PAPER
Synthesis of (Z)-2-(2H-Isoquinolin-1-ylidene)acetamides
827
(Z)-N-{3-(Morpholin-4-yl)-3-oxo-1-[2-(1-phenylvinyl)phe-
nyl]propenyl}acetamide (3c)
Yellow viscous oil; Rf = 0.23 (EtOAc–hexane, 1:1).
IR (neat): 3402, 1713, 1622 cm–1.
1H NMR (500 MHz): d = 1.97 (s, 3 H), 3.07 (br s, 2 H), 3.45–3.62
(m, 6 H), 4.96 (s, 1 H), 5.28 (d, J = 1.4 Hz, 1 H), 5.70 (d, J = 1.4 Hz,
1 H), 7.21–7.42 (m, 9 H), 11.54 (br s, 1 H).
mL). The combined extracts were washed with sat. aq NaHCO3 (20
mL) and then brine (10 mL), and dried (K2CO3). Evaporation of the
solvent gave a residue, which was purified by preparative TLC on
silica gel to afford 4a; yield: 0.13 g (51%); pale-yellow solid; mp
167–168 °C (hexane–CH2Cl2).
IR (KBr): 1664 cm–1.
1H NMR (500 MHz): d = 2.26 (s, 3 H), 2.28 (s, 3 H), 2.62 (s, 3 H),
5.45 (s, 1 H), 6.36 (s, 1 H), 7.23 (td, J = 7.3, 1.4 Hz, 1 H), 7.31 (td,
J = 7.3, 1.4 Hz, 1 H), 7.33 (d, J = 7.3 Hz, 1 H), 7.40–7.49 (m, 4 H),
7.59 (dd, J = 8.2, 1.4 Hz, 2 H).
Anal. Calcd for C23H24N2O3: C, 73.38; H, 6.43; N, 7.44. Found: C,
73.27; H, 6.71; N, 7.39.
(Z)-3-Acetylamino-3-{2-[1-(4-chlorophenyl)vinyl]phenyl}-N,N-
dimethylpropenamide (3d)
Yellow oil; Rf = 0.22 (EtOAc–pentane, 1:2).
IR (KBr): 3404, 1709, 1622 cm–1.
MS: m/z (%) = 332 (7.3, [M+]), 272 (18), 231 (87), 189 (100).
Anal. Calcd for C21H20N2O2: C, 75.88; H, 6.06; N, 8.43. Found: C,
76.00; H, 6.12; N, 8.32.
(Z)-2-(2-Acetyl-4-phenyl-2H-isoquinolin-1-ylidene)-N,N-di-
ethylacetamide (4b)
Pale-yellow solid; mp 157–158 °C (hexane–CH2Cl2).
IR (KBr): 1661 cm–1.
1H NMR (500 MHz): d = 1.95 (s, 3 H), 2.82 (s, 3 H), 2.93 (s, 3 H),
5.02 (s, 1 H), 5.30 (d, J = 0.9 Hz, 1 H), 5.62 (d, J = 0.9 Hz, 1 H),
7.20 (br s, 4 H), 7.27 (dd, J = 8.7, 2.3 Hz, 1 H), 7.33–7.40 (m, 3 H,),
11.75 (br s, 1 H).
Anal. Calcd for C21H21ClN2O2: C, 68.38; H, 5.74; N, 7.59. Found:
C, 68.29; H, 5.77; N, 7.41.
1H NMR (500 MHz): d = 0.73 (t, J = 7.3 Hz, 3 H), 0.84 (t, J = 7.3
Hz, 3 H), 2.28 (s, 3 H), 2.41 (dq, J = 15.3, 7.3 Hz, 1 H), 2.83–2.91
(m, 2 H), 3.37 (dq, J = 15.3, 7.3 Hz, 1 H), 5.37 (s, 1 H), 6.35 (s, 1
H), 7.20 (td, J = 7.3, 1.4 Hz, 1 H), 7.28 (ddd, J = 7.8, 7.3, 1.4 Hz, 1
H), 7.38–7.50 (m, 5 H), 7.59 (dd, J = 8.2, 1.4 Hz, 2 H).
(Z)-3-Acetylamino-N,N-dimethyl-3-[2-(1-methylvinyl)phe-
nyl]propenamide (3e)
Pale-yellow viscous oil; Rf = 0.36 (EtOAc–hexane, 1:1).
IR (neat): 3402, 1713, 1622 cm–1.
1H NMR (500 MHz): d = 2.02 (s, 3 H), 2.07 (s, 3 H), 3.02 (s, 3 H),
3.03 (s, 3 H), 4.99 (d, J = 0.9 Hz, 1 H), 5.09 (d, J = 0.9 Hz, 1 H),
5.33 (s, 1 H), 7.21–7.32 (m, 4 H), 11.92 (br s, 1 H).
MS: m/z (%) = 360 (6.2, [M+]), 300 (11), 231 (100).
Anal. Calcd for C23H24N2O2: C, 76.64; H, 6.71; N, 7.77. Found: C,
76.31; H, 6.81; N, 7.39.
(Z)-2-(2-Acetyl-4-phenyl-2H-isoquinolin-1-ylidene)-1-(mor-
pholin-4-yl)ethanone (4c)
Pale-yellow solid; mp 204–205 °C (hexane–CH2Cl2).
IR (KBr): 1670, 1655 cm–1.
1H NMR (500 MHz): d = 2.28 (s, 3 H), 2.29–2.32 (m, 1 H), 2.61–
2.65 (m, 1 H), 2.91–2.94 (m, 1 H), 2.99–3.09 (m, 2 H), 3.30–3.33
(m, 1 H), 3.51–3.54 (m, 1 H), 3.67–3.70 (m, 1 H), 5.37 (s, 1 H), 6.33
(s, 1 H), 7.27 (t, J = 7.3 Hz, 1 H), 7.33–7.40 (m, 2 H), 7.41–7.49 (m,
4 H), 7.57 (d, J = 8.2 Hz, 2 H).
13C NMR: d = 14.27, 41.71, 44.70, 65.49, 66.22, 78.71, 83.49,
121.28, 125.50, 127.02, 127.50, 128.78, 128.88, 128.99, 134.03,
135.12, 142.28, 144.86, 146.29, 165.56, 168.56.
Anal. Calcd for C16H20N2O2: C, 70.56; H, 7.40; N, 10.29. Found: C,
70.52; H, 7.40; N, 10.28.
(Z)-3-Acetylamino-3-[2-(1-ethylvinyl)phenyl]-N,N-dimethyl-
propenamide (3f)
Colorless viscous oil; Rf = 0.39 (EtOAc–hexane, 1:1).
IR (neat): 3402, 1713, 1622 cm–1.
1H NMR (500 MHz): d = 1.00 (t, J = 7.3 Hz, 3 H), 2.06 (s, 3 H),
2.33 (q, J = 7.3 Hz, 2 H), 3.02 (s, 3 H), 3.03 (s, 3 H), 4.99 (s, 1 H),
5.08 (q, J = 1.4 Hz, 1 H), 5.34 (s, 1 H), 7.18 (dd, J = 7.3, 1.4 Hz, 1
H), 7.23 (dd, J = 7.3, 1.4 Hz, 1 H), 7.25 (td, J = 7.3, 1.4 Hz, 1 H),
7.30 (td, J = 7.3, 1.4 Hz, 1 H), 11.87 (br s, 1 H).
MS: m/z (%) = 374 (6.4, [M+]), 314 (15), 231 (83), 189 (100).
Anal. Calcd for C17H22N2O2: C, 71.30; H, 7.74; N, 9.78. Found: C,
71.28; H, 7.78; N, 9.53.
Anal. Calcd for C23H22N2O3: C, 73.78; H, 5.92; N, 7.48. Found: C,
73.86; H, 5.75; N, 7.18.
(Z)-3-Acetylamino-3-[4-methoxy-2-(1-phenylvinyl)phenyl]-
N,N-dimethylpropenamide (3g)
(Z)-2-[2-Acetyl-4-(4-chlorophenyl)-2H-isoquinolin-1-ylidene]-
N,N-dimethylacetamide (4d)
Pale-yellow solid; mp 179–181 °C (hexane–CH2Cl2).
IR (KBr): 1658 cm–1.
1H NMR (500 MHz): d = 2.24 (s, 3 H), 2.27 (s, 3 H), 2.62 (s, 3 H),
5.44 (s, 1 H), 6.36 (s, 1 H), 7.24 (td, J = 7.3, 0.9 Hz, 1 H), 7.32 (td,
J = 7.3, 0.9 Hz, 1 H), 7.33 (d, J = 7.3 Hz, 1 H), 7.38 (d, J = 7.3 Hz,
1 H), 7.44 (d, J = 8.7 Hz, 2 H), 7.52 (d, J = 8.7 Hz, 2 H).
Yellow viscous oil; Rf = 0.26 (EtOAc–hexane, 3:2).
IR (neat): 3410, 1709, 1622 cm–1.
1H NMR (400 MHz): d = 1.94 (s, 3 H), 2.74 (s, 3 H), 2.89 (s, 3 H),
3.82 (s, 3 H), 5.04 (s, 1 H), 5.29 (d, J = 1.0 Hz, 1 H), 5.66 (d, J = 1.0
Hz, 1 H), 6.82 (d, J = 2.4 Hz, 1 H), 6.88 (dd, J = 8.2, 2.4 Hz, 1 H),
7.19–7.30 (m, 6 H), 11.65 (br s, 1 H).
Anal. Calcd for C22H24N2O3: C, 72.50; H, 6.64; N, 7.69. Found: C,
72.29; H, 6.68; N, 7.77.
MS: m/z (%) = 366 (2.9, [M+]), 306 (11), 265 (46), 189 (100).
Anal. Calcd for C21H19ClN2O2: C, 68.76; H, 5.22; N, 7.64. Found:
C, 68.89; H, 5.37; N, 7.51.
2-(2H-Isoquinolin-1-ylidene)acetamides 4; (Z)-2-(2-Acetyl-4-
phenyl-2H-isoquinolin-1-ylidene)-N,N-dimethylacetamide(4a);
Typical Procedure
To a stirred solution of 3a (0.25 g, 0.74 mmol) in MeCN (5 mL)
containing NaHCO3 (0.19 g, 2.2 mmol) at 0 °C, was added I2 (0.56
g, 2.2 mmol) in portions and the mixture was stirred for 1 h at the
same temperature. Aq 10% Na2S2O3 was added until the color of I2
had disappeared, and the mixture was extracted with Et2O (3 × 15
(Z)-2-(2-Acetyl-4-methyl-2H-isoquinolin-1-ylidene)-N,N-di-
methylacetamide (4e)
Pale-yellow solid; mp 123–127 °C (hexane–CH2Cl2).
IR (KBr): 1653 cm–1.
Synthesis 2007, No. 6, 824–828 © Thieme Stuttgart · New York