The general procedure for the synthesis of 4-phenoxyphenylhydrazine hydrochloride from 4-aminodiphenyl ether is as follows: to a concentrated solution of 4-phenoxyaniline (2 g, 10.8 mmol, 1 equiv). A solution of ice-cold sodium nitrite (1.49 g, 21.6 mmol, 2.0 eq.) in water (7.6 mL) was added dropwise to hydrochloric acid (22 mL) over a period of 15 min while maintaining the reaction temperature below 10 °C. The reaction mixture was cooled to 0 °C and stirred continuously for 1 hour. Subsequently, sulfamic acid (1.05 g, 10.8 mmol, 1 eq.) was added to the reaction mixture in batches over 20 minutes. Next, a concentrated hydrochloric acid solution of tin(II) chloride dihydrate (9.78 g, 43.2 mmol, 4 eq.) was added. Hydrochloric acid (8.2 mL) was added dropwise over a period of 20 minutes while the reaction temperature was controlled to be below 15 °C. The reaction mixture was continued to be stirred at 0 °C for 2 h and then alkalized to pH 14 with 5 M aqueous sodium hydroxide solution, during which the reaction temperature was kept below 30 °C. After completion of the reaction, the reaction mixture was rapidly extracted with dichloromethane (2 x 100 mL). The organic phases were combined, dried with anhydrous sodium sulfate, and the solvent was removed by filtration and vacuum. The unstable (4-phenoxyphenyl) hydrazine was converted to its hydrochloride salt by using an ether (20 mL) solution of 2M hydrochloric acid. The precipitate formed was collected and dried under reduced pressure to give the final 4-phenoxyphenylhydrazine hydrochloride as a light brown solid (1.2 g, 44% yield).
