S. J. Connon, A. F. Hegarty
FULL PAPER
1449, 1363, 1223, 1135, 1071, 745, 685 cmϪ1. 1H NMR (270 MHz,
CDCl3): δ ϭ 6.87 [dd, J(H,H) ϭ 5 Hz, 2 Hz, 1 H], 7.05 [d,
hexane, 2.48 mmol), 2-chloro-4-thiophenoxypyridine (0.504 g,
2.27 mmol) and furan (3.4 mL, 46.74 mmol). After workup, flash
J(H,H) ϭ 2 Hz, 1 H], 7.45Ϫ7.6 (m, 5 H), 8.08 [d, J(H,H) ϭ 5 Hz, chromatography (EtOAc/CHCl3, 80:20) gave 30 (0.166 g, 29%) as
1 H] ppm. 13C NMR (67.5 MHz, CDCl3): δ ϭ 119.6, 123.8, 128.2, an amber oil. 1H NMR (270 MHz, CDCl3): δ ϭ 5.55 (m, 2 H),
130.1, 130.2, 135.4, 142.4, 149.3, 153.8 ppm. MS EI (70 eV): m/z 6.52 [d, J(H,H) ϭ 6 Hz, 1 H], 6.83 [dd, J(H,H) ϭ 6 Hz, 2 Hz, 1
(%) ϭ 221 (7) [Mϩ], 186, 144, 112, 109, 77. C11H8ClNS (221.7): H], 7.08 [dd, J(H,H) ϭ 6 Hz, 2 Hz, 1 H], 7.4Ϫ7.5 (m, 5 H), 7.83
calcd. C 59.59, H 3.64, Cl 15.99, N 6.32; found C 59.34, H 3.91,
Cl 15.85, N 6.39.
[d, J(H,H) ϭ 6 Hz, 1 H] ppm. 13C NMR (67.5 MHz, CDCl3): δ ϭ
80.5, 82.7, 118.6, 129.2, 129.8, 130.8, 134.0, 139.4, 140.6, 142.3,
143.0, 143.9, 172.4 ppm. MS EI (70 eV): m/z (%) ϭ 253 (6) [Mϩ],
237, 225, 176, 147, 109, 77. C15H11NOS (253.3): calcd. C 71.12, H
4.38, N 5.53; found C 70.90, N 4.26, N 5.38.
2-Chloro-4-(4-methoxyphenoxy)pyridine (25): Procedure B was ap-
plied using 4-methoxyphenol (1.07 g, 8.62 mmol), dry 1,4-dioxane
(12 mL), sodium hydride (0.281 g, 11.71 mmol) and 2-chloro-4-
nitropyridine (1.24 g, 7.82 mmol). Workup (as per procedure B)
5,8-Dihydro-5,8-epoxy-4-(4-methoxyphenoxy)quinoline (31): Pro-
and flash chromatography (CHCl3/EtOAc, 90:10) gave a colourless cedure C was applied using dry diisopropylamine (0.30 mL,
oil, which was further purified by kugelrohr distillation to give 25 2.14 mmol), dry THF (3 ϩ 2 mL), n-butyllithium (1.35 mL of a
(1.14 g, 62%) as a colourless viscous oil. IR (neat): ν˜ ϭ 3061, 2836, 1.6 solution in hexane, 2.16 mmol), 2-chloro-4-(4-methoxy-
1608, 1594, 1557, 1503, 1292, 1234 1034, 907, 866 cmϪ1. 1H NMR
phenoxy)pyridine (0.450 g, 1.91 mmol) and furan (2.8 mL,
(270 MHz, CDCl3): δ ϭ 3.85 (s, 3 H), 6.79 [dd, J(H,H) ϭ 6 Hz, 38.50 mmol). After workup, flash chromatography (EtOAc/CHCl3,
2 Hz, 1 H], 6.95 [d, J(H,H) ϭ 9.5 Hz, 2 H], 7.02 [d, J(H,H) ϭ 80:20) gave 31 (0.295 g, 58%) as a viscous amber oil. IR (neat): ν˜ ϭ
9.5 Hz, 2 H], 7.05 [d, J(H,H) ϭ 2 Hz, 1 H], 8.18 [d, J(H,H) ϭ 6 Hz,
1 H] ppm. 13C NMR (67.5 MHz, CDCl3): δ ϭ 55.7, 111.4, 115.2, 907 cmϪ1. 1H NMR (270 MHz, CDCl3): δ ϭ 3.83 (s, 3 H), 5.17 [d,
115.3, 121.9, 143.0, 146.6, 151.0, 157.4, 166.7 ppm. MS EI (70 eV): J(H,H) ϭ 2 Hz, 1 H], 5.53 [d, J(H,H) ϭ 2 Hz, 1 H], 6.46 [d,
m/z (%) ϭ 235 (11) [Mϩ], 220, 200, 156, 129, 112, 77. C12H10ClNO2 J(H,H) ϭ 6 Hz, 1 H], 6.88 [dd, J(H,H) ϭ 5.5 Hz, 2 Hz, 1 H], 6.94
3021, 2852, 1608, 1594, 1557, 1503, 1462, 1292, 1234, 1194, 1034,
(235.7): calcd. C 61.16, H 4.28, Cl 15.04, N 5.94; found C 60.89,
H 4.17, Cl 15.11, N 5.73.
[d, J(H,H) ϭ 7 Hz, 2 H], 6.99 [d, J(H,H) ϭ 7 Hz, 2 H], 7.05 [dd,
J(H,H) ϭ 5.5 Hz, 2 Hz, 1 H], 7.91 [d, J(H,H) ϭ 6 Hz, 1 H] ppm.
13C NMR (67.5 MHz, CDCl3): δ ϭ 55.7, 80.0, 82.7, 110.2, 115.2,
121.7, 127.7, 142.1, 143.4, 146.0, 148.4, 157.2, 157.3, 175.5 ppm.
MS EI (70 eV): m/z (%) ϭ 267 (7) [Mϩ], 252, 251, 237, 221, 160,
109, 77. C16H13NO3 (267.3): calcd. C 71.90, H 4.90, N 5.24; found
C 71.78, H 5.12, N 5.46.
5,8-Dihydro-5,8-epoxy-4-methoxyquinoline (28). Procedure C: A 25-
mL round-bottomed flask under N2 (balloon) was charged with
dry diisopropylamine (0.40 mL, 2.86 mmol), dry THF (3 mL) and
cooled to Ϫ78 °C. After 15 min at this temperature, n-butyllithium
(1.8 mL of a 1.6 solution in hexane, 2.88 mmol) was added by
syringe. The solution was stirred at Ϫ78 °C for 20 min, and 2-
2-Chloro-4-(trimethylsilylmethyl)pyridine (32). Procedure D: A 10-
chloro-4-methoxypyridine (0.363 g, 2.53 mmol) in THF (2 mL) was mL round-bottomed flask under N2 (balloon) was charged with
added by syringe. After stirring for a further 20 min, furan (3.7
mL, 50.87 mmol) was added and the reaction mixture warmed to
dry diisopropylamine (0.18 mL, 1.29 mol), dry THF (3 mL) and
cooled to Ϫ78 °C. After 15 min, n-butyllithium (0.8 mL of a 1.6
room temperature overnight. After workup, flash chromatography solution in hexane, 1.28 mmol) was added by syringe. The solution
(EtOAc/CHCl3, 80:20) gave 28[10] (0.165 g, 37%) as a dark amber
oil. Note: The chromatography is greatly simplified by the product
was stirred at Ϫ78 °C for 20 min, and a solution of 2-chloro-4-
methylpyridine (0.152 g, 1.19 mmol) in THF (2 mL) was added by
being visible as an amber band. 1H NMR (270 MHz, CDCl3): δ ϭ syringe to give a yellow solution, which was stirred for 20 min,
3.87 (s, 3 H), 5.59 (s, 1 H), 5.98 (s, 1 H), 6.48 [d, J(H,H) ϭ 6 Hz,
quenched with TMSCl (0.6 mL, 4.73 mmol) by a syringe and
1 H], 7.11 (m, 2 H), 7.96 [d, J(H,H) ϭ 6 Hz, 1 H] ppm. MS EI (70 warmed to room temperature overnight. The resulting suspension
eV): m/z (%) ϭ 175 (3) [Mϩ], 159, 145, 117, 104, 77. C10H9NO2
(175.2): calcd. C 68.56, H 5.18, N 8.00; found C 68.40, H 5.09,
N 7.88.
was poured slowly into 30 mL of saturated NaHCO3 solution and
extracted with CHCl3 (3 ϫ 40 mL). The organic extracts were com-
bined, dried (MgSO4), and the solvent was removed in vacuo to
give a yellow oil (1.87 g). Compound 32 was identified as the sole
silylated product from 1H NMR spectroscopic analysis of the crude
5,8-Dihydro-5,8-epoxy-4-phenoxyquinoline (29): Procedure C was
applied using dry diisopropylamine (0.25 mL, 1.79 mmol), dry
THF (3 ϩ 2 mL), n-butyllithium (1.1 mL of a 1.6 solution in
1
material. H NMR (270 MHz, CDCl3): δ ϭ 0.03 (s, 9 H), 2.11 (s,
2 H), 6.84 [dd, J(H,H) ϭ 5 Hz, 1 Hz, 1 H], 6.96 [d, J(H,H) ϭ 1 Hz,
1 H], 8.17 [d, J(H,H) ϭ 5 Hz, 1 H] ppm. MS EI (70 eV): m/z (%) ϭ
199 (19) [Mϩ], 184, 169, 127, 91, 73.
hexane;
1.76 mmol),
2-chloro-4-phenoxypyridine
(0.330 g,
1.60 mmol) and furan (2.3 mL, 31.62 mmol). After workup, flash
chromatography (EtOAc/CHCl3 80:20) gave 29 (0.094 g, 25%) as
an amber oil. IR (neat): ν˜ ϭ 3025, 1605, 1580, 1509, 1490, 1263, 2-Chloro-4-methoxy-3-trimethylsilylpyridine (33): Procedure D was
726, 996 cmϪ1 1H NMR (270 MHz, CDCl3): δ ϭ 5.21 [d, applied using dry diisopropylamine (0.20 mL, 1.43 mol), dry THF
J(H,H) ϭ 2 Hz, 1 H], 5.55 [d, J(H,H) ϭ 2 Hz, 1 H], 6.51 [d, (3 ϩ 2 mL), n-butyllithium (0.9 mL of a 1.6 solution in hexane,
J(H,H) ϭ 6 Hz, 1 H], 6.90 [dd, J(H,H) ϭ 6 Hz, 2 Hz, 1 H], 7.07 1.44 mmol) and 2-chloro-4-methoxypyridine (0.188 g, 1.31 mmol).
.
(m, 3 H), 7.28 (m, 1 H), 7.44 (m, 2 H), 7.95 [d, J(H,H) ϭ 6 Hz, 1 Workup (as per procedure D) gave a light yellow oil (2.76 g). Com-
H] ppm. 13C NMR (67.5 MHz, CDCl3): δ ϭ 79.9, 82.7, 110.7,
pound 33 was identified as the sole product from 1H and 13C NMR
1
120.3, 125.5, 128.5, 130.3, 142.2, 143.3, 146.1, 155.2, 156.4, 175.6 spectroscopic analyses of the crude material. H NMR (270 MHz,
ppm. MS EI (70 eV): m/z (%) ϭ 237 (4) [Mϩ], 221, 209, 180, 160, CDCl3): δ ϭ 0.39 (s, 9 H), 3.83 (s, 3 H), 6.68 [d, J(H,H) ϭ 6 Hz,
131, 116, 104. C15H11NO2 (237.3): calcd. C 75.94 H 4.67 N 5.90;
found C 75.68, H 4.84, N 5.65.
1 H], 8.22 [d, J(H,H) ϭ 6 Hz, 1 H] ppm. 13C NMR (67.5 MHz,
CDCl3): δ ϭ 1.5, 55.5, 105.2, 121.6, 151.2, 157.5, 172.3.
5,8-Dihydro-5,8-epoxy-4-thiophenoxyquinoline (30): Procedure C
was applied using dry diisopropylamine (0.35 mL, 2.50 mmol), dry
THF (5 ϩ 2 mL), n-butyllithium (1.55 mL of a 1.6 solution in
2-Isopropoxypyridine (34): Procedure A was applied using a 100-
mL round-bottomed flask fitted with a stirring bar, sodium metal
(about 1.5 g), dry propan-2-ol (70 mL) and 2-chloropyridine
3482
2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2004, 3477Ϫ3483