Method for preparing high-purity (3,4-diaminophenyl)(4-fluorophenyl) ketone by virtue of catalytic hydrogenation

Abstract

The invention relates to a method for preparing high-purity (3,4-diaminophenyl)(4-fluorophenyl) ketone by virtue of catalytic hydrogenation, belonging to the technical field of pharmaceutical and chemical engineering. The method comprises the following steps: adding (4-amino-3-nitrophenyl)(4-fluorophenyl) ketone (I) and a catalyst into an organic solvent, introducing hydrogen, and performing hydrogenation reduction reaction to obtain a flubendazole intermediate namely (3,4-diaminophenyl)(4-fluorophenyl) ketone (II). The method disclosed by the invention has the advantages that compared with a reduction method using sodium hydrosulfide, the method is simple in process, small in solvent dosage and short in reaction time, can be used for solving the problem that a large amount of sulfide-containing wastewater is difficult to be treated, and is beneficial for industrial production; meanwhile, a novel catalyst preparation method is simple, and has the characteristics of high reaction activity, good selectivity and recycled catalyst; compared with a pure Pt / C catalyst, the novel catalyst can be used for effectively inhibiting the phenomenon that carbanyl groups are reduced into methylene and inhibiting the occurrence of the defluorination phenomenon, and is relatively high in product yield and purity.

Description

technical field [0001] The invention relates to a flubendazole intermediate, in particular to a method for preparing a flubendazole intermediate (3,4-diaminophenyl)(4-fluorophenyl) ketone by catalytic hydrogenation, which belongs to medicine and chemical technology field. Background technique [0002] (3,4-Diaminophenyl)(4-fluorophenyl)ketone is a key intermediate in the production of commonly used anthelmintic drug flubendazole, mainly composed of (4-amino-3-nitrophenyl)(4-fluorophenyl) Phenyl) ketone reduction preparation. The reduction methods reported in the literature include iron powder, stannous chloride, alkali sulfide reduction method, silicon carbide catalysis, Pt / C catalytic hydrogenation method, and Raney Ni catalytic hydrogenation method. Mainly adopt sodium hydrosulfide reduction method in industry at present, and general chemical reduction method pollutes seriously, produces a large amount of sulfide-containing waste waters and is difficult to handle, and pr...

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Problems solved by technology

Mainly adopt sodium hydrosulfide reduction method in industry at present, and general chemical reduction method pollutes seriously, produces a large amount of sulfide-containing waste waters and is difficult to handle, and product quality is poor; 1997 Victor, Frantz etc. (Journal of Medicinal Chemistry, vol.40; nb. 24) Reported the preparation of (3,4-diaminophenyl) (4-fluorophenyl) ketone by nickel-catalyzed hydrogenation in tetrahydrofuran for 12 hours. When active nickel was used as catalyst, the amount of by-products in the reaction was large, and the product yield Low, while active nickel is very easy to catch fire in the air, there is a huge potential safety hazard in production; the catalytic hydrogenation method reported by US5693661 has a relatively high operating pressure, and carbonyl is easily reduced to methylene to generate by-product 4-(4 -Fluorophenyl) phenyl-1,2-diamine and the by-product (3,4-diaminophenyl) phenyl ketone of hydrodefluorination not only reduce the reaction yield, but also reduce the purity of the product

Although adding a defluorination inhibitor can improve the selectivity of the reaction, the introduction of the defluorination inhibitor in the reaction system reduces the product quality and increases the production cost

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