The Journal of Organic Chemistry
Article
Synthesis of 7-Fluoro-3,4-dihydro-2H-isoquinolin-1-one 2g. Yield
91% (145 mg, 0.877 mmol, from 0.962 mmol of 1g). Mp: 117.5−
118.5 (colorless needles, recrystallized from CH2Cl2 and n-hexane).
1H NMR (400 MHz, CDCl3) δ (ppm): 7.76 (dd, J = 9.2, 2.8 Hz, 1H),
7.14−7.20 (m, 2H), 6.17 (brs, 1H), 3.57 (dt, J = 6.8, 3.2 Hz, 2H), 2.98
(t, J = 6.0 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ (ppm): 165.7,
161.6 (d, J = 244 Hz), 134.4 (d, J = 3 Hz), 130.7 (d, J = 7 Hz), 128.8
(d, J = 7 Hz), 118.9 (d, J = 22 Hz), 114.2 (d, J = 22 Hz), 39.9, 27.3.
Anal. Calcd for C9H8FNO: C, 65.45; H, 4.88; N, 8.48. Found: C,
65.24; H, 5.03; N, 8.37. MS (ESI+): 188 ([M + Na]+).
6-Fluoro-3,4-dihydro-2H-isoquinolin-1-one (2h-1) and 8-Fluoro-
3,4-dihydro-2H-isoquinolin-1-one (2h-2). Mixture of 2h-1 and 2h-2
(199.6 mg, 1.21 mmol, from 1.25 mmol of 1h) (2c-1:2c-2 = 92:8, the
ratio was determined by 1H NMR) was obtained after column
chromatography (MeOH/CHCl3 = 1:10). The mixture was separated
roughly (column chromatography with less polar solvent) and pure
products were obtained after recrystallization.
CDCl3) δ (ppm): 164.6, 135.2, 133.4, 133.3, 132.3, 131.8, 126.8, 39.2.
25.0. ESI-HRMS: Calcd for C9H7Cl2NNaO+ ([M + Na]+): 237.9797.
Found: 237.9796.
Synthesis of 2-Methyl-3,4-dihydro-2H-isoquinolin-1-one 2q. Yield
88% (120 mg, 0.744 mmol, from 0.845 mmol of 1q). Colorless oil. 1H
NMR (400 MHz, CDCl3/TMS) δ (ppm): 8.10 (d, J = 7.6 Hz, 1H),
7.42 (dd, J = 7.6, 7.2 Hz, 1H), 7.37 (dd, J = 7.6, 7.2 Hz, 1H), 7.19 (dd,
J = 7.2 Hz, 1H), 3.59 (t, J = 6.8 Hz, 2H), 3.18 (s, 3H), 3.03 (t, J = 6.8
Hz, 2H). 13C NMR (100 MHz, CDCl3) δ (ppm): 164.8, 137.9, 131.5,
129.4, 128.1, 127.0, 126.9, 48.1, 35.2, 27.9. ESI-HRMS: Calcd for
C10H11NNaO+ ([M + Na]+): 184.0738. Found: 184.0737.
Synthesis of 7-Chloro-2-methyl-3,4-dihydro-2H-isoquinolin-1-
one 2r. Yield 78% (156 mg, 0.799 mmol, from 1.03 mmol of 1r).
Colorless oil. 1H NMR (400 MHz, CDCl3/TMS) δ (ppm): 8.06 (d, J
= 2.0 Hz, 1H), 7.42 (dd, J = 8.0, 2.4 Hz, 1H), 7.12 (d, J = 8.0, 7.2 Hz,
1H), 3.57 (t, J = 6.8 Hz, 2H), 3.16 (s, 3H), 2.99 (t, J = 6.8 Hz, 2H).
13C NMR (100 MHz, CDCl3) δ (ppm): 163.6, 136.2, 133.1, 131.4,
2h-1: 89% Yield. Mp.: 111.0−112.0 °C (colorless needles,
130.9, 128.4, 128.1, 48.0, 35.2, 27.3. ESI-HRMS: Calcd for
1
recrystallized from n-hexane and diethylether). H NMR (400 MHz,
C10H10ClNNaO+ ([M + Na]+): 218.0349. Found: 218.0337.
CDCl3) δ (ppm): 8.08 (dd, J = 8.8, 5.6 Hz, 1H), 7.21 (brs, 1H), 7.03
(dt, J = 8.8, 2.8 Hz, 1H), 6.92 (dd, J = 8.8, 2.8 Hz, 1H), 3.59 (dt, J =
6.4, 2.8 Hz, 2H), 2.99 (t, J = 6.4 Hz, 2H). 13C NMR (100 MHz,
CDCl3) δ (ppm): 166.1, 164.7 (d, J = 219 Hz), 141.7 (d, J = 9 Hz),
130.7 (d, J = 10 Hz), 125.3, 114.2 (d, J = 19 Hz), 114.0 (d, J = 19 Hz),
40.0, 28.4 (d, J = 1 Hz). ESI-HRMS: Calcd for C9H8FNNaO+ ([M +
Na]+): 188.0488. Found: 188.0490.
Synthesis of 4-Methyl-3,4-dihydro-2H-isoquinolin-1-one 2s. Yield
88% (138 mg, 0.855 mmol, from 0.977 mmol of 1s). Colorless oil. 1H
NMR (400 MHz, CDCl3/TMS) δ (ppm): 8.08 (dd, J = 8.0, 1.6 Hz,
1H), 7.49 (dt, J = 7.6, 1.6 Hz, 1H), 7.36 (dt, J = 7.6, 0.8 Hz, 1H), 7.26
(d, J = 7.6 Hz, 1H), 7.11 (1H, brs), 3.66 (dq, J = 8.4, 2.4 Hz, 1H), 3.31
(dq, J = 8.0, 3.2 Hz, 1H), 3.12 (h, J = 6.8 Hz, 1H), 1.36 (d, J = 6.8 Hz,
1H). 13C NMR (100 MHz, CDCl3) δ (ppm): 166.4, 143.9, 132.3,
128.1, 128.0, 126.9, 125.8, 46.4, 32.3, 18.4. ESI-HRMS: Calcd for
C10H11NNaO+ ([M + Na]+): 184.0738. Found: 184.0737.
2h-2: 8% Yield. Mp.: 127.0−128.0 °C (colorless needles, recrystal-
1
lized from n-hexane/diethylether). H NMR (400 MHz, CDCl3) δ
(ppm): 7.43−7.38 (m, total 1H), 7.08−7.03 (m, total 2H), 6.79 (brs,
1H), 3.54 (dt, J = 6.8, 3.2 Hz, 2H), 3.00 (t, J = 6.4 Hz, 2H). 13C NMR
(100 MHz, CDCl3) δ (ppm): 163.6, 162.3 (d, J = 257 Hz), 141,8,
133.2 (d, J = 10 Hz), 123.0 (d, J = 4 Hz), 117.3 (d, J = 7 Hz), 115.8 (d,
J = 23 Hz), 39.8, 29.2 (d, J = 2 Hz). ESI-HRMS: Calcd for
C9H8FNNaO+ ([M + Na]+): 188.0488. Found: 188.0499.
Synthesis of 5-Fluoro-3,4-dihydro-2H-isoquinolin-1-one 2i. Yield
85% (158 mg, 0.959 mmol, from 1.13 mmol of 1i). Mp.: 151.0−152.0
°C (colorless needles, recrystallized from n-hexane and diethylether).
1H NMR (400 MHz, CDCl3) δ (ppm): 7.88 (dd, J = 8.0, 0.8 Hz, 1H),
7.35−7.18 (m, total 2H), 6.53 (s, 1H), 3.59 (dt, J = 6.4, 2.8 Hz, 2H),
3.03 (t, J = 6.8 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ (ppm):
165.3, 159.4 (d, J = 245 Hz), 130.8 (d, J = 3 Hz), 127.8 (d, J = 7 Hz),
125.7, 123.6 (d, J = 3 Hz), 118.8 (d, J = 21 Hz), 39.7, 20.9. ESI-
HRMS: Calcd for C9H8FNNaO+ ([M + Na]+): 188.0488. Found:
188.0498.
Synthesis of 2,3,4,5-Tetrahydro-benzo[c]azepin-1-one 2t. 80%
Yield (156.3 mg, 0.970 mmol, from 1.22 mmol of 1t). Mp.: 94−95 °C
1
(white powder, recrystallized from n-hexane and CHCl3). H NMR
(400 MHz, CDCl3/TMS) δ (ppm): 7.73 (d, J = 7.2 Hz, 1H), 7.43 (dd,
J = 7.2, 7.2 Hz, 1H), 7.36 (dd, J = 7.6, 7.2 Hz, 1H), 7.21 (d, J = 7.6 Hz,
1H), 6.69 (br, 1H), 3.15 (q, J = 6.4 Hz, 2H), 2.89 (t, J = 7.2 Hz, 2H),
2.08 - 2.01 (m, total 2H). 13C NMR (100 MHz, CDCl3) δ (ppm):
173.9, 138.3, 135.0, 131.3, 128.8, 128.6, 127.0, 39.6, 30.5, 30.3. Anal.
Calcd for C10H11NO: C, 74.51; H, 6.88 N, 8.69. Found: C, 74.21; H,
6.99; N, 8.54. MS (ESI+): 184 ([M + Na]+) (M: C10H11NO)
Synthesis of 8-Fluoro-2,3,4,5-tetrahydro-benzo[c]azepin-1-one
2u. Yield 9% (16.2 mg, 0.090 mmol, from 1.06 mmol of 1u). Mp.:
166.0−167.0 °C (colorless needles, recrystallized from n-hexane and
1
diethylether). H NMR (400 MHz, CDCl3) δ (ppm): 7.44 (dd, J =
8.8, 2.8 Hz, 1H), 7.20−7.11 (m, total 2H), 6.47 (brs, 1H), 3.16 (q, J =
6.4 Hz, 2H), 2.86 (t, J = 7.2 Hz, 2H), 2.03 (m, total 2H). 13C NMR
(100 MHz, CDCl3) δ (ppm): 172.7 (d, J = 2 Hz), 162.2 (d, J = 245
Hz), 136.7 (d, J = 8 Hz), 134.0, 130.3 (d, J = 8 Hz), 118.0 (d, J = 21
Hz), 115.7 (d, 21 Hz), 39.5, 30.3 (d, J = 1 Hz), 29.5. ESI-HRMS:
Calcd for C10H10FNNaO+ ([M + Na]+): 202.0644. Found: 202.0645.
Synthesis of 7-Hydroxy-3,4-dihydro-2H-isoquinolin-1-one 2k.
Yield 82% (138 mg, 0.701 mmol, from 1.03 mmol of 1j), 84% Yield
(133 mg, 0.816 mmol, from 0.968 mmol of 1k). Mp. 204.0−206.0 °C
1
(white powder, recrystallized from AcOEt/CHCl3). H NMR (400
1
2-(4-Chlorophenyl)ethanamine 3d. Colorless oil. H NMR (400
MHz,DMSO-d6) δ (ppm): 9.49 (s, 1H), 7.85 (s, 1H), 7.25 (d, J = 2.8
Hz, 1H), 7.09 (d, J = 8.4 Hz, 1H), 6.85 (dd, J = 7.6, 2.8 Hz, 1H), 3.32
(dt, J = 6.8, 2.8 Hz, 2H), 2.76 (t, J = 6.8 Hz, 2H). 13C NMR (100
MHz, CDCl3) δ (ppm): 165.1, 156.5, 130.8, 129.9, 128.9, 119.3, 113.7,
MHz, CDCl3) δ (ppm): 7.25 (d, J = 6.4 Hz, 2H), 7.11 (d, J = 6.4 Hz,
2H), 2.93 (t, J = 6.8 Hz, 2H), 2.70 (t, J = 6.8 Hz, 2H), 1.30 (brs, 2H).
13C NMR (100 MHz, CDCl3) δ (ppm): 138.3, 131.9, 130.2, 128.5,
43.4, 39.4. ESI-HRMS: Calcd for C8H11ClN+ ([M + H]+): 156.0575.
Found: 156.0564.
+
39.9, 27.3. ESI-HRMS: Calcd for C9H9NNaO2 ([M + Na]+):
186.0531. Found: 186.0542.
1
2-(4-Fluorophenyl)ethanamine 3g. Colorless oil. H NMR (400
Synthesis of 5-Fluoro-8-methyl-3,4-dihydro-2H-isoquinolin-1-
one 2l. Yield 97% (195 mg, 1.09 mmol, from 1.12 mmol of 1l).
Mp.: 115.5−116.0 °C (white powder, recrystallized from n-hexane/
MHz, CDCl3) δ (ppm): 7.16−7.12 (m, 2H), 7.00−6.95 (m, 2H), 2.93
(t, J = 6.8 Hz, 2H), 2.71 (t, J = 6.8 Hz, 2H), 1.51 (brs, 2H).13C NMR
(100 MHz, CDCl3) δ (ppm): 162.3 (d, J = 43 Hz), 135.3 (d, J = 4
Hz), 130.0 (d, J = 8 Hz), 115.0 (d, J = 21 Hz), 43.4, 39.0. ESI-HRMS:
Calcd. for C8H11FN+ ([M+H]+): 140.0870. Found: 140.0881.
2-(2,4-Dichlorophenyl)ethanamine 3m. Yield 44% (83.4 mg,
0.439 mmol, from 1.00 mmol of 1m). Yellow oil. 1H NMR (400
MHz, CDCl3) δ (ppm): 7.37 (d, J = 1.6 Hz, 1H), 7.20−7.15 (m, 2H),
2.95 (dt, J = 8.0, 1.2 Hz, 2H), 2.85 (dt, J = 7.2, 0.8 Hz, 2H), 1.48 (brs,
2H). 13C NMR (100 MHz, CDCl3) δ (ppm): 136.0, 134.8, 132.6,
131.6, 129.3, 127.0, 41.8, 37.2. ESI-HRMS: Calcd for C8H10Cl2N+ ([M
+ H]+): 190.0185. Found: 190.0176.
1
diethylether). H NMR (400 MHz, CDCl3) δ (ppm): 7.11−7.03 (m,
total 2H), 6.17 (brs, 1H), 3.48 (dt, J = 6.4, 3.2 Hz, 2H), 2.96 (t, J = 6.4
Hz, 2H), 2.65 (3H, s). 13C NMR (100 MHz, CDCl3) δ (ppm): 166.4
(d, J = 3 Hz), 157.1 (d, J = 241 Hz), 136.4 (d, J = 4 Hz), 131.1 (d, J =
7 Hz), 128.5 (d, J = 3 Hz), 126.7 (d, J = 8 Hz), 117.7 (d, J = 22 Hz),
39.4, 22.0 (d, J = 4 Hz), 21.5. ESI-HRMS: Calcd for
C10H10FNNaO+([M + Na]+): 202.0644. Found: 202.0655.
Synthesis of 5,7-dichloro-3,4-dihydro-2H-isoquinolin-1-one 2m.
Yield 40% (87.0 mg, 0.403 mmol, from 1.00 mmol of 1m). Mp.:
195.0−195.5 °C (white powder, recrystallized from n-hexane/
1
dichloromethane). H NMR (400 MHz, CDCl3) δ (ppm): 8.02 (d,
2-(4-Nitrophenyl)ethanamine 3n. Yield 72% (35.7 mg, 0.215
1
J = 2.0 Hz, 1H), 7.54 (d, J = 2.4 Hz, 1H), 6.04 (brs, 1H), 3.59 (dt, J =
mmol, from 0.297 mmol of 1n). Yellow oil. H NMR (400 MHz,
6.7, 2.9 Hz, 2H), 2.93 (t, J = 6.8 Hz, 2H). 13C NMR (100 MHz,
CDCl3) δ (ppm): 8.16 (dd, J = 6.8, 2.0 Hz, 2H), 7.37 (dd, J = 6.8, 2.0
9325
dx.doi.org/10.1021/jo3020566 | J. Org. Chem. 2012, 77, 9313−9328