Pechmann reaction in non-chloroaluminate acidic ionic liquids under solvent-free conditions

Article abstract of DOI:10.1002/adsc.200404316

Four non-chloroaluminate acidic ionic liquids have been used as catalysts for Pechmann condensations of phenols under solvent-free conditions. SO ₃H-functionalized trifluoromethanesulfonate imidazolium ionic liquid has proved to be the most active catalyst. Ionic liquid loads as low as 5 mol % can be used leading to high yields with activated phenols at an oil bath temperature of 80°C. The acidities of the four ionic liquids have also been tested using the Hammett method in dichloromethane. The results are consistent with their catalytic activities as observed in the Pechmann reaction of resorcinol. This methodology offers significant improvements for the synthesis of coumarins with regard to yield of products, simplicity in operation, and green aspects by avoiding toxic catalysts and solvents.

Full text of DOI:10.1002/adsc.200404316

COMMUNICATIONS
Pechmann Reaction in Non-Chloroaluminate Acidic Ionic
Liquids under Solvent-Free Conditions
a, b
a
a
a,
Yanlong Gu, Juan Zhang, Zhiying Duan, Youquan Deng *
a
Center for Green Chemistry and Catalysis, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences,
Lanzhou 730000, Peopleꢀs Republic of China
Fax: (þ86)-931-496-8116, e-mail: ydeng@ns.lzb.ac.cn
b
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, Peopleꢀs Republic of China
Received: October 13, 2004; Accepted: January 17, 2005
Abstract: Four non-chloroaluminate acidic ionic liq-
uids have been used as catalysts for Pechmann con-
densations of phenols under solvent-free conditions.
conditions, sometimes, however, many of these proce-
dures are associated with one or more disadvantages
such as expensive reagents, long reaction time, tedious
work-up, low selectivity, and large amounts of solid sup-
ports which would eventually result in the generation of
a large amount of toxic waste.
It is also noteworthy that a majority of existing cata-
lysts used in Pechmann condensation are solid acids.
In many cases the key drivers for the use of solid acids
are their lack of vapor pressure and their phase hetero-
geneity, the latter facilitating product isolation. Even so,
solid acids are fraught with drawbacks of their own, in-
cluding heterogeneous kinetics and a susceptibility to
ready deactivation. Consequently, a valuable middle
ground would be found in chemically functional liquids
that, like solids, have no vapor pressure and which can
also act as acidic catalysts in catalytic reactions.
SO H-functionalized trifluoromethanesulfonate imi-
3
dazolium ionic liquid has proved to be the most ac-
tive catalyst. Ionic liquid loads as low as 5 mol %
can be used leading to high yields with activated phe-
nols at an oil bath temperature of 808C. The acidities
of the four ionic liquids have also been tested using
the Hammett method in dichloromethane. The re-
sults are consistent with their catalytic activities as
observed in the Pechmann reaction of resorcinol.
This methodology offers significant improvements
for the synthesis of coumarins with regard to yield
of products, simplicity in operation, and green as-
pects by avoiding toxic catalysts and solvents.
Keywords: acid catalysis; coumarins; determination
of acidity; ionic liquids; Pechmann condensation
The recently emerged chloroaluminate ionic liquids
hold great potential in meeting these demands, as evi-
denced by their increasing popularity as catalysts and re-
[
10]
action media. Pechmann reactions have also been
[
11]
conducted in chloroaluminate ionic liquids. Never-
theless, chloroaluminates are very sensitive to hydroly-
Coumarin and its derivatives have been attracting great sis. Traces of water can change the composition of the
interest because of their importance in synthetic organic melt and the concentration of protons. As a result, it is
chemistry. Many products which contain the subunit of difficult to accurately control the acidity of these ionic
[
1]
coumarin exhibit useful and diverse biological activity.
liquids. Another disadvantage is that the chloroalumi-
These compounds find application in pharmaceuticals, nate ionic liquids, which cannot be stored for a long
[
2]
fragrances, agrochemicals, and insecticides. Avery val- time, should be prepared at the time of the catalytic re-
uable method for the synthesis of coumarins is the Pech- actions. Non-chloroaluminate acidic ionic liquids which
mann reaction, which starts from phenols. In the con- are air and moisture stable, have hence been developed
[
12]
ventional production of coumarins by the Pechmann re- and applied for acidic reactions. As a part of our stud-
action, concentrated sulfuric acid is used as the cata- ies to explore the utility of existing ionic liquids in chem-
[3]
lyst. This process causes formation of by-products, ical reactions, we have investigated many acid-catalyzed
needs long reaction time, and introduces corrosion reactions, including alkylation, esterification, Beck-
[4]
problems. For these reasons, there have been some at- mann rearrangement, cyclization of 1-dodecene, acetal-
[13]
tempts to find alternative, environmentally benign syn- ization and oligomerization of branched olefins. In
[
5]
thesis routes. Nafion-H, zeolite H-BEA, Amberlyst continuation of our work in studying acid-catalyzed re-
[
6]
[7]
[8]
1
5, montmorillonite clay, and other solid acids
actions in ionic liquids, we report in this paper the syn-
have been employed for this purpose in the Pechmann thesis of coumarin derivatives by the Pechmann conden-
condensation. Some organic acids and metal Lewis acids sation in non-chloroaluminate acidic ionic liquids.
[
9]
have also been examined in this transformation. Al-
We initial tested the Pechmann condensation between
though these methods are suitable for certain synthetic resorcinol and methyl acetoacetate at 808C under sol-
512
ꢁ 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/adsc.200404316
Adv. Synth. Catal. 2005, 347, 512–516

Pechmann Reaction
COMMUNICATIONS
mann condensation of resorcinol in the presence of
5
mol % catalyst was undertaken. The result is reported
in Table 1. It is shown that with 5 mol % [MBsIm]
CF SO ], the reaction went to completion in 1 hour,
[
3
3
[
4,7b]
which is quite remarkable (Entry 7).
The resorcinol
could not be completely consumed when the
[
2
MBsIm][CF SO ] amount was further decreased to
3 3
mol % even at prolonged reaction time (3 h) (En-
Scheme 1. Four non-chloroaluminate acidic ionic liquids used
in Pechmann condensation
try 8). Similarly, a decrease of the reaction temperature
seems to be unfavorable because the yield of 7-hydroxy-
4-methylcoumarin was only 53% at 508C (Entry 9).
vent-free conditions. Four existing non-chloroaluminate
The Pechmann reaction proceeds through transester-
acidic ionic liquids, including [MBsIm][CF SO ], ification and intramolecular hydroxyalkylation, fol-
3
3
[
BMIm][HSO ], [BMIm][H PO ] and [HMIm]BF , lowed by dehydration according to the descriptions in
4 2 4 4
[2,6]
have been used (Scheme 1). Table 1 shows the results previous reports.
These three steps are all typical
of the experiments carried out under the same condi- acid-catalyzed reactions. Therefore, the outcome of
tions for comparing the catalytic performances of these the Pechmann reaction depends very much on the
[
4]
acidic ionic liquids. In our hands, [MBsIm][CF SO ] Brønsted acidity of catalyst. However, acidity deter-
3
3
proved to be very active, leading to 95% yield of 7-hy- minations based on room temperature ionic liquids is a
droxy-4-methylcoumarin within 15 min (Entry 1) when relatively new subject. The determination of the Brønst-
1
0 mol % ionic liquid was used. [BMIm][HSO ] could ed acidity of a non-chloroaluminate ionic liquid has not
4
also used as catalyst to promote the Pechmann conden- even been considered yet. A commonly used method to
sation, but its activity seems to be slightly inferior as evaluate the acidity of a Brønsted acid in solution is the
compared with that of [MBsIm][CF SO ] because the Hammett method, wherein a basic indicator has been
3
3
reaction time has to prolonged to 1 hour for the com- used to trap the dissociative proton. The properties of
plete conversion of resorcinol (Entries 2 and 3). At- the protons depend on both the nature of the solvent
tempts to perform the reaction with [BMIm][H PO ] and the nature and concentration of the chosen acid.
2
4
and [HMIm]BF led only to recovery of unreacted start- The Brønsted acidity was evaluated from the determina-
4
ing material even at elevated temperature and pro- tion of the Hammett acidity functions, using UV-visible
longed reaction time (Entries 4 and 5). Similarly, no re- spectroscopy. In the present case, this method consists of
action was observed in the absence of ionic liquid (En- evaluating the protonation extent of the uncharged indi-
try 6). In view of the foregoing, [MBsIm][CF SO ] cator bases (named I) in a solution, in terms of the meas-
3
3
þ
should be a suitable catalyst for the Pechmann conden- urable ratio [I]/[IH ]. In a given solvent (s), assumed as
sation.
We then addressed the question of what would be the as:
smallest amount of [MBsIm][CF SO ] that could be em-
being dissociating, the Hammettfunction (H ) is defined
0
3
3
þ
ployed in this reaction. Therefore, a study of the Pech- H ¼pK(I) þlog ([I] /[IH ] )
0
aq
s
s
[a]
Table 1. Pechmann condensation between resorcinol and methyl acetoacetate in different ionic liquids.
o
Entry
Ionic liquids
Ratio of IL/
Time [min]
Temp. [ C]
Yield [%]
resorcinol [M/M%]
1
2
3
4
5
6
7
8
9
[MBsIm][CF SO ]
[BMIm][HSO4]
10
10
10
10
10
–
5
2
5
15
15
60
180
180
180
60
180
60
80
80
80
100
100
80
80
80
50
95
35
89
0
0
0
95
77
53
3
3
[BMIm][HSO4]
[BMIm][H PO ]
2
4
[HMIm]BF4
–
[MBsIm][CF SO ]
3
3
[MBsIm][CF SO ]
3
3
[MBsIm][CF SO ]
3
3
[
a]
Reaction conditions: resorcinol, 15 mmol; methyl acetoacetate, 15 mmol.
Adv. Synth. Catal. 2005, 347, 512–516
asc.wiley-vch.de
ꢁ 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
513

COMMUNICATIONS
Yanlong Gu et al.
Gilbert and co-workers have described a procedure to
The smallest H was obtained in a 10 mmol/L CH Cl
2
0
2
evaluate the Brønsted acidity of HNTf2 in solution of [MBsIm][CF SO ], it indicated that ionic liq-
3
3
[
BMIm][NTf ] ionic liquid using the Hammett meth- uid [MBsIm][CF SO ] exhibits a stronger Brønsted
2
3
3
[
14]
od. However, the acidity determination of apure acid- acidity than the other three non-chloroaluminate ionic
ic ionic liquid without a solvent should be impossible be- liquids used in this work. The Brønsted acidity of
cause the initial absorbance of the total unprotonated [BMIm][HSO ] is slightly inferior as compared with
4
form of the indicator (blank value) cannot be obtained. [MBsIm][CF SO ], but stronger than those of
3
3
For the comparison purposes, the acidities of these four [HMIm]BF and [BMIm][H PO ]. It should be pointed
4
2
4
non-chloroaluminate ionic liquids have been examined out that, although this method cannot yet offer an accu-
using 4-nitroanline (Hammett constant is 0.99) as indi- rate quantitative value for acidic ionic liquids, these re-
cator in dichloromethane and the results are shown in sults should be applicable for an acidity comparison of
Figure 1. In this experiment, dichloromethane was chos- existing non-chloroaluminate acidic ionic liquids. This
en as test solvent at first glance because it is an aprotic order of ionic liquid acidity is consistent with the se-
polar solvent, stable under acidic conditions and has quence of catalytic activity observed in the reaction of
considerable solubility for all tested ionic liquids. The resorcinol, indicating the determining role of catalyst
maximal absorbance of the unprotonated form of the in- acidity on the Pechmann condensation.
dicator was observed at 349 nm in CH Cl . When an
Having these results in hand, other phenols have been
2
2
acidic ionic liquid was added, the absorbance of the un- subjected to the conditions of run 7 in Table 1, and the
protonated form of the indicator decreased. As shown in results are listed in Table 3. The ionic liquid
Figure 1, the absorbance of the unprotonated form of [MBsIm][CF SO ] proved to be active towards all sub-
3
3
the indicator on four non-chloroaluminate acidic ionic strates. Many phenols, such as resorcinol, pyrogallol,
liquids decreased as follows: [BMIm][H PO ]> phloroglucinol, 3-methoxyphenol and 2-methylresorci-
2
4
[
HMIm]BF >[BMIm][HSO ]>[MBsIm][CF SO ].
nol could be converted to corresponding coumarins in
4
4
3
3
By taking as the initial reference the total unprotonated excellent yields (Entries 1–5). The reactivities of 3-
form of the indicator (when no acid is added to the methylphenol and 1-naphthol seem to be inferior as
CH Cl solution, spectrum a), we could determine the compared with that of the former; yields of 4,7-dime-
2
2
þ
[
I]/[IH ] ratio from the measured absorbances after thylcoumarin and 4-methyl-7,8-benzocoumarin were
each ionic liquid (spectra b–e), and then the Hammett 76% and 61%, respectively (Entries 6 and 7). One of
function (H ) is calculated (see Table 2).
the main aims of using non-chloroaluminate ionic liq-
uids as catalysts was to study the possibility of their recy-
cle and reuse. Because [MBsIm][CF SO ] is an air and
0
3
3
moisture stable ionic liquid, it could be recycled after re-
action from the aqueous solution by means of removal of
volatile components under vacuum conditions. And it
was reused in the Pechmann condensation between re-
sorcinol and methyl acetoacetate. The reaction was car-
ried out three times in consecutive runs with only a slight
decrease in isolated yields (Table 3, entry 8). Obviously,
the recycling procedure is analogous to that of sulfuric
acid system, complex and time and energy consuming.
However, in the current context of environmental im-
pact, the sulfuric acid system is not attractive as it re-
[
15]
quires catalyst in 10–12 equivalent amounts.
In summary, the use of non-chloroaluminate acidic
ionic liquids as catalysts for the Pechmann condensation
avoids the use of moisture sensitive reagents or high
Figure 1. Absorption spectra of 4-nitroaniline for various ion-
ic liquids in dichloromethane.
[a]
Table 2. H values of various ionic liquids in dichloromethane.
0
þ
Ionic liquids
Absorbance [AU]
[I] [%]
[HI ] [%]
H0
–
2.350
2.286
1.734
0.837
0.223
100
97.3
73.8
35.6
9.5
0
2.7
26.2
64.4
90.5
–
[
[
[
[
BMIm][H PO ]
HMIm]BF4
BMIm][HSO4]
MBsIm][CF SO ]
2.55
1.44
0.73
0.01
2
4
3
3
[
a]
Concentration: 10 mmol/L; indicator: 4-nitroanline.
514
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asc.wiley-vch.de
Adv. Synth. Catal. 2005, 347, 512–516

Pechmann Reaction
COMMUNICATIONS
[a]
Table 3. Pechmann reactions between phenols and methyl acetoacetate in ionic liquid [MBsIm][CF SO ].
3
3
Entry
1
Phenols
Products
Time [h]
1
Yields [%]
95
mp [ 8C]
[
[
[
9d]
183–186 (185–187
)
11a]
2
3
4
1
90
92
92
182–185 (180–185
161–162 (160–162
137–139 (138–139
)
9d]
1
)
[
[
9d]
9d]
1.5
)
5
6
0.5
4
94
76
236–239 (236–239
)
[
7b]
130–132 (131.5–132
)
[
9d]
7
6
1
61
89
155–156 (154–156
183–186 (185–187
)
)
[
b]
[9d]
8
[
[
a]
b]
Reaction conditions: ionic liquid, 0.75 mmol; phenols, 15 mmol; methyl acetoacetate, 15 mmol; 808C.
Reused a third time.
temperature reaction conditions to promote the reac- Experimental Section
[
9b,11]
tion.
mol % can be used leading to good to high yields
with activated phenols at an oil bath temperature of
Catalyst ([MBsIm][CF SO ]) loads as low as
3 3
5
Preparation of Ionic Liquids
08C. This clearly indicates the efficiency of the ionic All used ionic liquids were prepared according previous meth-
8
[12g, h,13e, f]
ods.
liquid [MBsIm][CF SO ] for this transformation. Pre-
3
3
liminary acidity determinations of four non-chloroalu-
minate acidic ionic liquids revealed that the Brønsted
acidities of the ionic liquids play a determining role in
Typical Procedure
the rate acceleration of the Pechmann condensation. In a typical experiment, ionic liquid (0.75 mmol) was dissolved
in a mixture of resorcinol (15.0 mmol) and methyl acetoacetate
The ionic liquid [MBsIm][CF SO ] can be recovered
3
3
(
15.0 mmol) in a 25-mL round-bottom flask equipped with a
conveniently and reused up to three times, although
with some loss of activity. Moreover, this methodology
offers significant improvements with regard to yield of
products, simplicity in operation, and green aspects by
avoiding toxic catalysts and solvents. These advantages
of this novel catalytic system are expected to contribute
distillation condenser. The content was stirred vigorously for
the desired time at 808C. At the end of reaction, the reaction
mixture was cooled to room temperature. The liquid mixture
should be solidified at ambient temperature. Ethanol
(
10 mL) was added and heated at 508C until complete dissolu-
tion of the solid. This ethanol solution was then put into a 100-
to the development of more benign Pechmann conden- mL beaker containing a lot of water. Crystalline products were
sations of phenols with methyl acetoacetate.
collected by filtration to give 7-hydroxy-4-methylcoumarin in
Adv. Synth. Catal. 2005, 347, 512–516
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ꢁ 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
515

COMMUNICATIONS
Yanlong Gu et al.
9
5% yield; the crude crystals thus obtained were recrystallized
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Dichloromethane solutions of ionic liquids were prepared
from dried CH Cl and ionic liquids that have been treated un-
2
2
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with an Agilent B453 spectrophotometer.
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ꢁ 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Adv. Synth. Catal. 2005, 347, 512–516