KHSO4 · H2O/SiO2-catalyzed, one-pot, solvent-free synthesis of pyrazolines, tetrahydrocarbozoles and indoles using microwave irradiation

Article abstract of DOI:10.1080/00397910600764766

A new high-yielding, operationally simple, solvent-free, and mild method for preparation of pyrazolines, tetrahydrocarbazoles, and indoles has been developed using KHSO₄ · H₂O impregnated on SiO ₂. The reactions have been probed under microwave irradiation (MWI), and ultrasonic and thermal conditions, employing different solid supports. The data revealed that KHSO₄ · H₂O impregnated on SiO₂ under MWI provides the best yields in a shorter time under solvent-free reaction conditions. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910600764766

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KHSO4 · H2O/SiO2‐Catalyzed, One‐Pot,
Solvent‐Free Synthesis of Pyrazolines,
Tetrahydrocarbozoles and Indoles using
Microwave Irradiation
Kamal K. Kapoor a , Bilal A. Ganai a , Satish Kumar a & Charanjeet S.
Andotra a
a Department of Chemistry, University of Jammu, Jammu, India
Published online: 16 Feb 2007.
To cite this article: Kamal K. Kapoor , Bilal A. Ganai , Satish Kumar & Charanjeet S. Andotra (2006)
KHSO4 · H2O/SiO2‐Catalyzed, One‐Pot, Solvent‐Free Synthesis of Pyrazolines, Tetrahydrocarbozoles
and Indoles using Microwave Irradiation, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 36:18, 2727-2735, DOI: 10.1080/00397910600764766
To link to this article: http://dx.doi.org/10.1080/00397910600764766
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Synthetic Communicationsw, 36: 2727–2735, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600764766
.
KHSO4 H2O/SiO2-Catalyzed, One-Pot,
Solvent-Free Synthesis of Pyrazolines,
Tetrahydrocarbozoles and Indoles using
Microwave Irradiation
Kamal K. Kapoor, Bilal A. Ganai, Satish Kumar,
and Charanjeet S. Andotra
Department of Chemistry, University of Jammu, Jammu, India
Abstract: A new high-yielding, operationally simple, solvent-free, and mild method
for preparation of pyrazolines, tetrahydrocarbazoles, and indoles has been developed
.
using KHSO4 H2O impregnated on SiO2. The reactions have been probed under
microwave irradiation (MWI), and ultrasonic and thermal conditions, employing
.
different solid supports. The data revealed that KHSO4 H2O impregnated on SiO2
under MWI provides the best yields in a shorter time under solvent-free reaction
conditions.
.
Keywords: Indoles, KHSO4 H2O/SiO2, MWI, pyrazolines, sonication, tetra-
hydrocarbazoles
INTRODUCTION
Among a wide range of biologically active heterocycles, a significant amount
of research activity has been directed toward the study of pyrazolines, tetrahy-
drocarbazoles, and indoles, owing to their wide variety of therapeutic activi-
ties.[1–4] A classical synthesis of these compounds involves formation of
hydrazones obtained from ketones and arylhydrazines, which can sub-
sequently be cyclized to products in the presence of acid catalysts[5] like
acetic acid, ZnCl2, H2SO4, HCl, p-toluenesulfonic acid, PCl3, PPA, BF3,
Received in India February 15, 2006
Address correspondence to Kamal K. Kapoor, Department of Chemistry, University
of Jammu, Jammu 180 006, India. E-mail: k2kapoor@yahoo.com
2727

2728
K. K. Kapoor et al.
.
.
sulphosalicylic acid, and CuCl2 KHSO4 H2O/SiO2 has been used in many
organic transformations such as deprotection,[6] oxidation,[7] dehydration,[8]
esterification,[9] and acetylation.[10] It has also proven to be a good catalyst
for synthesis of some heterocyclic compounds.[11–13] We thought that the
use of this reagent[14] to prepare pyrazolines, tetrahydrocarbazles, and
indoles might be a smart choice in terms of efficiency, convenience, and
less hazardous handling.
RESULTS AND DISCUSSION
An initial examination was carried out for condensation of cyclohexanone
.
with phenylhydrazine in the presence of KHSO4 H2O adsorbed on
different solid supports and in different solvents, and the results are shown
in Table 1. When the experiments were carried out under microwave
irradiation (MWI), no solvent was used. From the data it is clear that SiO2
is a better adsorbent, and the best results were obtained when for 2 molar
.
equiv of the substrates (i.e., ketones) and 1 molar equiv of KHSO4 H2O as
.
KHSO4 H2O impregnated on SiO2 was used either thermally or under
.
.
MW KHSO4 H2O alone could also bring about the reaction, but in this
case the reactions took longer to reach completion. Sonication also effected
the reaction but the time taken for completion of reaction was comparatively
longer (Table 1).
The use of a SiO2 support facilitates the workup of the reaction
mixtures[15] and gave better yields of products, presumably by acting as a
carrier to increase the surface area in the reaction. In the case of a,b-unsatu-
rated ketones as substrates, the required pyrazolines 1a–e were formed under
MWI and solvent-free conditions (Table 2). At room temperature and under
ultrasonication, only hydrazones were formed and their further cyclization
to products did not occur even after 24 h. The structures of all products
1
have been confirmed by spectral means (IR, H NMR, and high resolution
mass spectrometry (HRMS)) and by comparison with the literature data.
A variety of ketones were reacted under similar conditions to produce
products in more than 90% isolated yields except for 3-pentanone (entry 6),
where the reaction was performed at room temperature in acetonitrile
(Table 3).
CONCLUSIONS
In summary, this work demonstrates a new high-yielding, operationally
simple, solvent-free, and mild method for preparation of pyrazolines, tetra-
.
hydrocarbazoles, and indoles using KHSO4 H2O impregnated on SiO2.

Table 1. Scrutiny of the solid supports and solvents for the condensation reactions
Time (yield %)
MW (no solvent)
Substrate
reagent ratio
Adsorbent
Solvent
Thermally
50 min (50)
Sonication
Silica gel
Silica gel
CH3CN
CH3CN
CH3CN
THF
1.0
0.5
2.0
2.0
2.0
2.0
2.0
2.0
2.0
10 min (50)
2 min (decomposition)
1 min (98)
—
3 h (40)
—
30 min (decomposition)
15 min (94)
1 h (76)
Silica gel
Silica gel
2.5 h (90)
3 h (60)
2.5 h (55)
4 h (48)
2.5 h (78)
4 h (67)
4 h (62)
Silica gel
Silica gel
Dioxane
CH2Cl2
CH3CN
CH3CN
CH3CN
1 h (70)
1.5 h (60)
—
—
Neutral alumina
Bentonite
No adsorbent
20 min (70)
20 min (76)
1.5 h (82)
1 min (85)
2.5 min (80)
8 min (70)

Table 2. Synthesis of pyrazolines
MW time
(min), no
solvent
MP (8C)
Yield
(%)
Entry
Substrate
Product
Exp.
Lit.
1
2.5
3.5
5.0
94
98
94
128–130
78–80
108
138[16]
2
3
80–82[16]
107–110[17]

4
4.5
96
87–89
—
5
3.5
97
168
167–168[18]
1
Notes: All compounds were characterized by H NMR, IR, and finally by comparison with authentic samples prepared by
known methods. Blank spaces indicate that no reference has been found; MWI was performed at power level 3 (400 W) with
a 20-s pause after every 30-s.

Table 3. Synthesis of tetrahydrocarbazoles and indoles
Time
MP (8C)
MW (min),
no solvent
RT in
CH3CN (h)
Yield
(%)
Entry
1
Substrate
Product
Exp.
115
Lit.
0.83
4
5
99
95
114[16]
2
1
258
260[19]
3
4
2
6.5
6
94
98
162
184
163[20]
2.5
186[16]

5
4.2
8
93
123
125[19]
6
7
—
4
7
7
94
92
65
93
65[19]
93[21]
8
2.5
5.5
90
73
72[22]
1
Notes: All compounds were characterized by H NMR, IR, and finally by comparison with authentic samples prepared by
known methods. Blank space indicates that reaction has not been done. MWI was performed at power level 3 (400 W) with
pause of 20-s. after every 30-s.

2734
K. K. Kapoor et al.
EXPERIMENTAL
Melting points were measured in open capillaries on a Perfit melting-point
apparatus and are uncorrected. IR on KBr were recorded on Brucker-4800
1
infrared spectrometer. H NMR and HRMS spectra were recorded on Bruker
AC-200 (200-MHz) spectrometer and JEOL D-300 mass spectrometer at 70 eV
respectively. TLC was performed on 0.5-mm-thick plates using BDH silica gel
G as adsorbent. The plates were developed with iodine vapors, ceric ammonium
sulfate in H2SO4, and the compounds were observed as black spots. All solvents
were distilled before use. Recrystallization was achieved with aqueous MeOH.
General Procedure for the Preparation of 1a–e and 2a–h
Phenylhydrazine (10 mmol), the appropriate ketone (10 mmol), and
.
.
KHSO4 H2O/SiO2 (5 mmol with respect to KHSO4 H2O) were mixed
thoroughly in a 100-mL beaker with glass rod. The mixture was irradiated
in a microwave oven at power level 3 until the completion of the reaction
(TLC monitored). The resultant mixture was cooled and stirred with EtOAc
(40-mL) and filtered through Celite under suction. The filtrate was washed
with cold water (10-mL), saturated NaHCO3 (10-mL), and brine (10-mL)
and dried over anhydrous Na2SO4. The solvent was evaporated in vacuo,
and products were recrystallized from aqueous methanol (yield 90–95%).
1,5-diphenyl-3-[(E)]-2-arylethenyl]-4,5-dihydro-1H-pyrazoline
(1d).
Yield: 96%. Mp 87–898C; IR: 2920, 1660, 1606, 1558, 1274, 1168, 139,
1
771 cm21; H NMR (CDCl3): d 2.88 (dd, 1H, J ¼ 16 and 14 Hz), 3.32 (dd,
1H, J ¼ 16 and 10 Hz), 4.17 (dd, 1H, J¼ 14 and 10 Hz), 6.52 (d, 1H,
J ¼ 17 Hz), 7.10 (d, 1H, J ¼ 17 Hz), 7.24–7.68 (m, 15 H); HRMS: m/z at
324.4188 (M1) 100% (calc. for C23H20N2, 324.4184).
ACKNOWLEDGMENTS
One of the authors (S.K.) is thankful to C.S.I.R (New Delhi) for a junior
research fellowship.
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Solvent-Free Synthesis using Microwave Irradiation
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