Regioselective hetero-Michael addition of oxygen, sulfur, and nitrogen nucleophiles to maleimides catalyzed by BF3·OEt2

Article abstract of DOI:10.1055/s-0034-1380404

Abstract A practical BF₃·OEt₂-catalyzed regioselective 1,2-addition or 1,4-hetero-Michael addition of oxygen, sulfur, and nitrogen nucleo philes to maleimides has been developed for the synthesis of alkyl fumarate derivatives or 3-su

Full text of DOI:10.1055/s-0034-1380404

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2015, 47, 1581–1592
paper
1581
Y.-L. An et al.
Paper
Synthesis
Regioselective Hetero-Michael Addition of Oxygen, Sulfur, and
Nitrogen Nucleophiles to Maleimides Catalyzed by BF3·OEt2
Yu-Long Ana
Yun-Xia Dengb
Wei Zhanga
R2
R2
O
N
BF3•OEt2
O
O
HN
R1
X
O
R1
X
X = S, N
Sheng-Yin Zhao*a,c
X = O
BF3
R2
N
F
R2
N
F
a Department of Chemistry, Donghua University,
No. 2999 North Renmin Road, Shanghai 201620,
P. R. of China
O
O
B
F
R2
N
F
O
O
F
B
O
O
F
R2
X
syzhao8@dhu.edu.cn
X
R1
H
F
R2
N
H
b Department of Biological Engineering, Donghua
University, No. 2999 North Renmin Road, Shanghai
201620, P. R. of China
F
B
O
O
F
c State Key Laboratory of Bioorganic & Natural Prod-
ucts Chemistry, Shanghai Institute of Organic Chem-
istry, Chinese Academy of Sciences, Shanghai
200032, P. R. of China
X = S, N 1,4-Michael addition
X = O 1,2-addition
R1
X
H
Received: 17.12.2014
O
Accepted after revision: 23.01.2015
Published online: 05.03.2015
DOI: 10.1055/s-0034-1380404; Art ID: ss-2014-h0760-op
O
N
polyamide
N
N
S
R1
O
O
Abstract A practical BF3·OEt2-catalyzed regioselective 1,2-addition or
1,4-hetero-Michael addition of oxygen, sulfur, and nitrogen nucleo-
philes to maleimides has been developed for the synthesis of alkyl fu-
marate derivatives or 3-substituted succinimides, respectively. This re-
action system has wide substrate scope and gives moderate to excellent
yields (up to 96%) of the desired products. In contrast to the base-cata-
lyzed methods, this strategy is very general, simple, environmentally
friendly, and tolerant of oxygen.
O
O
R2
S
polycyclic succinimide
peptide succinimide
Me
N
Me
N
O
O
O
O
Key words Michael addition, maleimide, oxygen nucleophiles, sulfur
nucleophiles, nitrogen nucleophiles, boron trifluoride diethyl etherate
H
H
N
N
N
3-Substitued maleimide and succinimide compounds
are versatile building blocks in organic synthesis. They not
only constitute as valuable intermediates for the synthesis
of various polycyclic compounds1 and peptide substances,2
but also serve as key precursors in the synthesis of a variety
of natural products3 and pharmaceuticals (Figure 1).4 The
development of efficient methods for their synthesis has
continuously attracted the attentions of many chemists.
In view of the synthetic expediency of 3-substituted
succinimides, many methods have been developed for their
synthesis. Generally, 3-alkyloxy-substitued succinimides
were obtained by base-catalyzed addition and solvolysis re-
action of maleimides in alcohol solution.5 Organocatalytic
ring expansion of β-lactam aldehydes was also developed to
provide 3-alkoxy-substituted succinimides.6 However, the
above synthetic method gave a low yield and involved te-
dious procedures. During the past few years, Michael and
Boc
granulatimide analogue
phensuximide
Figure 1 Examples of polycyclic compounds, peptides, natural prod-
ucts, and pharmaceuticals containing 3-substituted succinimide motif
hetero-Michael addition provided a direct protocol for the
formation of carbon–carbon and carbon–heteroatom
bonds, and attracted much attention.7 Generally, either the
donor or the acceptor component needs to be activated in
hetero-Michael addition reactions. Fortunately, important
advances have been made with Lewis acids, which activate
the acceptor component with catalytic amounts and
avoid/reduce the polymerization of starting olefins.
Bi(NO3)3, Pd(OAc)2, [Rh(COD)2]BF4, InCl3, Ph3PAuCl/AgOTf,
La(OTf)3, and related Lewis acids have been used successful-
ly in hetero-Michael addition.8 Most of the reactions usual-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 1581–1592

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Y.-L. An et al.
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Synthesis
ly demand high catalyst loadings, long reaction times rang-
ing from several hours to several days in some cases, expen-
sive and hazardous reagents, and special reaction
conditions to enhance reactivity, such as ultrasounds and
ultra-high pressures,9 microwave irradiation,10 or ionic liq-
uids.11 Furthermore, most of the reaction substrates were
focused on α,β-unsaturated carbonyl compounds, such as
acrylic esters and nitroalkenes. However, only few reports
on maleimides serving as Michael addition acceptors using
Lewis acid as catalysis have appeared until now. The ma-
leimides are unstable in the presence of strong acids and
bases, and are apt to polymerize and decompose. Thus, an
efficient, economical and environmentally benign Lewis
acid catalyst is highly desirable for this process. In our con-
tinued research program directed toward the synthesis of
maleimide derivatives in this area,12 we have successfully
developed a highly efficient synthetic strategy for Michael
addition of indoles and pyrroles to maleimides using AlCl3
as catalyst.12d Thus, we became intrigued by the idea of us-
ing catalytic amounts of cheap Lewis acids to catalyze hetero-
Michael reactions of maleimides, since β-oxy-, β-thio-, and
β-aminocarbonyl functionalities are ubiquitous motifs in
Table 1 Optimization of the Reaction Conditionsa
O
HN
Lewis acid
O
O
CH2CH2OH
3a
N
Lewis acid
O
O
O
O
1
2a
N
O
4a
Entry
Catalyst
Solvent
Time (h)
Yield (%)b
1
2
–
CH2Cl2
CH2Cl2
CH2Cl2
DCE
12
24
24
24
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
0
34
42
45
trace
0c
0c
0
ZnCl2
3
ZnBr2
ZnBr2
FeCl3
4
5
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
DCE
6
AlCl3
7
TiCl4
8
ZrCl4
9
InBr3
0
10
11
12
13
14
15
16
17
18
19
AgBF4
RuCl3
0
0
Zn(OTf)2
Y(OTf)3
BiCl3
34
32
26
92
89
0
1,4-dioxane
CH2Cl2
DCE
BF3·OEt2
BF3·OEt2
BF3·OEt2
BF3·OEt2
BF3·OEt2
1,4-dioxane
THF
0
DMF
0
a Reaction conditions: N-phenylmaleimide (1; 2.0 mmol), 2-phenylethanol (2a; 2.0 mmol), and catalyst (20 mol%) were refluxed in the respective solvent (15 mL)
under air.
b Isolated yields.
c 3-Chloro-1-phenylsuccinimide (8) was obtained as the main product in 70% yield.
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O
O
SOCl2
toluene
O
O
O
+
Δ
MeOH, reflux
HN
HN
OH
OMe
NH2
O
O
5
6
7
3b
Scheme 1 Synthesis of compound 3b
most important synthetic intermediates.13 Boron trifluoride
diethyl etherate (BF3·OEt2), an inexpensive Lewis acid, could
work well in a series of organic synthesis reaction.14 Herein,
we describe BF3·OEt2-catalyzed regioselective 1,2-addition
or 1,4-hetero Michael addition of OH, SH, and NH groups to
maleimides in moderate to excellent yields (up to 96%). In
addition, the notable advantages of this method are mild
conditions, short reaction times, high yields, and lack of any
side reaction products.
Our studies were initiated by examining catalyst useful-
ness and reaction conditions using N-phenylmaleimide (1)
and 2-phenylethanol (2a) as a model system because the
product is easy to detect and isolate (Table 1). The reaction
between 1 and 2a in the presence of Lewis acid is accom-
plished by heating the reagents in dichloromethane at re-
flux for several hours. Under catalyst-free condition, no re-
action took place and only the starting material 1 was re-
covered (Table 1, entry 1). At first, this reaction was run
using the classical Lewis acids, such as ZnCl2, ZnBr2, FeCl3,
AlCl3, and TiCl4. The product was obtained as a white solid
in ca. 40% yield using 0.2 equivalent of ZnCl2 or ZnBr2 as cat-
alyst. The yields cannot be improved by prolonging the re-
action time.
Next, this product was analyzed spectroscopically to
confirm the formation of the desired 1,4-Michael addition
product 4a. The analysis of NMR spectral data showed sev-
enteen hydrogen and eighteen carbons signals. Further-
more, the EI mass spectrum of this compound showed a
molecular ion at 295 (M+). High-resolution mass spectrum
suggested a molecular formula of C18H17NO3. The molecular
formula is consistent with the desired compound 4a. Lucki-
ly, chemical shifts in 1H NMR spectrum gave us a clue to de-
termine the structure of the product. A chemical shift at
10.9 ppm suggested that an active hydrogen should exist in
the isolated compound, but it was not found in the isolated
compound 4a. In order to understand this problem, we
used methanol as the nucleophile to run this reaction since
the desired product was reported in the literature.7e
Though analytical data similar to Xia’ s results were ob-
tained,7e the structure could not be assigned to the desired
3-methoxy-1-phenylpyrrolidine-2,5-dione. On the other
hand, hydrogen signals at 6.21 and 6.42 ppm with a cou-
pling constant of J = 13.3 Hz suggested that a trans-double
bond should exist in this isolated compound. Finally, we
presumed that a 1,2-addition of maleimide with methanol
might have proceeded in this reaction, which subsequently
undergoes ring-opening to provide methyl (E)-4-oxo-4-
(phenylamino)but-2-enoate (3b). Fortunately, Bello et al.
had reported the data of the 1,2-addition product in their
work on antibacterial agents,15 by preparing it from aniline
and maleic anhydride as shown in Scheme 1. Our results
were consistent with Bello’s data. On the basis of spectral
data, we believe that a 1,2-addition reaction had taken
place between maleimide and methanol. To the best of our
knowledge, this is the first example of Lewis acid catalyzed
1,2-addition to maleimide.
After confirming the structure of the 1,2-addition prod-
uct, methanol was used as the solvent to obtain only the
1,2-addition product 3b. No 1,4-Michael addition product
was obtained in this reaction. This indicated that the excess
oxygen nucleophile did not react with the C=C bond of ma-
leimide to form 3-methoxysuccinimide derivative. Our at-
tention was then turned to continue the screening of the
Lewis acids to improve the yield. However, when this reac-
tion was carried out with 0.2 equivalent of FeCl3, only a
trace amount of the product was observed (entry 5). The
possible reason is that FeCl3 led to the partial polymeriza-
tion of maleimides due to its oxidation property. Interest-
ingly, 3-chloro-1-phenylsuccinimide (8) was obtained in
70% yield in the place of phenethyl (E)-4-oxo-4-(phenyl-
amino)but-2-enoate (3a) when AlCl3 or TiCl4 was used as
catalysts (entries 6, 7). Based on the work of Coskun’s
group,16 it is known that N-phenylmaleimide (1) can direct-
ly be converted into 3-chloro-1-phenylsuccinimide (8) in
the presence of HCl. TiCl4 and AlCl3 can react with alcohol to
provide aluminum alkoxide and titanium alkoxide releasing
HCl in the reaction system. Then, N-phenylmaleimide re-
acts immediately with HCl to give 3-chloro-1-phenylsuc-
cinimide (8) in this reaction medium. It should be noted
that without any alcohol, the reaction could not generate
any of the product 8. The results support this hypothesis. A
plausible reaction process for the product 8 is proposed in
Scheme 2.
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Synthesis
+
ROH
HCl
+
AlCl3
Al(OR)3
CH2Cl2
reflux
+
HCl
N
N
O
O
O
O
Cl
1
8
Scheme 2 Proposed reaction process for the product 8
Next, in order to improve the yield, the reaction was
performed in the presence of other Lewis acids such as
BiCl3, ZrCl4, InBr3, AgBF4, RuCl3, Zn(OTf)2, Y(OTf)3, and
BF3·OEt2. Unfortunately, ZrCl4, InBr3, AgBF4, and RuCl3 did
not function as catalysts in this reaction (entries 8–11), and
the starting materials were recovered. The desired product
3a was obtained in the presence of BiCl3, Zn(OTf)2, or
Y(OTf)3 in a low yield of 30% (entries 12–14). To our delight,
use of 0.2 equivalent of BF3·OEt2 afforded the compound 3a
in 92% yield (Table 1, entry 15). Encouraged by this result,
the reaction conditions were then optimized. Rapid conver-
sion was observed when the reaction was carried out in di-
chloromethane (92% yield, entry 15) or 1,2-dichloroethane
(89% yield, entry 16). The reaction did not work by using
DMF, THF, and 1,4-dioxane as solvent (entries 17–19). The
above results demonstrated that BF3·OEt2 is a more effective
catalyst in comparison to ZnCl2. It should be noted that
without any catalyst, the reaction did not generate the de-
sired product at all.
Figure 2 Effect of BF3·OEt2 loading on the yield of 3a. Reaction condi-
tions: N-phenylmaleimide (1; 2.0 mmol), 2-phenylethanol (2a; 2.0
mmol), CH2Cl2 (15 mL), 12 h, reflux.
On the other hand, thiols have long been known to act
as metal catalyst poisons because of their strong coordinat-
ing and adsorptive properties, and often rendered the metal
catalytic reactions totally ineffective.18 Therefore, develop-
ing a more efficient catalyst system for S-Michael addition
remains open to study. To further illustrate the utility of
this method, a series of sulfur and nitrogen nucleophiles in-
cluding NH-containing heterocycles were applied to this
protocol (Table 3). Fortunately, further experiments re-
vealed that the BF3·OEt2-catalyzed reaction system could be
applied successfully to Michael addition of thiols and nitro-
gen nucleophiles to maleimide.
Though the yields were satisfactory, the structures of
the products were not assigned as 1,2-addition products by
analyzing the NMR spectral data. The reaction, however,
proceeded according to our initial hypothesis. Both the sul-
fur and nitrogen nucleophiles reacted with the C=C double
bond of the maleimides in a 1,4-addition manner (Scheme
3), and therefore no 1,2-addition product was observed.
Subsequently, the influence of the amount of the cata-
lyst on the reaction was also evaluated under identical reac-
tion conditions, as illustrated in Figure 2. Increasing the
loading of BF3·OEt2 initially led to a sharp increase in the
yield and further to a steady state. The yield approached to
92% by using 20 mol% of BF3·OEt2 as catalyst.
With the above optimal conditions in hand, the present
catalyst system was applied to examine the utility and gen-
erality of this method for hetero-Michael addition of oxy-
gen, sulfur, and nitrogen nucleophiles to maleimides. First,
1,2-addition of maleimides with oxygen nucleophiles cata-
lyzed by BF3·OEt2 was examined. In some cases, the isolated
yields were moderate to excellent (Table 2). It was found
that 2-phenylethanol and methanol were better nucleop-
hiles than the secondary alcohols (Table 2, entries 1–8) pro-
viding yields around 50–90%. However, tertiary alcohols
(e.g., tert-butyl alcohol) gave only trace yield and was un-
suitable for this method. As the steric hindrance of alkyl
chain for alcohol increased, the yields gradually decreased
(entries 4–6). In addition, two single broad peak around 5.8
ppm and 8.4 ppm were assigned to the amide group in the
1H NMR spectra due to hydrogen bonding (NH–O) interac-
tion of compounds 3g and 3h.17
R1
N
O
O
Lewis acid
Lewis acid
R1
N
R2X
R2 XH
4
X = S, N
O
O
O
R1
HN
1
2
X = S, N
R2
X
O
3
X = S, N
Scheme 3 1,4-Addition of the S and NH nucleophiles to maleimides
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Synthesis
It should be noted that without BF3·OEt2, the reaction
worked with a poor yield (26% yield, Table 3, entry 1) and
the yield was sharply raised under the optimal condition
(93% yield, entry 1). Since the reaction did not proceed with
the nitrogen nucleophiles in dichloromethane solution in
reflux condition, the temperature was increased by using
Table 2 BF3·OEt2-Catalyzed 1,2-Hetero-Michael Addition to Maleimidesa
Entry
Maleimide
Alcohol
Time (h)
Product
Yield (%)b
Ph
O
N
1
CH2CH2OH
12
3a
92
O
O
O
O
O
O
HN
HN
HN
O
O
Ph
N
O
2
3
MeOH
12
12
3b
3c
85
72
OMe
O
Ph
N
O
O
O
EtOH
O
O
O
O
Ph
N
4
5
6
i-PrOH
24
24
24
3d
3e
3f
52
45
53
O
O
O
O
O
O
HN
HN
O
O
Ph
N
s-BuOH
Ph
N
O
O
O
OH
HN
H2N
H2N
O
O
O
O
O
O
H
N
O
O
O
O
7
8
16
24
3g
3h
80
62
CH2CH2OH
H
N
OH
a Reaction conditions: maleimide (2.0 mmol), alkanol (2.0 mmol), catalyst (20 mol%), CH2Cl2 (15 mL), reflux.
b Isolated yield.
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1,2-dichloroethane as the solvent. The yields went up to
86% (entry 11). The results also revealed that the reactivity
decreased with the reducing number of N atoms in azoles
(entries 10–12). Besides this, p-toluenesulfonamide was
also used as the Michael addition acceptor. Unfortunately,
the reaction did not work well. By prolonging the refluxing
time to 36 hours, only a 34% yield could be obtained (entry
13).
Table 3 BF3·OEt2-Catalyzed 1,4-Hetero-Michael Addition to Maleimidesa
Entry
Maleimide
Nucleophile
Time (h)
Product
Yield (%)b
Ph
N
Ph
O
O
93
N
1
HSCH2CO2Me
12
4b
26c
O
O
O
O
SCH2CO2Me
Ph
N
Ph
N
O
O
2
12
4c
96
SH
S
Bn
N
Bn
N
O
O
O
3
4
5
EtSH
12
12
12
4d
4e
4f
90
77
91
O
O
O
O
SEt
H
N
H
N
O
HSCH2CO2Me
HSCH2CO2Me
SCH2CO2Me
Bn
N
Bn
N
O
O
O
O
O
O
SCH2CO2Me
Ph
N
Ph
N
Ph
N
O
O
O
O
6d
HSCH2CH2CH2SH
12
16
4g
4h
80
63
SCH2CH2CH2S
Ph
N
Ph
N
O
O
H
N
Ph
N
7
O
O
O
O
N
N
N
N
N
Ph
N
H
N
O
O
H
H
N
N
Ph
8
16
4i
61
N
N
N
N
N
N
Ph
N
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Table 3 (continued)
Entry
Maleimide
Nucleophile
Time (h)
Product
Yield (%)b
Me
N
Me
N
O
O
H
N
Ph
9
16
4j
55
O
O
N
N
N
N
N
N
Ph
N
Ph
N
Ph
N
O
O
N
N
10
16
4k
90
O
O
N
H
N
N
N
O
Ph
N
Ph
N
O
N
11
16
4l
86
O
O
N
H
N
N
O
Ph
N
Ph
N
O
N
12
13
16
36
4m
75
34
O
O
N
H
N
N
Me
N
O
4n
Me
O
O
O
N
SO2
SO2NH2
N
H
a Reaction conditions: maleimide (2.0 mmol), S and N nucleophiles (2.0 mmol), catalyst (20 mol%), DCE (15 mL), reflux.
b Isolated yield.
c Without BF3·OEt2.
d N-Phenylmaleimide (4.0 mmol).
The addition of acrylic acid derivatives to 5-phenyl-1H-
tetrazole has been reported to provide the addition product
at the N2 position of the 1H-tetrazoles.19 In order to con-
firm the result of 1,4-Michael addition in the same way,
single crystal of compound 4i suitable for X-ray analysis
was obtained by slow evaporation of a solution of this com-
pound in ethanol. The X-ray structure is shown in Figure 3.
The packing view of 4i in the unit cell and tables of X-ray
crystallographic data can be found in the Supporting Infor-
mation. The crystal data suggested that 5-phenyl-1H-tetra-
zole rearranged in the reaction and gave the N2-substitu-
tion product exclusively (Figure 3). No N1-substitution
product and 1,2-addition products were isolated. The target
compounds were obtained in moderate to excellent yields
with no formation of side products, such as polymers, that
are frequently encountered under the influence of strong
base.
We believe that BF3·OEt2 works well as an efficient cata-
lyst in our selected hetero-Michael addition protocol for ox-
ygen, sulfur, and nitrogen nucleophiles to maleimides. A
plausible mechanism for BF3·OEt2-catalyzed regioselective
hetero-Michael addition is proposed in Scheme 4. Although
we do not have additional evidence for this, we assume that
BF3·OEt2 readily coordinates to the oxygen atom of the car-
bonyl group.20 Presumably the intermediate 9 is formed,
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Synthesis
by increasing the electrophilic character of enal. A mecha-
nistic study in our laboratory to clarify the pathways for
BF3·OEt2 employing selected hetero-Michael addition is un-
der way.
In summary, BF3·OEt2 has been demonstrated to be an
efficient and green catalyst for the regioselective 1,2-addi-
tion or 1,4-hetero-Michael addition of oxygen, sulfur, and
nitrogen nucleophiles to maleimides. The reactions were
performed smoothly to generate the desired products in
moderate to excellent yields under safe experimental con-
ditions. Apart from the atom economy, the advantage of
this protocol is the use of a cheaper, milder, and more effi-
cient catalyst for the selective 1,2-addition or 1,4-hetero-
Michael addition reaction of maleimides. This method of-
fers one of the important motifs for the synthesis of alkyl
fumarates and 3-substituted succinimides as natural prod-
ucts, biologically active compounds, and pharmaceutical
agents.
Melting points were determined with RY-1 apparatus and are uncor-
rected. IR spectra were recorded as KBr pellets on a Shimadzu model
470 spectrophotometer. NMR (1H and 13C) spectra were recorded us-
ing a Bruker AV 400 MHz spectrometer in CDCl3 with TMS as internal
standard. Chemical shifts (δ) are expressed in ppm. EI mass spectra
were recorded on Shimadzu QP-2010 GC-MS system and Waters
Micromass GCT system. Silica gel (100–200 microns) was used for all
chromatographic separations. All materials were obtained from com-
mercial suppliers and were used as received. Petroleum ether (PE) re-
fers to a hydrocarbon mixture with a boiling range of 60–90 °C. The
purity of substrates and the monitoring of reactions were performed
by TLC on silica gel polygram SILG/UV 254 plates. Crystals of 3-(5-
phenyl-2H-tetrazol-2-yl)pyrrolidine-2,5-dione (4i) were obtained by
dissolving 4i (0.15 g) in EtOH (2 mL) and evaporating the solvent
Figure 3 The X-ray crystal structure of 3-(5-phenyl-2H-tetrazol-2-
yl)pyrrolidine-2,5-dione (4i)
which possibly reduces the activation energy required for
selective hetero-Michael addition. Next, the nucleophiles
are added to labile intermediates 9 in 1,2-addition or 1,4-
addition according to the different nucleophilic atoms to
furnish the corresponding hetero-Michael adducts 10 and
11. These adducts upon subsequent electron reorganization
followed by hydrogen transfer yield compounds 3 and 4, re-
spectively, releasing the catalyst for next cycle. In the cata-
lytic cycle, it is thought that BF3·OEt2 promotes the reaction
R2
N
R2
HN
O
BF3•OEt2
BF3
O
O
R1
X
O
R1
X
X = S, N
4
3
X = O
R2
N
F
R2
N
F
O
O
B
F
R2
N
F
O
O
F
B
1
O
O
F
R2
X
11
X
R1
H
F
H
R2
N
F
10
B
O
O
F
9
X = S, N 1,4-Michael addition
X = O 1,2-addition
R1
X
H
2
Scheme 4 Proposed mechanism for regioselective hetero-Michael addition catalyzed by BF3·OEt2
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slowly at r.t. over a week. The data were collected on CAD-4 diffrac-
tometer equipped with graphite-monochromatic MoKα radiation (λ =
0.71073 Å) by using a ω scan mode at 293(2) K. The structure of 4i is
shown in Figure 3. X-ray crystallographic data for compound 4i can be
found in the Supporting Information.
Isopropyl (E)-4-Oxo-4-(phenylamino)but-2-enoate (3d)15
Yield: 242 mg (52%); white solid; mp 58–60 °C.
IR (KBr): 3437, 2986, 2929, 1716, 1666, 1545, 1500, 1445, 1232, 1105,
754 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 1.32 (d, J = 6.3 Hz, 6 H, CH3), 5.10–5.18
(m, 1 H, CH), 6.18 (d, J = 13.4 Hz, 1 H, =CH), 6.41 (d, J = 13.4 Hz, 1 H,
=CH), 7.13 (d, J = 7.4 Hz, 1 Harom), 7.34 (t, J = 7.9 Hz, 2 Harom), 7.68 (d, J =
7.9 Hz, 2 Harom), 11.06 (s, 1 H, NH).
Selective Hetero-Michael Addition of Nucleophiles to Maleimides;
General Procedure
A mixture of the nucleophile (2.0 mmol), maleimide 1 (2.0 mmol),
BF3·OEt2 (20 mol%, 0.4 mmol) and CH2Cl2 (15 mL) was stirred at reflux
for the specified time (TLC monitoring, eluent: PE–EtOAc, 4:1). After
completion of the reaction, the mixture was cooled to r.t., and H2O (15
mL) was added. The mixture was extracted with EtOAc (2 × 15 mL),
and the combined organic phases were washed with H2O (2 × 10 mL),
and dried (Na2SO4). The solvent was removed and the residue was pu-
rified by silica gel column chromatography (PE–EtOAc, 6:1) as eluent
to yield the pure product. For compounds 4h–n, DCE was used as the
solvent instead of CH2Cl2. The products were characterized by IR, 1H
NMR, 13C NMR, and HRMS analyses. All the products are known com-
pounds, and the mp, IR, and NMR data are in accordance with those
reported in the literature.
13C NMR (101 MHz, CDCl3): δ = 21.68, 70.03, 120.06, 124.51, 125.83,
128.99, 137.96, 140.32, 161.63, 166.39.
MS (EI): m/z = 233 [M]+, 191, 174, 146, 120, 99, 93, 77.
HRMS (EI): m/z calcd for C13H15NO3: 233.1052; found: 233.1055.
sec-Butyl (E)-4-Oxo-4-(phenylamino)but-2-enoate (3e)15
Yield: 222 mg (45%); white solid; mp 40–42 °C.
IR (KBr): 3432, 2970, 2917, 1715, 1360, 1545, 1390, 1231, 754, 698
cm–1
.
1H NMR (400 MHz, CDCl3): δ = 0.93 (t, J = 7.3 Hz, 3 H, CH3), 1.30 (d, J =
6.1 Hz, 3 H, CH3), 1.61–1.70 (m, 2 H, CH2), 4.98–5.01 (m, 1 H, CH), 6.21
(d, J = 12.8 Hz, 1 H, =CH), 6.42 (d, J = 12.7 Hz, 1 H, =CH), 7.14 (t, J = 6.9
Hz, 1 Harom), 7.34 (t, J = 7.3 Hz, 2 Harom), 7.68 (d, J = 7.6 Hz, 2 Harom),
11.12 (s, 1 H, NH).
Phenethyl (E)-4-Oxo-4-(phenylamino)but-2-enoate (3a)
Yield: 542 mg (92%); white solid; mp 100–102 °C.
13C NMR (101 MHz, CDCl3): δ = 9.60, 19.26, 28.63, 74.61, 120.08,
IR (KBr): 3439, 2913, 1721, 1630, 1545, 1494, 1228, 749 cm–1
.
124.51, 125.79, 128.98, 137.93, 140.44, 161.60, 166.57.
MS (EI): m/z = 247 [M]+, 191, 174, 146, 120, 93, 77.
1H NMR (400 MHz, CDCl3): δ = 3.07 (t, J = 7.0 Hz, 2 H, CH2), 4.51 (t, J =
7.0 Hz, 2 H, CH2), 6.26 (d, J = 13.3 Hz, 1 H, =CH), 6.48 (d, J = 13.3 Hz, 1
H, =CH), 7.18 (t, J = 7.3 Hz, 1 Harom), 7.27–7.37 (m, 3 Harom), 7.38 (dd, J =
16.6, 8.0 Hz, 4 Harom), 7.71 (d, J = 7.9 Hz, 2 Harom), 10.92 (s, 1 H, NH).
HRMS (EI): m/z calcd for C14H17NO3: 247.1208; found: 247.1211.
13C NMR (101 MHz, CDCl3): δ = 34.84, 66.41, 120.10, 124.60, 125.10,
126.87, 128.67, 128.89, 129.02, 137.10, 137.83, 140.61, 161.47,
166.76.
Cyclohexyl (E)-4-Oxo-4-(phenylamino)but-2-enoate (3f)
Yield: 289 mg (53%); white solid; mp 90–92 °C.
IR (KBr): 3434, 2932, 2851, 1715, 1629, 1547, 1387, 1227, 1024, 750
MS (EI): m/z = 295 [M]+, 191, 173, 146, 105, 91, 77.
cm–1
.
HRMS (EI): m/z calcd for C18H17NO3: 295.1208; found: 295.1203.
1H NMR (400 MHz, CDCl3): δ = 1.32 (dd, J = 36.0, 11.4 Hz, 2 H, CH2),
1.41–1.52 (m, 4 H, CH2), 1.75–1.78 (m, 2 H, CH2), 1.90–1.92(m, 2 H,
CH2), 4.86–4.94 (m, 1 H, CH), 6.21 (d, J = 13.4 Hz, 1 H, =CH), 6.43 (d, J =
13.3 Hz, 1 H, =CH), 7.13 (d, J = 7.4 Hz, 1 Harom), 7.34 (t, J = 7.8 Hz, 2
Methyl (E)-4-Oxo-4-(phenylamino)but-2-enoate (3b)15,21
Yield: 348 mg (85%); white solid; mp 72–75 °C.
H
arom), 7.68 (d, J = 7.9 Hz, 2 Harom), 11.15 (s, 1 H, NH).
IR (KBr): 3445, 3137, 2949, 1726, 1670, 1631, 1605, 1544, 1495, 1441,
13C NMR (101 MHz, CDCl3): δ = 23.65, 25.20, 31.39, 74.92, 120.07,
1232, 1173, 754 cm–1
.
124.53, 125.94, 128.99, 137.94, 140.36, 161.63, 164.21.
MS (EI): m/z = 273 [M]+, 191, 173, 146, 132, 93, 77.
1H NMR (400 MHz, CDCl3): δ = 3.85 (s, 3 H, CH3), 6.23 (d, J = 13.3 Hz, 1
H, =CH), 6.44 (d, J = 13.3 Hz, 1 H, =CH), 7.26 (t, J = 7.3 Hz, 1 Harom), 7.35
(t, J = 7.6 Hz, 2 Harom), 7.67 (d, J = 7.9 Hz, 2 Harom), 10.86 (s, 1 H, NH).
HRMS (EI): m/z calcd for C16H19NO3: 273.1365; found: 273.1363.
13C NMR (101 MHz, CDCl3): δ = 52.84, 120.12, 124.64, 125.01, 129.03,
137.81, 140.35, 161.51, 167.31.
Phenethyl (E)-4-Amino-4-oxobut-2-enoate (3g)
MS (EI): m/z = 205 [M]+, 173, 146, 113, 93, 77.
Yield: 350 mg (80%); white solid; mp 50–52 °C.
IR (KBr): 3426, 3182, 1723, 1675, 1424, 1224, 1183, 746 cm–1
.
Ethyl (E)-4-Oxo-4-(phenylamino)but-2-enoate (3c)15,22
Yield: 315 mg (72%); white solid; mp 57–60 °C.
1H NMR (400 MHz, CDCl3): δ = 3.02 (t, J = 7.0 Hz, 2 H, CH2), 4.43 (t, J =
7.0 Hz, 2 H, CH2), 5.94 (s, 1 H, NH2), 6.19 (d, J = 13.1 Hz, 1 H, =CH), 6.33
(d, J = 13.1 Hz, 1 H, =CH), 7.27 (dd, J = 12.4, 6.1 Hz, 3 Harom), 7.35 (t, J =
7.3 Hz, 2 Harom), 8.14 (s, 1 H, NH).
IR (KBr): 3436, 3313, 3129, 2986, 1722, 1671, 1604, 1544, 1494, 1225,
755 cm–1
.
13C NMR (101 MHz, CDCl3): δ = 34.82, 66.10, 126.05, 126.82, 128.65,
128.90, 137.24, 137.96, 165.87, 165.99.
MS (EI): m/z = 219 [M]+, 122, 104, 98, 91, 77.
1H NMR (400 MHz, CDCl3): δ = 1.34 (t, J = 7.0 Hz, 3 H, CH3), 4.30 (q, J =
6.9 Hz, 2 H, CH2), 6.21 (d, J = 13.3 Hz, 1 H, =CH), 6.44 (d, J = 13.2 Hz, 1
H, =CH), 7.13 (t, J = 7.2 Hz, 1 Harom), 7.34 (t, J = 7.5 Hz, 2 Harom), 7.67 (d,
J = 7.8 Hz, 2 Harom), 11.01 (s, 1 H, NH).
HRMS (EI): m/z calcd for C12H13NO3: 219.0895; found: 219.0896.
13C NMR (101 MHz, CDCl3): δ = 14.02, 62.12, 120.09, 124.59, 125.44,
129.01, 137.85, 140.36, 161.58, 166.88.
MS (EI): m/z = 219 [M]+, 173, 146, 99, 93, 77.
Cyclohexyl (E)-4-Amino-4-oxobut-2-enoate (3h)
Yield: 245 mg (62%); white solid; mp 104–108 °C.
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IR (KBr): 3430, 2934, 2855, 1715, 1637, 1386, 1223, 1012 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 1.28 (t, J = 7.4 Hz, 3 H, CH3), 2.53 (dd,
J = 18.7, 3.6 Hz, 1 H, CH2), 2.77–2.72 (m, 1 H, CH2), 2.90–2.85 (m, 1 H,
CH2), 3.13 (dd, J = 18.7, 9.1 Hz, 1 H, CH2), 3.74 (dd, J = 9.1, 3.6 Hz, 1 H,
CH), 4.62–4.71 (m, 2 H, CH2), 7.27–7.33 (m, 3 Harom), 7.37–7.38 (m, 2
1H NMR (400 MHz, CDCl3): δ = 1.19–1.55 (m, 6 H, CH2), 1.74–1.90 (m,
4 H, CH2), 4.83–4.87 (m, 1 H, CH), 5.87 (s, 1 H, NH), 6.18 (d, J = 13.1 Hz,
1 H, =CH), 6.29 (d, J = 13.1 Hz, 1 H, =CH), 8.43 (s, 1 H, NH).
13C NMR (101 MHz, CDCl3): δ = 23.64, 25.22, 31.38, 74.54, 126.93,
137.56, 165.51, 166.02.
MS (EI): m/z = 198 [M + H]+, 116, 98.
HRMS (EI): m/z [M+ + H] calcd for C10H16NO3: 198.1130; found:
H
arom).
13C NMR (101 MHz, CDCl3): δ = 14.16, 25.80, 36.11, 38.80, 42.61,
128.02, 128.68, 128.70, 135.45, 174.40, 176.32.
MS (EI): m/z = 249 [M]+, 189, 132, 91, 77.
HRMS (EI): m/z calcd for C13H15NO2S: 249.0824; found: 249.0827.
198.1132.
Methyl 2-[(2,5-Dioxopyrrolidin-3-yl)thio]acetate (4e)
Yield: 312 mg (77%); light yellow oil.
3-Chloro-1-phenylpyrrolidine-2,5-dione (8)16,23
Yield: 292.6 mg (70%); white solid; mp 114–116 °C.
IR (KBr): 3436, 3252, 2949, 1777, 1714, 1629, 1339, 1282, 1177, 775,
IR (KBr): 2916, 2848, 1789, 1718, 1499, 1388, 1276, 1179, 952, 744,
690 cm–1
.
695 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 2.57 (dd, J = 18.9, 4.1 Hz, 1 H, CH2), 3.21
(dd, J = 18.9, 9.3 Hz, 1 H, CH2), 3.39 (d, J = 15.8 Hz, 1 H, CH2), 3.77 (s, 3
H, CH3), 3.89 (d, J = 15.8 Hz, 1 H, CH2), 4.08 (dd, J = 9.2, 4.1 Hz, 1 H,
CH), 8.83 (s, 1 H, NH).
13C NMR (101 MHz, CDCl3): δ = 32.87, 36.57, 39.73, 52.76, 170.14,
174.73, 176.71.
1H NMR (400 MHz, CDCl3): δ = 3.10 (dd, J = 18.9, 3.9 Hz, 1 H, CH2), 3.49
(dd, J = 18.9, 8.7 Hz, 1 H, CH2), 4.79 (dd, J = 8.7, 3.9 Hz, 1 H, CH), 7.31
(d, J = 7.6 Hz, 2 Harom), 7.44 (t, J = 7.2 Hz, 1 Harom), 7.50 (t, J = 7.5 Hz, 2
H
arom).
13C NMR (101 MHz, CDCl3): δ = 39.43, 48.96, 126.28, 129.17, 129.37,
131.17, 171.97, 172.00.
MS (EI): m/z = 209 [M]+, 174, 146, 119, 91, 77.
MS (EI): m/z = 203 [M]+, 171, 144, 130, 99.
HRMS (EI): m/z calcd for C7H9NO4S: 203.0252; found: 203.0253.
Methyl 2-[(2,5-Dioxo-1-phenylpyrrolidin-3-yl)thio]acetate (4b)8f
Yield: 519 mg (93%); light yellow oil.
Methyl-2-[(1-Benzyl-2,5-dioxopyrrolidin-3-yl)thio]acetate (4f)
Yield: 533 mg (91%); light yellow oil.
IR (KBr): 3456, 2945, 1704, 1495, 1395, 1165, 739, 700 cm–1
.
IR (KBr): 3456, 2945, 1715, 1605, 1495, 1384, 1290, 1182, 743, 698
cm–1
.
1H NMR (400 MHz, CDCl3): δ = 2.69 (dd, J = 18.9, 3.9 Hz, 1 H, CH2), 3.32
(dd, J = 18.9, 9.3 Hz, 1 H, CH2), 3.43 (d, J = 15.9 Hz, 1 H, CH2), 3.76 (s, 3
H, CH3), 3.94 (d, J = 9.3, 15.9 Hz, 1 H, CH2), 4.19 (dd, J = 9.3, 3.9 Hz, 1 H,
CH), 7.27–7.33 (m, 2 Harom), 7.37–7.44 (m, 1 Harom), 7.49 (dd, J = 10.3,
4.7 Hz, 2 Harom).
1H NMR (400 MHz, CDCl3): δ = 2.51 (dd, J = 18.8, 3.9 Hz, 1 H, CH2), 3.13
(dd, J = 18.8, 9.2 Hz, 1 H, CH2), 3.35 (d, J = 15.9 Hz, 1 H, CH2), 3.73 (s, 3
H, CH3), 3.90 (d, J = 15.9 Hz, 1 H, CH2), 4.02 (dd, J = 9.2, 3.9 Hz, 1 H,
CH), 4.61–4.69 (m, 2 H, CH2), 7.27–7.31 (m, 3 Harom), 7.35–7.37 (m, 2
H
arom).
13C NMR (101 MHz, CDCl3): δ = 32.87, 35.49, 38.53, 52.74, 126.44,
13C NMR (101 MHz, CDCl3): δ = 32.85, 35.41, 38.38, 42.66, 52.66,
128.87, 129.24, 131.53, 170.06, 173.38, 175.19.
128.08, 128.71, 135.34, 170.02, 174.01, 176.01.
MS (EI): m/z = 279 [M]+, 263, 247, 220, 206, 175, 147, 119, 91.
MS (EI): m/z = 293 [M]+, 261, 234, 220, 189, 160, 132, 106, 91, 78.
HRMS (EI): m/z calcd for C14H15NO4S: 293.0722; found: 293.0725.
3-(Cyclohexylthio)-1-phenylpyrrolidine-2,5-dione (4c)24
Yield: 555 mg (96%); white solid; mp 102–104 °C.
3,3′-[Propane-1,3-diylbis(sulfanediyl)]bis(1-phenylpyrrolidine-
2,5-dione) (4g)
IR (KBr): 3437, 2929, 2847, 1772, 1714, 1630, 1491, 1381, 1177, 739,
694 cm–1
.
Yield: 726 mg (80%); light yellow solid; mp 107–109 °C.
1H NMR (400 MHz, CDCl3): δ = 1.25–1.49 (m, 5 H, CH2), 1.59–1.69 (m,
1 H, CH2), 1.80 (dd, J = 12.3, 2.8 Hz, 2 H, CH2), 1.95 (s, 1 H, CH2), 2.18
(d, J = 11.2 Hz, 1 H, CH2), 2.68 (dd, J = 18.7, 3.6 Hz, 1 H, CH), 3.29 (dt, J =
22.9, 11.5 Hz, 2 H, CH2), 3.97 (dd, J = 9.1, 3.5 Hz, 1 H, CH), 7.30 (d, J =
7.6 Hz, 2 Harom), 7.40 (t, J = 7.4 Hz, 1 Harom), 7.48 (t, J = 7.5 Hz, 2 Harom).
IR (KBr): 3447, 2917, 1781, 1712, 1637, 1495, 1382, 1177, 1029, 743,
690 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 2.12–2.04 (m, 2 H, CH2), 2.66 (dd, J =
18.8, 3.5 Hz, 2 H, CH2), 2.95–2.90 (m, 2 H, CH2), 3.12–3.17 (m, 2 H,
CH2), 3.30 (dd, J = 18.8, 9.2 Hz, 2 H, CH2), 3.92–3.86 (m, 2 H, CH), 7.29
(d, J = 7.4 Hz, 4 Harom), 7.36–7.44 (m, 2 Harom), 7.48 (t, J = 7.5 Hz, 4
13C NMR (101 MHz, CDCl3): δ = 25.68, 25.75, 25.96, 32.91, 33.55,
36.52, 37.75, 43.89, 126.42, 128.72, 129.19, 131.73, 173.88, 175.76.
Harom).
MS (EI): m/z = 289 [M]+, 207, 175, 147, 119, 91.
13C NMR (101 MHz, CDCl3): δ = 28.17, 28.42, 30.60, 30.75, 36.00,
38.93, 39.11, 126.41, 128.83, 129.23, 131.60, 173.55, 175.39.
MS (EI): m/z = 454 [M]+, 280, 208, 175, 146, 119, 91.
1-Benzyl-3-(ethylthio)pyrrolidine-2,5-dione (4d)
Yield: 448 mg (90%); light yellow solid; mp 58–60 °C.
HRMS (EI): m/z calcd for C23H22N2O4S2: 454.1021; found: 454.1025.
IR (KBr): 3460, 2970, 2925, 1772, 1705, 1486, 1393, 1345, 1166, 694
cm–1
.
1-Phenyl-3-(5-phenyl-2H-tetrazol-2-yl)pyrrolidine-2,5-dione (4h)
Yield: 366 mg (63%); white solid; mp 154–156 °C.
IR (KBr): 3437, 1726, 1634, 1495, 1454, 1387, 1192, 743, 694 cm–1
.
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1H NMR (400 MHz, CDCl3): δ = 3.57 (dd, J = 18.4, 5.7 Hz, 1 H, CH2), 3.66
(dd, J = 18.5, 9.4 Hz, 1 H, CH2), 6.19 (dd, J = 9.2, 5.9 Hz, 1 H, CH), 7.40
(d, J = 7.5 Hz, 2 Harom), 7.45–7.53 (m, 6 Harom), 8.18–8.17 (m, 2 Harom).
13C NMR (101 MHz, CDCl3): δ = 35.39, 59.82, 126.29, 126.56, 127.12,
129.02, 129.40, 129.46, 130.94, 166.27, 168.99, 171.31.
MS (EI): m/z = 319 [M]+, 263, 234, 208, 180, 144, 119, 104, 91, 77.
HRMS (EI): m/z [M+ – N2] calcd for C17H13N3O2: 291.1008; found:
3-(1H-Indazol-1-yl)-1-phenylpyrrolidine-2,5-dione (4m)
Yield: 436 mg (75%); white solid; mp 158–160 °C.
IR (KBr): 3437, 2929, 1789, 1721, 1629, 1503, 1384, 1188, 747, 694
cm–1
.
1H NMR (400 MHz, CDCl3): δ = 3.49 (dd, J = 18.3, 9.3 Hz, 1 H, CH2), 3.86
(dd, J = 18.4, 4.9 Hz, 1 H, CH2), 5.56 (dd, J = 9.0, 5.0 Hz, 1 H, CH), 7.12–
7.19 (m, 1 Harom), 7.28–7.60 (m, 6 Harom), 7.68 (t, J = 8.9 Hz, 2 Harom),
8.17 (s, 1 Harom).
291.1011.
13C NMR (101 MHz, CDCl3): δ = 35.61, 60.10, 117.61, 120.38, 121.85,
122.54, 124.75, 126.43, 127.06, 129.06, 129.28, 131.37, 149.66,
171.26, 172.59.
3-(5-Phenyl-2H-tetrazol-2-yl)pyrrolidine-2,5-dione (4i)
Yield: 296 mg (61%); white solid; mp 160–162 °C.
MS (EI): m/z = 291 [M]+, 173, 144, 118, 91, 77.
IR (KBr): 3442, 3227, 2953, 1797, 1711, 1454, 1384, 1274, 1163, 935,
714, 677 cm–1
.
HRMS (EI): m/z calcd for C17H13N3O2: 291.1008; found: 291.1002.
1H NMR (400 MHz, CDCl3): δ = 3.43–3.59 (m, 2 H, CH2), 6.08 (t, J = 8.0
Hz, 1 H, CH), 7.51 (s, 3 Harom), 8.15 (s, 2 Harom), 8.36 (s, 1 H, NH).
4-Methyl-N-(1-methyl-2,5-dioxopyrrolidin-3-yl)benzenesulfon-
amide (4n)
13C NMR (101 MHz, CDCl3): δ = 36.31, 60.64, 126.49, 127.11, 129.03,
Yield: 191 mg (34%); white solid; mp 154–156 °C.
130.97, 166.29, 169.27, 171.38.
MS (EI): m/z = 243 [M]+, 215, 186, 159, 144, 116, 104, 89, 77.
IR (KBr): 3440, 3256, 2917, 2847, 1781, 1706, 1605, 1442, 1389, 1335,
1290, 1158, 1029, 816, 661 cm–1
.
HRMS (EI): m/z calcd for C11H9N5O2: 243.0756; found: 243.0758.
1H NMR (400 MHz, CDCl3): δ = 2.45 (s, 3 H, CH3), 2.82 (dd, J = 18.2, 5.6
Hz, 1 H, CH2), 2.98 (s, 3 H, CH3), 3.10 (dd, J = 18.3, 8.5 Hz, 1 H, CH2),
4.09 (s, 1 H, NH), 5.29 (s, 1 H, CH), 7.35 (t, J = 9.7 Hz, 2 Harom), 7.80 (t,
J = 11.3 Hz, 2 Harom).
13C NMR (101 MHz, CDCl3): δ = 21.62, 25.25, 37.07, 51.62, 127.44,
130.08, 135.47, 144.61, 173.63, 174.54.
1-Methyl-3-(5-phenyl-2H-tetrazol-2-yl)pyrrolidine-2,5-dione (4j)
Yield: 282 mg (55%); white solid; mp 134–136 °C.
IR (KBr): 3448, 2921, 1771, 1643, 1440, 1383, 1282, 1117, 792, 735,
681 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 3.18 (s, 3 H, CH3), 3.40 (dd, J = 18.3, 5.6
Hz, 1 H, CH2), 3.49 (dd, J = 18.3, 9.3 Hz, 1 H, CH2), 6.03 (dd, J = 9.2, 5.7
Hz, 1 H, CH), 7.47–7.55 (m, 3 Harom), 8.20–8.08 (m, 2 Harom).
MS (EI): m/z = 282 [M]+, 218, 155, 133, 127, 91.
HRMS (EI): m/z calcd for C12H14N2O4S: 282.0674; found: 282.0669.
13C NMR (101 MHz, CDCl3): δ = 25.79, 35.29, 59.73, 126.59, 127.08,
128.97, 130.86, 166.17, 169.98, 172.26.
MS (EI): m/z = 257 [M]+, 229, 200, 172, 144, 115, 104, 89, 77.
Acknowledgment
The authors acknowledge the financial support from the National
Natural Science Foundation of China (Grant 21072029), Shanghai Mu-
nicipal Natural Science Foundation (No. 15ZR1401400), and the Open
Funds from the State Key Laboratory of Bioorganic & Natural Products
for financial support. Furthermore, the authors declare that they have
no conflicts of interest in the financial aspect of the research project.
HRMS (EI): m/z calcd for C12H11N5O2: 257.0913; found: 257.0917.
3-(1H-Benzotriazol-1-yl)-1-phenylpyrrolidine-2,5-dione (4k)25
Yield: 525 mg (90%); white solid; mp 146–148 °C.
IR (KBr): 3440, 2925, 1723, 1629, 1495, 1387, 1194, 745, 696 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 3.64 (dd, J = 18.5, 9.6 Hz, 1 H, CH2), 3.86
(dd, J = 18.4, 5.4 Hz, 1 H, CH2), 5.97 (dd, J = 9.5, 5.6 Hz, 1 H, CH), 7.37
(d, J = 7.6 Hz, 2 Harom), 7.40–7.55 (m, 4 Harom), 7.56–7.71 (m, 2 Harom),
8.13 (d, J = 8.4 Hz, 1 Harom).
13C NMR (101 MHz, CDCl3): δ = 34.87, 55.67, 108.99, 120.63, 124.76,
126.32, 128.57, 129.24, 129.39, 131.13, 133.19, 146.24, 170.69,
171.93.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1380404.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
o
nrtogI
f
rmoaitn
MS (EI): m/z = 292 [M]+, 263, 236, 117, 103, 91, 76.
References
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3-(1H-Benzimidazol-1-yl)-1-phenylpyrrolidine-2,5-dione (4l)26
Yield: 500 mg (86%); light brown solid; mp 176–178 °C.
IR (KBr): 3436, 2917, 1719, 1632, 1493, 1384, 1183, 747, 697 cm–1
.
1H NMR (400 MHz, CDCl3); δ = 3.25 (dd, J = 18.6, 5.8 Hz, 1 H, CH2), 3.56
(dd, J = 18.6, 9.7 Hz, 1 H, CH2), 5.62 (dd, J = 9.5, 6.0 Hz, 1 H, CH), 7.18–
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171.27, 171.66.
MS (EI): m/z = 291 [M]+, 173, 144, 118, 91, 77.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 1581–1592

1592
Y.-L. An et al.
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