A convenient synthesis of 2,4-diarylpolyhydroquinoline derivations in the presence of ammonium acetate

Article abstract of DOI:10.1081/SCC-120014775

A series of substituted 5-oxo-1,2,3,4,5,6,7,8-octahydroquinoline derivatives have been synthesized from 5,5-dimethyl-1,3-cyclohexane-dione (dimedone) and 1,3-diaryl-2-propen-1-one in DMF at 80°C in the presence of ammonium acetate with high yields (64-98%

Full text of DOI:10.1081/SCC-120014775

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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 22, pp. 3449–3454, 2002
A CONVENIENT SYNTHESIS OF
2,4-DIARYLPOLYHYDROQUINOLINE
DERIVATIONS IN THE PRESENCE OF
AMMONIUM ACETATE
*
Xiang-Shan Wang, Da-Qing Shi, and Shu-Jiang Tu
Department of Chemistry, Xuzhou Normal University,
Xuzhou Jiangsu, 221009, China
ABSTRACT
A
series of substituted 5-oxo-1,2,3,4,5,6,7,8-octahydro-
quinoline derivatives have been synthesized from
5,5-dimethyl-1,3-cyclohexane-dione (dimedone) and 1,3-
diaryl-2-propen-1-one in DMF at 80ꢀC in the presence of
ammonium acetate with high yields (64–98%), the structure
of the product was confirmed by X-ray analysis.
Key Words: 2,4-Diarylpolyhydroquinoline; 1,3-Diaryl-2-
propen-1-one; Ammonium acetate
1,4-Dihydropyridines (1,4-DHPS) are well-known compounds as a
consequence of their pharmacological profile as calcium channel modula-
tors.[1] The chemical modifications carried on the DHP ring such as the
presence of different substituents[2] or heteroatoms[3] have allowed expan-
sion of the structure activity relationship and afforded some insight into the
*Corresponding author. E-mail: wxs2001z@sina.com.cn
3449
DOI: 10.1081/SCC-120014775
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3450
WANG, SHI, AND TU
molecular interactions at the receptor level. The usual method for 1,4-DHPS
synthesis is from meldrum’s acid and dimedone in the presence of different
aldehydes catalyzed by ammonium acetate[4] or NH3H2O.[5] In our previous
paper,[6] we have reported one step synthesis of 4-arylpolyhydroquinoline
derivatives from aromatic aldehyde, dimedone, ammonium acetate and
ethyl acetoacete using microwave irradiation. In this paper we describe
the synthesis of the 5-oxo-1,2,3,4,5,6,7,8-octahydroquinoline derivatives
from dimedone 2 and 1,3-diaryl-2-propen-1-one 1 in the presence of
ammonium acetate.
When 1,3-diaryl-2-propen-1-one 1 and dimedone 2 were treated with
ammonium acetate in DMF at 80ꢀC for 1–2 h (Sch. 1), the desired 5-oxo-
1,2,3,4,5,6,7,8-octahydroquinoline derivatives 3 were obtained in good
yields (64–98%) (Table 1).
1
The H NMR spectra of compound 3d show the NH proton ꢁ 8.64 ppm,
the proton on C(9) exhibit double peaks at 4.54–4.63 ppm and form part of an
AX system which is confirmed by another double peaks at 5.25–5.34 ppm cor-
responding to the proton on C(8) (J ¼ 5.4 Hz). In order to confirm the structure
of the product, the X-ray crystallographic study was carried out.[7] Figure 1
shows the molecular structure of the compound 3d.
Scheme 1.
Table 1. The Yields of the Products
Entry
Ar
Ar0
Yield (%)
3a
3b
3c
3d
3e
3f
C6H5
C6H5
4-ClC6H4
C6H5
C6H5
4-ClC6H4
3,4-(CH3O)2C6H3
3,4-OCH2OC6H3
C6H5
C6H5
4-ClC6H4
C6H5
4-BrC6H4
2,4-Cl2-5-FC6H2
2,4-Cl2-5-FC6H2
C6H5
C6H5
4-CH3C6H4
4-ClC6H4
85.1
64.7
78.5
94.3
98.0
97.7
72.6
92.0
68.5
90.5
3g
3h
3i
3j
3,4-OCH2OC6H3

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2,4-DIARYLPOLYHYDROQUINOLINE DERIVATIVES
3451
Figure 1. The structure of compound 3d.
AQ1
In conclusion, with high yields and mild conditions, we think that the
present work described here in provide a useful method for the preparation
of substituted 5-oxo-1,2,3,4,5,6,7,8-octahydroquinoline derivatives.
EXPERIMENTAL
Melting points were determined in open capillaries and are uncor-
rected. IR spectra were recorded on a FT IR-8101 spectrometer in KBr.
1H NMR spectra were obtained for solution in DMSO-d6 with Me4Si as
internal standard using an Inova-400 or R-1500A spectrometer. Elemental
analyses were carried out using Carlo Erba 1110 analyzer. X-ray diffraction
were measured on a Siemens P4 diffractometer.
General Procedure
A dry 50 mL flask was charged with 1,3-diaryl-2-propen-1-one 1
(2 mmol), 5,5-dimethyl-1,3-cyclohexanedione 2 (2.5 mmol), ammonium
acetate (5 mmol) and DMF (10 mL). The mixture was stirred at 80ꢀC for
1–2 h, then cooled to room temperature. The mixture was poured into

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3452
WANG, SHI, AND TU
200 mL water, the yellow solid was filtered off and washed with water. The
crude product was purified by recrystallization from 95% EtOH to give 3.
3a: M.p. 206–208ꢀC; IR (KBr, ꢀ, cmꢂ1): 3260, 3030, 2990, 1660, 1630,
1
1590, 1490, 1450, 770, 760, 695; H NMR (DMSO-d6, ꢁ, ppm): 0.96 (3H, s,
CH3), 1.04 (3H, s, CH3), 1.98–2.02 (1H, d, J ¼ 16.0 Hz, C12-H), 2.16–2.20
(1H, d, J ¼ 16.0 Hz, C12-H), 2.48 (2H, s, CH2), 4.56–4.57 (1H, d, J ¼ 5.6 Hz,
C9-H), 5.21–5.22 (1H, dd, J ¼ 2.0 Hz, J0 ¼ 3.6 Hz, C8-H), 7.09–7.50 (10H, m,
ArH), 8.63 (1H, s, NH); Elemental analysis: Found (%): C, 83.93; H, 6.86;
N, 4.03. Calcd. for C23H23NO: C, 83.85; H, 7.04; N, 4.25.
3b: M.p. 250–252ꢀC; IR (KBr, ꢀ, cmꢂ1): 3240, 3020, 2980, 1665, 1610,
1
1580, 1500, 1450, 835, 760, 690; H NMR (DMSO-d6, ꢁ, ppm): 0.98 (3H, s,
CH3), 1.06 (3H, s, CH3), 2.10 (2H, s, CH2), 2.14 (2H, s, CH2), 4.54–4.63
(1H, d, J ¼ 5.4 Hz, C9-H), 5.24–5.33 (1H, d, J ¼ 5.4 Hz, C8-H), 7.24 (5H, s,
ArH), 7.50 (4H, s, ArH), 8.69 (1H, b, NH); Elemental analysis: Found (%):
C, 76.04; H, 5.94; N, 3.68. Calcd. for C23H22ClNO: C, 75.91; H, 6.10;
N, 3.85.
3c: M.p. 224–226ꢀC; IR (KBr, ꢀ, cmꢂ1): 3250, 3030, 2980, 1665, 1610,
1
1580, 1500, 1450, 830, 770, 700; H NMR (DMSO-d6, ꢁ, ppm): 0.94 (3H, s,
CH3), 1.06 (3H, s, CH3), 1.98–2.02 (1H, d, J ¼ 16.4 Hz, C12-H), 2.16–2.20
(1H, d, J ¼ 16.4 Hz, C12-H), 2.46 (1H, s, C16-H), 2.48 (1H, s, C16-H),
4.57–4.58 (1H, d, J ¼ 5.2 Hz, C9-H), 5.18–5.20 (1H, dd, J ¼ 1.2 Hz,
J0 ¼ 4.0 Hz, C8-H), 7.23–7.50 (9H, m, ArH), 8.68 (1H, s, NH); Elemental
analysis: Found (%): C, 75.98; H, 5.90; N, 3.69. Calcd. for C23H22ClNO: C,
75.91; H, 6.10; N, 3.85.
3d: M.p. 264–266ꢀC; IR (KBr, ꢀ, cmꢂ1): 3250, 3010, 2980, 1670, 1610,
1
1590, 1510, 1490, 830, 770, 695; H NMR (DMSO-d6, ꢁ, ppm): 0.99 (3H, s,
CH3), 1.06 (3H, s, CH3), 2.10 (2H, s, CH2), 2.13 (2H, s, CH2), 4.54–4.63 (1H,
d, J ¼ 5.4 Hz, C9-H), 5.25–5.34 (1H, d, J ¼ 5.4 Hz, C8-H), 7.24 (5H, s, ArH),
7.54 (4H, s, ArH), 8.64 (1H, b, NH); Elemental analysis: Found (%): C, 67.82;
H, 5.29; N, 3.21. Calcd. for C23H22BrNO: C, 67.65; H, 5.43; N, 3.43.
3e: M.p. 166–168ꢀC; IR (KBr, ꢀ, cmꢂ1): 3280, 3010, 2990, 1670, 1600,
1510, 1470, 830, 680; 1H NMR (DMSO-d6, ꢁ, ppm): 0.91 (3H, s, CH3), 1.06
(3H, s, CH3), 1.96–2.00 (1H, d, J ¼ 16.0 Hz, C12-H), 2.15–2.19 (1H, d,
J ¼ 16.0 Hz, C12-H), 2.26–2.30 (1H, d, J ¼ 16.4 Hz, C16-H), 2.37–2.42
(1H, d, J ¼ 16.4 Hz, C16-H), 4.56–4.57 (1H, d, J ¼ 5.6 Hz, C9-H), 4.92–4.94
(1H, dd, J ¼ 1.6 Hz, J0 ¼ 3.6 Hz, C8-H), 7.08–7.91 (7H, m, ArH), 10.61
(1H, s, NH); Elemental analysis: Found (%): C, 66.52; H, 4.64; N, 3.13.
Calcd. for C23H20Cl2FNO: C, 66.35; H, 4.84; N, 3.36.
3f: M.p. 238–239ꢀC; IR (KBr, ꢀ, cmꢂ1): 3250, 3020, 2980, 1670, 1600,
1510, 1470, 830, 680; 1H NMR (DMSO-d6, ꢁ, ppm): 0.91 (3H, s, CH3), 1.06
(3H, s, CH3), 1.96–2.00 (1H, d, J ¼ 16.0 Hz, C12-H), 2.15–2.19 (1H, d,
J ¼ 16.0 Hz, C12-H), 2.26–2.30 (1H, d, J ¼ 16.4 Hz, C16-H), 2.37–2.42

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2,4-DIARYLPOLYHYDROQUINOLINE DERIVATIVES
3453
(1H, d, J ¼ 16.4 Hz, C16-H), 4.56–4.57 (1H, d, J ¼ 5.6 Hz, C9-H), 4.92–4.94
(1H, dd, J ¼ 1.6 Hz, J0 ¼ 3.6 Hz, C8-H), 7.31–7.92 (6H, m, ArH), 8.85 (1H,
s, NH); Elemental analysis: Found (%): C, 61.44; H, 4.01; N, 3.00. Calcd.
for C23H19Cl3FNO: C, 61.28; H, 4.25; N, 3.11.
3g: M.p. 196–198ꢀC; IR (KBr, ꢀ, cmꢂ1): 3260, 3020, 2990, 2980, 1660,
1
1620, 1590, 1510, 1495, 1460, 760, 700; H NMR (DMSO-d6, ꢁ, ppm): 0.98
(3H, s, CH3), 1.04 (3H, s, CH3), 1.98–2.02 (1H, d, J ¼ 16.0 Hz, C12-H),
2.17–2.21 (1H, d, J ¼ 16.0 Hz, C12-H), 2.46 (1H, s, C16-H), 2.48 (1H, s,
C16-H), 3.68 (6H, s, 2 ꢃ OCH3), 4.49–4.50 (1H, d, J ¼ 5.2 Hz, C9-H),
5.20–5.22 (1H, dd, J ¼ 1.6 Hz, J0 ¼ 4.0 Hz, C8-H), 6.70–7.49 (8H, m, ArH),
8.59 (1H, s, NH); Elemental analysis: Found (%): C, 77.28; H, 6.72; N, 3.37.
Calcd. for C25H27NO3: C, 77.09; H, 6.99; N, 3.60.
3h: M.p. 236–238ꢀC; IR (KBr, ꢀ, cmꢂ1): 3240, 3020, 2980, 1660, 1600,
1570, 1500, 1480, 830, 770, 700; 1H NMR (DMSO-d6, ꢁ, ppm): 0.96
(3H, s, CH3), 1.03 (3H, s, CH3), 1.99–2.03 (1H, d, J ¼ 16.0 Hz, C12-H),
2.15–2.19 (1H, d, J ¼ 16.0 Hz, C12-H), 2.47 (2H, s, CH2), 4.48–4.50 (1H,
d, J ¼ 5.2 Hz, C9-H), 5.18–5.20 (1H, dd, J ¼ 2.0 Hz, J0 ¼ 3.6 Hz, C8-H),
5.92 (2H, s, OCH2O), 6.67–7.50 (8H, m, ArH), 8.61 (1H, s, NH);
Elemental analysis: Found (%): C, 77.36; H, 6.07; N, 3.54. Calcd. for
C24H23NO3: C, 77.19; H, 6.21; N, 3.75.
3i: M.p. 210–212ꢀC; IR (KBr, ꢀ, cmꢂ1): 3250, 3010, 2995, 2980, 1650,
1
1620, 1590, 1490, 830, 770, 695; H NMR (DMSO-d6, ꢁ, ppm): 0.96 (3H, s,
CH3), 1.06 (3H, s, CH3), 1.97–2.01 (1H, d, J ¼ 16.4 Hz, C12-H), 2.15–2.19
(1H, d, J ¼ 16.4 Hz, C12-H), 2.30 (3H, s, CH3), 2.48 (2H, s, CH2), 4.54–
4.55 (1H, d, J ¼ 5.6 Hz, C9-H), 5.17–5.18 (1H, dd, J ¼ 1.6 Hz, J0 ¼ 4.0 Hz,
C8-H), 7.08–7.65 (9H, m, ArH), 8.56 (1H, s, NH); Elemental analysis:
Found (%): C, 84.05; H, 7.18; N, 3.89. Calcd. for C24H25NO: C, 83.93;
H, 7.34; N, 4.08.
3j: M.p. 176–177ꢀC; IR (KBr, ꢀ, cmꢂ1): 3250, 3020, 2990, 2980, 1675,
1
1620, 1590, 1500, 1480, 810; H NMR (DMSO-d6, ꢁ, ppm): 0.93 (3H, s,
CH3), 1.01 (3H, s, CH3), 1.97–2.01 (1H, d, J ¼ 16.0 Hz, C12-H), 2.14–2.18
(1H, d, J ¼ 16.0 Hz, C12-H), 2.26–2.30 (1H, d, J ¼ 16.4 Hz, C16-H), 2.36–2.40
(1H, d, J ¼ 16.4 Hz, C16-H), 4.48–4.49 (1H, d, J ¼ 4.8 Hz, C9-H), 4.92–4.93
(1H, dd, J ¼ 1.2 Hz, J0 ¼ 4.0 Hz, C8-H), 6.77–7.91 (7H, m, ArH), 8.77 (1H, s,
NH); Elemental analysis: Found (%): C, 70.86; H, 5.23; N, 3.15. Calcd. for
C24H22ClNO3: C, 70.67; H, 5.44; N, 3.43.
ACKNOWLEDGMENT
We are grateful to the Foundation of the ‘‘Surpassing Project’’ of
Jiangsu Province for financial support.

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WANG, SHI, AND TU
REFERENCES
1. Janis, R.A.; Silver, P.J.; Triggle, D.J. Adv. Drug. Res. 1987, 16,
309–591.
2. Eisner, V.; Kuthan, J. Chen. Rev. 1972, 72, 1.
3. Chorvat, R.T.; Rorig, K.J. J. Org. Chem. 1988, 53, 5779–5781.
4. Marqarita, S.; Estael, O.; Yamila, V.; Beatriz, P. Tetrahedron 1999, 55,
875–884.
5. Sainani, J.B.; Shah, A.C. Indian J. Chem. 1994, 33B, 516.
6. Tu, S.J.; Zhou, J.F.; Deng, X.; Feng, J.C. Youji Huaxue 2001, 21(4),
313–316.
7. X-ray crystallography for 3d: Empirical formula C23H22BrNO, F.W.
408.33, T ¼ 297(2) K, Monoclinic, space group C2/c, a ¼ 1.9687(4) nm,
b ¼ 1.3571(2) nm, c ¼ 1.7311(3) nm, ꢂ ¼ 90ꢀ, ꢃ ¼ 118.740(10)ꢀ, ꢄ ¼ 90ꢀ,
V ¼ 4.0553(12) nm3, Z ¼ 8, Dc ¼ 1.338 Mg/m3, l(MOKa) ¼ 0.071073 nm,
ꢅ ¼ 2.038 mmꢂ1, F(000) ¼ 1680. 1.91ꢀ<ꢆ<25.00ꢀ, R ¼ 0.0539, wR ¼
0.1369, S ¼ 0.831, Largest diff. Peak and hole: 812 and ꢂ 313 e ꢄ nmꢂ3
.
Received in Japan August 10, 2001