Method for catalyzing coupling reaction of aryl halide and carbon monoxide by using composite catalyst

Abstract

The invention discloses a method for catalyzing a coupling reaction of aryl halide and carbon monoxide by using a composite catalyst, which comprises the following steps: introducing CO into aryl halide as shown in a formula I and raw materials as shown in a formula II under the action of an acid-binding agent and the composite catalyst, and carrying out the coupling reaction to prepare a compound as shown in a formula III. According to the method disclosed by the invention, palladium and carbon with relatively high catalytic activity are adopted to form a composite catalyst, and a coupling reaction of aryl halide and carbon monoxide can be effectively catalyzed to generate benzoic acid, benzoate and benzamide compounds. The method has the advantages of high catalytic efficiency, reduction of the content of noble metal palladium, mild reaction conditions, high product purity, wide substrate applicability and low production cost, and is suitable for industrial production. # imgabs0 #

Description

Technical Field

[0001] The invention belongs to the field of organic chemistry, and in particular relates to a method for catalyzing a coupling reaction between an aryl halide and carbon monoxide by using a composite catalyst. Background Art

[0002] The coupling reaction of aryl halides with carbon monoxide is an important synthesis method that can be used to prepare various useful compounds, such as benzoic acid, benzoic acid esters, benzamide compounds, etc. This reaction usually requires the use of a catalyst to improve reaction efficiency, reduce reaction conditions, and reduce the generation of side reactions. The prior art mainly uses transition metal complexes as catalysts to achieve efficient catalysis of the reaction by regulating the structure and properties of the catalyst. For example, metal complexes such as palladium, nickel, and copper have been widely used in this reaction. However, these catalysts usually require a higher dosage, and palladium, as a heavy metal, will increase the cost if used in large amounts. And the applicability of existing catalysts to substrates is limited, and they can only be used for specific substrates, and cannot be applied to multiple substrates. The reaction conditions of existing catalytic reactions are relatively harsh, and the catalyst is difficult to separate and recover from the product, which further increases the production cost.

[0003] In view of the above problems, it is necessary to develop a catalyst and process method for the coupling reaction of halogenated compounds with carbon monoxide, which has low cost, mild reaction conditions and is suitable for industrial production. Summary of the invention

[0004] The present invention aims at the existing technical problems and provides a method for catalyzing the coupling reaction of aryl halides and carbon monoxide by using a composite catalyst. The method adopts a composite catalyst composed of multiple metal elements or non-metal elements with high catalytic activity and selectivity, and can effectively catalyze the coupling reaction of aryl halides and carbon monoxide to generate benzoic acid, benzoic acid esters, and benzamide compounds. The method has high catalytic efficiency, mild reaction conditions, high product purity, wide substrate applicability, low production cost, and is suitable for industrial production.

[0005] In order to achieve the purpose of the above invention, the technical solution adopted by the present invention is:

[0006] A method for catalyzing the coupling reaction of an aryl halide and carbon monoxide using a composite catalyst, the method being one of the following:

[0007] (I) The aryl halide represented by formula I and the raw material represented by formula II are subjected to coupling reaction by introduction of CO under the action of an acid binding agent and a composite catalyst to obtain a compound represented by formula III.

[0008] The reaction formula is as follows:

[0009]

[0010] In the formula I, R1 is a substituent on the benzene ring, which may not exist, that is, the benzene ring is not substituted, or R1 is a C1-C10 alkyl group, or Cl;

[0011] In the formula II, R2 is a C1-C5 alkoxy group or a C1-C5 alkylamine group;

[0012] Furthermore, when R2 is a C1-C5 alkoxy group, the obtained compound represented by formula III is a benzoate compound;

[0013] When R2 is a C1-C5 alkylamine group, the obtained compound represented by formula III is a benzamide compound;

[0014] (ii) introducing CO into the aryl halide represented by formula (I) and sodium hydroxide under the action of an acid binding agent and a composite catalyst to carry out a coupling reaction, and acidifying the obtained product to obtain a benzoic acid compound;

[0015] The acid binding agent is an inorganic base, preferably one or more of potassium carbonate, sodium carbonate, potassium phosphate and sodium phosphate.

[0016] The molar ratio of the acid binding agent to the aryl halide represented by formula I is (1-5):1.

[0017] The molar ratio of the aryl halide represented by formula I to carbon monoxide is 1:1-5.

[0018] The molar ratio of the aryl halide represented by formula I to the raw material represented by formula II is 1:1-5.

[0019] The reaction of the present invention may be carried out by adding an organic solvent, or using the raw material represented by formula II as a solvent.

[0020] When the raw material represented by formula II is also used as a solvent, the molar ratio of the aryl halide represented by formula I to the raw material represented by formula II is preferably 1:3-5.

[0021] When the raw material represented by formula II is not used as a solvent, the molar ratio of the aryl halide represented by formula I to the raw material represented by formula II is preferably 1:1-2.

[0022] The added organic solvent may be halogen-free aromatic hydrocarbons such as toluene and xylene.

[0023] In the method (ii), the molar ratio of the aryl halide represented by formula (I) to sodium hydroxide is 1:0.2-2.

[0024] The composite catalyst is a mixture of a palladium catalyst, a phosphine catalyst and a copper catalyst.

[0025] The palladium catalyst is palladium carbon, and the loading amount of Pd is 5-10%.

[0026] The phosphorus catalyst is one or more of triphenylphosphine, tri-n-butylphosphine, 1,1'-binaphthyl-2,2'-bisdiphenylphosphine, carboxymethyldiphenylphosphine, and tributyltetradecylphosphine chloride.

[0027] The copper catalyst is cuprous iodide or cuprous bromide, preferably cuprous iodide.

[0028] The mass ratio of the palladium catalyst, the phosphine catalyst and the copper catalyst in the composite catalyst is (0.5-1): (0.5-2): (0.5-1);

[0029] The mass ratio of the aryl halide represented by formula I to the composite catalyst is 1:0.003-0.2, preferably 1:0.004-0.01, and more preferably 1:0.004-0.008.

[0030] Furthermore, the coupling reaction temperature of the present invention is 120-190° C. and the pressure is 2-4 MPa.

[0031] The coupling reaction time is preferably 6-24 hours.

[0032] In the method (I), after the coupling reaction is completed, the reaction solution is post-treated to obtain the compound shown in formula III; the method for post-treatment of the reaction solution is preferably: after the reaction is completed, the reaction solution is cooled and depressurized, then filtered, and the obtained filtrate is washed, concentrated and the solvent is removed to obtain the compound shown in formula III;

[0033] In the method (ii), after the coupling reaction is completed, the reaction solution is post-treated and acidified to obtain a benzoic acid compound; the method for post-treatment and acidification of the reaction solution is preferably: after the reaction is completed, the reaction solution is cooled and depressurized, then filtered, the obtained filtrate is phase-separated, and the aqueous phase is acidified to obtain a benzoic acid compound.

[0034] The filter cake obtained by filtration is palladium carbon and can be recycled.

[0035] Beneficial effects of the present invention:

[0036] 1. A composite catalyst is used, wherein the palladium catalyst is palladium carbon, and the loading rate is only 5-10%. Compared with the palladium dosage of the conventional palladium catalyst, the palladium dosage is reduced by more than 5 times, but combined with the composite catalyst, the same catalytic effect as the non-loaded palladium catalyst of the same weight can be achieved. The composite catalyst of the present invention has high catalytic activity and selectivity, and can effectively catalyze the coupling reaction of aryl halides and carbon monoxide to generate benzoic acid, benzoic acid esters, and benzamide compounds. The use of this composite catalyst can significantly reduce the dosage of the catalyst, thereby reducing production costs and reducing the risk of pollution to the environment.

[0037] 2. Optimize the ratio of catalysts: By adjusting the ratio of each component in the composite catalyst, its catalytic performance can be changed to adapt it to different substrates, thereby expanding its application range and meeting different production needs.

[0038] 3. Optimize reaction conditions: By optimizing reaction temperature, pressure, time and other parameters, the catalytic efficiency of the catalyst can be improved, and the harshness of the reaction conditions can also be reduced, making the reaction process milder and more suitable for actual production applications.

[0039] 4. Improved catalyst recovery and reuse methods: The catalyst of the present invention can be recovered and reused, which can further reduce production costs and reduce pressure on the environment. It can also increase the service life of the catalyst and improve production efficiency.

[0040] The method of the invention has high catalytic efficiency, mild reaction conditions, high product purity, wide substrate applicability, low production cost and is suitable for industrial production. DETAILED DESCRIPTION

[0041] The present invention is further described below in conjunction with specific embodiments. Those of ordinary skill in the art will be able to implement the present invention based on these descriptions. In addition, the embodiments of the present invention involved in the following description are generally only embodiments of a part of the present invention, rather than all embodiments. Therefore, based on the embodiments in the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative work should fall within the scope of protection of the present invention.

[0042] Example 1

[0043] Preparation of methyl benzoate: 156 g of bromobenzene, 100 g of methanol, 212 g of potassium phosphate, and 1 g of a composite catalyst (palladium on carbon (Pd loading 10%): triphenylphosphine: cuprous iodide = 1:2:1 mass ratio) are added to a high-pressure reactor, and 56 g of carbon monoxide is charged. The temperature in the reactor is raised to 150-160°C, and the pressure is raised to 2-3 MPa, and the reaction is maintained under this condition for 12 hours. After the reaction is completed, the temperature in the reactor is lowered to room temperature, the pressure is lowered to normal pressure, the reaction product is taken out and filtered, the composite catalyst is removed, and then the filtrate is concentrated and the solvent is distilled to obtain methyl benzoate with a yield of 91%.

[0044] In this embodiment, the amount of palladium carbon used is 0.25 g, of which the loaded Pd is 0.025 g, that is, the amount of Pd used is 0.016% of the mass of the substrate bromobenzene.

[0045] Example 2

[0046] Preparation of methyl benzoate: 156 g of bromobenzene, 100 g of methanol, 212 g of potassium phosphate, and 1 g of composite catalyst (palladium chloride: triphenylphosphine: cuprous iodide = 1:2:1 mass ratio) are added to a high-pressure reactor, and 56 g of carbon monoxide is charged. The temperature in the reactor is raised to 150-160°C, and the pressure is raised to 2-3 MPa, and the reaction is maintained under this condition for 12 hours. After the reaction is completed, the temperature in the reactor is lowered to room temperature, the pressure is lowered to normal pressure, the reaction product is taken out and filtered, the composite catalyst is removed, and then the filtrate is concentrated and the solvent is distilled to obtain methyl benzoate with a yield of 90%.

[0047] In this embodiment, the dosage of palladium chloride is 0.25 g, of which the Pd element is 0.15 g, that is, the dosage of the Pd element is 0.096% of the mass of the substrate bromobenzene, which is 6 times that of Embodiment 1.

[0048] Therefore, compared with Example 2, Example 1 significantly reduces the amount of precious metal palladium used.

[0049] Comparative Example 1

[0050] Preparation of methyl benzoate: 156 g of bromobenzene, 100 g of methanol, 212 g of potassium phosphate, and 0.25 g of palladium carbon (Pd loading 10%) are added to a high-pressure reactor, and 56 g of carbon monoxide is charged. The temperature in the reactor is raised to 150-160°C, and the pressure is raised to 2-3 MPa, and the reaction is maintained under this condition for 12 hours. After the reaction is completed, the temperature in the reactor is lowered to room temperature, the pressure is lowered to normal pressure, the reaction product is taken out and filtered, the composite catalyst is removed, and then the filtrate is concentrated and the solvent is distilled to obtain methyl benzoate, with a yield of 40%.

[0051] Comparative Example 2

[0052] Preparation of methyl benzoate: 156 g of bromobenzene and 100 g of methanol, 212 g of potassium phosphate, 0.25 g of palladium carbon (Pd loading 10%), and 0.5 g of triphenylphosphine are added to an autoclave, and 56 g of carbon monoxide is charged. The temperature in the reactor is raised to 150-160°C, and the pressure is raised to 2-3 MPa, and the reaction is maintained under this condition for 12 hours. After the reaction is completed, the temperature in the reactor is lowered to room temperature, the pressure is lowered to normal pressure, the reaction product is taken out and filtered, the composite catalyst is removed, and then the filtrate is concentrated with solvent, and redistilled to obtain methyl benzoate, with a yield of 30%.

[0053] Comparative Example 3

[0054] Preparation of methyl benzoate: 156 g of bromobenzene and 100 g of methanol, 212 g of potassium phosphate, 0.25 g of palladium carbon (Pd loading 10%), and 0.25 g of cuprous iodide are added to an autoclave, and 56 g of carbon monoxide is charged. The temperature in the reactor is raised to 150-160° C., and the pressure is raised to 2-3 MPa, and the reaction is maintained under this condition for 12 hours. After the reaction is completed, the temperature in the reactor is lowered to room temperature, the pressure is lowered to normal pressure, the reaction product is taken out and filtered, the composite catalyst is removed, and then the filtrate is concentrated with solvent, and redistilled to obtain methyl benzoate, with a yield of 42%.

[0055] The results of Comparative Examples 1 to 3 show that the composite catalyst significantly improves the catalytic effect. The yields of the catalytic reactions of single palladium carbon or palladium carbon and triphenylphosphine or palladium carbon and cuprous iodide are very low.

[0056] Comparative Example 4

[0057] Preparation of methyl benzoate: 156 g of bromobenzene, 100 g of methanol, 212 g of potassium phosphate, and 0.17 g of a composite catalyst (palladium chloride: triphenylphosphine: cuprous iodide = 1:2:1 mass ratio) are added to a high-pressure reactor, and 56 g of carbon monoxide is charged. The temperature in the reactor is raised to 150-160°C, and the pressure is raised to 2-3 MPa, and the reaction is maintained under this condition for 12 hours. After the reaction is completed, the temperature in the reactor is lowered to room temperature, the pressure is lowered to normal pressure, the reaction product is taken out and filtered, the composite catalyst is removed, and then the filtrate is concentrated and the solvent is distilled to obtain methyl benzoate with a yield of 83%.

[0058] In this embodiment, the amount of palladium chloride used is 0.0425 g, wherein the Pd element is 0.025 g, which is equivalent to the content of the Pd element in Example 1, but when palladium chloride is used as a catalyst, the reaction yield is significantly reduced. It can be seen that under the same low content of palladium element, the use of palladium-carbon catalyst significantly improves the catalytic effect.

[0059] Example 3

[0060] Preparation of benzamide: 156 g of bromobenzene, 30 g of ammonia, 100 g of toluene, 212 g of potassium phosphate, and 1 g of composite catalyst (mass ratio of palladium chloride: triphenylphosphine: cuprous iodide = 1:2:1) are added to a high-pressure reactor, and 56 g of carbon monoxide is charged. The temperature in the reactor is raised to 150-160°C, and the pressure is raised to 2-3 MPa, and the reaction is maintained under this condition for 12 hours. After the reaction is completed, the temperature in the reactor is lowered to room temperature, the pressure is lowered to normal pressure, the reaction product is taken out and filtered, the composite catalyst is removed, and then the filtrate is phase-separated, alkali-washed, and the solvent is concentrated to obtain benzamide with a yield of 90%.

[0061] Example 4

[0062] Preparation of benzoic acid: 156 g of bromobenzene, 30 g of 30% sodium hydroxide, 100 g of toluene, 212 g of potassium phosphate, and 1 g of a composite catalyst (palladium on carbon (Pd loading 10%): triphenylphosphine: cuprous iodide mass ratio = 1:2:1) are added to a high-pressure reactor, and 56 g of carbon monoxide is charged. The temperature in the reactor is raised to 150-160°C, and the pressure is raised to 2-3 MPa, and the reaction is maintained under this condition for 12 hours. After the reaction is completed, the temperature in the reactor is lowered to room temperature, the pressure is lowered to normal pressure, the reaction product is taken out and filtered, the composite catalyst is removed, and then the filtrate is phase-separated, and the aqueous phase is acidified to obtain benzoic acid with a yield of 94%.

[0063] Example 5

[0064] Preparation of methyl m-chlorobenzoate: 190 g m-chlorobromobenzene, 100 g methanol, 212 g potassium phosphate, and 1 g composite catalyst (palladium carbon (Pd loading 10%): triphenylphosphine: cuprous iodide mass ratio = 1:2:1) are added to a high-pressure reactor, and 56 g carbon monoxide is charged. The temperature in the reactor is raised to 150-160°C, and the pressure is raised to 2-3 MPa, and the reaction is maintained under this condition for 12 hours. After the reaction is completed, the temperature in the reactor is lowered to room temperature, the pressure is lowered to normal pressure, the reaction product is taken out and filtered, the composite catalyst is removed, and then the filtrate is concentrated and the solvent is distilled to obtain methyl m-chlorobenzoate with a yield of 93%.

[0065] Example 6

[0066] Preparation of o-methylbenzamide: 170 g of o-bromotoluene, 30 g of ammonia, 100 g of toluene, 212 g of potassium phosphate, and 1 g of a composite catalyst (palladium on carbon (Pd loading 10%): tri-n-butylphosphine: cuprous iodide mass ratio = 1:2:1) are added to a high-pressure reactor, and 56 g of carbon monoxide is charged. The temperature in the reactor is raised to 150-160°C, the pressure is raised to 2-3MPa, and the reaction is maintained under this condition for 12 hours. After the reaction is completed, the temperature in the reactor is lowered to room temperature, the pressure is lowered to normal pressure, the reaction product is taken out and filtered, the composite catalyst is removed, and then the filtrate is phase-separated, alkali-washed, and the solvent is concentrated to obtain o-methylbenzamide with a yield of 88%.

[0067] Example 7

[0068] Preparation of 3-chloro-N-methylbenzamide: 190 g of m-chlorobromobenzene, 40 g of methylamine, 100 g of toluene, 138 g of potassium carbonate, and 1 g of composite catalyst (mass ratio of palladium carbon: tri-n-butylphosphine: cuprous bromide = 1:2:1) are added to a high-pressure reactor, and 56 g of carbon monoxide is charged. The temperature in the reactor is raised to 150-160°C, the pressure is raised to 2-3MPa, and the reaction is maintained under this condition for 12 hours. After the reaction is completed, the temperature in the reactor is lowered to room temperature, the pressure is lowered to normal pressure, the reaction product is taken out and filtered, the composite catalyst is removed, and then the filtrate is phase-separated, alkali-washed, and the solvent is concentrated to obtain 3-chloro-N-methylbenzamide with a yield of 89%.

[0069] Example 8

[0070] Preparation of methyl p-chlorobenzoate: 190 g of p-chlorobromobenzene, 100 g of methanol, 212 g of potassium phosphate, and 1 g of a composite catalyst (mass ratio of palladium carbon: tri-n-butylphosphine: cuprous bromide = 1:2:1) are added to a high-pressure reactor, and 56 g of carbon monoxide is charged. The temperature in the reactor is raised to 150-160°C, and the pressure is raised to 2-3 MPa, and the reaction is maintained under this condition for 12 hours. After the reaction is completed, the temperature in the reactor is lowered to room temperature, the pressure is lowered to normal pressure, the reaction product is taken out and filtered, the composite catalyst is removed, and then the filtrate is concentrated and the solvent is distilled to obtain methyl p-chlorobenzoate with a yield of 95%.

[0071] Example 9

[0072] Preparation of methyl o-toluene: 170 g of o-bromotoluene, 100 g of methanol, 212 g of potassium phosphate, and 1 g of a composite catalyst (mass ratio of palladium carbon: 1,1'-binaphthyl-2,2'-bisdiphenylphosphine: cuprous bromide = 1:2:1) are added to a high-pressure reactor, and 56 g of carbon monoxide is charged. The temperature in the reactor is raised to 150-160°C, and the pressure is raised to 2-3 MPa, and the reaction is maintained under this condition for 12 hours. After the reaction is completed, the temperature in the reactor is lowered to room temperature, the pressure is lowered to normal pressure, the reaction product is taken out and filtered, the composite catalyst is removed, and then the filtrate is concentrated and the solvent is distilled to obtain methyl o-toluene, with a yield of 93%.

[0073] Example 10

[0074] Preparation of 3,4-dichlorobenzamide: 224 g of 3,4-dichlorobromobenzene, 30 g of ammonia, 100 g of toluene, 138 g of potassium carbonate, and 1 g of composite catalyst (mass ratio of palladium carbon: carboxymethyldiphenylphosphine: cuprous iodide = 1:2:1) are added to a high-pressure reactor, and 56 g of carbon monoxide is charged. The temperature in the reactor is raised to 150-160°C, the pressure is raised to 2-3MPa, and the reaction is maintained under this condition for 12 hours. After the reaction is completed, the temperature in the reactor is lowered to room temperature, the pressure is lowered to normal pressure, the reaction product is taken out and filtered, the composite catalyst is removed, and then the filtrate is phase-separated, alkali-washed, and the solvent is concentrated to obtain 3,4-dichlorobenzamide with a yield of 90%.

[0075] Embodiment 11

[0076] Preparation of 3-chloro-N-methylbenzamide: 190 g of m-chlorobromobenzene, 40 g of methylamine, 100 g of toluene, 138 g of potassium carbonate, and 1 g of composite catalyst (mass ratio of palladium carbon: tributyl tetradecylphosphine chloride: cuprous iodide = 1:2:1) are added to a high-pressure reactor, and 56 g of carbon monoxide is charged. The temperature in the reactor is raised to 150-160°C, the pressure is raised to 2-3MPa, and the reaction is maintained under this condition for 12 hours. After the reaction is completed, the temperature in the reactor is lowered to room temperature, the pressure is lowered to normal pressure, the reaction product is taken out and filtered, the composite catalyst is removed, and then the filtrate is phase-separated, alkali-washed, and the solvent is concentrated to obtain 3-chloro-N-methylbenzamide with a yield of 89%.

[0077] Example 12

[0078] Preparation of 3,5-dichloro-N-methylbenzamide: 224 g of 3,5-dichlorobromobenzene, 40 g of methylamine, 100 g of toluene, 138 g of potassium carbonate, and 1 g of composite catalyst (mass ratio of palladium carbon: tri-n-butylphosphine: cuprous bromide = 1:2:1) are added to a high-pressure reactor, and 56 g of carbon monoxide is charged. The temperature in the reactor is raised to 150-160°C, the pressure is raised to 2-3 MPa, and the reaction is maintained under this condition for 12 hours. After the reaction is completed, the temperature in the reactor is lowered to room temperature, the pressure is lowered to normal pressure, the reaction product is taken out and filtered, the composite catalyst is removed, and then the filtrate is phase-separated, alkali-washed, and the solvent is concentrated to obtain 3,5-dichloro-N-methylbenzamide with a yield of 92%.

[0079] Example 13

[0080] Preparation of 3-chloro-5-methyl-N-methylbenzamide: 204 g of 3-chloro-5-methylbromobenzene, 40 g of methylamine, 100 g of toluene, 138 g of potassium carbonate, and 1 g of composite catalyst (mass ratio of palladium carbon: tri-n-butylphosphine: cuprous bromide = 1:2:1) are added to a high-pressure reactor, and 56 g of carbon monoxide is charged. The temperature in the reactor is raised to 150-160°C, the pressure is raised to 2-3MPa, and the reaction is maintained under this condition for 12 hours. After the reaction is completed, the temperature in the reactor is lowered to room temperature, the pressure is lowered to normal pressure, the reaction product is taken out and filtered, the composite catalyst is removed, and then the filtrate is phase-separated, alkali-washed, and the solvent is concentrated to obtain 3-chloro-5-methyl-N-methylbenzamide with a yield of 90%.

[0081] Embodiment 14

[0082] Preparation of methyl 2-amino-4-chlorobenzoate: 205 g of 2-bromo-4-chloroaniline, 100 g of methanol, 212 g of potassium phosphate, and 1 g of a composite catalyst (mass ratio of palladium carbon: triphenylphosphine: cuprous bromide = 1:2:1) are added to a high-pressure reactor, and 56 g of carbon monoxide is charged. The temperature in the reactor is raised to 150-160°C, and the pressure is raised to 2-3 MPa, and the reaction is maintained under this condition for 12 hours. After the reaction is completed, the temperature in the reactor is lowered to room temperature, the pressure is lowered to normal pressure, the reaction product is taken out and filtered, the composite catalyst is removed, and then the filtrate is concentrated and the solvent is distilled to obtain methyl o-toluate with a yield of 93%.

[0083] Embodiment 15

[0084] Preparation of 2-amino-3-methyl-4-chloro-N-methylbenzamide: 219 g of 2-bromo-4-chloro-5-methylaniline and 40 g of methylamine, 100 g of toluene, 138 g of potassium carbonate, and 1 g of a composite catalyst (mass ratio of palladium carbon: tri-n-butylphosphine: cuprous iodide = 1:2:1) are added to a high-pressure reactor, and 56 g of carbon monoxide is charged. The temperature in the reactor is raised to 150-160°C, the pressure is raised to 2-3MPa, and the reaction is maintained under this condition for 12 hours. After the reaction is completed, the temperature in the reactor is lowered to room temperature, the pressure is lowered to normal pressure, the reaction product is taken out and filtered, the composite catalyst is removed, and then the filtrate is phase-separated, alkali-washed, and the solvent is concentrated to obtain 2-amino-3-methyl-4-chloro-N-methylbenzamide with a yield of 88%.

Claims

1. A method for catalyzing the coupling reaction of aryl halides and carbon monoxide using a composite catalyst, characterized in that The method is one of the following: (i) introducing CO into the aryl halide of formula I and the raw material of formula II under the action of an acid binding agent and a composite catalyst to carry out a coupling reaction to obtain a compound of formula III; The reaction formula is as follows: In the formula I, R1 is a substituent on the benzene ring, which may not exist, that is, the benzene ring is not substituted, or R1 is a C1-C10 alkyl group or Cl; In the formula II, R2 is a C1-C5 alkoxy group or a C1-C5 alkylamine group; (ii) introducing CO into the aryl halide represented by formula (I) and sodium hydroxide under the action of an acid binding agent and a composite catalyst to carry out a coupling reaction, and acidifying the obtained product to obtain a benzoic acid compound; In the methods (i) and (ii), the composite catalyst is a mixture of a palladium catalyst, a phosphine catalyst and a copper catalyst; the palladium catalyst is palladium carbon, and the Pd loading is 5-10%.

2. The method according to claim 1, characterized in that The phosphorus catalyst is one or more of triphenylphosphine, tri-n-butylphosphine, 1,1'-binaphthyl-2,2'-bisdiphenylphosphine, carboxymethyldiphenylphosphine, and tributyltetradecylphosphine chloride.

3. The method according to claim 1, characterized in that The copper catalyst is cuprous iodide or cuprous bromide.

4. The method according to claim 1, characterized in that The mass ratio of the palladium catalyst, the phosphine catalyst and the copper catalyst in the composite catalyst is 0.5-1:0.5-2:0.5-1; the mass ratio of the aryl halide represented by formula I to the composite catalyst is 1:0.003-0.

2.

5. The method according to claim 1, characterized in that The acid binding agent is an inorganic base.

6. The method according to claim 1, characterized in that The molar ratio of the acid binding agent to the aryl halide represented by formula I is 1 to 5:

1.

7. The method according to claim 1, characterized in that The molar ratio of the aryl halide represented by formula I to carbon monoxide is 1:1-5; the molar ratio of the aryl halide represented by formula I to the raw material represented by formula II is 1:1-5.

8. The method according to claim 1, characterized in that The temperature of the coupling reaction is 120-190° C., the pressure is 2-4 MPa, and the coupling reaction time is 6-24 hours.

9. The method according to claim 1, characterized in that In the method (I), after the coupling reaction is completed, the reaction solution is post-treated to obtain the compound shown in formula III; the method for post-treatment of the reaction solution is preferably: after the reaction is completed, the reaction solution is cooled and depressurized, then filtered, and the obtained filtrate is washed, concentrated and the solvent is removed to obtain the compound shown in formula III; In the method (ii), after the coupling reaction is completed, the reaction solution is post-treated and acidified to obtain a benzoic acid compound; the method for post-treatment and acidification of the reaction solution is preferably: after the reaction is completed, the reaction solution is cooled and depressurized, then filtered, the obtained filtrate is phase-separated, and the aqueous phase is acidified to obtain a benzoic acid compound.

10. The method according to claim 9, characterized in that The filter cake obtained by filtration is palladium carbon, which can be recycled and used in coupling reactions.

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