An efficient synthesis of N-substituted-3-aryl-3-(4-hydroxy-6-methyl-2-oxo- 2H-pyran-3-yl)propanamides by four-component reaction in aqueous medium

Article abstract of DOI:10.1002/jhet.1000

A mild and efficient synthesis of N-substituted-3-aryl-3-(4-hydroxy-6- methyl-2-oxo-2H-pyran-3-yl)propanamides via four-component reaction of an aldehyde, amine, Meldrum's acid, and 4-hydroxy-6-methyl-2H-pyran-2-one in the presence of benzyltriethylammonium chloride (TEBAC) in aqueous medium is described. This method has the advantages of accessible starting materials, good yields, mild reaction conditions, and begin environmentally friendly.

Full text of DOI:10.1002/jhet.1000

January 2013 An Efficient Synthesis of N-Substituted-3-aryl-3-(4-hydroxy-6-methyl-2-
oxo-2H-pyran-3-yl)propanamides by Four-Component Reaction in
Aqueous Medium
99
a
a
a
b
*
Guo-Lan Dou, De-Ming Wang, Xiao-Xing Zhong, and Da-Qing Shi
aSchool of Safety Engineering, China University of Mining & Technology, Xuzhou 221116, China
bKey Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials
Science, Soochow University, Suzhou 215123, People’s Republic of China
*
E-mail: wdmcumt@163.com
Received March 19, 2011
DOI 10.1002/jhet.1000
View this article online at wileyonlinelibrary.com.
A mild and efficient synthesis of N-substituted-3-aryl-3-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)propanamides
via four-component reaction of an aldehyde, amine, Meldrum’s acid, and 4-hydroxy-6-methyl-2H-pyran-2-one in the
presence of benzyltriethylammonium chloride (TEBAC) in aqueous medium is described. This method has the
advantages of accessible starting materials, good yields, mild reaction conditions, and begin environmentally friendly.
J. Hetercyclic Chem., 50, 99 (2013).
INTRODUCTION
reactions, such as Diels–Alder reactions [16], Claisen rear-
rangement reactions [17], Reformatsky reactions [18], and
Pinacol-coupling reactions [19], not only for the advantages
concerning the avoidance of expensive drying reactions,
catalysts, and solvents, but also for some unique reactivity
and selectivity [20]. On the other hand, organic reactions in
water without using harmful organic solvents is one of the
current focuses today especially in the environmentally
conscious society, because water is abundant, nontoxic,
and environment-friendly when compared with organic
solvents used accordingly.
The amide bond plays an important role in the elaboration
and composition of biological and chemical systems [1].
Amides are traditionally synthesized by the reaction of
amines with activated carboxyl acid derivatives [2]. And
amides can also be synthesized by the Staudinger reaction
[3], the Beckmann rearrangement [4], Schmidt reaction [5],
aminocarbonylation of alkenes [6], haloarenes [7] and
alkynes [8], oxidative amidation of alhydes [9], hydrative
amide synthesis with alkynes [10], and the amidation of thio
acids with azides [11]. Jia X. S. [12] recently reported
Samarium-mediated facile method for the formation of
amide bonds by the reaction of acyl chlorides and amines.
However, the amides synthesized by most of the methods
are traditional, few of them contain heterocyclic substitu-
tional groups. Thus, the synthesis of amides containing
heterocyclic substitutional groups is a challenging goal.
Multicomponent reactions (MCRs), in which multiple
reactions are combined into the synthetic operation have
been used extensively to form carbon—carbon bonds in
the synthetic chemistry [13]. Such reactions offer a wide
range of possibilities for the efficient construction of highly
complex molecules in a single procedural step, thus avoiding
the complicated purification operations and allowing savings
of both solvents and reagents. In the past decade, there has
been tremendous development in three and four-component
reactions, and great efforts continue to be made to develop
new MCRs [14].
RESULTS AND DISCUSSION
As a continuation of our interest in green synthesis and
our previous work [21] on MCR in aqueous medium, herein
we report a green, one-pot, efficient synthesis of novel
propanamide derivatives in aqueous medium (Scheme 1).
The choice of an appropriate reaction media is of crucial
importance for successful organic synthesis. Initially, the
four-component reaction of 4-chlorobenzaldehyde 1a,
Meldrum’s acid 2, 4-hydroxy-6-methyl-2H-pyran-2-one
3, and 4-methylaniline 4a was investigated to establish
the optimization of the reaction conditions; reaction
temperature and different solvents were screened in the
model reaction. The results were summarized in Table 1. It
can been seen from Table 1 that water showed a superior
advantage not only in promoting the reaction but also in iso-
lation procedure, and the best yield was achieved (Table 1,
entry 2). In this reaction, catalyst benzyltriethylammonium
chloride (TEBAC) (N-benzyl-N,N,N-triethylammonium)
can provide the yield (Table 1, entry 1). Thus, water
employed as the reaction media for the following reactions.
Science Breslow demonstrated hydrophobic efforts could
strongly enhance the rate of some organic reactions and
rediscovered the use of water as solvent in organic synthesis
in 1980s [15], there has been a growing recognition that
water has become an attractive medium for many organic
© 2013 HeteroCorporation

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G.-L. Dou, D.-M. Wang, X.-X. Zhong, and D.-Q. Shi
Vol 50
Scheme 1
Table 1
and 4a as model substrates showed that the recovered reac-
tion solution could be successively recycled in subsequent
reaction without any decrease of yield (Table 3).
Optimization of solvent in the synthesis of 5a.
Temperature
(ꢀC)
Reaction
time (h)
Yield
(%)
1
All the products were characterized by H-NMR, IR,
Entry
Solvent
and HRMS spectra. The structure of 5e was further
confirmed by X-ray diffraction analysis. The molecular
structure of the product 5e is shown in Figure 1.
Although the mechanism of the reaction has not yet
been established, a possible explanation is proposed in
Scheme 2.
1
2
3
4
5
6
7
H2O, TEBAC
H2O
CH3COCH3
C2H5OH
CH3CN
CH3COOC2H5
ClCH2CH2Cl
90
90
5
7
98
70
0
Reflux
Reflux
Reflux
Reflux
Reflux
10
10
10
10
10
0
48
29
43
The reaction might proceed via sequential condensation,
addition, cyclization, and elimination. First, a Knoevenagel
condensation between aldehydes 1 with Meldrum’s acid 2
to afford intermediate A. The Michael addition of A with
4-hydroxy-6-methyl-2H-pyran-2-one 3 would then furnish
the intermediate product B, which subsequently underwent
intramolecular cyclization and then released acetone and
carbon dioxide to give intermediate product C. The
intermediate product C then attacked by amine 4 to give
the product 5.
In summary, a series of N-substituted-3-aryl-3-(4-
hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-propanamides were
synthesized via four-component reaction of aldehyde, amine,
Meldrum’s acid, and 4-hydroxy-6-methyl-2H-pyran-2-one in
the presence of TEBAC in aqueous medium. This protocol
has the advantages of accessible starting materials, high yield,
mild reaction condensations, and environmentally friendly.
Under the conditions described earlier (H2O, TEBAC,
90ꢀC), the scope of these MCRs was examined (Table 2).
A range of novel valuable structures of 5 were synthesized
in good to excellent yields by simply four-component
reaction in aqueous media. The results are summarized in
Table 2.
Apart from the mild conditions of the process and its
excellent results, the simplicity of product isolation and
the possibility to recycle the reaction solution offer a
significant advantage. Because TEBAC is soluble in water
and the desired product is less soluble in water, the
products can be directly separated by cooling to RT, and
filtering after the reaction is completed. The remaining
reaction solution can be recycled. Studies using 1a, 2, 3,
Table 2
Synthesis of compounds 5 in aqueous media.
Entry
Product
Ar
R
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
5a
5b
5c
5d
5e
5f
5g
5h
5i
4-ClC6H4
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
3-ClC6H4
4-FC6H4
4-NO2C6H4
2-ClC6H4
3-Cl-4-CH3C6H3
C6H5CH2
5
10
6
10
8
5
11
8
10
14
15
6
98
97
95
88
90
90
87
90
95
85
70
98
96
4-CH3C6H4
4-CH3OC6H4
3-ClC6H4
2-NO2C6H4
3,4-OCH2OC6H3
Thiophen-2-yl
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
9
10
11
12
13
5j
5k
5l
5m
4-ClC6H4
4
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2013 An Efficient Synthesis of N-Substituted-3-aryl-3-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)
101
propanamides by Four-Component Reaction in Aqueous Medium
Table 3
crystallographic analysis was performed with a Rigaku Mercury
diffractometer.
Reuse of aqueous medium containing TEBAC in the preparation of 5a.
Preparation of propanamides 5; general procedure.
mixture of the aldehyde (2 mmol), Meldrum’s acid
(2 mmol), 4-hydroxy-6-methyl-2H-pyran-2-one
A
2
1
Round
1
2
3
4
5
6
3
(2 mmol),
Yield (%)
98
98
96
92
95
92
amine 4 (2 mmol), and TEBAC (0.1 g) in water (10 mL) was
stirred for 4–20 h at 90ꢀC, then cooled to RT. The crystalline
powder formed was collected by filtration, washed with water,
and recrystallized from ethanol to give pure 5.
3-(4-Chlorophenyl)-3-(4-hydroxy-6-methyl-2-oxo-2H-pyran-
3-yl)-N-p-tolylpropanamide (5a). This compound was obtained
as solid with mp 221–222ꢀC. IR (KBr) n: 3287, 3206, 3064, 1695,
EXPERIMENTAL
Commercial solvents and reagents were used as received.
IR spectra were obtained on a Tensor 27 spectrophotometer.
1H-NMR spectra were recorded using Bruker DPX-400 MHz
instrument, at 293 K unless otherwise noted, with residue peaks
of the solvents DMSO-d6 (d = 2.50) used for reference. HRMS
were obtained on a microma GCT–TOF instrument. X-ray
1653, 1602, 1551, 1512, 1489, 403, 1259, 997, 811, 790, 719 cmÀ1
.
1H-NMR (400 MHz, DMSO-d6): d = 2.12 (s, 3H, CH3), 2.22 (s, 3H,
CH3), 2.92 (dd, J1 = 6.8 Hz, J2 = 15.2Hz, 1H, CH), 3.33 (dd,
J1 = 8.8 Hz, J2 = 15.2Hz, 1H, CH), 4.76 (t, J = 7.6 Hz, 1H, CH),
5.99 (s, 1H, CH), 7.05 (d, J = 8.4 Hz, 2H, ArH), 7.29 (d,
Figure 1. Molecular structure of 5e.
Scheme 2. Possible mechanism for the formation of product 5.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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G.-L. Dou, D.-M. Wang, X.-X. Zhong, and D.-Q. Shi
Vol 50
J = 8.8 Hz, 2H, ArH), 7.35 (d, J = 8.8 Hz, 2H, ArH), 7.41 (d,
3-(3,4-Methylenedioxyphenyl)-3-(4-hydroxy-6-methyl-2-oxo-
2H-pyran-3-yl)-N-p-tolylpropanamide (5f). This compound was
obtained as solid with mp 228–230ꢀC. IR (KBr) n: 3297, 3208,
3033, 1680, 1650, 1603, 1543, 1515, 1446, 1252, 1041, 939, 817,
783 cmÀ1. 1H-NMR (400 MHz, DMSO-d6): d = 2.11 (s, 3H, CH3),
2.22 (s, 3H, CH3), 2.90 (dd, J1 = 6.8Hz, J2 = 15.2 Hz, 1H, CH),
3.28 (dd, J1 = 8.8Hz, J2 = 15.2Hz, 1H, CH), 4.69 (t, J = 7.6 Hz,
1H, CH), 5.91 (s, 2H, OCH2O), 5.98 (s, 1H, CH), 6.73–6.80
(m, 2H, ArH), 6.94 (s, 1H, ArH), 7.04 (d, J = 8.0Hz, 2H, ArH),
7.42 (d, J = 8.0Hz, 2H, ArH), 9.86 (s, 1H, NH), 11.46 (s, 1H,
OH). HRMS: m/z Calcd for C23H21NO6: 430.1267 (M+ Na);
found 430.1271.
J = 8.0 Hz, 2H, ArH), 9.90 (s, 1H, NH), 11.58 (s, 1H, OH).
35
20
HRMS: m/z Calcd for C22H ClNO4: 420.0979 (M+ Na); found
420.0992.
3-(4-Hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-N,3-di(p-tolyl)
propanamide (5b). This compound was obtained as solid with
mp 250–252ꢀC. IR (KBr) n: 3287, 3194, 3031, 1682, 1638, 1602,
1541, 1514, 1404, 1256, 996, 940, 818, 782 cmÀ1 1H-NMR
.
(400MHz, DMSO-d6): d = 2.10 (s, 3H, CH3), 2.21 (s, 6H,
2 Â CH3), 2.94 (dd, J1 = 6.8 Hz, J2 = 15.2Hz, 1H, CH), 3.30
(dd, J1 =8.4Hz, J2 = 15.2 Hz, 1H, CH), 4.73 (t, J= 7.6 Hz, 1H,
CH), 5.97 (s, 1H, CH), 7.05–7.00 (m, 4H, ArH), 7.24
(d, J= 8.0 Hz, 2H, ArH), 7.42 (d, J= 8.4 Hz, 2H, ArH), 9.87
(s, 1H, NH), 11.57 (s, 1H, OH). HRMS: m/z Calcd for
C23H23NO4: 378.1705 (M + H); found 378.1725.
3-(4-Hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-3-(4-methoxy-
phenyl)-N-p-tolylpropanamide (5c). This compound was obtained
as solid with mp 230–232ꢀC. IR (KBr) n: 3232, 3113, 3071, 1684,
1645, 1606, 1565, 1512, 1456, 1253, 1167, 998, 932, 824, 782,
764 cmÀ1. 1H-NMR (400 MHz, DMSO-d6): d = 2.12 (s, 3H, CH3),
2.21 (s, 3H, CH3), 2.90 (dd, J1 =6.8 Hz, J2 = 15.2Hz, 1H, CH),
3.32 (dd, J1 = 8.8Hz, J2 = 15.2Hz, 1H, CH), 3.69 (s, 3H, CH3O),
4.76 (t, J = 7.6 Hz, 1H, CH), 5.99 (s, 1H, CH), 6.82 (d, J = 8.8Hz,
2H, ArH), 7.28 (d, J = 8.4 Hz, 2H, ArH), 7.36 (d, J = 8.4Hz, 2H,
ArH), 7.44 (d, J = 8.8 Hz, 2H, ArH), 9.84 (s, 1H, NH), 11.54
(s, 1H, OH). HRMS: m/z Calcd for C23H23NO5: 416.1474
(M +Na); found 416.1467.
3-(4-Hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-3-(thiophen-
2-yl)-N-p-tolylpropanamide (5g). This compound was obtained
as solid with mp 263–265ꢀC. IR (KBr) n: 3287, 3206, 3079,
1684, 1651, 1603, 1541, 1515, 1445, 1128, 997, 851, 818, 783,
697 cmÀ1 1H-NMR (400 MHz, DMSO-d6): d = 2.12 (s, 3H,
.
CH3), 2.22 (s, 3H, CH3), 3.00 (dd, J1 = 6.8 Hz, J2 = 15.2 Hz, 1H,
CH), 3.31 (dd, J1 = 8.8 Hz, J2 = 15.2 Hz, 1H, CH), 5.00
(t, J = 7.6 Hz, 1H, CH), 6.00 (s, 1H, CH), 6.89–6.85 (m, 2H,
ArH), 7.05 (d, J = 8.4 Hz, 2H, ArH), 7.21 (d, J = 4.4 Hz, 2H,
ArH), 7.44 (d, J = 8.4 Hz, 2H, ArH), 9.92 (s, 1H, NH), 11.60
(s, 1H, OH). HRMS: m/z Calcd for C20H19NO4S: 392.0933
(M + Na); found 392.0928.
N-(3-Chlorophenyl)-3-(4-chlorophenyl)-3-(4-hydroxy-6-
methyl-2-oxo-2H-pyran-3-yl)propanamide (5h). This compound
was obtained as solid with mp 272–274ꢀC. IR (KBr) n: 3276, 3192,
3078, 1682, 1647, 1594, 1541, 1490, 1446, 1221, 1059, 973, 818,
3-(3-Chlorophenyl)-3-(4-hydroxy-6-methyl-2-oxo-2H-pyran-
3-yl)-N-p-tolylpropanamide (5d). This compound was obtained as
solid with mp 259–261ꢀC. IR (KBr) n: 3287, 3155, 3067, 1681,
1638, 1604, 1541, 1515, 1474, 1318, 1255, 1128, 998, 817, 775,
731, 718, 685 cmÀ1 1H-NMR (400 MHz, DMSO-d6): d = 2.12
.
(s, 3H, CH3), 3.00 (dd, J1 = 6.8 Hz, J2 = 15.2 Hz, 1H, CH), 3.35
(dd, J1 = 8.8 Hz, J2 = 15.2 Hz, 1H, CH), 4.75 (t, J = 7.6 Hz, 1H,
CH), 6.00 (s, 1H, CH), 7.05 (d, J = 7.6 Hz, 1H, ArH), 7.28–7.40
697 cmÀ1 1H-NMR (400 MHz, DMSO-d6): d = 2.12 (s, 3H,
.
(m, 6H, ArH), 7.77 (s, 1H, ArH), 10.21 (s, 1H, NH), 11.65 (s, 1H,
OH). HRMS: m/z Calcd for C21H Cl2NO4: 440.0433 (M+ Na);
found 440.0411.
CH3), 2.22 (s, 3H, CH3), 2.93 (dd, J1 = 6.8 Hz, J2 = 15.2Hz, 1H,
CH), 3.35 (dd, J1 = 8.8 Hz, J2 = 15.2Hz, 1H, CH), 4.76
(t, J = 7.6 Hz, 1H, CH), 6.00 (s, 1H, CH), 7.05 (d, J = 8.4 Hz, 2H,
ArH), 7.20 (d, J = 7.2 Hz, 1H, ArH), 7.43–7.28 (m, 5H, ArH),
35
17
3-(4-Chlorophenyl)-N-(4-fluorophenyl)-3-(4-hydroxy-6-methyl-
2-oxo-2H-pyran-3-yl)propanamide (5i). This compound was
obtained as solid with mp 225–227ꢀC. IR (KBr) n: 3292, 3156,
3090, 1677, 1643, 1616, 1587, 1510, 1445, 1289, 1257, 978, 835,
9.92 (s, 1H, NH), 11.64 (s, 1H, OH). HRMS: m/z Calcd for
35
20
C22H ClNO4: 420.0979 (M+ Na); found 420.0974.
3-(4-Hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-3-(2-nitrophenyl)-
N-p-tolylpropanamide (5e). This compound was obtained as
solid with mp 232–234ꢀC. IR (KBr) n: 3270, 3190, 3039, 1685,
1655, 1602, 1569, 1522, 1448, 1383, 1271, 1251, 1106, 997,
789, 768, 709cmÀ1 1H-NMR (400 MHz, DMSO-d6): d = 2.12
.
(s, 3H, CH3), 2.95 (dd, J1 = 6.8 Hz, J2 = 15.2Hz, 1H, CH), 3.32
(dd, J1 = 8.8 Hz, J2 = 15.2Hz, 1H, CH), 4.76 (t, J = 7.6Hz, 1H,
CH), 5.99 (s, 1H, CH), 7.09 (t, J = 8.8 Hz, 2H, ArH), 7.29
(d, J = 8.4 Hz, 2H, ArH), 7.35 (d, J = 8.4Hz, 2H, ArH), 7.53–7.57
1
855, 821, 781, 712, 699 cmÀ1. H-NMR (400 MHz, DMSO-d6):
d = 2.10 (s, 3H, CH3), 2.22 (s, 3H, CH3), 3.08 (dd, J1 = 6.8 Hz,
J2 = 15.2 Hz, 1H, CH), 3.30 (dd, J1 = 8.8 Hz, J2 = 15.2 Hz, 1H,
CH), 5.09 (t, J = 7.6 Hz, 1H, CH), 5.94 (s, 1H, CH), 7.06
(d, J = 8.4 Hz, 2H, ArH), 7.36–7.44 (m, 3H, ArH), 7.60
(t, J = 7.6 Hz, 1H, ArH), 7.70 (d, J = 8.0 Hz, 1H, ArH), 7.81
(d, J = 8.0 Hz, 1H, ArH), 9.91 (s, 1H, NH), 11.64 (s, 1H, OH).
HRMS: m/z Calcd for C22H20N2O6: 431.1219 (M + Na); found
431.1212.
(m, 2H, ArH), 10.05 (s, 1H, NH), 11.55 (s, 1H, OH). HRMS: m/z
35
17
Calcd for C21H ClFNO4: 424.0728 (M+ Na); found 424.0717.
3-(4-Chlorophenyl)-3-(4-hydroxy-6-methyl-2-oxo-2H-pyran-
3-yl)-N-(4-nitrophenyl)propanamide (5j). This compound was
obtained as solid with mp 246–247ꢀC. IR (KBr) n: 3217, 3047,
1684, 1652, 1615, 1584, 1557, 1511, 1446, 1381, 1242, 1091,
1
977, 858, 778, 733, 712, 689 cmÀ1. H-NMR (400 MHz, DMSO-
d6): d = 2.12 (s, 3H, CH3), 3.10 (dd, J1 = 6.8 Hz, J2 = 15.2Hz, 1H,
CH), 3.43 (dd, J1 = 8.8 Hz, J2 = 15.2Hz, 1H, CH), 4.76
(t, J = 7.6 Hz, 1H, CH), 6.00 (s, 1H, CH), 7.30 (d, J = 8.4 Hz, 2H,
ArH), 7.36 (d, J = 8.4 Hz, 2H, ArH), 7.79 (d, J = 8.8 Hz, 2H,
Crystal data. C25H27N3O7; M= 481.50, yellow block crystals,
0.60 Â 0.44 Â 0.30 mm, triclinic, space group P-1, a= 9.4431(14) Å,
b= 10.0026(15) Å, c= 13.382(2) Å, a = 83.674(9)ꢀ, b = 80.784(9)ꢀ,
g = 77.878(8)ꢀ, V= 1216.0(3) Å3, Z=2, Dc =1.315gcmÀ1
, F
(000) = 508, m(MoKa) = 0.097 mmÀ1. Intensity data were collected
on a diffractometer with graphite monochromated MoKa radiation
(l = 0.71070 Å) using o scan mode with 3.09ꢀ < θ< 25.34ꢀ. 4411
unique reflections were measured, and 3574 reflections with I> 2s
(I) were used in the refinement. The structure was solved by direct
methods and expanded using Fourier techniques. The final cycle of
full-matrix least squares technique to R1 = 0.0723 and wR2 = 0.1766.
ArH), 8.18 (d, J = 8.8 Hz, 2H, ArH), 10.64 (s, 1H, NH), 11.65
35
17
(s, 1H, OH). HRMS: m/z Calcd for C21H ClN2O6: 451.0673
(M+ Na); found 451.0665.
N-(2-Chlorophenyl)-3-(4-chlorophenyl)-3-(4-hydroxy-6-methyl-
2-oxo-2H-pyran-3-yl)propanamide (5k).
This compound was
obtained as solid with mp 220–222ꢀC. IR (KBr) n: 3224, 3195,
3038, 1681, 1616, 1586, 1544, 1490, 1475, 1443, 1255, 1061, 996,
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January 2013 An Efficient Synthesis of N-Substituted-3-aryl-3-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)
103
propanamides by Four-Component Reaction in Aqueous Medium
859, 812, 778, 731, 705 cmÀ1 1H-NMR (400 MHz, DMSO-d6):
.
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[11] (a) Zhang, X.; Li, F.; Lu, X. W.; Liu, C. F. Bioconjugate
Chem. 2009, 20, 197 (b) Kolakowski, R. V.; Shangguan, N.; Sauers,
R. R.; Williams, L. J. J Am Chem Soc 2006, 128, 5695.
d = 2.13 (s, 3H, CH3), 3.03 (dd, J1 =6.8Hz, J2 = 15.2 Hz, 1H, CH),
3.30 (dd, J1 =8.8Hz, J2 = 15.2 Hz, 1H, CH), 4.74 (t, J= 7.6 Hz, 1H,
CH), 6.00 (s, 1H, CH), 7.17 (t, J= 6.8 Hz, 1H, ArH), 7.26–7.31 (m,
3H, ArH), 7.38 (d, J= 8.4 Hz, 2H, ArH), 7.45 (d, J= 6.8 Hz, 1H,
ArH), 7.53 (d, J= 7.2 Hz, 1H, ArH), 9.56 (s, 1H, NH), 11.57 (s, 1H,
35
17
OH). HRMS: m/z Calcd for C21H Cl2NO4: 440.0433 (M + Na);
found 440.0422.
N-(3-Chloro-4-methylphenyl)-3-(4-chlorophenyl)-3-(4-
hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)propanamide (5l). This
compound was obtained as solid with mp 238–240ꢀC. IR (KBr)
n: 3293, 3194, 3060, 1677, 1646, 1597, 1538, 1498, 1446, 1254,
1
1106, 978, 867, 817, 786, 709, 694 cmÀ1. H-NMR (400 MHz,
DMSO-d6): d = 2.12 (s, 3H, CH3), 2.23 (s, 3H, CH3), 2.98 (dd,
J1 = 6.8 Hz, J2 = 15.2Hz, 1H, CH), 3.33 (dd, J1 = 8.8 Hz,
J2 = 15.2Hz, 1H, CH), 4.76 (t, J = 7.6 Hz, 1H, CH), 6.00 (s, 1H,
CH), 7.21 (d, J = 8.4 Hz, 1H, ArH), 7.28–7.30 (m, 3H, ArH), 7.35
(d, J = 8.4 Hz, 2H, ArH), 7.75 (s, 1H, ArH), 10.10 (s, 1H, NH),
35
19
11.56 (s, 1H, OH). HRMS: m/z Calcd for C22H Cl2NO4:
454.0589 (M+ Na); 454.0587.
N-Benzyl-3-(4-chlorophenyl)-3-(4-hydroxy-6-methyl-2-oxo-
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2H-pyran-3-yl)propanamide (5m).
This compound was
obtained as solid with mp 223–225ꢀC. IR (KBr) n: 3260, 3101,
3027, 1683, 1646, 1600, 1507, 1559, 1490, 1446, 1318, 1267,
996, 791, 696 cmÀ1 1H-NMR (400 MHz, DMSO-d6): d = 2.12
.
(s, 3H, CH3), 2.80 (dd, J1 = 6.8 Hz, J2 = 15.2 Hz, 1H, CH), 3.17
(dd, J1 = 8.8 Hz, J2 = 15.2 Hz, 1H, CH), 4.13–4.25 (m, 2H, CH2),
4.70 (t, J = 8.0 Hz, 1H, CH), 5.99 (s, 1H, CH), 7.00 (d,
J = 6.0 Hz, 2H, ArH), 7.18–7.22 (m, 3H, ArH), 7.28 (d,
J = 8.8 Hz, 2H, ArH), 7.35 (d, J = 8.4 Hz, 2H, ArH), 8.39 (s, 1H,
NH), 11.52 (s, 1H, OH).
Acknowledgments. We are grateful to the Fundamental Research
Funds for the Central Universities for financial support
(2010QNB03) and A Project Funded by the Priority Academic
Program Development of Jiangsu Higher Education Institutions.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet