LETTER
Synthesis of Tetrahydroquinolinone and Nicotinonitrile Derivatives
2241
7,7-Dimethyl-2-morpholino-7,8-dihydroquinolin-5(6H)-
one (11c)
(s, 2 H, CH2), 7.32–7.68 (m, 5 H, PhH), 7.88 (s, 1 H, CH),
12.36 (s, 1 H, NH, D2O exchangeable). 13C NMR (100 MHz,
DMSO): d = 206.54 (CO), 193.34 (CO), 162.09, 154.88,
135.83, 133.69, 128.38 (2 C), 128.13 (2 C), 111.88, 50.10,
32.72 (2 C), 30.70, 27.76 (2 C). MS: m/z (%) = 267 (100)
[M+], 224 (5), 211 (40), 183 (20), 183 (20), 154 (25), 128
(20), 115 (10), 77 (10).
Yield 96%; mp 130–31 °C. Anal. Calcd for C15H20N2O2
(260.34): C, 69.20; H, 7.74; N, 10.76. Found: C, 69.26; H,
7.82; N; 10.75. IR (KBr): 1655 (CO) cm–1. 1H NMR (400
MHz, DMSO): d = 1.00 (s, 6 H, 2 CH3), 2.37 (s, 2 H, CH2),
2.74 (s, 2 H, CH2), 3.64–3.69 (m, 8 H, morpholin-H), 6.77
(d, 1 H, J = 8 Hz, CH), 7.88 (d, 1 H, J = 8 Hz, CH). 13C NMR
(100 MHz, DMSO): d = 195.23 (CO), 162.50, 159.88,
135.35, 117.17, 104.80, 65.86 (2 C), 51.06, 46.00, 44.32 (2
C), 32.48, 27.87 (2 C). MS: m/z (%) = 260 (65) [M+], 229
(100), 203 (75), 175 (45), 146 (15), 119 (10), 91 (15), 77 (5).
(11) Al-Saleh, B.; Al-Awadi, N.; Al-kandari, H.; Abdel-Khalik,
M. M.; Elnagdi, M. H. J. Chem. Res. 2000, 1, 16.
(15) CCDC 821559 contains the supplementary crystallographic
data for compound 18. These data can be obtained free of
charge from the Cambridge Crystallographic Data Centre
(16) Synthesis of 2-Benzoyl-4-[hydroxy(phenyl)methylene]-
pent-2-enedinitrile (23)
A solution of 2-benzoyl-3-(dimethylamino)acrylonitrile (1d,
2.00 g, 0.01 mol) and 3-oxo-3-phenylpropanenitrile (19,
1.45 g, 0.01 mol) in EtOH (15 mL) was treated with
piperidine (5 drops). The mixture was stirred at reflux for 20
h [reaction progress monitored by using TLC with EtOAc–
PE (1:1) as eluent]. The solid, obtained by pouring the
reaction mixture into H2O, was collected by filtration and
crystallized from EtOH to give yellow crystals; yield 75%;
mp 163–65 °C. Anal. Calcd for C19H12N2O2 (300.32): C,
75.99; H, 4.03; N, 9.33. Found: C, 76.02; H, 4.12; N; 9.42.
IR (KBr): 3431 (OH), 2209 (CN), 2196 (CN), 1611 (CO)
cm–1. 1H NMR (400 MHz, DMSO): d = 7.38–7.51 (m, 10 H,
Ph-H), 8.02 (s, 1 H, CH), 8.21 (s, 1 H, OH). 13C NMR (100
MHz, DMSO): d = 190.11 (CO), 152.56, 139.80, 130.27 (2
C), 128.27 (4 C), 127.80 (4 C), 118.65, 86.73, 83.26, 54.48,
54.44, 54.40. MS: m/z (%) = 300(70) [M+], 271 (30), 255
(10), 223 (30), 195 (5), 140 (10), 105 (50), 84 (100), 77 (30).
(17) Synthesis of 5-Benzoyl-6-hydroxy-2-phenylnico-
tinonitrile (25)
A solution of 2-benzoyl-3-(dimethylamino)acrylonitrile (1d,
2.00 g, 0.01 mol), 3-oxo-3-phenylpropanenitrile (19, 1.45 g,
0.01 mol) and NH4OAc (1 g) in AcOH (15 mL) was stirred
at reflux for 3–4 h [reaction progress monitored by using
TLC with EtOAc–PE (1:1) as eluent]. The solid, obtained by
pouring the reaction mixture into H2O, was collected by
filtration and crystallized from EtOH to give colorless
crystals; yield 70%; mp 272–74 °C. Anal. Calcd for
C19H12N2O2 (300.32): C, 75.99; H, 4.03; N, 9.33. Found: C,
75.85; H, 4.09; N; 9.49. IR (KBr): 3448 (OH), 2220 (CN),
1657 (CO) cm–1. 1H NMR (400 MHz, DMSO): d = 7.50–
7.97 (m, 10 H, PhH), 8.17 (br, 1 H, OH), 8.53 (s, 1 H, CH).
13C NMR (100 MHz, DMSO): d = 168.76, 159.79, 158.16,
142.56, 138.52, 137.26, 131.22, 130.85, 130.28, 129.37 (2
C), 129.31 (2 C), 129.15 (2 C), 128.79 (2 C), 117.87, 104.85.
MS: m/z (%) = 299 (100) [M – 1], 283 (25), 255 (35), 227
(15), 201 (5), 177 (5), 151 (10), 127 (10), 77 (15).
(18) CCDC 821551 contains the supplementary crystallographic
data for compound 23. These data can be obtained free of
charge from the Cambridge Crystallographic Data Centre
(12) Synthesis of 2-(Dimethylamino)-6-(4-hydroxy-6-methyl-
2-oxo-2H-pyran-3-yl)nicotinonitrile (17)
A solution of malononitrile (0.66 g, 0.01 mol) and 3-[3-
(dimethylamino)acryloyl]-4-hydroxy-6-methyl-2H-pyran-
2-one (13, 2.23 g, 0.01 mol) in EtOH (15 mL) was treated
with piperidine (5 drops). The reaction mixture was stirred at
reflux for 3–4 h [reaction progress monitored by using TLC
with EtOAc–PE (1:1) as eluent]. The solid obtained by
pouring the reaction mixtures into H2O was collected by
filtration and crystallized from benzene to give yellow
crystals; yield 50%; mp 275–76 °C. Anal. Calcd for
C14H13N3O3 (271.28): C, 61.99; H, 4.83; N, 15.49. Found: C,
62.01; H, 4.89; N; 15.56. IR (KBr): 3429 (OH), 2209 (CN),
1698 (CO) cm–1. 1H NMR (400 MHz, DMSO): d = 2.09 (s,
6 H, 2 CH3), 2.19 (s, 3 H, CH3), 6.02 (br, 1 H, OH), 7.91 (d,
1 H, J = 8 Hz, CH), 8.11 (d, 1 H, J = 8 Hz, CH). 13C NMR
(100 MHz, DMSO): d = 206.57 (CO), 179.81, 164.13,
155.31, 147.55, 118.07, 108.23, 91.95, 87.03, 79.01, 40.79,
30.72 (2 C), 19.46. MS: m/z (%) = 271 (100) [M+], 242
(100), 228 (15), 186 (10), 172 (30), 158 (45), 144 (15), 117
(15), 90 (5), 85 (15), 69 (5).
(13) CCDC 821560 contains the supplementary crystallographic
data for compound 17. These data can be obtained free of
charge from the Cambridge Crystallographic Data Centre
(14) Synthesis of 7,7-Dimethyl-3-phenyl-7,8-dihydro-
quinoline-2,5(1H,6H)-dione (18)
A solution of 2-phenyl-3-(piperidin-1-yl)acrylonitrile (1c,
2.12 g, 0.01 mol) and dimedone (2a, 1.40 g, 0.01 mol) in
EtOH (15 mL) was treated with piperidine (5 drops). The
reaction mixture was stirred at reflux for 3–4 h [reaction
progress monitored by using TLC with EtOAc–PE (1:1) as
eluent], and the solid, obtained by pouring the reaction
mixture into H2O, was collected by filtration and crystallized
from EtOH to give colorless crystals; yield 85%; mp 157–58
°C. Anal. Calcd for C17H17NO2 (267.33): C, 76.38; H, 6.41;
N, 5.24. Found: C, 76.29; H, 6.42; N; 5.18. IR (KBr): 3450
(NH), 1672 (CO),16636 (CO) cm–1. 1H NMR (400 MHz,
DMSO): d = 1.05 (s, 6 H, 2 CH3), 2.38 (s, 2 H, CH2), 2.75
Synlett 2011, No. 15, 2237–2241 © Thieme Stuttgart · New York