Three-component one-pot synthesis of unsymmetrical 1,4-dihydropyridine derivatives in aqueous media

Article abstract of DOI:10.3184/030823408X339791

A series of methyl ethyl 2,6-dimethyl-4-substituted-1,4-dihydropyridine-3, 5-dicarboxylates were synthesised by the three-component reaction of aldehydes, ethyl acetoacetate and methyl β-aminocrotonate in the presence of triethylbenzylammonium chloride (T

Full text of DOI:10.3184/030823408X339791

JOURNAL OF CHEMICAL RESEARCH 2008
AUGUST, 441–443
RESEARCH PAPER 441
Three-component one-pot synthesis of unsymmetrical
1,4-dihydropyridine derivatives in aqueous media
Da-Qing Shi,a,b* Chen-Xia Yub and Qi-Ya Zhuangb
aCollege of Chemistry and Chemical Engineering, Key Laboratory of Organic Synthesis of Jiangsu Province, Suzhou University,
Suzhou 215123, P.R. China
bCollege of Chemistry and Chemical Engineering, Xuzhou Normal University, Xuzhou 221116, P.R. China
A series of methyl ethyl 2,6-dimethyl-4-substituted-1,4-dihydropyridine-3,5-dicarboxylates were synthesised by
the three-component reaction of aldehydes, ethyl acetoacetate and methyl E-aminocrotonate in the presence of
triethylbenzylammonium chloride (TEBAC) in aqueous medium. This method has the advantage of good yields.
Keywords: unsymmetrical Hantzsch 1,4-dihydropyridines, multi-component reactions, aqueous media
The need to reduce the amount of toxic waste and by-
products arising from chemical processes requires increasing
emphasis on the use of environmentally compatible materials
in the design of new synthetic methods.1-3 One of the most
promising approaches uses water as a reaction medium.4-6
Breslow and Rideout,7,8 who showed that hydrophobic effects
could strongly enhance the rates of several organic reactions,
rediscovered the use of water as a solvent in organic reactions
in the 1980s. In recent years there has been increasing
recognition that water is an attractive medium for many
organic reactions.9-14 The aqueous medium is not expensive,
dangerous or environmentally unfriendly in comparison with
organic solvents. Generally, the low solubility15 of most
reagents in water is not an obstacle to the reactivity, which, on
the contrary, is reduced by the use of co-solvents.
Table 1 The synthesis of unsymmetrical 1,4-DHPs in aqueous
media
Compd
R
Time/h
Yield/%
4a
4b
4c
4d
4e
4f
4-CH3C6H4
4-NO2C6H4
4-FC6H4
15
15
17
16
14
16
17
13
20
24
71
80
70
86
76
76
71
76
56
43
4-ClC6H4
4-CH3OC6H4
4-BrC6H4
3,4-(CH3)2C6H3
3,4-(CH3O)2C6H3
CH3CH2CH2
c-C6H11
4g
4h
4i
4j
irradiation. Wang et al.33,34 reported the one-pot synthesis and
aromatisation of symmetrical 1,4-DHPs in water. Memarian
et al.35 reported the preparation of some new unsymmetrical
substituted 1,4-DHPs, which have ethoxycarbonyl and acetyl
groups on 3- and 5-positions. Khadilkar et al.36 reported
WKHꢀ V\QWKHVLVꢀ RIꢀ +DQW]VFKꢀ HVWHUVꢀ E\ꢀ FRQGHQVLQJꢀ DON\Oꢀ ȕꢃ
aminocrotonate, aldehyde and alkyl acetoacetate in aqueous
sodium butylmonoglycolsulfate as a safe reaction medium
LQꢀ DQꢀ XQPRGL¿HGꢀ GRPHVWLFꢀ PLFURZDYHꢀ RYHQꢂꢀ EXWꢀ RQO\ꢀ RQHꢀ
unsymmetrical 1,4-DHP was prepared in 64% yield. Thus,
WKHꢀGHYHORSPHQWꢀRIꢀDQꢀHI¿FLHQWꢀDQGꢀYHUVDWLOHꢀPHWKRGꢀIRUꢀWKHꢀ
preparation of other unsymmetrical 1,4-DHPs is an active
research area and there is scope for further improvement
toward milder reaction conditions and improved yields. In
the course of our search for green methods of construction
of the 1,4-DHP nucleus, we have reported the synthesis of
symmetrical 1,4-DHPs by one-pot three-component reaction
of aldehyde, ethyl or methyl acetoacetate, and ammonium
acetate catalysed by TEBAC in aqueous media.37 Here we
report the synthesis of unsymmetrical 1,4-DHPs in aqueous
media.
1,4-Dihydropyridines
(1,4-DHPs)
are
well-known
EHFDXVHꢀRIꢀWKHLUꢀSKDUPDFRORJLFDOꢀSUR¿OHꢀDVꢀFDOFLXPꢀFKDQQHOꢀ
modulators.16 Among various cardiovascular 1,4-DHP
calcium channel antagonists,17,18 Darodipine, Nifedipine
and Flordipine are compounds containing symmetrical
structure in their ester functionality at 3- and 5-position;19,20
other drugs such as Amlodipine, Nimodipine, Nicardipine,
Nilvodipine, Falodipine, Isradipine, Reodipine, Nitrendipine,
Lacidipine, Bernidipine, Benidipine, Furaldipine, Manidipine,
Sangandipine, and Toludipine are unsymmetrical, with
different groups in the 3- and 5-positions of the ring.21-23
The usual method for the synthesis of 1,4-DHPs is that of
Hantzsch.24 This reaction involves a one-pot condensation of
an aldehyde with ethyl acetoacetate, and ammonia either in
DFHWLFꢀRUꢀE\ꢀUHÀX[LQJꢀLQꢀDOFRKROꢀIRUꢀDꢀORQJHUꢀWLPHꢁꢀ+RZHYHUꢂꢀ
the yields of 1,4-DHPs obtained by the Hantzsch method are
JHQHUDOO\ꢀORZꢁꢀ(YHQꢀWKRXJKꢀDꢀQXPEHUꢀRIꢀPRGL¿HGꢀPHWKRGV25-31
under improved conditions have been reported, some of them
suffer from drawbacks such as unsatisfactory yields, high
temperature, long reaction times, use of organic solvents,
and environmental unfriendliness. Recently, the preparation
of 1,4-DHPs in water has been reported. Salehi and Guo32
reported the synthesis of substituted symmetrical 1,4-DHPs
in water using phase-transfer catalyst under microwave
Results and discussion
When an aldehyde (1), ethyl acetoacetate (2) and methyl ȕ-
aminocrotonate (3) were stirred for 13-24 h at 90°C in aqueous
R
O
O
TEBAC
NH2
O
OEt
MeO
MeCOCH2CO2Et
RCHO
H2O, 90oC
Me
OMe
Me
Me
N
H
4
1
3
2
Scheme 1 Preparation of unsymmetrical dihydropyridines.
* Correspondent. E-mail: dqshi@263.net

442 JOURNAL OF CHEMICAL RESEARCH 2008
Ethyl methyl 4-(4-methoxyphenyl)-2,6-dimethyl-1,4-dihydro-
pyridine-3,5-dicarboxylate (4e): M.p. 145-146°C (lit.23 m.p. 112–
113 °C: The molecular formula in the literature was stated as
C19H23NO5·0.21EtOAc). IR: Ȟmax 3344, 2991, 2955, 1693, 1651,
1611, 1500, 1377, 1302, 1263, 1212, 1123, 1089, 1024, 901, 835,
749, 683 cm-1. NMR (DMSO-d6ꢊꢎꢀįH 1.13 (3H, t, Jꢀ ꢀꢅꢁꢏꢀ+]ꢂꢀ&+3),
2.24 (6H, s, 2 × CH3), 3.53 (3H, s, CH3O), 3.67 (3H, s, CH3O), 3.97
(2H, q, Jꢀ ꢀꢅꢁꢏꢀ+]ꢂꢀ&+2O), 4.79 (1H, s, CH), 6.76 (2H, d, Jꢀ ꢀꢇꢁꢋꢀ+]ꢂꢀ
ArH), 7.03 (2H, d, J ꢀꢇꢁꢋꢀ+]ꢂꢀ$U+ꢊꢂꢀꢇꢁꢅꢐꢀꢄꢍ+ꢂꢀVꢂꢀ1+ꢊꢁꢀ$QDOꢁꢀFDOFGꢀ
for C19H23NO5: C 66.07, H 6.71, N 4.06; found C 66.25, H 6.53,
N 3.96%.
Ethyl methyl 4-(4-bromophenyl)-2,6-dimethyl-1,4-dihydropyridine-
3,5-dicarboxylate (4f): M.p. 153–155°C. IR: Ȟmax 3361, 2991, 2955,
1699, 1656, 1489, 1373, 1300, 1213, 1104, 1017, 828, 770, 741, 669
cm-1. NMR (DMSO-d6ꢊꢎꢀįH 1.12 (3H, t, Jꢀ ꢀꢈꢁꢇꢀ+]ꢂꢀ&+3), 2.25 (6H,
s, 2 × CH3), 3.53 (3H, s, CH3O), 4.01 (2H, q, Jꢀ ꢀꢈꢁꢇꢀ+]ꢂꢀ&+2O), 4.83
(1H, s, CH), 7.08 (2H, d, Jꢀ ꢀꢇꢁꢇꢀ+]ꢂꢀ$U+ꢊꢂꢀꢅꢁꢑꢇꢀꢄꢏ+ꢂꢀGꢂꢀJꢀ ꢀꢇꢁꢇꢀ+]ꢂꢀ
ArH), 8.85 (1H, s, NH). Anal. calcd for C18H20BrNO4: C 54.84, H
5.11, N 3.55; found C 55.06, H 4.97, N 3.47%.
Ethyl methyl 2,6-dimethyl-4-(3,4-dimethylphenyl)-1,4-dihydro-
pyridine-3,5-dicarboxylate (4g): M.p. 112–113°C. IR: Ȟmax 3361,
2990, 2945, 1698, 1660, 1485, 1373, 1336, 1215, 1162, 1055, 1017,
886, 800, 785, 755, 726, 663 cm-1. NMR (DMSO-d6ꢊꢎꢀįH 1.14 (3H, t,
Jꢀ ꢀꢅꢁꢏꢀ+]ꢂꢀ&+3), 2.11 (3H, s, CH3), 2.13 (3H, s, CH3), 2.24 (6H, s,
2 × CH3), 3.52 (3H, s, CH3O), 3.98 (2H, q, J ꢀꢅꢁꢏꢀ+]ꢂꢀ&+2O), 4.79
(1H, s, CH), 6.80-6.98 (3H, m, ArH), 8.74 (1H, s, NH). Anal. calcd
for C20H25NO4: C 69.95, H 7.34, N 4.08; found C 70.16, H 7.19, N
3.94%.
suspension in the presence of triethylbenzylammonium
chloride (TEBAC), the unsymmetrical 1,4-DHPs – methyl
ethyl
4-substituted
1,4-dihydro-2,6-dimethylpyridine-
3,5-dicarboxylates (4) were obtained in excellent yields
(Scheme 1). The results are summarised in Table 1.
Table 1 shows the results using a series of aromatic
aldehydes and aliphatic aldehydes that undergo the reaction to
JLYHꢀH[FHOOHQWꢀ\LHOGVꢀꢄꢅꢆ±ꢇꢈꢉꢊꢀRIꢀWKHꢀSURGXFWVꢁꢀ7KLVꢀSURFHGXUHꢀ
does not require the use of any organic solvent. In fact the
target compounds (4) were isolated in a practically pure form
E\ꢀVLPSOHꢀ%XFKQHUꢀ¿OWUDWLRQꢀRIꢀWKHꢀ¿QDOꢀDTXHRXVꢀPL[WXUHꢁ
1
All the products were characterised by IR and H NMR
analysis. The IR spectra of compound 4 show the NH stretching
in the region 3360–3325 cm-1, the CO groups at around 1700
cm-1. The 1H NMR spectra of compound 4 show the NH proton
DEVRUSWLRQꢀDVꢀDꢀEURDGꢀVLQJOHWꢀLQꢀWKHꢀUHJLRQꢀįꢀꢇꢁꢅꢋ±ꢌꢁꢆꢍꢀSSPꢁꢀ
The lone proton on C-4 gives a singlet at 4.79–4.97 ppm.
,Qꢀ FRQFOXVLRQꢂꢀ ZHꢀ KDYHꢀ GHYHORSHGꢀ Dꢀ IDFLOHꢀ DQGꢀ HI¿FLHQWꢀ
procedure for the synthesis of methyl ethyl 2,6-dimethyl-
4-substituted-1,4-dihydropyridine-3,5-dicarboxylates
from
aldehyde, ethyl acetoacetate and methyl ȕ-aminocrotonate in
water in the presence of TEBAC. Compared to the classical
synthetic method, this method has the advantages of excellent
yields, inexpensive operation and environmental friendliness.
Ethyl methyl 4-(3,4-dimethoxyphenyl)-2,6-dimethyl-1,4-dihydro-
pyridine-3,5-dicarboxylate (4h): M.p. 135–137°C. IR: Ȟmax 3343,
2989, 2946, 1692, 1650, 1591, 1518, 1483, 1375, 1336, 1302, 1260,
1215, 1129, 1089, 1020, 853, 767, 690 cm-1. NMR (DMSO-d6ꢊꢎꢀįH
1.15 (3H, t, Jꢀ ꢀꢅꢁꢏꢀ+]ꢂꢀ&+3), 2.25 (6H, s, 2 × CH3), 3.55 (3H, s,
CH3O), 3.68 (6H, s, 2 × CH3O), 4.00 (2H, q, Jꢀ ꢀꢅꢁꢏꢀ+]ꢂꢀ&+2O), 4.81
(1H, s, CH), 6.59–6.65 (1H, m, ArH), 6.74 (1H, s, ArH), 6.80 (1H,
d, Jꢀ ꢀꢅꢁꢏꢀ+]ꢂꢀ$U+ꢊꢂꢀꢇꢁꢇꢆꢀꢄꢍ+ꢂꢀVꢂꢀ1+ꢊꢁꢀ$QDOꢁꢀFDOFGꢀIRUꢀ&20H25NO6: C
63.99, H 6.71, N 3.73; found C 64.08, H 6.73, N 3.56%.
Experimental
Melting points were determined on a XT-5 apparatus. IR spectra were
recorded on a Tensor 27 spectrometer; samples in KBr. 1H NMR
spectra were determined on a Bruker DPX 400 MHz spectrometer in
DMSO-d6ꢀVROXWLRQꢁꢀ&KHPLFDOꢀVKLIWVꢀDUHꢀH[SUHVVHGꢀLQꢀSSPꢀGRZQ¿HOGꢀ
from internal TMS. Microanalyses were carried out on Perkin-Elmer
2400 II instruments.
Ethyl methyl 2,6-dimethyl-4-propyl-1,4-dihydropyridine-3,5-di-
carboxylate (4i): M.p. 98–100°C (lit.23 m.p. 95–96°C). IR: Ȟmax 3350,
2950, 1699, 1647, 1495, 1436, 1378, 1324, 1302, 1216, 1140, 1083,
1010, 792, 729 cm-1. NMR (DMSO-d6ꢊꢎꢀįH 0.78 (3H, t, Jꢀ ꢀꢈꢁꢋꢀ+]ꢂꢀ
CH3), 1.14–1.22 (7H, m, CH2CH2CH3), 2.20 (6H, s, 2 × CH3), 3.60
(3H, s, CH3O), 3.77 (1H, t, Jꢀ ꢀꢋꢁꢈꢀ+]ꢂꢀ&+ꢊꢂꢀꢋꢁꢆꢈꢀꢄꢏ+ꢂꢀTꢂꢀJꢀ ꢀꢈꢁꢋꢀ
Hz, CH2O), 8.67 (1H, s, NH). Anal. calcd for C15H23NO4: C 64.03,
H 8.24, N 4.98; found C 64.37, H 8.06, N 5.13%.
Ethyl methyl 4-cyclohexyl-2,6-dimethyl-1,4-dihydropyridine-3,5-
dicarboxylate (4j): M.p. 102–104°C. IR: Ȟmax 3339, 2928, 1694,
1652, 1491, 1383, 1370, 1325, 1298, 1218, 1173, 1096, 1053, 1015,
784, 773, 739 cm-1. NMR (DMSO-d6ꢊꢎꢀįH 0.72–0.85 (2H, m, CH2),
0.98–1.06 (2H, m, CH2), 1.19 (3H, t, Jꢀ ꢀꢅꢁꢏꢀ+]ꢂꢀ&+3), 1.31-1.59
(7H, m, 3 × CH2, CH), 2.21 (6H, s, 2 × CH3), 3.34 (3H, s, CH3O),
3.74 (1H, d, Jꢀ ꢀꢐꢁꢈꢀ+]ꢂꢀ&+ꢊꢂꢀꢋꢁꢆꢍ±ꢋꢁꢍꢆꢀꢄꢏ+ꢂꢀPꢂꢀ&+2O), 8.68 (1H, s,
NH). Anal. calcd for C18H27NO4: C 67.26, H 8.47, N 4.36; found C
67.54, H 8.11, N 4.55%.
All the products described in this paper are racemic.
Synthesis of methyl ethyl 4-substituted-2,6-dimethyl-1,4(R,S)-
dihydropyridine-3,5-dicarboxylates (4): general procedure
A mixture of aldehyde 1 (2 mmol), ethyl acetoacetate (2) (2 mmol),
methyl ȕ-aminocrotonate (3) (2 mmol) and TEBAC (0.15 g) in
water (10 ml) was stirred for 13–17 h at 90°C, then cooled to room
WHPSHUDWXUHꢁꢀ7KHꢀVROLGꢀPDWHULDOꢀIRUPHGꢀZDVꢀFROOHFWHGꢀE\ꢀ¿OWUDWLRQꢂꢀ
washed with water and recrystallised from ethanol to give pure 4.
Ethylmethyl4-(4-methylphenyl)-2,6-dimethyl-1,4-dihydropyridine-
3,5-dicarboxylate (4a): M.p. 128–129°C. IR: Ȟmax 3355, 2990, 2947,
1699, 1652, 1489, 1432, 1377, 1337, 1301, 1215, 1125, 1090, 1052,
1019, 786, 748 cm-1. NMR (DMSO-d6ꢊꢎꢀįH 1.13 (3H, t, J ꢀꢅꢁꢏꢀ+]ꢂꢀ
CH3), 2.20 (3H, s, CH3), 2.24 (6H, s, 2 × CH3), 3.53 (3H, s, CH3O),
3.99 (2H, q, J ꢀꢅꢁꢏꢀ+]ꢂꢀ&+2O), 4.81 (1H, s, CH), 6.90–7.11 (4H,
m, ArH), 8.79 (1H, s, NH). Anal. calcd for C19H23NO4: C, 69.28; H,
7.04; N, 4.25; found C, 69.52; H, 6.93; N, 4.07%.
Ethyl methyl 2,6-dimethyl-4-(4-nitrophenyl)-1,4-dihydropyridine-
3,5-dicarboxylate (4b): M.p. 151–153°C (lit.23 m.p. 151–152°C). IR:
Ȟmax 3325, 2990, 2950, 1704, 1651, 1595, 1520, 1484, 1437, 1382,
1346, 1306, 1260, 1215, 1121, 1090, 1018, 866, 827, 754, 704 cm-1.
NMR (DMSO-d6ꢊꢎꢀįH 1.13 (3H, t, J ꢀꢅꢁꢏꢀ+]ꢂꢀ&+3), 2.27 (6H, s,
2 × CH3), 3.54 (3H, s, CH3O), 3.99 (2H, q, Jꢀ ꢀꢅꢁꢏꢀ+]ꢂꢀ&+2O), 4.97
(1H, s, CH), 7.42 (2H, d, Jꢀ ꢀꢇꢁꢋꢀ+]ꢂꢀ$U+ꢊꢂꢀꢇꢁꢍꢆꢀꢄꢏ+ꢂꢀGꢂꢀJꢀ ꢀꢇꢁꢋꢀ+]ꢂꢀ
ArH), 9.01 (1H, s, NH). Anal. calcd for C18H20N2O6: C 59.99, H
5.59, N 7.77; found C 60.17, H 5.36, N 7.85%.
(WK\OꢀPHWK\OꢀꢁꢂꢃꢁꢂÀXRURSKHQ\OꢄꢂꢅꢆꢇꢂGLPHWK\OꢂꢈꢆꢁꢂGLK\GURS\ULGLQHꢂ
3,5-dicarboxylate (4c): M.p. 122–124°C. IR: Ȟmax 3349, 3070, 2988,
1695, 1653, 1610, 1496, 1378, 1305, 1214, 1125, 1089, 1048, 1018,
849, 753, 680 cm-1. NMR (DMSO-d6): įꢀ1.12 (3H, t, Jꢀ ꢀꢅꢁꢏꢀ+]ꢂꢀ
CH3), 2.25 (6H, s, 2 × CH3), 3.53 (3H, s, CH3O), 3.98 (2H, q,
Jꢀ ꢀꢅꢁꢏꢀ+]ꢂꢀ&+2O), 4.84 (1H, s, CH), 6.99–7.05 (2H, m, ArH), 7.13–
7.17 (2H, m, ArH), 8.84 (1H, s, NH). Anal. calcd for C18H20FNO4:
C 64.85, H 6.05, N 4.20; found C 65.02, H 5.86, N 3.95%.
Ethyl methyl 4-(4-chlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-
3,5-dicarboxylate (4d): M.p. 138–139°C. IR: Ȟmax 3354, 2991, 2955,
1692, 1648, 1489, 1373, 1300, 1213, 1090, 1053, 1017, 843, 785,
741, 690 cm-1. NMR (DMSO-d6ꢊꢎꢀįH 1.12 (3H, t, J ꢀꢅꢁꢏꢀ+]ꢂꢀ&+3),
2.25 (6H, s, 2 × CH3), 3.53 (3H, s, CH3O), 3.99 (2H, q, Jꢀ ꢀꢅꢁꢏꢀ+]ꢂꢀ
CH2O), 4.84 (1H, s, CH), 7.13 (2H, d, Jꢀ ꢀꢇꢁꢋꢀ+]ꢂꢀ$U+ꢊꢂꢀꢅꢁꢏꢅꢀꢄꢏ+ꢂꢀ
d, Jꢀ ꢀꢇꢁꢋꢀ+]ꢂꢀ$U+ꢊꢂꢀꢇꢁꢇꢌꢀꢄꢍ+ꢂꢀVꢂꢀ1+ꢊꢁꢀ$QDOꢁꢀFDOFGꢀIRUꢀ&18H20ClNO4:
C 61.80, H 5.76, N 4.00; found C 61.98, H 5.63, N 3.95%.
We are grateful to the “Surpassing Project” Foundation of
Jiangsu Province and the Foundation of the Key Laboratory
of Biotechnology on Medical Plants of Jiangsu Province for
¿QDQFLDOꢀVXSSRUWꢁ
Received 21 March; accepted 19 June 2008
Paper 08/5170 doi:10.3184/030823408X339791
Published online: 26 August 2008
References
1
2
3
4
J. Amato, Science, 1993, 259, 1538.
D.L. Illman, Chem. Eng. News, 1993, 71, 5.
D.L. Illman, Chem. Eng. News, 1994, 72, 22.
C.J. Li and T.H. Chang, Organic reactions in aqueous media, Wiley,
New York, 1997.
5
F. Fringuelli, O. Piematti, F. Pizzo and L. Vaccaro, Eur. J. Org. Chem.,
2001, 439.
S.C. Stinson, Chem. Eng. News, 1996, 74, 39.
R. Breslow and D.C. Rideout, J. Am. Chem. Soc., 1980, 102, 1816.
R. Breslow, Acc. Chem. Res., 1991, 24, 59.
C.J. Li, Chem. Rev., 1993, 93, 2023.
6
7
8
9
10 R. Ballini and G. Bosica, Tetrahedron Lett., 1996, 37, 8027.
11 R. Ballini, G. Bosica and T. Mecozzi, Tetrahedron, 1997, 53, 1341.
12 A. Meijer, S. Otto and J.B.F.N. Engberts, J. Org. Chem., 1998, 63, 8989.

JOURNAL OF CHEMICAL RESEARCH 2008 443
13 F. Bigi, L. Chesini, R. Maggi and G. Sartori, J. Org. Chem., 1999, 64,
1033.
26 J.G. Breitenbucher and G. Figliozzi, Tetrahedron Lett., 2000, 41, 4311.
27 L. Ohberg and J. Westman, Synlett, 2001, 1296.
28 A.G.J. Anderson and G. Berkelhammer, J. Am. Chem. Soc., 1958, 80, 992.
29 A.P. Phillips, J. Am. Chem. Soc., 1949, 71, 4003.
30 A. Maquestiau, A. Maeyence and J.J. Vanden Eynde, Tetrahedron Lett.,
1991, 32, 3839.
14 F. Bigi, S. Carloni, L. Ferrari, R. Maggi, A. Mazzacani and G. Sartori,
Tetrahedron Lett., 2001, 42, 5203.
15 F. Fringuelli, G. Pani, O. Piermatti and F. Pizzo, Tetrahedron, 1994, 50,
1499.
16 R.A. Janis, P.J. Silver and D.J. Triggle, Adv. Drug. Res., 1987, 16, 30.
17 J.A.M. Christiaans, A.D. Windhorst, P.M. Gronenberg, H. van der Goot
and H. Timmerman, Eur. J. Med. Chem., 1993, 28, 859.
18 J.A.M. Christiaans and H. Timmerman, Eur. J. Pharm. Sci., 1996, 4, 1.
19 R.A. Janis and D.J. Triggle, J. Med. Chem., 1983, 26, 773.
20 J.E. Lawson, Bioorg. Med. Chem. Lett., 1993, 3, 561.
21 M. Mahendra, B.H. Doreswamy, D. Manvar, G. Patel, Y. Naliapara,
A. Shah, S.M. Anandalwar and J.S. Prasad, J. Chem. Res. (S), 2004, 843.
22 A.C. Shah, V.P. Arya and J.B. Sainani, Ind. J. Chem., 1995, 34B, 17.
23 A.M. van Rhee, J. Jiang, N. Melman, M.E. Olah, G.L. Stiles and
K.A. Jacobson, J. Med. Chem., 1996, 39, 2980.
31 G. Sabitha, G.S. Kiran Kumar Reddy, C. Srinivas and J.S. Yadav,
Tetrahedron Lett., 2003, 44, 4129.
32 H. Salehi and Q.X. Guo, Synth. Commun., 2004, 34, 4349.
33 J.J. Xia and G.W. Wang, Synthesis, 2005, 2379.
34 G.W. Wang, J.J. Xia, C.B. Miao and X.L. Wu, Bull. Chem. Soc. Jpn.,
2006, 79, 454.
35 H.R. Memarian, M. Abdoli-Senejani and D. Döpp, Z. Naturforsch., 2006,
61b, 50.
36 B.M. Khadilkar, V.G. Gaikar and A.A. Chitnavis, Tetrahedron Lett., 1995,
36, 8083.
24 A. Hantzsch, Justus Liebigs Ann. Chem., 1882, 215, 1
25 M.F. Gordeev, D.V. Patel and E.M. Gordon, J. Org. Chem., 1996,
61, 924.
37 D.Q. Shi, J. Mou, Q.Y. Zhuang, X.S. Wang and S.J. Tu, Chin. J. Org.
Chem., 2004, 24, 1042.