Biginelli-like cyclocondensation reaction: Efficient synthesis of 4,6-diarylpyrimidin-2(1H)-one under solvent-free conditions

Article abstract of DOI:10.1080/00397911.2010.516619

An efficient and facile synthesis of 4,6-diarylpyrimidin-2(1H)-one via a Biginelli-like reaction of aromatic aldehydes, aromatic ketones, and urea in the presence of NaOH under solvent-free conditions using a heating method has been developed. Compared wi

Full text of DOI:10.1080/00397911.2010.516619

This article was downloaded by: [LMU Muenchen]
On: 05 July 2014, At: 00:23
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
Biginelli-Like Cyclocondensation
Reaction: Efficient Synthesis of 4,6-
Diarylpyrimidin-2(1H)-one Under
Solvent-Free Conditions
Yisi Dai a , Minxiang Cao a , Mengjie Zhuang a , Sheng Xia a , Shujiang
Tu a b & Liangce Rong a b
a College of Chemistry and Chemical Engineering , Xuzhou Normal
University , Xuzhou , Jiangsu , China
b Jiangsu Key Laboratory of Green Synthetic Chemistry for
Functional Materials , Xuzhou , Jiangsu , China
Published online: 11 Jul 2011.
To cite this article: Yisi Dai , Minxiang Cao , Mengjie Zhuang , Sheng Xia , Shujiang Tu &
Liangce Rong (2011) Biginelli-Like Cyclocondensation Reaction: Efficient Synthesis of 4,6-
Diarylpyrimidin-2(1H)-one Under Solvent-Free Conditions, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 41:20, 3039-3044, DOI:
10.1080/00397911.2010.516619
To link to this article: http://dx.doi.org/10.1080/00397911.2010.516619
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.

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. Terms &
Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Synthetic Communications1, 41: 3039–3044, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.516619
BIGINELLI-LIKE CYCLOCONDENSATION REACTION:
EFFICIENT SYNTHESIS OF
4,6-DIARYLPYRIMIDIN-2(1H)-ONE UNDER
SOLVENT-FREE CONDITIONS
Yisi Dai,1 Minxiang Cao,1 Mengjie Zhuang,1 Sheng Xia,1
Shujiang Tu,1,2 and Liangce Rong1,2
1College of Chemistry and Chemical Engineering, Xuzhou Normal University,
Xuzhou, Jiangsu, China
2Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional
Materials, Xuzhou, Jiangsu, China
GRAPHICAL ABSTRACT
Abstract An efficient and facile synthesis of 4,6-diarylpyrimidin-2(1H)-one via
a
Biginelli-like reaction of aromatic aldehydes, aromatic ketones, and urea in the presence
of NaOH under solvent-free conditions using a heating method has been developed. Com-
pared with the classical reaction conditions, this new synthetic method has the advantages
of excellent yields, shorter reaction time, and mild reaction conditions.
Keywords Biginelli-like reaction; 4,6-diarylpyrimidin-2(1H)-one; green chemistry;
solvent-free synthesis
INTRODUCTION
The N-heterocyclic compounds, such as hydropyrimidinones, are very useful
intermediates for the development of molecules of pharmaceutical or biological
interest. These compounds show variable biological activities, such as antimalarial,
anticonvulsant, anesthetic, antioxidant, antibacterial, and antiparasitic proper-
ties.[1–3] In addition, hydropyrimidinones have also attracted much attention in pre-
vious years because of their large is range of biological activities, including as
calcium channel blockers.[4,5] So, synthesis of these compounds is an important topic
in organic chemistry.
Received July 16, 2009.
Address correspondence to Liangce Rong, College of Chemistry and Chemical Engineering,
Xuzhou Normal University, Xuzhou, Jiangsu, China. E-mail: lcrong2005@yahoo.com
3039

3040
Y. DAI ET AL.
Scheme 1. Reaction of aromatic aldehydes, aromatic ketones, and urea.
The Biginelli reaction is one of the most important reactions to synthesize
3,4-dihydropyrimidin-2-(1H)-one in a one-pot reaction of aldehyde, a-ketoester,
and urea. In past years, many methods have been reported to improve this reaction
because of its harsh reaction conditions, such as long reaction times, high tempera-
tures, low yields, expensive catalysts, and harmful and difficult-to-handle reagents,
especially on a large scale.[6] At the same time, many Biginelli-like reactions also have
been reported and many pyridine-like derivatives have been synthetized.[7]
Because it avoids using an organic solvent in the reactions, solvent-free
synthesis is regarded as one of the important methods in current green chemis-
try. Herein, we report a Biginelli-like cyclocondensation reaction to prepare
4,6-diarylpyrimidin-2(1H)-one derivatives from aromatic aldehydes, aromatic
ketones, and urea using NaOH as catalyst under solvent-free conditions (Scheme 1).
The reaction process could be depicted as follows: the aromatic aldehydes 1,
aromatic ketones 2, and urea 3 were put in a mortar to blend together in the presence
Table 1. Synthesis of 4,6-diarylpyrimidin-2(1H)-one
Entry
R1
R2
Product
Yields (%)
1
2
H
H
4-CH3O
3-Cl
4-Cl
4-CH3
H
4a
4b
4c
4d
4e
4f
90
85
91
80
85
88
92
82
86
92
90
88
3
H
4
3,4-(CH3)2
4-CH3
4-F
5
6
H
7
4-Br
2-Cl
H
4g
4h
4i
8
H
9
3-Cl
4-Cl
H
10
11
12
H
4j
2,4-Cl2
3,4-Cl2
H
4k
4l
H

SYNTHESIS OF 4,6-DIARYLPYRIMIDIN-2(1H)-ONE
3041
Figure 1. Structure of compound 4a.
of a small amount of NaOH (0.2 g) as catalyst, and then the mixture was placed into
a round flask and left at 70 ꢀC to react. The reactions could be finished in about
10–15 min and the product, 4,6-diarylpyrimidin-2(1H)-one 4, could be gained with
excellent yields. The results of reactions are listed in Table 1. Previously,[7a]
3,4-dihydropyrimidin-2(1H)-ones 5 has been prepared from the reaction of aromatic
aldehydes, aromatic ketones, and urea using a Lewis acid (FeCl3 ꢁ 6H2O-TMSCl) as
catalyst; however, in our research, we did not find 3,4-dihydropyrimidin-2(1H)-ones
5. Instead, 4,6-diarylpyrimidin-2(1H)-one 4 was obtained with good yields. We think
the different catalysts resulted in the different results of the reaction.
From Table 1, we saw that the all reactions were carried out smoothly, and we
also found that the nature of substitute groups in the aldehydes or ketones has no sig-
1
nificant effect on this reaction. The structures of 4 were characterized by H NMR,
infrared (IR) and high-resolution mass spectrometry (HRMS). In particular, the mea-
sured data of HRMS was in accord with the corresponding calculated data, so the
deduced structures of products were right. The structure of 4a was additionally con-
firmed by x-ray diffraction analysis. The crystal structure of 4a is shown in Fig. 1.
In conclusion, we have successfully developed an efficient and facile method to
prepare a variety of 4,6-diarylpyrimidin-2(1H)-one derivatives via the multicompo-
nent reactions of different aromatic aldehydes, aromatic ketones, and urea under
solvent-free conditions. Because no toxic organic solvent was used and the basic
catalyst (NaOH) was employed, this method presents an efficient and facile route
for the synthesis of these compounds.
EXPERIMENTAL
Melting points were uncorrected. IR spectra were recorded on a Tensor 27 spec-
1
trometer in KBr. H NMR spectra were obtained in dimethylsulfoxide (DMSO-d6)
solution with Me4Si as internal standard using a Bruker-400 spectrometer. HRMS
spectra were obtained with a Bruker micrOTOF-Q 134 instrument. X-ray diffractions
were recorded on a Siemens P4 or Simart-1000 diffractometer.

3042
Y. DAI ET AL.
General Procedure for the Syntheses of 4,6-Diarylpyrimidin-2
(1H)-one Derivatives
Aromatic aldehyde 1 (2 mmol), aromatic ketone 2 (2 mmol), urea 3 (3 mmol), and
NaOH (0.2 g) were added to a mortar. The mixture was blended together and then shifted
into a round flask. The reagent was heated about 70 ꢀC under atmospheric conditions,
and the reaction could be finished within 10–15 min. The reaction mixture was poured
into water, and the product was filtered, dried, and recrystallized from 95% ethanol.
Data
6-(4-Methoxyphenyl)-4-phenylpyrimidin-2(1H)-one (4a). Mp 252–253 ꢀC;
IR (KBr, n, cmꢂ1): 3279, 3095, 2998, 2834, 1618, 1514, 1459, 1420, 1394, 1339, 1262,
1174, 1038, 991, 821, 776 cmꢂ1; 1H NMR (400 MHz, DMSO-d6) (d, ppm): 3.86 (3H,
s, OCH3), 7.10 (2H, d, J ¼ 8.8 Hz, ArH), 7.50 (1H, s, C5-H), 7.54–7.59 (3H, m,
ArH,), 8.14–8.19 (4H, m, ArH), 11.96 (1H, s, NH); HRMS m=z calculated for
C17H14N2O2 [M þ H]: 279.1134; found: 279.1144.
6-(3-Chlorophenyl)-4-phenylpyrimidin-2(1H)-one (4b). Mp 219–220 ꢀC;
IR (KBr, n, cmꢂ1): 3305, 3069, 2886, 1625, 1496, 1456, 1398, 1329, 1197, 995, 858,
1
764, 682 cmꢂ1; H NMR (400 MHz, DMSO-d6) (d, ppm): 7.50–7.57 (5H, m, ArH),
7.62–7.65 (1H, m, ArH), 8.18–8.19 (3H, m, ArH), 8.30 (1H, s, C5-H), 12.16 (1H,
s, NH); HRMS m=z calculated for C16H11ClN2O [M þ H]: 283.0638; found:
283.0643.
6-(4-Chlorophenyl)-4-phenylpyrimidin-2(1H)-one (4c). Mp 192–194 ꢀC;
IR (KBr, n, cmꢂ1): 3324, 3060, 1653, 1556, 1489, 1358, 1175, 1091, 1013, 998, 820,
1
700, 694, 648 cmꢂ1; H NMR (400 MHz, DMSO-d6) (d, ppm): 7.20 (1H, s, C5-H),
7.46–7.48 (3H, m, ArH), 7.52 (2H, dd, J ¼ 1.6 Hz, J ¼ 1.6 Hz, ArH), 8.10–8.12
(2H, m, ArH), 8.17 (2H, d, J ¼ 8.0 Hz, ArH), 12.12 (1H, s, NH); HRMS m=z calcu-
lated for C16H11ClN2O [M þ H]: 283.0638; found: 283.0636.
4-(3,4-Dimethylphenyl)-6-p-tolylpyrimidin-2(1H)-one (4d). Mp > 300 ꢀC;
IR (KBr, n, cmꢂ1): 3330, 3100, 2918, 1623, 1538, 1506, 1455, 1418, 1392, 1338,
1250, 1185, 990, 915, 808, 715, 596 cmꢂ1 1H NMR (400 MHz, DMSO-d6) (d,
;
ppm): 2.31 (3H, s, CH3), 2.33 (3H, s, CH3), 2.40 (3H, s, CH3), 7.32 (1H, d,
J ¼ 8.0 Hz, ArH), 7.37 (2H, d, J ¼ 8.0 Hz, ArH), 7.47 (1H, m, ArH), 7.88–7.90
(1H, m, ArH), 7.97 (1H, s, C5-H), 8.06 ꢃ 8.08 (2H, m, ArH), 11.98 (1H, s, NH);
HRMS m=z calculated for C19H18N2O [M þ H]: 291.1497; found: 291.1496.
6-Phenyl-4-p-tolylpyrimidin-2(1H)-one (4e). Mp 271–273 ꢀC (lit.[6e]
287–290 ꢀC); IR (KBr, n, cmꢂ1): 3298, 3097, 3007, 2901, 1616, 1460, 1393, 1339,
1
1183, 994, 919, 809, 774, 689, 596 cmꢂ1; H NMR (400 MHz, DMSO-d6) (d, ppm):
2.41 (3H, s, CH3), 7.37 (2H, d, J ¼ 8.4 Hz, ArH), 7.54–7.60 (4H, m, ArH, C5-H),
8.09 (2H, s, ArH), 8.16 (2H, br, ArH), 12.08 (1H, s, NH); HRMS m=z calculated
for C17H14N2O [M þ H]: 263.1184; found: 263.1192.
4-(4-Fluorophenyl)-6-phenylpyrimidin-2(1H)-one (4f). Mp 159–161 ꢀC; IR
(KBr, n, cmꢂ1): 3301, 3059, 2906, 1614, 1557, 1509, 1356, 1231, 1155, 993, 821, 766,
690 cmꢂ1
;
1H NMR (400 MHz, DMSO-d6) (d, ppm): 7.27 (2H, t, J ¼ 8.4 Hz,

SYNTHESIS OF 4,6-DIARYLPYRIMIDIN-2(1H)-ONE
3043
J ¼ 8.4 Hz, ArH), 7.35 (1H, s, C5-H), 7.46–7.47 (3H, m, ArH), 8.15 (2H, d,
J ¼ 4.0 Hz, ArH), 8.23 (2H, dd, J ¼ 6.0 Hz, J ¼ 6.0 Hz, ArH), 11.99 (1H, s, NH);
HRMS m=z calculated for C16H11FN2O [M þ H]: 267.0934; found: 267.0945.
4-(4-Bromophenyl)-6-phenylpyrimidin-2(1H)-one (4g). Mp 255–256 ꢀC
(lit.>[6e] 251–254 ꢀC); IR (KBr, n, cmꢂ1): 3401, 3058, 1647, 1610, 1488, 1447, 1072,
1
1010, 821, 768, 697 cmꢂ1; H NMR (400 MHz, DMSO-d6) (d, ppm): 7.60 (4H, t,
J ¼ 8.0 Hz, J ¼ 8.0 Hz, ArH), 7.66 (1H, d, J ¼ 8.0 Hz, ArH), 7.71 (1H, m, ArH),
8.18 (3H, d, J ¼ 6.8 Hz, ArH), 8.27 (1H, s, C5-H), 12.17 (1H, s, NH); HRMS m=z
calculated for C16H11BrN2O [M þ H]: 327.0133; found: 327.0137.
4-(2-Chlorophenyl)-6-phenylpyrimidin-2(1H)-one (4h). Mp 220–223 ꢀC;
IR (KBr, n, cmꢂ1): 3342, 3030, 2926, 1659, 1577, 1538, 1455, 1396, 1337, 1053,
1
994, 758, 689 cmꢂ1; H NMR (400 MHz, DMSO-d6) (d, ppm): 7.24 (1H, s, C5-H),
7.54–7.57 (5H, m, ArH), 7.64 (2H, d, J ¼ 7.2 Hz, ArH), 8.14 (2H, d, J ¼ 7.2 Hz,
ArH), 12.24 (1H, s, NH); HRMS m=z calculated for C16H11ClN2O [M þ H]:
283.0638; found: 283.0643.
4-(3-Chlorophenyl)-6-phenylpyrimidin-2(1H)-one (4i). Mp 210–212 ꢀC;
IR (KBr, n, cmꢂ1): 3214, 3078, 2888, 1625, 1576, 1497, 1339, 1330, 1198, 995, 765,
1
683, 593 cmꢂ1; H NMR (400 MHz, DMSO-d6) (d, ppm): 7.56–7.62 (4H, m, ArH),
7.66 (2H, d, J ¼ 8.0 Hz, ArH), 8.20 (3H, s, ArH), 8.30 (1H, s, C5-H), 12.17 (1H, s,
NH); HRMS m=z calculated for C16H11ClN2O [M þ H]: 283.0638; found: 283.0645.
4-(4-Chlorophenyl)-6-phenylpyrimidin-2(1H)-one (4j). Mp 242–244 ꢀC
(lit.[6e] 258–260 ꢀC); IR (KBr, n, cmꢂ1): 3311, 3105, 3059, 2900, 1614, 1538, 1438,
1337, 1178, 1090, 994, 821, 764, 685 cmꢂ1 1H NMR (400 MHz, DMSO-d6) (d,
;
ppm): 7.37 (1H, s, C5-H), 7.47–7.48 (3H, m, ArH), 7.51 (2H, d, J ¼ 8.0 Hz, ArH),
8.14 (2H, d, J ¼ 8.4 Hz, ArH), 8.20 (2H, d, J ¼ 8.4 Hz, ArH), 12.18 (1H, s, NH);
HRMS m=z calculated for C16H11ClN2O [M þ H]: 283.0638; found: 283.0644.
4-(2,4-Dichlorophenyl)-6-phenylpyrimidin-2(1H)-one (4k). Mp 223–
225 ꢀC; IR (KBr, n, cmꢂ1): 3315, 3027, 2932, 1664, 1587, 1448, 1393, 1142, 1098,
1
995, 777, 689 cmꢂ1; H NMR (400 MHz, DMSO-d6) (d, ppm): 7.55–7.69 (6H, m,
ArH), 7.85 (1H, s, C5-H), 8.12–8.13 (2H, br, ArH), 12.26 (1H, s, NH); HRMS
m=z calculated for C16H10Cl2N2O [M þ H]: 317.0248; found: 317.0248.
4-(3,4-Dichlorophenyl)-6-phenylpyrimidin-2(1H)-one (4l). Mp > 290 ꢀC;
IR (KBr, n, cmꢂ1): 3280, 3094, 2893, 1616, 1578, 1536, 1497, 1475, 1442, 1398,
1331, 1269, 1229, 1202, 1163, 1133, 1097, 1026, 997, 909, 855, 832, 767, 684, 645,
1
595 cmꢂ1; H NMR (400 MHz, DMSO-d6) (d, ppm): 7.56–7.59 (3H, m, ArH), 7.80
(1H, s, C5-H), 7.84 (1H, d, J ¼ 8.8 Hz, ArH), 8.19–8.24 (3H, m, ArH), 8.51 (1H,
d, J ¼ 2.0 Hz, ArH), 12.16 (1H, s, NH); HRMS m=z calculated for C16H10Cl2N2O
[M þ H]: 317.0248; found: 317.0243.
X-ray crystallography for 4a. Empirical formula C17H14N2O2, Fw ¼ 278.30,
˚
˚
T ¼ 298(2) K, orthorhombic, a ¼ 7.3081 (17) A, b ¼ 13.462 (3) A, c ¼ 27.986 (7)
3
3
ꢀ
ꢀ
ꢀ
˚
˚
A, a ¼ 90 , b ¼ 90 , c ¼ 90 , V ¼ 2753.2 (11) A , Z ¼ 8, Dc ¼ 1.343 Mg=m , k
ꢂ1
(MoKa) ¼ 0.71073 A, m ¼ 0.090 mm , F(000) ¼ 1168. 1.46ꢀ < h < 25.01ꢀ,ꢂR3 ¼ 0.0671,
˚
˚
wR ¼ 0.2225, S ¼ 1.034, largest diff. peak and hole: 0.633 and ꢂ0.345 e A
.

3044
Y. DAI ET AL.
ACKNOWLEDGMENTS
We thank the Natural Science Foundation of Jiangsu Education Department
(No. 08KJB150017) and the Foundation of Xuzhou Normal University (No.
10XLS02) for financial support.
REFERENCES
1. Morita, H.; Sato, Y.; Chang, K.-L.; Choo, C. Y.; Itokawa, H.; Takeya, K.; Kobayashi, J.
Samoquasine A, a benzoquinazoline alkaloid from the seeds of Annona squamosa. J. Nat.
Prod. 2000, 63, 1707–1708.
2. Rosowsky, A.; Huang, P. C.; Papathanasopoulos, N.; Modest, E. J. Quinazolines, 12:
1,3-Diaminobenzo[f]quinazolines containing long-chain alkyl or chloro substituents on
the central ring: Synthesis and biological evaluation as candidate antifolate and antimalar-
ial agents. J. Med. Chem. 1974, 17, 1217–222.
3. Godde, F.; Toulme, J. J.; Moreau, S. Benzoquinazoline derivatives as substitutes for thy-
mine in nucleic acid complexes: Use of fluorescence emission of benzo[g]quinazoline-2,4-(1-
H,3H)-dione in probing duplex and triplex formation. Biochemistry 1998, 37, 13765–13775.
4. Ballard, P.; Bradbury, R. H.; Hennequin, L. F. A.; Hickinson, M.; Johnson, P. D.; Kettle,
J. G.; Klinowska, T.; Morgentin, R.; Ogilvie, D. J.; Olivier, A. 5-Substituted
4-anilinoquinazolines as potent, selective, and orally active inhibitors of erbB2 receptor
tyrosine kinase. Bioorg. Med. Chem. Lett. 2005, 15, 4226–4229.
5. Pendergast, W.; Dickerson, S. H.; Johnson, J. V.; Dev, I. K.; Ferone, R.; Duch, D. S.;
Smith, G. K. Benzoquinazoline inhibitors of thymidylate synthase: Enzyme inhibitory
activity and cytotoxicity of some sulfonamidobenzoylglutamate and related derivatives.
J. Med. Chem. 1993, 36, 3464–3471.
6. (a) Singh, K.; Singh, J.; Deb, P. K.; Singh, H. An expedient protocol of the Biginelli dihy-
dropyrimidine synthesis using carbonyl equivalents. Tetrahedron 1999, 55, 12873–12880;
(b) Shaabani, A.; Bazgir, A.; Teimouri, F. Ammonium chloride–catalyzed one-pot syn-
thesis of 3,4-dihydropyrimidin-2-(1H)-ones under solvent-free conditions. Tetrahedron
Lett. 2003, 44, 857–859; (c) Mabry, J.; Ganem, B. Studies on the Biginelli reaction: A mild
and selective route to 3,4-dihydropyrimidin-2(1H)-ones via enamine intermediates.
Tetrahedron 2006, 47, 55–56; (d) Wang, X. C.; Quan, Z. G.; Wang, F.; Wang, M. G.;
Zhang, Z.; Li, Z. PEG-SO3H as catalyst for 3,4-dihydropyrimidones via Biginelli reaction
under microwave and solvent-free condition. Synth. Commun. 2006, 36, 451–456; (e)
Heravi, M. M.; Ranjbar, L.; Derikvand, F.; Alimadadi, B. Three-component one-pot syn-
thesis of 4,6-diarylpyrimidin-2(1H)-ones under solvent-free conditions in the presence of
sulfamic acid as a green and reusable catalyst. Mol. Divers. 2008, 12, 191–196.
7. (a) Wang, Z. T.; Xu, L. W.; Xia, C. G.; Wang, H. Q. Novel Biginelli-like three-component
cyclocondensation reaction: Efficient synthesis of 5-unsubstituted 3,4-dihydropyrimidin-
2(1H)-ones. Tetrahedron Lett. 2004, 45, 7951–7953; (b) Wang, L. M.; Sheng, J.; Zhang,
L.; Han, J. W.; Fan, Z. Y.; Tian, H.; Qian, C. T. Facile Yb(OTf)3 promoted one-pot syn-
thesis of polyhydroquinoline derivatives through Hantzsch reaction. Tetrahedron 2005, 61,
1539–1543; (c) Yarım, M.; Sarac, S.; Kılıc, F. S.; Erol, K. Synthesis and in vitro calcium
antagonist activity of 4-aryl-7,7-dimethyl=1,7,7-trimethyl-1,2,3,4,5,6,7,8-octahydroquina-
zoline-2,5-dione derivatives. Farmaco 2003, 58, 17–24; (d) Abelman, M. M.; Smith, St
C.; Jamesa, D. R. Cyclic ketones and substituted-keto acids as alternative substrates for
novel Biginelli-like scaffold syntheses. Tetrahedron Lett. 2003, 44, 4559–4562.