An efficient and facile procedure for the synthesis of 4,6-diaryl-2(1H)- pyridones under solvent-free conditions

Article abstract of DOI:10.1002/jhet.5570440641

(Chemical Equation Presented) An efficient and convenient method for the preparation of 4,6-diaryl-2(1H)-pyridones by the one-pot reaction of aromatic aldehydes, aromatic ketones and malononitrile, in the presence of sodium hydroxide under solvent-free co

Full text of DOI:10.1002/jhet.5570440641

Nov-Dec 2007
1505
An Efficient and Facile Procedure for the Synthesis of 4,6-Diaryl-
2(1H)-pyridones under Solvent-free Conditions
Liangce Rong *, Haiying Wang, Jingwen Shi, Fang Yang, Hao Yao, Shuajiang Tu
and Daqing Shi
Department of Chemistry, Xuzhou Normal University, Key Laboratory of Biotechnology for medicinal Plant,
Xuzhou, Jiangsu, 221116, P. R. China
E-mail: lcrong2005@yahoo.com
Received November 12, 2006
Ar1
Ar2COCH3
CN
O
NaOH
75 oC
2
Ar1CHO
1
+
Ar2
N
H
4
CH2(CN)2
3
An efficient and convenient method for the preparation of 4,6-diaryl-2(1H)-pyridones by the one-pot reaction
of aromatic aldehydes, aromatic ketones and malononitrile, in the presence of sodium hydroxide under solvent-
free condition is reported. This method has the advantages of good yields, mild reaction conditions, easy work-
up, inexpensive reagents and being environmentally friendly over the existing procedures.
J. Heterocyclic Chem., 44, 1505 (2007).
various aromatic aldehydes 1 and aromatic ketones 2 with
malononitrile 3 were carried out respectively to afford the
corresponding products 4 (Table 1). All reactions were
completed in about 30 min and the yields of products
were high. As shown in Table 1, we can see a series of 1
and 2, either bearing electron-withdrawing groups (such
as halide) or electron-donating groups (such as methyl
group and alkoxyl group), reacting with 3 to give the
corresponding products 4 under same reaction conditions.
Therefore we concluded that the electronic nature of the
substituents has no significant effect on this reaction.
Because the reaction worked under solvent-free condition,
the handling procedure of reaction was very simple.
INTRODUCTION
The nucleus of 2-pyridone occurs widely in the
structures of biologically natural alkaloids [1]. Many
derivatives of 2-pyridone are frequently used as inter-
mediates for the construction of alkaloids [2]. Even some
derivatives of 4,6-diaryl-2-pyridone, such as the simple
structural related 2-pyridones, are recognized as potent
LTB4 antagonist [3]. Numerous methods [4] have been
reported for the synthesis of 2-pyridone derivatives,
because of the biological importance associated with these
compounds. However, these methods suffer from several
drawbacks such as a long reaction time, an excess of
volatile organic solvent, lower product yields, and harsh
refluxing conditions. Therefore, the development of a
simple and efficient method for the preparation of 2-
pyridone derivatives is an active area of research and
there is scope for further improvement involving milder
reaction conditions and higher product yields.
Scheme I
Ar1
CN
NaOH
75 oC
+ Ar2COCH
1
CH2(CN)2
+
Ar CHO
3
Ar2
N
H
O
In recent years, solvent-free organic reactions [5] have
caused great interests, which have many advantages such
as high efficiency and selectivity, easy separation and
purification, mild reaction conditions, and benefit to
industry as well as environment. Some solvent-free
reactions can be carried out with just heating [6]. In
continuation to our ongoing endeavour on the application
of solvent-free condition for the synthesis of organic
compounds [7], we herein describe a practical and simple
method to prepare 4,6-diaryl-2-pyridone with heating raw
material under dry conditions.
2
3
4
1
The structure of each product 4a-r was established on
the basis of spectroscopic data and confirmed by X-ray
diffraction studies on single crystals of 4c [8] (X-ray
crystal structure of 4c shown in Figure 1).
Although the detailed mechanism of the above reaction
has not been clarified yet, the formation of compound 4
could be explained by a possible mechanism presented in
Scheme 2. At first, the Aldol condensation takes place from
aromatic aldehydes 1 and aromatic ketones 2 to give
intermediate 5, or alternatively, the Knoevenagel conden–
sation takes place by aldehydes 1 and malono–nitrile 3 to
give intermediate 6. Then, the intermediate 5 and 6 under-
goes the Michael reaction with malononitrile 3 and
RESULTS AND DISCUSSION
The synthesis of 4,6-diaryl-2-pyridone is illustrated in
Scheme 1. In the presence of NaOH, the reactions of

1506
L. Rong, H. Wang, J. Shi, F. Yang, H. Yao, S. Tu and D. Shi
Vol 44
the intramolecule nucleophilic addition and dehydration.
The formation product 4 from 10 could be due to
dehydrogenation by the atmospheric oxygen.
In conclusion, we have developed a simple and novel
method for the synthesis of 4,6-diaryl-2-pyridone under
solvent-free condition by one-pot reactions of aromatic
aldehydes, aromatic ketones, and malononitrile. Because
of avoiding the use of toxic organic solvent, this protocol
has advantages of cheap starting materials, excellent
yield, mild reaction conditions, simple experimental
procedure and friendly environment. We believe that the
present methodology addresses the current devise toward
green chemistry.
Figure 1. The structure of compound 4c.
Table
Synthesis of product 4 under solvent-free conditions
Entry
Ar1
Ar2
Product
Yeilds
1
2
C6H5
4-CH3OC6H4
4-ClC6H4
C6H5
4a
4b
4c
4d
4e
4f
80
78
83
81
81
83
85
79
80
78
87
84
80
72
78
77
76
80
C6H5
3
4-FC6H4
4
4-ClC6H4
C6H5
5
2-ClC6H4
C6H5
6
2,4-Cl2C6H3
3,4-Cl2C6H3
4-BrC6H4
C6H5
7
C6H5
4g
4h
4i
8
C6H5
9
3,4-(CH3O)2C6H3
3,4-OCH2OC6H3
4-CH3C6H4
4-CH3C6H4
4-BrC6H4
C6H5
10
11
12
13
14
15
16
17
18
C6H5
4j
4-BrC6H4
4-CH3C6H4
4-ClC6H4
4-CH3C6H4
4-CH3C6H4
4-CH3OC6H4
4-CH3OC6H4
4-CH3OC6H4
4k
4l
4m
4n
4o
4p
4q
4r
3,4-(CH3)2C6H3
3,4-Cl2C6H3
4-ClC6H4
4-CH3OC6H4
2,4-Cl2C6H3
aromatic ketones 2 respectively and the same 2-(3-oxo-1,3-
diarylpropyl)malononitrile 7 is obtained. Subsequently, 7 is
hydrolyzed to form the amide 8. The 10 was gained from
Scheme II
Ar1
OH-
CH2(CN)2
3
OH-
Ar1
Ar1CHO
Ar2COCH3
+
-H2O
NC
2
2
O
Ar1
Ar2
1
5
CN
OH-
Ar2
CN
OH-
-H2O
O
7
CN
Ar1CHO
+
Ar2COCH3
CN
CN
2
1
3
H2O
Ar1
6
Ar1
Ar1
Ar1
NC
H
NC
NC
O
NC
[O]
-H2O
Ar2
O
NH2
O
Ar2
N
H
Ar2
O
N
H
O
N
H
Ar2
OH
10
8
4
9

Nov-Dec 2007
An Efficient and Facile Procedure for the Synthesis of 4,6-Diaryl-2(1H)-pyridones
1507
(4H, m, ArH), 6.82 (1H, s, C5ꢀH). Anal. Calcd. For C18H10Cl2N2O: C
63.36, H 2.95, N 8.21. Found: C 63.43, H 2.94, N 8.26.
EXPERIMENTAL
4-(3,4-Dichlorophenyl)-1,2-dihydro-2-oxo-6-phenylpyri-
dine-3-carbonitrile (4g). This compound was obtained as
yellow crystals, m.p. >300 °ꢀ; ir (KBr, ꢀ, cm-1): 3130 (NH),
Melting points were determined on XT-5 microscopic melting-
point apparatus and were uncorrected. IR spectra were recorded on
a FT Bruker Tensor 27 spectrometer. 1H NMR spectra were
obtained from solution in DMSO-d6 with Me4Si as internal
standard using a Bruker-400 spectrometer. Microanalyses were
carried out using a Perkin-Elmer 2400 II analyzer. X-ray diffraction
was measured on a Siemens P4 diffractometer.
1
2220 (CN), 1651 (CO); H nmr (400MHz, DMSO-d6) (ꢁ, ppm):
12.86 (1H, s, NH), 7.50ꢀ7.92 (8H, m, ArH), 6.93 (1H, s, C5ꢀH).
Anal. Calcd. For C18H10Cl2N2O: C 63.36, H 2.95, N 8.21. Found:
C 63.50, H 2.71, N 8.37.
4-(4-Bromophenyl)-1,2-dihydro-2-oxo-6-phenylpyridine-3-
carbonitrile (4h). This compound was obtained as yellow
crystals, mp 293ꢀ295 °ꢀ; ir (KBr, ꢀ, cm-1): 3139 (NH), 2219
(CN), 1648 (CO); 1H nmr (400MHz, DMSO-d6) (ꢁ, ppm): 12.90
(1H, s, NH), 7.88 (2H, m, ArH), 7.80 (2H, d, J = 8.4 Hz, ArH),
7.71 (2H, d, J = 8.4 Hz, ArH), 7.53ꢀ7.58 (3H, dd, J = 8.4 Hz, J =
8.4 Hz, ArH), 6.80 (1H, s, C5ꢀH). Anal. Calcd. For C18H11Br-
N2O: C 61.56, H 3.16, N 7.98. Found: C 61.45, H 3.28, N 7.80.
1,2-Dihydro-4-(3,4-dimethoxyphenyl)-2-oxo-6-phenylpyri-
dine-3-carbonitrile (4i). This compound was obtained as yellow
crystals, mp 276ꢀ277 °ꢀ; ir (KBr, ꢀ, cm-1): 3136 (NH), 2219
(CN), 1649 (CO); 1H nmr (400MHz, DMSO-d6) (ꢁ, ppm): 12.76
(1H, s, NH), 7.88 (2H, d, J = 6.0 Hz, ArH), 7.55 (2H, d, J = 6.0
Hz, ArH), 7.36 (2H, d, J = 8.0 Hz, ArH), 7.14 (2H, d, J = 8.0 Hz,
ArH), 6.84 (1H, s, C5ꢀH), 3.85 (3H, s, OCH3), 3.38 (3H, s,
OCH3). Anal. Calcd. For C20H16N2O3: C 72.28, H 4.85, N 8.43.
Found: C 72.45, H 4.73, N 8.30.
General Procedure. A mixture of aromatic aldehydes 1 (2
mmol), aromatic ketones 2 (2 mmol), malononitrile 3 (3 mmol)
and NaOH (3 mmol) was put in a reaction flask and heated to a
temperature of 75 °C for about 30 min. After completing the
reaction, the reaction mixture was poured into water, and then
washed with water thoroughly. The product was collected bt
filtration, dried, and recrystallized from 95% ethanol.
1,2-Dihydro-6-(4-methoxyphenyl)-2-oxo-4-phenylpyridine-
3-carbonitrile (4a). This compound was obtained as yellow
crystals, mp 255ꢀ257 °ꢀ; ir (KBr, ꢀ, cm-1): 3180 (NH), 2220
(CN), 1625 (CO); 1H nmr (400MHz, DMSO-d6) (ꢁ, ppm): 12.71
(1H, s, NH), 7.91 (2H, d, J = 8.4 Hz, ArH), 7.72ꢀ7.74 (2H, dd, J
= 3.2 Hz, J = 3.2 Hz, ArH), 7.57 (3H, t, J = 3.2 Hz, J = 3.2 Hz,
ArH), 7.08 (2H, d, J = 8.4 Hz, ArH), 6.78 (1H, s, C5ꢀH), 3.84
(3H, s, OCH3). Anal. Calcd. For C19H14N2O2: C 75.48, H 4.67, N
9.27. Found: C 75.65, H 4.41, N 9.20.
6-(4-Chlorophenyl)-1,2-dihydro-2-oxo-4-phenylpyridine-3-
carbonitrile (4b). This compound was obtained as yellow
crystals, mp 284ꢀ286 °ꢀ; ir (KBr, ꢀ, cm-1): 3142 (NH), 2220
(CN), 1636 (CO); 1H nmr (400MHz, DMSO-d6) (ꢁ, ppm): 12.89
(1H, s, NH), 7.96 (2H, d, J = 8.4 Hz, ArH), 7.73ꢀ7.96 (2H, m,
ArH), 7.58ꢀ7.63 (5H, m, ArH), 6.87 (1H, s, C5ꢀH). Anal. Calcd.
For C18H11ClN2O: C 70.48, H 3.61, N 9.13. Found: C 70.62, H
3.55, N 9.01.
4-(4-Fluorophenyl)-1,2-dihydro-2-oxo-6-phenylpyridine-3-
carbonitrile (4c). This compound was obtained as yellow
crystals, mp 271ꢀ272 °ꢀ; ir (KBr, ꢀ, cm-1): 3144 (NH), 2218
(CN), 1641 (CO); 1H nmr (400MHz, DMSO-d6) (ꢁ, ppm): 12.81
(1H, s, NH), 7.91 (2H, d, J = 8.4 Hz, ArH), 7.81ꢀ7.85 (2H, m,
ArH), 7.52ꢀ7.60 (3H, m, ArH), 7.43 (2H, t, J = 8.0 Hz, ArH),
6.87 (1H, s, C5ꢀH). Anal. Calcd. For C18H11FN2O: C 74.47, H
3.82, N 9.65. Found: C 74.6ꢀ, H 3.78, N 9.62.
4-(4-Chlorophenyl)-1,2-dihydro-2-oxo-6-phenylpyridine-3-
carbonitrile (4d). This compound was obtained as yellow
crystals, mp 289ꢀ291 °ꢀ; ir (KBr, ꢀ, cm-1): 3150 (NH), 2220
(CN), 1645 (CO); 1H nmr (400MHz, DMSO-d6) (ꢁ, ppm): 13.71
(1H, s, NH), 8.18 (2H, m, ArH), 8.03ꢀ8.05 (3H, m, ArH), 7.88
(2H, m, ArH), 7.74ꢀ7.80 (2H, m, ArH), 7.48 (1H, s, C5ꢀH).
Anal. Calcd. For C18H11ClN2O: C 70.48, H 3.61, N, 9.13. Found:
C 70.58, H 3.50, N 9.04.
4-(2-Chlorophenyl)-1,2-dihydro-2-oxo-6-phenylpyridine-3-
carbonitrile (4e). This compound was obtained as yellow
crystals, mp 290ꢀ291 °ꢀ; ir (KBr, ꢀ, cm-1): 3140 (NH), 2221
(CN), 1643 (CO); 1H nmr (400MHz, DMSO-d6) (ꢁ, ppm): 12.88
(1H, s, NH), 7.91 (2H, d, J = 8.0 Hz, ArH), 7.60ꢀ7.64 (4H, m,
ArH), 7.43ꢀ7.50 (3H, m, ArH), 6.72 (1H, s, C5ꢀH). Anal. Calcd.
For C18H11ClN2O: C 70.48, H 3.61, N 9.13. Found: C 70.53, H
3.48, N 9.03.
4-(3,4-Methylenedioxylphenyl)-1,2-dihydro-2-oxo-6-
phenylpyridine-3-carbonitrile (4j). This compound was
obtained as yellow crystals, mp 290ꢀ291 °ꢀ; ir (KBr, ꢀ, cm-1):
1
3160 (NH), 2220 (CN), 1653 (CO); H nmr (400MHz, DMSO-
d6) (ꢁ, ppm): 12.78 (1H, s, NH), 7.88ꢀ7.91 (1H, m, ArH),
7.53ꢀ7.55 (3H, m, ArH), 7.29 (2H, d, J = 8.0 Hz, ArH), 7.11
(2H, d, J = 8.0 Hz, ArH), 6.76 (1H, s, C5ꢀH), 6.15 (2H, s,
OCH2O). Anal. Calcd. For C19H12N2O3: C 72.15, H 3.82, N 8.86.
Found: C 72.02, H 3.79, N 8.80.
6-(4-Bromophenyl)-1,2-dihydro-2-oxo-4-p-tolylpyridine-3-
carbonitrile (4k). This compound was obtained as yellow
crystals, mp 294ꢀ296 °C; ir (KBr, ꢀ, cm-1): 3160 (NH), 2222
1
(CN), 1660 (CO); H nmr (400MHz, DMSO-d6) (ꢁ, ppm): 12.84
(1H, s, NH), 7.85 (2H, m, ArH), 7.75 (2H, d, J = 8.4 Hz, ArH),
7.66 (2H, d, J = 8.4 Hz, ArH), 7.39 (2H, d, J = 8.4 Hz, ArH), 6.86
(1H, s, C5ꢀH), 3.34 (3H, s, CH3). Anal. Calcd. For C19H13BrN2O:
C 62.48, H 3.59, N 7.67. Found: C 62.37, H 3.63, N 7.61.
1,2-Dihydro-2-oxo-4,6-di-p-tolylpyridine-3-carbonitrile (4l).
This compound was obtained as yellow crystals, mp 295ꢀ297
°C; ir (KBr, ꢀ, cm-1): 3142 (NH), 2220 (CN), 1627 (CO); 1H nmr
(400MHz, DMSO-d6) (ꢁ, ppm): 12.74 (1H, s, NH), 7.80 (2H, d,
J = 8.4 Hz, ArH), 7.65 (2H, d, J = 8.4 Hz, ArH), 7.33ꢀ7.40 (4H,
m, ArH), 6.75 (1H, s, C5ꢀH), 2.40 (3H, s, CH3), 2.38 (3H, s,
CH3). Anal. Calcd. For C20H16N2O: C 79.98, H 5.37, N 9.33.
Found: C 79.85, H 5.48, N 9.39.
4-(4-Bromophenyl)-6-(4-chlorophenyl)-1,2-dihydro-2-oxo-
pyrid-ine-3-carbonitrile (4m). This compound was obtained as
yellow crystals, mp 282ꢀ284 °C; ir (KBr, ꢀ, cm-1): 3160 (NH),
1
2222 (CN), 1665 (CO); H nmr (400MHz, DMSO-d6) (ꢁ, ppm):
12.74 (1H, s, NH), 7.80 (2H, d, J = 8.4 Hz, ArH), 7.65 (2H, d, J
= 8.4 Hz, ArH), 7.34ꢀ7.40 (4H, m, ArH), 6.76 (1H, s, C5ꢀH).
Anal. Calcd. For C18H10BrClN2O: C 56.06, H 2.61, N 7.26.
Found: C 56.16, H 2.64, N 7.30.
1,2-Dihydro-4-(3,4-dimethylphenyl)-2-oxo-6-p-tolylpyrid-
ine-3-carbonitrile (4n). This compound was obtained as yellow
crystals, mp 260ꢀ262 °C; ir (KBr, ꢀ, cm-1): 3150 (NH), 2217
4-(2,4-Dichlorophenyl)-1,2-dihydro-2-oxo-6-phenylpyridine-
3-carbonitrile (4f). This compound was obtained as yellow crystals,
mp 279ꢀ280 °ꢀ; ir (KBr, ꢀ, cm-1): 3138 (NH), 2220 (CN), 1648
1
(CO); H nmr (400MHz, DMSO-d6) (ꢁ, ppm): 13.03 (1H, s, NH),
7.91 (2H, d, J = 8.0 Hz, ArH), 7.62ꢀ7.67 (2H, m, ArH), 7.52ꢀ7.58

1508
L. Rong, H. Wang, J. Shi, F. Yang, H. Yao, S. Tu and D. Shi
Vol 44
(CN), 1645 (CO); 1H nmr (400MHz, DMSO-d6) (ꢀ, ppm): 12.77
(1H, s, NH), 7.80 (2H, d, J = 8.0 Hz, ArH), 7.47 (2H, d, J = 8.0
Hz, ArH), 7.32ꢀ7.40 (3H, m, ArH), 6.76 (1H, s, C5ꢀH), 2.38
(3H, s, CH3), 2.30 (6H, s, 2 ꢁ CH3). Anal. Calcd. For C21H18N2O:
C 80.23, H 5.77, N 8.91. Found: C 80.38, H 5.74, N 8.87.
4-(3,4-Dichlorophenyl)-1,2-dihydro-2-oxo-6-p-tolylpyridine-
3-carbonitrile (4o). This compound was obtained as yellow
crystals, mp 197ꢀ198 °C; ir (KBr, ꢁ, cm-1): 3180 (NH), 2222 (CN),
1650 (CO); 1H nmr (400MHz, DMSO-d6) (ꢀ, ppm): 1H nmr
(400MHz, DMSO-d6) (ꢀ, ppm): 12.88 (1H, s, NH), 8.00 (1H, m,
ArH), 7.84 (2H, d, J = 8.4 Hz, ArH), 7.70 (1H, d, J = 8.4 Hz, ArH),
7.32 (1H, d, J = 8.0 Hz, ArH), 7.14 (2H, d, J = 8.0 Hz, ArH), 6.48
(1H, s, C5ꢀH), 2.32 (3H, s, CH3). Anal. Calcd. For C19H12Cl2N2O:
C 64.24, H 3.41, N 7.89. Found: C 64.16, H 3.44, N 7.86.
Med. Chem. 1999, 42, 446; [c] Jayaraman, M.; Fox, B. M.;
Hollingshead, M.; Kohlhgen, G.; Pommioer, Y. J. Med. Chem. 2002, 45,
242.
[2a] Lee, F.; Normansell, J. E. J. Org. Chem. 1990, 55, 2964; [b]
Murry, T. J.; Zimmerman, S. C. Tetrahedron Lett. 1995, 36, 7627.
[3a] Curran, D. P.; Liu, H. J. Am. Chem. Soc. 1992, 114, 5863; [b]
Liu, H.; Ko, S.; Curran, D. P. Tertahedron Lett. 1992, 36, 8917; [c]
Carles, L.; Narkunan, K.; Penlou, S.; Rousset, L.; Bouchu, D.; Ciufolini,
M. A. J. Org. Chem. 2002, 67, 4304.
[4a] Al-Hajjar, F. H.; Jarrar, A. A. J. Heterocycl. Chemꢀ1980, 17,
1521; [b] Moussa, H. H.; Chabaka, L. M. Egypt. J. Chem. 1983, 26, 267;
[c] Dobaria, V.; Patel, J. R.; Parekh, H. H. J. Indian Chem. Soc. 2002,
79, 772; [d] Desai, J. M.; Shah, V. H. Indian J. Chem., Sect. B 2003, 42,
382; [e] Desai, J. M.; Shah, V. H. Indian J. Chem., Sect. B 2003, 42,
2595; [f] Chaitanya, G. D.; Dhaval, A. S.;. Yadvendra, K. A. Indian J.
Chem., Sect. B 2004, 43, 885; [g] Alberola, A.; Andres, C.; Gonzalez, O.
A.; Pedrosa, R.; Vincente, M. J. Heterocycl. Chem. 1987, 24, 709; [h]
Isao, S. Bull Chem. Soc. Jpn. 1979, 52, 1235; [i] Rastogi, R. R.; Kumar,
A.; Ila, H.; Junjappa, H. J. Chem. Soc., Perkins Trans. 1 1978, 549; [j]
Otto, H. H.; Schmelz, H. Arch. Pharm. 1982, 315, 526; [k] Aggarwal,
V.; Singh, G.; Ila, H.; Junjappa, H. Synthesis 1982, 214; [l] Wang, S. Z.;
Yu, G.; Lu, J.; Xiao, K.; Hu, Y. F.; Hu, H. W. Synthesis 2003, 487; [m]
Alberola, A.; Calvo, L. A.; Ortega, A. G.; Sanudo-Ruiz, M. C.; Yustos,
P. J. Org. Chem. 1999, 64, 9493; [n] Rong, L. C.; Li, X. Y.; Wang, H.
Y.; Shi, D. Q.; Tu, S. J. Chem. Lett. 2006, 35, 1314..
4-(4-Chlorophenyl)-1,2-dihydro-6-(4-methoxyphenyl)-2-
oxopyridine-3-carbonitrile (4p). This compound was obtained
as yellow crystals, mp 275ꢀ276 °C; ir (KBr, ꢁ, cm-1): 3190
1
(NH), 2218 (CN), 1652 (CO); H nmr (400MHz, DMSO-d6) (ꢀ,
ppm): 12.68 (1H, s, NH), 7.08ꢀ7.92 (9H, m, ArH, C5ꢀH), 3.85
(3H, s, OCH3). Anal. Calcd. For C19H13ClN2O: C 67.76, H 3.89,
N 8.32. Found: C 67.65, H 3.78, N 8.39.
1,2-Dihydro-4,6-bis(4-methoxyphenyl)-2-oxopyridine-3-
carbonitrile (4q). This compound was obtained as yellow
crystals, mp 232ꢀ234 °C; ir (KBr, ꢁ, cm-1): 3140 (NH), 2220
(CN), 1655 (CO); 1H nmr (400MHz, DMSO-d6) (ꢀ, ppm): 12.59
(1H, s, NH), 7.07ꢀ7.91 (9H, m, ArH, C5ꢀH), 3.86 (3H, s,
OCH3), 3.85 (3H, s, OCH3). Anal. Calcd. For C20H16N2O3: C
72.28, H 4.85, N 8.43. Found: C 72.40, H 4.75, N 8.30.
[5a] Tanaka, K.; Toda, F. Chem. Rev. 2000, 100, 1025; [b]
Tanaka, K.; Kishigami, S.; Toda, F. J. Org. Chem. 1996, 56, 4333; [c]
Toda, F.; Tanaka, K.; Hamai, K. J. Chem., Soc. Perkin Trans. 1 1990,
3207; [d] Toda, F.; Suzuki, T.; Higa, S. J. Chem. Soc., Perkin Trans. 1
1998, 3521; [e] Toda, F.; Tanaka, K.; Iwata, S. J. Org. Chem. 1989, 54,
3007.
4-(3,4-Dichlorophenyl)-1,2-dihydro-6-(4-methoxyphenyl)-
2-oxopyridine-3-carbonitrile (4r). This compound was
obtained as yellow crystals, mp > 300 °C; ir (KBr, ꢁ, cm-1): 3170
[6a] Kaupp, G.; Naimi-Jamal, M. R.; Schmeyers, J. Tetrahedron
2003, 59, 3753; [b] Zolfigol, M. A.; Safaiee, M. Synth. Lett. 2004, 5,
827; [c] Shaabani, A.; Bazgir, A.; Teimour, F. Tetrahedron Lett. 2003,
44, 857.
1
(NH), 2221 (CN), 1642 (CO); H nmr (400MHz, DMSO-d6) (ꢀ,
ppm): 12.83 (1H, s, NH), 7.11ꢀ7.85 (8H, m, ArH, C5ꢀH), 3.85
(3H, s, OCH3). Anal. Calcd. For C19H12Cl2N2O: C 61.47, H 3.26,
N 7.55. Found: C 61.35, H 3.38, N 7.15.
[7a] Rong, L. C.; Li, X. Y.; Wang, H. Y.; Shi, D. Q.; Tu, S. J.;
Zhuang, Q. Y. Synth. Commun. 2006, 36, 2363; [b] Rong, L. C.; Li, X.
Y.; Wang, H. Y.; Shi, D. Q.; Tu, S. J.; Zhuang, Q. Y. Synth. Commun.
2006, 36, 2407; [c] Rong, L. C.; Li, X. Y.; Yao, C. S.; Wang, H. Y.; Shi,
D. Q. Acta Crystallogr. Sect. E: Struct. Rep. Online 2006, E62, o35; [d]
Rong, L. C.; Li, X. Y.; Yao, C. S.; Wang, H. Y.; Shi, D. Q. Acta
Crystallogr. Sect. E: Struct. Rep. Online 2006, E62, o3004.
Acknowledgements. We thank the National Natural Science
Foundation of China (No. 20372057), the Key Lab of
Biotechnology for Medicinal Plants of Jiangsu Province
(01AXL14) and Natural Science Foundation (06XLA09) of
Xuzhou Normal University for financial support.
[8] X-ray crystallography for 4c: Empirical formula C18H11FN2O,
Fw = 290.29, T = 173(2) K, monoclinic, space group p 21/c, a = 8.705
(2) ꢀ, b = 7.9408(18) ꢀ, c = 20462(5) ꢀ, ꢁ = 90°, ꢂ = 97.309(5)°, ꢃ =
90°, V = 14029(6) ꢀ3, Z = 4, Dcalcd. = 1.374 Mg/m3, ꢄ (MoKꢁ) =
0.71070 ꢀ, μ = 0.096 mm-1, F(000) = 600. 3.26°< <25.34°, R =
0.0624, wR = 0.1373. s = 1.173. largest diff. peak and hole: 0.207 and -
0.218 e. ꢀ-3.
REFERENCES
[1a] Schultz, A. G. Chem. Rev. 1973, 73, 385; [b] Strumberg, D.;
Pommier, Y.; Paull, K.; Jayaraman, M.; Nagafuji, P.; Cushman, M. J.