Method for synthesizing 2, 6-disubstituted-4-aryl methylene-2, 5-cyclohexadiene-1-one by one-step method

Abstract

The invention relates to a method for synthesizing 2, 6-disubstituted-4-aryl methylene-2, 5-cyclohexadiene-1-one by a one-step method. The method only uses a catalyst pyrrolidine, pyrrolidine and aryl formaldehyde are condensed to obtain imine salt, the imine salt is used as an electrophilic reagent to attack electron-rich 2, 6-disubstituted phenol, and then 2, 6-disubstituted-4-aryl methylene-2, 5-cyclohexadiene-1-one is obtained. Mannich base is not generated, the elimination reaction treatment step is not needed, and the final product is obtained through one-step reaction. The used raw materials are cheap and easy to obtain, the synthesis operation steps are simple and mild, a large amount of wastewater and byproducts are avoided, good yield and high purity can be obtained, and the method is suitable for large-scale preparation and large-scale production.

Description

technical field [0001] The invention relates to a method for synthesizing 2,6-disubstituent-4-aryl methylene-2,5-cyclohexadien-1-one in one step, and belongs to the field of preparation of organic compounds. Background technique [0002] 2,6-disubstituent-4-arylmethylene-2,5-cyclohexadien-1-one belongs to p-methylene quinone compounds (Formula 1), because of its unique skeleton structure and special The electrophilic activity and the ability to more easily undergo nucleophilic addition-aromatization reactions to construct a series of different structures and different types of compounds make this type of reaction substrate favored by scientific researchers, and has great potential in the field of organic synthesis. pivotal position. At the same time, 2,6-disubstituent-4-arylmethylene-2,5-cyclohexadien-1-one can also be used as an enzyme inhibitor of 5-lipoxygenase and cyclooxygenase, which can be applied It is used in the treatment of various diseases, and can also be used...

AI Technical Summary

Problems solved by technology

For example, U.S. patent document US4032547 discloses a new synthesis process method of p-methylene quinone compounds, which uses an aqueous solution of sodium hydroxide, sodium ferricyanide and 2,6-di-tert-butyl-4 -Ethylphenol is dissolved in the mixed solution of hexane, and the aqueous solution of sodium persulfate is added dropwise within 1.8 hours under stirring, the reaction temperature is controlled at 27-33 °C and the reaction is continued for 4 hours with stirring, liquid separation, drying, evaporation of the solvent and After recrystallization, 2,6-di-tert-butyl-4-vinyl-2,5-cyclohexadienyl ketone is obtained, and the highest yield can reach 92%; but the invention uses sodium hydroxide, sodium ferricyanide The aqueous solution is a catalyst, sodium persulfate is an oxidant, and 2,6-di-tert-butyl-4-ethylphenol is a catalytic oxidation method of a raw material. The raw materials used are not easy to obtain, the cost is high, and the amount of waste water is large; as another example, the Chinese patent Document CN105418395A discloses a preparation method of 2,6-di-tert-butyl-4-benzylidene-2,5-cyclohexadienyl-1-one, which uses hexahydropyridine as a condensation agent, 2 , 6-di-tert-butylphenol and benzaldehyde are refluxed in toluene solvent for more than 3 hours to separate water, the intermediate Mannich base is first formed in the reaction, then acetic anhydride is added to eliminate the reaction, add toluene, wash with water, wash with saturated saline, anhydrous Dry over sodium sulfate, filter, evaporate the solvent under reduced pressure, and recrystallize from a mixed solvent (ethyl acetate:n-hexane volume ratio=3:1) to obtain 2,6-di-tert-butyl-4-benzylidene-2, 5-cyclohexadienyl-1-one, yield: 79.1%; This invention is actually a two-step reaction in one pot, that is, the Mannich base is first generated, and the Mannich base does not separate the acetic anhydride that is directly added and added later. Elimination reaction occurs; therefore, more than stoichiometric hexahydropyridine and acetic anhydride will be consumed, and an equivalent amount of N-acetylhexahydropyridine by-product will be produced at the same time, the process is cumbersome and the cost is higher

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