Reference of 78703-53-4, A common heterocyclic compound, 78703-53-4, name is 1,3-Dimethyl-1H-pyrazole-4-carboxylic acid, molecular formula is C6H8N2O2, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
A solution of ethyl acetoacetate (40 mmol) and triethyl orthoformate (60 mmol) in acetic anhydride (0.12 mol) was refluxed for 8 hours. After completion of the reaction, the product was distilled under reduced pressure to give crude product (1).Then, the intermediate (1) (40 mmol) was added dropwise to a mixture of methylhydrazine (60 mmol) and ethanol (20 mL) and reacted at 60 C for 8 hours. After completion of the reaction, the residue was distilled under reduced pressure, (20 mL) was extracted with saturated brine, and the organic layer was partitioned with anhydrous sodium sulfate and evaporated to give 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylate (2) The pyrazole ester 2 was stirred at room temperature for 12 hours in a solution of sodium hydroxide in ethanol. After removing the solvent ethanol, the solid was dissolved in water, hydrochloric acid was added, and a white solid 3 was precipitated.A solution of 14 g (0.1 mol) of 1,3-dimethyl-1H-pyrazole-4-carboxylic acid (3) was charged into a 250 mL single-necked flask, 75 mL of SOCl2 was added slowly, heated under reflux for 4 h, and the reaction was complete by TLC. SOCl2 to give a pale yellow solid. 2.5 mmol of thiocyanate was dissolved in 15 ml of anhydrous acetonitrile, and then two drops of PEG-200 were added to the mixture, followed by stirring at room temperature for 5 min.Subsequently, 1 mmol of the acetonitrile solution of the compound 4 was added, and the mixture was stirred at room temperature for 40 minutes. The mixture was filtered to obtain an acetonitrile solution of pyrazolecarbonyl isothiocyanate and then substituted aniline (0.85 mmol) was added.After stirring at room temperature for 3-4 hours, the reaction mixture was evaporated in vacuo and the residue was subjected to silica gel column chromatography using petroleum ether and ethyl acetate as the solvent to give the product.
The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.
Reference:
Patent; Zhejiang University of Technology; Liu Xinghai; Wang Han; Zhai Zhiwen; Shen Zhonghua; Tan Chengxia; Weng Jianquan; Wu Hongke; Sun Nabo; (10 pag.)CN107033082; (2017); A;,
Pyrazole – Wikipedia,
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