Preparation method of 4-(methylmercapto)phenyl]hydrazine hydrochloric acid_Kain Industrial Additive

Background and overview^[1]

4-(Methylmercapto)phenyl]hydrazine hydrochloride can be used as a pharmaceutical synthesis intermediate. If 4-(methylmercapto)phenyl]hydrazine hydrochloride is inhaled, move the patient to fresh air; if skin contact occurs, take off contaminated clothing, rinse the skin thoroughly with soap and water, and seek medical attention if you feel unwell. .

Preparation^[1]

4-(Methylmercapto)phenyl]hydrazine hydrochloric acid is prepared as follows:

1) 4-(methylmercapto)-aniline

Put 4-(methylmercapto)-nitrophenyl (13.4mmol), ethanol (10mL), and water (10mL) into a 100-mL 3-neck round-bottom flask equipped with a magnetic stirring bar, condenser and thermometer. , iron (2.5g, 44.8mmol), ammonium chloride (2.1g, 39.3mmol) and tetrahydrofuran (10mL). The resulting mixture was stirred at 80°C for 1 hour. After cooling to 23°C, the solids were removed by filtration and the filtrate was concentrated under vacuum. The residue was diluted with water (100 mL) and the resulting mixture was extracted with ethyl acetate (3 x 100 mL). The combined organic layers were washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford 4-(methylmercapto)-aniline as a pale yellow solid.

2) 4-Chloro-1-(4-hydrazinophenyl)-1H-pyrazole hydrochloride

Put 4-(methylmercapto)-aniline (10.33mmol), hydrochloric acid (12N, 20mL) and ethanol (10mL) into a 100-mL 3-neck round-bottom flask equipped with a magnetic stirring bar and thermometer. The resulting solution was cooled to -20°C, then sodium nitrite (1.06 g, 15.4 mmol) in water (5 mL) was added dropwise with stirring at -20°C. After stirring the mixture for 0.5 hours at -10°C, tin (II) chloride (4.6 g, 20.4 mmol) was added in portions at -10°C. The resulting solution was then stirred at -10°C for an additional 0.5 hours. The solid was collected by filtration and dried in an oven to give 4-(methylmercapto)phenyl]hydrazine hydrochloride.

Main reference materials

[1] (CN107406451) Pyrrolopyrimidines and pyrazolopyrimidines as ubiquitin-specific proteinase 7 inhibitors