66–7.69
(m, 2H), 7.74 (d, 2H, J = 8.4 Hz), 7.89 (s, 1H) 8.28 (m, 1H), and
8.68 (m, 1H); 13C-NMR (CDCl3) d: 59.1, 59.3, 92.6, 113.1, 114.2,
119.3, 120.8, 122.1, 122.4, 125.1, 125.5, 126.3, 126.4, 126.8, 129.3,
130.1, 134.2, 138.3, 139.1, 142.2, 144.9, 156.3, and 157.1; ms: m/z
584(M+), 569, 553, 505,456, 397, 326, 287, 201, 179, 158, and 44.
Anal. Calcd. for C25H18BrIN2O2: C, 51.31; H, 3.10; N, 4.79. Found:
C, 51.29; H, 3.11; N, 4.82.
5-Bromo-3-(3,4,5-trimethoxyphenyl)-2-phenyl-2H-benzo[g]
indazole (7d). Yield: 92%; mp: 174ꢀC; IR (KBr) n = 3056, 2945,
1614, 1519, 1445, 1379, and 1110 cmÀ1 1H-NMR (CDCl3)
;
5-Bromo-2-(4-iodophenyl)-3-(3,4,5-trimethoxyphenyl)-2H-
benzo[g]indazole(8d). Yield: 88%; mp: 192ꢀC; IR (KBr) n = 3043,
d: 3.56 (s, 6H), 3.68 (s, 3H), 6.41 (s, 2H), 7.28–7.31 (m, 5H),
7.61 (d, 2H, J = 7.8 Hz), 7.91 (s, 1H), 8.01–8.04 (m, 1H), and
8.52–8.53 (m, 1H); 13C-NMR (CDCl3) d: 55.6, 55.9, 104.3,
114.1, 122.1, 123.9, 124.7, 124.9, 125.2, 125.3, 125.4, 126.9,
127.2, 128.3, 131.3, 131.4, 133.0, 143.6, 146.2, 148.3, and
153.4; ms: m/z 488(M+), 457, 407, 372, 345, 294, 201, 159, and
44. Anal. Calcd. for C26H21BrN2O3: C, 63.81; H, 4.33; N, 5.72.
Found: C, 63.80; H, 4.33; N, 5.69.
2938, 1610, 1590, 1485, 1168, 1041, and 959 cmÀ1 1H-NMR
;
(CDCl3) d: 3.76 (s, 6H), 3.98 (s, 3H), 6.41 (s, 2H), 7.19 (d, 2H, J = 9
Hz), 7.61–7.65 (m, 2H), 7.76 (d, 2H, J = 9 Hz), 7.83 (s, 1H), 8.19
(m, 1H), and 8.71(m, 1H); 13C-NMR (CDCl3) d: 55.9, 56.3, 92.0,
103.4, 114.1, 119.9, 121.8, 122.0, 126.1, 126.8, 126.9, 127.3, 127.4,
131.3, 133.9, 138.3, 138.8, 140.7, 145.1, 149.3, and 154.7; ms: m/z
614(M+), 599, 583, 486, 533, 498, 449, 315, 301, 298, 204, 155, and
43. Anal. Calcd. for C26H20BrIN2O3: C, 50.76; H, 3.28; N, 4.55.
Found: C, 50.78; H, 3.29; N, 4.52.
5-Bromo-3-(4-chlorophenyl)-2-phenyl-2H-benzo[g]indazole
(7e). Yield: 93%; mp: 168ꢀC; IR (KBr) n = 3057, 1593, 1501,
1457, 1350, 1256, 1182, 1095, 1021, 927, 868, and 837 cmÀ1
;
5-Bromo-3-(4-chlorophenyl)-2-(4-iodophenyl)-2H-benzo[g]
indazole (8e). Yield: 91%; mp: 210ꢀC; IR (KBr) n = 3068, 1615,
1595, and 1465 cmÀ1; 1H-NMR (CDCl3) d: 7.13 (d, 2H, J = 8.4
Hz), 7.29 (d, 2H, J = 7.8 Hz 7.59–7.62 (m, 2H), 7.66 (d, 2H,
J = 7.8 Hz), 7.69 (d, 2H, J = 8.4 Hz), 7.87 (s, 1H), 8.16
(m, 1H), and 8.68 (m, 1H); 13C-NMR (CDCl3) d: 92.4, 114.4,
121.7, 121.8, 122.1, 123.2, 127.1, 127.3, 127.8, 128.6, 129.6,
130.0, 131.1, 133.9, 136.3, 139.3, 140.5, 142.8, and 144.6; ms:
m/z 558(M+), 512, 478, 432, 341, 316, 214, 199, 158, 145, 105,
and 76. Anal. Calcd. for C23H13BrClIN2: C, 49.36; H, 2.34;
N, 5.01. Found: C, 49.34; H, 2.34; N, 5.03.
1H-NMR (CDCl3) d: 7.28–7.35 (m, 5H), 7.45 (d, 2H, J = 8.7
Hz), 7.55 (d, 2H, J = 8.7 Hz), 7.66–7.69 (m, 2H), 7.84 (s, 1H),
8.27–8.30 (m, 1H), and 8.65–8.69 (m, 1H); 13C-NMR (CDCl3)
d: 114.3, 119.9, 122.9, 124.1, 125.7, 125.8, 127.2, 127.3, 127.9,
128.1, 128.8, 131.3, 131.4, 131.8, 131.9, 133.2, 141.3, 143.2,
and 144.3; ms: m/z 432 (M+), 397, 353, 316, 289, 241,214, 199,
158, 144, 131, and 75. Anal. Calcd. for C23H14BrClN2: C,
63.69; H, 3.25; N, 6.46. Found: C, 63.67; H, 3.24; N, 6.44.
General procedure for preparation 5-bromo-2-(4-iodophenyl)-
3-aryl-2H-benzo[g]indazole (8a-e). To a solution of 6 (0.54 mmol)
in CCl4 (100 mL) were added NBS (0.19 g, 1.08 mmol) and
a catalytic amount of benzoyl peroxide, and the mixture
was refluxed for 3 h. The mixture was cold-filtered and
evaporated to dryness. The crud product was crystallized
from methanol.
Crystallography.
Diffraction data were measured with a
Bruker SMART Apex II CCD area-detector diffractometer
(graphite-monochromated Mo-Ka radiation, g = 0.71073 Å).
The orientation matrix, unit-cell refinement, and data reduction
were all handled by the Apex2 software (SAINT integration,
SADABS absorption correction [38]). The structure was solved
using direct method in the program SHELXS-97 and refined by
the full matrix least-squares method on F2 with SHELXL-97
[39]. All the nonhydrogen atoms were refined anisotropically,
and all the hydrogen atoms were placed at calculated positions
and refined isotropically. Drawing of the molecule was
produced with XSEED [40]. Crystal data and refinement are
summarized in Table 5. CCDC 819875 contains the
supplementary crystallographic data for the crystal. These data
can be obtained free of charge via www.ccdc.cam.ac.uk/conts/
retrieving.html (or from the Cambridge Crystallographic Data
5-Bromo-2-(4-iodophenyl)-3-phenyl-2H-benzo[g]indazole (8a).
Yield: 89%; mp: 180ꢀC; IR (KBr) n = 3054, 1620, 1585, 1494,
1038, 832, 761, and 695 cmÀ1 1H-NMR (CDCl3) d: 7.22
;
(d, 2H, J = 8.7 Hz), 7.35–7.38 (m, 2H), 7.44–7.48 (m, 3H),
7.66–7.70 (m, 2H), 7.72 (d, 2H, J = 8.7 Hz), 7.88 (s, 1H), 8.28
(m, 1H), and 8.68 (m, 1H); 13C-NMR (CDCl3) d: 92.9, 113.9,
119.9, 122.8, 123.1, 125.7, 127.6, 127.9, 128.1, 128.8, 129.6,
130.1, 130.2, 132.3, 133.7, 135.0, 139.1, 141.6, and 148.3; ms:
m/z 524(M+), 444, 396, 317, 289, 256, 214, 199, 159, 144, 76,
and 44. Anal. Calcd. for C23H14BrIN2: C, 52.60; H, 2.69; N,
5.33. Found: C, 52.58; H, 2.68; N, 5.33.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1406
P. D. Lokhande, K. Hasanzadeh, H. Khaledi, and H. Mohd Ali
Vol 49
Table 5
Werbel, L. M.; Worth, D. F.; Elslager, E. F.; Leopald, W. R.; Shillis, J.
L. J Med Chem 1988, 31, 1527.
Crystal data and structure refinement for 8b.
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Chem 2005, 44B, 2338.
Empirical formula
C24 H16 Br I N2O
Formula weight
Temperature (K)
Crystal system, space group
Unit-cell dimensions
a (Å)
b (Å)
555.20
100(2) K
Triclinic, P-1
9.4851(3)
10.5697(3)
11.9829(3)
114.723(2)
91.544(2)
111.295(2)
993.76(5)
2, 1.855
c (Å)
a (ꢀ)
b (ꢀ)
g (ꢀ)
Volume (Å3)
Z, Density (calculated; g cmÀ3
)
)
Absorption coefficient (mmÀ1
F(000)
3.640
540
Crystal size (mm3)
θ range for data collection (ꢀ)
Index ranges
0.15 Â 0.11 Â 0.02
2.23–25.24
À11< = h< = 11, À12<
= k< = 12, À14< = l< = 14
7616/3578 [R(int) = 0.0659]
To θ = 25.00: 99.2%
0.9308 and 0.6112
3578/0/263
Reflections collected/unique
Completeness
Max. and min. transmission
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I > 2s (I)]
R indices (all data)
0.958
R1 = 0.0560, wR2 = 0.1233
R1 = 0.1033, wR2 = 0.1401
1.107 and À0.737
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet