Magnesium bis(trifluoromethane)sulfonimide: An efficient catalyst for the synthesis of coumarins under solvent-free conditions

Article abstract of DOI:10.1007/s00706-012-0823-4

Magnesium bis(trifluoromethane)sulfonimide [Mg(NTf₂) ₂] is an efficient catalyst for the synthesis of coumarins via the Pechmann condensation reaction of phenols and β-ketoesters under solvent-free conditions.

Full text of DOI:10.1007/s00706-012-0823-4

Monatsh Chem (2013) 144:411–414
DOI 10.1007/s00706-012-0823-4
ORIGINAL PAPER
Magnesium bis(trifluoromethane)sulfonimide: an efficient catalyst
for the synthesis of coumarins under solvent-free conditions
Hongshe Wang
Received: 16 November 2011 / Accepted: 9 July 2012 / Published online: 2 August 2012
Ó Springer-Verlag 2012
Abstract Magnesium bis(trifluoromethane)sulfonimide
Mg(NTf ) ] is an efficient catalyst for the synthesis of
[22], NaHSO ÁSiO [23], CAN [24], LiClO [25], KAl-
4
2
4
[
(SO ) Á12H O [26], nanocrystalline sulfated zirconia [27],
2
2
4 2
2
2-
zeolite [28], and SO /Ce Zr O solid acid [29] are
4 x 1-x 2
coumarins via the Pechmann condensation reaction of
phenols and b-ketoesters under solvent-free conditions.
known to affect the Pechmann condensation. This reaction
was also reported using ionic liquids [30, 31], ultrasound
[32], and microwave irradiation [33]. Although each of the
above methods has its own merits, some of the methods
employed earlier for this conversion are associated with
certain drawbacks such as long reaction times and the use
of a large amount of catalyst.
Keywords Coumarins Á Mg(NTf ) Á
2
2
Pechmann condensation Á Solvent-free
Introduction
In recent years, metal bis(trifluoromethane)sulfonimides
have been successfully used for the acetylation of phenols
and alcohols [34], [2 ? 2] cycloadditions of siloxyalkynes
with carbonyl compounds [35], Friedel–Crafts acylation
reactions [36], cycloisomerization of 1,6-dienes [37], and
aminolysis of lactones with amines [38]. However, many
metal bis(trifluoromethane)sulfonimides are not available
commercially and involve high cost for their preparation
and therefore are not a good contender for general use.
Mg(NTf ) is commercially available and cheaper, and
Coumarin and its derivatives are important owing to their
wide use in synthetic chemistry and their biological
activities. They are widely used as additives in food, per-
fumes, agrochemicals, cosmetics, pharmaceuticals [1], and
in the preparation of insecticides, optical brighteners [2],
and dispersed fluorescent and laser dyes [3]. A large
number of natural products containing the coumarin moiety
are also known [4]. Coumarins can be synthesized by
various methods such as Pechmann [5], Perkin [6], Knoe-
venagel [7], Reformatsky [8], and Wittig [9] reactions.
Among these, the Pechmann reaction is one of the most
common procedures for the preparation of coumarin and its
derivatives. This method involves the condensation of
phenols with b-ketoesters in the presence of condensing
agents. Different reagents such as H SO [5], AlCl [10],
2
2
therefore better suited for catalytic use. Previously, we
reported the use of Eu(NTf ) [39] and Mg(NTf ) [40] as
2
3
2 2
efficient catalysts for organic synthesis. In continuation to
our work, I herein report an efficient procedure for the
synthesis of coumarins from phenols and b-ketoesters in
the presence of 1 mol% of Mg(NTf ) under solvent-free
2 2
2
4
3
P O [11], CF COOH [12], p-TsOH [13], BiCl [14], silica
2
conditions (Scheme 1).
5
3
3
sulfuric acid [15], H PW O [16], Sm(NO ) Á6H O [17],
3
12 40
3 3
2
TiCl [18], InCl [19], I [20], ZrCl [21], HClO ÁSiO
4
3
2
4
4
2
Results and discussion
H. Wang (&)
Shaanxi Key Laboratory for Phytochemistry,
Department of Chemistry and Chemical Engineering,
Baoji University of Arts and Sciences, Baoji 721013, China
e-mail: hongshewang@126.com
The reaction of phenol and ethyl acetoacetate in the pres-
ence of Mg(NTf ) was chosen as a model to optimize the
2
2
reaction conditions and the results are listed in Table 1. No
product was detected in the absence of the catalyst. It was
123

4
12
H. Wang
R5
R5 R1
Table 3 Effect of solvent on the reaction of phenol and ethyl ace-
toacetate using Mg(NTf ) as a catalyst
2 2
R4
R3
R4
R3
O
O
Mg(NTf2)2 (1 mol%)
Solvent-free, 80 o
+
R1
a
OEt
OH
C
O
O
Entry
Solvent
Time/min
Yield/%
R2
R2
1
2
3
1
2
3
4
5
Dioxane
120
75
50
74
70
52
87
Acetonitrile
Scheme 1
1,2-Dichloroethane
Toluene
90
120
60
None
Table 1 Effect of the amount of catalyst on the reaction of phenol
and ethyl acetoacetate under solvent-free conditions using Mg(NTf
as a catalyst
2
)
2
Reaction conditions: phenol (1 mmol) and ethyl acetoacetate
3
(1 mmol) in the indicated solvent (5 cm ) or under solvent-free
conditions at 80 °C
Isolated yields
a
Entry
Catalyst loading/mol%
Time/min
Yield/%
a
1
2
3
4
5
9
7
0
120
90
60
60
60
60
60
0
41
76
87
87
87
87
0.25
0.5
1
significant increase in the yield was observed when the
reaction temperature was raised from 80 to 90 °C. There-
fore, 80 °C was chosen as the reaction temperature for all
further reactions.
3
5
The reaction was carried out in different solvents such as
dioxane, MeCN, 1,2-dichloroethane, and toluene, and also
without solvent. As shown in Table 3, the best result was
obtained when the reaction was carried out under solvent-
free conditions and the catalyst worked in heterogeneous
conditions. The lower isolated yields in solvents may be
due to the decreased concentrations of substrates. The use
of solvent-free conditions is advantageous because it
avoids the use of potentially toxic and non-environmentally
friendly organic solvents.
10
Reaction conditions: phenol (1 mmol) and ethyl acetoacetate
(1 mmol) at 80 °C in the presence of the indicated amount of catalyst
under solvent-free conditions
a
Isolated yields
Table 2 Effect of temperature on the reaction of phenol and ethyl
as a
acetoacetate under solvent-free conditions using Mg(NTf
catalyst
2
)
2
To show the general applicability of the method, the
reaction of various phenols and b-ketoesters in the pres-
ence of 1 mol% of Mg(NTf ) at 80 °C under solvent-free
a
Entry
Temperature/°C
Time/min
Yield/%
2
2
1
2
3
4
5
6
40
60
70
80
85
90
180
90
75
60
55
50
32
67
81
87
87
83
conditions was investigated and the results are summarized
in Table 4. In all cases, various substituted phenols reacted
smoothly with b-ketoesters to give a range of coumarin
derivatives. Short reaction times were observed (25–60 min)
regardless of structural variations in the phenols or b-keto-
esters. Phenols carrying either electron-donating or electron-
withdrawing substituents all reacted smoothly to give the
corresponding 4-substituted coumarins in high yields. Ethyl
acetoacetate, ethyl benzoylacetate, and ethyl trifluoroace-
toacetate reacted similarly to produce coumarins. For phenol
(Table 4, entry 1), the reaction time is reduced drastically in
contrast to the reported procedure [14]. According to the
literature, 4-nitrophenol failed to give a coumarin derivative
Reaction conditions: phenol (1 mmol) and ethyl acetoacetate
(
1 mmol) at the indicated temperature under solvent-free conditions
a
Isolated yields
surprising to discover that 0.25 mol% of Mg(NTf ) could
2
2
accelerate the reaction, but the reaction afforded the cor-
responding product in a low yield. Further study showed
that the use of 1 mol% of Mg(NTf ) was sufficient to
in the presence of TiCl
Mg(NTf afforded the coumarin 3f in high yield (Table 4,
entry 6).
In addition, we compared the efficacy of Mg(NTf
against other catalysts such as Mg(ClO , LiNTf
Mg(OTf) , and Cu(OTf)
at 80 °C under solvent-free
as the catalyst [18]. In contrast,
2
2
4
provide a satisfactory yield in 60 min. An increase in the
amount of catalyst did not produce a better result.
)
2 2
Then, the effect of temperature on the reaction was
studied and the results are listed in Table 2. No reaction
was observed after stirring the reaction mixture at room
temperature for 240 min under solvent-free conditions. The
reaction proceeded smoothly with increasing tempera-
ture; the yield increased to 87 % at 80 °C. However, no
)
2 2
)
,
2
4
2
2
2
conditions. No 4-methylcoumarin (3a) was obtained after
8 h by the treatment of phenol with ethyl acetoacetate in
the presence of Cu(OTf) (1 mol%). LiNTf (5 mol%)
2 2
1
23

Magnesium bis(trifluoromethane)sulfonimide
413
1
Table 4 Synthesis of coumarins via Pechmann condensation of phenols with b-ketoesters (R –CO–CH
2 2 2
–COOEt) catalyzed by Mg(NTf )
1
a
Entry
Phenol
R
Product
Time/min
Yield/%
M.p./°C
Found
Reported
1
2
3
4
5
6
7
8
9
C
6
H
5
–OH
CH
CH
CH
CH
CH
CH
Ph
3
3
3
3
3
3
3a
3b
3c
3d
3e
3f
60
25
25
25
25
60
60
35
35
25
25
45
87
96
95
98
97
92
85
95
96
97
98
94
82–83
80–81 [15]
182–184 [28]
131–132 [18]
156–158 [18]
285–287 [15]
151–154 [17]
100–102 [41]
255–257 [15]
241–242 [15]
–
3-HO–C
6
H
4
–OH
–OH
–OH
–OH
–OH
183–184
131–133
156–157
286–288
150–152
102–104
253–255
243–245
178–179
221–223
154–155
3-CH –C
3
6
H
4
3-CH O–C
3
6 4
H
3,5-(HO)
4-NO –C
–OH
3-HO–C
3,5-(HO)
3-HO–C
3-NH –C
2
–C
H
6 4
2
6 4
H
C
6
H
5
3g
3h
3i
6
H
4
–OH
–C –OH
–OH
–OH
Ph
2
H
6 4
Ph
10
11
12
6
H
4
CF
CF
CH
3
3j
2
6
H
4
3
3k
3l
–
1-Naphthol
3
152–153 [15]
Reaction conditions: phenols (1 mmol) and b-ketoesters (1 mmol) in the presence of 1 mol% of Mg(NTf
conditions
2
)
2
at 80 °C under solvent-free
a
Isolated yields
Table 5 Reuse of the catalyst
for the synthesis of 3a
a
Table 6 Comparison of efficiency of various catalysts in the syn-
thesis of 3a under solvent-free conditions
Entry
Yield/%
0
1
2
3
4
87
86
84
83
78
Catalyst (mol%)
Temp./
C
Time/
min
Yield/
a
Ref.
°
%
BiCl
3
(5)
125
240
120
45
73
70
95
50
60
65
76
80
40
87
[14]
Silica sulfuric acid (15) 80
[15]
a
Isolated yields
H PW O (2)
90
O (10) 80
r.t.
[16]
3
12 40
Sm(NO
3
)
3
Á6H
2
90
[17]
TiCl
InCl
(1)
KAl(SO
4
(50)
70 s
240
180
180
120
60
[18]
afforded 3a in 61 % yield after 2 h. Mg(ClO ) (10 mol%)
2
3
(10)
130
[19]
4
and Mg(OTf) (10 mol%) afforded 3a in yields of 48 and
2
I
2
80
[20]
3
0 % after 2 and 3 h, respectively. The above representa-
4
)
2
Á12H
2
O (40) 80
[26]
tive examples demonstrated the superiority of Mg(NTf ) .
2
[bmim]ClÁ2AlCl
3
(100) 120
80
[31]
2
We also investigated the reusability and recycling of
Mg(NTf ) . After the reaction of phenol with ethyl aceto-
Mg(NTf
2
)
2
(1)
This work
2
2
a
Isolated yields
acetate at 80 °C under solvent-free conditions, more than
0 % of Mg(NTf ) could be easily recovered by a simple
9
2
2
extraction with water. The recovered Mg(NTf ) catalyzed
2
2
procedure, high yields, and the use of a catalytic amount of
a commercially available catalyst.
the same reaction without significant decrease in catalytic
activity even after the fourth run (Table 5).
In order to evaluate the efficiency of this work in
comparison with previously reported procedures, synthesis
of 4-methylcoumarin (3a) was considered as a represen-
tative example. As shown in Table 6, the yield of the
present method is better or comparable with those of oth-
ers. Furthermore, Mg(NTf2)2 is stable in water, easily
recovered, and reusable.
Experimental
All reagents were commercially available and were used
without further purification. Melting points were deter-
mined on an XT4A electrothermal apparatus equipped with
a microscope. NMR spectra were recorded on a Bruker
In conclusion, Mg(NTf ) is an efficient catalyst for the
2
2
synthesis of coumarins from phenols and b-ketoesters
under solvent-free conditions. The advantages of this pro-
tocol include short reaction times, a simple work-up
Avance 400 spectrometer in DMSO-d with TMS as an
6
internal standard. Mass spectra were recorded on a Waters
Micromass GCT. IR spectra were recorded on a Nicolet
123

4
14
H. Wang
FTIR-750 spectrometer. Elemental analyses were per-
formed on a Perkin Elmer 240-C instrument. All solvents
were dried by standard procedures.
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Acknowledgments
Shaanxi Province (no. 12JK0615) and Baoji University of Arts and
Sciences (no. ZK1053) for financial support.
We thank the Educational Committee of
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23