Paper
Organic & Biomolecular Chemistry
160.0, 145.1, 135.7, 135.4, 131.1, 129.7, 128.6, 128.6, 128.4, was subjected to General procedure E with 2-phenylaceto-
128.3, 126.0, 124.8, 114.6, 55.8, 15.7; IR νmax (thin film)/cm−1 nitrile, 7a. Purification by flash column chromatography
2992, 2955, 2930, 2832, 1607, 1593, 1513, 1490, 1462, 1423, [petrol/Et2O 19 : 1 grading to 1 : 1] furnished nitrile 8b
1384, 1315, 1288, 1243, 1203, 1164, 1146, 1107, 1029, 1002, (72.6 mg, 0.223 mmol, 73%) as prisms. M.p. 57–59 °C (petrol/
970, 943, 894, 872, 850; HRMS (ESI-TOF) m/z: [M + H]+ Calcd CH2Cl2); 1H NMR (400 MHz, CDCl3) δH: 7.37–7.36 (4H, m),
for C17H16NO2 266.1176; Found 266.1166.
7.34–7.31 (1H, m), 7.11 (1H, s), 6.84 (1H, s), 5.82 (1H, s), 5.82
6,7-Dimethoxy-4-methyl-3-phenylisoquinoline-N-oxide 5r. (1H, s), 4.17–4.02 (4H, m), 3.91 (3H, s), 3.81 (3H, s);
Ketone 3r (57.8 mg, 0.205 mmol) (synthesis10) was subjected 13C[1H] NMR (100 MHz, CDCl3) δC: 149.9, 148.6, 135.9, 129.0,
to General procedure D. Purification by flash column chrom- 128.0, 127.6, 127.4, 126.7, 120.0, 112.2, 110.1, 101.8, 65.1, 65.0,
atography on alumina [EtOAc/MeOH 19 : 1 grading to 3 : 1] 56.0, 56.0, 37.4; IR νmax (thin film)/cm−1 2960, 2893, 2243,
furnished isoquinoline-N-oxide 5r (41.3 mg, 0.188 mmol, 92%) 1609, 1518, 1494, 1453, 1402, 1351, 1290, 1268, 1201, 1180,
as prisms. M.p. 193–195 °C (petrol/CH2Cl2); 1H NMR 1114, 1066, 1030, 1003, 959, 940, 913, 868; HRMS (ESI-TOF)
(400 MHz, CDCl3) δH: 8.72 (1H, s), 7.54–7.50 (2H, m), 7.48–7.44 m/z: [M + Na]+ Calcd for C19H19NNaO4 348.1206; Found
(1H, m), 7.40–7.38 (2H, m), 7.11 (1H, s), 6.98 (1H, s), 4.04 (3H, 348.1203.
s), 4.03 (3H, s), 2.35 (3H, s); 13C[1H] NMR (75 MHz, CDCl3) δC:
2-(2-(1,3-Dioxolan-2-yl)phenyl)-2-(thiophen-2-yl)acetonitrile
151.8, 151.6, 144.5, 133.8, 133.3, 130.1, 129.1, 128.7, 128.6, 8c. Aryl bromide 1a (107 mg, 0.467 mmol) was subjected to
125.7, 124.6, 103.5, 102.8, 56.2, 56.1, 16.3; IR νmax (thin film)/ General procedure E with 2-thiopheneacetonitrile, 7b. Purifi-
cm−1 2926, 1622, 1506, 1465, 1423, 1388, 1364, 1312, 1254, cation (twice) by flash column chromatography [petrol/EtOAc
1208, 1167, 1072, 1030, 990; HRMS (ESI-TOF) m/z: [M + Na]+ 9 : 1 then petrol/CH2Cl2 1 : 1] furnished nitrile 8c (48.1 mg,
Calcd for C18H17NNaO3 318.1101; Found 318.1101.
0.177 mmol, 38%) as an oil. 1H NMR (400 MHz, CDCl3) δH:
2,4-Dimethyl-3-phenylisoquinolin-2-ium chloride 6a. A solu- 7.59 (2H, m), 7.45 (1H, td, J 7.5, 1.6), 7.39 (1H, td, J 7.5, 1.3),
tion of MeNH3Cl (2.47 mL, 1.0 M in 19 : 1 EtOH/H2O) was 7.27 (1H, dd, J 5.2, 1.2), 7.11 (1H, dt, J 3.5, 1.1), 6.97 (1H, dd,
added to ketone 3a (69.7 mg, 0.247 mmol) (synthesis10) in a J 5.1, 3.6), 6.09 (1H, s), 5.90 (1H, s), 4.20–4.05 (4H, m);
resealable reaction tube containing a magnetic follower. The 13C[1H] NMR (100 MHz, CDCl3) δC: 138.5, 134.5, 134.2, 130.0,
tube was sealed with a screw cap and heated at 90 °C for 18 h. 129.2, 128.6, 127.6, 126.9, 126.8, 126.4, 119.3, 102.2, 65.1, 65.0,
The reaction was then cooled to room temperature and 33.6; IR νmax (thin film)/cm−1 2959, 2925, 2891, 2855, 1738,
quenched by the addition of saturated aqueous NaHCO3 1601, 1470, 1389, 1259, 1216, 1074, 1043, 1023, 969, 942, 910;
(25 mL). The aqueous layer was extracted with EtOAc (3 × HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C15H13NNaO2S
25 mL) and the combined organics were dried over Na2SO4, fil- 294.0559; Found 294.0554.
tered and the solvent removed in vacuo. Purification by flash
2-(2-(1,3-Dioxolan-2-yl)phenyl)malononitrile
8d. Malono-
column chromatography on alumina [EtOAc/MeOH nitrile, 7c, (26.4 mg, 0.400 mmol) and aryl bromide 1a
4 : 1 grading to MeOH] furnished isoquinolinium salt 6a (110 mg, 0.480 mmol) were subjected to General procedure F
(63.6 mg, 0.237 mmol, 96%) as prisms. M.p. 280 °C (decom- for 4 h. Purification by flash column chromatography [petrol/
posed) (MeOH/EtOAc); 1H NMR (400 MHz, CDCl3) δH: 11.49 CH2Cl2 1 : 3] furnished nitrile 8d (72.5 mg, 0.338 mmol, 85%)
(1H, s), 8.81 (1H, d, J 8.3), 8.18–8.12 (2H, m), 7.90 (1H, td, as an oil. 1H NMR (400 MHz, CDCl3) δH: 7.75 (1H, dd, J 7.5,
J 7.3, 1.7), 7.63–7.61 (3H, m), 7.35 (2H, dd, J 6.5, 3.0), 4.31 (3H, 1.3), 7.60–7.48 (3H, m), 5.89 (1H, s), 5.87 (1H, s), 4.21–4.14
s) 2.46 (3H, s); 13C[1H] NMR (100 MHz, CDCl3) δC: 151.9, 143.5, (2H, m), 4.14–4.07 (2H, m); 13C[1H] NMR (100 MHz, CDCl3) δC:
137.4, 137.1, 133.1, 132.6, 131.4, 130.9, 130.7, 130.0, 129.1, 126.9, 134.6, 130.7, 130.3, 129.3, 129.2, 125.5, 112.3, 102.8, 65.0, 24.9;
123.9, 48.2, 16.1; IR νmax (thin film)/cm−1 1633, 1597, 1500, 1481, IR νmax (thin film)/cm−1 2899, 2257, 1459, 1405, 1289, 1228,
1445, 1376, 1343, 1269, 1189, 1077, 1007, 811; HRMS (ESI-TOF) 1114, 1075, 1043; HRMS (ESI-TOF) m/z: [M − H]− Calcd for
m/z: M+ Calcd for C17H16N 234.1278, Found 234.1281.
C12H9N2O2 213.0670; Found 213.0662.
2-(2-(1,3-Dioxolan-2-yl)phenyl)-2-phenylacetonitrile 8a. Aryl
2-(2-(1,3-Dioxolan-2-yl)phenyl)-2-(phenylsulfonyl)acetonitrile
bromide 1a (82.2 mg, 0.359 mmol) was subjected to General 8e. (Phenylsulfonyl)acetonitrile, 7d, (92.2 mg, 0.509 mmol)
procedure E with 2-phenylacetonitrile, 7a. Purification by flash and aryl bromide 1a (140 mg, 0.611 mmol) were subjected to
column chromatography [petrol/EtOAc 39 : 1 grading to 9 : 1] General procedure F for 18 h. Purification by flash column
furnished nitrile 8a (65.6 mg, 0.247 mmol, 69%) as an oil. chromatography [petrol/EtOAc 7 : 3] furnished nitrile 8e
1H NMR (400 MHz, CDCl3) δH: 7.62 (1H, d, J 7.7), 7.45 (1H, d, (158 mg, 0.480 mmol, 94%) as a solid. M.p. 99–101 °C;
J 8.2), 7.42–7.32 (7H, m,), 5.95 (1H, s), 5.90 (1H, s), 4.16–4.03 1H NMR (400 MHz, CDCl3) δH: 7.83 (2H, dd, J 8.3, 1.2), 7.75
(4H, m); 13C NMR[1H] (100 MHz, CDCl3) δC: 135.8, 134.9, (1H, td, J 7.5, 1.1), 7.68 (1H, d, J 7.6), 7.60–7.56 (2H, m), 7.47
134.7, 130.0, 129.7, 129.1, 128.3, 128.1, 127.9, 127.6, 120.0, (1H, ddd, J 7.9, 6.3, 2.5), 7.37–7.31 (2H, m), 6.38 (1H, s), 6.18
102.3, 65.2, 65.1, 37.8; IR νmax (thin film)/cm−1 2892, 2244, (1H, s), 4.10–3.94 (4H, m); 13C[1H] NMR (100 MHz, CDCl3) δC 138.1,
1601, 1494, 1452, 1406, 1217, 1112, 1075, 1043, 970, 943, 894; 135.2, 135.0, 130.6, 130.4, 129.9, 129.2, 129.1, 127.0, 123.7,
HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C17H15NNaO2 114.1, 101.4, 65.0, 64.9, 58.9; IR νmax (powder)/cm−1 2936,
288.0995; Found 288.0992.
2891, 1691, 1582, 1447, 1391, 1327, 1310, 1154, 1104, 1064,
2-(2-(1,3-Dioxolan-2-yl)-4,5-dimethoxyphenyl)-2-phenylaceto- 1027; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C17H15NNaO4S
nitrile 8b. Aryl bromide 1e (87.8 mg, 0.304 mmol) (synthesis10) 352.0614; Found 352.0605.
Org. Biomol. Chem.
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