Glycine-catalyzed easy and efficient one-pot synthesis of polyhydroquinolines through hantzsch multicomponent condensation under controlled microwave

Article abstract of DOI:10.1002/jhet.308

(Chemical Equation Presented) Glycine, a novel heterogeneous organocatalyst, is found to be highly effective for the synthesis of polyhydroquinoline derivatives in a one-pot multicomponent reaction via Hantzsch condensation under controlled microwave (MW)

Full text of DOI:10.1002/jhet.308

194
Glycine-Catalyzed Easy and Efficient One-Pot Synthesis of
Polyhydroquinolines Through Hantzsch Multicomponent
Condensation under Controlled Microwave
Vol 47
Satish Kumar Singh and Krishna Nand Singh*
Department of Chemistry, Banaras Hindu University, Varanasi-221005, India
*E-mail: knsinghbhu@yahoo.co.in
Received September 19, 2009
DOI 10.1002/jhet.308
Published online 8 January 2010 in Wiley InterScience (www.interscience.wiley.com).
Glycine, a novel heterogeneous organocatalyst, is found to be highly effective for the synthesis of
polyhydroquinoline derivatives in a one-pot multicomponent reaction via Hantzsch condensation under
controlled microwave (MW) irradiation. The combination of glycine and MW has promising features
for the reaction response, such as the shortest reaction time, excellent product yields, and simple work-
up of the products.
J. Heterocyclic Chem., 47, 194 (2010).
INTRODUCTION
thermal energy [12], ionic liquid [13], TMSCl-NaI [14],
metal triflates [15], grinding [16], Hy-Zeolite [17],
montmorillonite K-10 [18], cerium(IV) ammonium ni-
trate [19], iron(III) trifluoroacetate [20], HClO4-SiO2
[21], heteropoly acid [22], molecular iodine [23], PTSA
[24], L-proline and derivatives [25], nickel [26], poly-
mers [27], and Baker’s yeast [28]. Most of these proc-
esses, however, suffer from one or other drawbacks such
as longer reaction time, lower product yield, harsh con-
ditions, high costs, and use of hazardous catalysts. As a
result, an eco-safe and efficient alternative method for
the preparation of polyhydroquinoline is highly desira-
ble. As there is no report on the use of glycine as an
organocatalyst in the Hantzsch condensation, we wish to
demonstrate the catalytic activity of this organocatalyst
in the synthesis of polyhydroquinolines.
Microwave (MW) irradiation has evolved as a power-
ful method to perform organic synthesis with great suc-
cess, particularly in the light of the current paradigm
shift to ‘‘green chemistry.’’ It provides chemical proc-
esses with special attributes, such as enhanced reaction
rates, higher yields of pure products, better selectivity,
improved ease of manipulation, rapid optimization of
reactions, and several eco-friendly advantages [1]. An
important way to improve synthetic efficiency and to
give access to a multitude of diversified molecules from
simple building blocks is the development of multicom-
ponent synthesis. Multicomponent reactions (MCRs)
have recently taken a new dimension in organic synthe-
sis, as they comply well with the requirements for ideal
organic syntheses [2,3]. According to the current syn-
thetic and environmental requirements, MCRs using
MW methodology are of great interest.
RESULTS AND DISCUSSION
Polyhydroquinoline derivatives have a great deal of
importance because of their diverse medicinal applica-
tions, which include calcium channel activity, vasodila-
tors, bronchodilators, antiatherosclerotics, hepatoprotec-
tive, antidiabetic, antihypertensive, neuroprotectant, pla-
telet antiaggregatory activity, cerebral antischemic activ-
ity, and chemosensitizer activity [4–10]. Owing to the
remarkable potential of these compounds as a source of
valuable drugs, various methods have been reported
using conditions such as conventional heating [11], solar
We report herein a benign, rapid, and efficient four-
component, one-pot synthesis of polyhydroquinolines in
excellent yields using aromatic aldehydes, dimedone,
ethyl acetoacetate, and ammonium acetate in the pres-
ence of catalytic amount of glycine (10 mol %) in ace-
tonitrile under monomode MW irradiation (Scheme 1).
To optimize the synthesis, a typical four-component
reaction of benzaldehyde 1a, dimedone 2, ethyl acetoac-
etate 3, and ammonium acetate 4 was undertaken using
C
V
2010 HeteroCorporation

January 2010
Glycine-Catalyzed Easy and Efficient One-Pot Synthesis of Polyhydroquinolines
through Hantzsch Multicomponent Condensation under Controlled Microwave
195
Scheme 1
a catalytic amount of different amino acids such as L-
alanine, L-valine, and glycine in different solvents such
as acetonitrile, ethanol, and water under varying reac-
tion conditions to obtain the corresponding polyhydro-
quinoline derivative 5a (Table 1). Consistent with
Table 1, the optimum yield (95%) of product 5a was
obtained in the presence of catalytic amount of glycine
(10 mol %) in solvent acetonitrile (entry 6) in 1 min
under single-mode MW heating (180 W, 80ꢀC).
Decreasing the catalyst levels, MW power or tempera-
ture reduced the product yield considerably (Table 1;
Entries 13, 16, and 17). An increase in the molar pro-
portion of catalyst, MW power, and temperature did
not bring about any further increase in the product
yield, rather, a bit diminution was observed (Table 1;
entries 14, 15, 18, and 19). It is assumed that the
acidic hydrogen of carboxylic function and the small
size of glycine play a key role in the catalysis of the
reaction. Under the optimized set of reaction conditions
(entry 6), a number of aromatic aldehydes 1 were
allowed to undergo MCR with 2, 3, and 4 in a molar
ratio of 1:1:1:1.2 in the presence of glycine (10 mol
%) in acetonitrile under MW (180 W, 80ꢀC) heating.
The results are given in Table 2. All the electron-rich
and electron-deficient aldehydes worked well leading to
excellent yields of products.
After completion of the reaction, the resulting precipi-
tate was filtered and recrystallized from methanol to
yield pure substituted polyhydroquinolines 5a–5n. All
the products were crystalline and fully characterized on
the basis of their melting points, elemental analyses, and
1
spectral data (IR, H-NMR, and 13C-NMR).
Table 1
Optimization of reaction conditions for the multicomponent synthesis of 4a.
Reaction conditions
Room temperature
Time (h) Yield (%)
Reflux
Time (min)
Microwaveb
Entry
Catalysta
Solvent
Yield (%)
Time (min)
Yield (%)
1
2
3
–
Water
3.0
3.0
3.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
–
14
15
15
54
57
64
42
46
52
46
50
56
57
64
63
–
60
60
60
30
20
20
20
20
20
20
20
20
30
30
30
–
28
29
32
61
68
86
51
58
66
57
61
72
79
84
80
–
5
5
5
1
1
1
1
1
1
1
1
1
3
2
2
3
3
2
2
46
50
54
75
84
95
63
72
78
70
78
86
87
95
93
89
88
93
95
–
–
Ethanol
MeCN
Water
Ethanol
MeCN
Water
Ethanol
MeCN
Water
4
5
Glycine
Glycine
Glycine
L-Alanine
L-Alanine
L-Alanine
L-Valine
L-Valine
L-Valine
Glycine
Glycine
Glycine
Glycine
Glycine
Glycine
Glycine
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Ethanol
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
–
–
–
–
–
–
–
–
–
–
–
–
a Catalyst concentration 10 mol % except for entries 13 (5 mol %), 14 (15 mol %), and 15 (20 mol %).
b Microwave heating performed on 180 W power and 80ꢀC temperature except for entries 16 (120 W, 80ꢀC), 17 (180 W, 50ꢀC), 18 (250 W,
80ꢀC), and 19 (180 W, 100ꢀC).
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

196
S. K. Singh and K. N. Singh
Vol 47
Table 2
Glycine-catalyzed Hantzsch condensation to polyhydroquinoline derivatives.a
Mp (ꢀC)
Product
Ar
Time (min)
Yieldb (%)
Obs
Lit
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
C6H5
4-CH3C6H4
4-CH3OC6H4
4-ClC6H4
1
1
1
2
2
2
2
2
3
3
2
2
2
2
95
96
98
97
94
96
93
95
93
91
94
95
90
94
203–205
259–260
256–257
246–248
192–193
254–256
235–237
184–186
243–245
176–177
211–213
232–233
247–249
243–245
202–204 [15(a)]
260–261 [15(a)]
257–259 [15(a)]
245–246 [21]
–
3-ClC6H4
4-BrC6H4
3-BrC6H4
4-FC6H4
253–255 [15(a)]
234–236 [16]
184–186 [15(a)]
243–244 [21]
178–179 [21]
211–212 [21]
229–231 [15(a)]
246–248 [15(a)]
242–244 [21]
4-NO2C6H4
3-NO2C6H4
4-OH-3-CH3OC6H3
4-(CH3)2NC6H4
2-Furyl
2,4-Cl2C6H3
a Microwave heating performed on 180 W power and 80ꢀC temperature.
b Isolated yield.
product was finally recrystallized from methanol to afford the
pure products 5a–5n.
Ethyl 2,7,7-trimethyl-5-oxo-4-phenyl-1,4,5,6,7,8-hexahydro-
quinoline-3-carboxylate (5a). IR (KBr): 3289, 3080, 2961,
CONCLUSIONS
In conclusion, the present MW irradiation procedure
provides an easy and efficient access to polyhydroquino-
lines via Hantzsch condensation using glycine as an
organocatalyst. The mildness of the conversion, experi-
mental simplicity, compatibility with various functional
groups, excellent product yield, shorter reaction time,
and the easy work-up procedure make this approach
more attractive in synthesizing a variety of such
derivatives.
1699, 1612 cmꢁ1
;
1H-NMR (300 MHz, CDCl3): d ¼ 7.26–
7.31 (m, 2H), 7.17–7.22 (m, 2H), 7.07–7.11 (m, 1H), 5.85 (s,
1H), 5.05 (s, 1H), 4.05 (q, J ¼ 7.2 Hz, 2H), 2.38 (s, 3H),
2.18–2.31 (m, 4H), 1.19 (t, J ¼ 7.2 Hz, 3H), 1.08 (s, 3H),
0.94 (s, 3H); 13C-NMR (75 MHz, CDCl3): d ¼ 195.70,
167.47, 148.72, 147.05, 143.67, 127.96, 127.83, 125.98,
111.92, 105.93, 59.78, 50.72, 40.85, 36.55, 32.64, 29.41,
27.08, 19.24, 14.17; Anal. Calcd. for C21H25NO3: C, 74.31; H,
7.42; N, 4.13; Found: C, 74.23; H, 7.48; N, 4.19.
Ethyl 4-(4-methylphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-
hexahydroquinoline-3-carboxylate (5b). IR (KBr): 3276,
EXPERIMENTAL
1
3078, 2960, 1702, 1646 cmꢁ1; H-NMR (300 MHz, CDCl3): d
All the chemicals were procured from Aldrich, USA and E.
Merck, Germany and were purified before use. IR spectra were
recorded on a JASCO FT/IR-5300 spectrophotometer. NMR
spectra were run on a JEOL AL300 FTNMR spectrometer;
chemical shifts are given in d ppm, relative to TMS as an in-
ternal standard. Elemental microanalysis was performed on
Exeter Analytical Model CE-440 CHN analyzer. Melting
points were measured in open capillaries and are uncorrected.
The MW irradiation was effected using the CEM’s Discover
Bench Mate (magnetron frequency 2455 MHz) single-mode
MW synthesis system using safe pressure regulation 10-mL
pressurized vials with ‘‘snap-on’’ cap.
General procedure for the synthesis of polyhydroquino-
lines 5. A mixture of aldehyde 1 (1 mmol), dimedone 2 (1
mmol), ethyl acetoacetate 3 (1 mmol), ammonium acetate 4
(1.2 mmol), glycine (10 mol %), and acetonitrile (1 mL) was
placed in a sealed pressure regulation 10-mL pressurized vial
with ‘‘snap-on’’ cap and was irradiated in the single-mode
MW synthesis system at 180 W power and 80ꢀC temperature
for 1–3 min. After completion of reaction (TLC), the mixture
was cooled and the resulting product was washed with cold
water to remove any unreacted ammonium acetate. The crude
¼ 7.16 (d, J ¼ 8.4 Hz, 2H), 7.03 (d, J ¼ 8.4 Hz, 2H), 5.69 (s,
1H), 5.07 (s, 1H), 4.09 (q, J ¼ 7.2 Hz, 2H), 2.37 (s, 3H), 2.32
(s, 3H), 2.16–2.29 (m, 4H), 1.23 (t, J ¼ 7.2 Hz, 3H), 1.06 (s,
3H), 0.95 (s, 3H); 13C-NMR (75 MHz, CDCl3): d ¼ 195.68,
167.39, 148.74, 146.95, 143.71, 127.97, 127.83, 126.07,
112.01, 105.98, 59.83, 50.77, 40.92, 36.59, 32.73, 29.45,
27.06, 19.81, 19.23, 14.16; Anal. Calcd. for C22H27NO3: C,
74.76; H, 7.70; N, 3.96; Found: C, 74.85; H, 7.66; N, 3.90.
Ethyl 4-(4-methoxyphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-
hexahydroquinoline-3-carboxylate (5c). IR (KBr): 3279, 3079,
2959, 1702, 1646 cmꢁ1
;
1H-NMR (300 MHz, CDCl3): d ¼
7.21 (d, J ¼ 8.4 Hz, 2H), 6.73 (d, J ¼ 8.4 Hz, 2H), 5.75 (s,
1H), 4.99 (s, 1H), 4.06 (q, J ¼ 7.2 Hz, 2H), 3.74 (s, 3H), 2.37
(s, 3H), 2.17–2.30 (m, 4H), 1.20 (t, J ¼ 7.2 Hz, 3H), 1.07 (s,
3H), 0.94 (s, 3H); 13C-NMR (75 MHz, CDCl3): d ¼ 195.65,
167.51, 157.72, 148.18, 143.21, 139.60, 128.91, 113.20,
112.21, 106.24, 59.75, 55.08, 50.73, 40.95, 35.67, 32.64,
29.41, 27.13, 19.31, 14.21; Anal. Calcd. for C22H27NO4: C,
71.52; H, 7.37; N, 3.79; Found: C, 71.61; H, 7.40; N, 3.70.
Ethyl 4-(4-chlorophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-
hexahydroquinoline-3-carboxylate (5d). IR (KBr): 3274, 3206,
3085, 2938, 1705, 1606 cmꢁ1 1H-NMR (300 MHz, CDCl3):
;
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2010
Glycine-Catalyzed Easy and Efficient One-Pot Synthesis of Polyhydroquinolines
through Hantzsch Multicomponent Condensation under Controlled Microwave
197
d ¼ 7.14–7.23 (m, 2H), 7.05–7.11 (m, 2H), 5.77 (s, 1H), 5.02
(s, 1H), 4.05 (q, J ¼ 7.2 Hz, 2H), 2.41 (s, 3H), 2.16–2.37 (m,
4H), 1.19 (t, J ¼ 7.2 Hz, 3H), 1.08 (s, 3H), 0.94 (s, 3H); 13C-
NMR (75 MHz, CDCl3): d ¼ 195.64, 167.31, 149.20, 144.53,
133.55, 129.11, 128.08, 126.23, 111.14, 105.12, 59.79, 50.67,
40.64, 36.58, 32.59, 29.34, 27.01, 19.06, 14.13; Anal. Calcd.
for C21H24ClNO3: C, 67.46; H, 6.47; N, 3.75; Found: C,
67.34; H, 6.52; N, 3.78.
27.01, 19.37, 14.15; Anal. Calcd. for C21H24N2O5: C, 65.61;
H, 6.29; N, 7.29; Found: C, 65.56; H, 6.33; N, 7.37.
Ethyl 4-(3-nitrophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-
hexahydroquinoline-3-carboxylate (5j). IR (KBr): 3283, 3210,
3079, 2958, 1705, 1608, 1532 cmꢁ1 1H-NMR (300 MHz,
;
CDCl3): d ¼ 8.10 (s, 1H), 7.98 (d, J ¼ 8.1 Hz, 1H), 7.73 (d, J
¼ 7.5 Hz, 1H), 7.35 (t, J ¼ 7.8 Hz, 1H), 5.88 (s, 1H), 5.15 (s,
1H), 4.06 (q, J ¼ 6.9 Hz, 2H), 2.41 (s, 3H), 2.12–2.36 (m,
4H), 1.19 (t, J ¼ 6.9 Hz, 3H), 1.10 (s, 3H), 0.94 (s, 3H); 13C-
NMR (75 MHz, CDCl3): d ¼ 195.52, 166.90, 149.15, 148.20,
144.52, 134.73, 128.54, 122.81, 121.23, 111.09, 104.99, 60.02,
50.54, 40.84, 36.95, 32.70, 29.32, 27.02, 19.33, 14.13; Anal.
Calcd. for C21H24N2O5: C, 65.61; H, 6.29; N, 7.29; Found: C,
65.70; H, 6.34; N, 7.20.
Ethyl 4-(3-chlorophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-
hexahydroquinoline-3-carboxylate (5e). IR (KBr): 3274,
3202, 3074, 2934, 1704, 1605 cmꢁ1 1H-NMR (300 MHz,
;
CDCl3): d ¼ 7.08–7.24 (m, 4H), 5.78 (s, 1H), 5.03 (s, 1H),
4.06 (q, J ¼ 7.2 Hz, 2H), 2.43 (s, 3H), 2.19–2.39 (m, 4H),
1.20 (t, J ¼ 7.2 Hz, 3H), 1.09 (s, 3H), 0.95 (s, 3H); 13C-NMR
(75 MHz, CDCl3): d ¼ 195.66, 167.25, 149.28, 144.41,
133.53, 129.10, 128.05, 126.19, 111.11, 105.10, 59.78, 50.64,
40.61, 36.57, 32.55, 29.31, 27.04, 19.05, 14.13; Anal. Calcd.
for C21H24ClNO3: C, 67.46; H, 6.47; N, 3.75; Found: C,
67.51; H, 6.44; N, 3.70.
Ethyl 4-(4-hydroxy-3-methoxyphenyl)-2,7,7-trimethyl-5-
oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate (5k). IR
(KBr): 3399, 3292, 2934, 1698, 1591 cmꢁ1 1H-NMR (300
;
MHz, DMSO-d6): d ¼ 8.99 (s, 1H), 8.63 (s, 1H), 6.69 (s, 1H),
6.49–6.58 (m, 2H), 4.74 (s, 1H), 4.40 (q, J ¼ 6.9 Hz, 2H),
2.50 (s, 3H), 1.95–2.39 (m, 7H), 1.16 (t, J ¼ 6.9 Hz, 3H),
1.01 (s, 3H), 0.88 (s, 3H); 13C-NMR (75 MHz, DMSO-d6): d
¼ 194.49, 167.10, 149.39, 146.78, 144.49, 139.10, 119.59,
114.98, 112.03, 110.22, 104.14, 59.05, 55.49, 50.35, 35.07,
32.16, 29.29, 26.42, 18.28, 14.28; Anal. Calcd. for
C22H27NO5: C, 68.55; H, 7.06; N, 3.63; Found: C, 68.61; H,
7.11; N, 3.58.
Ethyl 4-(4-bromophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-
hexahydroquinoline-3-carboxylate (5f). IR (KBr): 3274, 3205,
1
3072, 2955, 1702, 1604 cmꢁ1; H-NMR (300 MHz, CDCl3): d
¼ 7.18–7.23 (m, 2H), 7.02–7.08 (m, 2H), 6.56 (s, 1H), 5.03 (s,
1H), 4.02–4.11 (m, 2H), 2.34 (s, 3H), 2.12–2.28 (m, 4H), 1.22
(t, J ¼ 7.2 Hz, 3H), 1.08 (s, 3H), 0.95 (s, 3H); 13C-NMR (75
MHz, CDCl3): d ¼ 195.38, 167.76, 148.87, 145.69, 143.71,
131.03, 129.73, 111.14, 106.05, 59.79, 50.67, 40.64, 36.28,
32.59, 29.34, 27.01, 19.16, 14.15; Anal. Calcd. for
C21H24BrNO3: C, 60.29; H, 5.78; N, 3.35; Found: C, 60.42; H,
5.71; N, 3.29.
Ethyl
1,4,5,6,7,8-hexahydroquinoline-3-carboxylate (5l). IR (KBr):
3280, 3207, 3079, 2954, 1700, 1607 cmꢁ1 1H-NMR (300
4-(4-dimethylaminophenyl)-2,7,7-trimethyl-5-oxo-
;
MHz, CDCl3): d ¼ 7.15 (d, J ¼ 8.4 Hz, 2H), 6.59 (d, J ¼ 8.7
Hz, 2H), 5.70 (s, 1H), 4.95 (s, 1H), 4.06 (q, J ¼ 7.2 Hz, 2H),
2.87 (s, 6H), 2.18–2.36 (m, 7H), 1.22 (t, J ¼ 7.2 Hz, 3H),
1.07 (s, 3H), 0.97 (s, 3H); 13C-NMR (75 MHz, CDCl3): d ¼
195.56, 167.65, 148.97, 147.59, 142.75, 135.81, 128.58,
112.47, 106.55, 59.72, 50.76, 40.94, 35.29, 32.70, 29.41,
27.33, 19.42, 14.25; Anal. Calcd. for C23H30N2O3: C, 72.22;
H, 7.91; N, 7.32; Found: C, 72.10; H, 7.95; N, 7.38.
Ethyl 4-(3-bromophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-
hexahydroquinoline-3-carboxylate (5g). IR (KBr): 3275, 3204,
1
3074, 2957, 1703, 1605 cmꢁ1; H-NMR (300 MHz, CDCl3): d
¼ 7.40 (s, 1H), 7.21–7.26 (m, 2H), 7.04–7.09 (m, 1H), 6.60 (s,
1H), 5.02 (s, 1H), 4.02–4.12 (m, 2H), 2.35 (s, 3H), 2.13–2.29
(m, 4H), 1.21 (t, J ¼ 7.2 Hz, 3H), 1.07 (s, 3H), 0.95 (s, 3H);
13C-NMR (75 MHz, CDCl3): d ¼ 195.56, 167.16, 149.08,
144.00, 131.04, 129.25, 126.87, 122.02, 111.42, 105.43, 59.90,
50.67, 40.89, 36.63, 32.69, 29.36, 27.13, 19.31, 14.17; Anal.
Calcd. for C21H24BrNO3: C, 60.29; H, 5.78; N, 3.35; Found:
C, 60.20; H, 5.83; N, 3.42.
Ethyl 4-(furan-2-yl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexa-
hydroquinoline-3-carboxylate (5m). IR (KBr): 3287, 3220,
1
3086, 2932, 1675, 1605 cmꢁ1; H-NMR (300 MHz, CDCl3): d
¼ 7.18 (s, 1H), 6.20 (s, 1H), 6.00 (s, 1H), 5.89 (s, 1H), 5.25
(s, 1H), 4.12–4.16 (m, 2H), 2.19–2.39 (m, 7H), 1.25 (t, J ¼
6.9 Hz, 3H), 1.10 (s, 3H), 1.02 (s, 3H); 13C-NMR (75 MHz,
CDCl3): d ¼ 195.57, 167.34, 157.94, 150.61, 144.26, 140.85,
111.13, 105.03, 103.07, 59.83, 50.63, 36.88, 32.48, 29.71,
27.03, 19.08, 14.17; Anal. Calcd. for C19H23NO4: C, 69.28; H,
7.04; N, 4.25; Found: C, 69.17; H, 7.10; N, 4.28.
Ethyl 4-(4-fluorophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-
hexahydroquinoline-3-carboxylate (5h). IR (KBr): 3287, 3209,
2960, 1697, 1615 cmꢁ1
;
1H-NMR (300 MHz, CDCl3): d ¼
7.21–7.26 (m, 2H), 6.89–7.03 (m, 2H), 5.69 (s, 1H), 5.11 (s,
1H), 4.07 (q, J ¼ 7.2 Hz, 2H), 2.35 (s, 3H), 2.14–2.28 (m,
4H), 1.20 (t, J ¼ 7.2 Hz, 3H), 1.08 (s, 3H), 0.94 (s, 3H); 13C-
NMR (75 MHz, CDCl3): d ¼ 195.65, 167.55, 153.72, 149.27,
144.60, 138.63, 129.51, 112.17, 106.25, 59.84, 50.78, 40.97,
36.12, 32.71, 29.42, 27.15, 19.31, 14.22; Anal. Calcd. for
C21H24FNO3: C, 70.57; H, 6.77; N, 3.92; Found: C, 70.46; H,
6.74; N, 3.88.
Ethyl 4-(2,4-dichlorophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-
hexahydroquinoline-3-carboxylate (5n). IR (KBr): 3287, 3204,
1
3088, 2936, 1703, 1607 cmꢁ1; H-NMR (300 MHz, CDCl3): d
¼ 7.30 (d, 1H), 7.22 (s, 1H), 7.10 (d, 1H), 6.13 (s, 1H), 5.23
(s, 1H), 3.97–4.06 (m, 2H), 2.38 (s, 3H), 2.18–2.36 (m, 4H),
1.18 (t, J ¼ 7.2 Hz, 3H), 1.07 (s, 3H), 0.94 (s, 3H); 13C-NMR
(75 MHz, CDCl3): d ¼ 195.41, 167.23, 149.38, 142.42,
133.67, 132.78, 132.04, 129.13, 126.86, 111.13, 104.59, 60.11,
50.58, 41.07, 32.73, 29.12, 27.37, 19.11, 14.17; Anal. Calcd.
for C21H23Cl2NO3: C, 61.77; H, 5.68; N, 3.43; Found: C,
61.84; H, 5.71; N, 3.39.
Ethyl 4-(4-nitrophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-
hexahydroquinoline-3-carboxylate (5i). IR (KBr): 3285, 3203,
3078, 2964, 1676, 1605, 1515 cmꢁ1 1H-NMR (300 MHz,
;
CDCl3): d ¼ 8.07 (d, J ¼ 8.4 Hz, 2H), 7.47 (d, J ¼ 8.4 Hz,
2H), 5.75 (s, 1H), 5.15 (s, 1H), 4.04 (q, J ¼ 7.2 Hz, 2H), 2.42
(s, 3H), 2.11–2.35 (m, 4H), 1.17 (t, J ¼ 7.2 Hz, 3H), 1.09 (s,
3H), 0.91 (s, 3H); 13C-NMR (75 MHz, CDCl3): d ¼ 195.38,
166.82, 154.50, 148.88, 146.16, 144.48, 128.92, 123.28,
110.99, 104.83, 60.04, 50.57, 40.93, 37.18, 32.67, 29.32,
Acknowledgments. The authors are thankful to the Department
of Biotechnology, New Delhi, for financial assistance.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

198
S. K. Singh and K. N. Singh
Vol 47
[13] (a) Ji, S. J.; Jiang, Z. Q.; Lu, J.; Loa, T. P. Synlett 2004,
831; (b) Zhang, X. Y.; Li, Y. Z.; Fan, X. S.; Qu, G. R.; Hu, X. Y.;
Wang, J. J Chin Chem Lett 2006, 17, 150.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet