Biological Activity
4-CHLORO-5-FLUORO-O-PHENYLENEDIAMINE has been shown to have a high frequency of human activity using a patch clamp technique on human erythrocytes and also inhibits bacterial growth by binding to DNA dependent RNA polymerase, thereby preventing transcription and replication.
Synthesis
The general procedure for the synthesis of 4-chloro-5-fluoro-o-phenylenediamine from 5-chloro-4-fluoro-2-nitroaniline was as follows: first, the reducing agent, hydrazine monocarbonate, was prepared by slow neutralization of 12.5 mL of hydrazine hydrate with 12.5 mL of 90% formic acid under ice-bath conditions. Subsequently, the compound 5-chloro-4-fluoro-2-nitroaniline (6 g, 0.03 mol) was dissolved in 20 mL of methanol and zinc powder (4 g, 0.06 mol) was added. The above solution was mixed with the prepared hydrazine monocarbonate solution and stirred at room temperature under nitrogen protection (Note: the reaction is exothermic and accompanied by gas production). The progress of the reaction was monitored by thin layer chromatography (TLC). After completion of the reaction, the reaction mixture was filtered and the filtrate concentrated. The residue was dissolved in dichloromethane and washed twice with saturated brine solution to remove excess of hydrazine monoformate. The organic layers were combined, dried over anhydrous sodium sulfate and subsequently concentrated under reduced pressure to afford the target product 4-chloro-5-fluoro-o-phenylenediamine (89% yield, melting point 84-86 °C).
References
[1] European Journal of Medicinal Chemistry, 2016, vol. 117, p. 230 - 240
