Synthesis of 3-(2-(4-chlorophenylimino)-3-(4-chlorophenyl)-2,3- dihydrothiazol-4-yl)-2 h-chromen-2-one via multicomponent approach

Article abstract of DOI:10.1080/00397911.2013.854915

A simple and highly efficient one-pot, three-component synthesis of 3-(2-(4-chlorophenylimino)-3-(4-chlorophenyl)-2,3-dihydrothiazol-4-yl) -2H-chromen-2-ones has been reported by the reaction of 3-(2-bromoacetyl)-2H- chromen-2-one, primary amines, and phenyl isothiocyanates in presence of dimethylformamide as a solvent. The structures of newly synthesized compounds were confirmed by their analytical and spectral data.

Full text of DOI:10.1080/00397911.2013.854915

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Synthesis of 3-(2-(4-
Chlorophenylimino)-3-(4-
chlorophenyl)-2,3-dihydrothiazol-4-
yl)-2 h-Chromen-2-one via
Multicomponent Approach
Raj Kumar Ramagiri a & Rajeswar Rao Vedula a
a Department of Chemistry , National Institute of Technology ,
Warangal , India
Accepted author version posted online: 02 Dec 2013.Published
online: 28 Mar 2014.
To cite this article: Raj Kumar Ramagiri & Rajeswar Rao Vedula (2014) Synthesis of 3-(2-
(4-Chlorophenylimino)-3-(4-chlorophenyl)-2,3-dihydrothiazol-4-yl)-2 h-Chromen-2-one via
Multicomponent Approach, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 44:9, 1301-1306, DOI: 10.1080/00397911.2013.854915
To link to this article: http://dx.doi.org/10.1080/00397911.2013.854915
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Synthetic Communications®, 44: 1301–1306, 2014
Copyright © Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397911.2013.854915
SYNTHESIS OF 3-(2-(4-CHLOROPHENYLIMINO)-3-
(4-CHLOROPHENYL)-2,3-DIHYDROTHIAZOL-4-YL)-2H-
CHROMEN-2-ONEVIA MULTICOMPONENT APPROACH
Raj Kumar Ramagiri and Rajeswar Rao Vedula
Department of Chemistry, National Institute of Technology, Warangal, India
Abstract A simple and highly efficient one-pot, three-component synthesis of
3-(2-(4-chlorophenylimino)-3-(4-chlorophenyl)-2,3-dihydrothiazol-4-yl)-2H-chromen-
2-ones has been reported by the reaction of 3-(2-bromoacetyl)-2H-chromen-2-one, primary
amines, and phenyl isothiocyanates in presence of dimethylformamide as a solvent. The
structures of newly synthesized compounds were confirmed by their analytical and spectral
data.
Keywords Coumarin; isothiocyanate; multicomponent reaction; phenyl; primary amines;
thiazol-2-imine
INTRODUCTION
In multicomponent reactions (MCRs) more than two components are assembled
into the product in a one-step reaction. The advantages of MCRs are atom economy,
simplicity, and time-saving features. These are useful for the synthesis of biologically
active compounds such as drugs and agrochemicals, and diversity is achieved easily
by varying the components.[1–3]
Coumarin (benzopyran-2-one) derivatives have found various medicinal appli-
cations as antibacterial,[4,5] antifungal,[6,7] herbicidal,[8] antitumoral,[9] cytotoxic,[10]
and anti-HIV agents.[11,12] The compounds containing the coumarin motif are widely
used as additives in food and cosmetic products and known as luminescent materials.
[13] They also act as anticoagulants,[14] free radical scavengers,[15] antioxidant,[16] lipoxy-
genase,[17] and cyclooxygenase inhibitors.[18]
Received July 19, 2013.
Address correspondence to Rajeswar Rao Vedula, Department of Chemistry, National Institute of
Technology, Warangal 506004, AP, India. E-mail: vrajesw@yahoo.com
1301

1302
R. K. RAMAGIRI AND R. R. VEDULA
Heterocyclic systems having nitrogen and sulfur are very interesting because of
their physicochemical properties with relevance to the design of new drugs. In particu-
lar the thiazoline ring system has attracted considerable attention because of its pres-
ence in several drug molecules with different biological activities such as antifungal,[19]
anti-inflammatory,[20] anti-HIV,[21] analgesic, kinase inhibition,[22] and melanin-reducing
activity.[23] These are also applied in agriculture as acricides, insecticides, and plant-
growth regulators.
Our current studies are focused on the development of new routes for the syn-
thesis of thiazol-2-imine incorporating coumarin moieties.
RESULTS AND DISCUSSION
Reaction of 3-(2-bromoacetyl)-2H-chromen-2-one 1, primary amines 2 with dif-
ferent phenyl isothiocyanates 3 in presences of dimethylformamide (DMF) gave thia-
zole-2-imine 4 in good yields (Table 1). All the synthesized compounds are new and not
reported in the literature (Scheme 1).
The mechanism for the formation of these products is discussed in Scheme 2.
In this procedure we have modified the known Hantzsch method for thiazole
synthesis involving the reaction of phenyl isothiocyanates, primary amines, and
3-(2-bromoacetyl)-2H-chromen-2-one compounds. In the literature[24] the synthesis
of 3-(4-phenyl thiazoline-2-anil)-2H-1-benzopyran-2-ones 9 by the condensation of
3-(2-bromoacetyl)-2H-chromen-2-ones 1 with symmetrical thiourea such as diphe-
nylthiourea 8 (Scheme 3) has been reported. As the scope for the synthesis of these
compounds is rather limited, we tried to develop the present one-pot multicompo-
nent synthesis of the title compounds. This procedures may find extensive applica-
tions in the synthesis of a wide variety of substituted thiazolines. This procedure is
Scheme 1. Three component one pot synthesis of thiazole-2-imines.
Scheme 2. Mechanism for the formation of 4.

ARYLIMINOTHIAZOLE DERIVATIVES OF COUMARIN
1303
Scheme 3. Literature method.
Table 1. Synthesis of compounds 4 and their corresponding yields
Product 4
R1
R2
R3
R4
R5
Yield (%)
a
b
c
d
e
f
g
h
i
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Cl
Cl
OCH3
Cl
OCH3
H
H
CH3
Cl
H
H
H
Cl
Cl
CH3
H
Cl
H
CH3
Cl
Cl
69
79
64
62
68
63
74
78
76
H
NO2
NO2
H
H
H
5,6-benzo
Cl
also novel compared to existing literature procedure. The structures of compounds
4a–i were confirmed by their infrared (IR), 1H NMR, and 13C NMR spectral data.
1
The H NMR spectrum of 4a in dimethylsulfoxide (DMSO) showed thiazole pro-
ton as a singlet at 6.92 and C4 proton of coumarin appeared at 8.30δppm. In the
13C NMR spectrum of 4a the imino and carbonyl carbons resonate at 157.7 and
158.8δppm respectively. The mass spectrum of 4a exhibited the [M+H]+ peak
at m/z 465. The reaction is presumed to start with interaction of primary amine
with phenyl isothiocyanate to give unsymmetrical thiourea 5. Then 5 reacts with
3-(2-bromoacetyl)-2H-chromen-2-one to form intermediate 6, which cyclizes to
result in 7. On loss of a water molecule this gives the end product 4.
CONCLUSIONS
This article reports an efficient, one-pot, three-component method for the
synthesis of 3-(2-(4-chlorophenylimino)-3-(4-chlorophenyl)-2,3-dihydrothiazol-4-yl)-
2H-chromen-2-ones from the reaction of 3-(2-bromoacetyl)-2H-chromen-2-ones in
good yields. The experimental conditions are simple and inexpensive and have easy
workup and clean reaction profiles. This multicomponent approach may be useful in
the synthesis of derivatives of medicinal importance.
EXPERIMENTAL
All the reagents and solvents were pure, purchased from commercial sources,
and used without further purification unless otherwise stated. 3-(2-Bromo-acetyl)-
2H-chromen-2-ones were prepared by the literature procedure.[25] Melting points
were determined in open capillaries with a Cintex melting-point apparatus (Mumbai,
India) and were uncorrected. CHN analysis was carried out by Carlo Erba EA 1108
automatic elemental analyzer. The purity of the compounds was checked by thin-layer

1304
R. K. RAMAGIRI AND R. R. VEDULA
chromatography (TLC) plates (E. Merck, Mumbai, India). IR spectra were recorded
on a thermo Nicolet Nexus 670 Q8 instrument (KBr pellets). 1H NMR spectra were
recorded on a Bruker WM-400 spectrometer in δ ppm using tetramethylsilane (TMS)
as the standard. Mass spectra (EI-MS) were determined on a Perkin-Elmer spectrom-
eter (SCIEX API-2000, ESI) at 12.5eV.
General Procedure for 4
A mixture of 3-(2-bromoacetyl)-2H-chromen-2-one 1 (1mmol), primary amine
2 (1mmol), and phenyl isothiocyanate 3 (1mmol) were taken in DMF (10ml) and
refluxed for 1h. After completion of the reaction, the resulting mixture was cooled,
filtered, and recrystallized from ethanol.
3-(2-(4-Chlorophenylimino)-3-(4-chlorophenyl)-2,3-dihydrothiazol-4-yl)-
2H-chromen-2-one (4a)
A mixture of 3-(2-bromoacetyl)-2H-chromen-2-one (1mmol), 4-chloro aniline
(1mmol), and 4-chlorophenyl isothiocyanate (1mmol) were taken in DMF (10 ml)
and refluxed for 1h. After completion of the reaction, the resulting mixture was
cooled, filtered, and recrystallized from ethanol. Color: white solid, mp: 298–300 °C,
yield: 69%; IR (KBr) cm−1: 1718 (lactone C=O), 1636 (C=N), 1599 (C=C); 1H NMR
(400MHZ, DMSO-d6): δ 6.92 (1H, s, =CH), 7.11 (2H, d, J=8Hz, ArH), 7.36–7.49
(8H, m, ArH), 7.64–7.68 (1H, m, ArH), 7.77 (1H, d, J=8Hz, ArH), 8.30 (1H, s, C-4
of coumarin) ppm, 13C NMR (DMSO-d6): δ 101.6, 116.2,118.3, 118.6, 122.8, 124.9,
126.8, 128.7, 129, 129.4 130.2, 132.2, 132.8, 133.6, 135.9, 145, 149.9, 153.3, 157.7,
158.8ppm; ESI-MS: m/z (%); 465 [M+H]+. Anal. calcd for C24H14Cl2N2O2S: C, 61.94;
H, 3.03; N, 6.02. Found: C, 61.90; H, 3.12; N, 6.12.
SUPPLEMENTAL MATERIAL
Supplemental data for this article can be accessed on the publisher’s website.
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