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Green Chemistry
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ARTICLE
Journal Name
DOI: 10.1039/C9GC00938H
H] ) Calcd For C12H12F4NO2: 278.0799, found:278.0801.
2-Methoxy-4-(2,2,2-trifluoroethyl)-6-(trifluoromethoxy)-3,4-
+
1
dihydroisoquinolin-1(2H)-one (3n). Pale yellow oil, 61% yield. H
NMR (400 MHz, CDCl3) δ: 8.21 (d, J = 8.6 Hz, 1H), 7.26 (dd, J1 =
8.6 Hz, J2 = 1.2 Hz, 1H), 7.08 (s, 1H), 4.07 (dd, J1 = 12.0 Hz, J2 =
4.0 Hz, 1H), 3.90 (s, 3H), 3.80 (dd, J1 = 12.2 Hz, J2 = 2.8 Hz, 1H),
3.47–3.44 (m, 1H), 2.75–2.66 (m, 1H), 2.42–2.37 (m, 1H); 13C NMR
(100 MHz, CDCl3) δ: 162.0, 152.3, 141.2, 131.3, 126.4, 125.9 (q, J
= 275.6 Hz), 121.5, 120.2, 118.7, 61.9, 51.3, 37.3 (q, J = 28.4 Hz),
33.8 (q, J = 2.8 Hz). 19F NMR (376 MHz, CDCl3) δ: 57.65, 63.62.
HRMS (ESI) ([M + H]+) Calcd For C13H12F6NO3: 344.0716, found:
344.0719.
Chloro-2-methoxy-4-(2,2,2-trifluoroethyl)-3,4-
dihydroisoquinolin-1(2H)-one (3r). White solid. M. p. 68.1–70.8
1
°C. H NMR (400 MHz, CDCl3) δ: 8.04 (dd, J1 = 7.0 Hz, J2 = 1.2
Hz, 1H), 7.50 (dd, J1 = 6.9 Hz, J2 = 1.2 Hz, 1H), 7.32 (t, J = 7.9 Hz,
1H), 3.93 (dd, J1 = 8.8 Hz, J2 = 3.8 Hz, 1H), 3.85 (d, J = 1.2 Hz,
1H), 3.83 (s, 3H), 3.75 (d, J = 11.2 Hz, 1H), 2.66–2.52 (m, 1H),
2.31–2.18 (m, 1H); 13C NMR (100 MHz, CDCl3) δ: 161.9, 136.6,
133.6, 132.1, 130.1, 129.3, 127.6, 126.0 (q, J = 276.2 Hz), 61.9,
49.8, 34.2 (q, J = 28.4 Hz), 31.4 (q, J = 2.6 Hz). 19F NMR (376
MHz, CDCl3) δ: 63.69. HRMS (ESI) ([M
C12H12ClF3NO2: 294.0503, found: 294.0506.
+
H]+) Calcd For
2-Methoxy-7-methyl-4-(2,2,2-trifluoroethyl)-3,4-
dihydroisoquinolin-1(2H)-one (3o) and 2-Methoxy-5-methyl-4-
(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1(2H)-one
(1:2.2)
5-Bromo-2-methoxy-4-(2,2,2-trifluoroethyl)-3,4-
(3o’). Pale yellow oil. 1H NMR (400 MHz, CDCl3) δ: 8.03 (dd, J1 =
7.4 Hz, J2 = 0.56 Hz, 0.71H), 7.96 (d, J = 0.6 Hz, 0.29H), 7.37–7.29
(m, 1.74H), 7.12 (d, J = 7.8 Hz, 0.28H), 3.99 (td, J1 = 26.9 Hz, J2 =
4.1 Hz, 1H), 3.89 (m, 1.98 H), 3.88 (m, 1.06H), 3.80 (td, J1 = 35.1
Hz, J2 = 2.7 Hz, 1H), 3.55–3.53 (m, 0.77H), 3.49–3.38 (m, 0.34H),
2.79–2.64 (m, 1H), 2.38 (s, 0.93H), 2.36 (s, 2.09H), 2.34–2.03 (m,
1H); 13C NMR (100 MHz, CDCl3) δ: 163.3, 163.1, 138.2, 137.4,
136.1, 134.8, 134.1, 133.6, 130.3, 129.1, 128.3, 128.0, 127.7, 127.6,
126.9, 126.7, 126.2 (q, J = 275.7 Hz), 124.8, 61.7, 61.7, 51.4, 50.3,
37.3 (q, J = 27.8 Hz), 34.8 (q, J = 27.8 Hz), 33.3 (q, J = 2.7 Hz),
30.6 (q, J = 2.4 Hz), 20.9, 18.2. 19F NMR (376 MHz, CDCl3) δ:
63.70, 64.11. HRMS (ESI) ([M + H]+) Calcd For C13H15F3NO2:
274.1049; found: 274.1049.
dihydroisoquinolin-1(2H)-one (3s). White solid. M. p. 70.1–72.4
°C. 1H NMR (400 MHz, CDCl3) δ: 8.15 (d, J = 7.8 Hz, 1H), 7.74 (d,
J = 8.0 Hz, 1H), 7.31 (t, J = 7.9 Hz, 1H), 4.01 ( dd, J1 = 12.4 Hz, J2
= 3.4Hz, 1H), 3.93 (s, 1H), 3.90 (s, 3H), 3.80 (d, J = 12.0 Hz, 1H),
2.69–2.60 (m, 1H), 2.37–2.31 (m, 1H); 13C NMR (100 MHz, CDCl3)
δ: 161.7, 138.2, 137.0, 130.2, 129.6, 128.4, 126.0 (q, J = 276.3 Hz),
122.3, 61.9, 49.6, 34.4 (q, J = 28.2 Hz), 33.9 (q, J = 2.9 Hz). 19F
NMR (376 MHz, CDCl3) δ: 63.51. HRMS (ESI) ([M + H]+) Calcd
For C12H12BrF3NO2: 337.9998, found: 337.9998.
2-Methoxy-8-methyl-4-(2,2,2-trifluoroethyl)-3,4-
dihydroisoquinolin-1(2H)-one (3t). White solid. M. p. 59.1–59.4
°C. 1H NMR (400 MHz, CDCl3) δ: 8.03 (d, J = 7.5 Hz, 1H), 7.37 (d,
J = 6.8 Hz, 1H), 7.32 (t, J = 7.6 Hz, 1H), 3.98 (dd, J1 = 12.2 Hz, J2 =
3.5 Hz, 1H), 3.90 (s, 3H), 3.86 (d, J = 1.5 Hz, 1H), 3.55 (d, J = 11.0
Hz, 1H), 2.79–2.70 (m, 1H), 2.37 (s, 3H), 2.17–2.07 (m, 1H); 13C
NMR (100 MHz, CDCl3) δ: 163.1, 137.4, 134.8, 134.1, 128.2, 128.0,
126.8, 126.2 (q, J = 276.1 Hz), 61.6, 50.2, 34.7 (q, J = 27.7 Hz), 30.5
(q, J = 2.4 Hz), 18.2. 19F NMR (376 MHz, CDCl3) δ: 64.12. HRMS
2,5-Dimethoxy-4-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-
1
1(2H)-one (3p). White solid. M. p. 91.3–92.7 °C. H NMR (400
MHz, CDCl3) δ: 7.76 (dd, J1 = 7.8 Hz, J2 = 0.6 Hz, 1H), 7.38 (t, J =
8.0 Hz, 1H), 7.05 (dd, J1 = 8.2 Hz, J2 = 0.7 Hz, 1H), 3.94 (dd, J1 =
12.3 Hz, J2 = 4.0 Hz, 1H), 3.90 (s, 3H), 3.88 (s, 3H), 3.85 (dd, J1 =
12.1 Hz, J2 = 1.2 Hz, 1H), 3.76 (d, J = 10.9 Hz, 1H), 2.62–2.53 (m,
1H), 2.32–2.20 (m, 1H); 13C NMR (100 MHz, CDCl3) δ: 163.2,
155.0, 129.2, 128.9, 127.4, 126.4 (q, J = 275.8 Hz), 120.4, 114.1,
61.7, 55.8, 50.4, 34.6 (q, J = 27.8 Hz), 27.8 (q, J = 2.8 Hz). 19F NMR
(376 MHz, CDCl3) δ: 63.80. HRMS (ESI) ([M + H]+) Calcd For
C13H15F3NO3 : 290.0999, found: 290.1001.
(ESI) ([M
274.1054.
+
H]+) Calcd For C13H15F3NO2: 274.1049, found:
2-Methoxy-5,7-dimethyl-4-(2,2,2-trifluoroethyl)-3,4-
dihydroisoquinolin-1(2H)-one (3u). White solid. M. p. 71.8–74.7
1
°C. H NMR (400 MHz, CDCl3) δ: 7.84 (s, 1H), 7.19 (s, 1H), 3.96
(dd, J1 = 12.1 Hz, J2 = 3.6 Hz, 1H), 3.89 (s, 3H), 3.85 (dd, J1 = 12.1
Hz, J2 = 1.6 Hz, 1H), 3.51 (d, J = 10.9 Hz, 1H), 2.77–2.68 (m, 1H),
2.34 (s, 3H), 2.33 (s, 3H), 2.14–2.05 (m, 1H); 13C NMR (100 MHz,
CDCl3) δ: 163.3, 137.8, 135.6, 134.5, 133.9, 128.0, 127.1, 126.2 (q,
J = 276.0 Hz), 61.6, 50.3, 34.8 (q. J =27.5 Hz), 30.2 (q, J = 2.4 Hz),
20.7, 18.0. 19F NMR (376 MHz, CDCl3) δ: 64.13. HRMS (ESI)
([M + H]+) CalcdFor C14H17F3NO2: 288.1206, found: 288.1210.
7-Fluoro-2-methoxy-4-(2,2,2-trifluoroethyl)-3,4-
dihydroisoquinolin-1(2H)-one (3q) and 5-Fluoro-2-methoxy-4-
(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1(2H)-one
(1:1.4)
1
(3q’). White solid. H NMR (400 MHz, CDCl3) δ: 7.96 (d, J = 7.7
Hz, 0.59H), 7.82 (dd, J1 = 9.0 Hz, J2 = 2.6 Hz, 0.41H), 7.45–7.39
(m, 0.65H), 7.29–7.19 (m, 1.44H), 4.05 (td, J1 = 24.6 Hz, J2 = 3.4
Hz, 1H), 3.90 (s, 3H), 3.86–3.71 (m, 1.51H), 3.48–3.43 (m, 0.52H),
2.77–2.62 (m, 1H), 2.44–2.27 (m, 1H); 13C NMR (100 MHz, CDCl3)
δ: 163.6, 162.1 (d, J = 3.0 Hz), 161.8 (d, J = 2.2 Hz), 161.1, 159.6,
157.2, 134.7 (d, J = 3.4 Hz), 130.2, 130.1, 129.9 (d, J = 2.9 Hz),
129.6, 129.5, 128.9, 128.8, 127.2, 126.2, 126.0, 124.54 (q, J = 275.9
Hz), 124.48, 124.4 (d, J = 3.3 Hz), 120.0, 119.8, 119.6, 119.4, 115.4,
115.2, 61.8, 51.3, 50.5, 37.3 (q, J = 28.3 Hz), 35.5 (q, J = 28.2 Hz),
33.1 (q, J = 2.5 Hz), 27.3 (q, J = 2.6 Hz). 19F NMR (376 MHz,
5,7-Dichloro-2-methoxy-4-(2,2,2-trifluoroethyl)-3,4-
dihydroisoquinolin-1(2H)-one (3v). White solid. M. p. 98.3–99.7
°C. 1H NMR (400 MHz, CDCl3) δ: 8.01 (d, J = 2.2 Hz, 1H), 7.50 (d,
J = 2.2 Hz, 1H), 3.93 (dd, J1 = 8.8 Hz, J2 = 3.8 Hz, 1H), 3.85 (dd, J1
= 6.8 Hz, J2 = 1.5 Hz, 1H), 3.82 (s, 3H), 3.71 (d, J = 11.2 Hz, 1H),
2.64–2.50 (m, 1H), 2.27–2.15 (m, 1H); 13C NMR (100 MHz, CDCl3)
δ: 160.7, 135.2, 134.9, 133.1, 132.9, 131.0, 127.6, 125.9 (q, J =
276.2 Hz), 61.9, 49.6, 34.2 (q, J = 28.4 Hz), 31.0 (q, J = 2.6 Hz). 19
F
6 | Green Chem., 2016, 00, 1-7
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