Microwave assistant synthesis and biological activity
763
N-(3,4-Dimethoxyphenethyl)-2-hydroxy-2-(1-(2,2,2-trifluoroethyl)-1H-1,2,3-triazol-
-yl)acetamide (7) Method A: To a solution of 2-(3,4-dimethoxyphenyl)ethyla-
4
mine (0.43 g, 2.37 mmol) in a microwave vial, ethyl 2-hydroxy-2-(1-(2,2,2-
trifluoroethyl)-1H-1,2,3-triazol-4-yl)acetate 6 (0.5 g, 1.97 mmol) was added. The
vial was sealed and irradiated in a microwave reactor at 125 °C (10 bar) for 30 min.
The reaction mixture was diluted with water and extracted several times with
dichloromethane. The combined organic phases were washed with brine, dried over
MgSO , and evaporated. The residue was purified by chromatography on silica gel,
4
using petroleum ether (60–90 °C) and ethyl acetate as eluents, to afford 7 in 91.3 %
1
yield as a white solid; m.p. 66–67 °C; H NMR (CDCl ): 2.76–2.79 (m, 2H,
3
ArCH CH ), 3.56–3.58 (m, 2H, ArCH CH ), 3.85 (s, 3H, OCH ), 3.86 (s, 3H,
OCH ), 4.98 (q, 2H, J = 7.81 Hz, JH2 = 15.87 Hz, CF CH ), 5.25 (s, 1H,
2
2
2
2
3
3
H1
3
2
COCH), 6.67–6.71 (m, 2H, Ar–H), 6.78–6.80 (m, 1H, Ar–H), 7.05 (br, 1H, NH),
.74 (s, 1H, triazole). Method B: A mixture of 2-(3,4-dimethoxyphenyl)ethylamine
0.43 g,128 2.37 mmol) and ethyl 2-hydroxy-2-(1-(2,2,2-trifluoroethyl)-1H-1,2,3-
7
(
triazol-4-yl)acetate (0.5 g, 1.97 mmol) was stirred at 130–140 °C for 10 h, then the
product was purified by chromatography on silica gel to afford 7 in 25 % yield.
General process for title compounds 8 RX (7.56 mmol) was added to a mixture of 7
(3.78 mmol), 30 % aqueous sodium hydroxide solution (18.9 mmol), and a catalytic
amount of hexadecyltrimethylammonium bromide (0.4 mmol) in 6 mL CH Cl at
2
2
room temperature. The reaction mixture was heated at reflux for 24 h. Subsequently
the mixture was diluted with water and extracted several times with dichloromethane.
The combined organic phases were washed with brine, dried over MgSO , and
4
evaporated. The residue was purified by chromatography on silica gel, using
petroleum ether (60–90 °C) and ethyl acetate as eluents, to afford the title compounds
2
PhCH Br.
a–2d. The alkyl halides were C H Br, CH:CCH Br, CH =CHCH Br, and
2
5
2
2
2
2
N-(3,4-Dimethoxyphenethyl)-2-ethoxy-2-(1-(2,2,2-trifluoroethyl)-1H-1,2,3-triazol-
-yl)acetamide (8a) The compound was obtained in 46.6 % yield as a light yellow
4
1
solid; m.p. 112–113 °C; H NMR (CDCl ): 1.21 (t, 3H, J = 7.0 Hz, CH CH O),
3
3
2
2
CH CH O), 3.84(s, 3H, OCH ), 3.87 (s, 3H, OCH ), 4.91–4.96 (m, 2H, CF CH O),
.75–2.90 (m, 2H, ArCH CH ), 3.53–3.61 (m, 2H, ArCH CH ), 3.63–3.73 (m, 2H,
2 2 2 2
3
2
3
3
3
2
4
triazole); HRMS (ESI) m/z Calcd. for C H F N O Na (M ? Na)
.97 (s, 1H, COCH), 6.75–6.84 (m, 3H, Ar–H), 6.96 (br, 1H, NH), 7.42 (s, 1H,
?
439.1564,
1
8 23 3 4 4
found 439.1569.
N-(3,4-dimethoxyphenethyl)-2-(prop-2-yn-1-yloxy)-2-(1-(2,2,2-trifluoroethyl)-1H-
,2,3-triazol-4-yl)acetamide (8b) The compound was obtained in 54.9 % yield as a
1
1
light yellow solid; m.p. 130–131 °C; H NMR (CDCl ): 2.49 (t, 1H, J = 2.37 Hz,
3
H
CHCCH O), 2.75–2.90 (m, 2H, ArCH CH ), 3.51–3.57 (m, 1H, ArCH CH ),
.65–3.72 (m, 1H, ArCH CH ), 3.84(s, 3H, OCH ), 3.87 (s, 3H, OCH ), 4.10–4.14
2 2 3 3
2
2
2
2
2
3
(
m, 1H, COCH), 4.24–4.38 (m, 2H, CHCCH O), 4.92–5.00 (m, 2H, CF CH ),
2 3 2
6
z Calcd. for C H F N O Na (M ? Na) 449.1407, found 449.1413.
.75–6.84 (m, 3H, Ar–H), 6.92 (br, 1H, NH), 7.50 (s, 1H, triazole); HRMS (ESI) m/
?
1
9 21 3 4 4
123