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Discrimination in resolving systems. III: Pseudoephedrine‐mandelic acid
Author(s) -
Valente Edward J.,
WilliamsKnight Pamela M.,
Moore Michael C.
Publication year - 1998
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/(sici)1520-636x(1998)10:4<325::aid-chir7>3.0.co;2-6
Subject(s) - chemistry , monoclinic crystal system , orthorhombic crystal system , solubility , diastereomer , pseudoephedrine , mandelic acid , double salt , salt (chemistry) , crystallography , stereochemistry , solvent , enantiomer , crystal structure , medicinal chemistry , ephedrine , organic chemistry , neuroscience , biology
(+)‐(1S;2S)‐Pseudoephedrine and racemic mandelic acid form three distinct diastereomeric salts from solutions in 95% ethanol. The least‐soluble phase, a hemihydrate, contains the (2R)‐mandelate. A salt phase of intermediate solubility is the unsolvated double salt, containing both the (2R)‐ and the (2S)‐mandelate. The most‐soluble salt phase contains the (2S)‐mandelate. Mandelate configuration and order of solubility (based on the heats of fusion) is inverted from that found in the same system synthesized from chiral base and acid, and then crystallized from benzene solution. The (2R)‐mandelate hemihydrate (−H 2 O at 349.5K, mp 391K), monoclinic, P2 1 , a = 6.788(5), b = 29.415(35), c = 9.488(10)Å, β = 108.91(8)°, Z = 4 (2 ion‐pairs/asymmetric unit). Intermediate double salt (2S)‐ and (2R)‐mandelate, mp 377.6K, anorthic, P1, a = 7.758(4), b = 9.966(5), c = 13.366(6)Å, α = 72.99(4), β = 79.98(4), γ = 70.51(4)°, Z = 1 (2 ion‐pairs/asymmetric unit). The (2S)‐mandelate (mp 386.2K), orthorhombic, P2 1 2 1 2 1 , a = 7.079(6), b = 13.443(10), c = 18.820(14)Å, Z = 4 is identical to a salt made from a combination of enantiomeric moieties from benzene solution. While differing from ephedrine mandelates in configuration at one center, solubilities of pseudoephedrine mandelates in 95% ethanol are much larger. A comparison of molecular structure (non‐polar and H‐bonding) regions of pseudoephedrine and ephedrine mandelates shows similarities and differences that are tentatively linked to crystal properties. This study reemphasizes the necessity for consistency in solvent use in resolution and in phase identification and comparison because the phases produced are frequently dependent upon the solvent. Chirality 10:325–337, 1998. © 1998 Wiley‐Liss, Inc.