The role of solvates in optical resolution. A study of the diastereoisomeric salts formed from enantiomeric 2-amino-2-phenylethanol and (R)-mandelic acid, their crystal structures and physico-chemical properties

Abstract

The reactions between (R)-mandelic acid and the pure enantiomers of 2-amino-2-phenylethanol in water saturated ethyl acetate resulted in the diastereoisomeric salts, (R)-2-hydroxy-1-phenylethylammonium (R)-mandelate hydrate, (R-APE)(R-MA)·H₂O and (S)-2-hydroxy-1-phenylethylammonium (R)-mandelate, (S-APE)(R-MA). Similar reactions from pure ethyl acetate gave the latter salt and unhydrated (R-APE)(R-MA). The crystal structures at 122 K have been determined for the salts obtained from water-saturated ethyl acetate. The less soluble salt, (R-APE)(R-MA)·H₂O, crystallizes in C2, a= 18.407(2), b= 5.5940(6), c= 15.1863(10)Å, β= 105.735(6)°, Z= 4, R= 0.029 based on 2950 observed reflections. (S-APE)(R-MA) crystallizes in P1, a= 10.0046(12), b= 10.2466(11), c= 15.869(2)Å, α= 100.347(10), β= 98.770(10), γ= 108.437(9)°, Z= 4, R= 0.033 based on 6085 contributing reflections. Five independent cations and anions are found in different conformations. Hydrogen bonding is important for the crystal packing in both structures. The water molecule in (R-APE)(R-MA)·H₂O plays an important role linking cations and anions. The solubilities in pure and water saturated ethyl acetate and the thermal behaviour have been investigated for the three compounds (R-APE)(R-MA)·H₂O, (R-APE)(R-MA) and (S-APE)(R-MA). The difference in thermochemical properties can be related to the differences in the crystal packing and explain why the resolution of 2-amino-2-phenylethanol with (R)-mandelic acid can only be achieved in water-saturated ethyl acetate.

From the measured solubilities ΔG^⊖ has been calculated for the reaction: (R-APE)(R-MA)+(H₂O →(R-APE)(R-MA)·H₂O; ΔG^⊖=–3.4 kJ mol^–1.