GENERAL STEPS: This is a modified protocol of the previous study method. A suspension of pre-distilled p-chlorobenzaldehyde (50 mmol) with ammonium acetate (150 mmol) was heated and stirred at 120°C for 3 hours. After completion of the reaction, the mixture was cooled to room temperature and the gelatinous residue was washed with hexane. The crude product was alkalized with 4 M NaOH aqueous solution to pH >10 and subsequently extracted with ether (4 x 20 mL). The organic phases were combined, dried and filtered, and the solvent was evaporated under reduced pressure. The resulting intermediate was suspended directly in 50% aqueous H2SO4 (40 mL) without further purification and the mixture was heated at 170 °C overnight. The reaction solution was cooled in an ice bath and water (20 mL) was added slowly. After returning the solution to room temperature, it was extracted with ether (4 x 60 mL). The aqueous phase was neutralized with concentrated ammonia and extracted again with ether (4 x 60 mL). The organic phases were combined, dried and filtered, and the solvents were evaporated under reduced pressure to give endo-1,2-bis(4-chlorophenyl)ethane-1,2-diamine as a white, yellow or brown solid (isolated yield 40-98%). Endo-1,2-bis(4-chlorophenyl)ethane-1,2-diamine (2c) was a yellow solid (3.43 g, 98% isolated yield). Thin-layer chromatography Rf value (60% methanol/ethyl acetate): 0.47; Melting point: 126-128 °C; IR spectrum (KBr, cm?1): 3380, 2950, 1600, 1202, 980, 820; 1H NMR (300.13 MHz, CDCl3, Me4Si): δ 1.53 (br s, 4H), 4.00 (s, 2H), 7.27-7.34 (m, 8H); 13C NMR (75.5 MHz, CDCl3, Me4Si): δ 62.0 (2CH), 128.5 (4CH), 128.9 (4CH), 133.4 (2C), 140.9 (2C); Mass Spectra (ESI+, m/z): 281.0 [(M+H)+, 100%]; high-resolution mass spectrum (ESI+, m/z) C14H15Cl2N2 (M+H)+ Calculated: 281.0607, measured: 281.0592 (35Cl,35Cl), 283.0563 (35Cl,37Cl).
