Efficient microwave-assisted synthesis of 3-benzothiazolo and 3-benzothiazolino coumarin derivatives catalyzed by heteropoly acids

Article abstract of DOI:10.1007/BF03246560

Heteropoly acids are reported as efficient catalysts for the microwave-assisted synthesis of 3-benzothiazolo and 3-benzothiazolino coumarin from o-aminothiophenol derivatives with 3-acetly and 3-cyanochromen-2-one in good to excellent isolated yields (73-95%). This study suggests new techniques for the synthesis of chromene derivatives using an inexpensive and easily available catalyst, a simple procedure, short reaction time, and good to excellent yields of the products.

Full text of DOI:10.1007/BF03246560

J. Iran. Chem. Soc., Vol. 8, No. 4, December 2011, pp. 1036-1042.
JOURNAL OF THE
Iranian
Chemical Society
ꢀꢀꢀꢀꢀꢀ
ꢀ
Efficient Microwave-Assisted Synthesis of 3-Benzothiazolo and 3-Benzothiazolino
Coumarin Derivatives Catalyzed by Heteropoly Acids
M. Khoobia, A. Ramazania, A.R. Foroumadib, H. Hamadic, Z. Hojjatia and A. Shafieeb,*
aChemistry Department, Zanjan University, P.O. Box 45195-313, Zanjan, Iran
bDepartment of Medicinal Chemistry, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran
University of Medical Sciences, Tehran 14176, Iran
cDepartment of Chemistry, Chamran University, Ahvaz 61357-4-3169, Iran
ꢀ
(Received 21 January 2011, Accepted 22 April 2011)
Heteropoly acids are reported as efficient catalysts for the microwave-assisted synthesis of 3-benzothiazolo and 3-
benzothiazolino coumarin from o-aminothiophenol derivatives with 3-acetly and 3-cyanochromen-2-one in good to excellent
isolated yields (73-95%). This study suggests new techniques for the synthesis of chromene derivatives using an inexpensive and
easily available catalyst, a simple procedure, short reaction time, and good to excellent yields of the products.
Keywords: o-Aminothiophenol, 3-Benzothiazolino coumarin, 3-Benzothiazolo coumarin, Heteropoly acid
INTRODUCTION
pharmacological importance of the benzothiazoline and
benzothiazole ring systems, we have focused on the synthesis
of new 3-benzothiazolino and dihydrothiazolino coumarins.
For the synthesis of benzothiazoline and benzothiazole
moieties several methods have been reported which typically
involve the reaction of carboxylic acids [16-18] and their
derivatives like orthoesters [19-21], esters [22], nitriles [23-
26], amides [27], aldehydes [28-30] and ketones [31] with 2-
aminothiophenol in the presence of an acidic catalyst at
elevated temperatures.
3-Benzothiazolo coumarins have been synthesized using
benzothiazol-2-yl-acetic acid ethyl ester with o-hydroxy-
benzaldehyde [32]. Recently, a one pot synthesis of 3-
benzothiazolo coumarins was reported from salicylaldehydes,
ethyl cyanoacetate and o-aminothiophenols in the presence of
piperidine as a base [33]. Different methods for the synthesis
of 3-benzothiazolo coumarins, have been reported, but none of
them starts from 3-cyanocoumarin under acidic conditions.
Also, condensation of o-aminothiophenol with carbonyl
Benzothiazoline and benzothiazole derivatives have
received considerable attention in organic synthesis and
pharmaceutical chemistry [1-5]. These heterocycles have
varied pharmacological activities such as antibiotic [6],
anticancer [7], antiviral [8], antifungal [9], antimicrobial [10]
and antiparkinson [11] properties.
On the other hand, several coumarin derivatives have
pronounced medicinal value as antibacterial and antifungal
agents [12]. Others have varied bioactivity such as anticancer
[13], antitumor, antiviral [14] and inhibition of HIV-1 protease
[15].
The approach to the preparation of potentially-biologically
active compounds today is predominantly based on the
combination of different substructures which enhance the
biological activity of known active substances. Given the
*Corresponding author. E-mail: ashafiee@ams.ac.ir

Khoobiꢀet al8
compounds has been reported in the presence of alumina [31],
water. Further purifications were carried out by crystallization
from EtOH. Similar procedure can be performed in the
presence of 3 ml absolute EtOH and HPMo (5 mol%, 0.09 g)
as the catalyst. The mixture was irradiated for 10 min (5 × 2
min). The reaction mixture, after each 2-minute irradiation
was thoroughly mixed outside the microwave oven for 1 min
with ultrasound and again irradiated for another 2 min. This
cycle was repeated for the total irradiation time. Upon the
completion of the reaction monitored by (TLC), the solvent
was evaporated and dichloromethane (10 ml) was added to the
residue. The catalyst was filtered and washed with
dichloromethane (3 × 5 ml) and the solvent was dried over
anhydrous sodium sulfate and was evaporated under reduced
pressure. The residue was purified by silica gel column
chromatography (n-hexane/ethyl acetate = 8:2) to give the
pure product. The same procedure was followed for the
synthesis of compound 5; however, 30 and 15 min were used
for the completion of the reaction in the presence of acetic
acid or HPMo in ethanol, respectively. All the products were
identified by their NMR, IR and Mass spectral data.
p-toluenesulfonic acid [34], hydrochloric acid [35] and a
Lewis acid such as Ga(OTf)3 [36]. However, heteropoly acid
was not used for this condensation.
Due to the interesting properties of coumarin derivatives,
and since close attention has been paid to the use of
heteropoly acid in the organic reactions for the last decade
[37], we thus present our research findings on the synthesis of
3-benzothiazolo coumarin and 3-benzothiazolino coumarin
derivatives, using o-aminothiophenol with 3-acetly and 3-
cyanochromen-2-one catalyzed by heteropoly acids as a new
catalyst for this reaction in good to excellent isolated yields
(62-97%) under thermal condition and or microwave
irradiation.
EXPERIMENTAL
Chemicals were obtained from commercial sources. The 3-
cyano and 3-acetylcoumarins were prepared using reported
methods [38]. Melting points were measured on a Kofler hot
1
stage apparatus and are uncorrected. H NMR and 13C NMR
3-(2-Methyl-2,3-dihydrobenzo[d]thiazol-2-yl)-2H-
spectra were recorded on a Bruker FT-500 spectrometer in
CDCl3 or DMSO-d6, and TMS was used as the internal
standard at 500 and 125.7 MHz respectively. Mass spectra
were recorded on a Finnigan Mat TSQ-70 spectrometer.
Infrared (IR) spectra were acquired on a Nicollet Magna 550-
FT spectrometer. The experiments were performed using a
microwave oven (ETHOS 1600, Milestone) with a power of
600 W specially designed for an organic synthesis and
modified with a condenser and mechanical stirrer. Elemental
analyses were carried out with a Perkin-Elmer model 240-C
apparatus. The results of elemental analyses (C, H, N) were
within 0.4% of the calculated values.
chromen-2-one (3a). Yellow solid; Yield: 95%; m.p.: 159-
161 °C; IR (KBr, cm-1) νmax: 3344 (NH), 3074, 2988, 1705
1
(C=O); H NMR (500 MHz, CDCl3) δ: 2.19 (s, 3H), 5.03 (bs,
1H, NH), 6.76 (m, 2H), 6.95 (t, J = 7.5 Hz, 1H), 7.07 (t, J =
7.5 Hz, 1H), 7.27 (t, J = 7.5 Hz, 1H), 7.33 (d, J = 8.5 Hz, 1H),
7.50 (m, 2H), 8.10 (s, 1H); 13C NMR (125 MHz, CDCl3) δ:
28.2, 76.9, 111.3, 116.2, 118.9, 121.1, 121.8, 124.5, 125.4,
127.3, 128.4, 131.5, 138.4, 145.1, 153.1, 160.2; Anal. Calcd.
for C17H13NO2S: C, 69.13; H, 4.44; N, 4.74. Found: C, 69.26;
H, 4.23; N, 4.62.
Compound 3a was also prepared in the following way. A
mixture of 3-acetylcoumarins 1a (1 mmol), 2-aminothiophenol
2a (1.2 mmol) and H3PW12O40 (5 mol%, 0.14 g) in ethanol
was stirred for 12 h at room temperature. The solid was
filtered and the crude mixture was washed with water to yield
pure product 3a.
General Procedure for the Synthesis of 3-
Benzothiazolo and 3-Benzothiazolino Coumarin
Derivatives
To a mixture of 3-acetylcoumarins 1 (1 mmol) and 2-
aminothiophenols 2 (1.2 mmol) was added 3 ml AcOH as
solvent and catalyst and the mixture was irradiated with
microwaves at 300 W for 7 min under reflux conditions. After
completion of the reactions, the mixture was cooled and the
precipitated solid was filtered out and washed with Et2O and
3-(6-Chloro-2-methyl-2,3-dihydrobenzo[d]thiazol-2-yl)-
2H-chromen-2-one (3b). Yellow solid; Yield: 73%; m.p.:
190-192 °C; IR (KBr, cm-1) νmax: 3334 (NH), 3068, 2987,
1705 (C=O); 1H NMR (500 MHz, CDCl3) δ: 2.16 (s, 3H), 5.21
(bs, 1H, NH), 6.69 (m, 2H), 6.92 (d, J = 8.5 Hz, 1H), 7.26 (t,
J = 8.0 Hz, 1H), 7.33 (d, J = 8.5 Hz, 1H), 7.51 (m, 2H), 8.07
ꢀ
1037

Efficient Microwave-Assisted Synthesis of 3-Benzothiazolo and 3-Benzothiazolino Coumarin
(s, 1H); 13C NMR (125 MHz, CDCl3) δ: 28.4, 77.8, 110.8,
10.59 (s, 1H); 13C NMR (125 MHz, DMSO-d6) δ: 19.0, 76.2,
102.1, 110.0, 111.2, 113.9, 119.4, 121.4, 125.6, 126.5, 128.2,
130.5, 137.5, 146.2, 154.9, 160.0, 161.6; MS, m/z (%) 311
(M•+, 25%), 296 (100), 150 (8), 109 (7). Anal. Calcd. for
C17H13NO3S:ꢀC, 65.58; H, 4.21; N, 4.50. Found: C, 65.24; H,
4.58; N, 4.21.
116.3, 118.8, 120.5, 122.3, 124.6, 125.0, 128.4, 131.0, 131.7,
136.6, 146.3, 153.1, 160.2; Anal. Calcd. for C17H12ClNO2S: C,
61.91; H, 3.67; N, 4.25. Found: C, 61.76; H, 3.83; N, 4.02.
8-Methoxy-3-(2-methyl-2,3-dihydrobenzo[d]thiazol-2-
yl)-2H-chromen-2-one (3c). Yellow solid; Yield: 93%; m.p.:
187-189 °C; IR (KBr, cm-1) νmax: 3348 (NH), 3076, 2965,
1700 (C=O); 1H NMR (500 MHz, CDCl3) δ: 2.18 (s, 3H), 3.95
(s, 3H), 5.10 (bs, 1H, NH), 6.74 (m, 2H), 6.94 (t, J = 7.5 Hz,
1H), 7.04 (m, 3H), 7.18 (t, J = 8.0 Hz, 1H), 8.08 (s, 1H); 13C
NMR (125 MHz, CDCl3) δ: 28.3, 56.2, 76.7, 111.1, 113.3,
119.6, 119.8, 120.9, 121.8, 124.3, 125.4, 127.0, 131.7, 138.6,
142.8, 145.2, 146.9, 159.7; Anal. Calcd. for C18H15NO3S: C,
66.44; H, 4.65; N, 4.30. Found: C, 66.36; H, 4.43; N, 4.49.
6-Bromo-3-(2-methyl-2,3-dihydrobenzo[d]thiazol-2-yl)-
2H-chromen-2-one (3d). Yellow solid; Yield: 91%; m.p.:
109-111 °C; IR (KBr, cm-1) νmax: 3351 (NH), 3052, 2970,
1697 (C=O); 1H NMR (500 MHz, CDCl3) δ: 2.17 (s, 3H), 5.20
(bs, 1H, NH), 6.77 (m, 2H), 6.94 (t, J = 7.5 Hz, 1H),7.04 (t,
J = 7.5 Hz, 1H), 7.19 (d, J = 8.5 Hz, 1H), 7.56 (dd, J = 8.5 Hz
and J = 2.2, 1H), 7.62 (d, J = 2.2, 1H), 7.98 (s, 1H) ; 13C NMR
(125 MHz, CDCl3) δ: 27.8, 76.5, 111.8, 117.0, 117.9, 120.5,
121.6, 121.8, 125.5, 127.9, 130.6, 132.7, 134.2, 136.9, 144.9,
151.9, 159.6; MS, m/z (%) 375 (M•++2, 17%), 373 (M•+,
17%), 360 (100), 358 (89), 251 (17), 150 (20), 109 (17); Anal.
Calcd. for C17H12BrNO2S: C, 54.56; H, 3.23; N, 3.74. Found:
C, 54.50; H, 3.03; N, 3.86.
3-(Benzo[d]thiazol-2-yl)-2H-chromen-2-one
(5a).
Yellow solid; Yield: 88%; m.p.: 215-217 °C; IR (KBr, cm-1)
1
νmax: 3048, 3025, 1716 (C=O), 1607, 1557 (C=N); H NMR
(500 MHz, CDCl3) δ: 7.40 (td, J = 8.0 Hz, J = 1.4 Hz, 1H),
7.45-7.47 (m, 2H), 7.55 (td, J = 8.0 Hz, J = 1.4 Hz, 1H), 7.66
(td, J = 8.0 Hz, J = 1.4 Hz, 1H), 7.75 (dd, J = 8.5 Hz, J = 2.4
Hz, 1H), 7.99 (d, J = 8.0 Hz, 1H), 8.11 (d, J = 8.0 Hz, 1H),
9.10 (s, 1H); 13C NMR (125 MHz, CDCl3) δ: 116.7, 118.6,
120.3, 121,7, 122.9, 125.2, 125.4, 126.5, 129.3, 133.2, 136.8,
141.4, 152.4, 153.8, 159.8, 159.9; Anal. Calcd. for
C16H9NO2S: C, 68.80; H, 3.25; N, 5.01. Found: C, 68.75; H,
3.49; N, 4.82.
3-(Benzo[d]thiazol-2-yl)-8-hydroxy-2H-chromen-2-one
(5b). Orange solid; Yield: 68%; m.p.: 284-286 °C; IR (KBr,
1
cm-1) νmax: 3429 (OH), 1745 (C=O), 1553 (C=N); H NMR
(400 MHz, DMSO-d6) δ: 7.24 (m, 2H), 7.48 (m, 2H), 7.58 (t,
J = 8.4 Hz, 1H), 8.09 (d, J = 8.1 Hz, 1H), 8.18 (d, J = 8.1 Hz,
1H), 9.19 (s, 1H), 10.41 (s, 1H); Anal. Calcd. for C16H9NO3S:
C, 65.07; H, 3.07; N, 4.74. Found: C, 65.33; H, 2.83; N, 4.39.
3-(6-Chlorobenzo[d]thiazol-2-yl)-2H-chromen-2-one
(5c). Yellow solid; Yield: 62%; m.p.: 269-271 °C; IR (KBr,
1
6-Hydroxy-3-(2-methyl-2,3-dihydrobenzo[d]thiazol-2-
yl)-2H-chromen-2-one (3e). Green solid; Yield: 94%; m.p.:
189-191 °C; IR (KBr, cm-1) νmax: 3442 (OH), 2967, 1726
cm-1) νmax: 1711 (C=O), 1548 (C=N); H NMR (400 MHz,
CDCl3) δ: 7.48 (m, 2H), 7.50 (d, J = 8.5 Hz, 1H), 7.69 (t, J =
8.5 Hz, 1H), 7.69 (t, J = 8.5 Hz, 1H), 7.82 (d, J = 7.7 Hz, 1H),
7.94 (d, J = 8.5 Hz, 1H), 9.23 (s, 1H); Anal. Calcd. for
C16H8ClNO2S: C, 61.25; H, 2.57; N, 4.46. Found: C, 61.41; H,
2.22; N, 4.73.
1
(C=O); H NMR (400 MHz, DMSO-d6) δ: 1.98 (s, 3H), 4.92
(bs, 1H, NH), 6.59 (t, J = 7.6 Hz, 1H), 6.72 (d, J = 7.6 Hz,
1H), 6.89 (t, J = 7.6 Hz, 1H), 6.94 (d, J = 7.6 Hz, 1H), 7.03 (m,
2H), 7.26 (d, J = 7.6 Hz, 1H), 7.92 (s, 1H), 9.79 (s, 1H). Anal.
Calcd. for C17H13NO3S: C, 65.58; H, 4.21; N, 4.50. Found: C,
65.35; H, 4.50; N, 4.17.
3-(Benzo[d]thiazol-2-yl)-6-bromo-2H-chromen-2-one
(5d). Yellow solid; Yield: 84%; m.p.: 276-278 °C; IR (KBr,
1
cm-1) νmax: 1725 (C=O), 1569 (C=N); H NMR (400 MHz,
7-Hydroxy-3-(2-methyl-2,3-dihydrobenzo[d]thiazol-2-
yl)-2H-chromen-2-one (3f). Yellow solid; 91%; m.p.: 101-
103 °C; IR (KBr, cm-1) νmax: 3343 (OH), 3052, 2912, 1704
DMSO-d6) δ: 7.52 (m, 2H), 7.59 (t, J = 8.4 Hz, 1H), 7.88 (d,
J = 8.0 Hz, 1H), 8.11 (d, J = 8.4 Hz, 1H), 8.20 (d, J = 8.0 Hz,
1H), 8.35 (s, 1H), 9.23 (s, 1H); Anal. Calcd. for
C16H8BrNO2S: C, 53.65; H, 2.25; N, 3.91. Found: C, 53.83; H,
2.42; N, 3.76.
1
(C=O); H NMR (500 MHz, CDCl3) δ 2.07 (s, 3H), 4.99 (bs,
1H, NH), 6.57 (t, J = 7.5 Hz, 1H), 6.70 (d, J = 7.7 Hz, 1H),
6.73 (s, 1H), 6.77 (d, J = 8.5 Hz, 1H), 6.87 (t, J = 7.7 Hz, 1H),
6.92 (d, J = 7.5 Hz, 1H), 7.56 (d, J = 8.5 Hz, 1H), 7.87 (s, 1H),
3-(Benzo[d]thiazol-2-yl)-7-hydroxy-2H-chromen-2-one
(5e). Red solid; Yield: 87%; m.p.: 293-295 °C; IR (KBr, cm-1)
ꢀ
1038

Khoobiꢀet al8
O
O
HN
O
H2N
S
Cat., solvent
+
O
1a
HS
O
3a
2a
ꢀ
Sheme 1. Model reaction for catalyst screening under thermal and microwave irradiation
Table 1. Screening of some Acidic Catalysts for Model Reaction under Thermal and Microwave Irradiationa
Entry
1
Catalyst
Conditions
Reflux
Solvent
Time (min)
360
Yield (%)b
90
p-TsOH (30 mol%)
Benzene
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Al2O3 (1 g)
80 °C
r.t.
-
300
720
360
360
720
360
360
30
10
10
10
10
40
97
94
72
94
10
20
HPW (5 mol%)
HPW (5 mol%)
HPMo (5 mol%)
AcOH (3 cc)
HPMo (5 mol%)
HPW (5 mol%)
-
EtOH
EtOH
EtOH
-
DMSO
DMSO
CH3CN
-
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
Reflux
Reflux
Reflux
Reflux
Reflux
MW
MW
MW
MW
MW
No reaction
Al2O3 (1 g)
30
10
20
46
32
57
AlCl3 (10 mol%)
p-TsOH (1 mmol)
HClO4-SiO2 (10 mol%)c
SSA (10 mol%)d
HPW (5 mol%)
MW
MW
10
10
16
17
18
19
20
21
22
HPMo (5 mol%)
HSiW (5 mol%)e
ZnCl2 (5 mol%)
AcOH (3 cc)
AcOH (3 cc)
HPMo (3 mol%)
HPMo (5 mol%)
MW
MW
MW
MW
MW
MW
MW
CH3CN
CH3CN
CH3CN
-
10
10
10
5
7
10
10
93
72
37
83
95
87
95
-
EtOH
EtOH
23
24
HPMo (7 mol%)
HPW (5 mol%)
MW
MW
EtOH
EtOH
10
10
95
53
aReaction condition: 3-acetylcoumarins, 1 mmol; o-aminothiophenol, 1.2 mmol; Cat.; solvent, 3 cc. The
experiments were performed using a modified microwave oven (ETHOS 1600, Milestone with a power of
600 W specially designed for organic synthesis) which modified with condenser and mechanical stirrer at
b
300 W. Isolated yield. cThe catalyst HClO4-SiO2 was prepared according to the reported procedure [40] in
d
which 1 g of silica gel contains 0.37 mmol HClO4. SSA (silica sulfuric acid) was prepared following the
reported procedure [41]. eHSiW (H4SiW12O40).
ꢀ
1039

Efficient Microwave-Assisted Synthesis of 3-Benzothiazolo and 3-Benzothiazolino Coumarin
1
νmax: 3421 (OH), 1722 (C=O), 1565 (C=N); H NMR (400
Table 2. MW-Assisted Synthesis of 3-Benzothiazolino
MHz, DMSO-d6) δ: 6.84 (s, 1H), 6.91 (d, J = 8.4 Hz, 1H),
7.44 (t, J = 7.4 Hz, 1H), 7.55 (t, J = 7.4 Hz, 1H), 7.89 (d, J =
8.4 Hz, 1H), 8.03 (d, J = 8.0 Hz, 1H), 8.13 (d, J = 8.0 Hz, 1H),
9.12 (s, 1H), 11.01 (bs, 1H); 13C NMR (125 MHz, CDCl3) δ:
101.9, 111.3, 114.3, 114.4, 121.9, 122.0, 124.8, 126.3, 131.8,
135.5, 142.5, 151.9, 155.6, 159.6, 160.2, 163.4; Anal. Calcd.
for C16H9NO3S: C, 65.07; H, 3.07; N, 4.74. Found: C, 65.32;
H, 3.36; N, 4.51.
Coumarin Derivatives
R'
O
HN
O
HS
S
HPMo (5 mol%), EtOH
+
MW (150 oC, 15 min)
O
O
H2N
R'
O
R
R
1
3
2
ꢀ
ꢀ
Entry
Product 3
R
R'
Yield (%)a
1
2
3
4
5
6
3a
3b
3c
3d
3e
3f
H
H
H
Cl
H
H
H
H
95
73
93
91
94
91
RESULTS AND DISCUSSION
8-OMe
6-Br
6-OH
7-OH
In this work, we extended our previous study [39]
concerning the synthesis of novel derivatives of 3-
benzothiazolino coumarin. In order to get the best reaction
conditions, the efficiency of a variety of solvents and catalysts
in the reaction of 3-acetylcoumarin 1a and 2-aminothiophenol
2a as a model reaction was studied (Scheme 1).
Based on the previous reports for the condensation of o-
aminothiophenol with carbonyl compounds in the presence of
alumina and p-TsOH as best reaction conditions [31,34], and
the use of heteropolyacids as environmentally benign catalysts
with strong acidity [37], initially we examined the
applicability of these catalysts in a model reaction under
thermal conditions.
As shown in Table 1, under thermal conditions, the best
results in terms of yield and temperature were achieved by
using HPW (H3PW12O40) in ethanol (Table 1, entry 3) as
compared with the literature procedure [31,34] (Table 1,
entries 1 and 2). Also the use of acetic acid under reflux
condition was excellent (Table 1, entry 6). The use of other
catalysts or solvents did not yield satisfactory results (Table 1,
entries 5, 7 and 8). In order to reduce the reaction time, the
same procedure was adopted under microwave irradiation
(Table 1, entries 9 and 24).
aIsolated yield.
Table 3. MW-assisted Synthesis of 3-Benzothiazolo
Coumarin Derivatives
R'
N
O
HS
CN
O
S
HPMo (5 mol%), EtOH
MW (150 oC, 15 min)
+
O
H2N
R'
R
O
R
2
6
7
ꢀ
ꢀ
Entry
Product 5
R
R'
Yield (%)a
1
2
3
4
5
5a
5b
5c
5d
5e
H
8-OH
H
6-Br
7-OH
H
H
Cl
H
H
88
68
62
84
87
aIsolated yield.
Under this condition, the time was reduced significantly
from 6 h to 7-10 min. As indicated in Table 1, acetic acid and
HPMo (5 mol%) in ethanol (3 ml) were preferred to other
acidic catalysts for this reaction (Table 1, entries 20 and 22).
The applicability of the present method to a large scale process
was also examined with 50 mmol of 3-acetylcoumarin and 55
mmol of o-aminothiophenol which gave 3a in 92% yield. In
order to extend the scope of this reaction, the same procedure
was followed for the reaction of 3-acetylcoumarins 1 with o-
aminothiophenol derivatives 2 (Table 2).
It was found that the introduction of Cl substituent to o-
aminothiophenol 2 resulted in the decrease of the yields of the
reactions. The same reaction was caused by the replacement of
3-cyanocoumarins derivatives 5 with o-aminothiophenols 2
which resulted in the formation of 3-benzothiazolo coumarin
derivatives in good to moderate yields (Table 3).
ꢀ
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Khoobiꢀet al8
No drastic change in yields was observed in comparison
[7]
[8]
D. Kumar, M.R. Jacob, M.B. Reynolds, S.M. Kerwin,
Bioorg. Med. Chem. 10 (2002) 3997.
X. Song, B.S. Vig, P.L. Lorenzi, J.C. Drach, L.B.
Townsend, G.L. Amidon, J. Med. Chem. 48 (2005)
1274.
with the previous reactions. Similar to the reaction explained
previously, slight decrease in yield was observed by the
introduction of Cl substituent to o-aminothiophenol 2. Finally,
no predictable change in yields was observed by the
replacement of the substituent in coumarin derivatives in all
reactions. The acceleration of the reaction under microwave
irradiation may be rationalized on the basis of the high polarity
of the reaction mixtures. The results obtained show that HPMo
(5 mol%) or AcOH provide excellent media for this reaction
under microwave irradiation.
[9]
M. Yamato, J. Pharm. Soc. Jpn. 112 (1992) 81.
[10] I. Yildiz-Oren, I. Yalcin, E. Aki-Sener, N. Carturk, Eur.
J. Med. Chem. 39 (2004) 291.
[11] A. Benazzouz, T. Boraud, P. Dubédat, A. Boireau,
Stutzmann, J.M.C. Gross, Eur. J. Pharmacol. 284
(1995) 299.
[12] H.H. Sayed, A.H. Shamroukh, A.E. Rashad, Acta
Pharm. 56 (2006) 231.
[13] C.J. Wang, Y.J. Hsieh, C.Y. Chu, Y.L. Lin, T.H. Tseng,
Cancer Lett. 183 (2002) 163.
[14] N.A. Al-Masoudi, I.A. Al-Masoudi, A.I. Ali, Y.A. Al-
Soud, B. Saeed, P. La Colla, Acta Pharm. 56 (2006)
175.
[15] S. Kirkiacharian, D.T. Thuy, S. Sicsic, R. Bakhchinian,
R. Kurkjian, T. Tonnaire, Farmaco, 57 (2002) 703.
[16] Y.H. So, J.P. Heeschen, J. Org. Chem. 62 (1997) 3552.
[17] N. Morakot, W. Ngeontae, W. Aeungmaitrepirom, T.
Tuntulani, Bull. Korean Chem. Soc. 29 (2008) 221.
[18] J.H. Lee, S.R. Byeon, S.J. Lim, S.J. Oh, D.H. Moon,
K.H. Yoo, B.Y. Chung, Kim, D.J. Bioorg. Med. Chem.
Lett. 18 (2008) 1534.
CONCLUSIONS
In summary, we have developed and introduced a rapid,
simple and convenient microwave-assisted method for the
synthesis of 3-substituted coumarin derivatives from the
reaction of 3-acetyl and 3-cyanocoumarins with o-
aminothiophenol derivatives in the presence of acetic acid or
catalytic amount of the HPMo (5 mol%). This procedure
offers several advantages including generality, simplicity, easy
work up, clean reactions, scale up and improved yields.
ACKNOWLEDGEMENTS
This work was financially supported by grants from the
Research Council of Tehran University of Medical Sciences
and INSF (Iran National Science Foundation).
[19] D. Villemin, M. Hammadi, B. Martin, Synth. Commun.
26 (1996) 2895.
[20] M. Doise, F. Dennin, D. Blondeau, H. Sliwa,
Tetrahedron Lett. 31 (1990) 1155.
[21] G.L. Jenkins, A.M. Knevel, C.S. Davis, J. Org. Chem.
26 (1961) 274.
[22] A.K. Chakraborti, S. Rudrawar, G. Kaur, L. Sharma,
Synlett (2004) 1533.
[23] D.W. Hein, R.J. Alheim, J. Leavitt, J. Am. Chem. Soc.
79 (1957) 427.
[24] B. Sun, J.X. Guan, L. Xu, B.L. Yu, L. Jiang, J.F. Kou,
L. Wang, X.D. Ding, H. Chao, L.N. Ji, Inorg. Chem. 48
(2009) 4637.
[25] M.C. Van Zandt, B. Doan, D.R. Sawicki, J. Sredy, A.D.
Podjarny,ꢀBioorg. Med. Chem. Lett. 19 (2009) 2006.
[26] A.P. Kourounakis, C. Charitos, E.A. Rekka, P.N.
Kourounakis, J. Med. Chem. 51 (2008) 5861.
REFERENCES
[1]
[2]
[3]
[4]
[5]
[6]
G. Frachy, C. Crestini, R. Berini, R. Salidino, E.
Micione, Heterocycles 38 (1994) 2621.
J. Kondo, N. Suzuki, T. Imaoka, T. Kawasaki, A.
Nakanishi, Y. Kawahara, Anal. Sci. 10 (1994) 17.
M. Zhao, M. Samoc, P.N. Prasad, B.A. Reinhardt, M.
Sinky, Chem. Mater. 2 (1992) 670.
W. Kasel, M. Dolezal, E. Sidoova, Z. Odlerova,
Drsata, J. Chem. Abstr. 110 (1989) 128063e.
N. de Souza, M. Vinicius, J. Sulfur Chem. 26 (2005)
429.
D.A. Evans, C.E. Sacks, W.A. Kleschick, T.R. Taber, J.
Am. Chem. Soc. 101 (1979) 6789.
ꢀ
1041

Efficient Microwave-Assisted Synthesis of 3-Benzothiazolo and 3-Benzothiazolino Coumarin
[27] M. Terashima, M. Ishii, Synthesis (1982) 484.
[35] L. Jain, B.S. Saraswat, R.C. Mehrotra, Indian J. Chem.
[28] P. Salehi, M. Dabiri, M.A. Zolfigol, S. Otokesh, M.
Baghbanzadeh, Tetrahedron Lett. 47 (2006) 2557.
[29] G. Buehrdel, R. Beckert, P. Herzigova, E. Petrlikova,
D. Schuch, E. Birckner, H. Goerls, Europ. J. Org.
Chem. 20 (2009) 3404.
A 21 (1982) 583.
[36] G.K.S. Prakash, T. Mathew, C. Panja, H. Vaghoo, K.
Venkataraman, G.A. Olah, Org. Lett. 9 (2007) 179.
[37] a) H. Firouzabadi, A.A. Jafari, J. Iran. Chem. Soc. 2
(2005) 85; b) M.M. Heravi, S. Sadjadi, H.A. Oskooie,
R. Hekmat Shoar, F.F. Bamoharram, Tetrahedron Lett.
50 (2009) 662.
[30] Y. Kawashita,ꢀJ. Yanagi, T. Fujii, M. Hayashi, Bull.
Chem. Soc. Japan 82 (2009) 482.
[31] M. Kodomari, A. Satoh, R. Nakano, Synth. Commun.
37 (2007) 3329.
[38] a) D. Bogdal, J. Chem. Res. (S), (1998) 468; b) S.
Khode, V. Maddi, P. Aragade, M. Palkar, P.K. Ronad,
[32] a) M.T. Lee, C.K. Yen, W.P. Yang, H.H. Chen, C.H.
Liao, C.H. Tsai, C.H. Chen, Org. Lett. 6 (2004) 1241;
b) J. Wang, X. Qian, J. Cui, J. Org. Chem. 71 (2006)
4308; c) A.M. Youssef, H.M. Mohamed, C. Czezowski,
A. Ata, A.S. Abd-El-Aziz, Heterocycles 68 (2006) 347;
d) S. Lee, K. Sivakumar, W.S. Shin, F. Xie, Q. Wang,
Bioorg. Med. Chem. Lett. 16 (2006) 4596.
S.
Mamledesai,
A.H.M.
Thippeswamy,
D.
Satyanarayana, Europ. J. Med. Chem. (2008) 1.
[39] a) M. Khoobi, S. Emami, G. Dehghan, A. Foroumadi,
A. Shafiee, Arch. Pharm. 344 (2011) 588; b) M.R.
Ganjali, S. Aghabalazadeh, M. Khoobi, A. Ramazani,
A. Foroumadi, A. Shafiee, P. Norouzi, Int. J.
Electrochem. Sci. 6 (2011) 52.
[33] S. Zhou, J. Jia, J. Gao, L. Han, Y. Li, W. Sheng, Dyes
and Pigments 86 (2010) 123.
[40] A. Misra, P. Tiwari, G. Agnihotri, Synthesis (2005)
260.
[34] G. Liso, G. Trapani, A. Latrofa, P. Marchini, J.
Heterocyclic. Chem. 18 (1981) 279.
[41] M.A. Zolfigol, Tetrahedron 57 (2001) 9509.
ꢀ
1042