A one-pot green synthesis of alkylidenesuccinimides

Article abstract of DOI:10.1002/cjoc.201180332

A mild and facile Wittig reaction between N-substituted maleimides and aldehydes has been developed. Various synthetically valuable alkylidenesuccinimides were obtained from this one-pot reaction in high yields (up to 99%). The product was obtained by simple filtration and no extra purification was necessary. Ethanol, an environment-benign solvent, was found to be a suitable reaction medium. We have developed a mild and convenient one-pot Wittig reaction for the green synthesis of alkylidenesuccinimides. Under the established reaction conditions, a number of various synthetically valuable alkylidenesuccinimides were obtained in high yields (up to 99%). Copyright

Full text of DOI:10.1002/cjoc.201180332

FULL PAPER
A One-pot Green Synthesis of Alkylidenesuccinimides
Yan, Lin*,a,b(严琳)
Yang, Wenguob(杨文国)
Li, Lixinb(李立新)
Shen, Yangb(沈阳)
Jiang, Zhiyong*,a,b(江智勇)
a Institute of Chemical Biology, Henan University, Kaifeng, Henan 475004, China
b Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Henan University,
Kaifeng, Henan 475004, China
A mild and facile Wittig reaction between N-substituted maleimides and aldehydes has been developed. Various
synthetically valuable alkylidenesuccinimides were obtained from this one-pot reaction in high yields (up to 99%).
The product was obtained by simple filtration and no extra purification was necessary. Ethanol, an environ-
ment-benign solvent, was found to be a suitable reaction medium.
Keywords alkylidenesuccinimides, N-substituted maleimides, aldehydes, Wittig reaction, one-pot
phosphine by an one-pot process has been described.3,7
However, these methods required flash column chro-
matography (FC) separation and high temperature. It is
cleary that these methods also can not be applied in the
large scale preparation. Therefore, it is of a synthetic
interest to develop a convenient, practical and green
synthetic protocol for preparing alkylidenesuccinimides.
Herein, we report a one-pot Wittig reaction for the green
synthesis of alkylidenesuccinimides in high yields with
a simple purification technique. Environment-benign
ethanol is used as a solvent and eluent for the reaction.
Introduction
Alkylidenesuccinimides are recognized as useful in-
termediates as they contain condensed functionalities
such as activated exocyclic double bond and enolizable
amide moieties, which can act as either nucleophiles or
electrophiles under different reaction conditions. For
instance, N-itaconimides bearing a 1,1-disubstituted
exocyclic double bond, an important class of alkylide-
nesuccinimides, have been used as electrophiles. They
can react with diarylphosphine oxides or thiols in bi-
cyclic guanidine-catalyzed enantioselective protonation
reactions.1 And their nucleophilic ability has been dem-
onstrated in bicyclic guanidine-catalyzed asymmetric
allylic addition to N-Eoc imines as well.2 They were
also used as building blocks in the synthesis of a range
of bioactive compounds, such as dispiropyrrolidines
which exhibit potent antibacterial activity.3
The preparation of alkylidenesuccinimides could go
through the Wittig reaction between aldehydes and
phosphorus ylides.4 In this two-step and non-one-pot
protocol, the phosphorus ylides were firstly generated
from N-maleimides and triphenylphosphine in acetic
acid, which should be purified before reacting with al-
dehydes as the second step. At the same time, the yields
were unsatisfying. Thus, this protocol was not practical
for large scale synthesis at all. Pyridinium methylide as
N-ylide was also developed in the preparation of the
alkylidenesuccinimides. However, the methodology was
only utilized to prepare N-itaconimides due to the limi-
tation of N-ylide.5 Consequently, the phosphoniosilyla-
tion of N-maleimides via Wittig reaction was a more
complicated protocol and gave poor yields.6 Most re-
cently, the synthesis of dispiropyrrolidines from
N-methyl maleimides and aldehydes with triphenyl
Results and discussion
We proposed that the Wittig reaction goes through
the formation of the phosphrous ylides from
N-substituted maleimides and triphenylphosphine
(Scheme 1). We postulated that protic solvents would
accelerate the proton shift and the reaction might pro-
ceed without heating. Since alkylidenesuccinimides
have poor solubilities in protic solvents,4 the products
could be purified and collected via a simple filtration,
making it a practical approach for scale-up reactions.
Our initial investigation was carried out with ben-
zaldehyde (1a), N-phenyl maleimide (2a), and Ph3P in
1.2∶1.0∶1.2 molar ratio at room temperature. Among
the solvents screened (Table 1, Entries 1—5), ethanol
gave the best result, which was consistent with our hy-
pothesis that protic solvent should accelerate the rate of
proton shift (Scheme 1). The desired product 3a was
obtained in 75% yield using FC after 6 h (Table 1, Entry
1). The use of water as solvent led to the desired product,
but in poor yield (Table 1, Entry 2). We suspected that
the poor solubilities of starting materials in water might
*
E-mail: chmjzy@henu.edu.cn
Received March 26, 2011; revised April 30, 2011; accepted May 10, 2011.
Project supported by the National Natural Science Foundation of China (No. 21072044) and International Cooperation Foundation of Henan Prov-
ince (No. 104300510062).
1906
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 1906— 1910

A One-pot Green Synthesis of Alkylidenesuccinimides
Scheme 1 Proposed mechanism of Wittig reaction
impede the reaction. Furthermore, the reaction in aprotic
solvents, such as dichloromethane and toluene, pro-
ceeded in moderate yield (Table 1, Entries 3, 4). We
also examined the yield of 3a by changing the ratio of
1a, 2a, and Ph3P in ethanol as solvent (Table 1, Entries
6—8). It was shown that the best ratio of 1a∶2a∶Ph3P
was 1.4∶1.0∶1.2 for the reaction (Table 1, Entry 8).
As expected, the product 3a could be efficiently isolated
in 82% yield by filtration due to its poor solubility in
ethanol.
Entry 15) and N-cyclohexyl maleimide 2c (Table 2, En-
try 16) in the presence of triphenylphosphine. Both
yields from filtration or FC were good to excellent.
Table 2 The synthesis of different alkylidenesuccinimidesa
Entry
R1
Reactant R2 Reactant Product Yieldb/%
Table 1 Investigation of reaction conditionsa
1
2
3
4
5
6
7
8
9
p-CF3C6H4
m-CF3C6H4
p-FC6H4
1b
1c
1d
1e
1f
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Bn
Cy
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2c
3b
3c
3d
3e
3f
83 (64)
70 (83)
84 (82)
74 (73)
70 (68)
78 (97)
80 (82)
78 (88)
85 (97)
84 (93)
75 (94)
77 (96)
59 (99)
(88)c
p-BrC6H4
o-ClC6H4
p-MeC6H4
p-iPrC6H4
1-Naphthyl
m-MeOC6H4
Entry
Ratio of 1a∶ 2a∶ Ph3P
1.2∶ 1.0∶ 1.2
1.2∶ 1.0∶ 1.2
1.2∶ 1.0∶ 1.2
1.2∶ 1.0∶ 1.2
1.2∶ 1.0∶ 1.2
1.0∶ 1.0∶ 1.2
1.0∶ 1.2∶ 1.2
1.4∶ 1.0∶ 1.2
Solvent
EtOH
H2O
Yieldb/%
1g
1h
1i
3g
3h
3i
1
2
3
4
5
6
7
8
75
16
DCM
Toluene
THF
66
1j
3j
60
10 p-MeOC6H4
11 3-thienyl
12 PhCH2CH2
13 PhCH2
14 CH3(CH2)3
1k
1l
3k
3l
12
EtOH
EtOH
EtOH
70
1m
1n
1o
1a
1a
3m
3n
3o
3p
3q
80
93 (82)c
—
a
b
Reactions were conducted with 0.025 mmol scale. Flash col-
umn chromatography (FC) yield. Filtration yield, 0.25 mmol
scale.
c
15
16
Ph
Ph
83 (91)
80 (87)
a
Reactions were conducted with 0.25 mmol scale, the ratio of
With the optimized conditions in hand, we started to
explore the reaction scope. First, a variety of aromatic
aldehydes (1b—1l) were investigated with N-phenyl
maleimide 2a and triphenylphosphine (Table 2, Entries
1—11). It was found that all of these reactions were
completed in 6 h to afford excellent yields of 3b—3l by
either purification methods (filtration or FC). The elec-
tronic effect of the substituent on the aromatic ring was
not obvious. Subsequently, aliphatic aldehydes 1m—1o
were subjected to the Wittig reaction condition (Table 2,
Entries 12—14). The desired products (3m, 3n) were
isolated in better yields by filtration than by FC. Only in
the case of 3o, flash chromatography was needed for its
isolation. Finally, we investigated the reactions of ben-
zylaldehyde 1a with N-benzyl maleimide 2b (Table 2,
b
1∶ 2∶ Ph3P＝ 1.4∶ 1.0∶ 1.2. Filtration yield (in parentheses of
FC yield). The product can not be filtered using ethanol as elu-
c
ent.
Activated aldehydes 4 with aromatic ketones located
at the alpha position of the aldehyde were conducted
under the same conditions (Table 3). The reactions
could be completed smoothly with excellent filtration
yields. However, prolonged reaction time (12 to 24 h)
was necessary. It was worth noting that only single iso-
1
mers were detected by H NMR spectra in all the prod-
ucts. The double bond in the products was assigned to E
configuration by NOE analysis.2
In these reactions, the environment-benign ethanol,
which was used as solvent and eluent, can be recycled
Chin. J. Chem. 2011, 29, 1906— 1910
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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1907

Yan et al.
FULL PAPER
Table 3 The synthesis of different alkylidenesuccinimides under
established reaction conditionsa
Experimental section
General methods
Experiments involving moisture and/or air sensitive
components were performed under a positive pressure of
nitrogen in oven-dried glassware equipped with a rubber
septum inlet. Dried solvents and liquid reagents were
transferred by oven-dried syringes or hypodermic sy-
ringe cooled to ambient temperature in a desiccator.
Moisture in non-volatile reagents/compounds was re-
moved in high vacuo by means of an oil pump and sub-
sequent purging with nitrogen. All experiments were
monitored by analytical thin layer chromatography
(TLC). Columns for flash chromatography (FC) con-
Entry
R
Reactant
Product
5a
Yieldb/%
1
2
3
4
5
Ph
4a
4b
4c
4d
4e
99
92
87
93
89
p-CF3C6H4
1-Naphthyl
m-MeOC6H4
p-MeOC6H4
5b
5c
5d
5e
1
tained silica gel (200—300 mesh). H (400 MHz), 13C
a
Reactions were conducted with 0.25 mmol scale, the ratio of
4∶ 2a∶ Ph3P＝ 1.4∶ 1.0∶ 1.2. b Filtration yields.
(100 MHz) with complete proton decoupling, were per-
formed on a Bruker AVANCE-III (400MHz) spec-
trometer. Chemical shifts are reported using the residual
solvent signal as an internal standard: CDCl3 (1H NMR:
δ 7.26, singlet; 13C NMR: δ 77.0, triplet). Low resolu-
tion mass spectra were obtained on a Finnigan/
TraceDse2 spectrometer in EI mode. Melting points
were determined on an X-6 microscopic melting point
apparatus. All commercial reagents were purchased
from Aladdin® and Darui® of the highest purity grade.
They were used without further purification unless
specified.
by a simple distillation. We also conducted gram-scale
synthesis of 3a, which could be obtained in excellent
yield by filtration (90%). Furthermore, triphenyl-
phosphine oxide was obtained in 82% yield after re-
crystalization as the only side product (Scheme 2). It
was well known that triphenylphosphine oxide is a ver-
satile and useful Lewis base.8 Therefore, we believed
that this efficient protocol belongs to the domain of
green chemistry.9
Scheme 2 The gram-scale synthesis of 3a
Representative procedure
N-Phenyl maleimide 2a (866 mg, 5 mmol) and PPh3
(1.573 g, 6 mmol) were dissolved in ethanol (40.0 mL)
and stirred at room temperature for about 5 min, then
benzaldehyde 1a (707 µL, 7 mmol) was added. The re-
action mixture was stirred at room temperature and
monitored by TLC. After 6 h, upon complete consump-
tion of 2a, the resultant mass was filtered through
Buckner funnel, and the resulted solid was rinsed with
ethanol. Finally, 1.184 g 3a was obtained with 90%
yield as white solid after pump dried. The surplus etha-
nol was distilled and reused as solvent and eluent. 1.148
g triphenylphosphine oxide (82% yield) was achieved
after recrystalization using ethyl acetate and petroleum
ether.
Conclusions
Characterization data
In summary, we have developed a mild and conven-
ient one-pot Wittig reaction for the green synthesis of
alkylidenesuccinimides. Under the established reaction
conditions, a number of alkylidenesuccinimides derived
from various N-substituted maleimides and aldehydes
were synthesized in high yields by FC or filtration (up to
99%) as well as in high E-diasteroselectivities. The
gram-scale synthesis of 3a was demonstrated through a
direct filtration purification technique. To expand the
scope of this synthetic methodology, the reactions are
under investigation in our laboratory by using ketones
and linear activated alkenes as the corresponding start-
ing materials to prepare interesting synthetic intermedi-
ates.
3-Benzylidene-1-phenyl-pyrrolidine-2,5-dione (3a)
1
White solid, m.p. 202—204 ℃; H NMR (CDCl3, 400
MHz) δ: 7.75 (t, J＝2.4 Hz, 1H), 7.56—7.38 (m, 10H),
3.78 (d, J＝2.4 Hz, 2H); 13C NMR (CDCl3, 100 MHz) δ:
173.0, 170.0, 135.3, 133.9, 131.9, 130.3, 130.2, 129.2,
129.1, 128.5, 126.4, 123.0, 34.2; LRMS (EI) m/z: 262.9
(M＋).
1-Phenyl-3-(4-trifluoromethyl-benzylidene)-pyrro-
lidine-2,5-dione (3b) White solid, m.p. 222—224 ℃;
1H NMR (CDCl3, 400 MHz) δ: 7.77—7.73 (m, 3H), 7.64
(d, J＝8.0 Hz, 2H), 7.52 (d, J＝8.0 Hz, 2H), 7.43—7.37
(m, 3H), 3.78 (d, J＝2.4 Hz, 2H); 13C NMR (CDCl3,
100 MHz) δ: 172.4, 169.5, 137.3, 133.5, 131.8, 130.2,
1908
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© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 1906— 1910

A One-pot Green Synthesis of Alkylidenesuccinimides
129.2, 128.7, 126.4, 126.1 (two peaks), 126.0, 125.7,
34.1; LRMS (EI) m/z: 330.9 (M＋).
7.51 (t, J＝7.6 Hz, 2H), 7.43—7.37 (m, 4H), 7.13 (d, J＝
7.6 Hz, 1H), 7.04 (s, 1H), 7.00 (dd, J＝7.6, 2.4 Hz, 1H),
3.86 (s, 3H), 3.76 (d, J＝2.4 Hz, 2H); 13C NMR (CDCl3,
100 MHz) δ: 173.0, 170.0, 159.9, 135.4, 135.3, 131.9,
130.1, 129.1, 128.6, 126.4, 123.2, 122.6, 116.0, 115.5,
55.3, 34.3; LRMS (EI) m/z: 293.0 (M＋).
1-Phenyl-3-(3-trifluoromethyl-benzylidene)-pyrro-
lidine-2,5-dione (3c) White solid, m.p. 160—162 ℃;
1H NMR (CDCl3, 400 MHz) δ: 7.76—7.60 (m, 5H),
7.52—7.37 (m, 5H), 3.78 (d, J＝2.0 Hz, 2H); 13C NMR
(CDCl3, 100 MHz) δ: 172.5, 169.5, 134.7, 133.5, 133.0,
131.8, 129.7, 129.2, 128.7, 126.7, 126.6, 126.5 (t＋wo
peaks), 126.3, 125.1, 34.0; LRMS (EI) m/z: 330.9 (M ).
3-(4-Fluoro-benzylidene)-1-phenyl-pyrrolidine-2,5-
3-(4-Methoxy-benzylidene)-1-phenyl-pyrrolidine-
1
2,5-dione (3k) White solid, m.p. 175—177 ℃; H
NMR (CDCl3, 400 MHz) δ: 7.69 (t, J＝2.4 Hz, 1H),
7.52—7.48 (m, 4H), 7.42—7.37 (m, 3H), 7.00 (d, J＝
8.8 Hz, 2H), 3.87 (s, 3H), 3.72 (d, J＝2.4 Hz, 2H); 13C
NMR (CDCl3, 100 MHz) δ: 1173.2, 170.3, 161.2, 135.1,
132.1, 132.0, 129.1, 128.4, 126.8, 126.4, 120.1, 114.6,
55.4, 34.3; LRMS (EI) m/z: 292.9 (M＋).
1
dione (3d) White solid, m.p. 232—233 ℃; H NMR
(CDCl3, 400 MHz) δ: 7.71 (t, J＝2.4 Hz, 1H), 7.55—
7.37 (m, 7H), 7.18 (t, J＝8.6 Hz, 2H), 3.73 (d, J＝2.4
Hz, 2H); 13C NMR (CDCl3, 100 MHz) δ: 172.8, 169.9,
164.9, 162.4, 134.1, 132.3, 132.2, 132.0, 130.4 (two
peaks), 129.2, 128＋.6, 122.7, 116.6, 116.4, 34.1; LRMS
(EI) m/z: 280.9 (M ).
1-Phenyl-3-thiophen-3-yl-methylene-pyrrolidine-
1
2,5-dione (3l) White solid, m.p. 202—204 ℃; H
NMR (CDCl3, 400 MHz) δ: 7.76 (t, J＝2.4 Hz, 1H),
7.62 (d, J＝2.4 Hz, 1H), 7.52—7.37 (m, 6H), 7.29 (dd,
J＝5.0, 1.0 Hz, 1H), 3.69 (d, J＝2.4 Hz, 2H); 13C NMR
(CDCl3, 100 MHz) δ: 172.9, 170.0, 136.4, 132.0, 130.1,
129.1, 128.8, 128.5, 127.＋4, 127.3, 126.4, 121.4, 34.2;
LRMS (EI) m/z: 268.9 (M ).
3-(4-Bromo-benzylidene)-1-phenyl-pyrrolidine-2,5-
dione (3e) White solid, m.p. 235—236 ℃; 1H NMR
(CDCl3, 400 MHz) δ: 7.68 (t, J＝2.4 Hz, 1H), 7.63—
7.37 (m, 9H), 3.72 (d, J＝2.4 Hz, 2H); 13C NMR
(CDCl3, 100 MHz) δ: 172.6, 169.8, 134.0, 132.9, 132.5,
131.9, 131.5, 129.2, 128.＋6, 126.4, 124.9, 123.8, 34.2;
LRMS (EI) m/z: 340.8 (M ).
1-Phenyl-3-(3-phenyl-propylidene)-pyrrolidine-2,5-
1
dione (3m) White solid, m.p. 145—147 ℃; H NMR
3-(2-Chloro-benzylidene)-1-phenyl-pyrrolidine-2,5-
(CDCl3, 400 MHz) δ: 7.50—7.20 (m, 10H), 7.00—6.95
(m, 1H), 3.18 (t, J＝1.2 Hz, 2H), 2.85 (t, J＝7.4 Hz, 2H),
2.56 (q, J＝7.4 Hz, 2H); 13C NMR (CDCl3, 100 MHz) δ:
173.0, 168.6, 140.2, 138.4, 131.8, 129.0, 128.5, 128.4,
128.3, 126.4, 126.3, 126.0, 34.1, 31.9, 31.8; LRMS (EI)
m/z: 291.0 (M＋).
1
dione (3f) White solid, m.p. 145—147 ℃; H NMR
(CDCl3, 400 MHz) δ: 8.10 (t, J＝2.4 Hz, 1H), 7.51—
7.33 (m, 9H), 3.67 (d, J＝2.4 Hz, 2H); 13C NMR
(CDCl3, 100 MHz) δ: 172.7, 169.3, 135.8, 132.2, 131.8,
131.5, 131.0, 130.4, 129.1 (two peaks), 128＋.5, 127.0,
126.3, 125.7, 33.7; LRMS (EI) m/z: 296.9 (M ).
3-Phenethylidene-1-phenyl-pyrrolidine-2,5-dione
(3n) White solid, m.p. 165 — 167 ℃ ; 1H NMR
(CDCl3, 400 MHz) δ: 7.53—7.12 (m, 11H), 3.61 (t, J＝
4.8 Hz, 2H), 3.43 (d, J＝4.8 Hz, 2H); 13C NMR (CDCl3,
100 MHz) δ: 173.0, 168.8, 137.6, 137.2, 132.0, 129.1,
129.0, 128.6, 127.0, 126.5, 126.0, 36.1, 32.2; LRMS (EI)
m/z: 277.0 (M＋).
3-(4-Methyl-benzylidene)-1-phenyl-pyrrolidine-2,5-
1
dione (3g) White solid, m.p. 204—205 ℃; H NMR
(CDCl3, 400 MHz) δ: 7.74 (t, J＝2.3 Hz, 1H), 7.54—
7.30 (m, 9H), 3.77 (d, J＝2.3 Hz, 2H), 2.44 (s, 3H); 13C
NMR (CDCl3, 100 MHz) δ: 173.2, 170.2, 141.0, 135.5,
132.1, 131.4, 130.4, 130.0, 129.1, 128.5, 126.5, 121.9,
34.4, 21.5; LRMS (EI) m/z: 276.9 (M＋).
3-Pentylidene-1-phenyl-pyrrolidine-2,5-dione (3o)
1
3-(4-Isopropyl-benzylidene)-1-phenyl-pyrrolidine-
White solid, m.p. 115—116 ℃; H NMR (CDCl3, 400
1
2,5-dione (3h) White solid, m.p. 167—169 ℃; H
MHz) δ: 7.49—7.30 (m, 5H), 6.97—6.92 (m, 1H), 3.39
(t, J＝1.2 Hz, 2H), 2.24 (q, J＝7.2 Hz, 2H), 1.56—1.34
(m, 4H), 0.94 (t, J＝7.2 Hz, 3H); 13C NMR (CDCl3, 100
MHz) δ: 173.1, 168.9, 140.2, 131.9, 129.0, 128.4, 126.4,
125.1, 32.1, 30.1, 29.6, 22.4, 13.8; LRMS (EI) m/z:
242.9 (M＋).
NMR (CDCl3, 400 MHz) δ: 7.75 (t, J＝2.2 Hz, 1H),
7.54—7.36 (m, 9H), 3.76 (d, J＝2.2 Hz, 2H), 3.03—
2.96 (m, 1H), 1.32 (d, J＝6.9 Hz, 6H); 13C NMR
(CDCl3, 100 MHz) δ: 173.2, 170.2, 151.8, 135.4, 132.1,
131.8, 130.5, 129.1, 128.5, 127.3, 126.5, 122.0, 34.4,
34.1, 23.7; LRMS (EI) m/z: 305.0 (M＋).
1-Benzyl-3-benzylidene-pyrrolidine-2,5-dione (3p)
1
3-Naphthalen-1-yl-methylene-1-phenyl-pyrrolidine-
White solid, m.p. 208—210 ℃; H NMR (CDCl3, 400
1
2,5-dione (3i) White solid, m.p. 170—172 ℃; H
MHz) δ: 7.62 (t, J＝2.4 Hz, 1H), 7.48—7.27 (m, 10H),
4.78 (s, 2H), 3.55 (d, J＝2.4 Hz, 2H); 13C NMR (CDCl3,
100 MHz) δ: 173.6, 170.6, 135.8, 134.5, 134.0, 130.1
(two peaks), 129.0, 128.8, 128.6, 127.9, 123.3, 42.4,
34.0; LRMS (EI) m/z: 276.9 (M＋).
NMR (CDCl3, 400 MHz) δ: 8.52 (t, J＝2.3 Hz, 1H),
8.18 (d, J＝8.2 Hz, 1H), 7.97—7.93 (m, 2H), 7.63—
7.43 (m, 9H), 3.71 (d, J＝2.3 Hz, 2H); 13C NMR
(CDCl3, 100 MHz) δ: 173.1, 169.6, 133.6, 132.5, 131.9,
131.8, 130.7, 130.5, 129.1, 128.8, 128.5, 127.1, 126.5,
126.4, 125.6, 125.1, 123.6, 33.9; LRMS (EI) m/z: 313.0
(M＋).
3-Benzylidene-1-cyclohexyl-pyrrolidine-2,5-dione
(3q) White solid, m.p. 177 — 179 ℃ ; 1H NMR
(CDCl3, 400 MHz) δ: 7.56 (t, J＝2.4 Hz, 1H), 7.48—7.37
(m, 5H), 4.14—4.06 (m, 1H), 3.51 (d, J＝2.4 Hz, 2H),
2.26—2.16 (m, 2H), 1.86—1.62 (m, 5H), 1.39—1.22 (m,
3H); 13C NMR (CDCl3, 100 MHz) δ: 174.1, 171.0,
3-(3-Methoxy-benzylidene)-1-phenyl-pyrrolidine-
1
2,5-dione (3j) White solid, m.p. 191—192 ℃; H
NMR (CDCl3, 400 MHz) δ: 7.70 (t, J＝2.4 Hz, 1H),
Chin. J. Chem. 2011, 29, 1906— 1910
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1909

Yan et al.
FULL PAPER
134.2, 133.7, 130.0, 129.9, 129.0, 123.5＋, 51.7, 34.0,
3-[2-(4-Methoxy-phenyl)-2-oxo-ethylidene]-1-phe-
28.9, 25.8, 25.0; LRMS (EI) m/z: 269.0 (M ).
nyl-pyrrolidine-2,5-dione (5e) Yellow solid, m.p.
1
3-(2-Oxo-2-phenyl-ethylidene)-1-phenyl-pyrroli-
dine-2,5-dione (5a) Yellow solid, m.p. 169—171 ℃;
1H NMR (CDCl3, 400 MHz) δ: 8.08—8.06 (m, 2H),
8.03 (t, J＝2.4 Hz, 1H), 7.68—7.36 (m, 8H), 4.00 (d,
J＝2.4 Hz, 2H); 13C NMR (CDCl3, 100 MHz) δ: 189.6,
173.0, 168.8, 139.3, 137.2, 134.1, 131.6, 129.2, 129.0,
128.9, 128.6, 126.3, 124.0, 34.9; LRMS (EI) m/z: 290.9
(M＋).
159—161 ℃; H NMR (CDCl3, 400 MHz) δ: 8.06 (d,
J＝8.8 Hz, 2H), 8.00 (t, J＝2.4 Hz, 1H), 7.51 (t, J＝7.6
Hz, 2H), 7.43 (t, J＝7.6 Hz, 1H), 7.37 (d, J＝7.6 Hz,
2H), 7.00 (d, J＝8.8 Hz, 2H), 3.98 (d, J＝2.4 Hz, 2H),
3.90 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ: 187.8,
173.2, 169.0, 164.4, 138.5, 131.6, 131.1, 130.4, 129.2,
128.8, 12＋6.3, 124.3, 114.2, 55.6, 34.8; LRMS (EI) m/z:
321.1 (M ).
3-[2-Oxo-2-(4-trifluoromethyl-phenyl)-ethylidene]-
1-phenyl-pyrrolidine-2,5-dione (5b) Yellow solid,
m.p. 179—181 ℃; 1H NMR (CDCl3, 400 MHz) δ: 8.18
(d, J＝8.0 Hz, 2H), 8.00 (t, J＝2.6 Hz, 1H), 7.82 (d, J＝
8.0 Hz, 2H), 7.53 (t, J＝7.6 Hz, 2H), 7.46 (d, J＝7.6 Hz,
1H), 7.37 (d, J＝7.6 Hz, 2H), 4.01 (d, J＝2.6 Hz, 2H);
13C NMR (CDCl3, 100 MHz) δ: 188.7, 172.7, 168.5,
140.7, 139.8, 131.4, 129.3, 129.0, 128.9, 126.2, 126.1
(two peaks), 123.0, 35.0; LRMS (EI) m/z: 359.1 (M＋).
3-(2-Naphthalen-1-yl-2-oxo-ethylidene)-1-phenyl-
pyrrolidine-2,5-dione (5c) Yellow solid, m.p. 168—
References
1
(a) Leow, D.; Lin, S.; Chittimalla, S. K.; Fu, X.; Tan, C. H.
Angew. Chem., Int. Ed. 2008, 47, 5641.
(b) Lin, S.; Leow, D.; Huang, K.-W.; Tan, C. H. Chem.
Asian J. 2009, 4, 1741.
2
3
Wang, J.; Liu, H.; Fan, Y.; Yang, Y.; Jiang, Z.; Tan, C. H.
Chem. Eur. J. 2010, 16, 12534.
Karthikeyan, K.; Sivakumar, P. M.; Doble, M.; Perumal, P.
T. Eur. J. Med. Chem. 2010, 45, 3446.
1
4
5
Hedaya, E.; Theodoropulos, S. Tetrahedron 1968, 24, 2241.
Tsuge, O.; Kanemasa, S.; Kuraoka, S.; Takenaka, S. Chem.
Lett. 1984, 279, 281.
170 ℃; H NMR (CDCl3, 400 MHz) δ: 8.68 (d, J＝8.4
Hz, 1H), 8.09 (d, J＝8.4 Hz, 1H), 8.03 (d, J＝6.8 Hz,
1H), 7.34 (t, J＝2.8 Hz, 1H), 7.69—7.38 (m, 8H), 4.04
(d, J＝2.4 Hz, 2H); 13C NMR (CDCl3, 100 MHz) δ:
192.6, 173.0, 168.8, 138.7, 135.2, 134.2, 134.0, 131.6,
130.3, 129.4, 129.2, 128.9, 128.7, 128.6, 127.6, 126.9,
126.3, 125.4, 124.5, 34.8; LRMS (EI) m/z: 341.1 (M＋).
3-[2-(3-Methoxy-phenyl)-2-oxo-ethylidene]-1-phe-
nyl-pyrrolidine-2,5-dione (5d) Yellow solid, m.p.
6
7
8
Jung, S. H.; King, J. H.; Lee, J. H. Bull. Korean Chem. Soc.
2004, 25, 1088.
(a) Mangaleswaran, S.; Argade, N. P. Synthesis 2003, 343.
(b) Haval, K. P.; Argade, N. P. Tetrahedron 2006, 62, 3557.
For selected examples, see:
(a) Cao, J. J.; Zhou, F.; Zhou, J. Angew. Chem., Int. Ed.
2010, 49, 4976.
(b) Sugiura, M.; Sato, N.; Kotani, S.; Nakajima, M. Chem.
Commun. 2008, 4309.
1
180—181 ℃; H NMR (CDCl3, 400 MHz) δ: 8.00 (t,
J＝2.4 Hz, 1H), 7.66 (d, J＝8.0 Hz, 1H), 7.57—7.36 (m,
7H), 7.20 (dd, J＝2.4, 8.0 Hz, 1H), 3.99 (d, J＝2.4 Hz,
2H), 3.89 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ: 189.4,
173.0, 168.8, 160.2, 139.3, 138.6, 131.6, 130.0, 129.2,
128.9, 126.3, 124.1, 121＋.3, 120.9, 112.4, 55.5, 34.9;
LRMS (EI) m/z: 321.1 (M ).
9
For selected reviews, see:
(a) Anastas, P.; Eghbali, N. Chem. Soc. Rev. 2010, 39, 301.
(b) Horváth, I. T.; Anastas, P. T. Chem. Rev. 2007, 107,
2169.
(E1103261 Sun, H.; Zheng, G.)
1910
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© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 1906— 1910