ETHYL 2-CHLORO-2-[2-(2-CHLOROPHENYL)HYDRAZONO]-ACETATE synthesis

Yield:28317-49-9 79.8%

Reaction Conditions:

Stage #1: o-chloroanilinewith hydrogenchloride;sodium nitrite in ethanol;water at 0 - 5; for 0.5 h;
Stage #2: ethyl 2-chloro-3-oxo-butyratewith sodium acetate in ethanol;water at 0 - 25;

Steps:

7 General procedure for preparation intermediates of ethyl 2-chloro-2-(2-arylhydrazono)acetate (21a-21j)

General procedure: Commercially available substituted aniline (63.4mmol) was portionwise added to a solution of concentrated HCl (13mL), ethanol (20mL) and water (7mL). To the above mixture was added dropwise a solution of NaNO₂ (4.69g, 69.7mmol) in water (15mL) at 0-5°C. After the completion of addition, the reaction mixture was stirred at this temperature for 30min, and then added into a mixture of ethyl 2-chloroacetoacetate (10.88g, 63.4mmol), anhydrous sodium acetate (15.60g, 190.10mmol), and water (90mL) at 0°C. The reaction mixture was stirred at 0°C for 10min and then at room temperature for 4h. The solid which precipitated was collected by filtration and recrystallized from ethanol to afford light yellow solids (21a-21m) in 75.2-90% yields.
6.3.7
Ethyl 2-chloro-2-(2-(2-chlorophenyl)hydrazono)acetate (21g)
Light yellow solid; Yield: 79.8%; M.p.: 90.9-92.8 °C; IR (KBr) cm^-1: 3314.7, 2984.0, 1725.9, 1598.7, 1558.9, 1514.4, 1367.9, 1324.8, 1278.7, 1236.7, 1178.7, 1081.9, 1009.3, 858.1, 748.6; MS (ESI) m/z(%): 283.0 [M+Na]⁺.

References:

Liu, Ju;Nie, Minhua;Wang, Yanjing;Hu, Jinxing;Zhang, Feng;Gao, Yanlin;Liu, Yajing;Gong, Ping [European Journal of Medicinal Chemistry,2016,vol. 123,p. 431 - 446]