Synthesis of 3-(2-(4,5-Dihydro-3,5-diphenylpyrazol-1-yl)thiazol-4-yl)-2H- chromen-2-one Derivatives via Multicomponent Approach

Article abstract of DOI:10.1080/00397911.2013.796522

An efficient synthesis of 3-(2-(4,5-dihydro-3,5-diphenylpyrazol-1-yl) thiazol-4-yl)-2H-chromen-2-one derivatives by a simple, atom-economical, and multicomponent reaction of chalcones, thiosemicarbazide, and 3-(2-bromoacetyl) coumarins in the presence of

Full text of DOI:10.1080/00397911.2013.796522

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Synthesis of 3-(2-(4,5-Dihydro-3,5-
diphenylpyrazol-1-yl)thiazol-4-
yl)-2H-chromen-2-one Derivatives via
Multicomponent Approach
Sreenu Pavurala a & Rajeswar Rao Vedula a
a Department of Chemistry , National Institute of Technology ,
Warangal , Andhra Pradesh , India
Accepted author version posted online: 28 Oct 2013.Published
online: 27 Dec 2013.
To cite this article: Sreenu Pavurala & Rajeswar Rao Vedula (2014) Synthesis of 3-(2-(4,5-Dihydro-3,5-
diphenylpyrazol-1-yl)thiazol-4-yl)-2H-chromen-2-one Derivatives via Multicomponent Approach,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 44:5, 583-588, DOI: 10.1080/00397911.2013.796522
To link to this article: http://dx.doi.org/10.1080/00397911.2013.796522
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Synthetic Communications1, 44: 583–588, 2014
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2013.796522
SYNTHESIS OF 3-(2-(4,5-DIHYDRO-3,5-
DIPHENYLPYRAZOL-1-YL)THIAZOL-4-YL)-2H-
CHROMEN-2-ONE DERIVATIVES VIA
MULTICOMPONENT APPROACH
Sreenu Pavurala and Rajeswar Rao Vedula
Department of Chemistry, National Institute of Technology, Warangal,
Andhra Pradesh, India
GRAPHICAL ABSTRACT
Abstract An efficient synthesis of 3-(2-(4,5-dihydro-3,5-diphenylpyrazol-1-yl)thiazol-4-
yl)-2H-chromen-2-one derivatives by a simple, atom-economical, and multicomponent
reaction of chalcones, thiosemicarbazide, and 3-(2-bromoacetyl) coumarins in the presence
of aqueous sodium hydroxide in refluxing ethanol is reported. The structures of newly
prepared compounds have been confirmed by their analytical and spectral (IR, 1HNMR,
13CNMR and mass) data.
[Supplementary materials are available for this article. Go to the publisher’s online
edition of Synthetic Communications1 for the following free supplemental resource(s):
Full experimental and spectral details.]
Keywords Chalcone; coumarin; multicomponent; pyrazole; thiazole
INTRODUCTION
Thiazole ring-containing compounds show pharmacological activities such as
antimicrobial,[1] antiinflammatory,[2] antitubercular,[3] antitumor,[4] cardiotonic,[5]
analgesic,[6] anti-HIV,[7] and anti-allergenic[8] activities. These are used in drug
development for the curing of allergies,[9] schizophrenia,[10] and as hypnotics,[11]
and the different substituents of pyrazolines show various pharmacological activities
such as antinociceptive,[12] anticancer,[13] antidepressant,[14] and antidiabetic[15]
activities.
Received January 27, 2013.
Address correspondence to Rajeswar Rao Vedula, Department of Chemistry, National Institute of
Technology, Warangal 506 004, Andhra Pradesh, India. E-mail: vrajesw@yahoo.com
583

584
S. PAVURALA AND R. R. VEDULA
Chalcones have good pharmacological properties such as nitric oxide
inhibition,[16] and antioxidant,[17] antimalarial,[18] analgesic,[19] antiviral,[20] and
antitubercular[21] activity.
Coumarin-containing compounds show a broad range of biological activities
such as anthelmintic insecticide,[22] antifungal,[23] and herbicidal[24] activities. Its
derivatives show various pharmacological and physiological activities such as antico-
agulant,[25] antiviral,[26] bactericidal,[27] and anti-inflammatory[28] activity.
Recently multicomponent reactions have been widely used in organic synthesis
because of their advantages such as high efficiency, atom economy, convergence,
exploratory power, and greater yield, leading to the straightforward synthesis of
new structures.[29]
In continuation of our earlier work[30,31] on the synthesis of a heterocyclic
system derived from coumarin, we report here in the facile one-pot synthesis of 3-
(2-(4,5-dihydro-3,5-diphenylpyrazol-1-yl)thiazol-4-yl)-2H-chromen-2-one derivatives.
RESULTS AND DISCUSSION
Synthesis of 3-(2-(4,5-dihydro-3,5-diphenylpyrazol-1-yl)thiazol-4-yl)-2H-chromen-
2-ones (4) if has been achieved in one pot by using different substituted chalcones (1), thio-
semicarbazide (2), and different substituted 3-(2-bromoacetyl)-2H-chromen-2-ones (3) in
ethanol containing aqueous NaOH. These compounds are obtained in good yields.
Method 1
The structures (4) of newly prepared compounds were confirmed by unambigu-
ous synthesis. In this method chalcones were reacted with thiosemicarbazide to give
a
thioamide intermediate. These compounds were reacted with various
3-(2-bromoacetyl) coumarins in absolute ethanol to yield the compounds 4. This is
a stepwise and unambiguous process. The products (4) obtained by both methods
were found to be identical by their mixed melting points and thin-layer chromato-
graphic (TLC) and infrared (IR) spectra (Scheme 1).
Method 2
The structures of the title compounds have been identified by analytical and
spectral data (Scheme 2). In the IR spectrum the compound 4a showed lactone
ꢀ1
ꢀ1
=
C O stretching vibration at 1719 cm and C N stretching vibration at 1545 cm
=
.
Scheme 1. Synthesis of 3-(2-(4,5-dihydro-3,5-diphenylpyrazol-1-yl)thiazol-4-yl)-2H-chromen-2-one
derivatives via multicomponent approach.

THIAZOLYL PYRAZOLINE
585
Scheme 2. Unambiguous synthesis of 3-(2-(4,5-dihydro-3,5-diphenylpyrazol-1-yl)thiazol-4-yl)-2H-
chromen-2-one.
The 1HNMR spectrum of 4a showed three double doublets (ABX pattern) at d 3.36,
3.93, and 5.64, integrating for one proton each, and assigned to HA, HB, HX proton
of pyrazolone[32] ring respectively. Aromatic protons appeared at d 7.25–7.80 and
C-4 of coumarin proton appeared at d 8.17. The 13CNMR spectrum of 4a shows ali-
phatic carbons at d 43.4, 64.2 and the lactone carbonyl carbon appeared at 151.5. In
the mass spectrum (ESI-MS) compound 4a showed quasi-molecular-ion peak at m=z
450. See Scheme 3 and Table 1.
CONCLUSION
In summary we have synthesized 3-(2-(4,5-dihydro-3,5-diphenylpyrazol-1-
yl)thiazol-4-yl)-2H-chromen-2-ones via multicomponent reaction of different chal-
cones, thiosemicarbazide, and substituted 3-(2-bromoacetyl)-2H-chromen-2-ones in
ethanol containing aqueous NaOH in a one-pot reaction. It is a more efficient
synthesis because of short reaction time, few steps, and high yields.
EXPERIMENTAL
All the reagents and solvents were purchased from commercial sources and
were used without further purification unless otherwise stated. 3-(2-Bromoacetyl)-
coumarins[34] were prepared by the literature procedure. Melting points were deter-
mined in open capillaries with a Stuart melting-point apparatus (Mumbai, India)
and were uncorrected. CHNS analysis was done on a Carlo Erba EA 1108 automatic
elemental analyzer. The purity of the compounds was checked by TLC plates (E.
Merck Mumbai, India). IR spectra (KBr) were recorded on a Perkin-Elmer spectrum
100S. 1H NMR spectra were recorded on a Bruker WM-400 spectrometer in d parts

586
S. PAVURALA AND R. R. VEDULA
Scheme 3. Mechanism[33] for the formation of product 4.
Table 1. Times and yields of compounds prepared
Entry
4
R1
R2
R3
Time (h)
Yield (%)
1
2
4a
4b
4c
4d
4e
4f
H
H
H
H
Br
H
Cl
H
H
H
H
Br
H
Cl
H
Br
4
4
6
4
6
5
4
4
4
6
4
6
85
80
82
80
84
78
80
85
82
80
76
85
3
H
Br
Cl
4
H
5
H
Cl
6
H
NO2
OCH3
H
7
4g
4h
4i
H
8
Br
Br
Br
Br
Br
9
Br
Br
10
11
12
4j
4k
4l
Cl
Cl

THIAZOLYL PYRAZOLINE
587
per million (ppm) using tetramethylsilane (TMS) as the standard. Electronspray
ionization mass spectra (ESI-MS) were determined on Perkin-Elmer instrument
(SCIEX API-2000, ESI) at 12.5 eV.
A mixture of 1,3-diphenyl-propenone (1 mmol), thiosemicarbazide (1 mmol),
3-(2-bromoacetyl)-2H-chromen-2-ones (1 mmol), and aqueous NaoH (0.08 in 1 ml
of water) in ethanol (10 ml) was refluxed for 4 h and cooled, and the solid separated
1
was filtered and recrystallized from methanol. Yellow solid, mp 261–263 ꢁC. H
NMR (400 MHz, DMSO-d6) (d, ppm): 3.36 (dd, J ¼ 17.4 Hz, 7.4 Hz, 1H, HA),
3.93 (dd, J ¼ 17.4 Hz, 11.8 Hz, 1H, HB), 5.64 (dd, J ¼ 11.8 Hz, 7.4 Hz, 1H, HX),
7.25–7.46 (m, 13H, ArH), 7.76–7.80 (m, 2H, ArH), 8.17 (s, 1H, C-4 of coumarin);
13C NMR (DMSO-d6, d ppm): 43.0, 64.4, 111.0, 115.8, 119.0, 120.4, 124.7, 126.4,
127.0, 127.6, 128.5, 128.8, 130.0, 130.8, 131.6, 138.2, 141.5, 143.7, 152.2, 153.3,
158.5, 163.5; IR (KBr, t, cmꢀ1): 1719 (lactone carbonyl), 1545 (C N); ESI-MS:
=
m=z ¼ 450 (M þ 1) Anal. calcd. for C27H19N3O2S: C, 72.14; H, 4.26; N, 9.35. Found:
C, 71.18; H, 4.22; N, 9.32.
Spectral and analytical data for other synthesized compounds are available in
the online supplemental section.
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