3864
Y. Yadav et al. / European Journal of Medicinal Chemistry 46 (2011) 3858e3866
pressure. Water (15 ml) was added and the reaction mixture was
extracted with ethyl acetate (3 ꢀ 50 ml). The organic layer was
washed with water (3 ꢀ 50 ml) and dried over anhydrous sodium
sulfate. The solvent was removed under reduced pressure and dried
under high vacuum to afford the desired alcohols 5aeh as colorless
oils in 76e95% yields. The structures of the compounds 5aeh were
unambiguously established by comparing their spectral data with
reported values [14]. Compound 5g was found to be new to chemical
literature; its spectral data is reported below.
J ¼ 8.1 Hz, AreH), 7.89 (1H, d, J ¼ 8.4 Hz, AreH). 13C NMR (75.5 MHz,
CDCl3):
d
10.70 (2ꢀ CH3), 29.82 (ArCH2Ar), 47.32 (2ꢀ NCH2), 51.57
(NCH2), 65.39 (OCH2), 114.41 (Ar), 118.33 (Ar), 118.86 (Ar), 122.72 (Ar),
123.32 (Ar), 126.34 (Ar), 128.10 (Ar), 128.47 (Ar), 129.14 (Ar), 129.21
(Ar), 133.10 (Ar), 133.78 (Ar), 151.97 (Ar), 156.67 (Ar). HRMS m/z
calculated for C23H27NO2 [M þ H]þ 350.2115, observed [M þ H]þ
350.2101.
5.1.6.3. 1-[4-[2-(Diisopropylamino)ethoxy]benzyl]naphthalen-2-ol (3c).
Brown viscous oil, yield 68%. UV (EtOH) lmax: 229, 277 and 334 nm. IR
(nujol): 3385, 3057, 2967, 1610, 1507, 1436, 1359, 1242, 1174, 1029, 991
5.1.5.1. [4-[2-(4-Methylpiperidin-1-yl)ethoxy]phenyl]methanol (5g).
Colorless oil, yield 88%. UV (EtOH) lmax: 225 and 272 nm. IR (nujol):
3361, 2932, 2868, 1611, 1511, 1455,1321, 1298, 1244,1172, 1053, 1009
and 810 cmꢂ1. 1H NMR (300 MHz, CDCl3)
d
1.10 (12H, d, J ¼ 3.9 Hz,
4ꢀ CH3), 2.88 (2H, brs, eNCH2), 3.12 (2H, brs, 2ꢀ NCH), 3.92 (2H, brs,
OCH2), 4.40 (2H, s, ArCH2Ar), 6.79 (2H, d, J ¼ 7.2 Hz, 2ꢀ AreH), 7.14 (2H,
d, J ¼ 7.2 Hz, 2ꢀ AreH), 7.20 (1H, d, J ¼ 8.7 Hz, AreH), 7.36 (1H, t,
J ¼ 6.6 Hz, AreH), 7.48 (1H, t, J ¼ 6.3 Hz, AreH), 7.71 (1H, d, J ¼ 8.4 Hz,
AreH), 7.82 (1H, d, J ¼ 7.5 Hz, AreH), 7.95 (1H, d, J ¼ 8.1 Hz, AreH). 13C
and 821 cmꢂ1. 1H NMR (300 MHz, CDCl3):
d
0.95 (3H, d, J ¼ 5.4 Hz,
CH3), 1.28e1.36 (3H, m, CH2 & CH), 1.63e1.67 (2H, m, CH2),
2.08e2.16 (2H, m, NCH2), 2.79 (2H, t, J ¼ 6.0 Hz, NCH2), 2.96e3.00
(2H, m, NCH2), 4.10 (2H, t, J ¼ 5.7 Hz, OCH2), 4.62 (2H, s, CH2OH),
6.89 (2H, d, J ¼ 7.8 Hz, 2ꢀ AreH), 7.30 (2H, d, J ¼ 7.5 Hz, 2ꢀ AreH).
NMR (75.0 MHz, CDCl3):
d
20.55 (4ꢀ CH3), 29.85 (ArCH2Ar), 44.67
13C NMR (75.5 MHz, CDCl3):
d
21.81 (CH3), 30.51(CH), 34.10 (2ꢀ
(2ꢀ NCH), 50.14 (NCH2), 68.74 (OCH2), 114.57 (Ar), 118.18 (Ar), 118.73
(Ar), 123.03 (Ar), 123.37 (Ar), 126.53 (Ar), 128.30 (Ar), 128.53 (Ar),
129.19 (Ar), 129.40 (Ar), 132.23 (Ar), 133.72 (Ar), 151.49 (Ar), 157.16 (Ar).
HRMS m/z calculated for C25H31NO2 [M þ H]þ 378.2428, observed
[M þ H]þ 378.2417.
CH2), 54.46 (2ꢀ NCH2), 57.48 (NCH2), 64.88 (CH2OH), 66.00 (OCH2),
114.65 (C-2 & C-6), 128.55 (C-3 & C-5), 133.56 (C-1), 158.36 (C-4).
HRMS m/z calculated for C15H23NO2 [M þ H]þ 250.1802, observed
[M þ H]þ 250.1802.
5.1.6. General procedure for the synthesis of compounds 3aeh
To a solution of 4aeh (12.7 mmol) and 2-naphthol (12.7 mmol)
in dry 1,4-dioxane (60 ml), boron trifluoride etherate (38 mmol)
was added slowly at 0 ꢃC. After the addition of boron trifluoride
etherate, the reaction mixture was stirred at room temperature
until TLC showed completion of reaction. The reaction was gener-
ally complete in 3e5 h. After the completion of reaction, ethyl
acetate was added and the reaction mixture was washed with
saturated solution of sodium bicarbonate (3 ꢀ 100 ml), followed by
water (3 ꢀ 100 ml) and with brine (3 ꢀ 100 ml). The organic layer
was dried over anhydrous sodium sulfate. It was then evaporated
under reduced pressure to obtain the crude product, which was
purified by column chromatography over silica gel using methanol-
dichloromethane (8e10%) as eluent to afford pure compounds
3aeh in 45e70% yields.
5.1.6.4. 1-[4-[2-(Pyrrolidin-1-yl)ethoxy]benzyl]naphthalen-2-ol (3d).
Off white solid, yield 56%, m.p.117e119 ꢃC. UV (EtOH) lmax: 229, 278
and 337 nm. IR (KBr): 3436, 3054, 2930, 2874,1626, 1511, 1438, 1357,
1242, 1174, 1057, 1000 and 812 cmꢂ1 1H NMR (300 MHz, CDCl3):
.
d
1.87 (4H, brs, 2ꢀ CH2), 2.84 (4H, brs, 2ꢀ NCH2), 3.00 (2H, brs,
NCH2), 4.06 (2H, t, J ¼ 4.8 Hz, OCH2), 4.35 (2H, s, ArCH2Ar), 6.64 (2H,
d, J ¼ 7.5 Hz, 2ꢀ AreH), 7.06 (2H, d, J ¼ 7.8 Hz, 2ꢀ AreH), 7.20e7.30
(2H, m, AreH), 7.40 (1H, t, J ¼ 7.2 Hz, AreH), 7.64 (1H, d, J ¼ 8.7 Hz,
AreH), 7.75 (1H, d, J ¼ 8.1 Hz, AreH), 7.86 (1H, d, J ¼ 8.4 Hz, AreH).
13C NMR Data (75.5 MHz, CDCl3):
d
23.28 (2ꢀ CH2), 29.76 (ArCH2Ar),
54.47 (2ꢀ NCH2), 54.75 (NCH2), 65.45 (OCH2), 114.42 (Ar), 118.24
(Ar), 118.67 (Ar), 122.63 (Ar), 123.28 (Ar), 126.30 (Ar), 128.08 (Ar),
128.46 (Ar), 129.05 (Ar), 129.23 (Ar), 133.44 (Ar), 133.77 (Ar), 152.17
(Ar), 156.40 (Ar). HRMS m/z calculated for C23H25NO2 [M þ H]þ
348.1958, observed [M þ H]þ 348.1952.
5.1.6.1. 1-[4-[2-(Dimethylamino)ethoxy]benzyl]naphthalen-2-ol (3a).
Off white solid, yield 45%, m.p.122e125 ꢃC. UV (EtOH) lmax: 229, 280
and 334 nm. IR (KBr): 3370, 3060, 2938, 2825,1593,1507,1465,1369,
5.1.6.5. 1-[4-[2-(Piperidin-1-yl)ethoxy]benzyl]naphthalen-2-ol
(3e). Off white solid, yield 52%, m.p. 171e173 ꢃC. UV (EtOH) lmax
:
227, 279 and 334 nm. IR (KBr): 3358, 3055, 2937, 2845, 1582, 1508,
1244,1176,1078,1045 and 806 cmꢂ1.1H NMR (300 MHz, CDCl3)
d 2.43
1435, 1355, 1274, 1174, 1039, 996 and 810 cmꢂ1. 1H NMR (300 MHz,
(6H, s, 2ꢀ NCH3), 2.83 (2H, t, J ¼ 5.4 Hz, eNCH2), 4.01 (2H, t, J ¼ 5.4 Hz,
OCH2), 4.37 (2H, s, ArCH2Ar), 6.66 (2H, d, J ¼ 8.1 Hz, 2ꢀ AreH), 7.08
(2H, d, J ¼ 8.1 Hz, 2ꢀ AreH), 7.18 (1H, d, J ¼ 9.0 Hz, AreH), 7.30 (1H, t,
J ¼ 6.9 Hz, AreH), 7.42 (1H, t, J ¼ 7.8 Hz, AreH), 7.66 (1H, d, J ¼ 8.7 Hz,
AreH), 7.77 (1H, d, J ¼ 8.1 Hz, AreH), 7.88 (1H, d, J ¼ 8.7 Hz, AreH).13C
CDCl3)
d
1.38e1.78 (6H, m, 3ꢀ CH2), 2.97 (2H, brs, NCH2), 3.44 (4H,
brs, 2ꢀ NCH2), 4.24 (2H, brs, OCH2), 4.30 (2H, s, ArCH2Ar), 6.87
(2H, d, J ¼ 7.8 Hz, 2ꢀ AreH), 7.19 (2H, d, J ¼ 8.1 Hz, 2ꢀ AreH), 7.27
(2H, d, J ¼ 8.1 Hz, 2ꢀ AreH), 7.40 (1H, t, J ¼ 7.2 Hz, AreH), 7.71
(1H, d, J ¼ 8.7 Hz, AreH), 7.79 (1H, d, J ¼ 8.1 Hz, AreH), 7.86 (1H, d,
J ¼ 8.4 Hz, AreH), 9.63 (IH, brs, OH). 13C NMR (75.5 MHz, CDCl3):
NMR (75.5 MHz, CDCl3):
d
29.77 (ArCH2Ar), 45.22 (2ꢀ NCH3), 57.89
(NCH2), 64.81 (OCH2),114.42 (Ar),118.26 (Ar),118.72 (Ar),122.64 (Ar),
123.29 (Ar), 126.31 (Ar), 128.08 (Ar), 128.46 (Ar), 129.04 (Ar), 129.22
(Ar), 133.39 (Ar), 133.78 (Ar), 152.16 (Ar), 156.50 (Ar). HRMS m/z
calculated for C21H23NO2 [M þ H]þ 322.1802, observed [M þ H]þ
322.1790.
d
21.60 (CH2), 22.91 (2ꢀ CH2), 29.47 (ArCH2Ar), 53.19 (2ꢀ NCH2),
55.36 (NCH2), 62.54 (OCH2), 114.97 (Ar), 118.63 (Ar), 118.69 (Ar),
122.70 (Ar), 123.47 (Ar), 126.55 (Ar), 128.20 (Ar), 128.79 (Ar),
129.66 (Ar), 133.68 (Ar), 134.79 (Ar), 152.92 (Ar), 155.99 (Ar). HRMS
m/z calculated for C24H27NO2 [M þ H]þ 362.2115, observed
[M þ H]þ 362.2112.
5.1.6.2. 1-[4-[2-(Diethylamino)ethoxy]benzyl]naphthalen-2-ol (3b). Off
white solid, yield 65%, m.p. 105e107 ꢃC. UV (EtOH) lmax: 229, 279 and
334 nm. IR (KBr): 3411, 3059, 2973, 2935, 2857, 1582, 1507, 1443, 1354,
5.1.6.6. 1-[4-(2-Morpholinoethoxy)benzyl]naphthalen-2-ol (3f). Off
white solid, yield 70%, m.p. 129e132 ꢃC. UV (EtOH) lmax: 227, 277
and 336 nm. IR (KBr): 3378, 2935, 2866, 2813, 1610, 1511, 1438,
1241, 1176, 1036, 994 and 804 cmꢂ1. 1H NMR (300 MHz, CDCl3):
d 1.18
(6H, t, J ¼ 7.2 Hz, 2ꢀ CH3), 2.76 (4H, q, J ¼ 7.2 Hz, 2ꢀ NCH2), 2.93 (2H, t,
J ¼ 6.0 Hz, eNCH2), 4.02 (2H, t, J ¼ 6.0 Hz, OCH2), 4.37 (2H, s,
ArCH2Ar), 6.68 (2H, d, J ¼ 8.4 Hz, 2ꢀ AreH), 7.09 (2H, d, J ¼ 8.4 Hz,
2ꢀ AreH), 7.17 (1H, d, J ¼ 8.7 Hz, AreH), 7.32 (1H, t, J ¼ 7.8 Hz, AreH),
7.43 (1H, t, J ¼ 6.9 Hz, AreH), 7.65 (2H, d, J ¼ 9.0 Hz, AreH), 7.76 (1H, d,
1358, 1297, 1240, 1059, 982 and 815 cmꢂ1 1H NMR (300 MHz,
.
CDCl3):
d
2.69 (4H, brs, 2ꢀ NCH2), 2.86 (2H, t, J ¼ 5.1 Hz, NCH2), 3.78
(4H, brs, 2ꢀ OCH2), 4.07 (2H, t, J ¼ 4.8 Hz, OCH2), 4.37 (2H, s,
ArCH2Ar), 6.69 (2H, d, J ¼ 8.1 Hz, 2ꢀ AreH), 7.08 (2H, d, J ¼ 8.1 Hz,
2ꢀ AreH), 7.19 (1H, d, J ¼ 8.7 Hz, AreH), 7.82e7.34 (1H, m, AreH),