阅读说明：本技术 一种球磨法氧化甲苯及其衍生物选择性制备苯甲酸及其衍生物的方法 (Method for selectively preparing benzoic acid and derivatives thereof by oxidizing toluene and derivatives thereof through ball milling method ) 是由 佘远斌 叶宏亮 沈海民 于 2019-08-19 设计创作，主要内容包括：一种球磨法氧化甲苯及其衍生物选择性制备苯甲酸及其衍生物的方法,将甲苯及其衍生物、钴(II)盐催化剂、氧化剂和分散剂置于玛瑙球磨罐中,密封球磨罐,室温下球磨,每隔1.0h停止球磨一次,放出球磨罐中气体；反应完毕,将所得反应混合物溶于无水乙醇,室温下搅拌30min,过滤,无水乙醇洗涤所得固体,并合并所得乙醇溶液,定容；以2-萘甲酸为内标,进行液相色谱分析,或柱层析分离所得反应混合物,计算甲苯及其衍生物的转化率,苯甲酸及其衍生物的选择性。本发明催化剂用量少,不使用溶剂,无需加热,反应温度低,操作方便,苯甲酸选择性高,未检测到明显的过氧化物残留,安全系数高,可以实现多种甲苯及其衍生物的选择性氧化。(A method for selectively preparing benzoic acid and derivatives thereof by oxidizing toluene and derivatives thereof by a ball milling method comprises the steps of placing toluene and derivatives thereof, a cobalt (II) salt catalyst, an oxidant and a dispersant in an agate ball milling tank, sealing the ball milling tank, carrying out ball milling at room temperature, stopping ball milling once every 1.0h, and discharging gas in the ball milling tank; after the reaction is finished, dissolving the obtained reaction mixture in absolute ethyl alcohol, stirring for 30min at room temperature, filtering, washing the obtained solid by the absolute ethyl alcohol, combining the obtained ethanol solution, and fixing the volume; and (3) performing liquid chromatography analysis or column chromatography separation on the obtained reaction mixture by taking 2-naphthoic acid as an internal standard, and calculating the conversion rate of the toluene and the derivatives thereof and the selectivity of the benzoic acid and the derivatives thereof. The method has the advantages of low catalyst consumption, no solvent, no need of heating, low reaction temperature, convenient operation, high benzoic acid selectivity, no obvious peroxide residue, high safety coefficient and capability of realizing the selective oxidation of various methylbenzenes and derivatives thereof.)

1. A method for selectively preparing benzoic acid and derivatives thereof by oxidizing toluene and derivatives thereof by a ball milling method is characterized by comprising the following steps: placing toluene and derivatives thereof, a cobalt (II) salt catalyst, an oxidant and a dispersant in an agate ball milling tank, sealing the ball milling tank, ball milling for 3.0-24.0 hours at the room temperature at the rotating speed of 100-800 rpm, stopping ball milling once every 1.0 hour, and discharging gas in the ball milling tank; after the reaction is finished, dissolving the obtained reaction mixture in absolute ethyl alcohol, stirring for 30min at room temperature, filtering, washing the obtained solid by the absolute ethyl alcohol, combining the obtained ethanol solution, and fixing the volume; and (3) performing liquid chromatography analysis or column chromatography separation on the obtained reaction mixture by taking 2-naphthoic acid as an internal standard, and calculating the conversion rate of the toluene and the derivatives thereof and the selectivity of the benzoic acid and the derivatives thereof.

2. The method for selectively preparing benzoic acid and derivatives thereof by ball milling toluene and derivatives thereof oxidation according to claim 1, wherein the reaction mode is ball milling.

3. The method for selectively preparing benzoic acid and derivatives thereof by ball milling oxidation of toluene and derivatives thereof as claimed in claim 1 or 2, wherein the structural formula of toluene and derivatives thereof is shown as formula (I), and the structural formula of the obtained benzoic acid and derivatives thereof is shown as formula (II).

In the formulae (I) and (II), R₁、R₂、R₃、R₄And R₅Each independently hydrogen, methyl, ethyl, propyl, butyl, isopropyl, tert-butyl, phenyl, 1-naphthyl, 2-naphthyl, methoxy, ethoxy, hydroxy, mercapto, amino, methylamino, ethylamino, dimethylamino, 1-hydroxyethyl, nitro, cyano, carboxy, benzyl, fluoro, chloro, bromo, or iodo.

4. The method for selectively preparing benzoic acid and derivatives thereof through ball milling toluene oxidation and derivatives thereof according to claim 1 or 2, wherein the catalyst cobalt (II) salt is anhydrous cobalt acetate and hydrates thereof, anhydrous cobalt sulfate and hydrates thereof, anhydrous cobalt chloride and hydrates thereof, anhydrous cobalt nitrate and hydrates thereof, anhydrous cobalt carbonate and hydrates thereof, anhydrous cobalt acetylacetonate and hydrates thereof, or any combination thereof, and the molar ratio of the cobalt (II) salt catalyst to toluene and derivatives thereof is 1: 2000-1: 400.

5. The method for selectively preparing benzoic acid and derivatives thereof through ball milling oxidation of toluene and derivatives thereof as claimed in claim 1 or 2, wherein the oxidant is t-butyl hydroperoxide, hydrogen peroxide, sodium chlorite or sodium hypochlorite, and the molar ratio of toluene and derivatives thereof to the oxidant is 1: 1-1: 30.

6. The method for selectively preparing benzoic acid and derivatives thereof through ball milling toluene oxide and derivatives thereof according to claim 1 or 2, wherein the dispersant is silica gel, neutral aluminum oxide, anhydrous sodium sulfate or anhydrous magnesium sulfate or any combination thereof, and the mass ratio of toluene and derivatives thereof to the dispersant is 1: 0.01-1: 10.

7. The method for selectively preparing the benzoic acid and the derivatives thereof through oxidizing the toluene and the derivatives thereof through the ball milling method according to claim 1 or 2, wherein the ball milling time is 3.0-24.0 h.

8. The method for selectively preparing benzoic acid and derivatives thereof through ball milling oxidation of toluene and derivatives thereof as claimed in claim 1 or 2, wherein the ball milling rotation speed is 100-800 rpm.

9. The method for selectively preparing benzoic acid and derivatives thereof through ball milling toluene oxidation and derivatives thereof as claimed in claim 1 or 2, wherein the air-bleeding time interval is 1.0-3.0 h.

Technical Field

The invention relates to a novel method for preparing benzoic acid and derivatives thereof by selective oxidation of toluene and derivatives thereof, belonging to the field of organic chemical industry and fine organic synthesis.

Background

Benzoic acid and derivatives thereof are important fine chemical intermediates and widely applied to synthesis of fine chemical products such as medicines, pesticides, dyes, spices and the like (WO 2019028362; CN 108774228; CN 108774218; Bioorganic and Medicinal Chemistry Letters 2019, 29: 115-12910; Journal of Agricultural and food Chemistry 2018, 66: 12898-12910). At present, the synthesis of benzoic acid and derivatives thereof is mainly realized by taking toluene, benzyl alcohol, benzaldehyde and derivatives thereof as raw materials through oxidation reaction (CN 107805194; CN 108467342; ACSCatalysis 2017, 7: 2786-. Wherein, the method takes toluene and derivatives thereof as raw materials and oxygen as an oxidant, and is a reaction route commonly adopted in industry. However, because aromatic hydrocarbon benzyl primary C-H bond has higher bond energy, the oxidation of toluene and its derivatives usually needs higher reaction temperature, the energy consumption is large, and the reaction is not easy to control; meanwhile, toxic and harmful organic solvents such as acetonitrile or corrosive auxiliaries such as acetic acid or nitric acid are used in the reaction process, so that the environmental compatibility of the existing industrial synthetic route of the benzoic acid and the derivatives thereof is poor, and the actual requirement of the existing 'green chemical process' is not met. Therefore, the development of a new method for oxidizing toluene and its derivatives to realize the selective synthesis of benzoic acid and its derivatives in a simple reaction manner under mild conditions is an urgent need for the oxidation conversion of toluene and its derivatives in the industry at present.

The solid phase ball milling reaction is characterized in that the interaction between interface materials is promoted by the actions of shearing, rubbing, impacting, extruding and the like between two interfaces which move relatively, so as to realize chemical reaction (Green Chemistry 2018, 20: 1435-. The solid-phase ball-milling reaction does not need a solvent, the reaction can be carried out at room temperature, the use of toxic and harmful organic solvents is effectively avoided, the materials do not need to be subjected to heat treatment, the energy consumption is low, and the safety coefficient is high. Meanwhile, due to the solid phase ball milling process, mechanical force is directly applied to the reaction mass, often resulting in a product distribution different from that of the liquid phase reaction. Under the urgent social requirements of development environment, society and human body compatibility chemical process, the solid phase ball milling is used for the catalytic oxidation of toluene and the derivatives thereof, so that the catalytic oxidation of toluene and the derivatives thereof can be realized at room temperature, the use of toxic and harmful organic solvents can be reduced, the distribution of oxidation products can be even changed, and the practical requirements of society and production are met.

According to the invention, catalytic oxidation of toluene and the derivatives thereof is carried out by using cobalt (II) salt as a catalyst and t-butyl hydroperoxide, hydrogen peroxide, sodium chlorite or sodium hypochlorite with good environmental compatibility as an oxidant through a solid-phase ball milling method, so that the toluene and the derivatives thereof are simply oxidized and converted under mild conditions, the use of toxic and harmful organic solvents is effectively avoided, the selectivity of benzoic acid and the derivatives thereof is remarkably improved, the social requirements of the current green chemical process, environmental compatibility chemical process and biological compatibility chemical process are met, and the method has important application value and theoretical research significance.

Disclosure of Invention

The invention aims to provide a novel method for preparing benzoic acid and derivatives thereof by selective oxidation of toluene and derivatives thereof.

In order to achieve the purpose, the invention adopts the following technical scheme:

a method for selectively preparing benzoic acid and derivatives thereof by oxidizing toluene and derivatives thereof by a ball milling method comprises the following steps:

placing toluene and derivatives thereof, a cobalt (II) salt catalyst, an oxidant (t-butyl hydroperoxide, hydrogen peroxide, sodium chlorite or sodium hypochlorite) (preferably t-butyl hydroperoxide and hydrogen peroxide) and a dispersant (silica gel, neutral aluminum oxide, anhydrous sodium sulfate or anhydrous magnesium sulfate) (preferably anhydrous sodium sulfate and anhydrous magnesium sulfate) in an agate ball milling tank, sealing the ball milling tank, ball milling for 3.0-24.0 h (preferably 8.0-16.0 h) at the rotating speed of 100-800 rpm (preferably 500-800 rpm) at room temperature, stopping ball milling once every 1.0h, and discharging gas in the ball milling tank; after the reaction is finished, dissolving the obtained reaction mixture in absolute ethyl alcohol, stirring for 30min at room temperature, filtering, washing the obtained solid by the absolute ethyl alcohol, combining the obtained ethanol solution, and fixing the volume; and (3) performing liquid chromatography analysis or column chromatography separation on the obtained reaction mixture by taking 2-naphthoic acid as an internal standard, and calculating the conversion rate of the toluene and the derivatives thereof and the selectivity of the benzoic acid and the derivatives thereof.

Further, the reaction mode is ball milling.

And further, the structural formulas of the toluene and the derivatives thereof are shown as a formula (I), and the structural formulas of the obtained benzoic acid products and the derivatives thereof are shown as a formula (II) respectively.

In the formulae (I) and (II), R₁、R₂、R₃、R₄And R₅Each independently hydrogen, methyl, ethyl, propyl, butyl, isopropyl, tert-butyl, phenyl, 1-naphthyl, 2-naphthyl, methoxy, ethoxy, hydroxy, mercapto, amino, methylamino, ethylamino, dimethylamino, 1-hydroxyethyl, nitro, cyano, carboxy, benzyl, fluoro, chloro, bromo, or iodo.

The catalyst cobalt (II) salt is anhydrous cobalt acetate and hydrate thereof, anhydrous cobalt sulfate and hydrate thereof, anhydrous cobalt chloride and hydrate thereof, anhydrous cobalt nitrate and hydrate thereof, anhydrous cobalt carbonate and hydrate thereof, anhydrous cobalt acetylacetonate and hydrate thereof or any combination thereof, and the molar ratio of the cobalt (II) salt catalyst to toluene and derivatives thereof is 1: 2000-1: 400, preferably 1: 1000-1: 500.

The reaction mode is ball milling; the oxidant is t-butyl hydroperoxide, hydrogen peroxide, sodium chlorite or sodium hypochlorite, and the t-butyl hydroperoxide and the hydrogen peroxide are preferred; the molar ratio of the toluene and the toluene derivatives to the oxidant is 1: 1-1: 30, preferably 1: 2-1: 5; the dispersing agent is silica gel, neutral aluminum oxide, anhydrous sodium sulfate or anhydrous magnesium sulfate or any combination thereof, and preferably, the anhydrous sodium sulfate; the mass ratio of the toluene and the derivatives thereof to the dispersant is 1: 0.01-1: 10, preferably 1: 3-1: 5; the ball milling time is 3.0-24.0 h, preferably 8.0-16.0 h; the ball milling rotating speed is 100-800 rpm, preferably 500-800 rpm; the air bleeding time interval is 1.0-3.0 h, and preferably 1.0 h.

The invention has the following beneficial effects: according to the method for preparing the benzoic acid and the derivatives thereof through selective oxidation of the toluene and the derivatives thereof, the oxidation conversion of the toluene and the derivatives thereof is realized through solid-phase ball milling, the reaction mode is novel, and the operation is convenient; the reaction is carried out at room temperature, heating is not needed, and the energy consumption is low; organic solvent and other auxiliary agents are not needed, so that the use of toxic and harmful organic reagents is effectively avoided, and the environment is protected; the peroxide content is low, and the safety coefficient is high; the benzoic acid and the derivatives thereof have high selectivity, and meet the social requirements of the current green chemical process, the environmental compatibility chemical process and the biological compatibility chemical process. The invention is a high-efficiency, green, environment-friendly, safe and feasible method for oxidizing the toluene and the derivatives thereof.

Detailed Description

The invention will be further illustrated with reference to specific examples, without limiting the scope of the invention thereto. All reagents used were commercially available analytical grade.