Molecular diversity of three-component reactions of aromatic aldehydes, arylamines, and acetylenedicarboxylates

Article abstract of DOI:10.1002/ejoc.201100008

The three-component reactions of aromatic aldehydes, arylamines, and acetylenedicarboxylates show very interesting molecular diversity. In an aqueous ethanol solution the three-component reaction gave polysubstituted 2-hydroxyhydropyridines. In absolute ethanol 1,4-dihydropyridines were produced in satisfactory yields. Finally, under acid catalysis, this three-component reaction afforded polysubstituted 2-pyrrolidinones. The reaction mechanism for the formation of the three products is briefly explained. Polysubstituted 2-hydroxyhydropyridines, 1,4-dihydropyridines, and 2-pyrrolidinones were selectively obtained from the multicomponent reactions of aromatic aldehydes, arylamines, and acetylenedicarboxylates.

Full text of DOI:10.1002/ejoc.201100008

FULL PAPER
DOI: 10.1002/ejoc.201100008
Molecular Diversity of Three-Component Reactions of Aromatic Aldehydes,
Arylamines, and Acetylenedicarboxylates
Jing Sun,[a] Qun Wu,[a] Er-Yan Xia,[a] and Chao-Guo Yan*[a]
Keywords: Multicomponent reactions / Domino reactions / Nitrogen heterocycles / Aldehydes / Amines /
Acetylenedicarboxylates
The three-component reactions of aromatic aldehydes, aryl- produced in satisfactory yields. Finally, under acid catalysis,
amines, and acetylenedicarboxylates show very interesting
molecular diversity. In an aqueous ethanol solution the three-
component reaction gave polysubstituted 2-hydroxyhy-
dropyridines. In absolute ethanol 1,4-dihydropyridines were
this three-component reaction afforded polysubstituted 2-
pyrrolidinones. The reaction mechanism for the formation of
the three products is briefly explained.
ponent reactions of aromatic aldehydes, arylamines, and
acetylenedicarboxylates, as well as an efficient synthesis for
hydroxy-substituted hydropyridine and pyrrolidinone deriv-
atives.
Introduction
Enaminones and enamino esters combine the nucleo-
philic enamine and the electrophilic enone (ester) moieties
into one molecule. They are readily obtainable and versatile
reagents, and their chemistry has received considerable at-
tention in recent years.[1,2] Besides their use as bidentate li-
gands in metal-complex synthesis, β-enaminones and en-
amino esters have been extensively employed as synthons
for the synthesis of a wide variety of heterocycles and phar-
maceutical compounds.[3,4] The most well-known synthetic
route to β-enaminones and enamino esters is the direct con-
densation of β-dicarbonyl compounds with primary and
secondary amines in the appropriate solvent. For this pur-
pose, various improved procedures have been developed.[5]
The Huisgen addition is the addition of nitrogen-containing
heterocycles such as pyridine and isoquinoline to electron-
deficient alkynes giving a very potent intermediate, which
can then be trapped by various reagents.[3c,6] In fact, the
Huisgen addition is also a convenient method for the prepa-
ration of β-enaminones and esters by adding aliphatic and
aromatic amines to activated alkynes with carbonyl
groups.[7,8] The domino reactions of a primary amine, an
acetylenedicarboxylate, and a third component have pro-
vided elegant procedures for the synthesis of various N- and
N,O-heterocycles.[9–11] Recently, we have found that the
four-component reactions of arylamines, acetylenedicarb-
oxylate, aromatic aldehydes, and acetonitrile derivatives
provide an efficient and practical method for the synthesis
of 1,4-dihydropyridines.[12] In this paper we report the new
molecular diversity that can be achieved by the three-com-
Results and Discussion
It is known that the conjugate addition of aniline to ace-
tylenedicarboxylate rapidly gives 2-(phenylamino)but-2-en-
edioate.[8,13] We believe that a double conjugate adduct
could be achieved if a second molecule of acetylenedicar-
boxylate was added to the reaction system, and that this
adduct might be useful as a potential synthon for tandem
reactions. Recently, the AgBF4-catalyzed addition and oxi-
dative cyclization of two molecules of alkynoates with ben-
zylamine to give polysubstituted pyrroles[14] and the one-
pot sequential reaction of benzoylacetylene with 2-furylme-
thylamine to give 1,4-dihydropyridines[15] have been re-
ported as two successful examples of this synthetic method-
ology. With this concept in mind, we began to investigate
the reaction with dimethyl acetylenedicarboxylate. An etha-
nol solution of 1 m aniline and 2 m dimethyl acetylenedicar-
boxylate was stirred at room temperature for 10 min. A 1 m
solution of p-methylbenzaldehyde was then added, and the
whole mixture was stirred at room temperature for an ad-
ditional 48 h. After workup, we were very pleased to find
that the polysubstituted 2-hydroxyhydropyridine 1a was
produced in satisfactory yield (71%). In fact, it was con-
structed from the corresponding units of one molecule of
aniline, one molecule of p-methylbenzaldehyde, and two
molecules of dimethyl acetylenedicarboxylate. The existence
of one hydroxy group at the C-2 position was totally unex-
pected, which clearly resulted from a hydration step in the
reaction process. Next, the reaction conditions of the three-
component reaction were examined with regard to base cat-
[a] College of Chemistry & Chemical Engineering,
Yangzhou University,
Yangzhou 225002, China
E-mail: cgyan@yzu.edu.cn
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201100008.
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J. Sun, Q. Wu, E.-Y. Xia, C.-G. Yan
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alyst, solvent, temperature, and sequence of the addition of
substrates. The reaction was much slower in solvents such
as acetonitrile, tetrahydrofuran, dichloromethane, or chlo-
roform. If the reaction was carried out at an elevated tem-
perature or with the addition of a base catalyst, a compli-
cated mixture was formed. Although the reaction time was
a little longer, it was best to conduct this three-component
reaction in alcohol at room temperature over 2 d. Under
identical conditions, reactions between similar aromatic al-
dehydes and arylamines gave the corresponding polysubsti-
tuted 2-hydroxyhydropyridines 1b–1n in high yields
(Table 1). Aromatic aldehydes and amines with either elec-
tron-donating or -withdrawing substituents showed similar
reactivity and efficiently afforded the desired products. Both
α-naphthylamine and benzylamine were used in the reac-
tion and resulted in good yields of products (Table 1, En-
tries 12 and 13), and diethyl acetylenedicarboxylate also
showed very high reactivity (Table 1, Entry 14). These re-
sults indicate that this three-component reaction is general
and has a very broad substrate scope. The structures of 2-
hydroxyhydropyridines 1a–1n were supported by elemental
Figure 1. Molecular structure of 2-hydroxyhydropyridine 1d.
anol under nitrogen using a Schlenk line. Under these ab-
solutely dry conditions, we successfully obtained the ex-
pected polysubstituted 1,4-dihydropyridines 2a–2f in 68–
81% yields (Table 2).
1
analysis, H and 13C NMR and IR spectroscopy as well as
mass spectrometry. Further confirmation of the structure
with single-crystal X-ray diffraction was used for com-
pounds 1b and 1d (Figure 1). From Figure 1 it is clear that
the hydroxy group is connected to the C-2 atom of the pyr-
idyl ring. The tetrahydropyridine ring exists in a boat con-
formation, and the two ester groups at C-2 and C-3 are in
the trans position. The other two ester groups are attached
to the C=C bond.
Table 2. Synthesis of polysubstituted 1,4-dihydropyridines.
Table 1. Synthesis of polysubstituted 2-hydroxytetrahydropyridines.
Entry Product
Ar
ArЈ
R
Yield [%]
1
2
3
4
5
6
2a
2b
2c
2d
2e
2f
p-CH3OC6H4 p-CH3C6H4
m-O2NC6H4 p-CH3C6H4
p-CH3OC6H4 p-CH3OC6H4 Me
Me
Me
69
77
75
81
68
71
m-O2NC6H4
m-O2NC6H4
m-O2NC6H4
p-ClC6H4
C6H5
p-ClC6H4
Me
Et
Et
Entry Product
Ar
ArЈ
R
Yield [%]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
p-CH3C6H4
m-O2NC6H4
C6H5
p-ClC6H4
p-BrC6H4
m-O2NC6H4 p-CH3C6H4
C6H5
p-CH3OC6H4 p-CH3OC6H4 Me
m-O2NC6H4 p-CH3OC6H4 Me
C6H5
C6H5
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
Me
Me
Me
Me
Me
Me
71
81
73
79
72
84
78
78
86
74
87
68
70
74
To examine the reaction mechanism of this three-compo-
nent reaction, we tested the reactivity of the prepared 2-
hydroxytetrahydropyridines in a dehydration reaction. In
the presence of the catalyst p-toluenesulfonic acid (TsOH),
a solution of the 2-hydroxyhydropyridines in ethanol was
heated to reflux for approximately 1 h. The 2-hydroxypyr-
idines were successfully dehydrated to give the correspond-
ing 1,4-dihydropyridines in nearly quantitative yields
(Table 3). It should be pointed out that 1,4-dihydropyr-
idines 2b and 2c (Table 3, Entries 1 and 2) were also pre-
pared directly by a three-component reaction in absolute
p-CH3OC6H4 Me
C6H5
p-ClC6H4
p-ClC6H4
α-naphthyl
C6H5CH2
Me
Me
Me
Me
m-O2NC6H4
m-O2NC6H4
p-CH3OC6H4
m-O2NC6H4 p-CH3OC6H4 Et
The formation of 2-hydroxytetrahydropyridine from the ethanol (Table 2, Entries 2 and 3). The other 1,4-dihydropy-
three-component reaction of an aldehyde, an amine, and an ridines 2g–2j (Table 3, Entries 3–6) were new products, pre-
acetylenedicarboxylate indicated that water in the alcohol pared by this acid-catalyzed dehydration reaction. The crys-
participated in the reaction. It was very interesting to inves- tal structure of 1,4-dihydropyridine 2i was determined by
tigate this three-component reaction in a strictly nonaque- X-ray diffraction (Figure 2). It is noteworthy that 1,4-dihy-
ous system. Thus, we carried out the three-component reac- dropyridines in an aqueous ethanol solution at either room
tions of aromatic aldehydes and arylamines in absolute eth- temperature or at an elevated temperature did not convert
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Molecular Diversity of Three-Component Reactions
to 2-hydroxypyridines, which indicates that 1,4-dihydropyr- tions of 1-azabutadienes in the preparation of pyridines and
idines might not result from the hydration of 2-hydroxypyr- dihydropyridines[16] which might support the present
idines.
mechanism.
Table 3. Synthesis of polysubstituted 1,4-dihydropyridines.
Entry Product
Ar
ArЈ
R
Yield [%]
1
2
3
4
5
6
2b
2c
2g
2h
2i
m-O2NC6H4 p-CH3C6H4
p-CH3OC6H4 p-CH3OC6H4 Me
Me
97
97
95
98
95
95
m-O2NC6H4
C6H5
p-CH3C6H4
Me
Me
C6H5
m-O2NC6H4 p-CH3OC6H4 Me
m-O2NC6H4 p-CH3OC6H4 Et
2j
Scheme 1. Proposed mechanism for the three-component reaction.
Encouraged by the above results, we turned our attention
to combine the three-component reaction and acid-cata-
lyzed dehydration reaction into a more convenient one-step
process. The reaction of benzaldehyde, aniline, dimethyl
acetylenedicarboxylate, and a catalytic amount of p-toluen-
sulfonic acid in ethanol did not give the expected 1,4-dihy-
droxypyridine, but resulted in 2-hydroxytetrahydroxypyr-
idine and a new pyrrolidinone derivative as the main prod-
ucts. This result is very interesting, because there have been
no reports for the preparation of pyrrolidinones from an
addition reaction to electron-deficient alkynes. To obtain
pyrrolidinone as the main product, reaction conditions for
this acid-catalyzed three-component reaction were carefully
Figure 2. Molecular structure of 1,4-dihydropyridine 2i.
On the basis of the results from the three-component and examined. It was best to combine benzaldehyde, aniline,
acid dehydration reactions, a possible mechanism is pro- and 20 mol-% of p-toluensulfonic acid as the catalyst in eth-
posed in Scheme 1. First, arylamine adds to the acetylened- anol, and stir the mixture at room temperature for 30 min.
icarboxylate to give 1,3-dipolar intermediate A. Secondly, The acetylenedicarboxylate was then introduced, and the
the nucleophilic addition of 1,3-dipolar intermediate A to entire reaction was terminated after 24 h to give polysubsti-
the aromatic aldehyde produces intermediate B. Thirdly, in- tuted pyrrolidinone 3a in 62% yield (Table 4). With the op-
termediate B is dehydrated to yield 1-aza-1,3-diene interme- timized conditions in hand, we turned our attention to ex-
diate D. Finally, the hetero-Diels–Alder reaction of 1-aza- amine the scope of the reaction. Other aromatic aldehydes
1,3-diene D with a second molecule of acetylenedicarboxyl- and arylamines were treated with dimethyl or diethyl ace-
ate results in 1,4-dihydropyridine 2. In an aqueous ethanol tylenedicarboxylate to give the corresponding pyrrolidinone
solution, the nucleophilic addition of water to the second derivatives 3b–3j in good yields (Table 4, Entries 2–10).
molecule of acetylenedicarboxylate gives the 2-hydroxy-but- Benzylamine was also successfully used in the reactions to
2-enedioate C. A similar hetero-Diels–Alder reaction of 1- give N-benzylpyrrolidinone derivatives 3k–3n in 56–62%
aza-1,3-diene D with 2-hydroxy-but-2-enedioate C yields 2- yields (Table 4, Entries 11–14). These results demonstrate
hydroxyhydropyridine 1 as the final product. It should be that a domino reaction for the efficient synthesis of versatile
noted that at present this mechanism including the hetero- and functionalized N-arylpyrrolidinones has been success-
Diels–Alder reaction is only theoretical. The exact reaction fully established. The structures of the prepared polysubsti-
mechanism requires more experimental support. There are tuted pyrrolidinones 3a–3n were supported by elemental
1
many examples in the literature of hetero-Diels–Alder reac- analysis, H and 13C NMR and IR spectroscopy as well as
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J. Sun, Q. Wu, E.-Y. Xia, C.-G. Yan
FULL PAPER
mass spectrometry. In addition, the structures of com- polar intermediate B to imine A gives intermediate C. The
pounds 3c and 3h were confirmed by single-crystal X-ray intramolecular attack of the amino group on one of the
diffraction (Figure 3).
esters results in the formation of the nitrogen-containing
five-membered ring. Finally, the protonated alcohol is elim-
inated to yield the final pyrrolidinone product. In this reac-
tion pathway, the key step is the acid-catalyzed reaction of
the imine with the hydroxylated acetylenedicarboxylate. Re-
actions of an imine with an activated alkyne or the multi-
component reactions of an aldehyde, an amine, and an elec-
tron-deficient alkyne have been extensively investigated by
several groups, and versatile N- and N,O-containing hetero-
cyclic systems have been prepared from these reac-
tions.[17–21] Jiang and co-workers have described a similar
one-pot multicomponent reaction with acetylenedicarboxy-
lates, amines, and aldehydes in the presence of acetic acid
to give 3-arylamino-2-pyrrolidinone derivatives in good
yields.[22] Here our result provides an unprecedented syn-
thetic method for the preparation of 3-hydroxy-2-pyrrol-
idinone derivatives.
Table 4. Synthesis of polysubstituted pyrrolidinones.
Entry Product
Ar
ArЈ
R
Yield [%]
1
2
3
4
5
6
7
8
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
C6H5
m-O2NC6H4
C6H5
p-CH3OC6H4
m-O2NC6H4
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
Me
Me
Et
Et
Et
62
76
61
52
72
54
59
60
61
65
60
56
62
60
p-CH3C6H4
p-CH3OC6H4 Me
Me
C6H5
C6H5
p-ClC6H4
p-ClC6H4
p-ClC6H4
C6H5CH2
C6H5CH2
C6H5CH2
C6H5CH2
Me
Me
Me
Me
Me
Me
Et
9
p-ClC6H4
m-O2NC6H4
p-FC6H4
p-ClC6H4
m-O2NC6H4
m-O2NC6H4
10
11
12
13
14
Scheme 2. Mechanism of the acid-catalyzed three-component reac-
tion.
Conclusions
We investigated the three-component reaction of an aro-
matic aldehyde, an arylamine, and an acetylenedicarboxyl-
ate under different reaction conditions and found very
interesting molecular diversity for this multicomponent re-
action based on the easy formation and versatile reactivity
of β-enamino esters. This reaction provides a convenient
and selective procedure for the preparation of function-
alized 2-hydroxyhydropyridines, 1,4-dihydropyridines, and
2-pyrrolidinones in satisfactory yields. Furthermore, we
have proposed rational reaction mechanisms and have es-
tablished the scope and limitation for this reaction, which
enabled further modification and led to molecular diversity.
The potential uses for the reaction in synthetic and medici-
nal chemistry might be quite significant.
Figure 3. Molecular structure of pyrrolidinone 3h.
1
The H NMR spectra of pyrrolidinones 3a–3n typically
had one broad peak at δ ≈ 9.00 ppm assigned to the 3-
hydroxy group, which suggests that the product is predomi-
nately in the enol form. The crystal structures of 3c and 3h
clearly indicate the existence of a carbonyl group at C-2 and
a hydroxy group at C-3 of the pyrrolidine ring.
The formation of pyrrolidinones suggests that the acid-
catalyzed three-component reaction of the aldehyde, amine,
and acetylenedicarboxylate proceeded according to an al-
ternative reaction path, which is tentatively proposed in
Scheme 2. First, the acid-catalyzed condensation of the aro-
matic aldehyde with the arylamine in ethanol produces im-
ine A. When acetylenedicarboxylate is added to the mixture,
water undergoes a nucleophilic addition to the dicarboxyl-
Experimental Section
General Procedure for the Synthesis of Polysubstituted 2-Hydroxy-
ate giving 1,3-dipolar intermediate B. Addition of 1,3-di- hydropyridines: In a round-bottomed flask a solution of arylamine
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Molecular Diversity of Three-Component Reactions
(2.0 mmol) and dimethyl acetylenedicarboxylate (0.284 g,
2.0 mmol) in ethanol (5 mL) was stirred at room temperature for
10 min. The aromatic aldehyde (2.0 mmol) was then added, and the
mixture was stirred at room temperature for 48 h. The resulting
precipitates were collected and washed with cold ethanol to give
7.8 Hz, 2 H, Ar), 7.29–7.26 (m, 4 H, Ar), 7.24 (d, J = 6.6 Hz, 3 H,
Ar), 7.11 (t, J = 7.8 Hz, 1 H, Ar), 5.75 (s, 1 H, CH), 3.76 (s, 3 H,
OCH3) ppm. 13C NMR (150 MHz, CDCl3): δ = 165.2, 162.9, 156.1,
136.2, 135.0, 129.0, 128.7, 128.6, 127.5, 125.9, 122.4, 112.9, 61.7,
52.1 ppm. IR (KBr): ν = 3209, 2956, 1681, 1596, 1498, 1458, 1382,
˜
1
pure white solid 1a (71%). M.p. 160–162 °C. H NMR (600 MHz,
1303, 1234, 1196, 1131, 996, 928, 833, 759 cm–1. MS: m/z (%) =
CDCl3): δ = 7.62 (s, 1 H, Ar), 7.34–7.32 (m, 2 H, Ar), 7.29 (d, J = 308.77 (100) [M – 1]+. C18H15NO4 (309.32): calcd. C 69.89, H 4.89,
7.8 Hz, 3 H, Ar), 7.09 (br., 1 H, Ar), 7.06 (d, J = 7.8 Hz, 2 H, Ar),
4.62 (d, J = 6.6 Hz, 1 H, CH), 4.26 (s, 1 H, OH), 3.98 (d, J =
6.0 Hz, 1 H, CH), 3.74 (s, 3 H, OCH3), 3.52 (s, 3 H, OCH3), 3.45
(s, 3 H, OCH3), 3.43 (s, 3 H, OCH3), 2.31 (s, 3 H, CH3) ppm. 13C
NMR (150 MHz, CDCl3): δ = 171.2, 170.1, 166.4, 164.7, 147.7,
138.3, 136.4, 135.2, 129.4, 129.1, 128.4, 99.8, 85.4, 53.3, 52.3, 52.1,
N 4.53; found C 69.64, H 5.27, N 4.16.
CCDC-804511 (1b), -804512 (1d), -805708 (2i), -805782 (3c),
-805709 (3h) contain the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
51.6, 50.4, 37.6, 21.1 ppm. IR (KBr): ν = 3472, 2955, 1756, 1696,
˜
Supporting Information (see footnote on the first page of this arti-
cle): Molecular structures of 1b to 3c; experimental procedures and
spectroscopic data for all new compounds.
1596, 1498, 1441, 1337, 1236, 1159, 1116, 1059, 975, 892, 854,
809 cm–1. MS: m/z (%) = 496.71 (100) [M – 1]+. C26H27NO9
(497.49): calcd. C 62.77, H 5.47, N 2.82; found C 62.46, H 5.71, N
2.57.
Acknowledgments
General Procedure for the Synthesis of Polysubstituted Dihydropyr-
idines: Under nitrogen a solution of arylamine (2.0 mmol) and di-
methyl acetylenedicarboxylate (0.284 g, 2.0 mmol) in absolute etha-
nol (5 mL, distilled before use from Mg) was stirred at room tem-
perature for 10 min. The aromatic aldehyde (2.0 mmol) in absolute
ethanol (2 mL) was then added by syringe, and the mixture was
stirred at room temperature for 48 h. The resulting precipitates
were collected and washed with cold ethanol to give pure yellow
This work was financially supported by the National Natural Sci-
ence Foundation of China (Grant No. 20972132).
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M. R. Saidi, Tetrahedron Lett. 2008, 49, 1244–1248; c) X. Li,
J. Y. Wang, W. Yu, L. M. Wu, Tetrahedron 2009, 65, 1140–1146;
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1
solid 2a (69%). M.p. 169–170 °C. H NMR (600 MHz, CDCl3): δ
= 7.36 (br. s, 2 H, Ar), 7.20 (br. s, 2 H, Ar), 7.16 (br. s, 2 H, Ar),
6.88 (br. s, 2 H, Ar), 4.99 (s, 1 H, CH), 3.80 (s, 3 H, OCH3), 3.65
(s, 6 H, OCH3), 3.46 (s, 6 H, OCH3), 2.36 (s, 3 H, CH3) ppm. 13C
NMR (150 MHz, CDCl3): δ = 165.9, 163.6, 158.7, 141.8, 140.0,
137.2, 134.4, 130.0, 129.5, 129.0, 114.0, 106.1, 55.2, 52.5, 52.0, 36.3,
21.3 ppm. IR (KBr): ν = 3008, 2951, 1748, 1706, 1643, 1595, 1508,
˜
1439, 1328, 1218, 1115, 1079, 1030, 975, 851 cm–1. MS: m/z (%) =
508.36 (100) [M – 1]+. C27H27NO9 (509.5): calcd. C 63.65, H 5.34,
N 2.75; found C 63.41, H 5.63, N 2.69.
General Procedure for the Synthesis of Polysubstituted Dihydropyr-
idines from the Acid-Catalyzed Dehydration of 2-Hydroxyhydropyr-
idines: A solution of the 2-hydroxyhydropyridines (1.0 mmol) and
p-toluenesulfonic acid (0.5 mmol) in ethanol (10 mL) was refluxed
for about 1 h. The solution was then concentrated to half the vol-
ume. The resulting precipitates were collected and washed with cold
ethanol to give pure light-yellow solid 2g (95%). M.p. 185–186 °C.
1H NMR (600 MHz, CDCl3): δ = 8.40 (s, 1 H, Ar), 8.14 (d, J =
7.8 Hz, 1 H, Ar), 7.80 (d, J = 6.6 Hz, 1 H, Ar), 7.54 (t, J = 7.2 Hz,
1 H, Ar), 7.44–7.41 (m, 5 H, Ar), 5.20 (s, 1 H, CH), 3.67 (s, 6 H,
OCH3), 3.45 (s, 6 H, OCH3) ppm. 13C NMR (150 MHz, CDCl3):
δ = 165.2, 163.0, 148.7, 146.7, 142.6, 136.6, 134.0, 130.3, 130.2,
129.5, 129.1, 123.0, 122.3, 105.1, 52.7, 52.2, 37.2 ppm. IR (KBr): ν
˜
= 3003, 2952, 1747, 1709, 1648, 1594, 1526, 1489, 1437, 1318, 1223,
1117, 1078, 978, 946, 901, 856, 814, 770 cm–1. MS: m/z (%) = 509.48
(100) [M – 1]+. C25H22N2O10 (510.45): calcd. C 58.82, H 4.34, N
5.49; found C 58.74, H 4.49, N 5.23.
General Procedure for the Synthesis of Polysubstituted Pyrrolidin-
ones: In a 50 mL flask, a solution of an aromatic aldehyde
(2.0 mmol), an arylamine (2.0 mmol), and p-toluenesulfonic acid
(0.4 mmol) in ethanol (5 mL) was stirred at room temperature for
approximately 30 min. Acetylenedicarboxylate (2.0 mmol) was then
added, and the mixture was stirred at room temperature for 48 h.
The resulting precipitates were collected and washed with cold eth-
anol to give pure light yellow solid 3a (62%). M.p. 180–182 °C. 1H
NMR (600 MHz, CDCl3): δ = 8.97 (s, 1 H, OH), 7.47 (d, J =
Eur. J. Org. Chem. 2011, 2981–2986
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Received: January 5, 2011
Published Online: April 26, 2011
2986
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 2981–2986