阅读说明：本技术 甲苯类化合物选择性氧化的方法 (Method for selective oxidation of toluene compounds ) 是由 沈海民 齐备 佘远斌 于 2019-08-28 设计创作，主要内容包括：一种甲苯类化合物选择性氧化的方法,所述方法为：将式(I)所示甲苯类化合物、金属卟啉催化剂、氧化剂、分散剂置于球磨罐中,密封球磨罐,室温下,以100～800rpm的转速球磨3～24h,在球磨过程中,每隔1～3h停止球磨一次,放出球磨罐中气体,反应完毕,反应混合物经后处理,得到产物式(II)所示苯甲酸类化合物；本发明通过固相球磨实现甲苯及其衍生物的氧化转化,反应方式新颖,操作方便,能耗低；无需有机溶剂及其他助剂,有效避免了有毒有害有机试剂的使用,绿色环保；过氧化物含量低,安全系数高；苯甲酸及其衍生物的选择性高,符合目前绿色化工过程,环境兼容性化工过程,生物兼容性化工过程的社会需求。(A method for selective oxidation of toluene compounds, the method comprising: placing a toluene compound shown as a formula (I), a metalloporphyrin catalyst, an oxidant and a dispersing agent into a ball milling tank, sealing the ball milling tank, ball milling at the rotating speed of 100-800 rpm for 3-24 h at room temperature, stopping ball milling once every 1-3 h in the ball milling process, discharging gas in the ball milling tank, and after the reaction is finished, carrying out post-treatment on a reaction mixture to obtain a benzoic acid compound shown as a formula (II); according to the invention, the oxidation conversion of the toluene and the derivatives thereof is realized by solid-phase ball milling, the reaction mode is novel, the operation is convenient, 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.)

1. A method for selectively oxidizing a toluene compound is characterized by comprising the following steps:

Placing a toluene compound shown as a formula (I), a metalloporphyrin catalyst, an oxidant and a dispersing agent into a ball milling tank, sealing the ball milling tank, ball milling at the rotating speed of 100-800 rpm for 3-24 h at room temperature, stopping ball milling once every 1-3 h in the ball milling process, discharging gas in the ball milling tank, and after the reaction is finished, carrying out post-treatment on a reaction mixture to obtain a benzoic acid compound shown as a formula (II);

The mass ratio of the metalloporphyrin catalyst to the toluene compound shown in the formula (I) is 1: 200000 to 500;

The mass ratio of the toluene compound shown in the formula (I) to the oxidant is 1: 1-30;

The mass ratio of the toluene compound shown in the formula (I) to the dispersing agent is 1: 0.01 to 10;

The oxidant is t-butyl hydroperoxide, hydrogen peroxide, sodium chlorite or sodium hypochlorite;

The dispersing agent is one or more than two compounds in any proportion of silica gel, neutral aluminum oxide, anhydrous sodium sulfate or anhydrous magnesium sulfate;

The metalloporphyrin catalyst is at least one of compounds shown in a formula (III):

In the formula (III), the compound represented by the formula (III),

R_a、R_b、R_c、R_d、R_eEach independently hydrogen, methyl, ethyl, propyl, butyl, isopropyl, tert-butyl, phenyl, methoxy, ethoxy, hydroxy, mercapto, amino, methylamino, ethylamino, dimethylamino, 1-hydroxyethyl, nitro, cyano, carboxy, benzyl, fluoro, chloro, bromo, or iodo;

M is Co²⁺、Mn²⁺、Ni²⁺、Fe²⁺、Cu²⁺Or Zn²⁺；

The structural formula of the toluene compound is shown as the formula (I), and the structural formula of the corresponding obtained product benzoic acid compound is shown as the formula (II):

in the formula (I) or (II),

R₁、R₂、R₃、R₄、R₅Each independently is: 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.

2. The method for selective oxidation of toluene compounds as claimed in claim 1 wherein the ratio of the quantity of metalloporphyrin catalyst to the quantity of toluene compounds of formula (I) is 1: 20000 to 4000.

3. The method for selective oxidation of toluene-based compounds according to claim 1 wherein the mass ratio of toluene-based compounds of formula (I) to oxidant is 1: 2 to 5.

4. The method for selectively oxidizing the toluene compounds according to claim 1, wherein the mass ratio of the toluene compounds represented by the formula (I) to the dispersant is 1: 3 to 5.

5. The method for selective oxidation of toluenes according to claim 1, wherein the oxidant is t-butyl hydroperoxide or hydrogen peroxide.

6. The method for selective oxidation of toluenes according to claim 1, wherein the dispersant is anhydrous sodium sulfate or anhydrous magnesium sulfate.

7. The method for selective oxidation of toluene compounds according to claim 1, wherein the metalloporphyrin catalyst is 5,10,15, 20-tetrakis (4-chlorophenyl) porphyrin cobalt (II), 5,10,15, 20-tetrakis (2, 6-dichlorophenyl) porphyrin cobalt (II), 5,10,15, 20-tetrakis (2, 4-dichlorophenyl) porphyrin cobalt (II), or 5,10,15, 20-tetrakis (2,3,4,5, 6-pentafluorophenyl) porphyrin cobalt (II) iron.

Technical Field

The invention relates to a novel method for preparing benzoic acid compounds by selective oxidation of toluene compounds, and belongs 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 & Medicinal Chemistry Letters 2019, 29: 115-118; 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: 2786-2790; ACS Sustainable Chemistry & Engineering 2018, 6: 4916-4921; ChemCatchem 2018, 10: 1253-1257; Green Chemistry 2007, 9: 1238-1245). 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 to promote the interaction between the interface materials by the actions of shearing, rubbing, impacting, extruding and the like between two interfaces in relative motion, thereby realizing chemical reaction (Green Chemistry 2018, 20: 1435-1443; Angewandte Chemistry International Edition 2018, 57: 10718-10722). 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.

In the field of environmental and biocompatible catalysts, the model compound metalloporphyrin of cytochrome P450 is widely Applied to catalytic oxidation of hydrocarbons (ChemSusChem 2019, 12: 684-691; Applied Surface Science2017, 402: 436-443), and because metalloporphyrin has high catalytic activity, reaction substrates are 1/10⁶～1/10⁵The catalytic conversion can be completed by the amount of (mol/mol), and the pollution of the metal catalyst to oxidation products and downstream products can be effectively avoided. Therefore, the catalytic oxidation of the toluene and the derivatives thereof is carried out by using the metal porphyrin as the catalyst and the t-butyl hydroperoxide, the hydrogen peroxide, the sodium chlorite or the sodium hypochlorite with good environmental compatibility as the oxidant through the 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 the benzoic acid and the derivatives thereof is obviously improved, the social requirements of the current green chemical process, the environmental compatibility chemical process and the 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 a benzoic acid compound by selectively oxidizing a toluene compound.

the technical scheme of the invention is as follows:

A method for selective oxidation of toluene compounds, the method comprising:

Placing a toluene compound shown as a formula (I), a metalloporphyrin catalyst, an oxidant and a dispersing agent into a ball milling tank, sealing the ball milling tank, ball milling at the room temperature (20-30 ℃) for 3-24 h (preferably 8-16 h) at the rotation speed of 100-800 rpm (preferably 500-800 rpm), stopping ball milling once every 1-3 h (preferably 1h) in the ball milling process, discharging gas in the ball milling tank, and after the reaction is finished, performing post-treatment on a reaction mixture to obtain a benzoic acid compound shown as a product formula (II);

The material of ball-milling jar is agate, is furnished with the ball-milling pearl that the material is agate likewise, and ball-milling pearl diameter is 8.00mm usually, and the total mass of ball-milling pearl is about 3 with the total mass of reaction material ratio: 1;

The mass ratio of the metalloporphyrin catalyst to the toluene compound shown in the formula (I) is 1: 200000 to 500, preferably 1: 20000 to 4000;

the mass ratio of the toluene compound shown in the formula (I) to the oxidant is 1: 1-30, preferably 1: 2-5;

The mass ratio of the toluene compound shown in the formula (I) to the dispersing agent is 1: 0.01 to 10, preferably 1: 3-5;

The post-treatment method comprises the following steps: after the reaction is finished, dissolving the reaction mixture in absolute ethyl alcohol, stirring for 30min at room temperature, filtering, washing a filter cake with absolute ethyl alcohol, combining filtrate and washing liquid, recovering solvent ethyl alcohol through atmospheric distillation, recovering unreacted raw materials through reduced pressure distillation, and recrystallizing to obtain a benzoic acid oxidation product;

the method for analyzing the reaction result comprises the following steps: after the reaction is finished, dissolving the reaction mixture in absolute ethyl alcohol, stirring for 30min at room temperature, filtering, washing a filter cake with absolute ethyl alcohol, combining filtrate and washing liquid, sampling for analysis, performing liquid chromatography analysis by taking 2-naphthoic acid as an internal standard, and calculating the conversion rate of the toluene compound shown in the formula (I) as a raw material and the selectivity of the benzoic acid compound shown in the formula (II) as a product;

In the invention, the oxidant is t-butyl hydroperoxide, hydrogen peroxide, sodium chlorite or sodium hypochlorite, preferably t-butyl hydroperoxide or hydrogen peroxide;

The dispersing agent is one or more than two compounds in any proportion of silica gel, neutral aluminum oxide, anhydrous sodium sulfate or anhydrous magnesium sulfate, and preferably, the anhydrous sodium sulfate or the anhydrous magnesium sulfate;

the metalloporphyrin catalyst is at least one of compounds shown in a formula (III), preferably 5,10,15, 20-tetra (4-chlorphenyl) cobalt porphyrin (II), 5,10,15, 20-tetra (2, 6-dichlorophenyl) cobalt porphyrin (II), 5,10,15, 20-tetra (2, 4-dichlorophenyl) cobalt porphyrin (II) or 5,10,15, 20-tetra (2,3,4,5, 6-pentafluorophenyl) cobalt (II) iron;

in the formula (III), the compound represented by the formula (III),

R_a、R_b、R_c、R_d、R_eEach independently hydrogen, methyl, ethyl, propyl, butyl, isopropyl, tert-butyl, phenyl, methoxy, ethoxy, hydroxy, mercapto, amino, methylamino, ethylamino, dimethylamino, 1-hydroxyethyl, nitro, cyano, carboxy, benzyl, fluoro, chloro, bromo, or iodo;

M is Co²⁺、Mn²⁺、Ni²⁺、Fe²⁺、Cu²⁺Or Zn²⁺；

the structural formula of the toluene compound is shown as the formula (I), and the structural formula of the corresponding obtained product benzoic acid compound is shown as the formula (II):

In the formula (I) or (II),

R₁、R₂、R₃、R₄、R₅Each independently is: 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 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.

The metalloporphyrins used in the present invention are referred to Journal of the American Chemical Society 2017,139: 18590-18597; journal of the American Chemical Society 2018,140:6383-6390 synthesis.

All reagents used were commercially available analytical grade.

The 100mL agate ball-milling pot is provided with 50 agate ball-milling beads, each ball-milling bead has a diameter of 8.0mm and a mass of 0.9 g.