Diels-Alder reactions in pyridinium based ionic liquids

Article abstract of DOI:10.1016/j.tetlet.2004.09.070

Diels-Alder reactions have been investigated in pyridinium based ionic liquids. These solvents are found to be more effective compared to the organic solvent studied, in enhancing the reaction rate and product yields. Recycled ionic liquids also gave exce

Full text of DOI:10.1016/j.tetlet.2004.09.070

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 8339–8342
Diels–Alder reactions in pyridinium based ionic liquids
Ying Xiao and Sanjay V. Malhotra*
Department of Chemistry and Environmental Science, New Jersey Institute of Technology, University Heights, Newark,
NJ 07102, USA
Received 11 June 2004; revised 8 September 2004; accepted 9 September 2004
Available online 25 September 2004
Abstract—Diels–Alder reactions have been investigated in pyridinium based ionic liquids. These solvents are found to be more effec-
tive compared to the organic solvent studied, in enhancing the reaction rate and product yields. Recycled ionic liquids also gave
excellent results.
Ó 2004 Elsevier Ltd. All rights reserved.
1. Introduction
age of cyclic and acyclic ethers,15 and polymerization.16
As highly ordered media with environmentally friendly
properties, ionic liquids have the potential to influence
the outcome of Diels–Alder reaction. There have been
reports on the use of ionic liquids for Diels–Alder reac-
tions.17–24 However, all these studies have focused only
on solvents derived from imidazole. Here we wish to
report the first study on the application of pyridinium
based ionic liquids as solvent for the Diels–Alder
reaction.
Diels–Alder reaction is one of the most important tools
for carbon–carbon bond formation. It is a widely used
reaction in organic synthesis,1 and in the chemical indus-
try.2 It is well established that the reactivity and selectiv-
ity of Diels–Alder reactions are strongly influenced by
the Lewis acidity of the medium. Therefore, the reaction
has been investigated using water,3 surfactants,4 lithium
amides,5 alkylammonium nitrate,6 borane–THF com-
plex,7 etc., and rate enhancement has been seen in differ-
ent solvents and catalysts systems. Considering the
practical importance and wide applications of Diels–
Alder reaction in organic synthesis and chemical indus-
try, lately an increased attention has been focused on the
development of ÔgreenÕ methods for the purpose of
improving rate and selectivity of this reaction.
2. Results and discussion
The utility of two ionic liquids (Scheme 1) namely, 1-
ethyl-pyridinium tetrafluoroborate ([EtPy]+[BF4]À) and
1-ethyl-pyridinium trifluoroacetate ([EtPy]+[CF3COO]À)
was investigated in reactions of isoprene (1) with
acrylonitrile 2, acrylic acid 3, and methacrylic acid 4
(Scheme 2).
In recent years, ionic liquids have gained a lot of atten-
tion as green solvents in organic synthesis and other
chemical processes. This is mainly due to their favorable
inherent properties such as chemical and thermal stabil-
ity, no measurable vapor pressure, nontoxicity, non-
flammability, catalytic ability, high polarity, ease to
recycle, etc.8–10 As such, they have been investigated as
reaction media in many organic and organometallic
syntheses such as Heck reactions,11 Friedel–Crafts
reactions,11 alkylation,11 hydrogenation,12 hydroformyl-
ation,12 dimerization,13 condensation,14 acylative cleav-
In a typical reaction,25 the diene (1) and the dienophile
(2, 3, 4) were added to the ionic liquid directly, and
the mixture was stirred (400rpm) at the desired reaction
-
-
BF4
-
CF COO
3
N
N
+
+
Keywords: Ionic liquid; Diels–Alder reaction; 1-Ethyl-pyridinium
tetrafluoroborate; 1-Ethyl-pyridinium trifluoroacetate.
+
-
+
[EtPy] [BF ]
[EtPy] [CF COO]
4
3
*
Corresponding author. Tel.: +1 973 596 5583; fax: +1 973 596
3586; e-mail: malhotra@njit.edu
Scheme 1. Pyridinium based ionic liquids studied.
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.09.070

8340
Y. Xiao, S. V. Malhotra / Tetrahedron Letters 45 (2004) 8339–8342
CN
+
+
(1)
(2)
+
CN
2
CN
5
1
6
COOH
+
COOH
3
COOH
COOH
7
1
8
CH3
COOH
CH3
+
+
(3)
COOH
4
CH3
10
9
1
Scheme 2. Reactions of isoprene with different dienophiles.
temperature for the specified time period. The molar
ratio of isoprene–dienophile–ionic liquid is 1.5:1:1. All
reactions are heterogeneous in nature. At the end of
the reaction, organic layer could be easily decanted from
the ionic liquid, and any organic residues removed by
extraction with ether. The purified ionic liquid could
be reused without loss of activity. As shown in Scheme
2 (Eqs. 1–3), both Ôpara likeÕ (5, 7, 9) and Ômeta likeÕ
(6, 8, 10) products were obtained in each case. However,
in all cases the major products are Ôpara likeÕ. Table 1
shows the results of reaction of isoprene with various
dienophiles.
investigate this reaction in pyridinium based ionic liq-
uids. The ionic liquids were prepared following a meth-
od reported earlier in the literature.29 A comparison of
the results with literature data of reactions using bor-
ane–THF complex (entries 8, 14), improved yields were
obtained using ionic liquids in relatively short reaction
period. Also, much better yields were obtained using
our reaction protocol, compared to the other ionic liq-
uids for the same system reported in the literature (entry
2). When [EtPy]+[BF4]À was used as solvent medium the
reaction occurred slowly, but at a relatively faster rate
than seen in CH2Cl2. The same reactions when carried
out in [EtPy]+[CF3COO]À, occurred rapidly with much
higher product yields. Interestingly though, as the reac-
tion is continued beyond 2h there is a decrease in Ôpara/
meta likeÕ product ratio, while overall yield of the com-
bined products increased. This was true in case of all
reactions irrespective of the ionic liquid used. Figure 1
shows the effect of various solvents on the rate of reac-
As data show, the reaction rate and yields of Diels–
Alder reaction are dependent on the solvent. An initial
study of reactions carried out in CH2Cl2 as solvent gave
low product yields (entries 1, 7, 13), indicating the need
for a polar medium for the reaction. These observations
and results of our earlier studies,27,28 prompted us to
Table 1. Diels–Alder reactions of isoprene 1 with dienophiles at 20°C
Entry
Solvent
Dienophile
Time (h)
Yielda (%)
Selectivitya (Ôpara likeÕ:Ômeta likeÕ)
1
CH2Cl2
Acrylonitrile, 2
Acrylonitrile, 2
Acrylonitrile, 2
Acrylonitrile, 2
Acrylonitrile, 2
Acrylonitrile, 2
Acrylic acid, 3
72
24
12
38
64:36
69:31b
2c
3
Phosphonium tosylates
[EtPy]+[CF3COO]À
[EtPy]+[CF3COO]À
[EtPy]+[BF4]À
2 (24)
72
90 (97)
99
89:11b (75:25)
75:25
4
5
2 (24)
72
72
42 (64)
83
27
84:16b (66:34)
58:42
70:30
6
[EtPy]+[BF4]À
7
CH2Cl2
8d
9
Borane–THF + CH2Cl2
[EtPy]+[CF3COO]À
[EtPy]+[CF3COO]À
[EtPy]+[BF4]À
Acrylic acid, 3
Acrylic acid, 3
30
2 (24)
72
75
97 (98)
98
—
95:5b (85:15)
80:20
82:18b (65:35)
62:38
58:42
10
11
12
13
14e
15
16
17
18
Acrylic acid, 3
Acrylic acid, 3
Acrylic acid, 3
2 (24)
72
72
32 (50)
55
[EtPy]+[BF4]À
CH2Cl2
Methacrylic acid, 4
Methacrylic acid, 4
Methacrylic acid, 4
Methacrylic acid, 4
Methacrylic acid, 4
Methacrylic acid, 4
5
66
Borane–THF + CH2Cl2
[EtPy]+[CF3COO]À
[EtPy]+[CF3COO]À
[EtPy]+[BF4]À
68
—
2 (24)
72
24
55 (64)
67
18
62:38 (54:46)
1:1b
66:34
55:45b
[EtPy]+[BF4]À
72
22
a Determined by GC.
b Ratio determined by 1H NMR.
c Ref. 26, 80°C.
d Ref. 7, 0°C.
e Ref. 7.

Y. Xiao, S. V. Malhotra / Tetrahedron Letters 45 (2004) 8339–8342
8341
With a decrease in temperature to 0°C, the selectivity in-
creased slightly, but the overall yield decreased. On the
other hand at 45°C the rate of reaction was accelerated,
while selectivity dropped significantly. It is also impor-
tant to note that at 0 and 20°C, the reactions mixtures
were in two phases and on increasing the reaction tem-
perature to 45°C gave a homogenous mixture.
Finally, we investigated the reusability and efficiency of
ionic liquid [EtPy]+[CF3COO]À. After the first reaction
the ionic liquid was separated from the organic layer.
Any leftover organic material was extracted with ethyl
ether and the ionic liquid dried at 65°C under vacuum.
Successive runs were performed with the recovered ionic
liquid [EtPy]+[CF3COO]À for reaction between isoprene
and acrylonitrile (Scheme 2, Eq. 1), at 20°C for 24h. As
results in Table 3 show, the ionic liquid could be recov-
ered quantitatively and without loss of activity. This is
evident from the fact that the overall product yield of
the Diels–Alder reaction is not affected even after six
runs with the recovered ionic liquid.
Figure 1. Diels–Alder reactions of isoprene with acrylic acid in
different solvents at 20°C.
tion between isoprene and acrylic acid at 20°C. In each
solvent initially the reaction occurs rapidly and there is
only little change with prolonged time period. Ionic
liquid [EtPy]+[BF4]À has an effect in enhancing the
rate of reaction. However, [EtPy]+[CF3COO]À seems
to be ideal and has the greatest effect on increasing the
reaction rate.
Table 2. Diels–Alder reactions in [EtPy]+[CF3COO]À at 0 and 45°C
b
Entry Dienophile
Time Temp Yielda Selectivity
The varied effect on the rate could be attributed to the
difference in coordination of cation and anion in these
two solvents. As Lewis acids, ionic liquids form complex
with the substituents (such as –C(O)R and –CN) on
dienophiles. A complexed dienophile is then more reac-
tive toward diene. The complexation accentuates both
the energy and orbital distortion effects of the substitu-
ents and, therefore, enhances both the selectivity and
reactivity of dienophiles. In other words, the interaction
between dienophile and ionic liquid increases the coeffi-
cient of C-2 in lowest unoccupied molecular orbital
(LUMO) of dienophile and make it more efficient to
react with C-1 in highest occupied molecular orbital
(HOMO) of isoprene as shown in Scheme 3. Hence,
there is a change in the ratio of Ôpara likeÕ to Ômeta likeÕ
products.
(h)
(°C)
(%)
to main
product (%)
1
2
3
4
5
6
Acrylic acid
Acrylic acid
Acrylonitrile
Acrylonitrile
2 (24)
0
91 (98) 98 (90)
98 (98) 74 (56)
81 (94) 98 (84)
98 (98) 67 (50)
40 (61) 72 (60)
62 (69) 50 (50)
2 (24) 45
2 (24)
2 (24) 45
0
Methacrylic acid 2 (24)
Methacrylic acid 2 (24) 45
0
a Determined by GC.
b Determined by 1H NMR.
Table 3. Recovery and reuse of [EtPy]+[CF3COO]À in reaction of
isoprene and acrylonitrile at 20°C
Recycling #
Recovered ionic liquid
yield (wt%)a
Overall product
Yield (%)b
Similarly, due to its inductive effect the methyl group
makes the methacrylic acid relatively less electrophilic
than acrylic acid. As a result overall yields are lower
than those seen in the case of reaction with acrylic acid.
We further investigated the effect of temperature on
Diels–Alder reaction in ionic liquid [EtPy]+[CF3COO]À.
These reactions were also carried out at 0 and 45°C.
Results are shown in Table 2.
1
2
3
4
5
6
96
97
95
96
97
96
97
97
95
96
94
92
a Isolated yield.
b GC yield.
C1
C2
C1
R
C1
C2
C4
C1
R
"Para like" product
+
C1
R
R
C4
R
C1
C2
C4
"Meta like" product
Scheme 3. The mechanism of Diels–Alder reactions.

8342
Y. Xiao, S. V. Malhotra / Tetrahedron Letters 45 (2004) 8339–8342
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Our study has shown for the first time that pyridinium
based ionic liquids can be used effectively as solvent
in the Diels–Alder reaction. The ionic liquid [EtPy]+-
[CF3COO]À is found to be an excellent reaction solvent
with significantly increased rate for this reaction com-
pared to organic solvent. Applications of this solvent
for number of other reactions are under investigation
in our laboratory.
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procedure: Isoprene (4.09g, 60mmol) was added slowly
to a mixture of 2 (1.64g, 40mmol) and ionic liquid
[EtPy]+[CF3COO]À (8mL, 46mmol) under argon at room
temperature. The biphasic reaction mixture was allowed to
stir (400rpm) at room temperature for the desired time
period. After the reaction was over, the mixture was
diluted with 3mL water and 3mL petroleum ether, and
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ratio of isomers confirmed by 1H NMR (500Hz, in
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