Print version Print setup

Calcium triflate catalyzed regioselective nucleophilic ring opening of epoxides to afford beta-aminoalcohols; 1-Chloro-3-(3'-chlorophenylamino)-propan-2-ol 

SyntheticPage 560
DOI: 10.1039/SP560
Submitted May 18, 2012, published May 21, 2012
Ashish Dhawan (ashishdhawan78@gmail.com)
Reaction Scheme: <IMG src="/images/empty.gif"><IMG src="/images/empty.gif"><SPAN id=csm1337854989782 class=csm-chemical-name title="Calcium triflate" grpid="2">Calcium triflate</SPAN> catalyzed regioselective&nbsp;nucleophilic&nbsp;ring opening of epoxides to afford beta-aminoalcohols<IMG src="/images/empty.gif"><IMG src="/images/empty.gif">

Chemicals Used

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's 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.
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.

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.

This page has been viewed approximately 8284 times since records began.

Get structure file (.cdx, .sk2, .mol)

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