2538-61-6

2,6-Dimethylphenylhydrazine Hydrochloride is used as a reagent in the synthesis of 3-arylimino-2,3,5,6-tetrahydro-4H-1,4-thiazines and related cyclic amidines which exhibit potential antihypertensive activity.

Under stirring conditions, 2,6-dimethylaniline (5.0 g, 41.3 mmol) was dissolved in 50% aqueous HCl solution (45 mL) and cooled to 0°C. At the same temperature, NaNO2 solution (2.85 g, 41.3 mmol dissolved in 22.5 mL of water) was slowly added. The temperature was strictly controlled not to exceed 5 °C during addition. After addition, the resulting bright orange diazonium salt solution was continued to be stirred at 0 °C for 20 min. Subsequently, a pre-cooled (0 °C) solution of SnCl2 (11.0 g, 57.8 mmol) in concentrated HCl (30 mL) was added to the reaction mixture over 5 min. The reaction mixture was gradually warmed to room temperature with continuous stirring for 6 hours. Upon completion of the reaction, the precipitate was collected by filtration, washed with a little cold water and dried under vacuum to afford (2,6-dimethylphenyl)hydrazine hydrochloride as a white amorphous solid (7.00 g, 98% yield). The product was detected by ES-MS showing m/z 137.0 (MH+) and HPLC retention time of 1.09 min, which can be directly used in the subsequent reaction without further purification.

[1] Patent: US2005/192294, 2005, A1. Location in patent: Page/Page column 10