Simple protic ionic liquid [Et3NH][HSO4] as a proficient catalyst for facile synthesis of biscoumarins

Article abstract of DOI:10.1007/s11164-017-2932-5

Abstract: We have explored a number of protic ionic liquids (PILs) as a catalyst for the synthesis of biscoumarins by condensation of 4-hydroxycoumarin with an aromatic aldehyde. Methylimidazolium- and triethylammonium-based PILs were synthesized by simple neutralization reaction with protic acids. Triethylammonium hydrogen sulfate [Et₃NH][HSO₄] was found to be the best among the studied PILs concerning the yield of products and reaction time period. Different biscoumarin derivatives were synthesized based on 4-hydroxycoumarin and various substituted aromatic aldehydes at optimum reaction conditions. Obtained products were separated just by simple filtration. The facile method does not require additional purification for formed products. The catalyst has shown better yields along with outstanding recyclability, providing an environmental benign protocol for the synthesis of biscoumarin derivatives. Graphical Abstract: Screening of simple protic ionic liquids as a catalyst in the synthesis of biscoumarins, out of which [Et₃NH][HSO₄] was found to be best among the studied PILs.

Full text of DOI:10.1007/s11164-017-2932-5

Res Chem Intermed
DOI 10.1007/s11164-017-2932-5
Simple protic ionic liquid [Et3NH][HSO4]
as a proficient catalyst for facile synthesis
of biscoumarins
Sandip K. Patil1 Deepak V. Awale1 Madagonda M. Vadiyar1
•
•
•
Suryakant A. Patil1 Sagar C. Bhise1
Sanjay S. Kolekar1
•
•
Received: 22 December 2016 / Accepted: 4 March 2017
Ó Springer Science+Business Media Dordrecht 2017
Abstract We have explored a number of protic ionic liquids (PILs) as a catalyst for the
synthesis of biscoumarins by condensation of 4-hydroxycoumarin with an aromatic
aldehyde. Methylimidazolium- and triethylammonium-based PILs were synthesized by
simple neutralization reaction with protic acids. Triethylammonium hydrogen sulfate
[Et3NH][HSO4] was found to be the best among the studied PILs concerning the yield of
products and reaction time period. Different biscoumarin derivatives were synthesized
based on 4-hydroxycoumarin and various substituted aromatic aldehydes at optimum
reaction conditions. Obtained products were separated just by simple filtration. The
facile method does not require additional purification for formed products. The catalyst
has shown better yields along with outstanding recyclability, providing an environmental
benign protocol for the synthesis of biscoumarin derivatives.
Graphical Abstract Screening of simple protic ionic liquids as a catalyst in the
synthesis of biscoumarins, out of which [Et3NH][HSO4] was found to be best among the
studied PILs.
Electronic supplementary material The online version of this article (doi:10.1007/s11164-017-2932-5)
contains supplementary material, which is available to authorized users.
&
Sanjay S. Kolekar
sskolekar@gmail.com
1
Analytical Chemistry and Material Science Research Laboratory, Department of Chemistry,
Shivaji University, Kolhapur, Maharashtra 416004, India
123

S. K. Patil et al.
Keywords Protic ionic liquid Á [Et3NH][HSO4] Á 4-Hydroxycoumarin Á
Biscoumarins Á Recyclability
Introduction
Ionic liquids (ILs) have been successfully employed in a variety of reactions as
environmentally benign catalysts and solvents; indeed, they provide the possibility
for green manufacturing in the chemical industry [1]. They have attracted increasing
interest in the context of green organic syntheses, and in fact were initially
introduced as alternative green reaction media because of their unique chemical and
physical properties, such as non-volatility, non-flammability, thermal stability and
controlled miscibility, as well as excellent recyclability, showing their significant
role in monitoring reactions as solvent or catalyst in both homogeneous and
heterogeneous systems [1–5]. Brønsted or Lewis acidic ionic liquids have been used
extensively for organic transformations as environmentally friendly catalysts [6].
Brønsted acidic or protic ionic liquids (PILs), a class of ionic liquids, are easily
produced through the combination of a Brønsted acid and Brønsted base. PILs
encompass a proton available for hydrogen bonding which differentiate them from
aprotic ILs [7]. PILs having the useful characteristics of solid acids and mineral
liquid acids, and are designed to replace traditional mineral liquid acids such as
sulfuric acid and hydrochloric acid in chemical procedures; in fact, they have
potential as dual solvent–catalysts in organic reactions [8–10].
The acid strength of PILs is an important factor for their use as catalysts in organic
transformations. The structure of the cations and anions as well as their combination
decides the Brønsted acidity of a PIL. Such acidic character makes them especially
different from other ILs and enhances their applicability as selective catalysts in
organic synthesis. PILs are of special importance because they simultaneously
possess proton acidity and the characteristic properties of ionic liquids [11]. Various
methods have been used to measure the acidity of PILs including the determination
of basicity of associated anions, the proton NMR technique [12, 13], the Hammett
acidity indicator with UV–visible spectroscopy [14] or titration against alkalis [15].
123

Simple protic ionic liquid [Et3NH][HSO4] as a proficient…
As the acid strength of a PIL is strongly correlated to its catalytic activity, it greatly
affects the product formation. For instance, in the case of Friedel–Crafts alkylation of
phenol with tert-butyl alcohol, a weak acid catalyst gave 2-tert-butylphenol, a
medium acid catalyst providing 4-tert-butylphenol, while in the presence of a strong
acid catalyst, 2,4-di-tert-butylphenol is formed. Accordingly, Duan et al. have tested
a series of pyridinium-based PILs as catalysts for this alkylation. On the basis of
acidity, the selectivity in the reaction varies, as an IL with bis(trifluoromethylsul-
fonyl)imide anion showed a strong acidic nature, whereas an IL with methanesul-
fonate demonstrated weak acidity [16]. Similarly, for the same reaction, a series of
SO3H functionalized imidazolium PILs along with [HSO4] anions and having
moderate acidity exhibited almost similar selectivities [17]. In another example, in
the Saucy–Marbet reaction, the PIL [Et3NH][HSO4] furnished the best results among
the five studied PILs incorporated with [HSO4] anions. Also, due to their lipohilic
nature, the conversion efficiency and the selectivity of the PILs was seen to be
decreased as the alkyl chain length in the IL moiety increased [18].
Due to their specific, selective and excellent catalytic performances, PILs have
been employed in numerous organic transformations, a few of them to be listed as,
Knoevenagel [19, 20] and Pechmann [21] and in other condensation reactions
[22, 23], the Diels–Alder reaction [24], the multicomponent Hantzsch reaction [25],
the Mannich reaction [26], esterification [27], the Biginelli reaction [28], the
Beckmann rearrangement [29], etc.
Biscoumarins are vital organic compounds which have received considerable
attention in synthetic and medicinal chemistry because of their broad spectrum of
biological activities as well as interesting potential in therapeutic applications. They
often possess interesting pharmacological properties such as antitumor and
antibacterial [30–32], anticancer [33], urease and a-glucosidase inhibitors [34, 35],
antifungal [36], antiproliferative activities [37], etc. 3,30-Arylmethylene-bis-4-
hydroxycoumarins, commonly known as biscoumarins, are usually synthesized by
condensation of 4-hydroxycoumarin with various substituted aldehydes [38]. Several
attempts have been made in the synthesis of biscoumarins with different catalysts and
media such as molecular iodine [39], metal salts as homogeneous catalysts [40, 41],
heterogeneous solid acid catalysts [42–44], nanocomposites and nanoparticles
[45, 46], and bio-supported acidic catalysts [47], while in a few cases mineral acids
like H2SO4 have been engaged [48]. However, many reported methods are associated
with inherent disadvantages like harsh reaction conditions, prolonged reaction times,
and expensive and less reusable catalysts, as well as time-consuming work-up
procedures. To overcome such circumstances and to obtain a more advantageous
method, a new environmentally benign protocol needs to be developed. Concerning
green methodology, ionic liquids are one of the best choices as catalysts. Many
researchers have explored a variety of ILs in the synthesis of biscoumarin
derivatives, for example, 1-butyl-3-methylimidazolium bromide, [bmim][Br] [49],
polymeric IL, poly(4-vinylpyridine-co-1-sulfonic acid butyl-4-vinylpyridinium)
hydrogen sulfate [50], benzimidazolium-based ILs [51], N-hydroxyethylammonium
formate/acetate [52], [pyridine–SO3H][Cl] [53], etc.
Ionic liquids have emerged as strong alternatives for conventional catalytic
systems in synthetic chemistry. In the synthesis of biscoumarins, the environmentally
123

S. K. Patil et al.
benign properties of ILs, such as non-toxic, easy to handle, negligible vapor pressure,
high thermal stability, etc., have made them able to replace the traditional catalysts
like mineral acids, heterogeneous or supported acid catalysts, metal salts, etc.
Reusability of catalysts is the most vital part in any synthesis. After a reaction, ILs
can be easily separated and reused for five to six more reaction cycles without
significant loss in catalytic activity, thus emphasizing their cost-effectiveness in
biscoumarin synthesis [51]. ILs can also reduce costs by avoiding the use of
expensive metal salts like ruthenium chloride [41]. ILs are more advantageous
materials for modifying inconvenient operating conditions; for instance, [pyridine–
SO3H][Cl] [53] and [MIM(CH2)4SO3H][HSO4] [54] have reduced the reaction time
up to 10–12 min, and the reaction temperature has been possibly minimized almost
to room temperature instead of high refluxing temperatures [52]; also, the yield of
biscoumarins can be increased above 90% by using minimum amounts of catalyst
(10–20 mol%) along with easy work-up procedures in the synthesis of biscoumarins
[49–51]. However, comparatively few reports are found that describe ILs as effective
catalysts for the synthesis of biscoumarins.
Taking into account the requirements in the synthesis of biscoumarins, we have
developed a new straightforward protocol by using simple protic ionic liquids
(PILs) as cost-effective catalysts. Ten numbers of PILs based on 1-methylimida-
zolium and triethylammonium cations were synthesized and tested in the synthesis
of biscoumarin derivatives. The reaction conditions including the reflux temper-
ature, catalyst loading, and time span for reaction were optimized; also, the
recyclability of catalyst was investigated.
Our aim was to develop a simple and cost-effective protocol for the synthesis of
biscoumarins. The imidazolium- and triethylammonium-based PIL catalysts studied
in this work are easily prepared by one-step neat neutralization reactions with easily
available mineral acids like H2SO4, HCl, HNO3, H3PO4 and CH3COOH. We are
proposing a facile synthetic method for biscoumarins by using these PILs as
catalysts under mild reaction conditions.
Experimental
Materials and equipments
All chemicals were purchased from commercial sources and used without any
further purification. Melting points were recorded on a Buchi B-545 apparatus in
open capillary tubes and are uncorrected. IR spectra were recorded on a Perkin-
Elmer FT-IR-1600 spectrophotometer. 1HNMR and 13C NMR spectra were
recorded on a Bruker Avance (300 and 75 MHz, respectively) spectrometer. Mass
spectra were recorded on a Shimadzu QP2010 GCMS.
Syntheses of PILs
PILs were synthesized by simple neutralization reactions (Scheme 1). To
1-methylimidazole was slowly added an equimolar amount of an acid, i.e.
123

Simple protic ionic liquid [Et3NH][HSO4] as a proficient…
0°C
N+
H
N
N
N
+
HX
-
X
-
[MIM][X]
0°C
N
N+
H
+
HX
X
[Et3NH][X]
X = HSO4, Cl, NO3, H2PO4, CH3COO
Scheme 1 Syntheses of 1-methylimdazolium- and triethylammonium-based PILs
Table 1 Screening of PILs in
the synthesis of biscoumarins
Entry
PIL used
Time (min.)
Yield (%)a
1.
–
480
30
–
2.
[MIM][HSO4]
[MIM][Cl]
85
49
44
59
34
88
73
71
66
46
3.
60
4.
[MIM][NO3]
[MIM][H2PO4]
[MIM][CH3COO]
[Et3NH][HSO4]
[Et3NH][Cl]
60
Selected catalyst with best
performance in bold
5.
90
Reaction conditions:
benzaldehyde:4-
6.
120
30
7.
hydroxycoumarin, 1:2 (molar
ratio); reflux temperature 80 °C;
catalyst 10 mol%; solvent
ethanol
8.
60
9.
[Et3NH][NO3]
[Et3NH][H2PO4]
[Et3NH][CH3COO]
60
10.
11.
90
a
Yields refer to isolated
products
120
H2SO4, HCl, HNO3, H3PO4 or CH3COOH under ice-cold conditions. The reaction
mixture was stirred for an appropriate time to form the corresponding ionic liquids
(Table 1, entries 2–6). The formed ILs were washed with ethyl acetate (3 9 10 mL)
followed by n-hexane, and dried in vacuum under reduced pressure. A similar
methodology was used for the synthesis of the respective triethylammonium-based
PILs (Table 1, entries 7–11).
General procedure for synthesis of biscoumarins
A typical procedure involves, in a round-bottom flask equipped with a reflux
condenser, in which a mixture of 4-hydroxycoumarin (2 mmol), arylaldehyde
(1 mmol), PIL catalyst (10 mol%) and 5 mL of ethanol was stirred at 80 °C.
The reaction was monitored by TLC. After completion of the reaction, a solid
product is obtained which is filtered and recrystallized with ethanol
(Scheme 2).
123

S. K. Patil et al.
Ar
OH
O
OH
OH
O
PIL (10 mol%)
EtOH, 80°C
+
Ar-CHO
2
O
O
O
O
(1 - 14)
Scheme 2 Typical condensation reaction of 4-hydroxycoumarin and arylaldehydes in the presence of
PIL for the synthesis of biscoumarins
Spectral data of ionic liquids
1. Triethylammonium hydrogen sulfate [Et3NH][HSO4] (Entry 7, Table 1) 1HNMR
(300 MHz, DMSO d6): d (ppm) 1.15–1.19 (t, 9H), 3.04–3.12 (m, 6H), 8.98 (s, 1H);
13CNMR (75 MHz, DMSO d6): d (ppm) 8.88, 46.40.
2. 3-Methylimidazolium hydrogen sulfate [MIM][HSO4] (Entry 2, Table 1) 1HNMR
(300 MHz, DMSO d6): d (ppm) 3.77 (s, 3H), 4.35 (s, 1H), 7.32 (s, 1H), 7.42 (s, 1H),
8.43 (s, 1H).
3. 3-Methylimidazolium chloride [MIM][Cl] (Entry 3, Table 1) 1HNMR
(300 MHz, DMSO d6): d (ppm) 3.88 (s, 3H), 5.45 (s, 1H), 7.55–7.56 (t, 1H),
7.63 (d, 1H), 9.02 (s, 1H).
4. 3-Methylimidazolium nitrate [MIM][NO3] (Entry 4, Table 1) 1HNMR
(300 MHz, DMSO d6): d (ppm) 3.88 (s, 3H), 5.45 (s, 1H), 7.55 (d, 1H), 7.63 (s,
1H), 9.02 (s, 1H).
5. 3-Methylimidazolium dihydrogen phosphate [MIM][H2PO4] (Entry 5,
Table 1) 1HNMR (300 MHz, DMSO d6): d (ppm) 3.72 (s, 3H), 4.54 (s, 1H),
7.07 (s, 1H), 7.20 (s, 1H), 8.00 (s, 1H).
6. 3-Methylimidazolium acetate [MIM][CH3COO] (Entry 6, Table 1) 1HNMR
(300 MHz, DMSO d6): d (ppm) 1.89 (s, 3H), 3.64 (s, 3H), 5.16 (s, 1H), 6.88 (s, 1H),
7.01 (s, 1H), 7.54 (s, 1H).
7. Triethylammonium chloride [Et3NH][Cl] (Entry 8, Table 1) 1HNMR
(300 MHz, DMSO d6): d (ppm) 1.21–1.26 (t, 9H), 3.03–3.10 (m, 6H), 10.38 (s, 1H).
8. Triethylammonium nitrate [Et3NH][NO3] (Entry 9, Table 1) 1HNMR
(300 MHz, DMSO d6): d (ppm) 1.21–1.26 (t, 9H), 3.03–3.10 (m, 6H), 10.38 (s, 1H).
9. Triethylammonium dihydrogen phosphate [Et3NH][H2PO4] (Entry 10,
Table 1) 1HNMR (300 MHz, DMSO d6): d (ppm) 1.20 (s, 9H), 3.00 (s, 6H),
9.85 (s, 1H).
123

Simple protic ionic liquid [Et3NH][HSO4] as a proficient…
10. Triethylammonium acetate [Et3NH][CH3COO] (Entry 11, Table 1) 1HNMR
(300 MHz, DMSO d6): d (ppm) 1.12 (s, 3H), 1.87 (s, 9H), 2.91–2.93 (d, 6H), 9.98
(s, 1H).
Spectral data of selected biscoumarins
1. 3,30-(phenylmethylene)bis(4-hydroxy-2H-1-benzopyran-2-one) (Entry 1, Table 3)
White solid, IR (KBr, cm-1) data: 3417, 3069, 2924, 2739, 1659, 1615, 1568, 1496,
1
1346, 1308, 756; HNMR (300 MHz, DMSO d6): d (ppm) 6.21 (s, 1H), 7.02–7.07
(t, 2H, J = 15 Hz), 7.09–7.12 (d, 1H, J = 9 Hz), 7.15–7.20 (t, 2H, J = 15 Hz),
7.25–7.30 (t, 4H, J = 15 Hz), 7.51–7.57 (m, 2H), 7.80–7.82 (t, 2H, J = 6 Hz),
13CNMR (75 MHz, DMSO d6): d (ppm) 36.47, 104.34, 118.99, 123.98, 124.43,
125.82, 127.12, 128.43, 132.10, 141.10, 152.74, 165.26, 166.57; Anal. Calcd. C,
72.81, H 3.91; Found C, 72.67, H 3.98; GC–MS, m/z = 412.
2. 3,30-(4-methoxyphenylmethylene)bis(4-hydroxy-2H-1-benzopyran-2-one) (Entry
2, Table 3) White solid, IR (KBr, cm-1) data: 3372, 2938, 2728, 1667, 1605,
1
1569, 1510, 1356, 1306, 1258, 1219, 1093, 769; HNMR (300 MHz, DMSO d6): d
(ppm) 3.68 (s, 3H), 6.24 (s, 1H), 6.75–6.78 (d, 2H, J = 9 Hz), 7.00–7.03 (d, 2H,
J = 9 Hz), 7.26–7.33 (m, 4H), 7.53–7.58 (q, 2H), 7.84–7.87 (t, 2H, J = 9 Hz);
13CNMR (75 MHz, DMSO d6): d (ppm) 35.72, 55.40, 104.64, 113.68, 116.29,
118.84, 124.04, 124.38, 128.16, 132.14, 132.54, 152.68, 157.66, 165.26, 166.27;
Anal. Calcd. C, 70.58, H 4.10; Found C, 71.57, H 3.93; GC–MS, m/z = 442.
3. 3,30-[(1H-imidazol-2-yl)methylene]bis(4-hydroxy-2H-1-benzopyran-2-one) (En-
try 6, Table 3) White solid, IR (KBr, cm-1) data: 3358, 3110, 2918, 2684, 1671,
1
1610, 1556, 1498, 1405, 1276, 1186, 1049, 760; HNMR (300 MHz, DMSO d6): d
(ppm) 6.53–6.54 (d, 1H, J = 3 Hz), 7.15 (s, 1H), 7.18 (s, 2H), 7.20 (s, 2H),
7.43–7.46 (d, 2H, J = 9 Hz), 7.84–7.87 (t, 2H, J = 9 Hz), 13.58 (s, 1H); 13CNMR
(75 MHz, DMSO d6): d (ppm) 30.93, 57.00, 99.65, 115.90, 118.47, 120.12, 123.24,
124.79, 131.67, 149.38, 153.18, 164.71, 169.69; Anal. Calcd. C, 65.67, H 3.51, N
6.96; Found C, 65.85, H 3.69, N 6.58; GC–MS, m/z = 402.
4.
3,30-[(2H-1,3-benzodioxol-5-yl)methylene]bis(4-hydroxy-2H-1-benzopyran-2-
one) (Entry 7, Table 3) White solid, IR (KBr, cm-1) data: 3428, 3075, 2898,
2725, 2605, 1662, 1615, 1568, 1504, 1488, 1436, 1345, 1309, 1234, 1098, 1040,
763; 1HNMR (300 MHz, DMSO d6): d (ppm) 5.90 (s, 2H), 6.29 (s, 1H), 6.59–6.70
(m, 3H), 7.30–7.32 (d, 4H, J = 6 Hz), 7.53–7.58 (t, 2H, J = 15 Hz), 7.92–7.94 (d,
2H, J = 6 Hz); 13CNMR (75 MHz, DMSO d6): d (ppm) 35.87, 101.13, 104.93,
107.64, 108.13, 116.42, 117.14, 119.73, 124.23, 124.44, 131.91, 132.59, 146.06,
147.98, 152.44, 164.56, 165.89; Anal. Calcd. C, 68.42, H 3.53; Found C, 68.88, H
3.26; GC–MS, m/z = 456.
5. 3,30-[(4-nitrophenyl)methylene]bis(4-hydroxy-2H-1-benzopyran-2-one) (Entry 9,
Table 3) Yellow solid, IR (KBr, cm-1) data: 3417, 3058, 2933, 2717, 2608, 1655,
1
1608, 1564, 1522, 1491, 1350, 1311, 1215, 1181, 1098, 773; HNMR (300 MHz,
DMSO d6): d (ppm) 6.50 (s, 1H), 7.27–7.32 (m, 4H, J = 9 Hz, J = 3 Hz),
123

S. K. Patil et al.
7.36–7.39 (d, 2H, J = 9 Hz), 7.54–7.59 (t, 2H, J = 15 Hz), 7.94–7.97 (dd, 2H),
8.05–8.08 (d, 2H, J = 9 Hz); 13CNMR (75 MHz, DMSO d6): d (ppm) 36.35,
104.04, 116.49, 116.77, 123.61, 124.34, 124.64, 127.92, 132.91, 146.18, 146.46,
152.45, 165.13, 166.36; Anal. Calcd. C 65.65, H 3.31, N 3.06; Found C 65.37, H
3.35, N 2.82; GC–MS, m/z = 457.
Results and discussion
A series of methylimidazolium- and triethylammonium-based simple protic ionic
liquids have been synthesized and their potential as a catalyst in the synthesis of
biscoumarin derivatives was studied. A condensation reaction between 4-hydrox-
ycoumarin and an aromatic aldehyde leads to the formation of biscoumarin in the
presence of the PIL as catalyst and ethanol as solvent (Scheme 2).
Synthesized PILs were screened as catalysts in a model reaction to select the best
one among them. In a model reaction, benzaldehyde was used to synthesize the
biscoumarin derivative with 4-hydroxycoumarin. On the basis of the results
summarized in Table 1, [Et3NH][HSO4] and [MIM][HSO4] have been found to be
superior catalysts concerning the yield of the product and the time required for
completion of the reaction. Also, this suggests that HSO4- is a better anion for PILs
due to its higher acidity among the other anions pertaining to the catalytic activities.
It was found that PILs based on [Et3NH] cation had a comparatively better catalytic
performance. Thus, [Et3NH][HSO4] was chosen as the catalyst for further
optimization of the reaction conditions and syntheses of biscoumarins. Additionally,
[Et3NH][HSO4] is more beneficial from the economical and accessibility point of
view, as well as being stable both in air and water [55].
The reaction temperature is the crucial factor in the succession of the reaction as
it significantly affects the rate of the reaction. To find out the optimum reflux
temperature, the reaction was carried out at different temperatures (Table 2). It was
Table 2 Optimization of reaction conditions for the synthesis of biscoumarin in the presence of [Et3-
NH][HSO4] as catalyst
Entry
Temperature (°C)
Catalyst (mol%)
Time (min.)
Yield (%)a
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
RT
40
60
80
100
80
80
80
80
80
10
10
10
10
10
5
240
120
60
44
67
81
88
88
87
88
85
83
83
30
30
30
20
30
40
50
30
30
30
30
Reaction conditions: benzaldehyde:4-hydroxycoumarin, 1:2 (molar ratio); solvent—EtOH
a
Isolated yields
123

Simple protic ionic liquid [Et3NH][HSO4] as a proficient…
found that, at room temperature, for a prolonged time it generated a negligible yield,
while increases in temperature improved the product yield. The maximum product
formation was found at 80 and 100 °C, and therefore the reflux temperature was
fixed at 80 °C in the synthesis of biscoumarins. The optimum loading of the catalyst
for completion of the reaction was demonstrated with different amounts of PIL, i.e.
5, 10, 20, 30, 40 and 50 mol% (Table 2). However, higher amounts of PIL did not
show any improvement in the yield of the product, and 10 mol% of catalyst was
sufficient to promote the reaction. Therefore, further syntheses of biscoumarins
from various aromatic aldehydes were carried at 80 °C in the presence of 10 mol%
of [Et3NH][HSO4] and ethanol as solvent.
Under optimized conditions, [Et3NH][HSO4] was explored as the catalyst in the
preparation of different biscoumarin derivatives from various aromatic aldehydes. A
series of arylaldehydes containing both electron-donating and -withdrawing
substituents rendered good to excellent yields (Table 3). It can be seen that
aldehydes comprising electron-donating substituents provide relatively better yields
within shorter reaction times. The formation of the products was confirmed by
comparing their melting points with literature values, while the structures of the
1
selected biscoumarin derivatives were established by IR, HNMR, 13CNMR and
GC–MS spectra. All the characterizations and interpretations are in good agreement
with the expected structures of the biscoumarins.
In the view of green chemistry, the reusability of the catalyst is a vital part in its
application. After completion of the reaction, the product can be easily separated
Table 3 Synthesis of various biscoumarin derivatives by condensation of arylaldehydes with 4-hy-
droxycoumarin in the presence of [Et3NH][HSO4] as catalyst
Entry
Ar
Time (min.)
Yield (%)a
Melting point (°C)
Found
Literature
1.
C6H5
30
30
88
87
87
89
91
95
83
70
87
89
68
90
86
88
226–228
240–242
246–248
218–220
262–264
260–262
256–258
216–218
234–236
262–264
250–252
260–262
242–244
272–274
228–230 [47]
242–244 [47]
246–248 [44]
215–218 [42]
266–268 [44]
–
2.
4-OMe C6H4
4-Cl C6H4
3.
90
4.
4-N(CH3)2 C6H4
4-CH3 C6H4
C2H3N2 (imidazole-2-)
Piperonyl
30
5.
30
6.
30
7.
25
260 [38]
8.
4-OH,3-OMe C6H3
4-NO2 C6H4
3,4-OMe C6H3
2-OH C6H4
150
30
–
9.
232–234 [47]
264–266 [41]
250–252 [44]
263–265 [42]
240–242 [41]
270–272 [42]
10.
11.
12.
13.
14.
25
180
60
4-Br C6H4
4-CN C6H4
90
Pyridine-3-
20
Reaction conditions: aryl aldehyde (1 mmmol), 4-hydroxycoumarin (2 mmol); [Et3NH][HSO4]
(10 mol%); solvent EtOH; temperature 80 °C
a
Isolated yields
123

S. K. Patil et al.
just by filtration, and the filtrate containing the PIL was evaporated to regain the
catalyst. The obtained PIL was again washed with ethyl acetate followed by n-
hexane and dried in vacuum. The rejuvenated catalyst was again employed in the
model reaction to test its consistency in performance. Astoundingly, [Et3-
NH][HSO4] showed efficient catalytic activity for up to six cycles without a
significant decrease in product yield (Fig. 1).
The plausible reaction mechanism in the synthesis of biscoumarin involves the
Knoevenagel condensation followed by a Michael addition. An aldehyde is initially
Fig. 1 Reusability of
[Et3NH][HSO4] in the synthesis
of biscoumarins
Et
O
Et
H
N
Et
H
O
O
OH
H
O
S
O
H
O
Ar
C
H
O
O
Ar
C
H
O
O
O
Et
Et
H
N
O
S
Et
O
O
H
O
Ar
H
O
O
OH
OH
O
C
H
Ar
O
O
O
O
O
O
O
Ar
O
O
OH
O
H
O O
Scheme 3 Plausible reaction mechanism in the synthesis of biscoumarins
123

Simple protic ionic liquid [Et3NH][HSO4] as a proficient…
activated by the catalyst through hydrogen bonding, which facilitates the
nucleophilic attack of 4-hydroxycoumarin followed by the loss of H2O to form
an intermediate. Further, this intermediate is activated again by the PIL catalyst and,
due to the nucleophilic attack of the second molecule of 4-hydroxycoumarin, a
Michael addition product that is biscoumarin is formed [47, 56] (Scheme 3).
Conclusion
In conclusion, we have developed an efficient and environmentally benign synthesis
route for biscoumarin derivatives in the presence of a simple protic ionic liquid,
[Et3NH][HSO4]. The synthesized inexpensive PIL catalyst provides a green
protocol through good to excellent yields, moderate reaction time, and easy
work-up procedure as well as exceptional recyclability. Hence, our proposed
method offers a better alternative to existing methods. However, based on this
study, we are proceeding to develop a more facile biscoumarin synthesis protocol by
using ionic liquids, which can optimistically alter the reaction operating conditions
such as reaction time, reflux temperature or reusability of the catalyst.
Supporting information
Electronic supplementary material contents 1HNMR, 13CNMR spectra of [Et3-
NH][HSO4]; 1HNMR, 13CNMR and GC–MS spectra of selected biscoumarin
derivatives.
Acknowledgements Authors SKP and MMV under UGC-BSR Meritorious Students fellowship and SCB
under RGNF are grateful to the University Grants Commission (UGC), India, for financial support and
DST-FIST, New Delhi, India, for instrument facilities at the Department of Chemistry, Shivaji
University, Kolhapur.
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