Bismuth triflate: A highly efficient catalyst for the synthesis of bio-active coumarin compounds via one-pot multi-component reaction

Article abstract of DOI:10.1016/S1872-2067(14)60308-9

A series of coumarin-chalcone hybrid compounds and coumarins linked to pyrazoline was synthesized in good yield and short time using a simple and efficient method. This method involved the one-pot reaction of salicylaldehyde, an α-ketoester and an aromatic aldehyde (in the case of the coumarin-chalcone derivatives) in addition to hydrazine hydrate (in the case of the pyrazolyl coumarins) in the presence of a catalytic amount of bismuth triflate [Bi(OTf)₃, 5 mol%]. The synthesized compounds showed scavenging activity towards the free radical 2,2-diphenyl-1-picrylhydrazyl. All compounds were characterized using IR, ¹H NMR and ¹³C NMR spectroscopy.

Full text of DOI:10.1016/S1872-2067(14)60308-9

Chinese Journal of Catalysis 36 (2015) 1124–1130
a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m
j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / c h n j c
Article
Bismuth triflate: A highly efficient catalyst for the synthesis of
bio-active coumarin compounds via one-pot multi-component
reaction
Mahmoud. Abd El Aleem. Ali. Ali. El-Remaily *
Department of Chemistry, Faculty of Science, Sohag University- 82524, Sohag, Egypt
A R T I C L E I N F O
A B S T R A C T
Article history:
A series of coumarin-chalcone hybrid compounds and coumarins linked to pyrazoline was synthe-
sized in good yield and short time using a simple and efficient method. This method involved the
one-pot reaction of salicylaldehyde, an α-ketoester and an aromatic aldehyde (in the case of the
coumarin-chalcone derivatives) in addition to hydrazine hydrate (in the case of the pyrazolyl cou-
marins) in the presence of a catalytic amount of bismuth triflate [Bi(OTf)3, 5 mol%]. The synthesized
compounds showed scavenging activity towards the free radical 2,2-diphenyl-1-picrylhydrazyl. All
compounds were characterized using IR, 1H NMR and 13C NMR spectroscopy.
Received 9 January 2015
Accepted 2 February 2015
Published 20 July 2015
Keywords:
Coumarin
Chalcone
Pyrazoline
© 2015, Dalian Institute of Chemical Physics, Chinese Academy of Sciences.
Published by Elsevier B.V. All rights reserved.
One-pot multi-component reaction
Salicylaldehyde
α-Ketoester
Bismuth triflate [Bi(OTf)3]
1. Introduction
malarial [18], antituberculosis [19], analgesic [20], anti-HIV
[21] and antitumor [22] properties. Linking coumarins to py-
The coumarin moiety is an important structural motif in
natural products and highly bioactive compounds. Couma-
rin-containing compounds exhibit broad biological activity
with, for example, antioxidant, anticoagulant, antifungal, an-
thelmintic, cytotoxic or hypnotic properties [1–10]. Because of
their fluorescent properties, coumarins are also widely applied
as agrochemicals; used in optical brighteners, cosmetics and
food; and employed as scattered fluorescent and disciplined
laser-dye optical agents [11,12]. Chalcones, one of the major
classes of natural products prevalent in fruits, vegetables, spic-
es and soy-based foodstuffs, have been reported to have sever-
al biological properties [13,14]. The chalcone moiety imparts
biological activity upon the molecule, giving it, for example,
anti-inflammatory [15], antifungal [16], antioxidant [17], anti-
razoline rings may lead to compounds with important proper-
ties, as pyrazoline itself shows anti-inflammatory, antidiabetic,
anesthetic, analgesic, and other potent selective activity, such
as behavior as a nitric oxide synthase (NOS) inhibitor or a can-
nabinoid CB1 receptor antagonist [23].
Multi-component reactions (MCRs) are processes in which
three or more reactants are joined in a single step to produce
products that combine substantial portions of all the reactants
[24–27]. In recent years, MCRs have unfolded as a powerful
tool for creating the substructures of novel and complex mole-
cules due to their advantages over traditional multi-step syn-
thesis. The major advantages of MCRs include their lower cost,
shorter reaction time and high atom economy, lower energy
requirements, and the avoidance of time consuming and ex-
* Corresponding author. Tel: +201143627127; Fax: +2093601159; E-mail: msremaily@yahoo.com
DOI: 10.1016/S1872-2067(14)60308-9 | http://www.sciencedirect.com/science/journal/18722067 | Chin. J. Catal., Vol. 36, No. 7, July 2015

Mahmoud. Abd El Aleem. Ali. Ali. El-Remaily / Chinese Journal of Catalysis 36 (2015) 1124–1130
1125
pensive purification processes. MCRs are generally more
Second step: Synthesis of 5a–5n
eco-friendly than traditional syntheses, and offer fast access to
wide libraries of compounds with different functionalities
[28–32]. During recent years, Bi(III) salts have caught the at-
tention of synthetic organic chemists as effective catalysts be-
cause of their low toxicity, eco friendliness, ease of handling,
low cost and relative insensitivity to air and moisture [33–38].
Among the Bi(III) salts, bismuth triflate [Bi(OTf)3] is the most
efficient catalyst, and is particularly attractive because it is
commercially available or easily prepared from commercially
available starting materials [39–46].
One of my aims in recent years has been the development of
new tools and methodologies for the synthesis of heterocyclic
compounds using an efficient catalyst. Following this aim I de-
signed hybrid molecules based on naturally occurring com-
pounds, coumarin-chalcone moieties and coumarines linked to
pyrazolines, using multi-component reaction techniques in the
presence of a catalytic amount (5 mol%) of the green catalyst
Bi(OTf)3.
A mixture of 3-acetylcoumarin 4 (1 eq.) and the corre-
sponding aldehyde (1.2 eq.) were mixed in the presence of
Bi(OTf)3 (5 mol%) in DCM (5 mL). The reaction mixture was
stirred at 50 °C for a specified time. The progress of the reac-
tion was monitored by TLC. The products precipitated slowly
after 4 h. The solid material was filtered off, washed with water,
dried, and recrystallized from ethanol.
1-(3'-Coumarinyl)-3-phenyl-2-propen-1-one (5a). Yield
89%; M.P. 180–182 °C; IR (KBr, cm−1): 3037 (Ar, C–H str), 2968
(alkane, C–H str), 1714 (C=O), 1683 (C=O), 1610 (C=C); 1H NMR
(CDCl3, δ/ppm): 8.61 (s, 1H, C–H), 7.90 (d, 1H, =CH), 7.71–7.54
(m, 4H, coumarin), 7.419–7.266 (m, 5H, Ar–H), 6.87 (d, 1H,
=C–H); 13C NMR (CDCl3, δ/ppm): 196.52, 161.23, 153.22,
147.36, 138.69, 133.25, 132.00, 130.78, 129.89, 129.14, 128.55,
127.19, 124.74, 124.10, 122.05, 114.36; Anal. Calc. for C18H12O3
(276.29): C 78.25%, H 4.38%; Found: C 78.17%, H 4.28%.
1-(3'-Coumarinyl)-3-(4″-methoxyphenyl)-2-propen-1-one
(5b). Yield 91%; M.P. 140–142 °C; IR (KBr, cm−1): 3052 (Ar,
C–H str), 1705 (C=O), 1681 (C=O), 1604 (C=C str), 1612 (C=C );
1H NMR (CDCl3, δ/ppm): 8.54 (s, 1H, C–H), 7.80 (d, 1H, =C–H),
7.68–7.63 (m, 4H, coumarin), 7.44–7.21(m, 4H, Ar–H), 6.91 (d,
1H, =C–H), 2.74 (s, 3H, O–CH3); 13C NMR (CDCl3, δ/ppm):
190.12, 162.20, 161.54, 154.79, 147.30, 138.89, 131.88, 130.07,
130.78, 128.84, 128.04, 127.14, 124.80, 124.09, 122.08, 114.36,
55.20; Anal. Calc. for C19H14O4 (306.32): C 74.50%, H 4.61%;
Found: C 74.44%, H 4.58%.
2. Experimental
All melting points were recorded on a Melt-Temp II melting
point apparatus. IR spectra were measured as KBr pellets on a
Shimadzu DR-8001 spectrometer. 1H NMR spectra were rec-
orded on a Bruker DRX 300 or 400 MHz spectrometer using
TMS as an internal reference and DMSO-d6 or CDCl3 as the sol-
vent. The purity of all compounds was checked on thin layer
chromatography (TLC) plates. All the synthesized compounds
were prepared according to the method described by Sugino et
al. [47] and Bhatnagar et al. [48]. Confirmation of the proposed
1-(3'-Coumarinyl)-3-(4″-chlorophenyl)-2-propen-1-one
(5c). Yield 96%; M.P. 188–190 °C; IR (KBr, cm−1): 3031 (Ar, C–H
str), 1715 (C=O), 1679 (C=O); 1610 (C=C); 1H NMR (CDCl3,
δ/ppm): 8.59 (s, 1H, C–H), 7.98 (d, 1H, =C–H), 7.67–7.52 (m, 4H,
structures of all prepared compounds by IR, 1HNMR and 13
C
coumarin), 7.41–7.26 (m, 4H, Ar–H), 6.84 (d, 1H, =C–H); 13
C
NMR spectroscopy are also reported.
NMR (CDCl3, δ/ppm): 194.50, 162.20, 154.77, 147.47, 138.78,
135.54, 134.11, 130.78, 129.98, 129.41, 128.05, 127.84, 124.64,
124.09, 122.07, 114.62; Anal. Calc. for C18H11O3Cl (310.74): C
69.58%, H 3.57%, Cl 11.41%; Found: C 69.55%, H 3.59%, Cl
11.09%.
2.1. General procedure for the synthesis of 3-cinnamoyl
coumarins (5a–5n)
Method A
1-(3'-Coumarinyl)-3-(2″-chlorophenyl)-2-propen-1-one
(5d). Yield 89%; M.P. 204–206 °C; IR (KBr, cm−1): 3054 (Ar,
C–H str), 1721 (C=O), 1684(C=O), 1610 (C=C); 1H NMR (CDCl3,
δ/ppm): 8.61 (s, 1H, C–H), 7.96 (d, 1H, =C–H), 7.70–7.65 (m, 4H,
coumarin), 7.45–7.26 (m, 4H, Ar–H), 6.26 (d, 1H, =C–H); 13C
NMR (CDCl3, δ/ppm): 193.41, 162.13, 154.77, 143.44, 138.58,
134.04, 133.57, 130.87, 130.08, 129.94, 128.76, 128.14, 127.84,
127.04, 124.71, 124.13, 122.06, 114.60; Anal. Calc. for
In a 50 mL round bottom flask, salicylaldehyde 1 (1 mmol),
methyl acetoacetate or ethyl acetoacetate 2 (1 mmol) and aro-
matic aldehyde 3 (1 mmol) were mixed in the presence of
Bi(OTf)3 (5 mol%) in dichloromethane (DCM, 5 mL). The reac-
tion mixture was stirred at 50 °C for a specified time. The pro-
gress of the reaction was monitored by TLC. The products pre-
cipitated rapidly after 15 to 30 min (see Table 2). The solid
material was filtered off, washed with water, dried, and recrys-
tallized from ethanol to furnish pure 3-cinnamoylcoumarin
derivatives (5a–5n).
C18H11O3Cl (310.74): C 69.58%, H 3.57%, Cl 11.41%; Found: C
69.55%, H 3.59%, Cl 11.09%.
1-(3'-Coumarinyl)-3-(4″-hydroxyphenyl)-2-propen-1-one
(5e). Yield 91%; M.P. 176–178 °C; IR (KBr, cm−1): 3389 (OH),
Method B
1
First step: Synthesis of 3-acetylcoumarin (4)
3038 (Ar, C–H), 1702 (C=O), 1689 (C=O), 1612 (C=C); H NMR
A mixture of salicylaldehyde (1 eq.), methyl acetoacetate or
ethyl acetoacetate (1 eq.) and a few drops of piperidine were
stirred at room temperature without any solvent. Precipitation
occurred immediately. The compound was then recrystallized
(CDCl3, δ/ppm): 9.73 (s, 1H, OH), 8.67 (s, 1H,C–H), 7.95 (d,1H,
=C–H), 7.77–7.60 (m, 4H, coumarin), 7.50–7.32 (m, 4H, Ar–H),
6.86 (d, 1H, =C–H); 13C NMR (CDCl3, δ/ppm): 189.18, 162.38,
161.74, 154.77, 147.32, 138.30, 131.54, 130.04, 128.17, 127.79,
127.09, 124.64, 124.09, 122.07, 116.41, 114.62; Anal. Calc. for
1
from ethanol [47]. Yield 89%; M.P. 119–121 °C; H NMR (300
MHz, CDCl3, δ/ppm) 8.34 (s, 1H), 7.54–7.42 (m, 2H), 7.26–7.12
C18H12O4 (292.29): C 73.97%, H 4.14%; Found: C 73.81%, H
(m, 2H), 2.56 (s, 3H).
4.11%.

1126
Mahmoud. Abd El Aleem. Ali. Ali. El-Remaily / Chinese Journal of Catalysis 36 (2015) 1124–1130
1-(3'-Coumarinyl)-3-(2″-hydroxyphenyl)-2-propen-1-one
73.22%, H 4.10%, F 6.43%; Found: C 73.35%, H 4.03%, F
6.29%.
(5f). Yield 90%; M.P. 78–79 °C; IR (KBr, cm−1): 3412 (OH str),
1
3041 (Ar, C–H), 1712 (C=O), 1680 (C=O), 1610 (C=C); H NMR
1-(3'-Coumarinyl)-3-(4″-bromophenyl)-2-propen-1-one
(5l). Yield 89%; M.P. 189–191 °C; IR (KBr, cm−1): 3034 (Ar,
C–H), 1710 (C=O),1680 (C=O), 1610 (C=C); 1H NMR (CDCl3,
δ/ppm): 8.57 (s, 1H, C–H), 7.90 (d, 1H, =C–H), 7.71–7.50 (m, 4H,
coumarin), 7.40–7.16 (m, 4H, Ar–H), 6.59 (d, 1H,=C–H); 13C
NMR (CDCl3, δ/ppm): 190.44, 162.24, 154.27, 147.47, 138.47,
135.66, 134.04, 130.78, 129.78, 129.21, 128.07, 127.64, 124.64,
124.10, 122.02, 114.60; Anal. Calc. for C18H11O3Br (356.19): C
60.70%, H 3.40%, Br 22.43%; Found: C 60.63%, H 3.98%, Br
22.20%.
(CDCl3, δ/ppm): 9.67 (s, 1H, OH), 8.76 (s, 1H, C–H), 7.75 (d, 1H,
=C–H), 7.48–7.42 (m, 4H, coumarin), 7.10–6.93 (m, 4H, Ar–H),
6.64 (d, 1H, =C–H); 13C NMR (CDCl3, δ/ppm): 191.47, 162.10,
154.79, 143.04, 138.78, 134.14, 133.47, 130.37, 130.08, 129.91,
128.74, 128.14, 127.84, 127.04, 124.71, 124.13, 122.06, 114.62;
Anal. Calc. for C18H12O4 (292.29): C 73.97%, H 4.14%; Found: C
73.81%, H 4.11%.
1-(3'-Coumarinyl)-3-(2″-furyl)-2-propen-1-one (5g). Yield
89%; M.P. 101–103 °C; IR (KBr, cm−1): 3037 (Ar, C–H), 1716
1
(C=O), 1680 (C=O), 1608 (C=C); H NMR (CDCl3, δ/ppm): 8.58
1-(3'-Coumarinyl)-3-(4″-nitrophenyl)-2-propen-1-one
(5m). Yield 89%; M.P. 154–156 °C; IR (KBr, cm−1): 3045 (Ar,
C–H), 1714 (C=O), 1678 (C=O), 1611 (C=C); 1H NMR (CDCl3,
δ/ppm): 8.74 (s, 1H, C–H), 7.65 (d, 1H, =C–H), 7.55–7.48 (m, 4H,
(d, 1H, =C–H), 7.83 (d, 1H, =C–H), 7.70–7.60 (m, 4H, coumarin),
7.45–7.34 (m, 3H, furyl), 6.85 (d, 1H, =C–H); 13C NMR (CDCl3,
δ/ppm): 188.40, 162.65, 154.79, 151.32, 145.00, 138.84,
133.40, 130.07, 127.69, 125.61, 125.04, 124.54, 122.44, 120.32,
114.74, 106.47; Anal. Calc. for C16H10O4 (266.25): C 72.18%, H
3.79%; Found: C 72.01%, H 3.61%.
1-(3'-Coumarinyl)-3-(2″,4″,6″-trimethoxyphenyl)-2-propen-
1-one (5h). Yield 89%; M.P. 158–160 °C; IR (KBr, cm−1): 3045
(Ar, C–H ), 1720 (C=O), 1680 (C=O), 1610 (C=C); 1H NMR
(CDCl3, δ/ppm): 8.61 (s, 1H, C–H), 7.89 (d, 1H, =C–H), 7.78–7.60
(d, 4H, coumarin), 7.44–7.32 (s, 2H, Ar–H), 6.92 (d, 1H, =C–H),
3.94 (s, 9H, 3OCH3); 13C NMR (CDCl3, δ/ppm): 189.10, 162.38,
161.74, 161.05, 154.78, 147.29, 138.82, 130.04, 127.65, 126.78,
124.64, 124.19, 122.04, 114.66, 105.27, 90.81, 55.64, 55.18;
Anal. Calc. for C21H18O6 (366.37): C 68.85%, H 4.95%; Found: C
68.80%, H 4.91%.
1-(3'-Coumarinyl)-3-(3″,5″-dimethoxyphenyl)-2-propen-1-
one (5i). Yield 88%; M.P. 147–149 °C; IR (KBr, cm−1): 3026 (Ar,
C–H), 1722(C=O), 1685 (C=O), 1606 (C=C); 1H NMR (CDCl3,
δ/ppm): 8.61 (s, 1H, C–H), 7.89 (d, 1H, =C–H), 7.78–7.60 (d, 4H,
coumarin), 7.44–7.36 (s, 3H, Ar–H), 6.84 (d, 1H, =C–H), 3.90 (s,
6H, 2OCH3); 13C NMR (CDCl3, δ/ppm): 188.19, 162.65, 161.45,
154.84, 147.58, 138.83, 137.33, 130.04, 128.08, 127.69, 124.78,
124.14, 122.02, 114.74, 109.81, 100.04, 55.63; Anal. Calc. for
coumarin), 7.37–7.20 (m, 4H, Ar–H), 6.56 (d, 1H, =C–H); 13
C
NMR (CDCl3, δ/ppm): 190.50, 162.20, 154.27, 147.47, 138.38,
135.78, 134.01, 130.78, 129.78, 129.21, 128.07, 127.64, 124.64,
124.06, 122.04, 114.60; Anal. Calc. for C18H11O5N (321.29): C
67.29%, H 3.45%, N 4.36%; Found: C 67.31%, H 3.38%, N
4.22%.
1-(3'-Coumarinyl)-3-(3″-nitrophenyl)-2-propen-1-one (5n).
Yield 88%; M.P. 205–207 °C; IR (KBr, cm−1): 3030 (Ar, C–H),
1710 (C=O), 1683 (C=O), 1610 (C=C); 1H NMR (CDCl3, δ/ppm):
8.97 (s, 1H, C–H), 7.87 (d, 1H, =C–H), 7.65–7.49 (m, 4H, couma-
rin), 7.44–7.21 (m, 4H, Ar–H), 6.68 (d, 1H, =C–H); 13C NMR
(CDCl3, δ/ppm): 188.51, 162.65, 154.84, 149.57, 147.25,
138.89, 138.28, 135.19, 130.88, 130.08, 128.24, 127.67, 125.61,
124.54, 122.02, 121.64, 114.47; Anal. Calc. for C18H11O5N
(321.29): C 67.29%, H 3.45%, N 4.36%; Found: C 67.31%, H
3.38%, N 4.22%.
2.2. General procedure for the synthesis of pyrazolyl coumarins
(7a–7h) [35]
A mixture of salicylaldehyde 1 (1 mmol), methyl acetoace-
tate or ethyl acetoacetate 2 (1 mmol), aromatic aldehyde 3 (1
mmol) and hydrazine hydrate 6 (1 mmol) were mixed in the
presence of Bi(OTf)3 (5 mol%) in DCM (5 mL). The reaction
mixture was stirred at 50 °C for the specified time (see Table
3). The progress of the reaction was monitored by TLC. After
completion of the reaction, the reaction mixture was allowed to
stand overnight. The solid material was filtered off, washed
with water, dried, and recrystallized from ethanol to furnish
pure pyrazolyl coumarin derivatives.
3-(4,5-Dihydro-5-(4-methoxyphenyl)-1H-pyrazol-3-yl)-2H-
chromen-2-one (7a). Yield 90%; M.P. 183–185 °C; IR (KBr;
cm–1): 1634 (C=N), 3268 (Ar N–H), 1172 (–OCH3); 1H NMR
(CDCl3, δ/ppm): 6.72–7.27 (m, 13H, Ar), 7.46 (s, 1H, coumarin),
4.80 (d, 1H, 5-H of pyrazoline), 3.301 (d, 1H, 4-Htrans of pyrazo-
line), 3.305 (d, 1H, 4-Hcis of pyrazoline), 3.73 (s, 3H, –OCH3);
Anal. Calc. for C19H16O3N2: C 71.24%, N 8.74%; Found: C
70.68%, N 8.55%.
C
20H16O5 (336.34): C 71.42%, H 4.79%; Found: C 71.50%, H
4.63%.
1-(3'-Coumarinyl)-3-(4″-dimethylaminophenyl)-2-propen-1-
one (5j). Yield 89%; M.P. 108–110 °C; IR (KBr, cm−1): 3035 (Ar,
C–H), 1714 (C=O), 1681 (C=O), 1606 (C=C); 1H NMR (CDCl3,
δ/ppm): 8.58 (s, 1H, C–H), 7.92 (d, 1H, =C–H), 7.77–7.66 (m, 4H,
coumarin), 7.66 (d, 2H, Ar–H), 7.44 (d, 1H, =C–H), 6.72 (d, 2H,
Ar–H), 3.07 (s, 6H, 2CH3); 13C NMR (CDCl3, δ/ppm): 188.51,
162.65, 154.77, 151.10, 147.23, 138.83, 131.29, 130.04, 128.07,
127.78, 124.64, 124.54, 123.47, 122.02, 114.71, 112.02, 39.71;
Anal. Calc. for C20H17NO3 (319.36): C 75.22%, H 5.37%, N
4.39%; Found: C 75.02%, H 5.29%, N 4.20%.
1-(3'-Coumarinyl)-3-(4″-fluorophenyl)-2-propen-1-one
(5k). Yield 88%; M.P. 171–173 °C; IR (KBr, cm−1): 3031 (Ar,
C–H), 1718 (C=O), 1666 (C=O), 1612 (C=C); 1H NMR (CDCl3,
δ/ppm): 8.59 (s, 1H, C–H), 7.98 (d, 1H, =C–H), 7.67–7.52 (m, 4H,
coumarin), 7.41–7.26 (m, 4H, Ar–H), 6.84 (d, 1H, =C–H); 13
C
NMR (CDCl3, δ/ppm): 191.50, 162.20, 154.27, 147.47, 138.38,
135.78, 134.01, 130.78, 129.78, 129.21, 128.07, 127.64, 124.64,
124.06, 122.04, 114.60; Anal. Calc. for C18H11O3F (295.29): C
3-(4,5-dihydro-5-(2-methoxyphenyl)-1H-pyrazol-3-yl)-2H-
chromen-2-one (7b). Yield 88%; M.P. 166–168 °C; IR (KBr;
cm–1): 1554 (C=N), 3245 (ArN–H); 1H NMR (CDCl3/DMSO-d6,

Mahmoud. Abd El Aleem. Ali. Ali. El-Remaily / Chinese Journal of Catalysis 36 (2015) 1124–1130
1127
δ/ppm): 6.72–7.27 (m, 13H, Ar), 7.65 (s, 1H, coumarin), 4.82 (d,
1H, 5-H of pyrazoline), 3.23 (d, 1H, 4-Htrans of pyrazoline), 3.30
(d, 1H, 4-Hcis of pyrazoline), 3.73 (s, 3H, –OCH3); Anal. Calc. for
(d, 1H, 4-Hcis of pyrazoline); Anal. Calc. for C18H13O4N3: C
64.47%, N 12.53%; Found: C 64.52%, N 11.98%.
3-(4,5-Dihydro-5-p-tolyl-1H-pyrazol-3-yl)-2H-chromen-2-
one (7h). Yield 90%; M.P. 160–162 °C; IR (KBr; cm–1): 1620
(C=N), 3284 (ArN–H); 1H NMR (CDCl3/DMSO-d6, δ/ppm):
7.00–7.27 (m, 13H, Ar), 7.42 (s, 1H, coumarin), 4.55 (d, 1H, 5-H
of pyrazoline), 3.29 (d, 1H, 4-Htrans of pyrazoline), 3.31 (d, 1H,
4-Hcis of pyrazoline), 2.35 (s, 3H, CH3); Anal. Calc. for
C19H16O3N2: C 71.24%, N 8.74%; Found: C 70.85%, N 8.34%.
3-(5-(4-Chlorophenyl)-4,5-dihydro-1H-pyrazol-3-yl)-2H-
chromen-2-one (7c). Yield 95%; M.P. 175–177 °C; IR (KBr;
cm–1): 1622 (C=N), 3282 (ArN–H), 1091 (Ar–Cl); 1H NMR
(CDCl3/DMSO-d6, δ/ppm): 7.01–7.28 (m, 13H, Ar), 7.40 (s, 1H,
coumarin), 5.01 (d, 1H, 5-H of pyrazoline), 3.30 (d, 1H, 4-Htrans
of pyrazoline), 3.33 (d, 1H, 4-Hcis of pyrazoline); Anal. Calc. for
C19H16O2N2 C 74.98%, N 9.20%; Found: C 73.84%, N 8.56%.
C18H13ClO2N2: C 66.57%, N 8.63%; Found: C 66.43%, N 8.27%.
3. Results and discussion
3-(5-(4-Fluorophenyl)-4,5-dihydro-1H-pyrazol-3-yl)-2H-
chromen-2-one (7d): Yield 91%; M.P. 180–182 °C; IR (KBr;
cm–1): 1634 (C=N), 3268 (Ar N–H), 1042 (Ar C–F); 1H NMR
(CDCl3/DMSO-d6, δ/ppm): 6.813–7.5 (m, 13H, Ar), 7.49 (s, 1H,
coumarin), 4.86 (d, 1H, 5-H of pyrazoline), 3.25 (d, 1H, 4-Htrans
of pyrazoline), 3.307 (d,1H, 4-Hcis of pyrazoline); Anal. Calc. for
3.1. The reaction conditions
Initially, the synthesized compounds 5a–5n were obtained
from the three-component reaction of salicylaldehyde, an
α-ketoester (methyl acetoacetate or ethyl acetoacetate) and
various aromatic aldehydes in DCM with the addition of a cata-
lytic amount of the green catalyst Bi(OTf)3 (5 mol%) (Scheme
1).
The optimization of the reaction conditions was then stud-
ied for 5c. No product was obtained from the reaction of salic-
ylaldehyde, ethyl acetoacetate and 4-chlorobenzaldehyde in the
absence of the catalyst at 50 °C in DCM (Table 1, entry 1). The
reaction was then performed in the presence of various simple
metal complexes such as those of Fe, Zn, Mg and Cu to examine
their catalytic activity (Table 1, entries 2–9). Among these met-
al salts (5 mol%), Bi(OTf)3 was found to be the most effective
catalyst and afforded the desired product 5c in 96% yield (Ta-
ble 1, entry 11). When using methanol (MeOH), N,N-dimethyl-
formamide (DMF), toluene (PhCH3) and acetonitrile (CH3CN)
instead of DCM, relatively lower yields were observed (Table 1,
entries 16–19). The desired products were rapidly precipitated
in good yield on warming for 15–30 min (see Table 2).
C18H13FO2N2. C 70.12%, N 9.09%; Found: C 69.86%, N 9.13%.
3-(5-(4-Bromophenyl)-4,5-dihydro-1H-pyrazol-3-yl)-2H-
chromen-2-one (7e). Yield 89%; M.P. 176–178 °C; IR (KBr;
cm–1): 1623.53 (C=N), 3257 (Ar N–H), 658 (C–Br); 1H NMR
(CDCl3/DMSO-d6, δ/ppm): 7.01–7.38 (m, 13H, Ar), 7.46 (s, 1H,
coumarin), 4.89 (d, 1H, 5-H of pyrazoline), 3.28 (d, 1H, 4-Htrans
of pyrazoline), 3.33 (d, 1H, 4-Hcis of pyrazoline); Anal. Calc. for
C18H13BrO2N2. C 58.56%, N 7.59%; Found: C 59.02%, N 7.11%.
3-(4,5-dihydro-5-(4-nitrophenyl)-1H-pyrazol-3-yl)-2H-chro
men-2-one (7f): Yield 86%; M.P. 199–201 °C; IR (KBr; cm–1):
1558 (C=N), 3234 (Ar N–H), 1519 (Symmt =N–O of NO2), 1340
(Asymmt =N–O of NO2); 1H NMR (CDCl3/DMSO-d6, δ/ppm):
7.02–8.14 (m, 13H, Ar), 7.46 (s, 1H, coumarin), 4.86 (d, 1H, 5-H
of pyrazoline), 3.301 (d, 1H, 4-Htrans of pyrazoline), 3.305 (d, 1H,
4-Hcis of pyrazoline); Anal. Calc. for C18H13O4N3: C 64.47%, N
12.53%; Found: C 64.30%, N 12.81%.
3-(4,5-Dihydro-5-(3-nitrophenyl)-1H-pyrazol-3-yl)-2H-
chromen-2-one (7g). Yield 87%; M.P. 189–190 °C; IR (KBr;
cm–1): 1622 (C=N), 3274 (Ar N–H), 1488 (Symmt =N–O of NO2),
1350 (Asymmt=N–O of NO2); 1H NMR (CDCl3/DMSO-d6,
δ/ppm): 6.90–8.07 (m, 13H, Ar), 7.49 (s, 1H, coumarin), 4.86 (d,
1H, 5-H of pyrazoline), 3.30 (d, 1H, 4-Htrans of pyrazoline), 3.33
Compounds 7a–7h were synthesized using
a one-pot
four-component reaction between salicylaldehyde, an
α-ketoester (methyl acetoacetate or ethyl acetoacetate), several
aromatic aldehydes and hydrazine hydrate in DCM under the
same conditions used for the synthesis of 5. The products were
O
O
O
CHO
OH
DCM/ 5 mol% Bi(OTf)3
50 oC, 15-30 min
Ar
+
OR'
2
O
O
R'= CH3 or C2H5
1
+
5 a-n
5a-5n
CHO
R
Ar= R
3
5h: R = -C6H2-(OMe)3 (2,4,6)
5i: R = -C6H3-(OMe)2 (3,5)
5j: R = -C6H4-N(CH3)2 (p)
5k: R = -C6H4-F (p)
5l: R = -C6H4-Br (p)
5m: R = -C6H4-NO2 (p)
5n: R = -C6H4-NO2 (m)
5a: R = -C6H5
5b: R = -C6H4-OMe (p)
5c: R = -C6H4-Cl (p)
5d: R = -C6H4-Cl (m)
5e: R = -C6H4-OH (p)
5f: R = -C6H4-OH (o)
5g: R = (o-Furyl)
Scheme 1. Synthesis of 3-cinnamoyl coumarin derivatives (5a–5n).

1128
Mahmoud. Abd El Aleem. Ali. Ali. El-Remaily / Chinese Journal of Catalysis 36 (2015) 1124–1130
Table 1
Table 2
Optimization of the conditions for the synthesis of 5c.
Reaction time for the synthesis of 5a–5n using a one-pot reaction pro-
tocol.
Entry
1
2
Catalyst (mol%)
No catalyst
FeCl3·6H2O(5)
Fe(OTf)3(5)
ZnBr2(5)
Zn(OTf)2(5)
MgCl2(5)
Mg(OTf)2(5)
CuCl2(5)
Cu(OTf)2(5)
Bi(OTf)3(6)
Bi(OTf)3(5)
Bi(OTf)3(4)
Bi(OTf)3(3)
Bi(OTf)3(2)
Bi(OTf)3(1)
Bi(OTf)3(5)
Bi(OTf)3(5)
Bi(OTf)3(5)
Bi(OTf)3(5)
Conditions
DCM, 50 °C, 6 h
Yield * (%)
None
44
Compd. Reaction time (min)
Compd.
5h
5i
5j
5k
5l
5m
5n
Reaction time (min)
5a
5b
5c
5d
5e
5f
22
18
15
25
20
20
20
20
30
30
25
25
30
30
DCM, 50 °C, 15 min
DCM, 50 °C, 15 min
DCM, 50 °C, 15 min
DCM, 50 °C, 15 min
DCM, 50 °C, 15 min
DCM, 50 °C, 15 min
DCM, 50 °C, 15 min
DCM, 50 °C, 15 min
DCM, 50 °C, 15 min
DCM, 50 °C, 15 min
DCM, 50 °C, 15 min
DCM, 50 °C, 15 min
DCM, 50 °C, 15 min
DCM, 50 °C, 15 min
MeOH, 50 °C, 15 min
DMF, 50 °C, 15 min
PhCH3, 50 °C, 15 min
CH3CN, 50 °C, 15 min
3
56
4
5
6
7
8
9
51
58
50
68
54
66
5g
Table 3
10
11
12
13
14
15
16
17
18
19
96
96
90
86
73
64
Reaction time for the synthesis of 7a–7h using the one-pot reaction
protocol.
Compd.
7a
7b
7c
7d
Reaction time (h)
Compd.
7e
7f
7g
7h
Reaction time (h)
3
3
2
2
4
3
4
4
15
56
44
62
Reaction conditions: 1 (1 mmol), 2 (1 mmol), 3c (1 mmol) and catalyst
(0.05 mmol) in solvent (5 mL). *Isolated yields based on 5c.
3.2. DPPH radical scavenging assay
The 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was based
on the reported method [49,50]. A rapid, simple and inexpen-
sive method to measure antioxidant capacity of substances
involves the use of the free radical, DPPH. DPPH is widely used
to test the ability of compounds to act as free radical scaven-
gers or hydrogen donors. Antioxidants tested on DPPH were
also found extremely effective in cell systems. This simple test
further provides information on the ability of a compound to
donate electrons during antioxidant action [51]. The radical
scavenging mechanism is based on the transfer of acidic
H-atom from the compound to DPPH radical to form DPPH-H.
A DMSO sample of the compounds at 50 μg/mL was diluted
to 4 mL using MeOH. To this, 1 mL of DPPH solution in MeOH
was added. The mixed solution was incubated at room temper-
ature for 30 min. The absorbance of stable DPPH was deter-
precipitated after cooling for 2–4 h (see Table 3 and Scheme 2).
To gain further insights into the reaction, products 5a–5n
were synthesized in two steps. In the first step, the precursor
3-acetylcoumarin 4 was prepared by a Knoevenagel reaction
between salicylaldehyde and an α-ketoester (methyl acetoace-
tate or ethyl acetoacetate) under basic conditions in 89% yield
[47,48]. In the second step, 4 was reacted with various aro-
matic aldehydes to give the final products 5a–5n by a
Claisen-Schmidt aldolic condensation. Under the same condi-
tions as those used in the one-pot reaction, these reactions take
a long time and have low yields. The same result was also seen
for products 7a–7h, which were obtained from couma-
rin-chalcone compounds with hydrazine hydrate (Scheme 3).
Ar
H
H
NH
O
O
CHO
OH
DCM/ 5 mol% Bi(OTf)3
50 oC, 2h - 4h
N
+
OR'
2
O
O
R'= CH3 or C2H5
1
+
7a-h
7a-7h
Ar=
a= 4-OCH C H
7a: R =
6 5
b= 2-OCH3C6H
3
= 2-OCH5 C H
CHO
7b: R =
3
6 5
c= 4-ClC H
7c: R =
d= 4-FC H5
6
5
=64-FC H
7d: R =
+
NH2
H2N
6
5
R
7e: R =
e= 4-BrC6H5
f= 4-NO 2C6H5
7f: R =
4-NO 2C6H5
6
g= 3-NO C H
7g: R =
6 5
h= 4-CH3C6H5
3
2
= 4-CH C H
7h: R =
6 5
3
R
Ar =
Scheme 2. Synthesis of coumarins linked to pyrazoline.

Mahmoud. Abd El Aleem. Ali. Ali. El-Remaily / Chinese Journal of Catalysis 36 (2015) 1124–1130
1129
O
O
CHO
CH3
DCM/5mol % Bi(OTf)
DCM/ 5 mol% Bi(OTf)
Ar
3
3
+
50 oC, 4h
O
O
O
O
O
R
4
3
5
Ar
H
H
NH
Ar
+
DCM/5mol % Bi(OTf)
DCM/ 5 mol% Bi(OTf)
N
3
3
NH2
H2N
50 oC, 10h
O
O
O
O
5
7
CHO
Ar=
R= 4 - Cl
R
Scheme 3. Control experiments for the synthesis of 5c and 7c in a stepwise reaction.
mined at 517 nm using UV/Vis spectroscopy, and the remain-
ing amount of DPPH was calculated. Ascorbic acid (50 μg/mL)
was used as a standard. The free radical scavenging activity
was expressed as follows:
Acknowledgments
The author expresses his deep gratitude to Sohag University
in Egypt for supporting and facilitating this study.
DPPH scavenging activity (%) = [Ac−As] / [Ac−Ab] × 100
where Ac, As and Ab are the absorbance of the control, the sam-
ple and the blank (MeOH+DMSO), respectively. Each sample
was assayed at 50 μg/mL and all experiments were carried out
in triplicate. The radical scavenging activity is shown in Table 4.
References
[1] Sethna S M, Shah N M. Chem Rev, 1945, 36: 1
[2] Riveiro M E, De Kimpe N, Moglioni A, Vazquez R, Monczor F, Shayo
C, Davio C. Curr Med Chem, 2010, 17: 1325
4. Conclusions
[3] Riveiro M E, Maes D, Vazquez R, Vermeulen M, Mangelinckx S, Ja-
cobs J, Debenedetti S, Shayo C, De Kimpe N, Davio C. Bioorg Med
Chem, 2009, 17: 6547
[4] O’Kennedy R, Thornes R D. Coumarins: Biology, Applications, and
Mode of Action. Chichester (UK): Wiley, 1997
[5] Yu D L, Suzuki M, Xie L, Morris-Natschke S L, Lee K H. Med Res Rev,
2003, 23: 322
[6] Zhang Q Y, Qin L P, He W D, Van Puywelde L, Maes D, Adams A, De
Kimpe N. Planta Medica, 2007, 73: 13
[7] Riveiro M E, Shayo C, Monczor F, Fernandez N, Baldi A, De Kimpe
N, Rossi J, Debenedetti S, Davio C. Cancer Lett, 2004, 210: 179
[8] Murray R D H, Mendez J, Brown S A. The Natural Coumarins: Oc-
currence, Chemistry, and Biochemistry. Chichester (UK): Wiley,
1982
The synthesis of potential bio-active hybrid molecules ob-
tained from naturally occurring coumarin-chalcone moieties
and coumarins linked to pyrazoline using Bi(OTf)3 as a highly
efficient catalyst has been achieved using a one-pot mul-
ti-component reaction protocol. This method has the ad-
vantages of low cost, short reaction time, high atom economy,
convenience and efficiency. It also offers a selective approach to
the synthesis of coumarins, a structural motif found in a large
number of natural products, pharmaceuticals and functional-
ized materials. Such a selective procedure offers energy saving
advantages and reduces the expense of the purification process.
The synthesized compounds showed DPPH scavenging activity.
Applications of this protocol to the selective synthesis of bioac-
tive molecules are in progress in our research group.
[9] Nguyen V T, Debenedetti S, De Kimpe N. Tetrahedron Lett, 2003,
44: 4199
[10] Maes D, Vervisch S, Debenedetti S, Davio C. Mangelinckx S, Giubel-
lina N, De Kimpe N. Tetrahedron, 2005, 61: 2505
[11] Ngameni B, Watchueng J, Boyom F F, Keumedjio F, Ngadjui B T,
Gut J, Abegaz B M, Rosenthal P J. ARKIVOC, 2007: 116
[12] Okwu D E, Ukanwa N. Chem Sin, 2010, 1(2): 21
[13] Ballesteros J F, Sanz M J, Ubeda A, Miranda M A, Iborra S, Paya M,
Alcaraz M. J Med Chem, 1995, 38: 2794
[14] Go M L, Wu X, Liu X L. Curr Med Chem, 2005, 12: 483
[15] Mukherjee S, Kumar V, Prasad A K, Raj H G, Bracke M E, Olsen C E,
Jain S C, Parmar V S. Bioorg Med Chem, 2001, 9: 337
[16] Liu M, Wilairat P, Croft S L, Tan A L G, Go M L. Bioorg Med Chem,
2003, 11: 2729
Table 4
DPPH radical scavenging assay of compounds 7a–7h.
Compound
7a
7b
7c
7d
7e
DPPH scavenging (%)
44.85 ± 0.32
59.29 ± 0.24
36.56 ± 0.37
78.10 ± 0.42
51.23 ± 0.45
28.57 ± 0.31
56.42 ± 0.32
27.30 ± 0.34
94.56 ± 0.34
7f
7g
7h
[17] Sivakumar P M, Babu S K G, Mukesh D. Chem Pharm Bull, 2007, 55:
44
[18] Viana G S B, Bandeira M A M, Mantos F J A. Phytomedicine, 2003,
10: 189
Ascorbic acid

1130
Mahmoud. Abd El Aleem. Ali. Ali. El-Remaily / Chinese Journal of Catalysis 36 (2015) 1124–1130
Graphical Abstract
Chin. J. Catal., 2015, 36: 1124–1130 doi: 10.1016/S1872-2067(14)60308-9
Bismuth triflate: A highly efficient catalyst for the synthesis of
bio-active coumarin compounds via one-pot multi-component
reaction
O
O
Mahmoud. Abd El Aleem. Ali. Ali. El-Remaily *
Sohag University- 82524, Sohag, Egypt
O
O
CHO
OH
DCM/ 5 mol% Bi(OTf)3
50 oC, 15-30 min
+
OR'
R'= CH3 or C2H5
CHO
2
O
R
5
A series of coumarin-chalcone hybrid compounds and coumarins linked to
pyrazoline was synthesized in good yields and short time using a simple
and efficient method. This method involved the one-pot reaction of salic-
ylaldehyde, an α-ketoester and an aromatic aldehyde (in the case of the
coumarin-chalcone derivatives) in addition to hydrazine hydrate (in the
case of the pyrazolyl coumarins) in the presence of a catalytic amount of
bismuth triflate [Bi(OTf)3, 5 mol%]. The synthesized compounds showed
scavenging activity towards the free radical 2,2-diphenyl-1-picrylhydrazyl.
1
+
96 - 88 % Yield
R
R
NH2
6
3
H2
N
NH
N
DCM/ 5 mol% Bi(OTf)
DCM/5 mol% Bi(OTf)3
3
2h - 4h
O
O
7
95 - 86 % Yield
1
All compounds were characterized by IR, H NMR and 13C NMR spectros-
copy.
[19] Xia Y, Yang Z Y, Xia P, Bastow K F, Nakanishi Y, Lee K H. Bioorg
Med Chem lett, 2000, 10: 699
[20] Ducki S, Forrest R, Hadfield J A, Kendall A, Lawrence N J, McGown
A T, Rennison D. Bioorg Med Chem Lett, 1998, 8: 1051
[21] Wagner B D. Molecules, 2009, 14: 210
[22] Dorlars A, Schellhammer C W, Schroeder J. Angew Chem Int Ed,
1975, 14: 665
[23] Kumar S, Bawa S, Drabu S, Kumar R, Gupta H. Recent Patents on
Anti-Infective Drug Discovery, 2009, 4: 154
[36] Antoniotti S, Dunach E. C R Chim, 2004, 7: 679
[37] Mohammadpoor-Baltork I, Khosropour A R, Moghadam M, Tang-
estaninejad S, Mirkhani V, Baghersad S, Mirjafari A. C R Chim,
2011, 14: 944
[38] Wang Z Z, Fang S Y. Eur J Org Chem, 2009: 5505
[39] Ollevier T. Org Biomol Chem, 2013, 11: 2740
[40] Ollevier T. Top Curr Chem, 2012, 311: 69
[41] Pin F, Comesse S, Garrigues B, Marchaln S, Daich A. J Org Chem,
2007, 72: 1181
[24] Zhu J P, Bienayme H. Multicomponent Reactions. Weinheim:
WILEY-VCH, 2005
[25] Tejedor D, Garcia-Tellado F. Chem Soc Rev, 2007, 36: 484
[26] Ugi I. Pure Appl Chem, 2001, 73: 187
[42] Anzalone P W, Baru A R, Danielson E M, Hayes P D, Nguyen M P,
Panico A F, Smith R C, Mohan R S. J Org Chem, 2005, 70: 2091
[43] Rueping M, Nachtsheim B J, Ieawsuwan W. Adv Synth Catal, 2006,
348: 1033
[27] Lieby-Muller F, Simon C, Constantieux T, Rodriguez, J. QSAR Comb
Sci, 2006, 25: 432
[44] Ollevier T, Li Z Y. Adv Synth Catal, 2009, 351: 3251
[45] Venkat Narsaiah A, Reddy B V S, Premalatha K, Reddy S S, Yadav J
S. Catal Lett, 2009, 131: 480
[46] Podgorski D M, Krabbe S W, Le L N, Sierszulski P R, Mohan R S.
Synthesis, 2010: 2771
[47] Sugino T, Tanaka K. Chem Lett, 2001, 30: 110
[48] Bhatnagar A, Sharma P K, Kumar N, Upadhyay A. Pharm Chem J,
2012, 46: 482
[28] Trost B M. Angew Chem Int Ed, 1995, 34: 259
[29] Wender P A, Handy S T, Wright D L. Chem Ind, 1997: 767
[30] Weber L. Curr Opin Chem Biol, 2000, 4: 295-302
[31] El-Remaily M A A. Tetrahedron, 2014, 70: 2971
[32] Domling A. Curr Opin Chem Biol, 2002, 6: 306
[33] Leonard N M, Wieland L C, Mohan R S. Tetrahedron, 2002, 58:
8373
[49] Blois M S. Nature, 1958, 181: 1199
[34] Thirupathi P, Kim S S. Tetrahedron, 2009, 65: 5168
[35] Rivera S, Bandyopadhyay D, Banik B K. Tetrahedron Lett, 2009, 50:
5445
[50] Samshuddin S, Narayana B, Sarojini B K, Yathirajan H S,
Raghavendra R. Pharm Chem, 2012, 4: 1445
[51] Tiwari A K. Curr Sci, 2004, 86: 1092