Ionic-liquid-supported 1,5,7-triazabicyclo[4.4.0]dec-5-ene - An efficient and recyclable organocatalyst for Michael addition to α,β-unsaturated ketones

Article abstract of DOI:10.1139/v11-162

A novel ionic-liquid-supported 1,5,7-triazabicyclo[4.4.0]dec-5-ene (IL-TBD) was synthesized and investigated for its ability to act as an active organocatalyst in the Michael addition of active methylene compounds and thiophenols to chalcones under solven

Full text of DOI:10.1139/v11-162

290
Ionic-liquid-supported 1,5,7-triazabicyclo[4.4.0]
dec-5-ene — An efficient and recyclable
organocatalyst for Michael addition to α,β-
unsaturated ketones
Manoj Kumar Muthyala, Bhupender S Chhikara, Keykavous Parang, and Anil Kumar
Abstract: A novel ionic-liquid-supported 1,5,7-triazabicyclo[4.4.0]dec-5-ene (IL–TBD) was synthesized and investigated for
its ability to act as an active organocatalyst in the Michael addition of active methylene compounds and thiophenols to chal-
cones under solvent-free conditions. The IL–TBD afforded Michael addition products in excellent yields (82%–94%) at
room temperature, and it was simply recycled and reused at least five times without significant loss of catalytic activity.
Key words: ionic liquid, supported catalysis, organocatalyst, Michael addition, a,b-unsaturated ketones.
Résumé : On a réalisé la synthèse d’un liquide ionique supporté par du 1,5,7-triazabicyclo[4.4.0]déc-5-ène (LI–TBD) et on
a étudié ses capacités d’agir comme organocatalyseur dans l’addition de Michael de composés comportant des méthylènes
actifs et des thiophénols à des chalcones, dans des conditions sans solvant. Le LI–TBD permet d’obtenir des produits d’ad-
dition de Michael avec d’excellents rendements (82 % à 94 %), à la température ambiante; il peut être recyclé facilement et
réutilisé jusqu’à cinq fois sans perte significative de son activité catalytique.
Mots‐clés : liquide ionique, catalyseur sur un support, organocatalyseur, addition de Michael, cétones a,b-insaturées.
[Traduit par la Rédaction]
functionalized with basic organic molecules such as proline23–25
Introduction
and pyrrolidine26–32 have been extensively studied for Michael
additions. FILs not only overcome the problems of lower reac-
tion rate and longer validation reaction time but also provide re-
agents with tuneable properties and “green” credentials.
Organocatalyses have emerged as new and powerful tools
in organic synthesis.1–4 Lower cost, operational simplicity,
easy availability, efficiency, and less toxicity make organoca-
talysts attractive alternatives to organometallic catalysts in or-
ganic synthesis. The major problems associated with most
homogeneous organocatalyst systems are high organocatalyst
loadings to afford efficient synthesis, long and tedious prepa-
ration steps, and separation and recycling of these catalysts.
To overcome these difficulties catalysts have been immobi-
lized on various solid supports. However, reaction rates are
lower with solid-supported reagents and require longer vali-
dation times.
Ionic liquids (ILs) are fascinating materials for chemists as
they offer new chemical and physical properties such as high
thermal stability, very low to negligible vapor pressure, good
solvating ability, a noncoordinating nature, and ease of recy-
clability.5–10 In recent years, functionalized ionic liquids
(FILs) synthesized with properties for specific desired chemi-
cal tasks have attracted the attention of chemists.11,12 Several
ILs functionalized with catalytically active groups have been
developed and used effectively as recyclable organocatalysts
for various organic transformations.13–22 Imidazolium ILs
1,5,7-Triazabicyclo[4,4.0]dec-5-ene (TBD) is a versatile bi-
cyclic guanidine with nucleophilic and basic properties that
render this compound an extremely useful catalyst for many
organic transformations.33–37 Several methods have been re-
ported for the preparation of heterogeneous basic catalysts in
which TBD is covalently attached with polymer support or
silica.38–40 The solid-supported TBDs have efficiently pro-
moted some fundamental base-catalyzed organic transforma-
tions such as the Nef reaction,41 alkylation,42 1,2-epoxide
ring opening,43 aldol-type condensation,43 Knoevenagel con-
densation,43,44 Michael addition,44 synthesis of thioureas,45
aryl ether synthesis,46 synthesis of benzofuran47 and thia-
zoles,48 and transesterification of soybean oil.49 However,
heterogeneous TBD usually suffers from the disadvantage of
being only slightly recyclable, requires a compatible solvent
for swelling, and has prolonged reaction times. In continua-
tion of our effort to develop IL-based catalysts,50 herein, we
report the synthesis of a novel IL-functionalized TBD (IL–TBD)
Received 10 July 2011. Accepted 30 November 2011. Published at www.nrcresearchpress.com/cjc on 14 February 2012.
M.K. Muthyala and A. Kumar. Department of Chemistry, Birla Institute of Technology and Science, Pilani 333 031 Rajasthan, India.
B.S. Chhikara and K. Parang. Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02881,
USA.
Corresponding author: Anil Kumar (email: anilkadian@gmail.com)
Can. J. Chem. 90: 290–297 (2012)
doi:10.1139/V11-162
Published by NRC Research Press

Muthyala et al.
291
Scheme 1. Michael addition of active methylene compounds and thiophenols to chalcones. EWG, electron-withdrawing group.
NC EWG
O
NC
EWG
5
IL-TBD ( )
X
Y
O
7-16
Ar
O
S
X
Y
N
6
ArSH
IL-TBD (5)
X
Y
17-32
N
N
IL-TBD
N
Br-
N
and its use as an organocatalyst for the Michael addition of
active methylene compounds and thiophenols to chalcones
(Scheme 1).
Scheme 2. Synthesis of ionic-liquid-supported 1,5,7-triazabicyclo
[4.4.0]dec-5-ene (TBD) (IL–TBD).
N
N
Reflux
Cl
N
N
1
Results and discussion
Br
+
3
Cl
Synthesis of IL–TBD was achieved following the reaction
sequences shown in Scheme 2. Initially, the reaction of 1-
methylimidazole (1) with 1-bromo-4-chlorobutane (2) at
room temperature afforded (4′-chlorobutyl)-3-methylimidazo-
lium bromide (3). Subsequent reaction of 3 with 1.5 equiv of
TBD (4) at 100 °C for 6 h gave IL–TBD 5 with bromide as
the anion. The excess TBD was removed by washing with di-
chloromethane, and the IL–TBD was purified by column
chromatography on silica gel. The structure of 5 was con-
firmed by 1H NMR, 13C NMR, and high-resolution mass
Br
H
N
2
N
100 °C
N
N
N
N
4
N
N
Br
5
1
spectrometry. The H NMR spectrum showed multiplets in
Table 1. Optimization of reaction conditions for Michael addi-
tion.
the range of 3.24 to 3.04, representing the methylene protons
of TBD adjacent to nitrogens. In 13C NMR, six carbons ap-
peared in the aliphatic region in addition to methyl and meth-
ylene carbons of the IL, which corresponds to the methylene
carbon of TBD. In HRMS peaks appeared at 356.1260 [M]+,
358.1257 [M + 2]+, and 276.1889 [M – Br]+, which con-
firmed the structure of 5.
Catalyst
(mol %)
Time
(h)
24
12
4
4
4
4
8
Entry
1
2
3
4
5
6
7
8
Solvent
—
Yield (%)a,b
10
30
50
60
50
50
50
50
50
50
50
50
50
50
60
75
87
86
85
80
72
70
58
70
—
—
—
CH3CN
CH3OH
DMF
Ethanol
DCM
Toluene
H2O
[bmim]Br
[bmim]PF6
[bmim]BF4
The catalytic activity of IL–TBD as an organocatalyst was
evaluated for the Michael addition of malononitrile to chal-
cones. The reaction conditions were optimized by taking the
reaction of 3-(2-fluorophenyl)-1-(4-methoxyphenyl)prop-2-
en-1-one with malononitrile to give 7 as model reaction (Ta-
ble 1). Loading studies using different concentrations of cata-
lyst showed the requirement of 50 mol % of IL–TBD to
catalyze the reaction to maximum yields (Table 1, entries 1–
4). The yield of Michael addition product was higher under
solvent-free conditions (87%; Table 1, entry 3) as compared
with the reaction in different organic solvents (58%–85%; Ta-
ble 1, entries 5–9). The aqueous medium served as a poor
system for this reaction giving no product over the period
under similar reaction conditions (Table 1, entry 11). This
may be due to the insolubility of both chalcone and the cata-
lyst in water. The product yield was low (17%–20%) when
the reaction was performed in ILs ([bmim]Br, [bmim]BF4,
and [bmim]PF6) as solvents. The low yield in these ILs may
8
8
9
10
11
12
13
14
36
36
12
12
12
c
—
18
17 (10)d
20
aReaction conditions: chalcone (1 mmol), malononitrile (1 mmol), cat-
alyst 5 (10–50 mol %), at room temperature.
bIsolated yield.
cNo product formation was observed.
dYield without catalyst.
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292
Can. J. Chem. Vol. 90, 2012
probably be due to the slight acidic nature of the IL and the
poor solubility of the reactant at room temperature in [bmim]
Br. The role of IL–TBD as catalyst is confirmed by the fact
that no product was formed in the absence of this catalyst.
The reaction seems to proceed with a general base-catalyzed
pathway. A plausible mechanism is shown in Scheme 3.
Furthermore, the catalyst was evaluated for its general appli-
cation in Michael addition reactions by performing the reaction
with different chalcones having electron-releasing and electron-
withdrawing groups on either side as Michael acceptors and
malononitrile and ethyl cyanoacetate as Michael donors (Table 2).
It was observed that chalcones with both electron-withdrawing
and electron-releasing groups resulted in high yields of Mi-
chael products. The presence of electron-withdrawing or
electron-releasing groups had a negligible effect on the yield
of the product. Malononitrile was found to be a better donor
(Table 2, entries 1 and 8) when compared with ethyl cyanoace-
tate (Table 2, entries 9 and 10). The structure of the synthesized
compound was confirmed by 1H NMR and 13C NMR.
The catalytic scope of the IL–TBD was also assessed for
the thia-Michael addition to chalcones. As expected, thia-
Michael addition of thiophenols to chalcones was extraordi-
narily fast with thiols in the presence of IL–TBD
(10 mol %) and gave high yields with short reaction times
(3–5 min) at room temperature (Table 3). Although the re-
action also proceeded in [bmim][PF6] alone to give 7 in
10% yield, the yield of product was greater (87%) and it re-
quired a shorter reaction time in the presence of a catalytic
amount of IL–TBD under solvent-free conditions.
(60–120 mesh, S. D. Fine, India). NMR spectra were re-
corded on Brucker Heaven Avance 11 400 and Varian (500
MHz) spectrometers using CDCl3 and DMSO-d6 as solvents,
and the chemical shifts are expressed in ppm. Mass spectra
were recorded on a QSTAR ELITE LX/MS/MS mass spec-
trometer from Applied Biosystems. The purity of the products
was determined on silica-coated aluminum plates (Merck).
Synthesis of 1-methyl-3-(4′-TBD-butyl)imidazolium
bromide (IL–TBD) (5)
1-Bromo-4-chlorobutane (2, 2.09 g, 12 mmol) was added
dropwise to 1-methylimidazole (1, 1.0 g, 12 mmol) at room
temperature, and the reaction mixture was stirred for 4 h.
The mixture turned viscous over this time. After completion
of the reaction as indicated by thin-layer chromatography
(TLC), the reaction mixture was extracted with ethyl acetate
(3 × 10 mL) to remove unreacted starting materials. The
trapped ethyl acetate was removed on a rotatory evaporator
under reduced pressure to obtain the product 3 in 2.7 g
(89% yield). IL 3 (2.7 g, 10.7 mmol) was added to TBD (4,
3.71 g 17.7 mmol) and the mixture was heated at 100 °C for
6 h. After completion of the reaction, the reaction mixture
was cooled to room temperature and washed with DCM
(5 × 15 mL) to remove unreacted TBD and TBD salt. The
resulting IL was dried under reduced pressure to form a thick
light yellow liquid, which was purified by column chroma-
tography on silica gel to give 5. Viscous liquid. Yield:
3.48 g (92%). 1HNMR (500 MHz, DMSO-d6) d: 9.30 (s,
1H), 7.73 (s, 1H), 7.62 (s, 1H), 4.06 (t, J = 6.8 Hz, 2H),
3.69 (s, 3H), 3.24–3.19 (m, 2H), 3.13–3.04 (m, 6H), 3.00 (s,
2H), 1.74–1.56 (m, 6H), 1.32–1.23 (m, 2H). 13C NMR
(126 MHz, DMSO-d6) d: 150.2, 137.0, 123.9, 122.7, 48.9,
48.7, 47.7, 47.2, 46.1, 38.5, 36.2, 26.5, 23.6, 20.9, 20.7.
HRMS calcd for C15H26N5Br: 356.14; found: 356.1260 [M]+,
358.1257 [M + 2]+, 276.1889 [M – Br]+.
Finally, the recyclability of catalyst 5 was investigated in
the model reaction. Addition of malononitrile to chalcone (3-
(2-fluorophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one) afforded
7. After extracting 7, the recovered 5 was again used for the
model reaction and it was found that catalyst 5 can be effi-
ciently reused for up to five cycles without much loss in the
yield of 7 (Fig. 1).
General procedure for the Michael addition of active
methylene compounds and thiophenols to chalcones
Malononitrile / ethyl 2-cyanoacetate / thiophenol (1.0 mmol)
was added to a solution of chalcone (1.0 mmol) and 5
(0.5 mmol or 0.1 mmol for thiophenols). The reaction mix-
ture was stirred vigorously until reaction completions (see
Tables 2 and 3 for reaction times). The progress of the re-
action was monitored by TLC. After completion of the re-
action, the product was extracted from the catalyst by ethyl
acetate (2 × 5 mL), leaving the IL–TBD catalyst in the
flask. The ethyl acetate layer was evaporated and washed
with diethyl ether to afford the pure product.
Conclusion
We have described the synthesis of a novel IL–TBD and
its ability to act as an active organocatalyst in the Michael
addition of active methylene compounds and thiophenols to
chalcones under solvent-free conditions. The IL–TBD af-
forded Michael addition products in excellent yields (82%–
94%) at room temperature, and it was easily recycled and
reused at least five times without significant loss of catalytic
activity. This is the first example of an IL–TBD and its use in
organic synthesis. The present study shows that high catalytic
efficacy can be achieved by functionalizing ILs with organo-
catalysts under greener reaction conditions.
2-(1-(2-Fluorophenyl)-3-(4-methoxyphenyl)-3-oxopropyl)
malononitrile (7)
Experimental section
1H NMR (400 MHz, DMSO) d: 7.87 (d, J = 7.4 Hz, 2H),
7.68–6.68 (m, 6H), 5.32 (d, J = 6.3 Hz, 1H), 4.58–4.19 (m,
1H), 3.80 (s, 3H), 3.71–3.57 (m, 1H). 13C NMR (101 MHz,
DMSO) d: 194.81, 163.96, 161.93, 159.54, 130.92, 129.29,
125.24, 116.17, 116.00, 114.39, 113.63, 113.44, 56.00,
39.98, 33.72, 28.92. HRMS calcd for C19H15FN2O2:
322.1118; found: 323.1016 [M]+.
General
1-Methylimidazole, 1-bromo-4-chlorobutane, and TBD
were purchased from Sigma-Aldrich, India. All other re-
agents and solvents were purchased from S. D. Fine, India,
and used without further purification unless otherwise speci-
fied. Column chromatography was carried out over silica gel
Published by NRC Research Press

Muthyala et al.
293
Scheme 3. Plausible mechanism for the catalytic activity of ionic-liquid-supported 1,5,7-triazabicyclo[4.4.0]dec-5-ene (IL–TBD).
EWG
NC
EWG
NC
EWG
NC
O
IL
HO
EWG
H
X
NC
N
-
N
O
Y
Y
H
X
X
N
Y
EWG
NC
NH
N
IL
N
O
X
Y
Table 2. Michael addition of active methylene compounds to
chalcones catalyzed by 5.
Table 3. Michael addition of thiophenols to chalcones catalyzed by
5.
Time Yield
(h)
4
Time
(min)
Yield
(%)a,b
Product
7
8
X
Y
2-F
2-F
3-NO2
4-NO2
H
4-NO2
4-OCH3
4-OCH3
H
EWG
CN
CN
CN
CN
CN
CN
CN
CN
(%)a,b
87
Product
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
X
4-Cl
4-OCH3
H
Y
2-F
2-F
4-Cl
H
3-NO2
4-NO2
4-Cl
4-OCH3
4-OCH3
4-OCH3
H
H
H
3-NO2
3-NO2
H
Ar
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
4-OCH3
4-Cl
4-Cl
4-Cl
4-Cl
4-OCH3
4-OCH3
H
4-Cl
4-OCH3
2
2
2
2
5
5
3
2
2
2
4
5
2
5
5
4
93
92
91
92
90
92
92
94
93
92
92
90
93
92
91
90
1.5
2
90
87
9
10
11
12
13
14
15
16
2
87
4-CH3
4-OCH3
4-OCH3
4-CH3
4-Cl
4-CH3
4-OCH3
4-Cl
4-NO2
4-OCH3
4-CH3
H
2
92
4
86
3
86
3
85
CO2Et
CO2Et
3
87
2-F
6
82
Note: EWG, electron-withdrawing group.
aAll the compounds showed satisfactory H NMR and 13C NMR.
1
bIsolated yield.
2-(3-(4-Chlorophenyl)-1-(2-fluorophenyl)-3-oxopropyl)
4-Cl
4-CH3OPh
malononitrile (8)
aAll the compounds showed satisfactory H NMR and 13C NMR.
1
1H NMR (500 MHz, DMSO) d: 7.98 (d, J = 7.28 Hz, 2H),
7.60–7.58 (m, 3H), 7.40–7.35 (m, 1H), 7.26–7.20 (m, 2H),
5.25 (d, J = 6.5 Hz, 1H), 4.36–4.32 (m, 1H), 3.90 (dd, J =
18.3, 8.65 Hz, 1H), 3.69 (dd, J = 18.3, 5.4 Hz, 1H). 13C
NMR (126 MHz, DMSO) d: 195.66, 139.03, 135.00,
130.76, 130.70, 130.45, 129.33, 125.25, 116.16, 115.98,
113.55, 113.35, 40.48, 33.60, 28.85. HRMS calcd for
C18H12ClFN2O: 326.0622; found: 327.0006 [M]+.
bIsolated yield.
J = 7.3 Hz, 2H), 5.32 (d, J = 6.3 Hz, 1H), 4.32–4.26 (m,
1H), 4.06–3.96 (m, 1H), 3.81–3.69 (m, 1H). 13C NMR (101
MHz, DMSO) d: 195.68, 147.86, 145.87, 139.15, 134.99,
130.57, 130.36, 129.39, 124.17, 113.60, 113.36, 40.47,
40.16, 29.30. HRMS calcd for C18H12ClN3O3: 353.0567;
found: 375.0484 [M – H + Na]+.
2-(3-(4-Chlorophenyl)-1-(3-nitrophenyl)-3-oxopropyl)
malononitrile (9)
2-(3-(4-Chlorophenyl)-3-oxo-1-phenylpropyl)malononitrile
(11)
1H NMR (400 MHz, DMSO) d: 8.00 (d, J = 6.8 Hz, 2H),
7.65–7.61 (m, 3H), 7.42–7.38 (m, 1H), 7.26 (d, J = 6.68 Hz,
2H), 5.26 (d, J = 6.5 Hz, 1H), 4.41–4.32 (m, 1H), 3.95–3.89
(m, 1H), 3.73–3.68 (m, 1H). 13C NMR (101 MHz, DMSO)
d: 195.73, 139.09, 135.01, 130.84, 130.74, 130.54, 129.37,
125.29, 116.23, 115.98, 113.66, 113.43, 40.93, 33.52, 28.93.
HRMS calcd for C18H12ClN3O3: 353.0567; found: 375.0487
[M – H + Na]+.
1H NMR (400 MHz, DMSO) d: 8.02–7.98 (m, 2H), 7.64–
7.54 (m, 3H), 7.53–7.41 (m, 2H), 7.39–7.35 (m, 2H), 5.25–
5.20 (m, 1H), 4.07–4.03 (m, 1H), 3.88–3.84 (m, 1H), 3.68–
3.64 (m, 1H). 13C NMR (101 MHz, DMSO) d: 196.02,
139.07, 138.20, 135.18, 130.54, 129.37, 129.11, 128.74,
113.93, 113.65, 40.67, 40.50, 29.77. HRMS calcd for
C18H13ClN2O: 308.0716; found: 309.0701 [M]+.
2-(3-(4-Chlorophenyl)-1-(4-nitrophenyl)-3-oxopropyl)
malononitrile (10)
2-(3-(4-Methoxyphenyl)-1-(4-nitrophenyl)-3-oxopropyl)
malononitrile (12)
1H NMR (400 MHz, DMSO) d: 8.26 (d, J = 7.27 Hz, 2H),
8.01 (d, J = 7.3 Hz, 2H), 7.82 (d, J = 7.3 Hz, 2H), 7.61 (d,
1H NMR (400 MHz, DMSO) d: 8.22 (d, J = 7.12 Hz, 2H),
7.84 (d, J = 6.9 Hz, 2H), 7.43 (d, J = 6.9 Hz, 2H), 6.89 (d,
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294
Can. J. Chem. Vol. 90, 2012
Fig. 1. Recycling of ionic-liquid-supported 1,5,7-triazabicyclo[4.4.0]
dec-5-ene (IL–TBD) for the Michael addition reaction.
Ethyl 2-cyano-3-(2-fluorophenyl)-5-(4-methoxyphenyl)-5-
oxopentanoate (16)
1H NMR (400 MHz, DMSO) d: 7.99 (d, J = 5.9, Hz, 2H),
7.62–7.58 (m, 2H), 7.53–7.45 (m, 1H), 7.35–7.30 (m, 1H),
7.18 (d, J = 6.6 Hz, 2H), 4.60 (d, J = 4.5 Hz, 1H), 4.37–
4.28 (m, 1H), 4.11–4.04 (m, 2H), 3.88–3.57 (m, 2H), 1.01
(t, J = 6.7 Hz, 3H). 13C NMR (101 MHz, DMSO) d:
196.23, 165.85, 139.25, 135.49, 132.83, 130.46, 130.06,
129.50, 129.39, 125.22, 116.71, 115.94, 62.80, 43.49, 43.16,
41.60, 32.61, 14.09. HRMS calcd for C21H20FNO4:
369.1376; found: 370.1288 [M]+.
1-(4-Chlorophenyl)-3-(2-fluorophenyl)-3-(phenylthio)
propan-1-one (17)
1H NMR (400 MHz, DMSO) d: 8.21–8. 13 (m, 1H), 7.97
(d, J = 6.9 Hz, 2H), 7.57–7.09 (m, 10H), 5.18–4.98 (m, 1H),
3.90–3.81 (m, 1H), 3.79–3.72 (m, 1H). 13C NMR (101 MHz,
DMSO) d: 196.32, 138.93, 135.32, 133.89, 133.39, 132.49,
131.02, 130.48, 129.56, 129.35, 128.76, 125.43, 124.91,
116.09, 115.59, 43.36, 40.83. HRMS calcd for
C21H16ClFOS: 370.0594; found: 392.0561 [M – H + Na]+.
J = 7.1 Hz, 2H), 5.23 (d, J = 6.5 Hz, 1H), 4.43–4.36 (m, 1H),
4.01–3.96 (m, 1H), 3.83–3.72 (m, 1H), 3.78 (s, 3H). 13C
NMR (101 MHz, DMSO) d: 195.78, 144.87, 143.97,
139.25, 135.69, 130.64, 130.23, 128.59, 128.23, 114.64,
113.86, 55.53, 40.87, 41.26, 29.45. HRMS calcd for
C19H15N3O4: 349.1063; found: 371.0978 [M – H + Na]+.
3-(2-Fluorophenyl)-1-(4-methoxyphenyl)-3-(phenylthio)
propan-1-one (18)
1H NMR (400 MHz, DMSO) d: 7.95 (d, J = 6.87 Hz, 2H),
7.54–7.46 (m, 1H), 7.36–7.18 (m, 6H), 7.15–7.05 (m, 2H),
7.01 (d, J = 6.85 Hz, 2H), 5.21–5.08 (m, 1H), 3.83 (s, 3H),
3.83–3.78 (m, 1H), 3.72–3.58 (m, 1H). 13C NMR (101 MHz,
DMSO) d: 195.48, 163.83, 161.33, 158.89, 134.17, 132.36,
130.92, 129.67, 129.55, 129.46, 129.04, 128.91, 128.07,
124.90, 115.82, 115.60, 114.40, 56.03, 42.87, 40.96. HRMS
calcd for C22H19FO2S: 366.1090; found: 367.1062 [M]+.
2-(1,3-Bis(4-methoxyphenyl)-3-oxopropyl)malononitrile (13)
1H NMR (400 MHz, DMSO) d: 8.01–7.96 (m, 2H), 7.45–
7.37 (m, 2H), 7.04–7.02 (m, 2H), 7.01–6.98 (m, 2H), 5.21
(d, J = 6.5 Hz, 1H), 4.03–3.98 (m, 1H), 3.82 (s, 3H), 3.77–
3.73 (m, 1H), 3.72 (s, 3H), 3.55–3.53 (m, 1H). 13C NMR
(101 MHz, DMSO) d: 195.22, 163.92, 159.50, 130.95,
130.12, 129.88, 129.53, 114.41, 114.11, 113.80, 56.03,
55.50, 40.34, 40.31, 29.99. HRMS calcd for C20H18N2O3:
334.1317; found: 335.1187 [M]+.
3-(4-Chlorophenyl)-1-phenyl-3-(phenylthio)propan-1-one
(19)
1H NMR (400 MHz, CDCl3) d: 7.89 (d, J = 7.3 Hz, 2H),
7.59–7.55 (m, 1H), 7.46 (d, J = 7.5, 2H), 7.38–7.16 (m, 9H),
4.94–4.90 (m, 1H), 3.67–3.55 (m, 2H). 13C NMR (101 MHz,
CDCl3) d: 196.50, 139.62, 136.31, 133.47, 133.24, 132.78,
128.97, 128.77, 128.49, 128.38, 127.85, 127.63, 47.41,
44.27. HRMS calcd for C21H17ClOS: 352.0689; found:
353.0597 [M]+.
2-(1-(4-Methoxyphenyl)-3-oxo-3-phenylpropyl)malononitrile
(14)
1H NMR (400 MHz, DMSO) d: 7.99 (d, J = 7.3 Hz, 2H),
7.71–7.62 (m, 1H), 7.60–7.49 (m, 2H), 7.45–7.36 (m, 2H),
7.03–6.89 (m, 2H), 5.24–5.05 (m, 1H), 4.06–3.98 (m, 1H),
3.82–3.78 (m, 1H), 3.73 (s, 3H), 3.63–3.57 (m, 1H). 13C
NMR (101 MHz, DMSO) d: 196.95, 159.51, 136.54,
134.12, 130.06, 129.89, 129.28, 128.58, 114.43, 114.08,
113.76, 55.54, 40.78, 40.58, 29.98. HRMS calcd for
C19H16N2O2: 304.1212; found: 333.1114 [M – H + K]+.
3-Phenyl-3-(phenylthio)-1-p-tolylpropan-1-one (20)
1H NMR (400 MHz, CDCl3) d: 7.79 (d, J = 7.4, 2H),
7.33–7.22 (m, 12H), 4.95 (t, J = 7.0 Hz, 1H), 3.63–3.50 (m,
2H), 2.39 (s, 3H). 13C NMR (101 MHz, CDCl3) d: 195.63,
132.50, 129.09, 128.63, 128.23, 128.00, 127.60, 127.28,
127.13, 48.01, 44.27, 21.46. HRMS calcd for C22H20OS:
332.1235; found: 333.1187 [M]+.
Ethyl 5-(4-chlorophenyl)-2-cyano-5-oxo-3-phenylpentanoate
(15)
1-(4-Methoxyphenyl)-3-(3-nitrophenyl)-3-(phenylthio)
propan-1-one (21)
1H NMR (400 MHz, DMSO) d: 8.01 (d, J = 7.5 Hz, 2H),
7.59 (d, J = 7.1 Hz, 2H), 7.35–7.26 (m, 5H), 4.69–4.46 (m,
1H), 4.08–3.97 (m, 3H), 3.72–3.65 (m, 2H), 1.08 (t, J =
7.1 Hz, 3H). 13C NMR (101 MHz, DMSO) d: 196.24,
165.75, 138.93, 135.39, 130.48, 129.39, 128.93, 128.57,
128.42, 128.20, 62.58, 44.11, 41.75, 40.86, 14.22. HRMS
calcd for C20H18ClNO3: 355.0975; found: 356.0798 [M]+.
1H NMR (400 MHz, CDCl3) d: 8.18 (s, 1H), 8.04 (d, J =
6.5 Hz, 1H), 7.88 (d, J = 7.5 Hz, 2H), 7.62 (d, J = 6.7 Hz,
1H), 7.48–7.35 (m, 1H), 7.31–7.23 (m, 5H), 6.93 (d, J =
7.5 Hz, 2H), 5.01 (t, J = 6.0 Hz, 1H), 3.86 (s, 3H), 3.63 (d,
J = 6.8 Hz, 2H). 13C NMR (101 MHz, CDCl3) d: 194.46,
163.68, 143.64, 134.13, 133.19, 130.20, 129.14, 129.01,
Published by NRC Research Press

Muthyala et al.
295
2H). 13C NMR (101 MHz, CDCl3) d: 195.69, 140.77,
139.55, 134.78, 133.86, 132.60, 129.29, 128.74, 128.71,
128.32, 127.57, 127.44, 127.28, 48.02, 44.44. HRMS calcd
for C21H17ClOS: 352.0689; found: 353.0582 [M]+.
128.88, 128.04, 122.42, 122.09, 113.69, 55.34, 47.64, 43.46.
HRMS calcd for C22H19NO4S: 393.1035; found: 394.0985
[M]+.
1-(4-Methoxyphenyl)-3-(4-nitrophenyl)-3-(phenylthio)
propan-1-one (22)
1-(4-Nitrophenyl)-3-phenyl-3-(phenylthio)propan-1-one (28)
1H NMR (400 MHz, CDCl3) d: 8.26 (d, J = 8.80, 2H),
8.00 (d, J = 8.74 Hz, 2H), 7.37–7.17 (m, 10H), 4.90 (dd,
J = 7.6, 6.0 Hz, 1H), 3.70–3.57 (m, 2H). 13C NMR
(101 MHz, CDCl3) d: 195.45 141.18, 139.45, 134.96,
133.98, 132.60, 129.64, 128.84, 128.61, 128.46, 127.12,
127.44, 127.28, 48.10, 44.42. HRMS calcd for C21H17NO3S:
363.0929; found: 385.0879 [M – H + Na]+.
1H NMR (400 MHz, DMSO) d: 8.09 (d, J = 5.6 Hz, 2H),
7.95 (d, J = 5.2 Hz, 4H), 7.64 (d, J = 5.1 Hz, 2H), 7.31–
7.19 (m 5H), 7.03 (d, J = 5.37 Hz, 2H), 5.07–4.98 (m, 1H),
3.83 (s, 3H), 3.73–3.68 (m, 2H). 13C NMR (101 MHz,
DMSO) d: 195.27, 163.88, 150.24, 146.80, 133.74, 132.35,
130.99, 129.62, 128.12, 124.26, 123.79, 114.42, 47.42,
42.48. HRMS calcd for C22H19NO4S: 393.1035; found:
394.0989 [M]+.
1-(4-Methoxyphenyl)-3-phenyl-3-(phenylthio)propan-1-one
(29)
3-(4-Chlorophenyl)-3-(phenylthio)-1-p-tolylpropan-1-one (23)
1H NMR (400 MHz, CDCl3) d: 7.79 (d, J = 8.0 Hz, 2H),
7.42–7.14 (m, 11H), 4.91 (dd, J = 6.1, 7.8 Hz, 1H), 3.69–
3.46 (m, 2H), 2.41 (s, 3H). 13C NMR (101 MHz, CDCl3) d:
196.11, 144.13, 139.69, 133.87, 133.53, 132.74, 129.99,
129.16, 128.97, 128.74, 128.35, 127.98, 127.57, 47.47,
44.10, 21.48. HRMS calcd for C22H19ClOS: 366.0845;
found: 367.0782 [M]+.
1H NMR (400 MHz, CDCl3) d: 8.00–7.79 (m, 2H), 7.34–
7.24 (m, 10H), 6.98–6.84 (m, 2H), 4.97 (m, 1H), 3.85 (s,
3H), 3.61–3.51 (m, 2H). 13C NMR (101 MHz, CDCl3) d:
195.32, 163.40, 141.08, 132.45, 130.20, 129.60, 128.64,
128.24, 127.61, 127.26, 127.12, 113.54, 55.29, 48.10, 44.02.
HRMS calcd for C22H20O2S: 348.1184; found: 349.1079 [M]+.
3-(3-Nitrophenyl)-3-(phenylthio)-1-p-tolylpropan-1-one (30)
1H NMR (400 MHz, CDCl3) d: 8.18 (s, 1H), 8.04 (d, J =
6.1 Hz, 1H), 7.90–7.74 (m, 2H), 7.62 (d, J = 6.3 Hz, 1H),
7.42–7.35 (m, 1H), 7.32–7.25 (m, 7H), 5.09–4.90 (m, 1H),
3.67–3.56 (m, 2H), 2.41 (s, 3H). 13C NMR (101 MHz,
CDCl3) d: 195.62, 147.98, 144.42, 143.59, 134.11, 133.59,
133.22, 132.65, 129.24, 129.02, 128.89, 128.07, 127.99,
122.44, 122.11, 47.58, 43.72, 21.49. HRMS calcd for
C22H19NO3S: 377.1086; found: 378.1023 [M]+.
1-(4-Chlorophenyl)-3-(4-methoxyphenyl)-3-(phenylthio)
propan-1-one (24)
1H NMR (400 MHz, CDCl3) d: 7.81 (d, J = 8.1 Hz, 2H),
7.48–7.17 (m, 9H), 6.79 (d, J = 8.1 Hz, 2H), 4.98–4.82 (m,
1H), 3.76 (s, 3H), 3.63–3.48 (m, 2H). 13C NMR (101 MHz,
CDCl3) d: 195.85, 158.57, 139.52, 132.65, 132.52, 129.28,
128.72, 128.69, 128.63, 127.35, 113.65, 55.01, 47.44, 44.58.
HRMS calcd for C22H19ClO2S: 382.0794; found: 383.0703
[M]+.
3-(3-Nitrophenyl)-1-phenyl-3-(phenylthio)propan-1-one (31)
1H NMR (400 MHz, CDCl3) d: 8.18 (s, 1H), 8.05 (d, J =
7.1 Hz, H), 7.91 (d, J = 7.0 Hz, 2H), 7.71–7.54 (m, 2H),
7.54–7.36 (m, 3H), 7.36–7.17 (m, 5H), 5.01 (t, J = 6.7 Hz,
1H), 3.69 (d, J = 6.7 Hz, 2H). 13C NMR (101 MHz, CDCl3)
d: 196.00, 143.51, 136.03, 134.10, 133.46, 133.26, 129.05,
128.91, 128.58, 128.12, 127.86, 122.44, 122.15, 47.51,
43.90. HRMS calcd for C21H17NO3S: 363.0929; found:
364.00875 [M]+.
3-(4-Methoxyphenyl)-3-(phenylthio)-1-p-tolylpropan-1-one
(25)
1H NMR (400 MHz, CDCl3) d: 7.79 (d, J = 8.1 Hz, 2H),
7.33–7.22 (m, 9H), 6.79 (d, J = 8.6 Hz, 2H), 4.94 (dd, J =
5.6, 8.4 Hz, 1H), 3.76 (s, 3H), 3.65–3.49 (m, 2H), 2.40 (s,
3H). 13C NMR (101 MHz, CDCl3) d: 196.61, 158.48,
143.90, 134.06, 132.94, 132.41, 129.08, 128.67, 128.64,
128.00, 127.20, 113.59, 55.00, 47.45, 44.42, 21.46. HRMS
calcd for C23H22O2S: 362.1341; found: 363.1274 [M]+.
3-(4-Methoxyphenylthio)-1-(4-chlorophenyl)-3-
phenylpropan-1-one (32)
1,3-Bis(4-methoxyphenyl)-3-(phenylthio)propan-1-one (26)
1H NMR (400 MHz, CDCl3) d: 7.87 (d, J = 8.0 Hz, 2H),
7.32–7.13 (m, 7H), 6.90 (d, J = 7.9 Hz, 2H), 6.79 (d, J =
6.4 Hz, 2H), 4.94 (m, 1H), 3.85 (s, 3H), 3.75 (s, 3H), 3.63–
3.50 (m, 2H). 13C NMR (101 MHz, CDCl3) d: 195.49,
176.44, 163.37, 158.47, 132.98, 132.36, 130.19, 128.66,
127.17, 113.58, 113.52, 55.28, 55.00, 47.52, 44.16. HRMS
calcd for C23H22O3S: 378.129; found: 390.1205 [M – H +
Na]+.
1H NMR (400 MHz, CDCl3) d: 7.79 (d, J = 8.6 Hz, 2H),
7.38 (d, J = 8.6 Hz, 2H), 7.29–7.17 (m, 7H), 6.74 (d, J =
8.7 Hz, 2H), 4.70 (m, 1H), 3.75 (s, 3H), 3.53–3.57 (m, 2H).
13C NMR (101 MHz, CDCl3) d: 195.99, 159.92, 141.19,
139.69, 136.28, 135.11, 129.50, 128.93, 128.43, 127.80,
127.35, 124.06, 123.51, 121.93, 114.41, 55.29, 49.40, 44.26.
HRMS calcd for C22H19ClO2S: 382.0794; found: 404.0703
[M – H + Na]+.
1-(4-Chlorophenyl)-3-phenyl-3-(phenylthio)propan-1-one
(27)
General procedure for recycling the catalyst
Malononitrile (1.0 mmol) was added to the solution of 3-
(2-fluorophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one
1H NMR (400 MHz, CDCl3) d: 7.82 (d, J = 7.6 Hz, 2H),
7.42–2.24 (m, 12H), 4.94 (t, J = 7.8 Hz, 1H), 3.66–3.52 (m,
and
Published by NRC Research Press

296
Can. J. Chem. Vol. 90, 2012
(20) Xiao, J.-C.; Twamley, B.; Shreeve, J. M. Org. Lett. 2004, 6
(21), 3845. doi:10.1021/ol048327i.
(21) Yao, Q.; Zhang, Y. Angew. Chem. Int. Ed. 2003, 42 (29), 3395.
IL–TBD (5) (0.5 mmol). The reaction mixture was stirred
vigorously until reaction completion. The product was then
extracted from the catalyst by ethyl acetate (2 × 5 mL) leav-
ing the IL–TBD catalyst in the flask. The IL–TBD was
washed with diethyl ether and dried under reduced pressure.
The recovered IL was again used as a catalyst for a fresh
batch of chalcone and malononitrile (1.0 mmol) under the
same experimental conditions. The process was repeated five
times without much loss in catalytic activity.
doi:10.1002/anie.200351222.
(22) Siyutkin, D. E.; Kucherenko, A. S.; Zlotin, S. G. Tetrahedron
2009, 65 (7), 1366. doi:10.1016/j.tet.2008.12.045.
(23) Miao, W.; Chan, T. H. Adv. Synth. Catal. 2006, 348 (12–13),
1711. doi:10.1002/adsc.200606059.
(24) Luo, S.; Mi, X.; Zhang, L.; Liu, L.; Xu, H.; Cheng, J.-P.
Angew. Chem. Int. Ed. 2006, 45 (19), 3093–3097. doi:10.1002/
anie.200600048.
Acknowledgement
(25) Luo, S.; Zhang, L.; Mi, X.; Qiao, Y.; Cheng, J.-P. J. Org.
Chem. 2007, 72 (24), 9350. doi:10.1021/jo7020357.
(26) Ni, B. K.; Zhang, Q. Y.; Headley, A. D. Green Chem. 2007, 9
(7), 737. doi:10.1039/b702081c.
(27) Ni, B. K.; Zhang, Q. Y.; Headley, A. D. Tetrahedron Lett.
2008, 49 (7), 1249–1252. doi:10.1016/j.tetlet.2007.12.024.
(28) Li, P.; Wang, L.; Zhang, Y.; Wang, G. Tetrahedron 2008, 64
(32), 7633. doi:10.1016/j.tet.2008.05.039.
This work was financially supported by the Council of Sci-
entific and Industrial Research (CSIR), New Delhi (Project
No. 01(2214)/08/EMR-II) and the US National Science
Foundation, Grant No. CHE 0748555. M.M.K. thanks CSIR,
New Delhi, for a junior research fellowship.
(29) Wu, L.-Y.; Yan, Z.-Y.; Xie, Y.-X.; Niu, Y.-N.; Liang, Y.-M.
Tetrahedron Asymmetry 2007, 18 (17), 2086. doi:10.1016/j.
tetasy.2007.08.029.
(30) Zhang, Q.; Ni, B.; Headley, A. D. Tetrahedron 2008, 64 (22),
5091. doi:10.1016/j.tet.2008.03.073.
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