Nucleophilic Substitution in Tetrafluoro-4-nitropyridine Derivatives and the Corresponding Fluorinated Diazepines: HPLC Resolution of Their Isomers

Abstract

Tetrafluoro-4-nitropyridine derivatives have been synthesized and separated successfully by HPLC. The resulting fluorinated amines and 4-amino-3-chlorotrifluoropyridine have also been diazotized and the resulting diazonium ions coupled to mesitylene giving the corresponding azo-compounds: 2,3,4,6-tetrafluoro-4-(2,4,6-trimethylphenylazo)pyridine (9) (80%), 3-chloro-2,5,6-trifluoro-4-(2,4,6-trimethylphenylazo)pyridine (23) (83%), 2,3,6-trifluoro-4-nitro-5-(2,4,6-trimethylphenylazo)pyridine (20) (80%), 2,3,5-trifluoro-4-nitro-6-(2,4,6-trimethylphenylazo)pyridine (21) (84%). Treatment of these azo-compounds mentioned earlier with sodium methoxide in methanol/tetrahydro furan gave 3,6-difluoro-2-methoxy-4-nitro-5-(2,4,6-trimethylphenylazo)pyridine (24) (37%), 3-fluoro-2,5-dimethoxy-4-nitro-6-(2,4,6-trimethyl-phenylazo)pyridine (26) (49%), 2,3-difluoro-4,5-dimethoxy-6-(2,4,6-trimethylphenylazo)pyridine (25) (32%), 3-chloro-2,3,5-trifluoro-6-methoxy-4-(2,4,6-trimethylphenylazo) pyridine 24 (87%), 3-chloro-3,5-difluoro-2,6-dimethoxy-4-(2,4,6-trimethylphenylazo)-pyridine 23 (83%). The two diazepines 25 and 26 were successfully separated by HPLC. The thermolysis of the synthesized azo-compounds in boiling mestylene gave the corresponding diazepines: 1,2,4-trifluoro-7,9-dimethyl-11-H-pyrido[4,3-c]benzo[1,2]diazepine (15) (75%), 1,4-difluoro-3-methoxy-7,9-dimethyl-11-H-pyrido[4,3-c]benzo[1,2]diazepine (32) (80%) and 3,4-difluoro-1-methoxy-7,9-dimethyl-11-H-pyrido[4,3-c]benzo[1,2]diazepine (33) (9%). The structural diazepine-isomers 32 and 33 were also separated by HPLC.