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Chiral separation of pheniramine‐like 3‐phenyl‐3‐heteroarylpropylamines by CE and HPLC methods
Author(s) -
Schuster Andreas,
Götte Carsten,
Bernhardt Günther,
Buschauer Armin
Publication year - 2001
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/chir.1033
Subject(s) - chemistry , diastereomer , enantiomer , propylamine , high performance liquid chromatography , stereochemistry , enantiomeric excess , chromatography , enantioselective synthesis , organic chemistry , amine gas treating , catalysis
Analytical CE and HPLC methods were developed for the chiral separation of halogen‐substituted 3‐phenyl‐3‐(2‐pyridyl)propylamines 1–4 ( 1: 3‐(4‐fluorophenyl)∼, 2: 3‐(3,4‐difluorophenyl)∼, 3: 3‐(4‐chlorophenyl)∼, 4: 3‐(3,4‐dichlorophenyl)∼), 3‐(4‐fluorophenyl)‐3‐(2‐thiazolyl)propylamine (5), and 3‐(4‐fluorophenyl)‐3‐(1‐benzylimidazol‐2‐yl)propylamine (6), which are building blocks for the preparation of very potent arpromidine‐type histamine H 2 receptor agonists. All amines were enantioseparated by CE with resolutions of at least 1.8 using α‐, β‐, or γ‐cyclodextrin (CD) as chiral selectors. With heparin as buffer additive for CE the optical antipodes of 1–4 and 6 were separated with resolutions ≥1.8. On RP‐18 columns the separation of the (+)‐( S )‐acetylmandelic acid amides of racemic 2 (R = 0.9, α = 1.07) and the thioureas prepared by addition of 6 to 2,3,4,6‐tetra‐O‐acetyl‐β‐ D ‐glucopyranosyl isothiocyanate (R = 2.0, α = 1.20) was successful, whereas the diastereomeric ureas prepared from 3 and (+)‐( S )‐1‐(1‐naphthyl)ethyl isocyanate could not be resolved. Separation of the diastereomeric isoindoles prepared from 1–5, o‐phthaldialdehyde and 2,3,4,6‐tetra‐O‐acetyl‐1‐thio‐β‐ D ‐glucopyranoside was achieved on a RP‐18 phase (R ≥ 0.4, a ≥ 1.02). Direct separation of the enantiomers of 3 and 4 was achieved on a Cyclobond I column (R ≥ 0.9, α ≥ 1.07). α‐ and β‐CD were also useful as mobile phase additives for HPLC ( 3 and 4: RP‐18 column, β‐CD, R ≥ 0.4, α ≥ 1.03; 3: RP‐18 column, α‐CD: R = 0.5, α = 1.04). Chirality 13:285–293, 2001. © 2001 Wiley‐Liss, Inc.