Synthesis of Tetrahydrobenzo[g]Quinoline Derivatives Using Recoverable Carbonaceous Material as Heterogeneous Catalyst

Article abstract of DOI:10.1002/jhet.2799

A variety of substituted benzo[g]quinoline-5,10-dione derivatives were synthesized via one-pot three-component reaction of 2-hydroxynaphthalene-1,4-dione, aromatic aldehydes, and (E)-3-aminobut-2-enoates using carbonaceous material as the heterocyclic catalyst. This procedure is simple and efficient owing to short reaction times, easy work-up, and recovery of heterogeneous catalyst. This procedure develops an efficient and promising synthetic method to construction of the benzo[g]quinoline-5,10-dione skeleton.

Full text of DOI:10.1002/jhet.2799

Month 2017 Synthesis of Tetrahydrobenzo[g]Quinoline Derivatives Using Recoverable
Carbonaceous Material as Heterogeneous Catalyst
*
*
Jialing Lin, Jiameng Chen, Hongfu Ji, Jun Zhao, Furen Zhang, and Chunmei Li
School of Chemistry and Chemical Engineering, Zhejiang Key Laboratory of Alternative Technologies for Fine Chemicals
Process, Shaoxing University, Shaoxing, Zhejiang Province 312000, China
*
E-mail: frzhang@usx.edu.cn; lchm@usx.edu.cn
Additional Supporting Information may be found in the online version of this article.
Received July 19, 2016
DOI 10.1002/jhet.2799
Published online 00 Month 2017 in Wiley Online Library (wileyonlinelibrary.com).
A variety of substituted benzo[g]quinoline-5,10-dione derivatives were synthesized via one-pot three-
component reaction of 2-hydroxynaphthalene-1,4-dione, aromatic aldehydes, and (E)-3-aminobut-2-enoates
using carbonaceous material as the heterocyclic catalyst. This procedure is simple and efficient owing to
short reaction times, easy work-up, and recovery of heterogeneous catalyst. This procedure develops an ef-
ficient and promising synthetic method to construction of the benzo[g]quinoline-5,10-dione skeleton.
J. Heterocyclic Chem., 00, 00 (2017).
INTRODUCTION
as their stability and efficiency, easy preparation and
recoverability, simple synthetic procedure, and eco-
friendly nature [29–33], and has attracted more and more
attention and became a powerful catalyst for organic
synthesis [32]. Recently, Liang synthesized a novel
sulfonated carbonaceous material with polyvinyl alcohol
and hydroxyethylsulfuric acid and studied its features
through esterification and oxathioketalization [34]. In the
past several years, our group has developed a series of
synthetic methods that could provide easy access to
nitrogen-containing structures of chemical and biological
interest [35–37]. As a continuous work, herein we report
a simple and efficient method for the synthesis of benzo
[g]quinoline-5,10-dione derivatives through the one-pot
Nitrogen-containing heterocycles are of great importance
to both medicinal and organic chemists, and the design and
synthesis of these compounds continue to represent a
challenge from both an academic and industrial
perspective [1]. The benzo[g]quinoline-5,10-dione system
[2–4] represents the core skeleton of a pharmaceutically
important class of heterocyclic compounds that exhibits
lots of special biological activities, such as antimicrobial
activity [5], anticancer activity [6], antifungal agent
and sampangine [7–9], cytotoxic activity [10–13],
and cytotoxic activity [14]. Owing to the important
biological activities they exhibit, these compounds have
distinguished themselves as heterocycles of important
chemical and biological significance. Thus, developing an
efficient approach to the synthesis of these azaheterocycles
is of significance. Recently, many synthetic methods
for tetrahydrobenzo[g]quinoline derivatives have been
reported [15–28]. However, these methods usually
suffer from one or more disadvantages, such as use of
expensive substrates, poor chemoselectivity, limited
tolerance of functional groups, and unreusability of the
catalysts. Furthermore, the substrate scope for suitably
functionalized benzo[g]quinoline-5,10-dione building
blocks for the synthesis of structurally diverse libraries
also is limited. Therefore, the development of simple and
efficient synthetic routes for such azaheterocycles is a
great challenge in modern organic synthesis.
condensation
of
2-hydroxynaphthalene-1,4-dione,
aromatic aldehydes, and (E)-3-aminobut-2-enoates
using reusable sulfonated carbonaceous material as
heterogeneous catalyst.
RESULTS AND DISCUSSION
To a method from the literature [34], the sulfonated
carbonaceous material (C-SO3H) was prepared by mixing
polyvinyl alcohol, hydroxyethylsulfuric acid, and
deionized water, which was heated in an oven. Then, the
mixture was filtered, washed, and dried in a vacuum
oven. The acidity of the carbonaceous material (C-SO3H)
was 2.4 mmol/g.
Compared with liquid acid catalysts, carbonaceous
material as solid acid catalyst has many advantages, such
We began our study by mixing 2-hydroxynaphthalene-
1,4-dione (1), benzaldehyde (2a), and methyl (E)-3-
© 2017 Wiley Periodicals, Inc.

J. Lin, J. Chen, H. Ji, J. Zhao, F. Zhang, and C. Li
Vol 000
Table 1
Reaction conditions for the synthesis of benzo[g]quinoline-5,10-dione 4a.a
aminobut-2-enoate (3a) as the model reaction for condition
screening (Scheme 1). First, the catalyst for the synthesis of
4a was optimized, and the results were induced in Table 1.
We found that no product was given even after 24 h at 80°C
in the absence of catalyst (Table 1, entry 1). HY zeolite
and Amberlyst-15 as inorganic solid acid exhibit low
activity and only give low yields of product 4a (Table 1,
entries 2-3). The traditional liquid acid such as HOAc,
TsOH, and TFA also exhibit only moderate activities and
give 44–55% goal products (Table 1, entries 4–6). The
solid acid catalyst obtained single polyvinyl alcohol
(carbon) showed almost no activity because of little
functionalities on the surface (Table 1, entry 7).
However, the sulfonated carbonaceous material (C-SO3H)
showed very high activity in model reaction for product 4a
(Table 1, entry 8). Subsequently, the model reaction was
repeated many times with different amount of catalyst
loading. When the catalyst loading was increased from
10mg to 20mg, the yield of 4a was only subtly increased
from 89% to 90% (Table 1, entries 8–10). However,
when the catalyst loading was decreased from 10mg to
5 mg, the yield of 4a was decreased from 89% to 70%
(Table 1, entries 8, 11). Thus, the sulfonated
carbonaceous material (10 mg) was considered to be most
suitable.
Entry
Catalyst (mg)
Solvent
T (°C)
Yield (%)b
1
2
3
4
5
6
7
8
—
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
20
40
60
100
0
31
21
44
55
51
10
89
89
90
70
55
76
23
41
52
31
40
10
30
72
88
HY zeolite (10)
Amberlyst-15 (10)
HOAc (10)c
TsOH (10)c
TFA (10)c
Carbon (10)d
C-SO3H (10)
C-SO3H (15)
C-SO3H (20)
C-SO3H (5)
C-SO3H (10)
C-SO3H (10)
C-SO3H (10)
C-SO3H (10)
C-SO3H (10)
C-SO3H (10)
C-SO3H (10)
C-SO3H (10)
C-SO3H (10)
C-SO3H (10)
C-SO3H (10)
9
10
11
12
13
14
15
16
17
18
19
20
21
22
H2O
H2O
MeOH
EtOH
CH2Cl2
CHCl3
CH3CN
THF
Toluene
H2O
H2O
H2O
H2O
aReaction conditions: 1 (1.0 mmol), 2a (1.0 mmol), 3a (1.0 mmol),
C-SO3H (10 mg), and solvent (3.0 mL) in the sealed tube in 6 h.
bIsolated yields.
c10 mol%.
dThe carbonaceous material obtained from the single polyvinyl alcohol.
To further screen the reaction condition for
the synthesis, the model reaction was carried out
in different solvent, such as water, methanol,
ethanol, dichloromethane, chloroform, acetonitrile,
tetrahydrofuran, and toluene (Table 1, entries 12–18).
As illustrated in Table 1, the reaction using water as
solvent resulted in highest yields (Table 1, entries 12–18).
Thus, water was chosen as the solvent for subsequent
reactions. Then, the model substrates were mixed in
water at temperatures ranging from 20°C to 100°C
(Table 1, entries 8, 19–22), with an increment of 20°C.
The yield of product 4a was increased from 10% to
89% as the reaction temperature was raised from 20°C
to 80°C (Table 1, entries 8, 19–21). However, the yield
almost leveled off when the temperature was further
increased from 80°C to 100°C (Table 1, entries 8, 22).
Therefore, 80°C was considered to be most suitable and
chosen as the reaction conditions for all the following
reactions.
Using the most suitable condition, the reaction scope was
evaluated by using different substrates 2 and 3 (Scheme 2).
To our delight, aromatic aldehydes bearing either electron-
withdrawing or electron-donating functional groups, such
as fluoro, chloro, nitro, trifluoromethyl, methyl, methoxyl,
or isopropyl, were all found to be suitable for the reaction
with 2-hydroxynaphthalene-1,4-dione (1), and methyl (E)-
3-aminobut-2-enoate (3a) to obtain benzo[g]quinoline-5,
10-diones (4) in good to excellent yields (Table 2).
Meanwhile, we also noted that the aromatic aldehydes
with electron-deficient functional groups, such as chloro,
fluoro, bromo, nitro, or trifluoromethyl showed higher
reactivities than those with electron-rich functional
groups, such as methyl, methoxyl, or isopropyl and gave
higher yields. We attributed the higher reactivities of
electron-deficient functional groups aromatic aldehydes to
their electron absorption effect. Particularly noteworthy
was the fact that the bulky aromatic aldehyde, such as
1-naphthaldehyde and less reactive heterocyclic aldehyde,
Scheme 1. Synthesis of benzo[g]quinoline-5,10-dione 4a.
Scheme 2. Synthesis of benzo[g]quinoline-5,10-diones 4a–4t.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2017
Synthesis of Tetrahydrobenzo[g]Quinolines Using Sulfonated
Carbonaceous Material
Table 2
Synthesis of benzo[g]quinoline-5,10-dione derivatives catalyzed by sulfonated carbonaceous material.a
Mp (°C)
Reported [15]
Entry
Ar
R
Product
Time (h)
Yield (%)b
Found
1
2
3
4
5
6
7
8
C6H5
4-FC6H4
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
4a
4b
4c
4d
4e
4f
4 g
4 h
4i
6
6
6
6
6
6
6
6
6
6
6
8
8
8
6
6
6
6
6
8
89
87
89
86
83
80
82
85
81
82
84
76
80
68
83
88
83
84
81
71
250–252
246–248
221–222
228–230
235–236
238–240
199–200
201–202
298–300
210–212
229–230
202–204
185–186
208–210
236–238
206–208
184–186
200–202
225–226
203–204
248
—
225
—
—
239
—
199
—
207
—
—
189
—
232
209
182
198
222
207
4-ClCC6H4
4-NO2C6H4
4-CF3C6H4
2-ClC6H4
2-NO2C6H4
2,4-Cl2C6H3
2,6-Cl2C6H3
4-MeC6H4
4-OMeC6H4
4-iPrC6H4
1-Naphthyl
2-Thienyl
C6H5
9
10
11
12
13
14
15
16
17
18
19
20
4j
4 k
4 l
4 m
4n
4o
4p
4q
4r
4-ClC6H4
2,4-Cl2C6H3
4-NO2C6H4
4-MeC6H4
2-Thienyl
Et
Et
Et
Et
4 s
4 t
Et
aReaction conditions: 1 (1.0 mmol), 2 (1.0 mmol), 3 (1.0 mmol), C-SO3H (10 mg), and water (3.0 mL) at 80°C.
bIsolated yields.
such as thiophene-2-carbaldehyde, also exhibited good
reactivities and gave corresponding products with 80%
and 68% yields, respectively.
corresponding goal product was not obtained under
similar reaction conditions, probably because of the low
reactivity of aliphatic aldehyde.
To further study the scope of this methodology, a variety
of aromatic aldehydes were submitted to react with 2-
hydroxynaphthalene-1,4-dione (1), and ethyl (E)-3-
aminobut-2-enoate (3b). In all these cases, the reaction
proceeded smoothly to give the corresponding
goal products with 71% to 88% yields. Additionally, to
further demonstrate the efficiency of the methodology,
aliphatic aldehyde such as 3-methylbutanal was also
employed with 2-hydroxynaphthalene-1,4-dione (1), and
methyl (E)-3-aminobut-2-enoate (3a). Unfortunately, the
The domino reaction of 2-hydroxynaphthalene-1,4-
dione, aromatic aldehydes, and (E)-3-aminobut-2-enoate
probably follows the regular mechanism of acid-catalyzed
condensations. We speculated that the mechanism of the
domino reaction involves the reaction of sulfonated
carbonaceous material with the 2-hydroxynaphthalene-
1,4-dione by acting as an acid and playing a complex role
to give radical condensation intermediate between
2-hydroxynaphthalene-1,4-dione
(Scheme 3).
and
benzaldehyde
Scheme 3. Mechanism of the synthesis of 4.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

J. Lin, J. Chen, H. Ji, J. Zhao, F. Zhang, and C. Li
Vol 000
The reaction proceeds via intermediate A, formed by the
activation of 1 with solid acid. Subsequently, the
intermediate B, which could be isolated from the reaction
mixture [38], was formed via dehydration reaction under
the effect of catalyst. Then, the intermediate C was
on
a
400-MHz instrument (Bruker Avance 400
Spectrometer). Chemical shifts (δ) are given in ppm
relative to TMS as the internal reference, with coupling
constants (J) in Hz. 13C-NMR spectra were recorded at
100 MHz. Chemical shift were reported in ppm with the
internal chloroform signal at 77.0 ppm as a standard.
Elemental analysis was carried out on EuroEA elemental
analyzer.
generated from the reaction of enamine
3 with
intermediate B. Ultimately, the goal product 4 was given
followed by regioselective intramolecular condensation of
cyclization and dehydration. The differences of
electrophilicity of carbonyl and steric hindrance of
intermediate B explained that the formation of benzo[g]
quinoline-5,10-diones was highly regioselective. In
addition, the stabilizing electron-withdrawing group of
benzo[g]quinoline-5,10-dione [15,39,40] prevents the
aromatization of it even under severe reaction condition,
such as microwave or high reaction temperature, or high
active oxidants such as peroxide [41].
Subsequently, the recoverability of the sulfonated
carbonaceous material catalyst was examined using the
model reaction of 2-hydroxynaphthalene-1,4-dione (1),
benzaldehyde (2a), and methyl (E)-3-aminobut-2-enoate
(3a) under optimized conditions. Upon completion, the
crude solid was resolved with hot ethanol, and the
catalyst was filtered and dried in vacuum oven at 100°C
for 4–6h, it was used. To our delight, the recycled
catalyst could be reused four times without any further
treatment and only subtle loss in the catalytic activity was
observed. We attribute the slight loss in the catalytic
activity after the several runs to the minor losses in the
recyclability process.
Synthesis and characterization of the sulfuric acid groups
functionalized carbon [34].
method,
According to literature
the
polyvinyl alcohol (5.0 g),
hydroxyethylsulfuric acid (3.5 g), and deionized water
(50 mL) were added in Teflon-lined stainless steel
autoclaves, and heated at 180°C for 4h. Then, the
resulting mixture were filtered, washed with water and
methanol, and dried in a vacuum oven at 100°C for 4h.
The black goal product was obtained with about 50%
yield (according to polyvinyl alcohol).
Neutralization titration indicated that the acidity of the
solid acid was 2.4 mmol/g. According to XPS analysis,
almost all the S existed in the forms of sulfonic acid
groups, and many oxygen-containing groups besides the
carbonyl acid groups exist. The BET surface of the solid
acid was 146 m2/g. The 1040 and 1195cmꢀ1
absorbability of IR spectra indicated the existence of the
sulfuric acid groups. FT-IR spectra showed that the solid
acid contains resident functionalities such as hydroxyl
(3500 cmꢀ1), carboxylate (1704 cmꢀ1), C¼C groups
(1604 cmꢀ1), and C―O groups (1204 cmꢀ1).
General procedure for the synthesis of benzo[g]quinoline-
5,10-dione derivatives 4a–4t. 2-Hydroxynaphthalene-1,4-
dione (1, 1.0 mmol), aromatic aldehyde (2, 1.0mmol),
(E)-3-aminobut-2-enoate (3, 1.0 mmol), C-SO3H (10 mg),
and water (3.0 mL) were mixed and heated at 80°C for 6–
8 h. When the reaction was finished indicated by TLC
monitoring, the precipitate was filtered and dried along
with the catalyst. Then, the catalyst was recovered by
filtration, and the goal product was further purified by
recrystalization from EtOH (95%) to give the pure goal
CONCLUSIONS
In conclusion, we have developed sulfonated
carbonaceous material as heterogeneous catalyst catalyzed
domino reaction leading to synthesis of benzo[g]quinoline-
5,10-dione derivatives in good to excellent yields. The
reactions were conducted in water using readily available
and inexpensive substrates. This procedure shows several
advantages, such as concise reaction condition, water as
eco-friendly media, short reaction periods, the structural
diversity of products, and using sulfonated carbonaceous
material as recoverable catalyst.
product 4a–t.
Methyl 2-methyl-5,10-dioxo-4-phenyl-1,4,5,10-tetrahydrobenzo[g]
quinoline-3-carboxylate (4a) [15].
Red brown solid. M.p.
250–252°C. 1H-NMR (400MHz, CDCl3, δ ppm): 8.04 (d,
2H, J = 7.2 Hz, ArH), 7.64–7.71 (m, 2H, ArH), 7.35–7.37
(m, 2H, ArH), 7.22–7.24 (m, 2H, ArH), 7.12–7.16 (m,
2H, ArH + NH), 5.37 (s, 1H, CH), 3.66 (s, 3H, OMe),
2.54 (s, 3H, CH3). 13C-NMR (100MHz, CDCl3, δ ppm):
182.5, 180.1, 167.3, 145.1, 144.0, 136.8, 134.7, 133.0,
132.8, 130.3, 128.2, 128.1, 126.8, 126.5, 126.1, 119.4,
104.6, 51.2, 37.6, 19.5.
EXPERIMENTAL
General. Analytical thin layer chromatography (TLC)
was performed using Merck silica gel GF254 plates. Flash
column chromatography was performed on silica gel (300–
400mesh). Melting points were measured on an X-4
Methyl
4-(4-fluorophenyl)-2-methyl-5,10-dioxo-1,4,5,10-
tetrahydrobenzo[g]quinoline-3-carboxylate (4b). Red brown
1
solid. M.p. 246–248°C. H-NMR (400MHz, CDCl3, δ ppm):
8.04–8.06 (m, 2H, ArH), 7.71–7.75 (m, 1H, ArH), 7.64–7.68
(m, 1H, ArH), 7.31–7.35 (m, 2H, ArH), 7.10 (s, 1H, NH), 5.37
1
melting point apparatus. H-NMR spectra were recorded
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2017
Synthesis of Tetrahydrobenzo[g]Quinolines Using Sulfonated
Carbonaceous Material
(s, 1H, CH), 3.67 (s, 3H, OMe), 2.54 (s, 3H, CH3). 13C-NMR
(100MHz, CDCl3, δ ppm): 180.1, 179.9, 156.9, 155.4, 133.4,
132.8, 129.8, 126.6, 126.1, 124.9, 115.3, 115.1, 112.0, 51.3,
36.8, 19.6. Anal. Calcd for C22H16FNO4 (377.37): C 70.02, H
4.27, N 3.71; Found: C 69.87, H 4.57, N 3.66.
135.1, 133.0, 132.9, 132.6, 131.2, 129.9, 127.7, 126.8,
126.1, 124.5, 104.4, 51.4, 33.2, 19.7. Anal. Calcd for
C22H16N2O6 (404.38): C 65.35, H 3.99, N 6.93; Found:
C 64.98, H 4.06, N 7.11.
Methyl 4-(2,4-dichlorophenyl)-2-methyl-5,10-dioxo-1,4,5,10-
tetrahydrobenzo[g]quinoline-3-carboxylate (4h) [15].
Red
Methyl
4-(4-chlorophenyl)-2-methyl-5,10-dioxo-1,4,5,10-
tetrahydrobenzo[g]quinoline-3-carboxylate (4c).
[15]. Red
brown solid. M.p. 201–202°C. 1H-NMR (400MHz,
CDCl3, δ ppm): 8.01–8.07 (m, 2H, ArH), 7.62–7.74 (m,
2H, ArH), 7.31–7.36 (m, 2H, ArH), 7.11–7.14 (m, 2H,
ArH +NH), 5.71 (s, 1H, CH), 3.65 (s, 3H, OMe), 2.49 (s,
3H, CH3). 13C-NMR (100 MHz, CDCl3, δ ppm): 182.1,
179.9, 167.1, 143.8, 142.1, 137.3, 134.8, 134.0, 133.0,
132.8, 132.5, 129.5, 128.2, 127.2, 126.5, 126.1, 118.2,
brown solid. M.p. 221–222°C. 1H-NMR (400MHz,
CDCl3, δ ppm): 8.03–8.06 (m, 2H, ArH), 7.63–7.74 (m,
2H, ArH), 7.19–7.30 (m, 2H, ArH), 7.12 (s, 1H, NH),
5.36 (s, 1H, CH), 3.66 (s, 3H, OMe), 2.53 (s, 3H, CH3).
13C-NMR (100 MHz, CDCl3, δ ppm): 182.4, 179.9,
167.2, 144.3, 136.8, 134.8, 132.8, 132.7, 132.6, 130.1,
129.5, 128.5, 126.5, 126.1, 118.9, 104.3, 51.2, 37.1, 19.6.
104.4, 51.2, 36.2, 19.4.
Methyl 4-(2,6-dichlorophenyl)-2-methyl-5,10-dioxo-1,4,5,10-
tetrahydrobenzo[g]quinoline-3-carboxylate (4i). Red brown
Methyl
4-(4-nitrophenyl)-2-methyl-5,10-dioxo-1,4,5,10-
(4d).
tetrahydrobenzo[g]quinoline-3-carboxylate
Red
brown solid. M.p. 228–230°C. 1H-NMR (400MHz,
CDCl3, δ ppm): 8.12 (d, 2H, J = 8.8 Hz, ArH), 8.03–8.09
(m, 2H, ArH), 7.74 (t, 1H, J =7.6 Hz, ArH), 7.68 (t, 1H,
J =7.6 Hz, ArH), 7.55 (d, 2H, J = 8.8 Hz, ArH), 7.17 (s,
1H, NH), 5.50 (s, 1H, CH), 3.67 (s, 3H, OMe), 2.57 (s,
3H, CH3). 13C-NMR (100 MHz, CDCl3, δ ppm): 182.5,
179.6, 167.1, 152.4, 137.1, 135.1, 133.1, 133.0, 129.2,
126.6, 126.2, 123.8, 117.9, 113.8, 51.5, 37.9, 19.8. Anal.
Calcd for C22H16N2O6 (404.38): C 65.35, H 3.99, N
solid. M.p. 298–300°C. 1H-NMR (400MHz, CDCl3, δ
ppm): 8.04–8.06 (m, 1H, ArH), 7.99–8.01 (m, 1H, ArH),
7.76–7.77 (m, 1H, ArH), 7.62–7.71 (m, 2H, ArH), 7.23–
7.25 (m, 1H, ArH), 7.22 (s, 1H, NH), 7.04 (t, 1H,
J = 8.0 Hz, ArH), 6.26 (s, 1H, CH), 3.59 (s, 3H, OMe),
2.42 (s, 3H, CH3). 13C-NMR (100MHz, CDCl3, δ ppm):
182.3, 179.7, 167.3, 145.0, 138.7, 138.2, 135.0, 132.7,
129.8, 128.3, 127.9, 126.5, 126.0, 116.0, 101.5, 50.8,
36.5, 19.5. Anal. Calcd for C22H15Cl2NO4 (428.27): C
6.93; Found: C 65.08, H 4.28, N 6.68.
61.70, H 3.53, N 3.27; Found: C 61.52, H 3.67, N 2.96.
Methyl 2-methyl-5,10-dioxo-4-(p-tolyl)-1,4,5,10-tetrahydrobenzo[g]
quinoline-3-carboxylate (4j) [15]. Red brown solid. M.p. 210–
Methyl 2-methyl-5,10-dioxo-4-(4-(trifluoromethyl)phenyl)-
1,4,5,10-tetrahydrobenzo[g] quinoline-3-carboxylate (4e).
1
1
Red brown solid. M.p. 235–236°C. H-NMR (400MHz,
212°C. H-NMR (400MHz, CDCl3, δ ppm): 8.04 (d, 2H,
CDCl3, δ ppm): 8.06 (t, 2H, J = 7.6 Hz, ArH), 7.71–7.75
(m, 1H, ArH), 7.63–7.69 (m, 1H, ArH), 7.48–7.52 (m,
4H, ArH), 7.14 (s, 1H, NH), 5.46 (s, 1H, CH), 3.67 (s,
3H, OMe), 2.56 (s, 3H, CH3). 13C-NMR (100MHz,
CDCl3, δ ppm): 182.3, 179.7, 167.3, 152.4, 138.8, 137.1,
135.2, 133.0, 129.1, 126.6, 126.3, 123.9, 117.8, 104.3,
52.1, 37.9, 19.8. Anal. Calcd for C23H16F3NO4 (427.38):
C 64.64, H 3.77, N 3.28; Found: C 64.55, H 4.01, N 3.00.
J=8.0Hz, ArH), 7.68–7.73 (m, 1H, ArH), 7.62–7.66 (m, 1H,
ArH), 7.25 (d, 2H, J=8.0Hz, ArH), 7.10 (s, 1H, NH), 7.05 (d,
2H, J=8.0Hz, ArH), 5.35 (s, 1H, CH), 3.67 (s, 3H, OMe),
2.54 (s, 3H, CH3), 2.26 (s, 3H, CH3). 13C-NMR (100MHz,
CDCl3, δ ppm): 182.4, 180.1, 167.4, 143.9, 142.5, 136.8,
136.4, 134.7, 132.9, 132.6, 130.6, 129.1, 128.1, 126.6, 125.9,
119.4, 104.6, 51.2, 36.9, 21.0.
Methyl 4-(4-methoxyphenyl)-2-methyl-5,10-dioxo-1,4,5,10-
tetrahydrobenzo[g]quinoline-3-carboxylate
(4k).
Red
Methyl
4-(2-chlorophenyl)-2-methyl-5,10-dioxo-1,4,5,10-
tetrahydrobenzo[g]quinoline-3-carboxylate (4f) [15].
Red
brown solid. M.p. 229–230°C. 1H-NMR (400MHz,
CDCl3, δ ppm): 8.05 (d, 2H, J= 7.6 Hz, ArH), 7.73 (t,
1H, J = 6.8 Hz, ArH), 7.65 (t, 1H, J= 7.6 Hz, ArH),
7.30 (d, 2H, J = 8.4 Hz, ArH), 7.08 (s, 1H, NH), 6.78
(d, 2H, J = 8.4 Hz, ArH), 5.33 (s, 1H, CH), 3.74 (s,
3H, OMe), 3.67 (s, 3H, OMe), 2.53 (s, 3H, CH3).
13C-NMR (100MHz, CDCl3, δ ppm): 183.9, 182.6,
168.4, 158.4, 143.8, 137.8, 136.6, 134.8, 132.7, 130.2,
129.2, 126.5, 126.0, 113.8, 55.2, 51.3, 36.5, 19.6.
1
brown solid M.p. 238–240°C. H-NMR (400 MHz, CDCl3,
δ ppm): 8.01–8.06 (m, 2H, ArH), 7.63–7.72 (m, 2H, ArH),
7.37–7.41 (m, 2H, ArH), 7.26–7.32 (m, 1H, ArH), 7.07–
7.16 (m, 3H, ArH+NH), 5.75 (s, 1H, CH), 3.66 (s, 3H,
OMe), 2.49 (s, 3H, CH3). 13C-NMR (100 MHz, CDCl3, δ
ppm): 182.2, 179.9, 167.3, 143.8, 143.6, 137.3, 134.7,
133.2, 132.8, 132.6, 131.5, 130.1, 129.7, 128.0, 126.8,
126.5, 126.0, 118.8, 104.6, 51.0, 36.2, 19.4.
Methyl
4-(2-nitrophenyl)-2-methyl-5,10-dioxo-1,4,5,10-
(4g).
Anal. Calcd for C23H19NO5 (389.41): C 70.94, H
4.92, N 3.60; Found: C 70.83, H 4.60, N 3.89.
Methyl 4-(4-isopropylphenyl)-2-methyl-5,10-dioxo-1,4,5,10-
tetrahydrobenzo[g]quinoline-3-carboxylate
Red
brown solid. M.p. 199–200°C. 1H-NMR (400MHz,
CDCl3, δ ppm): 8.06 (t, 2H, J = 8.4 Hz, ArH), 7.81 (m,
1H, J = 8.0Hz, ArH), 7.66–7.72 (m, 2H, ArH), 7.46–7.48
(m, 2H, ArH), 7.12 (s, 1H, NH), 6.22 (s, 1H, CH), 3.62
(s, 3H, OMe), 2.52 (s, 3H, CH3). 13C-NMR (100MHz,
CDCl3, δ ppm): 182.0, 179.8, 167.0, 144.5, 140.2, 137.4,
tetrahydrobenzo[g]quinoline-3-carboxylate (4l).
Red brown
solid. M.p. 202–204°C. 1H-NMR (400 MHz, CDCl3, δ
ppm): 8.06 (d, 2H, J=7.6 Hz, ArH), 7.65–7.72 (m, 2H,
ArH), 7.26–7.28 (m, 3H, ArH+NH), 7.10 (d, 2H,
J= 8.0Hz, ArH), 5.39 (s, 1H, CH), 3.69 (s, 3H, OMe),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

J. Lin, J. Chen, H. Ji, J. Zhao, F. Zhang, and C. Li
Vol 000
2.80–2.83 (m, 1H, CH), 2.55 (s, 3H, CH3), 1.19 (d, 6H,
J=6.8Hz, CH3). 13C-NMR (100 MHz, CDCl3, δ ppm):
182.5, 180.1, 167.3, 144.0, 142.3, 136.8, 136.6, 134.7,
132.8, 132.6, 130.2, 129.3, 128.0, 126.5, 125.9, 119.0,
104.2, 51.0, 37.0, 32.9, 23.5, 19.5. Anal. Calcd for
C25H23NO4 (401.46): C 74.80, H 5.77, N 3.49; Found: C
75.12, H 6.01, N 3.31.
CDCl3, δ ppm): 8.01–8.06 (m, 2H, ArH), 7.61–7.73 (m,
2H, ArH), 7.31–7.36 (m, 2H, ArH), 7.11–7.16 (m, 2H,
ArH +NH), 5.70 (s, 1H, CH), 4.08–4.16 (m, 2H, CH2),
2.42 (s, 3H, CH3), 1.23 (t, 3H, J =7.2 Hz, CH3). 13C-
NMR (100 MHz, CDCl3, δ ppm): 182.2, 179.8, 166.7,
144.1, 143.8, 142.0, 137.4, 135.0, 133.8, 133.0, 132.8,
132.6, 130.3, 129.4, 127.1, 126.5, 126.1, 117.8, 104.4,
60.2, 36.1, 19.5, 14.2.
Methyl
2-methyl-4-(naphthalen-1-yl)-5,10-dioxo-1,4,5,10-
tetrahydrobenzo[g]quinoline-3-carboxylate (4m) [15].
Red
Ethyl
2-methyl-4-(4-nitrophenyl)-5,10-dioxo-1,4,5,10-
brown solid. M.p. 185–186°C. 1H-NMR (400MHz,
CDCl3, δ ppm): 8.88 (d, 1H, J=8.4Hz, ArH), 8.04–8.08
(m, 1H, ArH), 7.90–7.93 (m, 1H, ArH), 7.78 (d, 1H,
J=8.0Hz, ArH), 7.58–7.72 (m, 4H, ArH), 7.45–7.50 (m,
2H, ArH), 7.30–7.35 (m, 1H, ArH), 7.15 (s, 1H, NH),
6.12 (s, 1H, CH), 3.54 (s, 3H, OMe), 2.55 (s, 3H, CH3).
13C-NMR (100MHz, CDCl3, δ ppm): 182.4, 180.2, 167.4,
144.7, 142.9, 136.8, 134.7, 133.4, 133.0, 132.7, 130.9,
130.3, 128.2, 127.8, 127.5, 126.6, 126.5, 126.1, 125.8,
125.6, 125.1, 120.6, 106.6, 50.9, 32.7, 19.5.
tetrahydrobenzo[g]quinoline-3-carboxylate (4r) [15].
Red
brown solid. M.p. 200–202°C. 1H-NMR (400MHz,
CDCl3, δ ppm): 8.11 (d, 2H, J = 8.8 Hz, ArH), 8.01–8.07
(m, 2H, ArH), 7.65–7.75 (m, 2H, ArH), 7.56 (d, 2H,
J = 8.8 Hz, ArH), 7.18 (s, 1H, NH), 5.50 (s, 1H, CH),
4.09-4.17 (m, 2H, CH2), 2.56 (s, 3H, CH3), 1.21 (t, 3H,
J = 7.2 Hz, CH3). 13C-NMR (100MHz, CDCl3, δ ppm):
182.2, 179.6, 166.4, 152.6, 144.6, 137.2, 135.0, 133.1,
132.6, 130.1, 129.4, 126.6, 126.3, 123.6, 117.9, 104.0,
60.2, 38.4, 19.5, 14.2.
Methyl
2-methyl-5,10-dioxo-4-(thiophen-2-yl)-1,4,5,10-
Ethyl 2-methyl-5,10-dioxo-4-(p-tolyl)-1,4,5,10-tetrahydrobenzo[g]
quinoline-3-carboxy-late (4s) [15]. Red brown solid. M.p.
tetrahydrobenzo[g]quinoline-3-carboxylate (4n). Red brown
solid. M.p. 208–210°C. 1H-NMR (400MHz, CDCl3, δ
ppm): 8.12 (d, 1H, J=6.8Hz, ArH), 8.07 (d, 1H, J=7.2Hz,
ArH), 7.73–7.77 (m, 1H, ArH), 7.68 (t, 1H, J=7.2Hz,
ArH), 7.41–7.43 (m, 1H, ArH), 7.21 (s, 1H, NH), 7.10–7.12
(m, 1H, ArH), 6.88-6.90 (m, 1H, ArH), 5.72 (s, 1H, CH),
3.68 (s, 3H, OMe), 2.58 (s, 3H, CH3). 13C-NMR (100MHz,
CDCl3, δ ppm): 182.9, 180.3, 167.1, 157.4, 142.9, 137.9,
136.5, 132.5, 130.3, 129.1, 126.0, 104.8, 55.6, 36.4, 19.6.
Anal. Calcd for C20H15NO4S (365.40): C 65.74, H 4.14, N
1
225–226°C. H-NMR (400MHz, CDCl3, δ ppm): 8.01–
8.06 (m, 2H, ArH), 7.61–7.71 (m, 2H, ArH), 7.24–7.27
(m, 2H, ArH), 7.03–7.07 (m, 2H, ArH), 5.33 (s, 1H, CH),
4.09–4.15 (m, 2H, CH2), 2.52 (s, 3H, CH3), 2.25 (s, 3H,
CH3), 1.22 (t, 3H, J=7.2Hz, CH3). 13C-NMR (100MHz,
CDCl3, δ ppm): 182.4, 178.0, 166.8, 143.3, 142.7, 136.8,
136.3, 134.7, 132.8, 132.5, 130.2, 129.0, 128.2, 126.5,
125.9, 119.4, 104.9, 60.0, 37.1, 20.9, 19.5, 14.1.
Ethyl
2-methyl-5,10-dioxo-4-(thiophen-2-yl)-1,4,5,10-
tetrahydrobenzo[g]quinoline-3-carboxylate (4t) [15].
Red
3.83; Found: C 65.58, H 4.41, N 4.11.
brown solid. M.p. 203–204°C. 1H-NMR (400MHz,
CDCl3, δ ppm): 8.05–8.12 (m, 2H, ArH), 7.64–7.77
(m, 2H, ArH), 7.20 (s, 1H, ArH), 7.09–7.11 (m, 1H, ArH),
6.85–6.89 (m, 2H, ArH), 5.71 (s, 1H, CH), 4.14–4.20
(m, 2H, CH2), 2.53 (s, 3H, CH3), 1.25 (t, 3H, J=7.2Hz,
CH3). 13C-NMR (100MHz, CDCl3, δ ppm): 182.3, 179.9,
166.7, 148.9, 144.1, 136.8, 134.7, 132.8, 130.2, 126.8, 126.7,
126.1, 124.6, 124.3, 118.1, 104.5, 60.2, 32.1, 19.4, 14.2.
Ethyl 2-methyl-5,10-dioxo-4-phenyl-1,4,5,10-tetrahydrobenzo[g]
quinoline-3-carboxylate (4o) [15]. Red brown solid. M.p. 236–
1
238°C. H-NMR (400 MHz, CDCl3, δ ppm): 8.03 (d, 2H,
J= 7.6 Hz, ArH), 7.60–7.70 (m, 2H, ArH), 7.36–7.39 (m, 2H,
ArH), 7.22–7.25 (m, 2H, ArH), 7.12–7.16 (m, 2H, ArH+ NH),
5.37 (s, 1H, CH), 4.10 (m, 2H, CH2), 3.66 (s, 3H, OMe), 2.52
(s, 3H, CH3), 1.20 (t, 3H, J=7.2Hz, CH3). 13C-NMR
(100MHz, CDCl3, δ ppm): 182.4, 179.9, 166.8, 145.4, 143.6,
136.8, 134.7, 132.8, 132.6, 130.2, 128.3, 128.1, 126.7, 126.5,
125.1, 119.3, 104.6, 60.0, 37.6, 19.4, 14.1.
Ethyl
4-(4-chlorophenyl)-2-methyl-5,10-dioxo-1,4,5,10-
Acknowledgments. This work was supported by the Natural
Science Foundation of Zhejiang Province (No. LY16B020007)
and the Foundation of Education Department of Zhejiang
Province (No. Y201533906).
tetrahydrobenzo[g]quinoline-3-carboxylate (4p) [15].
Red
brown solid M.p. 206–208°C. 1H-NMR (400MHz,
CDCl3, δ ppm): 8.01–8.05 (m, 2H, ArH), 7.60–7.72 (m,
2H, ArH), 7.31 (d, 2H, J = 8.0 Hz, ArH), 7.21 (d, 2H,
J =8.4 Hz, ArH), 7.13 (s, 1H, NH), 5.35 (s, 1H, CH),
4.08–4.15 (m, 2H, CH2), 2.53 (s, 3H, CH3), 1.22 (t, 3H,
J =7.2 Hz, CH3). 13C-NMR (100 MHz, CDCl3, δ ppm):
182.4, 179.9, 166.7, 144.1, 143.8, 136.8, 134.7, 132.8,
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet