Three component reactions of N-nucleophiles and activated acetylenes with NH-acids: A facile synthesis in water

Article abstract of DOI:10.1002/jhet.738

A straightforward and efficient method for the synthesis of 1,2-dihydroisoquinolines via a one-pot, three-component reaction of isoquinoline, activated acetylenes, and NH-acids in water at 70°C without using any catalyst is reported. The method offers several advantages including high yields of products and an easy workup procedure..

Full text of DOI:10.1002/jhet.738

154
Three Component Reactions of N-Nucleophiles and Activated
Acetylenes with NH-Acids: A Facile Synthesis in Water
Vol 49
Faramarz Rostami Charati,a Zinatossadat Hossaini,b*
and Mohammad R. Hosseini-Tabatabaeic
aFaculty of Science, Gonbad Higher Education Center, Gonbad, Iran
bDepartment of Chemistry, Islamic Azad University, Qaemshahr Branch, 163 Mazandaran, Iran
cDepartment of Chemistry, Islamic Azad University, Zabol Branch, Zabol, Iran
*E-mail: zshossaini@yahoo.com
Received July 19, 2010
DOI 10.1002/jhet.738
Published online 17 October 2011 in Wiley Online Library (wileyonlinelibrary.com).
A straightforward and efficient method for the synthesis of 1,2-dihydroisoquinolines via a one-pot,
three-component reaction of isoquinoline, activated acetylenes, and NH-acids in water at 70ꢀC without
using any catalyst is reported. The method offers several advantages including high yields of products
and an easy workup procedure.
J. Heterocyclic Chem., 49, 154 (2012).
INTRODUCTION
dihydroisoquinolines 4 via the reaction of isatin 1 with
activated acetylenes 2 and isoquinoline 3 in water at
70ꢀC (Scheme 1).
The organic reactions in aqueous media have attracted
much attention in synthetic organic chemistry, not only
because water is one of the most abundant, cheap, and
environmentally friendly solvents but also because water
exhibits unique reactivity and selectivity properties that
are different from those of conventional organic solvents.
Thus, development of novel reactivity as well as selectiv-
ity that cannot be attained in conventional organic sol-
vents is one of the challenging goals of aqueous chemis-
try. Multicomponent reactions (MCRs) are fast and
appropriate solutions for the synthesis of different classes
of compounds and are important in synthetic organic
chemistry [1–4]. 1,2-Dihydroisoquinolines, as basic scaf-
folds in many natural products and pharmaceuticals that
show significant biological activities [5–11] have pro-
moted considerable efforts toward their synthesis [12–17].
Thus, it is desired to increase novel methods to buildup
the new 1,2-dihydroisoquinoline-based structures. At the
present, it has been expected that chemical reactions in
aqueous solutions frequently give better results than in or-
ganic solvents and often the insolubility of the last prod-
ucts facilitates their isolation [18,19].
RESULT AND DISCUSSION
As indicated in Scheme 1, isatin 1, activated acety-
lenes 2, and isoquinoline 3 undergo a smooth 1:1:1 addi-
tion reaction in water at 70ꢀC (the activated acetylenes
and isatin are mixed first, and then isoquinoline is added)
to produce 1,2-dihydroisoquinolines 4 in 82–96% yields
(Scheme 1). We examined the diversity of reaction with
different substitution as indicated in the Table 1.
Under similar conditions, the reaction of quinoline, pyri-
dine, or phenanthridine with DMAD in the presence of
various NH-acids led to dimethyl 2-[1(2H)-quinolinyl]-2-
butenedioate (7), dimethyl 2-[1(2H)-pyridinyl]-2-butene-
dioate (8), or dimethyl 2-[1(2H)-phenanthridinyl]-2-butene-
dioate (9) in excellent yields (Table 2).
The reactions between isoquinoline, quinoline, pyridine,
or phenanthridine with dimethyl acetylenedicarboxylate
as a Michael acceptor [23–30] in the presence of hetero-
cyclic NH acids were carried out in water and finished
after ꢁ10 h at room temperature. Products 4h–4j and
9a–9e are known compounds [30]. Structures of com-
pounds 4a–4i, 7a–7c, 8a–8c, and 9a–9e were deduced
from their IR, mass, 1H-NMR, and 13C-NMR spectra.
As part of our continuing interest in the development
of new synthetic methods in heterocyclic chemistry and
our interest in isoquinoline-based multicomponent reac-
tions [20–22], we describe an efficient synthesis of 1,2-
C
V
2011 HeteroCorporation

January 2012
Three Component Reactions of N-Nucleophiles and Activated Acetylenes with
NH-Acids: A Facile Synthesis in Water
155
Scheme 1
(2 mmol) was added, and the reaction was heated for 10 h at
70ꢀC. The completion of reaction was confirmed by TLC
(EtOAc–hexane 6:1). The resulting precipitate was separated
by filtration and recrystallized from EtOH to afford the pure
title compounds.
Dimethyl 2-[1-(2,3-dioxo-2,3-dihydro-1H-indol-1-yl)-2(1H)-
isoquinolinyl]-2-butenedioate (4a). Pale yellow powder, mp
162–164ꢀC, yield: 0.74 g (89%). IR(KBr) mmax (cmꢂ1): 1738,
The mass spectra of these compounds displayed molecu-
lar ion peaks at the appropriate m/z values.
The 1H-NMR spectrum of 4a exhibited four singlets
for the methoxy (d 3.88 and 3.94 ppm), olefinic (d 5.39
ppm), and methin (d 7.82 ppm) protons along with mul-
tiplets for the isoquinoline moiety. The proton-decoupled
13C-NMR spectrum of 4a showed 23 distinct resonances
in agreement with the proposed structure. Partial assign-
ments of these resonances are given in Experimental
Section.
1732, 1723, 1692, and 1245 cmꢂ1
.
s, MeO), 3.94 (3 H, s, MeO), 5.39 (1 H, s, CH), 7.54 (1 H, d,
1H-NMR: d ¼ 3.88 (3 H,
3J ¼ 7.6 Hz, CH), 7.69 (2 H, t, 3J ¼ 7.2 Hz, 2 CH), 7.73
3
(2 H, t, J ¼ 7.2 Hz, 2 CH), 7.82 (1 H, s, CH), 7.93 (2 H, d,
Although the mechanistic details of the reaction are
not known, a plausible rationalization may be advanced
to explain the product formation. Presumably, the reac-
tion involves the initial formation of a 1:1 zwitterionic
intermediate 5 between isoquinoline and the activated
acetylene, [31–36]. This intermediate is protonated by
NH-acids and then attacked by the conjugate base of the
NH-acids to produce 4 (Scheme 2).
In conclusion, we have reported an efficient and environ-
mentally friendly approach for the synthesis of 1,2-disubsti-
tuted nitrogen containing heterocycles via condensation of
activated acetylenes and isoquinoline, quinoline, pyridine,
or phenanthridine in the presence of NH-acids using water
as the solvent. To the best of our knowledge, this is the
first report on the synthesis of compounds of type 4, 7, 8,
or 9 in water and this new procedure opens an important
alternative to the use of volatile organic solvents.
3J ¼ 7.5 Hz, 2 CH), 8.69 (2 H, d, J ¼ 7.5 Hz, 2 CH), 9.31
3
3
(1 H, d, J ¼ 7.6 Hz, CH) ppm. 13C-NMR: d ¼ 51.6 (MeO),
52.3 (MeO), 58.8 (CH), 94.6 (CH), 108.2 (CH), 122.4 (CH),
123.5 (2 CH), 124.7 (2 CH), 126.2 (2 CH), 128.4 (CH), 128.5
(C), 128.6 (C), 134.5 (CH), 1365.4 (C), 148.5 (C), 152.7 (C),
159.7 (C¼¼O), 160.6 (C¼¼O), 163.4 (C¼¼O), 185.7 (C¼¼O)
ppm. MS: m/z (%) ¼ 418 (Mþ, 15), 387 (45), 272 (58), 146
(94), 129 (100), 31(100). Anal. Calc. for C23H18N2O6
(418.40): C, 66.03; H, 4.34; N, 6.70; found: C, 65.94; H, 4.23;
N, 6.62%.
Diethyl 2-[1-(2,3-dioxo-2,3-dihydro-1H-indol-1-yl)-2(1H)-
isoquinolinyl]-2-butenedioate (4b). Yellow powder, mp 140–
142ꢀC. yield: 0.84 g (94%). IR(KBr) mmax (cmꢂ1): 1738, 1735,
1
3
1724, 1682, and 1195 cmꢂ1. H-NMR: d ¼ 1.41 (3 H, t, J ¼
7.2 Hz, Me), 1.47 (3 H, t, 3J ¼ 7.2 Hz, Me), 4.50 (2 H, q,
3J ¼ 7.2 Hz, CH2O), 4.57 (2 H, q, J ¼ 7.2 Hz, CH2O), 5.27
3
(1 H, s, CH), 7.49 (1 H, d, 3J ¼ 7.6 Hz, CH), 7.56 (1 H, s,
3
3
CH), 7.65 (2 H, t, J ¼ 7.3 Hz, 2 CH), 7.68 (2 H, t, J ¼ 7.3
Hz, 2 CH), 7.88 (2 H, d, 3J ¼ 7.5 Hz, 2 CH), 8.65 (2 H, d,
3J ¼ 7.5 Hz, 2 CH), 9.27 (1 H, d, 3J ¼ 7.6 Hz, CH) ppm.
13C-NMR: d ¼ 14.3 (Me), 14.5 (Me), 58.5 (CH), 60.3
(CH2O), 61.4 (CH2O), 95.2 (CH), 108.5 (CH), 123.4 (2 CH),
124.7 (CH), 125.1 (CH), 126.7 (2 CH), 127.2 (CH), 128.4
(CH), 129.2 (C), 134.5 (CH), 135.3 (C), 137.6 (C), 147.8 (C),
152.6 (C), 160.4 (C¼¼O), 161.2 (C¼¼O), 164.5 (C¼¼O), 185.5
(C¼¼O) ppm. MS: m/z (%) ¼ 446 (Mþ, 15), 368 (62), 290
(100), 253 (38), 146 (88), 129 (100), 31 (100). Anal. Calc. for
C25H22N2O6 (446.46): C, 67.26; H, 4.97; N, 6.27; found: C,
67.14; H, 4.85; N, 6.13%.
EXPERIMENTAL
All chemicals were obtained from commercial sources.
Melting points were measured on a Kofler hot stage apparatus
and are uncorrected. 1H-NMR and 13C-NMR spectra were
obtained with a Bruker FT-500 spectrometer in chloroform-d1,
and tetramethylsilane (TMS) was used as an internal standard.
Mass spectra were recorded with a Finnigan Mat TSQ-70
spectrometer. Infrared (IR) spectra were acquired on a Nicollet
Magna 550-FT spectrometer. Elemental analyses were carried
out with a Perkin-Elmer model 240-C apparatus. The results of
elemental analyses (C, H, and N) were within 60.4% of the
calculated values.
Di(tert-butyl)
2(1H)-isoquinolinyl]-2-butenedioate (4c). Yellow powder, mp
2-[1-(2,3-dioxo-2,3-dihydro-1H-indol-1-yl)-
145–147ꢀC, yield: 0.92 g (92%). IR(KBr) mmax (cmꢂ1): 1735,
1730, 1725, 1687, and 1278 cmꢂ1
s, 3 Me), 1.71 (9 H, s, 3 Me), 5.48 (1 H, s, CH), 7.48 (1 H, s,
.
1H-NMR: d ¼ 1.59 (9 H,
General procedure for the preparation of compounds 4,
7, 8, and 9. To a magnetically stirred solution of NH-acids
(2 mmol) and dialkyl acetylenedicarboxylate (2 mmol) in H2O
(20 mL), isoquinoline, quinoline, pyridine, or phenanthridine
3
3
CH), 7.50 (1 H, d, J ¼ 7.7 Hz, CH), 7.71 (2 H, d, J ¼ 7.2
Hz, 2 CH), 7.73 (2 H, t, 3J ¼ 7.2 Hz, 2 CH), 7.93 (2 H, t,
3J ¼ 7.5 Hz, 2 CH), 8.55 (2 H, d, J ¼ 7.5 Hz, 2 CH), 9.22
3
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

156
F. R. Charati, Z. Hossaini, and M. R. Hosseini-Tabatabaei
Vol 49
Table 1
Synthesis of 1,2-dihydroisoquinoline derivatives in water.
Entry
NH-acid
R
Product
Yield (%)
1
2’
3
Me
89
94
92
94
84
89
94
82
Et
tBu
Me
Et
4
5
6
Me
tBu
Me
Me
7
8
9
95
(Continued)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2012
Three Component Reactions of N-Nucleophiles and Activated Acetylenes with
NH-Acids: A Facile Synthesis in Water
157
Table 1
(Continued)
Entry
NH-acid
R
Product
Yield (%)
10
Me
96
92
11
Me
3
(1 H, d, J ¼ 7.7 Hz, CH) ppm. 13C-NMR: d ¼ 28.3 (CMe3),
28.4 (CMe3), 59.4 (CH), 83.4 (CMe3), 84.0 (CMe3), 96.0
(CH), 109.2 (CH), 123.7 (2 CH), 125.4 (CH), 125.8 (CH),
127.2 (2 CH), 127.8 (CH), 128.8 (CH), 129.5 (C), 134.6 (CH),
135.5 (C), 136.8 (C), 147.2 (C), 151.7 (C), 160.5 (C¼¼O),
161.4 (C¼¼O), 164.3 (C¼¼O), 186.0 (C¼¼O) ppm. Anal. Calc.
for C29H30N2O6 (502.56): C, 69.31; H, 6.02; N, 5.57; found:
C, 69.24; H, 5.89; N, 5.46%.
Dimethyl 2-[1-{methyl[(methylamino)carbonyl]amino}-2(1H)-
isoquinolinyl]-2-butenedioate (4f). Pale yellow powder, mp
120–122ꢀC, yield: 0.64 g (89%). IR(KBr) mmax (cmꢂ1): 1730,
1727, 1717, 1712, and 1232 cmꢂ1
.
1H-NMR: d ¼ 3.17 (3 H,
s, NMe), 3.19 (3 H, s, NMe), 3.74 (3 H, s, MeO), 3.82 (3 H,
s, MeO), 5.94 (1 H, s, CH), 6.52 (1 H, s, NH), 7.25 (1 H, d,
3
3J ¼ 7.5 Hz, CH), 7.48 (1 H, t, J ¼ 7.5 Hz, CH), 7.57 (1 H,
t, 3J ¼ 7.6 Hz, CH), 7.62 (1 H, s, CH), 7.75 (1 H, d, 3J ¼
7.6 Hz, CH), 8.42 (1 H, d, 3J ¼ 7.5 Hz, CH), 8.97 (1 H, d,
3J ¼ 7.5 Hz, CH) ppm. 13C-NMR: d ¼ 27.8 (NMe), 33.4
(NMe), 52.4 (MeO), 53.6 (MeO), 65.4 (CH), 98.2 (CH), 102.3
(CH), 118.2 (CH), 124.3 (2 CH), 126.7 (CH), 128.5 (CH),
134.2 (C), 135.8 (C), 141.8 (C), 159.7 (C¼¼O), 161.4 (C¼¼O),
164.8 (C¼¼O) ppm. MS: m/z (%) ¼ 359 (Mþ, 5), 230 (45),
129 (100), 31(100). Anal. Calc. for C18H21N3O5 (359.38):
C, 60.16; H, 5.89; N, 11.69; found: C, 60.04; H, 5.75;
N, 11.58%.
Dimethyl 2-[1-(1H-midazol-1-yl)-2(1H)-isoquinolinyl]-2-
butenedioate (4d). Yellow powder, mp 124–126ꢀC, yield:
0.64 g (94%). IR(KBr) mmax (cmꢂ1): 1732, 1725, 1557, 1410,
and 1127 cmꢂ1. H-NMR: d ¼ 3.75 (3 H, s, MeO), 3.82 (3 H,
1
3
s, MeO), 5.98 (1 H, s, CH), 7.05 (1 H, d, J ¼ 5.7 Hz, CH),
7.24 (1 H, d, 3J ¼ 7.5 Hz, CH), 7.42 (1 H, d, 3J ¼ 5.7 Hz,
CH), 7.52 (1 H, t, 3J ¼ 7.5 Hz, CH), 7.58 (1 H, t, 3J ¼ 7.5
3
Hz, CH), 7.67 (1 H, s, CH), 7.70 (1 H, d, J ¼ 7.4 Hz, CH),
7.85 (1 H, d, 3J ¼ 7.4 Hz, CH), 8.02 (1 H, d, 3J ¼ 7.5 Hz,
CH), 8.25 (1 H, s, CH) ppm. 13C-NMR: d ¼ 51.5 (MeO), 52.2
(MeO), 60.4 (CH), 98.2 (CH), 103.0 (CH), 118.2 (CH), 120.7
(CH), 127.5 (2 CH), 127.9 (CH), 129.3 (CH), 130.1 (CH),
137.5 (CH), 138.2 (C), 140.0 (C), 141.2 (C), 165.4 (C¼¼O),
167.2 (C¼¼O) ppm. Anal. Calc. for C18H17N3O4 (339.35):
C, 63.71; H, 5.05; N, 12.38; found: C, 63.58; H, 4.92;
N, 12.27%.
Di(tert-butyl)2-[1-{methyl[(methylamino)carbonyl]amino}-
2(1H)-isoquinolinyl]-2-butenedioate (4g). Yellow powder,
mp 147–149ꢀC, yield: 0.83 g (94%). IR(KBr) mmax (cmꢂ1):
1728, 1718, 1654, and 1258 cmꢂ1
.
1H-NMR: d ¼ 1.54 (9 H,
s, 3 Me), 1.68 (9 H, s, 3 Me), 2.65 (3 H, s, NMe), 2.97 (3 H,
s, NMe), 5.58 (1 H, s, CH), 6.38 (1 H, s, NH), 7.48 (1 H, s,
CH), 7.52 (1 H, d, 3J ¼ 7.5 Hz, CH), 7.65 (1 H, d, 3J ¼
7.2 Hz, CH), 7.74 (1 H, t, 3J ¼ 7.3 Hz, CH), 7.84 (1 H, t,
Diethyl 2-[1-(1H-indol-1-yl)-2(1H)-isoquinolinyl]-2-butene-
dioate (4e). Yellow powder, mp 115–117ꢀC, yield: 0.75 g
(84%). IR(KBr) mmax (cmꢂ1): 1738, 1732, 1545, 1412, and
3
3J ¼ 7.4 Hz, CH), 8.58 (1 H, d, J ¼ 7.5 Hz, CH), 9.18 (1 H,
3
d, J ¼ 7.7 Hz, CH) ppm. 13C-NMR: d ¼ 27.6 (CMe3), 28.2
1175 cmꢂ1
.
1H-NMR: d ¼ 1.25 (3 H, t, 3J ¼ 7.3 Hz, Me),
(CMe3), 32.4 (NMe), 33.8 (NMe), 59.5 (CH), 82.8 (CMe3),
83.6 (CMe3), 96.4 (CH), 102.5 (CH), 118.6 (CH), 124.0
(2 CH), 127.2 (CH), 128.6 (CH), 134.4 (C), 136.0 (C), 142.2
(C), 160.4 (C¼¼O), 162.3 (C¼¼O), 165.7 (C¼¼O) ppm. Anal.
Calc. for C24H33N3O5 (443.54): C, 64.99; H, 7.50; N, 9.47;
found: C, 64.84; H, 7.42; N, 9.35%.
1.34 (3 H, t, 3J ¼ 7.3 Hz, Me), 4.21 (2 H, q, 3J ¼ 7.3 Hz,
3
CH2O), 4.32 (2 H, q, J ¼ 7.3 Hz, CH2O), 5.95 (1 H, s, CH),
6.87 (1 H, d, 3J ¼ 6.2 Hz, CH), 7.23 (1 H, d, 3J ¼ 7.7 Hz,
CH), 7.38 (1 H, d, 3J ¼ 6.2 Hz, CH), 7.56 (2 H, t, J ¼ 7.4
3
Hz, 2 CH), 7.63 (2 H, t, 3J ¼ 7.4 Hz, 2 CH), 7.67 (1 H, s,
3
3
CH), 7.74 (2 H, d, J ¼ 7.4 Hz, 2 CH), 8.40 (2 H, d, J ¼ 7.4
Dimethyl 2-[1-(1H-pyrroll-1-yl)-2(1H)-isoquinolinyl]-2-bute-
nedioate (4k). Yellow powder, mp 134–136ꢀC, yield: 0.62 g
(92%). IR(KBr) mmax (cmꢂ1): 1730, 1722, 1545, 1425, and
Hz, 2 CH), 9.25 (1 H, d, J ¼ 7.7 Hz, CH) ppm. 13C-NMR: d
3
¼ 13.8 (Me), 14.3 (Me), 60.0 (CH), 61.4 (CH2O), 62.6
(CH2O), 97.2 (CH), 103.4 (CH), 110.2 (CH), 115.6 (CH),
119.7 (2 CH), 121.3 (CH), 122.8 (CH), 125.5 (2 CH), 127.1
(CH), 128.6 (2 CH), 132.5 (C), 134.7 (C), 136.2 (C), 138.8
(C), 142.3 (C), 167.2 (C¼¼O), 168.4 (C¼¼O) ppm. MS: m/z (%)
¼ 416 (Mþ, 15), 371 (54), 272 (52), 129 (100), 116 (86),
45(100). Anal. Calc. for C25H24N2O4 (416.47): C, 72.10; H,
5.81; N, 6.73; found: C, 72.00; H, 5.74; N, 6.67%.
1
1167 cmꢂ1. H-NMR: d ¼ 3.80 (3 H, s, OMe), 3.85 (3 H, s,
OMe), 5.95 (1 H, s, CH), 6.84 (1 H, d, 3J ¼ 6.7 Hz, CH),
3
3
6.97 (2 H, t, J ¼ 5.8 Hz, 2 CH), 7.24 (1 H, d, J ¼ 7.2 Hz,
CH), 7.32 (2 H, t, 3J ¼ 6.2 Hz, 2 CH), 7.38 (1 H, t, 3J ¼
6.7 Hz, CH), 7.54 (1 H, d, 3J ¼ 7.5 Hz, CH), 7.68 (1 H, s,
CH), 7.78 (1 H, d, 3J ¼ 7.5 Hz, CH), 8.02 (1 H, d, 3J ¼
7.5 Hz, CH) ppm. 13C-NMR: d ¼ 51.5 (OMe), 52.7 (OMe),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

158
F. R. Charati, Z. Hossaini, and M. R. Hosseini-Tabatabaei
Vol 49
Table 2
Synthesis of 1,2-dihydroquinoline, 1,2-dihydropyridine, or 1,2-dihydrophenanthridine derivatives in water.
Entry
NH-acid
R
Product
Yield (%)
1
2
3
4
5
6
7
8
9
Me
88
86
89
86
90
89
92
94
Me
Me
Me
Me
Me
Me
Me
Me
97
(Continued)
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Three Component Reactions of N-Nucleophiles and Activated Acetylenes with
NH-Acids: A Facile Synthesis in Water
159
Table 2
(Continued)
Entry
NH-acid
R
Product
Yield (%)
10
Me
95
11
Me
96
3
58.7 (CH), 98.4 (CH), 104.2 (CH), 120.4 (CH), 122.8 (2 CH),
123.3 (2 CH), 127.5 (2 CH), 128.4 (CH), 131.5 (CH), 135.4
(C), 137.3 (C), 14.08 (C), 163.8 (C¼¼O), 165.7 (C¼¼O) ppm.
Anal. Calc. for C19H18N2O4 (338.36): C, 67.45; H, 5.36; N,
8.28; found: C, 67.32; H, 5.28; N, 8.19%.
3J ¼ 7.5 Hz, CH), 7.57 (1 H, m, CH), 7.62 (1 H, d, J ¼ 7.5
3
3
Hz, CH), 7.75 (1 H, d, J ¼ 7.5 Hz, CH), 7.82 (1 H, d, J ¼
7.5 Hz, CH) ppm. 13C-NMR: d ¼ 27.5 (NMe), 33.6 (NMe),
51.4 (OMe), 52.8 (OMe), 68.2 (CH), 98.5 (CH), 114.8 (CH),
117.5 (CH), 121.4 (CH), 126.7 (C), 128.5 (CH), 131.4 (CH),
133.8 (CH), 135.6 (C), 142.7 (C), 159.6 (C¼¼O), 163.8
(C¼¼O), 165.2 (C¼¼O) ppm. MS: m/z (%) ¼ 359 (Mþ, 10),
328 (45), 230 (52), 129 (100), 31 (100). Anal. Calc. for
C18H21N3O5 (359.38): C, 60.16; H, 5.89; N, 11.69; found: C,
60.23; H, 5.94; N, 11.76%.
Dimethyl 2-[2-(1H-indol-1-yl)-1(2H)-quinolinyl]-2-butene-
dioate (7a). Yellow powder, mp 135–137ꢀC, yield: 0.68 g
(88%). IR(KBr) mmax (cmꢂ1): 1732, 1728, 1694, 1548, and 1243
1
cmꢂ1. H-NMR: d ¼ 3.85 (3 H, s, OMe), 3.90 (3 H, s, OMe),
3
5.47 (1 H, s, CH), 6.38 (1 H, d, J ¼ 5.8 Hz, CH), 6.85 (1 H,
3
3
d, J ¼ 6.5 Hz, CH), 7.35 (1 H, d, J ¼ 6.5 Hz, CH), 7.55 (1 H,
Dimethyl 2-[2-(1H-pyrrol-1-yl)-1(2H)-quinolinyl]-2-butene-
dioate (7c). Yellow powder, mp 131–133ꢀC, yield: 0.60 g
(89%). IR(KBr) mmax (cmꢂ1): 1728, 1720, 1587, 1457, and
3
3
d, J ¼ 7.4 Hz, CH), 7.56 (2H, t, J ¼ 7.2 Hz, 2 CH), 7.60 (2 H,
t, 3J ¼ 7.2 Hz, 2 CH), 7.79 (2 H, d, 3J ¼ 7.7 Hz, 2 CH), 8.15 (2 H,
d, 3J ¼ 7.2 Hz, 2 CH), 8.21 (1 H, d, 3J ¼ 7.7 Hz, CH) ppm. 13C-
NMR: d ¼ 51.5 (OMe), 52.5 (OMe), 59.2 (CH), 97.5 (CH), 102.5
(CH), 113.4 (CH), 117.8 (2 CH), 120.4 (CH), 121.8 (2 CH), 122.5
(2 CH), 125.4 (CH), 127.6 (CH), 129.8 (C), 131.6 (CH), 133.2 (C),
136.3 (C), 138.7 (C), 141.8 (C), 165.4 (C¼¼O), 166.8 (C¼¼O) ppm.
MS: m/z (%) ¼ 388 (Mþ, 15), 357 (45), 129 (100), 116 (94), 31
(100). Anal. Calc. for C23H20N2O4 (388.42): C, 71.12; H, 5.19; N,
7.21; found: C, 70.98; H, 5.05; N, 7.12%.
1168 cmꢂ1. H-NMR: d ¼ 3.82 (3 H, s, MeO), 3.87 (3 H, s,
1
MeO), 5.87 (1 H, s, CH), 6.38 (2 H, t, 3J ¼ 5.7 Hz, 2 CH),
3
3
6.85 (1 H, d, J ¼ 6.2 Hz, CH), 6.96 (2 H, t, J ¼ 5.9 Hz, 2
3
CH), 7.23 (1 H, d, 3J ¼ 7.4 Hz, CH), 7.32 (1 H, t, J ¼ 7.2
3
3
Hz, CH), 7.40 (1 H, t, J ¼ 7.2 Hz, CH), 7.64 (1 H, d, J ¼
6.8 Hz, CH), 7.75 (1 H, d, 3J ¼ 7.2 Hz, CH), 8.25 (1 H, d,
3J ¼ 7.5 Hz, CH) ppm. 13C-NMR: d ¼ 52.3 (MeO), 52.7
(MeO), 60.3 (CH), 100.4 (CH), 117.4 (CH), 119.2 (CH), 121.5
(2 CH), 122.6 (2 CH), 124.3 (2 CH), 128.4 (CH), 131.4 (CH),
132.0 (C), 138.7 (C), 143.2 (C), 167.2 (C¼¼O), 169.0 (C¼¼O)
ppm. Anal. Calc. for C19H18N2O4 (338.36): C, 67.45; H, 5.36;
N, 8.28; found: C, 67.35; H, 5.30; N, 8.22%.
Dimethyl 2-[2-{methyl[(methylamino)carbonyl]amino}-1(2H)-
quinolinyl]-2-butenedioate (7b). Yellow powder, mp 128–130ꢀC,
yield: 0.64 g (86%). IR(KBr) mmax (cmꢂ1): 1735, 1727, 1695,
1
1547, and 1194 cmꢂ1. H-NMR: d ¼ 3.22 (3 H, s, NMe), 3.25
(3 H, s, NMe), 3.83 (3 H, s, OMe), 3.87 (3 H, s, OMe), 5.86
Dimethyl 2-[2-(1H-indol-1-yl)-1(2H)-pyridinyl]-2-butenedioate
(8a). Yellow powder, mp 119–121ꢀC, yield: 0.58 g (86%).
3
3
(1 H, s, CH), 6.38 (1H, d, J ¼ 8.2, NH), 7.35 (1 H, d, J ¼
7.3 Hz, CH), 7.40 (1 H, t, 3J ¼ 7.5 Hz, CH), 7.52 (1 H, t,
IR(KBr) mmax (cmꢂ1): 1740, 1735, 1674, 1453, and 1153 cmꢂ1
.
Scheme 2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

160
F. R. Charati, Z. Hossaini, and M. R. Hosseini-Tabatabaei
Vol 49
1H-NMR: d ¼ 3.73 (3 H, s, OMe), 3.80 (3 H, s, OMe), 5.56
(1 H, s, CH), 6.42 (1 H, d, 3J ¼ 6.3 Hz, CH), 6.52 (1 H, d,
[7] Bentley, K. W. The Isoquinoline Alkaloids; Pergamon
Press: London, 1965.
3
3J ¼ 6.8 Hz, CH), 6.68 (1 H, t, J ¼ 7.4 Hz, CH), 6.75 (H, t,
[8] Bentley, K. W. Nat Prod Rep 2001, 18, 148.
[9] Michael, J. P. Nat Prod Rep 2002, 19, 742.
[10] Scott, J. D.; Williams, R. M. Chem Rev 2002, 102, 1669.
[11] Hansch, C. P.; Sammes, G.; Taylor, J. B. Comprehensive
Medicinal Chemistry; Pergamon Press: Oxford, 1990.
[12] Obika, S.; Kono, H.; Yasui, Y.; Yanada, R.; Takemoto, Y.
J Org Chem 2007, 72, 4462.
3
3J ¼ 7.5 Hz, CH), 7.14 (1 H, t, J ¼ 7.4 Hz, CH), 7.35 (1 H,
d, 3J ¼ 6.8 Hz, CH), 7.48 (1 H, d, 3J ¼ 7.4 Hz, CH), 7.55
3
3
(1 H, d, J ¼ 7.4 Hz, CH), 7.63 (1 H, t, J ¼ 7.3 Hz, 2 CH),
3
3
7.95 (1 H, d, J ¼ 7.7 Hz, CH), 8.22 (2 H, d, J ¼ 6.9 Hz, 2
CH) ppm. 13C-NMR: d ¼ 51.2 (OMe), 52.4 (OMe), 59.6
(CH), 98.2 (CH), 114.5 (CH), 119.2 (CH), 120.4 (2 CH),
121.5 (CH), 122.2 (CH), 122.8 (2 CH), 125.6 (CH), 132.6 (C),
134.7 (CH), 136.5 (C), 138.5 (C), 167.2 (C¼¼O), 169.2 (C¼¼O)
ppm. Anal. Calc. for C19H18N2O4 (338.36): C, 67.45; H, 5.36;
N, 8.28; found: C, 67.38; H, 5.27; N, 8.16%.
[13] Asao, N.; Iso, K.; Yudha, S. S. Org Lett 2006, 8, 4149.
[14] Asao, N.; Chan, C. S.; Takahashi, K.; Yamamoto, Y. Tetra-
hedron 2005, 61, 11322.
[15] Shaabani, A.; Soleimani, E.; Khavasi, H. R. Tetrahedron
Lett 2007, 48, 4743.
Dimethyl 2-[2-(imidazol-1-yl)-1(2H)-pyridinyl]-2-butenedioate
(8b). Yellow powder, mp 115–117ꢀC, yield: 0.52 g (90%).
[16] Huang, Q.; Larock, R. C. J Org Chem 2003, 68, 980.
[17] Ding, Q.; Wang, Z.; Wu, J. Tetrahedron Lett 2009, 50, 198.
[18] Grieco, P. A. Organic Synthesis in Water; Blackie Aca-
demic & Professional: Glasgow, 1998.
IR(KBr) mmax (cmꢂ1): 1728, 1724, 1525, and 1147 cmꢂ1
.
1H-NMR: d ¼ 3.75 (3 H, s, MeO), 3.82 (3 H, s, MeO), 5.92
(1 H, s, CH), 6.75 (1 H, t, 3J ¼ 7.3 Hz, CH), 7.18 (1 H, t,
[19] Anastas, P.; Williamson, T. C. Green Chemistry Frontiers
in Benign Chemical Synthesis and Processes; Oxford University Press:
New York, 1998.
3J ¼ 7.4 Hz, CH), 7.27 (1 H, d, J ¼ 6.5 Hz, CH), 7.38 (1 H,
3
3
3
d, J ¼ 6.5 Hz, CH), 7.75 (1 H, d, J ¼ 6.4 Hz, CH), 7.86 (1
3
3
[20] Yavari, I.; Hossaini, Z.; Sabbaghan, M. Tetrahedron Lett
2006, 47, 6037.
H, s, CH), 8.35 (1 H, d, J ¼ 7.3 Hz, CH), 9.12 (1 H, d, J ¼
7.3 Hz, CH) ppm. 13C-NMR: d ¼ 51.6 (OMe), 52.4 (OMe),
62.2 (CH), 98.7 (CH), 116.8 (CH), 120.4 (2 CH), 123.2 (CH),
125.2 (CH), 129.8 (CH), 134.5 (C), 138.3 (CH), 162.4 (C¼¼O),
164.8 (C¼¼O) ppm. Anal. Calc. for C14H15N3O5 (289.29): C,
58.13; H, 5.23; N, 14.53; found: C, 58.25; H, 5.32; N,
15.61%.
[21] Yavari, I.; Ghazanfarpour-Darjani, M.; Sabbaghan, M.; Hos-
saini, Z. Tetrahedron Lett 2007, 48, 3749.
[22] Yavari, I.; Hossaini, Z.; Sabbaghan, M.; Ghazanfarpour-
Darjani, M. Chem Mon 2007, 138, 677.
[23] Hassani, Z.; Islami, M. R.; Sheibani, H.; Kalantari, M.;
Saidi, K. ARKIVOC 2006, 89.
Dimethyl 2-[2-{methyl[(methylamino)carbonyl]amino}-1(2H)-
pyridinyl]-2-butenedioate (8c). Yellow powder, mp 117–119ꢀC,
yield: 0.55 g (89%). IR(KBr) mmax (cmꢂ1): 1738, 1736, 1730,
[24] Islami, M. R.; Mollazehi, F.; Badiei, A.; Sheibani, H.
ARKIVOC 2006, xv, 25.
[25] Kalantari, M.; Islami, M. R.; Hassani, Z.; Saidi, K. ARKI-
VOC 2006, x, 55.
1625, 1584, and 1185 cmꢂ1
.
1H-NMR: d ¼ 3.27 (3 H, s,
NMe), 3.32 (3 H, s, NMe), 3.78 (3 H, s, OMe), 3.85 (3 H, s,
OMe), 5.86 (1 H, s, CH), 6.34 (1H, d, 3J ¼ 8.5, NH), 6.78
(1 H, t, 3J ¼ 7.3 Hz, CH), 7.03 (1 H, m, CH), 7.37 (1 H, t,
[26] Maghsoodlou, M. T.; HabibiKhorassani, S. M.; Rofouei, M.
K.; Adhamdoust, S. R.; Nassiri, M. ARKIVOC 2006, xii, 145.
[27] Maghsoodlou, M. T.; Hazeri, N.; Habibi Khorassani, S. M.;
Rofouei, M. K.; Rezaie, M. ARKIVOC 2006, xiii, 117.
[28] Yavari, I.; Mirzaei, A.; Hossaini, Z.; Souri, S. Mol Divers
2010, 14, 343.
3J ¼ 7.5 Hz, CH), 7.42 (1 H, m, CH), 7.97 (1 H, d, J ¼ 7.5
3
Hz, CH) ppm. 13C-NMR: d ¼ 28.2 (NMe), 32.5 (NMe), 51.5
(OMe), 52.6 (OMe), 67.4 (CH), 100.2 (CH), 109.4 (CH),
113.5 (CH), 120.8 (CH), 133.8 (C), 135.7 (CH), 159.8 (C¼¼O),
160.2 (C¼¼O), 165.2 (C¼¼O) ppm. Anal. Calc. for C14H19N3O5
(309.32): C, 54.36; H, 6.19; N, 13.58; found: C, 54.27; H,
6.04; N, 13.47%.
[29] Khalilzadeh, M. A.; Hossaini, Z.; Kharian, S. Mol Divers
2010, 14, 605.
[30] Nassiri, M.; Maghsoodlou, M. T.; Heydari, R.; Habibi
Khorassani, S. M. Mol Divers 2008, 12, 111.
[31] Winterfeldt, E. Angew Chem Int Ed Engl 1967, 6, 423.
[32] (a) Johnson, A. W.; Tebby, J. C. J Chem Soc 1961, 2126;
(b) Tebby, J. C.; Wilson, I. F.; Griffiths, D. V. J Chem Soc Perkin
Trans 1 1979, 2133; (c) Butterfield, P. J.; Tebby, J. C.; Griffiths, D. V.
J Chem Soc Perkin Trans 1 1979, 1189.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet