A novel and efficient synthesis of 3,3′-benzylidenebis(4-hydroxy-6- methylpyridin-2(1H)-one) derivatives through a multi-component reaction catalyzed by L-proline

Article abstract of DOI:10.1071/CH08113

N-Substituted pyridinone derivatives are well known for their variety of physiological activities. A series of new 3,3′-benzylidenebis(4-hydroxy-6- methylpyridin-2(1H)-one) derivatives were synthesized by a three-component reaction of an aldehyde, an aniline, and 6-methyl-4-hydroxypyran-2-one in EtOH catalyzed by l-proline. This method is novel and has the advantages of environmental friendliness, high yield, and ease of operation. CSIRO 2008.

Full text of DOI:10.1071/CH08113

Full Paper
CSIRO PUBLISHING
www.publish.csiro.au/journals/ajc
Aust. J. Chem. 2008, 61, 547–551
A Novel and Efficient Synthesis of 3,3ꢀ-Benzylidenebis(4-
hydroxy-6-methylpyridin-2(1H)-one) Derivatives Through
a Multi-Component Reaction Catalyzed by L-Proline
Chun-Ling Shi,A Da-Qing Shi,B,D Sung Hong Kim,C Zhi-Bin Huang,B
and Min JiA
ACollege of Chemistry and Chemical Engineering, Institute of Pharmaceutical Engineering,
Southeast University, Nanjing, Jiangsu 210096, China.
BCollege of Chemistry and Chemical Engineering, Key Laboratory of Organic Synthesis
of Jiangsu Province, Suzhou University, Suzhou 215123, China.
CAnalysis Research Division, Daegu Center, Korea Basic Science Institute, Daegu 702-701, Korea.
DCorresponding author. Email: dqshi@263.net
N-Substituted pyridinone derivatives are well known for their variety of physiological activities. A series of new 3,3ꢀ-
benzylidenebis(4-hydroxy-6-methylpyridin-2(1H)-one) derivatives were synthesized by a three-component reaction of an
aldehyde, an aniline, and 6-methyl-4-hydroxypyran-2-one in EtOH catalyzed by l-proline. This method is novel and has
the advantages of environmental friendliness, high yield, and ease of operation.
Manuscript received: 19 March 2008.
Final version: 13 May 2008.
Introduction
chemistry.[9] Suchreactionsofferawiderangeofpossibilitiesfor
the efficient construction of highly complex molecules in a sin-
gle procedural step, thus avoiding the complicated purification
operations and allowing savings of both solvents and reagents.
In the past decade there have been tremendous development in
three- and four-component reactions and great efforts continue
to be made to develop new multi-component reactions.[10]
However, the replacement of current chemical processes with
more environmentally benign alternatives is an increasingly
attractive goal in organic synthesis. Recently, organic reac-
tions catalyzed by small organic molecules have been studied
more and more extensively. A lot of small organic molecules,
for instance cinchona alkaloids, l-proline, and its deriva-
tives, have been used in various transformations with excellent
yields.[11] Enamine-based direct catalytic asymmetric Aldol,[12]
Mannich,[13] Michael,[14] Diels–Alder,[15] α-amination reac-
tions, and Knoevenagel-type reactions[15,16] using l-proline as
catalyst have also been reported. Recently, l-proline and its
derivatives have been used in multi-component unsymmetric
Biginelli[17] and Hantzsch reactions.[18] More recently, we have
reported the synthesis of furo[3ꢀ,4ꢀ:5,6]pyrido[2,3-c]pyrazole
derivatives catalyzed by organocatalysts.[19] Ammonization is
one of the most important methods for the formation of
carbon–nitrogen bonds. As part of our current studies on
the development of new routes to heterocyclic systems, we
now report an efficient and green synthetic route to 3,3ꢀ-
benzylidenebis(4-hydroxy-6-methylpyridin-2(1H)-ones) 4 by a
three-component reaction (which consists of condensation,
addition, and ammonization) of an aldehyde 1, aniline 2,
and 6-methyl-4-hydroxypyran-2-one 3 catalyzed by l-proline
(Scheme 1).
N-Substituted pyridinone derivatives are known to exhibit a
variety of physiological activities.[1] Milrinone is the prototype
of clinically useful ‘non-glycoside’ inotropes, indicated for the
short-term intravenous therapy of congestive heart failure.[2] In
the past two decades, using milrinone as the template, several
series of pyridin-2(1H)-ones, bearing different substituents at
positions C3, C5, and C6, have been synthesized and tested for
their ability to induce cardiotonic response on guinea-pig iso-
lated myocardial preparations.[3] The conventional synthesis of
pyridinones is carried out by ammonization of pyranone with
amines at a high temperature or in a sealed tube.[4,5] Recently,
several methods have been developed for the synthesis of this
heterocyclic system, e.g., Stoncius et al. reported the synthesis of
N-benzyl-4-hydroxy-2-pyridone by the reaction of 4-hydroxy-6-
methylpyran-2-one with an equimolar amount of benzylamine
in water in 56% yield,[6] and Lu et al. reported the synthe-
sis of N-aryl-2-ethyl-3-hydroxy-4-pyridinones under microwave
irradiation.[7] In addition, bis(pyridyl)methanes have also been
synthesized from aldehydes and 4-hydroxy-2-pyridones cat-
alyzed by piperidine.[8] However, these methods suffer from
many disadvantages such as multi-step procedures, long reac-
tion times, low yields, use of organic solvents, and use of toxic
reagents. Therefore, the development of more efficient meth-
ods for the preparation of this kind of compound is still an
active ongoing research area and there is scope for further
improvement towards milder reaction conditions and improved
yields.
Multi-component reactions, in which multiple reactions
are combined into one synthetic operation, have been
used extensively to form carbon–carbon bonds in synthetic
© CSIRO 2008
10.1071/CH08113
0004-9425/08/070547

548
C.-L. Shi et al.
OH
R1
OH
OH
O
EtOH, 80°C
R1
ϩ 2R2
2
CHO
NH2 ϩ
10 mol-% L-proline
H3C
O
H3C
N
O O
N
CH3
R2
R2
1
2
3
4
Scheme 1.
Table 1. Solvent optimization for the synthesis of 4a catalyzed by
Table 4. Studies on the catalytic efficiency of different organocatalysts
for the synthesis of 4aA
10 mol-% l-proline
Entry
Solvent
Temperature
[◦C]
Reaction time
[h]
Isolated yield
[%]
Entry
Catalyst
None
Reaction time
[h]
Isolated yield
[%]
1
2
3
4
5
6
7
EtOH
Water
80
100
60
1.5
4
4
4
4
90
0
0
0
0
1
2
4
35
90
COOH
COOH
Acetone
CHCl3
DMF
HOAc
CH3CN
1.5
N
H
70
5a
5b
100
100
70
4
4
0
0
S
3
4
5
2
2
2
74
73
76
N
H
HO
Table 2. Temperature optimization for the synthesis of 4a in EtOH
COOH
catalyzed by 10 mol-% l-proline
N
H
5c
Entry
Temperature [◦C]
Reaction time [h]
Isolated yield [%]
Ph
1
2
3
4
Room temp.
4
4
2.5
1.5
0
0
71
90
H2N
COOH
5d
40
60
80
H
N
HO
6
1.5
61
Table 3. Optimization of catalyst loading when synthesizing 4a in
ethanol at 80◦C
H
N
5e
Entry
Amount of l-proline
Reaction
time [h]
Isolated
yield [%]
[mol-%]
H
1
2
3
4
5
10
15
20
2
64
90
91
90
1.5
1.5
1.5
N
HO
7
2
58
H
N
5f
Result and Discussion
4-Methoxyaniline 2a has been used as the starting material
to synthesize bispyridinones. Therefore, we first chose 2a
and searched for optimized conditions for its reaction with
4-bromobenzaldehyde 1a and 6-methyl-4-hydroxypyran-2-one
3 to afford bispyridinones.
Different solvents were examined. The results of these com-
parative experiments are summarized inTable 1. From the results
it is obvious that ethanol is the best solvent among those exam-
ined, and therefore we chose ethanol as the solvent for this
reaction.
To optimize the reaction temperature, the synthesis of 4a
was studied in EtOH in the presence of 10 mol-% l-proline, at
different temperatures.The results are summarized inTable 2.As
shown inTable 2, the reaction at 80◦C proceeded in highest yield
and shortest reaction time among the four reaction temperatures
tested. Therefore, 80◦C was chosen for this reaction.
To optimize the catalyst loading, 5, 10, 15, and 20 mol-% of
l-proline was tested, respectively. The results are summarized in
NH
8
9
4
4
37
35
5g
5h Et3N
AReaction conditions: 4-methoxyaniline (2 mmol), 4-bromobenzaldehyde
(1 mmol), and 6-methyl-4-hydroxypyran-2-one (2 mmol), 10 mol-% cata-
lyst, EtOH, 80◦C.
Table 3. A 10 mol-% loading of l-proline was sufficient to push
the reaction forward and 5 mol-% of l-proline was not enough.
Higher amounts of l-proline did not lead to a significant change
in the reaction yields.
The catalytic efficiency of other organocatalysts in this reac-
tion was also studied. In all cases 10 mol-% of the catalyst was
used and the reaction was carried out in refluxing ethanol. As
shown inTable 4, the catalytic effects of 5a–c were similar, while
5d–h gave lower yields. The presence of a secondary amine and

Synthesis of N-Substituted Pyridinone Derivatives
Table 5. l-Proline catalyzed synthesis of 4
549
OH
COOϪ
Nϩ
R1
Product
R1
R2
Reaction
time [h]
Isolated
yield [%]
H3C
O
3
O
H
O
6
R1
H
4a
4b
4c
4d
4e
4f
4-BrC6H4
4-CH3C6H4
4-ClC6H4
4-OCH3C6H4
4-OCH3C6H4
4-ClC6H4
4-FC6H4
4-FC6H4
4-FC6H4
1
1
2
3
3
4
3
2
2.5
4
3
3
2
90
91
93
89
82
86
89
92
89
84
86
83
90
1
O
N
H
COOϪ
COOH
H
N
H
R1
H3C
O
O
4-ClC6H4
7
3,4-Cl2C6H3
4-OCH3C6H4
4-CH3C6H4
4-ClC6H4
4-OHC6H4
4-BrC6H4
4-OCH3C6H4
4-BrC6H4
4-BrC6H4
4g
4h
4i
4-FC6H4
R1
4-CH3C6H4
4-CH3C6H4
4-BrC6H4
C6H5
C6H5
4-CH3C6H5
O
O
OH
H
4j
H3C
O
O
O
CH3
4k
4l
3
8
4m
R1
OH R1
OH
O
O
OH
H3C
CH3
H3C
O
CH3
O
O
O O
O
10
O
9
R2 NH2
R2 NH2
carboxylic acid at the 2-position in the catalyst led to good yields
of products, while d,l-phenylglycine 5d with a primary amino
group, and (+)-cinchonine 5e, and cinchonidine 5f, with a ter-
tiary amino group, respectively, gave lower yields. Replacing
CH2 (in 5a) by S (in 5b) and with CHOH (in 5c) did not affect
yields significantly. Therefore, it was concluded that l-proline
was the best among the six catalysts in this study.
2
2
OH R1
O
N
OH R1
O
OH
O O
H3C
CH
3
N
H3C
HO
O
O
CH3
NH HN
R2
R2
R2
R2
4
11
Under these appropriate reaction conditions (2 mL EtOH,
80◦C, 10 mol-% l-proline), a series of 3,3ꢀ-benzylidenebis(4-
hydroxy-6-methylpyridin-2(1H)-one) derivatives 4 were synthe-
sized. The results are summarized in Table 5.
As shown in Table 2, this protocol could be applied to the
aromatic aldehydes with either electron-withdrawing groups
(such as halide groups) or electron-donating groups (such as
alkyl and hydroxy groups). Furthermore, it was particularly
noteworthy that the protocol could be applied not only to aro-
matic amines with electron-donating groups (such as alkyl and
alkoxy groups) but also to electron-withdrawing groups (such
as halide groups), which highlights the wide scope of this
three-component reaction.
OH R1
O
OH R1
O
H2O
O O
O
O O
N
O
H3C
CH3
OH
CH3
H3C
HO
N
R2
HN
R2
NH
R2
R2
13
12
Scheme 2.
products, shorter reaction times, environmental friendliness, and
straightforward procedure.
Although the detailed mechanism of the above reac-
tion remains to be fully clarified, the formation of 3,3ꢀ-
benzylidenebispyridinone derivatives could be explained by a
possible reaction sequence presented in Scheme 2. Product 4
may be synthesized by a sequential condensation addition,[20]
ammonization, stylization, and dehydration. We suggest that
l-proline catalyzes the formation of iminium ion 6 in a reversible
reaction with the aromatic aldehyde. The higher reactivity of the
iminium ion compared with the carbonyl species could facil-
itate Knoevenagel condensation between aldehyde 2 and one
molecule of 6-methyl-4-hydroxypyran-2-one 3, via intermediate
7 and, after the elimination of l-proline, 8 might be produced
as an intermediate. The addition of 8 to the other molecule
of 6-methyl-4-hydroxypyran-2-one 3 could then furnish the
intermediate product 10, which upon addition, intermolecular
stylization, and dehydration gave rise to product 4.
Experimental
Melting points were determined in open capillaries and are
uncorrected. IR spectra were recorded on a Tensor 27 spec-
trometer (Bruker Optics, Ettlingen, Germany). 1H NMR spectra
were determined on a Bruker DPX 400 MHz spectrometer using
tetramethylsilane as an internal standard and [D6]DMSO as sol-
vent. Mass spectra were obtained using a time-of-flight mass
spectrometry instrument.
General Procedure for the Synthesis of
3,3-Benzylidenebis(6-methyl-4-hydroxy-
1-arylpyridin-2(1H)-one) 4 (Scheme 2)
A mixture of aldehyde 1 (1 mmol), aniline 2 (2 mmol), and
6-methyl-4-hydroxypyran-2-one 3 (2 mmol) was suspended in
EtOH (2 mL) using 10 mol-% l-proline (0.0115 g) as catalyst
and the reaction mixture was stirred at 80◦C for 1–4 h. The reac-
tion was monitored by TLC. After completion of the reaction,
the reaction mixture was allowed to cool to room temperature
and was poured into the water. The precipitate was collected by
suction and recrystallized from ethanol to give products 4 with
high purity.
Conclusions
We have developed a novel and simple three-component reaction
of an aldehyde, 6-methyl-4-hydroxypyran-2-one, and aniline for
the synthesis of 3,3ꢀ-benzylidenbis(4-hydroxy-6-methylpyridin-
2(1H)-one) derivatives using l-proline as catalyst. Particularly
valuable features of this method include good yields of the

550
C.-L. Shi et al.
3,3ꢀ-((4-Bromophenyl)methylene)bis(4-hydroxy-1-
(4-methoxyphenyl)-6-methylpyridin-2(1H)-one) 4a
400 MHz) 1.94 (6H, s, 2 × CH3), 2.26 (3H, s, CH3), 5.97 (1H, s,
CH), 6.18 (2H, s, H5, H5ꢀ), 7.00–7.06 (4H, m, ArH), 7.32–7.38
(8H, m, ArH), 11.80 (2H, br, 2 × OH). Found: m/z 540.1866
(M+). Calc. for C32H26N2O4F2: M 540.1861.
Mp 273–274◦C. νmax (KBr)/cm−1 3056, 1646, 1508, 1399,
1248, 1040, 836. δH ([D6]DMSO, 400 MHz) 1.92 (6H, s,
2 × CH3), 3.80 (6H, s, 3 × OCH3), 5.96 (1H, s, CH), 6.17 (2H,
s, H5, H5ꢀ), 7.02–7.07 (6H, m, ArH), 7.18–7.22 (4H, m, ArH),
7.42 (2H, d, J 8.4, ArH), 11.93 (2H, br, 2 × OH). Found: m/z
628.1188 (M+). Calc. for C33H29N2O679Br: M 628.1209.
3,3ꢀ-((4-Chlorophenyl)methylene)bis(4-hydroxy-
6-methyl-1-p-tolylpyridin-2(1H)-one) 4h
Mp 290–292◦C. νmax (KBr)/cm−1 3029, 1646, 1539, 1369,
1266, 1198, 1091, 815. δH ([D6]DMSO, 400 MHz) 1.94 (6H,
s, 2 × CH3), 2.40 (6H, s, 2 × CH3), 6.02 (1H, s, CH), 6.19 (2H,
s, H5, H5ꢀ), 7.13–7.20 (6H, m, ArH), 7.30–7.35 (6H, m, ArH),
11.87 (2H, br, 2 × OH). Found: m/z 552.1824 (M+). Calc. for
C33H2935ClN2O4: M 552.1816.
3,3ꢀ-(p-Tolylmethylene)bis(4-hydroxy-1-(4-
methoxyphenyl)-6-methylpyridin-2(1H)-one) 4b
Mp 282–283◦C. νmax (KBr)/cm−1 3058, 1646, 1508, 1400,
1247, 1040, 835. δH ([D6]DMSO, 400 MHz) 1.92 (6H, s,
2 × CH3), 2.24 (3H, s, CH3), 3.80 (6H, s, 3 × OCH3), 5.91 (1H,
s, CH), 6.15 (2H, s, H5, H5ꢀ), 6.99 (2H, d, J 8.0, ArH), 7.04
(6H, d, J 8.8, ArH), 7.17–7.22 (4H, m, ArH), 11.96 (2H, br,
2 × OH). Found: m/z 564.2258 (M+). Calc. for C34H32N2O6:
M 564.2260.
3,3ꢀ-((4-Hydroxyphenyl)methylene)bis(4-hydroxy-
6-methyl-1-p-tolylpyridin-2(1H)-one) 4i
Mp 222–224◦C. νmax (KBr)/cm−1 3031, 1646, 1510, 1457,
1372, 1268, 1198, 1035, 816. δH ([D6]DMSO, 400 MHz) 2.04
(6H, s, 2 × CH3), 2.50 (6H, s, 2 × CH3), 5.99 (1H, s, CH), 6.28
(2H, s, H5, H5ꢀ), 6.75 (2H, d, J 8.4, ArH), 7.01 (2H, d, J 8.0,
ArH), 7.26–7.30 (4H, m, ArH), 7.44 (4H, d, J 6.0, ArH), 9.21
(1H, s, OH), 12.03 (2H, br, 2 × OH). Found: m/z 534.2137 (M+).
Calc. for C33H30N2O5: M 534.2155.
3,3ꢀ-((4-Chlorophenyl)methylene)bis(1-(4-
chlorophenyl)-4-hydroxy-6-methylpyridin-2(1H)-one) 4c
Mp 220–222◦C. νmax (KBr)/cm−1 3060, 1646, 1530, 1490,
1404, 1274, 1091, 1014, 826. δH ([D6]DMSO, 400 MHz) 1.93
(6H, s, 2 × CH3), 6.05 (1H, s, CH), 6.17 (2H, s, H5, H5ꢀ), 6.55
(1H, d, J 8.4, ArH), 7.00 (1H, d, J 8.0, ArH), 7.12 (2H, d, J
8.0, ArH), 7.27 (2H, d, J 8.0, ArH), 7.35 (3H, t, J 8.0, ArH),
7.58 (3H, s, ArH), 11.78 (2H, br, 2 × OH). Found: m/z 592.0743
(M+). Calc. for C31H23N2O435Cl3: M 592.0723.
3,3ꢀ-((4-Bromophenyl)methylene)bis(1-(4-bromophenyl)-
4-hydroxy-6-methylpyridin-2(1H)-one) 4j
Mp 180–182◦C. νmax (KBr)/cm−1 3072, 1648, 1530, 1487,
1399, 1268, 1197, 1010, 821. δH ([D6]DMSO, 400 MHz) 1.93
(6H, s, 2 × CH3), 6.03 (1H, s, CH), 6.18 (2H, s, H5, H5ꢀ), 7.06
(2H, d, J 8.0, ArH), 7.28–7.31 (4H, m, ArH), 7.41 (2H, d, J 8.8,
ArH), 7.71–7.74 (4H, m, ArH), 11.82 (2H, br, 2 × OH). Found:
m/z 723.9180 (M+). Calc. for C31H23N2O479Br3: M 723.9208.
3,3ꢀ-((4-Chlorophenyl)methylene)bis(1-(4-
fluorophenyl)-4-hydroxy-6-methylpyridin-2(1H)-one) 4d
Mp >300◦C. νmax (KBr)/cm−1 3080, 1647, 1549, 1505, 1400,
1220, 1151, 1090, 840. δH ([D6]DMSO, 400 MHz) 1.91 (6H, s,
2 × CH3), 6.04 (1H, s, CH), 6.18 (2H, s, H5, H5ꢀ), 7.12 (2H, d,
J 8.4, ArH), 7.28 (2H, d, J 8.4, ArH), 7.36 (8H, d, J 6.4, ArH),
11.86 (2H, br, 2 × OH). Found: m/z 560.1312 (M+). Calc. for
C31H23N2O4F235Cl: M 560.1314.
3,3ꢀ-((4-Methoxyphenyl)methylene)bis(4-hydroxy-
6-methyl-1-phenylpyridin-2(1H)-one) 4k
Mp 298–300◦C. νmax (KBr)/cm−1 3048, 1643, 1533, 1456,
1396, 1287, 1247, 1176, 1034, 839. δH ([D6]DMSO, 400 MHz)
1.91 (6H, s, 2 × CH3), 3.71 (3H, s, OCH3), 5.94 (1H, s, CH),
6.16 (2H, s, H5, H5ꢀ), 6.80 (2H, d, J 8.4, ArH), 7.03 (2H, d, J
8.4, ArH), 7.29 (4H, t, J 8.8, ArH), 7.47–7.52 (6H, m, ArH),
11.84 (2H, br, 2 × OH). Found: m/z 520.1996 (M+). Calc. for
C32H28N2O5: M 520.1998.
3,3ꢀ-((3,4-Dichlorophenyl)methylene)bis(1-(4-
fluorophenyl)-4-hydroxy-6-methylpyridin-2(1H)-one) 4e
Mp 280–282◦C. νmax (KBr)/cm−1 3030, 1647, 1540, 1502,
1460, 1399, 1285, 1218, 1151, 1089, 813. δH ([D6]DMSO,
400 MHz) 1.93 (6H, s, 2 × CH3), 6.10 (1H, s, CH), 6.19 (2H, s,
H5, H5ꢀ), 7.09–7.12 (1H, m, ArH), 7.26 (1H, s, ArH), 7.36 (6H,
d, J 7.6, ArH), 7.39–7.43 (2H, m, ArH), 7.49 (1H, d, J 8.4, ArH),
11.87 (2H, br, 2 × OH). Found: m/z 594.0899 (M+). Calc. for
C31H22N2O4F235Cl2: M 594.0925.
3,3ꢀ-((4-Bromophenyl)methylene)bis(4-hydroxy-
6-methyl-1-phenylpyridin-2(1H)-one) 4l
Mp >300◦C. νmax (KBr)/cm−1 3064, 1646, 1528, 1488, 1369,
1266, 1199, 1010, 815. δH ([D6]DMSO, 400 MHz) 1.91 (6H,
s, 2 × CH3), 6.01 (1H, s, CH), 6.19 (2H, s, H5, H5ꢀ), 7.07
(2H, d, J 8.0, ArH), 7.28–7.32 (4H, m, ArH), 7.43 (2H, d, J
8.8, ArH), 7.48 (2H, d, J 7.2, ArH), 7.51–7.55 (4H, m, ArH),
11.88 (2H, br, 2 × OH). Found: m/z 568.1003 (M+). Calc. for
C31H25N2O479Br: M 568.0998.
3,3ꢀ-((4-Methoxyphenyl)methylene)bis(1-(4-
fluorophenyl)-4-hydroxy-6-methylpyridin-2(1H)-one) 4f
Mp 299–301◦C. νmax (KBr)/cm−1 3067, 1646, 1542, 1506,
1462, 1399, 1218, 1151, 1091, 813. δH ([D6]DMSO, 400 MHz)
1.92 (6H, s, 2 × CH3), 3.71 (3H, s, OCH3), 5.95 (1H, s, CH),
6.17 (2H, s, H5, H5ꢀ), 6.80 (2H, d, J 8.8,ArH), 7.03 (2H, d, J 8.4,
ArH), 7.36 (8H, d, J 6.8, ArH), 11.85 (2H, br, 2 × OH). Found:
m/z 556.1824 (M+). Calc. for C32H26F2N2O5: M 556.1810.
3,3ꢀ-((4-Bromophenyl)methylene)bis(4-hydroxy-
6-methyl-1-p-tolylpyridin-2(1H)-one) 4m
Mp 300–302◦C. νmax (KBr)/cm−1 3028, 1646, 1534, 1368,
1265, 1198, 1107, 1010, 821. δH ([D6]DMSO, 400 MHz) 1.92
(6H, s, 2 × CH3), 2.38 (6H, s, 2 × CH3), 5.98 (1H, s, CH),
6.17 (2H, s, H5, H5ꢀ), 7.07 (2H, d, J 8.4, ArH), 7.16 (4H, t,
J 8.0, ArH), 7.31–7.34 (4H, m, ArH), 7.42 (2H, d, J 8.4, ArH),
11.88 (2H, br, 2 × OH). Found: m/z 596.1330 (M+). Calc. for
C33H29N2O479Br: M 596.1311.
3,3ꢀ-(p-Tolylmethylene)bis(1-(4-fluorophenyl)-4-hydroxy-
6-methylpyridin-2(1H)-one) 4g
Mp >300◦C. νmax (KBr)/cm−1 3059, 1675, 1648, 1533, 1506,
1457, 1399, 1298, 1219, 1151, 1092, 842. δH ([D6]DMSO,

Synthesis of N-Substituted Pyridinone Derivatives
551
Acknowledgements
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We are grateful to the Foundation of Key Laboratory of Organic Synthesis
of Jiangsu Province and the Key Laboratory of Biotechnology on Medical
Plants of Jiangsu Province.
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