Discrimination in resolving systems. V. Pseudoephedrine - fluoromandelic acid diastereomers

Resolution of the isomeric 2'-, 3'-, and 4'-fluoromandelic acids with (+)-(1S;2S)-pseudoephedrine in 95% ethanol produces both well and poorly discriminating, hydrated and unsolvated binary salts. Seven observed diastereomeric phases are represented by five crystal structure types including three of the four types observed in the pseudoephedrine mandelates. Type a: monoclinic hemihydrate less-soluble (L) (R)-3'-fluoromandelate and more-soluble (M) (R)-4'-fluoromandelate (I); type b: orthorhombic unsolvated M (S)-2'-fluoromandelate; type c: orthorhombic unsolvated L (R)-2'-fluoromandelate; type d: orthorhombic dihydrate M (S)-3'-fluoromandelate and L (S)-4'-fluoromandelate; type e: monoclinic unsolvated M (R)-4'-fluoromandelate (II). Largest (15-fold) discriminating solubilities in 95% ethanol are found between the diastereomers with 2'-fluoromandelic acid, 50% more than in the corresponding ephedrine system. Principle interionic interactions are hydrogen-bonds between protonated secondary ammonium ions and carboxylates. Infinite chains of these are found in type c, with a four-atom repeating unit H-N(+)-H.O(-C(-)-O) [C(2)(1)(4)], and in types b and d, with a six-atom repeating unit H-N(+)-H.O-C(-)-O [C(2)(2)(6)]. Water of crystallization intervenes in the chains of type a but not of type d hydrated salts, according with higher average dehydration temperatures in the former. Hydrated salts in general are excessively soluble in 95% ethanol.