Synthesis of zwitterionic salts via three-component reactions of pyridacylpyridinum iodide, aromatic aldehydes, and Meldrum acid or N,N-dimethylbarbituric acid

Article abstract of DOI:10.1016/j.tet.2010.07.073

New zwitterionic salts of pyridinium-Meldrum acid and pyridinium-barbituric acid are conveniently synthesized from the three-component reactions of 2-, 3-, or 4-pyridacylpyridinum iodides, aromatic aldehydes, and Meldrum acid or N,N-dimethylbarbituric aci

Full text of DOI:10.1016/j.tet.2010.07.073

Tetrahedron 66 (2010) 7743e7748
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of zwitterionic salts via three-component reactions of
pyridacylpyridinum iodide, aromatic aldehydes, and Meldrum acid
or N,N-dimethylbarbituric acid
*
Ying Han, Jiao Chen, Li Hui, 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:
Received 20 May 2010
Received in revised form 20 July 2010
Accepted 26 July 2010
Available online 3 August 2010
New zwitterionic salts of pyridiniumeMeldrum acid and pyridiniumebarbituric acid are conveniently
synthesized from the three-component reactions of 2-, 3-, or 4-pyridacylpyridinum iodides, aromatic
aldehydes, and Meldrum acid or N,N-dimethylbarbituric acid in the presence of triethylamine as base
promoter in acetonitrile.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Multicomponent reaction
Pyridinium salt
Zwitterionic salt
Meldrum acid
Barbituric acid
1. Introduction
as triphenyl phosphine, pyridine, tertiary amine, and dimethyl
sulfoxide to activated alkynes like dimethyl acetylenedicarboxylate
N-Alkylpyridinium salts are one kinds of heterocyclic ammo-
generate and then captured by suitable substrates to give versatile
heterocyclic compounds.15a,17e19 In order to further explore the
potential of our protocol and to evaluate the scope of this four-
component reaction we tested the reactivity of three kinds of
pyridacylpyridinium iodides in the reaction. Here we wish to report
the synthesis of new kinds of pyridinium zwitterionic salts con-
taining functional pyridacyl groups.
nium salts and have been used in a great variety of synthetic
reactions.1e4 Pyridinium salts derived from
a-halogenocarbonyl
compounds are easily deprotonated to give pyridinium ylide, which
are prone to be high potential synthons and underwent versatile
€
reactions, such as Krohnke synthesis of oligopyridines and 1,3-di-
polar cycloaddition for synthesis of indolizines.2bed,5e10 In the past
years we have successfully developed some new multicomponent
reactions by using the very easily in situ formed pyridinium salts as
one component of the reactions.11 Recently we found that the un-
usual charge-separated pyridiniumeMeldrum acid and barbituric
acid zwitterionic salts can be prepared by the four-component re-
action of pyridine, p-nitrobenzyl bromide, aromatic aldehydes, and
Meldrum acid or barbituric acid.12 This work successfully provided
one practical and efficient method for the preparation of the
functionalized pyridinium zwitterions. In the literature pyridinium
zwitterions are usually described as very reactive species and there
are only few reports about the synthesis of them.13e16 Huisgen
addition reaction might be the most widely used reaction for the
preparation of zwitterionic salts, in which the 1,4-dipolar zwitter-
ionic species were generated by the addition of nucleophiles, such
2. Results and discussion
Our recently developed one-pot synthesis of zwitterionic salts
involves in situ formation of pyridinium salts from the reaction of
pyridine with reactive
a-halogenocarbonyl compounds, such as
phenacyl bromide and p-nitrobenzyl bromide.12 But the corre-
sponding pyridacyl halides are not available and are not readily
accessible. It is well known that pyridacylpyridinium salts can be
directly prepared by heating 2-, 3-, or 4-acetylpyridine with iodine
in the solution of pyridine according to the OrtolevaeKing reaction
procedure.1b,20 At first we think to combine OrtolevaeKing
reaction procedure and formation of zwitterionic salts into one-pot
reaction and set out to test the multicomponent reaction by heating
a mixture of 3-actylpyridine, iodine, benzaldehyde, Meldrum acid,
and pyridine with triethylamine as base catalyst in acetonitrile. The
result is very disappointed to us and no main product could be
* Corresponding author. E-mail address: cgyan@yzu.edu.cn (C.-G. Yan).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.07.073

7744
Y. Han et al. / Tetrahedron 66 (2010) 7743e7748
separated from the reaction mixture. After testing several base,
solvent, and adding sequence of substrates we found that it is better
to get firstly the isolated pyridacylpyridinium iodides (1aec) by the
OrtolevaeKing reaction. Then we decided to test the three-compo-
nent reaction of aromatic aldehydes, Meldrum acid and previously
prepared 2-, 3-, or 4-pyridacylpyridinium salts in acetonitrile. After
stirring the three reactants in solution of acetonitrile with triethyl-
amine as base promoter for several hours, the expected pyr-
idiniumeMeldrum acid zwitterionic salts (3aeq) were formed as
yellow precipitates in moderate to good yields, which are conve-
niently separated as pure products by filtration and washed with
methanol. It should be pointed out that 3-pyridacylpyridinium
iodide (1b) and 4-pyridacylpyridinium iodide (1c) reacted more
smoothly than 2-pyridacylpyridinium iodide (1a), which need lon-
ger reaction time and gavelower yields of products (3aec). Aromatic
aldehydes carrying either electron-donating groups, such as
p-methoxyl group or electron-withdrawing substituents, such as
m-nitro and p-nitro groups showed similar reactivity and reacted
efficiently to give the final products in satisfied yields. Thus our pre-
sented three-component reaction provides one practical procedure
for the synthesis of reactive pyridinium zwitterions (Table 1).
Figure 1. Molecular structure of zwitterionic salt 3d.
one-pot three-component reaction of pyridine, acetylenedi-
carboxylate, and Meldrum acid.19
To evaluate the scope of this three-component reaction further,
other reactive dicarbonyl compounds, such as N,N-dimethylbarbi-
turic acid were also tested. The three-component reaction of aro-
matic aldehydes, N,N-dimethylbarbituric acid, and three kinds of
pyridacylpyridinium iodides in acetonitrile with triethylamine as
base catalyst went very smoothly at room temperature. A series of
pyridiniumebarbituric acid zwitterionic salts (4ael) were obtained
in good yields (Table 2). It should be indicated that the yields of
pyridiniumebarbituric acid zwitterionic salts (4ael) are usually
better than that of pyridiniumeMeldrum acid zwitterionic salts
(3aeq), which might be due to the effect of two bulk ortho-groups in
N,N-dimethylbarbituric acid. The structures of the prepared pyr-
idiniumebarbituric acid zwitterionic salts were fully characterized
by spectroscopic methods and elemental analysis. This result clearly
demonstrated that this three-component reaction has great gen-
erality and can be developed to other active methylene compounds.
Table 1
The synthesis of pyridiniumeMeldrum acid zwitterionic salts
O
O
O
O
O
O
Ar'
O
Et3N
I
+
+
Ar'CHO
N
O
CH3CN, r.t.
N
CH2COAr
O
Ar
Entry
Compd
Ar
Ar0
T (h)
Yield (%)
1
2
3
4
5
6
7
8
3a
3b
3c
3d
3e
3f
2-Py
2-Py
2-Py
3-Py
3-Py
3-Py
3-Py
3-Py
3-Py
3-Py
3-Py
4-Py
4-Py
4-Py
4-Py
4-Py
4-Py
p-ClC6H4
p-BrC6H4
13
14
12
9
9
9
10
8
9
8
8
9
8
8
10
8
44
52
58
61
74
67
57
71
67
80
78
55
70
69
66
72
70
m-NO2C6H4
Ph
p-CH3C6H4
p-CH3CH2C6H4
p- CH3OC6H4
p-BrC6H4
3g
3h
3i
Table 2
9
p-ClC6H4
The synthesis of pyridiniumebarbituric acid zwitterionic salts
10
11
12
13
14
15
16
17
3j
3k
3l
m-NO2C6H4
p-NO2C6H4
Ph
p-CH3C6H4
p-CH3CH2C6H4
p-CH3OC6H
p-BrC6H4
N
O
O
O
O
O
3m
3n
3o
3p
3q
N
N
N
Ar'
Et3N
I
O
+
+
Ar'CHO
N
O
CH3CN, r.t.
N
CH2COAr
m-NO2C6H4
8
Ar
The structures of zwitterionic salts were fully characterized by
1H and 13C NMR, MS, IR spectra, and elemental analysis were fur-
ther confirmed by single X-ray diffraction study performed for
a representative compound 3d (Fig. 1). In 1H NMR spectra the
methylene group connected with unit of Meldrum acid usually
Entry
Compd
Ar
Ar0
Ph
p-CH3C6H4
p-BrC6H4
Ph
p-CH3CH2C6H4
p-BrC6H4
p-ClC6H4
Ph
p-CH3CH2C6H4
p-CH3OC6H4
p-BrC6H4
p-ClC6H4
T (h)
Yield (%)
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4e
4f
4g
4h
4i
2-Py
2-Py
2-Py
3-Py
3-Py
3-Py
3-Py
4-Py
4-Py
4-Py
4-Py
4-Py
10
12
10
8
8
7
8
9
9
10
7
52
60
64
70
79
85
79
78
67
74
86
80
show one doublet at about
d 5.00 ppm with the vicinal coupling
constant J¼12.0 ppm. Due to connecting with two stronger elec-
tron-withdrawing pyridacyl and pyridinium groups the absorption
beak of another methylene group greatly shifts to the range of
7e8 ppm and overlaps with signs of aromatic protons. From the
Figure 1 it is clearly seen that the formed zwitterionic salt came
from all three components of the reaction. The pyridyl 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 3-pyridacyl and phenyl group exist on the other side. The
methylene carbon atom in Meldrum acid unit adopts a sp2 hybrid
and the negative charge is delocalized to two carbonyl groups. The
structure of this zwitterionic salt is very similar to that of our re-
cently prepared pyridiniumeMeldrum acid zwitterionic salts by
9
10
11
12
4j
4k
4l
8
This one-pot three-component reaction went very straightfor-
ward. The reaction mechanism is believed to be similar to our pre-
viously proposed course in recent work, which is illustrated in
Scheme 1. The first step is the formation of pyridacylpyridinium
ylide (A) from deprotonation of pyridacylpyridinium iodide by tri-
ethylamine. The second step is the formation of arylidene Meldrum

Y. Han et al. / Tetrahedron 66 (2010) 7743e7748
7745
Compound 3b (Ar¼2-pyridyl, Ar0¼p-BrC6H4): yield: 52%. Mp
Et3N
180e182 ꢀC. IR (KBr)
n: 3437(m), 3136(w), 3051(w),1705(s),1599(vs),
I
N
N
O
O
O
1489(s), 1383(w), 1257(m), 1010(m), 926(w), 770(m), 679(m) cmꢁ1
1H NMR (600 MHz, CDCl3)
;
CH2COAr
CHCOAr
d
(ppm):9.17 (d, J¼5.4 Hz, 2H, ArH), 8.60(d,
Ar'
O
(A)
1
J¼3.6 Hz, 1H, ArH), 8.46 (d, J¼12.0 Hz, 1H, CH), 8.36 (t, J¼7.2 Hz, 1H,
ArH), 7.92 (t, J¼6.6 Hz, 2H, ArH), 7.82 (d, J¼7.8 Hz, 1H, ArH), 7.76 (t,
J¼7.8 Hz, 1H, ArH), 7.48 (d, J¼7.8 Hz, 3H, ArH), 7.15 (d, J¼7.8 Hz, 2H,
ArH), 5.12 (d, J¼12.0 Hz,1H, CH),1.39 (s, 6H, 2CH3).13C NMR (150MHz,
O
N
O
O
O
Ar
O
O
Et3N
+
Ar'CH
Ar'CHO
O
3
CDCl3)
d (ppm): 195.3, 149.2, 145.6, 145.1, 139.4, 137.4, 137.1, 130.8,
O
O
128.3, 126.8, 123.2, 101.2, 44.8. MS (ESIꢁ): m/z¼509.6. Anal. Calcd for
C25H21BrN2O5: C 58.95, H 4.16, N 5.50; Found: C 58.67, H 4.43, N 5.29.
Compound 3c (Ar¼2-pyridyl, Ar0¼m-NO2C6H4): yield: 58%. Mp
(B)
Scheme 1. The formation mechanism of zwitterionic salts.
180e182 ꢀC. IR (KBr)
n: 3132(w), 3083(w), 1702(w), 1671(w), 1610
(vs), 1521(m), 1392(s), 1354(m), 1262(m), 1207(m), 1129(w), 1098
(w), 1038(w), 993(w), 813(w), 736(w) cmꢁ1 1H NMR (600 MHz,
CDCl3)
acid (B) by the Knoevenagel condensation of aromatic aldehyde with
Meldrum acid. The third step isMichael additionof a pyridiniumylide
(A) to arylidene Meldrum acid (B) to afford the zwitterionic salt 3.
This proposed reaction mechanism is also applied to the formation of
the pyridiniumebarbituric acid zwitterionic salts 4ael.
In summary, we extend our new convenient synthesis of zwit-
terionic salts via four-component reactions to the three-component
reaction of pyridacylpyridinium iodide, aromatic aldehyde,
Meldrum acid or N,N-dimethylbarbituric acid. A series of new
charge-separated pyridiniumeMeldrum acid and barbituric acid
zwitterionic salts are prepared in high yields in very convenient
manner. The most attractive features of the presented reactions are
the simplicity and one-pot multicomponent reaction procedure as
well as using commercially available starting materials.
;
d
(ppm): 9.18 (d, J¼6.0 Hz, 2H, ArH), 8.59 (d, J¼4.8 Hz, 1H,
ArH), 8.52 (d, J¼12.0 Hz, 1H, ArH), 8.39 (t, J¼6.6 Hz, 2H, ArH), 8.03
(d, J¼8.4 Hz, 1H, ArH), 7.95 (t, J¼7.2 Hz, 2H, ArH), 7.86 (d, J¼8.4 Hz,
2H, ArH), 7.75 (t, J¼7.8 Hz, 1H, ArH), 7.44 (t, J¼6.0 Hz, 1H, ArH), 7.25
(s, 1H, CH), 5.27 (d, J¼12.6 Hz, 1H, CH), 1.38 (s, 6H, CH3). 13C NMR
(150 MHz, DMSO-d6)
d (ppm): 195.0, 150.9, 149.4, 145.7, 145.2,
142.5, 137.5, 135.5, 129.1, 128.6, 126.8, 123.7, 123.6, 121.8, 101.4, 72.7,
71.8, 45.2. MS (ESIꢁ): m/z¼474.4. Anal. Calcd for C25H21N3O7: C
63.15, H 4.45, N 8.84; Found: C 62.86, H 4.79, N 8.41.
Compound 3d (Ar¼3-pyridyl, Ar0¼C6H5): yield: 61%. Mp
175e177 ꢀC. IR (KBr)
n: 3433(m), 3053(m), 2996(w), 1694(s), 1575
(vs), 1489(s), 1388(s), 1263(m), 1118(m), 772(m) cmꢁ1
(600 MHz, CDCl3)
;
1H NMR
d
(ppm): 9.13 (d, J¼6.0 Hz, 2H, ArH), 8.88 (s, 1H,
ArH), 8.61 (d, J¼4.8 Hz, 1H, ArH), 8.41 (t, J¼7.8 Hz, 1H, ArH), 7.95 (t,
J¼7.2 Hz, 2H, ArH), 7.89e7.86 (m, 2H, ArH, CH), 7.54 (d, J¼7.2 Hz, 2H,
ArH), 7.15e7.13 (m, 1H, ArH), 7.05 (t, J¼7.2 Hz, 2H, ArH), 6.98 (t,
3. Experimental section
3.1. General
J¼7.2 Hz, 1H, ArH), 5.01 (d, J¼12.0 Hz, 1H, CH), 1.46 (s, 6H, 2CH3). 13
C
NMR (150 MHz, CDCl3)
d (ppm): 200.9, 194.6, 154.2, 150.0, 145.6,
All reagents and solvents were commercially available with
analytical grade and used as received. All evaporations of organic
solvents were carried out with a rotary evaporator in conjunction
with a water aspirator. 2-, 3-, and 4-Pyridacylpyridinum iodides
(1aec) were prepared according to the OrtolevaeKing reaction
method.1,13 Melting points were taken on a hot-plate microscope
apparatus and were uncorrected. 1H and 13C NMR spectra were
recorded with a Bruker AV-600 instrument. IR spectra were
obtained on a Bruker Tensor27 spectrometer (KBr disc). HPLC/MS
were measured at Fennigan LCQ Deca XP MAX instrument. Ele-
mental analysis was determined on PE 240C instrument. X-ray data
were collected on a Bruker Smart APEX-2 diffractometer.
145.3, 139.5, 135.9, 129.5, 129.4, 128.7, 127.6, 123.1, 101.5, 47.8, 27.6.
MS (ESIꢁ): m/z¼429.8. Anal. Calcd for C25H22N2O5: C 69.76, H 5.15, N
6.51; Found: C 69.40, H 5.33, N 6.27.
Compound 3e (Ar¼3-pyridyl, Ar0¼p-CH3C6H4): yield: 74%. Mp
164e166 ꢀC. IR (KBr)
n: 3434(m), 3135(w), 3048(m), 2893(w), 1687
(s), 1577(vs), 1488(s), 1389(s), 1260(s), 1109(m), 699(m) cmꢁ1
;
1H
(ppm): 9.20 (d, J¼6.0 Hz, 2H, ArH), 8.89 (s,
NMR (600 MHz, CDCl3)
d
1H, ArH), 8.61 (d, J¼4.8 Hz, 1H, ArH), 8.40 (t, J¼7.8 Hz, 1H, ArH), 7.94
(t, J¼7.2 Hz, 3H, ArH), 7.89 (d, J¼11.4 Hz, 1H, CH), 7.42 (d, J¼7.8 Hz,
2H, ArH), 7.14e7.11 (m, 1H, ArH), 6.83 (d, J¼7.8 Hz, 2H, ArH), 4.98 (d,
J¼11.4 Hz, 1H, CH), 2.12 (s, 3H, CH3), 1.44 (s, 6H, 2CH3). 13C NMR
(150 MHz, CDCl3)
d (ppm): 194.9, 167.1, 153.9, 150.0, 145.7, 145.3,
137.2, 136.6, 136.1, 130.4, 129.3, 126.6, 123.0, 101.3, 47.4, 20.9. MS
(ESIꢁ): m/z¼443.8. Anal. Calcd for C26H24N2O5: C 70.26, H 5.44, N
6.30; Found: C 69.85, H 5.67, N 5.74.
3.1.1. The three-component reaction of pyridacylpyridinum iodide
with aromatic aldehyde and Meldrum acid. To the mixture of pyr-
idacylpyridinum iodide 1aec (2.4 mmol, 0.650 g), aromatic alde-
hydes (2.0 mmol), and Meldrum acid (2.0 mmol, 0.288 g) in
acetonitrile (10.0 mL) was added triethylamine (3.0 mmol, 0.30 g)
and the whole solution was stirred at room temperature for 8e14 h.
The resulting precipitates were collected by filtration and washed
with little methanol to give pure yellow solid for analysis.
Compound 3f (Ar¼3-pyridyl, Ar0¼p-CH3CH2C6H4): yield: 67%.
Mp 170e172 ꢀC. IR (KBr)
n: 443(m), 3133(w), 3048(m), 2967(w),
1686(m), 1581(vs), 1505(m), 1476(s), 1421(m), 1261(s), 1120(m), 819
(w), 757(m) cmꢁ1 1H NMR (600 MHz, CDCl3)
;
d
(ppm): 9.15 (d,
J¼6.0 Hz, 2H, ArH), 8.89 (s,1H, ArH), 8.58 (d, J¼4.2 Hz,1H, ArH), 8.40
(t, J¼7.2 Hz, 1H, ArH), 7.95 (t, J¼6.6 Hz, 2H, ArH), 7.88e7.86 (m, 2H,
ArH, CH), 7.43 (d, J¼7.2 Hz, 2H, ArH), 7.11 (t, J¼6.9 Hz, 1H, ArH), 6.85
(d, J¼7.8 Hz, 2H, ArH), 4.98 (d, J¼12.0 Hz, 1H, CH), 2.40 (q, J¼7.8 Hz,
2H, CH2), 1.45 (s, 6H, 2CH3), 1.03 (t, J¼7.8 Hz, 3H, CH3). 13C NMR
Compound 3a (Ar¼2-pyridyl, Ar0¼p-ClC6H4): yield: 44%. Mp
194e196 ꢀC. IR (KBr)
n: 3138(m), 3053(m), 2997(m), 2823(w), 1705
(s), 1600(vs), 1491(s), 1384(s), 1258(s), 1015(m), 771(m) cmꢁ1
NMR (600 MHz, CDCl3)
;
1H
d
(ppm): 9.17 (d, J¼6.0 Hz, 2H, ArH), 8.59 (s,
(150 MHz, CDCl3) d (ppm): 194.8, 167.2, 153.9, 150.0, 145.6, 145.3,
1H, ArH), 8.46 (d, J¼12.0 Hz, 1H, CH), 8.35 (t, J¼7.8 Hz, 1H, ArH), 7.91
(t, J¼6.9 Hz, 2H, ArH), 7.81 (d, J¼7.2 Hz, 1H, ArH), 7.75 (t, J¼7.8 Hz,
1H, ArH), 7.53 (d, J¼7.8 Hz, 2H, ArH), 7.45 (s, 1H, ArH), 6.99 (d,
143.7, 136.7, 136.0, 130.4, 129.4, 128.2, 126.6, 123.0 101.4, 47.5, 28.4,
15.7. MS(ESIꢁ): m/z¼457.7. Anal. Calcd for C27H26N2O5: C 70.73, H
5.72, N 6.11; Found: C 70.65, H 5.90, N 5.72.
J¼7.8 Hz, 2H, ArH), 5.13 (d, J¼12.0 Hz, 1H, CH), 1.39 (s, 6H, 2CH3). 13
C
Compound 3g (Ar¼3-pyridyl, Ar0¼p-CH3OC6H4): yield: 57%. Mp
NMR (150 MHz, CDCl3)
d
(ppm): 195.4, 149.2, 145.6, 145.0, 137.3,
172e174 ꢀC. IR (KBr)
n: 3427(m), 3136(m), 3066(w), 2996(w), 2937
130.5, 128.3, 128.2, 126.7, 123.2, 101.2, 44.9. MS (ESIꢁ): m/z¼463.9.
Anal. Calcd for C25H21ClN2O5: C 64.59, H 4.55, N 6.03; Found: C
64.71, H 4.81, N 5.68.
(w), 2837(w), 1700(s), 1592(vs), 1512(s), 1423(m), 1388(s), 1247(m),
1116(m), 779(m) cmꢁ1; 1H NMR (600 MHz, CDCl3)
(ppm): 9.10 (s,
2H, ArH), 8.91 (s, 1H, ArH), 8.63 (s, 1H, ArH), 8.41 (s, 1H, ArH),
d

7746
Y. Han et al. / Tetrahedron 66 (2010) 7743e7748
7.95e7.82 (m, 4H, ArH, CH), 7.45 (d, J¼7.8 Hz, 2H, ArH), 7.18 (s, 1H,
ArH), 6.57 (d, J¼7.8 Hz, 2H, ArH), 4.98 (d, J¼11.4 Hz, 1H, CH), 3.63 (s,
Compound 3m (Ar¼4-pyridyl, Ar0¼p-CH3C6H4): yield: 70%. Mp
184e187 ꢀC. IR (KBr)
n: 3434(m), 3133(w), 3050(m), 2910(m), 1686
3H, OCH3), 1.44 (s, 6H, 2CH3). 13C NMR (150 MHz, CDCl3)
d
(ppm):
(s), 1589(vs), 1508(s), 1480(s), 1389(s), 1261(s), 1008(m), 751(m),
194.8, 167.2, 158.9, 154.2, 150.0, 145.5, 145.3, 136.0, 130.5, 130.3, 126.6,
123.1 114.0, 101.4, 55.2, 47.1. MS(ESIꢁ): m/z¼459.8. Anal. Calcd for
C26H24N2O6: C 67.82, H 5.25, N 6.08; Found: C 67.55, H 5.84, N 5.80.
Compound 3h (Ar¼3-pyridyl, Ar0¼p-BrC6H4): 71%. Mp
682(m) cmꢁ1; 1H NMR (600 MHz, CDCl3)
d
(ppm): 9.18 (d, J¼6.0 Hz,
2H, ArH), 8.56 (d, J¼6.0 Hz, 2H, ArH), 8.41 (t, J¼7.2 Hz, 1H, ArH), 7.94
(t, J¼7.2 Hz, 2H, ArH), 7.88 (d, J¼11.4 Hz, 1H, CH), 7.45e7.39 (m, 4H,
ArH), 6.82 (d, J¼7.8 Hz, 2H, ArH), 4.99 (d, J¼11.4 Hz, 1H, CH), 2.13 (s,
176e178 ꢀC. IR (KBr)
n
: 3430(m), 3048(w), 2924(w), 1681(m), 1587
1H NMR
3H, CH3), 1.46 (s, 6H, 2CH3). 13C NMR (150 MHz, CDCl3)
d (ppm):
(vs), 1482(s), 1390(s), 1119(s), 1218(m), 702(m) cmꢁ1
(600 MHz, CDCl3)
;
195.9, 167.2, 150.6, 145.3, 137.5, 136.3, 129.3, 126.6, 121.3, 101.4, 47.6,
20.8. MS (ESIꢁ): m/z¼443.8. Anal. Calcd for C26H24N2O5: C 70.26, H
5.44, N 6.30; Found: C 70.51, H 5.80, N 6.42.
d
(ppm): 9.18 (d, J¼6.0 Hz, 2H, ArH), 8.96 (s, 1H,
ArH), 8.70 (d, J¼4.8 Hz, 1H, ArH), 8.43 (t, J¼7.8 Hz, 1H, ArH), 7.96 (d,
J¼6.6 Hz, 3H, ArH), 7.87 (d, J¼11.4 Hz, 1H, CH), 7.45 (d, J¼7.8 Hz, 2H,
ArH), 7.22e7.16 (m, 3H, ArH), 4.98 (d, J¼12.0 Hz, 1H, CH), 1.42 (s, 6H,
Compound 3n (Ar¼4-pyridyl, Ar0¼p-CH3CH2C6H4): 69%. Mp
168e170 ꢀC. IR (KBr)
n: 3428(w), 3044(w), 2963(m), 1691(m), 1583
2CH3). 13C NMR (150 MHz, CDCl3)
d
(ppm): 194.5, 167.1, 154.5, 150.0,
(vs), 1486(m), 1392(s), 1263(s), 1205(m), 1117(m), 1010(w), 826
145.5, 138.8, 136.0, 131.7, 131.0, 130.2, 126.8, 123.3, 121.6, 101.5, 47.1.
MS (ESIꢁ): m/z¼508.6. Anal. Calcd for C25H21BrN2O5: C 58.95, H
4.16, N 5.50; Found: C 58.47, H 4.50, N 5.27.
(w) cmꢁ1; 1H NMR (600 MHz, CDCl3)
d
(ppm): 9.10 (d, J¼5.4 Hz, 2H,
ArH), 8.55 (d, J¼4.2 Hz, 2H, ArH), 8.42 (t, J¼7.8 Hz, 1H, ArH) 7.95 (t,
J¼6.6 Hz, 2H, ArH), 7.85 (d, J¼11.4 Hz, 1H, CH), 7.41e7.37 (m, 4H,
ArH), 6.84 (d, J¼7.2 Hz, 2H, ArH), 4.99 (d, J¼12.0 Hz,1H, CH), 2.41 (q,
Compound 3i (Ar¼3-pyridyl, Ar0¼p-ClC6H4): yield: 67%. Mp
188e190 ꢀC. IR (KBr)
n
: 3432(m), 3041(m), 2990(m), 2958(m), 1692
J¼7.8 Hz, 2H, CH2), 1.47 (s, 6H, 2CH3), 1.04 (t, J¼7.2 Hz, 3H, CH3). 13
C
(s), 1590(vs), 1487(s), 1420(m), 1390(s), 1258(m), 1105(s), 779
NMR (150 MHz, CDCl3) d (ppm): 195.8, 167.2, 150.5, 145.6, 129.4,
(m) cmꢁ1; 1H NMR (600 MHz, CDCl3)
d
(ppm): 9.13 (d, J¼6.0 Hz, 2H,
128.2, 126.7, 121.2, 101.5, 77.2, 77.0, 76.8, 75.9, 73.4, 47.7, 28.4, 15.8.
MS (ESIꢁ): m/z¼457.8. Anal. Calcd for C27H26N2O5: C 70.73, H 5.72,
N 6.11; Found: C 70.55, H 5.48, N 6.40.
ArH), 8.95 (s, 1H, ArH), 8.69 (d, J¼4.2 Hz, 1H, ArH), 8.42 (t, J¼7.8 Hz,
1H, ArH), 7.96e7.92 (m, 3H, ArH), 7.86 (d, J¼12.0 Hz,1H, CH), 7.51 (d,
J¼7.8 Hz, 2H, ArH), 7.22e7.19 (m, 1H, ArH), 7.01 (d, J¼7.8 Hz, 2H,
ArH), 4.99 (d, J¼11.4 Hz, 1H, CH), 1.44 (s, 6H, 2CH3). 13C NMR
Compound 3o (Ar¼4-pyridyl, Ar0¼p-CH3OC6H4): yield: 66%. Mp
178e180 ꢀC. IR (KBr)
n: 3436(w), 3030(m), 2879(w), 1709(w), 1592
(150 MHz, CDCl3)
d
(ppm): 194.4, 182.9, 167.1, 154.6, 150.0, 145.5,
(vs), 1510(m), 1488(m), 1391(s), 1263(m), 1028(w), 751(m) cmꢁ1; 1H
NMR (600 MHz, CDCl3)
135.9, 130.7, 128.8, 126.8, 123.3, 101.6, 47.2. MS (ESIꢁ): m/z¼464.1.
Anal. Calcd for C25H21ClN2O5: C 64.59, H 4.55, N 6.03; Found: C
64.63, H 4.95, N 5.77.
d
(ppm): 9.10 (d, J¼6.0 Hz, 2H, ArH), 8.60 (d,
J¼4.8 Hz, 2H, ArH), 8.42 (d, J¼7.8 Hz, 1H, ArH), 7.95 (t, J¼7.2 Hz, 2H,
ArH), 7.83 (d, J¼12.0 Hz,1H, CH), 7.44e7.41 (m, 4H, ArH, CH), 6.56(d,
J¼8.4 Hz, 2H, ArH), 4.98 (d, J¼11.4 Hz, 1H, CH), 3.63 (s, 3H, OCH3),
Compound 3j (Ar¼3-pyridyl, Ar0¼m-NO2C6H4): yield: 80%. Mp
187e189 ꢀC. IR (KBr)
n: 3141(w), 3066(m), 2985(w), 1696(m), 1573
1.46 (s, 6H, 2CH3). 13C NMR (150 MHz, CDCl3)
d (ppm): 194.8, 167.2,
(vs), 1536(s), 1499(m), 1391(s), 1350(m), 1268(m), 1203(m), 1115(w),
158.9, 154.2, 150.0, 145.5, 145.3, 136.0, 130.5, 130.3, 126.6, 123.1
114.0, 101.4, 55.2, 47.1. MS (ESIꢁ): m/z¼459.8. Anal. Calcd for
C26H24N2O6: C 67.82, H 5.25, N 6.08; Found: C 67.44, H 5.59, N 5.83.
Compound 3p (Ar¼4-pyridyl, Ar0¼p-BrC6H4): 72%. Mp
1015(w), 925(w), 805(w), 766(w) cmꢁ1 1H NMR (600 MHz, CDCl3)
;
d
(ppm): 9.21 (d, J¼1.8 Hz, 1H, ArH), 8.85 (d, J¼6.4 Hz, 1H, ArH), 8.63
(d, J¼4.2 Hz, 2H, ArH), 8.32e8.27 (m, 3H, ArH), 8.04e8.01 (m, 1H,
ArH), 7.76 (d, J¼7.2 Hz, 1H, ArH), 7.71 (t, J¼7.8 Hz, 1H, ArH), 7.62 (t,
J¼8.4 Hz, 1H, ArH), 7.51e7.49 (m, 1H, ArH), 7.33e7.29 (m, 1H, ArH,
186e188 ꢀC. IR (KBr)
n
: 3436(m), 3135(w), 3083(w), 1708(m), 1594
1H
(ppm): 9.07 (s, 2H, ArH), 8.65 (s, 2H, ArH),
(vs), 1489(s), 1390(s), 1261(s), 1228(m), 1014(m), 827(w) cmꢁ1
NMR (600 MHz, CDCl3)
;
CH), 4.42 (d, J¼9.0 Hz, 1H, CH), 1.80 (s, 3H, CH3), 1.74 (s, 3H, CH3). 13
C
d
NMR (150 MHz, DMSO-d6)
d
(ppm): 194.8, 164.9, 164.2, 153.5, 149.6,
8.44 (t, J¼7.2 Hz, 1H, ArH), 7.97 (t, J¼6.0 Hz, 2H, ArH), 7.81 (d,
J¼11.4 Hz, 1H, CH), 7.42 (d, J¼4.8 Hz, 4H, ArH), 7.17 (d, J¼7.8 Hz, 2H,
ArH), 4.97 (d, J¼12.0 Hz, 1H, CH), 1.44 (s, 6H, 2CH3). 13C NMR
147.3, 146.1, 136.1, 135.6, 129.5, 127.8, 126.7, 123.6, 123.1, 121.6, 99.7,
73.8, 72.0, 46.5, 25.3. MS (ESIꢁ): m/z¼474.9. Anal. Calcd for
C25H21N3O7: C 63.15, H 4.45, N 8.84; Found: C 63.40, H 4.66, N 8.67.
Compound 3k (Ar¼3-pyridyl, Ar0¼p-NO2C6H4): yield: 78%. Mp
(150 MHz, CDCl3)
d (ppm): 194.5, 167.1, 154.5, 150.0, 145.5, 138.8,
136.0, 131.7, 131.0, 130.2, 126.8, 123.3, 121.6, 101.5, 47.1. MS (ESIꢁ):
m/z¼508.3. Anal. Calcd for C25H21BrN2O5: C 58.95, H 4.16, N 5.50;
Found: C 58.47, H 4.51, N 5.27.
158e160 ꢀC. IR (KBr)
n: 3076(w), 1687(w), 1589(vs), 1510(m), 1384(s),
1343(s), 1260(m), 1201(m), 1112(s), 1001(w), 916(w), 780(w), 744
(w) cmꢁ1; 1H NMR (600 MHz, CDCl3)
d
(ppm): 9.12 (d, J¼6.0 Hz, 2H,
Compound 3q (Ar¼4-pyridyl, Ar0¼m-NO2C6H4): yield: 70%. Mp
ArH), 8.98 (s, 1H, ArH), 8.68 (d, J¼4.8 Hz, 1H, ArH), 8.46 (d, J¼8.4 Hz,
1H, ArH), 8.11e8.06 (m, 1H, ArH), 8.00 (t, J¼6.6 Hz, 2H, ArH), 7.96 (d,
J¼8.4 Hz,1H, ArH), 7.94e7.89 (m, 3H, ArH), 7.78 (d, J¼8.4 Hz, 2H, ArH,
CH), 5.13 (d, J¼12.0 Hz, 1H, CH), 1.43 (s, 6H, CH3). 13C NMR (150 MHz,
179e181 ꢀC. IR (KBr)
n: 3141(w), 3069(m), 2985(w), 1705(m), 1572
(vs), 1498(m), 1391(s), 1352(m), 1265(m), 1202(m), 1117(w), 1015
(w), 923(w), 867(w), 768(w) cmꢁ1 1H NMR (600 MHz, CDCl3)
;
d
(ppm): 8.88 (d, J¼5.4 Hz, 2H, ArH), 8.64e8.62 (m, 2H, ArH),
DMSO-d6)
d
(ppm): 193.8, 164.0, 154.3, 150.1, 148.4, 146.5, 145.7,
8.33e8.27 (m, 2H, ArH), 8.03e7.92 (m, 1H, ArH), 7.56 (t, J¼6.0 Hz,
4H, ArH), 7.63 (t, J¼7.8 Hz, 1H, ArH), 7.49e7.44 (m, 1H, ArH), 7.35 (t,
J¼5.4 Hz,1H, CH), 4.41 (d, J¼9.6 Hz,1H, CH), 1.78 (s, 3H, CH3), 1.74 (s,
145.2, 136.4, 130.2, 130.0, 129.0, 127.8, 126.7, 123.5, 123.1, 122.8, 99.4,
70.8, 69.7, 45.9, 25.4. MS(ESIꢁ): m/z¼474.5. Anal. Calcd for
C25H21N3O7: C 63.15, H 4.45, N 8.84; Found: C 62.70, H 4.83, N 8.55.
Compound 3l (Ar¼4-pyridyl, Ar0¼C6H5): yield: 55%. Mp
3H, CH3). 13C NMR (150 MHz, DMSO-d6)
d (ppm): 196.8, 164.9, 164.1,
150.4, 150.0, 146.7, 146.1, 141.8, 135.7, 129.5, 127.8, 126.7, 123.7, 121.6,
121.6, 121.4, 99.7, 99.4, 74.0, 72.1, 46.3, 25.5. MS (ESIꢁ): m/z¼474.5.
Anal. Calcd for C25H21N3O7: C 63.15, H 4.45, N 8.84; Found: C 62.83,
H 4.65, N 8.70.
192e194 ꢀC. IR (KBr)
n: 3433(m), 3136(w), 3058(m), 2991(m), 1699
(s), 1664(m), 1631(s), 1570(vs), 1494(s), 1457(w), 1390(s), 1262(m),
1018(m), 773(w) cmꢁ1; 1H NMR (600 MHz, CDCl3)
d
(ppm): 9.09 (d,
J¼6.0 Hz, 2H, ArH), 8.57 (d, J¼6.0 Hz, 2H, ArH), 8.43 (t, J¼7.2 Hz, 1H,
ArH), 7.96 (t, J¼7.2 Hz, 2H, ArH), 7.85 (d, J¼11.4 Hz, 1H, CH), 7.52 (d,
J¼7.2 Hz, 2H, ArH), 7.38 (d, J¼6.0 Hz, 2H, ArH), 7.04e6.98 (m, 3H,
ArH), 5.01 (d, J¼12.0 Hz, 1H, CH), 1.47 (s, 6H, 2CH3). 13C NMR
3.1.2. The three-component reaction of pyridacylpyridinium iodides
with aromatic aldehydes and N,N-dimethylbarbituric acid. To the
mixture of N-pyridacylpyridinium iodides 1aec (2.4 mmol,
0.650 g), aromatic aldehydes (2.0 mmol), and N,N-dimethylbarbi-
turic acid (2.0 mmol, 0.312 g) in acetonitrile (10.0 mL) was added
triethylamine (3.0 mmol, 0.30 g) and the whole solution was stirred
at room temperature for 7e12 h. The resulting precipitates were
(150 MHz, CDCl3)
d (ppm): 202.2, 195.6, 167.2, 150.7, 145.5, 129.4,
128.7, 127.8, 126.7, 121.1, 101.5, 48.0. MS (ESIꢁ): m/z¼429.2. Anal.
Calcd for C25H22N2O5: C 69.76, H 5.15, N 6.51; Found: C 69.36, H
5.49, N 5.86.

Y. Han et al. / Tetrahedron 66 (2010) 7743e7748
7747
collected by filtration and washed with little methanol to give pure
yellow solid for analysis.
CH), 7.96e7.90 (m, 3H, ArH), 7.50 (d, J¼7.2 Hz, 2H, ArH), 7.23 (s, 1H,
ArH), 7.15 (d, J¼7.2 Hz, 2H, ArH), 5.15 (d, J¼11.4 Hz, 1H, CH), 3.16 (s,
Compound 4a (Ar¼2-pyridyl, Ar0¼C6H5): yield: 52%. Mp
6H, 2NCH3). 13C NMR (150 MHz, CDCl3)
d (ppm): 194.6, 154.5, 153.2,
178e180 ꢀC. IR (KBr)
n
: 3055(m), 2915(m), 1663(s), 1597(vs), 1492
150.1, 145.5, 138.5, 136.0, 131.8, 130.3, 126.7, 123.4, 121.7, 84.2, 47.6,
27.4. MS (ESIþ): m/z¼521.3. Anal. Calcd for C25H21BrN4O4: C 57.59, H
4.06, N 10.75; Found: C 57.28, H 4.33, N 10.69.
(m), 1424(s), 1380(m), 1292(m), 1173(m), 776(m) cmꢁ1
;
1H NMR
(ppm): 9.17 (d, J¼5.4 Hz, 2H, ArH), 8.83 (d,
(600 MHz, CDCl3)
d
J¼12.6 Hz, 1H, ArH), 8.62e8.59 (m, 2H, ArH), 8.29 (t, J¼7.2 Hz, 1H,
ArH), 7.82 (t, J¼6.6 Hz, 2H, ArH), 7.74 (d, J¼7.8 Hz, 1H, ArH), 7.64 (d,
J¼7.2 Hz, 2H, ArH), 7.36e7.33 (m, 2H, ArH), 7.01 (d, J¼7.2 Hz, 2H,
ArH), 5.35 (d, J¼12.6 Hz, 1H, CH), 3.15 (s, 6H, 2NCH3). 13C NMR
Compound 4g (Ar¼3-pyridyl, Ar0¼p-ClC6H4): yield: 79%. Mp
180e181 ꢀC. IR (KBr)
n: 3140(m), 3036(m), 2966(s), 1672(s), 1584
(vs), 1482(m), 1433(m), 1228(m), 1163(m), 1096(w), 776(m) cmꢁ1
1H NMR (600 MHz, CDCl3)
;
d
(ppm): 9.04 (d, J¼6.0 Hz, 2H, ArH), 8.98
(150 MHz, CDCl3)
d
(ppm): 196.0, 153.5, 151.5, 149.1, 145.7, 144.9,
(s, 1H, ArH), 8.70 (d, J¼4.8 Hz, 1H, ArH), 8.42 (t, J¼7.2 Hz, 1H, ArH),
8.16 (d, J¼12.0 Hz,1H, CH), 7.94e7.90 (m, 3H, ArH), 7.56 (d, J¼8.4 Hz,
2H, ArH), 7.22 (d, J¼12.6 Hz, 1H, ArH), 7.01 (d, J¼8.4 Hz, 2H, ArH),
5.16 (d, J¼12.0 Hz, 1H, CH), 3.16 (s, 6H, 2NCH3). 13C NMR (150 MHz,
139.8, 137.2, 129.1, 128.2, 128.1, 126.8, 126.4, 123.0, 84.4, 45.9, 27.3.
MS (ESIþ): m/z¼443.2. Anal. Calcd for C25H22N4O4: C 67.86, H 5.01,
N 12.66; Found: C 67.42, H 5.38, N 12.29.
Compound 4b (Ar¼2-pyridyl, Ar0¼p-CH3C6H4): yield: 60%. Mp
CDCl3) d (ppm): 194.6, 163.8, 154.7, 153.3, 150.0, 145.7, 145.5, 138.0,
144e146 ꢀC. IR (KBr)
n
: 3136(w), 3051 (m), 2965(m), 2871(w), 1701
135.9, 133.5, 130.1, 128.8, 126.6, 123.7, 123.3, 84.1, 47.8, 27.4. MS
(ESIþ): m/z¼478.9. Anal. Calcd for C25H21ClN4O4: C 62.96, H 4.44, N
11.75; Found: C 62.67, H 4.84, N 11.45.
(m), 1660(s), 1597(vs), 1381(s), 1342(m), 1221(m), 1020(m), 773(m),
703(m) cmꢁ1; 1H NMR (600 MHz, CDCl3)
d
(ppm): 9.16 (d, J¼6.0 Hz,
2H, ArH), 8.83 (d, J¼12.6 Hz, 1H, ArH), 8.63 (d, J¼4.2 Hz, 1H, ArH),
8.30 (t, J¼7.8 Hz, 1H, ArH), 7.83 (t, J¼6.9 Hz, 2H, ArH), 7.77e7.70 (m,
2H, ArH), 7.53 (d, J¼7.8 Hz, 2H, ArH), 7.44 (t, J¼6.0 Hz, 1H, ArH), 6.84
(d, J¼7.8 Hz, 2H, ArH), 5.35 (d, J¼12.6 Hz, 1H, CH), 3.15 (s, 6H,
Compound 4h (Ar¼4-pyridyl, Ar0¼C6H5): yield: 78%. Mp
151e153 ꢀC. IR (KBr)
n: 3428(m), 3054(w), 1672(s), 1567(vs), 1487
(s), 1433(s), 1263(m), 1227(m), 1026(w), 842(m), 682(w) cmꢁ1
;
1H
(ppm): 9.05 (d, J¼5.4 Hz, 2H, ArH), 8.58 (d,
NMR (600 MHz, CDCl3)
d
2NCH3), 2.11 (s, 3H, CH3). 13C NMR (150 MHz, CDCl3)
d
(ppm): 195.9,
J¼3.0 Hz, 2H, ArH), 8.40 (t, J¼7.2 Hz,1H, ArH), 8.18 (d, J¼12.0 Hz, 1H,
ArH), 7.90 (t, J¼6.0 Hz, 2H, ArH), 7.56 (d, J¼7.2 Hz, 2H, ArH), 7.43 (d,
J¼3.0 Hz, 2H, ArH), 7.02 (t, J¼7.2 Hz, 2H, ArH), 6.98 (d, J¼7.2 Hz, 1H,
ArH), 5.17 (d, J¼11.4 Hz, 1H, CH), 3.17 (s, 6H, 2NCH3). 13C NMR
153.5, 149.1, 145.6, 144.8, 137.2, 128.9, 128.1, 126.5, 123.1, 84.6, 71.5,
45.2, 27.3, 20.9. MS (ESIþ): m/z¼457.6. Anal. Calcd for C26H24N4O4: C
68.41, H 5.30, N 12.27; Found: C 68.60, H 5.75, N 11.86.
Compound 4c (Ar¼2-pyridyl, Ar0¼p-BrC6H4): yield: 64%. Mp
(150 MHz, CDCl3) d (ppm): 191.4, 151.5, 151.3, 150.7, 149.8, 145.5,
196e198 ꢀC. IR (KBr)
n
: 3053(m), 2925(w), 1664(s), 1596(vs), 1485
139.5, 138.8, 136.0, 129.5, 129.4, 129.0, 128.7, 128.6, 128.4, 127.2,
126.6, 123.7, 121.5, 121.1, 121.0, 91.7, 89.6, 48.8, 28.1. MS (ESIꢁ):
m/z¼441.8. Anal. Calcd for C25H22N4O4: C 67.86, H 5.01, N 12.66;
Found: C 67.49, H 5.37, N 12.55.
(m), 1428(m), 1382(s), 1292(m), 1071(w), 774(m) cmꢁ1
(600 MHz, CDCl3)
;
1H NMR
d
(ppm): 9.13 (d, J¼5.4 Hz, 2H, ArH), 8.79 (d,
J¼12.0 Hz, 1H ArH), 8.63 (s, 1H, ArH), 8.32 (t, J¼7.2 Hz, 1H, ArH),
7.86e7.75 (m, 4H, ArH), 7.56 (d, J¼7.8 Hz, 2H, ArH), 7.48 (s, 1H, ArH),
7.15 (d, J¼7.2 Hz, 2H, ArH), 5.32 (d, J¼12.0 Hz, 1H, CH), 3.15 (s, 6H,
Compound 4i (Ar¼4-pyridyl, Ar0¼p-CH3CH2C6H4): yield: 67%.
Mp 171 ꢀC. IR (KBr)
n: 3432(m), 3050(m), 2963(m), 1699(s), 1662(s),
2NCH3).13C NMR (150 MHz, CDCl3)
d
(ppm): 195.5,153.4,151.1,149.3,
1593(vs), 1494(s), 1422(s), 1379(s), 1263(m), 1223(m), 1010(m), 830
145.6, 145.1, 139.0, 137.4, 131.2, 130.8, 128.4, 126.6, 123.2, 120.8, 84.1,
71.2, 45.2, 27.3. MS (ESIþ): m/z¼521.6. Anal. Calcd for C25H21BrN4O4:
C 57.59, H 4.06, N 10.75; Found: C 57.30, H 4.46, N 10.43.
(m), 772(m) cmꢁ1 1H NMR (600 MHz, CDCl3)
;
d
(ppm): 9.03 (d,
J¼5.4 Hz, 2H, ArH), 8.56 (d, J¼2.4 Hz, 2H, ArH), 8.39 (t, J¼7.2 Hz, 1H,
ArH), 8.18 (d, J¼11.4 Hz, 1H, CH), 7.88 (t, J¼6.6 Hz, 2H, ArH),
7.46e7.41 (m, 4H, ArH), 6.83 (d, J¼7.8 Hz, 2H, ArH), 5.13 (d,
J¼11.4 Hz, 1H, CH), 3.16 (s, 6H, 2NCH3), 2.39 (q, J¼7.2 Hz, 2H, CH2),
Compound 4d (Ar¼3-pyridyl, Ar0¼C6H5): yield: 70%. Mp
140e142 ꢀC. IR (KBr)
n: 3067(m), 2955(w), 1663(s), 1589(vs), 1432
(s), 1386(m), 1293(m), 1164(m), 1029(w), 773(m) cmꢁ1
;
1H NMR
1.01 (t, J¼7.2 Hz, 3H, CH3). 13C NMR (150 MHz, CDCl3)
d (ppm): 196.1,
(600 MHz, CDCl3) (ppm): 9.05(s, 2H, ArH), 8.92 (s,1H ArH), 8.62 (s,
d
191.5, 161.6, 159.2, 151.3, 150.5, 149.8, 145.6, 144.5, 128.9, 123.8,
121.5, 91.8, 48.5, 29.9, 28.5, 28.0, 15.4. MS (ESIꢁ): m/z¼470.0. Anal.
Calcd for C27H26N4O4: C 68.92, H 5.57, N 11.91; Found: C 68.74, H
5.90, N 11.67.
1H ArH), 8.38 (s, 1H, ArH), 8.16 (d, J¼11.4 Hz, 1H, CH), 7.90e7.83 (m,
3H, ArH), 7.60 (d, J¼6.6 Hz, 2H, ArH), 7.15(d, J¼3.0 Hz, 1H, ArH), 7.03
(d, J¼6.0 Hz, 2H, ArH), 6.96 (d, J¼6.0 Hz, 1H, ArH), 5.17 (d, J¼11.4 Hz,
1H, CH), 3.17 (s, 6H, 2NCH3). 13C NMR (150 MHz, CDCl3)
d
(ppm):
Compound 4j (Ar¼4-pyridyl, Ar0¼p-CH3OC6H4): yield: 74%. Mp
194.8, 154.3, 153.3, 150.0, 145.5, 139.3, 135.9, 130.3, 129.4, 128.8,
127.8, 126.5, 123.2, 84.5, 48.4, 27.4. MS (ESIþ): m/z¼443.5. Anal.
Calcd for C25H22N4O4: C 67.86, H 5.01, N 12.66; Found: C 67.65, H
4.83, N 12.91.
134e138 ꢀC. IR (KBr)
n: 3393(m), 3065(w), 2963(w), 1666(s), 1567
(vs), 1509(m), 1435(m), 1255(m), 1174(m), 1111(m), 829(w), 687
(m) cmꢁ1; 1H NMR (600 MHz, CDCl3)
d
(ppm): 9.04 (d, J¼6.0 Hz, 2H,
ArH), 8.62 (d, J¼4.2 Hz, 2H, ArH), 8.40 (t, J¼7.8 Hz, 1H, ArH), 8.15 (d,
J¼11.4 Hz, 1H, CH), 7.91 (t, J¼7.2 Hz, 2H, ArH), 7.49e7.46 (m, 4H,
ArH), 6.55 (d, J¼8.4 Hz, 2H, ArH), 5.14 (d, J¼12.0 Hz, 1H, CH), 3.61 (s,
Compound 4e (Ar¼3-pyridyl, Ar0¼p-CH3CH2C6H4): yield: 79%.
Mp 130e132 ꢀC. IR (KBr)
n: 3138(w), 3087(m), 2965(m), 2830(w),
1672(s), 1572(vs), 1384(s), 1269(m), 1237(w), 1166(m), 1027(m), 774
3H, OCH3), 3.17 (s, 6H, 2NCH3) cmꢁ1 13C NMR (150 MHz, CDCl3)
.
(m) cmꢁ1; 1H NMR (600 MHz, CDCl3)
d
(ppm): 9.04 (d, J¼5.4 Hz, 2H,
d (ppm): 196.1, 163.8, 159.3, 153.3, 150.7, 145.5, 140.6, 131.0, 130.7,
ArH), 8.92 (s, 1H ArH), 8.60 (s, 1H ArH), 8.39 (s, 1H, ArH), 8.16 (d,
J¼11.4 Hz, 1H, CH), 7.90 (d, J¼6.6 Hz, 3H, ArH), 7.49 (d, J¼7.2 Hz, 2H,
ArH), 7.13 (s, 1H, ArH), 6.85 (d, J¼7.2 Hz, 2H, ArH), 5.14 (d, J¼11.4 Hz,
1H, CH), 3.16 (s, 6H, 2NCH3), 2.40e2.36 (m, 2H, CH2),1.00 (t, J¼7.2 Hz,
126.6, 121.2, 114.1, 84.7, 55.2, 47.9, 27.4. MS (ESIꢁ): m/z¼471.9. Anal.
Calcd for C26H24N4O5: C 66.09, H 5.12, N 11.86; Found: C 65.74, H
5.38, N 11.66.
Compound 4k (Ar¼4-pyridyl, Ar0¼p-BrC6H4): yield: 86%. Mp
3H, CH3). 13C NMR (150 MHz, CDCl3)
d
(ppm): 195.0, 154.1, 153.4,
180e182 ꢀC. IR (KBr)
n: 3429(m), 3135(w), 3059(m), 2979(m), 1674
150.0, 145.6, 145.4, 143.9, 136.4, 136.0, 130.4, 129.4, 128.3, 126.4,
123.0, 84.5, 48.2, 28.4, 15.8. MS (ESIþ): m/z¼471.5. Anal. Calcd for
C27H26N4O4: C 68.92, H 5.57, N 11.91; Found: C 68.68, H 5.90, N 11.47.
Compound 4f (Ar¼3-pyridyl, Ar0¼p-BrC6H4): yield: 85%. Mp
(s), 1567(vs), 1483(s), 1430(s), 1379(s), 1264(m), 1229(m), 1009(m),
819(m), 771(m) cmꢁ1; 1H NMR (600 MHz, CDCl3)
d
(ppm): 9.03 (d,
J¼6.6 Hz, 2H, ArH), 8.66 (d, J¼6.0 Hz, 2H, ArH), 8.42 (t, J¼7.8 Hz, 1H,
ArH), 8.15 (d, J¼12.0 Hz, 1H, CH), 7.91 (t, J¼7.2 Hz, 2H, ArH),
7.48e7.47 (m, 4H, ArH), 7.15 (d, J¼8.4 Hz, 2H, ArH), 5.13 (d,
J¼12.0 Hz, 1H, CH), 3.16 (s, 6H, 2NCH3). 13C NMR (150 MHz, CDCl3)
160e162 ꢀC. IR (KBr)
n: 3072(w), 1669(s), 1583(vs), 1482(s), 1436
(vs), 1385(m), 1285(m), 1168(m), 1012(w), 775(s), 702(w) cmꢁ1; 1H
NMR(600 MHz, CDCl3)
(ppm): 9.07 (d, J¼4.8 Hz, 2H, ArH), 9.00 (s,
1H, ArH), 8.70 (s, 1H, ArH), 8.41 (s, 1H, ArH), 8.14 (d, J¼11.4 Hz, 1H,
d
d (ppm): 193.8, 161.9, 151.4, 149.1, 143.9, 143.6, 138.6, 136.4, 129.9,
129.4, 124.8, 120.0, 119.2, 82.1, 72.7, 46.1, 25.5. MS(ESIꢁ): m/z¼521.3.

7748
Y. Han et al. / Tetrahedron 66 (2010) 7743e7748
R.; Raithby, P. R. J. Chem. Soc., Dalton Trans. 1995, 3253; (d) Constable, E. C.;
Edwards, A. J.; Raithby, P. R.; Soto, J.; Tendero, M. J. L.; Martínez-Mánez, R.
Polyhedron 1995, 14, 3061.
Anal. Calcd for C25H21BrN4O4: C 57.59, H 4.06, N 10.75; Found: C
57.71, H 4.25, N 10.38.
ꢀ
Compound 4l (Ar¼4-pyridyl, Ar0¼p-ClC6H4): yield: 80%. Mp
6. (a) Bora, U.; Saikia, A.; Boruah, R. C. Org. Lett. 2003, 5, 435; (b) Armstrong, R. W.;
Combs, A. P.; Tempest, P. A.; Brown, S. D.; Keating, T. A. Acc. Chem. Res. 1996, 29,
123; (c) Domling, A.; Ugi, I. Angew. Chem., Int. Ed. 2000, 39, 3168; (d) Sasaki, T.;
Kanematsu, K.; Yukimoto, Y.; Ochiai, S. J. Org. Chem. 1971, 36, 813; (e) Xia, Z. Q.;
Przewloka, T.; Koya, K.; Ono, M.; Chen, S. J.; Sun, L. J. Tetrahedron Lett. 2006, 47, 8817.
7. (a) Katritzky, A. R.; Grzeskowiak, N. E.; Alvarez-Buila, J. J. Chem. Soc., Perkin
Trans. 1981, 1180; (b) Druta, I. I.; Dinica, R. M.; Bacu, E.; Humelnicu, I. Tetrahe-
dron 1998, 54, 10811; (c) Dinica, R. M.; Druta, I. I.; Pettinari, C. Synlett 2000,
1013; (d) Druta, I. I.; Andrei, M. A.; Ganj, C. I.; Aburel, P. S. Tetrahedron 1999, 55,
13063; (e) Furdui, B.; Dinica, R.; Druta, I. I.; Demeunynck, M. Synthesis 2006, 16,
2640.
190e192 ꢀC. IR (KBr)
n: 3434(m), 3088(w),1667(s),1589(vs),1486(m),
1433(s), 1384(s), 1223(m), 1168(m), 1064(m), 821(w), 774(m) cmꢁ1
1H NMR (600 MHz, CDCl3)
;
d
(ppm): 9.07 (d, J¼5.4 Hz, 2H, ArH), 8.66
(d, J¼3.6 Hz, 2H, ArH), 8.43 (t, J¼7.2 Hz, 1H, ArH), 8.14 (d, J¼12.0 Hz,
1H, CH), 7.93 (t, J¼6.0 Hz, 2H, ArH), 7.54e7.49 (m, 4H, ArH), 7.00 (d,
J¼7.8 Hz, 2H, ArH), 5.16 (d, J¼12.0 Hz,1H, CH), 3.16 (s, 6H, 2NCH3). 13
C
NMR (150 MHz, CDCl3) d (ppm): 195.7,151.4,151.2,150.9,149.8,145.4,
130.9, 129.6, 128.8, 128.6, 126.7, 123.7, 121.4, 121.1, 120.9, 47.8, 27.4. MS
(ESIꢁ): m/z¼475.8. Anal. Calcd for C25H21ClN4O4: C 62.96, H 4.44, N
11.75; Found: C 62.83, H 4.69, N 11.55.
8. (a) Peng, W. M.; Zhu, S. Z. J. Chem. Soc., Perkin Trans. 1 2001, 3204; (b) Zhu, S. Z.;
Qin, C. Y.; Wang, Y. L.; Chu, Q. L. J. Fluorine Chem. 1999, 99, 183; (c) Zhang, X. C.;
Huang, W. Y. Synthesis 1999, 1, 51; (d) Wu, K.; Chen, Q. Y. Synthesis 2003, 35; (e)
Chuang, C. P.; Tsai, A. I. Synthesis 2006, 4, 675.
9. (a) Zhang, X. D.; Hu, Y. F.; Hu, H. W. J. Chem. Soc., Perkin Trans. 1 1993, 2487; (b)
Wang, B. X.; Zhang, X. C.; Li, J.; Jiang, X.; Hu, Y. F.; Hu, H. W. J. Chem. Soc., Perkin
Trans. 1 1999, 1571; (c) Hu, J. X.; Jiang, X.; He, T.; Zhou, J.; Hu, Y. F.; Hu, H. W.
J. Chem. Soc., Perkin Trans. 1 2001, 1820.
10. (a) Shestopalov, A. M.; Litvinov, V. P.; Rodinovskaya, L. A.; Sharanin, Y. A. Zh. Org.
Khim. 1991, 146; (b) Kojima, S.; Suzuki, M.; Watanabe, A.; Ohkata, K. Tetrahedron
Lett. 2006, 47, 9061.
4. Supporting information
Crystallographic data (3e: CCDC 777602) have been deposited at
the Cambridge Crystallographic Database Centre.
11. (a) Yan, C. G.; Cai, X. M.; Wang, Q. F.; Wang, T. Y.; Zheng, M. Org. Biomol. Chem.
2007, 5, 945; (b) Yan, C. G.; Song, X. K.; Wang, Q. F.; Sun, J.; Siemeling, U.; Bruhn, C.
Chem. Commun. 2008,1440; (c) Wang, Q. F.; Song, X. K.; Chen, J.; Yan, C. G. J. Comb.
Chem. 2009, 11,1007; (d) Wang, Q. F.; Hou, H.; Hui, L.; Yan, C. G. J. Org. Chem. 2009,
74, 7403; (e) Yan, C. G.; Wang, Q. F.; Song, X. K.; Sun, J. J. Org. Chem. 2009, 74, 710.
12. Wang, Q. F.; Hui, L.; Hou, H.; Yan, C. G. J. Comb. Chem. 2010, 12, 260.
13. (a) Visser, P.; Zuhse, R.; Wong, M. W.; Wentrup, C. J. Am. Chem. Soc. 1996, 118,
12598; (b) Kuhn, A.; Pluüg, C.; Wentrup, C. J. Am. Chem. Soc. 2000, 122, 1945; (c)
Zia-Ebrahimi, M.; Reutzel, S. M.; Dorman, D. E.; Spangle, L. A.; Deeter, J. B. Chem.
Mater. 1994, 6, 822; (d) Wenkert, E.; Michelotti, E. L.; St. Pyrek, J. J. Org. Chem.
1984, 49, 1832.
Acknowledgements
This work was financially supported by the National Natural
Science Foundation of China (Grant No. 20972132).
References and notes
€
€
1. (a) Krohnke, F.; Zecher, W. Angew. Chem., Int. Ed. Engl. 1962, 1, 626; (b) Krohnke, F.
€
Angew. Chem., Int. Ed. Engl. 1963, 2, 225; (c) Krohnke, F. Synthesis 1976, 1.
€
14. (a) Curtz, J.; Dach, R.; Duchardt, K. H.; Krohnke, F. Chem. Ber. 1979, 112, 2199; (b)
2. (a) Yamada, S.; Yamamoto, J.; Ohta, E. Tetrahedron Lett. 2007, 48, 855; (b)
Kojima, S.; Hiroikea, K.; Ohkata, K. Tetrahedron Lett. 2004, 45, 3565; (c) Kojima,
S.; Fujitomo, K.; Shinohara, Y.; Shimizu, M.; Ohkata, K. Tetrahedron Lett. 2000,
41, 9847; (d) Vo, N. N.; Eyermann, C. J.; Hodge, C. N. Tetrahedron Lett. 1997, 38,
7951.
3. (a) Tsuge, O.; Kanemasa, S.; Takenaka, S. Bull. Chem. Soc. Jpn. 1985, 58, 3137; (b)
Neve, F.; Crispini, A.; Campagna, S. Inorg. Chem. 1997, 36, 6150; (c) MacGillivray,
L. R.; Diamente, P. R.; Reid, J. L.; Ripmeester, J. A. Chem. Commun. 2000, 359; (d)
Barrio, M. C. G.; Barrio, J. R.; Walker, G.; Novelli, A.; Leonard, N. J. J. Am. Chem.
Soc. 1973, 95, 4891.
Jursic, B. S.; Neumann, D. M.; Moore, Z.; Stevens, E. D. J. Org. Chem. 2002, 67, 2372.
15. (a) Shaabani, A.; Rezayan, A. H.; Sarvary, A.; Heidary, M.; Ng, S. W. Tetrahedron
2009, 65, 6063; (b) Varga, L.; Nagy, T.; Dormán, G.; Kálmán, F.; Urge, L.; Darvas,
F. J. Comb. Chem. 2006, 8, 338; (c) Wamhoff, H.; Schmidt, A. J. Org. Chem. 1993,
58, 6976.
16. (a) Jursic, B. S.; Neumann, D. M.; Martin, K. L.; Stevens, E. D. Org. Lett. 2002, 4,
811; (b) Sosnovskikh, V. Y.; Usachev, B. I.; Sizov, A. Y.; Vorontsov, I. I.; Shklyaev,
Y. V. Org. Lett. 2003, 5, 3123; (c) Zhang, S. L.; Huang, Z. S.; An, L. K.; Bu, X. Z.; Ma,
L.; Li, Y. M.; Chan, A. S. C.; Gu, L. Q. Org. Lett. 2004, 6, 4853.
17. (a) Nair, V.; Rajesh, C.; Vinod, A. U.; Bindu, S.; Sreekanth, A. R.; Mathen, J. S.;
Balagopal, L. Acc. Chem. Res. 2003, 36, 899; (b) Nair, V.; Menon, R. S.; Sreekanth,
A. R.; Abhilash, N.; Biju, A. T. Acc. Chem. Res. 2006, 39, 520.
18. (a) Yavari, I.; Mokhtarporyani-Sanandaj, A.; Moradi, L. Tetrahedron Lett. 2007,
48, 6709; (b) Yavari, I.; Mirzaei, A.; Moradi, L.; Hosseini, N. Tetrahedron Lett.
2008, 49, 2355; (c) Yavari, I.; Anary-Abbasinejad, M.; Alizadeh, A. Monatsh.
Chem. 2002, 133, 1331.
4. (a) Ulrich, G.; Ziessel, R. J. Org. Chem. 2004, 69, 2070; (b) Yam, V. W. W.; Wong,
K. M. C.; Zhu, N. Angew. Chem., Int. Ed. 2003, 42, 1400; (c) Coppo, P.; Duati, M.;
Kozhevnikov, V. N.; Hofstraat, J. W.; De Cola, L. Angew. Chem., Int. Ed. 2005, 44,
1806; (d) Pabst, G. R.; Pfüller, O. C.; Sauer, J. Tetrahedron 1999, 55, 5047; (e)
Hovinen, J.; Hakala, H. Org. Lett. 2001, 3, 2473; (f) Kozhevnikov, V. N.;
Kozhevnikov, D. M.; Nikitina, T. V.; Rusinov, V. L.; Chupakhin, O. N.; Zabel, M.;
€
Konig, B. J. Org. Chem. 2003, 68, 2882; (g) Lai, S. W.; Chan, M. C. W.; Cheung, K. K.;
19. Xia, E. Y.; Sun, J.; Yao, R.; Yan, C. G. Tetrahedron 2010, 66, 3569.
Che, C. M. Inorg. Chem. 1999, 38, 4262.
20. (a) King, L. C. J. Am. Chem. Soc. 1944, 66, 894; (b) Dodso, R. M.; King, L. C.
5. (a) Eryazici, I.; Moorefield, C. N.; Durmus, S.; Newkone, G. R. J. Org. Chem. 2006,
71, 1009; (b) Tu, S. J.; Jia, R. H.; Jiang, B.; Zhang, J. Y.; Zhang, Y.; Yao, C. S.; Ji, S. J.
Tetrahedron 2007, 63, 381; (c) Constable, E. C.; Edwards, A. J.; Martínez-Mánez,
€
J. Am. Chem. Soc. 1946, 68, 871; (c) Krohnke, F.; Gross, K. F. Chem. Ber. 1959,
92, 22.
ꢀ