Synthesis of zwitterionic salts via three component reactions of nitrogen-containing heterocycles, acetylenedicarboxylate and cyclic 1,3-dicarbonyl compounds

Article abstract of DOI:10.1016/j.tet.2010.03.060

A practical synthetic procedure for the preparation of the charge-separated pyridinium-Meldrum acid zwitterionic salts was developed through a unique one-pot three component reaction of pyridine, acetylenedicarboxylate and Meldrum acid. Other nitrogen-containing heterocycles such as N-methylimidazole, 2-picoline, quinoline, isoquinoline and other cyclic 1,3-dicarbonyl compounds such as 1,3-cyclopentanedione, 1,3-cyclohexanedione, barbituric acid also took part in the reaction to give corresponding zwitterionic salts in moderate yields, respectively. In one case an unusual isoquinolinium 1,3-cyclopentanedionate was obtained. A feasible explanation is given for this novel one-pot tandem reaction and the formation of different kinds of products.

Full text of DOI:10.1016/j.tet.2010.03.060

Tetrahedron 66 (2010) 3569–3574
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of zwitterionic salts via three component reactions of nitrogen-
containing heterocycles, acetylenedicarboxylate and cyclic 1,3-dicarbonyl
compounds
*
Er-Yan Xia, Jing Sun, Rong Yao, Chao-Guo Yan
College of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou 225002, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A practical synthetic procedure for the preparation of the charge-separated pyridinium–Meldrum acid
zwitterionic salts was developed through a unique one-pot three component reaction of pyridine, ace-
tylenedicarboxylate and Meldrum acid. Other nitrogen-containing heterocycles such as N-methyl-
imidazole, 2-picoline, quinoline, isoquinoline and other cyclic 1,3-dicarbonyl compounds such as
1,3-cyclopentanedione, 1,3-cyclohexanedione, barbituric acid also took part in the reaction to give cor-
responding zwitterionic salts in moderate yields, respectively. In one case an unusual isoquinolinium
1,3-cyclopentanedionate was obtained. A feasible explanation is given for this novel one-pot tandem
reaction and the formation of different kinds of products.
Received 26 January 2010
Received in revised form 8 March 2010
Accepted 16 March 2010
Available online 20 March 2010
Keywords:
Multicomponent reaction
Zwitterionic salt
Acetylenedicarboxylate
Pyridine
Ó 2010 Elsevier Ltd. All rights reserved.
Quinoline
1. Introduction
text we wish to report the preliminarily interesting results of three
component reaction and the formation of the zwitterionic salts.
The reaction of nucleophiles with activated acetylenes has
attracted the attention of organic chemists for a long times, espe-
cially from the advantage point of heterocyclic synthesis.1 In this
class of reaction the addition of aprotic nucleophiles to activated
acetylenes generated a dipolar zwitterionic intermediate. This kind
of zwitterion can have a 1,3 or 1,4 disposition depending upon the
nature of the nucleophile. Subsequent interception of the zwitte-
rions with nucleophilic reagents gave versatile compounds.2 In
recent years more interest in this area has been given to the
reaction of nitrogen-containing heterocycles with activated acety-
lenes. The synthetic potential of the addition intermediate derived
from the reaction of nitrogen-containing heterocycles with acti-
vated acetylenes has been developed greatly especially by study of
Nair et al.3–10 and Yavari and Karimi11–13 as well as others.14–17 We
thought that the rich and fascinating chemistry that stems from the
addition of nucleophilic reagents to the activated acetylenes could
be used to design new multicomponent reactions, which are our
research interest. Thus we initiated the investigation of three
component reactions of nitrogen-containing heterocycles, dimethyl
acetylenedicarboxylateand cyclic 1,3-dicarbonyl compounds. In this
2. Results and discussion
Recently Issa Yavari reported that the 1:1 intermediate gener-
ated by the addition of quinoline to dialkyl acetylenedicarboxylates
is trapped by 1,3-indanedione to yield cycloaddition products in
good yields, while under similar reaction conditions, N-methyl-
imidazole, pyridine and 4-picoline produced the 1,4-zwitterionic
compounds, respectively.18–20 These results demonstrated that the
properties of nitrogen-containing heterocycles play a determining
rule in the reaction. It would be helpful to screen the scope and
limitations of this three component reaction. We began our
research by examining the reactivity of N-methylimidazole. The
three component reactions of N-methylimidazole (1a), dimethyl
acetylenedicarboxylate (2) with cyclic 1,3-dicarbonyl compounds
(3a–3d) in methylene dichloride proceeds smoothly at room
temperature to give the expected 1,4-zwitterionic salts 4a–4d in
higher yields in about 2 h. The used cyclic 1,3-dicarbonyl
compounds included Meldrum acid (3a), 1,3-cyclopentanedione
(3b), 1,3-cyclohexanedione (3c) and N,N-dimethylbarbituric acid
(3d) (Scheme 1). The structures of 1,4-zwitterionic salts 4a–4d
were fully characterized by IR, 1H, 13C NMR and MS spectra as well
as further confirmed by X-ray diffraction determination of one
representative compound 4a (Fig. 1). From Figure 1 it is clearly seen
* Corresponding author. E-mail address: cgyan@yzu.edu.cn.
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.03.060

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E.-Y. Xia et al. / Tetrahedron 66 (2010) 3569–3574
that the formed zwitterionic salt came from all three components
of the reaction. The imidazolyl group and Meldrum acid unit exist
in the same side of molecule, which cause the positive charge and
negative charge are in the shortest distance. The methylene carbon
atom in Meldrum acid unit adopts an sp2 hybrid and the negative
charge is delocalized to two carbonyl groups. The charge de-
localization increases the stability of the 1,4-zwitterionic salt and
makes it could be separated at room temperature. Very recently the
synthesis of highly stable unusual charge-separated pyridinium–
tetronic acid zwitterions from the reaction of nitrogen-containing
heterocycles with dialkyl acetylenedicarboxylates and 3-chlorote-
tronic acid in EtOH at room temperature is also described
(Scheme 1).21
Next the reactivity of pyridine, 2-picoline, quinoline and iso-
quinoline in this three component reaction was also investigated.
The reactions were also furnished at room temperature in 2–3 h
and the same kind of 1,4-zwitterionic salts 4e–4m were obtained in
high yields in most cases (Scheme 2). No any kinds of cycloaddition
products were separated. It should be pointed that the 1,4-zwit-
terionic salts 4e and 4g have been described by Yavari’s research
group.20 These results clearly demonstrated that this three
component reaction has great generality. Quinoline and isoquino-
line showed similar reactivity with pyridine. The structures of
1,4-zwitterionic salts 4e–4m were established by IR, 1H, 13C NMR
and MS spectra. The prepared 1,4-zwitterionic salts have high
polarity and usually dissolve in water very well. Most NMR spectra
are recorded in deuterium water. An interesting phenomenon was
found by careful analysis of 1H NMR spectra of the obtained
Figure 1. The molecular structure of compound 4a.
O
N
O
O
O
O
O
MeO2C
MeO2C
O
MeO2C
MeO2C
MeO2C
MeO2C
N
MeO2C
MeO2C
O
O
O
O
N
N
N
N
N
N
N
N
4a (85%)
4b (87%)
4c (85%)
4d (83%)
Scheme 1. The synthesized 1,4-zwitterionic salts 4a–4d.
O
O
O
N
O
O
N
O
O
O
O
O
MeO2C
O
MeO2C
MeO2C
N
MeO2C
MeO2C
MeO2C
MeO2C
O
MeO2C
MeO2C
N
O
O
O
O
MeO2C
N
N
N
N
N
4e (82%)
4f (66%)
4g (85%)
4h (85%)
4i (80%)
O
O
O
N
O
O
O
O
N
O
O
O
MeO2C
MeO2C
N
MeO2C
MeO2C
O
MeO2C
MeO2C
O
MeO2C
MeO2C
N
MeO2C
MeO2C
O
N
O
N
O
O
N
N
N
4j (65%)
4k (70%)
4l (72%)
4m (65%)
4n (68%)
Scheme 2. The synthesized 1,4-zwitterionic salts 4e–4m.

E.-Y. Xia et al. / Tetrahedron 66 (2010) 3569–3574
3571
1,4-zwitterionic salts. The 1H NMR spectra of 4a, 4e, 4f and 4j gave
two sets of peaks for each characteristic group, which indicates that
two isomers co-existed in the samples of these four products. The
ratio of two isomers in each pair can be also determined by
calculation of integration areas (4a/4a0¼3:1, 4e/4e0¼3:1, 4f/4f0¼3:1,
4j/4j0[5:2). These two isomers are obviously diastereomers due to
the existence of two chiral carbon atoms in the molecule. In order
to explain the formation of two diastereomers a plausible ration-
alization is tentatively proposed by using the formation of 4a and
4a0 as an example, which is illustrated in Scheme 3. The addition of
N-methylimidazole to dimethyl acetylenedicarboxylates gave
a 1,3-zwitterionic intermediate (A), which in turn is attacked by
Meldrum acid (3a) to give the final 1,4-zwitterionic salt 4a. On the
other hand the 1,3-zwitterionic intermediate (A) is a cis vinyl anion,
which could transferred partially to a trans intermediate (A0) by
racemization. Then Meldrum acid attacked intermediate (A0) to
give the product 4a0. It is the transformation of intermediates A
to A0 caused the formation of the formation of two diastereomers in
some cases.
crystal (Figs. 2 and 3). From Figure 3 it clearly seen that the cyclo-
pentanedione connected to C-6 atom of dimethyl fumarate and the
C(6)–C(9) bond is a double bond with the bond distance of 1.356
(8) Å, while the C(5)–C(6), C(6)–C(7) and C(9)–C(10) bonds are
single bonds with the distances of 1.446(3) Å, 1.507(3) Å and
1.453(3) Å, respectively. The negative charge is on the C-2 carbon
atom of cyclopentanedione ring with the existence of the separated
isoquinolinium cation. One intramolecular hydrogen bond existed
between the N–H and C]O bond with the N–H/O distance at
2.578(2) Å. The anions and cations form well separated columns
along the b-axis in the stacking structure of the compound (Fig. 4).
The H atoms of the cations are hydrogen bonded to the carbonyl
oxygen form adjacent anions. These intermolecular hydrogen
bonds play an important role in the stabilization of the whole
structure, which allows the compound to form a 3D network
structure. The formation of isoquinolinium salt 5 indicated that the
three component reaction of nitrogen-containing heterocycles,
DMAD and reactive methylene compounds has very potential ver-
satility and molecular diversity. Although the mechanistic details of
O
O
O
O
O
CO2Me
MeO2C
MeO2C
MeO2C
MeO2C
O
O
CO2Me
3a
3a
O
MeO2C
N
N
N
N
MeO2C
N
N
N
N
4a
A
A'
4a'
Scheme 3. The formation of two diastereomers 4a and 4a0.
Under similar reaction conditions the three component reaction
of isoquinoline (1e), dimethyl acetylenedicarboxylate (2) and
1,3-cyclopentanedione (3b) in dry methylene dichloride at room
temperature gave an isoquinolinium 1,3-pentanedionate 5 (80%) as
main product instead of the expected 1,4-zwitterionic salt (4n)
(Scheme 4). But when the three component reaction was carried
out in methanol the expected 1,4-zwitterionic salt (4n) could be
prepared in 68% yields. The structure of salts 4n and 5 were
established by spectroscopic data and X-ray determination of single
the reactions are not known, we proposed a plausible reaction
course for the formation of isoquinolinium salt, which is illustrated
in Scheme 2. In this three component reaction there are two
reaction paths. On path a isoquinoline added to DMAD to give
1,3-zwitterionic intermediate (A), which in turn is attacked by
cyclopentanedione to give another intermediate (B). Then it is
attacked by carbanium ion of cyclopentanedione to give the usual
1,4-zwitterionic salt 4n.20 But this common reaction did not
happen on this case and the reaction proceeded according to path b.
O
N
CO2Me
CO2Me
N
CO2Me
CO2Me
N
H
CO2Me
CO2Me
3b
O
O
O
A
B
4n
path a
O
O
CO2Me
CH2Cl2
r.t
MeO2C
MeO2C
HN
+
+
N
O
H
CO2Me
O
1
2
3b
5
path b
O
O
O
O
O
H
2
HN
CO2Me
CO2Me
CO2Me
CO2Me
O
C
D
E
Scheme 4. The proposed mechanism for the formation of salts 4 and 5.

3572
E.-Y. Xia et al. / Tetrahedron 66 (2010) 3569–3574
On reaction path b isoquinoline firstly deprotonated more acidic
cyclopentanedione to give a carbanion ion (C), which in turn acted
as nucleophile to add to triple bond of DMAD to yield intermediate
(D). This intermediate is converted to final product 5 via a 1,3-
proton shift process.
In summary we have demonstrated an interesting three com-
ponent reactions of nitrogen-containing heterocycles, acetylene and
cyclic 1,3-dicarbonyl compounds. A series of charge-separated
zwitterionic salts are prepared in high yields in very convenient
manner. Prominent among the advantages of this new method are
novelty, operational simplicity, and good yields. Further expansion of
the reaction scope and synthetic applications of this methodology
are in progress in our laboratory.
3. Experiment section
3.1. General procedure for the three component reaction
The cyclic amine 1a–1e (2.0 mmol) was added to a stirred so-
lution of dimethyl acetylenedicarboxylate 2 (2.0 mmol) and cyclic
1,3-dicarbonyl compounds 3a–3d (2.0 mmol) in dry methylene
dichloride at room temperature. The reaction mixture was then
stirred at room temperature for 2–3 h. The resulting precipitates
were collected by filtration and washed with a little of CH2Cl2 to
give the pure products for analysis.
Figure 2. The molecular structure of compound 4n.
3.1.1. Compound 4a. White solid, 85%, dec 208–210 ꢀC; 1H NMR
(600 MHz, D2O) d (4a): 8.78 (s, 1H, CH), 7.42 (s, 1H, CH), 7.33 (s, 1H,
CH), 5.73 (d, J¼8.4 Hz,1H, CH), 4.41 (d, J¼8.4 Hz,1H, CH), 3.79 (s, 3H,
OCH3), 3.74 (s, 3H, OCH3), 3.62 (s, 3H, NCH3), 1.41 (s, 6H, CH3); (4a0):
8.81 (s, 1H, CH), 7.45 (s, 1H, CH), 7.29 (s, 1H, CH), 5.36 (d, J¼6.0 Hz,
1H, CH), 4.49 (d, J¼6.6 Hz, 1H, CH), 3.81 (s, 3H, OCH3), 3.73 (s, 3H,
OCH3), 3.58 (s, 3H, NCH3), 1.49 (s, 6H, CH3); 13C NMR (150 MHz,
D2O)
123.0, 122.9, 122.8, 122.2, 103.4, 71.2, 70.5, 62.1, 60.5, 53.9, 53.8,
53.0, 52.9, 44.4, 43.8, 35.8, 24.4, 24.3; IR (KBr) : 3424, 3136, 3108,
d: 174.1, 173.7, 169.2, 168.8, 168.0, 167.8, 138.1, 137.0, 124.0,
n
3070, 2984,1741,1717,1678,1597,1434,1388,1368,1265,1212,1178,
1116, 1004, 978, 929, 893, 821, 783, 750 cmꢁ1; MS (m/z): 369.42
([Mþ1]þ) 100%. Anal. Calcd for C16H20N2O8: C, 52.17; H, 5.47; N,
7.61. Found: C, 52.45; H, 5.72; N, 7.39.
3.1.2. Compound 4b. White solid, 87%, mp 159–160 ꢀC; 1H NMR
Figure 3. The molecular structure of compound 5.
(600 MHz, D2O)d:8.69(s,1H, CH),7.35(s,1H, CH),7.26(s,1H, CH),5.80
(d, J¼6.6 Hz,1H, CH), 4.21 (d, J¼6.6 Hz,1H, CH), 3.77 (s, 3H, OCH3), 3.74
(s, 3H, OCH3), 3.59 (s, 3H, NCH3), 2.15 (s, 4H, CH2); 13C NMR (150 MHz,
D2O)
d: 204.3, 173.0, 173.0, 168.8, 137.1, 123.1, 122.4, 105.7, 60.1, 53.9,
52.9, 41.9, 35.8, 31.7; IR (KBr)
n
: 3429, 3063, 2947, 1736, 1716, 1645,
1534, 1435, 1345, 1290, 1173, 1109, 1016, 964, 771 cmꢁ1; MS (m/z):
323.54 ([Mþ1]þ) 100%. Anal. Calcd for C15H19N2O6: C, 55.72; H, 5.92;
N, 8.66. Found: C, 56.03; H, 5.84; N, 8.50.
3.1.3. Compound 4c. Light yellow solid, 85%, mp 134–135 ꢀC; 1H
NMR (600 MHz, D2O) d: 8.61 (s, 1H, CH), 7.29 (s, 1H, CH), 7.22 (s, 1H,
CH), 5.63 (d, J¼7.2 Hz, 1H, CH), 4.53 (d, J¼7.2 Hz, 1H, CH), 3.74 (s, 3H,
OCH3), 3.72 (s, 3H, OCH3), 3.54 (s, 3H, NCH3), 2.06–2.04 (m, 4H,
CH2), 1.65–1.62 (m, 2H, CH2); 13C NMR (150 MHz, D2O)
d: 195.2,
175.2, 174.9, 169.5, 169.1, 124.2,124.1, 123.2, 122.3, 121.7, 107.0, 106.4,
61.6, 60.4, 53.8, 53.6, 52.7, 52.6, 42.9, 42.8, 42.5, 35.9, 35.8, 34.5,
34.4, 20.7; IR (KBr) n: 3435, 3103, 3050, 2940,1732,1713,1582,1499,
1435, 1384, 1285, 1260, 1175, 1114, 1018, 873, 771 cmꢁ1; MS (m/z):
337.50 ([Mþ1]þ) 100%. Anal. Calcd for C16H21N2O6: C, 56.97; H,
6.27; N, 8.30. Found: C, 57.26; H, 6.51; N, 7.88.
3.1.4. Compound 4d. White solid, 83%, dec 198–199 ꢀC; 1H NMR
(600 MHz, D2O)
d: 8.70 (s, 1H, CH), 7.35 (s, 1H, CH), 7.22 (s, 1H, CH),
Figure 4. The packing diagram of a unit cell of compound 5 along the b-axis.
5.75 (d, J¼6.6 Hz, 1H, CH), 4.62 (d, J¼6.6 Hz, 1H, CH), 3.76 (s, 3H,

E.-Y. Xia et al. / Tetrahedron 66 (2010) 3569–3574
3573
OCH3), 3.73 (s, 3H, OCH3), 3.59 (s, 3H, NCH3), 3.03 (s, 6H, NCH3); 13
NMR (150 MHz, D2O) : 174.0, 169.2, 164.0, 154.0, 136.9, 123.2, 123.1,
122.4, 122.3, 82.9, 60.5, 53.8, 52.9, 44.3, 35.8, 27.6; IR (KBr) : 3435,
3131, 3071, 2954, 1732, 1678, 1595, 1425, 1380, 1321, 1249, 1172,
1100, 1051, 1007, 983, 888, 806, 780 cmꢁ1; MS (m/z): 381.59
([Mþ1]þ) 100%. Anal. Calcd for C16H20N4O7: C, 50.52; H, 5.30; N,
14.73. Found: C, 50.28; H, 5.61; N, 14.56.
C
3046, 2951, 1748, 1670, 1591, 1508, 1436, 1385, 1320, 1268, 1174,
1090, 1052, 1011, 974, 897, 853, 779 cmꢁ1; MS (m/z): 392.24
([Mþ1]þ) 100%. Anal. Calcd for C18H21N3O7: C, 55.24; H, 5.41; N,
10.74. Found: C, 55.15; H, 5.80; N, 10.40.
d
n
3.1.10. Compound 4j. Orange solid, 65%, mp 168–169 ꢀC; 1H NMR
(600 MHz, DMSO-d6)
d
(4j): 9.94 (d, J¼6.0 Hz, 1H, ArH), 9.29 (d,
J¼7.8 Hz, 1H, ArH), 8.50 (d, J¼9.0 Hz, 1H, ArH), 8.43 (d, J¼7.8 Hz, 1H,
ArH), 8.21–8.19 (m, 2H, ArH), 8.00–7.98 (m, 1H, ArH), 6.82 (d,
J¼7.2 Hz, 1H, CH), 4.86 (d, J¼6.6 Hz, 1H, CH), 3.77 (s, 3H, OCH3), 3.58
(s, 3H, OCH3), 1.00 (s, 6H, CH3); (4j0): 8.92 (br s, 1H, ArH), 8.39 (d,
J¼8.4 Hz, 1H, ArH), 8.03 (d, J¼8.4 Hz, 1H, ArH), 8.00–7.98 (m, 1H,
ArH), 7.78 (t, J¼7.8 Hz, 1H, ArH), 7.63 (t, J¼7.8 Hz, 1H, ArH), 7.56–7.54
3.1.5. Compound 4e. Orange solid, 82%, mp 180–182 ꢀC; 1H NMR
(600 MHz, D2O)
d
(4e): 8.96 (d, J¼6.0 Hz, 2H, CH), 7.98–7.94 (m, 3H,
CH), 5.71 (d, J¼7.8 Hz, 1H, CH), 4.67 (d, J¼7.8 Hz, 1H, CH), 3.74 (s, 3H,
OCH3), 3.55(s, 3H, OCH3),1.48 (s, 6H, CH3);(4e0):8.75(d, J¼6.6 Hz, 2H,
CH), 8.53–8.49 (m, 3H, CH), 6.09 (d, J¼9.0 Hz, 1H, CH), 4.61 (d,
J¼9.0 Hz, 1H, CH), 3.76 (s, 3H, OCH3), 3.64 (s, 3H, OCH3), 1.30 (s, 6H,
(m, 1H, ArH), 3.72 (s, 2H, CH), 3.66 (s, 6H, OCH3),1.83 (s, 6H, CH3); 13
C
CH3);13CNMR (150 MHz,D2O)
d: 173.6,173.3,168.3,167.9,167.8,147.5,
NMR (150 MHz, DMSO-d6)
128.7, 128.1, 127.9, 126.6, 121.4, 106.4, 99.6, 64.1, 53.5, 52.8, 36.7, 32.9,
26.8, 25.2; IR(KBr) : 3440, 3107, 3007, 2955, 1752, 1729, 1598, 1532,
d: 164.8, 163.4, 150.4, 147.5, 136.2, 129.6,
147.3, 146.2, 145.1, 127.3, 103.5, 103.4, 71.5, 70.8, 70.4, 70.2, 54.3, 54.0,
53.1, 53.0, 44.8, 44.0, 24.5, 24.3; IR(KBr) : 3426, 3030, 2961, 2902,
n
n
1749, 1723, 1596, 1491, 1435, 1403, 1263, 1242, 1215, 1167, 1119, 1070,
1000,816, 783 cmꢁ1;MS(m/z):366.42 ([Mþ1]þ)100%. Anal. Calcd for
C17H19NO8: C, 55.89; H, 5.24; N, 3.83. Found: C. 56.27; H, 5.40; N, 4.11.
1441, 1403, 1333, 1310, 1263, 1236, 1205, 1108, 1035, 996, 966, 911,
817, 776 cmꢁ1; MS (m/z): 416.42 ([Mþ1]þ) 100%. Anal. Calcd for
C21H21NO8: C, 60.72; H, 5.10; N, 3.37. Found: C, 60.53; H, 4.85; N, 3.64.
3.1.6. Compound 4f. Yellow solid, 66%, mp 141–142 ꢀC; 1H NMR
3.1.11. Compound 4k. Yellow solid, 70%, mp 143–144 ꢀC; 1H NMR
(600 MHz, D2O)
d
(4f): 8.61 (d, J¼6.0 Hz, 2H, CH), 8.47 (t, J¼7.8 Hz,
(600 MHz, D2O)
d
: 9.71 (d, J¼5.4 Hz, 1H, ArH), 8.96 (d, J¼7.8 Hz, 1H,
1H, CH), 7.89 (t, J¼7.2 Hz, 2H, CH), 6.01 (d, J¼8.4 Hz, 1H, CH), 4.78 (d,
J¼8.4 Hz, 1H, CH), 3.78 (s, 3H, OCH3), 3.59 (s, 3H, OCH3), 2.00–1.92
(m, 4H, CH2), 1.52–1.50 (m, 2H, CH2); (4f): 8.63 (d, J¼5.4 Hz, 2H, CH),
8.37 (t, J¼7.8 Hz, 1H, CH), 7.85 (t, J¼7.2 Hz, 2H, CH), 6.49 (s, 1H, CH),
3.66 (s, 3H, OCH3), 3.60 (s, 3H, OCH3), 2.26 (t, J¼6.6 Hz, 4H, CH2),
ArH), 8.12 (d, J¼8.4 Hz,1H, ArH), 7.99 (d, J¼9.6 Hz,1H, ArH), 7.92–7.88
(m, 2H, ArH), 7.33 (t, J¼7.8 Hz,1H, ArH), 6.62(d, J¼6.6 Hz,1H, CH), 5.02
(d, J¼6.6 Hz,1H, CH), 3.75 (s, 3H, OCH3), 3.48 (s, 3H, OCH3), 2.73 (s, 6H,
NCH3); 13C NMR (150 MHz, D2O)
d: 173.9, 168.5, 163.2, 153.3, 151.4,
148.9,139.5,135.1,130.7,129.4,129.3,121.0,116.7, 84.0, 62.8, 54.0, 53.8,
53.0, 44.9, 27.3; IR(KBr) : 3430, 3118, 2993, 2951, 1721, 1678, 1584,
1.84–1.82 (m, 2H, CH2); 13C NMR (150 MHz, D2O)
d: 197.5, 194.2,
n
191.6, 173.6, 172.6, 170.7, 170.4, 169.7, 168.4, 168.1, 161.7, 145.3, 142.5,
140.2, 140.1, 136.5, 130.8, 127.2, 126.8, 126.2, 110.9, 53.7, 53.0,52.9,
52.5, 52.2, 51.8, 48.8, 36.6, 36.4, 34.5, 33.9, 33.1, 28.0, 20.3, 20.0, 19.9,
1530, 1438, 1341, 1288, 1225, 1176, 1065,1033, 997, 968, 886, 808,
781 cmꢁ1
;
MS (m/z): 428.16 ([Mþ1]þ) 100%. Anal. Calcd for
C21H21N2O8: C, 59.01;H, 4.95; N, 9.83. Found: C, 58.69;H, 5.41;N, 9.57.
19.8, 19.3, 19.2; IR (KBr) n: 3434, 3133, 3070, 2953, 1743, 1726, 1633,
1580, 1494, 1438, 1390, 1284, 1175, 1127, 1019, 998, 969,853, 792,
3.1.12. Compound 4l. Yellow solid, 72%, mp 196–197 ꢀC; 1H NMR
(600 MHz, DMSO-d6) d: 10.10 (br s, 1H, ArH), 8.80 (s, 1H, ArH), 8.55–
768 cmꢁ1
;
MS (m/z): 334.24 ([Mþ1]þ) 100%. Anal. Calcd for
C17H20NO6: C, 61.07; H, 6.03; N, 4.19. Found: C, 59.76; H, 6.40; N, 3.79.
8.47(m, 2H, ArH), 8.31–8.26(m, 2H, ArH), 8.05–8.03(m,1H, ArH), 5.96
(br s,1H, CH), 4.97 (br s,1H, CH), 3.78 (d, J¼6.6 Hz, 3H, OCH3), 3.56 (d,
J¼6.6 Hz, 3H, OCH3), 1.30 (d, J¼6.6 Hz, 6H, CH3); 13C NMR (150 MHz,
3.1.7. Compound 4g. Yellow solid, 85%, mp 180–181 ꢀC; 1H NMR
(600 MHz, D2O)
d: 8.70–8.69 (m, 2H, CH), 8.46–8.43 (m, 1H, CH),
DMSO-d6) d: 173.9, 167.5, 164.5, 152.3, 152.0, 142.1, 137.5, 137.4, 137.0,
7.88–7.86 (m, 2H, CH), 6.14 (d, J¼7.8 Hz, 1H, CH), 4.84 (d, J¼7.8 Hz,
135.3, 131.1, 130.9, 128.1, 127.7, 127.1, 126.5, 126.3, 123.9, 120.6, 99.7,
72.0, 67.8, 56.0, 53.3, 52.8, 52.0, 45.3, 36.7, 30.6, 26.8, 25.6, 18.6; IR
(KBr) n: 3422, 3049, 3004, 2955, 1748, 1720, 1675, 1606,1514, 1471,
1H, CH), 3.79 (s, 3H, OCH3), 3.61 (s, 3H, OCH3), 2.95 (s, 6H, NCH3);
13C NMR (150 MHz, D2O)
d
: 173.5, 168.2, 163.9, 153.8, 147.2, 145.1,
127.4, 82.6, 70.2, 54.2, 53.1, 44.5, 27.6; IR (KBr) : 3430, 3132, 3055,
n
1441, 1402, 1368, 1336, 1246, 1207, 1167, 1126, 1060, 1024, 1002, 934,
827, 778 cmꢁ1; MS (m/z): 416.48 ([Mþ1]þ) 100%. Anal. Calcd for
C21H21NO8: C, 60.72; H, 5.10; N, 3.37. Found: C, 60.68; H, 5.42; N, 3.10.
3032, 2962, 1748, 1722, 1681, 1614, 1573, 1489, 1427, 1386, 1324,
1270, 1239,1176, 1052, 1009, 853, 810, 774 cmꢁ1; MS (m/z): 378.32
([Mþ1]þ) 100%. Anal. Calcd for C17H19N3O7: C, 54.11; H, 5.08; N,
11.14. Found: C, 53.75; H, 5.31; N, 10.83.
3.1.13. Compound 4m. Yellow solid, 65%, mp 180–181 ꢀC; 1H NMR
(600 MHz,CDCl3)
d
:8.16(s,1H, ArH),7.83(t, J¼7.2 Hz,1H, ArH),7.74(d,
3.1.8. Compound 4h. Light yellow solid, 85%, mp 192–193 ꢀC; 1H
J¼7.2 Hz, 1H, ArH), 7.69 (d, J¼7.8 Hz, 2H, ArH), 7.62 (t, J¼7.8 Hz, 1H,
ArH), 7.09 (d, J¼7.2 Hz, 1H, ArH), 6.05 (d, J¼6.6 Hz, 1H, CH), 5.00 (d,
J¼6.6 Hz, 1H, CH), 3.91 (s, 3H, OCH3), 3.70 (s, 3H, OCH3), 3.02 (s, 6H,
NMR (600 MHz, D2O)
d
: 9.13 (d, J¼6.6 Hz, 1H, CH), 8.34–8.31 (m, 1H,
CH), 7.86–7.82 (m, 2H, CH), 6.11 (d, J¼10.2 Hz, 1H, CH), 4.67 (d,
J¼9.6 Hz, 1H, CH), 3.68 (s, 3H, OCH3), 3.49 (s, 3H, OCH3), 2.83 (s, 3H,
NCH3); 13C NMR (150 MHz, DMSO-d6)
d: 172.3, 169.5, 168.5, 167.4,
CH3),1.49 (s, 6H, CH3); 13C NMR (150 MHz, D2O)
d: 173.3,168.0,167.6,
162.3, 161.5, 152.1, 151.7, 148.8, 148.5, 137.5, 136.9, 135.2, 134.2, 130.4,
130.3, 130.0, 129.8, 127.2, 127.1, 126.8, 125.9, 124.0, 102.6, 86.5, 78.5,
69.5, 53.5, 52.0, 50.9, 50.4 44.7, 27.0, 26.8; IR (KBr) n: 3464, 3073, 2955,
156.9,146.4,144.3,129.9, 125.4,103.7, 71.0, 64.2, 54.1, 53.0, 44.3, 24.4,
20.5; IR (KBr) : 3637, 3402, 3062, 3008, 2960, 2345,1758,1725,1609,
n
1513, 1444, 1402, 1319, 1261, 1209, 1166, 1117, 1072, 999, 968, 935, 911,
815, 785 cmꢁ1; MS (m/z): 380.32 ([Mþ1]þ) 100%. Anal. Calcd for
C18H21NO8: C, 56.99; H, 5.58; N, 3.69. Found: C, 57.20; H, 5.66; N, 3.83.
1739,1682,1647,1580,1432,1313,1266,1192,1170,1007, 941, 878, 837,
778 cmꢁ1
;
MS (m/z): 428.51 ([Mþ1]þ) 100%. Anal. Calcd for
C21H21N3O7: C, 59.01;H, 4.95; N, 9.83. Found: C, 58.70;H, 5.27;N, 9.77.
3.1.9. Compound 4i. Yellow solid, 80%, mp 170–172 ꢀC; 1H NMR
3.1.14. Compound 4n. Yellow solid, 68%, mp 134–136 ꢀC; 1H NMR
(600 MHz, D2O)
d
: 8.55 (d, J¼6.0 Hz, 1H, CH), 8.24 (t, J¼7.2 Hz, 1H,
(600 MHz, D2O) d: 9.46 (s, 1H, ArH), 8.27–8.25 (m, 2H, ArH), 8.19 (d,
CH), 7.76 (d, J¼7.8 Hz, 1H, CH), 7.71 (br s, 1H, CH), 6.26 (d, J¼10.2 Hz,
1H, CH), 4.91 (d, J¼9.6 Hz, 1H, CH), 3.76 (s, 3H, OCH3), 3.62 (s, 3H,
OCH3), 2.94 (s, 6H, NCH3), 2.78 (s, 3H, CH3); 13C NMR (150 MHz,
J¼6.6 Hz, 1H, ArH), 8.11–8.07 (m, 2H, ArH), 7.91–7.89 (m, 1H, ArH),
6.26 (d, J¼9.0 Hz, 1H, CH), 4.47 (d, J¼9.0 Hz, 1H, CH), 3.76 (s, 3H,
OCH3), 3.61 (s, 3H, OCH3), 1.83 (s, 4H, CH2); 13C NMR (150 MHz,
D2O)
d: 173.8, 168.6, 163.9, 157.0, 153.7, 146.4, 143.7, 130.0, 125.1,
D2O)
d: 204.2, 172.5, 168.2, 150.5, 138.2, 138.0, 134.1, 131.7, 130.6,
82.4, 64.1, 54.2, 53.9, 53.2, 43.4, 27.5, 20.1; IR (KBr)
n
: 3508, 3417,
127.2, 126.9, 125.5, 105.5, 69.5, 57.4, 54.3, 53.2, 48.8, 42.0, 31.5, 16.7;

3574
E.-Y. Xia et al. / Tetrahedron 66 (2010) 3569–3574
IR (KBr)
n
: 3419, 3073, 2955,1743,1645, 1537, 1470,1436,1399,1361,
References and notes
1313, 1274, 1238, 1165, 1131, 1012, 985, 930, 883, 834, 774 cmꢁ1; MS
(m/z): 370.58 ([Mþ1]þ) 100%. Anal. Calcd for C20H19NO6: C, 65.37;
H, 5.18; N, 3.79. Found: C, 65.58; H, 5.44; N, 3.56.
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3.1.15. Compound 5. White solid, 80%, mp 166–168 ꢀC; 1H NMR
(600 MHz, D2O)
8.08 (m, 2H, ArH), 7.89 (s, 1H, ArH), 3.74 (s, 3H, OCH3), 3.56 (s, 3H,
OCH3), 2.22 (s, 4H, CH2); 13C NMR (150 MHz, D2O)
: 205.7, 203.4,
172.6, 169.7, 146.7, 142.6, 138.8, 136.7, 130.9, 130.8, 130.1,127.4, 127.2,
125.4, 107.2, 52.8, 51.8, 32.4; IR (KBr) : 3430,3080, 3026, 2919,
2095, 1730, 1707, 1639, 1554, 1457, 1431, 1356, 1295, 1258, 1235,
1189, 1152, 1111, 1029, 1007, 971, 904, 874, 856, 749 cmꢁ1; MS (m/z):
239.41 ([M-C9H8N]þ) 100%. Anal. Calcd for C20H19NO6: C, 65.03; H,
5.18; N, 3.79. Found: C, 64.74; H, 5.52; N, 3.60.
d: 9.46 (s, 1H, ArH), 8.34–8.27 (m, 4H, ArH), 8.11–
d
n
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4. Supplementary data available
Crystallographic data (4a: CCDC 755770; 4i: CCDC 761762; 4n:
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Acknowledgements
This work was financially supported by the National Natural
Science Foundation of China (Grant No. 20972132).