A novel approach to 1,2-dihydro-2-oxo-3-pyridinecarboxylic ester via aromatization induced by deamidation

Article abstract of DOI:10.1055/s-2004-822325

A novel approach was developed for the preparation of 4,6-disubstituted-1, 2-dihydro-2-oxo-3-pyridinecarboxylic ester in moderate to good yields. This route involves a reaction sequence of Michael addition, transformation to ene-lactam, and aromatization, featuring easily available material, variable substituents, and good functional compatibility.

Full text of DOI:10.1055/s-2004-822325

PAPER
1021
A Novel Approach to 1,2-Dihydro-2-Oxo-3-Pyridinecarboxylic Ester via
Aromatization Induced by Deamidation
1
,2-Dihydro-2-Oxo
a
-3-Pyridin
n
ecarboxylic
E
ster via Aromatiz
Y
e
amidation, Shaozhong Wang,a Kai Wang,a Yuefei Hu,*a,b Hongwen Hua
a
Department of Chemistry, Nanjing University, Nanjing 210093, P. R. China
b
Department of Chemistry, Tsinghua University, Beijing 100084, P. R. China
Fax +86(25)83317761; E-mail: yfh@mail.tsinghua.edu.cn
Received 24 December 2003; revised 12 February 2004
fer from the limitation in the diversity of substituents in
the 4- and 6-positions on the pyridine ring.5 As a continu-
ation of our agrochemical research projects, we developed
a novel method to prepare the target compounds, substi-
Abstract: A novel approach was developed for the preparation of
4,6-disubstituted-1,2-dihydro-2-oxo-3-pyridinecarboxylic ester in
moderate to good yields. This route involves a reaction sequence of
Michael addition, transformation to ene-lactam, and aromatization,
featuring easily available material, variable substituents, and good tuted 1,2-dihydro-2-oxo-3-pyridinecarboxylic esters,
functional compatibility.
from commercially available starting materials. This new
approach involves a reaction sequence of Michael addi-
tion, transformation to ene-lactam and aromatization,
starting from chalcones and ethyl acetamidocyanoacetate.
Key words: synthesis, ethyl acetamidocyanoacetate, aromatization
via deamidation, sodium carbonate, 4,6-disubstituted-1,2-dihydro-
2-oxo-3-pyridinecarboxylic ester
Ethyl acetamidocyanoacetate (5) is a multifunctional
compound prepared from ethyl cyanoacetate by nitrosa-
tion, reduction, and acylation.6 However, the published
method suffered from either complicated work-up proce-
dures or poor yields. The preparation of compound 5
could be scaled up when the reduction and acylation of
oxime 4 is performed by using Zn/Ac2O–HOAc in one pot
(Scheme 1).
Functionalized 2(1H)-pyridones have long been of inter-
est in pharmaceutical and agrochemical research, and
their biological activities have attracted much attention.
Substituted
1,2-dihydro-2-oxo-3-pyridinecarboxylates
could serve as versatile precursors to synthesize herbi-
1
cides such as 1, as well as drugs such as inhibitors of
thrombin and human leukocyte elastase.2 Some 4-aryl-2-
oxo-3-pyridinecarboxylates 2 were also used to prevent
growth of neoplastic cells and precancerous lesions and
showed cytokine inhibitory activity.3 In addition, pyridox-
in isomers 3 obtained by reduction of the corresponding
ester exhibited vitamin B6 or anti-B6 activity (Figure 1).4
However, the Michael reaction between a chalcone and 5
has been rarely reported.7 By analogy with addition pro-
cedures for compounds similar to 5,8 we obtained d-keto-
nitriles in excellent yields under basic conditions
(Scheme 2). As shown in Table 1, different substituted d-
ketonitriles were obtained in good to excellent yield (65–
99%). When R1 was electron-withdrawing substituent (F,
Several methods were reported to synthesize 4,6-disubsti-
tuted-1,2-dihydro-2-oxo-3-pyridinecarboxylic esters, suf-
OMe
R4
R1
CO2Me
N
CH2OH
R1
O
R3
R2
CO2Et
N
OMe
N
R2
N
OH
N
R1
O
R2
1
2
3
Figure 1
NOH
CO2Et
NHAc
NaNO2/ HOAc, r.t.
Zn/ Ac2O-HOAc
NCCH2CO2Et
NC
NC
CO2Et
4
5
Scheme 1
SYNTHESIS 2004, No. 7, pp 1021–1028
x
x
.
x
x
.2
0
0
4
Advanced online publication: 02.04.2004
DOI: 10.1055/s-2004-822325; Art ID: F12803SS
© Georg Thieme Verlag Stuttgart · New York

1022
G. Yu et al.
PAPER
NO2), especially for nitro group, the yield was higher; ester and amide group intact. Compounds 7b–m were
whereas in the presence of an elctron-donating substituent synthesized via the same procedure in 70–92% yield
CH3O, always resulted in a decreased yield. Presumably, (Scheme 3, Table 2).
the existence of the EWG led to an increase in the electro-
philicity at C-3 of chalcones and promoted the attack by
the carbanion of 5. In addition, the steric effect of substit-
uents was not significant.
O
AcHN
AcHN
EtO2C
CN
HCl/ HOAc, r.t.
overnight
EtO2C
O
NH
Ar2
Ar1
Ar2
Ar1
6
7
Scheme 3
After obtaining ene-lactam, we had two choices: one was
dealkoxycarbonylation to give 3-acetamino-2-(1H)-pyri-
done, the other was deamidation to give 1,2-dihydro-2-
oxo-3-pyridinecarboxylic ester (Scheme 4). Attempts at
selective dealkoxycarbonylation according to Krapcho’s
method were unsuccessful.13 When heated at 160 °C in
DMSO/NaCl, ene-lactam 7a was almost consumed after 4
hours (monitored by TLC). Unexpectedly, the ethyl 4,6-
diphenyl-1,2-dihydro-2-oxo-3-pyridinecarboxylic ester
8a was afforded in 60% yield (Scheme 5). The acetamido
function rather than the ester group was eliminated under
this condition, which was very similar to the result we re-
ported before.14 Therefore, we tried to utilize bases such
as Cs2CO3 and K2CO3 to promote the reaction at 140 °C,
and we found that the reaction rate was accelerated and
was complete in 1 hour. However, this gave compound 8a
together with a byproduct which was identified as 4,6-
diphenyl-2(1H)-pyridone (9), in 40% and 35% yield, re-
spectively (Scheme 6).
Scheme 2
Although existing as two diastereomers, d-ketonitrile 6
could be used without separation of the isomers. It is
known that compound 6 could be transformed to ene-lac-
tam under acid or neutral conditions. However, a high re-
action temperature was necessary when acidic SnCl2 9 or
KHSO410 was employed. The transformation catalyzed by
RuH2(PPh3)4 also required relatively harsh conditions, the
reaction was carried out in a sealed tube.11 We successful-
ly obtained the desired ene-lactam 7a in 60% yield fol-
lowing the procedure reported by Kunstmann.12 However,
with the use of H3PO4/P2O5, the high viscosity of the reac-
tion mixture resulted in an unsatisfactory yield. Fortunate-
ly, we found that when d-ketonitrile was stirred overnight
in the mixture with acetic acid and concentrated hydro-
chloric acid (10:1) at room temperature, the expected
product 7a was also afforded in high yield (84%) with the
Table 1 Preparation of d-Ketonitriles
Table 2 Preparation of Ene-lactams 7
Product
6a
Ar1
Ar2
Yield (%)a
Product
7a
Ar1
Ar2
Yield (%)a
C6H5
C6H5
87
88
74
85
99
98
78
93
65
83
94
98
95
C6H5
C6H5
84
75
86
74
77
80
82
70
92
90
84
88
78
6b
6c
4-NO2C6H4
4-MeOC6H4
C6H5
C6H5
7b
7c
4-NO2C6H4
4-MeOC6H4
C6H5
C6H5
C6H5
C6H5
6d
6e
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
4-FC6H4
4-FC6H4
4-FC6H4
C6H5
7d
7e
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
4-FC6H4
4-FC6H4
4-FC6H4
C6H5
4-NO2C6H4
4-MeOC6H4
C6H5
4-NO2C6H4
4-MeOC6H4
C6H5
6f
7f
6g
7g
6h
6i
4-NO2C6H4
4-MeOC6H4
3,4-OCH2OC6H3
2-ClC6H4
3-MeOC6H4
4-MeC6H4
7h
7i
4-NO2C6H4
4-MeOC6H4
3,4-OCH2OC6H3
2-ClC6H4
3-MeOC6H4
4-MeC6H4
6j
7j
6k
6l
C6H5
7k
7l
C6H5
C6H5
C6H5
6m
4-MeC6H4
7m
4-MeC6H4
a Yield of isolated purified products.
a Yield of isolated purified products after recrystallization.
Synthesis 2004, No. 7, 1021–1028 © Thieme Stuttgart · New York

PAPER
Scheme 4
1,2-Dihydro-2-Oxo-3-Pyridinecarboxylic Ester via Aromatization Induced by Deamidation
1023
O
O
O
AcHN
EtO2C
AcHN
Ar1
EtO2C
Ar1
-CO2Et
-NHAc
NH
NH
NH
Ar2
Ar1
Ar2
Ar2
Scheme 5
Scheme 7
The formation of 3-unsubstituted 2(1H)-pyridone (9) re-
sulted from hydrolysis and decarboxylation of ester 8a un-
der basic conditions. When the temperature was raised or
the reaction time prolonged, the amount of 9 increased
while the yield of 8a reduced. Finally, when the weaker
base Na2CO3 was used instead of Cs2CO3 or K2CO3, 8a
was obtained in 80% yield within 1 hour. Furthermore, the
nitro group was tolerant of the reaction conditions. Other
1,2-dihydro-2-oxo-3-pyridinecarboxylic esters 8b–m
were conveniently prepared in the same manner in 66–
95% (Scheme 7, Table 3).
Table 3 Preparation of 1,2-Dihydro-2-oxo-3-pyridinecarboxylic
Esters
Product
8a
Ar1
Ar2
Yield (%)a
C6H5
C6H5
80
75
88
80
76
95
72
66
80
82
74
76
84
8b
8c
4-NO2C6H4
4-MeOC6H4
C6H5
C6H5
C6H5
8d
8e
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
4-F-C6H4
4-F-C6H4
4-F-C6H4
C6H5
4-NO2C6H4
4-MeOC6H4
C6H5
In conclusion, we have developed a convenient alternative
approach to 1,2-dihydro- 2-oxo-3-pyridine carboxylic es-
ter in moderate to good yields. This sequence of Michael
addition, transformation to ene-lactam, and aromatization
with the key step, aromatization via deamidation, differed
from the reported procedures mediated by oxidants such
as DDQ,15 NaNO2/HOAc,16 S817 etc. This procedure was
also characterized by using easily commercially available
starting material and was compatible with a wide range of
functional groups. The mechanism of the deamidation re-
action and its further application are also being studied.
We are currently investigating modifications to the reac-
tion conditions in the above sequence in attempt to expand
the method to aliphatic starting material.
8f
8g
8h
8i
4-NO2C6H4
4-MeOC6H4
3,4-OCH2OC6H3
2-ClC6H4
3-MeOC6H4
4-MeC6H4
8j
8k
8l
C6H5
C6H5
8m
4-MeC6H4
a Yield of isolated purified products after flash column chromatogra-
phy.
All melting points were determined on a Yanaco apparatus and are
uncorrected. The IR spectra were recorded on a Shimider IDP440
spectrometer with KBr pellets, 1H NMR spectra on a Bruker ACF-
300 spectrometer with TMS as internal reference and MS spectra on
a VG-ZAB-HS mass spectrometer at 70 eV. The elemental analyses
were performed on a Perkin-Elmer 240C instrument.
0.94 mol) over 1.5 h. After the addition was completed, the stirring
was continued at r.t. for 4 h. The reaction mixture was extracted
with Et2O (2 × 50 mL). The ethereal solution of ethyl isonitrosocy-
anoacetate (4) was immediately mixed with Ac2O (86 g, 0.84 mol)
and HOAc (225 mL, 40 mol) in a flask fitted with a mechanical stir-
rer. With vigorous stirring, zinc powder (65 g 1.0 mol) was added
in small portions and the stirring was then continued for 1 h. After
Ethyl Acetamidocyanoacetate (5)
To a stirred solution of ethyl cyanoacetate (35 g, 0.31 mol) and 45%
aq HOAc (140 mL) at 0 °C was added portion-wise NaNO2 (65 g,
Scheme 6
Synthesis 2004, No. 7, 1021–1028 © Thieme Stuttgart · New York

1024
G. Yu et al.
PAPER
filtering, the solvent was evaporated at reduced pressure to give the
product as a white solid (41 g, 80% yield based on ethyl cyanoace-
tate), mp 127 °C.
Ethyl 2-Acetylamino-2-cyano-3-(4-nitrophenyl)-5-oxo-5-(4-me-
thylphenyl)pentanoate (6e)
Pale yellow solid; mp 147–149 °C.
IR (KBr): 3289, 1740, 1685, 1666 cm–1.
d-Ketonitriles 6a–m; General Procedure
1H NMR (300 MHz, CDCl3): d = 0.94 (t, 3 H, J = 7.1 Hz), 2.11 (s,
3 H), 2.46 (s, 3 H), 3.77–4.14 (m, 5 H), 7.33 (d, 2 H, J = 7.9 Hz),
7.64 (d, 2 H, J = 8.7 Hz), 7.93 (d, 2 H, J = 8.3 Hz), 8.24 (s, 1 H),
8.25 (d, 2 H, J = 8.9 Hz).
Chalcone (5.0 mmol) and 5 (7.5 mmol) were dissolved in anhyd
THF (10 mL). To this mixture, t-BuONa (5% mol for 5) was added
and the mixture was stirred at r.t. (monitored by TLC). Upon remov-
al of THF on a rotary evaporator, an oily residue was obtained. The
residue was dissolved in EtOAc (60 mL), washed with cold sat. aq
solution of Na2CO3 (2 × 20 mL), and brine (10 mL), successively.
The organic layer was dried (Na2SO4) and solvent removed under
vacuum. The residue was washed with Et2O to give pure 6a–m.
MS: m/z (%) = 437 (1), 267 (66), 43 (100).
Anal. Calcd for C23H23N3O6: C, 63.15; H, 5.30; N, 9.61. Found: C,
63.18; H, 5.26; N, 9.59.
Ethyl 2-Acetylamino-2-cyano-3-(4-methoxyphenyl)-5-oxo-5-(4-
methylphenyl)pentanoate (6f)
White solid; mp 126–128 °C.
IR (KBr): 3315, 1754, 1685, 1675 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.93 (t, 3 H, J = 7.6 Hz), 2.08 (s,
3 H), 2.44 (s, 3 H), 3.77–4.04 (m, 5 H), 3.87 (s, 3 H), 6.88 (d, 2 H,
J = 9.0 Hz), 7.30 (d, 2 H, J = 8.7 Hz), 7.34 (d, 2 H, J = 8.7 Hz), 7.91
(d, 2 H, J = 8.5 Hz), 8.38 (s, 1 H).
Ethyl 2-Acetylamino-2-cyano-3-phenyl-5-oxo-5-phenylpen-
tanoate (6a)
White solid; mp 159–161 °C.
IR (KBr): 3380, 1762, 1690, 1670 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.87 (t, 3 H, J = 7.2 Hz), 2.09 (s,
3 H), 3.74–4.13 (m, 5 H), 7.35–7.65 (m, 8 H,), 8.03 (d, 2 H, J = 7.9
Hz), 8.31 (s, 1 H).
MS: m/z (%) = 378 (1), 208 (5), 105 (100).
MS: m/z (%) = 422 (1), 252 (69), 119 (100).
Anal. Calcd for C22H22N2O4: C, 69.84; H, 5.86; N, 7.40; Found: C,
69.77; H, 5.76; N, 7.32.
Anal. Calcd for C24H26N2O5: C, 68.23; H, 6.20; N, 6.63. Found: C,
68.49; H, 6.27; N, 6.57.
Ethyl 2-Acetylamino-2-cyano-3-(4-nitrophenyl)-5-oxo-5-phe-
nylpentanoate (6b)
Pale yellow solid; mp 143–145 °C.
IR (KBr): 3310, 1750, 1685, 1665 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.94 (t, 3 H, J = 7.14 Hz), 2.10 (s,
3 H), 3.80–4.18 (m, 5 H), 7.51–7.70 (m, 5 H), 8.03 (d, 2 H, J = 7.4
Hz), 8.13 (s, 1 H), 8.24 (d, 2 H, J = 4.3 Hz).
Ethyl 2-Acetylamino-2-cyano-3-phenyl-5-oxo-5-(4-fluorophe-
nyl)pentanoate (6g)
White solid; mp 144–146 °C.
IR (KBr): 3277, 1756, 1690, 1665 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.87 (t, 3 H, J = 7.1 Hz), 2.09 (s,
3 H), 3.70–4.11 (m, 5 H), 7.20 (t, 2 H, J = 8.8 Hz), 7.37 (m, 5 H),
8.06–8.11 (m, 2 H), 8.23 (s, 1 H).
MS: m/z (%) = 423 (1), 253 (33), 43 (100).
MS: m/z (%) = 396 (1), 226 (50), 124 (100).
Anal. Calcd for C22H21N3O6: C, 65.41; H, 5.00; N, 9.92. Found: C,
62.41; H, 5.13; N, 9.93.
Anal. Calcd for C22H21FN2O4: C, 66.66; H, 5.34; N, 7.07. Found: C,
66.68; H, 5.35; N, 7.19.
Ethyl 2-Acetylamino-2-cyano-3-(4-methoxyphenyl)-5-oxo-5-
phenylpentanoate (6c)
White solid; mp 134–138 °C.
IR (KBr): 3339, 1754, 1689, 1680 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.92 (t, 3 H, J = 14.3 Hz), 2.07 (s,
3 H), 3.76–4.07 (m, 5 H), 3.79 (s, 3 H), 6.87 (d, 2 H, J = 17.6 Hz),
7.33 (d, 2 H, J = 8.6 Hz), 7.50 (t, 2 H, J = 7.9 Hz), 7.66 (t, 1 H,
J = 6.6 Hz), 8.01 (d, 2 H, J = 7.2 Hz), 8.27 (s, 1 H).
Ethyl 2-Acetylamino-2-cyano-3-(4-nitrophenyl)-5-oxo-5-(4-flu-
orophenyl)pentanoate (6h)
Pale yellow solid; mp 179–181 °C.
IR (KBr): 3324, 1754, 1689, 1656 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.95 (t, 3 H, J = 7.2 Hz), 2.11 (s,
1 H), 3.78–4.18 (m, 5 H), 7.19–7.26 (m, 2 H), 7.63 (d, 2 H, J = 7.6
Hz), 8.03–8.10 (m, 3 H), 8.25 (d, 2 H, J = 4.42 Hz).
MS: m/z (%) = 441 (1), 271 (28), 123 (100).
MS: m/z (%) = 408 (1), 238 (88), 43 (100).
Anal. Calcd for C22H20FN3O6: C, 59.86; H, 4.57; N, 9.52. Found: C,
59.93; H, 4.50; N, 9.62.
Anal. Calcd for C23H24N2O5: C, 67.63; H, 5.92; N, 6.86. Found: C,
67.62; H, 6.09; N, 6.85.
Ethyl 2-Acetylamino-2-cyano-3-(4-methoxyphenyl)-5-oxo-5-(4-
fluorophenyl)pentanoate (6i)
White solid; mp 142–144 °C.
IR (KBr): 3349, 1754, 1689, 1666 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.93 (t, 3 H, J = 7.11 Hz), 2.08 (s,
3 H), 3.79–4.08 (m, 5 H), 3.85 (s, 3 H), 6.89 (d, 2 H, J = 8.53 Hz),
7.19 (t, 2 H, J = 9.25 Hz), 7.33 (d, 2 H, J = 4.30 Hz), 8.05–8.09 (m,
2 H), 8.18 (s, 1 H).
Ethyl 2-Acetylamino-2-cyano-3-phenyl-5-oxo-5-(4-methylphe-
nyl)pentanoate (6d)
White solid; mp 122–124 °C.
IR (KBr): 3319, 1756, 1690, 1665 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.84 (t, 3 H, J = 7.5 Hz), 2.07 (s,
3 H), 2.43 (s, 3 H), 3.72–4.07 (m, 5 H), 7.24–7.43 (m, 6 H), 7.91 (d,
2 H, J = 8.3 Hz), 8.42 (s, 1 H).
MS: m/z (%) = 392 (1), 222 (9), 119 (100).
MS: m/z (%) = 426 (1), 256 (37), 123 (100).
Anal. Calcd for C23H24N2O4: C, 70.39; H, 6.16; N, 7.14. Found: C,
70.44; H, 6.15; N, 7.15.
Anal. Calcd for C23H23FN2O5: C, 64.78; H, 5.44; N, 6.57. Found: C,
64.88; H, 5.48; N, 6.63.
Synthesis 2004, No. 7, 1021–1028 © Thieme Stuttgart · New York

PAPER
1,2-Dihydro-2-Oxo-3-Pyridinecarboxylic Ester via Aromatization Induced by Deamidation
1025
Ethyl 2-Acetylamino-2-cyano-3-(3,4-piperyl)-5-oxo-5-phenyl-
pentanoate (6j)
1H NMR (300 MHz, CDCl3): d = 1.23 (t, 3 H, J = 7.2 Hz), 2.18 (s,
3 H), 4.03–4.19 (m, 2 H), 5.08 (d, 1 H, J = 2.5 Hz), 5.49 (t, 1 H, J
White solid; mp 111–113 °C.
= 2.2 Hz), 6.74 (s, 1 H), 7.32–7.48 (m, 11 H).
IR (KBr): 3247, 1757, 1679, 1655 cm–1.
MS: m/z (%) = 378 (1), 319 (68), 305 (73), 263 (100), 247 (84).
1H NMR (300 MHz, CDCl3): d = 1.00 (t, 3 H, J = 7.1 Hz), 2.07 (s,
3 H), 3.88–4.06 (m, 5 H), 5.97 (s, 2 H), 6.75 (d, 1 H, J = 8.0 Hz),
6.81 (t, 1 H, J = 8.4 Hz), 6.97 (s, 1 H), 7.51 (t, 2 H, J = 8.1 Hz), 7.67
(t, 1 H, J = 7.0 Hz), 8.01(d, 2 H, J = 8.3 Hz), 8.21 (s, 1 H).
Anal. Calcd for C22H22N2O4: C, 69.83; H, 5.86; N, 7.40. Found: C,
69.91; H, 5.95; N, 7.57.
Ethyl 3-Acetylamino-3,4-dihydro-4-(4-nitrophenyl)-6-phenyl-
2(1H)pyridone-3-carboxylate (7b)
Pale yellow solid; mp 198–202 °C.
IR (KBr): 1741, 1704, 1644 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.26 (t, 3 H, J = 7.1 Hz), 2.20 (s,
3 H), 4.05–4.21 (m, 2 H), 5.25 (d, 1 H, J = 2.3 Hz), 5.41 (s, 1 H),
6.72 (s, 1 H), 7.39 (d, 2 H, J = 8.6 Hz), 7.40–7.54 (m, 6 H), 8.21 (d,
2 H, J = 8.6 Hz).
MS: m/z (%) = 422 (1), 252 (57), 43 (100).
Anal. Calcd for C23H22N2O6: C, 65.40; H, 5.25; N, 6.63. Found: C,
65.46; H, 5.46; N, 6.66.
Ethyl 2-Acetylamino-2-cyano-3-(2-chlorophenyl)-5-oxo-5-phe-
nylpentanoate (6k)
White solid; mp 173–175 °C.
IR (KBr): 3259, 1755, 1686, 1660 cm–1.
MS: m/z (%) = 423 (1), 364 (71), 350 (53), 308 (100), 292 (99).
1H NMR (300 MHz, CDCl3): d = 0.95 (t, 3 H, J = 7.2 Hz), 2.11 (s,
3 H), 3.71–4.16 (m, 5 H), 7.27 (d, 1 H, J = 5.9 Hz), 7.38 (t, 2 H,
J = 7.6 Hz), 7.52 (t, 2 H, J = 7.6 Hz), 7.89 (d, 2 H, J = 3.8 Hz), 8.02
(d, 2 H, J = 7.4 Hz), 8.28 (s, 1 H).
Anal. Calcd for C22H21N3O6: C, 62.41; H, 5.00; N, 9.92. Found: C,
62.54; H, 5.08; N, 9.94.
Ethyl 3-Acetylamino-3,4-dihydro-4-(4-methoxyphenyl)-6-phe-
nyl-2(1H)pyridone-3-carboxylate (7c)
White solid; mp 176–180 °C.
IR (KBr): 1744, 1690, 1669 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.24 (t, 3 H, J = 7.1 Hz), 2.18 (s,
3 H), 3.81 (s, 3 H), 4.06–4.18 (m, 2 H), 5.02 (d, 1 H, J = 2.5 Hz),
5.46 (d, 1 H, J = 4.3 Hz), 6.76 (s, 1 H), 6.86 (d, 2 H, J = 8.7 Hz),
7.12 (d, 2 H, J = 8.7 Hz), 7.39–7.50 (m, 6 H).
MS: m/z (%) = 412 (1), 242(5), 105 (100).
Anal. Calcd for C22H21ClN2O4: C, 64.00; H, 5.13; N, 6.79. Found:
C, 63.86; H, 5.13; N, 6.80.
Ethyl 2-Acetylamino-2-cyano-3-(3-methoxyphenyl)-5-oxo-5-
phenylpentanoate (6l)
White solid; mp 153–155 °C.
IR (KBr): 3381, 1740, 1693, 1666 cm–1.
MS: m/z (%) = 408 (1), 349 (95), 335 (69), 293 (100), 277 (83).
1H NMR (300 MHz, CDCl3): d = 0.92 (t, 3 H, J = 7.1 Hz), 2.10 (s,
3 H), 3.77–4.15 (m, 5 H), 3.83 (s, 3 H), 6.88–7.31 (m, 4 H), 7.53 (t,
2 H, J = 7.6), 7.69 (t, 1 H, J = 7.5 Hz), 8.05 (d, 2 H, J = 7.5 Hz), 8.29
(s, 1 H).
Anal. Calcd for C23H24N2O5: C, 67.63; H, 5.92; N, 6.86. Found: C,
67.76; H, 5.94; N, 6.71.
Ethyl 3-Acetylamino-3,4-dihydro-4-phenyl-6-(4-methylphe-
nyl)-2(1H)pyridone-3-carboxylate (7d)
White solid; mp 216–220 °C.
IR (KBr): 1732, 1702, 1665 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.23 (t, 3 H, J = 7.1 Hz), 2.19 (s,
3 H), 2.41 (s, 3 H), 4.03–4.21 (m, 2 H), 5.07 (s, 1 H), 5.45 (s, 1 H),
6.74 (s, 1 H), 7.19–7.59 (m, 10 H).
MS: m/z (%) = 408 (1), 238 (81), 43 (100).
Anal. Calcd for C23H24N2O5: C, 67.63; H, 5.92; N, 6.86. Found: C,
67.69; H, 5.95; N, 6.88.
Ethyl 2-Acetylamino-2-cyano-3-(4-methylphenyl)-5-oxo-5-(4-
methylphenyl)pentanoate (6m)
White solid; mp 137–139 °C.
IR (KBr): 3359, 1751, 1694, 1686 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.89 (t, 3 H, J = 7.1 Hz), 2.09 (s,
3 H), 2.35 (s, 3 H), 2.45 (s, 3 H), 3.80–4.08 (m, 5 H), 7.17 (d, 2 H,
J = 8.0 Hz), 7.28–7.38 (m, 4 H), 7.93 (d, 2 H, J = 8.3 Hz), 8.39 (s,
1 H).
MS: m/z (%) = 392 (1), 333 (86), 319 (66), 277 (100), 261 (93).
Anal. Calcd for C23H24N2O4: C, 70.39; H, 6.16; N, 7.14. Found: C,
70.22; H, 6.18; N, 7.35.
Ethyl 3-Acetylamino-3,4-dihydro-4-(4-nitrophenyl)-6-(4-meth-
ylphenyl)-2(1H)pyridone-3-carboxylate (7e)
Pale yellow solid; mp 225–229 °C.
IR (KBr): 1753, 1695, 1671 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.25 (t, 3 H, J = 7.1 Hz), 2.20 (s,
3 H), 2.42 (s, 3 H), 4.02–4.24 (m, 2 H), 5.24 (d, 1 H, J = 2.4 Hz),
5.37 (d, 1 H, J = 2.0 Hz), 6.71 (s, 1 H), 7.25–7.62 (m, 7 H), 8.21 (d,
2 H, J = 8.7 Hz).
MS: m/z (%) = 406 (1), 236 (9), 119 (100).
Anal. Calcd for C24H26N2O4: C, 70.92; H, 6.46; N, 6.89. Found: C,
70.75; H, 6.88; N, 7.08.
Ene-Lactams 7a–m; General Procedure
The d-ketonitrile (6a–m, 1.0 mmol) was dissolved in a solution of
HOAc (20 mL) and concentrated HCl (2 mL), after stirring at r.t.
overnight, the mixture was poured into cold water. The precipitate
was isolated by filtration, then washed with water and recrystallized
from EtOH to afford product 7a–m.
MS: m/z (%) = 437 (1), 378 (94), 364 (48), 322 (87), 306 (100).
Anal. Calcd for C23H23N3O6: C, 63.15; H, 5.30; N, 9.61. Found: C,
63.23; H, 5.32; N, 9.67.
Ethyl 3-Acetylmino-3,4-dihydro-4-(4-methoxyphenyl)-6-(4-me-
thylphenyl)-2(1H)pyridone-3-carboxylate (7f)
White solid; mp 212–216 °C.
IR (KBr): 1754, 1695, 1667 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.24 (t, 3 H, J = 6.9 Hz), 2.17 (s,
3 H), 2.41 (s, 3 H), 3.88 (s, 3 H), 4.03–4.00 (m, 2 H), 5.01 (d, 1 H,
Ethyl 3-Acetylamino-3,4-dihydro-4,6-diphenyl-2(1H)pyridone-
3-carboxylate (7a)
White solid; mp 212–216 °C.
IR (KBr): 1738, 1696, 1666 cm–1.
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J = 2.4), 6.76 (s, 1 H), 6.83 (d, 2 H, J = 6.6 Hz), 7.11 (d, 2 H, J = 8.6
Hz), 7.24 (d, 2 H, J = 7.7 Hz), 7.37 (d, 3 H, J = 8.1 Hz), 7.45 (s, 1 H).
1H NMR (300 MHz, CDCl3): = 1.26 (t, 3 H, J = 7.2 Hz), 2.13 (s, 3
H), 4.09–4.25 (m, 2 H), 5.29 (s, 1 H), 5.65 (d, 1 H, J = 2.4 Hz), 6.69
(s, 1 H,), 7.22–7.28 (m, 3 H), 7.41–7.48 (m, 7 H).
MS: m/z (%) = 422 (1), 363 (100), 349 (56), 307 (82), 291 (81).
MS: m/z (%) = 412 (1), 339 (68), 318 (49), 297 (90), 290 (100).
Anal. Calcd for C24 H26N2O5: C, 68.23; H, 6.20; N, 6.63. Found: C,
68.52; H, 6.55; N, 6.66.
Anal. Calcd for C22H21N2O4: C, 64.00; H, 5.13; N, 6.79. Found: C,
64.11; H, 5.17; N, 6.62.
Ethyl 3-Acetylamino-3,4-dihydro-4-phenyl-6-(4-fluorophenyl)-
2(1H)pyridone-3-carboxylate (7g)
White solid; mp 201–205 °C.
Ethyl 3-Acetylamino-3,4-dihydro-4-(3-methoxyphenyl)-6-phe-
nyl-2(1H)pyridone-3-carboxylate (7l)
White solid; mp 184–188 °C.
IR (KBr): 1741, 1714, 1650 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.24 (t, 3 H, J = 7.1 Hz), 2.19 (s,
3 H), 3.80 (s, 3 H), 4.05–4.21 (m, 2 H), 5.05 (d, 1 H, J = 2.4 Hz),
5.48 (d, 1 H, J = 4.3 Hz), 6.74–6.79 (m, 4 H), 7.23–7.50 (m, 7 H).
IR (KBr): 1737, 1702, 1659 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.24 (t, 3 H, J = 7.1 Hz), 2.18 (s,
3 H), 4.04–4.19 (m, 2 H), 5.06 (d, 1 H, J = 2.4 Hz), 5.43 (d, 1 H,
J = 2.1 Hz), 6.74 (s, 1 H), 7.14–7.50 (m, 10 H).
MS: m/z (%) = 397 (1), 337 (64), 323 (67), 281 (100), 265 (79).
MS: m/z (%) = 408 (1), 349 (66), 335 (75), 293 (100), 277 (37).
Anal. Calcd For C22H21FN2O4: C, 66.66; H, 5.34; N, 7.07. Found:
C, 66.48; H, 5.80; N, 7.48.
Anal. Calcd for C23H24N2O5: C, 67.63; H, 5.92; N, 6.86. Found: C,
67.63; H, 5.89; N, 7.20.
Ethyl 3-Acetylamino-3,4-dihydro-4-(4-nitrophenyl)-6-(4-fluo-
rophenyl)-2(1H)pyridone-3-carboxylate (7h)
Yellow solid; mp 244–248 °C.
IR (KBr): 1734, 1712, 1661 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.26 (t, 3 H, J = 7.2 Hz), 2.19 (s,
3 H), 4.05–4.22 (m, 2 H), 5.24 (d, 1 H, J = 2.3 Hz), 5.35 (d, 1 H,
J = 1.9 Hz), 6.72 (s, 1 H), 7.18 (t, 2 H, J = 8.5 Hz), 7.38 (d, 2 H,
J = 8.7 Hz), 7.48 (q, 2 H, J = 3.5 Hz), 7.57 (s, 1 H), 8.21 (d, 2 H,
J = 8.7 Hz).
Ethyl 3-Acetylamino-3,4-dihydro-4-(4-methylphenyl)-6-(4-me-
thylphenyl)-2(1H)pyridone-3-carboxylate (7m)
White solid; mp 214-218 °C.
IR (KBr): 1758, 1691, 1666 cm-1.
1H NMR (300 MHz, CDCl3): = 1.24 (t, 3 H, J = 7.1 Hz), 2.17 (s, 3
H), 2.35 (s, 3 H), 2.41 (s, 3 H), 4.01-4.19 (m, 2 H), 5.03 (d, 1 H,
J = 2.4 Hz), 5.43 (t, 1 H, J = 2.2 Hz), 6.74 (s, 1 H), 7.06-7.28 (m, 6
H), 7.36–7.39 (d, 3 H, J = 8.1 Hz).
MS: m/z (%) = 441 (1), 382 (100), 368 (12), 326 (21), 310 (60).
MS: m/z (%) = 406 (1), 347 (98), 333 (70), 291 (100), 275 (85).
Anal. Calcd for C22H20FN3O6: C, 59.86; H, 4.57; N, 9.52. Found: C,
59.71; H, 4.62; N, 9.55.
Anal. Calcd for C24 H26N2O4: C, 70.92; H, 6.45; N, 6.89; Found: C,
70.99; H, 6.79; N, 6.97.
Ethyl 3-Acetylamino-3,4-dihydro-4-(4-methoxyphenyl)-6-(4-
fluorophenyl)-2(1H)pyridone-3-carboxylate (7i)
White solid; mp 182–186 °C.
IR (KBr): 1745, 1692, 1670 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.24 (t, 3 H, J = 7.1 Hz), 2.18 (s,
3 H), 3.81 (s, 3 H), 4.07–4.20 (m, 2 H), 5.01 (d, 1 H, J = 2.5), 5.40
(s, 1 H), 6.75 (s, 1 H), 6.86 (d, 2 H, J = 8.6 Hz), 7.08–7.16 (m, 4 H),
7.36 (s, 1 H), 7.44–7.49 (m, 2 H).
1,2-Dihydro-2-oxo-3-pyridinecarboxylic Ester 8a–m; General
Procedure
Ene-Lactam (7a–m, 1.0 mmol), Na2CO3 (1.0 mmol) and a mixture
of DMSO–H2O (5:1, 12 mL) were placed in a three-necked flask
equipped with a reflux condenser and an internal thermometer. The
mixture was heated at 140 °C for 1 h, then cooled and added to cold
water (50 mL). The solution was extracted with EtOAc (3 × 50
mL). The combined organic layers were washed with brine (50
mL), dried (Na2SO4), and concentrated under vacuum. The residue
was purified by flash column chromatography (EtOAc–petroleum
ether, 1:2) on silica gel to afford the product 8a–m.
MS: m/z (%) = 426 (1), 367 (99), 353 (64), 311 (100), 295 (72).
Anal. Calcd for C23H23FN2O5: C, 64.78; H, 5.44; N, 6.57. Found: C,
64.83; H, 5.58; N, 6.56.
Ethyl 1,2-Dihydro-4,6-diphenyl-2-oxo-3-pyridinecarboxylate
(8a)
Ethyl 3-Acetylamino-3,4-dihydro-4-(3,4-piperyl)-6-phenyl-
2(1H)pyridone-3-carboxylate (7j)
White solid; mp 200–202 °C.
White solid; mp 200–202 °C.
IR (KBr): 1723 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.05 (t, 3 H, J = 7.1 Hz), 4.17 (q,
IR (KBr): 1740, 1712, 1657 cm–1.
2 H, J = 7.1 Hz), 6.67 (s, 1 H), 7.28–7.56 (m, 8 H), 7.81–7.88 (m, 2
1H NMR (300 MHz, CDCl3): d = 1.25 (t, 3 H, J = 7.1 Hz), 2.19 (s,
3 H), 4.06–4.23 (m, 2 H), 4.98 (d, 1 H, J = 2.5 Hz), 5.43 (t, 1 H,
J = 2.1 Hz), 5.97 (s, 2 H), 6.65–6.67 (m, 2 H), 6.75 (s, 1 H), 6.78 (s,
1 H), 7.36 (s, 1 H), 7.42–7.48 (m, 5 H).
H).
MS: m/z (%) = 319 (100), 245 (96).
Anal. Calcd for C20 H17NO3: C, 75.22; H, 5.37; N, 4.39. Found: C,
75.23; H, 5.39; N, 4.43.
MS: m/z (%) = 422 (1), 363 (100), 349 (60), 307 (91), 291 (73).
Anal. Calcd for C23H22N2O6: C, 65.40; H, 5.25; N, 6.63. Found: C,
65.24; H, 5.21; N, 6.67.
Ethyl 1,2-Dihydro-4-(4-nitrophenyl)-6-phenyl-2-oxo-3-pyridi-
necarboxylate (8b)
Yellow solid; mp 274–276 °C.
IR (KBr): 1735 cm–1.
Ethyl 3-Acetylamino-3,4-dihydro-4-(2-chlorophenyl)-6-phenyl-
2(1H)pyridone-3-carboxylate (7k)
1H NMR (300 MHz, CDCl3): s = 1.06 (t, 3 H, J = 7.0 Hz), 4.17 (q,
2 H, J = 7.1 Hz), 6.72 (s, 1 H), 7.55 (s, 3 H), 7.64 (d, 2 H, J = 8.5
Hz), 7.87 (d, 2 H, J = 3.6 Hz), 8.34 (d, 2 H, J = 8.3 Hz).
White solid; mp 208–212 °C.
IR (KBr): 1731, 1705, 1657 cm–1.
MS: m/z (%) = 364 (100), 290 (70).
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1,2-Dihydro-2-Oxo-3-Pyridinecarboxylic Ester via Aromatization Induced by Deamidation
1027
Anal. Calcd for C20 H16N2O5: C, 65.93; H, 4.43; N, 7.69. Found: C,
65.87; H, 4.27; N, 7.89.
Ethyl 1,2-Dihydro-4-(4-nitrophenyl)-6-(4-fluorophenyl)-2-oxo-
3-pyridinecarboxylate (8h)
Yellow solid; mp 209–211 °C.
Ethyl 1,2-Dihydro-4-(4-methoxyphenyl)-6-phenyl-2-oxo-3-py-
ridinecarboxylate (8c)
White solid; mp 206–208 °C.
IR (KBr): 1723 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.14 (t, 3 H, J = 7.1 Hz), 3.88 (s,
3 H), 4.24 (q, 2 H, J = 7.1 Hz), 6.99 (d, 2 H, J = 8.5 Hz), 7.48 (d, 2
H, J = 7.2 Hz), 7.56 (s, 3 H), 8.04 (s, 2 H).
IR (KBr): 1739 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.03 (t, 3 H, J = 6.9 Hz), 4.16 (q,
2 H, J = 7.0 Hz), 6.68 (1 H), 7.22 (t, 2 H, J = 8.0 Hz), 7.62 (d, 2 H,
J = 8.3 Hz), 7.91 (s, 2 H), 8.33 (d, 2 H, J = 8.1 Hz).
MS: m/z (%) = 382 (100), 308 (74).
Anal. Calcd for C21H15FN2O5: C, 62.83; H, 3.95; N, 7.33. Found: C,
62.85; H, 3.92; N, 7.37.
MS: m/z (%) = 349 (100), 275 (72).
Anal. Calcd for C21H19NO4: C, 72.19; H, 5.48; N, 4.01. Found: C,
72.16; H, 5.50; N, 4.03.
Ethyl 1,2-Dihydro-4-(4-methoxyphenyl)-6-(4-fluorophenyl)-2-
oxo-3-pyridinecarboxylate (8i)
White solid; mp 212–214 °C.
Ethyl 1,2-Dihydro-4-phenyl-6-(4-methylphenyl)-2-oxo-3-py-
ridinecarboxylate (8d)
White solid; mp 204–206 °C.
IR (KBr): 1729 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.03 (t, 3 H, J = 7.1 Hz), 2.44 (s,
3 H), 4.17 (q, 2 H, J = 7.1 Hz), 6.77 (s, 1 H), 7.29 (d, 2 H, J = 4.4
Hz), 7.47 (s, 5 H), 7.72 (d, 2 H, J = 8.2 Hz).
IR (KBr): 1732 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.13 (t, 3 H, J = 7.1 Hz), 3.88 (s,
3 H), 4.22 (q, 2 H, J = 7.1 Hz), 6.79 (s, 1 H), 6.95 (d, 2 H, J = 7.2
Hz), 7.22 (d, 2 H, J = 8.5 Hz), 7.44 (d, 2 H, J = 8.7 Hz), 7.87 (q, 2
H, J = 3.5 Hz).
MS: m/z (%) = 367 (100), 293 (80).
Anal. Calcd for C21H18FNO3: C, 68.66; H, 4.94; N, 3.81. Found: C,
68.56; H, 4.86; N, 3.85.
MS: m/z (%) = 333 (100), 259 (68).
Anal. Calcd for C21H19NO3: C, 75.66; H, 5.74; N, 4.20. Found: C,
75.66; H, 5.79; N, 4.30.
Ethyl 1,2-Dihydro-4-(3,4-piperyl)-6-phenyl-2-oxo-3-pyridine-
carboxylate (8j)
Ethyl 1,2-Dihydro-4-(4-nitrophenyl)-6-(4-methylphenyl)-2-
oxo-3-pyridinecarboxylate (8e)
Yellow solid; mp 259–261 °C.
IR (KBr): 1725 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.06 (t, 3 H, J = 7.1 Hz), 2.44 (s,
3 H), 4.16 (q, 2 H, J = 7.1 Hz), 6.62 (s, 1 H), 7.33 (d, 2 H, J = 8.0
Hz), 7.64 (d, 2 H, J = 8.6 Hz), 7.75 (d, 2 H, J = 8.1 Hz), 8.33 (d, 2
H, J = 8.6 Hz).
White solid; mp 242–244 °C.
IR (KBr): 1735 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.17 (t, 3 H, J = 7.1 Hz), 4.25 (q,
2 H, J = 6.7 Hz), 6.05 (s, 2 H), 6.67 (s, 1 H), 6.89 (d, 1 H, J = 8.4
Hz), 7.52 (s, 1 H), 7.53 (s, 1 H), 7.54 (s, 1 H), 7.77–7.82 (m, 2 H).
MS: m/z (%) = 363 (100), 289 (56).
Anal. Calcd for C21H17NO5: C, 69.41; H, 4.72; N, 3.85. Found: C,
69.47; H, 4.72; N, 3.70.
MS: m/z (%) = 378 (100), 304 (50).
Anal. Calcd for C21H18N2O5: C, 66.66; H, 4.79; N, 7.40. Found: C,
66.45; H, 4.87; N, 7.40.
Ethyl 1,2-Dihydro-4-(2-chlorophenyl)-6-phenyl-2-oxo-3-pyridi-
necarboxylate (8k)
White solid; mp 199–201 °C.
Ethyl 1,2-Dihydro-4-(4-methoxyphenyl)-6-(4-methylphenyl)-2-
oxo-3-pyridinecarboxylate (8f)
White solid; mp 255–257 °C.
IR (KBr): 1724 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.12 (t, 3 H, J = 7.0 Hz), 2.44 (s,
3 H), 3.88 (s, 3 H), 4.21 (q, 2 H, J = 7.1 Hz), 6.66 (s, 1 H), 6.98 (d,
2 H, J = 8.5), 7.33 (d, 2 H, J = 3.9 Hz), 7.44 (d, 2 H, J = 8.4 Hz),
7.67 (d, 2 H, J = 7.9 Hz).
IR (KBr): 1728 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.92 (t, 3 H, J = 7.1 Hz), 4.13 (q,
2 H, J = 8.4 Hz), 6.86 (s, 1 H), 7.31–7.41 (m, 3 H), 7.48–7.52 (m, 4
H), 7.94–7.96 (m, 2 H).
MS: m/z (%) = 353 (2), 290 (100).
Anal. Calcd for C20H16ClNO3: C, 67.90; H, 4.56; N, 3.96. Found: C,
67.97; H, 4.55; N, 3.86.
MS: m/z (%) = 363 (100), 289 (73).
Ethyl 1,2-Dihydro-4-(3-methoxyphenyl)-6-phenyl-2-oxo-3-py-
ridinecarboxylate (8l)
White solid; mp 192–194 °C.
Anal. Calcd for C22H21NO4: C, 72.71; H, 5.82; N, 3.85. Found: C,
72.69; H, 5.73; N, 3.86.
IR (KBr): 1719 cm–1.
Ethyl 1,2-Dihydro-4-phenyl-6-(4-fluorophenyl)-2-oxo-3-pyridi-
necarboxylate (8g)
White solid; mp 215–217 °C.
IR (KBr): 1724 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.04 (t, 3 H, J = 7.0 Hz), 4.16 (q,
2 H, J = 7.1 Hz), 6.66 (s, 1 H), 7.21 (t, 2 H, J = 8.5 Hz), 7.46 (s, 5
H), 7.90 (q, 2 H, J = 3.5 Hz).
1H NMR (300 MHz, CDCl3): = 1.09 (t, 3 H, J = 7.0 Hz), 3.87 (s, 3
H), 4.19 (q, 2 H, J = 7.1 Hz), 6.71 (s, 1 H), 6.98–7.08 (m, 3 H), 7.37
(t, 1 H, J = 7.8 Hz), 7.51 (s, 1 H), 7.52 (s, 1 H), 7.53 (s, 1 H, J = 7.8
Hz), 7.84 (s, 1 H), 7.86 (s, 1 H).
MS: m/z (%) = 349 (100), 275 (91).
Anal. Calcd for C21H19NO4: C, 72.19; H, 5.48; N, 4.01. Found: C,
72.10; H, 5.66; N, 4.14.
MS: m/z (%) = 337 (100), 263 (94).
Anal. Calcd for C20 H16FNO3: C, 71.21; H, 4.78; N, 4.15. Found: C,
71.27; H, 4.75; N, 4.11.
Ethyl 1,2-Dihydro-4-(4-methylphenyl)-6-(4-methylphenyl)-2-
oxo-3-pyridinecarboxylate (8m)
White solid; mp 238–240 °C.
Synthesis 2004, No. 7, 1021–1028 © Thieme Stuttgart · New York

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G. Yu et al.
PAPER
(5) (a) Bondavalli, F.; Bruno, O.; Presti, E. L.; Menozzi, G.;
IR (KBr): 1728 cm–1.
Mosti, L. Synthesis 1999, 1169. (b) Ito, K.; Yokokura, S.;
Miyajima, S. J. Heterocycl. Chem. 1989, 27, 773.
(c) Alberola, A.; Andres, C.; Ortega, A. G.; Pedrosia, R.;
Vicente, M. J. Heterocycl. Chem. 1987, 24, 709.
(d) Osman, A. N.; Ismail, M. M.; Barakat, M. A. Egypt J.
Pharm. Sci. 1987, 29, 87; Chem. Abstr. 1987, 106, 119644k.
(6) (a) Caille, J. C.; Didierlaurent, S.; Leftrancois, D.; Lelievre,
M. H.; Sury, C.; Aszodi, J. Synthesis 1995, 635.
(b) Logemann, F. I.; Shaw, G. Chem. Ind. (London) 1980,
541. (c) Conard, M.; Schulze, A. Ber. Dtsch. Chem. Ges.
1909, 42, 736.
(7) Owen, A. M.; Donald, T. W. J. Am. Chem. Soc. 1948, 70,
2763.
(8) (a) Mukund, P. S.; Shankar, M. Tetrahedron 2000, 56,
8033. (b) Lakhlifi, T.; Sedgui, A.; Fathi, T.; Laude, B.;
Robert, J. F. Can. J. Chem. 1994, 82, 1417.
1H NMR (300 MHz, CDCl3): d = 1.09 (t, 3 H, J = 7.2 Hz), 2.42 (s,
6 H), 4.19 (q, 2 H, J = 3.6 Hz), 6.61 (s, 1 H), 7.25 (d, 2 H, J = 7.9
Hz), 7.32 (d, 2 H, J = 7.9), 7.38 (d, 2 H, J = 8.0 Hz), 7.71 (d, 2 H, J
= 8.2 Hz).
MS: m/z (%) = 347 (100), 273 (79).
Anal. Calcd for C22H21NO3: C, 76.06; H, 6.09; N, 4.03%, Found: C,
76.13; H, 6.05; N, 4.07.
4,6-Diphenylpyridin-2(1H)-one (9)
White solid; mp 210–212 °C [lit.18 209–212 ° C].
1H NMR (300 MHz, CDCl3): d = 6.92 (d, 1 H, J = 1.2 Hz), 6.98 (d,
1 H, J = 1.3 Hz), 7.50–7.55 (m, 6 H), 7.67–7.70 (m, 2 H), 7.84–7.87
(m, 2 H).
(9) (a) Murahashi, S. I.; Sasao, S.; Saito, E.; Naota, T. J. Org.
Chem. 1992, 58, 2521. (b) Murahashi, S. I.; Sasao, S.; Saito,
E.; Naota, T. Tetrahedron 1993, 49, 8805.
(10) Zhang, Z.; Gao, S.; Sun, Q.; Sun, Y.; Mao, L. Youji Huaxue
1993, 49, 8805.
Acknowledgment
We are grateful to the National Natural Science Foundation of Chi-
na for financial support.
(11) Mao, L.; Gao, S.; Zhang, Z.; Sun, Q.; Sun, Y. Chin. Chem.
Lett. 1994, 11, 921.
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Synthesis 2004, No. 7, 1021–1028 © Thieme Stuttgart · New York