An expedient one-pot tandem method for the synthesis of 3-(2-(phenylamino)thiazol-4-yl)-2H-chromen-2-ones under green conditions

Article abstract of DOI:10.1007/s13738-019-01661-y

This paper describes a facile pathway for the one-pot three-component synthesis of 3-(2-(phenylamino)thiazol-4-yl)-2H-chromen-2-ones starting from ethyl-4-chloroacetoacetate by treating it with equimolar amounts of various phenylthioureas independently re

Full text of DOI:10.1007/s13738-019-01661-y

Journal of the Iranian Chemical Society
https://doi.org/10.1007/s13738-019-01661-y
ORIGINAL PAPER
An expedient one‑pot tandem method for the synthesis
of 3‑(2‑(phenylamino)thiazol‑4‑yl)‑2H‑chromen‑2‑ones under green
conditions
K. Kavitha1 · D. Srikrishna1 · Pramod Kumar Dubey1 · P. Aparna1
Received: 28 September 2018 / Accepted: 2 April 2019
© Iranian Chemical Society 2019
Abstract
This paper describes a facile pathway for the one-pot three-component synthesis of 3-(2-(phenylamino)thiazol-4-yl)-2H-
chromen-2-ones starting from ethyl-4-chloroacetoacetate by treating it with equimolar amounts of various phenylthioureas
independently reaction with Salicylaldehyde. Use of biosynthetically prepared l-proline as an efcient catalyst and naturally
extracted renewable poly(ethylene) glycol-600(PEG-600) as an efective green reaction media are the added advantages of
this method. Alternatively, tandem, stepwise methods have been proposed and isolated the intermediate, to study the pos-
sible reaction mechanism. These reactions are very simple, rapid, cost efective, industrially viable, which would be applied
for various biomass conversions.
Keywords Salicylaldehyde · Ethyl-4-chloroacetoacetate · Phenylthioureas · l-Proline · Environmentally benign conditions
Introduction
frame work. One of the most commonly used procedures
for the synthesis of the thiazole ring that fused to cou-
marin is based on the reaction of 3-(2-bromoacetyl)-2H-
chromen-2-one with thioureas. Thus, for the preparation of
3-(2-(phenylamino)thiazol-4-yl)-2H-chromen-2-ones, the
starting material is 3-(2-bromoacetyl)-2H-chromen-2-one.
Not only for the preparation of title compounds but also
for the synthesis of various other heterocyclic compounds
like triazole, thiadiazine, thiophene, imidazole, pyrazole,
pyran and pyridine derivatives the key starting material is
3-(2-bromoacetyl)-2H-chromen-2-one (Fig. 2).
Coumarin and coumarin-related compounds have proved
for many years to have signifcant therapeutic potential.
Observation of the literature on coumarin and its derivatives
exhibited potential biological activities such as anti-cancer
[1], anti-microbial [2], anti-HIV [3], anti-oxidant [4], anti-
tubercular [5], anti-asthmatic [6] and anti-convulsant [7].
Coumarins are also found to be active pharmacophores in
various drugs. Some of the coumarin nucleus containing
drugs with varied therapeutic activity are Chromonar, Ensa-
culin, Hymecromone, Warfarin, Bantoprazine, etc (Fig. 1).
Furthermore, thiazoles and its derivatives were found to
show potent pharmacological activities such as anti-HIV [8],
anti-tumor [9], anthelmintic [10], anti-infammatory [11],
anti-convulsant [12] and anti-fungal agents [13].
Thus, 3-(2-bromoacetyl)-2H-chromen-2-one is an impor-
tant precursor and has wide range of applications in the syn-
thesis of variety of heterocyclic compounds but sufering
from drawbacks such as its two step synthesis, bromination
reaction with liquid bromine is highly hazardous. Hence,
there is a need for the development of new fexible green
and efcient protocols that reduce the number of steps and
bypass 3-(2-bromoacetyl)-2H-chromen-2-one in order to
obtain the desired products. A high yield thiazole synthesis
approach allows us to begin from the commodity chemicals
(ethyl-4-chloroacetoacetate, phenylthiourea and salicylal-
dehyde) and bypass both 3-acetyl-2H-chromen-2-one and
3-(2-bromoacetyl)-2H-chromen-2-one intermediates (Fig. 3)
that are used in the original thiazole synthesis (Fig. 3a) by
In the view of importance of coumarin, thiazole deriva-
tives, it was considered worthwhile to synthesize the com-
pounds containing coumarin with thiazole ring in a single
* P. Aparna
aparnajntu5@gmail.com
1
Department of Chemistry, Jawaharlal Nehru Technological
University Hyderabad College of Engineering,
Kukatpally, Hyderabad, Telangana 500 085, India
Vol.:(0123456789)
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Journal of the Iranian Chemical Society
Fig. 1 Drugs with coumarin
nucleus and their structures
N
O
N
N
O
O
O
O
O
O
O
O
O
Ensaculin (KA-672) - Drug for Dementia
Chromonar - vasodilator.
O
OH
O
O
O
O
HO
O
O
N
H
Hymecromone-
antispasmodic drug
Warfarin - Anticoagualnt
Batoprazine - antiaggressive agent
Fig. 2 3-(2-bromoacetyl)-2H-
chromen-2-one: A key starting
material for the synthesis of
various heterocycles
using a one-pot method under green reaction conditions
(Fig. 3b).
One-pot synthesis constitute one of the most efective
tools in modern organic chemistry, since they have features
that contribute to an ideal synthesis such as atom economy,
rapid and easy implementation, energy and time saving,
eco-friendly methods and they ofer a target and diversity-
oriented synthesis. Development of new one-pot reactions
toward pharmacologically active scafolds is inevitable at the
present time whereby a reactant is subjected to successive
chemical operations in a single reaction vessel.
Siddiqui et al. reported [14] the synthesis of thiazoles
by treating 3-(2-bromoacetyl)-2H-chromen-2-one with
thiourea and its derivatives in refuxing ethanol. Rao et al.
reported [15] the tandem synthesis of coumarinyl thiazoles
by reacting 3-(2-bromoacetyl)-2H-chromen-2-ones with
potassium thiocyanate for 1 h followed by further addition
of arylamines at 60-65 °C for a period of 2 h. Koti et al.
[16] reported the reaction between 3-(2-bromoacetyl)-2H-
chromen-2-ones and substituted thiourea derivatives using
ethanol as a solvent under refux conditions for 12 h to give
thiazoles.
Thus, based on the above literature precedence and in
continuation of our previous work [17–22], it was thought
of interest to prepare the compounds containing coumarin
ring with thiazole moiety as hybrid molecules in a one-pot
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Journal of the Iranian Chemical Society
Fig. 3 Earlier approach versus present approach toward the synthesis of target compounds
three-component method under environmentally benign
conditions.
were screened. This optimization data (Table 1) revealed
that the reaction was found to be completed very smoothly
when Poly(ethylene glycol)-600 (PEG-600) was used as a
reaction media (Scheme 1). Further, interestingly, this reac-
tion completed at room temperature (RT) itself to give the
desired product with best purity and selectivity.
Results and discussion
In order to synthesize the target compounds, we began our
investigation by a stepwise strategy. Thus, in a model reac-
tion, equimolar amounts of ethyl-4-chloroacetoacetate (1)
and phenylthiourea (2a) were reacted together in refuxing
ethanol for 6 h to obtain ethyl 2-(2-(phenylamino)thiazol-
4-yl)acetate (3) in 65% yield. In order to obtain the product
3 in lesser time, higher yield with best purity at ambient tem-
perature, we have optimized the reaction and several solvents
The mechanism for the formation of 3 as well as the
reason for completion of reaction at RT itself when PEG-
600 has been used as solvent was studied (Scheme 2), and it
is probably due to the triple role of PEG as base, phase trans-
fer catalyst (PTC) and reaction media which was reported
earlier in the literature [23–28]. There are various litera-
ture reports where PEG has been utilized successfully in
enhancing the substitution reactions with excellent yields
Table 1 Optimization data for
the synthesis of 3 from 1 and 2
S. no.
Solvent
Reaction condition
Reaction time
Yield# (%)
1
2
3
4
5
6
7
8
Ethanol
Ethanol
RT
Refux
RT
Refux
RT
Refux
RT
100 °C
RT
100 °C
RT
100 °C
RT
100 °C
RT
15 h
6 h
15 h
7 h
15 h
6 ½ h
15 h
5 ½ h
15 h
5 h
Nil
65
Nil
58
Nil
68
Nil
76
Nil
77
93
90
Acetonitrile
Acetonitrile
Tetrahydrofuran
Tetrahydrofuran
Ethylene glycol
Ethylene glycol
Glycerol
Glycerol
PEG-600
PEG-600
9
10
11
12
13
14
15
16
4 h
3 ½ h
15 h
10 h
15 h
7 h
Dimethylformamide
Dimethylformamide
Acetone
Nil
42
Nil
64
Acetone
Refux
Bold specifes the efciency of the PEG-600 solvent among all chosen at RT
#Isolated yield
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Journal of the Iranian Chemical Society
Scheme 1 Synthesis of ethyl
2-(2-(phenylamino)thiazol-4-yl)
acetate (3)
O
O
O
O
H
N
H2N
H
N
N
PEG-600 / RT / 4 h
Cl
Ph
+
O
Ph
S
S
(1)
(2a)
(3)
Scheme 2 Plausible mecha-
nism for the formation of 3 in
PEG-600
H
H2N
N
Ph
S
O
O
PEG-600
O
O
O
O
O
H
H
acts as PTC
O
Cl
+
NH
O
N
& enhances the
NH
NH
Ph
(2a)
reaction progress
S
NH
Ph
S
N
Ph
HS
(1)
O
O
O
O
O
O
OH
NH
H
N
N
NH
Ph
N
H
N
Ph
S
Ph
S
S
H
(3)
[29–31]. The same is the case here also, where ethyl-4-chlo-
roacetoacetate (1) will undergo nucleophilic substitution
with phenylthiourea (2a) in its thiol form which typically
requires a PTC to forward the reaction smoothly. Thus,
for this reaction, PEG-600 acts as a PTC and enhances the
progress of reaction to give the corresponding condensed
compound which further undergoes cyclization to give ethyl
2-(2-(phenylamino)thiazol-4-yl)acetate (3). Also, PEG is a
hydrophilic polymer and many organic substrates are read-
ily soluble in PEG, and thus, they have been proposed as
solvents for organic reactions [32, 33].
even after heating the reaction mixture to 100 °C for 10 h
(Scheme 3).
With the above observations and to move further, the use
of a catalyst has been checked for this one-pot reaction to
facilitate the Knoevenagel condensation. Thus, equimolar
quantities of ethyl-4-chloroacetoacetate (1), phenylthiourea
(2a) and salicylaldehyde (4) were reacted together in PEG-
600 using l-proline as a green catalyst at RT. But the use
of catalyst in this one-pot method was also not successful
in giving the desired product and ended up with the forma-
tion of undesired compound, i.e., ethyl 2-(chloromethyl)-
2-hydroxy-2H-chromene-3-carboxylate (6) as the major
product along with very minute ethyl 2-(2-(phenylamino)
thiazol-4-yl)acetate (3) and un reacted phenylthiourea (2a)
(Scheme 4).
Having the optimization data in hand, it was thought
of interest to prepare the title compounds in a one-pot
method and the best result, i.e., PEG-600 as the reaction
media has been taken forward. Thus, equimolar quanti-
ties of ethyl-4-chloroacetoacetate (1), phenylthiourea (2a)
and salicylaldehyde (4) were reacted together in PEG-600
at RT for 10 h. From this experiment, we understood that
the reaction has not worked out to give the desired product
and instead it stopped at the intermediate stage, i.e., ethyl
2-(2-(phenylamino)thiazol-4-yl)acetate (3) and recovery of
salicylaldehyde (4). It can be understood and indeed a base
is required in order to carry the Knoevenagel condensation
between an active methylene compound and carbonyl com-
pound [34–37]. PEG-600 was not able to do the work here
In order to understand the reaction carefully, a separate
experiment was conducted between ethyl-4-chloroacetoac-
etate (1) and salicylaldehyde (4) assuming the formation
of 3-(2-chloroacetyl)-2H-chromen-2-one. But this experi-
ment showed the formation of ethyl 2-(chloromethyl)-2-hy-
droxy-2H-chromene-3-carboxylate (6) instead of expected
-(2-chloroacetyl)-2H-chromen-2-one. Use of other cata-
lysts like piperidine, triethylamine, pyridine and sulfamic
acid on this reaction also showed no change in the product
formation.
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Journal of the Iranian Chemical Society
Scheme 3 Attempts for the
one-pot synthesis of 3-(2-(phe-
nylamino)thiazol-4-yl)-2H-
chromen-2-one (5a) in PEG-600
O
O
N
PEG-600 / / RT / 10 h
H
N
Ph
S
(5a)
H
O
O
H2N
N
Cl
Ph
O
+
S
(1)
(2a)
PEG-600 / 100 0
/ 10 h
C
OH
CHO
(4)
O
O
OH
N
+
NH
Ph
PEG-600 / / RT / 10 h
CHO
S
(3)
(4)
Scheme 4 Attempts for the
one-pot synthesis of 3-(2-(phe-
nylamino)thiazol-4-yl)-2H-
chromen-2-one (5a) in PEG-600
using l-proline as a catalyst
O
O
N
PEG-600 / L-proline / RT / 4 h
H
N
Ph
S
(5)
H
O
O
H2N
N
Cl
Ph
(2a)
O
+
S
(1)
OH
CHO
(4)
OH
O
H
N
Cl
O
H2N
+
Ph
S
PEG-600 / L-proline / RT / 4 h
O
(2a)
(6)
H
N
Similarly, in order to clear the doubt on the formation of
Schif’s base, an experiment has been conducted between
salicylaldehyde (1) and phenylthiourea (2a) and progress
of the reaction was monitored by TLC for the possibility of
any product under same reaction conditions. Fortunately,
in this case, no reaction taken place between the substrates
and both the starting materials were recovered (Scheme 5).
Based on the above observations and to avoid the forma-
tion of undesired compound 6, a one-pot tandem method
has been carried out, where we have given enough time for
the complete consumption of starting materials to form 3,
and added equimolar amount of salicylaldehyde along with
catalytic amount of l-proline in the same reaction vessel
H2N
OH
OH
S
H
2a
(
N
N
)
CHO
(
)
4
PEG-600 / RT / 6 h
S
(
)
7
Scheme 5 Possibility for the formation of Schif’s base by reaction of
4 with 2a
and stirred for another 3 h. This one-pot method worked
well for the formation of desired compound 5a in good
yield with no other side products (Scheme 6).
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Journal of the Iranian Chemical Society
OH
O
O
O
O
O
O
H
N
PEG-600
RT / 4 h
CHO
N
N
H2N
(4)
H
N
Cl
NH
Ph
+
Ph
O
S
Ph
S
S
L-proline / RT / 3 h
(1)
(2)
(3)
(5a)
Scheme 6 One-pot, tandem strategy for the synthesis of 3-(2-(phenylamino)thiazol-4-yl)-2H-chromen-2-one (5a) in PEG-600 using l-proline as
a catalyst
Encouraged with the above result, we have extended the
scope of this one-pot protocol to various other phenylthiou-
rea derivatives to obtain the target thiazoles, i.e., 3-(2-(phe-
nylamino)thiazol-4-yl)-2H-chromen-2-ones (5) in good to
excellent yields (Scheme 7).
Experimental section
Melting points are uncorrected and were determined in open
capillary tubes using sulfuric acid bath. TLC analyses were
done on silica gel-G coated sheets supplied by Merck Com-
pany and visualization was done using UV lamp and iodine.
1H NMR spectra were recorded in DMSO-d6 using TMS as
an internal standard with a Bruker Avance DRX-400 instru-
ment at 400 MHz. Mass spectra were recorded on Agilent-
LCMS instrument. Starting materials like salicylaldehyde,
ethyl 4-chloroacetoacetate, o-phenylenediamines were pur-
chased from commercial suppliers and used as such.
Conclusion
In conclusion, we have demonstrated an efcient selective
one-pot three-component synthetic protocol providing an
easy access to a wide range of 3-(2-(phenylamino)thiazol-
4-yl)-2H-chromen-2-ones starting from simple chemicals.
With this protocol, we have reduced the three steps pro-
cess to a one-step process and also we have given a broad
scope for emerging researchers to explore further possibili-
ties. It has been found from these results, the substituents
with electron withdrawing groups were shown high yield
comparatively with the electron releasing groups. Apart
from all of these, mild reaction conditions, easy work-up
procedures, operational simplicity and cost efciency render
this approach as an interesting alternative to the existing
methods.
Preparation of 3 from 1 and 2a
A mixture of 1 (20 mmol), 2a (20 mmol) and PEG-600
(30 mL) was stirred at RT for 4 h. After completion of
the reaction, the mixture was poured into ice-cold water
(60 mL). The separated solid was fltered, washed with
water (2× 30 mL) and air-dried at RT. The crude product
was recrystallized from methanol to obtain pure 3. White
color solid. Yield: 4.55 g (87%). mp: 68–70 °C.
OH
O
O
O
O
O
O
H
N
PEG-600
RT / 4 h
CHO
N
N
H2N
H
N
(4)
Cl
+
NH
Ar
Ar
O
S
Ar
L-proline / RT / 2-3 h
S
S
(1)
3 (a-l)
5 (a-l)
2 (a-l)
5a: Ar=C6H5,
5b: Ar=(4)Cl-C6H5,
2a: Ar=C6H5,
2b: Ar=(4)Cl-C6H5,
5c: Ar=(2)Cl-C6H5,
5e: Ar=(4)F-C6H5,
5d: Ar=(2)Cl,(4)F-C6H5,
5f: Ar=(4)OCH3-C6H5,
2c: Ar=(2)Cl-C6H5,
2e: Ar=(4)F-C6H5,
2d: Ar=(2)Cl,(4)F-C6H5,
2f: Ar=(4)OCH3-C6H5,
5g: Ar=(4)CH3-C6H5, 5h: Ar=(4)NO2-C6H5,
5i: Ar=(4)Br-C6H5, 5j: Ar=(2)NO2-C6H5,
5k: Ar=(2)Br,(4)F-C6H5, 5l: Ar=(2)Br-C6H5
2g: Ar=(4)CH3-C6H5, 2h: Ar=(4)NO2-C6H5,
2i: Ar=(4)Br-C6H5, 2j: Ar=(2)NO2-C6H5,
2k: Ar=(2)Br,(4)F-C6H5, 2l: Ar=(2)Br-C6H5
Scheme 7 One-pot, tandem method for the synthesis of title compounds
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Journal of the Iranian Chemical Society
(d, J=8.0 Hz, 1H, Ar–H), 8.61 (s, 1H, Ar–H) and 9.81 (s,
1H, –NH); 13C-NMR (100 MHz, DMSO-d6): 109.4, 115.5,
118.1, 119.0, 120.3, 124.0, 125.4, 127.8, 128.2, 130.7,
136.9, 137.0, 138.1, 139.3, 143.5, 152.1, 159.0, 162.1;
HRMS calculated for C18H11ClN2O2S [M+H]+: 355.0308,
Found: 355.0310.
General procedure for the synthesis of 5 from 1, 2
via 3
A mixture of 1 (10 mmol), 2 (10 mmol) and PEG-600
(30 mL) was stirred at RT for 4–5 h. Then, salicylaldehyde
(10 mM) and l-proline (25 mol %) was added into the same
reaction vessel and the reaction mixture was stirred at RT
for a period of 2–3 h. After completion of the reaction, as
shown by TLC analysis, the mixture was poured into ice-
cold water (60 mL). The separated solid was fltered, washed
with water (2×30 mL) and air-dried at RT. The crude prod-
uct was recrystallized from suitable solvent to obtain pure 5.
3‑(2‑((2‑chloro‑4‑fuorophenyl)amino)
thiazol‑4‑yl)‑2H‑chromen‑2‑one (5d)
Yellow solid. Yield: 3.19 g (86%); mp 124–126 °C (Etha-
nol); IR(KBr) νmax/cm−1: 1713 cm−1 (strong, sharp, –CO
of coumarin ring), 3360–3450 cm−1 (broad, medium, –NH
group); 1H-NMR (400 MHz, DMSO-d6/TMS): δ=6.98 (d,
J=9.2 Hz, 2H, Ar–H), 7.40 (t, J=7.6 Hz, 1H, Ar–H), 7.47
(s, 1H, Ar–H), 7.61–7.68 (complex, m, 3H, Ar–H), 7.72 (s,
1H, Ar–H), 8.67 (s, 1H, Ar–H) and 10.15 (s, 1H, –NH);
13C-NMR (100 MHz, DMSO-d6): 117.7, 118.5, 119.6,
120.6, 125.2, 129.2, 132.1, 138.6, 139.6, 139.8, 143.9,
151.2, 152.7, 153.6, 159.1, 162.6; HRMS calculated for
C18H10ClFN2O2S [M+H]+: 373.0213, Found: 373.0402.
3‑(2‑(Phenylamino)thiazol‑4‑yl)‑2H‑chromen‑2‑one (5a)
Yellow solid. Yield: 2.78 g (87%); mp 244–246 °C (Metha-
nol); IR(KBr) νmax/cm−1: 1728 cm−1 (strong, sharp, –CO
of coumarin ring), 3390–3430 cm−1 (broad, medium, –NH
group); 1H-NMR (400 MHz, DMSO-d6/TMS): δ=6.98 (d,
J=8.8 Hz, 2H, Ar–H) 7.39-7.68 (complex, m, 6H, Ar–H),
7.72 (s, 1H, Ar–H), 7.96 (d, J = 6.8 Hz, 1H, Ar–H), 8.67
(s, 1H, Ar–H), 10.15 (s, 1H, –NH); 13C-NMR (100 MHz,
DMSO-d6): 110.3, 116.3, 117.5, 119.7, 120.7, 121.9, 125.1,
129.4, 129.6, 132.1, 139.0, 141.4, 144.0, 152.7, 159.2,
162.9; HRMS calculated for C18H12O2N2S [M + H]+:
321.0697, Found: 321.0707.
3‑(2‑((4‑Fluorophenyl)amino)
thiazol‑4‑yl)‑2H‑chromen‑2‑one (5e)
Yellow solid. Yield: 2.80 g (83%); mp 126–128 °C (Metha-
nol); IR(KBr) νmax/cm−1: 1717 cm−1 (strong, sharp, –CO
of coumarin ring), 3390–3450 cm−1 (broad, medium, –NH
group); 1H-NMR (400 MHz, DMSO-d6/TMS): δ=7.19–7.94
(complex, m, 8H, Ar–H), 7.96 (s, 1H, Ar–H), 8.69 (s, 1H,
Ar–H) and 10.38 (s, 1H, –NH); 13C-NMR (100 MHz,
DMSO-d6): 109.8, 115.4, 115.6, 115.8, 118.6, 118.6, 119.2,
120.2, 124.6, 128.9, 131.6, 137.4, 138.6, 143.5, 152.2, 155.7,
158.1, 158.7, 162.5; HRMS calculated for C18H11lFN2O2S
[M+H]+: 339.0603, Found: 339.0599.
3‑(2‑((4‑Chlorophenyl)amino)
thiazol‑4‑yl)‑2H‑chromen‑2‑one (5b)
Yellow solid. Yield: 2.90 g (82%); mp>250 °C (Ethanol);
IR(KBr) νmax/cm−1: 1701 cm−1 (strong, sharp, –CO of
coumarin ring), 3380–3460 cm−1 (broad, medium, –NH
1
group); H-NMR (400 MHz, DMSO-d6/TMS): δ = 7.13
(t, J=1.2 Hz, 1H, Ar–H), 7.36–7.66 (m, 5H, Ar–H), 7.82
(s, 1H, Ar–H), 7.92 (d, J = 1.2 Hz, 1H, Ar–H), 8.48 (d,
J = 1.2 Hz, 1H, Ar–H), 8.71 (s, 1H, Ar–H) and 9.79 (s,
1H, –NH); 13C-NMR (100 MHz, DMSO-d6): 115.0, 115.3,
115.8, 118.8, 118.9, 119.2, 120.6, 124.2, 127.9, 130.8,
136.9, 138.2, 143.7, 152.3, 156.0, 159.1, 159.3, 163.0;
HRMS calculated for C18H11O2N2SCl [M+H]+: 355.0308,
Found: 355.0321.
3‑(2‑((4‑Methoxyphenyl)amino)
thiazol‑4‑yl)‑2H‑chromen‑2‑one (5f)
Yellow solid. Yield: 2.76 g (79%); mp 192–194 °C (Acetoni-
trile); IR(KBr) νmax/cm−1: 1720 cm−1 (strong, sharp, –CO
of coumarin ring), 3395–3455 cm−1 (broad, medium, –NH
group); 1H-NMR (400 MHz, DMSO-d6/TMS): δ=3.75 (s,
3H, OCH3), 6.96–7.94 (complex, m, 8H, Ar–H), 7.96 (s,
1H, Ar–H), 8.67 (s, 1H, Ar–H) and 10.16 (s, 1H, –NH);
13C-NMR (100 MHz, DMSO-d6): 55.1, 109.2, 114.3, 115.8,
118.9, 119.2, 120.2, 124.6, 128.9, 131.6, 134.4, 138.4,
143.4, 152.2, 154.2, 158.7, 163.1; HRMS calculated for
C19H14N2O3S [M+H]+: 351.0803, Found: 351.0802.
3‑(2‑((2‑Chlorophenyl)amino)
thiazol‑4‑yl)‑2H‑chromen‑2‑one (5c)
Yellow solid. Yield: 3.00 g (85%); mp 154–156 °C (Etha-
nol); IR(KBr) νmax/cm−1: 1720 cm−1 (strong, sharp, –CO
of coumarin ring), 3390–3450 cm−1 (broad, medium, –NH
group); 1H-NMR (400 MHz, DMSO-d6/TMS): δ=7.11 (t,
J=7.6 Hz, 1H, Ar–H), 7.37–7.65 (complex, m, 5H, Ar–H),
7.82 (s, 1H, Ar–H), 7.91 (d, J = 7.6 Hz, 1H, Ar–H), 8.48
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Journal of the Iranian Chemical Society
3‑(2‑(4‑Tolylamino)thiazol‑4‑yl)‑2H‑chromen‑2‑one (5g)
7.84 (s, 1H, Ar–H), 7.93 (d, J = 6.8 Hz, 1H, Ar–H), 8.49
(d, J=7.6 Hz, 1H, Ar–H), 8.61 (s, 1H, Ar–H) and 9.94 (s,
1H, –NH); 13C-NMR (100 MHz, DMSO-d6): 110.0, 115.2,
118.2, 119.1, 120.5, 123.9, 125.2, 128.0, 128.6, 130.9,
136.9, 137.2, 138.4, 139.4, 144.2, 152.2, 159.1, 162.2;
HRMS calculated for C18H11N3O4S [M+H]+: 366.0545,
Found: 366.0548.
Yellow solid. Yield: 2.70 g (81%); mp 201–203 °C (Acetoni-
trile); IR(KBr) νmax/cm−1: 1716 cm−1 (strong, sharp, –CO
of coumarin ring), 3404–3450 cm−1 (broad, medium, –NH
group); 1H-NMR (400 MHz, DMSO-d6/TMS): δ=2.15 (s,
3H, –CH3), 7.40–7.67 (m, 5H, Ar–H), 7.72 (s, 1H, Ar–H),
7.79–7.98 (complex, m, 3H, Ar–H), 8.71 (s, 1H, Ar–H)
and 10.50 (s, 1H, –NH); 13C-NMR (100 MHz, DMSO-d6):
21.2, 110.0, 115.3, 119.1, 119.8, 120.8, 125.0, 128.1, 128.4,
133.2, 139.2, 140.1, 144.0, 152.4, 159.5, 162.2; HRMS
calculated for C19H14N2O2S [M + H]+: 335.0855, Found:
335.0853.
3‑(2‑(2‑bromo‑4‑fuorophenylamino)
thiazol‑4‑yl)‑2H‑chromen‑2‑one (5k)
Yellow solid. Yield: 3.33 g (80%); mp 153–155 °C (Etha-
nol); IR(KBr) νmax/cm−1: 1719 cm−1 (strong, sharp, –CO
of coumarin ring), 3345–3480 cm−1 (broad, medium, –NH
1
3‑(2‑((4‑Nitrophenyl)amino)
thiazol‑4‑yl)‑2H‑chromen‑2‑one (5h)
group); H-NMR (400 MHz, DMSO-d6/TMS): δ 6.95 (d,
J=8.0 Hz, 2H, Ar–H), 7.44 (t, J=7.2 Hz, 1H, Ar–H), 7.49
(s, 1H, Ar–H), 7.64–7.69 (complex, m, 3H, Ar–H), 7.75 (s,
1H, Ar–H), 8.68 (s, 1H, Ar–H) and 10.13 (s, 1H, –NH);
13C-NMR (100 MHz, DMSO-d6): 116.9, 118.1, 119.4,
120.3, 125.1, 129.2, 131.9, 138.5, 139.5, 139.9, 144.0,
150.9, 152.6, 154.1, 159.2, 163.1; HRMS calculated for
C18H10BrFN2O2S [M+H]+: 418.0325, Found: 418.0302.
Yellow solid. Yield: 3.07 g (84%); mp 170–172 °C (Metha-
nol); IR(KBr) νmax/cm−1: 1728 cm−1 (strong, sharp, –CO
of coumarin ring), 3404–3430 cm−1 (broad, medium, –NH
group); 1H-NMR (400 MHz, DMSO-d6/TMS): δ=7.11 (t,
J=8.0 Hz, 1H, Ar–H), 7.37–7.65 (complex, m, 5H, Ar–H),
7.82 (s, 1H, Ar–H), 7.91 (d, J = 9.2 Hz, 1H, Ar–H), 8.48
(d, J=7.6 Hz, 1H, Ar–H), 8.61 (s, 1H, Ar–H) and 9.81 (s,
1H, –NH); 13C-NMR (100 MHz, DMSO-d6): 110.7, 116.3,
119.0, 119.7, 120.6, 125.1, 129.3, 129.4, 132.1, 139.2,
140.3, 144.0, 152.7, 159.2, 162.6; HRMS calculated for
C18H11N3O4S [M+H]+: 366.0549, Found: 366.0548.
3‑(2‑((2‑Bromophenyl)amino)
thiazol‑4‑yl)‑2H‑chromen‑2‑one (5l)
Yellow solid. Yield: 3.31 g (83%); mp 189–191 °C (Etha-
nol); IR(KBr) νmax/cm−1: 1723 cm−1 (strong, sharp, –CO
of coumarin ring), 3382–3460 cm−1 (broad, medium, –NH
1
3‑(2‑((4‑Bromophenyl)amino)
thiazol‑4‑yl)‑2H‑chromen‑2‑one (5i)
group); H-NMR (400 MHz, DMSO-d6/TMS): δ 7.14 (t,
J=8.2 Hz, 1H, Ar–H), 7.38–7.66 (complex, m, 5H, Ar–H),
7.83 (s, 1H, Ar–H), 7.91 (d, J = 7.2 Hz, 1H, Ar–H), 8.46
(d, J=6.8 Hz, 1H, Ar–H), 8.60 (s, 1H, Ar–H) and 9.98 (s,
1H, –NH); 13C-NMR (100 MHz, DMSO-d6): 109.5, 115.6,
117.9, 119.1, 120.2, 123.9, 125.5, 128.0, 128.9, 131.5,
136.7, 137.1, 138.5, 139.8, 144.1, 152.8, 159.6, 162.5;
HRMS calculated for C18H11BrN2O2S [M+H]+: 398.9805,
Found: 398.9802.
Yellow solid. Yield: 3.07 g (77%); mp 177–179 °C (Chloro-
form); IR(KBr) νmax/cm−1: 1730 cm−1 (strong, sharp, –CO
of coumarin ring), 3380–3438 cm−1 (broad, medium, –NH
group); 1H-NMR (400 MHz, DMSO-d6/TMS): δ 7.43–7.48
(complex, m, 4H, Ar–H),7.63 (d, J = 6.8 Hz, 1H, Ar–H),
7.66 (s, 1H, Ar–H), 7.69 (d, J=7.6 Hz, 1H, Ar–H), 7.82 (t,
J=8.8 Hz, 1H, Ar–H), 7.98 (d, J=7.2 Hz, 1H, Ar–H), 8.73
(s, 1H, Ar–H) and 10.52 (s, 1H, –NH); 13C-NMR (100 MHz,
DMSO-d6): 111.2, 115.5, 117.5, 118.0, 118.9, 119.3, 121.2,
124.7, 128.7, 130.9, 135.1, 139.0, 143.4, 151.8, 158.5,
163.6; HRMS calculated for C18H11BrN2O2S [M + H] + :
398.9807, Found: 398.9802.
Acknowledgements The authors are thankful to the authorities of
Jawaharlal Nehru Technological University Hyderabad for providing
laboratory facilities. One of the authors (KK) is thankful to the Univer-
sity for the fnancial support in the form of Lectureship.
3‑(2‑((2‑Nitrophenyl)amino)
thiazol‑4‑yl)‑2H‑chromen‑2‑one (5j)
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Journal of the Iranian Chemical Society
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