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CN-121974790-A - Preparation method of 4,4' -disubstituted diphenyl ketone compound

CN121974790ACN 121974790 ACN121974790 ACN 121974790ACN-121974790-A

Abstract

A preparation method of 4,4' -disubstituted diphenyl ketone compounds comprises the following steps: sequentially adding a 4-bromoaromatic compound shown in a formula I, tert-butyl isonitrile, a catalyst and a reducing agent into an organic solvent in an inert gas atmosphere, stirring and reacting at 30-120 ℃ for 6-18 hours (preferably stirring and reacting at 90 ℃ for 12 hours), and performing aftertreatment on the obtained reaction liquid to obtain 4,4' -dimethoxy benzophenone shown in a formula II; the method takes stable nickel salt as a catalyst precursor, tertiary butyl isonitrile as a carbonyl source donor, bromoaromatic hydrocarbon as an electrophile, and has the advantages of low cost and easy acquisition of reagents and simple operation steps.

Inventors

  • ZHOU BINGWEI
  • LI KANGXUN
  • HU YUANYUAN
  • JIN HONGWEI

Assignees

  • 浙江工业大学

Dates

Publication Date
20260505
Application Date
20260123

Claims (6)

  1. 1. A preparation method of 4,4' -disubstituted diphenyl ketone compounds comprises the following steps: in an inert gas atmosphere, sequentially adding a 4-bromoaromatic compound shown in a formula I, a tert-butyl isonitrile, a catalyst and a reducing agent into an organic solvent, stirring and reacting for 6-18 hours at 30-120 ℃, and performing post-treatment on the obtained reaction liquid to obtain the 4,4' -dimethoxy benzophenone shown in a formula II. The ratio of the amounts of the substances of the 4-bromoaromatic compound shown in the formula I, the tertiary butyl isonitrile, the catalyst and the reducing agent is 3-1:1:0.1:2-6, and R is one of hydrogen, methyl and methoxy.
  2. 2. The method according to claim 1, wherein the organic solvent is one or more solvents selected from toluene, xylene, tetrahydrofuran, acetonitrile, and the like.
  3. 3. The method of claim 1, wherein the catalyst is NiBr 2 .
  4. 4. The method of claim 1, wherein the reducing agent is one or a mixture of zinc powder and manganese powder.
  5. 5. The method according to claim 1, wherein the organic solvent is added in an amount of 0.4 mmol/mL based on the amount of the substance of the 4-bromoaromatic compound represented by formula I, and the organic solvent is tetrahydrofuran.
  6. 6. The method according to claim 1, wherein the specific steps of the post-treatment include cooling the reaction liquid to room temperature, adding 100-300 mesh silica gel into the reaction liquid, removing the solvent by a rotary evaporator, then performing column chromatography separation, eluting by using a mixed solvent of petroleum ether and ethyl acetate with a volume ratio of 15:1 as an eluent, collecting the eluent containing the 4,4' -dimethoxy benzophenone as shown in the target product formula II, and removing the eluent by rotary evaporation to obtain the target product.

Description

Preparation method of 4,4' -disubstituted diphenyl ketone compound Technical Field The invention belongs to the field of organic raw material synthesis, in particular to a preparation method of 4,4' -disubstituted benzophenone compounds, Background Aromatic ketone compounds are important organic chemical raw materials, and the skeleton structure of the aromatic ketone compounds is commonly existing in molecules such as various natural products, medicines, resins and the like. In addition, aromatic ketones are also used as basic raw materials for the synthesis of functional molecules and fine chemicals such as photosensitizers, paints, dyes, medicines, pesticides, cosmetics, fragrances, and the like. Therefore, the development of the aryl ketone synthesis method which is economical, practical and convenient in process has important research significance and potential application value. To date, there are many documents reporting the synthesis of aromatic ketones. Among them, the most classical method is through nucleophilic addition/oxidation reaction of aryl grignard reagent with aromatic aldehyde, thereby obtaining aryl ketone product. However, the use of grignard reagents limits the functional group compatibility of the substrate to a large extent. It is worth mentioning that the coupling reaction catalyzed by transition metal enriches the synthetic method of aromatic ketone. The aromatic ketone product is obtained by designing a tandem coupling reaction by selecting a proper aryl electrophile or nucleophile and a carbonyl source donor. For example, the pyronine group of university of Beijing reported an example of the oxidative coupling of arylboronic acids with carbon monoxide by palladium-copper co-catalysis to give symmetrical diaryl ketone derivatives (chem Asian J.2014, 9, 2411-2414). To avoid the use of carbon monoxide, chemists have developed different carbonyl source donors in succession. Compared with the coupling reaction （Eur. J. Org. Chem. 2016, 2016, 4554-4560;Org. Lett. 2017, 19, 3954-3957; Org. Chem. Front. 2017, 4, 569-572;Org. Pro. Res. Dev. 2020, 24, 2665-2675; Chem. Eur. J. 2023, 29, e202301381; J. Org. Chem. 2025, 90, 52-58.）. of aryl boric acid under the catalysis of transition metal, the method for synthesizing aryl ketone through serial reduction coupling reaction is relatively less reported. In 2016, the Iranpoor group reported an example of reductive coupling of iodo aromatic hydrocarbons to chromium carbonyl, and the same diaryl ketone product was obtained (CHEMISTRYSELECT 2016, 1, 4300-4304.). However, it should be noted that the reaction uses a metal chromium carbonyl reagent as a carbonyl source and an iodo arene as an electrophile, which greatly increases the cost of the reaction. Disclosure of Invention The preparation method of the 4,4 '-disubstituted benzophenone compound comprises the following steps of sequentially adding a 4-bromoaromatic compound shown in a formula I, tert-butylisonitrile, a catalyst and a reducing agent into an organic solvent in an inert gas atmosphere, stirring and reacting for 6-18 hours at 30-120 ℃ and preferably stirring and reacting for 12 hours at 90 ℃, and performing post-treatment on the obtained reaction liquid to obtain the 4,4' -dimethoxybenzophenone shown in a formula II. The ratio of the amounts of the 4-bromoaromatic compound shown in the formula I, the tert-butyl isonitrile, the catalyst and the reducing agent is 3-1:1:0.1:2-6, and is preferably 2:1:0.1:3. And R is one of hydrogen, methyl and methoxy. Preferably, the organic solvent is one solvent or a mixed solvent of more than one solvents such as toluene, xylene, tetrahydrofuran, acetonitrile, etc., preferably tetrahydrofuran. Preferably, the catalyst is a nickel metal catalyst, preferably NiBr 2; Preferably, the reducing agent is one or two of zinc powder (Zn powder) and manganese powder, preferably Zn powder, and preferably, the organic solvent is added in an amount of 0.4 mmol/mL based on the amount of the substance of the 4-bromoaromatic compound shown in the formula I, and preferably, the organic solvent is tetrahydrofuran. More specifically, the post-treatment comprises the steps of cooling reaction liquid to room temperature after the reaction is finished, adding 100-300 mesh silica gel into the reaction liquid, removing solvent by a rotary evaporator, then performing column chromatography separation, eluting by using a mixed solvent of petroleum ether and ethyl acetate with the volume ratio of 15:1 as an eluent, collecting an eluent containing 4,4' -dimethoxy benzophenone shown in a target product formula II, and removing the eluent by rotary evaporation to obtain the target product. The method has the beneficial effects that stable nickel salt is used as a catalyst precursor, tert-butyl isonitrile is used as a carbonyl source donor, bromoarene is used as an electrophile, and the method has the advantages of low cost and easy acquisition of reagents and simple operation ste