Uses
4-Fluorophenylhydrazine hydrochloride is used as a chemical intermediate in the pharmaceutica1ls particularly of tryptamine drugs used in the treatment of migraine and cluster headaches. It is used to prepare agrochemical, and other chemical. It is used to detect sugars and aldehydes in analytical chemistry.
Synthesis
The general procedure for the synthesis of 4-fluorophenylhydrazine hydrochloride from 4-fluoroaniline was as follows: 4-fluoroaniline (127.6 g, 1 mol) was dissolved in concentrated hydrochloric acid (293 mL) and stirred for 2 hours at room temperature. Subsequently, the above solution was slowly added dropwise to a solution of sodium nitrite (72.5 g, 1.05 mol) in water (145 mL) at a temperature controlled below 5 °C. After the dropwise addition, stirring was continued for 1 hour, and then the filtrate was separated by filtration to obtain the filtrate. A solution of NaHSO3 (213.2 g, 2.05 mol) in water (500 mL) was slowly added dropwise to the filtrate over a temperature range of 0-10 °C while the pH was adjusted with 25% NaOH solution to maintain between 6-7. The reaction mixture was heated to 80 °C and maintained at this temperature for 1 hour. Upon completion of the reaction, the mixture was cooled to room temperature and then concentrated hydrochloric acid (600 mL) was added dropwise. Next, the mixture was heated to 90-100°C for 1 hour. Finally, the mixture was cooled to 10 °C and the precipitate was collected by filtration to give the light red solid product 4-fluorophenylhydrazine hydrochloride (129.3 g, 60% yield).
References
[1] European Journal of Medicinal Chemistry, 2011, vol. 46, # 7, p. 3149 - 3157
[2] Archiv der Pharmazie (Weinheim, Germany), 1994, vol. 327, # 2, p. 99 - 104
[3] Die Pharmazie, 1985, vol. 40, # 1, p. 21 - 22
[4] European Journal of Medicinal Chemistry, 2010, vol. 45, # 10, p. 4692 - 4696
[5] Angewandte Chemie - International Edition, 2010, vol. 49, # 50, p. 9769 - 9772
