2-Pyrazolin-5-One-Based Heterocycles: Synthesis and Characterization

Article abstract of DOI:10.1002/jhet.2225

A novel series of pyrazoline and thiazole derivatives incorporating 2-pyrazolin-5-one moiety were synthesized starting from α,β-unsaturated ketones under the effect of hydrazine derivatives and thiosemicarbazide. The obtained pyrazolines 4a, 4b were treated with different reagents to afford N-substituted pyrazolines 5a, 5b, 6a, 6b, 7a, 7b, 8a, 8b. N-Thiocarbamoyl pyrazolines 12a, 12b were cyclized using phenacyl bromide, 2,3-dichloroquinoxaline, and monochloroacetic acid afforded the novel pyrazolinyl thiazoles 13a, 13b, 14a, 14b, 15a, 15b, 16a, 16b, 16c, 16d, 16e, 16f. The newly synthesized compounds were characterized by analytical and spectral data.

Full text of DOI:10.1002/jhet.2225

Month 2014
2-Pyrazolin-5-One-Based Heterocycles: Synthesis and Characterization
*
Ahmed Abdou O. Abeed
Department of Chemistry, Faculty of Science, Assiut University, Assiut 71516, Egypt
*
E-mail: ahmed_abeed76@yahoo.com
Received January 6, 2014
DOI 10.1002/jhet.2225
Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com).
A novel series of pyrazoline and thiazole derivatives incorporating 2-pyrazolin-5-one moiety were
synthesized starting from α,β-unsaturated ketones under the effect of hydrazine derivatives and thiosemicarbazide.
The obtained pyrazolines 4a,b were treated with different reagents to afford N-substituted pyrazolines 5a,b–8a,b.
N-Thiocarbamoyl pyrazolines 12a,b were cyclized using phenacyl bromide, 2,3-dichloroquinoxaline, and
monochloroacetic acid afforded the novel pyrazolinyl thiazoles 13a,b–16a–f. The newly synthesized compounds
were characterized by analytical and spectral data.
J. Heterocyclic Chem., 00, 00 (2014).
INTRODUCTION
condensation of equimolar amounts of 4-acetyl-3-methyl-
1-phenyl-2-pyrazolin-5-one with benzaldehyde or p-
chlorobenzaldehyde in accordance with the method
described in the literature [25]. When chalcones 1a,b
treated with hydrazine hydrate in hot formic acid, N-formyl
pyrazoline derivatives 2a,b were obtained rather than the
non formylated ones due to heating in formic acid for long
periods of time. The presence of N-formyl group of 2a,
2-Pyrazolin-5-one derivatives are an important class of
heterocyclic compounds possessing wide variety in
synthetic chemistry [1–5]. Derivatives of 2-pyrazolin-5-
one are found to show remarkable anti-tubercular [6,7],
antimicrobial [8–10], and anti-inflammatory [11] activities.
On the other hand, the chemistry of thiazoles has received
considerable attention in recent years owing to their
synthetic [12–14] and biological [15,16] importance.
Among the analogs, pyrazoline compound; A [17,18] and
thiazole derivative especially BILS 179BS; B [19] were
reported to exhibit a high antiviral activity against hepatitis
A virus and hepatitis B virus HSV, respectively.
In view of these observations and in continuation of our
research program on the synthesis of some novel heterocy-
clic compounds related to 2-pyrazolin-5-one [20–24], the
present research concerns the synthesis of pyrazoline and
thiazole derivatives related to 2-pyrazolin-5-one nucleus.
1
e.g., was established using IR, H-NMR, and 13C-NMR
spectra whereas IR revealed a strong absorption band at
ν 1721 cmÀ1 for the carbonyl group, meanwhile, its 1H-NMR
spectra presented the presence of singlet signal integrating
one proton at δ 9.00 ppm due to the formyl group proton.
Further evidence was obtained from 13C-NMR spectra,
which showed signal at δ 161.1 ppm owing to the formyl
carbon. The evidence for the formation of pyrazoline ring
in N-formyl pyrazolines 2a,b was obtained from 1H-NMR
and 13C-NMR spectra, which provide diagnostic tools for
the positional elucidation of the protons. The geminal
pyrazoline protons (HA and HB) at C4 appeared in
the region of 3.41–3.46 and 3.79–3.85 ppm as doublet of
doublets in compounds 2a,b. The proton (HX) at
C5 also appears as doublet of doublets in the region of
4.76–4.81 ppm due to vicinal coupling with two non-
magnetically equivalent germinal protons of C4 carbon.
The signals obtained from 13C-NMR spectra further
confirmed the proposed structures; the C4 and C5 carbons of
the pyrazoline ring resonate at 40.8–41.1 and 57.3–57.9 ppm,
respectively. Furthermore, it presented signals at range of
δ 147.1–147.4 ppm, which assignable to azomethine
carbons of pyrazoline ring.
RESULTS AND DISCUSSION
The reaction sequences employed for synthesis of the
target pyrazoline, diazepine, quinoxaline, and thiazole
derivatives are illustrated in Schemes 1 and 2. The desired
chalcones 3-aryl-1-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-
4-yl) prop-2-en-1-ones 1a,b were synthesized through
On the other hand, upon using acetic acid instead of
formic acid in the previous reaction, the N-acetyl
© 2014 HeteroCorporation

A. A. O. Abeed
Vol 000
Scheme 1. Reagents: (i) NH2NH2.H2O/HCOOH; (ii) NH2NH2.H2O/AcOH; (iii) NH2NH2.H2O/EtOH; (iv) AcOH; (v) ClCH2COCl/toluene; (vi) PhNCS/
EtOH; (vii) PhSO2Cl/pyridine; (viii) PhCOCl/pyridine; (ix) PhNHNH2/EtOH; (x) NH2OH.HCl/EtOH, AcONa; (xi) o-phenylenediamine/EtOH.
pyrazolines 3a,b were formed. The presence of N-acetyl
group was established using IR and 1H-NMR spectra.
While condensing 1a,b with hydrazine hydrate in ethanol, 3-(3-
methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-aryl-2-pyrazolines
4a,b were obtained. The reaction includes formation of
hydrazones intermediate and then addition of NH2 of
hydrazones to the double bond. Upon acetylation of the
pyrazolines 4a,b by acetic acid, N-acetyl pyrazolines 3a,b
were obtained. Moreover, the aforementioned pyrazoline de-
rivatives 4a,b were converted into the corresponding
substituted N-pyrazolines 5a,b–8a,b through their reaction
with various reagents such as chloroacetyl chloride, phenyl
isothiocyanate, benzenesulfonyl chloride, and benzoyl
chloride, respectively.
The structures of products 5a,b–8a,b were evidenced by
1
their spectra (IR, H-NMR, 13C-NMR, and MS) and ele-
mental analyses (see Experimental section and Table 1).
N-phenyl pyrazolines 9a,b were obtained upon condens-
ing with phenyl hydrazine in hot ethanol. The presence of
N-phenyl group in 9a or 9b was elucidated from spectral
data and EIMS, which is in agreement with their molecular
weights. The isooxazoline derivatives 10a,b were obtained
through condensation of 1a,b with hydroxyl amine in
hot ethanol containing anhydrous sodium acetate. The
spectroscopic data and elemental analysis were constituent
with the structures of compounds 10a,b.
On the other hand, binucleophile compound like o-
phenylenediamine was condensed with 1a,b in ethanol
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
2-Pyrazolin-5-One-Based Heterocycles: Synthesis and Characterization
Scheme 2. Reagents: (i) NH2CSNHNH2/EtOH, NaOH; (ii) PhCOCH2Br/EtOH; (iii) 2,3-dichloroquinoxaline/EtOH; (iv) ClCH2COOH/AcOH, AcONa;
(v) ArCHO/AcOH, AcONa; (vi) ClCH2COOH, ArCHO/AcOH, AcONa.
containing few drops of TEA to give 4-(3-methyl-5-oxo-1-
phenyl-2-pyrazolin-4-yl)-2-aryl-2,3-dihydro-1H-benzo
[b][1,4]diazepines 11a,b with good yields (Scheme 1). IR
spectra of 11a showed a strong absorption band at ν
3295–3401 cmÀ1 due to NH2 group. Furthermore, 13C-
NMR spectra of 12a or 12b displayed a signal at δ 176.9
or 177.1 ppm assignable to thiocarbamoyl carbon (C═S).
The N-thiocarbamoyl pyrazolines 12a,b were cyclized to
pyrazolinyl thiazole derivatives 13a,b through their
reaction with phenacyl bromide in hot ethanol for 1 h.
The structures of the new thiazoles 13a,b were confirmed
1
3343 cmÀ1 due to NH group; meanwhile, the H-NMR
spectra revealed three doublet signals at δ 3.40–3.42,
3.92–4.08, and 4.78–4.99 ppm due to HA, HB, and HX
of diazepine ring. Further evidence for the formation of
diazepine ring was obtained from the 13C-NMR spec-
trum, which presents nine signals of benzo[b]diazepine
carbons at δ 121.2, 122.8, 125.5, 127.8, 129.8, 134.7,
135.9, 151.9, and 168.2. The novel key intermediates
1-thiocarbamoyl-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-
4-yl)-5-aryl-2-pyrazolines 12a,b were obtained by heating
at reflux equimolar amounts of thiosemicarbazide and α,β-
unsaturated ketones 1a,b in hot ethanolic NaOH solution
for 8 h. The structures of N-thiocarbamoyl pyrazolines
12a,b were characterized using IR and 13C-NMR spectra,
whereas IR showed strong absorption bands at range of ν
1
using H-NMR spectra, which revealed the appearance of
singlet signals around δ = 6.80–6.83 ppm integrating one
proton due to C5-H of the thiazole ring. Further evidence
for the formation of thiazole ring was obtained from the
13C-NMR spectra of compound 13a, which confirmed the
proposed structure due to the appearance of characteristic
signals at δ = 178.2 (azomethine carbon), 164.8 (C2 of
thiazole), 150.6 (C4 of thiazole), and 105.7 ppm indicating
the presence of thiazole ring.
3-(3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-aryl-1-
(thiazolo[4,5-b]quinoxalin-2-yl)-2-pyrazolines 14a,b were
produced through treatment of N-thiocarbamoyl pyrazolines
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. A. O. Abeed
Vol 000
Table 1
The elemental analyses of the prepared compounds 2a,b–10a,b.
Elemental analyses
N
Compound no.
Formula
Molecular weight
346.38
C
H
S
Cl
2a
C
20H18N4O2
Calcd
Found
Calcd
Found
Calcd
Found
Calcd
Found
Calcd
Found
Calcd
Found
Calcd
Found
Calcd
Found
Calcd
Found
Calcd
Found
Calcd
Found
Calcd
Found
Calcd
Found
Calcd
Found
Calcd
Found
Calcd
Found
Calcd
Found
Calcd
Found
69.35
69.33
63.08
63.04
69.98
69.96
63.88
63.86
71.68
71.65
64.68
64.67
63.88
63.85
58.75
58.73
68.85
68.82
63.99
63.96
65.48
65.51
60.91
60.93
73.92
73.89
68.34
62.36
76.12
76.15
70.01
70.03
71.46
71.45
64.50
64.53
5.24
5.26
4.50
4.53
5.59
5.56
4.85
4.84
5.70
5.72
4.86
4.85
4.85
4.87
4.23
4.26
5.11
5.14
4.54
4.56
4.84
4.87
4.29
4.26
5.25
5.23
4.63
4.65
5.62
5.65
4.93
4.90
5.37
5.35
4.56
4.53
16.17
16.15
14.71
14.69
15.55
15.53
14.19
14.17
17.60
17.58
15.88
15.90
14.19
14.16
13.05
13.03
15.44
15.47
14.35
14.32
12.22
12.18
11.36
11.39
13.26
13.28
12.26
12.23
14.20
14.24
13.06
13.08
13.16
13.19
11.88
11.85
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
7.07
7.03
6.57
6.59
6.99
6.96
6.50
6.47
—
—
—
—
—
—
—
—
—
—
—
—
—
—
9.31
9.35
—
2b
3a
3b
4a
4b
5a
5b
6a
6b
7a
7b
8a
8b
9a
9b
10a
10b
C20H17ClN4O2
C21H20N4O2
380.83
360.41
394.85
318.37
352.82
394.85
429.30
453.56
488.00
458.53
492.98
422.48
456.92
394.47
428.91
319.36
353.8
—
C21H19ClN4O2
C19H18N4O
8.98
9.03
—
—
C19H17ClN4O
C21H19ClN4O2
C21H18Cl2N4O2
C26H23N5OS
C26H22ClN5OS
C25H22N4O3S
C25H21ClN4O3S
C26H22N4O2
10.05
10.09
8.98
8.94
16.52
16.50
—
—
7.26
7.30
—
—
7.19
7.15
—
—
C26H21ClN4O2
C25H22N4O
7.76
7.72
—
—
C25H21ClN4O
C19H17N3O2
8.27
8.31
—
—
10.02
10.06
C19H16ClN3O2
12a,b with 2,3-dichloroquinoxaline in hot ethanol. On the
other hand, the thiocarbamoyl pyrazolines 12a,b were
cyclized to pyrazolinyl thiazolones 15a,b through their
reaction with chloroacetic acid and anhydrous sodium
acetate in acetic acid as a solvent. The structures of
new thiazolones 15a,b were confirmed using IR, which
through one-pot reaction of 12a,b with the aromatic
aldehydes and chloroacetic acid (Scheme 2). The structures
of the products 16a–f were confirmed based on their
analytical and spectral data (Table 2).
EXPERIMENTAL
revealed strong absorption bands at range of
ν
1715–1717 cmÀ1 due to carbonyl group of thiazole ring.
Melting points were determined on APP. Digital ST 15 melting
point apparatus and are corrected. The time required for each
reaction to complete was monitored by thin-layer chromatogra-
phy . Elemental analysis (C, H, N, S) was conducted using a
Vario EL C, H, N, S Analyzer; their results were found to be in
good agreement ( 0.3%) with the calculated values. FTIR spectra
(KBr disk) were recorded on a Pye-Unicam SP3-100 spectropho-
tometer. The 1H-NMR and 13C-NMR spectra were measured
on a JNM-LA Series 400 and a Varian 1H-Gemini 200 spec-
trometers with TMS as the internal standard and DMSO-d6 as
solvent. Mass spectra were recorded at 70 eV with JEOL JMS
600 spectrometer.
1
In addition, H-NMR showed the appearance of signals
(two doublets) around δ = 3.98–4.22 ppm integrating two
protons due to C5-H of the thiazolone ring. 13C-NMR
spectra of 15a established the proposed structure due to
the appearance of signal at δ = 189.2 ppm due to carbonyl
carbon as well as the presence of signal at δ = 35.3 ppm
assignable to C5 of thiazolone ring. Upon condensing
thiazolone derivatives 15a,b with a variety of aromatic
aldehydes, the corresponding arylidenes 16a–f were
obtained. The latter compounds were directly synthesized
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
2-Pyrazolin-5-One-Based Heterocycles: Synthesis and Characterization
Table 2
The elemental analyses of the prepared compounds 11a,b–16a–f.
Elemental analyses
Compound no.
Formula
Molecular weight
394.47
C
H
N
S
Cl
11a
C
25H22N4O
Calcd
Found
Calcd
Found
Calcd
Found
Calcd
Found
Calcd
Found
Calcd
Found
Calcd
Found
Calcd
Found
Calcd
Found
Calcd
Found
Calcd
Found
Calcd
Found
Calcd
Found
Calcd
Found
Calcd
Found
Calcd
Found
76.12
76.11
70.01
70.04
63.64
63.61
58.32
58.30
70.42
70.40
65.68
65.90
66.78
66.75
62.51
62.48
63.29
63.26
58.47
58.49
68.89
68.89
64.50
64.52
63.26
63.28
64.50
64.51
60.63
60.65
59.54
59.55
5.62
5.65
4.93
4.90
5.07
5.09
4.40
4.41
4.85
4.87
4.33
4.30
4.20
4.17
3.75
3.72
4.59
4.57
4.01
4.02
4.59
4.59
4.11
4.14
4.03
4.06
4.11
4.15
3.68
3.65
3.62
3.65
14.20
14.17
13.06
13.04
18.55
18.58
17.00
17.04
14.66
14.70
13.68
13.67
19.47
19.50
18.22
18.20
16.78
16.76
15.50
15.53
13.85
13.85
12.97
12.94
15.26
15.27
12.97
12.95
12.19
12.14
14.37
14.34
—
—
—
—
—
—
8.27
8.30
—
11b
12a
12b
13a
13b
14a
14b
15a
15b
16a
16b
16c
16d
16e
16f
C25H21ClN4O
C20H19N5OS
428.91
377.46
411.91
477.58
512.03
419.5
8.49
8.50
7.78
7.76
6.71
6.68
6.26
6.23
6.37
6.35
5.96
5.92
7.68
7.71
7.10
7.14
6.34
6.34
5.94
5.96
5.82
5.84
5.94
5.91
5.58
5.53
5.48
5.43
—
C20H18ClN5OS
C28H23N5OS
8.61
8.58
—
—
C28H22ClN5OS
C28H21N7OS
6.92
6.97
—
—
C28H20ClN7OS
C22H19N5O2S
C22H18ClN5O2S
C29H25N5O2S
C29H22ClN5O2S
C29H22N6O4S
C29H22ClN5O2S
C29H21Cl2N5O2S
C29H21ClN6O4S
453.94
417.48
451.93
505.59
540.04
550.59
540.04
574.48
585.03
6.59
6.63
—
—
7.84
7.83
—
—
6.56
6.60
—
—
6.56
6.53
12.34
12.30
6.06
6.10
General procedure for the synthesis of 2a,b.
The
(KBr): 3012 (Ar-H), 2991 (aliphatic-H), 1720 (C═O formyl),
1635 (C═O), 1615 (C═N), 1581, 1490 (C═C), 710 (C–Cl)
corresponding chalcones 1a,b (5 mmol) were refluxed in formic
acid (20 mL) with hydrazine hydrate (0.32 mL, 10 mmol) for
8 h. The mixture was cooled, poured into crushed ice, and then
neutralized by ammonia. The obtained product was washed by
cold water and crystallized from the proper solvent to give 2a
or 2b, respectively.
cmÀ1 1H-NMR (DMSO-d6, 400 MHz): δ = 2.35 (s, 3H, CH3),
.
3.43–3.46 (dd, J = 18.3, 4.3 Hz, HA, C4-H), 3.81–3.85 (dd,
J = 18.3,11.3 Hz, HB, C4-H), 4.77–4.81 (dd, J = 11.3, 4.3 Hz,
HX, C5-H), 7.07–7.41 (m, 6H, Ar-H + H4′), 7.48–7.53 (m, 4H,
Ar-H), 9.10 (s, 1H, CHO) ppm. 13C-NMR (DMSO-d6,
100 MHz): δ = 15.3, 41.1, 57.3, 117.4, 118.7, 121.3, 122.3,
127.4, 129.7, 132.8, 135.9, 137.3, 138.4, 139.3, 140.3, 144.2,
145.8, 147.4, 161.2, 169.9 ppm. EI ms: m/z: 380.79 [M+] (62),
382.86 [M+ + 2] (16).
General procedure for the synthesis of 3a,b. A mixture of
chalcones 1a,b (5 mmol), hydrazine hydrate (0.32 mL, 10 mmol)
and acetic acid (20 mL) was refluxed for 8 h. The resulting
mixture was poured into crushed ice and then neutralized by
ammonia. The obtained product was separated by filtration,
washed with cold water and then crystallized from suitable
solvent to give compounds 3a,b.
1-Formyl-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-
phenyl-2-pyrazoline (2a). Crystallized from ethanol to give
white powder, yield 1.27 g (73 %), mp 225–226°C. IR
(KBr): 3010 (Ar-H), 2933 (aliphatic-H), 1721 (C═O
formyl), 1633 (C═O), 1610 (C═N), 1584, 1497 (C═C)
cmÀ1
.
1H-NMR (DMSO-d6, 400 MHz): δ = 2.35 (s, 3H,
CH3), 3.41–3.45 (dd, J = 18.2, 4.2 Hz, HA, C4-H), 3.79–3.83
(dd, J = 18.2,11.3 Hz, HB, C4-H), 4.76–4.80 (dd, J = 11.3,
4.2 Hz, HX, C5-H), 7.05–7.40 (m, 6H, Ar-H + H4′), 7.49–7.51 (m,
5H, Ar-H), 9.00 (s, 1H, CHO) ppm. 13C-NMR (DMSO-d6,
100 MHz): δ = 15.2, 40.8, 57.9, 117.9, 118.8, 121.3, 122.3,
127.4, 129.7, 132.8, 135.8, 137.3, 138.4, 139.2, 140.2,
144.1, 145.8, 147.1, 161.1, 169.8 ppm. EI ms: m/z: 346.29
[M+] (70).
1-Acetyl-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-phenyl-
2-pyrazoline (3a).
Crystallized from ethanol to give pale
yellow powder, yield 1.22 g (68%), mp 200–202°C. IR (KBr):
3010 (Ar-H), 2944 (aliphatic-H), 1712 (C═O acetyl), 1640
(C═O), 1605 (C═N), 1588, 1497 (C═C) cmÀ1.1H-NMR
(DMSO-d6, 200 MHz): δ = 2.30 (s, 3H, COCH3), 2.39 (s, 3H,
1-Formyl-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-p-
chlorophenyl-2-pyrazoline (2b). Crystallized from ethanol to
afford white crystals, yield 1.44 g (76%), mp 220–221°C. IR
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. A. O. Abeed
Vol 000
CH3), 3.44–3.53 (dd, J = 17.5, 5.1 Hz, HA, C4-H), 3.74–3.82 (dd,
J = 17.5, 11.8 Hz, HB, C4-H), 4.61–4.80 (dd, J = 11.8, 5.1 Hz, HX,
C5-H), 7.01–7.60 (m, 6H, Ar-H + H4′), 7.61–7.91 (m, 4H, Ar-H)
ppm. 13C-NMR (DMSO-d6, 100 MHz): δ = 15.5, 29.4, 40.8, 57.8,
118.1, 118.7, 121.4, 122.5, 127.5, 129.8, 133.7, 135.7, 137.3,
138.3, 139.1, 141.4, 144.5, 145.8, 147.8, 169.1, 170.5 ppm. EI
ms: m/z: 360.31 [M+] (65).
was collected and crystallized from suitable solvent to give
products 5a,b.
1-Chloroacetyl-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-
5-phenyl-2-pyrazoline (5a). Crystallized from toluene to afford
red powder, yield 0.54 g (68%), mp 225–226°C. IR (KBr): 3032
(Ar-H), 2988 (aliphatic-H), 1680 (C═O), 1638 (C═O), 1594
(C═N), 1582, 1495 (C═C), 718 (C–Cl) cmÀ1
.
1H-NMR
1-Acetyl-3-(3-methyl-1-phenyl-5-oxo-2-pyrazolin-4-yl)-5-p-
chlorophenyl-2-pyrazoline (3b). Crystallized from methanol
to give yellow powder, yield 1.37 g (70%), mp 205–207°C.
IR (KBr): 3013 (Ar-H), 2943 (aliphatic-H), 1710 (C═O
acetyl), 1635 (C═O), 1605 (C═N), 1589, 1499 (C═C),
(DMSO-d6, 400 MHz): δ = 2.30 (s, 3H, CH3), 4.12 (s, 2H, CH2),
3.41–3.44 (dd, J = 18.1, 4.3 Hz, HA, C4-H), 3.76–3.78 (dd,
J = 18.1, 11.2 Hz, HB, C4-H), 4.74–4.79 (dd, J = 11.2, 4.3 Hz,
HX, C5-H), 7.04–7.42 (m, 6H, Ar-H + H4′), 7.53–7.79 (m, 5H,
Ar-H) ppm. 13C-NMR (DMSO-d6, 100 MHz): δ = 15.3, 41.2,
58.2, 64.1, 117.4, 119.2, 121.2, 123.8, 126.2, 127.8, 132.7,
134.7, 136.8, 138.7, 139.4, 141.1, 144.1, 145.9, 146.8, 169.5,
171.4 ppm. EI ms: m/z: 394.79 [M+] (71), 396.81 [M+ + 2] (23).
1-Chloroacetyl-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-
715 (C–Cl) cmÀ1 1H-NMR (DMSO-d6, 200 MHz): δ = 2.29
.
(s, 3H, COCH3), 2.38 (s, 3H, CH3), 3.45–3.54 (dd,
J = 17.5, 5.1 Hz, HA, C4-H), 3.72–3.81 (dd, J = 17.5,11.8 Hz,
HB, C4-H), 4.60–4.80 (dd, J = 11.8, 5.1 Hz, HX, C5-H),
7.00–7.60 (m, 6H, Ar-H + H4′), 7.76–7.91 (m, 5H, Ar-H)
ppm. 13C-NMR (DMSO-d6, 100 MHz): δ = 15.4, 29.2, 40.9,
58.1, 117.9, 118.8, 121.3, 122.3, 127.4, 129.7, 132.8, 135.8,
137.3, 138.4, 139.2, 141.1, 144.3, 145.9, 147.9, 169.3,
170.2 ppm. EI ms: m/z: 394.82 [M+] (63), 396.81 [M+ + 2]
(20).
General procedure for the synthesis of 4a,b. To a solution
of chalcones 1a,b (2 mmol) in ethanol (25 mL), hydrazine hydrate
(0.16 mL, 5 mmol) was added. The reaction mixture was refluxed
for 6 h. Left to cool to room temperature, and the obtained product
was filtered, dried and crystallized from an appropriate solvent to
afford 4a,b.
yl)-5-p-chlorophenyl-2-pyrazoline (5b).
Crystallized from
dioxane to give brown crystals, yield 0.60 g (70%), mp
241–243°C. IR (KBr): 3031 (Ar-H), 2991 (aliphatic-H), 1679
(C═O), 1637 (C═O), 1592 (C═N), 1580, 1490 (C═C), 712
1
(C–Cl) cmÀ1. H-NMR (DMSO-d6, 200 MHz): δ = 2.32 (s, 3H,
CH3), 4.17 (s, 2H, CH2), 3.40–3.43 (dd, J = 18.3, 4.5 Hz, HA,
C4-H), 3.69–3.77 (dd, J = 18.3, 11.1 Hz, HB, C4-H), 4.75–4.79
(dd, J = 11.1, 4.5 Hz, HX, C5-H), 7.10–7.52 (m, 6H, Ar-
H + H4′), 7.64–7.81 (m, 4H, Ar-H) ppm. 13C-NMR (DMSO-d6,
100 MHz): δ = 15.5, 41.5, 57.9, 63.9, 117.8, 118.9, 121.7,
124.1, 125.9, 128.1, 133.1, 134.5, 136.7, 139.1, 139.6, 141.8,
144.2, 146.1, 147.1, 169.3, 171.6 ppm. EI ms: m/z: 429.25 [M+]
(69), 431.23 [M+ + 2] (18), 433.25 [M+ + 4] (10).
General procedure for the synthesis of 6a,b. A mixture of
4a,b (2 mmol) and phenyl isothiocyanate (2 mmol, 0.27 g) in dry
ethanol (25 mL) was refluxed for 5 h. Cool to the room
temperature and the solid mass which separated out was filtered,
dried, and crystallized from an appropriate solvent to afford
products 6a,b.
3-(3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-phenyl-2-
pyrazoline (4a). Crystallized from ethanol to afford pale yellow
crystals, yield 0.44 g (70%), mp 200°C. IR (KBr): 3370 (N–H),
3030 (Ar-H), 2990 (aliphatic-H), 1633 (C═O), 1595 (C═N),
1580, 1499 (C═C) cmÀ1 1H-NMR (DMSO-d6, 400 MHz):
.
δ = 2.21 (s, 3H, CH3), 3.40–3.42 (dd, J = 18.2, 4.2 Hz, HA, C4-
H), 3.77–3.79 (dd, J = 18.2, 11.3 Hz, HB, C4-H), 4.76–4.78 (dd,
J = 11.3, 4.2 Hz, HX, C5-H), 7.03–7.36 (m, 6H, Ar-H + H4′),
7.42–7.47 (m, 5H, Ar-H), 7.99 (s, 1H, NH, D2O exchangeable)
ppm. 13C-NMR (DMSO-d6, 100 MHz): δ = 15.2, 40.8, 57.9,
117.5, 118.9, 121.5, 123.7, 126.3, 128.1, 132.2, 135.4, 136.9,
138.2, 139.1, 140.7, 144.4, 145.9, 146.7, 169.6 ppm. EI ms: m/z:
318.33 [M+] (83).
1-N-Phenylthiocarbamoyl-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-
4-yl)-5-phenyl-2-pyrazoline (6a). Crystallized from ethanol to
afford yellow crystals, yield 0.56 g (62%), mp 199–200°C. IR
(KBr): 3550 (N–H), 3063 (Ar-H), 2993 (aliphatic-H), 1639
(C═O), 1615 (C═S), 1592 (C═N), 1540, 1499 (C═C) cmÀ1
.
1H-NMR (DMSO-d6, 200 MHz): δ = 2.36 (s, 3H, CH3),
3.42–3.50 (dd, J = 18.0, 4.4 Hz, HA, C4-H), 3.74–3.80 (dd,
J = 18.0, 11.2 Hz, HB, C4-H), 4.78–4.81 (dd, J = 11.2, 4.4 Hz,
HX, C5-H), 7.10–7.80 (m, 11H, Ar-H + H4′), 7.90–8.30 (m, 5H,
Ar-H), 9.10 (s, 1H, NH D2O exchangeable) ppm. 13C-NMR
(DMSO-d6, 100 MHz): δ = 15.5, 40.7, 43.9, 65.1, 120.8, 121.4,
123.5, 124.8, 125.6, 128.6, 130.4, 132.4, 133.7, 134.5, 135.8,
136.5, 137.8, 138.4, 140.8, 141.5, 142.9, 147.9, 155.5, 157.4,
169.9, 177.9 ppm. EI ms: m/z: 453.51 [M+] (72).
3-(3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-p-chlorophenyl-
2-pyrazoline (4b).
Crystallized from ethanol to give white
crystals, yield 0.51 g (72%), mp 212°C. IR (KBr): 3372 (N–H),
3031 (Ar-H), 2993 (aliphatic-H), 1633 (C═O), 1590 (C═N),
1583, 1495 (C═C), 714 (C–Cl) cmÀ1 1H-NMR (DMSO-d6,
.
200 MHz): δ = 2.23 (s, 3H, CH3), 3.41–3.43 (dd, J = 18.2,
4.2 Hz, HA, C4-H), 3.77–3.79 (dd, J = 18.2, 11.3 Hz, HB,
C4-H), 4.76–4.79 (dd, J = 11.3, 4.2 Hz, HX, C5-H), 7.05–
7.40 (m, 6H, Ar-H + H4′), 7.47–7.51 (m, 4H, Ar-H), 7.99 (s,
1H, NH, D2O exchangeable) ppm. 13C-NMR (DMSO-d6,
100 MHz): δ = 15.4, 40.9, 57.7, 117.3, 118.8, 121.7, 123.5,
125.9, 127.9, 132.5, 134.9, 137.1, 138.4, 139.2, 140.9,
144.8, 146.1, 146.9, 169.1 ppm. EI ms: m/z: 352.51 [M+]
(63), 354.71 [M+ + 2] (18).
1-N-Phenylthiocarbamoyl-3-(3-methyl-5-oxo-1-phenyl-2-
pyrazolin-4-yl)-5-p-chlorophenyl-2-pyrazoline (6b). Crystallized
from toluene to give yellow powder, yield 0.61 g (63%), mp
203–304°C. IR (KBr): 3545 (N–H), 3062 (Ar-H), 2990
(aliphatic-H), 1640 (C═O), 1617 (C═S), 1590 (C═N), 1535,
1497 (C═C), 709 (C–Cl) cmÀ1
.
1H-NMR (DMSO-d6,
General procedure for the synthesis of 5a,b. The pyrazoline
derivatives 4a,b (2mmol) and triethyl amine (0.28 mL, 2 mmol)
were dissolved in dry toluene (15 mL) with stirring. Later, the
reaction mixture was cooled in an ice bath, and chloroacetyl
chloride (0.16 mL, 2 mmol) was added dropwise with stirring.
The reaction mixture thus obtained was further stirred for 2 h
at room temperature. The pale yellow solid thus formed
200 MHz): δ = 2.37 (s, 3H, CH3), 3.43–3.51 (dd, J = 18.0,
4.4 Hz, HA, C4-H4′), 3.73–3.81 (dd, J = 18.0, 11.2 Hz, HB,
C4-H), 4.78–4.82 (dd, J = 11.2, 4.4 Hz, HX, C5-H), 7.11–7.82
(m, 11H, Ar-H + H4′), 7.90–8.31 (m, 4H, Ar-H), 9.06 (s, 1H,
NH D2O exchangeable) ppm. 13C-NMR (DMSO-d6, 100 MHz):
δ = 15.7, 40.9, 44.1, 64.9, 121.2, 122.1, 123.7, 124.9, 125.8,
128.1, 130.8, 132.9, 134.1, 135.9, 136.8, 137.9, 138.1, 139.2,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
2-Pyrazolin-5-One-Based Heterocycles: Synthesis and Characterization
140.9, 142.1, 143.9, 147.5, 155.8, 160.1, 169.7, 177.9ppm. EI ms:
m/z: 487.95 [M+] (63), 490.10 [M+ + 2] (16).
3.41–3.54 (dd, J = 18.2, 4.6 Hz, HA, C4-H), 3.73–3.82 (dd,
J = 18.2, 11.2 Hz, HB, C4-H), 4.76–4.81 (dd, J = 11.2, 4.6 Hz,
HX, C5-H), 7.02–7.76 (m, 11H, Ar-H + H4′), 7.91–8.26 (m, 4H,
Ar-H) ppm. 13C-NMR (DMSO-d6, 100 MHz): δ = 16.1, 40.5,
44.4, 65.6, 121.8, 122.2, 123.9, 124.7, 126.0, 128.0, 130.9,
133.2, 133.5, 135.4, 136.7, 137.8, 138.4, 139.5, 141.6, 142.4,
143.7, 147.6, 155.8, 157.9, 170.9, 190.5 ppm. EI ms: m/z:
456.89 [M+] (76), 458.91 [M+ + 2] (19).
General procedure for the synthesis of 9a,b. To a solution
of the corresponding chalcones 1a,b (2 mmol) in ethanol (25 mL),
phenyl hydrazine (0.49 mL, 5 mmol) was added. The reaction
mixture was refluxed for 6 h. Left to cool to room temperature,
and the obtained product was filtered, dried, and crystallized
from suitable solvent to give 9a,b.
General procedure for the synthesis of 7a,b. To solution
of 4a,b (2 mmol) in dry pyridine (15 mL) cooled in an ice bath,
benzenesulfonyl chloride (2 mmol) was added. The reaction
mixture was heated on a water bath for 3 h, cooled, and then
poured into crushed ice. The solid product separated was
filtered, dried, and crystallized from suitable solvent to give 7a,b.
1-Benzenesulfonyl-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-
4-yl)-5-phenyl-2-pyrazoline (7a). Crystallized from toluene to
afford red crystals, yield 0.60 g (65%), mp 242–243°C. IR
(KBr): 3053 (Ar-H), 2991 (CH aliphatic), 1640 (C═O), 1594
(C═N), 1530, 1498 (C═C), 1344 (anti-symmetric SO2), 1090
.
(symmetric SO2) cmÀ1 1H-NMR (DMSO-d6, 400 MHz):
δ = 2.40 (s, 3H, CH3), 3.42–3.54 (dd, J = 18.1, 4.6Hz, HA, H4′),
3.75–3.82 (dd, J = 18.1, 11.3Hz, HB, C4-H), 4.77–4.80 (dd,
J = 11.3, 4.6 Hz, HX, C5-H), 7.10–7.79 (m, 11H, Ar-H + H4′),
7.90–8.31 (m, 5H, Ar-H) ppm. 13C-NMR (DMSO-d6,
100 MHz): δ = 15.4, 40.7, 44.3, 65.2, 121.2, 122.5, 123.6,
124.8, 125.7, 128.2, 130.5, 132.8, 133.0, 135.4, 136.5, 137.7,
138.5, 139.4, 141.0, 142.3, 143.7, 147.9, 155.7, 157.8,
170.1 ppm. EI ms: m/z: 458.51 [M+] (72).
3-(3-Methyl-1-phenyl-5-oxo-2-pyrazolin-4-yl)-1,5-diphenyl-
2-pyrazoline (9a).
Crystallized from methanol to produce
white crystals, yield 0.54 g (69%), mp 261–262°C. IR (KBr):
3029 (Ar-H), 2990 (aliphatic-H), 1639 (C═O), 1590 (C═N),
1580, 1495 (C═C) cmÀ1 1H-NMR (DMSO-d6, 200 MHz):
.
δ = 2.40 (s, 3H, CH3), 3.42–3.52 (dd, J = 18.1, 4.5 Hz, HA, C4-
H), 3.72–3.83 (dd, J = 18.1, 11.3 Hz, HB, C4-H), 4.76–4.82 (dd,
J = 11.3, 4.5 Hz, HX, C5-H), 7.10–7.77 (m, 11H, Ar-H + H4′),
7.90–8.20 (m, 5H, Ar-H) ppm. 13C-NMR (DMSO-d6,
100 MHz): δ = 15.7, 41.1, 57.8, 117.9, 118.8, 121.7, 122.5,
123.7, 124.6, 126.3, 127.6, 128.1, 129.6, 130.7, 132.2, 133.9,
135.5, 136.8, 138.4, 139.2, 140.8, 144.5, 145.8, 146.9,
170.1 ppm. EI ms: m/z: 394.43 [M+] (74).
1-Benzenesulfonyl-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-
4-yl)-5-p-chlorophenyl-2-pyrazoline (7b).
Crystallized from
toluene to afford red powder, yield 0.66 g (67%), mp 235–336°C.
IR (KBr): 3053 (Ar-H), 2991 (aliphatic-H), 1643 (C═O), 1594
(C═N), 1532, 1499 (C═C), 1349 (anti-symmetric SO2), 1093
(symmetric SO2), 710 (C–Cl) cmÀ1
.
1H-NMR (DMSO-d6,
3-(3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-p-chlorophenyl-
1-phenyl-2-pyrazoline (9b). Crystallized from ethanol to afford
white powder, yield 0.63 g (74%), mp 279–281°C. IR (KBr): 3031
(Ar-H), 2992 (aliphatic-H), 1640 (C═O), 1591 (C═N), 1582,
200 MHz): δ = 2.39 (s, 3H, CH3), 3.41–3.54 (dd, J = 18.1,
4.6 Hz, HA, C4-H), 3.76–3.82 (dd, J = 18.1, 11.3 Hz, HB, C4-H),
4.76–4.81 (dd, J = 11.3, 4.6 Hz, HX, C5-H), 7.11–7.79 (m, 11H,
Ar-H + H4′), 7.90–8.30 (m, 4H, Ar-H) ppm. 13C-NMR (DMSO-
d6, 100 MHz): δ = 15.5, 40.8, 44.5, 65.4, 120.9, 122.6, 123.7,
124.7, 125.8, 128.1, 130.7, 132.9, 133.4, 135.3, 136.7, 137.8,
138.4, 139.5, 141.2, 142.5, 143.8, 147.7, 155.6, 157.4,
170.3 ppm. EI ms: m/z: 492.95 [M+] (74), 494.89 [M+ + 2] (22).
1490 (C═C), 709 (C–Cl) cmÀ1
.
1H-NMR (DMSO-d6,
200 MHz): δ = 2.41 (s, 3H, CH3), 3.41–3.54 (dd, J = 18.2,
4.5 Hz, HA, C4-H), 3.72–3.84 (dd, J = 18.2, 11.3 Hz, HB, C4-H),
4.77–4.82 (dd, J = 11.3, 4.5 Hz, HX, C5-H), 7.11–7.76 (m, 11H,
Ar-H + H4′), 7.91–8.21 (m, 4H, Ar-H) ppm. 13C-NMR (DMSO-
d6, 100 MHz): δ = 15.8, 41.3, 57.7, 117.5, 118.7, 121.5, 122.6,
123.8, 124.5, 125.9, 127.7, 128.5, 129.7, 130.8, 132.4, 133.8,
135.6, 136.7, 138.4, 139.1, 140.9, 144.7, 145.5, 146.8,
170.5 ppm. EI ms: m/z: 428.89 [M+] (80), 430.90 [M+ + 2] (26).
General procedure for the synthesis of 10a,b. A mixture
of chalcones 1a,b (2 mmol), hydroxylamine hydrochloride
(0.35 g, 5 mmol), and sodium acetate (0.50 g) in ethanol (20 mL)
was refluxed for 8 h. The mixture was concentrated by distilling
out the solvent under reduced pressure and poured into crushed
ice. The obtained solid was filtered, washed, and crystallized
from suitable solvent to give 10a,b.
General procedure for the synthesis of 8a,b.
To
compounds 4a,b (2 mmol) in pyridine (10 mL), benzoyl chloride
(0.47 mL, 4 mmol) was added. The reaction mixture was heated
on water bath for 3 h and poured over crushed ice mixed with
diluted hydrochloric acid. The solid separated out was filtered,
washed with water, dried, and crystallized from suitable solvent
to give compounds 8a,b.
1-Benzoyl-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-
phenyl-2-pyrazoline (8a). Crystallized from ethanol to afford
white crystals, yield 0.61 g (72%), mp 274–276°C. IR (KBr):
3030 (Ar-H), 2990 (aliphatic-H), 1650 (C═O), 1639 (C═O),
1590 (C═N), 1580, 1491 (C═C) cmÀ1
.
1H-NMR (DMSO-d6,
3-(3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-phenylisooxazole
(10a). Crystallized from ethanol to afford white crystals, yield
0.46 g (72%), mp 298–299°C. IR (KBr): 3058 (Ar-H), 2999
(aliphatic-H), 1639 (C═O), 1590 (C═N), 1580 (C═C), 1435
400 MHz): δ = 2.38 (s, 3H, CH3), 3.40–3.53 (dd, J = 18.2,
4.6 Hz, 1 HA, C4-H), 3.74–3.82 (dd, J = 18.2, 11.2 Hz, HB, C4-
H), 4.77–4.81 (dd, J = 11.2, 4.6 Hz, HX, C5-H), 7.00–7.76
(m, 11H, Ar-H + H4′), 7.90–8.26 (m, 5H, Ar-H) ppm. 13C-NMR
(DMSO-d6, 100 MHz): δ = 15.9, 40.7, 44.3, 65.2, 121.1, 122.5,
123.8, 124.6, 125.9, 128.2, 130.8, 133.1, 133.3, 135.2, 136.8,
137.9, 138.3, 139.4, 141.5, 142.7, 143.9, 147.5, 155.4, 157.5,
170.7, 190.6 ppm. EI ms: m/z: 422.50 (M+).
(CH2 isoxazole), 1340 (C–N–C), 1120 (C–O–C) cmÀ1 1H-
.
NMR (DMSO-d6, 200 MHz): δ = 2.40 (s, 3H, CH3), 3.58–3.61
(dd, J = 17.9, 3.5 Hz, isoxazoline-H4), 3.86–3.90 (dd, J = 17.9,
3.5 Hz, isoxazoline-H4), 5.90 (dd, J = 17.9, 3.5 Hz, isoxazoline-
H5), 7.10–7.76 (m, 6H, Ar-H + H4′), 7.90–8.22 (m, 5H, Ar-H)
ppm. 13C-NMR (DMSO-d6, 100 MHz): δ = 15.5, 41.0, 58.0,
117.2, 118.5, 121.7, 123.8, 126.1, 128.5, 132.6, 135.5, 137.0,
138.1, 139.5, 140.8, 144.3, 146.0, 147.0, 169.8 ppm. EI ms: m/z:
319.29 [M+] (71).
1-Benzoyl-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-p-
chlorophenyl-2-pyrazoline (8b).
Crystallized from methanol
to afford gray powder, yield 0.68 g (74%), mp 262–263°C. IR
(KBr): 3031 (Ar-H), 2998 (aliphatic-H), 1649 (C═O), 1640
(C═O), 1589 (C═N), 1581, 1490 (C═C), 715 (C–Cl) cmÀ1
.
3-(3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-5-p-chlorophenyl-
1H-NMR (DMSO-d6, 200 MHz): δ = 2.39 (s, 3H, CH3),
isooxazole (10b).
Crystallized from ethanol to give white
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. A. O. Abeed
Vol 000
powder, yield 0.54 g (76%), mp 304–305°C. IR (KBr): 3055 (Ar-
H), 2990 (aliphatic-H), 1641 (C═O), 1589 (C═N), 1581 (C═C),
1433 (CH2 isoxazole), 1335 (C–N–C), 1122 (C–O–C), 709 (C–
J = 17.5,11.8Hz, HB, CH2), 4.97–5.05 (dd, J = 11.8, 5.1 Hz, HX,
CH), 7.01–7.62 (m, 6H, Ar-H+ H4′), 7.75–7.92 (m, 5H, Ar-H),
8.85 (s, 2H, NH2 D2O exchangeable) ppm. 13C-NMR (DMSO-
d6, 100 MHz): δ = 15.2, 42.9, 60.5, 117.9, 119.8, 120.3, 121.5,
122.3, 127.4, 129.7, 130.5, 132.8, 133.8, 135.8, 138.4, 139.2,
147.1, 154.2, 169.9, 176.9ppm. EI ms: m/z: 377.43 [M+] (81).
1-Thiocarbamoyl-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-
Cl) cmÀ1 1H-NMR (DMSO-d6, 200 MHz): δ = 2.38 (s, 3H,
.
CH3), 3.55–3.60(dd, J = 17.9, 3.4 Hz, isoxazoline-H4),
3.85–3.90 (dd, J= 17.9, 3.4 Hz, isoxazoline-H4), 5.91 (dd, J= 17.9,
3.4 Hz, isoxazoline-H5), 7.10–7.76 (m, 6H, Ar-H + H4′), 7.90–8.22
(m, 5H, Ar-H) ppm. 13C-NMR (DMSO-d6, 100 MHz): δ = 15.8,
41.1, 58.2, 117.3, 118.4, 121.9, 123.5, 126.2, 128.4, 132.3, 135.2,
137.1, 137.9, 139.4, 140.9, 144.1, 145.9, 147.1, 169.9 ppm. EI ms:
m/z: 353.73 [M+] (70), 455.76 [M+ + 2] (27).
General procedure for the synthesis of 11a,b. A mixture
of 1a,b (2 mmol) and o-phenylenediamine (0.22 g, 2 mmol) in
ethanol (15 mL) with a few drops of triethylamine was refluxed
for 10 h. The progress of the reaction was monitored by using
thin-layer chromatography. After completion of reaction, the
reaction mixture was cooled to 0°C and let overnight. The crude
solid product obtained was filtered, washed with water, and
crystallized from suitable solvent to produce 11a,b.
yl)-5-p-chlorophenyl-2-pyrazoline (12b).
Crystallized from
benzene to afford orange powder, yield 0.58 g (71%), mp
280–281°C. IR (KBr): 3401, 3296 (NH2), 3030 (Ar-H), 2910
(aliphatic-H), 1640 (C═O), 1595 (C═N), 1513, 1486 (C═C),
1328 (C═S), 716 (C–Cl) cmÀ1
.
1H-NMR (DMSO-d6,
200 MHz): δ = 2.37 (s, 3H, CH3), 3.41–3.52 (dd, J = 17.5,
5.1 Hz, HA, CH2), 3.74–3.84 (dd, J = 17.5,11.8 Hz, HB, CH2),
4.96–5.07 (dd, J = 11.8, 5.1 Hz, HX, CH), 7.00–7.62 (m, 6H,
Ar-H + H4′), 7.76–7.92 (m, 4H, Ar-H), 8.85 (s, 2H, NH2 D2O
exchangeable) ppm. 13C-NMR (DMSO-d6, 100 MHz): δ = 15.4,
42.9, 63.1, 117.9, 119.7, 120.2, 121.6, 122.3, 127.3, 129.8,
130.4, 132.7, 133.8, 135.3, 138.2, 139.3, 147.2, 154.3, 169.8,
177.1 ppm. EI ms: m/z: 411.87 [M+] (61), 413.88 [M+ + 2] (19).
General procedure for the synthesis of 13a,b. A mixture
of 12a,b (2 mmol) and phenacyl bromide (0.99 g, 2 mmol) in
absolute ethanol (20 mL) was refluxed for 1 h. After cooling, the
obtained product was collected by filtration, dried, and
crystallized from suitable solvent to afford compounds 13a,b.
2-(5-Phenyl-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-2-
4-(3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-2-phenyl-2,3-
dihydro-1H-benzo[b][1,4] diazepine (11a). Crystallized from
ethanol to afford yellow crystals, yield 0.55 g (70%), mp
237–238°C. IR (KBr): 3343 (N–H), 3138 (Ar-H), 2992
(aliphatic-H), 1632 (C═O), 1599 (C═N), 1580, 1489 (C═C)
cmÀ1 1H-NMR (DMSO-d6, 200 MHz): δ = 2.38 (s, 3H, CH3),
.
3.40–3.42 (dd, HA, J = 12.5, 9.2 Hz, CH2), 3.92–4.08 (dd, HB,
J = 12.5, 5.1 Hz, CH2), 4.15 (s, 1H, N1-H, D2O exchangeable),
4.78–4.99 (dd, HX, J = 9.2, 5.1 Hz, CH), 6.95–7.22 (m, 5H,
[H6 + H7+H8 + H9 + H4′]), 7.42–8.30 (m, 10H, Ar-H) ppm; 13C-
NMR (DMSO-d6, 100 MHz): δ = 15.4, 41.5, 58.6, 65.2, 115.4,
118.2, 121.2, 122.8, 125.5, 126.5, 127.8, 129.8, 132.7, 134.7,
135.9, 136.8, 138.7, 139.4, 141.1, 142.3, 144.1, 145.1, 145.9,
151.9, 168.2, 170.3 ppm. EI ms: m/z: 394.49 [M+] (82).
pyrazolin-1-yl)-4-phenylthiazole (13a).
Crystallized from
dioxane afford pale brown powder, yield 0.68 g (71%), mp
270–271°C. IR (KBr): 3031 (Ar-H), 2940 (aliphatic-H), 1638
(C═O), 1598 (C═N), 1510, 1484 (C═C) cmÀ1 1H-NMR
.
(DMSO-d6, 200 MHz): δ = 2.40 (s, 3H, CH3), 3.39–3.42 (dd,
J = 17.8, 3.9 Hz, HA, CH2), 3.80–3.83 (dd, J = 17.8, 11.2 Hz,
HB, CH2), 4.75–4.79 (dd, J = 11.2, 3.9 Hz, HX, CH), 6.83
(s, 1H, C5-H of thiazole), 7.15–8.20 (m, 16H, Ar-H + H4′) ppm.
13C-NMR (DMSO-d6, 100 MHz): δ = 15.4, 42.9, 60.4, 105.7,
117.9, 118.8, 119.6, 120.8, 121.3, 122.3, 124.3, 125.5, 127.5,
129.6, 130.7, 132.6, 134.1, 135.7, 136.4, 137.3, 138.1, 138.9,
140.5, 147.3, 150.6, 154.2, 164.8, 169.7, 178.2 ppm. EI ms: m/
z: 477.54 [M+] (86).
4-(3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-2-p-chlorophenyl-
2,3-dihydro-1H-benzo[b][1,4]diazepine (11b).
Crystallized
from ethanol to give pale yellow crystals, yield 0.61 g (71%),
mp 249–251°C. IR (KBr): 3345 (N–H), 3135 (Ar-H), 2990
(aliphatic-H), 1639 (C═O), 1595 (C═N), 1582, 1487 (C═C),
714 (C–Cl) cmÀ1 1H-NMR (DMSO-d6, 200 MHz): δ = 2.39
.
(s, 3H, CH3), 3.41–3.45 (dd, HA, J = 12.6, 9.3 Hz, CH2), 3.90–
4.04 (dd, HB, J = 12.6, 5.1 Hz, CH2), 4.17 (s, 1H, N1-H D2O
exchangeable), 4.80–5.00 (dd, HX, J = 9.3, 5.1 Hz, CH),
6.95–7.23 (m, 5H, [H6 + H7 + H8 + H9 + H4′]), 7.44–8.30 (m,
9H, Ar-H) ppm. 13C-NMR (DMSO-d6, 100 MHz): δ = 15.5,
41.8, 58.7, 65.1, 115.5, 118.3, 121.5, 122.9, 125.4, 126.3,
127.9, 129.7, 132.8, 134.5, 135.6, 136.7, 138.8, 139.5, 141.0,
142.2, 144.3, 145.2, 145.8, 152.0, 168.3, 170.2 ppm. EI ms: m/
z: 428.93 [M+] (76), 430.86 [M+ + 2] (26).
2-(5-p-Chlorophenyl-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-
4-yl)-2-pyrazolin-1-yl)-4-phenylthiazole (13b).
Crystallized
from dioxane to afford brown crystals, yield 0.75g (73%), mp
245–247°C. IR (KBr): 3035 (Ar-H), 2946 (aliphatic-H), 1641
1
(C═O), 1597 (C═N), 1515, 1489 (C═C), 713 (C–Cl) cmÀ1. H-
NMR (DMSO-d6, 200 MHz): δ = 2.41 (s, 3H, CH3), 3.38–3.41
(dd, J = 16.1, 3.5 Hz, HA, CH2), 3.70–3.80 (dd, J = 16.1, 11.0 Hz,
HB, CH2), 4.70–4.80 (dd, J = 11.0, 3.5 Hz, HX, CH), 6.80 (s, 1H,
C5-H of thiazole), 7.10–8.20 (m, 15H, Ar-H + H4′) ppm. 13C-
NMR (DMSO-d6, 100MHz): δ = 15.7, 42.8, 60.7, 105.2, 117.8,
118.9, 119.7, 120.9, 121.5, 122.7, 124.5, 125.4, 127.6, 129.7,
130.8, 132.7, 134.2, 135.8, 136.5, 137.4, 138.2, 138.8, 140.7,
147.4, 150.7, 154.3, 164.9, 170.0, 178.3 ppm. EI ms: m/z:
512.00 [M+] (81), 514.01 [M+ + 2] (27).
General procedure for the synthesis of 14a,b. A mixture
of 12a,b (2 mmol) and 2,3-dichloroquinoxaline (0.4 g, 2 mmol)
in ethanol (10 mL) was heated under reflux for 8 h. The solvent
was evaporated under reduced pressure. The residue was
crystallized to give 14a,b.
General procedure for the synthesis of 12a,b.
To a
suspension of chalcones 1a,b (5 mmol) and sodium hydroxide
(0.40 g, 10 mmol) in ethanol (25 mL), thiosemicarbazide (0.46 g,
5 mmol) was added. The mixture was refluxed for 8 h. The
products were poured into crushed ice, and the solid mass that
separated was filtered, dried, and crystallized from suitable
solvent to give compounds 12a,b.
1-Thiocarbamoyl-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-
yl)-5-phenyl-2-pyrazoline (12a). Crystallized from benzene to
afford orange powder, yield 0.52 g (69%), mp 291–292°C. IR
(KBr): 3400, 3295 (NH2), 3031 (Ar-H), 2900 (aliphatic-H),
1639 (C═O), 1593 (C═N), 1511, 1485 (C═C), 1325 (C═S)
3-[3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl]-5-phenyl-1-(thiazolo
[4,5-b]qunixalin-2-yl)-2-pyrazoline (14a). Crystallized from toluene
to afford red powder, yield 0.57 g (68%), mp 284–286°C. IR
(KBr): 3100 (Ar-H), 2986 (aliphatic-H), 1633 (C═O), 1590
cmÀ1 1H-NMR (DMSO-d6, 200 MHz): δ = 2.35 (s, 3H, CH3),
.
3.40–3.52 (dd, J = 17.5, 5.1 Hz, HA, CH2), 3.76–3.84 (dd,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
2-Pyrazolin-5-One-Based Heterocycles: Synthesis and Characterization
(C═N), 1517, 1490 (C═C) cmÀ1
.
1H-NMR (DMSO-d6,
by filtration, dried, and crystallized from suitable solvent to
afford products 16a–f.
200 MHz): δ = 2.35 (s, 3H, CH3), 3.39–3.50 (dd, J = 17.4,
5.1 Hz, HA, CH2), 3.77–3.84 (dd, J = 17.4, 11.8 Hz, HB, CH2),
4.96–5.06 (dd, J = 11.8, 5.1 Hz, HX, CH), 7.00–7.60 (m, 6H, Ar-
H + H4′), 7.74–7.92 (m, 9H, Ar-H) ppm. 13C-NMR (DMSO-d6,
100 MHz): δ = 15.5, 40.9, 58.1, 117.7, 118.5, 121.9, 122.5,
123.8, 125.1, 126.6, 128.2, 129.7, 130.5, 132.8, 134.6, 135.7,
137.1, 138.6, 139.3, 140.9, 143.5, 144.5, 145.7, 146.6, 147.9,
148.3, 163.8, 170.1 ppm. EI ms: m/z: 503.61 [M+] (70).
Another route for the synthesis of compounds 16a–f.
A
mixture of 15a,b (2 mmol), aromatic aldehydes (2 mmol), and
anhydrous sodium acetate (0.27 g) was refluxed in acetic acid
(10 mL) for 6 h. The mixture was cooled and poured into ice
water. The resulting solid was collected by filtration, dried, and
crystallized to give products identical in all aspects (mp, mixed
1
mp, IR, and H-NMR) with 16a–f.
3-[3-Methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl]-5-p-chlorophenyl-
1-(thiazolo[4,5-b] qunixalin-2-yl)-2-pyrazoline (14b). Crystallized
from toluene to give brown powder, yield 0.61 g (67%), mp
270–272°C. IR (KBr): 3099 (Ar-H), 2985 (aliphatic-H), 1633
(C═O), 1598 (C═N), 1515, 1494 (C═C), 715 (C–Cl) cmÀ1. 1H-
NMR (DMSO-d6, 200 MHz): δ = 2.39 (s, 3H, CH3), 3.38–3.50
(dd, J = 17.3, 5.2 Hz, HA, CH2), 3.75–3.83 (dd, J = 17.3, 11.8 Hz,
HB, CH2), 4.95–5.02 (dd, J = 11.8, 5.2 Hz, HX, CH), 7.00–7.65
(m, 6H, Ar-H + H4′), 7.72–7.99 (m, 8H, Ar-H) ppm. 13C-NMR
(DMSO-d6, 100 MHz): δ = 15.7, 41.1, 58.5, 117.8, 118.7, 121.5,
122.9, 123.7, 125.5, 126.7, 128.1, 129.8, 131.0, 132.9, 134.8,
135.6, 137.0, 138.8, 139.7, 141.0, 143.8, 144.7, 145.9, 146.7,
147.2, 148.4, 163.9, 170.0 ppm. EI ms: m/z: 537.98 [M+] (59),
540.01 [M+ + 2] (18).
5-Benzylidene-2-(5-phenyl-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-
4-yl)-2-pyrazolin-1-yl) thiazol-4-one (16a). Crystallized from
methanol to afford orange crystals, yield 0.73 g (72%), mp 212–
213°C. IR (KBr): 3102 (Ar-H), 2996 (aliphatic-H), 1715
(C═O), 1641 (C═O), 1598 (C═N), 1545, 1489 (C═C) cmÀ1
.
1H-NMR (DMSO-d6, 200 MHz): δ = 2.41 (s, 3H, CH3),
3.30–3.40 (dd, J = 15.4, 4.3 Hz, HA, CH2), 3.80–3.90 (dd,
J = 15.4, 11.6 Hz, HB, CH2), 4.70–4.80 (dd, J = 11.6, 4.3 Hz,
HX, CH), 7.10–8.20 (m, 17H, 15 Ar-H + H4′ + CH═) ppm. 13C-
NMR (DMSO-d6, 100 MHz): δ = 15.7, 40.9, 60.8, 117.9, 119.7,
121.6, 122.4, 123.8, 124.5, 125.9, 127.6, 129.7, 131.8, 132.8,
134.5, 135.6, 136.5, 137.7, 138.2, 139.9, 140.6, 142.8, 144.4,
147.5, 150.4, 152.9, 154.3, 170.3, 189.5 ppm. EI ms: m/z: 505.53
[M+] (79).
General procedure for the synthesis of 15a,b. A mixture
of 12a,b (2 mmol), chloroacetic acid (0.29 g, 3 mmol), and
anhydrous sodium acetate (0.27 g) was refluxed in acetic acid
(15 mL) for 3 h. The mixture was poured into crushed ice, and
the solid mass that separated out was filtered, dried, and
crystallized from an appropriate solvent to afford 15a,b.
5-p-Chlorobenzylidene-2-(5-phenyl-3-(3-methyl-5-oxo-1-phenyl-
2-pyrazolin-4-yl)-2-pyrazolin-1-yl) thiazol-4-one (16b). Crystallized
from ethanol to afford yellow crystals, yield 0.80 g (74%), mp
215–217°C. IR (KBr): 3105 (Ar-H), 2996 (aliphatic-H), 1717
(C═O), 1639 (C═O), 1598 (C═N), 1547, 1480 (C═C), 710
1
(C–Cl) cmÀ1. H-NMR (DMSO-d6, 200 MHz): δ = 2.40 (s, 3H,
2-(5-Phenyl-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-4-yl)-
2-pyrazolin-1-yl)thiazol-4(5H)-one (15a). Crystallized from
ethanol to afford yellow powder, yield 0.58 g (70%), mp 246–
248°C. IR (KBr): 3090 (Ar-H), 2980 (aliphatic-H), 1715 (C═O
CH3), 3.32–3.41 (dd, J = 15.4, 4.3 Hz, HA, CH2), 3.80–3.92 (dd,
J = 15.4, 11.6 Hz, HB, CH2), 4.72–4.80 (dd, J = 11.6, 4.3 Hz, HX,
CH), 7.10–8.20 (m, 16H, 14 Ar-H + H4′ + CH═) ppm. 13C-
NMR (DMSO-d6, 100 MHz): δ = 15.6, 40.8, 60.9, 117.5, 119.8,
121.7, 122.5, 123.9, 124.6, 125.8, 127.7, 129.5, 131.7, 132.6,
134.9, 135.7, 136.6, 137.9, 138.4, 140.2, 141.6, 142.9, 144.5,
147.7, 150.6, 152.8, 154.5, 170.8, 189.6 ppm. EI ms: m/z:
540.01 [M+] (79), 542.00 [M+ + 2] (28).
thiazole), 1636 (C═O), 1594 (C═N), 1540, 1489 (C═C) cmÀ1
.
1H-NMR (DMSO-d6, 200 MHz): δ = 2.39 (s, 3H, CH3), 3.37–
3.42 (dd, J = 17.8, 3.9 Hz, HA, CH2), 3.81–3.83 (dd, J = 17.8,
11.2 Hz, HB, CH2), 4.75–4.78 (dd, J = 11.2, 3.9 Hz, HX, CH),
3.99–4.22 (2 dd, 2H, C5-H of thiazolone), 7.11–8.23 (m,
11H, Ar-H + H4′) ppm. 13C-NMR (DMSO-d6, 100 MHz):
δ = 15.6, 35.3, 40.9, 60.5, 117.8, 119.5, 121.8, 122.3, 124.3,
129.6, 131.4, 134.3, 135.7, 136.4, 138.1, 138.9,140.5,
147.3, 150.3, 154.2, 173.8, 189.2 ppm. EI ms: m/z: 417.43
[M+] (79).
5-p-Nitrobenzylidene-2-(5-phenyl-3-(3-methyl-5-oxo-1-phenyl-
2-pyrazolin-4-yl)-2-pyrazolin-1-yl) thiazol-4-one (16c). Crystallized
from ethanol to afford pale yellow powder, yield 0.77 g (70%),
mp 223–225°C. IR (KBr): 3100 (Ar-H), 2990 (aliphatic-H),
1718 (C═O), 1641 (C═O), 1598 (C═N), 1545, 1482 (C═C)
cmÀ1 1H-NMR (DMSO-d6, 200 MHz): δ = 2.40 (s, 3H, CH3),
.
2-(5-p-Chlorophenyl-3-(3-methyl-5-oxo-1-phenyl-2-pyrazolin-
3.31–3.40 (dd, J = 15.3, 4.3 Hz, HA, CH2), 3.80–3.91 (dd,
J = 15.3, 11.6 Hz, HB, CH2), 4.71–4.78 (dd, J = 11.6, 4.3 Hz, HX,
CH), 7.10–8.22 (m, 16H, 14 Ar-H + H4′ + CH═) ppm. 13C-
NMR (DMSO-d6, 100 MHz): δ = 15.8, 41.1, 61.2, 117.4, 120.1,
121.8, 122.4, 123.8, 124.7, 125.9, 127.8, 129.4, 131.9, 132.7,
135.1, 136.1, 137.0, 138.0, 139.1, 140.5, 141.7, 142.8, 144.6,
147.8, 150.9, 152.9, 154.8, 170.7, 189.8 ppm. EI ms: m/z:
550.55 [M+] (81).
4-yl)-2-pyrazolin-1-yl) thiazol-4(5H)-one (15b).
Crystallized
from ethanol to give red crystals, yield 0.65 g (72%), mp 259–
260°C. IR (KBr): 3100 (Ar-H), 2990 (aliphatic-H), 1717 (C═O
thiazole), 1640 (C═O), 1598 (C═N), 1541, 1487 (C═C), 708
1
(C–Cl) cmÀ1. H-NMR (DMSO-d6, 200 MHz): δ = 2.39 (s, 3H,
CH3), 3.35–3.42 (dd, J = 17.7, 3.9 Hz, HA, CH2), 3.83–3.85 (dd,
J = 17.7, 11.2 Hz, HB, CH2), 4.75–4.79 (dd, J = 11.2, 3.9 Hz,
HX, CH), 3.98–4.22 (2 dd, 2H, C5-H of thiazolone), 7.10–8.20
(m, 10H, Ar-H + H4′) ppm. 13C-NMR (DMSO-d6, 100 MHz):
δ = 15.7, 35.4, 41.1, 61.1, 118.2, 119.4, 122.1, 123.0, 124.5,
129.7, 131.5, 134.4, 135.9, 136.2, 137.9, 139.0, 140.7, 148.1,
150.5, 154.6, 173.1, 189.1 ppm. EI ms: m/z: 451.90 [M+] (76),
453.92 [M+ + 2] (27).
5-Benzylidene-2-(5-p-chlorophenyl-3-(3-methyl-5-oxo-1-phenyl-
2-pyrazolin-4-yl)-2-pyrazolin-1-yl) thiazol-4-one (16d). Crystallized
from toluene to afford white crystals, yield 0.77 g (71%), mp
237–238°C. IR (KBr): 3108 (Ar-H), 2994 (aliphatic-H), 1715
(C═O), 1643 (C═O), 1599 (C═N), 1544, 1481 (C═C), 711
1
(C–Cl) cmÀ1. H-NMR (DMSO-d6, 200 MHz): δ = 2.38 (s, 3H,
General procedure for the synthesis of 16a–f. A mixture
of 12a,b (2 mmol), chloroacetic acid (0.29 g, 3 mmol), various
aromatic aldehydes (2 mmol), and anhydrous sodium acetate
(0.27 g) was refluxed in acetic acid (20 mL) for 6 h. The mixture
was poured into crushed ice, and the precipitate was collected
CH3), 3.31–3.38 (dd, J = 15.3, 4.2 Hz, HA, CH2), 3.80–3.88 (dd,
J = 15.3, 11.6 Hz, HB, CH2), 4.70–4.78 (dd, J = 11.6, 4.3 Hz, HX,
CH), 7.12–8.22 (m, 16H, 14 Ar-H + H4′ + CH═) ppm. 13C-
NMR (DMSO-d6, 100 MHz): δ = 15.4, 41.0, 61.1, 117.4, 120.1,
121.8, 122.4, 123.8, 124.8, 125.9, 127.5, 129.8, 131.4, 132.8,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. A. O. Abeed
Vol 000
REFERENCES AND NOTES
134.6, 135.4, 136.7, 137.6, 138.7, 140.9, 141.8, 142.7, 144.6,
147.9, 150.8, 152.9, 154.7, 170.8, 189.8 ppm. EI ms: m/z:
540.00 [M+] (82), 542.01 [M+ + 2] (23).
[1] El-Metwally, S.; Khalil, A. K. Acta Chim Slov 2010, 57, 941.
[2] Liu, C. B.; Chen, Y.; Yan, L. S.; Huang, D. H.; Xiong, Z. Q. J
Heterocycl Chem 2012, 49, 839.
5-p-Chlorobenzylidene-2-(5-p-chlorophenyl-3-(3-methyl-5-
oxo-1-phenyl-2-pyrazolin-4-yl)-2-pyrazolin-1-yl)thiazol-4-one
(16e). Crystallized from ethanol to give white powder, yield
0.83 g (72%), mp 241–243°C. IR (KBr): ν = 3101 (Ar-H), 2995
(aliphatic-H), 1718 (C═O), 1640 (C═O), 1598 (C═N), 1544,
[3] Molinari, A.; Oliva, A. J Heterocycl Chem 1996, 33, 479.
[4] Lesnov, A. E.; Sazonova, E. A. Russ J Inorg Chem 2007, 52, 979.
[5] Petrova, M. A.; Dukov, I. L. Chem Pap 2008, 62, 207.
[6] Ravala, J. P.; Shaha, A. B.; Patela, N. H.; Patela, H. V.; Patela,
P. S.; Bhattb, K. K.; Desaic, K. R. Eur J Chem 2011, 2, 238.
[7] Pattan, S. R.; Rabara, P. A.; Pattan, J. S.; Bukitagar, A. A.;
Wakale, V.; Musmade, D. S. Indian J Chem 2009, 48B, 1453.
[8] Joshi, K. T.; Pancholi, A. M.; Pandya, K. S.; Thakar, A. S. J
Chem Pharm Res 2011, 3, 741.
[9] Mostafa, M. S.; Abd El-Salam, N. M.; Alothman, O. Y. J
Chem 2013, 2013, 1.
[10] Thakar, A. S.; Friedrich, H. B.; Joshi, K. T. Res J Chem Envi-
ron 2013, 17, 53.
1480 (C═C), 714 (C–Cl) cmÀ1
.
1H-NMR (DMSO-d6,
200 MHz): δ = 2.40 (s, 3H, CH3), 3.30–3.38 (dd, J = 15.3,
4.2 Hz, HA, CH2), 3.82–3.88 (dd, J = 15.3, 11.6 Hz, HB, CH2),
4.70–4.76 (dd, J = 11.6, 4.3 Hz, HX, CH), 7.10–8.23 (m, 15H,
13 Ar-H + H4′ + CH═) ppm. 13C-NMR (DMSO-d6, 100 MHz):
δ = 16.0, 41.5, 61.3, 117.8, 121.0, 121.9, 122.8, 123.9, 124.9,
126.2, 127.8, 129.9, 131.6, 133.5, 134.7, 135.6, 136.8, 137.9,
138.8, 141.1, 141.9, 143.2, 144.8, 148.2, 150.9, 153.1, 155.0,
170.4, 188.9 ppm. EI ms: m/z: 574.42 [M+] (67), 576.41
[M+ + 2] (21), 578.38 [M+ + 4] (11).
[11] Tantawy, A.; Eisa, H.; Ismail, A.; Alexandria, M. E. J Pharm
Sci 1988, 2, 113.
5-p-Nitrobenzylidene-2-(5-p-chlorophenyl-3-(3-methyl-5-
oxo-1-phenyl-2-pyrazolin-4-yl)-2-pyrazolin-1-yl) thiazol-4-one
(16f). Crystallized from ethanol afford yellow powder, yield
0.82 g (70%), mp 239–240°C. IR (KBr): 3100 (Ar-H), 2991
(aliphatic-H), 1720 (C═O), 1638 (C═O), 1598 (C═N), 1546
[12] Yoshikawa, K.; Nagata, T.; Yoshino, T.; Nakamoto, Y.;
Haginoya, N.; Muto, R.; Mochizuki, A.; Kanno, H.; Ohta, T. Heterocycles
2012, 85, 1711.
[13] Gomha, S. M.; Abdel-Aziz, H. A. Heterocycles 2012, 85, 2291.
[14] Yavari, I.; Sayyed-Alangi, S. Z.; Hajinasiri, R.; Sajjadi-
Ghotbabadi, H. Monatsh Chem 2009, 140, 209.
[15] Singh, A. K.; Mishra, G.; Jyoti, K. J Appl Pharm Sci 2011, 1, 44.
[16] Aoyama, T.; Murata, S.; Arai, I.; Araki, N.; Takido, T.;
Suzuki, Y.; Kodomari, M. Tetrahedron 2006, 62, 3201.
[17] Ouyang, G.; Chen, Z.; Cai, X. J.; Song, B. A.; Bhadury, P. S.;
Yang, S.; Jin, L. H.; Xue, W.; Hu, D. Y.; Zeng, S. Bioorg Med Chem
2008, 16, 9699.
[18] Hashem, A. I.; Youssef, A. S. A.; Kandeel, K. A.; Abou-Elmagd,
W. S. I. Eur J Med Chem 2007, 42, 934.
[19] Crute, J. J.; Grygon, C. A.; Hargrave, K. D.; Simoneau, B.;
Faucher, A. M.; Bolger, G.; Kiber, P.; Liuzzi, M.; Cordingley, M. G.
Nat Med 2002, 8, 386.
(C═C), 1514, 1370 (NO2), 710 (C–Cl) cmÀ1
.
1H-NMR
(DMSO-d6, 200 MHz): δ = 2.41 (s, 3H, CH3), 3.32–3.36 (dd,
J = 15.3, 4.4 Hz, HA, CH2), 3.80–4.00 (dd, J = 15.3, 11.6 Hz,
HB, CH2), 4.72–4.76 (dd, J = 11.6, 4.3 Hz, HX, CH), 7.12–8.40
(m, 15H, 13 Ar-H + H4′ + CH═) ppm. 13C-NMR (DMSO-d6,
100 MHz): δ = 15.9, 41.4, 60.9, 118.2, 121.4, 121.5, 122.9,
123.7, 125.2, 126.6, 127.9, 130.1, 131.9, 133.8, 134.6, 135.5,
136.7, 137.6, 138.9, 141.4, 141.4, 143.6, 144.7, 148.3, 150.6,
153.0, 155.2, 170.3, 189.0 ppm. EI ms: m/z: 585.00 [M+] (76),
587.09 [M+ + 2] (27).
[20] Youssef, M. S. K.; Omar, A. A. Monatsh Chem 2007, 138, 989.
[21] Youssef, M. S. K.; Ahmed, R. A.; Abbady, M. S.; Omar, A. A.
Monatsh Chem 2008, 139, 553.
[22] Youssef, M. S. K.; Abbady, M. S.; Ahmed, R. A.; Omar, A. A.
Chin J Chem 2011, 29, 1473.
[23] Youssef, M. S. K.; Abbady, M. S.; Ahmed, R. A.; Omar, A. A.
J Heterocycl Chem 2013, 50, 179.
[24] Abeed, A. A. O.; Abdel Mohsen, S. A. Eur J Sci Res 2013, 108, 279.
[25] Mohanty, S. K.; Sridhar, R.; Padmanavan, S. Y.; Rao, S.;
Mittra, A. S. Indian J Chem 1977, 15B, 1146.
CONCLUSION
In conclusion, 2-pyrazolines 4a,b and N-thiocarbamoyl-
2-pyrazolines 12a,b incorporating 2-pyrazolin-5-one moi-
ety were used as efficient precursors for the synthesis of
new heterocycles including the 2-pyrazolin- 5-one moiety
with expected biological activities.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet