Chemical Properties
white to pink crystalline powder
Uses
4-Chlorophenylhydrazine hydrochloride is used as a pharmaceutical intermediates.
General Description
4-Chlorophenylhydrazine hydrochloride reacts with 3-acetonyl-5-cyano-1,2,4-thiadiazole to yield 5-cyano-3-(5-chloro-2-methylindol-3-yl)-1,2,4-thiadiazole and 5-cyano-3-[1-(4-chlorophenyl)-3,5-dimethylpyrazol-4-yl]-1,2,4-thiadiazole.
Synthesis
The general procedure for the synthesis of p-chlorophenylhydrazine hydrochloride from 4-bromochlorobenzene is as follows: 98.25 g of 4-bromochlorobenzene and 3.3 equivalents of 71% hydrazine hydrate were added to a reaction vessel, to which were added 10 wt.% of the phase transfer catalyst PEG400, 3 times the weight of the solvent acrylhydrazine, and 20 wt.% of a catalyst (copper sulfate in the ratio of copper sulfate to cobalt chloride by mass of 3:1). The reaction process consisted of slowly increasing the temperature to 152 °C, refluxing or packing pressure reaction at atmospheric pressure, and maintaining the reaction at this temperature for 10 hours. During this time, the reaction process was monitored by HPLC and stopped when the amount of p-chlorophenylhydrazone no longer increased. After completion of the reaction, the solid was separated by filtration and the filtrate was distilled to remove the solvent. To the obtained residue, 30% hydrochloric acid was added, the pH was adjusted to 3, and the residue was filtered with thorough stirring. The filtrate was washed with water and dried at 55°C to finally obtain p-chlorophenylhydrazine hydrochloride. In this embodiment, the yield of p-chlorophenylhydrazine hydrochloride was 88.1% and the HPLC purity was 99.29%.
References
[1] Patent: CN105968048, 2016, A. Location in patent: Paragraph 0030-0054; 0055-0059; 0060-0069
[2] Patent: CN106045876, 2016, A. Location in patent: Paragraph 0055; 0056; 0057; 0058; 0059
[3] Chinese Journal of Chemistry, 2018, vol. 36, # 11, p. 1003 - 1006
[4] Tetrahedron, 2014, vol. 70, # 26, p. 4043 - 4048
