A R T I C L E S
Wu¨rthner et al.
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m, 2CH3). Anal. Calcd for C26H35N3O2: C, 74.07; H, 8.37; N, 9.97.
Found: C, 74.08; H, 8.41; N, 9.95.
mp 105-108 °C. H NMR (200 MHz, CDCl3): δ 7.80 (1H, d, J )
14.8 Hz, methine-H), 7.68 (1H, d, J ) 14.8 Hz, methine-H), 7.21 (2H,
s, pyridine-H), 4.11 (2H, t, J ) 8.1 Hz, pyridine-NCH2), 3.95 (2H, m,
pyridone-NCH2), 3.18 (2H, m, CH), 2.84 (2H, t, J ) 7.9 Hz, pyridone-
4-CH2), 1.94 (1H, m, CH), 1.70 (4H, m, CH2), 1.41 (12H, d, J ) 6.4
Hz, (CH3)2), 1.27 (26H, m, CH2), 1.08 (3H, t, J ) 7.1 Hz, CH3), 0.87
(9H, m, CH3). HRMS (EI, 70 eV): M+ 646.5305 (calcd 646.5312).
Anal. Calcd for C42H67N3O2: C, 78.09; H, 10.45; N, 6.50. Found: C,
77.40; H, 10.45; N, 6.30.
1-Hexyl-4-methyl-2,6-dioxo-5-[2-(1-butyl-1-hydropyridin-4-yl-
idene)ethylidene]-1,2,5,6-tetrahydropyridine-3-carbonitrile (1d).
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Yield, 64%; mp 103-104 °C. H NMR (200 MHz, CDCl3): δ 7.74
(1H, d, J ) 14.8 Hz, methine-H), 7.64 (2H, d, J ) 7.4 Hz, pyridine-
2,6-H), 7.48 (1H, d, J ) 14.8 Hz, methine-H), 7.20 (2H, d, J ) 7.4
Hz, pyridine-3,5-H), 4.19 (2H, t, J ) 7.4 Hz, pyridine-NCH2), 3.95
(2H, t, J ) 7.6 Hz, pyridone-NCH2), 2.28 (3H, s, pyridone-4-CH3),
1.90 (2H, m, CH2), 1.63 (2H, m, CH2), 1.33-1.51 (m, 8H, CH2), 1.00
(3H, t, J ) 7.1 Hz, CH3), 0.88 (3H, t, J ) 6.9 Hz, CH3). Anal. Calcd
for C24H31N3O2: C, 73.25; H, 7.94; N, 10.68. Found: C, 73.00; H,
7.88; N, 10.55.
1-(1-Methylbutyl)-4-propyl-2,6-dioxo-5-[2-(1-dodecyl-2,6-diiso-
propyl-1-hydropyridin-4-ylidene)ethylidene]-1,2,5,6-tetrahydro-
pyridine-3-carbonitrile (1k). Yield, 52%; mp 160-162 °C. 1H NMR
(500 MHz, CDCl3): δ 7.75 (1H, d, J ) 14.7 Hz, methine-H), 7.68
(1H, d, J ) 14.7 Hz, methine-H), 7.19 (2H, s, pyridine-H), 5.23 (1H,
m, pyridone-NCH), 4.11 (2H, m, pyridine-NCH2), 3.16 (2H, m, CH),
2.81 (2H, m, pyridone-4-CH2), 2.10 (1H, br, CH), 1.94 (1H, m, CH),
1.70 (4H, m, CH2), 1.47 (3H, m, CH3), 1.40 (12H, d, J ) 6.5 Hz,
(CH3)2), 1.27 (20H, m, CH2), 1.08 (3H, t, J ) 7.35 Hz, CH3), 0.88
(6H, m, CH3). Anal. Calcd for C39H61N3O2: C, 77.56; H, 10.18; N,
6.96. Found: C, 77.94; H, 10.49; N, 7.00.
1-Hexyl-4-methyl-2,6-dioxo-5-[2-(1-isobutyl-1-hydropyridin-4-
ylidene)ethylidene]-1,2,5,6-tetrahydropyridine-3-carbonitrile (1e).
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Yield, 75%; mp 207-209 °C. H NMR (200 MHz, CDCl3): δ 7.78
(1H, d, J ) 14.8 Hz, methine-H), 7.75 (2H, d, J ) 6.9 Hz, pyridine-
2,6-H), 7.59 (1H, d, J ) 14.8 Hz, methine-H), 7.30 (2H, d, J ) 6.9
Hz, pyridine-3,5-H), 4.13 (1H, m, pyridine-NCH), 3.95 (2H, t, J ) 7.6
Hz, pyridone-NCH2), 2.37 (3H, s, pyridone-4-CH3), 1.93 (2H, m, CH2),
1.60-1.69 (5H, m, CH2 and CH3), 1.32 (6H, m, CH2), 0.84-0.99 (6H,
m, CH3). Anal. Calcd for C24H31N3O2: C, 73.25; H, 7.94; N, 10.68.
Found: C, 73.18; H, 8.01; N, 10.60.
1-Isopropyl-4-propyl-2,6-dioxo-5-[2-(1-propyl-2,6-diisopropyl-1-
hydropyridin-4-ylidene)ethylidene]-1,2,5,6-tetrahydropyridine-3-
carbonitrile (1l). Yield, 67%; mp 277-278 °C. H NMR (200 MHz,
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1-Hexyl-4-methyl-2,6-dioxo-5-[2-(1-tert-butyl-1-hydropyridin-4-
ylidene)ethylidene]-1,2,5,6-tetrahydropyridine-3-carbonitrile (1f).
Yield, 79%; mp 253-254 °C. H NMR (200 MHz, DMSO): δ 8.66
CDCl3): δ 7.77 (1H, d, J ) 14.8 Hz, methine-H), 7.67 (1H, d, J )
14.8 Hz, methine-H), 7.19 (2H, s, pyridine-H), 5.40 (1H, m, pyridone-
NCH), 4.08 (2H, t, J ) 8.4 Hz, pyridine-NCH2), 3.16 (2H, m, CH),
2.81 (2H, t, J ) 7.6 Hz, pyridone-4-CH2), 1.71 (4H, m, CH2), 1.51
(6H, d, J ) 6.9 Hz, CH3), 1.41 (12H, d, J ) 6.9 Hz, (CH3)2), 1.15-
1.05 (6H, m, CH3). Anal. Calcd for C28H39N3O2: C, 74.80; H, 8.74;
N, 9.35. Found: C, 74.68; H, 8.88; N, 9.30.
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(2H, d, J ) 7.1 Hz, pyridine-2,6-H), 7.81 (1H, d, J ) 15.3 Hz, methine-
H), 7.79 (2H, d, J ) 7.1 Hz, pyridine-3,5-H), 7.72 (1H, d, J ) 15.0
Hz, methine-H), 3.81 (2H, t, J ) 7.3 Hz, pyridone-NCH2), 2.41 (3H,
s, pyridone-4-CH3), 1.67 (9H, s, (CH3)3), 1.46 (2H, m, CH2), 1.26 (6H,
m, CH2), 0.86 (3H, t, J ) 6.4 Hz, CH3). Anal. Calcd for C24H31N3O2:
C, 73.25; H, 7.94; N, 10.68. Found: C, 73.17; H, 7.90; N, 10.62.
1,4-Dipropyl-2,6-dioxo-5-[2-(1-sec-butyl-1-hydropyridin-4-yl-
idene)ethylidene]-1,2,5,6-tetrahydropyridine-3-carbonitrile (1g).
3,4-Diethylthiophene (17). At room temperature and under an argon
atmosphere, 0.1 mol of ethylmagnesium bromide in 30 mL of ether
was added dropwise into a mixture of 9.40 g (0.039 mol) of
3,4-dibromothiophene 16, 217 mg (0.4 mmol) of NiCl2dppp, and 15
mL of anhydrous ether, and the mixture was refluxed for 24 h. The
resulting solution was hydrolyzed with 40 mL of 1 N HCl and 100
mL of ice-water. The organic layer and ether extracts from the aqueous
layer were combined, washed with water, and dried over Na2SO4. After
evaporation of the solvent, vacuum distillation afforded 3.8 g of 17 at
80 °C/11 mbar (ref 58: 70 °C/12 Torr); yield, 70%.
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Yield, 32%; mp 254-256 °C. H NMR (200 MHz, CDCl3): δ 8.03
(2H, d, J ) 7.4 Hz, pyridine-2,6-H), 7.89 (1H, d, J ) 14.8 Hz, methine-
H), 7.70 (1H, d, J ) 14.8 Hz, methine-H), 7.44 (2H, d, J ) 6.9 Hz,
pyridine-3,5-H), 4.31 (1H, m, pyridine-NCH), 3.96 (2H, m, pyridone-
NCH2), 2.81 (2H, t, J ) 7.6 Hz, pyridone-4-CH2), 1.96 (2H, m, CH2),
1.57-1.87 (7H, m, CH2 and CH3), 1.06 (3H, t, J ) 7.4 Hz, CH3),
0.89-0.99 (6H, m, CH3). Anal. Calcd for C23H29N3O2: C, 72.79; H,
7.70; N, 11.07. Found: C, 72.73; H, 7.67; N, 11.02.
2,5-Dibromo-3,4-diethylthiophene (18). To 17.0 g (0.12 mol)
of 3,4-diethylthiophene 17 in 200 mL of a 50:50 (v/v) mixture of
chloroform and acetic acid was added 47.0 g (0.26 mol) of N-bromo-
succinimide (NBS). The mixture was stirred at room temperature for
1 h and at 70 °C for another 4 h. The mixture was poured into ice-
water and extracted with dichloromethane. The combined organic
extracts were washed with water, 10% NaHCO3 (twice), and again with
water and dried over Na2SO4. Removal of the solvent afforded 32.05
1-Isopropyl-4-propyl-2,6-dioxo-5-[2-(1-sec-butyl-1-hydropyridin-
4-ylidene)ethylidene]-1,2,5,6-tetrahydropyridine-3-carbonitrile (1h).
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Yield, 56%; mp 274-275 °C. H NMR (200 MHz, CDCl3): δ 7.93
(2H, d, J ) 6.4 Hz, pyridine-2,6-H), 7.83 (1H, d, J ) 14.8 Hz, methine-
H), 7.69 (1H, d, J ) 14.3 Hz, methine-H), 7.40 (2H, d, J ) 6.9 Hz,
pyridine-3,5-H), 5.37 (1H, m, pyridone-NCH), 4.26 (1H, m, pyridine-
NCH), 2.78 (2H, t, J ) 7.6 Hz, pyridone-4-CH2), 1.93 (2H, m, CH2),
1.62-1.72 (5H, m, CH2 and CH3), 1.48 (6H, m, (CH3)2), 1.06 (3H, t,
J ) 7.1 Hz, CH3), 0.94 (3H, t, J ) 7.4 Hz, CH3). Anal. Calcd for
C23H29N3O2: C, 72.79; H, 7.70; N, 11.07. Found: C, 72.59; H, 7.65;
N, 10.97.
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g of 18 at a purity of 95% (from NMR); yield, 90%. H NMR (200
MHz, CDCl3): δ ) 2.59 (q, 4H, J ) 7.6 Hz, CH2), 1.11 (t, 3H, J )
7.6 Hz, CH3).
2-Bromo-3,4-diethyl-5-formylthiophene (19). A 2.56-mL (6.0
mmol) portion of a 15% solution of butyllithium in hexane was slowly
(1 h) added to 1.68 g (95%, 5.7 mmol) of 3,4-diethyl-2,5-dibromo-
thiophene 18 in 20 mL of dry ether under argon atmosphere at -70
°C and warmed to - 50 °C. Next, 0.52 mL (7.2 mmol) of DMF was
added dropwise and the mixture allowed to warm to room temperature
overnight. The mixture was poured into 1 mL of 12 M HCl in ice-
water and extracted with ether. The organic layers were combined,
washed with water, and dried over Na2SO4. Removal of the solvent
left 1.22 g (purity 90% from NMR); yield, 78%. Recrystallization from
toluene/hexane afforded pure 19, mp 58-59 °C. 1H NMR (200 MHz,
CDCl3): δ 9.93 (1H, s, CHO), 2.93 (2H, q, J ) 7.6 Hz, CH2), 2.62
1,4-Diisopropyl-2,6-dioxo-5-[2-(1-sec-butyl-1-hydropyridin-4-
ylidene)ethylidene]-1,2,5,6-tetrahydropyridine-3-carbonitrile (1i).
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Yield, 55%; mp 121-123 °C. H NMR (200 MHz, CDCl3): δ 7.97
(1H, d, J ) 14.3 Hz, methine-H), 7.89 (2H, d, J ) 7.4 Hz, pyridine-
2,6-H), 7.83 (1H, d, J ) 14.8 Hz, methine-H), 7.40 (2H, d, J ) 6.9
Hz, pyridine-3,5-H), 5.37 (1H, m, pyridone-NCH), 4.25 (1H, m,
pyridine-NCH), 3.55 (1H, m, pyridone-4-CH), 1.92 (2H, m, CH2), 1.62
(3H, d, J ) 6.4 Hz, CH3), 1.47 (12H, m, (CH3)2), 0.94 (3H, t, J ) 7.4
Hz, CH3). Anal. Calcd for C23H29N3O2: C, 72.79; H, 7.70; N, 11.07.
Found: C, 72.50; H, 7.77; N, 10.77.
1-(2-Ethylhexyl)-4-propyl-2,6-dioxo-5-[2-(1-dodecyl-2,6-diisopro-
pyl-1-hydropyridin-4-ylidene)ethylidene]-1,2,5,6-tetrahydropyridine-
3-carbonitrile (1j). Isolated by freeze-drying from dioxane; yield, 63%;
(58) Boelens, H.; Branksma, L. Recl. TraV. Chim. Pays-Bas 1972, 91, 141-
144.
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9446 J. AM. CHEM. SOC. VOL. 124, NO. 32, 2002