A novel and efficient one-pot method to Biginelli-like scaffolds

Article abstract of DOI:10.1007/BF03245888

A novel and efficient one-pot method for the preparation of fused ring 3,4-dihydropyrimidin-2(1H)-ones and thiones from cyclocondensation of aldehydes, cyclic ketones and urea or thiourea using a catalytic amount of cupric chloride under mild conditions reaction is described. This new method has the advantage to give high yields, to be completed in short reaction times and simple product isolation procedure.

Full text of DOI:10.1007/BF03245888

J. Iran. Chem. Soc., Vol. 7, No. 1, March 2010, pp. 269-274.
JOURNAL OF THE
Iranian
Chemical Society
A Novel and Efficient One-Pot Method to Biginelli-Like Scaffolds
M. Mirza-Aghayan*, A. Moradi and M. Bolourtchian
Chemistry and Chemical Engineering Research Center of Iran (CCERCI), P. O. BOX 14335-186, Tehran, Iran
(Received 14 February 2009, Accepted 15 May 2009)
A novel and efficient one-pot method for the preparation of fused ring 3,4-dihydropyrimidin-2(1H)-ones and thiones from
cyclocondensation of aldehydes, cyclic ketones and urea or thiourea using a catalytic amount of cupric chloride under mild
conditions reaction is described. This new method has the advantage to give high yields, to be completed in short reaction times
and simple product isolation procedure.
Keywords: Biginelli-like scaffold, Fused ring, 3,4-Dihydropyrimidin-2(1H)-ones, Thiones, Cupric chloride
INTRODUCTION
compound building blocks [8], including the use of ꢁ-keto
carboxylic acid [9], cycloalkanones [10] cyclic ketones and
substituted ꢀ-keto acids [11], or acyclic and cyclic ketones
[12]. For example, Abelman et al. [11a] described the HCl-
catalyzed synthesis of Biginelli-like scaffolds by the
condensation of cyclic ketones, urea, and aldehydes under
refluxing ethanol for 24 h.
In this connection, we have envisioned the use of cyclic
ketones instead of ꢁ-ketoester to prepare corresponding
Biginelli-like scaffolds. In continuation of our investigations
in the Biginelli reaction [13], herein we describe a simple and
efficient method for the novel Biginelli-like scaffolds three-
component cyclocondensation reactions of aldehydes, cyclic
ketones and urea or thiourea for the synthesis of fused ring
3,4-dihydropyrimidin-2(1H)-one and thione derivatives using
CuCl2 as catalyst under mild conditions.
The first reported synthesis of 3,4-dihydropyrimidin-
2(1H)-ones using a multicomponent reaction milieu was
described by Biginelli in 1893 [1]. This reaction was reported
over one century ago, and yet considerable interest in this
transformation has steadily increased [2]. Dihydro-
pyrimidinones derivatives have attracted great attention
recently in synthetic organic chemistry due to their
pharmacological and therapeutic properties such as the
antibacterial, antiviral, antitumor, anti-inflammatory [3] and
antihypertensive activity as well as calcium channel blockers
[4], ꢀ-1a-antagonists [5], and neuropeptide
antagonists [6].
Y (NPY)
The classical Biginelli reaction involves one-pot
condensation of an aldehyde, a ꢁ-ketoester and urea under
strongly acidic conditions. In recent years, interest in this
reaction has increased rapidly and several modified procedures
aimed at improving the efficiency of the Biginelli
dihydropyrimidine synthesis have been reported [7]. Biginelli
reaction was enlarged by the variation of the 1,3-dicarbonyl
EXPERIMENTAL
Melting points were determined in evacuated capillaries
with
a Buchi B-545 apparatus. GC/MS analysis was
performed on a FISON GC 8000 series TRIO 1000 gas
chromatograph equipped with a capillary column CP Sil.5 CB,
*Corresponding author. E-mail: m.mirzaaghayan@ccerci.ac.ir

Mirza-Aghayan et al.
1
60 M ꢂ 0.25 mm Id. H NMR spectra were recorded on a
Bruker 500 spectrometer using TMS as internal standard.
Infrared (IR) spectra were recorded from KBr disks with a
Bruker Vector 22 FT-IR spectrometer. Elemental analyses
were performed on a ThermoFinigan Flash EA 1112 series
elemental analyzer.
Hz, 1H, CH), 7.14-7.17 (m, 1H, CH arom.), 7.19 (br, s, 1H,
NH), 7.25-7.39 (m, 7H, CH arom.), 7.62 (d, J = 7.5 Hz, 1H,
CH arom.), 9.34 (s, 1H, NH); MS: m/z (%) 261 (50) (M+), 243
(3), 231 (4), 216 (17), 185 (100), 115 (22), 89 (7), 77 (28); IR
(KBr): ꢃ 3402, 3329, 3205, 3088, 2999, 2958, 2366, 1678,
1460, 1355, 773, 744 cm-1; Anal. Calcd. for C17H14N2O: C,
77.84; H, 5.38; N, 10.68%, Found: C, 77.46; H, 5.38; N,
10.60%.
Typical Procedure for Fused Ring 3,4-Dihydro-
pyrimidin-2(1H)-ones and Thiones Derivatives
To a solution of aldehyde 1-5 (2 mmol) and urea or
thiourea (3 mmol) in CH3CN (10 ml) was added cupric
chloride (10 mol%), TMSCl (2 mmol) and ꢀ-tetralone or 1-
indanone (2 mmol). The reaction mixture was heated at reflux
of solvent for 8 h. After the completion of the reaction, the
mixture was poured into crushed ice and after stirring, it was
directly filtrated through a sintered funnel and washed by
ethylacetate-hexane (1:3). For further purification, the product
was purified by recrystallization from ethanol. Spectroscopic
data for the compounds 6-12a-b:
Compound 6a [11a, b, 13b] (entry 1, Table 2). m.p.: 275-
277 °C; 1H NMR (DMSO-d6, 500 MHz): ꢁ 1.77 (m, 1H, CH2),
2.13 (m, 1H, CH2), 2.58 (m, 1H, CH2), 2.71 (m, 1H, CH2),
4.93 (s, 1H, CH), 7.14-7.38 (m, 9H, 8CH arom. and NH), 7.58
(d, J = 7.3 Hz, 1H, CH arom.), 8.53 (s, 1H, NH); MS: m/z (%)
276 (45) (M+), 260 (3), 248 (5), 232 (11), 199 (100), 181 (11),
114 (21), 89 (10), 77 (27); IR (KBr): ꢃ 3331, 3232, 3088,
2939, 2362, 1681, 1487, 1429, 1340, 1290, 763 cm-1; Anal.
Calcd. for C18H16N2O: C, 78.24; H, 5.84; N, 10.14%, Found:
C, 77.47; H, 5.82; N, 10.05%.
Compound 8a [13b] (entry 4, Table 2). m.p.: 219-221°C;
1H NMR (DMSO-d6, 500 MHz): ꢁ 1.76 (m, 1H, CH2), 2.17
(m, 1H, CH2), 2.59 (m, 1H, CH2), 2.73 (m, 1H, CH2), 5.14 (s,
1H, CH), 7.15-7.23 (m, 3H, CH arom.), 7.43 (s, 1H, NH),
7.60-7.62 (m, 3H, CH arom.), 8.25 (d, J = 8.7 Hz, 2H, CH
arom.), 8.67 (s, 1H, NH). MS: m/z (%) 321 (31) (M+), 320
(12), 274 (14), 305 (3), 293 (4), 277 (5), 199 (100), 181 (18),
115 (33), 89 (9), 76 (6); IR (KBr): ꢃ 3404, 3334, 3242, 3107,
2927, 2360, 1670, 1598, 1517, 1467, 1344, 1269, 826, 812,
763, 731 cm-1; Anal. Calcd. for C18H15N3O3: C, 67.28; H,
4.71; N, 13.08%, Found: C, 67.19; H, 4.55; N, 12.80%.
Compound 8b (entry 5, Table 2) firstly reported. m.p.:
1
199-200 °C; H NMR (DMSO-d6, 500 MHz): ꢁ 1.85 (m, 1H,
CH2), 2.24 (m, 1H, CH2), 2.62 (m, 1H, CH2), 2.75 (m, 1H,
CH2), 5.22 (s, 1H, CH), 7.17-7.25 (m, 3H, CH arom.), 7.61 (d,
J = 8.6 Hz, 2H, CH arom.), 7.75 (d, J = 6.9 Hz, 1H, CH
arom.), 8.28 (d, J = 8.6 Hz, 2H, CH arom.), 9.30 (s, 1H, NH),
9.92 (s, 1H, NH); MS: m/z (%) 337 (57) (M+), 336 (18), 305
(7), 290 (7), 215 (100), 127 (24), 115 (22), 76 (15); IR (KBr):
ꢃ 3186, 2972, 2935, 2366, 1674, 1566, 1500, 1346, 1195,
1018, 856, 815, 765, 734 cm-1.
Compound 6b (entry 2, Table 2) firstly reported. m.p.:
245-246 °C; H NMR (DMSO-d6, 500 MHz): ꢄ 1.86 (m, 1H,
Compound 9a [12a] (entry 6, Table 2) firstly reported.
m.p.: 229-231 °C; 1H NMR (DMSO-d6, 500 MHz): ꢁ 1.76 (m,
1H, CH2), 2.12 (m, 1H, CH2), 2.59 (m, 1H, CH2), 2.71 (m, 1H,
CH2), 4.97 (s, 1H, CH), 7.14-7.28 (m, 3H, CH arom.), 7.31 (s,
1H, NH), 7.35 (d, J = 8.4 Hz, 2H, CH arom.), 7.42 (d, J = 8.4
Hz, 2H, CH arom.), 7.58-7.64 (m, 1H, CH arom.), 8.59 (s, 1H,
NH); MS: m/z (%) 312 (6) (M+2)+, 310 (35) (M+), 309 (50),
307 (17), 294 (3), 281 (7), 266 (5), 251 (3), 199 (100), 181
(12), 115 (20), 89 (15), 77 (10); IR (KBr): ꢃ 3336, 3232, 3088,
2935, 2364, 1670, 1641, 1485, 1429, 1369, 1321, 1286, 769,
732 cm-1; Anal. Calcd. for C18H15ClN2O: C, 69.57; H, 4.86; N,
9.01%, Found: C, 68.96; H, 4.67; N, 9.08%.
1
CH2), 2.06 (m, 1H, CH2), 2.60 (m, 1H, CH2), 2.74 (m, 1H,
CH2), 4.98 (s, 1H, CH), 7.16-7.25 (m, 3H, CH arom.), 7.30-
7.41 (m, 5H, CH arom.), 7.71 (d, J = 7.4 Hz, 1H, CH arom.),
9.07 (s, 1H, NH), 9.68 (s, 1H, NH); MS: m/z (%) 292 (98)
(M+), 259 (22), 215 (100), 127 (60), 114 (36), 77 (26); IR
(KBr): ꢃ 3379, 3161, 2968, 2362, 1672, 1564, 1500, 1452,
1197, 1136, 823, 767, 734, 700 cm-1; Anal. Calcd. for
C18H16N2S: C, 73.94; H, 5.52; N, 9.58%, Found: C, 70.23; H,
5.33; N, 10.01%.
Compound 7a [11a, 13b] (entry 3, Table 2). m.p.: 276-
1
278 °C; H NMR (DMSO-d6, 500 MHz): ꢁ 2.80 (d, J = 22.6
Compound 9b (entry 7, Table 2) firstly reported. m.p.:
Hz, 1H, CH2), 3.27 (d, J = 22.7 Hz, 1H, CH2), 5.46 (d, J = 0.7
252-254 °C; 1H NMR (DMSO-d6, 500 MHz): ꢁ 1.85 (m, 1H,
270

A novel and Efficient One-Pot Method to Biginelli-Like Scaffolds
CH2), 2.19 (m, 1H, CH2), 2.62 (m, 1H, CH2), 2.74 (m, 1H,
Calcd. for C18H15BrN2S: C, 58.23; H, 4.07; N, 7.54%, Found:
CH2), 5.01 (d, J = 2.1 Hz, 1H, CH), 7.16-7.25 (m, 3H, CH
arom.), 7.35 (d, J = 8.4 Hz, 2H, CH arom.), 7.45 (d, J = 8.4
Hz, 2H, CH arom.), 7.71 (d, J = 7.4 Hz, 1H, CH arom.), 9.09
(s, 1H, NH), 9.73 (s, 1H, NH); MS: m/z (%) 328 (67) (M+2)+,
326 (100) (M+), 293 (14), 266 (27), 230 (28), 215 (98), 181
(22), 127 (38), 115 (32), 89 (73), 77 (33); IR (KBr): ꢃ 3194,
2987, 2935, 2875, 2825, 2360, 1647, 1500, 1400, 1292, 1192,
1138, 1085, 1014, 815, 773, 736 cm-1; Anal. Calcd. for
C18H15ClN2S: C, 66.15; H, 4.63; N, 8.57%, Found: C, 64.21;
H, 4.61; N, 8.56%.
C, 56.46; H, 4.11; N, 7.57%.
Compound 12b (entry 11, Table 2) firstly reported.
m.p.: 215-217 °C; 1H NMR (DMSO-d6, 500 MHz): ꢁ 1.85 (m,
1H, CH2), 2.17 (m, 1H, CH2), 2.29 (s, 3H, CH3), 2.60 (m, 1H,
CH2), 2.72 (m, 1H, CH2), 4.92 (s, 1H, CH), 7.16-7.24 (m, 7H,
CH arom.), 7.69 (d, J = 7.4 Hz, 1H, CH arom.), 9.02 (s, 1H,
NH), 9.64 (s, 1H, NH); MS: m/z (%) 306 (65) (M+), 305 (54),
303 (12), 273 (16), 246 (18), 215 (100), 127 (47), 115 (63), 91
(82), 78 (28); IR (KBr): ꢃ 3197, 2983, 2931, 2362, 1674,
1567, 1483, 1292, 1188, 1136, 815, 765, 734 cm-1; Anal.
Calcd. for C19H18N2S: C, 74.47; H, 5.92; N, 9.14%, Found: C,
70.75; H, 5.75; N, 9.57%.
Compound 10b (entry 8, Table 2) firstly reported. m.p.:
1
223-225 °C; H NMR (DMSO-d6, 500 MHz): ꢁ 2.92 (d, J =
23.0 Hz, 1H, CH2), 3.34 (d, J = 23.1 Hz, 1H, CH2), 5.54 (s,
1H, CH), 7.20 (t, J = 7.4 Hz, 1H, CH arom.), 7.27-7.32 (m,
3H, CH arom.), 7.38 (d, J = 7.4 Hz, 1H, CH arom.), 7.45 (d, J
= 8.3 Hz, 2H, CH arom.), 7.85 (d, J = 7.6 Hz, 1H, CH arom.),
9.02 (s, 1H, NH), 10.80 (s, 1H, NH); MS: m/z (%) 312 (85)
(M+), 310 (47), 279 (13), 251 (35), 201 (100), 114 (39), 75
(51); IR (KBr): ꢃ 3396, 3138, 2962, 2358, 1911, 1797, 1660,
1500, 1483, 1458, 1396, 1184, 1089, 1006, 831, 759, 709
cm-1; Anal. Calcd. for C17H13ClN2S: C, 65.27; H, 4.19; N,
8.96%, Found: C, 64.42; H, 4.04; N, 8.82%.
RESULTS AND DISCUSSION
At earlier stage of our work, an equimolar quantity of 4-
nitrobenzaldehyde and ꢀ-tetralone, 1.5 equimolar of urea in
acetonitrile were mixed and heated under reflux of solvent for
10 h by examining different catalysts (Scheme 1). Many
catalysts such as HCl, CuCl, CuCl2, I2 and Pd(OAc)2 were
used to explore the reaction. After 10 h, the crude products
poured into crushed ice after stirring were directly filtrated
through a sintered funnel and washed by ethylacetate-hexane
(1:3). For further purification, the product was recrystallized
from ethanol. The results are presented in Table 1 which
shows that CuCl2 and I2 were the best among tested catalysts,
but the yields were not so high.
To bypass this difficulty of low yield in the next step we
used trimethylchlorosilane (TMSCl) for activation of used
ketone. As previously, to a stirred mixture of 4-nitro-
benzaldehyde, ꢀ-tetralone, urea and a different catalyst in
acetonitrile, an amount of TMSCl (1 equimolar) was added.
With the TMSCl, the yields were higher and the time of
reaction decreased to 8 h. The results are presented in Table 1.
The addition of TMSCl accelerated the Biginelli-like
reaction and gave good results. Although the role of TMSCl is
not completely clear, it may be explainable in terms of Lewis
acid which activates the carbonyl group and the softness of
this reagent [14]. In the presence of TMSCl the yield increased
from 71 to 95% by using CuCl2 and from 78 to 93% by using
I2 as catalyst (Entry 4 and 5, Table 1). However, the
purification was not very simple by using I2 as a catalyst.
Compound 11a [13b] (entry 9, Table 2). m.p.: 258-260
1
°C; H NMR (DMSO-d6, 500 MHz): ꢁ 1.76 (m, 1H, CH2),
2.11 (m, 1H, CH2), 2.59 (m, 1H, CH2), 2.70 (m, 1H, CH2),
4.95 (s, 1H, CH), 7.14-7.22 (m, 3H, CH arom.), 7.29 (m, 3H,
CH arom. and NH), 7.57-7.59 (m, 3H, CH arom.), 8.58 (s, 1H,
NH); MS: m/z (%) 355 (25) (M+), 353 (27), 340 (3), 327 (4),
312 (4), 199 (100), 181 (12), 115 (21), 89 (9), 76 (6); IR
(KBr): ꢃ 3334, 3221, 3086, 2933, 2362, 1682, 1483, 1286,
769, 731 cm-1; Anal. Calcd. for C18H15BrN2O: C, 60.86; H,
4.26; N, 7.89%, Found: C, 60.48; H, 4.22; N, 7.97%.
Compound 11b (entry 10, Table 2) firstly reported.
m.p.: 249-250 °C; 1H NMR (DMSO-d6, 500 MHz): ꢁ 1.85 (m,
1H, CH2), 2.19 (m, 1H, CH2), 2.62 (m, 1H, CH2), 2.74 (m, 1H,
CH2), 5.00 (d, J = 2.1 Hz, 1H, CH), 7.17-7.25 (m, 3H, CH
arom.), 7.28 (d, J = 8.3 Hz, 2H, CH arom.), 7.59 (d, J = 8.3
Hz, 2H, CH arom.), 7.71 (d, J = 7.2 Hz, 1H, CH arom.), 9.10
(s, 1H, NH), 9.73 (s, 1H, NH); MS: m/z (%) 373 (36) (M+2)+,
371 (37) (M+), 370 (33), 339 (6), 215 (100), 127 (65), 115
(36), 75 (58); IR (KBr): ꢃ 3271, 3192, 2989, 2933, 1674,
1570, 1480, 1292, 1190, 1138, 1010, 831, 771, 738 cm-1; Anal.
271

Mirza-Aghayan et al.
NO2
O
O
O
catalyst
CH3CN
H
NH
+
+
H2N
NH2
O2N
N
H
O
Scheme 1
R
O
R
O
H
X
NH
n
cat., CuCl2
CH3CN
+
+
H2N
NH2
X= O, S
n
N
H
X
1-5
R= H, NO2, Cl, Br, Me
n = 0, 1
6-12 a-b
Scheme 2
Table 1. Effects on the Type of the Catalysts on the Formation
of Fused-Ring Pyrimidin-2(1H)-ones
Based on the above optimized results and in order to
examine the scope of this Biginelli-like scaffolds reaction,
various aromatic aldehydes 1-5 with ꢀ-tetralone or 1-
indanone, urea or thiourea in the presence of TMSCl and 10
mol% of CuCl2 as catalyst were used (Scheme 2). The results
are shown in the Table 2.
In all cases, the three component one-pot reaction
proceeded smoothly to afford the corresponding fused ring
pyrimidin-2(1H)-ones 6-11a derivatives in high yields and the
fused ring pyrimidin-2(1H)-thiones 6-12b derivatives in
moderate yields.
Entry
Catalyst
Free
Amount of catalyst Yield (%)a, b
39 (60)c
1
2
3
4
5
6
HCl
1 ml
44 (48)c
63 (81)c
71 (95)c
78 (93)c
30
CuCl
CuCl2
I2
10 mol%
10 mol%
10 mol%
10 mol%
Pd(OAc)2
aReaction conditions: 4-nitro benzaldehyde (2 mmol), ꢀ-
b
CONCLUSIONS
tetralone (2 mmol), urea (3 mmol), 10 ml CH3CN. Isolated
yield. cThe number in parentheses indicates the isolated yield
of product by using the catalyst in the presence of 2 mmol
TMSCl.
In conclusion, a mild and efficient method is proposed for
the three-component Biginelli-like reactions of aldehyde with
cyclic ketones and urea or thiourea using CuCl2 catalyst and
TMSCl for synthesis of fused ring pyrimidin-2(1H)-ones and
thiones. The inexpensive and ready availability of the catalyst,
the high yields and the simplicity of the procedure render this
methodology advantageous. This new method for the synthesis
of Biginelli-like scaffolds make this fused ring system
Furthermore, in the previous work, we synthesized the product
8a using LiClO4 [13b] and NH4Cl [13b] in 70 and 65% yield,
respectively, using the same conditions. Thus, we can
conclude that CuCl2 is the best catalyst for this reaction.
272

A novel and Efficient One-Pot Method to Biginelli-Like Scaffolds
Table 2. Cupric Chloride Catalyzed Preparation of Fused Ring Pyrimidin-2(1H)-ones and Thiones
Derivatives in the Presence of TMSCla, b
Entry
Aldehyde
Ketone
X
O
S
Products
6a [11a, b, 13b]
6b
Yield (%)c
m.p. (°C)
275-277
245-246
276-278
219-221
199-200
229-231
252-254
223-225
258-260
249-250
215-217
1
C7H6O
ꢀ-Tetralone
ꢀ-Tetralone
1-Indanone
ꢀ-Tetralone
ꢀ-Tetralone
ꢀ-Tetralone
ꢀ-Tetralone
1-Indanone
ꢀ-Tetralone
ꢀ-Tetralone
ꢀ-Tetralone
85
51
84
95
50
91
40
51
95
50
40
2
C7H6O
3
C7H6O
O
O
S
7a [11a, 13b]
8a [13b]
8b
4
4-NO2-C7H5O
4-NO2-C7H5O
4-Cl-C7H5O
4-Cl-C7H5O
4-Cl-C7H5O
4-Br-C7H5O
4-Br-C7H5O
4-Me-C7H5O
5
6
O
S
9a [12a]
9b
7
8
S
10b
9
O
S
11a [13b]
11b
10
11
S
12b
aReaction conditions: aldehyde (2 mmol), ꢀ-tetralone (2 mmol), urea (3 mmol), 10 ml CH3CN, reflux 8 h.
bAll products were characterized by 1H NMR, IR, mass spectra and elemental analysis. cIsolated yields.
accessible for inclusion into pharmacologically important
agents. Further investigations on the synthesis of analog
molecules using new methods are currently in progress.
B.C. O’Reilly, J. Schwartz, M.F. Malley, J. Med.
Chem. 35 (1992) 3254; c) G.J. Grover, S. Dzwonczyk,
D.M. McMullen, D.E. Normandin, C.S. Parham, P.G.
Sleph, S.J. Moreland, Pharmacol. 26 (1995) 289.
REFERENCES
[5]
a) D. Nagarathnam, S.W. Miao, B. Lagu, G. Chiu, J.
Fang, T.G.M. Dhar, J. Zhang, S. Tyagarajan, M.R.
Marzabadi, F.Q. Zhang, W.C. Wong, W.Y. Sun, D.
Tian, J.M. Wetzel, C. Forray, R.S.L. Chang, T.P.
Broten, R.W. Ransom, T.W. Schorn, T.B. Chen, S.
O’Malley, P. Kling, K. Schneck, R. Benedesky, C.M.
Harrel, K.P. Vyas, C. Gluchowski, J. Med. Chem. 42
(1999) 4764; b) T.G. Murali Dhar, D. Nagarathnam,
M.R. Marzabadi, B. Lagu, W.C. Wong, G. Chiu, S.
Tyagarajan, S.W. Miao, F. Zhang, W. Sun, D. Tian, Q.
Shen, J. Zhang, J.M. Wetzel, C. Forray, R.S.L. Chang,
T.P. Broten, T.W. Schorn, T.B. Chen, S. O’Malley, R.
Ransom, K. Sceneck, R. Bendesky, C.M. Harrell, K.P.
Vyas, K. Zhang, J. Gilbert, D.J. Pettibone, M.A. Patane,
M.G. Bock, R.M. Freidinger, C. Gluchowski, J. Med.
[1]
[2]
P. Biginelli, Gazz. Chim. Ital. 23 (1893) 360.
a) C.O. Kappe, Tetrahedron 49 (1993) 6937; b) E.H.
Hu, D.R. Sidler, U.H. Dolling, J. Org. Chem. 63 (1998)
3454; c) Y. Ma, C. Qian, L. Wang, M. Yang, J. Org.
Chem. 65 (2000) 3864; d) K. Ramalinga, P.
Vijayalaximi, T.N.B. Kaimal, Synlett. (2001) 863; e) J.
Lu, Y. Bai, L. Wang, B. Yang, H. Ma, Tetrahedron
Lett. 41 (2000) 9075.
[3]
[4]
C.O. Kappe, Eur. J. Med. Chem. 35 (2000) 1043.
a) K.S. Atwal, B.N. Swanson, S.E. Unger, D.M. Floyd,
S. Moreland, A. Hedberg, B.C. O’Reilly, J. Med.
Chem. 34 (1991) 806; b) G.C. Rovnyak, K.S. Atwal, A.
Hedberg, S.D. Kimball, S. Moreland, J.Z. Gougoutus,
273

Mirza-Aghayan et al.
Chem. 42 (1999) 4778.
M.A. Bruce, G.S. Pointdexter, G. Johnson, US
5,889,016, (1999).
a) J. Lu, H.R. Ma, Synlett. (2000) 63; b) F. Bigi, S.
Carloni, B. Frunllanti, R. Maggi, G. Sartori,
Tetrahedron Lett. 40 (1999) 3465; c) V.R. Choudhary,
V.H. Tillu, V.S Narkhede, H.B. Borate, R.D.
Wakharkar, Catal. Commun. 4 (2003) 449.
Z. Hassani, M.R. Islami, M. Kalantari, Bio. Org. Med.
Chem. Lett. 16 (2006) 4479.
Dominguez, D. Bernardi, G. Kirsch, Tetrahedron Lett.
48 (2007) 5777.
[6]
[7]
[12] a) Z.T. Wang, L.W. Xu, C.G. Xia, H.Q. Wang,
Tetrahedron Lett. 45 (2004) 7951; b) Z.T. Wang, L.W.
Xu, C.G. Xia, H.Q. Wang, Tetrahedron Lett. 47 (2006)
1361; c) G. Sabitha, K.B. Reddy, R. Srinivas, J.S.
Yadav, Helv. Chim. Acta 88 (2005) 2996; d) B. Liang,
X. Wang, J.-X. Wang, Z. Du, Tetrahedron 63 (2007)
1981.
[13] a) M. Mirza-Aghayan, M. Bolourtchian, M. Hoseini,
Synth. Commun. 34 (2004) 3335; b) M. Mirza-
Aghayan, A. Moradi, M. Bolourtchian, R.
Boukherroub, Synth. Commun. 40 (2010) 8.
[14] a) P.H. Lee, H.A.K. Lee, S. Sung, S. Kim, Tetrahedron
Lett. 42 (2001) 37; b) T. Ito, Y. Ishino, T. Mizuno, A.
Iswkawa, J. Kobayashi, Synlett (2002) 2116; c) M.
Bandini, M. Fagioli, A. Melloni, A. Umani-Ronchi,
Synthesis (2003) 397.
[8]
[9]
J. Bussolari, P.A. McDonnell, J. Org. Chem. 65 (2000)
6777.
[10] Y.L. Zhu, S.L. Huang, Y.J. Pan, Eur. J. Org. Chem.
(2005) 2354.
[11] a) M.M. Abelman, S.C. Smith, D.R. James,
Tetrahedron Lett. 44 (2003) 4559; b) J. Azizian, A.A.
Mohammadi, A.R. Karimi, M.R. Mohammadizadeh,
Appl. Catal. A-Gen. 300 (2006) 85; c) J.C. Rodriguez-
274