A solvent-free synthesis of coumarins using 1,3-disulfonic acid imidazolium hydrogen sulfate as a reusable and effective ionic liquid catalyst

Article abstract of DOI:10.1007/s11164-014-1733-3

Abstract 1,3-Disulfonic acid imidazolium hydrogen sulfate has been used as an effective and reusable ionic liquid catalyst for the synthesis of coumarins from phenol derivatives with β-ketoesters via the Von Pechmann condensation under solvent-free conditions. This method consistently has the advantages of excellent yields, easy and quick isolation of the products, short reaction times, and green aspects by avoiding toxic catalysts and solvents. Further, the catalyst can be recovered and reused for four times without loss of activity.

Full text of DOI:10.1007/s11164-014-1733-3

Res Chem Intermed
DOI 10.1007/s11164-014-1733-3
A solvent-free synthesis of coumarins using 1,3-
disulfonic acid imidazolium hydrogen sulfate
as a reusable and effective ionic liquid catalyst
•
Farhad Shirini Asieh Yahyazadeh
Kamal Mohammadi
•
Received: 5 January 2014 / Accepted: 29 May 2014
Ó Springer Science+Business Media Dordrecht 2014
Abstract 1,3-Disulfonic acid imidazolium hydrogen sulfate has been used as an
effective and reusable ionic liquid catalyst for the synthesis of coumarins from
phenol derivatives with b-ketoesters via the Von Pechmann condensation under
solvent-free conditions. This method consistently has the advantages of excellent
yields, easy and quick isolation of the products, short reaction times, and green
aspects by avoiding toxic catalysts and solvents. Further, the catalyst can be
recovered and reused for four times without loss of activity.
Keywords Coumarin Á Ionic liquid Á Catalyst Á Von Pechmann condensation Á
Solvent-free synthesis
Introduction
Coumarins and their derivatives have attracted considerable attention of organic and
medicinal chemists. These compounds have acquired significant importance due to
their wide use in synthetic chemistry and are much used as anticoagulants [1],
additives in food and cosmetics [2], in the preparation of insecticides [3, 4], optical
brighteners [5], and dispersed fluorescent and laser dyes [6]. In addition, coumarins
possess various and very important biological and pharmacological properties [7–
12] and also act as intermediates for the synthesis of furocoumarins, chromenes,
coumarones, and 2-acylresorcinols [13]. Thus, the synthesis of this heterocyclic
nucleus is of much current interest.
F. Shirini (&) Á A. Yahyazadeh (&) Á K. Mohammadi
Department of Chemistry, College of Science, University of Guilan, Post Box: 1914, 41335 Rasht,
Islamic Republic of Iran
e-mail: shirini@guilan.ac.ir
A. Yahyazadeh
e-mail: yahyazadehphd@yahoo.com
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F. Shirini et al.
Several methods have been developed for the synthesis of coumarin derivatives.
Among them, the Von Pechmann reaction has been widely used for the preparation
of these compounds, since it proceeds from simple and relatively inexpensive
starting materials [14–19]. This method involves the reaction between a phenol and
a b-ketoester in the presence of an acidic catalyst. Different acid catalysts such as
H2SO4, P2O5, FeCl3, ZnCl2, POCl3, AlCl3, PPA, HCl, phosphoric acid, trifluoro-
acetic acid, montmorillonite, and other clays are known to affect this condensation
[20–25]. However, most of these methods suffer from severe drawbacks like use of
a large amount of catalysts, unwanted side products, vigorous reaction conditions,
tedious work-up, and lower yields.
In some methods, several hours or even days are required to complete the
reaction even when heated above 150 °C. Other methods have utilized microwave
irradiation [26], but they generate strongly acidic by-products or they utilize highly
expensive, non-recyclable reagents and extreme precautions are necessary. There-
fore, the development of mild, efficient, and environmentally benign methodology
is still desirable.
On the other hand, the elimination of hazardous and volatile organic solvents in
organic synthesis is the most important goal in green chemistry. One of the most
efficient protocols to reach this aim is the substitution of volatile solvents with ionic
liquids (ILs). Recently, applications of ILs in synthetic chemistry have been
developed because of their special benefits.
In addition, the synthesis of task-specific ILs (TSILs), which have a functional
group in their framework, may expand the application of ILs in organic chemistry
[27]. Various TSILs have been designed and utilized as novel reaction media in
organic synthesis, catalysis, and preparation of nanomaterials [28–33]. Recently,
¨
Bronsted acidic ILs have been designed as an alternative to traditional mineral
liquid acids like sulfuric acid and hydrochloric acid in chemical procedures [34–38].
¨
Introduction of Bronsted-acidic functional groups into cations or anions of ILs,
especially SO3H and SO4H functional groups, obviously enhances their acidity and
water solubility [39, 40]. Moreover, the polar nature of ILs makes them ideal for use
in solvent-free organic synthesis.
Experimental
Chemicals were purchased from Fluka and Merck. Yields refer to isolated products.
Products were characterized by their physical constants, comparison with authentic
samples, and IR and NMR spectroscopy. The purity determination of the substrate
and reaction monitoring were accomplished by TLC on silica-gel polygram SIL
G/UV 254 plates. The IR spectra were run on a Perkin-Elmer model Spectrum One
FT-IR Spectrometer. Melting points were recorded on an electrothermal digital
melting point apparatus model IA9100 in open capillary tubes.
A mixture of the phenolic compound (1 mmol), ethyl acetoacetate (EAA) or
methyl acetoacetate (MAA, 1 mmol) and 1,3-disulfonic acid imidazolium hydrogen
sulfate (DSIMHS, 0.07 mmol, 22.75 mg) was heated in an oil bath (75 °C) under
stirring. The progress of the reaction was monitored by TLC. After completion, the
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Solvent-free synthesis of coumarins using DSIMHS
mixture was allowed to cool. Then, the resulting mixture was diluted with ethyl
acetate (5 mL) and the catalyst was separated through decantation. The organic
phase obtained was washed with water (2 9 5 mL) and the solvent was evaporated
under reduced pressure, which yielded the crude product. Recrystallization in
ethanol or an ethanol–water system gives the requested coumarin in high yields.
Selected spectral data
7,8-Dihydroxy-4-methylcoumarin (Table 3, entries 5, 16)
1
Solid, mp 243–245 °C, H NMR (300 MHz, DMSO-d6): d 2.36 (s, 3H), 6.12 (s,
1H), 6.86 (d, J = 8.6 Hz, 1H), 7.11 (d, J = 8.6 Hz, 1H), 9.42 (s, 1H), 10.01 (s, 1H),
IR (KBr): m = 3,417, 3,231, 1,675, 1,620, 1,584, 1,441, 1,155, 810 cm-1
.
7,8-Benzo-4-methylcoumarin (Table 3, entries 11, 21)
1
Solid, mp 153–155 °C, H NMR (400 MHz, DMSO-d6): d 2.56 (s, 3H), 6.53 (s,
1H), 7.72–7.75 (m, 2H), 7.83 (d, J = 8.8 Hz, 1H), 7.90 (d, J = 8.8 Hz, 1H),
8.06–8.08 (m, 1H), 8.38–8.41 (m, 1H), IR (KBr): m = 2,920, 1,675, 1,615, 1,561,
1,285, 1,167, 1,056 cm-1
.
Results and discussion
Very recently, we have reported the preparation of DSIMHS and its application in
the promotion of the protection of the hydroxyl and amino groups [41, 42]. In
continuation of these studies, we were interested to investigate the applicability of
this TSIL in the promotion of the other organic reactions. Our investigations
clarified that this reagent is efficiently able to catalyze the synthesis of different
types of coumarins via the Von Pechmann condensation.
For the beginning of this study, the reaction between pyrogallol and EAA in the
presence of DSIMHS was chosen as a model to optimize the reaction conditions. To
evaluate the effect of temperature on the reaction, the concentration of IL was kept
constant at 0.07 mmol and a mixture of equimolar ratio of pyrogallol and EAA was
treated with DSIMHS at different temperatures ranging from 25 to 85 °C under
solvent-free conditions. The yield of the corresponding product was low after
stirring the reaction mixture at room temperature for 360 min under solvent-free
conditions (Table 1, entry 1). Subsequently, the mixture was heated in oil bath.
When the temperature of the reaction was raised from 60 to 75 °C, the reaction
times and yields were considerably improved. Further increases in temperature did
not improve the results to a greater extent. Therefore, 75 °C was chosen as the
reaction temperature for all further reactions.
Then, the effect of the catalyst concentration on the reaction was studied and the
results are listed in Table 2. After stirring for 2 h in the absence of DSIMHS, the
reaction did not proceed as monitored by TLC, which indicated that the catalyst is
absolutely necessary for the Von Pechmann reaction (Table 2, entry 1). Hence, we
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F. Shirini et al.
Table 1 Temperature optimization for the synthesis of 7,8-dihydroxy-4-methylcoumarin
Entries
Temperature (°C)
Time (min)
Yield (%)a
1
2
3
4
5
25
50
60
75
85
360
135
30
20
48
56
96
96
10
10
Reaction condition: pyrogallol (1 mmol), EAA (1 mmol) and DSIMHS (0.07 mmol) at different tem-
perature under solvent free conditions
a
Isolated yield
Table 2 Effect of catalyst concentration for the synthesis of 7,8-dihydroxy-4-methylcoumarin
Entries
Catalyst concentration (mmol)
Time (min)
Yield (%)a
1
2
3
4
–
120
25
–
0.05
0.07
0.10
80
96
98
10
10
Reaction condition: pyrogallol (1 mmol), EAA (1 mmol) and different amount of DSIMHS at 75 °C
under solvent-free conditions
a
Isolated yield
Me
O
O
OH
DSIMHS, 0.07 mmol
Solvent-free, 75 oC
+
R
R
Me
OR'
O
O
R' = Me, Et
Scheme 1 The synthesis of substituted coumarins in the presence of DSIMHS under solvent-free
conditions
concluded that 0.07 mmol of DSIMHS was the optimum amount of the catalyst for
this reaction. The use of larger amounts of the catalyst neither further improves the
yield nor the reaction time.
Consequently, optimization of the reaction conditions showed that the best
results were obtained when the reaction was performed at 75 °C under solvent-free
conditions, while the relative ratio of the substrate/EAA/DSIMHS was 1.0/1.0/
0.07 mmol, respectively. Under the optimized conditions, the reaction gave 96 %
yield of 7,8-dihydroxy-4-methylcoumarin after 10 min (Table 2, entry 3).
Afterwards, different types of phenols and EAA were reacted in the presence of
DSIMHS under the optimized reaction conditions described above (Scheme 1).
The reactions were clean and afforded exclusively coumarins. The results are
summarized in Table 3.
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Solvent-free synthesis of coumarins using DSIMHS
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F. Shirini et al.
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Solvent-free synthesis of coumarins using DSIMHS
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F. Shirini et al.
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Solvent-free synthesis of coumarins using DSIMHS
H+ from
N
H
OH
O
O
HSO4
N
HO3S
SO3H
H
HO
HO
O
O
Me
O
OH
OH
Me
OEt
- EtOH
Pyrogallol
EAA
H
O
H
Me
OH
Me
O
Me
H
- H2O
H
HO
O
O
HO
O
O
HO
O
OH
OH
OH
7, 8 -Dihydroxy-4-methylcoumarin
Scheme 2 Suggested mechanism for the Von Pechmann condensation of pyrogallol with EAA at 75 °C
under solvent-free conditions
Fig. 1 Results of the reusability
of DSIMHS in the synthesis of
7,8-dihydroxy-4-
methylcoumarin under solvent-
free conditions (Table 3, entry
5)
Table 4 Comparison of some of the results obtained by the Von Pechmann reaction with EAA in the
presence of DSIMHS
Entries Catalysts
[References] Phloroglucinol
Pyrogallol
Time
(min)
Yield
(%)
Time
(min)
Yield
(%)
1
2
3
4
5
DSIMHS (0.07 mmol), solvent-free,
75 °C
[TMPSA]HSO4 (1 mmol), H2O,
This work
[49]
2
60
20
90
60
94
10
48
15
–
96
92
58
–
91
65
70
90
80 °C
[bmim][HSO4] (0.12 mmol), solvent- [50]
free, 80 °C
[BSMIm]Ts (10 mol%), solvent-free, [51]
85 °C
[MBsIm][CF3SO3] (0.75 mmol),
[52]
30
94
solvent-free, 80 °C
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F. Shirini et al.
It can easily be seen that the Von Pechmann condensation proceeded smoothly
under solvent-free conditions and gave good to high yields ranging from 80 to 96 %.
Many phenols, such as m-cresol, 3,4-dimethylphenol, pyrogallol, and phloroglu-
cinol, could be converted to their corresponding coumarins in high yields (Table 3,
entries 1, 3, 5, 6).
The electron-donating substituents in the meta-position to the phenolic-OH
facilitated the cyclization. Reaction of phloroglucinol with EAA (Table 3, entry 6)
took place faster within 2 min, whereas the reaction of pyrogallol with EAA
(Table 3, entry 5) proceeded for 10 min. The reactivity of phloroglucinol with EAA
was observed to be higher than pyrogallol due to two hydroxyl groups at the meta-
positions in phloroglucinol compared to one hydroxyl group in pyrogallol.
Similarly, in the case of p-cresol, the reaction with EAA (Table 3, entry 2) took
place somewhat slower than that of the reaction of m-cresol (Table 3, entry 1). The
reaction of 3, 4-dimethylphenol and 3, 5-dimethylphenol with EAA (Table 3,
entries 3, 4) occurred within 22 and 20 min. This could be due to the presence of
hydroxyl groups, which were meta to the phenolic-OH. Phenol and 4-nitrophenol
(Table 3, entries 10, 11) gave lesser yields and need longer time as no electron-
donating group is present.
Moreover, in order to compare the activities of various b-ketoesters with phenol
derivatives, we also used MAA as a different type of b-ketoesters. According to the
results in Table 3, we found that EAA is more reactive than MAA.
In Scheme 2, a mechanism has been suggested for the Von Pechmann
condensation of pyrogallol with EAA in the presence of DSIMHS as a promoter,
under solvent-free conditions. On the basis of this mechanism, DSIMHS catalyzes
the reaction by the activation of the EAA. The transesterification and elimination of
ethanol with ring closure occur at the same time. The final step is dehydration that
leading to the formation of corresponding coumarin products.
We also investigated the reusability and recycling performance of DSIMHS in
the reaction of pyrogallol with EAA at 75 °C under solvent-free conditions. More
than 95 % of the catalyst could be easily recovered from the reaction mixture by a
simple extraction with water. The results illustrated in Fig. 1 showed that the
recovered IL could be reused four times without significant decrease in catalytic
activity.
In order to compare the applicability and the efficiency of DSIMHS with some of
the other ILs reported in the literature, we have tabulated the results of these
catalysts in Table 4. As shown in the table, DSIMHS remarkably improved the Von
Pechmann reaction in different terms, for example shorter reaction times and high to
excellent yields that make this catalyst a better choice.
Conclusion
In conclusion, DSIMHS is an effective reagent and catalyst for the synthesis of
coumarins via the reaction of phenolic compounds with EAA or MAA under
solvent-free conditions. The attractive features of this procedure are shorter reaction
times, mild reaction conditions, high yields and no side reactions, ease of
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Solvent-free synthesis of coumarins using DSIMHS
preparation and handling of the catalyst, green aspects by avoiding toxic catalysts
and solvents, use of inexpensive catalyst with lower loading, recyclability of the IL,
and simple experimental procedure. This convenient technique is the most effective
compared with the existing methods for the synthesis of coumarins and its
derivatives.
Acknowledgments The authors are grateful to the Guilan University Research Council for the financial
support of this work. F. Shirini and K. Mohammadi also wish to thank the Sobhandarou Company for the
partial facilities.
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