Full Paper
(Method A): Na2S2O8 (2.0 mmol, 476.2 mg) was added to a solution
of lepidine (1a; 1.0 mmol, 143.2 mg) in a mixture of methanol and
6-Fluoro-4-hydroxymethyl-2-methylquinoline (2e): White solid
(149.2 mg, 78 %). M.p. 161–162 °C. IR (neat): ν = 3133, 2987, 1165,
˜
water (7:3; 10.0 mL) in a screw-capped flask (50 mL) at room tem- 1084, 822 cm–1. 1H NMR (400 MHz, CDCl3): δ = 2.73 (s, 3 H), 5.12 (s,
perature. The reaction flask was flushed with argon gas. The mixture
was stirred for 4 h at 70 °C. The reaction mixture was then cooled
to room temperature, and the reaction solvent was removed under
reduced pressure. Satd. aq. NaHCO3 solution (10 mL) was added to
the residue. The mixture was extracted with EtOAc (3 × 20 mL), and
the organic layer was washed with brine (20 mL). The resulting
organic layer was dried with Na2SO4, and filtered, and the solvent
was removed under reduced pressure. The residue was purified by
column chromatography on neutral silica gel (EtOAc/hexane, 1:1) to
give the desired product 2a (148.2 mg, 86 %).
2 H), 7.42–7.48 (m, 2 H), 7.52 (dd, J = 9.5, 2.7 Hz, 1 H), 8.04 (dd, J =
9.5, 5.5 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 25.1, 61.5,
106.6 (d, JC,F = 21.9 Hz), 119.2 (d, JC,F = 24.8 Hz), 119.8, 124.8 (d,
JC,F = 9.5 Hz), 131.3 (d, JC,F = 8.6 Hz), 144.6, 145.5 (d, JC,F = 4.8 Hz),
158.3, 160.0 (d, JC,F = 247.0 Hz) ppm. HRMS (ESI): calcd. for
C11H11FNO [M + H]+ 192.0819; found 192.0818.
6-Chloro-4-hydroxymethyl-2-methylquinoline (2f): White solid
(162.1 mg, 78 %). M.p. 159–160 °C. IR (neat): ν = 3189, 2816, 1603,
˜
1101, 820 cm–1. 1H NMR (400 MHz, CDCl3): δ = 2.70 (s, 3 H), 5.13 (s,
2 H), 7.43 (s, 1 H), 7.60 (dd, J = 8.8, 2.4 Hz, 1 H), 7.87 (d, J = 2.4 Hz,
1 H), 7.95 (d, J = 8.8 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 25.2, 61.3, 120.0, 121.9, 124.8, 130.1, 130.5, 131.6, 145.3, 145.9,
159.4 ppm. HRMS (ESI): calcd. for C11H11ClNO [M + H]+ 208.0524;
found 208.0522.
General Procedure for the Reaction of Quinolines 1 with
Na2S2O8 and Acid in a Mixture of Methanol and Water
(Method B or Method C): Na2S2O8 (2.0 mmol, 476.2 mg) and then
CF3CO2H (Method B: 1.3 mmol, 0.0995 mL) or p-TsOH·H2O
(Method C: 1.3 mmol, 223.9 mg) were added to a solution of
lepidine (1a; 1.0 mmol, 143.2 mg) in a mixture of methanol and
water (7:3; 10.0 mL)in a screw-capped flask (50 mL) at room temper-
ature. The reaction flask was flushed with argon gas. The mixture
was stirred for 4 h at 70 °C. The reaction mixture was then cooled
to room temperature, and the reaction solvent was removed under
reduced pressure. Satd. aq. NaHCO3 solution (10 mL) was added to
the residue. The mixture was extracted with CHCl3 (3 × 20 mL), and
the organic layer was washed with brine (20 mL). The resulting
organic layer was dried with Na2SO4, and filtered, and the solvent
was removed under reduced pressure. The residue was purified by
column chromatography on neutral silica gel (EtOAc/hexane, 1:1) to
give the desired product 2a (156.8 mg, 91 %).
7-Chloro-4-hydroxymethyl-2-methylquinoline (2g): White solid
(177.1 mg, 85 %). M.p. 183–184 °C. IR (neat): ν = 3127, 2837, 1605,
˜
1025, 873 cm–1
.
1H NMR (400 MHz, [D6]DMSO): δ = 2.64 (s, 3 H),
4.97 (d, J = 4.9 Hz, 2 H), 5.59 (t, J = 4.9 Hz, 1 H), 7.47 (s, 1 H), 7.55
(dd, J = 8.8, 2.3 Hz, 1 H), 7.95 (d, J = 2.3 Hz, 1 H), 8.01 (d, J = 8.8 Hz,
1 H) ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 25.0, 59.6, 119.2,
122.6, 125.6, 125.9, 127.3, 133.5, 147.7, 147.9, 160.2 ppm. HRMS
(ESI): calcd. for C11H11ClNO [M + H]+ 208.0524; found 208.0523.
6-Bromo-4-hydroxymethyl-2-methylquinoline (2h): Yellow solid
(180.5 mg, 73 %). M.p. 164–165 °C. IR (neat): ν = 3186, 2816, 1344,
˜
1101, 818 cm–1
.
1H NMR (400 MHz, [D6]DMSO): δ = 2.62 (s, 3 H),
4.94 (d, J = 5.2 Hz, 2 H), 5.60 (t, J = 5.2 Hz, 1 H), 7.47 (s, 1 H), 7.80
(dd, J = 9.1, 2.2 Hz, 1 H), 7.85 (d, J = 9.1 Hz, 1 H), 8.18 (d, J = 2.2 Hz,
1 H) ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 25.0, 59.7, 118.5,
119.8, 125.4, 125.8, 130.9, 132.0, 145.8, 147.0, 159.4 ppm. HRMS
(ESI): calcd. for C11H11BrNO [M + H]+ 252.0019; found 252.0015;
calcd. for [M + H]+ 253.9998; found 253.9995.
2-Hydroxymethyl-4-methylquinoline (2a): Yellow solid (156.8 mg,
91 %). M.p. 79–80 °C. IR (neat): ν = 3031, 2793, 1599, 1053, 762 cm–1
.
˜
1H NMR (400 MHz, CDCl3): δ = 2.70 (s, 3 H), 4.87 (s, 2 H), 7.12 (s, 1
H), 7.56 (t, J = 8.0 Hz, 1 H), 7.71 (t, J = 8.0 Hz, 1 H), 7.98 (d, J =
8.0 Hz, 1 H), 8.07 (d, J = 8.0 Hz, 1 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 18.7, 64.0, 118.9, 123.7, 126.0, 127.5, 129.0, 129.3, 145.0,
146.4, 158.7 ppm. HRMS (ESI): calcd. for C11H12NO [M + H]+
174.0913; found 174.0912.
4-Hydroxymethyl-6-methoxycarbonyl-2-methylquinoline (2i):
Yellow solid (160.9 mg, 70 %). M.p. 190–192 °C. IR (neat): ν = 3100,
˜
2826, 1715, 1277, 1044 cm–1
.
1H NMR (400 MHz, [D6]DMSO): δ =
2.67 (s, 3 H), 3.91 (s, 3 H), 5.02 (d, J = 5.0 Hz, 2 H), 5.65 (t, J = 5.0 Hz,
1 H), 7.52 (s, 1 H), 8.00 (d, J = 8.6 Hz, 1 H), 8.15 (dd, J = 8.6, 1.8 Hz,
1 H), 8.63 (d, J = 1.8 Hz, 1 H) ppm. 13C NMR (100 MHz, [D6]DMSO):
δ = 25.2, 52.4, 59.8, 120.0, 123.3, 126.1 (2 C), 128.0, 129.3, 148.7,
149.1, 161.5, 166.0 ppm. HRMS (ESI): calcd. for C13H14NO3 [M + H]+
232.0968; found 232.0966.
4,6-Dimethyl-2-hydroxymethylquinoline (2b): Yellow solid
(115.9 mg, 62 %). M.p. 136–137 °C. IR (neat): ν = 3121, 2909, 1599,
˜
1078, 817 cm–1. 1H NMR (400 MHz, CDCl3): δ = 2.57 (s, 3 H), 2.67 (s,
3 H), 4.85 (s, 2 H), 7.08 (s, 1 H), 7.54 (d, J = 8.6 Hz, 1 H), 7.73 (s, 1
H), 7.96 (d, J = 8.6 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
18.8, 21.8, 63.9, 118.9, 122.8, 127.5, 128.8, 131.5, 135.8, 144.3, 144.9,
157.6 ppm. HRMS (ESI): calcd. for C12H14NO [M + H]+ 188.1070;
found 188.1066.
6-Acetyl-4-hydroxymethyl-2-methylquinoline (2j): Yellow solid
(142.3 mg, 66 %). M.p. 179–180 °C. IR (neat): ν = 3100, 2816, 2838,
˜
1
1677, 1033, 831 cm–1. H NMR (400 MHz, [D6]DMSO): δ = 2.67 (s, 3
4-Hydroxymethyl-2-methylquinoline (2c): White solid (148.8 mg,
H), 2.71 (s, 3 H), 5.08 (d, J = 5.0 Hz, 2 H), 5.66 (t, J = 5.0 Hz, 1 H),
7.54 (s, 1 H), 7.98 (d, J = 8.8 Hz, 1 H), 8.15 (dd, J = 8.8, 1.9 Hz, 1 H),
8.59 (d, J = 1.9 Hz, 1 H) ppm. 13C NMR (100 MHz, [D6]DMSO): δ =
25.2, 26.9, 59.6, 119.7, 123.2, 125.6, 127.0, 129.2, 133.4, 149.1, 149.3,
161.4, 197.7 ppm. HRMS (ESI): calcd. for C13H14NO2 [M + H]+
216.1019; found 216.1017.
86 %). M.p. 145–146 °C. IR (neat): ν = 3120, 2848, 1604, 1096,
˜
1
748 cm–1. H NMR (400 MHz, CDCl3): δ = 2.69 (s, 3 H), 5.19 (s, 2 H),
7.42 (s, 1 H), 7.49 (t, J = 8.1 Hz, 1 H), 7.67 (t, J = 8.1 Hz, 1 H), 7.88
(d, J = 8.1 Hz, 1 H), 8.03 (d, J = 8.1 Hz, 1 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 25.1, 61.1, 119.0, 122.6, 124.1, 125.8, 128.8, 129.3, 146.5,
147.3, 159.0 ppm. HRMS (ESI): calcd. for C11H12NO [M + H]+
174.0913; found 174.0912.
4-Hydroxymethyl-2-Methyl-6-(trifluoromethyl)quinoline (2k):
2,6-Dimethyl-4-hydroxymethylquinoline (2d): Yellow solid
White solid (185.7 mg, 77 %). M.p. 164–165 °C. IR (neat): ν = 3203,
˜
(126.8 mg, 68 %). M.p. 149–150 °C. IR (neat): ν = 3128, 2919, 1373, 1613, 1301, 1104, 829 cm–1. 1H NMR (400 MHz, [D6]DMSO): δ = 2.69
˜
1084, 822 cm–1. 1H NMR (400 MHz, CDCl3): δ = 2.52 (s, 3 H), 2.67 (s,
3 H), 5.15 (s, 2 H), 7.37 (s, 1 H), 7.49 (d, J = 8.6 Hz, 1 H), 7.63 (s, 1
H), 7.92 (d, J = 8.6 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
21.7, 24.8, 60.9, 119.0, 121.6, 124.0, 128.2, 131.3, 135.5, 145.6, 146.2,
157.8 ppm. HRMS (ESI): calcd. for C12H14NO [M + H]+ 188.1070;
found 188.1066.
(s, 3 H), 5.04 (d, J = 5.2 Hz, 2 H), 5.66 (t, J = 5.2 Hz, 1 H), 7.57 (s, 1
H), 7.94 (d, J = 8.8 Hz, 1 H), 8.11 (d, J = 8.8 Hz, 1 H), 8.38 (s, 1 H)
ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 25.1, 59.8, 120.4, 121.9 (q,
J
C,F = 4.8 Hz), 123.3, 124.3 (q, JC,F = 271.8 Hz), 124.4 (q, JC,F = 2.9 Hz),
125.5 (q, JC,F = 31.5 Hz), 130.3, 148.4, 148.7, 161.6 ppm. HRMS (ESI):
calcd. for C12H11F3NO [M + H]+ 242.0787; found 242.0785.
Eur. J. Org. Chem. 2017, 6239–6245
6243
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim