One-pot synthesis of 4,6-diaryl-2-oxo-1,2-dihydropyridine-3-carbonitriles via three-component cyclocondensation under solvent-free conditions

Article abstract of DOI:10.1080/00397910701749682

An efficient and facile synthesis of 4,6-diaryl-2-oxo-1,2-dihydropyridine- 3-carbonitriles via three-component cyclocondensation from aromatic aldehydes, aromatic ketones, and 2-cyanoacetamide under solvent-free conditions is described. The mild reaction

Full text of DOI:10.1080/00397910701749682

This article was downloaded by: [University of Virginia, Charlottesville]
On: 19 March 2013, At: 09:33
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office:
Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International
Journal for Rapid Communication of
Synthetic Organic Chemistry
Publication details, including instructions for authors and subscription
information:
http://www.tandfonline.com/loi/lsyc20
One‐Pot Synthesis of
4,6‐Diaryl‐2‐oxo‐1,2‐dihydropyridine‐3‐carbonitr
via Three‐Component Cyclocondensation
under Solvent‐Free Conditions
Liangce Rong a b , Hongxia Han a , Hong Jiang b , Daqing Shi a b & Shujiang Tu
a b
a Department of Chemistry, Xuzhou Normal University, Xuzhou, China
b Key Laboratory of Biotechnology on Medical Plant, Jiangsu, Xuzhou, China
Version of record first published: 18 Jan 2008.
To cite this article: Liangce Rong , Hongxia Han , Hong Jiang , Daqing Shi & Shujiang Tu (2008): One‐Pot
Synthesis of 4,6‐Diaryl‐2‐oxo‐1,2‐dihydropyridine‐3‐carbonitriles via Three‐Component Cyclocondensation
under Solvent‐Free Conditions, Synthetic Communications: An International Journal for Rapid Communication
of Synthetic Organic Chemistry, 38:2, 217-224
To link to this article: http://dx.doi.org/10.1080/00397910701749682
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any substantial
or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or
distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation that the
contents will be complete or accurate or up to date. The accuracy of any instructions, formulae,
and drug doses should be independently verified with primary sources. The publisher shall not
be liable for any loss, actions, claims, proceedings, demand, or costs or damages whatsoever or
howsoever caused arising directly or indirectly in connection with or arising out of the use of this
material.

Synthetic Communicationsw, 38: 217–224, 2008
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701749682
One-Pot Synthesis of 4,6-Diaryl-2-oxo-1,2-
dihydropyridine-3-carbonitriles via
Three-Component Cyclocondensation
under Solvent-Free Conditions
Liangce Rong,1,2 Hongxia Han,1 Hong Jiang,2 Daqing Shi,1,2
and Shujiang Tu1,2
1Department of Chemistry, Xuzhou Normal University, Xuzhou, China
2Key Laboratory of Biotechnology on Medical Plant, Jiangsu, Xuzhou,
China
Abstract: An efficient and facile synthesis of 4,6-diaryl-2-oxo-1,2-dihydropyridine-3-
carbonitriles via three-component cyclocondensation from aromatic aldehydes,
aromatic ketones, and 2-cyanoacetamide under solvent-free conditions is described.
The mild reaction conditions, simple protocol, and clean reaction make this protocol
practical and economically attractive.
Keywords: heating, 2-pyridone, solvent-free condition
In recent years, emphasis in chemistry has shifted to develop environmentally
benign routes to a myriad of materials.[1] Green chemistry approaches hold
significant potential not only for reduction of by-products, a reduction in the
waste produced, and lowering of energy costs but also for the development
of new methodologies to achieve previously unobtainable materials, using
existing technologies.[2] Of all of the existing areas of chemistry, medicinal
and pharmaceutical chemistry, with their traditionally high ratio of waste/
product, are perhaps the most ripe for improvement.[3] Multicomponent
Received December 30, 2006
Address correspondence to Liangce Rong, Department of Chemistry, Xuzhou
Normal University, Xuzhou 221116, P. R. China. E-mail: lcrong@xznu.edu.cn
217

218
L. Rong et al.
coupling reactions (MCRs) are emerging as useful tools for carbon–carbon
and carbon–heteroatom bond-forming reactions and for the synthesis of
small druglike molecules with several degrees of structural diversity.[4] Devel-
opment of new solid-phase (solvent-free) MCRs is the subjects of recent
interest in organic synthesis.[5] Solvent-free reactions are well known as envir-
onmentally benign methods that also usually provide improved selectively,
enhanced reaction rates, cleaner products, and manipulative simplicity.[6]
Some solvent-free reactions could be carried out just by heating.[7]
Substituted six-membered lactams, 2-pyridones, and their hydrogenating
derivatives have attracted the attention of synthetic organic chemists for
many years because these structural features are found in a wide variety of
naturally occurring alkaloids.[8] Since compounds with these scaffolds have
been shown to exhibit significant pharmacological properties, medicinal
chemists often incorporate these motifs in the design of novel biologically
active molecules. Development of a general and efficient synthetic strategy
that could provide access to a wide range of nitrogen heterocycles with a six-
membered lactam core is therefore highly desired. Several novel synthetic
methodologies directed toward the preparation of six-membered nitrogen het-
erocycles have been reported.[9] However, preparations of these reactive inter-
mediates are not always straightforward to carry out because of various
drawbacks involved in these reactions, such as long reaction times, low
yields, and forced reaction conditions. Especially in these reactions, the
organic solvents are needed.[10] 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. In continuation of our ongoing
endeavor to apply solvent-free conditions to the synthesis of organic
compounds,[11] we herein describe a practical and simple MCR to prepare
4,6-diaryl-2-oxo-1,2-dihydropyridine-3-carbonitriles by heating starting
material under dry conditions. The aromatic aldehydes 1, aromatic ketones 2,
and 2-cyanoacetamide 3 were mixed together in a flask in the presence of
catalyst NaOH. The mixture was heated at 758C about 30 min, and the
reaction could be finished with good yields (Scheme 1). The results of
reaction are listed in Table 1. As shown in Table 1, we can see not only that
Scheme 1.

Cyclocondensation Under Solvent-Free Conditions
219
Table 1. Synthesis of 1,2-dihydro-2-oxo-4,6-diarylpyridine-3-carbonitrile under
solvent-free conditions
Entry
R1
R2
Product
Yields
1
2
4-F
H
H
H
H
H
H
H
H
4a
4b
4c
4d
4e
4f
88
85
89
84
80
83
80
81
80
85
78
86
4-Cl
4-Br
2-Cl
3
4
5
2,4-Cl2
3,4-Cl2
3,4-(CH3O)2
3,4-OCH2O
4-CH3
4-CH3
H
6
7
4g
4h
4i
8
9
4-CH3
4-Br
10
11
12
4j
4-CH3O
4-Cl
4k
4l
H
all the reactions can be completed smoothly but also that a series of aldehydes
or ketones bearing either electron-withdrawing or electron-donating groups
perform equally well in the reactions.
In conclusion, we have developed a rapid and highly efficient multicom-
ponent coupling reaction for the synthesis of 4,6-diaryl-2-oxo-1,2-dihydropyr-
idine-3-carbonitrile derivatives via the reaction of different aromatic
aldehydes, aromatic ketones, and 2-cyanoacetamide under solvent-free con-
ditions. The advantages of the present method in terms of avoiding toxic
organic solvent, ease of manipulation, fast reaction rates, and lower cost
should make this protocol a valuable alternative to the existing methods.
EXPERIMENTAL
Melting points were determined on an XT-5 microscopic melting-point
apparatus and are uncorrected. IR spectra were recorded on a FT IR-8101
1
spectrometer. H NMR spectra were obtained from solution in DMSO-d6
with Me4Si as internal standard using a Bruker-400 spectrometer. Microana-
lyses were carried out using a Perkin-Elmer 2400 II analyzer.
General Procedure for the Synthesis of 4,6-Diaryl-2-oxo-1,2-
dihydropyridine-3-carbonitriles (4)
The mixture of aromatic aldehydes (2 mmol), aromatic ketones (2 mmol),
2-cyanoacetamide (3 mmol), and NaOH (3 mmol) was put in a reaction

220
L. Rong et al.
flask at 708C for about 30 min. After completion, the reaction mixture was
poured into water and then washed with water thoroughly. The product was
filtered, dried, and recrystallized from 95% ethanol.
Spectral Data
4-(4-Fluorophenyl)-2-oxo-6-phenyl-1,2-dihydropyridine-3-carbonitrile (4a):
1
Mp 270–2728C; IR (KBr, n, cm21): 3146 (NH), 2220 (CN), 1643 (CO); H
NMR (400 MHz, DMSO-d6) (d, ppm): 12.80 (1H, s, NH), 7.92 (2H, d,
J ¼ 8.4 Hz, ArH), 7.83–7.88 (2H, m, ArH), 7.51–7.62 (3H, m, ArH), 7.43
(2H, t, J ¼ 8.0 Hz, ArH), 6.87 (1H, s, C5-H). Anal. calcd. for C18H11FN2O:
C, 74.47; H 3.82; N, 9.65. Found: C, 74.60; H, 3.63; N, 9.53.
4-(4-Chlorophenyl)-2-oxo-6-phenyl-1,2-dihydropyridine-3-carbonitrile (4b):
Mp 287–2888C (lit.[10d] 311–3128C); IR (KBr, n, cm21): 3150 (NH), 2221
(CN), 1644 (CO); H NMR (400 MHz, DMSO-d6) (d, ppm): 13.73 (1H, s,
1
NH), 8.19 (2H, m, ArH), 8.03–8.07 (3H, m, ArH), 7.88 (2H, m, ArH),
7.75–7.83 (2H, m, ArH), 7.48 (1H, s, C5-H). Anal. calcd. for
C18H11ClN2O: C, 70.48; H, 3.61; N, 9.13. Found: C, 70.55; H, 3.52; N, 9.07.
4-(4-Bromophenyl)-2-oxo-6-phenyl-1,2-dihydropyridine-3-carbonitrile (4c):
1
Mp 291–2938C; IR (KBr, n, cm21): 3141 (NH), 2220 (CN), 1652 (CO); H
NMR (400 MHz, DMSO-d6) (d, ppm): 12.91 (1H, s, NH), 7.89 (2H, m,
ArH), 7.82 (2H, d, J ¼ 8.4 Hz, ArH), 7.70 (2H, d, J ¼ 8.4 Hz, ArH), 7.51–
7.56 (3H, dd, J ¼ 8.4 Hz, J ¼ 8.4 Hz, ArH), 6.80 (1H, s, C5-H). Anal.
calcd. for C18H11BrN2O: C, 61.56; H, 3.16; N, 7.98. Found: C, 61.48; H,
3.24; N, 7.81.
4-(2-Chlorophenyl)-2-oxo-6-phenyl-1,2-dihydropyridine-3-carbonitrile (4d):
1
Mp 290–2928C; IR (KBr, n, cm21): 3145 (NH), 2222 (CN), 1645 (CO); H
NMR (400 MHz, DMSO-d6) (d, ppm): 12.86 (1H, s, NH), 7.91 (2H, d,
J ¼ 8.0 Hz, ArH), 7.61–7.66 (4H, m, ArH), 7.43–7.50 (3H, m, ArH), 6.72
(1H, s, C5-H). Anal. calcd. for C18H11ClN2O: C, 70.48; H, 3.61; N, 9.13.
Found: C, 70.50; H, 3.45; N, 9.01.
4-(2,4-Dichlorophenyl)-2-oxo-6-phenyl-1,2-dihydropyridine-3-carbonitrile
(4e): Mp 278–2808C; IR (KBr, n, cm21): 3141 (NH), 2221 (CN), 1650 (CO);
1H NMR (400 MHz, DMSO-d6) (d, ppm): 13.01 (s, 1H, NH), 7.90 (2H, d,
J ¼ 8.0 Hz, ArH), 7.62–7.67 (2H, m, ArH), 7.53–7.58 (4H, m, ArH), 6.82
(1H, s, C5-H). Anal. calcd. for C18H10Cl2N2O: C, 63.36; H, 2.95; N, 8.21.
Found: C, 63.44; H, 2.75; N, 8.33.
4-(3,4-Dichlorophenyl)-2-oxo-6-phenyl-1,2-dihydropyridine-3-carbonitrile (4f):
1
Mp . 3008C; IR (KBr, n, cm21): 3135 (NH), 2221 (CN), 1656 (CO); H

Cyclocondensation Under Solvent-Free Conditions
221
NMR (400 MHz, DMSO-d6) (d, ppm): 12.88 (1H, s, NH), 7.50–7.92 (8H, m,
ArH), 6.91 (1H, s, C5 2 H). Anal. calcd. for C18H10Cl2N2O: C, 63.36; H, 2.95;
N, 8.21. Found: C, 63.51; H, 2.70; N, 8.35.
4-(3,4-Dimethoxyphenyl)-2-oxo-6-phenyl-1,2-dihydropyridine-3-carbonitrile
(4g): Mp 273–2758C; IR (KBr, n, cm21): 3138 (NH), 2220 (CN), 1653 (CO);
1H NMR (400 MHz, DMSO-d6) (d, ppm): 12.78 (1H, s, NH), 7.87 (2H, d,
J ¼ 6.0 Hz, ArH), 7.55 (2H, d, J ¼ 6.0 Hz, ArH), 7.36 (2H, d, J ¼ 8.0 Hz,
ArH), 7.12 (2H, d, J ¼ 8.0 Hz, ArH), 6.85 (1H, s, C5-H), 3.84 (3H, s,
OCH3), 3.38 (3H, s, OCH3). Anal. calcd. for C20H16N2O3: C, 72.28; H,
4.85; N, 8.43. Found: C, 72.40; H, 4.73; N, 8.32.
4-(Benzo[d][1,3]dioxol-5-yl)-2-oxo-6-phenyl-1,2-dihydropyridine-3-carboni-
trile (4h): Mp 290–2918C; IR (KBr, n, cm21): 3165 (NH), 2221 (CN), 1657
(CO); 1H NMR (400 MHz, DMSO-d6) (d, ppm): 12.76 (s, 1H, NH), 7.88–7.91
(2H, m, ArH), 7.54–7.58 (2H, m, ArH), 7.29 (2H, d, J ¼ 8.0 Hz, ArH), 7.11
(2H, d, J ¼ 8.0 Hz, ArH), 6.76 (1H, s, C5-H), 6.15 (2H, s, OCH2O). Anal.
calcd. for C19H12N2O3: C, 72.15; H, 3.82; N, 8.86. Found: C, 72.02; H,
3.71; N, 8.89.
4,6-Dip-tolyl-2-oxo-1,2-dihydropyridine-3-carbonitrile (4i): Mp 291–2938C
(lit.[10b] 290–2918C); IR (KBr, n, cm21): 3148 (NH), 2221 (CN), 1629 (CO);
1H NMR (400 MHz, DMSO-d6) (d, ppm): 12.78 (1H, s, NH), 7.80 (2H, d,
J ¼ 8.4 Hz, ArH), 7.65 (2H, d, J ¼ 8.4 Hz, ArH), 7.33–7.43 (4H, m, ArH),
6.75 (1H, s, C5-H), 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, 79.87; H, 5.43; N, 9.41.
6-(4-Bromophenyl)-2-oxo-4-p-tolyl-1,2-dihydropyridine-3-carbonitrile (4j):
1
Mp 297–2988C; IR (KBr, n, cm21): 3165 (NH), 2220 (CN), 1661 (CO); H
NMR (400 MHz, DMSO-d6) (d, ppm): 12.82 (1H, s, NH), 7.88 (2H, m,
ArH), 7.75 (2H, d, J ¼ 8.4 Hz, ArH), 7.68 (2H, d, J ¼ 8.4 Hz, ArH), 7.39
(2H, d, J ¼ 8.4 Hz, ArH), 6.86 (1H, s, C5-H), 3.34 (3H, s, CH3). Anal.
calcd. for C19H13BrN2O: C, 62.48; H, 3.59; N, 7.67. Found: C, 62.37; H,
3.66; N, 7.61.
6-(4-Methoxyphenyl)-2-oxo-4-phenyl-1,2-dihydropyridine-3-carbonitrile
(4k): Mp 252–2548C (lit.[10b] 268–2698C); IR (KBr, n, cm21): 3181 (NH),
2219 (CN), 1628 (CO); H NMR (400 MHz, DMSO-d6) (d, ppm): 12.72
1
(1H, s, NH), 7.90 (2H, d, J ¼ 8.4 Hz, ArH), 7.70–7.76 (2H, dd, J ¼ 3.2 Hz,
J ¼ 3.2 Hz, ArH), 7.57 (3H, t, J ¼ 3.2 Hz, J ¼ 3.2 Hz,, ArH), 7.08 (2H, d,
J ¼ 8.4 Hz, ArH), 6.78 (1H, s, C5-H), 3.84 (3H, s, OCH3). Anal. calcd. for
C19H14N2O2: C, 75.48; H, 4.67; N, 9.27. Found: C, 75.60; H, 4.42; N, 9.35.
6-(4-Chlorophenyl)-2-oxo-4-phenyl-1,2-dihydropyridine-3-carbonitrile (4l):
Mp 282–2838C (lit.[10b] 294–2958C); IR (KBr, n, cm21): 3145 (NH), 2221
(CN), 1638 (CO); H NMR (400 MHz, DMSO-d6) (d, ppm): 12.91 (1H, s,
1

222
L. Rong et al.
NH), 7.98 (2H, d, J ¼ 8.4 Hz, ArH), 7.73–7.95 (2H, m, ArH), 7.58–7.66 (5H,
m, ArH), 6.87 (1H, s, C5-H). Anal. calcd. for C18H11ClN2O: C, 70.48; H, 3.61;
N, 9.13. Found: C, 70.61; H, 3.58; N, 9.00.
ACKNOWLEDGMENT
We thank the National Natural Science Foundation of China (No. 20372057)
and Natural Science Foundation (No. 06XLA09) of Xuzhou Normal Univer-
sity for financial support.
REFERENCES
1. Anastas, P.; Williamson, T. Green Chemistry: Frontiers in Benign Chemical
Synthesis and Procedures; Oxford Science Publications, London: 1998.
2. Cave, G. W. V.; Raston, C. L.; Scott, J. L. Recent advances in solventless organic
reactions: towards benign synthesis with remarkable versatility. Chem. Commun.
2001, 2159.
3. Sheldon, R. A. As estimated by determination of E-factor. Chem. Ind. 1997, 12.
4. (a) Montgomery, J. Nickel-catalysted cyclizations, couplings, and cycloadditions
involving three reactive components. Acc. Chem. Res. 2000, 33, 467;
(b) Sabitha, G.; Kiran Kumar Reddy, G. S.; Rsddy, K. B.; Yadav, J. S.
Vanadium (III) chloride catalyzed biginelli condensation:solution phase library
generation of dihydropyrimidin-(2H)-ones. Tetrahedron Lett. 2003, 44, 6497;
(c) Labrie, P. NiCl2 and NiCl2 ¼ 6H2O: A very useful mild lewis acid in
organic synthesis. Synlett 2003, 279; (d) Varala, R.; Alam, M. M.; Adapa, S. R.
Bismuth triflate catalyzed one-pot synthesis of 3.4-dihydropyrimidin-2(1H)-
ones: an improced protocol for the biginelli reaction. Synlett 2003, 67;
(e) Dondoni, A.; Massi, A.; Minghini, E.; Sabbatini, S.; Bertolasi, V. Model
studies toward the synthesis of dihydropyrimidinyl and pyridyl-amino acids via
three-component biginelli and hantzsch cyclocondensations. J. Org. Chem.
2003, 68, 6172; (f) Hanselmann, R.; Zhou, J. C.; Ma, P.; Confalone, P. N.
Synthesis of cyclic and acyclic-amino acids via chelation-controlled 1,3-dipolar
cycloaddition. J. Org. Chem. 2003, 68, 8739; (g) Nair, V.; Mathai, S.;
Varma, R. L. The three-component reaction of dicarbomethoxycarbene,
aldehydes, and nitrostyrenes: a stereoselective synthesis of substituted tetrahydro-
furans. J. Org. Chem. 2004, 69, 1413; (h) Gao, X.; Hall, D. G. H. 3-Boronoacrolein
as an exceptional heterodiene in the highly enantio- and diastereoselective Cr(III)-
catalyzed three-component [4 þ 2]/allylboration. J. Am. Chem. Soc. 2003, 125,
9308.
5. Tanaka, T.; Toda, F. Solvent-free organic synthesis. Chem. Rev. 2000, 100, 1025.
6. (a) Cave, G. W. V.; Raston, C. L. Toward benign syntheses of pyridines involving
sequential solvent free aldol and Michael addition reactions. J. Chem. Soc., Chem.
Commun. 2000, 2199; (b) Shinobu, W.; Hitomi, S. Calcite and fluorite as catalyst
¨
for the Knovenagel condensation of malononitrile and methyl cyanoacetate under
solvent-free conditions. Tertahedron Lett. 2003, 44, 399; (c) Liu, X. X.;
Shen, Z. X. Highly chemoselective synthesis of 1,2,3,4,5-pentasub-stituted cyclo-
hexanols under solvent-free condition. Tetrahedron Lett. 2006, 47, 5623;

Cyclocondensation Under Solvent-Free Conditions
223
(d) Liu, W. Y.; Xu, Q. H.; Liang, Y. M.; Chen, B. H.; Liu, W. M.; Ma, Y. X. Prep-
aration of ferrocenyl mono-and dienone derivatives through aldol condensation of
1.10-diacetylferrocene with aromatic aldehydes in dry conditions. J. Organom.
Chem. 2001, 637–639, 719.
7. (a) Kaupp, G.; Naimi-Jamal, M. R.; Schmeyers, J. Solvent-free konenenagel con-
densations and michial additions in the solid state and in the melt with guantitative
yield. Tetrahedron 2003, 59, 3753; (b) Zolfigol, M. A.; Safaiee, M. Synthesis of
1,4-dihydropyridines under solvent-free conditions. Synth. Lett. 2004, 5, 827;
(c) Shaabani, A.; Bazgir, A.; Teimour, F. Ammonium chloride-catalyzed one-
pot synthesis of 3.4-dihydropynidin-2(1H)-ones under solvent conditions. Tetrahe-
dron Lett. 2003, 44, 857.
8. (a) Jones, T. H.; Blum, M. S. In Alkaloids: Chemical and Biological Perspectives;
Pelletier, S. W. Ed.; Wiley: New York, 1983, Vol. 1, p. 33; (b) Fodor, G. B.;
Colasanti, B. In Alkaloids: Chemical and Biological Perspectives;
Pelletier, S. W. Ed.; Wiley: New York, 1985, Vol. 3, p. 1; (c) Strunz, G. M.;
Findlay, J. A In The Alkaloids; Brossi, A. Ed.; Academic Press: Orlando, 1985,
Vol. 26, p. 89; (d) Daly, J. W. J. Nat. Prod. 1998, 61, 162; (e) Plunkett, A. O.
Pyrrole, pyrrolidine, pyridine, piperidine, and azepine alkaloids. Nat. Prod. Rep.
1994, 11, 581; (f) Balasubramanian, M.; Keay, J. G. Comprehensive Heterocyclic
Chemistry II; Katritzky, A. R., Rees, C. W. and Scriven, E. F. V., Eds.; Pergamon
Press, 1996, Vol. 5, p. p. 245; (g) Rubiralta, M.; Giralt, E.; Diez, A. Piperidine:
Structure, Preparation, Reactivity, and Synthetic Applications of Piperidine and
Its Derivatives; Elsevier: Amsterdam, 1991.
9. (a) Freeman, F. Chemistry of malononitrile. Chem. Rev. 1969, 5, 591;
(b) Rastogi, R. R.; Kumar, A.; Ila, H.; Junjappa, H. Reaction of -oxo- and
-cyano-ketene SS-acetals with cyanoacetamide: a new general method for substi-
tuted and fused 4-alkylthio-3-cyano-2(1H)-pyridones and formation of novel
pyridones through base-induced rearrangements. J. Chem. Soc., Perkins Trans. 1
1978, 6, 549; (c) Otto, H. H.; Schmelz, H. Reactions of (hydroxymethylene)tetra-
lone with derivatives of cyanoacetic acid. Arch. Pharm. 1982, 315, 526;
(d) Aggarwal, V.; Singh, G.; Ila, H.; Junjappa, H. Reaction of a-ketoketene S,N-
acetals with cyanoacetamide: A new general method for substituted and fused 4-
(N-alkylamino-, N-arylamino-, or N-morpholino)-3-cyano-2(1H)-pyridones.
´
´
Synthesis 1982, 214; (e) Alberola, A.; Andres, C.; Gonzalez-Ortega, A.;
Pedrosa, R.; Vicente, M. The reaction of b-aminoenones with substituted aceto-
nitriles. regiospecific synthesis of 2(1H)-pyridones. J. Heterocycl. Chem. 1987,
24, 709; (f) Purkayastha, M. L.; Bhat, L.; Ila, H.; Junjappa, H. 4-Alkoxy-3-
cyano-2(1H)-pyridones and 5-alkoxyisoxazoles and their aryl substituted and
snnulated derivatives from acylketene O,S-acetals. Synthesis 1995, 641;
(g) Krstic, V.; Misic-Vukovic, M.; Radojkovic-Velickovic, M. Synthesis and
identification of isomeric 4(6)-methyl-6(4)-(substituted phenyl)-3-cyano-2-
pyridones. J. Chem. Res. Syno. 1991, 82; (h) Lorente, A.; Cosme, A.;
Coronada, P.; Soto, J. L. Synthesis of 4,6-diaryl-2-cyanoimin- opiperidines from
N-cyanocinnamamidines. Synthesis 1988, 739; (i) Rastogi, R. R.; Kumar, A.;
Iia, H.; Junjappa, H. Reaction of a-oxoketene SS-acetals with N-alkylcyanoaceta-
mides: a new general method for substituted and fused 2,7-dialkyl-8-amino-5-
cyano-2,7-naphth- yridine-1,6(2H,7H)-diones. J. Chem. Soc. Perkin Trans. 1
1978, 554; (j) Alberola, A.; Calvo, L. A.; Ortega, A. J.; Rurz, M. C. S.;
Yustos, Pedro. Regioselective synthesis of 2(1H)-pyridinones from b-amino-
enones and malononitrile. reaction mechanism. J. Org. Chem. 1999, 64, 9493.

224
L. Rong et al.
10. (a) Li, W. W.; Chen, Y.; Lam, Y. L. A facile solid-phase synthesis of 3,4,6-trisub-
stituted-2-pyridones using sodium benzenesulfinate as a traceless linker. Tetrahe-
dron Lett. 2004, 45, 6545; (b) Dave, C. G.; Shah, D. A.; Agrawal, Y. K. A simple
and convenient synthesis of 4,6-disubstituted-3-cyanopyridin-2(1H)-ones under
solvent-free microwave conditions. Indian J. Chem., Sec. B 2004, 43B, 885;
(c) Kandeel, K. A.; Vernon, J. M.; Dransfield, T. A.; Fouli, F. A.;
Youssef, A. S. A. Reactions of malononitrile with acetylenic esters and ketones.
J. Chem. Res. Syno. 1990, 276; (d) Soto, J. L.; Seoane, C.; Mansilla, A. M. A
simple one-step synthesis of 2-pyridones from benzylidenacetophenones. Org.
Prep. Proced. Int. 1981, 13, 331; (e) Kuthan, J.; Nesv-adba, P.; Popl, M.;
Fahnrich, J. Some 3-cyano-4,6-diaryl- 2-pyridones with luminescent properties.
Coll. Czech. Chem. Commun. 1979, 44, 2409; (f) Kambe, S.; Saito, K.;
Sakurai, A.; Hayashi, T. A convenient method for the preparation of 2-pyridone
derivatives. Synthesis 1977, 841.
11. (a) Rong, L. C.; Li, X. Y.; Wang, H. Y.; Shi, D. Q.; Tu, S. An efficient and facile
synthesis of 2-amino-4,6-diarylbenzene-1,3-dicarbonitrile and 1,2-dihydro-2-oxo-
4,6-diarylpyridine-3-carbonitrile under solvent-free conditions. Chem. Lett. 2006,
10, 1314; (b) Rong, L. C.; Li, X. Y.; Wang, H. Y.; Shi, D. Q.; Tu, S. J.;
Zhuang, Q. Y. Efficient synthesis of tetrahydrobenzo[b] pyrans under solvent-
free conditions at room temperature. Synth. Commun. 2006, 36, 2363;
(c) Rong, L. C.; Li, X. Y.; Wang, H. Y.; Shi, D. Q.; Tu, S. J.; Zhuang, Q. Y.
Efficient green procedure for the Knoevenagel Condensation under solvent-free
conditions. Synth. Commun. 2006, 36, 2407; (d) Rong, L. C.; Li, X. Y.;
Yao, C. S.; Wang, H. Y.; Shi, D. Q. 2-[1-(3,4-Dichlorophenyl)-3-oxo-3-phenylpro-
pyl]-3,4-dihydro-2H-naphthalen-1-one. Acta Crys. 2006, E62, o35;
(e) Rong, L. C.; Li, X. Y.; Wang, H. Y.; Yao, C. S.; Shi, D. Q. 2-Amino-
5,6,7,8-tetrahydro-4-p-tolylnaphthalene-1,3-dicarbonitrile. Acta Crys. 2006, E62,
o3004.