FeCl3-catalysed ultrasonic-assisted, solvent-free synthesis of 4-substituted coumarins. A useful complement to the Pechmann reaction

Article abstract of DOI:10.1016/j.ultsonch.2013.10.018

The catalytic activity of FeCl₃ for the synthesis of a variety of 4-substituted coumarins using high energy techniques has been investigated. The ultrasonic-assisted conditions provide a useful complement to the Pechmann reaction, affording the coumarin derivatives in excellent yields, under solvent-free conditions, in short reaction times using an inexpensive, mild and benign Lewis acid catalyst.

Full text of DOI:10.1016/j.ultsonch.2013.10.018

Ultrasonics Sonochemistry 21 (2014) 937–942
Contents lists available at ScienceDirect
Ultrasonics Sonochemistry
journal homepage: www.elsevier.com/locate/ultson
Short Communication
FeCl3-catalysed ultrasonic-assisted, solvent-free synthesis
of 4-substituted coumarins. A useful complement to the Pechmann
reaction
Kyriakos C. Prousis, Nicolaos Avlonitis 1, Georgios A. Heropoulos , Theodora Calogeropoulou
⇑
⇑
Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, 11635 Athens, Greece
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 8 August 2013
Received in revised form 17 October 2013
Accepted 17 October 2013
Available online 29 October 2013
The catalytic activity of FeCl3 for the synthesis of a variety of 4-substituted coumarins using high energy
techniques has been investigated. The ultrasonic-assisted conditions provide a useful complement to the
Pechmann reaction, affording the coumarin derivatives in excellent yields, under solvent-free conditions,
in short reaction times using an inexpensive, mild and benign Lewis acid catalyst.
Ó 2013 Elsevier B.V. All rights reserved.
Keywords:
Pechmann reaction
FeCl3 catalyst
Ultrasound
Microwave
Solvent-free
1. Introduction
Further modifications involve the use of solid acid catalysts or
exchange resins as alternatives to conventional acid catalysts, such
3-Oxo-3H-benzopyrans, commonly designated as coumarins,
are widely encountered in nature [1]. These compounds find
application in pharmaceuticals, fragrances, agrochemicals, and
insecticides [2–4] since they possess a wide range of pharmacolog-
ical activities including anticancer [5], antioxidant [6,7], anti-
inflammatory, anti-HIV, anticoagulant, antibacterial, analgesic and
immunomodulatory [8]. In addition, they represent one of the most
sensitive and widely employed category of reagents for fluorescent
derivatization [9–11].
The widespread biological activities of coumarin derivatives
have aroused great interest in the development of new methods
for their synthesis. Coumarins and their derivatives can be synthe-
sized by various methods, such as the Pechmann [12,13], Perkin
[14], Knoevenagel [15], Reformatsky [16], and Wittig reactions
[17]. More specifically, the Pechmann reaction is widely used for
preparing 4-substituted coumarins and involves the coupling of
phenols and b-ketoesters, in the presence of acid catalysts includ-
ing sulfuric acid [18], trifluoroacetic acid [19], P2O5 [20], or Lewis
acids such as ZnCl3, AlCl3, gallium triiodide [21], AgOTf [22] and
SnCl2Á2H2O [23].
as sulphamic acid [24], pentafluorophenylammonium triflate [25],
sulphated zirconia [26], nanocrystalline ZnO/pyridine dicarboxylic
acid [27], nafion resins [28] or cation exchange resins [29] how-
ever, very often they require high temperatures, long reaction
times and in some cases result in lower yields. Recently, metal–or-
ganic frameworks (MOFs) Fe- and Cu-benzene-1,3,5-tricarboxylate
(Fe- and CuBTC) have been investigated as solid acid catalysts for
the synthesis of coumarins using the Pechmann reaction [30].
A number of literature reports have focused on the synthesis of
heterocycles, including coumarins, under solvent-free conditions
as an eco-friendly strategy since it significantly reduces waste pro-
duction and precludes the use of organic solvents [31]. More, spe-
cifically for the solvent-free Pechmann reaction a variety of
catalysts (Brønsted, Lewis or solid acids) have been employed
which include samarium(III) nitrate hexahydrate [32], boron tri-
fluoride dihydrate [33], BiCl3 [34], Bi(NO3)3Á5H2O [35], Sc(OTf)3
[36], LiBr [37], BaCl2 [38], TiCl4 [39], ZrCl4 [40,41], silica gel sup-
ported zirconyl chloride octahydrate [42], HClO4ÁSiO2 [43], alumina
sulfuric acid [44], poly(4-vinylpyridine)-supported copper iodide
[45], PEG-SO3H [46], Zirconium(IV) Phosphotungstate and 12-
Tungstophosphoric acid supported onto ZrO2 [47]. In addition,
the use of ionic liquids has also been explored in the solvent-free
Pechmann reaction of coumarins [48].
⇑
Corresponding authors. Tel.: +30 210 7273833; fax: +30 210 7273831.
E-mail address: tcalog@eie.gr (T. Calogeropoulou).
Current address: Centre for Inflammation Research, The Queen’s Medical
1
The search of environmentally friendly and efficient synthetic
approaches represents a new trend in organic synthesis during
Research Institute, MRC/University of Edinburgh, 47 Little France Crescent, EH16
4TJ Edinburgh, UK.
1350-4177/$ - see front matter Ó 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.ultsonch.2013.10.018

938
K.C. Prousis et al. / Ultrasonics Sonochemistry 21 (2014) 937–942
Table 1
the last years. Synthetic chemists are increasingly paying attention
to enabling technologies aiming at achieving high efficiency and
meeting the green criteria of energy savings and the absence of
dangerous or harsh reagents. In this respect there is a tendency
to employ microwaves and/or ultrasound to accelerate organic
reactions. The use of microwaves has emerged as a powerful tool
for organic transformations since it reduces considerably the reac-
tion time providing remarkable rate enhancement in a number of
classical organic reactions, thus, leading to the high-speed con-
struction of versatile chemical entities [49].
Optimisation of the Pechmann reaction conditions using microwave irradiation.
Entry
Reaction conditions microwave irradiation
Yield of 3a (%)
1
2
3
80 °C/150 W 20 mina
100 °C/150 W 10 mina
120 °C/150 W 10 mina
84
99
55
a
The disappearance of phloroglucinol, checked by TLC, determined the reaction
time in each case.
Recent reports have demonstrated acceleration of the Pech-
mann reaction by microwave irradiation catalysed by H2SO4 [50],
TSA [51], wet phosphoric acid imidazolium dihydrogen phosphate
[52], P2O5/molecular sieves 3 Å [53], mesoporous zirconium phos-
phate [54], dipyridine copper chloride [55], and graphite:montmo-
rillonite K10 [56].
Ultrasound irradiation has been increasingly used in organic
synthesis in the last three decades. Ultrasonic-assisted organic syn-
thesis (UAOS) is a powerful and green approach which is becoming
popular for accelerating organic compound synthesis [57]. Com-
paring with traditional methods, this method is more conveniently
and easily controlled. A large number of organic reactions have
been carried out in higher yield, shorter reaction times and milder
conditions under ultrasound irradiation.
Recently, there is increasing interest in the application of ultra-
sound in the Pechmann reaction in the presence of various cata-
lysts including BiCl3 [58], poly(4-vinylpyridinium) hydrogen
sulphate as solid catalyst [59], copper perchlorate [60], and acid
zeolites [61].
In the context of our work on bioactive heterocyclic compounds
[62–64] we set out to investigate the microwave- and ultrasound-
assisted synthesis of 4-substituted coumarins under solvent-free
conditions using FeCl3 as catalyst. The development of environ-
mentally benign protocols has received impressive attention dur-
ing the last years and in this context iron can be considered as a
desirable alternative, due to its non toxicity, low price and eco-
friendly properties. Under this scope a number of iron-mediated
organic transformations have appeared in the literature [65].
To the best of our knowledge, this is the first report of the effect
of this eco-friendly Lewis acid in the Pechmann reaction using high
energy techniques and solvent-free conditions.
Subsequently, we set out to optimize the amount of catalyst and
we observed that the highest yield is obtained with 10 mol% FeCl3
for both the microwave- and ultrasound-assisted Pechmann reac-
tion (Table 2, entry 2). Use of 5 mol% FeCl3 resulted in a lower yield
of 3a (Table 2, entry 1) and increase of catalyst amount to 20 mol%
led to a more pronounced reduction of the obtained product 3a
(Table 2, entry 3), while no product formation was observed in
the absence of catalyst (Table 2, entry 4).
Thus, we proceeded to investigate the scope of the reaction
using our optimized conditions and a series of phenols and poly-
phenols with a variety of b-ketoesters (Scheme 2). The results of
the comparative study between microwave and ultrasonic irradia-
tion are described in Table 3. In addition, to investigate the effect of
the two high energy techniques we compared the results with con-
ventional heating at 70 °C. This temperature was selected in order
to compare directly our results with the previously reported meth-
od by Kumar et al. [66] who employed 20% mol anhydrous FeCl3, as
a Lewis acid in an ionic liquid medium at 70 °C. Furthermore, aim-
ing at obtaining a direct comparison with our microwave-assisted
conditions, we performed the Pechmann reaction between phloro-
glucinol and ethyl acetoacetate in the presence of 10% mol anhy-
drous FeCl3 with heating at 100 °C and the desired product 3a
was formed in 3 h in 98% yield (data not shown). In the absence
of FeCl3 no product formation was observed with heating either
at 70° or 100 °C. As illustrated in Table 3 the yields obtained were
good to excellent. It is clear that the reaction time is reduced from
several hours (5–12 h) to only a few minutes by using microwave
or ultrasonic irradiation. However, the effect of ultrasound is more
pronounced on the reaction outcome, resulting in high yields and
in several occasions (Table 3, entries 5, 7, 9 and 10) higher than
with the other two techniques.
The highest yields were obtained with phloroglucinol (1a) and
resorcinol (1b) and ethyl acetoacetate (Table 3, entries 1 and 4)
due to the presence of three and two hydroxyl groups, respectively,
which resulted in activation of the benzene ring for hydroxyl alkyl-
ation. The yield of the corresponding reaction with pyrogallol (1e)
(Table 3, entry 10) was lower, probably due to steric hindrance
and/or oxidation to a quinone. The dialkoxyphenol 1c bearing
two methoxy groups at the meta position of the hydroxyl group
gave the corresponding 4-substituted coumarins in very good to
excellent yields without observing any dealkylation products (Ta-
ble 3, entries 6–8). The reaction of phenol and nitrophenols with
ethyl acetoacetate failed to give the corresponding coumarin deriv-
atives under our conditions (data not shown).
2. Results and discussion
The reaction of phloroglucinol (1a) (1 mmol) with ethyl aceto-
acetate (2a) (2 mmol) was selected as a model for the optimization
of the reaction parameters (Scheme 1). Initially, we set out to select
the best conditions using sealed-vessel microwave processing and
10 mol% catalyst. As can be seen in Table 1 use of microwave irra-
diation for 10 min at 100 °C using 150 W, afforded the highest yield
(99%) (Table 1, entry 2). Reduction of the temperature led to a de-
crease in the yield of product 3a (84%) (Table 1, entry 1) while, in-
crease in temperature decreased the yield even further (55%)
(Table 1, entry 3).
O
OH Me
HO
OH
Me
FeCl3
+
OEt
µW
HO
O
O
OH
O
1a
2a
3a
Scheme 1. Microwave-assisted synthesis of 5,7-dihydroxy-4-methyl-2H-1-benzopyran-2-one (3a) catalysed by FeCl3.

K.C. Prousis et al. / Ultrasonics Sonochemistry 21 (2014) 937–942
939
Table 2
compared the results obtained by our method to others reported
in the literature, focusing mainly on solvent-free conditions in
the presence of homo or heterogeneous catalysts (Table 4).
Overall, as can be seen our reaction conditions afford the de-
sired product 3a either in higher yields, or in shorter reaction
times, or both in comparison to literature reports.
Optimisation of FeCl3 amount under microwave or ultrasound irradiation.
Entry
Catalyst (mol%)
Yield of 3a (%)a
Yield of 3a (%)b
1
2
3
4
FeCl3 (5)
FeCl3 (10)
FeCl3 (20)
FeCl3 (0)
79
99
54
0
82
99
60
0
a
Microwave irradiation, 100 °C/150 W, 10 min.
Ultrasound 20 kHz, nominal power 130 W, 18 min.
3. Experimental section
b
3.1. General remarks
Our reaction conditions can be applied for the Pechmann reac-
1H NMR spectra were recorded at 600 or 300 MHz, and 13C NMR
spectra at 75 MHz. 1H and 13C NMR spectra are internally refer-
enced to residual solvent signals (CDCl3, DMSO-d6, CD3OD-d4). Data
for 1H NMR are reported as follows: chemical shift (d ppm), multi-
plicity (s = singlet, d = doublet, dd = doublet of doublet, m = multi-
plet), coupling constant and integration. Data for 13C NMR are
reported in terms of chemical shift (d ppm). Melting points (°C)
are uncorrected. Microwave-assisted reactions were performed in
a microwave reactor CEM Discover LabMate. The ultrasound-as-
sisted reactions were carried out using a Sonics & Material INC. Vi-
bra-Cell VCX-130 Titanium alloy Ti-6Al-4V probe (20 kHz, 130 W)
with a Stepped Micro Tip 3 mm diameter. The HR-MS spectrum
was obtained using a UHPLC-MSn Orbitrap Velos-Thermo mass
spectrometer.
tion using phenols substituted by electron donating groups and b-
keto esters bearing either electron donating (Table 3, entries 1, 2, 4,
5, 6, 7, 9 and 10) or electron withdrawing substituents (Table 3, en-
tries 3 and 8). In addition, the previously reported method using
20% mol anhydrous FeCl3, as a Lewis acid in an ionic liquid medium
at 70 °C [66] suffered from lower yields, with longer reaction times
and twice the amount of catalyst, as compared to our sonochemical
reaction.
The Pechmann reaction is exergonic but does not take place in
measurable amounts at room temperature and thus, requires ini-
tialisation through various sources including microwave and ultra-
sound. A recent theoretical study on the mechanism of the
Pechmann reaction [67] suggests that three possible routes featur-
ing (A) trans-esterification; electrophilic attack; water elimination
(B) electrophilic attack; water elimination; trans-esterification (C)
electrophilic attack; trans-esterification; water elimination, oper-
ate simultaneously. Furthermore, the oxo form of the b-keto-ester
can perform the electrophilic attack to the phenolic substrate in an
energetically more favourable way, thus precluding the participa-
tion of its enolic form in the reaction mechanism.
Formation of the desired compounds was accelerated by micro-
wave irradiation (10 min) albeit in lower yields as compared with
the conventional heating method. Only in the case of phloroglu-
cinol and ethyl acetoacetate we had comparable high yields.
Apparently, the microwave intrinsic effects which were not influ-
enced by solvents (solvent-free conditions), were less pronounced
than the thermal effects, may be due to the predominating reaction
pathway, as mentioned above. Conversely, our results underline
the positive effect of ultrasound on the reaction outcome. Ultrason-
ication is linked to the cavitation phenomenon which causes high
speed impinging liquid jets and strong hydrodynamic shear-forces.
It is well known that when ultrasound irradiation is applied to a
mixture, it generates alternating low-pressure and high-pressure
waves in liquids, leading to the formation and violent collapse of
small vacuum bubbles. When these bubbles burst, it results in high
temperature and high pressure and drive high-speed jets of the b-
keto ester into the FeCl3 surface which in turn, exposes fresh sur-
face of the Lewis acid catalyst, resulting in the enhancement of
its efficiency. Furthermore, the cavitation effect via the energy in-
put and material transfer between the reactants facilitates the
intermolecular reaction between the phenol and the b-keto ester.
Using the synthesis of compound 3a as a model reaction we
3.2. General procedure for the Pechmann reaction
3.2.1. Ultrasound method
A mixture of the appropriate phenol 1a–e (3.73 mmol), b-keto-
ester 2a–c (7.46 mmol) and anhydrous FeCl3 (0.373 mmol, 81 mg)
was placed in a 10 mL glass tube and was sonicated (20 kHz, 130 W
nominal power) for 1–20 min until completion of the reaction
checked by TLC. The tube during sonication was immersed in a
cooling bath set at 20 °C. For compounds 3a, 3b, 3c, 3f, 3j the reac-
tion mixture solidified upon completion of the reaction, due to
product precipitation. Subsequently, ethanol (5 mL) was added,
and the product 3a–j crystallized upon dropwise addition of water
(15 mL). The solid was filtered washed with water and was recrys-
tallized from ethanol/water. The final product was then dried un-
der high vacuum over P2O5.
3.2.2. Microwave method
A mixture of the appropriate phenol 1a–e (3.73 mmol), b-keto-
ester 2a–c (7.46 mmol) and anhydrous FeCl3 (0.373 mmol, 81 mg)
were added to a thick-wall borosilicate glass tube 10 mL. The tube
was sealed, was placed in a CEM Discover LabMate microwave
reactor and was irradiated 100 °C (150 W) for 10 min. After cooling
to room temperature, ethanol (5 mL) was added, and the product
3a–j crystallized upon dropwise addition of water (15 mL). The so-
lid was filtered washed with water and was recrystallized from
ethanol/water. The final product was then dried under high vac-
uum over P2O5.
R2
O
R2
cat. FeCl3
R1
+
R1
OEt
OH
µW or )))))
O
O
O
2a: R2 = Me
1a-1e
3a-3j
2b: R2 = Propyl
2c: R2 = CH2Cl
Scheme 2. Synthesis of coumarins catalysed by FeCl3 under solvent-free conditions, using microwave or ultrasound irradiation.

940
K.C. Prousis et al. / Ultrasonics Sonochemistry 21 (2014) 937–942
Table 3
Pechmann synthesis of 4-substituted coumarins in the presence of cat. amount FeCl3 under microwave or ultrasonic irradiation, or conventional heating.
Entry
1
Phenol
b-Keto ester
Product
Ultrasonic irradiationa
Microwave irradiationb
Coventional heatingc
Time (min)
18
Yield (%)d
Time (min)
10
Yield (%)d
Time (h)
12
Yield (%)d
2a
99
99
98
HO
OH
1a
OH
3a
1a
2
3
2b
2c
15
1
60
10
10
62
12
5
99
3b
3c
75
68
95
4
5
2a
2b
20
20
97
81
10
10
76
44
12
12
99
75
HO
OH
1b
1b
3d
3e
6
7
2a
2b
11
20
80
87
10
10
52
31
12
12
97
64
MeO
OH
1c
OMe
3f
1c
3g
3h
8
9
2c
2a
20
20
96
87
–
–
–
–
10
40
12
54
OH
1d
1d
3i
10
2a
12
55
10
39
12
36
OH
HO
1e
OH
1e
3j
a
b
c
Reaction conditions: phenol, 1.0 mmol;, b-keto ester 2.0 mmol, solvent-free, ultrasonic probe 3 mm diameter, 20 kHz, 130 W nominal power.
Reaction conditions: phenol, 1.0 mmol;, b-keto ester 2.0 mmol, solvent-free, W, 150 W, 100 °C.
Reaction conditions: phenol 1.0 mmol;, b-keto ester 2.0 mmol, solvent-free, heated at 70 °C.
l
d
Isolated yield.
3.2.3. Conventional heating method
3.2.4. 5,7-Dihydroxy-4-methyl-2H-1-benzopyran-2-one (3a)
A mixture of the appropriate phenol 1a–e (3.73 mmol), b-keto-
ester 2a–c (7.46 mmol) and anhydrous FeCl3 (0.373 mmol, 81 mg)
was heated at 70 °C. After completion of the reaction (TLC), ethanol
(5 mL) was added, and the product 3a–j crystallized upon drop-
wise addition of water (15 mL). The solid was filtered washed with
water and was recrystallized from ethanol/water. The final product
was then dried under high vacuum over P2O5.
Starting from phloroglucinol (1a) (3.73 mmol, 0.470 g) and
ethyl 3-oxobutanoate (2a) (7.46 mmol, 0.971 g) the title compound
3a was obtained as a beige solid. Mp: 293–295 °C (lit: 289–290 °C
dec.) [72]. 1H NMR (600 MHz, DMSO-d6): d 2.48 (3H, d, J = 1.2 Hz),
5.85 (1H, s), 6.16 (1H, d, J = 2.4 Hz), 6.25 (1H, d, J = 2.4 Hz), 10.30 (s,
1H), 10.53 (s, 1H). 13C NMR (75 MHz, DMSO-d6): d 23.5, 94.6, 99.1,
102.1, 108.9, 155.1, 156.6, 158.0, 160.2, 161.1.

K.C. Prousis et al. / Ultrasonics Sonochemistry 21 (2014) 937–942
941
Table 4
Comparison of the results obtained in this work for compound 3a to those reported by other groups.
Entry
Catalyst
Reaction conditions
Time
Yield (%)
Refs.
1
2
3
4
5
6
7
8
Sulphated zirconia
Neat/80 °C
Neat/80 °C
Neat/80 °C
Neat/100 °C
Neat/130 °C
Neat/80 °C
Neat/80 °C
Neat/40 °C
MW heating oven/140 W
Neat/ultrasonic bath (33–35 kHz, 85 W)
Neat/US (35KHz, 200 W)
Neat/70 °C
Neat/60 °C
Neat/130 °C
Neat/80 °C
Neat/85 °C
Neat/US (20 kHz, 130 W)
24 h
52
95
92
90
97
92
89
96
78
92
91
77
81
98
90
91
99
[26]
[32]
[35]
[38]
[43]
[45]
[46]
[48]
[52]
[58]
[59]
[66]
[68]
[69]
[70]
[71]
Sm(NO3)3Á6H2O
25 min
20 min
25 min
60 min
10 min
15 min
22 min
25 min
15 min
3 min
10 h
10 min
48 min
2 h
1 h
18 min
Bi(NO3)3Á5H2O
BaCl2
HClO4ÁSiO2
P4VPy–CuI
PEG–SO3H
3-methyl-1-sulfonic acid imidazolium hydrogen sulfate
Phosphoric acid imidazolium dihydrogenphosphate
BiCL3
Poly(4-vinylpyridinium) hydrogen sulfate
[BMIM] [Tf2N], FeCl3
p-TsOH
9
10
11
12
13
14
15
16
17
Wells–Dawson heteropolyacid H6P2W18O62Á24H2O
KAl(SO4)2Á12H2O
Yb(OTf)3
FeCl3
This work
3.2.5. 5,7-Dihydroxy-4-propyl-2H-1-benzopyran-2-one (3b)
Starting from phloroglucinol (1a) (3.73 mmol, 0.470 g) and
ethyl 3-oxohexanoate (2b) (7.46 mmol, 1.18 g) the title compound
3b was obtained as a beige solid. Mp: 241–243 °C (lit: 244 °C) [73].
1H NMR (600 MHz, DMSO-d6): d 0.94 (3H, t, J = 7.2 Hz), 1.56–1.62
(2H, m), 2.85 (2H, t, J = 7.2 Hz), 5.82 (1H, s), 6.17 (1H, d,
J = 2.4 Hz), 6.26 (1H, d, J = 2.4 Hz), 10.26 (s, 1H), 10.54 (s, 1H). 13C
NMR (75 MHz, DMSO-d6): d 13.9, 22.6, 37.3, 94.8, 99.3, 101.4,
108.3, 156.9, 157.5, 158.5, 160.2, 160.9.
3.2.10. 5,7-Dimethoxy-4-propyl-2H-1-benzopyran-2-one (3g)
Starting from 3,5-dimethoxyphenol (1c) (3.73 mmol, 0.575 g)
and ethyl 3-oxohexanoate (2b) (7.46 mmol, 1.18 g) the title com-
pound 3g was obtained as a beige solid. Mp 119–121 °C (lit:
117–119 °C) [75]. 1H NMR (300 MHz, CDCl3): d 0.99 (3H, t,
J = 7.2 Hz), 1.53–1.64 (2H, m), 2.84 (3H, t, J = 7.5 Hz), 3.84/3.86
(6H, 2s), 5.96 (1H, s), 6.29 (1H, d, J = 2.4 Hz), 6.44 (1H, d,
J = 2.4 Hz); 13C NMR (75 MHz, CDCl3): d 14.1, 22.8, 38.5, 55.7,
55.8, 93.6, 95.5, 104.3, 110.7, 157.3, 158.2, 158.6, 161.3, 162.6.
3.2.11. 4-(Chloromethyl)-5,7-dimethoxy-2H-chromen-2-one (3h)
Starting from 3,5-dimethoxyphenol (1c) (3.73 mmol, 0.575 g)
and ethyl 4-chloro-3-oxobutanoate 2c (7.46 mmol, 1.23 g) the title
compound 3h was obtained as a beige solid. Mp 155–157 °C. 1H
NMR (300 MHz, DMSO-d6): d 3.86/3.90 (6H, 2s), 4.90 (2H, s), 6.33
(1H, d, J = 2.4 Hz), 6.46 (1H, s), 6.48 (1H, d, J = 2.4 Hz); 13C NMR
(75 MHz, CDCl3): d 45.5, 56.0, 56.3, 94.0, 96.0, 102.7, 111.4,
151.2, 157.1, 158.4, 160.9, 163.3; HRMS (ESI+): [M + H]+, found
255.04190. C12H12Cl35O4 requires 255.04186.
3.2.6. 4-(Chloromethyl)-5,7-dihydroxy-2H-1-benzopyran-2-one (3c)
Starting from phloroglucinol (1a) (3.73 mmol, 0.470 g) and
ethyl 4-chloro-3-oxobutanoate (2c) (7.46 mmol, 1.23 g) the title
compound 3c was obtained as a beige solid. Mp: 251–253 °C, (lit:
246–248 °C) [72]; 1H NMR (600 MHz, DMSO-d6): d 5.04 (2H, s),
6.22 (1H, s), 6.23 (1H, d, J = 2.4 Hz), 6.28 (1H, d, J = 2.4 Hz), 10.42
(s, 1H), 10.89 (s, 1H); 13C NMR (75 MHz, DMSO-d6): d 45.1, 94.9,
99.3, 99.9, 108.9, 152.0, 156.6, 157.2, 160.2, 161.6.
3.2.7. 7-Hydroxy-4-methyl-2H-1-benzopyran-2-one (3d)
3.2.12. 1-Methyl-3H-benzo[f]chromen-3-one (3i)
Starting from resorcinol (1b) (3.73 mmol, 0.411 g) and ethyl 3-
oxobutanoate (2a) (7.46 mmol, 0.971 g) the title compound 3d was
obtained as a beige solid. Mp 184–186 °C (lit: 185–187 °C) [36]. 1H
NMR (DMSO-d6, 600 MHz): d 2.37 (3H, d, J = 1.2 Hz), 6.13 (1H, s),
6.70 (1H, d, J = 2.4 Hz), 6.80 (1H, dd, J = 2.4, 8.4 Hz), 7.60 (1H, d,
J = 3.0 Hz), 10.50 (1H, s), 13C NMR (75 MHz, DMSO-d6): d 18.2,
102.2, 110.3, 112.0, 112.9, 126.6, 153.6, 154.9, 160.3, 161.2.
Starting from 1-naphthol (1d) (3.73 mmol, 0.538 g) and ethyl 3-
oxobutanoate (2a) (7.46 mmol, 0.971 g) the title compound 3i was
obtained as a beige solid. Mp 167–169 °C (lit: 152–154 °C) [52]. 1H
NMR (CDCl3, 600 MHz): d 2.54 (3H, s), 6.37 (1H, d, J = 2.4 Hz), 7.57–
7.71 (4H, m), 7.84–7.88 (1H, m), 8.53–8.57 (1H, m); 13C NMR
(CDCl3, 75 MHz): d 19.4, 114.5, 115.3, 120.4, 122.8, 123.3, 124.3,
127.3, 127.8, 128.7, 134.9, 150.7, 153.6, 161.1.
3.2.8. 7-Hydroxy-4-propyl-2H-1-benzopyran-2-one (3e)
3.2.13. 7,8-Dihydroxy-4-methyl-2H-1-benzopyran-2-one (3j)
Starting from pyrogallol (1e) (3.73 mmol, 0.470 g) and ethyl 3-
oxobutanoate (2a) (7.46 mmol, 0.971 g) the title compound 3j was
obtained as a beige solid. Mp 240–242 °C (lit: 242–244 °C) [72]. 1H
NMR (600 MHz, DMSO-d6): d 2.35 (3H, s), 6.09 (1H, s), 6.78 (1H, d,
J = 8.4 Hz), 7.06 (1H, d, J = 8.4 Hz), 9.59 (br s, 2H). 13C NMR
(75 MHz, CD3OD-d4): d 18.8, 111.1, 113.3, 114.5, 116.7, 133.4,
144.4, 150.6, 156.4, 163.5.
Starting from resorcinol (1b) (3.73 mmol, 0.411 g) and ethyl 3-
oxohexanoate (2b) (7.46 mmol, 1.18 g) the title compound 3e was
obtained as a beige solid. Mp 129–131 °C (lit: 127–128 °C) [74]. 1H
NMR (300 MHz, CDCl3/DMSO-d6): d 0.95 (3H, t, J = 7.5 Hz), 1.56–
1.67 (2H, m), 2.59 (2H, t, J = 7.5 Hz), 5.94 (1H, s), 6.68–6.71 (2H,
m), 7.35 (1H, d, J = 3.6 Hz), 9.69 (1H, br s), 13C NMR (75 MHz,
CDCl3/DMSO-d6): d 18.8, 21.4, 33.6, 103.1, 109.6, 111.7, 113.0,
125.3, 155.3, 156.6, 160.9, 161.8.
3.2.9. 5,7-Dimethoxy-4-methyl-2H-1-benzopyran-2-one (3f)
4. Conclusion
Starting from 3,5-dimethoxyphenol (1c) (3.73 mmol, 0.575 g)
and ethyl 3-oxobutanoate (2a) (7.46 mmol, 0.971 g) the title com-
pound 3f was obtained as a beige solid. Mp 170–172 °C (lit: 171–
173 °C) [41]. 1H NMR (600 MHz, DMSO-d6): d 2.53 (3H, s), 3.85/
3.86 (6H, 2s), 5.95 (1H, s), 6.29 (1H, d, J = 2.4 Hz), 6.44 (1H, d,
J = 2.4 Hz); 13C NMR (75 MHz, DMSO-d6): d 24.4, 55.80, 55.84,
93.4, 95.5, 105.0, 111.4, 154.6, 157.1, 159.2, 161.2, 162.9.
In conclusion, we have successfully demonstrated the catalytic
activity of FeCl3 for the synthesis of a variety of 4-substituted cou-
marins under ultrasound and microwave conditions. Moreover, the
ultrasound-assisted conditions provide a useful complement to the
Pechmann reaction and leads to excellent yields of the coumarin
derivatives under mild conditions, in short reaction time using an

942
K.C. Prousis et al. / Ultrasonics Sonochemistry 21 (2014) 937–942
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http://dx.doi.org/10.1155/2012/306162.
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Acknowledgments
Funding from the European Union (FP7-REGPOT-2009-1) under
grant agreement No. 245866 ‘‘ARCADE’’, is gratefully acknowledged.
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