Synthesis and characterization of a new series of hydroxy pyrazolines

Article abstract of DOI:10.1080/00397910802241407

3-Phenyl-1-(thiophen-2-yl)prop-2-en-1-one obtained by Claisen-Schmidt condensation of 2-acetyl thiophene with benzaldehyde was converted into 2,3-dibromo-3-phenyl-1-(thiophen-2-yl)propan-1-one, which on treatment with various thiosemicarbazides in the presence of triethylamine in absolute ethanol, yielded the corresponding hydroxy pyrazolines 3a-h. All the compounds were characterized by IR, 1H NMR, and 13C NMR spectra. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910802241407

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Synthesis and Characterization
of a New Series of Hydroxy
Pyrazolines
Humaira Parveen a , Prince Firdoos Iqbal a & Amir
Azam a
a Department of Chemistry, Jamia Millia Islamia,
Jamia Nagar, New Delhi, India
Version of record first published: 20 Oct 2008
To cite this article: Humaira Parveen, Prince Firdoos Iqbal & Amir Azam (2008):
Synthesis and Characterization of a New Series of Hydroxy Pyrazolines, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 38:22, 3973-3983
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Synthetic Communications1, 38: 3973–3983, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802241407
Synthesis and Characterization of a New Series
of Hydroxy Pyrazolines
Humaira Parveen, Prince Firdoos Iqbal, and Amir Azam
Department of Chemistry, Jamia Millia Islamia, Jamia Nagar,
New Delhi, India
Abstract: 3-Phenyl-1-(thiophen-2-yl)prop-2-en-1-one obtained by Claisen–
Schmidt condensation of 2-acetyl thiophene with benzaldehyde was converted
into 2,3-dibromo-3-phenyl-1-(thiophen-2-yl)propan-1-one, which on treatment
with various thiosemicarbazides in the presence of triethylamine in absolute
ethanol, yielded the corresponding hydroxy pyrazolines 3a–h. All the compounds
1
were characterized by IR, H NMR, and 13C NMR spectra.
Keywords: Chalcone, chalcone dibromide, hydroxy pyrazoline, pyrazoline
INTRODUCTION
Chalcones constitute an important class of naturally occurring flavonoid
compounds that exhibit a wide spectrum of biological activities and are
well-known intermediates for synthesizing various heterocycles. Chalcone
dibromides are useful synthons in the synthesis of a large number of
bioactive molecules such as pyrazolines, hydroxy pyrazolines, and isoxa-
zoles. Pyrazoles and their reduced forms, pyrazolines, are well-known
nitrogen-containing heterocyclic compounds, and various procedures
have been developed for their syntheses.[1,2] The discovery of this class
of compounds provides an outstanding case history of modern drug
development and also points out the unpredictability of biological
Received April 1, 2008.
Address correspondence to Amir Azam, Department of Chemistry, Jamia
Millia Islamia, Jamia Nagar, New Delhi 110025, India. E-mail: amir_sumbul@
yahoo.co.in
3973

3974
H. Parveen, P. F. Iqbal, and A. Azam
activity from structural modification of a prototype drug molecule. Con-
siderable interest has been focused on the pyrazoline structure, which has
been known to possess a broad spectrum of biological activities such as
antitumor,[3] immunosuppressive,[4] antibacterial,[5] anti-inflammatory,[6]
anticancer,[7] antidiabetic,[8] and antidepressant.[9]
Stable and isolable representatives of 5-hydroxy-2-pyrazolines have
been described in the literature.[10] They were mostly obtained by the
reaction of 1,3-diketones with derivatives of hydrazine in which there is
a strong electron-withdrawing group (aryl, thioacyl, carbamoyl, thiocar-
bamoyl, etc.). 5-Hydroxy-2-pyrazolineses are of interest as polydendate
ligands; their copper and nickel chelates exhibit enhanced antimicrobial
activity.[10] In view of the versatile applications of chalcones, pyrazolines,
and hydroxy pyrazolines, we herein report the synthesis of a new series of
hydroxy pyrazolines.
RESULTS AND DISCUSSION
3-Phenyl-1-(thiophen-2-yl)prop-2-en-1-one (chalcone 1) was obtained by
Claisen–Schmidt condensation of 2-acetyl thiophene with benzaldehyde.
The chalcone 1 was converted into 2,3-dibromo-3-phenyl-1-(thiophen-
2-yl)propan-1-one (chalcone dibromide 2), which, on treatment with dif-
ferent thiosemicarbazides in the presence of triethylamine in absolute
ethanol, yielded corresponding hydroxy pyrazolines 3a–h (Scheme 1).
1
All the compounds were characterized by IR, H NMR, and 13C NMR
spectra. The purity of the compounds was confirmed by elemental analy-
sis, ꢀ0.3%.
The formation of chalcone 1 and chalcone dibromide 2 was con-
firmed by IR spectra. The absence of a band at or around 2660 cmꢁ1
due to the aldehydic proton and the appearance of characteristic bands
at 1620–1650 cmꢁ1 and 1415–1450 cmꢁ1 due to a,b-unsaturated carbonyl
group and n(C¼C), respectively, suggested the condensation of 2-acetyl
1
thiophene and benzaldehyde. In the H NMR spectrum of chalcone 1,
two doublets at 7.47 (H-a, J ¼ 15.2 Hz) and 7.89 (H-b, J ¼ 15.2 Hz) sug-
gested the presence of olefinic protons at the a,b-position to the carbonyl
group, whereas two doublets at 6.38 (H-a, J ¼ 10.5 Hz) and 5.59 (H-b,
J ¼ 10.5 Hz) suggested the formation of chalcone dibromide 2. The struc-
ture of these compounds was further confirmed by 13C NMR spectra. A
characteristic signal for the chalcone (C¼O) appeared in the range of
180–182 ppm, and signals at 121.89 ppm and 143.20 ppm revealed the
presence of a,b-unsaturated keto function in chalcone 1. In the chalcone
dibromide 2, a signal at 185.27 due to (C¼O) and two signals at 47.55

New Series of Hydroxy Pyrazolines
3975
Scheme 1. Synthesis of hydroxy pyrazolines.
(C-a) and 50.91 (C-b) suggested the conversion of chalcone 1 to chalcone
bromide 2.
In the IR spectra of hydroxy pyrazolines 3a–h, a characteristic broad
band appeared at 3360–3390 cmꢁ1, indicating the presence of a hydrogen-
bonded hydroxyl group. The thionyl n(C¼S) stretching frequency was
observed at 1121–1190 cmꢁ1. The other prominent absorption bands

3976
H. Parveen, P. F. Iqbal, and A. Azam
Figure 1. Methylene protons of pyrazoline ring.
observed in the IR spectrum of compound 3a are 3280 (N–H), 3075 (Ar–H),
2921 (C–H), 1532 (C¼N), and 1447 (C¼C). The 1H NMR spectra
showed that the proton of the hydroxyl group resonated as a singlet at
4.61–4.91 ppm. The methylene protons of hydroxy pyrazoline ring
(Fig. 1) appeared as two doublets, one at 5.03–5.17 ppm (H4a,
J ¼ 16.6–17.4 Hz) and the other at 5.17–5.42 (H4b, J ¼ 16.2–17.4 Hz).
The appearance of these two doublets clearly revealed the magnetic non-
equivalence of the two protons of the CH2 group adjacent to a chiral
center. The protons of the phenyl ring resonated as a multiplet at 7.01–
7.65 ppm. A double doublet at 7.34–7.65 ppm (J ¼ 2.1–3.4, 1.0–2.0 Hz)
integrating for one proton was attributed to the C3 proton of thiophenyl
moiety, and a double doublet at 7.72–7.81 ppm (J ¼ 4.3–5.5, 1.0–1.8 Hz)
was due to the C5 proton of the thiophenyl moiety. The C4 proton of the
thiophenyl moiety resonated as a multiplet at 7.01–7.35 ppm.
Further evidence for the formation of hydroxy pyrazolines 3a–h was
obtained from 13C NMR spectra. A signal at 179.2–184.8 ppm and 153.4–
159.8 ppm was attributed to (C¼S) and (C¼N) respectively in all the
compounds. The (C–OH) signal due to C5 of pyrazoline ring in the range
of 87.4–91.5 ppm and a characteristic signal for C4 of pyrazoline ring
found in the range of 49.1–54.5 ppm clearly favored the formation of
hydroxy pyrazolines. The signals due to the phenyl ring and thiophenyl
ring resonate at their usual positions, and the values are given in the
Experimental section.
EXPERIMENTAL
Precoated aluminium sheets (Merck silica gel 60 F254) were used for
thin-layer chromatography (TLC). Column chromatography was

New Series of Hydroxy Pyrazolines
3977
˚
accomplished using silica gel, 60 A (200–400 mesh). Elemental analyses
were performed at Central Drug Research Institute, Lucknow, India,
using an Elementar Vario EL III analyzer, and the results were within
ꢀ0.3% of the theoretical values. IR spectra were taken as KBr pellets
on a Perkin-Elmer model 1600 Fourier transform infrared (FT-IR)
spectrum RX1 spectrophotometer. 1H and 13C NMR spectra were
recorded on a Bruker Avance 400 spectrometer using dimethyl sulfoxide
(DMSO)-d6 as solvent with TMS as internal standard. Splitting patterns
are designated as follows: s, singlet; d, doublet; dd, double doublet; t, tri-
plet; m, multiplet. Chemical shift (d) values are given in parts per million
(ppm) and coupling constant (J) in hertz (Hz).
Procedure for the Preparation of 3-Phenyl-1-(thiophen-2-yl)prop-
2-en-1-one: Chalcone 1
To a mixture of 2-acetyl thiophene (0.01 mol) and benzaldehyde
(0.01 mol) in ethanol (50 ml), a solution of potassium hydroxide (5%,
25 ml) was added slowly. The mixture was stirred for 24 h. The precipi-
tated solid was filtered, washed with water, dried, and recrystallized from
ethanol.
Yield: 98%; mp: 55 ꢂC; cream-colored crystals. Anal. calc. for
C13H10OS: C, 72.89; H, 4.67; O, 7.47%. Found: C, 72.62; H, 4.51; O,
7.71%. IR nmax cmꢁ1: 3090 (Ar–H), 2921 (C–H), 1640 (C¼O), 1447
1
(C¼C); H NMR (DMSO-d6) d (ppm): 8.37–8.02 (m, 5H, phenyl), 7.94
(dd, 1H, H5, J ¼ 3.7, 1.5 Hz, thiophene), 7.89 (d, 1H, H-b, J ¼ 15.2 Hz),
7.73 (dd, 1H, H3, J ¼ 2.3, 1.3 Hz, thiophene), 7.47 (d, 1H, H-a,
J ¼ 15.2 Hz), 7.33 (m, 1H, H4, thiophene); 13C NMR (DMSO-d6)
d (ppm): 181.65 (C¼O), 143.20 (C-b), (145.50, 135.65, 133.77, 130.71,
thiophene), (134.51, 128.95, 128.22, 127.63, phenyl), 121.89 (C-a).
Procedure for the Preparation of 2,3-Dibromo-3-phenyl-1-(thiophen-
2-yl)propan-1-one: Chalcone Dibromide 2
Bromine (0.01 mol) in chloroform (25 ml) was added slowly to a solution
of 3-phenyl-1-(thiophen-2-yl)prop-2-en-1-one 1 (0.01 mol) in chloroform
(50 ml) with stirring. After the addition of the bromine solution, the reac-
tion mixture was stirred for 24 h. Excess chloroform was distilled off
under reduced pressure. The precipitated solid was filtered, dried, and
recrystallized from chloroform.
Yield: 96%; mp: 135 ꢂC; white crystals. Anal. calc. for C13H10OSBr2:
C, 41.73; H, 2.67; O, 4.28%. Found: C, 41.61; H, 2.64; O, 4.33%. IR nmax
1
cmꢁ1: 3090 (Ar–H), 2930 (C–H), 1665 (C¼O), 1415 (C¼C); H NMR

3978
H. Parveen, P. F. Iqbal, and A. Azam
(DMSO-d6) d (ppm): 8.0–8.09 (m, 5H, phenyl), 7.68 (dd, 1H, H5, J ¼ 3.6,
1.2 Hz, thiophene), 7.39 (dd, 1H, H3, J ¼ 2.2, 1.4 Hz, thiophene), 7.24 (m,
1H, H4, thiophene), 6.38 (d, 1H, H-a, J ¼ 10.5 Hz), 5.59 (d, H-b,
J ¼ 10.5 Hz); 13C NMR (DMSO-d6) d (ppm): 185.27 (C¼O), 47.55
(C-a), (141.10, 138.54, 138.18, 129.60, thiophene), (135.99, 129.52,
129.03, 128.9, phenyl), 50.91 (C-b).
General Procedure for the Synthesis of Substituted
Thiosemicarbazides (a–h)
Substituted thiosemicarbazides a–h were prepared by a reported
method.[11]
Preparation of Substituted Thioglycolic Acid
Carbon disulphide (1 equiv.) was added dropwise to a solution of primary
or secondary amines (1 equiv.) containing potassium hydroxide (1 equiv.)
in a water–ethanol (1:3) mixture. The temperature of the reaction was
maintained at less than 10 ꢂC. Sodium chloroacetate (1 equiv.) was added,
and the reaction mixture was left overnight at room temperature.
Addition of conc. hydrochloric acid (pH ꢃ 1) precipitated substituted
thioglycolic acid, which was crystallized by the appropriate solvent.
Conversion of Thioglycolic Acid into Thiosemicarbazides (a–h)
A solution of thioglycolic acid (1 equiv.) in water (15 ml) containing
sodium hydroxide (1 equiv.) and hydrazine hydrate (1 equiv.) was
refluxed for 2 h with continuous stirring. The compound separated out
during the reaction or on cooling at 0 ꢂC for 12 h. The product was
filtered and crystallized from a suitable solvent.
Procedure for the Synthesis of Hydroxy Pyrazolines (3a–h)
Thiosemicarbazides a–h (0.01 mol) and triethylamine (10 ml) were added
to a mixture of chalcone dibromide 2 (0.01 mol) in absolute ethanol
(75 ml). The reaction mixture was refluxed for 24 h. The contents were
reduced, cooled, and poured onto crushed ice and kept overnight. The
resulting hydroxy pyrazolines 3a–h were collected by filtration and
purified by column chromatography using hexane–dichloromethane
(80:20, v=v) as eluent.

New Series of Hydroxy Pyrazolines
3979
4,5-Dihydro-5-hydroxy-3-phenyl-5-(thiophen-2-yl)pyrazole-1-
carbothioamide (3a)
Yield: 35%; oil. Anal. calc. for C14H13OS2N3: C, 55.44; H, 4.29; O,
13.86%. Found: C, 55.49; H, 4.36; O, 13.66%. IR nmax cmꢁ1: 3377
(O–H), 3075 (Ar–H), 2921 (C–H), 3280 (N–H), 1532 (C¼N), 1447
1
(C¼C), 1121 (C¼S); H NMR (DMSO-d6) d (ppm): 9.12 (s, 2H, NH),
7.81, (dd, 1H, H5, J ¼ 4.3, 1.1 Hz, thiophene), 7.65 (dd, 1H, H3,
J ¼ 2.6, 1.4 Hz, thiophene), 7.45–7.02 (m, 5H, phenyl), 7.35 (m, 1H,
H4, thiophene), 5.31 (d, 1H, H4b, J ¼ 17.2 Hz, pyrazoline ring), 5.09
(d, 1H, H4a, J ¼ 17.2 Hz, pyrazoline ring), 4.70 (s, 1H, OH); 13C NMR
(DMSO-d6) d (ppm): 181.5 (C¼S), 153.4 (C¼N), (144.6, 141.9, 134.5,
126.3, thiophene), (135.2, 132.4, 128.3, 127.6, phenyl), 88.7 (C5, pyrazo-
line ring), 53.5 (C4, pyrazoline ring).
N-Adamantyl-4,5-dihydro-5-hydroxy-3-phenyl-5-(thiophen-2-yl)
pyrazole-1-carbothioamide (3b)
Yield: 25%; oil. Anal. calc. for C24H27OS2N3: C, 65.90; H, 6.17; O,
9.61%. Found: C, 65.83; H, 6.27; O, 9.58%. IR nmax cmꢁ1: 3380 (O–
H), 3225 (N–H), 3031 (Ar–H), 2920 (C–H), 1616 (C¼N), 1434 (C¼C),
1185 (C¼S); 1H NMR (DMSO-d6) d (ppm): 8.60 (s, 1H, NH), 7.84
(dd, 1H, H5, J ¼ 4.5, 0.9 Hz, thiophene), 7.52 (dd, 1H, H3, J ¼ 3.4,
1.9 Hz, thiophene), 7.34–7.11 (m, 5H, phenyl), 7.16 (m, 1H, H4, thio-
phene), 5.29 (d, 1H, H4b, J ¼ 16.2 Hz, pyrazoline ring), 5.17 (d, 1H,
H4a, J ¼ 16.2 Hz, pyrazoline ring), 4.62 (s, 1H, OH), 2.33–1.12 (m,
15H, adamantyl ring); 13C NMR (DMSO-d6) d (ppm): 182.8 (C¼S),
154.1 (C¼N), (146.2, 141.2, 133.5, 126.2, thiophene), (134.4, 131.2,
128.4, 127.9, phenyl), 84.7 (C5, pyrazoline ring), 52.4 (C4, pyrazoline
ring), 49–23 (adamantyl ring).
(4-Benzylpiperidin-1-yl)(4,5-dihydro-5-hydroxy-3-phenyl-5-(thiophen-
2-yl)pyrazol-1-yl)methanethione (3c)
Yield: 18%; oil. Anal. calc. for C26H27OS2N3: C, 67.67; H, 5.85; O, 9.11%.
Found: C, 67.52; H, 5.75; O, 9.27%. IR nmax cmꢁ1: 3385 (O–H), 3080
1
(Ar–H), 2915 (C–H), 1630 (C¼N), 1444 (C¼C), 1124 (C¼S); H NMR
(DMSO-d6) d (ppm): 7.79 (dd, 1H, H5, J ¼ 5.25, 1.3 Hz, thiophene),
7.63–7.02 (m, 10H, phenyl), 7.43 (dd, 1H, H3, J ¼ 2.7, 1.13 Hz,
thiophene), 7.13 (m, 1H, H4, thiophene), 5.17 (d, 1H, H4b, J ¼ 16.6 Hz,
pyrazoline ring), 5.04 (d, 1H, H4a, J ¼ 16.6 Hz, pyrazoline ring), 4.88

3980
H. Parveen, P. F. Iqbal, and A. Azam
(s, 1H, OH), 3.13–2.51 (m, 4H, CH2, piperidine), 2.54 (d, 2H, CH2,
J ¼ 6.7 Hz), 1.69–1.33 (m, 4H, CH2, piperidine), 1.83–1.60 (m, 1H, CH,
piperidine); 13C NMR (DMSO-d6) d (ppm): 179.2 (C¼S), 159.8 (C¼N),
(146.5, 138.2, 132.5, 125.5, thiophene), (138.4, 134.6, 131.3, 129.4,
129.9, 128.6, 128.2, 124.0, phenyl), 84.3 (C5, pyrazoline ring), 50.8 (C4,
pyrazoline ring), 50.2 (2 ꢄ CH2, piperidine), 42.7 (CH2), 31.9 (CH, piper-
idine), 29.7 (2 ꢄ CH2, piperidine).
4,5-Dihydro-5-hydroxy-3-phenyl-5-(thiophen-2-yl)-N-p-tolylpyrazole-1-
carbothioamide (3d)
Yield: 31%; oil. Anal. calc. for C21H19OS2N3: C, 64.12; H, 4.83; O,
10.68%. Found: C, 64.16, H, 4.66; O, 10.73%. IR nmax cmꢁ1: 3390 (O–
H), 3254 (N–H), 3066 (Ar–H), 2890 (C–H), 1660 (C¼N), 1450 (C¼C),
1123 (C¼S); 1H NMR (DMSO-d6) d (ppm): 8.62 (s, 1H, NH), 7.77
(dd, 1H, H5, J ¼ 4.1, 1.3 Hz, thiophene), 7.43 (dd, 1H, H3, J ¼ 3.12,
1.6 Hz, thiophene), 7.20 (m, 1H, H4, thiophene), 7.22–7.01 (m, 5H,
phenyl), 6.97 (d, 2H, J ¼ 7.6 Hz, phenyl), 6.53 (d, 2H, J ¼ 7.6 Hz, phenyl),
5.33 (d, 1H, H4b, J ¼ 16.4 Hz, pyrazoline ring), 5.13 (d, 1H, H4a,
J ¼ 16.4 Hz, pyrazoline ring), 4.82 (s, 1H, OH), 2.32 (s, 3H, CH3);
13C NMR (DMSO-d6) d (ppm): 184.4 (C¼S), 153.9 (C¼N), (145.4,
138.6, 131.4, 126.5, thiophene), (134.8, 134.0, 134.4, 131.3, 129.5, 129.2,
128.9, 126.2, phenyl), 87.4 (C5, pyrazoline ring), 52.6 (C4, pyrazoline
ring), 25.3 (CH3).
N-Benzyl-4,5-dihydro-5-hydroxy-N-methyl-3-phenyl-5-(thiophen-2-
yl)pyrazole-1-carbothioamide (3e)
Yield: 23%; oil. Anal. calc. for C22H21OS2N3: C, 62.41; H, 4.96; O,
9.92%. Found: C, 62.24; H, 4.72; O, 9.73%. IR nmax cmꢁ1: 3380
(O–H), 3070 (Ar–H), 2885 (C–H), 1613 (C¼N), 1436 (C¼C), 1124
(C¼S); 1H NMR (DMSO-d6) d (ppm): 7.79 (dd, 1H, H5, J ¼ 5.3,
1.22, thiophene), 7.63 (m, 10H, phenyl), 7.34 (dd, 1H, H3, J ¼ 2.3,
1.6, thiophene), 7.01 (m, 1H, H4, thiophene), 5.31 (d, 1H, H4b,
J ¼ 17.2 Hz, pyrazoline ring), 5.09 (d, 1H, H4a, J ¼ 17.2 Hz, pyrazoline
ring), 4.86 (s, 1H, OH), 4.67 (s, 2H, CH2), 2.53–2.02 (s, 3H, CH3);
13C NMR (DMSO-d6) d (ppm): 182.2 (C¼S), 159.3 (C¼N), (143.5,
138.7, 128.4, 126.6, thiophene), (136.5, 134.4, 132.6, 129.2, 128.7,
128.4, 128.2, 127.1, phenyl), 88.3 (C5, pyrazoline ring), 60.1 (CH2),
51.6 (C4, pyrazoline ring), 42.8 (CH3).

New Series of Hydroxy Pyrazolines
3981
(4,5-Dihydro-5-hydroxy-3-phenyl-5-(thiophen-2-yl)pyrazol-1-yl)(4-
methylpiperidin-1-yl)methanethione (3f)
Yield: 39%; oil. Anal. calc. for C20H23OS2N3: C, 62.33; H, 5.97; O,
10.90%. Found: C, 62.12, H, 5.92; O, 10.77%. IR nmax cmꢁ1: 3372
(O–H), 3095 (Ar–H), 2870 (C–H), 1620 (C¼N), 1460 (C¼C), 1143
(C¼S); 1H NMR (DMSO-d6) d (ppm): 7.72 (dd, 1H, H5, J ¼ 5.4,
1.7 Hz, thiophene), 7.43–7.02 (m, 5H, phenyl), 7.40 (dd, 1H, H3,
J ¼ 3.1, 2.0 Hz, thiophene), 7.12 (m, 1H, H4, thiophene), 5.42 (d, 1H,
H4b, J ¼ 16.6 Hz, pyrazoline ring), 5.13 (d, 1H, H4a, J ¼ 16.6 Hz, pyrazo-
line ring), 4.90 (s, 1H, OH), 3.47 (m, 4H, CH2, piperidine), 1.68 (m, 4H,
CH2, piperidine), 1.49 (m, 1H, CH, piperidine), 1.02 (d, 3H, CH3,
J ¼ 5.4 Hz); 13C NMR (DMSO-d6) d (ppm): 181.2 (C¼S), 157.3
(C¼N), (144.4, 138.2, 133.5, 126.2, thiophene), (134.4, 131.6, 129.2,
128.6, phenyl), 84.3 (C5, pyrazoline ring), 53.7 (C4, pyrazoline ring),
46.7 (2 ꢄ CH2, piperidine), 32.8 (2 ꢄ CH2, piperidine), 35.3 (CH, piperi-
dine), 14.4 (CH3).
(4,5-Dihydro-5-hydroxy-3-phenyl-5-(thiophen-2-yl)pyrazol-1-
yl)(pyrrolidin-1-yl)methanethione (3g)
Yield: 21%; oil. Anal. calc. for C18H19OS2N3: C, 60.50; H, 5.32;
O, 11.76%. Found: C, 60.32; H, 5.46; O, 11.73%. IR nmax cmꢁ1: 3376
(O–H), 3033 (Ar–H), 2920 C–H), 1595 (C¼N), 1437 (C¼C), 1145
(C¼S); 1H NMR (DMSO-d6) d (ppm): 7.66 (dd, 1H, H5, J ¼ 4.3,
1.3 Hz, thiophene), 7.39 (dd, 1H, H3, J ¼ 3.4, 2.2 Hz, thiophene), 7.23–
7.01 (m, 5H, phenyl), 7.13 (m, 1H, H4, thiophene), 5.25 (d, 1H, H4b,
J ¼ 16.4 Hz, pyrazoline ring), 5.08 (d, 1H, H4a, J ¼ 16.4 Hz, pyrazoline
ring), 4.91 (s, 1H, OH), 2.15–3.23 (m, 4H, CH2, pyrolidine), 1.23–2.02
(m, 4H, CH2, pyrolidine); 13C NMR (DMSO-d6) d (ppm): 179.5
(C¼S), 157.6 (C¼N), (144.4, 138.6, 132.8, 126.3, thiophene), (134.7,
130.2, 129.6, 128.9, phenyl), 89.6 (C5, pyrazoline ring), 53.2 (C4, pyrazo-
line ring), 45.2 (2 ꢄ CH2), 31.6 (2 ꢄ CH2).
N-Cyclohexyl-4,5-dihydro-5-hydroxy-3-phenyl-5-(thiophen-2-yl)pyrazole-
1-carbothioamide (3h)
Yield: 27%; oil. Anal. calc. for C20H23OS2N3: C, 62.33; H, 5.97;
O, 10.90%. Found: C, 62.24; H, 5.93; O, 10.81%. IR nmax cmꢁ1: 3375
(O–H), 3085 (Ar–H), 2915 (C–H), 1559 (C¼N), 1453 (C¼C), 1166
1
(C¼S); H NMR (DMSO-d6) d (ppm): 8.57 (d, 1H, NH, J ¼ 6.8 Hz),

3982
H. Parveen, P. F. Iqbal, and A. Azam
7.67 (dd, 1H, H5, J ¼ 4.5, 0.9 Hz, thiophene), 7.36–7.01 (m, 5H, phenyl),
7.35 (dd, 1H, H3, J ¼ 2.8, 1.2 Hz, thiophene), 7.11 (m, 1H, H4,
thiophene), 5.23 (d, 1H, H4b, J ¼ 16.2 Hz, pyrazoline ring), 5.03
(d, 1H, H4a, J ¼ 16.2 Hz, pyrazoline ring), 4.67 (s, 1H, OH), 3.72 (m,
1H, CH, cyclohexyl ring), 2.37–1.15 (m, 10H, CH2, cyclohexyl ring);
13C NMR (DMSO-d6) d (ppm): 184.8 (C¼S), 156.8 (C¼N), (142.1,
138.5, 132.8, 126.2, thiophene), (134.4, 131.2, 129.5, 128.6, phenyl),
91.5 (C5, pyrazoline ring), (53.2, 31.5, 26.5, 22.5, cyclohexyl ring), 49.5
(C4, pyrazoline ring).
ACKNOWLEDGMENTS
This work was supported by the Department of Science and Technology
(Grant No. Vll-PRDSF=44=2004-05=TT), New Delhi, India.
REFERENCES
1. Elguero, J. In Comprehensive Heterocyclic Chemistry; A. R. Katritzky, C. W.
Rees (Eds.); Pergamon: Oxford, 1984; vol. 5, pp. 167–302.
2. Elguero, J. In Comprehensive Heterocyclic Chemistry II; A. R. Katritzky,
C. W. Rees, E. F. Scriven (Eds.); Pergamon: Oxford, 1996; vol. 3, pp. 1–75.
3. Taylor, E. C.; Patel, H.; Kumar, H. Synthesis of pyrazolo 3,4-dpyrimidine
analogues of the potent agent N-4-2-2-amino-4 3H-oxo-7H-pyrrolo 2,3-d
pyrimidin-5-yl ethylbenzoyl-L-glutamic acid (LY231514). Tetrahedron.
1992, 48, 8089–8100.
4. Karthikeyan, M. S.; Holla, B. S.; Kumari, N. S. Synthesis and antimicrobial
studies on novel chloro-fluorine containing hydroxy pyrazolines. Eur. J. Med.
Chem. 2007, 42, 30–36.
5. Holla, B. S.; Akberali, P. M.; Shivananda, M. K. Studies on arylfuran
derivatives, Part X: Synthesis and antibacterial properties of arylfuryl-D2-
pyrazolines. Farmaco 2000, 55, 256–263.
6. Bansal, E.; Srivatsava, V. K.; Kumar, A. Synthesis and anti-inflammatory
activity of 1-acetyl-5-substitute daryl-3-(b-aminonaphthyl)-2-pyrazolines
and b-(substitute daminoethyl) amidonaphthalenes. Eur. J. Med. Chem.
2001, 36, 81–92.
7. Manna, F.; Chimenti, F.; Fioravanti, R.; Bolasco, A.; Seecci, D.; Chimenti,
P.; Ferlini, C.; Scambia, G. Synthesis of some pyrazole derivatives and preli-
minary investigation of their affinity binding to P-glycoprotein. Bioorg. Med.
Chem. Lett. 2005, 15, 4632–4635.
8. Ahn, J. H.; Kim, H. M.; Jung, S. H.; Kang, S. K.; Kim, K. R.; Rhee, S. D.;
Yang, S. D.; Cheon, H. G.; Kim, S. S. Synthesis and DP-IV inhibition of
cyano-pyrazoline derivatives as potent anti-diabetic agents. Bioorg. Med.
Chem. Lett. 2004, 14, 4461–4465.

New Series of Hydroxy Pyrazolines
3983
9. Rajendera Prasad, Y.; Lakshmana Rao, A.; Prasoona, L.; Murali, K.; Ravi
Kumar, P. Synthesis and antidepressant activity of some 1,3,5-triphenyl-2-
pyrazolines and 3-(200-hydroxy naphthalen-100-yl)-1,5-diphenyl-2-pyrazolines.
Bioorg. Med. Chem. Lett. 2005, 15, 5030–5034.
10. Zelenin, K. N.; Tugusheva, A. R.; Yakimovich, S. I.; Alekseev, V. V.; Zerova,
E. V. 5-Hydroxy-2-pyrazolines and their 1-substituted analogs. Chem.
Heterocyc. Comp. 2002, 38, 668–676.
11. Budakoti, A.; Abid, M.; Azam, A. Synthesis and antiamoebic activity of
new 1-N-substituted thiocarbamoyl-3,5-diphenyl-2-pyrazoline derivatives
and their Pd(II) complexes. Eur. J. Med. Chem. 2006, 41, 63–70.