Novel One-Pot Synthesis of Functionalized Quinolines from Isocyanides, Aniline, and Acetylene Dicarboxylate via Cu-Catalyzed Intramolecular C─H Activation Reactions

Article abstract of DOI:10.1002/jhet.3477

The one-pot synthesis of a novel class of substituted quinoline derivatives with good yields is achieved via the Cu-catalyzed intramolecular C─H activation reaction between isocyanides, aniline, and acetylene dicarboxylate in MeCN at room temperature. The

Full text of DOI:10.1002/jhet.3477

Month 2019 Novel One-Pot Synthesis of Functionalized Quinolines from Isocyanides,
Aniline, and Acetylene Dicarboxylate via Cu-Catalyzed Intramolecular
C─H Activation Reactions
a
a
b
a
*
Manijeh Nematpour, Elham Rezaee, Mehdi Jahani, and Sayyed Abbas Tabatabai
aDepartment of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran,
Iran
bDepartment of Chemistry, Sharif University of Technology, Tehran, Iran
*E-mail: sa_tabatabai@sbmu.ac.ir
Received July 8, 2018
DOI 10.1002/jhet.3477
Published online 00 Month 2019 in Wiley Online Library (wileyonlinelibrary.com).
The one-pot synthesis of a novel class of substituted quinoline derivatives with good yields is achieved via
the Cu-catalyzed intramolecular C─H activation reaction between isocyanides, aniline, and acetylene
dicarboxylate in MeCN at room temperature. The existence of one-pot conditions, availability of a starting
material-catalyst, the absence of column chromatography, and a high yield of products are among the
advantages of this method. The structures are confirmed spectroscopically (1H NMR and 13C NMR, IR,
and EI-MS) and through elemental analyses.
J. Heterocyclic Chem., 00, 00 (2019).
INTRODUCTION
unintended by-products [12]. Against this backdrop, this
study has aimed to develop an efficient and practical
method for the synthesis of functionalized quinolines
derivatives under mild conditions with biological
activities. It is, then, no wonder that direct
functionalization of unreactive C─H bonds using
transition-metal catalysis has become a major topic of
research in organic synthesis. In fact, this methodology,
the intramolecular heterofunctionalization of C─H bonds
based on atom-economic and step-economic principles,
plays a crucial role in the synthesis of new heterocyclic
structures. Different types of heterocycles, especially those
containing nitrogen, have been synthesized using this
novel strategy in recent years [13]. As part of our studies
on the synthesis of heterocycle compounds by copper-
catalyzed C─H activation reactions [14], we report a
novel protocol for the synthesis of various quinoline
derivatives via the Cu-catalyzed C─H activation reaction
of isocyanides, aniline, and acetylene dicarboxylate in
MeCN at room temperature with good yields (see
Scheme 1). Compared with conventional methods, this
method offers some obvious advantages such as the
Quinoline compounds, an important group of
heterocyclic scaffolds, perform some useful biological
activities
– among others, they have antibacterial,
antimalarial, antihypertensive, anti-asthmatic, and
anti-inflammatory functions [1–3]. In addition, they can be
used as valuable synthons for the synthesis of
mesostructures and nanostructures with photonic functions
and enhanced electronics [4,5]. Also, quinolines make up
the core structure in many alkaloids [6,7] and are used for
forming polymers and conjugated molecules [8].
Moreover, they play a crucial role in the study of bio-
organic, bio-organometallic processes, agro-chemicals,
dyestuffs, and synthetic building blocks [9,10].
Accordingly, the importance of developing efficient
synthetic routes with simple protocols for the synthesis of
functionalized quinoline derivatives can hardly be missed.
There are several reported methods for these scaffolds
[11], which often require costly catalysts, toxic reagents,
harsh conditions, inconvenient multi-step processes, high
temperatures, and long reaction times and often result in
© 2019 Wiley Periodicals, Inc.

M. Nematpour, E. Rezaee, M. Jahani, and S. A. Tabatabai
Vol 000
Scheme 1. Synthesis of various quinoline derivatives by Cu-catalyzed intramolecular C─H activation reaction of isocyanides, aniline, and acetylene
dicarboxylate.
existence of mild conditions, easier work-up, the
availability of starting materials involving a catalyst, and
purer products with high yields.
15 mol % of L-proline as the ligand, 2.0 mmol of
isocyanides, 1.5 mmol of acetylene dicarboxylate, and
2.0 mmol of aniline. Also, we tested the reaction
isocyanides, acetylene dicarboxylate, and aniline in the
absence of the CuI catalyst and L-proline for 7 h, but we
were not able to isolate the various quinoline derivatives
(see Table 1).
RESULTS AND DISCUSSION
In order to obtain optimal catalysis conditions, we
screened various catalysts, solvents, and bases using
aniline, acetylene dicarboxylate, and isocyanides as
model substrates. As shown in Table 1, copper salts, CuI,
CuBr, CuCl, CuSO4, and Cu (OAc)2 (10 mol % amount),
were tested. CuI was found to be the most effective
catalyst. MeCN, as the best solvent for this reaction, was
also screened. Several bases such as Cs2CO3, K2CO3,
KOt-Bu, NaOH, and KOH were tested, and finally,
Cs2CO3 was found to produce the best results. Therefore,
the reaction was checked out in MeCN using 10 mol% of
CuI as the catalyst, 1.5 mmol of Cs2CO3 as the base,
Various quinoline derivatives were synthesized using
the optimized conditions from CuI as the catalyst,
Cs2CO3 as the base, L-proline as the ligand, acetylene
dicarboxylate, isocyanides, and anilines. Anilines with
various electron-withdrawing substituents on the aromatic
rings readily participates in the formation of quinolines
derivatives in good yields compared with anilines with
various electron-donating substituents. Di-tert-butyl
acetylenedicarboxylate served as low-yielding substrates
compared with dimethyl(ethyl)acetylenedicarboxylate.
Aromatic and aliphatic isocyanides reacted efficiently
with acetylene dicarboxylate and anilines the
corresponding products 5a–k were obtained in good
yields (see Table 2). We have used propiolate ester
instead of acetylene dicarboxylate derivative under CuI as
the catalyst, Cs2CO3 as the base, and L-proline as the
ligand for 7 h at room temperature and for 14 h under
reflux conditions. Finally, the reaction mixture was very
complex, and we were not able to isolate product 5.
The structures of compounds 5a–k were assigned by IR,
1H NMR, 13C NMR, and mass spectral data. The 1H NMR
spectrum of 5a exhibited three singlets for two OMe
groups (δ = 3.56, 3.77 ppm) and the NH group
(δ = 6.43 ppm), along with characteristic multiplets for
the aromatic protons. The 13C NMR spectrum of 5a
exhibited 16 signals in full agreement with the proposed
structure. The NMR spectra of other compounds were
like those of 5a, except for the substituents, which
showed characteristic signals in the appropriate regions of
the spectra. The mass spectrum of 5a displayed the
molecular ion peak at m/z = 336.
Table 1
Optimization of reaction conditions for the formation of product 5a.
Entry
Catalyst
Solvent
Base
Yield (%)a
1b
2
3
4
5
6
7
8
9
10
11
12
13
14
CuI
CuI
CuI
CuI
CuCl
CuCl
CuBr
CuBr
CuBr
Cu (OAc)2
Cu (OAc)2
CuSO4
CuSO4
—
MeCN
MeCN
DMF
DMF
THF
Cs2CO3
NaOH
KOt-Bu
Cs2CO3
K2CO3
KOH
Cs2CO3
KOH
NaOH
Cs2CO3
KOt-Bu
K2CO3
Cs2CO3
Cs2CO3
82
68
22
70
44
37
59
42
38
29
21
26
34
—
THF
MeCN
DMF
DMF
MeCN
DMF
THF
MeCN
MeCN
aReaction time 7 h.
b5 mol% catalyst, reaction time was 12 h.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2019
Synthesis of Functionalized Quinolines
Table 2
Synthesis of various quinolines derivatives.
A possible reaction mechanism is shown in Scheme 2. It
is proposed that reaction of CuI with L-proline produced a
five-membered chelate A. The chelated Cu (I) was
oxidativelly added to the CH moiety of nucleophilic
adduct 3 (generated from 1 and 2) to obtain the
intermediate B, stabilized by Cu-coordinated isocyanide
carbon atom. Reductive elimination of B gave compound
6 leaving the chelate A and the catalyst. Compound 6,
which undergoes tautomerization, was converted to
product 5.
Scheme 2. Possible formation mechanism of compound 5.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

M. Nematpour, E. Rezaee, M. Jahani, and S. A. Tabatabai
Vol 000
EXPERIMENTAL
Melting points (mp) on an
(26), 169 (54), 154 (100), 76 (79), 59 (16). Anal. Calcd for
C19H15BrN2O4 (415.24): C, 54.96; H, 3.64; N, 6.75.
Found: C, 54.92; H, 3.66; N, 6.72.
Materials and methods.
Dimethyl
4-((4-nitrophenyl)amino)quinoline-2,3-
Electrothermal 9100 apparatus were measured. Elemental
analyses C, H, N using a Heraeus CHN-O-Rapid analyzer
were performed. IR spectra on a Shimadzu IR-460
spectrometer were registered. Mass spectra applying
FINNIGAN-MAT 8430 mass spectrometer of 70 eV
were received. 1H NMR (500.1 MHz) and 13C NMR
(125.7 MHz) spectra on a BRUKER DRX 500-AVANCE
FT-NMR instrument in CDCl3 as solvent were afforded.
All solvents and reagents have been purchased from
Merck without purification.
dicarboxylate (5c). Yellow powder; yield: 0.30 g (79%);
mp: 183–185°C. IR (KBr) (νmax, cmÀ1): 3298, 1732,
1721, 1634, 1552, 1343, 1215. 1H NMR (500 MHz,
CDCl3): δH = 3.60 (s, 3 H, OMe), 3.90 (s, 3 H, OMe),
3
6.01 (s, 1 H, NH), 7.42 (d, J = 8.2, 2 H, Ar), 7.51–7.58
(m, 3 H, Ar), 7.80 (d, 3J = 8.2, 2 H, Ar), 7.93 (d, 3J = 8.0,
1 H, Ar). 13C NMR (125.7 MHz, CDCl3): δC = 55.9
(OMe), 57.8 (OMe), 127.9 (2 CH), 128.2 (CH), 129.5
(CH), 130.0 (2 CH), 131.4 (C), 133.3 (2 CH), 134.2 (C),
141.9 (C), 142.8 (C), 146.3 (C), 148.0 (C), 164.8 (C),
174.8 (C), 177.9 (C). MS: m/z (%) = 381 (M+, 6), 322
(17), 259 (29), 244 (43), 122 (100), 59 (37). Anal. Calcd
for C19H15N3O6 (381.34): C, 59.84; H, 3.96; N, 11.02.
Found: C, 59.80; H, 3.92; N, 11.10.
General procedure for the synthesis of compound 5.
A
mixture of aniline
2 (2.0 mmol) and acetylene
dicarboxylate 1 (1.5 mmol) for 5 min was stirred. Then,
isocyanides 4 (2.0 mmol), CuI (0.10 mmol), 15 mol % of
L-proline, and Cs2CO3 (1.5 mmol) in MeCN (2 mL) were
added to the first solution, and the mixture was stirred at
room temperature for 7 h. After the finalization of the
reaction [TLC (AcOEt/hexane 1:5) monitoring], the
mixture was stirred for 20 min by adding aqueous NH4Cl
solution (2 mL) and CH2Cl2 (2 mL). And then the layers
were separated. The aqueous layer under reduced pressure
concentrated. The final solid product was washed with
acetone.
Dimethyl
(5d).
4-(tert-butylamino)quinoline-2,3-dicarboxylate
Cream powder; yield: 0.26 g (83%); mp: 123–
125°C. IR (KBr) (νmax, cmÀ1): 3367, 1724, 1709, 1622,
1
1211. H NMR (500 MHz, CDCl3): δH = 1.59 (s, 9 H,
Me3C), 3.68 (s, 3 H, OMe), 3.89 (s, 3 H, OMe), 6.31 (s,
3
1 H, NH), 7.32–7.36 (m, 3 H, Ar), 7.50 (d, J = 8.0, 1 H,
Ar). 13C NMR (125.7 MHz, CDCl3): δC = 26.4 (Me3C),
54.3 (Me3C), 56.7 (OMe), 58.7 (OMe), 127.2 (2 CH),
128.0 (CH), 129.5 (C), 130.0 (CH), 133.3 (C), 143.0 (C),
145.3 (C), 166.7 (C), 176.0 (C), 178.8 (C). MS: m/z
(%) = 316 (M+, 13), 259 (24), 244 (25), 198 (28), 76
(100), 72 (30), 57 (39). Anal. Calcd for C17H20N2O4
(316.35): C, 64.54; H, 6.37; N, 8.86. Found: C, 64.58; H,
6.32; N, 8.90.
Dimethyl
(5a).
4-(phenylamino)quinoline-2,3-dicarboxylate
Cream powder; yield: 0.27 g (82%); mp: 148–
150°C. IR (KBr) (νmax, cmÀ1): 3210, 1718, 1700, 1613,
1
1245. H NMR (500 MHz, CDCl3): δH = 3.56 (s, 3 H,
OMe), 3.77 (s, 3 H, OMe), 6.43 (s, 1 H, NH), 7.32–7.36
(m, 3 H, Ar), 7.51 (d, 3J = 7.7, 2 H, Ar), 7.64 (t, 3J = 7.7,
2 H, Ar), 7.77 (t, 3J = 8.0, 1 H, Ar), 8.06 (d, 3J = 8.0, 1 H,
Ar). 13C NMR (125.7 MHz, CDCl3): δC = 57.8 (OMe),
59.9 (OMe), 128.1 (2 CH), 129.5 (CH), 130.0 (CH), 130.9
(2 CH), 133.3 (C), 136.4 (2 CH), 136.9 (C), 137.2 (CH),
138.3 (C), 142.5 (C), 145.5 (C), 166.7 (C), 172.0 (C),
175.8 (C). MS: m/z (%) = 336 (M+, 8), 260 (12), 244 (16),
218 (24), 92 (100), 77 (56), 76 (60). Anal. Calcd for
C19H16N2O4 (336.34): C, 67.85; H, 4.79; N, 8.33. Found:
C, 67.88; H, 4.75; N, 8.31.
Dimethyl
4-(cyclohexylamino)-6-methylquinoline-2,3-
dicarboxylate (5e). Cream powder; yield: 0.28 g (80%);
mp: 109–111°C. IR (KBr) (νmax, cmÀ1): 3300, 1715,
1703, 1626, 1249. 1H NMR (500 MHz, CDCl3):
δH = 1.00–1.07 (m, 4 H, CH2), 1.93–1.95 (m, 2 H, CH2),
1.97–2.10 (m, 2 H, CH2), 2.18–2.21 (m, 2 H, CH2), 2.35
(s, 3 H, Me), 3.31–3.35 (m, 1 H, CH), 3.64 (s, 3 H,
OMe), 3.87 (s, 3 H, OMe), 6.35 (s, 1 H, NH), 7.41 (d,
3
3J = 8.1, 1 H, Ar), 7.49 (s, 1 H, Ar), 7.94 (d, J = 8.1, 1
H, Ar). 13C NMR (125.7 MHz, CDCl3): δC = 14.7 (CH2),
19.2 (2 CH2), 22.7 (2 CH2), 30.8 (Me), 50.1 (CH), 58.8
(OMe), 60.1 (OMe), 127.9 (C), 128.3 (CH), 128.4 (CH),
130.4 (CH), 131.5 (C), 138.6 (C), 142.8 (C), 148.0 (C),
164.6 (C), 173.9 (C), 178.0 (C). MS: m/z (%) = 356 (M+,
13), 273 (28), 258 (21), 238 (39), 90 (78), 83 (100).
Anal. Calcd for C20H24N2O4 (356.42): C, 67.40; H, 6.79;
N, 7.86. Found: C, 67.38; H, 6.82; N, 7.82.
Dimethyl
4-((4-bromophenyl)amino)quinoline-2,3-
dicarboxylate (5b). Cream powder; yield: 0.33 g (80%);
mp: 166–168°C. IR (KBr) (νmax, cmÀ1): 3365, 1723,
1710, 1636, 1277. 1H NMR (500 MHz, CDCl3): δH = 3.58
(s, 3 H, OMe), 3.74 (s, 3 H, OMe), 6.25 (s, 1 H, NH), 7.49
3
3
(d, J = 7.9, 2 H, Ar), 7.55 (t, J = 8.0, 1 H, Ar), 7.63 (t,
3
3J = 8.0, 1 H, Ar), 7.90 (d, J = 7.9, 2 H, Ar), 8.02 (d,
3
3J = 8.0, 1 H, Ar), 8.26 (d, J = 8.0, 1 H, Ar). 13C NMR
Dimethyl
4-(cyclohexylamino)-6-nitroquinoline-2,3-
(125.7 MHz, CDCl3): δC = 57.3 (OMe), 59.8 (OMe),
127.2 (CH), 127.9 (2 CH), 128.2 (CH), 129.9 (CH), 130.2
(CH), 131.4 (2 CH), 133.8 (C), 141.8 (C), 142.8 (C),
148.0 (C), 149.8 (C), 158.0 (C), 168.2 (C), 174.9 (C),
177.1 (C). MS: m/z (%) = 414 (M+, 14), 337 (11), 259
dicarboxylate (5f). Yellow powder; yield: 0.33 g (85%);
mp: 176–178°C. IR (KBr) (νmax, cmÀ1): 3345, 1732,
1721, 1622, 1543, 1351, 1205. 1H NMR (500 MHz,
CDCl3): δH = 0.98–1.04 (m, 4 H, CH2), 1.48–1.55 (m, 2
H, CH2), 1.93–1.96 (m, 2 H, CH2), 2.17–2.22 (m, 2 H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2019
Synthesis of Functionalized Quinolines
CH2), 3.32–3.36 (m, 1 H, CH), 3.69 (s, 3 H, OMe), 3.89 (s,
3 H, OMe), 5.94 (s, 1 H, NH), 7.64 (d, 3J = 8.1, 1 H, Ar),
(125.7 MHz, CDCl3): δC = 14.8 (Me), 17.9 (Me), 22.6
(Me3C), 52.5 (Me3C), 60.9 (OCH2), 63.3 (OCH2), 125.3
(CH), 129.4 (CH), 130.4 (CH), 130.9 (CH), 132.5 (C),
135.4 (C), 141.8 (C), 144.1 (C), 162.0 (C), 177.9 (C),
179.2 (C). MS: m/z (%) = 344 (M+, 11), 287 (16), 268
(39), 272 (16), 198 (55), 76 (100), 73 (84). Anal. Calcd
for C19H24N2O4 (344.40): C, 66.26; H, 7.02; N, 8.13.
Found: C, 66.30; H, 7.04; N, 8.17.
3
7.77 (s, 1 H, Ar), 8.05 (d, J = 8.1, 1 H, Ar). 13C NMR
(125.7 MHz, CDCl3): δC = 14.7 (CH2), 19.2 (2 CH2),
23.0 (2 CH2), 55.8 (CH), 55.8 (OMe), 58.2 (OMe), 128.1
(C), 130.8 (CH), 134.0 (CH), 136.4 (C), 139.9 (CH),
142.0 (C), 145.5 (C), 151.0 (C), 165.6 (C), 176.1 (C),
178.8 (C). MS: m/z (%) = 387 (M+, 9), 304 (22), 289
(19), 269 (42), 121 (100), 98 (41). Anal. Calcd for
C19H21N3O6 (387.39): C, 58.91; H, 5.46; N, 10.85.
Found: C, 58.95; H, 5.50; N, 10.90.
Di-tert-butyl 6-chloro-4-((4-chlorophenyl)amino)quinoline-
2,3-dicarboxylate (5j).
Yellow powder; yield: 0.37 g
(77%); mp: 195–197°C. IR (KBr) (νmax, cmÀ1): 3366,
1
Diethyl
6-bromo-4-(phenylamino)quinoline-2,3-
1721, 1714, 1619, 1255. H NMR (500 MHz, CDCl3):
dicarboxylate (5g). Cream powder; yield: 0.38 g (86%);
mp: 164–166°C. IR (KBr) (νmax, cmÀ1): 3299, 1712,
1703, 1645, 1241. 1H NMR (500 MHz, CDCl3): δH = 1.58
(t, 3J = 6.8, 3 H, Me), 1.94 (t, 3J = 6.8, 3 H, Me), 4.47 (q,
3J = 6.8, 2 H, OCH2), 4.53 (q, 3J = 6.8, 2 H, OCH2), 6.00
(s, 1 H, NH), 7.63 (t, 3J = 7.7, 2 H, Ar), 7.68 (t, 3J = 7.7, 1
δH = 1.60 (s, 9 H, Me3C), 1.72 (s, 9 H, Me3C), 5.98 (s, 1
3
3
H, NH), 7.49 (d, J = 7.7, 2 H, Ar), 7.75 (d, J = 8.0, 1
3
H, Ar), 8.00–8.06 (m, 3 H, Ar), 8.30 (d, J = 8.0, 1 H,
Ar). 13C NMR (125.7 MHz, CDCl3): δC = 29.9 (Me3C),
30.7 (Me3C), 68.9 (Me3C), 70.2 (Me3C), 130.3 (CH),
130.4 (CH), 131.6 (2 CH), 132.0 (C), 132.4 (2 CH),
133.5 (C), 135.9 (CH), 136.5 (C), 142.2 (C), 145.5 (C),
148.7 (C), 158.7 (C), 163.0 (C), 177.6 (C), 178.8 (C).
MS: m/z (%) = 488 (M+, 3), 377 (15), 362 (34), 286 (55),
111 (100), 101 (59). Anal. Calcd for C25H26Cl2N2O4
(489.39): C, 61.36; H, 5.35; N, 5.72. Found: C, 61.34; H,
5.33; N, 5.70.
3
3
H, Ar), 8.05 (d, J = 7.7, 2 H, Ar), 8.10 (d, J = 8.0, 1 H,
3
Ar), 8.13 (s, 1 H, Ar), 8.40 (d, J = 8.0, 1 H, Ar). 13C
NMR (125.7 MHz, CDCl3): δC = 16.9 (Me), 18.6 (Me),
60.1 (OCH2), 62.4 (OCH2), 127.1 (2 CH), 128.0 (2 CH),
128.5 (CH), 129.3 (CH), 129.6 (CH), 130.3 (CH), 132.5
(C), 134.5 (C), 136.4 (C), 139.4 (C), 144.0 (C), 145.4 (C),
164.9 (C), 173.6 (C), 177.4 (C). MS: m/z (%) = 442 (M+,
8), 350 (15), 287 (23), 153 (32), 92 (100), 73 (66). Anal.
Calcd for C21H19BrN2O4 (443.29): C, 56.90; H, 4.32; N,
Di-tert-butyl
6-methyl-4-(phenylamino)quinoline-2,3-
dicarboxylate (5k). Cream powder; yield: 0.33 g (75%);
mp: 149–151°C. IR (KBr) (νmax, cmÀ1): 3344, 1723,
1715, 1624, 1225. 1H NMR (500 MHz, CDCl3):
δH = 1.26 (s, 9 H, Me3C), 1.67 (s, 9 H, Me3C), 2.08 (s, 3
H, Me), 5.99 (s, 1 H, NH), 7.31–7.35 (m, 3 H, Ar), 7.50
6.32. Found: C, 56.93; H, 4.37; N, 6.30.
Diethyl 4-((4-bromophenyl)amino)-6-methylquinoline-2,3-
dicarboxylate (5h). Cream powder; yield: 0.35 g (76%);
mp: 177–179°C. IR (KBr) (νmax, cmÀ1): 3222, 1714,
3
3
(d, J = 7.7, 2 H, Ar), 7.67 (s, 1 H, Ar), 8.05 (d, J = 8.0,
1 H, Ar), 8.32 (d, 3J = 8.0, 1 H, Ar). 13C NMR
(125.7 MHz, CDCl3): δC = 26.0 (Me), 29.1 (Me3C), 30.8
(Me3C), 69.5 (Me3C), 71.2 (Me3C), 128.4 (CH), 128.9
(CH), 129.1 (CH), 129.2 (CH), 129.5 (2 CH), 130.0
(CH), 133.2 (C), 133.4 (2 CH), 138.9 (C), 139.5 (C),
144.4 (C), 147.9 (C), 166.2 (C), 178.8 (C), 179.2 (C).
MS: m/z (%) = 434 (M+, 15), 357 (17), 342 (22), 232
(42), 101 (100), 92 (74), 77 (50). Anal. Calcd for
C26H30N2O4 (434.53): C, 71.87; H, 6.96; N, 6.45. Found:
C, 71.85; H, 6.95; N, 6.48.
1706, 1619, 1209. 1H NMR (500 MHz, CDCl3):
3
3
δH = 1.44 (t, J = 6.8, 3 H, Me), 1.90 (t, J = 6.8, 3 H,
3
Me), 2.43 (s, 3 H, Me), 4.40 (q, J = 6.8, 2 H, OCH2),
4.57 (q, J = 6.8, 2 H, OCH2), 6.12 (s, 1 H, NH), 7.41
(d, J = 7.7, 2 H, Ar), 7.92 (d, J = 7.7, 2 H, Ar), 8.07
3
3
3
3
3
(d, J = 8.0, 1 H, Ar), 8.13 (s, 1 H, Ar), 8.37 (d, J = 8.0,
1 H, Ar). 13C NMR (125.7 MHz, CDCl3): δC = 15.5
(Me), 18.7 (Me), 29.9 (Me), 61.4 (OCH2), 64.9 (OCH2),
127.2 (2 CH), 128.1 (CH), 128.4 (CH), 129.7 (CH),
130.8 (C), 131.4 (2 CH), 132.9 (C), 138.2 (C), 140.0 (C),
141.0 (C), 145.8 (C), 148.0 (C), 163.8 (C), 175.9 (C),
178.8 (C). MS: m/z (%) = 456 (M+, 5), 310 (16), 286
(25), 169 (49), 154 (100), 73 (70). Anal. Calcd for
C22H21BrN2O4 (457.32): C, 57.78; H, 4.63; N, 6.13.
Found: C, 57.72; H, 4.60; N, 6.19.
CONCLUSION
In conclusion, various quinoline derivatives via an
intramolecular C─H activation reaction as a novel and
one-pot protocol were synthesized from isocyanides,
aniline, and acetylene dicarboxylate. This reaction was
catalyzed by copper (I) and performed under mild
conditions. The availability of starting material-catalyst,
the ease of purification procedure, the absence of column
chromatography, and the high yield render this reaction
suitable for the synthesis of various quinoline derivatives.
Diethyl
(5i).
4-(tert-butylamino)quinoline-2,3-dicarboxylate
Cream powder; yield: 0.27 g (78%); mp: 110–
112°C. IR (KBr) (νmax, cmÀ1): 3298, 1719, 1710, 1634,
1231. 1H NMR (500 MHz, CDCl3): δH = 1.40 (t,
3J = 6.8, 3 H, Me), 1.52 (s, 9 H, Me3C), 1.85 (t, J = 6.8,
3
3 H, Me), 4.50 (q, 3J = 6.8, 2 H, OCH2), 4.58 (q,
3J = 6.8, 2 H, OCH2), 6.09 (s, 1 H, NH), 7.68 (t,
3J = 8.0, 1 H, Ar), 7.75 (t, J = 8.0, 1 H, Ar), 8.10 (d,
3
3J = 8.0, 1 H, Ar), 8.40 (d, J = 8.0, 1 H, Ar). 13C NMR
3
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

M. Nematpour, E. Rezaee, M. Jahani, and S. A. Tabatabai
Vol 000
Acknowledgment. This work was supported by the Research
Council of Shahid Beheshti University of Medical Sciences.
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SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of the
article.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet