Synthesis of N-Substituted Phenylenediamine Derivatives

Tert-butyl ((S)-1-((R)-oxiran-2-yl)-2-phenylethyl)carbamate (epoxide) (1.9 mmol), anilines (1.9 mmol), nitromethane (5 mL) were taken in a round-bottomed flask and microwave heated to 80°C (300 W) for 20 minutes. Afterwards, nitromethane was removed on a rotary evaporator, and the obtained material was recrystallized from ethyl acetate and hexane in 1:9 ratio to isolate BOC-protected intermediates. In the next step, deprotection was carried out by treating the BOC-protected intermediates with 15% trifluoroacetic acid (TFA) solution in dichloromethane (1.5 mL of TFA, dissolved in 10 mL of dichloromethane) at room temperature for 3–4 hrs. Excess TFA present in the reaction flask was washed with dichloromethane and removed under reduced pressure. The obtained crude product was extracted from ethyl acetate (15 mL x 3) and alkaline water (1N KOH) at a pH range of 8–9. The obtained ethyl acetate layer was removed on a rotary evaporator that afforded the listed compounds (i.e., LTC 1026, 1027, 1028, 1029, 1031, 1032, 1034, 1041, 1042, and 1043). The chemical composition of all newly synthesized compounds was confirmed by NMR (¹H & ¹³C) and mass spectrometry.