Calcium triflate catalyzed regioselective nucleophilic ring opening of epoxides to afford beta-aminoalcohols; 1-Chloro-3-(3'-chlorophenylamino)-propan-2-ol
Submitted May 18, 2012, published May 21, 2012
Epichlorohydrin (99%, Aldrich)
Calcium triflate (99.9 %, Aldrich)
3-Chloroaniline (99%, Fluka)
Acetonitrile (99%, Aldrich)
To a solution of epichlorohydrin (1.4 mL, 10 mmol) and 3-chloroaniline (2.3 mL,10 mmol) in acetonitrile (30 ml), calcium triflate (1.8 g, 5 mmol) was added and the reaction mixture was stirred at 60 oC overnight. The solvent was evaporated under reduced pressure and water (20 ml) was added to the residue. The product was extracted with dichloromethane (3 x 20 ml) and the combined organic layer was washed with brine (2 x 20 ml), dried over anhydrous Na2SO4 and evaporated under reduced pressure to obtain the crude product, which was purified by column chromatography over silica gel using ethyl acetate-petroleum ether (3:97 to 12:88) as eluent to afford pure 1-Chloro-3-(3'-chlorophenylamino)-propan-2-ol (92 % yield).
The compound was obtained as a reddish oil (2.09 g) in 92 % yield.
Rf = 0.25 in 15 % ethyl acetate in petroleum ether.
IR (nujol): 3401 (NH, OH), 2923, 1599, 1504, 1251, 1091, 988, 766 cm-1.
1H NMR (CDCl3): d 3.17 (1H, dd, J = 13.2 and 7.2 Hz), 3.42 (1H, dd, J = 13.2 and 4.3 Hz), 3.63 (2H, m), 4.04 (1H, m), 6.48 (1H, d, J = 8.0 Hz), 6.61 (1H, brs), 6.69 (1H, d, J= 7.7 Hz) and 7.07 (1H, t, J = 8.1 Hz).
13C NMR (CDCl3): d 45.82 and 46.61 (C-1 and C-3), 68.79 (C-2), 110.60, 115.12 and 117.02 (C-2', C-4' and C-6' ), 129.33 (C-5'), 134.12 (C-3') and 144.05 (C-1').
HRMS: m/z calculated for C9H11NOCl2+ 219.0218, observed 219.0220.
A mild, calcium trifluoromethanesulfonate-catalyzed aminolysis of epoxides is very efficient in the synthesis of various β-amino alcohols with high regio- and stereoselectivity.
I. Cepanec, M. Litvic, H. Mikuldas, A. Bartolincic, V. Vinkovic, Tetrahedron, 2003, 59, 2435-2439.
Keywords: beta-aminoalcohols, calcium triflate, nucleophilic, regioselective, ring opening