Carbinolamines, imines, and oxazolidines from fluorinated propranolol analogs. F-19 NMR and mass spectral characterization and evidence for formationas intermediates in cytochrome P450-catalyzed N-dealkylation

Formation of carbinolamine, imine, and oxazolidines from the reactions of d esisopropylpropranolol (5), its O-methyl ether (10), and 3-(1-naphthoxy)pro pylamine (11) with trifluoroacetone and trifluoroacetaldehyde methyl hemiac etal was investigated by F-19 NMR and tandem mass spectrometry. Products fr om the metabolism of the related secondary amine substrates trifluoropropra nolol (7), its O-methyl ether (23), and its N-trifluoroethyl-O-methyl ether analog (24) in the presence of rat liver microsomes and CYP1A2 were examin ed to determine whether these species were formed. The F-19 NMR experiments showed the presence of carbinolamine and imine species from these primary amines and fluorinated carbonyl compounds in solution. Mass spectral experi ments under atmospheric pressure chemical ionization and electrospray ioniz ation-ion trap conditions showed formation of imine metabolites (and/or oxa zolidine from 7) as well as products of N-dealkylation and aromatic hydroxy lation when the secondary amine substrates were incubated with rat liver mi crosomes or CYP1A2. In spite of mass spectral evidence for these imines as metabolites, we were unable to detect the carbinolamines under the conditio ns used in these studies. Their presence is inferred from the results of th e F-19 NMR experiments.