3294
A. Varela-Fernández et al.
PRACTICAL SYNTHETIC PROCEDURES
2-Butyl-2H-1,2-benzothiazine 1,1-Dioxide (4d)
Methyl 1H-Indole-5-carboxylate (2f)
The general heterocyclization procedure was followed using 1f
(0.088 g, 0.50 mmol), CpRuCl(PPh3)2 (0.036 g, 0.050 mmol), and
pyridine (3.30 mL). Upon completion (30 min) and workup, the res-
idue was purified by flash column chromatography through silica
gel using a 1:4 mixture of EtOAc–hexanes as eluent to give 2f
(0.086 g, 98%) as a yellow solid; mp 125–127 °C.
The general heterocyclization procedure was followed using 3d
(0.118 g, 0.50 mmol), CpRuCl(PPh3)2 (0.036 g, 0.050 mmol), and
pyridine (3.30 mL). Upon completion (6 h) and workup, the residue
was purified by flash column chromatography through silica gel us-
ing a 1:4 mixture of EtOAc–hexanes as eluent to give 4d (0.072 g,
61%) as a brown oil.
1H NMR (300 MHz, CDCl3): δ = 8.85 (s, 1 H), 8.43 (s, 1 H), 7.89
(dd, J = 8.6, 1.5 Hz, 1 H), 7.37 (d, J = 8.6 Hz, 1 H), 7.23–7.21 (m,
1 H), 6.61 (br s, 1 H), 3.92 (s, 3 H).
13C NMR, DEPT (75 MHz, CDCl3): δ = 168.4 (C=O), 138.4 (C),
128.8 (C), 125.9 (CH), 123.7 (CH), 123.1 (CH), 121.6 (C), 110.8
(CH), 103.7 (CH), 51.8 (CH3).
1H NMR (400 MHz, CDCl3): δ = 7.91 (d, J = 7.9 Hz, 1 H), 7.56 (t,
J = 7.6 Hz, 1 H), 7.47–7.35 (m, 2 H), 6.56 (d, J = 7.9 Hz, 1 H), 6.24
(d, J = 7.9 Hz, 1 H), 3.76–3.71 (m, 2 H), 1.75–1.67 (m, 2 H), 1.35
(dd, J = 15.1, 7.5 Hz, 2 H), 0.92 (t, J = 7.5 Hz, 3 H).
13C NMR, DEPT (75 MHz, CDCl3): δ = 133.2 (C), 131.9 (CH),
131.3 (CH), 131.1(C), 127.3 (CH), 126.5 (CH), 121.6 (CH), 107.1
(CH), 48.0 (CH2), 32.3 (CH2), 19.6 (CH2), 13.6 (CH3).
MS (EI, 70 eV): m/z (%) = 175 (M+, 67), 144 (100), 116 (55), 89
(21), 58 (44).
MS (CI): m/z (%) = 238 (M+ + 1, 100), 182 (6), 174 (4).
HRMS-EI: m/z calcd for C10H9NO2 [M+]: 175.0633; found:
175.0633.
HRMS (ESI): m/z calcd for C12H16NO2S [M+ + 1]: 238.0902; found:
238.0896.
Methyl 1H-Indole-6-carboxylate (2g)
1-[Isoquinolin-2(1H)-yl]ethanone (4f)
The general heterocyclization procedure was followed using 1g
(0.088 g, 0.50 mmol), CpRuCl(PPh3)2 (0.036 g, 0.050 mmol), and
pyridine (3.30 mL). Upon completion (90 min) and workup, the res-
idue was purified by flash column chromatography through silica
gel using a 1:4 mixture of EtOAc–hexanes as eluent to give 2g
(0.081 g, 92%) as a yellow solid; mp 78–80 °C.
The general heterocyclization procedure was followed using 3f
(0.086 g, 0.50 mmol), CpRuCl(PPh3)2 (0.036 g, 0.050 mmol), and
pyridine (3.30 mL). Upon completion (5 h) and workup, the residue
was purified by flash column chromatography through silica gel us-
ing a 1:4 mixture of EtOAc–hexanes as eluent to give 4f (0.048 g,
56%) as a yellowish oil.
1H NMR (250 MHz, CDCl3): δ = 8.70 (br s, 1 H), 8.16 (br s, 1 H),
7.82 (dd, J = 8.4, 1.4 Hz, 1 H), 7.62 (d, J = 8.4 Hz, 1 H), 7.32 (t, J =
2.8 Hz 1 H), 6.57 (m, 1 H), 3.92 (s, 3 H).
1H NMR (250 MHz, CDCl3): δ = 7.20-7.04 (m, 4 H), 6.65 (d, J =
7.8 Hz, 1 H), 5.82 (d, J = 7.8 Hz, 1 H), 4.94 (s, 2 H), 2.20 (s, 3 H).
13C NMR, DEPT (75 MHz, CDCl3): δ = 168.8 (C=O), 130.4 (C),
129.4 (C), 127.6 (CH), 127.3 (CH), 126.0 (CH), 125.9 (CH), 124.6
(CH), 109.6 (CH), 44.3 (CH2), 21.2 (CH3).
MS (CI): m/z (%) = 174 (M+ + 1, 100), 132 (30).
HRMS (ESI): m/z calcd for C11H12NO [M+ + 1]: 174.0919; found:
Isoquinolin-1(2H)-one (4b)
The general heterocyclization procedure was followed using 3b
(0.072 g, 0.50 mmol), CpRuCl(PPh3)2 (0.036 g, 0.050 mmol), and
pyridine (3.30 mL). Upon completion (60 min) and workup, the res-
idue was purified by flash column chromatography through silica
gel using a 1:1 mixture of EtOAc–hexanes as eluent to give 4b
(0.058 g, 80%) as a yellow solid; mp 209–210 °C.
174.0913.
2-Tosyl-1,2-dihydroisoquinoline (4g)
1H NMR (300 MHz, CDCl3): δ = 11.49 (s, 1 H), 8.43 (d, J = 8.0 Hz,
1 H), 7.68 (t, J = 6.9 Hz, 1 H), 7.59–7.51 (m, 2 H), 7.20 (d, J = 7.1
Hz, 1 H), 6.58 (d, J = 7.1 Hz, 1 H).
13C NMR, DEPT (75 MHz, CDCl3): δ = 164.4 (C=O), 138.1 (C),
132.5 (CH), 127.6 (CH), 127.3 (CH), 126.8 (CH), 126.2 (CH),
126.1 (C), 106.7 (CH).
MS (EI, 70 eV): m/z (%) = 145 (M+, 100), 118 (36), 90 (29).
HRMS-EI: m/z calcd for C9H7NO [M+]: 145.0528; found 145.0528.
The general heterocyclization procedure was followed using 3g
(0.142 g, 0.50 mmol), CpRuCl(PPh3)2 (0.036 g, 0.050 mmol), and
pyridine (3.30 mL). Upon completion (4 h) and workup, the residue
was purified by flash column chromatography through silica gel us-
ing a 1:4 mixture of EtOAc–hexanes as eluent to give 4g (0.116 g,
82%) as a brown solid; mp 184–186 °C.
1H NMR (250 MHz, CDCl3): δ = 7.69 (d, J = 8.3 Hz, 2 H), 7.27 (d,
J = 8.0 Hz, 2 H), 7.15–7.05 (m, 2 H), 6.98–6.90 (m, 2 H), 6.76 (d,
J = 7.8 Hz, 1 H), 5.83 (d, J = 7.8 Hz, 1 H), 4.56 (s, 2 H), 2.37 (s, 3
H).
13C NMR, DEPT (75 MHz, CDCl3): δ = 144.1 (C), 134.4 (C), 130.4
(C), 129.8 (2 × CH), 128.0 (CH), 127.3 (C), 127.2 (CH), 127.1 (2 ×
CH), 126.4 (CH), 125.5 (CH), 124.4 (CH), 110.0 (CH), 47.1 (CH2),
21.5 (CH3).
2-Butylisoquinolin-1(2H)-one (4c)
The general heterocyclization procedure was followed using 3c
(0.100 g, 0.50 mmol), CpRuCl(PPh3)2 (0.036 g, 0.050 mmol), and
pyridine (3.30 mL). Upon completion (6 h) and workup, the residue
was purified by flash column chromatography through silica gel us-
ing a 1:4 mixture of EtOAc–hexanes as eluent to give 4c (0.074 g,
74%) as a brown oil.
HRMS-EI: m/z calcd for C16H15NO2S [M+]: 285.0823; found:
285.0823.
1H NMR (500 MHz, CDCl3): δ = 8.44 (d, J = 8.1 Hz, 1 H), 7.64–
7.60 (m, 1 H), 7.51–7.46 (m, 2 H), 7.06 (d, J = 7.3 Hz, 1 H), 6.48
(d, J = 7.3 Hz, 1 H), 4.02–3.98 (m, 2 H), 1.80–1.74 (m, 2 H), 1.40
(td, J = 14.8, 7.4 Hz, 2 H), 0.96 (t, J = 7.4 Hz, 3 H).
13C NMR, DEPT (75 MHz, CDCl3): δ = 162.1 (C=O), 137.0 (C),
132.0 (CH), 131.7 (CH), 127.8 (CH), 126.7 (CH), 126.3 (C), 125.8
(CH), 105.8 (CH), 49.1 (CH2), 31.4 (CH2), 20.0 (CH2), 13.8 (CH3).
1-Tosyl-1,4-dihydroquinoline (6)
The general heterocyclization procedure was followed using 5
(0.142 g, 0.50 mmol), CpRuCl(PPh3)2 (0.036 g, 0.050 mmol), and
pyridine (3.30 mL). Upon completion (12 h) and workup, the resi-
due was purified by flash column chromatography through silica gel
using a 1:4 mixture of EtOAc–hexane as eluent to give 6 (0.085 g,
60%) as a brown oil.
MS (EI, 70 eV): m/z (%) = 202 (M+ + 1, 100), 149 (8), 123 (16).
HRMS (ESI): m/z calcd for C13H16NO [M+ + 1]: 202.1232; found:
1H NMR (500 MHz, CDCl3): δ = 7.81 (d, J = 8.2 Hz, 1 H), 7.44 (d,
J = 8.1 Hz, 2 H), 7.26–7.22 (m, 1 H), 7.15 (d, J = 8.1 Hz, 3 H), 6.89
(d, J = 7.5 Hz, 1 H), 6.71 (d, J = 7.3 Hz, 1 H), 5.54–5.49 (m, 1 H),
2.73 (d, J = 3.6 Hz, 2 H), 2.37 (s, 3 H).
202.1226.
13C NMR, DEPT (75 MHz, CDCl3): δ = 143.9 (C), 135.5 (C), 134.5
(C), 129.9 (C), 129.3 (2 × CH), 128.3 (CH), 127.6 (CH), 127.3 (2 ×
Synthesis 2012, 44, 3285–3295
© Georg Thieme Verlag Stuttgart · New York