Ionic liquid promoted knoevenagel and michael reactions

Article abstract of DOI:10.1071/CH04060

The utilization of the ionic liquid [bmim][BF₄] as both reaction medium and promoter for the Knoevenagel condensation and Michael addition reactions is described in this paper. Through these reactions, several useful electrophilic alkenes and chromene derivatives are obtained in high yields. The advantages of these two novel procedures include their environmentally benign nature, atom economy, simple operation process, and mild reaction conditions.

Full text of DOI:10.1071/CH04060

Full Paper
CSIRO PUBLISHING
www.publish.csiro.au/journals/ajc
Aust. J. Chem. 2004, 57, 1067–1071
Ionic Liquid Promoted Knoevenagel and Michael Reactions
Xuesen Fan,A,C Xueyuan Hu,A,B Xinying Zhang,A and Jianji WangA
A
School of Chemical and Environmental Sciences, Henan Key Laboratory for Environmental
Pollution Control, Henan Normal University, Xinxiang, Henan 453007, China.
B Chongqing University of Medical Sciences, Chongqing 400016, China.
C Corresponding author. Email: fanxs88@263.net
The utilization of the ionic liquid [bmim][BF4] as both reaction medium and promoter for the Knoevenagel conden-
sation and Michael addition reactions is described in this paper.Through these reactions, several useful electrophilic
alkenes and chromene derivatives are obtained in high yields. The advantages of these two novel procedures include
their environmentally benign nature, atom economy, simple operation process, and mild reaction conditions.
Manuscript received: 7 March 2004.
Final version: 9 July 2004.
Introduction
and coworkers reported a glycine-promoted Knoevenagel
condensation of benzaldehyde with malononitrile in ionic liq-
uid, but only one example was examined.[7] As an alternative,
Chen and coworkers reported that this classical reaction can
also be well realised in ionic liquids by using ethylenedi-
ammonium diacetate (EDDA) as a catalyst.[8a] Very recently,
two greener processes for the Knoevenagel reaction have
also been realized efficiently in water or in the absence of
solvent.[8b,8c] However, to our knowledge, there are no prece-
dents in terms of using ionic liquids as both reaction media
and promoter in Knoevenagel condensation and Michael
addition reactions. As continuation of our interest in the area
of green synthesis,[9] we then checked the improvement that
can be expected if these reactions can be carried out in ionic
liquid without any such added catalysts as mentioned above.
Herein we report our preliminary results on the using of an
ionic liquid, 1-butyl-3-methylimidazolium tetrafluoroborate
([bmim][BF4]), as a recyclable alternative to classical molec-
ular solvents and a promoter for Knoevenagel condensation
and Michael addition reactions.
The development of environmentally friendly catalysts and
solvents for organic chemistry is an area of considerable
importance. From both economical and environmental points
of view, the use of non-volatile solvents and non-metallic
catalysts is very promising. In the last few years room-
temperature ionic liquids (RTILs), especially those based on
1,3-dialkylimidaxolium cations,[1] have been recognized as
a possible environmentally benign alternative to chemical
volatile solvents because, in contrast with the conventional
organic solvents, they are non-volatile, recyclable, non-
explosive, easy to handle, and thermally robust.[2] Further-
more, in many cases, the products are weakly soluble in the
ionic phase so that they can be easily separated by simple fil-
tration or extraction with ether.[3] On the other hand, because
of the great potential of RTILs as novel reaction media for
catalytic processes, much attention has also been currently
focussed on organic reactions promoted by ionic liquids.
Knoevenagel condensations of aldehydes with active
methylene compounds, and Michael additions of active
methylene compounds to α,β-unsaturated compounds are of
great importance in the construction of new carbon–carbon
bonds. Usually, they are carried out in the presence of either
base or acid catalysts in volatile organic solvents and thus
create much waste.[4,5] Recently, there are several reports
on the new versions of Knoevenagel condensations in ionic
liquids; for example, Salunkhe and coworkers reported a
Knoevenagel condensation involving the use of Lewis acidic
ionic liquids [bmim]Cl · xAlCl3 and [bpy]Cl · xAlCl3.[6]
Although the experimental procedure is simple, the ionic liq-
uids are sensitive to moisture and air. Therefore, the reaction
must be carried out in an inert-atmosphere glove box and the
ionic liquid used cannot be recycled. In another case, Forbes
Results and Discussion
We began our work by examining the Knoevenagel con-
densation between benzaldehyde 1a and malononitrile 2 in
[bmim][BF4] (Scheme 1).
Though almost all the Knoevenagel condensation proce-
dures in ionic liquids mentioned above necessitated the use
of additional catalysts, we found that this reaction did occur
in the presence of [bmim][BF4] alone and afforded the cor-
responding product 3a with considerably high yields under
optimized reaction conditions.As shown inTable 1, when the
mixture of 2 and 1a was stirred in [bmim][BF4] for just 1 h
at room temperature, the yield of 3a is disappointingly low
© CSIRO 2004
10.1071/CH04060
0004-9425/04/111067

1068
X. Fan et al.
CN
CN
CN
Table 1. Knoevenagel condensation between 1a and
[bmim][BF4]
Reaction conditions: 1 mL [bmim][BF4], 0.5 mmol benzaldehyde,
0.5 mmol malononitrile
2 in
[bmim][BF4]
PhCHO ꢀ
Ph CH
C
CN
1a
2
3a
Entry
Reaction temp.
[◦C]
Reaction time
[h]
Isolated yield
Scheme 1.
[%] 3a
1
2
3
4
5
6
7
Room temp.
1
1
2
4
4
2
4
5
11
28
42
65
62
85
CN
R
CN
[bmim][BF4]
40
40
40
60
80
80
ArCHO ꢀ
Ar CH
C
R
1
2
3
R ꢁ CN, CO2Et
Scheme 2.
Table 2. Knoevenagel condensation of aldehydes with malono-
nitrile or ethyl cyanoacetate in [bmim][BF4] at 80◦C
O
Ar
R
CN
R
O
O
[bmim][BF4]
Ar CH
C
ꢀ
Entry
Ar
R
Reaction Products
time [h]
Isolated
O
NH2
yield [%]
3
4
5
1
2
3
4
5
6
7
8
C6H5
p-NO2C6H4
p-CH3OC6H4 CN
CN
CN
4
2
4
3
3
2
4
4
4
3
5
5
5
6
6
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
85
95
83
91
92
89
78
85
88
86
78
68
70
58
60
R ꢁ CN, CO2Et
Scheme 3.
p-ClC6H4
p-BrC6H4
p-FC6H4
CN
CN
CN
p-CH3C6H4
o-BrC6H4
o-ClC6H4
m-NO2C6H4
p-NO2C6H4
p-ClC6H4
m-NO2C6H4
CN
CN
CN
CN
CO2Et
CO2Et
CO2Et
(Table 1, entry 1). However, with a higher reaction tempera-
ture along with longer reaction time, the yield of 3a can be
improved considerably. In fact, it turned out that 3a can be
obtained with a yield as high as 85% when the reaction was
conducted at 80◦C for 4 h (Table 1, entry 7).This result is well
comparable to the yields reported in the literature involving
additional catalysts.
9
10
11
12
13
14
15
p-CH3OC6H4 CO2Et
o-ClC6H4 CO2Et
With the above results in hand, we then turned our
attention to the condensation of other structurally var-
ied aldehydes with malononitrile or ethyl cyanoacetate by
using [bmim][BF4] as both reaction medium and promoter
(Scheme 2, Table 2). As can be seen in Table 2, the reac-
tions were found to be general. Aldehydes with various
substituents, such as chloro, bromo, fluoro, nitro, or methoxy
groups, all gave the corresponding products in fairly good
results. It should be noted that with ethyl cyanoacetate, a
prolonged reaction time was needed to give reasonably high
yields because of its lower nucleophilic activity compared
with malononitrile.
Considering that the electron-poor alkenes 3 are good
Michael addition receptors, we then started to check the pos-
sibility of performing the 1,4-addition of dimedone 4 to 3 in
the presence of ionic liquids (Scheme 3), which has been used
as an efficient method to prepare the chromene derivatives 5
(Scheme 3). When the mixture of 3a and 4 was stirred in
[bmim][BF4] at 40◦C for 4 h without any additional catalyst,
the corresponding product was formed almost quantitatively.
In addition, the separation process of the final product is quite
simple, just through adding a little amount of H2O to the
mixture and then subsequent suction to collect the product
crystals. Moreover, this simple process is also applicable to
other electron-poor alkenes and they all give the chromene
derivatives in good yields under mild conditions (shown in
Table 3).
Table 3. Michael addition reactions of
[bmim][BF4] at 40◦C
3
and
4
in
Entry
Ar
R
Reaction Products
time [h]
Isolated
yield [%]
1
2
3
4
5
6
7
8
C6H5
CN
4
4
2
3
4
4
3
2
4
4
3
3
3
3
5
5
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
88
85
96
95
83
84
90
95
79
86
89
86
93
91
82
83
p-CH3C6H4
p-NO2C6H4
p-ClC6H4
o-ClC6H4
p-CH3OC6H4 CN
CN
CN
CN
CN
m-NO2C6H4
p-FC6H4
CN
CN
9
m-BrC6H4
o-ClC6H4
m-NO2C6H4
p-NO2C6H4
p-FC6H4
p-ClC6H4
p-CH3C6H4
C6H5
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
10
11
12
13
14
15
16
By thoroughly referenced screening, we found that this
kind of reaction is frequently performed in solution or
solvent-free under base catalysis,[10,11] or under acid[12]
or Lewis acid[13] catalysis, and required chromatographic

Ionic Liquid Promoted Knoevenagel and Michael Reactions
1069
O
Ar
O
O
Ph
CN
CO2Et
NH2
O
O
CN
[bmim][BF4]
ArCHO ꢀ
ꢀ
CN
O
O
NH2
O
O
5
CN
[bmim][BF4]
1
2
4
5
PhCHO ꢀ
ꢀ
CO2Et
Ph
O
Scheme 4.
1
2
4
Table 4. Three-component coupling reaction of 1, 2 and 4 in
[bmim][BF4] at 40◦C
OH OH
6
Reaction conditions: 1 mL [bmim][BF4], 0.5 mmol aldehyde,
0.5 mmol malononitrile, 0.5 mmol dimedone
Scheme 5.
Entry
Ar
R
Reaction
time [h]
Products
Isolated
yield [%]
react with benzaldehyde before cyanoacetate and afforded the
corresponding product 6 exclusively.
1
2
3
4
5
6
7
C6H5
p-NO2C6H4
p-ClC6H4
CN
CN
CN
CN
CN
CN
CN
5
3
4
4
5
3
3
5a
5c
5d
5e
5f
84
90
88
80
82
85
87
One important feature of the use of ionic liquids as reac-
tion medium is the possibility of its recyclability and reuse for
the same, as well as for different, types of reactions. We found
that the recyclability and reuse of [bmim][BF4] is feasible in
all the above procedures. At completion of the reactions, the
products were isolated by filtration and the filtered solution
was heated in an oven with reduced pressure to remove water.
The residue was then reloaded with the initial reagents and
this solution was re-submitted to the usual reaction condi-
tions. No decrease in the efficiency of the reused ionic liquid
was observed after several rounds.
In summary, we have demonstrated that the ionic liq-
uid [bmim][BF4] can be used as both reaction medium and
promoter for the Knoevenagel condensation and Michael
addition reactions, which usually involve the use of addi-
tional catalyst when they are carried out in conventional
organic solvents. In addition, it has also been demonstrated
that[bmim][BF4]isausefulmediumforthethree-component
coupling reaction of aldehydes, malononitrile, and dimedone
to give chromene derivatives in high yields. Compared with
the reported methods, the notable features of the above pro-
cedures are atom economy, mild conditions, cleaner reaction
profiles, and simple operational process, together with con-
venient and efficient recovery and reuse of this novel reaction
medium.
o-ClC6H4
p-CH3OC6H4
m-NO2C6H4
p-FC6H4
5g
5h
purification techniques to give the pure products. Other
methods such as dry solid supports and microwave heat-
ing were also applied, but the situation did not improve
significantly.[14] With the process presented in this paper,
the Michael addition and the subsequent rearrangement and
cyclization of the Michael adducts to give the corresponding
chromene derivatives were achieved efficiently without any
conventional solvents, base or acid catalyst, or microwave
irradiation conditions.
Currently, the art of performing efficient chemical trans-
formations, coupling three or more components in a single
operation by a catalytic process and avoiding stoichiometric
toxic reagents, large amounts of solvents, and costly purifi-
cation procedures represents a fundamental target of modern
organic synthesis. It has been reported that RTILs are able
to efficiently catalyze the three-component coupling reac-
tions of aldehydes, amines, and homophthalic anhydrides to
give the corresponding cis-isoquinolonic acids in excellent
yields.[15] This result promoted us to study the potential role
of RTILs in promoting the three-component coupling reac-
tion of aldehyde 1, malononitrile or ethyl cyanoacetate 2,
and dimedone 4 to afford the corresponding chromenes 5
in a one-pot reaction. To our delight, treatment of benzalde-
hyde, malononitrile, and dimedone in [bmim][BF4] at 40◦C
afforded the corresponding chromene derivative 5 in 84%
yield (Scheme 4).
Experimental
Melting points were measured by a Kofler micromelting point apparatus
and were uncorrected. Infrared spectra were recorded on a BrukerVector
22 spectrometer in KBr with absorption values quoted in cm−1 1H
.
NMR spectra were determined on a Bruker AC 400 spectrometer as
CDCl3 solutions. Chemical shifts (δ) were expressed in ppm downfield
from the internal standard tetramethylsilane, and coupling constants J
were given in Hz. 13C NMR spectra were recorded on a Bruker AC
100 spectrometer as CDCl3 solutions. Mass spectra were recorded on
a HP5989B mass spectrometer. Elemental analyses were performed on
an EA-1110 instrument.
Similarly, several other aryl aldehydes also reacted
smoothly with malononitrile and dimedone to give the
corresponding chromenes in reasonably high yields (Table 4).
However, when benzaldehyde and ethyl cyanoacetate were
treated with dimedone in [bmim][BF4] at ambient tem-
perature, no chromene derivative was obtained. Instead,
almost quantitative formation of 6, a condensation prod-
uct of benzaldehyde and dimedone occurred (Scheme 5).
It is probably attributable to the much weaker nuleophilic
activity of cyanoacetate compared with dimedone, which can
General Procedure for the Knoevenagel Condensation
in [bmim][BF4]
The aromatic aldehyde 1 (0.5 mmol) and active methylene compound
2 (0.5 mmol) were added to a round bottom flask containing 1 mL of
[bmim][BF4]. The mixture was stirred at 80◦C for a certain time to
complete the reaction (monitored by TLC). At completion, water was
added. The precipitates in the reaction mixture were then collected and
further purified by recrystallization with 95% ethanol to give the pure

1070
X. Fan et al.
products 3. The aqueous solution of ionic liquid was concentrated at
reduced pressure to recover the ionic liquid for subsequent use.
3n, mp 81–83◦C (lit.[4a] 86◦C). δH (CDCl3, 400 MHz) 1.40 (3H,
t, J 7.2, CH3), 3.88 (3H, s, OCH3), 4.28 (2H, q, J 7.2, OCH2), 6.97
(2H, d, J 8.8, ArH), 7.99 (2H, d, J 8.8, ArH), 8.12 (1H, s, HC=C). νmax
(KBr/cm−1) 3019, 2240, 1738, 1605, 1310.
General Procedure for the Michael Addition Reactions
in [bmim][BF4]
3o, mp 46–48◦C (Found: C 61.1, H 4.4, N 5.9. C12H10ClNO2
requires C 61.2, H 4.3, N 5.9%). δH (CDCl3, 400 MHz) 1.43 (3H, t,
J 7.2, CH3), 4.42 (2H, q, J 7.2, OCH2), 7.41–7.54 (3H, m, ArH), 8.25
(1H, dd, J 8.0, 1.2, ArH), 8.71 (1H, s, HC=C). δC (CDCl3, 100 MHz)
162.35, 151.65, 136.98, 134.18, 130.88, 130.49, 130.41, 128.01, 115.32,
106.83, 63.48, 14.67. νmax (KBr/cm−1) 3032, 2245, 1728, 1583. m/z
(70 eV) 235 (M+).
The alkene 3 (0.5 mmol) and dimedone 4 (0.5 mmol) were added to a
round bottom flask containing 1 mL of [bmim][BF4]. The mixture was
stirred at 40◦C for a certain time to complete the reaction (monitored by
TLC). At completion, water was added. The precipitates in the reaction
mixture were then collected and further purified by recrystallization
with 95% ethanol to give the pure chromenes 5. The aqueous solution
of ionic liquid was concentrated at reduced pressure to recover the ionic
liquid for subsequent use.
5a, mp 222–224◦C (lit.[19] 226–228◦C). δH (CDCl3, 400 MHz) 1.05
(3H, s, CH3), 1.10 (3H, s, CH3), 2.19 (2H, s, CH2), 2.49 (2H, s, CH2),
4.31 (1H, s, CH), 4.57 (2H, br s, NH2), 6.89 (2H, d, J 6.8, ArH), 7.25
(3H, m, ArH). νmax (KBr/cm−1) 3330, 3247, 3040, 2985, 2963, 2145,
1650, 1608, 1461.
General Procedure for the Three-Component Coupling
Reactions in [bmim][BF4]
5b, mp 207–209◦C (lit.[19] 208–210◦C). δH (CDCl3, 400 MHz) 1.00
(3H, s, CH3), 1.07 (3H, s, CH3), 2.21 (5H, m, CH2, CH3), 2.37 (2H, s,
CH2), 4.28 (1H, s, CH), 4.53 (2H, br s, NH2), 6.86 (2H, d, J 6.8, ArH),
7.19 (2H, d, J 6.8, ArH). νmax (KBr/cm−1) 3325, 3241, 3040, 2985,
2963, 2194, 1680, 1606, 1510, 1463.
Aldehyde 1 (0.5 mmol), malononitrile 2 (0.5 mmol), and dimedone 4
(0.5 mmol) were added to a round bottom flask containing 1 mL of
[bmim][BF4]. The mixture was stirred at 40◦C for a certain time to
complete the reaction (monitored by TLC). At completion, water was
added. The precipitates in the reaction mixture were then collected and
further purified by recrystallization with 95% ethanol to give the pure
chromenes 5. The aqueous solution of ionic liquid was concentrated at
reduced pressure to recover the ionic liquid for subsequent use.
3a, mp 78–80◦C (lit.[16] 84◦C). δH (CDCl3, 400 MHz) 7.50–7.73
(3H, m, ArH), 7.90 (1H, s, HC=C), 8.13 (2H, d, J 5.6, ArH). νmax
(KBr/cm−1) 3020, 2250, 1592, 1081.
5c, mp 124–126◦C (lit.[19] 130–132◦C). δH (CDCl3, 400 MHz) 1.09
(3H, s, CH3), 1.15 (3H, s, CH3), 2.24 (2H, s, CH2), 2.49 (2H, s, CH2),
4.80 (1H, s, CH), 6.27 (2H, br s, NH2), 7.47 (2H, d, J 8.0, ArH), 8.12
(2H, d, J 8.0, ArH). νmax (KBr/cm−1) 3370, 3186, 2961, 2194, 1680,
1600, 1510.
5d, mp 201–203◦C (lit.[19] 207–209◦C). δH (CDCl3, 400 MHz) 1.08
(3H, s, CH3), 1.13 (3H, s, CH3), 2.21 (2H, s, CH2), 2.46 (2H, s, CH2),
4.53 (1H, s, CH), 6.26 (2H, br s, NH2), 7.41 (2H, d, J 8.0, ArH), 7.99
(2H, d, J 8.0, ArH). νmax (KBr/cm−1) 3367, 3191, 2969, 2194, 1687,
1658, 1606, 1510, 1490.
3b, mp 161–163◦C (lit.[16] 159◦C). δH (CDCl3, 400 MHz) 7.83 (1H,
s, HC=C), 8.12 (2H, d, J 7.2, ArH), 8.34 (2H, d, J 7.2, ArH). νmax
(KBr/cm−1) 3020, 2245, 1595, 1528.
3c, mp 111–113◦C (lit.[16] 114◦C). δH (CDCl3, 400 MHz) 3.87 (3H,
s, OCH3), 6.89 (2H, d, J 9.2, ArH), 7.58 (1H, s, HC=C), 7.84 (2H, d,
J 9.2, ArH). νmax (KBr/cm−1) 3021, 2245, 1590.
5e, mp 206–208◦C (lit.[19] 200–202◦C). δH (CDCl3, 400 MHz) 1.08
(3H, s, CH3), 1.14 (3H, s, CH3), 2.19 (2H, s, CH2), 2.42 (2H, s, CH2),
4.60 (1H, s, CH), 6.26 (2H, br s, NH2), 7.39 (1H, m, ArH), 7.65 (2H,
m, ArH), 8.09 (1H, d, J 7.4, ArH). νmax (KBr/cm−1) 3367, 3191, 2963,
2194, 1680, 1658, 1600, 1502, 1451.
3d, mp 161–163◦C (lit.[17] 161–162◦C). δH (CDCl3, 400 MHz) 7.53
(2H, d, J 9.0, ArH), 7.69 (1H, s, HC=C), 7.86 (2H, d, J 9.0, ArH). νmax
(KBr/cm−1) 3012, 2225, 1563.
5f, mp 193–195◦C (lit.[19] 198–200◦C). δH (CDCl3, 400 MHz) 1.05
(3H, s, CH3), 1.20 (3H, s, CH3), 2.23 (2H, s, CH2), 2.45 (2H, s, CH2),
3.78 (3H, s, OCH3), 4.38 (1H, s, CH), 4.53 (2H, br s, NH2), 6.83 (2H,
d, J 6.8, ArH), 7.16 (2H, d, J 6.8, ArH). νmax (KBr/cm−1) 3377, 3186,
2963, 2194, 1680, 1658, 1606, 1510, 1463.
3e, mp 160–162◦C (lit.[17] 159–160◦C). δH (CDCl3, 400 MHz) 7.50
(2H, d, J 9.0, ArH), 7.65 (1H, s, HC=C), 7.79 (2H, d, J 9.0, ArH). νmax
(KBr/cm−1) 3011, 2228, 1563.
3f, mp 124–125◦C (lit.[18] 126.8–127.2◦C). δH (CDCl3, 400 MHz)
7.60 (2H, d, J 8.0, ArH), 7.70 (1H, s, HC=C), 7.98 (2H, d, J 8.0, ArH).
νmax (KBr/cm−1) 3010, 2230, 1542.
5g, mp 208–210◦C (Found: C 63.6, H 5.0, N 12.3. C18H17N3O4
requires C 63.7, H 5.1, N 12.4%). δH (CDCl3, 400 MHz) 1.05 (3H, s,
CH3), 1.13 (3H, s, CH3), 2.25 (2H, s, CH2), 2.53 (2H, s, CH2), 4.53 (1H,
s, CH), 4.81 (2H, br s, NH2), 7.49 (1H, t, J 8.0, ArH), 7.68 (1H, d, J 8.0,
ArH), 8.07 (1H, d, J 8.0, ArH), 8.10 (1H, s, ArH). δC (CDCl3, 100 MHz)
196.32, 162.87, 158.40, 149.19, 145.98, 134.93, 130.02, 122.89, 113.55,
62.54, 51.12, 41.23, 36.20, 32.78, 29.37, 28.17. νmax (KBr/cm−1) 3429,
3336, 3202, 3103, 2957, 2875, 2187, 1681, 1600, 1532, 1427, 1418,
1375. m/z (70 eV) 339 (M+).
3g, mp 130–133◦C (lit.[16] 135◦C). δH (CDCl3, 400 MHz) 2.33 (3H,
s, CH3), 7.20 (2H, d, J 8.2, ArH), 7.61 (1H, s, HC=C), 7.62 (2H, d,
J 8.2, ArH). νmax (KBr/cm−1) 3022, 2245, 1593.
3h, mp 83–85◦C (lit.[18] 90.5–91.0◦C). δH (CDCl3, 400 MHz)
7.31–8.03 (4H, m, ArH), 8.15 (1H, s, HC=C). νmax (KBr/cm−1) 3030,
2245, 1581.
3i, mp 85–86◦C (lit.[17] 93–94◦C). δH (CDCl3, 400 MHz) 7.38–8.11
(4H, m,ArH), 8.23 (1H, s, HC=C). νmax (KBr/cm−1) 3032, 2245, 1583.
3j, mp 99–100◦C (lit.[16] 100◦C). δH (CDCl3, 400 MHz) 7.58 (1H,
t, J 8.0, ArH), 7.80 (1H, s, HC=C), 8.24 (1H, d, J 8.0, ArH), 8.39 (1H,
d, J 8.0, ArH), 8.64 (1H, s, ArH). νmax (KBr/cm−1) 3018, 2235, 1583.
3k, mp 168–170◦C (lit.[4a] 170◦C). δH (CDCl3, 400 MHz) 1.49 (3H,
t, J 7.2, CH3), 4.38 (2H, q, J 7.2, OCH2), 8.12 (2H, d, J 8.8, ArH), 8.30
(1H, s, HC=C), 8.34 (2H, d, J 8.8, ArH). νmax (KBr/cm−1) 3017, 2241,
1728, 1595, 1528, 1348.
5h, mp 184–186◦C (Found: C 69.1, H 5.4, N 9.0. C18H17FN2O2
requires C 69.2, H 5.5, N 9.0%). δH (CDCl3, 400 MHz) 1.04 (3H,
s, CH3), 1.13 (3H, s, CH3), 2.23 (2H, s, CH2), 2.45 (2H, s, CH2),
4.46 (1H, s, CH), 6.88 (2H, br s, NH2), 6.99 (2H, d, J 8.0, ArH),
7.11 (2H, d, J 8.0, ArH). δC (CDCl3, 100 MHz) 196.34, 161.93,
161.62, 157.86, 129.78, 129.70, 128.83, 116.08, 115.86, 51.28, 51.22,
41.26, 35.49, 32.72, 29.43, 28.25. νmax (KBr/cm−1) 3392, 3326,
3214, 2951, 2875, 2193, 1683, 1656, 1607, 1514, 1369. m/z (70 eV)
312 (M+).
3l, mp 85–87◦C (lit.[4a] 87◦C). δH (CDCl3, 400 MHz) 1.45 (3H, t,
J 7.2, CH3), 4.32 (2H, q, J 7.2, OCH2), 7.46 (2H, d, J 8.8, ArH), 7.95
(2H, d, J 8.8, ArH), 8.17 (1H, s, HC=C). νmax (KBr/cm−1) 3019, 2227,
1728, 1591, 1532, 1250.
5i, mp 133–135◦C (Found: C 5.70, H 5.2, N 3.3. C20H22BrNO4
requires C 57.2, H 5.3, N 3.3%). δH (CDCl3, 400 MHz) 1.00 (3H, s,
CH3), 1.11 (3H, s, CH3), 1.18 (t, 3H, J 8.0, CH3), 2.22 (2H, s, CH2),
2.45 (2H, s, CH2), 4.05 (q, 2H, J 8.0, OCH2), 4.67 (1H, s, CH), 6.23
(2H, br s, NH2), 7.09 (1H, t, J 8.0, ArH), 7.22 (1H, d, J 8.0, ArH), 7.24
(1H, d, J 8.0, ArH), 7.39 (1H, s, ArH). δC (CDCl3, 100 MHz) 196.72,
169.42, 162.14, 158.86, 148.72, 131.93, 129.86, 129.72, 127.62, 122.42,
116.72, 80.79, 60.32, 51.25, 41.23, 34.39, 32.81, 29.57, 28.01, 14.74.
νmax (KBr/cm−1) 3410, 3298, 2959, 2928, 1695, 1658, 1622, 1525,
1471, 1369. m/z (70 eV) 419 (M+).
3m, mp 131–133◦C (Found: C 58.4, H 4.1, N 11.4. C12H10N2O4
requires C 58.5, H 4.1, N 11.4%). δH (CDCl3, 400 MHz) 1.44 (3H,
t, J 7.2, CH3), 4.44 (2H, q, J 7.2, OCH2), 7.74–7.81 (1H, m, ArH),
7.91 (1H, s, HC=C), 8.33–8.41 (2H, m, ArH), 8.72 (1H, s, ArH). δC
(CDCl3, 100 MHz) 162.01, 152.31, 149.22, 135.21, 133.48, 132.58,
131.51, 128.74, 113.13, 107.32, 63.81, 14.65. νmax (KBr/cm−1) 3018,
2245, 1730, 1600, 1352. m/z (70 eV) 246 (M+).

Ionic Liquid Promoted Knoevenagel and Michael Reactions
1071
5j, mp 179–181◦C (lit.[19] 181–183◦C). δH (CDCl3, 400 MHz) 1.00
(3H, s, CH3), 1.14 (3H, s, CH3), 1.19 (3H, t, J 8.0, CH3), 2.19 (2H, s,
CH2), 2.42 (2H, s, CH2), 4.03 (2H, q, J 8.0, OCH2), 4.60 (1H, s, CH),
6.26 (2H, br s, NH2), 7.39 (1H, m, ArH), 7.65 (2H, m, ArH), 8.09 (1H,
d, J 7.4, ArH). νmax (KBr/cm−1) 3367, 3191, 2963, 2194, 1680, 1658,
1600, 1502, 1451.
(b) D. B. Zhao, M. Wu, Y. Kou, E. Z. Min, Catal. Today 2002,
74, 157. doi:10.1016/S0920-5861(01)00541-7
(c) H. Olivier-Bourbigou, L. Magna, J. Mol. Catal. A: Chem.
2002, 182, 419. doi:10.1016/S1381-1169(01)00465-4
(d) Z. Li, C. G. Xia, Tetrahedron Lett. 2003, 44, 2069.
doi:10.1016/S0040-4039(03)00190-4
5k, mp 180–182◦C (lit.[20] 172–174◦C) (Found: C 62.1, H 5.7, N 7.2.
C20H22N2O6 requires C 62.2, H 5.7, N 7.3%). δH (CDCl3, 400 MHz)
0.99 (3H, s, CH3), 1.12 (3H, s, CH3), 1.16 (3H, t, J 8.0, CH3), 2.22
(2H, s, CH2), 2.49 (2H, s, CH2), 4.04 (2H, q, J 8.0, OCH2), 4.80 (1H,
s, CH), 6.27 (2H, br s, NH2), 7.39 (1H, t, J 8.0, ArH), 7.67 (1H, d,
(e) J. S. Yadav, B. V. B. Reddy, A. K. Basak, A. Venkat
Narsaiah, Tetrahedron Lett. 2003, 44, 1047. doi:10.1016/S0040-
4039(02)02735-1
[3] (a)
R.
Sheldon,
Chem.
Commun.
2001,
2399.
doi:10.1039/B107270F
(b) V. Le Boulaire, R. Gree, Chem. Commun. 2000, 2195.
doi:10.1039/B006666O
J 8.0,ArH), 8.00 (1H, d, J 8.0,ArH), 8.11 (1H, s,ArH). νmax (KBr/cm−1
)
3442, 3302, 2986, 2956, 2903, 1693, 1673, 1623, 1523, 1475.
5l, mp 185–187◦C (Found: C 62.1, H 5.7, N 7.2. C20H22N2O6
requires C 62.2, H 5.7, N 7.3%). δH (CDCl3, 400 MHz) 0.97 (3H, s,
CH3), 1.12 (3H, s, CH3), 1.14 (3H, t, J 8.0, CH3), 2.21 (2H, s, CH2),
2.46 (2H, s, CH2), 4.03 (2H, q, J 8.0, OCH2), 4.80 (1H, s, CH), 6.27
(2H, br s, NH2), 7.44 (2H, d, J 8.0, ArH), 8.09 (2H, d, J 8.0, ArH).
δC (CDCl3, 100 MHz) 196.69, 169.13, 162.47, 158.97, 153.97, 146.93,
129.74, 123.73, 116.18, 80.00, 60.43, 51.17, 41.24, 34.85, 32.79, 29.60,
27.88, 14.75. νmax (KBr/cm−1) 3377, 3186, 2963, 2194, 1680, 1658,
1606, 1510, 1463, 1369. m/z (70 eV) 386 (M+).
[4] (a) B. M. Choudary, M. Lakshmi Kantam, B. Kavita,
C. Venkat Reddy, F. Figueras, Tetrahedron 2000, 56, 9357.
doi:10.1016/S0040-4020(00)00906-6
(b) T. Sugino, K. Tanaka, Chem. Lett. 2001, 110.
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doi:10.1039/B006704K
(b) R. H. Khan, R. K. Mathur, A. C. Ghosh, Synth. Commun.
1996, 26, 683.
5m, mp 152–155◦C (Found: C 66.7, H 6.1, N 3.8. C20H22FNO4
requires C 66.8, H 6.2, N 3.9%). δH (CDCl3, 400 MHz) 0.98 (3H, s,
CH3), 1.11 (3H, s, CH3), 1.16 (3H, t, J 8.0, CH3), 2.20 (2H, s, CH2),
2.43 (2H, s, CH2), 4.04 (2H, q, J 8.0, OCH2), 4.69 (1H, s, CH), 6.20
(2H, br s, NH2), 6.89 (2H, d, J 8.0, ArH), 7.23 (2H, d, J 8.0, ArH).
δC (CDCl3, 100 MHz) 196.87, 169.54, 163.02, 161.83, 160.60, 158.86,
142.19, 130.22, 117.23, 115.13, 114.92, 81.21, 60.23, 51.28, 41.22,
33.81, 32.76, 29.61, 27.90, 14.75. νmax (KBr/cm−1) 3402, 3289, 2998,
2964, 2940, 2914, 1693, 1614, 1527, 1479, 1371, 1287, 1203. m/z
(70 eV) 359 (M+).
[6] J. R. Harjani, S. J. Nara, M. M. Salunkhe, Tetrahedron Lett.
2002, 43, 1127. doi:10.1016/S0040-4039(01)02341-3
[7] D. W. Morrison, D. C. Forbes, J. H. Davis, Jr, Tetrahedron Lett.
2001, 42, 6053. doi:10.1016/S0040-4039(01)01228-X
[8] (a) C. Su, Z. C. Chen, Q. G. Zheng, Synthesis 2003, 555.
(b) A. McCluskey, P. J. Robinson, T. Hill, J. L. Scott,
J. K. Edwards, Tetrahedron Lett. 2002, 43, 3117. doi:10.1016/
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(c) W. H. Korrea, J. K. Edwards, A. McCluskey, L. Mckinnon,
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(b) X. Zhang, L. Li, G. Zhang, Green Chem. 2003, 5, 646.
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(c) X. Zhang, H. Niu, J. Wang, J. Chem. Res. 2003, 33.
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(b) S. O. A. Allah, H. A. N. Ead, A. Kassab, N. H. Metwali,
Heterocycles 1983, 20, 637.
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doi:10.1039/B007431O
(b) R. Ballini, P. Marziali, A. Mozzicafreddo, J. Org. Chem.
1996, 61, 3209. doi:10.1021/JO9520553
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1999, 64, 3770. doi:10.1021/JO982521Z
5n, mp 152–154◦C (lit.[19] 150–152◦C). δH (CDCl3, 400 MHz) 0.97
(3H, s, CH3), 1.10 (3H, s, CH3), 1.14 (3H, t, J 8.0, CH3), 2.14 (2H, s,
CH2), 2.42 (2H, s, CH2), 4.03 (2H, q, J 8.0, OCH2), 4.61 (1H, s, CH),
6.20 (2H, br s, NH2), 6.80 (2H, d, J 8.0, ArH), 7.16 (2H, d, J 8.0, ArH).
νmax (KBr/cm−1) 3400, 3280, 2991, 1680, 1658, 1513, 1474.
5o, mp 160–162◦C (lit.[19] 156–157◦C). δH (CDCl3, 400 MHz) 0.96
(3H, s, CH3), 1.05 (3H, s, CH3), 1.10 (3H, t, J 8.0, CH3), 2.12 (2H, s,
CH2), 2.30 (3H, s, CH3), 2.40 (2H, s, CH2), 4.01 (2H, q, J 8.0, OCH2),
4.59 (1H, s, CH), 6.20 (2H, br s, NH2), 6.80 (2H, d, J 8.0, ArH), 7.12
(2H, d, J 8.0, ArH). νmax (KBr/cm−1) 3370, 3175, 2969, 2194, 1682,
1658, 1600, 1511, 1463.
5p, mp 154–156◦C (lit.[19] 158–156◦C). δH (CDCl3, 400 MHz) 0.96
(3H, s, CH3), 1.08 (3H, s, CH3), 1.12 (3H, t, J 8.0, CH3), 2.12 (2H, s,
CH2), 2.42 (2H, s, CH2), 4.01 (2H, q, J 8.0, OCH2), 4.38 (1H, s, CH),
4.53 (2H, br s, NH2), 6.85 (2H, d, J 6.8, ArH), 7.21 (3H, m, ArH). νmax
(KBr/cm−1) 3365, 3171, 2963, 2194, 1680, 1610, 1510, 1460.
[13] T. P. Loh, L. L. Wei, Tetrahedron 1998, 54, 7615.
doi:10.1016/S0040-4020(98)00394-9
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1997, 38, 7563. doi:10.1016/S0040-4039(97)10035-1
(b) B. C. Ranu, M. Saha, S. Bhar, Synth. Commun. 1997,
27, 621.
Acknowledgment
This work was financially supported by the National Natural
Science Foundation of China (no. 20273019).
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D. Francisco, Synth. Commun. 1998, 28, 4649.
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