Synthesis and conformational features of 4-(cyclohexylsulfanyl)-1-(2,4- dinitrophenyl)-3-aryl-1H-pyrazole

Article abstract of DOI:10.1080/00397911.2010.493628

A set of new 4-(cyclohexylsulfanyl)-1,3-diaryl-1H-pyrazoles has been synthesized using Vilsmeier's reagent. It is found that 4-(cyclohexylsulfanyl)- 1-(2,4-dinitrophenyl)-3-(4-methoxyphenyl)-1H-pyrazole exists with the arylthio group in the equatorial pos

Full text of DOI:10.1080/00397911.2010.493628

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Synthesis and Conformational Features
of 4-(Cyclohexylsulfanyl)-1-(2,4-
dinitrophenyl)-3-aryl-1H-pyrazole
Ramaiyan Manikannan a , Ramaiyan Venkatesan a & Shanmugam
Muthusubramanian a
a Department of Organic Chemistry , Madurai Kamaraj University ,
Madurai, India
Published online: 02 May 2011.
To cite this article: Ramaiyan Manikannan , Ramaiyan Venkatesan & Shanmugam Muthusubramanian
(2011) Synthesis and Conformational Features of 4-(Cyclohexylsulfanyl)-1-(2,4-dinitrophenyl)-3-
aryl-1H-pyrazole, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 41:13, 1916-1928, DOI: 10.1080/00397911.2010.493628
To link to this article: http://dx.doi.org/10.1080/00397911.2010.493628
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Synthetic Communications1, 41: 1916–1928, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.493628
SYNTHESIS AND CONFORMATIONAL FEATURES OF
4-(CYCLOHEXYLSULFANYL)-1-(2,4-DINITROPHENYL)-
3-ARYL-1H-PYRAZOLE
Ramaiyan Manikannan, Ramaiyan Venkatesan, and
Shanmugam Muthusubramanian
Department of Organic Chemistry, Madurai Kamaraj University,
Madurai, India
GRAPHICAL ABSTRACT
Abstract A set of new 4-(cyclohexylsulfanyl)-1,3-diaryl-1H-pyrazoles has been synthesized
using Vilsmeier’s reagent. It is found that 4-(cyclohexylsulfanyl)-1-(2,4-dinitrophenyl)-3-
(4-methoxyphenyl)-1H-pyrazole exists with the arylthio group in the equatorial position of
the cyclohexyl group in solution, whereas it has the arylthio group in the axial position of
the cyclohexyl group in crystal state as evidenced by NMR and single-crystal x-ray analysis
respectively.
Keywords Conformation; 4-(cyclohexylsulfanyl)-1,3-diaryl-1H-pyrazoles; NMR; Vilsme-
ier’s reagent; X-ray studies
Pyrazole derivatives show significant biological activities.[1–25] Presence of sulfur as a
substituent in the pyrazole ring may enhance the biological activity of this ring system,
and hence it has been planned to synthesize 4-(cyclohexylsulfanyl)-1,3-diaryl-1H-
pyrazoles using Vilsmeier’s reagent.[26–28] The interesting structural features of
the synthesized compounds, analyzed by NMR and x-ray methods, are described in
this article.
The starting materials identified for this synthesis are the hydrazones of
2-(cyclohexylsulfanyl)-1-aryl-1-ethanones 3. The hydrazones, in turn, were obtained
by the reaction of 2,4-dinitrophenylhydrazine with the sulfide 2. The keto sulfides 2
Received November 2, 2009.
Address correspondence to Shanmugam Muthusubramanian, Department of Organic Chemistry,
Madurai Kamaraj University, Madurai 625 021, India. E-mail: muthumanian2001@yahoo.com
1916

4-(CYCLOHEXYLSULFANYL) 1,3-DIARYL-1H-PYRAZOLE
1917
Scheme 1. Synthesis of hydrazones.
can be obtained by the reaction of differently substituted phenacyl bromide 1 with
cyclohexane thiol (Scheme 1). Previously, other bases such as
diisopropylethylamine[29] have been employed for the latter reaction with poor yield,
and it is now found that triethylamine is the base of choice for this reaction.
Compounds 2a and 2c were reported in the literature,[29,30] and compounds 2b, 2d,
2e, 2f, 2g, and 2h are previously unknown but now well characterized by NMR spec-
tral studies.
Hydrazones 3 were prepared by the conventional procedure, and all the synthe-
sized hydrazones are new. Arylpyrazoles have been synthesized from hydrazones by
Vilsmeier’s reagent[31] upon treatment with phosphorous oxychloride and dimethyl-
formamide at 80 ꢀC or under microwave irradiation. The hydrazones 3 were
quantitatively converted to the respective target compounds, 4-(cyclohexylsulfa-
nyl)-1,3-diaryl-1H-pyrazoles 4, with a trace amount of compound 5 (Scheme 2).
The synthesized compounds 3, 4, and 5 have been fully characterized by NMR
spectral data.
The pyrazoles synthesized (Table 1) have a downfield singlet in the aromatic
region. Thus, in the 1H NMR spectrum of 4c, this signal appears at 7.83 ppm.
The presence of a 2,4-dinitrophenyl ring is well documented by the signals at 7.91,
8.52, and 8.71 ppm as doublet, doublet of doublets, and doublet respectively. The
hydrogens of the phenyl ring appear as a pair of doublets at 6.99 ppm and 8.02
Scheme 2. Synthesis of pyrazoles.

1918
R. MANIKANNAN, R. VENKATESAN, AND S. MUTHUSUBRAMANIAN
Table 1. Synthesis of pyrazole from 2,4-dinitrophenylhydrazone
Reaction time
Conventional (h)
Yield (%)
Conventional
Entry
Ar
MW (s)
MW
Mp (ꢀC)
4a
4b
4c
4d
4e
4f
C6H5
4
4
4
4
4
4
5
5
60
30
30
30
30
30
60
60
94
93
91
92
87
88
80
85
96
95
96
97
92
91
89
92
115–116
138–139
130–131
124–125
Viscous
Viscous
132–133
175–176
p-CH3C6H4
p-OCH3C6H4
p-ClC6H4
o-CH3C6H4
m-OCH3C6H4
1-Naphthyl
2-Naphthyl
4g
4h
(J ¼ 8.7 Hz) ppm. The other 10 hydrogens of the cyclohexyl ring appear between
1.20 ppm to 1.92 ppm. The distortionless enhancement by polarization transfer
(DEPT) 135 spectrum indicates that the methylene carbons appear at 25.5, 25.9,
and 33.0 ppm. The methine carbon is found to absorb at 47.6 ppm. Six CH carbons
are noticed in the region between 113.8 ppm to 134.7 ppm, while the remaining quat-
ernary carbons appear at 113.3, 123.9, 136.6, 142.5, 145.0, 155.6, and 160.2 ppm. The
fact that the signal at 2.79 ppm has two different off diagonal contours with the
hydrogens at 1.20 and 1.92 ppm in the H,H-COSY (correlation spectroscopy) spec-
trum indicates that the nearby axial and equatorial hydrogens have vast differences
in their absorption position. The ortho hydrogens of the aryl ring and the singlet at
7.83 ppm give a common heteronuclear multiple-bond correlation (HMBC) contour
with the carbon at 155.6 ppm, suggesting that this carbon is the C-3 of the pyrazolyl
ring. The singlet also gives a HMBC contour with the carbon at 113.8 ppm, and this
carbon may be the C-4 carbon of the pyrazolyl ring. The carbons at 142.5 ppm and
145.0 ppm have a HMBC relationship with the doublet at 7.91 ppm. These carbons
must be ipso to nitro groups. The doublet of doublets at 8.52 ppm has a strong
HMBC contour with the carbon at 136.6 ppm, which has already been identified
as a CH carbon, indicating this carbon to be the C-3 of the 2,4-dinitrophenyl group.
The NMR spectral features clearly suggest that the conformation of the com-
pound 4c in solution to be the one in which the cyclohexylthio group occupies the
equatorial position, leaving the hydrogen at that carbon to be in axial. Though this
hydrogen signal is not well resolved, the base and half-height widths of the signal are
very much in favor of the axial nature of this hydrogen. It must be mentioned that
the methine hydrogen of the cyclohexyl ring of 3c appears as a triplet of triplets with
couplings of 10.8 Hz and 3.6 Hz, revealing the axial nature of this hydrogen. It is
interesting to point out that when the solid-state structure of 4c was analyzed by
single-crystal x-ray analysis, the observed conformation around the cyclohexyl group
was different. The ORTEP diagram (Fig. 1, Table 2) clearly shows that the substitu-
ents in the cyclohexyl system prefer an axial orientation rather than an equatorial
one. The crystal data have been submitted to CCDC, CCDC number 741901. This
is not surprising, as there are reports that the solid-state conformation and the sol-
ution conformation are found to be different in several cases. For example,
N-cyclohexyloxy-2(1H)-pyridione has this different conformational behavior in solid

4-(CYCLOHEXYLSULFANYL) 1,3-DIARYL-1H-PYRAZOLE
1919
Figure 1. ORTEP diagram of 4-(cyclohexylsulfanyl)-1-(2,4-dinitrophenyl)-3-(4-methoxyphenyl)-1H-
pyrazole (4c).
Table 2. Crystal data and structural refinement for 4c
Parameter
Value
Empirical formula
Formula weight
Temperature
C22H22N4O5S
454.50
293(2) K
˚
Wavelength
0.71073 A
Monoclinic
P21=c
Crystal system
Space group
Unit cell dimensions
˚
a ¼ 7.6153(9) A, a ¼ 90 deg.
˚
b ¼ 12.7689(10) A, b ¼ 94.016(9) deg.
˚
c ¼ 12.3488(9) A, c ¼ 90 deg.
Volume
Z
2167.8(3) A3
4
Density (calculated)
Absorption coefficient
F(000)
1.393 Mg=m3
0.19 mmꢁ1
952
Crystal size
0.32 ꢂ 0.28 ꢂ 0.20
2.4 to 25.0 deg.
4505
Theta range for data collection
Reflections collected
Independent reflections
Absorption correction
Max. and min. transmission
Refinement method
Data=restraints=parameters
Goodness of fit on F2
R indices (all data)
Extinction coefficient
Largest diff. peak and hole
2573 [R(int) ¼ 0.026]
Psi scans
0.9996 and 0.9801
Full-matrix least-squares on F2
3801=0=290
0.96
R1 ¼ 0.041, wR2 ¼ 0.125
0.0079(14)
0.23 and ꢁ0.25 eAꢁ3

1920
R. MANIKANNAN, R. VENKATESAN, AND S. MUTHUSUBRAMANIAN
Scheme 3. Conformations of 4c.
and solution state.[32] Thus 4c is found to have different conformations in solid and
solution (Scheme 3).
It is interesting that the reaction also leads to a trace amount of another pro-
duct 5 in all the cases. However, isolation of this compound in the pure form proved
difficult as the compound is obtained in a trace amount only, as indicated by the
NMR spectrum of the crude reaction product. Nevertheless, in two cases (5b and
5d), this minor product has been successfully separated from the reaction mixture.
Structure analysis of these compounds has been achieved by the NMR spectral
method.
1
The H NMR spectrum of 5b does not have signals for the 2,4-dinitrophenyl
group. Apart from the pair of doublets, each accounting for two hydrogens for
the p-tolyl group (7.38 ppm and 7.91 ppm, J ¼ 8.0 Hz), there is another pair of doub-
lets, each accounting for one hydrogen, appearing at 9.02 ppm and 9.06 ppm
(J ¼ 1.8 Hz). There is a singlet at 10.32 ppm, which exchanges with D2O, suggesting
that this hydrogen is attached to a hetero atom. The pair of doublets may be the
meta coupled aryl hydrogens and hence the 6 position of the 2,4-dinitrophenyl group
is now bearing no hydrogen. The cyclohexyl hydrogens appear in the same region as
in the case of 4. Only four CH carbons are noticed in the aromatic region of the
DEPT 135 spectrum and thus the pyrazole ring is not present in this compound.
There are eight quaternary carbons in the aromatic region. The HMBC spectrum
indicates the presence of a contour between the methyl carbon and the hydrogens
at 7.38 ppm. These latter hydrogens are therefore the hydrogens ortho to the methyl
group. The hydrogens at 7.91 ppm, the hydrogens meta to methyl, have HMBC con-
tours with the quaternary carbons, 140.4 ppm and 146.4 ppm. A mere count of the
remaining carbons suggests that the compound is an indole derivative with nitro
groups at 5 and 7 positions, the p-tolyl group at the 2 position, and the cyclohex-
ylthio group at the 3 position. This assignment has further support from the HMBC
spectrum of the compound. Single-crystal x-ray analysis also proves the structure of
5b (Fig. 2).[33]
The formation of 5 from 3 can be easily explained by considering the Fisher
indole transformation. Before the Vilsmeier’s reagent attacks the hydrazones, the
hydrozone undergoes thermal Fisher indole reaction initiated by the Lewis acid.

4-(CYCLOHEXYLSULFANYL) 1,3-DIARYL-1H-PYRAZOLE
1921
Figure 2. ORTEP diagram of 3-(cyclohexylsulfanyl)-2-(4-methylphenyl)-5,7-dinitro-1H-indole (5b).
A separate work to optimize the yield of indole without the Vilsmeier’s reagent is
under way in this laboratory.
While synthesizing
a new set of pyrazoles, 4-(cyclohexylsulfanyl)-1-
(2,4-dinitrophenyl)-3-(aryl)-1H-pyrazoles, it has been found that in 4-(cyclohexylsul-
fanyl)-1-(2,4-dinitrophenyl)-3-(4-methoxyphenyl)-1H-pyrazole, the pyrazolyl ring
occupies the equatorial position of the cyclohexyl ring in chloroform and the axial
position in the crystal state as evidenced by the NMR and single-crystal x-ray
analyses respectively.
EXPERIMENTAL
All melting points were recorded in open capillaries and are uncorrected. The
1H NMR spectra were recorded on Bruker 300-MHz spectrometers for samples in
CDCl3. The signals are expressed as parts per million downfield from tetramethyl-
silane (TMS), used as an internal standard (d value). Splitting patterns are indicated
as s, singlet; d, doublet; and m, multiplets. Microanalyses were carried out on a
Perkin-Elmer instrument. Microwave-assisted reactions were carried out in a Biotage
Microwave Synthesizer. All chromatographic separations were performed on silica
gel (60–120 mesh) using petroleum ether–ethyl acetate as eluent. Single-crystal
x-ray diffraction (XRD) data were collected on a Nonius Mach3=CAD-4 (MoKa,
k ¼ 0.71073 area detector diffractometer.

1922
R. MANIKANNAN, R. VENKATESAN, AND S. MUTHUSUBRAMANIAN
General Procedure for the Synthesis of 1-Aryl-2-
[cyclohexylsulfanyl]-1-ethanone (2)
A mixture of substituted phenacyl bromide 1 (0.005 m) and cyclohexane thiol
(0.005 mol) along with triethylamine (0.010 m) in 30 ml of ethanol was stirred for
90 min at room temperature. After the completion of the reaction, the reaction
mixture was poured onto crushed ice and filtered off. The product was recrystallized
from ethanol to obtain 1-aryl-2-[cyclohexylsulfanyl]-1-ethanone 2 in good yield.
Selected Data for Compounds 2
2-(Cyclohexylsulfanyl)-1-(4-methylphenyl)-1-ethanone (2b). Viscous
1
liquid, yield 97%. H NMR (300 MHz, CDCl3): d 1.25–2.00 (m, 10H); 2.38 (s, 3H);
2.70–2.72 (m, 1H); 3.77 (s, 2H); 7.23 (d, J ¼ 8.0 Hz, 2H); 7.85 (d, J ¼ 8.0 Hz, 2H)
ppm. 13C NMR (75 MHz, CDCl3): d 21.5, 25.5, 25.6, 32.7, 35.5, 43.7, 128.8,
129.3, 132.6, 143.9, 194.8 ppm.
2-(Cyclohexylsulfanyl)-1-(4-chlorophenyl)-1-ethanone (2d). Colorless
crystal, yield 95%, mp 63–64 ꢀC. Anal. calcd. for C14H17ClOS: C, 62.56; H, 6.37.
1
Found: C, 62.61; H, 6.49. H NMR (300 MHz, CDCl3): d ¼ 1.24–2.00 (m, 10H);
2.69–2.71 (m, 1H); 3.77 (s, 2H); 7.42 (d, J ¼ 9.0 Hz, 2H); 7.90 (d, J ¼ 9.0 Hz, 2H)
ppm. 13C NMR (75 MHz, CDCl3): d ¼ 25.7, 25.9, 33.0, 35.6, 43.9, 128.9, 130.2,
133.5, 139.7, 193.9 ppm.
2-(Cyclohexylsulfanyl)-1-(2-methylphenyl)-1-ethanone (2e). Colorless
crystal, yield 97%, mp 55–56 ꢀC. Anal. calcd. for C15H20OS: C, 72.53; H, 8.12.
1
Found: C, 72.63; H, 8.19. H NMR (300 MHz, CDCl3): d ¼ 1.25–2.00 (m, 10H);
2.38 (s, 3H); 2.70–2.72 (m, 1H); 3.77 (s, 2H); 7.23–7.45 (m, 2H); 7.60–7.85 (m,
2H) ppm. 13C NMR (75 MHz, CDCl3): d ¼ 21.5, 25.6, 25.7, 32.7, 35.6, 43.7, 125.5,
127.9, 129.8, 130.5, 136.7, 138.6, 191.0 ppm.
2-(Cyclohexylsulfanyl)-1-(3-methoxyphenyl)-1-ethanone (2f). Viscous
1
liquid, yield 92%. H NMR (300 MHz, CDCl3): d ¼ 1.24–1.99 (m, 10H); 2.69–2.70
(m, 1H); 3.78 (s, 2H); 3.81 (s, 3H); 7.07 (dd, J ¼ 7.7, 2.7 Hz, 1H); 7.32 (t, J ¼ 7.7 Hz,
1H); 7.47–7.51 (m, 2H) ppm. 13C NMR (75 MHz, CDCl3): d ¼ 25.3, 25.4, 32.6, 35.3,
43.3, 54.8, 112.5, 119.1, 120.9, 129.1, 136.2, 159.3, 194.3 ppm.
2-(Cyclohexylsulfanyl)-1-(1-naphthyl)-1-ethanone (2g). Viscous liquid,
yield 90%. 1H NMR (300 MHz, CDCl3): d ¼ 1.32–2.04 (m, 10H); 2.72–2.82
(m, 1H); 3.91 (s, 2H); 7.45–7.91 (m, 5H); 7.99 (d, J ¼ 8.1 Hz, 1H); 8.11 (d, J ¼ 8.4 Hz,
1H) ppm. 13C NMR (75 MHz, CDCl3): d ¼ 25.6, 25.9, 32.7, 38.8, 43.8, 124.2, 125.6,
126.4, 127.9ꢃ, 128.4, 130.7, 132.9, 133.9, 134.2, 198.8 ppm. (ꢃOne carbon merged with
another.)
2-(Cyclohexylsulfanyl)-1-(2-naphthyl)-1-ethanone (2h). Viscous liquid,
yield 92%. 1H NMR (300 MHz, CDCl3): d ¼ 1.32–2.04 (m, 10H); 2.68–2.78 (m,
1H); 3.94 (s, 2H); 7.51–8.04 (m, 6H); 8.49 (s, 1H) ppm. 13C NMR (75 MHz, CDCl3):
d ¼ 25.6, 25.9, 32.7, 35.7, 43.8, 124.3, 126.7, 127.6, 128.4, 128.5, 129.5, 130.5, 132.3,
132.5, 135.5, 195.1 ppm.

4-(CYCLOHEXYLSULFANYL) 1,3-DIARYL-1H-PYRAZOLE
1923
General Procedure for the Synthesis of 2-[Cyclohexylsulfanyl]-1-
(aryl)-1-ethanone N-(2,4-dinitrophenyl)hydrazones (3)
2,4-Dinitrophenylhydrazine (0.004 m) was dissolved in 10 ml of methanol, and
a few drops of concentrated sulfuric acid were added to the mixture to get a clear
solution. The warm solution was filtered, and a solution of 1-aryl-2[cyclohexyl
sulfanyl]-1-ethanones 2 (0.004 m) dissolved in ethanol (20 ml) was added to the sol-
ution. The solid obtained was suction filtered and washed with a little ethanol. The
product was recrystallized from dichloromethane to obtain 2-(cyclohexyl
sulfanyl)-1-aryl-1-ethanone N-(2,4-dinitrophenyl)hydrazones 3 in good yield.
Selected Data for Compounds 3
2-(Cyclohexylsulfanyl)-1-phenyl-1-ethanone N-(2,4-dinitrophenyl)hydrazone
(3a). Yellow crystal, yield 94%, mp 133–134 ꢀC. Anal. calcd. for C20H22N4O4S: C,
1
57.96; H, 5.35; N, 13.52. Found: C, 57.99; H, 5.32; N, 13.55. H NMR (300 MHz,
CDCl3): d ¼ 1.29–1.66 (m, 6H); 1.81–1.84 (m, 2H); 2.07–2.12 (m, 2H); 2.94–2.95
(m, 1H); 3.93 (s, 2H); 7.46–7.47 (m, 3H); 7.86–7.89 (m, 2H); 8.11 (d, J ¼ 9.6 Hz,
1H); 8.36 (dd, J ¼ 9.6, 2.7 Hz, 1H); 9.18 (d, J ¼ 2.7 Hz, 1H); 11.90 (s, 1H) ppm.
13C NMR (75 MHz, CDCl3): d ¼ 25.6, 25.9, 26.5, 33.2, 45.6, 116.9, 123.4, 126.4,
128.8, 129.9, 130.1, 130.3, 136.4, 138.4, 144.9, 151.7 ppm.
2-(Cyclohexylsulfanyl)-1-(4-methylphenyl)-1-ethanone
N-(2,4-dinitro-
phenyl) hydrazone (3b). Yellow crystal, yield 98%, mp 161–162 ꢀC. Anal. calcd.
for C21H24N4O4S: C, 58.86; H, 5.65; N, 13.07. Found: C, 58.84; H, 5.62; N, 13.01.
1H NMR (300 MHz, CDCl3): d ¼ 1.29–1.66 (m, 6H); 1.81–1.83 (m, 2H); 2.07–2.11
(m, 2H); 2.42 (s, 3H); 2.87–3.00 (m, 1H); 3.91 (s, 2H); 7.27 (d, J ¼ 8.4 Hz, 2H);
7.77 (d, J ¼ 8.4 Hz, 2H); 8.10 (d, J ¼ 9.6 Hz, 1H); 8.35 (dd, J ¼ 9.6, 2.4 Hz, 1H);
9.18 (d, J ¼ 2.4 Hz, 1H); 11.80 (s, 1H) ppm. 13C NMR (75 MHz, CDCl3): d ¼ 21.4,
25.6, 25.9, 26.4, 33.2, 45.5, 116.9, 123.5, 126.4, 129.5, 129.9, 130.0, 133.5, 138.2,
140.7, 144.9, 151.9 ppm.
2-(Cyclohexylsulfanyl)-1-(4-methoxyphenyl)-1-ethanone N-(2,4-dinitro-
phenyl) hydrazone (3c). Yellow crystal, yield 93%, mp 158–159 ꢀC. Anal. calcd.
for C21H24N4O5S: C, 56.74; H, 5.44; N, 12.60. Found: C, 56.78; H, 5.49; N, 12.68.
1H NMR (300 MHz, CDCl3): d ¼ 1.29–1.66 (m, 6H); 1.81–1.84 (m, 2H); 2.07–2.11
(m, 2H); 2.87–3.00 (tt, J ¼ 10.8, 3.6 Hz, 1H); 3.88 (s, 3H); 3.89 (s, 2H); 6.97 (d,
J ¼ 9.0 Hz, 2H); 7.83 (d, J ¼ 9.0 Hz, 2H); 8.07 (d, J ¼ 9.6 Hz, 1H); 8.34 (dd,
J ¼ 9.6, 2.4 Hz, 1H); 9.17 (d, J ¼ 2.4 Hz, 1H); 11.75 (s, 1H) ppm. 13C NMR
(75 MHz, CDCl3): d ¼ 25.6, 25.9, 26.3, 33.2, 45.5, 55.4, 114.2, 116.8, 123.5, 128.0,
128.7, 129.9, 129.9, 138.1, 144.9, 151.6, 161.4 ppm.
2-(Cyclohexylsulfanyl)-1-(4-chlorophenyl)-1-ethanone N-(2,4-dinitrophenyl)
hydrazone (3d). Brown crystal, yield 99%, mp 132–133 ꢀC. Anal. calcd. for
C20H21ClN4O4S: C, 53.51; H, 4.72; N, 12.48. Found: C, 53.55; H, 4.76; N, 12.53.
1H NMR (300 MHz, CDCl3): d ¼ 1.40–1.74 (m, 6H); 1.88–2.19 (m, 4H); 2.97–3.16
(m, 1H); 3.97 (s, 2H); 7.51 (d, J ¼ 8.6 Hz, 2H); 7.89 (d, J ¼ 8.6 Hz, 2H); 8.15
(d, J ¼ 9.6 Hz, 1H); 8.44 (dd, J ¼ 9.6, 1.2 Hz, 1H); 9.25 (d, J ¼ 1.2 Hz, 1H); 11.85

1924
R. MANIKANNAN, R. VENKATESAN, AND S. MUTHUSUBRAMANIAN
(s, 1H) ppm. 13C NMR (75 MHz, CDCl3): d ¼ 25.6, 25.9, 26.4, 33.2, 45.7, 116.8,
123.4, 127.7, 129.0, 129.9, 130.3, 134.8, 136.3, 138.6, 144.8, 150.4 ppm.
2-(Cyclohexylsulfanyl)-1-(2-methylphenyl)-1-ethanone N-(2,4-dinitrophenyl)
hydrazone (3e). Yellow crystal, yield 99%, mp 131–132 ꢀC. Anal. calcd. for
1
C21H24N4O4S: C, 58.86; H, 5.65; N, 13.07. Found: C, 58.89; H, 5.67; N, 13.09. H
NMR (300 MHz, CDCl3): d ¼ 1.28–1.46 (m, 6H); 1.79–1.80 (m, 2H); 2.02–2.06 (m,
2H); 2.50 (s, 3H); 2.87–2.94 (m, 1H); 3.86 (s, 2H); 7.26–7.48 (m, 4H); 7.96 (d,
J ¼ 9.2 Hz, 1H); 8.31 (dd, J ¼ 9.2, 1.5 Hz, 1H); 9.16 (d, J ¼ 1.5 Hz, 1H); 11.95 (s,
1H) ppm. 13C NMR (75 MHz, CDCl3): d ¼ 21.1, 25.6, 25.9, 30.1, 32.9, 45.5, 116.7,
123.4, 126.1, 128.2, 129.3, 129.9, 130.0, 131.3, 135.9, 137.5, 138.4, 144.9, 153.7 ppm.
2-(Cyclohexylsulfanyl)-1-(3-methoxyphenyl)-1-ethanone N-(2,4-dinitro-
phenyl) hydrazone (3f). Orange crystal, yield 99%, mp 128–129 ꢀC. Anal. calcd.
for C21H24N4O5S: C, 56.74; H, 5.44; N, 12.60. Found: C, 56.79; H, 5.46; N, 12.63.
1H NMR (300 MHz, CDCl3): d ¼ 1.29–2.10 (m, 10H); 2.85–3.00 (m, 1H); 3.87
(s, 3H); 3.89 (s, 2H); 6.98–8.12 (m, 5H); 8.34 (dd, J ¼ 9.6, 2.6 Hz, 1H); 9.15 (d,
J ¼ 2.6 Hz, 1H); 11.77 (s, 1H) ppm. 13C NMR (75 MHz, CDCl3): d ¼ 25.6, 25.9,
26.6, 33.1, 45.6, 55.4, 112.3, 116.8, 118.9, 119.0, 123.4, 129.7, 129.8, 129.9, 130.1,
137.8, 144.8, 151.5, 159.8 ppm.
2-(Cyclohexylsulfanyl)-1-(1-naphthyl)-1-ethanone N-(2,4-dinitrophenyl)-
hydrazone (3g). Orange red crystal, yield 87%, mp 111–112 ꢀC, Anal. calcd. for
1
C24H24N4O4S: C, 62.05; H, 5.21; N, 12.06. Found: C, 62.09; H, 5.27; N, 12.11. H
NMR (300 MHz, CDCl3): d ¼ 1.26–1.77 (m, 8H); 1.98–2.02 (m, 2H); 2.87–2.97 (m,
1H); 4.04 (s, 2H); 7.53–8.32 (m, 9H); 9.20 (d, J ¼ 2.1 Hz, 1H); 12.00 (s, 1H) ppm.
13C NMR (75 MHz, CDCl3): d ¼ 25.5, 25.8, 30.8, 32.9, 45.4, 116.8, 123.3, 124.9,
125.1, 126.2, 126.5, 126.9, 128.7, 129.9, 130.0, 130.3, 133.8, 135.7, 138.4, 138.5,
144.9, 153.2 ppm.
2-(Cyclohexylsulfanyl)-1-(2-naphthyl)-1-ethanone N-(2,4-dinitrophenyl)-
hydrazone (3h). Orange red crystal, yield 90%, mp 152–153 ꢀC. Anal. calcd. for
1
C24H24N4O4S: C, 62.05; H, 5.21; N, 12.06. Found: C, 62.13; H, 5.29; N, 12.13. H
NMR (300 MHz, CDCl3): d ¼ 1.25–1.67 (m, 6H); 1.82–1.86 (m, 2H); 2.12–2.16 (m,
2H); 2.96–3.04 (m, 1H); 4.02 (s, 2H); 7.46–8.19 (m, 8H); 8.36 (dd, J ¼ 9.6, 2.4 Hz,
1H); 9.15 (d, J ¼ 2.4 Hz, 1H); 11.81 (s, 1H) ppm. 13C NMR (75 MHz, CDCl3):
d ¼ 25.6, 25.9, 26.3, 33.2, 45.7, 116.9, 123.3, 123.4, 126.7, 126.7, 127.4, 127.7,
128.5, 128.7, 129.9, 130.1, 133.0, 133.6, 134.0, 138.4, 144.8, 151.4 ppm.
General Procedure for the Synthesis of 4-(Cyclohexylsulfanyl)-1-
(2,4-dinitrophenyl)-3-(aryl)-1H-pyrazoles (4) and 2-Aryl-3-
(cyclohexylsulfanyl)-5,7-dinitro-1H-Indole (5)
A mixture of 2-(arylsulfanyl)-1-aryl-1-ethanone N-(2,4-dinitrophenyl)hydra-
zones 3 (0.001 m) dissolved in dimethylformamide (5 ml) was allowed to cool in ice
with stirring. To this stirred solution, phosphorus oxychloride (0.008 m) was added
dropwise, and the mixture was subjected to microwave irradiation for 30–60 s. The
reaction was monitored by thin-layer chromatography (TLC), and after completion
of the reaction, the reaction mixture was poured onto crushed ice. The solid was

4-(CYCLOHEXYLSULFANYL) 1,3-DIARYL-1H-PYRAZOLE
1925
suction filtered and washed with plenty of water. The different products were
purified by column chromatography using petroleum ether–ethyl acetate as eluent.
Selected Data for Compounds 4
4-(Cyclohexylsulfanyl)-1-(2,4-dinitrophenyl)-3-phenyl-1H-pyrazole (4a).
Yellow crystal. Anal. calcd. for C21H20N4O4S: C, 59.42; H, 4.75; N, 13.20. Found:
1
C, 59.45; H, 4.79; N, 13.24. H NMR (300 MHz, CDCl3): d ¼ 1.18–1.71 (m, 8H);
1.86–1.90 (m, 2H); 2.74–2.80 (m, 1H); 7.46–7.48 (m, 3H); 7.84 (s, 1H); 7.91 (d,
J ¼ 9.0 Hz, 1H); 8.05–8.08 (m, 2H); 8.52 (dd, J ¼ 9.0, 2.4 Hz, 1H); 8.72 (d, J ¼ 2.4 Hz,
Hz, 1H) ppm. 13C NMR (75 MHz, CDCl3): d 25.5, 25.8, 33.0, 47.7, 113.7, 121.3
125.1, 127.5 127.9, 128.4, 129.1, 131.4, 134.7, 136.7, 142.6, 145.3, 155.9 ppm.
4-(Cyclohexylsulfanyl)-1-(2,4-dinitrophenyl)-3-(4-methylphenyl)-1H-
pyrazole (4b). Yellow crystal. Anal. calcd. for C22H22N4O4S: C, 60.26; H, 5.06; N,
1
12.78. Found: C, 60.29; H, 5.09; N, 12.81. H NMR (300 MHz, CDCl3): d ¼ 1.23–
1.88 (m, 10H); 2.41 (s, 3H); 2.71–2.79 (m, 1H); 7.25 (d, J ¼ 7.2 Hz, 2H); 7.81 (s,
1H); 7.88 (d, J ¼ 9.0 Hz, 1H); 7.96 (d, J ¼ 7.2 Hz, 2H); 8.49 (dd, J ¼ 1.8, 9.0 Hz,
1H); 8.69 (d, J ¼ 1.8 Hz, 1H) ppm. 13C NMR (75 MHz, CDCl3): d ¼ 21.4 25.5,
25.8, 33.0, 47.6, 113.6, 121.2, 124.9, 127.4, 127.8, 128.5, 129.1, 134.6, 136.6, 139.0,
142.4, 145.1, 155.9 ppm.
4-(Cyclohexylsulfanyl)-1-(2,4-dinitrophenyl)-3-(4-methoxyphenyl)-1H-
pyrazole (4c). Yellow crystal. Anal. calcd. for C22H22N4O5S: C, 58.14; H, 4.88; N,
1
12.33. Found: C, 58.19; H, 4.91; N, 12.36. H NMR (300 MHz, CDCl3): d ¼ 1.20–
1.92 (m, 10H); 2.76–2.83 (m, 1H); 3.88 (s, 3H); 6.99 (d, J ¼ 8.7 Hz, 2H); 7.83 (s,
1H); 7.91 (d, J ¼ 9.0 Hz, 1H); 8.02 (d, J ¼ 8.7 Hz, 2H); 8.52 (dd, J ¼ 2.4, 9.0 Hz,
1H); 8.71 (d, J ¼ 2.4 Hz, 1H) ppm. 13C NMR (75 MHz, CDCl3): d ¼ 25.5, 25.9,
33.0, 47.6, 55.3, 113.3, 113.8, 121.2, 123.9, 124.8, 127.4, 129.3, 134.7, 136.6, 142.5,
145.0, 155.6, 160.2 ppm.
3-(4-Chlorophenyl)-4-(cyclohexylsulfanyl)-1-(2,4-dinitrophenyl)-1H-
pyrazole (4d). Yellow crystal. Anal. calcd. for C21H19ClN4O4S: C, 54.96; H, 4.17;
N, 12.21. Found: C, 54.91; H, 4.13; N, 12.26. 1H NMR (300 MHz, CDCl3): d ¼ 0.86–
1.89 (m, 10H); 2.77–2.79 (m, 1H); 7.42 (d, J ¼ 8.4 Hz, 2H); 7.85 (s, 1H); 7.90 (d,
J ¼ 9.0 Hz, 1H); 8.05 (d, J ¼ 8.4 Hz, 2H); 8.54 (dd, J ¼ 2.1, 9.0 Hz, 1H); 8.73 (d,
J ¼ 2.1 Hz, 1H) ppm. 13C NMR (75 MHz, CDCl3): d ¼ 25.5, 25.8, 33.0, 47.9,
113.5, 121.3, 125.2, 127.5, 128.3, 128.6, 129.2, 129.9, 135.1, 136.6, 142.7, 145.4,
154.9 ppm.
4-(Cyclohexylsulfanyl)-1-(2,4-dinitrophenyl)-3-(2-methylphenyl)-1H-
pyrazole (4e). 1H NMR (300 MHz, CDCl3): d ¼ 1.69–1.75 (m, 10H); 2.32 (s, 3H);
2.43–2.60 (m, 1H); 7.27–7.88 (m, 5H); 7.88 (s, 1H); 8.52 (dd, J ¼ 9.0, 2.4 Hz, 1H); 8.
71 (d, J ¼ 2.4 Hz, 1H) ppm. 13C NMR (75 MHz, CDCl3): d 20.1, 25.5, 25.8, 32.9,
47.2, 115.3, 121.2, 125.3, 125.3, 127.5, 128.9, 130.4, 130.5, 130.5, 133.3, 136.9,
137.3, 142.9, 145.30, 158.3 ppm.
4-(Cyclohexylsulfanyl)-1-(2,4-dinitrophenyl)-3-(3-methoxyphenyl)-1H-
pyrazole (4f). 1H NMR (300 MHz, CDCl3): d ¼ 1.22–1.91 (m, 10H); 2.79–2.80

1926
R. MANIKANNAN, R. VENKATESAN, AND S. MUTHUSUBRAMANIAN
(m, 1H); 3.88 (s, 3H); 6.98 (dd, J ¼ 8.6, 1.8 Hz, 1H); 7.36 (t, J ¼ 8.6 Hz, 1H);
7.68–7.70 (m, 2H); 7.84 (s, 1H); 7.90 (d, J ¼ 9.0 Hz, 1H); 8.52 (dd, J ¼ 9.0, 2.4 Hz,
1H); 8.71 (d, J ¼ 2.4 Hz, 1H) ppm. 13C NMR (75 MHz, CDCl3): d 25.5, 25.8, 33.0,
47.7, 55.3, 112.8, 113.7, 115.2, 115.4, 120.3, 121.2, 125.0, 127.4, 129.4, 132.6,
134.8, 136.6, 145.2, 155.5, 159.4 ppm.
4-(Cyclohexylsulfanyl)-1-(2,4-dinitrophenyl)-3-(1-naphthyl)-1H-pyrazole
(4g). Yellow crystal. Anal. calcd. for C25H22N4O4S: C, 63.28; H, 4.67; N, 11.81.
1
Found: C, 63.34; H, 4.82; N, 11.91. H NMR (300 MHz, CDCl3): d ¼ 1.05–1.72
(m, 10H); 2.65–2.72 (m, 1H); 7.50–7.93 (m, 8H); 7.89 (d, J ¼ 8.7 Hz, 1H); 8.51 (dd,
J ¼ 8.7, 2.4 Hz, 1H); 8.74 (d, J ¼ 2.4 Hz, 1H) ppm. 13C NMR (75 MHz, CDCl3):
d ¼ 25.7, 25.9, 33.4, 47.9, 114.3, 121.8, 125.2, 125.5, 126.6, 126.9, 127.7, 127.7,
127.9, 128.3, 128.5, 128.9, 133.2, 133.5, 135.4, 136.8, 142.8, 145.6, 156.6 ppm.
4-(Cyclohexylsulfanyl)-1-(2,4-dinitrophenyl)-3-(2-naphthyl)-1H-pyrazole
(4h). Yellow crystal. Anal. calcd. for C25H22N4O4S: C, 63.28; H, 4.67; N, 11.81.
1
Found: C, 63.32; H, 4.80; N, 11.85. H NMR (300 MHz, CDCl3): d ¼ 1.20–1.93
(m, 10H); 2.79–2.86 (m, 1H); 7.52–7.95 (m, 8H); 8.15 (d, J ¼ 9.0 Hz, 1H); 8.53 (dd,
J ¼ 9.0, 2.4 Hz, 1H); 8.71 (d, J ¼ 2.4 Hz, 1H) ppm. 13C NMR (75 MHz, CDCl3):
d ¼ 25.5, 25.8, 33.1, 47.8, 113.9, 121.2, 125.2, 125.3, 126.3, 126.7, 127.5, 127.6,
127.7, 128.1, 128.7, 128.9, 133.1, 133.4, 135.0, 136.7, 142.6, 145.2, 155.4 ppm.
3-(Cyclohexylsulfanyl)-2-(4-methylphenyl)-5,7-dinitro-1H-indole (5b).
Yellow crystal, yield 5%, mp 167–168 ꢀC. Anal. calcd. for C21H21N3O4S: C, 61.30;
H, 5.14; N, 10.21. Found: C, 61.39; H, 5.23; N, 10.28. 1H NMR (300 MHz, CDCl3):
d ¼ 0.90–1.91 (m, 10H); 2.47 (s, 3H); 2.80–2.87 (m, 1H); 7.38 (d, J ¼ 8.0 Hz, 2H); 7.91
(d, J ¼ 8.0 Hz, 2H); 9.02 (d, J ¼ 1.8 Hz, 1H); 9.06 (d, J ¼ 1.8 Hz, 1H); 10.32 (s, 1H)
ppm. 13C NMR (75 MHz, CDCl3): d ¼ 21.5, 25.4, 25.9, 33.4, 48.7, 106.2, 114.9,
122.5, 126.9, 128.2, 129.8, 131.2, 131.7, 136.3, 140.4, 141.3, 146.4 ppm.
2-(4-Chlorophenyl)-3-(cyclohexylsulfanyl)-5,7-dinitro-1H-indole (5d).
Viscous liquid, yield 4%. 1H NMR (300 MHz, CDCl3): d ¼ 1.14–1.78 (m, 10H);
2.81–2.83 (m, 1H); 7.56 (d, J ¼ 8.7 Hz, 2H); 7.96 (d, J ¼ 8.7 Hz, 2H); 9.03 (d,
J ¼ 2.0 Hz, 1H); 9.07 (d, J ¼ 2.0 Hz, 1H); 10.33 (s, 1H) ppm. 13C NMR (75 MHz,
CDCl3): d ¼ 25.4, 25.8, 33.5, 48.9, 115.4, 122.8, 128.2, 128.3, 128.6, 129.4ꢃ, 129.7,
131.9, 136.1, 141.5, 145.0 ppm. (ꢃOne carbon merged with another.)
ACKNOWLEDGMENTS
We thank the Department of Science and Technology, New Delhi, for assist-
ance under the Intensification of Research in High Priority Area (IRHPA) program
for the NMR facility. One of the authors (R. M.) thanks Madurai Kamaraj Univer-
sity for a research fellowship.
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