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

Abstract

Perfluoroalkyl- or nonafluoro- tert-butoxy-alkyl-substituted enantiopure amines having the structure PhCHCH 3(NR 1R 2) [R 1 = H, CH 3; R 2 = (CH 2) 3C 8F 17, (CH 2) 2OC(CF 3) 3; R 1 = R 2 = (CH 2) 3C 8F 17, (CH 2) 2OC(CF 3) 3] are obtained in high yields, when ( S)-(−)-1-phenylethylamine is reacted with readily accessible alkylating reagents or fluorous 2° amines (R 1 = H; R 2 = (CH 2) 3C 8F 17, (CH 2) 2OC(CF 3) 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)-(−)-PhCHCH 3[NH(CH 2) 3C 8F 17] 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.