α-Oxoketene dithioacetals mediated heteroaromatic annulation protocol for benzoheterocycles: An efficient regiocontrolled synthesis of highly substituted and annulated indazoles

Article abstract of DOI:10.1016/j.tet.2004.02.029

An efficient regiocontrolled synthesis of highly substituted and annulated indazoles involving base induced addition-elimination of 1,3-diphenyl-5- cyanomethylpyrazole to a variety of acyclic and cyclic α-oxoketene, followed by acid assisted cycloaromatization of the resulting conjugate adducts has been reported.

Full text of DOI:10.1016/j.tet.2004.02.029

Tetrahedron 60 (2004) 3457–3464
a-Oxoketene dithioacetals mediated heteroaromatic annulation
protocol for benzoheterocycles: an efficient regiocontrolled
synthesis of highly substituted and annulated indazoles
b
S. Peruncheralathan,a T. A. Khan,a H. Ilaa and H. Junjappa
,
,
*
*
aDepartment of Chemistry, Indian Institute of Technology, Kanpur 208016, India
bBioOrganics and Applied Materials Pvt. Ltd, # B-64/1, III Stage, Peenya Industrial Area, Peenya, Bangalore 560058, India
Received 23 November 2003; revised 26 January 2004; accepted 12 February 2004
Abstract—An efficient regiocontrolled synthesis of highly substituted and annulated indazoles involving base induced addition–elimination
of 1,3-diphenyl-5-cyanomethylpyrazole to a variety of acyclic and cyclic a-oxoketene, followed by acid assisted cycloaromatization of the
resulting conjugate adducts has been reported.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
a-oxoketene dithioacetals initially in conjugate addition–
elimination fashion,5h–i,15b whereas the corresponding
lithiomethyl species generated by deprotonation of
methyl-substituted heterocycles were found to be less
discriminate displaying either 1,2- or 1,4-addition
pattern.15d,e,15g,15j – m Subsequent acid induced (or
spontaneous) cycloaromatization of these adducts leads to
the formation of either linearly substituted/annulated (1,2-
addition) or angularly substituted/annulated (conjugate
addition–elimination) benzoheterocycles (or bridged
azaheterocycles) in highly regiospecific fashion.14,15 We
have shown in our earlier studies that the lithium
5-lithiomethyl-3-methylpyrazole-1-carboxylate generated
by deprotonation-protection of 3,5-dimethylpyrazole under-
goes 1,2-addition with various a-oxoketene dithioacetals to
give carbinol acetals15e which on acid induced cyclo-
aromatization afford the pyrazolo[1,5-a]pyridines instead of
the expected indazoles via intramolecular cyclization at
electron-rich nitrogen of the pyrazole ring rather than at C-4
position. We have also reported in our earlier work, the
regiospecific deprotonation of 2,3-dimethyl-1-phenyl-
pyrazolin-5-one (antipyrine) to give the corresponding
3-lithiomethyl species which was shown to undergo highly
regioselective g-1,4 addition to a-oxoketene dithioacetals
followed by cycloaromatization in the presence of BF3·Et2O
to afford a range of novel substituted and condensed
indazolones in good yields.13a Also in a recent paper, we
have developed another approach for substituted and fused
indazolones by anionic [4þ2] cycloaddition of dihydro-
pyrazolin-5-one dienolate (generated by deprotonation of
2,3-dimethyl-4-formyl-1-phenylpyrazolin-5-one) with a
variety of dienophiles.13b In continuation of these studies,
we now report an efficient synthesis of angularly substituted
Indazole and its derivatives have gained considerable
importance in medicinal chemistry in view of their
promising pharmacological properties.1,2 Several indazoles
are found to exhibit significant levels of activity as HIV
protease inhibitors,3,4 serotonin 5-HT1a, 5-HT25 and 5-HT3
receptor antagonists,6,7 acetylcholinesterase inhibitors8 and
aldol reductase inhibitors,9 whereas 1-[3-(dimethylamino)-
propyl]-5-methyl-3-phenyl-1H-indazole (FS-32) has been
shown to be a potent antidepressant drug candidate.2 Several
methods for the synthesis of indazoles and their derivatives
have been reported in the literature,1–3,10–12 most of them
involving construction of the pyrazole moiety on pre-
constructed benzenoid derivatives. On the other hand, the
methods based on the more easily accessible pyrazole
precursors are scantily described in the literature.13 During
the course of our heteroaromatic annulation14 studies
involving [3þ3] cyclocondensation of a-oxoketene dithio-
acetals (1,3-bielectrophilic components) with various
heteroallyl anions (1,3-binucleophilic components), we
had demonstrated earlier that it is possible to tune up the
reactivity of ambident heteroallyl anions derived from
various methyl-substituted heterocycles towards a-oxo-
ketene dithioacetals in either regiospecific 1,2-addition
fashion or conjugate 1,4-addition–elimination pathway.15
In general, the heteroallyl anions stabilized by electron
withdrawing group such as nitrile are shown to add to
Keywords: a-Oxoketene dithioacetals; Heteroaromatic annulation;
Benzoheterocycles; Indazoles.
*
Corresponding authors. Tel.: þ91-512-2597870; fax: þ91-512-2597426;
e-mail address: hila@iitk.ac.in
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.02.029

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S. Peruncheralathan et al. / Tetrahedron 60 (2004) 3457–3464
and fused indazoles involving base-induced conjugate
addition of 1,3-diphenyl-5-cyanomethylpyrazole 2 with
a-oxoketene dithioacetals followed by acid induced
cycloaromatization of the resulting conjugate adducts.
a-oxoketene dithioacetal 1d (from pyruvaldehyde
dimethylacetal) with 2 under similar conditions furnished
directly the corresponding 7-cyano-4-formylindazole 4d in
55% yield via in situ hydrolysis of the acetal group
(Scheme 2). The structures of all these newly synthesized
indazoles 4a-d were established with the help of spectral
and analytical data. In one of the experiments, the
7-cyanoindazole 4c was subjected to acid induced
hydrolysis–decarboxylation to give the corresponding
1,3,4-tris(phenyl)-6-(methylthio)indazole 5c (88%), which
on Raney-Ni dethiomethylation afforded the corresponding
sulfur free indazole 6c in 92% yield (Scheme 3).
2. Results and discussion
Our previous studies on the synthesis of carbazoles,15i
indoles15h and benzothiophenes15b via [3þ3] cyclo-
aromatization of a-oxoketene dithioacetals with various
heteroallyl anions have demonstrated that the cyano group is
especially useful for stabilizing the negative charge on the
heterocyclic side chain of 1,3-binucleophilic component.
We therefore selected 1,3-diphenyl-5-cyanomethylpyrazole
(2) as an anionic component in the present benzoannulation
process. Thus in a typical experiment, the a-oxoketene
dithioacetal 1a was reacted with 2 in the presence of sodium
hydride in THF at 0 8C to give the adduct 3a (R1¼Me,
R2¼H) in 90% yield. The adduct 3a was purified by
crystallization for spectral characterization which showed it
to exist in the tautomeric b,g-unsaturated keto form 3a
exclusively. The adduct 3a was subjected to cycloaroma-
tization in the presence of various protic (H3PO4, TFA,
PTSA) and Lewis acids (BF3·Et2O, SnCl4), when the
cyclization was found to be most efficient (in terms of
yield and work-up) in the presence of p-toluenesulfonic
acid (PTSA) in refluxing benzene yielding 7-cyano-1,3-
diphenyl-4-methyl-6-(methylthio)indazole (4a) in 70%
yield (Scheme 1). This reaction sequence could also be
extended for the synthesis of other substituted indazole
derivatives 4b-c from the respective a-oxoketene dithio-
acetals 1b-c in good yields with full regiocontrol of the
substitutent positions (Scheme 1). Cycloaromatization of
Scheme 3.
The conjugate addition–cycloaromatization protocol was
next extended for the synthesis of annulated indazoles and
the results are shown in Schemes 4–7. Thus, the base-
induced conjugate addition of 2 with cyclic ketene
dithioacetals 7a-b from cyclopentanone and cyclohexanone,
respectively, proceeded smoothly to give the respective
adducts 8a-b in high yields, these underwent facile
Scheme 1.
Scheme 2.
Scheme 4.

S. Peruncheralathan et al. / Tetrahedron 60 (2004) 3457–3464
3459
cyclization in the presence of PTSA/benzene yielding the
corresponding tricyclic indazoles 9a-b in 70 and 75%
yields, respectively. The regiochemistry of one of the
annulated indazole 9b was established by its acid-induced
hydrolysis–decarboxylation followed by reductive dethio-
methylation of the resulting 10 to furnish 1,3-diphenyl-
6,7,8,9-tetrahydrobenzo[e] indazole 11 in 80% yield
(Scheme 4). The 1H NMR spectrum of 11 displayed signals
due to the two aromatic protons (Ha and Hb) as ortho
coupled doublets (J¼8.8 Hz) at d 7.16 and 7.50,
respectively, which unequivocally established the angular
regiochemistry of the product 9b formed through conjugate
1,4-addition–elimination of the carbanion from 2 with 7b.
Interestingly, the base-induced addition of the pyrazole 2
with ketene dithioacetal 7c from cyclooctanone did not give
the expected conjugate adduct 8c and the product isolated
(85%) was characterized as the adduct 12 formed by aldol
condensation of pyrazoleacetonitrile 2 with 7c. Apparently,
the conformationally flexible cyclooctane ring of 7c disturbs
the planar structure of its enone functionality resulting in the
nucleophilic attack of the carbanion derived from 2 on more
electrophilic carbonyl group to give the aldol condensation
product 12 exclusively. Subsequent cycloaromatization of
12 (via electrocyclization) on prolonged refluxing in
benzene in the presence of PTSA afforded the correspond-
ing linearly fused indazole 13 in 52% yield (Scheme 5). The
structure of 13 was fully established with help of spectral
and analytical data.
Scheme 5.
The versatility of our heteroaromatic annulation protocol
was further demonstrated by the synthesis of tetracyclic
angularly fused indazoles 15 and 19 by extrapolation of this
reaction sequence under standard conditions to a-oxoketene
dithioacetals 14 and 18 derived from indan-1-one and
a-tetralone, respectively (Schemes 6 and 7). The annulated
indazoles 15 and 19 on sequential hydrolysis–decarboxyl-
ation and Raney-Ni dethiomethylation of the resulting 16
and 20 under earlier reported conditions afforded the
corresponding sulfur free tetracyclic angularly fused
indazoles 17 and 21 in overall high yields (Schemes 6 and
7). The dihydroindazole 21 was transformed into the
Scheme 6.
Scheme 7.

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S. Peruncheralathan et al. / Tetrahedron 60 (2004) 3457–3464
25, the product (72%) isolated after work-up was charac-
terized as the pyrano[3,2-c]quinoline 26 on the basis of its
spectral and analytical data. Our attempts to obtain indazole
25 from 24 in the presence of other protic and Lewis acids
were not successful yielding only intractable reaction
mixtures. The possible mechanism for the formation of
the observed product 26 from 24 is shown in Scheme 9. The
hydroxyquinoline intermediate 28 formed by debenzene-
sulfonylation16 and tautomerization of the adduct 24 (via
intermediate 27) undergoes intramolecular nucleophilie
attack of hydroxy group on nitrile functionality to give
imine intermediate 29 which on subsequent hydrolysis
affords the pyrano[3,2-c]quinoline 26 (Scheme 9).
3. Conclusion
In summary, the two steps [3þ3] annulation of 1,3-
diphenyl-5-cyanomethylindazole (2) with a range of
a-oxoketene dithioacetals affords a variety of novel
substituted and annulated indazoles in good yields with
high regioselectivity. The above study has clearly demon-
strated that the a-oxoketene dithioacetal mediated aromatic
and heteroaromatic annulation protocol14a provides a
general route for the construction of complex hetero-
aromatics from easily available precursors in highly
regioselective manner. In view of the wide range of
biological activities displayed by indazole derivatives, the
above methodology can be extended for generating library
of substituted indazoles. Our efforts in this direction are in
progress.
Scheme 8.
corresponding fully aromatic tetracyclic indazole 22 (93%)
by dehydrogenation with DDQ (Scheme 7). The structures
of all the newly synthesized indazoles 15-17 and 19-22 were
established with the help of spectral and analytical data.
Finally, we have extended our studies to oxoketene
dithioacetal 23 obtained from N-(benzenesulfonyl)-4-
quinolone with a view to synthesize the tetracyclic
azaindazole framework 25 (Scheme 8). Thus, the ketene
dithioacetal 23 underwent facile base-induced conjugate-
addition–elimination with 2 to afford the corresponding
adduct 24 in nearly quantitative yield. However, the acid-
induced cycloaromatization of 24 under earlier described
conditions did not yield the expected tetracyclic azaindazole
4. Experimental
4.1. General
1H NMR (400 MHz) and 13C NMR (100 MHz) spectra were
recorded in CDCl3 and TMS was used as an internal
standard. Melting points were uncorrected. Chromato-
graphic purification was conducted by column chromato-
graphy using 100–200 mesh silica gel obtained from
standard firms. Raney-Nickel was prepared according to
the reported method.17 The 1,3-diphenyl-5-cyanomethyl-
pyrazole (2) was prepared according to literature method.18
The known a-oxoketene dithioacetals were prepared
according to the earlier reported procedure.14a,19
4.2. General procedure for base induced addition of 1,3-
diphenyl-5-cyanomethylpyrazole (2) to a-oxoketene
dithioacetals
A solution of 1,3-diphenyl-5-cyanomethylpyrazole (2)
(0.57 g, 2.2 mmol) in THF (15 mL) was added dropwise
to a stirring suspension of NaH (0.1 g, 2.4 mmol, 60%) in
THF (15 mL) at 0 8C under N2 atmosphere. After 1 h, a
solution of the appropriate a-oxoketene dithioacetal
(2 mmol) in THF (15 mL) was slowly added at 0 8C and
the reaction mixture was allowed to warm to room
temperature with stirring during 8–10 h. It was then poured
into cold saturated ammonium chloride solution (50 mL)
and extracted with DCM (3£20 mL). The organic layer was
washed with H2O (3£50 mL), brine (50 mL), dried
Scheme 9.

S. Peruncheralathan et al. / Tetrahedron 60 (2004) 3457–3464
3461
(Na2SO4) and the solvent evaporated in vacuo. A few of the
adducts 3a, 3c and 12 were purified by crystallization
(ether–DCM) for characterization and their spectral and
analytical data are given below. The other adducts were
used as such for further cyclization.
(25 mL), p-toluenesulphonic acid (0.35 g, 2 mmol) was
added and the reaction mixture was refluxed with stirring for
10–14 h (monitored by TLC). It was neutralized with
NaHCO3 solution and extracted with benzene (3£20 mL).
The combined extracts were washed with H2O (3£100 mL),
brine (100 mL), dried (Na2SO4) and the solvent evaporated
at reduced pressure. The crude product was purified by
column chromatography using EtOAc/hexane (1:9) as
eluent to give pure indazole.
4.2.1. 2-(1,3-Diphenyl-1H-5-pyrazolyl)-3-methylthio-5-
oxo-hexen-2-carbonitrile (3a). Yield (0.56 g, 75%,
isolated yield) as a pale yellow solid, mp 151–2 8C;
[found: C, 70.78; H, 5.11; N, 11.29. C22H19N3SO requires
C, 70.75; H, 5.13; N, 11.25%]; Rf (20% EtOAc/hexane)
0.38; nmax(KBr) 3066, 2924, 2201, 1719, 1498 cm21; dH
(400 MHz, CDCl3) 7.81–7.87 (2H, m, ArH), 7.57–7.60
(2H, m, ArH), 7.49–7.45 (2H, m, ArH), 7.39–7.43 (3H, m,
ArH), 7.30–7.34 (1H, m, ArH), 6.87 (1H, s, ArH), 3.89 (2H,
s, CH2), 2.23 (3H, s, SCH3), 2.22 (3H, s, CH3); dC
(100 MHz, CDCl3) 200.8 (CvO), 160.2 (C(SCH3)-
vC(CN)), 152.1 (C), 139.1 (C), 134.0 (C), 132.4 (C),
129.2 (CH), 128.6 (CH), 128.3 (CH), 128.2 (CH), 125.7
(CH), 124.3 (CH), 115.9 (CN), 107.2 (CH), 98.9 (C(SCH3)-
vC(CN)), 48.7 (CH2), 29.5 (CH3), 15.0 (SCH3); m/z 374
(100 MHþ).
4.3.1. 7-Cyano-1,3-diphenyl-4-methyl-6-methylthio-1H-
indazole (4a). Yield (0.25 g, 70%) as a colourless solid, mp
167–8 8C; [found: C, 74.39; H, 4.84; N, 11.80. C22H17N3S
requires C, 74.34; H, 4.82; N, 11.82%]; Rf (20% EtOAc/
hexane) 0.58; nmax(KBr) 2918, 2211, 1514, 1433 cm21; dH
(400 MHz, CDCl3) 7.53–7.59 (6H, m, ArH), 7.50–7.52
(2H, m, ArH), 7.45–7.46 (2H, m, ArH), 6.91 (1H, s, ArH),
2.60 (3H, s, SCH3), 2.39 (3H, s, CH3); dC (100 MHz,
CDCl3) 148.1 (C), 146.6 (C), 139.8 (C), 138.7 (C), 138.0
(C), 132.9 (C), 129.9 (CH), 129.4 (CH), 128.8 (CH), 128.7
(CH), 128.0 (CH), 127.3 (CH), 121.2 (C), 120.4 (CH), 113.7
(CN), 90.3 (C), 20.7 (CH3), 16.2 (SCH3); m/z 355 (80 Mþ),
352 (100 M23þ).
4.2.2. 2-(1,3-Diphenyl-1H-5-pyrazolyl)-3-methylthio-5-
oxo-5-phenyl-penten-2-carbonitrile (3c). Yield (0.61 g,
70%) as a colourless solid, mp 169–170 8C; [found: C,
74.41; H, 4.90; N, 9.68. C27H21N3SO requires C, 74.46; H,
4.86; N, 9.65%]; Rf (20% EtOAc/hexane) 0.30; nmax (KBr)
3059, 2923, 2199, 1680, 1593, 1535 cm21; dH (400 MHz,
CDCl3) 8.00 (2H, d, J¼8.0 Hz, ArH), 7.90 (2H, d,
J¼8.0 Hz, ArH),7.69 (2H, d, J¼8.3 Hz, ArH), 7.64 (1H, t,
J¼7.8 Hz, ArH), 7.51 (4H, dt, J¼1.7, 7.8 Hz, ArH), 7.40–
7.45 (3H, m, ArH), 7.33–7.38 (1H, m, ArH), 6.96 (1H, s,
ArH), 4.52 (2H, s, CH2), 2.22 (3H, s, SCH3); dC (100 MHz,
CDCl3) 192.6 (CvO), 160.8 (C(SCH3)vC(CN)), 152.0
(C), 139.2 (C), 135.5 (C), 134.17 (CH), 134.11 (C), 132.6
(C), 129.2 (CH), 128.9 (CH), 128.7 (CH), 128.20 (CH),
128.18 (CH), 128.08 (CH), 125.8 (CH), 124.2 (CH), 115.9
(CN), 107.5 (CH), 99.4 (C(SCH3)vC(CN)), 44.1 (CH2),
15.2 (SCH3); m/z 436 (100 MHþ).
4.3.2. 7-Cyano-4,5-dimethyl-1,3-diphenyl-6-methylthio-
1H-indazole (4b). Yield (0.26 g, 69%) as a colourless
solid, mp 165–6 8C; [found: C, 74.73; H, 5.21; N, 11.40.
C23H19N3S requires C, 74.77; H, 5.18; N, 11.37%]; Rf (20%
EtOAc/hexane) 0.54; nmax(KBr) 2922, 2219, 1653, 1573,
1497 cm21; dH (400 MHz, CDCl3) 7.57–7.59 (4H, m,
ArH), 7.51–7.56 (4H, m, ArH), 7.46–7.49 (2H, m, ArH),
2.62 (3H, s, SCH3), 2.48 (3H, s, CH3), 2.36 (3H, s, CH3); dC
(100 MHz, CDCl3) 147.7 (C), 142.9 (C), 138.3 (C), 138.1
(C), 137.3 (C), 133.5 (C), 133.4 (C), 130.2 (CH), 129.4
(CH), 128.8 (CH), 128.6 (CH), 128.2 (CH), 127.5 (CH),
123.8 (C), 114.9 (CN), 98.2 (C), 19.8 (CH3), 18.16 (CH3),
17.4 (SCH3); m/z 369 (100 Mþ), 354 (21).
4.3.3. 7-Cyano-6-methylthio-1,3,4-tris(phenyl)-1H-
indazole (4c). Yield (0.27 g, 65%) as a colourless solid,
mp 201–2 8C; [found: C, 77.71; H, 4.61; N, 10.02.
C27H19N3S requires C, 77.67; H, 4.59; N, 10.06%]; Rf
(20% EtOAc/hexane) 0.59; nmax(KBr) 3060, 2920, 2214,
1496, 1425 cm21; dH (400 MHz, CDCl3) 7.62–7.64 (2H, m,
ArH), 7.57–7.59 (2H, m, ArH), 7.56 (1H, s, ArH), 7.22 (1H,
t, J¼7.1 Hz, ArH), 7.12–7.18 (4H, m, ArH), 7.08–7.10
(4H, m, ArH), 7.01–7.05 (2H, m, ArH), 2.63 (3H, s, SCH3);
dC (100 MHz, CDCl3) 148.0 (C), 146.6 (C), 142.1 (C),
140.6 (C), 138.1 (C), 137.5 (C), 132.1 (C), 129.6 (CH),
129.3 (CH), 129.1 (CH), 128.9 (CH,), 128.2 (CH), 127.8
(CH), 127.7 (CH), 127.6 (CH), 127.4 (CH), 120.2 (CH),
119.1 (C), 113.6 (CN), 91.2 (C), 16.3 (SCH3); m/z 417 (100,
Mþ), 370 (20).
4.2.3. 2-[2-Bis(methylthio)methylenecyclooctylidene]-2-
(1,3-diphenyl-1H-5-pyrazolyl) acetonitrile (12). Yield
(0.80 g, 85%) as a yellow solid, mp 158–9 8C; [found: C,
71.33; H, 6.16; N, 8.95. C28H29N3S2 requires C, 71.30; H,
6.20; N, 8.91%]; Rf (40% EtOAc/hexane) 0.28; nmax(KBr)
2919, 2210, 1666, 1595 cm21; dH (400 MHz, CDCl3) 7.92
(2H, d, J¼7.8 Hz, ArH), 7.78 (2H, d, J¼7.8 Hz, ArH),
7.39–7.50 (4H, m, ArH), 7.29–7.33 (2H, m, ArH), 6.85
(1H, s, ArH), 2.56–2.62 (1H, m, CH), 2.44–2.49 (1H, m,
CH), 2.26–2.32 (1H, m, CH2), 2.24 (3H, s, SCH3), 2.09–
2.14 (1H, m, CH2), 1.96 (3H, s, SCH3), 1.76–1.79 (2H, m,
CH2), 1.52–1.73 (6H, m, CH2); dC (100 MHz, CDCl3)
166.8 (C), 155.6 (C), 151.9 (C), 140.0 (C), 139.2 (C), 134.8
(C), 133.0 (C), 131.9 (C), 128.7 (CH), 128.5 (CH), 127.9
(CH), 127.5 (CH), 125.8 (CH), 124.4 (CH), 118.8 (CN),
106.4 (CH), 34.3 (CH2), 29.1 (CH2), 28.9 (CH2), 28.0
(CH2), 27.1 (CH2), 24.8 (CH2), 14.8 (SCH3), 14.3 (SCH3).
4.3.4. 7-Cyano-1,3-diphenyl-4-formyl-6-methylthio-1H-
indazole (4d). Yield (0.20 g, 55%) as a yellow solid, mp
200–1 8C; [found: C, 71.49; H, 4.11; N, 11.42. C22H15N3SO
requires C, 71.52; H, 4.09; N, 11.37%]; Rf (20% EtOAc/
hexane) 0.45; nmax(KBr) 2922, 2854, 2212, 1695, 1570,
1496 cm21; dH (400 MHz, CDCl3), 10.34 (1H, s, CHO),
7.74 (1H, s, ArH), 7.66–7.69 (2H, m, ArH), 7.58–7.61 (5H,
m, ArH), 7.52–7.55 (3H, m, ArH), 2.70 (3H, s, SCH3); dC
(100 MHz, CDCl3) 188.8 (CHO), 147.8 (C), 146.6 (C),
4.3. General procedure for the synthesis of substituted
indazoles 4a-d, 9a-b, 13, 15, 19 and pyranoquinoline 26
To a solution of adduct (ca. 1 mmol) in dry benzene

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S. Peruncheralathan et al. / Tetrahedron 60 (2004) 3457–3464
141.1 (C), 137.5 (C), 133.1 (C), 131.9 (C), 130.1 (CH),
129.5 (CH), 129.4 (CH), 129.1 (CH), 129.0 (CH), 127.63
(CH), 127.59 (C), 120.5 (C), 117.5 (CH), 112.6 (CN), 16.1
(SCH3); m/z 370 (100 MHþ), 342 (20).
6.57 (1H, d, J¼7.8 Hz, ArH), 4.15 (2H, s, CH2), 2.66 (3H, s,
SCH3); dC (100 MHz, CDCl3) 147.0 (C), 145.2 (C), 141.3
(C), 140.6 (C), 139.8 (C), 139.5 (C), 139.4 (C), 138.3 (C),
134.1 (C), 130.5 (CH), 129.8 (CH), 129.2 (CH), 128.9 (CH),
128.5 (CH), 128.2 (CH), 127.8 (CH), 126.6 (CH), 126.4
(CH), 124.6 (CH), 118.7 (C), 113.8 (CN), 96.6 (C), 38.3
(CH2), 19.2 (SCH3); m/z 430 (100 MHþ), 414 (20), 279
(20).
4.3.5. 4-Cyano-1,3-diphenyl-5-methylthio-3,6,7,8-tetra-
hydrocyclopenta[e]indazole (9a). Yield (0.29 g, 70%) as
a colourless solid, mp 197–8 8C; [found: C, 75.59; H, 5.04;
N, 11.08. C24H19N3S requires C, 75.56; H, 5.02; N,
11.01%]; Rf (20% EtOAc/hexane) 0.59; nmax(KBr) 2980,
2949, 2831, 2217, 1586, 1553, 1498 cm21; dH (400 MHz,
CDCl3) 7.68 (2H, dd, J¼2.0, 8.0 Hz, ArH), 7.56–7.60 (3H,
m, ArH), 7.52–7.55 (2H, m, ArH), 7.43–7.51 (3H, m,
ArH), 3.13 (4H, quint, J¼7.8, CH2–CH2–CH2), 2.56 (3H,
s, SCH3), 2.14 (2H, q, J¼7.6 Hz, CH2–CH2–CH2); dC
(100 MHz, CDCl3) 147.2 (C), 142.9 (C), 141.3 (C), 140.4
(C), 139.9 (C), 138.3 (C), 132.2 (C), 129.5 (CH), 129.4
(CH), 128.8 (CH), 128.7 (CH), 128.3 (CH), 127.5 (CH),
120.7 (C), 114.7 (CN), 96.5 (C), 34.3 (CH2), 32.8 (CH2),
24.8 (CH2), 18.9 (SCH3); m/z 381 (100 Mþ), 366 (40), 333
(26), 289 (20).
4.3.9. 4-Cyano-1,3-diphenyl-5-methylthio-6,7-dihydro-
3H-naphtho[1,2-e]indazole (19). Yield (0,29 g, 65%) as a
colourless solid, mp 220–1 8C; [found: C, 78.49; H, 4.81; N,
9.50. C29H21N3S requires C, 78.53; H, 4.77; N, 9.47%]; Rf
(20% EtOAc/hexane) 0.50; nmax(KBr) 3210, 3062, 2924,
2214, 1594, 1539 cm21; dH (400 MHz, CDCl3) 7.62–7.66
(2H, m, ArH), 7.54–7.62 (3H, m, ArH), 7.24–7.29 (4H, m,
ArH), 7.16–7.19 (2H, m, ArH), 7.12 (1H, t, J¼7.6 Hz,
ArH), 6.83 (1H, d, J¼7.6 Hz, ArH), 6.59 (1H, t, J¼7.6Hz,
ArH), 3,23 (2H, t, J¼6.8 Hz, CH2), 2.92 (2H, t, J¼6.8 Hz,
CH2), 2.51 (3H, s, SCH3); dC (100 MHz, CDCl3) 147.3 (C),
141.4 (C), 140.5 (C), 138.9 (C), 138.3 (C), 136.6 (C), 135.7
(C), 133.2 (C), 131.2 (CH), 130.9 (C), 129.7 (CH), 129.5
(CH), 128.9 (CH), 128.7 (CH), 128.0 (CH), 127.9 (CH),
127.8 (CH), 126.7 (CH), 125.0 (CH), 119.2 (C), 114.7 (CN),
98.7 (C), 29.2 (CH2), 27.4 (CH2), 19.6 (SCH3); m/z 444
(MHþ).
4.3.6. 4-Cyano-1,3-diphenyl-5-methylthio-6,7,8,9-tetra-
hydro-3H-benzo[e]indazole (9b). Yield (0.30 g, 70%) as
a colourless solid, mp 198–9 8C; [found: C, 75.95; H, 5.39;
N, 10.64. C25H21N3S requires C, 75.92; H, 5.35; N,
10.62%]; Rf (20% EtOAc/hexane) 0.42; nmax(KBr) 2941,
2856, 2217, 1595, 1569, 1496 cm21; dH (400 MHz, CDCl3)
7.54–7.60 (5H, m, ArH), 7.50–7.52 (3H, m, ArH), 7.45–
7.47 (2H, m, ArH), 3.06 (2H, t, J¼6.4 Hz, CH2), 2.75 (2H, t,
J¼6.4 Hz, CH2), 2.51 (3H, s, SCH3), 1.82–1.88 (2H, m,
CH2), 1.63–1.69 (2H, m, CH2); dC (100 MHz, CDCl3)
147.7 (C), 143.9 (C), 138.19 (C), 138.16 (C), 138.0 (C),
133.8 (C), 133.3 (C), 130.1 (CH), 129.4 (CH), 128.8 (CH),
128.6 (CH), 128.1 (CH), 127.5 (CH), 122.9 (C), 114.7 (CN),
98.4 (C), 28.9 (CH2), 28.6 (CH2), 22.9 (CH2), 21.8 (CH2),
19.6 (SCH3); m/z 396 (100 MHþ), 380 (43), 348 (20).
4.3.10. 3-(1,3-Diphenyl-1H-5-pyrazolyl)-4-methylthio-
2H-pyrano[3,2-c]quinolin-2-one (26). Yield (0.33 g,
72%) as a yellow solid, mp 224–225 8C; [found: C,
72.91; H, 4.19; N, 9.12. C28H19N3O2S requires C,
72.87; H, 4.15; N, 9.10%]; Rf (20% EtOAc/hexane) 0.35;
n
max(KBr) 3048, 2928, 1723, 1594, 1567 cm21; dH
(400 MHz, CDCl3) 9.37 (1H, s, ArH), 8.47 (1H, d,
J¼8.3 Hz, ArH), 8.17 (1H, d, J¼8.3 Hz, ArH), 7.94 (2H,
d, J¼7.6 Hz, ArH), 7.89 (1H, t, J¼7.7 Hz, ArH), 7.71 (1H, t,
J¼7.7 Hz, ArH), 7.56 (2H, d, J¼7.6 Hz, ArH), 7.40–7.46
(2H, m, ArH), 7.36–7.39 (2H, m, ArH), 7.29–7.34 (2H, m,
ArH), 6.99 (1H, s, ArH), 2.18 (3H, s, SCH3); dC (100 MHz,
CDCl3) 157.2 (CvO), 155.1 (C), 154.9 (C), 152.3 (C),
148.8 (C), 147.0 (CH), 140.1 (C), 135.6 (C), 132.58 (CH),
132.53 (CH), 129.3 (CH), 129.0 (C), 128.7 (CH), 128.3
(CH), 128.2 (CH), 127.9 (CH), 125.9 (CH), 123.4 (CH),
122.5 (CH), 117.4 (C), 117.1 (C), 110.7 (C), 108.6 (CH),
17.1 (SCH3); m/z 462 (100 MHþ), 414 (20) 386 (20).
4.3.7. 11-Cyano-1,3-diphenyl-4-methylthio-5,6,7,8,9,10-
hexahydro-1H-cycloocta[f]indazole (13). Yield (0.22 g,
52%) as a colourless solid, mp 197–8 8C; [found: C, 76.51;
H, 5.99; N, 9.97. C27H25N3S requires C, 76.56; H, 5.95; N,
9.92%]; Rf (20% EtOAc/hexane) 0.52; nmax(KBr): 2924,
2218, 1594, 1499 cm21; dH (400 MHz, CDCl3) 7.60–7.62
(2H, m, ArH), 7.52–7.58 (5H, m, ArH), 7.43–7.49 (3H, m,
ArH), 3.24 (2H, t, J¼6.1 Hz, CH2), 2.94 (2H, t, J¼6.1 Hz,
CH2), 2.55 (3H, s, SCH3), 1.76–1.78 (2H, m, CH2), 1.40–
1.43 (2H, m, CH2), 1.26–1.32 (4H, m, CH2); dC (100 MHz,
CDCl3) 147.6 (C), 143.2 (C), 142.5 (C), 138.6 (C), 138.2
(C), 137.5 (C), 133.9 (C), 130.1 (CH), 129.4 (CH), 128.83
(CH), 128.78 (CH), 128.1 (CH), 127.5 (CH), 123.1 (C),
114.9 (CN), 98.8 (C), 31.3 (CH2), 31.1 (CH2), 28.8 (CH2),
28.5 (CH2), 26.5 (CH2), 25.9 (CH2), 20.8 (SCH3); m/z 424
(100, MHþ).
4.4. General procedure for acid induced hydrolysis–
decarboxylation indazoles 4c, 9b, 15 and 19
A solution of the respective indazole (1 mmol) in glacial
AcOH/H2O/conc. H2SO4 (1:1:1, 10 mL) was refluxed at
180 8C for 7–10 h (monitored by TLC). It was cooled and
neutralized with sat. NaHCO3 solution and extracted with
DCM (3£25 mL), and the extract washed with H2O
(50 mL), brine (50 mL), dried (Na2SO4) and the solvent
evaporated in vacuo to give crude product which was
purified by column chromatography over silica gel using
EtOAc/hexane (1:20) as eluent.
4.3.8. 4-Cyano-1,3-diphenyl-5-methylthio-3,6-dihydro-
indeno[1,2-e]indazole (15). Yield (0.29 g, 68%) as a
colourless solid, mp 267–8 8C; [found: C, 79.25; H, 4.49;
N, 9.80. C28H19N3S requires C, 79.29; H, 4.46; N, 9.78%];
Rf (20% EtOAc/hexane) 0.60; nmax(KBr) 3054, 2919, 2214,
1555, 1497 cm21; dH (400 MHz, CDCl3) 7.64–7.67 (4H, m,
ArH), 7.56–7.61 (5H, m, ArH), 7.51–754 (2H, m, ArH),
7.31 (1H, t, J¼7.8 Hz, ArH), 6.99 (1H, t, J¼7.8 Hz, ArH),
4.4.1. 6-Methylthio-1,3,4-tris(phenyl)-1H-7-indazole
(5c). Yield (0.35 g, 88%) as a colourless solid, mp 189–
190 8C; [found: C, 79.58; H, 5.17; N, 7.19. C26H20N2S
requires C, 79.56; H, 5.14; N, 7.14%]; Rf (20% EtOAc/

S. Peruncheralathan et al. / Tetrahedron 60 (2004) 3457–3464
3463
hexane) 0.65;
n
max(KBr) 3048, 2919, 1962, 1592,
4.5. General procedure for dethiomethylation of
indazoles 5c, 10, 16 and 20 with Raney Nickel
1493 cm21; dH (400 MHz, CDCl3) 7.79 (2H, d, J¼7.3 Hz,
ArH), 7.55–7.59 (3H, m, ArH), 7.40 (1H, t, J¼7.6 Hz,
ArH), 7.13–7.19 (6H, m, ArH), 7.12 (1H, d, J¼1.4 Hz,
ArH), 7.09 (2H, d, J¼7.3 Hz, Ar H), 7.05 (2H, d, J¼7.6 Hz,
ArH), 2.57 (3H, s, SCH3); dC (100 MHz, CDCl3) 147.6 (C),
141.3 (C), 139.8 (C), 138.7 (C), 138.5 (C), 137.4 (C), 133.1
(C), 129.5 (CH), 129.32 (CH), 129.30 (CH), 127.6 (CH),
127.33 (CH), 127.28 (CH), 127.23 (CH), 127.0 (CH), 123.5
(CH), 122.43 (CH), 118.9 (C), 105.8 (CH), 16.1 (SCH3); m/z
393 (100 MHþ), 392 (80, Mþ).
To a solution of corresponding indazole (1 mmol) in ethanol
(30 mL), was added Raney Nickel (W4, four times by
weight) and the suspension was stirred at 70–80 8C for
2–6 h (monitored by TLC). The reaction mixture was
filtered through sintered funnel and the residue was washed
with ethanol. The filtrate was concentrated in vacuo and
passed through small silica gel column using 2% EtOAc/
hexane as eluent.
4.4.2. 1,3-Diphenyl-5-methylthio-6,7,8,9-tetrahydro-3H-
benzo[e]indazole (10). Yield (0.30 g, 82%) as a colourless
solid, mp 151–152 8C; [found: C, 77.71; H, 5.94; N, 7.60.
C24H22N2S requires C, 77.80; H, 5.98; N, 7.56%]; Rf (20%
EtOAc/hexane) 0.58; nmax(KBr) 3053, 2937, 1956, 1588,
1497 cm21; dH (400 MHz, CDCl3) 7.75 (2H, d, J¼7.6 Hz,
ArH), 7.59–7.62 (2H, m, ArH), 7.53 (2H, t, J¼7.8 Hz,
ArH), 7.43–7.48 (3H, m ArH), 7.35 (1H, t, J¼7.8 Hz ArH),
7.32 (1H, s, ArH), 2.75 (2H, t, J¼6.3 Hz CH2), 2.69 (2H, t,
J¼6.3 Hz, CH2) 2.49 (3H, s, SCH3), 1.83–1.87 (2H, m,
CH2), 1.64–1.68 (2H, m, CH2); dC [100 MHz, CDCl3]
147.6 (C), 140.4 (C), 139.9 (C), 138.7 (C), 134.8 (C), 131.2
(C), 130.2 (CH), 129.5 (CH), 128.2 (CH), 127.9 (CH), 127.6
(C), 126.6 (CH), 123.2 (CH), 120.2 (C), 102.3 (CH), 28.4
(CH2), 26.6 (CH2), 22.9 (CH2), 22.3 (CH2), 15.3 (SCH3);
m/z 372 (100, MHþ) 323 (25).
4.5.1. 1,3,4-Tris(phenyl)-1H-7-indazole (6c). Yield
(0.32 g, 92%) as a colourless solid, mp 159–60 8C;
[found: C, 86.71; H, 5.21; N, 8.11. C25H18N2 requires C,
86.68; H, 5.24; N, 8.09%]; Rf (20% EtOAc/hexane) 0.68;
n
max(KBr) 3071, 1591, 1563, 1495, 1444 cm21; dH
(400 MHz, CDCl3) 7.76–7.82 (3H, m, ArH), 7.53–7.57
(2H, m, ArH), 7.48–7.52 (1H, m, ArH), 7.37 (1H, dt, J¼1.2,
7.6 Hz, ArH), 7.13–7.22 (7H, m, ArH), 7.03–7.09 (4H, m,
ArH); dC (100 MHz, CDCl3) 147.6 (C), 140.6 (C), 139.9
(C), 139.2 (C), 137.3 (C), 133.3 (C), 129.42 (CH), 129.40
(CH), 129.37 (CH), 127.5 (CH), 127.3 (CH), 127.2 (CH),
127.1 (CH), 126.9 (CH), 126.8 (CH), 123.4 (CH), 123.0
(CH) 120.7 (C), 109.3 (CH); m/z 347 (100, MHþ), 346 (60,
Mþ).
4.5.2. 1,3-Diphenyl-6,7,8,9-tetrahydro-3H-benzo[e]inda-
zole (11). Yield (0.26 g, 80%) as a colourless solid, mp
116–7 8C; [found: C, 85.18; H, 6.19; N, 8.59. C23H20N2
requires C, 85.15; H, 6.21; N, 8.63%]; Rf (20% EtOAc/
4.4.3. 1,3-Diphenyl-5-methylthio-3,6-dihydroindeno[1,2-
e]indazole (16). Yield (0.32 g, 78%) as a colourless solid,
mp 172–3 8C; [found: C, 80.13; H, 5.01; N, 6.94.
C27H20N2S requires C, 80.16; H, 4.98; N, 6.92%]; Rf
(20% EtOAc/hexane) 0.60; nmax(KBr) 3042, 2914, 1592,
1497 cm21; dH (400 MHz, CDCl3) 7.80 (2H, d, J¼8.0 Hz,
ArH), 7.69 (2H, d, J¼6.4 Hz, ArH), 7.50–7.59 (6H, m,
ArH), 7.48 (1H, s, ArH), 7.41 (1H, t, J¼7.3 Hz, ArH), 7.21
(1H, t, J¼7.8 Hz, ArH), 6.96 (1H, t, J¼7.8 Hz, ArH), 6.56
(1H, d, J¼7.8 Hz, ArH), 3.89 (2H, s, CH2), 2.60 (3H, s,
SCH3); dC (100 MHz, CDCl3) 146.9 (C), 144.1 (C), 141.5
(C), 140.9 (C), 140.0 (C), 135.9 (C), 135.6 (C), 135.2 (C),
134.4 (C), 130.6 (CH), 129.6 (CH), 128.8 (CH), 128.2 (CH),
127.0 (CH), 126.3 (CH), 126.2 (CH), 125.1 (CH), 124.3
(CH), 123.7 (CH), 116.8 (C), 103.5 (CH), 36.6 (CH2), 15.0
(SCH3); m/z 406 (100, M2Hþ), 405 (90, MHþ), 357 (20).
hexane) 0.61;
nmax(KBr) 3046, 2935, 1592, 1495,
1442 cm21; dH (400 MHz, CDCl3) 7.75 (2H, d, J¼7.8 Hz,
ArH), 7.60–7.63 (2H, m, ArH), 7.51–7.54 (2H, m, ArH),
7.50 (1H, d, J¼8.8 Hz), 7.41–7.47 (3H, m, ArH), 7.33 (1H,
t, J¼7.3 Hz, ArH), 7.16 (1H, d J¼8.8 Hz, ArH), 2.87 (2H, t,
J¼6.4 Hz, CH2), 2.68 (2H, t, J¼6.4 Hz, CH2), 1.78–1.84
(2H, m, CH2), 1.66–1.72 (2H, m, CH2); dC (100 MHz,
CDCl3) 147.5 (C), 140.1 (C), 138.5 (C), 134.9 (C), 130.9
(C), 130.3 (CH), 129.8 (CH), 129.7 (C), 129.3 (CH), 128.1
(CH), 127.8 (CH), 126.5 (CH), 123.1 (CH), 122.8 (C), 107.9
(CH), 29.4 (CH2), 27.8 (CH2), 23.0 (CH2), 22.9 (CH2); m/z
325 (100 MHþ), 324 (70, Mþ).
4.5.3. 1,3-Diphenyl-3,6-dihydroindeno[1,2-e]indazole
(17). Yield (0.27 g, 75%) as a colourless solid, mp 135–
6 8C; [found: C, 87.16; H, 5.09; N, 7.79. C26H18N2 requires
C, 87.12; H, 5.06; N, 7.82%]; Rf (20% EtOAc/hexane) 0.65;
4.4.4. 1,3-Diphenyl-5-methylthio-6,7-dihydro-3H-
naphtho[1,2-e]indazole (20). Yield (0.36 g, 85%) as
colourless solid, mp 192–3 8C; [found: C, 80.39; H, 5.27;
N, 6.72. C28H22N2S requires C, 80.35; H, 5.30; N, 6.69%];
Rf (20% EtOAc/hexane) 0.65; nmax(KBr) 3046, 2950, 2833,
1595, 1544, 1494 cm21; dH (400 MHz, CDCl3) 7.8 (2H, d,
J¼8.0 Hz, ArH), 7.57 (2H, t, J¼8.0 Hz, ArH), 7.52 (1H, s,
ArH), 7.37–7.43 (2H, m, ArH), 7.19–7.28 (5H, m, ArH),
7.05 (1H, t, J¼7.6 Hz, ArH), 6.82 (1H, d, J¼7.6 Hz, ArH),
6.59 (1H, t, J¼7.6 Hz, ArH), 2.89–2.96 (4H, m, CH2–
CH2), 2.52 (3H, s, SCH3); dC (100 MHz, CDCl3) 147.1 (C),
141.0 (C), 139.9 (C), 137.9 (C), 137.8 (C), 134.3 (C), 131.8
(C), 131.6 (C), 130.7 (CH), 130.0 (C), 129.6 (CH), 129.5
(CH), 127.7 (CH), 127.6 (CH), 127.0 (CH), 126.9 (CH),
126.5 (CH), 124.8 (CH), 123.6 (CH), 116.6 (C), 105.0 (CH),
29.1 (CH2), 25.7 (CH2), 16.0 (SCH3); m/z 419 (100 MHþ),
418 (90, Mþ), 370 (25).
n
max(KBr) 3051, 2920, 1952, 1592, 1495 cm21; dH
(400 MHz, CDCl3) 7.81 (2H, d, J¼7.8 Hz, ArH), 7.73
(1H, d, J¼8.8 Hz, ArH), 7.71 (2H, d, J¼7.8 Hz, ArH), 7.63
(1H, d, J¼8.8 Hz, ArH), 7.51–7.58 (6H, m, ArH), 7.39 (1H,
t, J¼7.6 Hz, ArH), 7.19 (1H, t, J¼7.6 Hz, ArH), 6.96 (1H, t,
J¼7.6 Hz, ArH), 6.55 (1H, d, J¼7.6 Hz, ArH), 3.99 (2H, s,
CH2); dC (400 MHz, CDCl3) 146.8 (C), 144.5 (C), 141.2
(C), 140.5 (C), 140.0 (C), 137.9 (C), 135.4 (C), 134.8 (C),
130.6 (CH), 129.4 (CH), 128.7 (CH), 128.2 (CH), 126.9
(CH), 126.2 (CH), 125.9 (CH), 124.9 (CH), 124.3 (CH),
124.1 (CH), 123.7 (CH), 118.9 (C), 108.9 (CH), 37.5 (CH2);
m/z 359 (100, MHþ), 358 (60, Mþ), 281 (20) 254 (30).
4.5.4. 1,3-Diphenyl-6,7-dihydro-3H-naphtho[1,2-e]inda-
zole (21). Yield (0.35 g, 95%) as a colourless solid, mp

3464
S. Peruncheralathan et al. / Tetrahedron 60 (2004) 3457–3464
D. R.; Nagel, A. A.; Nason, D. M.; Nielsen, J. A.; Shalaby,
I. A.; White, W. F. J. Med. Chem. 1994, 37, 2721.
63–65 8C; [found: C, 87.10; H, 5.39; N, 7.48. C27H20N2
requires C, 87.07; H, 5.41; N, 7.52%]; Rf (20% EtOAc/
hexane) 0.69; nmax(KBr) 3045, 2954, 2935, 2886, 1591,
1493, 1450 cm21; dH (400 MHz, CDCl3) 7.80 (2H, d,
J¼7.8 Hz, ArH), 7.66 (1H, d, J¼8.5 Hz, ArH), 7.55 (2H, t,
J¼7.8 Hz, ArH), 7.40 (2H, d, J¼7.8 Hz, ArH), 7.38 (1H, d,
J¼8.5 Hz, ArH), 7.21–7.28 (5H, m, ArH), 7.05 (1H, t,
J¼7.6 Hz, ArH), 6.82 (1H, d, J¼7.6 Hz, ArH), 6.60 (1H, t,
J¼7.6 Hz, ArH), 2.90 (4H, s, CH2–CH2); dC (100 MHz,
CDCl3) 146.9 (C), 141.1 (C), 139.9 (C), 138.2 (C), 134.7
(C), 133.2 (C), 131.9 (C), 130.6 (CH), 129.6 (CH), 129.4
(CH), 127.75 (CH), 127.7 (CH), 127.6 (CH), 126.89 (C),
126.86 (CH), 126.83 (CH), 126.6 (CH), 124.8 (CH), 123.61
(CH), 118.7 (C), 109.2 (CH), 29.5 (CH2), 29.4 (CH2); m/z
373 (100 MHþ), 372 (80 Mþ).
9. Mylari, B. L.; Zembrowski, W. J.; Beyer, T. A.; Aldinger,
C. E.; Siegel, T. W. J. Med. Chem. 1992, 35, 2155.
10. (a) Elguero, J. Pyrazole and their benzo derivatives.
Comprehensive heterocyclic chemistry; Katritzkey, A. R.,
Rees, C. W., Potts, K. T., Eds.; Pergamon: New York, 1984;
Vol. 5, p 167. (b) Behr, L. C.; Fusco, R.; Jarobe, C. H. In
Pyrazoles, pyrazolines, pyrazolidines, indazoles and
condensed rings; Wiley, R. H., Ed.; Wiley Science: New
York, 1969; p 289. (c) Sainsbury, M.; 2nd ed. Rodd’s
chemistry of carbon compounds; Caffey, S., Ansell, M. F.,
Eds.; Elsevier: New York, 1986; Vol. 4, p 93 part C.
11. (a) Ruechardt, C.; Hassmann, V. Liebigs Ann. Chem. 1980,
908. (b) Dell’Erba, C.; Novi, M.; Petrillo, G.; Tavani, C.
Tetrahedron 1992, 48, 325.
4.5.5. Dehydrogenation of indazole 21 with DDQ. A
solution of 21 (0.37 g, 1 mmol) and DDQ (0.45 g, 2 mmol)
was refluxed in dioxane for 6 h. The reaction mixture was
cooled and poured into ice-cold water and extracted with
DCM (3£20 mL). The organic layer was washed with brine
(30 mL), dried (Na2SO4) and evaporated under reduced
pressure. The crude product was passed through small silica
gel column using 2% EtOAc/hexane as eluent to give 22
(0.34 g, 93%) as a colourless solid, mp 153–154 8C; [found:
C, 87.56; H, 4.93; N, 7.59. C27H18N2 requires C, 87.54; H,
4.90; N, 7.56%]; Rf (20% EtOAc/hexane) 0.69; nmax(KBr)
3047, 1950, 1886, 1589, 1499, 1450 cm21; dH (400 MHz,
CDCl3) 7.86–7.93 (5H, m, ArH), 7.82–7.85 (3H, m, ArH),
7.59 (2H, t, J¼7.7 Hz, ArH), 7.52–7.55 (2H, m, ArH),
7.39–7.46 (2H, m, ArH), 7.32–7.38 (3H, m, ArH), 6.95
(1H, dt, J¼1.2, 7.7 Hz, ArH); dC (100 MHz, CDCl3) 148.6
(C), 140.5 (C), 139.6 (C), 136.1 (C), 133.1 (C), 130.6 (CH),
129.5 (CH), 129.3 (CH), 129.2 (CH), 128.8 (C), 128.2 (CH),
127.9 (CH), 127.8 (C), 127.5 (CH), 127.3 (CH), 126.9 (CH),
126.2 (CH), 125.8 (CH), 125.7 (C), 124.2 (CH), 124.1 (CH),
117.1 (C), 110.7 (CH); m/z 371 (100 MHþ), 370 (90, Mþ),
267 (20).
12. (a) Kunka, C. P. A.; Warkentin, J. Can. J. Chem. 1990, 68,
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`
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References and notes
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