Calcium triflate catalyzed regioselective nucleophilic ring opening of epoxides to afford beta-aminoalcohols

SyntheticPage 560

DOI:

Submitted: May 18, 2012, published: May 21, 2012

Authors

Ashish Dhawan (ashishdhawan78@gmail.com)

Chemicals

Epichlorohydrin (99%, Aldrich)
Calcium triflate (99.9 %, Aldrich)
3-Chloroaniline (99%, Fluka)
Acetonitrile (99%, Aldrich)

Procedure

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).

Author Comments

This procedure works very well to synthesize beta-aminoalchols by nucleophilic ring opening of epoxide ring.
Reaction conditions are milder compared to other reported methods using catalysts such as, zirconium sulfophenyl phosphonate, cerium (III) chloride, diisopropoxyaluminium trifluoroacetate,tantalum(V) chloride (TaCl₅) and zirconium sulfophenyl phosphonate, cerium(III) chloride, diisopropoxyaluminium trifluoroacetate,tantalum(V) chloride (TaCl₅), etc.
We did this reaction using commerical calcium triflate (obtained from Sigma-Aldrich) as well as freshly prepared calcium triflate.Calcium triflate was prepared in laboratory by reaction of two equivalents of trifluoromethanesulfonic acid with calcium carbonate suspended in toluene at room temperature. Freshly prepared calicum triflate gave slighly higher yields.

Data

The compound was obtained as a reddish oil (2.09 g) in 92 % yield.
R_f = 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.

Lead Reference

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.

Get structure file (.cdx)

Keywords

beta-aminoalcohols, calcium triflate, nucleophilic, regioselective, ring opening