Reaction of heteroaryl hydrazines with 3-Cinnamoyl-4-hydroxy-6-methyl-2H-pyran-2-ones: Synthesis of some novel pyrazolines and their iodine(III) mediated conversion to corresponding pyrazoles

Article abstract of DOI:10.14233/ajchem.2014.17145

A series of some novel 5-aryl-3-(4-hydroxy-6-methyl-2H-pyran-2-oxo-3-yl)-1-heteroaryl pyrazolines have been prepared by the reaction of 3-cinnamoyl-4-hydroxy-6-methyl-2H-pyran-2-ones i.e., chalcone analogues of dehydroacetic acid (DHA) with various heteroaryl hydrazines and converted to corresponding pyrazoles with iodobenzene diacetate in good yields.

Full text of DOI:10.14233/ajchem.2014.17145

Asian Journal of Chemistry; Vol. 26, No. 23 (2014), 8084-8086
ASIAN JOURNAL OF CHEMISTRY
http://dx.doi.org/10.14233/ajchem.2014.17145
Reaction of Heteroaryl Hydrazines with 3-Cinnamoyl-4-hydroxy-6-methyl-2H-
pyran-2-ones: Synthesis of Some Novel Pyrazolines and their Iodine(III)
Mediated Conversion to Corresponding Pyrazoles
*
MAYANK KINGER , V. D. GUPTA, JOGINDER SINGH, AVNISH KUMAR ARORA and VIVEK SHEEL JASWAL
Depatment of Chemistry, Maharishi Markandeshwar University, Mullana, Ambala-133 207, India
*
Corresponding author: Fax: +91 1731 274375; Tel: +91 1731 304100; E-mail: mayank.kinger@yahoo.com
Received: 30 January 2014; Accepted: 9 June 2014; Published online: 15 November 2014;
AJC-16298
A series of some novel 5-aryl-3-(4-hydroxy-6-methyl-2H-pyran-2-oxo-3-yl)-1-heteroaryl pyrazolines have been prepared by the reaction
of 3-cinnamoyl-4-hydroxy-6-methyl-2H-pyran-2-ones i.e., chalcone analogues of dehydroacetic acid (DHA) with various heteroaryl
hydrazines and converted to corresponding pyrazoles with iodobenzene diacetate in good yields.
Keywords: Chalcone, Dehydroacetic acid, Heteroaryl hydrazines, Pyrazolines, Iodobenzene diacetate, Pyrazoles.
11,12
dehydrogenated in to pyrazoles using iodobenzene diacetate
.
INTRODUCTION
But effect of the nature of heterocyclic moiety on the reaction
of hydrazines with 3-cinnamoyl-4-hydroxy-6-methyl-2H-
pyran-2-ones i.e., chalcone analogues of dehydroacetic acid
particularly having pyran moiety has not been explored yet.
Prompted by these observations, it was thought of interest
to investigate the reaction of heteroaryl hydrazines with
3-cinnamoyl-4-hydroxy-6-methylpyran-2-ones (3a-f) and to
further study the iodine(III) mediated oxidative approach for
the transformation of 5-aryl-3-(4-hydroxy-6-methyl-2H-
pyran-2-oxo-3-yl)-1-hetarylpyrazolines (7a-f) into the corres-
ponding 5-aryl-3-(4-hydroxy-6-methyl-2H-pyran-2-oxo-3-
yl)-1-hetarylpyrazoles (8a-f).
Pyrazoles are one of the most important classes of com-
pounds among heterocycles.A great deal of attention has been
devoted to the chemistry of pyrazoles due to varied pharma-
cological applications such as CNS depressant, neuroleptic,
tuberculostatic, antihypertensive, antileishmanial, analgesic,
1
-7
antidiabetic, antitumor, antimicrobial, antipyretic . Pyrazole
plays an important role in synthetic as well as medicinal chemistry
as they constitute the framework of numerous drugs and dyes.
Efforts are still continuously being made to evolve newer and
facile procedures for the synthesis of this class of compounds.
Among a number of methods reported in literature, one invol-
ving oxidation of pyrazolines with various oxidizing agents
such as manganese dioxide, colloidal platinum, mercuric
acetate, mercuric oxide and lead tetra- acetate, lead oxide etc.,
EXPERIMENTAL
Melting points were determined in open capillaries and
1
are uncorrected. H NMR spectra were recorded on Bruker
8,9
finds significant use in this area . Thus there is a great demand
for developing newer methods involving non-toxic oxidizing
agents to effect such conversions.
300 MHz spectrophotometer. The internal standard used for
these spectra was TMS. IR spectra (KBr) were recorded on a
Bruker-Vector 22 instrument. The stationary phases used for
column chromatography (Silica gel 60, 70-230 mesh) and TLC
plates (Silica-gel 60 F254) were purchased form Merck KGaA.
All the chemicals were purchased from commercial suppliers
and used without further purification.
Recent publications from our lab have emphasized the
advantageous use of versatile organohypervalent iodine(III)
reagents such as iodobenzene diacetate, hydroxytosyloxy
iodobenzene (HTIB) etc., over toxic oxidizing reagents such
1
0
as Pb(IV), Tl(III), or Hg(III) salts . Relevant to the present study
on the oxidation of pyrazolines with iodobenzene diacetate to
General procedure for the synthesis of 5-aryl-3-(4-
hydroxy-6-methyl-2H-pyran-2-oxo-3-yl)-1-(2-benzo-
thiazolyl)pyrazolines (7a-f): A mixture of 3-cinnamoyl-4-
hydroxy-6-methyl-2-pyrones (3) (0.001 mol) and 2-hydrazino-
benzothiazole (6) (0.001 mol) in ethanol (25 mL) was heated
11,12
the pyrazoles
.
In literature, the reaction of phenyl and 6-fluorobenzo-
thiazolyl hydrazines with various 1,3-diarylprop-2-en-1-ones
have been studied and obtained pyrazolines were successfully

Vol. 26, No. 23 (2014)
Reaction of Heteroaryl Hydrazines with 3-Cinnamoyl-4-hydroxy-6-methyl-2H-pyran-2-ones 8085
under reflux for 2 h. The preparation of compound 3 was done
5-Phenyl-3-(4-hydroxy-6-methyl-2H-pyran-2-oxo-3-
yl)-1-(2-benzothiazolyl)pyrazole (8a):Yield 72 %; m.p. 188-
1
3,14
according to literature procedure . The progress of the
reaction was monitored by TLC. After completion, the excess
of ethanol was distilled off under reduced pressure. On cooling
the reaction mixture, the product which separated out was
filtered, washed with ethanol, dried and recrystallized from
ethanol to afford compound 7a-f in excellent yields.
-1
1
190 °C; IR (KBr, νmax, cm ): 1728, (C=O); H NMR (CDCl
300 MHz, δ): 2.27 (s, 3H, CH ), 6.02 (s, 1H, C5'-H, DHA),
7.10 (s, 1H, C4-H), 7.28 (m, 9H, Ar), 13.54 (s, 1H, OH);Anal.
3
,
3
found: C, 65.82; H, 3.77; N, 10.47; C22
65.80; H, 3.74; N, 10.49 %.
15 3 3
H N O S requires: C,
5
yl)-1-(2-benzothiazolyl)pyrazoline (7a): Yield 75 %; m.p.
-Phenyl-3-(4-hydroxy-6-methyl-2H-pyran-2-oxo-3-
5-(4-Methylphenyl)-3-(4-hydroxy-6-methyl-2H-pyran-
2-oxo-3-yl)-1-(2-benzothiazolyl)pyrazole (8b):Yield 74 %;
-
1
1
-1
1
1
88-190 °C; IR (KBr, νmax, cm ): 1728, (C=O); H NMR
CDCl , 300 MHz, δ): 2.21 (s, 3H, CH ), 3.65 (dd, 1H, C -H
J = 17.7, 5.2 Hz), 4.12 (dd, 1H, C -H , J = 17.7, 10.1 Hz),
-H, J = 5.2, 10.1 Hz), 6.04 (s, 1H, C5'-H, DHA),
.26 (m, 9H, Ar), 13.52 (s, 1H, OH).
-(4-Methylphenyl)-3-(4-hydroxy-6-methyl-2H-pyran-
-oxo-3-yl)-1-(2-benzothiazolyl)pyrazoline (7b):Yield 78 %;
m.p. 213-215 °C; IR (KBr, νmax, cm ): 1725, (C=O); H NMR
(CDCl , 300 MHz, δ): 2.22 (s, 3H, CH ), 2.41 (s, 3H, CH ),
(
3
3
4
A
,
3
3
3
4
B
6.02 (s, 1H, C5'-H, DHA), 7.32 (s, 1H, C4-H), 7.28 (m, 8H,
Ar), 13.53 (s, 1H, OH); Anal. found: C, 66.49; H, 4.12; N,
5.61 (dd, 1H, C
3
7
17 3 3
10.11; C23H N O S requires: C, 66.43; H, 4.09; N, 10.19 %.
5
5-(4-Chlorophenyl)-3-(4-hydroxy-6-methyl-2H-pyran-
2-oxo-3-yl)-1-(2-benzothiazolyl)pyrazole (8c): Yield 74 %;
2
-1
1
-1
1
m.p. 238-240 °C; IR (KBr, νmax, cm ): 1725, (C=O); H NMR
m.p. 170-172 °C; IR (KBr, νmax, cm ): 1723, (C=O); H NMR
(CDCl , 300 MHz, δ): 2.29 (s, 3H, CH ), 6.01 (s, 1H, C5'-H,
DHA), 7.42 (s, 1H, C -H), 7.31 (m, 8H,Ar), 13.5 (s, 1H, OH);
(
CDCl
3
, 300 MHz, δ): 2.30 (s, 3H, CH
.73 (dd, 1H, C -H , J = 17.5, 5.4 Hz), 4.18 (dd, 1H, C
17.5, 11.1 Hz), 5.68 (dd, 1H, C
3
), 2.31 (s, 3H, CH
3
),
3
3
3
4
A
-H
4 B
J
4
=
3
-H, J = 11.1, 5.4 Hz), 6.08
Anal. found: C, 60.62; H, 3.24; N, 9.69; C22
requires: C, 60.67; H, 3.21; N, 9.72 %.
14 3 3
H N O SCl
(
s, 1H, C5'-H, DHA), 7.27 (m, 8H, Ar), 13.53 (s, 1H, OH).
-(4-Chlorophenyl)-3-(4-hydroxy-6-methyl-2H-pyran-
-oxo-3-yl)-1-(2-benzothiazolyl)pyrazoline (7c):Yield 76 %;
5
5-(2-Methoxyphenyl)-3-(4-hydroxy-6-methyl-2H-
pyran-2-oxo-3-yl)-1-(2-benzothiazolyl)pyrazole (8d):Yield
-1
78 %; m.p. 208-210 °C; IR (KBr, νmax, cm ): 1723, (C=O);
2
-1
1
m.p. 198-200 °C; IR (KBr, νmax, cm ): 1723, (C=O); H NMR
CDCl , 300 MHz, δ): 2.28 (s, 3H, CH ), 3.68 (dd, 1H, C -H
J = 17.2, 5.3 Hz), 4.19 (dd, 1H, C -H , J = 17.2, 10.5 Hz),
-H, J = 10.5, 5.3 Hz), 6.02 (s, 1H, C5'-H, DHA),
.47 (m, 8H, Ar), 13.52 (s, 1H, OH).
-(2-Methoxyphenyl)-3-(4-hydroxy-6-methyl-2H-
pyran-2-oxo-3-yl)-1-(2-benzothiazolyl)pyrazoline (7d):
1
(
3
3
4
A
,
H NMR (CDCl
3
, 300 MHz, δ): 2.22 (s, 3H, CH
-H), 7.29 (m, 8H, Ar), 13.5
(s, 1H, OH); Anal. found: C, 64.03; H, 3.94; N, 9.74;
S requires: C, 64.08; H, 3.96; N, 9.76 %.
5-(4-Fluorophenyl)-3-(4-hydroxy-6-methyl-2H-pyran-
2-oxo-3-yl)-1-(2-benzothiazolyl)pyrazole (8e): Yield 76 %;
3
), 6.02 (s,
4
B
1H, C5'-H, DHA), 7.41 (s, 1H, C
4
5.65 (dd, 1H, C
3
7
23 17 3 4
C H N O
5
-1
-1
1
Yield 79 %, m.p. 246-248 °C; IR (KBr, νmax, cm ): 1725, (C=O);
m.p. 178-179 °C; IR (KBr, νmax, cm ): 1723, (C=O); H NMR
(CDCl , 300 MHz, δ): 2.23 (s, 3H, CH ), 6.02 (s, 1H, C5'-H,
DHA), 7.39 (s, 1H, C4-H), 7.30 (m, 8H,Ar), 13.5 (s, 1H, OH);
1
H NMR (CDCl
CH ), 3.51 (dd, 1H, C
, J = 17.4, 10.6 Hz), 5.84 (dd, C
s, 1H, C5'-H, DHA), 7.28 (m, 8H, Ar), 13.52 (s, 1H, OH).
-(4-Fluorophenyl)-3-(4-hydroxy-6-methyl-2H-pyran-
-oxo-3-yl)-1-(2-benzothiazolyl)pyrazoline (7e):Yield 78 %;
3
, 300 MHz, δ): 2.20 (s, 3H, CH
-H , J = 17.4, 5.5 Hz), 4.07 (dd, 1H, C
-H, J = 10.6, 5.5 Hz), 6.08
3
), 3.85 (s, 3H,
3
3
3
4
A
4
-
H
B
3
Anal. found: C, 63; H, 3.36; N, 10.02; C22
C, 63.08; H, 3.39; N, 10.07 %.
14 3 3
H N O SF requires:
(
5
5-(2-Chlorophenyl)-3-(4-hydroxy-6-methyl-2H-pyran-
2-oxo-3-yl)-1-(2-benzothiazolyl)pyrazole (8f): Yield 75 %;
2
-1
1
-1
1
m.p. 228-230 °C; IR (KBr, νmax, cm ): 1725, (C=O); H NMR
CDCl , 300 MHz, δ): 2.23 (s, 3H, CH ), 3.63 (dd, 1H, C -H
J = 17, 5.6 Hz), 4.11 (dd, 1H, C -H , J = 17, 10.6 Hz), 5.60
dd, 1H, C -H, J = 10.6, 5.6 Hz), 6.08 (s, 1H, C5'-H, DHA),
.28 (m, 8H, Ar), 13.51 (s, 1H, OH).
-(2-Chlorophenyl)-3-(4-hydroxy-6-methyl-2H-pyran-
-oxo-3-yl)-1-(2-benzothiazolyl)pyrazoline (7f):Yield 76 %;
m.p. 165-167 °C; IR (KBr, νmax, cm ): 1723, (C=O); H NMR
(CDCl , 300 MHz, δ): 2.25 (s, 3H, CH ), 6.01 (s, 1H, C5'-H,
DHA), 7.38 (s, 1H, C4-H), 7.28 (m, 8H,Ar), 13.5 (s, 1H, OH);
(
3
3
4
A
,
3
3
4
B
(
3
Anal. found: C, 60.62; H, 3.24; N, 9.64; C22
requires: C, 60.69; H, 3.26; N, 9.69 %.
14 3 3
H N O SCl
7
5
2
RESULTS AND DISCUSSION
-
1
1
m.p. 223-225 °C; IR (KBr, νmax, cm ): 1725, (C=O); H NMR
CDCl , 300 MHz, δ): 2.21 (s, 3H, CH ), 3.54 (dd, 1H, C -H
J = 17.4, 5.6 Hz), 4.21 (dd, 1H, C -H , J = 17.4, 10.8 Hz),
-H, J = 10.8, 5.6 Hz), 6.08 (s, 1H, C5'-H, DHA),
(
3
3
4
A
,
The 3-cinnamoyl-4-hydroxy-6-methylpyran-2-ones (3a-f)
i.e., chalcone analogues of dehydroacetic acid (DHA) were
prepared according to literature procedure by the reaction of
dehydroacetic acid (1) with various aromatic aldehydes on
refluxing in chloroform having few drops of piperidine for
4
B
5
.92 (dd, 1H, C
3
7
.27 (m, 8H, Ar), 13.51 (s, 1H, OH).
General procedure for the synthesis of 5-aryl-3-(4-
1
3,14
hydroxy-6-methyl-2H-pyran-2-oxo-3-yl)-1-(2-benzothia-
zolyl)-pyrazoles (8a-f): To a stirred solution of 7 (0.001 mol) in
dichloromethane (15 mL) was added iodobenzene diacetate
6-8 h
(Scheme-I). In order to prepare pyrazolines deriva-
tives, the chalcones (3a-f) were treated with various heteroaryl
hydrazines namely 2-hydrazino-4,6-dimethylpyrimidine (4),
2-hydrazino-4-methylquinoline (5) and 2-hydrazino-benzo-
thiazole (6), in ethanol under reflux. Surprisingly, the reaction
afforded the desired pyrazolines (7a-f) only in the case of 2-
hydrazinobenzothiazole (6). In other cases the starting materials
were recovered, (Scheme-II). Repeated efforts by changing
the reaction conditions did not show any significant improvement
(0.0012 mol) at room temperature. The reaction mixture was
stirred for 5 h. The progress of the reaction was monitored by
TLC. Dichloromethane was distilled off on a steam bath and the
residual gummy mass was triturated with petroleum ether to
remove iodobenzene and was purified by recrystallization from
ethanol to afford compound 8a-f in excellent yield.

8
086 Kinger et al.
Asian J. Chem.
OH
O
OH
O
O
Confirmation of the occurrence of the transformation of
pyrazolines 7a-f to pyrazoles 8a-f was based upon a careful
comparison of 1H NMR spectra. The spectra of pyrazolines
showed three characteristic signals due diastereotopic protons
CH3
CHCl3
Ar
+
ArCHO
piperidine
Reflux
H C
3
O
O
H C
3
O
2
3
1
(
HA, HB and HX). The proton which is cis to HX resonates
upfield in the range of δ 3.63-3.72 as a doublet of doublet (dd,
HAHB = ~17.7, JHAHX = ~5.2 Hz) while HB which is trans to
HX resonates downfield in the range of δ 4.18-4.24 as a dd
dd, JHAHB = ~17.7, JHBHX = ~10.1 Hz). The HX which is vicinal
to two methylene protons (H and H ) resonates as dd in the
Scheme-I: Synthesis of 3-cinnamoyl-4-hydroxy-6-methyl-2H-pyran-2-ones (3a-f)
J
CH3
N
(
A
B
H C
3
N
NHNH2
range of δ 5.62-5.68 (dd, JHAHX = ~5.2, JHBHX = ~10.1 Hz),
respectively. On the other hand, the spectra of the correspon-
ding oxidized products pyrazoles, which showed a characte-
ristic singlet at around δ ~7.4 due to C4 of the pyrazole, were
devoid of all the characteristic signals of starting pyrazoline.
4
Starting material
Starting materials
CH
3
Conclusion
N
NHNH
2
EtOH
5
In conclusion, we have prepared a series of novel pyrazo-
lines from the reaction of chalcone analogues of dehydroacetic
acid with various heteroaryl hydrazines and successfully
converted in to pyrazole using hypervalent iodine(III) mediated
oxidative approach, thereby emphasizing further utility of
iodine(III) reagents.
3
Reflux
N
N
S
S
NHNH2
OH
O
N
O
N
6
Ar
ACKNOWLEDGEMENTS
3
H C
7
The authors are thankful to Maharishi Markandeshwar
University, Mullana, India for financial assistance.
Scheme-II: Synthesis of 5-aryl-3-(4-hydroxy-6-methyl-2H-pyran-2-oxo-3-
yl)-1-hetarylpyrazolines (7a-f)
REFERENCES
in the formation of desired or undesired products. Therefore
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1
2
.
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.
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-yl)-1-(2-benzothiazolyl)pyrazoles (8a-f) in excellent yield,
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8
9
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(
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(
1
1
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N
N
S
S
(
1955).
OH
N
O
N
PhI(OAc)2
CH Cl
Stir, r.t.
OH
N
O
N
Ar
2
2
Ar
H
3
C
O
H
3
C
O
7
8
Scheme-III: Synthesis of 5-aryl-3-(4-hydroxy-6-methyl-2H-pyran-2-oxo-
-yl)-1-hetarylpyrazoles (8a-f); 8a: Phenyl; 8b: 4-
Methylphenyl; 8c: 4-Chlorophenyl; 8d: 2-Methoxyphenyl; 8e:
-Fluorophenyl; 8f: 2-Chlorophenyl
3
4