Selective synthesis of some 4,5-dihydro-2H-benzo[g]indazoles and 8,9-dihydro-2H-benzo[e]indazoles via the Vilsmeier-Haack reaction under thermal and microwave assisted conditions

Article abstract of DOI:10.1002/jhet.5570430219

A selective and easy method is described for the synthesis of 4,5-dihydro-2H-benzo[g]indazoles and 8,9-dihydro-2H-benzo[e]indazoles by the Vilsmeier-Haack reaction of various tetralone phenylhydrazones under thermal and microwave irradiation conditions.

Full text of DOI:10.1002/jhet.5570430219

Mar-Apr 2006
389
Selective Synthesis of Some 4,5-Dihydro-2H-benzo[g]indazoles and
8,9-Dihydro-2H-benzo[e]indazoles Via the Vilsmeier-Haack Reaction
Under Thermal and Microwave Assisted Conditions
Ganesabaskaran Sivaprasad, Radhakrishnan Sridhar and Paramasivan T. Perumalꢀ
Organic Chemistry Division,
Central Leather Research Institute, Adyar, Chennai – 600 020, INDIA
Fax: 91- 44-24911589; E-mail: ptperumal2002@yahoo.com
Received July 17, 2005
R5
R5
R4
R4
NH
N
N
N
DMF/POCl3
R3
R2
R3
R2
R1
1a-j
R1 = R2 = R3 = H, OCH3 ; R4 = R5 = H, NO2
R1
2a-j
Conditions: DMF/POCl3, (Solvent-DMF), 60-65 0C, 6 hrs. (or)
DMF/POCl3,, MWI, 1 1/2 min.
A selective and easy method is described for the synthesis of 4,5-dihydro-2H-benzo[g]indazoles and
8,9-dihydro-2H-benzo[e]indazoles by the Vilsmeier-Haack reaction of various tetralone phenylhydrazones
under thermal and microwave irradiation conditions.
J. Heterocyclic Chem., 43, 389 (2006).
Several indazoles are reliable pharmacophores
of 4,5-dihydro-2H-benzo[g]indazoles require several
steps with low yield with formation of other
isomers. For example, the 4,5-dihydro-2H-benzo[g]-
indazole derivatives were prepared along with 4,5-
dihydro-1H-benzo[g]indazole derivatives in 35%
yield from 2,4-diketoester [6] and in 19% yield from
dithioketeneacetal [8]. Hence a selective and general
procedure for the formation of substituted 4,5-
dihydro-2H-benzo[g]indazoles from easily accessible
starting materials is desirable.
and proved to possess significant levels of activity
as HIV protease inhibitors, serotonin 5-HT1ꢁ, 5-
HT2,
5-HT3
receptor
antagonists,
acetyl
cholinesterase inhibitors and aldol reductase
inhibitors [1]. In particular, examples of differently
substituted
dihydrobenzo[g]indazoles
showing
antimicrobial, antiallergic and non-estrogenic
contraceptive activities have been cited in the
literature. More recently also tyrosine kinase
inhibitors, dopamine receptor ligands, anti-
inflammatory and analgesic compounds have been
reported quite extensively in the patent literature
[2]. The benzoindazoles have attracted considerable
attention in recent years due to the discovery of
their potential usage as anticryptosporidial [3],
selective cyclooxygenase-2 inhibitor [4], human
dopamine D4 receptor [5], antiproliferative [6], and
fungal enzyme inhibitor [7]. bis-Benzo[g]indazole
derivatives were found to possess antiproliferative
activity. Many synthetic methods for the synthesis
Vilsmeier-Haack reaction is primarily concerned
with the facile synthesis of aldehydes [9]. The halo-
methyleneiminium salts [10] generated under
Vilsmeier-Haack reaction are capable of producing
iminium
species
from
numerous
aromatic
compounds [11], alkene derivatives [12], carbonyl
compounds [13] and in addition, oxygen and
nitrogen nucleophiles [14]. The presence of proton
source facilitates cyclisation to produce wide variety
of carbocyclic as well as heterocyclic compounds.
Earlier reports from our laboratory have described

390
G. Sivaprasad, R. Sridhar and P. T. Perumal
Vol 43
the synthesis of pyran, quinoline, pyrrole, pyridine,
quinazolinone, oxazole, imidazole and pyrazole
derivatives [15] using Vilsmeier reagent. The Vilsmeier
reagent has been extensively utilized to generate a variety
of precursors for the synthesis of condensed heterocycles,
and a large number of fluorescent compounds viz,
indazole, coumarin and quinoline derivatives for dyeing
polyester and polyamide [16]. The Vilsmeier-Haack
cyclisation of iminium species provides access to a large
number of heterocyclic systems [17]. Hydrazones and
semicarbazones cyclise under Vilsmeier –Haack reaction
condition to give pyrazole aldehydes. Though a wide
variety of hydrazones of aromatic ketones like aceto-
phenones and aliphatic ketones [18,19,20] were studied
under Vilsmeier-Haack condition, the cylization potential
of hydrazones of cyclic keto compounds remains
unexplored which prompted us to carry out the cyclization
of various tetralone hydrazones and semicarbazones under
Vilsmeier-Haack reaction conditions.
Accordingly the reaction of 1-tetralone phenyl-
hydrazones (1a-j) with 6 equivalents of Vilsmeier-
Haack reagent yielded 4,5-dihydro-2H-benzo[g]-
indazoles (2a-j).
Scheme 1
In case of compounds containing active methylene
group, (for example hydrazones of ꢀ-ketoesters) the
cyclisation occurs at active methylene carbon atom
under Vilsmeier-Haack reaction condition [20].
Similarly when 2-tetralone phenylhydrazones (3a,b)
were subjected to Vilsmeier-Haack reaction condition,
only 8,9-dihydro-2H-benzo[e]indazoles (4a,b) were
obtained and there was no formation of 2-phenyl-4,9-
dihydro-2H-benzo[f]indazole (5a,b). Of the two
possible attacks of Vilsmeier-Haack reagent on the
substrate, only one isomer is obtained.
R5
R5
R4
R4
DMF/POCl3
NH
N
N
N
R3
R2
R3
R2
R1
1a-j
R1
2a-j
The reaction of 1-tetralonesemicarbazones (6a,b) with
Vilsmeier-Haack reagent (6 eq.) yielded 4,5-dihydro-2H-
benzo[g]indazole (7a,b) in very low yields along with the
formation of ꢀ-chloroaldehyde (8a,b) [22,23] of the corre-
sponding tetralone. Moreover no cyclised products could be
R1 = R2 = R3 = H, OCH3 ; R4 = R5 = H, NO2
Conditions: DMF/POCl3, (Solvent-DMF), 60-65 0C, 6 hrs. (or)
DMF/POCl3,, MWI, 1 1/2 min.
Scheme 2
R5
R5
R4
DMF/POCl3
N
N
R4
HN
N
4a, b
3a, b
DMF/POCl3
N
N
R5
R4
5a, b
R4 = H, NO2 ; R5 = NO2
Conditions: DMF/POCl3, (Solvent-DMF), 60-65 °C, 6 hrs. (or)
DMF/POCl3,, MWI, 1 1/2 min.

Mar-Apr 2006
Selective Synthesis of Some 4,5-Dihydro-2H-benzo[g]indazoles
391
Scheme 3
H
N
H
N
NH2
Cl
N
N
CHO
O
DMF/POCl3
+
R2
R2
R2
6a, b
7a, b
8a, b
R2 = H, OCH3
Conditions: DMF/POCl3, (Solvent-DMF), 60-65 0C, 6 hrs.
The prepared indazoles were found to exhibit
fluorescence. The fluorescence emission spectra of 2-
(4-nitrophenyl)-4,5-dihydro-2H-benzo[g]indazole is
given below as representative.
obtained from cyclohexanone semicarbazones due to steric
configuration that does not favour cyclisation [21].
The reaction products are summarised in Table 1.
Table 1
Synthesis of various 4,5-dihydro-2H-benzo[g]indazoles and 8,9-dihydro-2H-benzo[e]indazoles by the
Vilsmeier-Haack reaction under thermal and microwave assisted condition.
R1
R2
R3
R4
R5
Product a
Yield b
%
Entry
Method A
Method B
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
H
OCH3
H
H
H
OCH3
H
H
H
H
H
H
H
H
H
H
H
H
OCH3
H
H
H
OCH3
H
H
OCH3
H
H
H
H
H
OCH3
H
H
H
H
H
H
NO2
NO2
NO2
NO2
2a
2b
2c
2d
2e
2f
2g
2h
2i
71
72
74
74
64
71
67
72
74
77
70
67
15
16
78
74
79
81
83
82
71
80
77
81
85
87
79
76
-
NO2 NO2
NO2 NO2
NO2 NO2
H
OCH3 NO2 NO2
H
H
H
H
H
H
H
H
H
H
H
H
H
NO2
2j
4a
4b
7a
7b
8a
8b
NO2 NO2
H
OCH3
H
-
-
-
-
-
-
-
-
-
-
-
OCH3
a
b
All the products were characterized by IR, NMR and Mass spectrum; The yield is based on
isolation by column chromatography for products obtained by conventional heating (Method A)
and microwave irradiation condition (Method B).
A selective, convenient and easy method for the
preparation of various benzo[g]indazoles and benzo-
[e]indazoles by microwave irradiation under solvent
free condition is described and a comparison is made
between the conventional method and microwave
assisted solvent free method. The solvent free method
affords easy methodology as well as reduced reaction
time along with only slightly higher yield (11-15%).
The reaction of phenyl hydrazones of 2-tetralones afforded
benzo[e]indazole as the exclusive single product. This may
be due to the stabilization of the benzylic position by the
benzene ring. These compounds not only possess proven
biological activity but also the dyeing property. This
encouraged us to synthesize them in this new methodology.
Figure 1. Fluorescence emission spectra of 2-(4-nitrophenyl)-4,5-dihydro-
2H-benzo[g]indazole at 1) 230 nm, 2) 273 nm, 3) 358 nm and 4) 396 nm.
The spectral properties of the prepared indazoles were
studied qualitatively using UV-Visible absorption as well

392
G. Sivaprasad, R. Sridhar and P. T. Perumal
Vol 43
wise with stirring over a period of 20–30 minutes. The reaction
mixture was stirred for 1 hr. at room temperature and then stirred at
60-65 °C for 6 hr. After completion of the reaction (monitored by
TLC), the reaction mixture was cooled and neutralized by pouring
into crushed ice. The precipitate was collected by filtration and
purified by column chromatography using silica gel (60–120
mesh), eluting with petroleum ether:ethyl acetate (75:25), to
afford 2-(4-nitrophenyl)-4,5-dihydro-2H-benzo[g]indazole 2a as
a yellowish solid. The same procedure was followed to prepare
other compounds in the series.
as fluorescent emission techniques. The results were
summarized in Table 2.
Table 2
UV-Visible absorption and fluorescence emission spectral data of
various 4,5-dihydro-2H-benzo[g]indazoles and 8,9-dihydro-2H-
benzo[e]indazoles.
UV-Visible
absorption ꢀ
max
fluorescence
emission ꢀ
max
Entry
Synthesis of 2-(4-Nitrophenyl)-4,5-dihydro-2H-benzo[g]indazole
(2a) Under Solvent Free Microwave Irradiation.
2a
2b
2c
2d
2e
2f
2g
2h
2i
345
343
345
360
345
345
380
372
302
302
344
345
421
418
426
423
445
372
492
457
346
355
423
447
Method B.
The 3,4-dihydronaphthalen-1(2H)-one (4-nitrophenyl)hydrazone
(1.4 mmol) 1a is taken in a flat bottomed flask fitted with a
calcium chloride guard tube. The Vilsmeier reagent (6
equivalents) is added and then irradiated with microwaves for 1
ꢀ min. with 50% power with a pulse rate of 5 sec. After
completion of the reaction (monitored by TLC), the reaction
mixture was poured into crushed ice and the purification
procedure of Method A was followed to afford 2a as a yellowish
solid. The same procedure was adhered to prepare other
compounds in the series.
2j
4a
4b
EXPERIMENTAL
2-(4-Nitrophenyl)-4,5-dihydro-2H-benzo[g]indazole (2a).
This compound was obtained as yellow colour solid, mp 178
°C; IR (KBr): 3126, 2927, 2839, 2440, 1596, 1510, 1373, 1111,
1049, 945, 746, 685, 555 cm-1; 1H NMR (500 MHz, CDCl3): ꢁ =
2.86 (t, 2H, J= 7.45 Hz), 2.98 (t, 2H, J= 7.45Hz), 7.25-7.34 (m,
3H), 7.79 (s, 1H), 7.87 (d, 2H, J= 9.2 Hz), 7.97-7.98 (m, 1H),
8.30 (d, 2H, J= 9.2 Hz); 13C NMR (125 MHz, CDCl3): ꢁ =
19.32, 29.33, 117.87, 120.92, 123.06, 123.53, 125.50, 127.19,
128.64, 128.68, 128.70, 128.71, 137.39, 144.80, 151.69; MS:
m/z 291 (M+).
Melting points were determined in capillary tubes and are
uncorrected. Analytical TLC was performed on pre-coated
plastic sheets of silica gel G/UV-254 of 0.2 mm thickness
(Machery-Nagel, Germany). IR spectra were taken as KBr
1
pellets on a Perkin Elmer RXI FT-IR spectrometer. H NMR
(500 MHz) and 13C NMR (100 MHz) spectra were recorded in
CDCl3 solutions with TMS as internal standard. Column
chromatography was performed on silica gel (60 – 120 mesh,
SRL, India). The p-nitrophenylhydrazones, 2,4-dinitrophenyl-
hydrazones, phenylhydrazones and semicarbazones of various
tetralones (1a-j, 3a,b and 5a,b) were prepared by standard
procedure. The Vilsmeier-Haack reagent is prepared by
dropwise addition of one equivalent of POCl3 to one equivalent
of DMF in ice cold condition with stirring and the resulting
semi-solid is refrigerated. The microwave reactions were carried
out in a domestic microwave oven. A BPL microwave cooking
system, Model BMO-7000T, manufactured by BPL-SANYO
Utilities and Appliances Ltd., Bangalore, India was used in the
present studies. The overall dimensions of the domestic oven are
525(W) x 419 (D) x 281 (H) mm with a chamber of 350 (W) x
370 (D) x 208 (H) mm. The microwave frequency is 50 Hz and
the oven capacity is 26 liters. The absorbance and fluorescence
spectra were measured on a CARY 50 CONC. UV-Visible and
fluorescence spectrophotometer using methanol as solvent.
Anal. Calcd. for C17H13N3O2: C, 70.09; H, 4.50; N, 14.42.
Found: C, 70.10; H, 4.49; N, 14.41.
6-Methoxy-2-(4-nitrophenyl)-4,5-dihydro-2H-benzo[g]indazole (2b).
This compound was obtained as yellow colour solid, mp 186
°C; IR (KBr): 3431, 3125, 2934, 2838, 2440, 1566, 1511, 1448,
1
1370, 1178, 1103, 1029, 948, 748, 683, 545 cm-1; H NMR (500
MHz, CDCl3): ꢁ = 2.83 (t, 2H, J= 7.45 Hz), 3.00 (t, 2H, J= 7.45
Hz), 3.87 (s, 1H), 6.88-6.87 (d, 1H, J= 7.45 Hz), 7.29 (t, 1H, J=
7.45 Hz), 7.62-7.63 (d, 1H, J=7.45 Hz), 7.79 (s, 1H), 7.87-7.88
(d, 2H, J= 7.45 Hz), 8.30-8.32 (d, 2H, J= 7.45Hz); 13C NMR
(125 MHz, CDCl3): ꢁ = 18.69, 21.15, 55.64, 110.61, 115.52,
117.87, 120.87, 123.43, 125.52, 125.75, 127.89, 129.67, 144.76,
144.80, 151.73, 156.95; MS: m/z 321 (M+).
Anal. Calcd. for C18H15N3O3: C, 67.28; H, 4.71; N, 13.08.
Found: C, 67.30; H, 4.72; N, 13.09.
General Procedure for the Synthesis of 2-(4-Nitrophenyl)-
4,5-dihydro-2H-benzo[g]indazole (2a) Under Conventional
Conditions.
7-Methoxy-2-(4-nitrophenyl)-4,5-dihydro-2H-benzo[g]indazole (2c).
This compound was obtained as yellow colour solid, mp 206
°C; IR (KBr): 3432, 3134, 2930, 2830, 1571, 1506, 1461, 1370,
Method A.
1
1178, 1111, 1040, 940, 746, 674, 604, 500 cm-1; H NMR (500
The 3,4-dihydronaphthalen-1(2H)-one (4-nitrophenyl)hydrazone
(1.4 mmol) 1a was dissolved in DMF (10 mL) in a RB flask fitted
with calcium chloride guard tube through a pressure equalizer and
cooled to 0° C. POCl3 (6 equivalents, 11.5 mmol) was added drop-
MHz, CDCl3): ꢁ = 2.84 (t, 2H, J= 7.45, Hz), 2.95 (t, 2H, J= 7.45
Hz), 3.84 (s, 3H), 6.81 (d, 1H, J= 2.3 Hz), 6.86 (dd, 1H, J= 8.6
Hz), 7.77 (s, 1H), 7.85 (d, 2H, J= 8.6 Hz), 7.89 (d, 1H, J= 8.6
Hz), 8.29 (d, 2H, J= 8.6 Hz); 13C NMR (125 MHz, CDCl3): ꢁ =

Mar-Apr 2006
Selective Synthesis of Some 4,5-Dihydro-2H-benzo[g]indazoles
393
19.40, 29.70, 55.42, 112.60, 114.15, 117.66, 120.31, 121.59,
123.40, 124.48, 125.53, 139.28, 144.58, 144.84, 151.74, 160.09;
MS: m/z 321 (M+).
Anal. Calcd. For C18H15N3O3: C, 67.28; H, 4.71; N, 13.08.
Found: C, 67.27; H, 4.72; N, 13.07.
Anal. Calcd. for C18H14N4O5: C, 59.02; H, 3.85; N, 15.29.
Found: C, 59.04; H, 3.86; N, 15.28.
2-(2,4-Dinitrophenyl)-8-methoxy-4,5-dihydro-2H-benzo[g]-
indazole (2h).
This compound was obtained as yellow colour solid, mp 134
°C; IR (KBr): 3368, 2931, 2856, 2370, 1603, 1533, 1462, 1338,
1075, 945, 832, 739, 671 cm-1; 1H NMR (500 MHz, CDCl3): ꢀ =
2.83 (t, 2H, J= 8.05 Hz), 2.91 (t, 2H, J= 8.05 Hz), 3.85 (s, 3H),
6.84 (dd, 1H, J= 8.6 Hz), 7.16 (d, 1H, J= 8.6 Hz), 7.38 (d, 1H,
J= 2.85 Hz), 7.5 (s, 1H), 7.89 (d, 1H, J= 8.6 Hz), 8.47 (dd, 1H,
J= 8.6 Hz), 8.65 (d, 1H, J= 2.3 Hz); 13C NMR (125 MHz,
CDCl3): ꢀ = 19.48, 28.26, 55.58, 107.57, 115.87, 121.34,
121.97, 124.90, 125.73, 127.44, 128.84, 129.64, 129.75, 137.57,
142.27, 144.58, 153.05, 158.85; MS: m/z 366 (M+).
8-Methoxy-2-(4-nitrophenyl)-4,5-dihydro-2H-benzo[g]indazole
(2d).
This compound was obtained as yellow colour solid, mp 179
°C; IR (KBr): 3429, 3126, 2938, 2836, 2434, 1568, 1511, 1440,
1
1372, 1178, 1108, 1038, 945, 745, 686, 602 cm-1; H NMR (500
MHz, CDCl3): ꢀ = 2.83 (t, 2H, J= 8 Hz), 2.91 (t, 2H, J= 8 Hz),
3.88 (s, 1H), 6.84 (dd, 1H, J= 8 Hz), 7.16 (d, 1H, J= 8 Hz), 7.51
(d, 1H, J= 8 Hz), 7.79 (s, 1H), 7.88 (d, 2H, J= 8 Hz), 8.30 (d,
2H, J= 8 Hz); 13C NMR (125 MHz, CDCl3): ꢀ = 19.53, 28.48,
55.63, 107.20, 115.47, 117.91, 121.10, 123.62, 125.52, 129.53,
129.63, 129.66, 144.76, 144.80, 151.78, 158.87; MS: m/z 321
(M+).
Anal. Calcd. for C18H14N4O5: C, 59.02; H, 3.85; N, 15.29.
Found: C, 59.01; H, 3.84; N, 15.30.
2-Phenyl-4,5-dihydro-2H-benzo[g]indazole (2i).
Anal. Calcd. for C18H15N3O3: C, 67.28; H, 4.71; N, 13.08.
Found: C, 67.29; H, 4.70; N, 13.09.
This compound was obtained as yellow colour solid, mp 94 °C;
IR (KBr): 3111, 3051, 2927, 2831, 1594, 1500, 1468, 1374, 1199,
1049, 954, 745, 684 cm-1; 1H NMR (500 MHz, CDCl3): ꢀ = 2.85 (t,
2H, J= 6.9 Hz), 2.98 (t, 2H, J= 6.9 Hz), 7.25-7.31 (m, 4H), 7.46 (t,
2H, J= 7.45 Hz), 7.70 (s, 1H), 7.73 (d, 2H, J= 7.45 Hz), 7.99 (d,
1H, J= 7.45 Hz); 13C NMR (125 MHz, CDCl3): ꢀ = 19.41, 29.65,
118.92, 122.70, 123.55, 125.96, 127.02, 127.86, 128.47, 129.48,
129.64, 137.01, 140.59, 149.93; MS: m/z 246 (M+).
2-(2,4-Dinitrophenyl)-4,5-dihydro-2H-benzo[g]indazole (2e).
This compound was obtained as yellow colour solid, mp 176
°C; IR (KBr): 3430, 2931, 1604, 1526, 1469, 1339, 1079, 949,
1
830, 740 cm-1; H NMR (500 MHz, CDCl3): ꢀ = 2.86 (t, 2H, J=
7.45 Hz), 2.98 (t, 2H, J= 7.45 Hz), 7.23-7.31 (m, 3H,), 7.54 (s,
1H), 7.84-7.85 (m, 1H), 7.86 (d, 1H, J=9.15 Hz), 8.46 (dd, 1H,
J= 9.15 Hz), 8.63 (d, 1H, J= 2.3 Hz); 13C NMR (125 MHz,
CDCl3): ꢀ = 19.28, 29.08, 121.33, 121.80, 123.47, 124.58,
125.56, 127.28, 127.41, 128.00, 128.62, 129.20, 137.46, 137.50,
142.25, 144.51, 152.98; MS: m/z 336 (M+).
Anal. Calcd. for C17H14N2: C, 82.90; H, 5.73; N, 11.37.
Found: C, 82.89; H, 5.74; N, 11.37.
8-Methoxy-2-phenyl-4,5-dihydro-2H-benzo[g]indazole (2j).
Anal. Calcd. for C17H12N4O4: C, 60.71; H, 3.60; N, 16.66.
Found: C, 60.72; H, 3.61; N, 16.65.
This compound was obtained as yellow colour solid, mp 113
°C; IR (KBr): 3430, 3125, 3000, 2934, 2833, 1594, 1508, 1368,
1
1276, 1122, 1036, 941, 741, 681 cm-1; H NMR (500 MHz,
2-(2,4-Dinitrophenyl)-6-methoxy-4,5-dihydro-2H-benzo[g]-
indazole (2f).
CDCl3): ꢀ = 2.85 (t, 2H, J=6.85 Hz), 2.98 (t, 2H, J= 6.85 Hz),
3.84 (s, 3H), 6.80 (d, 1H, J=2.3 Hz), 6.84 (dd, 1H, J= 8.55),
7.23 (t, 1H, J= 8.55 Hz), 7.43 (t, 2H, J= 8.55 Hz), 7.68 (s, 1H),
7.72 (d, 2H, J= 8.55 Hz), 7.91 (d, 1H, J= 8.55 Hz); 13C NMR
(125 MHz, CDCl3): ꢀ = 19.45, 30.01, 55.38, 112.24, 114.12,
118.18, 118.80, 122.57, 123.47, 124.01, 125.77, 129.46, 138.83,
140.59, 149.92, 159.43; MS: m/z 276 (M+).
This compound was obtained as yellow colour solid, mp 160
°C; IR (KBr): 3432, 2925, 2852, 2363, 1604, 1533, 1465, 1340,
1080, 948, 835, 735, 670 cm-1; 1H NMR (500 MHz, CDCl3): ꢀ =
2.83 (t, 2H, J= 7.45 Hz), 2.98 (t, 2H, J= 7.45 Hz), 3.90 (s, 3H),
6.87 (d, 1H, J=7.45 Hz), 7.25 (t, 1H, J=7.45 Hz), 7.49 (d, 1H,
J=7.45 Hz), 7.53 (s, 1H), 7.85 (d, 1H, J= 7.45 Hz), 8.45 (dd,
1H, J= 8.6 Hz), 8.63 (d, 1H, J= 2.25 Hz); 13C NMR (125 MHz,
CDCl3): ꢀ = 18.63, 20.98, 55.65, 110.99, 115.86, 121.31,
121.76, 124.51, 125.43, 125.90, 127.38, 127.58, 128.95, 137.48,
142.20, 144.44, 152.99, 156.92; MS: m/z 366 (M+).
Anal. Calcd. for C18H16N2O: C, 78.24; H, 5.84; N, 10.14.
Found: C, 78.25; H, 5.83; N, 10.15.
2-(4-Nitrophenyl)-8,9-dihydro-2H-benzo[e]indazole (4a).
This compound was obtained as yellow colour solid, mp 182
°C; IR (KBr): 3125, 2924, 2837, 2438, 1594, 1508, 1467, 1371,
1108, 1047, 943, 744, 683, 554 cm-1; 1H NMR (500 MHz,
CDCl3): ꢀ = 2.99 (t, 2H, J= 7.45 Hz), 3.06 (t, 2H, J= 7.45 Hz),
7.18-7.28 (m, 3H), 7.45-7.47 (m, 1H), 7.86 (d, 2H, J= 9.15 Hz),
7.16 (s, 1H), 8.32 (d, 2H, J= 9.15 Hz); 13C NMR (125 MHz,
CDCl3): ꢀ = 22.01, 29.51, 117.90, 120.81, 121.54, 123.73,
125.58, 127.20, 127.26, 128.74, 128.87, 135.21, 144.53, 144.92,
154.36; MS: m/z 291 (M+).
Anal. Calcd. for C18H14N4O5: C, 59.02; H, 3.85; N, 15.29.
Found: C, 59.00; H, 3.86; N, 15.30.
2-(2,4-Dinitrophenyl)-7-methoxy-4,5-dihydro-2H-benzo[g]-
indazole (2g).
This compound was obtained as yellow colour solid, mp 116
°C; IR (KBr): 3405, 2927, 2846, 2365, 1598, 1530, 1465, 1337,
1079, 938, 827, 735, 674 cm-1; 1H NMR (500 MHz, CDCl3): ꢀ =
2.84 (t, 2H, J= 7.45 Hz), 2.95 (t, 2H, J= 7.45 Hz), 3.83 (s, 3H),
6.79 (d, 1H, J= 2.3 Hz), 6.83 (dd, 1H, J= 8.6 Hz), 7.51 (s, 1H),
7.77 (d, 1H, J=8.6 Hz), 7.86 (d, 1H, J=8.6 Hz), 8.44 (dd, 1H, J=
8.6 Hz), 8.62 (d, 1H, J= 2.9 Hz); 13C NMR (125 MHz, CDCl3):
ꢀ = 19.34, 29.44, 55.42, 112.73, 114.06, 121.13, 121.35, 123.97,
124.31, 124.98, 125.36, 127.37, 137.50, 139.36, 141.99, 144.22,
152.99, 160.44; MS: m/z 366 (M+).
Anal. Calcd. for C17H13N3O2: C, 70.09; H, 4.50; N, 14.42.
Found: C, 70.07; H, 4.51; N, 14.43.
2-(2,4-Dinitrophenyl)-8,9-dihydro-2H-benzo[e]indazole (4b).
This compound was obtained as yellow colour solid, mp 192
°C; IR (KBr): 3431, 2932, 1605, 1528, 1471, 1341, 1081, 951,
1
831, 742 cm-1; H NMR (500 MHz, CDCl3): ꢀ = 2.96 (t, 2H, J=

394
G. Sivaprasad, R. Sridhar and P. T. Perumal
Vol 43
Keithly, H. Laatsch and A. F. Kiderlen J. Antimicrobial Chemotherapy,
50, 975 (2002).
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(2001).
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S. Patel, A.Fletcher, I. C. Ragan, P. D. Leeson, A. L. scott and T. Broten,
Bioorg. Med. Chem., 9, 1655 (1998).
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and G. E. Grella, Il Farmaco, 58, 749, (2003).
6.3 Hz), 3.05 (t, 2H, J= 6.3 Hz), 7.19-7.27 (m, 3H), 7.43-7.45
(m, 1H), 7.86 (d, 1H, J= 9.15 Hz), 7.90 (s, 1H), 8.48 (dd, 1H,
J= 9.15 Hz), 8.66 (d, 1H, J= 9.15 Hz); 13C NMR (125 MHz,
CDCl3): ꢀ = 21.93, 29.31, 121.38, 122.42, 122.94, 124.07,
124.90, 127.24, 127.52, 127.66, 128.16, 128.91, 135.34, 137.34,
142.37, 144.73, 155.70; MS: m/z 336 (M+).
Anal. Calcd. for C17H12N4O4: C, 60.71; H, 3.60; N, 16.66.
Found: C, 60.73; H, 3.59; N, 16.67.
[7] B. J. Douglas, S. B. Gregory, Der-Ing Liao, M. P. J. Wynona,
N. W. Kevin and A. W. David J. Mol.Graphics Modell., 19, 435 (2001).
[8] I. Collins, M. Rowley, W. B. Davey, F. Emms, R. Marwood,
S. Patel, S. Patel, A. Fletcher, I. C. Ragan, P. D. Leeson, A. L. Scott and
T. Broten, Biorg. Med. Chem. 6, 743 (1998).
[9] For Reviews on the Vilsmeier-Haack Reaction. [a] C. M.
Marson, Tetrahedron 48, 3659 (1992); [b] S. Seshadri, J. Sci. Ind. Res.
32, 128 (1973); [c] O. Meth-Cohn and S. P. Stanforth, Comprehensive
Organic Synthesis, eds B. M. Trost and I. Fleming, Vol. ed. C. H.
Heathcock, Pergamon, Oxford, 2, 777 (1991).
4,5-Dihydro-2H-benzo[g]indazole (7a).
This compound was obtained as yellow colour solid, mp 78 °C; IR
(KBr): 3353, 3156, 2934, 2323, 1681, 1469, 1433, 1316, 1085, 953,
770, 720 cm-1; 1H NMR (500 MHz, CDCl3): ꢀ = 2.78 (2H, J = 6.85
Hz), 2.95 (2H, J = 6.85 Hz), 7.18-7.25 (m, 3H), 7.39 (s, 1H), 7.77 (d,
1H, J = 7.45 Hz), 8.76 (bs, 1H); 13C NMR (125 MHz, CDCl3): ꢀ =
19.29, 29.88, 116.16, 122.11, 126.94, 127.67, 128.17, 128.56,
129.03, 136.92, 146.05; MS: m/z 170 (M+).
Anal. Calcd. for C11H10N2: C, 77.62; H, 5.92; N,16.46. Found:
C, 77.60; H, 5.93; N, 16.45.
[10] C. Jutz, Advances in Organic Chemistry, ed. E. C. Taylor,
John Wiley & Sons, New York, 9, 225 (1976).
[11] G. Jones and S. P. Stanforth, Org. React., 49, 1 (1997).
[12] S. Seshadri, J. Sci. Ind. Res., 32, 128 (1973).
[13] C. M. Marson, Tetrahedron, 48, 3659 (1992).
[14] O. Meth-Cohn and S. P. Stanforth, Comprehensive Organic
Synthesis, eds B. M. Trost and I. Fleming, Vol. ed. C. H. Heathcock,
Pergamon, Oxford, 2, 777 (1991).
[15a] V. J. Majo and P. T. Perumal, Tetrahedron Lett. 37, 5015
(1996); [b] V. J. Majo and P. T. Perumal, J. Org. Chem. 61, 6525
(1996); [c] R. R. Amaresh and P. T. Perumal, Tetrahedron Lett., 38,
7287 (1997); [d] S. Selvi and P. T. Perumal, Tetrahedron Lett., 38, 6263
(1997); [e] V. J. Majo and P. T. Perumal, J. Org. Chem., 63, 7136
(1998).
7-Methoxy-4,5-dihydro-2H-benzo[g]indazole (7b).
This compound was obtained as Viscous liquid; IR (KBr):
3345, 3155, 2936, 2335, 1614, 1487, 1279, 1215, 1034, 957,
856, 814 cm-1; 1H NMR (500 MHz, CDCl3): ꢀ = 2.74 (t, 2H, J =
6.9 Hz), 2.85 (t, 2H, J = 6.9 Hz), 3.73 (s, 3H), 6.75 (dd, 1H, J =
8.6 Hz), 7.13 (d, 1H, J = 8.6 Hz), 7.34 (d, 1H, J = 2.3 Hz), 7.37,
(s, 1H), 8.94, (bs, 1H); 13C NMR (125 MHz, CDCl3): ꢀ = 19.51,
29.01, 55.38, 106.87, 113.92, 116.35, 127.89, 129.09, 129.44,
129.99, 146.48, 158.66; MS: m/z 200 (M+).
Anal. Calcd. for C12H12N2O: C, 71.98; H, 6.04; N, 13.99.
Found: C, 71.97; H, 6.05; N, 13.98.
[16] R. Rajagopal and S. Seshadri, Dyes and Pigments, 17, 57
(1991).
[17a] O. Meth-Cohn and B. Tarnowski, Adv. Heterocycl. Chem.,
31, 207 (1982); [b] O. Meth-Cohn, Heterocycles, 35, 539 (1993).
[18] M. A. Kira, M. D. Abdel-Rehman and K. Z. Gadella,
Tetrahedron Lett., 109, (1969).
Acknowledgement.
Authors G. S. and R. S. are thankful to CSIR, New Delhi for
the award of Research Fellowship.
[19] S. Selvi and P. T. Perumal, Indian J. Chem., 39B, 163 (2000).
[20] R. Sridhar, G. Sivaprasad and P. T. Perumal, J. Heterocyclic
Chem., 41, 405 (2004).
REFERENCES AND NOTES
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