A method for synthesizing 3-amino-4-methoxy biphenyl

Abstract

The present application relates to the technical fields of pesticide synthesis, and discloses a synthesis method of 3-amino-4-methoxydiphenyl, which takes 4-hydroxydiphenyl as a starting material, and 3-amino-4-methoxydiphenyl can be obtained through insertion carbonylation reaction, methylation esterification, amine ester exchange and rearrangement reaction.The present application has the following advantages and effects: compared with the prior art, the synthesis method of 3-amino-4-methoxydiphenyl has the advantages of green environmental protection, low cost, safety and economy, and the specific advantages are as follows: 1. the reaction condition is mild, the operation is convenient, the production equipment is simple, and the whole process is very suitable for industrialized mass production; 2. the present application avoids dangerous reactions such as nitration reaction and catalytic hydrogenation reaction, and reduces the production safety risk.

Description

Technical Field

[0001] This invention relates to the field of pesticide synthesis technology, and in particular to a method for synthesizing 3-amino-4-methoxybiphenyl. Background Technology

[0002] 3-Amino-4-methoxybiphenyl is an important intermediate that can be used in pesticides, dyes, resins and rubber.

[0003] The structural formula is as follows: ; 3-Amino-4-methoxybiphenyl is a key intermediate in the synthesis of biphenylhydrazine ester. CAS No.: 39811-17-1, Molecular Formula: C13H13NO, Molecular Weight: 199.25 In the existing technology, the synthesis method of 3-amino-4-methoxybiphenyl is roughly as follows: Method 1: ; This method involves nitration and hydrogenation reactions, which are dangerous reactions and pose significant safety hazards in production. It also has high requirements for production equipment and problems such as high energy consumption, expensive catalytic hydrogenation catalysts, and catalyst deactivation.

[0004] Method 2: ; This method is the SUZUKI coupling reaction, which requires the use of palladium as a catalyst. It is expensive and costly, making it unsuitable for industrial production.

[0005] Method 3: ; This method has high requirements for production equipment, and the high-temperature reaction has problems such as high energy consumption and troublesome post-processing of copper catalyst.

[0006] In summary, the existing synthetic methods for 3-amino-4-methoxybiphenyl suffer from challenges such as high requirements for production equipment, high energy consumption, expensive catalysts, and high production costs. Therefore, there is an urgent need to find a new, environmentally friendly method with high yield and low production cost to meet the market's pressing demand for this product. Summary of the Invention

[0007] The purpose of this invention is to provide a method for synthesizing 3-amino-4-methoxybiphenyl, which has the advantages of being green and environmentally friendly, low in cost, safe and economical.

[0008] The above-mentioned technical objective of this invention is achieved through the following technical solution: a method for synthesizing 3-amino-4-methoxybiphenyl, using 4-hydroxybiphenyl as a starting material, and obtaining 3-amino-4-methoxybiphenyl through carbonylation reaction, methylation esterification, amino ester exchange and rearrangement reaction, specifically including the following steps: Step A - Carbonyl insertion reaction Add 4-hydroxybiphenyl and solvent, stir to dissolve and clear, then add alkali, and at a certain temperature, pass carbon dioxide gas under the liquid surface, and continue the reaction at a certain temperature to obtain 3-carboxy-4-hydroxybiphenyl; The reaction equation is as follows: ; Step B - Methylation and Esterification The obtained 3-carboxy-4-hydroxybiphenyl was added to a certain amount of alkali and a certain amount of solvent, and a methylating agent was added dropwise at a certain temperature. The reaction was maintained at the temperature to obtain methyl 3-formate-4-methoxybiphenyl. The reaction equation is as follows: ; Step C-amino ester exchange reaction The obtained methyl 3-carboxylate-4-methoxybiphenyl was added to ammonia water, heated to a certain temperature, and kept at that temperature to produce 3-formamide-4-methoxybiphenyl. The reaction equation is as follows: ; Step D - Rearrangement reaction 3-Formamido-4-methoxybiphenyl was added to alkali and sodium hypochlorite, heated to a certain temperature, and the reaction was maintained at the temperature to obtain 3-amino-4-methoxybiphenyl. The reaction equation is as follows: .

[0009] A further provision of the present invention is that the alkali in step A is selected from sodium tert-butoxide, potassium tert-butoxide, and sodium methoxide.

[0010] A further provision of the present invention is that the solvent in step A is selected from acetonitrile, tetrahydrofuran, and dioxane.

[0011] A further setting of the present invention is that the reaction temperature in step A is between 70-90°C, and the molar ratio of materials in step A is 4-hydroxybiphenyl:base is 1:(1-1.5).

[0012] A further provision of the present invention is that the alkali in step B is selected from sodium carbonate, potassium carbonate, potassium hydroxide, and sodium hydroxide, and the reaction temperature in step B is 90-100℃.

[0013] A further setting of the present invention is that the molar ratio of materials in step B, namely 3-carboxy-4-hydroxybiphenyl: base: methylating agent, is 1: (1.5-2): (2-2.2).

[0014] A further setting of the present invention is that the reaction temperature in step C is 25-50°C, and the molar ratio of materials in step C is methyl 3-formate-4-methoxybiphenyl:ammonia water is 1:(1-3).

[0015] A further provision of the present invention is that the alkali in step D is selected from sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate.

[0016] A further setting of the present invention is that the reaction temperature in step D is between 20-70°C.

[0017] A further setting of the present invention is that the molar ratio of materials in step D is 3-formamide-4-methoxybiphenyl: base: sodium hypochlorite 1: (1-1.5): (1-1.2).

[0018] The beneficial effects of this invention are: 1. The reaction conditions are mild, the operation is convenient, the production equipment is simple, and the whole process is very suitable for large-scale industrial production; 2. This invention avoids dangerous reactions such as nitration and catalytic hydrogenation, thus reducing production safety risks. Attached Figure Description

[0019] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0020] Figure 1 This is the 1H NMR spectrum of 3-amino-4-methoxybiphenyl in this invention. Detailed Implementation

[0021] The technical solution of the present invention will now be clearly and completely described with reference to specific embodiments. Obviously, the described embodiments are merely some, not all, of the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0022] A method for synthesizing 3-amino-4-methoxybiphenyl, using 4-hydroxybiphenyl as a starting material, involves carbonylation, methylation-esterification, amino-ester exchange, and rearrangement reactions to obtain 3-amino-4-methoxybiphenyl. The specific steps include: Step A - Carbonyl insertion reaction In a 500mL three-necked flask, 20g of 4-hydroxybiphenyl was added to 200mL of acetonitrile at room temperature and stirred. Then, 17g of sodium tert-butoxide was added while stirring. The temperature was raised to 70℃, and carbon dioxide gas was slowly introduced under the liquid surface (at a rate of 50mL / min). The reaction was maintained at 70-75℃ for 4 hours. During the reaction, a sample was taken for monitoring. The reaction was considered complete when the conversion rate of 4-hydroxybiphenyl was >99%. The acetonitrile was collected by vacuum concentration, and the residue was added to 500mL of ice water. The pH was adjusted to 3-4 with hydrochloric acid, causing solid precipitation. The solid was filtered, and the filter cake was washed with water and dried to obtain 24.42g of solid 3-carboxy-4-hydroxybiphenyl, with a purity of 99% and a yield of 97.7%.

[0023] Step B - Methylation and Esterification In a 500mL three-necked flask, 24.42g of 3-carboxy-4-hydroxybiphenyl, 24.2g of sodium carbonate, and 200mL of toluene were added sequentially. The mixture was stirred and heated to 90°C. At 90°C, 31.63g of dimethyl sulfate was slowly added dropwise. The reaction was maintained at 90-100°C for 3 hours. During the reaction, the conversion rate of 3-carboxy-4-hydroxybiphenyl was measured to be >99%, indicating the end of the reaction. 200mL of water was added, and the mixture was stirred thoroughly for 10 minutes. The mixture was then allowed to stand and separate into layers. The upper organic layer was collected and dissolved under reduced pressure to obtain 27g of the intermediate methyl 3-formate-4-methoxybiphenyl, with a purity of 98.1% and a yield of 98%.

[0024] Step C-amino ester exchange reaction Take a 250ml reaction flask, add 27g of methyl 3-formate-4-methoxybiphenyl and 46.8g of ammonia water at room temperature, slowly heat the system to 50℃, and keep the reaction at this temperature for 4-5 hours; take samples for control, and stop the reaction when the conversion rate of methyl 3-formate-4-methoxybiphenyl is >99%; add 200ml of ice water to the system, cool and crystallize to precipitate solid, filter, wash the filter cake with a small amount of water 1-2 times, and dry to obtain 24.56g of 3-formamide-4-methoxybiphenyl, with a purity of 97.5% and a yield of 97.4%.

[0025] Step D - Rearrangement reaction Take a 250ml reaction flask, add 24.56g of 3-formamide-4-methoxybiphenyl and 64.91g of 10% sodium hydroxide aqueous solution at room temperature, stir, and slowly add 107.5g of sodium hypochlorite dropwise at room temperature. Keep the system at 20-25℃ for 2-3 hours, then slowly raise the temperature to 60-70℃ and keep the system at this temperature for 1-2 hours. Take samples for monitoring, and stop the reaction when the conversion rate of 3-formamide-4-methoxybiphenyl is >99%. Add 300ml of toluene to the system for extraction, allow it to stand and separate into layers, take the upper organic layer, and desolvent under reduced pressure to obtain 21.16g of intermediate 3-amino-4-methoxybiphenyl with a purity of 97.8% and a yield of 98.3%.

[0026] The synthetic route of the synthetic method described in this invention is as follows: ; Compared with existing technologies, the synthesis method of 3-amino-4-methoxybiphenyl of the present invention has the advantages of being green and environmentally friendly, low-cost, safe and economical, as follows: 1. The reaction conditions are mild, the operation is convenient, the production equipment is simple, and the entire process is very suitable for large-scale industrial production. 2. The present invention avoids dangerous reactions such as nitration and catalytic hydrogenation, reducing production safety risks.

Claims

1. A method for synthesizing 3-amino-4-methoxybiphenyl, characterized in that: Starting with 4-hydroxybiphenyl, 3-amino-4-methoxybiphenyl can be obtained through carbonylation, methylation, esterification, amino-ester exchange, and rearrangement reactions. The specific steps include the following: Step A - Carbonyl insertion reaction 4-hydroxybiphenyl and solvent are added, stirred and dissolved, then alkali is added, carbon dioxide gas is introduced under the liquid surface at a certain temperature, and the reaction is continued at a certain temperature to obtain 3-carboxy-4-hydroxybiphenyl. The reaction equation is as follows: ; Step B - Methylation and Esterification The obtained 3-carboxy-4-hydroxybiphenyl was added to a certain amount of alkali and a certain amount of solvent, and a methylating agent was added dropwise at a certain temperature. The reaction was maintained at the temperature to obtain methyl 3-formate-4-methoxybiphenyl. The reaction equation is as follows: ; Step C-aminoester exchange reaction The obtained methyl 3-carboxylate-4-methoxybiphenyl was added to ammonia water, heated to a certain temperature, and kept at that temperature to produce 3-formamide-4-methoxybiphenyl. The reaction equation is as follows: ; Step D - Rearrangement reaction 3-Formamido-4-methoxybiphenyl was added to alkali and sodium hypochlorite, heated to a certain temperature, and the reaction was maintained at the temperature to obtain 3-amino-4-methoxybiphenyl. The reaction equation is as follows: .

2. The method for synthesizing 3-amino-4-methoxybiphenyl according to claim 1, characterized in that: In step A, the alkali is selected from one of sodium tert-butoxide, potassium tert-butoxide, and sodium methoxide.

3. The method for synthesizing 3-amino-4-methoxybiphenyl according to claim 1, characterized in that: In step A, the solvent can be selected from acetonitrile, tetrahydrofuran, or dioxane.

4. The method for synthesizing 3-amino-4-methoxybiphenyl according to claim 1, characterized in that: The reaction temperature in step A is between 70-90℃, and the molar ratio of 4-hydroxybiphenyl to base in step A is 1:(1-1.5).

5. The method for synthesizing 3-amino-4-methoxybiphenyl according to claim 1, characterized in that: In step B, the alkali is selected from sodium carbonate, potassium carbonate, potassium hydroxide, and sodium hydroxide, and the reaction temperature in step B is 90-100℃.

6. The method for synthesizing 3-amino-4-methoxybiphenyl according to claim 1, characterized in that: In step B, the molar ratio of 3-carboxy-4-hydroxybiphenyl: base: methylating agent is 1: (1.5-2): (2-2.2).

7. The method for synthesizing 3-amino-4-methoxybiphenyl according to claim 1, characterized in that: The reaction temperature in step C is 25-50℃, and the molar ratio of methyl 3-formate-4-methoxybiphenyl to ammonia in step C is 1:(1-3).

8. The method for synthesizing 3-amino-4-methoxybiphenyl according to claim 1, characterized in that: In step D, the alkali is selected from one of sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate.

9. The method for synthesizing 3-amino-4-methoxybiphenyl according to claim 1, characterized in that: The reaction temperature in step D is between 20-70℃.

10. The method for synthesizing 3-amino-4-methoxybiphenyl according to claim 1, characterized in that: In step D, the molar ratio of 3-formamide-4-methoxybiphenyl: base: sodium hypochlorite is 1:(1-1.5):(1-1.2).

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