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 discrim inating, hydrated and unsolvated binary salts. Seven observed diastereomeri c phases are represented by five crystal structure types including three of the four types observed in the pseudoephedrine mandelates. Type a: monocli nic hemihydrate less-soluble (L) (R)3'-fluoromandelate and more-soluble (M) (R)-4'-fluoromandelate (I); type b: orthorhombic unsolvated M (S)-2'-fluor omandelate; type c: orthorhombic unsolvated L (R)-2'-fluoromandelate; type d: orthorhombic dihydrate M (S)-3'-fluoromandelate and L (S)-4'-fluoromande late; type e: monoclinic unsolvated M (R)-3'-fluoromandelate (IT). Largest (15-fold) discriminating solubilities in 95% ethanol are found between the diastereomers with 2'-fluoromandelic acid, 50% more than in the correspondi ng ephedrine system. Principle interionic interactions are hydrogen-bonds b etween 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 ch ains of type a but not of type d hydrated salts, according with higher aver age dehydration temperatures in the former. Hydrated salts in general are e xcessively soluble in 95% ethanol. (C) 2000 Wiley-Liss, Inc.