Title
Synthesis and characterization of fluorous (S)- and (R)-1-phenylethylamines that effect heat facilitated resolution of ()-2-(8-carboxy-1-naphthylsulfinyl)benzoic acid via diastereomeric salt formation and study of their circular dichroism
Author
Denes Szabo, Anikó Nemes, István Kövesdi, Viktor Farkas, Miklós Hollósi, József Rábai
Year
2006
Journal
Journal of Fluorine Chemistry
Abstract
Perfluoroalkyl- or nonafluoro-tert-butoxy-alkyl-substituted enantiopure amines having the structure PhCHCH3(NR1R2) [R1 = H, CH3; R2 = (CH2)3C8F17, (CH2)2OC(CF3)3; R1 = R2 = (CH2)3C8F17, (CH2)2OC(CF3)3] are obtained in high yields, when (S)-(−)-1-phenylethylamine is reacted with readily accessible alkylating reagents or fluorous 2° amines (R1 = H; R2 = (CH2)3C8F17, (CH2)2OC(CF3)3) are methylated in a Leuckart–Wallach reaction. The solubility patterns of these novel chiral amines and their hydrochlorides are qualitatively described for a broad spectrum of solvents and the fluorous partition coefficients of the free bases are determined by GC. A novel method for the resolution of enantiomers is disclosed here, which involves the use a half-equivalent of the selected resolving agent in solvent water that displays low solubility for the crystalline diastereomeric salt(s) formed even at temperatures near to its boiling point. Compound (S)-(−)-PhCHCH3[NH(CH2)3C8F17] is found to satisfy all the latter conditions and successfully used for the heat facilitated resolution of the title racemic acid. The circular dichroism (CD) spectra of six novel fluorous (S)-(−)-1-phenylethylamine derivatives are measured in ethanol, trifluoroethanol and hexafluoropropan-2-ol and discussed in detail.
Instrument
J-810
Keywords
Circular dichroism, Stereochemistry, Pharmaceutical