Acetic Acid → 1-(2-Benzoyl-4-chlorophenyl)-3,5-pyrazole dicarboxylic acid, dimethyl ester

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Reaction Steps

To a solution of 13.1 g. (34.5 mmol) of the final product of Example 2 in 50 ml. HOAc and 75 ml. of 3N HCl, stirred at 3°, was added dropwise so as to maintain a temperature of 3°-6°, a solution of 2.50 g. (36.3 mmol) of sodium nitrite in 25 ml. H2O. When the addition was complete, the reaction was stirred at 3° for 20 minutes. A fresh solution of cuprous chloride in concentrated hydrochloric acid (prepared from 27 g. cupric sulfate pentahydrate*) was mixed with an equal volume of water and cooled to 3°. The diazotized solution, which had to be kept cold (<5°) at all times, was slowly poured into the vigorously stirred 5° cuprous chloride solution in several portions, in order to control foaming. When addition was complete, the reaction was stirred for one hour while slowly warming to room temperature, then heated on a steam bath to an internal temperature of 95°. After cooling to room temperature, the reaction was made basic with NH4OH and extracted well with CH2Cl2. The combined extracts were washed with brine, dried (Na2SO4) and concentrated in vacuo to a brown oil. This crude product was chromatographed on silica gel using a 2% EtOAc in benzene solution as eluent to give the final product. An analytical sample was prepared by recrystallization from ether/hexane and was obtained as colorless crystals: mp 118°-120°.

Provenance & Evidence