A process for the synthesis of 2,4-dimethoxybenzoyl chloride and 2,4-dimethoxybenzoic acid

Abstract

The application discloses a method for synthesizing 2,4-dimethoxybenzoyl chloride, characterized by using m-xylene dimethyl ether and oxalyl chloride as raw materials, in the presence of an organic solvent and a catalyst, at 50-80 DEG C, until the reaction is completed, evaporating the solvent, and then performing vacuum distillation to obtain 2,4-dimethoxybenzoyl chloride, wherein the catalyst is azobisdimethylvaleronitrile or benzoyl peroxide. The method for synthesizing 2,4-dimethoxybenzoic acid is characterized by preparing 2,4-dimethoxybenzoyl chloride according to any one of claims 1-5, adding water to hydrolyze, and then performing recrystallization to obtain 2,4-dimethoxybenzoic acid. The reaction condition is mild, the synthesis steps are short, the cost is low, the influence on the environment is small, the yield is high, and the product quality is good.

Description

Technical Field

[0001] This invention relates to a method for synthesizing 2,4-dimethoxybenzoyl chloride and 2,4-dimethoxybenzoic acid, belonging to the field of organic synthesis technology. Background Technology

[0002] 2,4-Dimethoxybenzoic acid is an important chemical intermediate that can be widely used in the synthesis of antibacterial synergists, anti-anxiety drugs, coronary vasodilators, etc. Its synthesis method has been reported in *Synthetic Chemistry Journal* (Synthetic Chemistry, Vol. 15, 200, No. 6, 789-791). This method uses 2,4-dihydroxybenzoic acid as a raw material and reacts with dimethyl sulfate, involving thionyl chloride. Alternatively, it uses resorcinol as a raw material, first reacting it with carbon dioxide in the presence of sodium bicarbonate to obtain 2,4-dihydroxybenzoic acid, and then reacting it with dimethyl sulfate. Dimethyl sulfate is a highly toxic substance, and the reaction with thionyl chloride causes significant environmental pollution. The process is lengthy, has low yield, is cumbersome, and has high production costs. Summary of the Invention

[0003] To address the aforementioned problems, the first objective of this invention is to provide a method for synthesizing 2,4-dimethoxybenzoyl chloride, and the second objective of this invention is to provide a 2,4-dimethoxybenzoic acid method with simple process steps, mild reaction conditions, low environmental pollution, and high yield.

[0004] To achieve the aforementioned first objective, the technical solution of the present invention is as follows: a method for synthesizing 2,4-dimethoxybenzoyl chloride, characterized in that: using m-phenylene dimethyl ether and oxaloyl chloride as raw materials, the reaction is carried out in the presence of an organic solvent and a catalyst until the reaction is complete, and then the organic solvent is removed by vacuum distillation to obtain 2,4-dimethoxybenzoyl chloride, wherein the catalyst is azobisisobutyronitrile or benzoyl peroxide. The reaction formula is:

[0005]

[0006] In the above scheme: the amount of catalyst used is 1%-2% of the mass of m-phenylenediamine. The amount of organic solvent added is approximately 1 ml of solvent per 1 g of m-phenylenediamine.

[0007] In the above scheme, the catalyst is added in batches.

[0008] In the above scheme, the organic solvent is one of toluene, xylene, 1,2-dichloroethane, carbon tetrachloride, chloroform, dichlorobenzene, and petroleum ether.

[0009] In the above scheme, the molar ratio of m-phenylenediamine to oxalyl chloride is 1:1 to 1:1.2.

[0010] In the above scheme, the operation steps are as follows: take m-phenylenedimethyl ether into the reaction vessel, stir, add some catalyst, heat to 50-60℃, add dropwise a mixed solution of oxalyl chloride and organic solvent, after the dropwise addition is complete, control the temperature at 70-90℃ for reaction, add the remaining catalyst in batches during the dropwise addition of oxalyl chloride and reaction, and after the reaction is complete, remove the organic solvent by vacuum distillation to obtain 2,4-dimethoxybenzoyl chloride.

[0011] The second objective of this invention is achieved as follows: a method for synthesizing 2,4-dimethoxybenzoic acid, characterized in that: 2,4-dimethoxybenzoyl chloride is first prepared according to the above method, hydrolyzed with water, and then recrystallized to obtain 2,4-dimethoxybenzoic acid.

[0012] In the above scheme, the solvent used for recrystallization is water.

[0013] Compared with the prior art, the beneficial effects of the present invention are as follows: the method of the present invention does not require dimethyl sulfate, does not contain thionyl chloride, and has less environmental pollution. The present invention uses m-phenylenedimethyl ether and oxalyl chloride as raw materials, the reaction operation is simple, the synthesis steps are short, the cost is low, and the yield of 2,4-dimethoxybenzoic acid is as high as 95% or more, and the purity is 99.5% or more. It can be widely used in chemical, pharmaceutical and other fields. Detailed Implementation

[0014] The present invention will be further illustrated below through examples:

[0015] In Example 1, 13.8 g of m-phenylenediamine was placed in a three-necked flask, and 0.05 g of azobisisobutyronitrile was added. After adding a magnetic stir bar and turning on the stirrer, the temperature was raised to the indicated temperature of 50°C. A solution consisting of 12.8 g of oxalyl chloride and 15 ml of chlorobenzene was then added dropwise over 15 minutes, with the temperature controlled not to exceed 70°C. During the addition of oxalyl chloride and the reaction, azobisisobutyronitrile was added in batches, in 3-4 batches, for a total of 0.15 g of azobisisobutyronitrile. After the addition was complete, the temperature was controlled at 70°C and the reaction was carried out for 5 hours. The reaction was stopped after monitoring that the reaction was complete, and the chlorobenzene was removed by vacuum distillation to obtain 2,4-dimethoxybenzoyl chloride. The obtained 2,4-dimethoxybenzoyl chloride was added to sufficient water for hydrolysis (the water, in molar amounts, should be more abundant than the 2,4-dimethoxybenzoyl chloride). The solution was filtered, washed with water, recrystallized with water, and dried to obtain 17.2 g of 2,4-dimethoxybenzoic acid. Yield: 95.2%, Purity: 99.5%.

[0016] In Example 2, 13.8 g of m-phenylenediamine was added to a three-necked flask, along with 0.05 g of azobisisobutyronitrile (AIBN). A magnetic stir bar was added and stirred. The mixture was heated to the indicated temperature of 50°C. A solution of 12.8 g of oxaloyl chloride and 15 ml of toluene was then added dropwise over 15 minutes, with the temperature controlled to not exceed 70°C. A BIBN was added in batches during the addition of oxaloyl chloride and the reaction, in 3-4 batches, for a total addition of 0.15 g of ABN. After the addition was complete, the reaction was carried out at 70°C for 5 hours. The reaction was then stopped, and toluene was removed by vacuum distillation to obtain 2,4-dimethoxybenzoyl chloride. The obtained 2,4-dimethoxybenzoyl chloride was hydrolyzed in sufficient water, filtered, washed with water, recrystallized with water, and dried to obtain 17.1 g of 2,4-dimethoxybenzoic acid, with a yield of 95% and a purity of 99.5%.

[0017] In Example 3, 13.8 g of m-phenylenediamine was added to a three-necked flask, along with 0.05 g of azobisisobutyronitrile. A magnetic stir bar was then added and stirred. The mixture was heated to the indicated temperature of 50°C. A solution consisting of 12.8 g of oxaloyl chloride and 15 ml of 1,2-dichloroethane was then added dropwise over 15 minutes, with the temperature controlled to not exceed 70°C. Azobisisobutyronitrile was added in batches during the dropwise addition of oxaloyl chloride and the reaction process, in 3-4 batches, for a total addition of 0.15 g of azobisisobutyronitrile. After the addition was complete, the temperature was controlled at 70°C for 5 hours. The reaction was then stopped, and 1,2-dichloroethane was removed by vacuum distillation to obtain 2,4-dimethoxybenzoyl chloride. The obtained 2,4-dimethoxybenzoyl chloride was added to sufficient water for hydrolysis, filtered, and crude 2,4-dimethoxybenzoic acid was obtained. The crude product was then recrystallized with water to obtain 2,4-dimethoxybenzoic acid with a yield of 96% and a purity of 99.5%.

[0018] In Example 4, 13.8 g of m-phenylenediamine was added to a three-necked flask, along with 0.05 g of azobisisobutyronitrile (AIBN). A magnetic stir bar was added and stirred. The mixture was heated to the indicated temperature of 50°C. A solution of 12.8 g of oxaloyl chloride and 15 ml of xylene was then added dropwise over 15 minutes, with the temperature controlled to not exceed 70°C. During the addition of oxaloyl chloride and the reaction, AIBN was added in batches, approximately 3-4 batches, for a total addition of 0.15 g. After the addition was complete, the reaction was stopped at 70°C for 5 hours. The reaction was then stopped, and xylene was removed by vacuum distillation to obtain 2,4-dimethoxybenzoyl chloride. The obtained 2,4-dimethoxybenzoyl chloride was hydrolyzed in sufficient water, filtered, and crude 2,4-dimethoxybenzoic acid was obtained. Recrystallization with water yielded 2,4-dimethoxybenzoic acid with a yield of 95.7% and a purity of 99.5%.

[0019] In Example 5, 13.8 g of m-phenylenediamine was added to a three-necked flask, along with 0.05 g of azobisisobutyronitrile (AIBN). A magnetic stir bar was added and stirred. The mixture was heated to the indicated temperature of 50°C. A solution consisting of 12.8 g of oxaloyl chloride and 15 ml of carbon tetrachloride was then added dropwise over 15 minutes, with the temperature controlled to not exceed 70°C. During the addition of oxaloyl chloride and the reaction, AIBN was added in batches, approximately 3-4 batches, for a total addition of 0.15 g. After the addition was complete, the reaction was carried out at 70°C for 5 hours. The reaction was then stopped, and carbon tetrachloride was removed by vacuum distillation to obtain 2,4-dimethoxybenzoyl chloride. The obtained 2,4-dimethoxybenzoyl chloride was hydrolyzed in sufficient water, filtered, and crude 2,4-dimethoxybenzoic acid was obtained. Recrystallization with water yielded 2,4-dimethoxybenzoic acid with a yield of 96.1% and a purity of 99.5%.

[0020] In Example 6, 13.8 g of m-phenylenediamine was added to a three-necked flask, along with 0.05 g of azobisisobutyronitrile (AIBN). A magnetic stir bar was added and stirred. The mixture was heated to the indicated temperature of 50°C. A solution of 12.8 g of oxaloyl chloride and 15 ml of chloroform was then added dropwise over 15 minutes, with the temperature controlled to not exceed 70°C. During the addition of oxaloyl chloride and the reaction, AIBN was added in batches, approximately 3-4 batches, for a total addition of 0.15 g. After the addition was complete, the reaction was carried out at 70°C for 5 hours. The reaction was then stopped, and the chloroform was removed by vacuum distillation to obtain 2,4-dimethoxybenzoyl chloride. The obtained 2,4-dimethoxybenzoyl chloride was hydrolyzed in sufficient water, filtered, and crude 2,4-dimethoxybenzoic acid was obtained. Recrystallization with water yielded 2,4-dimethoxybenzoic acid with a yield of 95.8% and a purity of 99.5%.

[0021] In Example 7, 13.8 g of m-phenylenediamine was added to a three-necked flask, along with 0.05 g of azobisisobutyronitrile (AIBN). A magnetic stir bar was added and stirred. The mixture was heated to the indicated temperature of 60°C. A solution of 12.8 g of oxaloyl chloride and 15 ml of dichlorobenzene was then added dropwise over 15 minutes, with the temperature controlled not to exceed 90°C. During the addition of oxaloyl chloride and the reaction, AIBN was added in batches, approximately 3-4 batches, for a total addition of 0.15 g. After the addition was complete, the reaction was carried out at 90°C for 5 hours. The reaction was then stopped, and dichlorobenzene was removed by vacuum distillation to obtain 2,4-dimethoxybenzoyl chloride. The obtained 2,4-dimethoxybenzoyl chloride was hydrolyzed in sufficient water, filtered, and crude 2,4-dimethoxybenzoic acid was obtained. Recrystallization with water yielded 2,4-dimethoxybenzoic acid with a yield of 95% and a purity of 99.5%.

[0022] In Example 8, 13.8 g of m-phenylenediamine was added to a three-necked flask, along with 0.05 g of azobisisobutyronitrile (AIBN). A magnetic stir bar was added and stirred. The mixture was heated to the indicated temperature of 60°C. A solution of 12.8 g of oxaloyl chloride and 15 ml of petroleum ether was then added dropwise over 15 minutes, with the temperature controlled not to exceed 90°C. During the addition of oxaloyl chloride and the reaction, AIBN was added in batches, approximately 3-4 batches, for a total addition of 0.15 g. After the addition was complete, the reaction was carried out at 90°C for 5 hours. The reaction was then stopped, and the petroleum ether was removed by vacuum distillation to obtain 2,4-dimethoxybenzoyl chloride. The obtained 2,4-dimethoxybenzoyl chloride was hydrolyzed in sufficient water, filtered, and crude 2,4-dimethoxybenzoic acid was obtained. Recrystallization with water yielded 2,4-dimethoxybenzoic acid with a yield of 95.1% and a purity of 99.5%.

[0023] Example 9

[0024] 13.8 g of m-phenylenediamine was added to a three-necked flask, along with 0.05 g of benzoyl peroxide. A magnetic stirrer was added and stirred. The mixture was heated to the indicated temperature of 60°C. A solution of 12.8 g of oxaloyl chloride and 15 ml of petroleum ether was then added dropwise over 15 minutes, with the temperature controlled not to exceed 90°C. Benzoyl peroxide was added in batches during the dropwise addition of oxaloyl chloride and the reaction, in 3-4 batches, for a total addition of 0.276 g of benzoyl peroxide. After the addition was complete, the reaction was stopped at 90°C for 5 hours. The reaction was then stopped, and the petroleum ether was removed by vacuum distillation to obtain 2,4-dimethoxybenzoyl chloride. The obtained 2,4-dimethoxybenzoyl chloride was hydrolyzed in sufficient water, filtered, and crude 2,4-dimethoxybenzoic acid was obtained. Recrystallization with water yielded 2,4-dimethoxybenzoic acid with a yield of 94.8% and a purity of 99.5%.

[0025] Example 10

[0026] 13.8 g of m-phenylenediamine was added to a three-necked flask, followed by 0.05 g of azobisisobutyronitrile (AIBN). A magnetic stirrer was added and stirred. The mixture was heated to the indicated temperature of 50°C. A solution of 12.8 g of oxaloyl chloride and 15 ml of toluene was then added dropwise over 15 minutes, with the temperature controlled to not exceed 70°C. A BIBN was added in 3-4 batches during the addition of oxaloyl chloride and the reaction, for a total addition of 0.138 g of ABN. After the addition was complete, the reaction was stopped at 70°C for 5 hours. The reaction was then stopped, and the toluene was removed by vacuum distillation to obtain 2,4-dimethoxybenzoyl chloride. The obtained 2,4-dimethoxybenzoyl chloride was hydrolyzed in sufficient water, filtered, washed with water, recrystallized with water, and dried to obtain 17.1 g of 2,4-dimethoxybenzoic acid, with a yield of 95.1% and a purity of 99.5%.

[0027] Example 11

[0028] 13.8 g of m-phenylenediamine was added to a three-necked flask, followed by 0.05 g of azobisisobutyronitrile (AIBN). A magnetic stirrer was added and stirred. The mixture was heated to the indicated temperature of 50°C. A solution of 12.69 g of oxaloyl chloride and 15 ml of toluene was then added dropwise over 15 minutes, with the temperature controlled to not exceed 70°C. A BIBN was added in 3-4 batches during the addition of oxaloyl chloride and the reaction, for a total addition of 0.15 g of ABN. After the addition was complete, the reaction was stopped at 70°C for 5 hours. The reaction was then stopped, and the toluene was removed by vacuum distillation to obtain 2,4-dimethoxybenzoyl chloride. The obtained 2,4-dimethoxybenzoyl chloride was hydrolyzed in sufficient water, filtered, washed with water, recrystallized with water, and dried to obtain 17.1 g of 2,4-dimethoxybenzoic acid, with a yield of 94.8% and a purity of 99.5%.

[0029] Example 12

[0030] 13.8 g of m-phenylenediamine was added to a three-necked flask, followed by 0.05 g of azobisisobutyronitrile (AIBN). A magnetic stir bar was added and stirred. The mixture was heated to the indicated temperature of 50°C. A solution of 15.2 g of oxaloyl chloride and 15 ml of toluene was then added dropwise over 15 minutes, with the temperature controlled to not exceed 70°C. A BIBN was added in 3-4 batches during the addition of oxaloyl chloride and the reaction, for a total addition of 0.15 g of ABN. After the addition was complete, the reaction was stopped at 70°C for 5 hours. The reaction was then stopped, and the toluene was removed by vacuum distillation to obtain 2,4-dimethoxybenzoyl chloride. The obtained 2,4-dimethoxybenzoyl chloride was hydrolyzed in sufficient water, filtered, washed with water, recrystallized with water, and dried to obtain 17.1 g of 2,4-dimethoxybenzoic acid, with a yield of 95.3% and a purity of 99.5%.

[0031] Example 13

[0032] 13.8 g of m-phenylenediamine was added to a three-necked flask, along with 0.05 g of benzoyl peroxide. A magnetic stirrer was added and stirred. The mixture was heated to the indicated temperature of 60°C. A solution of 12.8 g of oxaloyl chloride and 15 ml of petroleum ether was then added dropwise over 15 minutes, with the temperature controlled not to exceed 90°C. Benzoyl peroxide was added in batches during the dropwise addition of oxaloyl chloride and the reaction, in 3-4 batches, for a total addition of 0.15 g of benzoyl peroxide. After the addition was complete, the reaction was carried out at 90°C for 5 hours. The reaction was then stopped, and the petroleum ether was removed by vacuum distillation to obtain 2,4-dimethoxybenzoyl chloride. The obtained 2,4-dimethoxybenzoyl chloride was hydrolyzed in sufficient water, filtered, and crude 2,4-dimethoxybenzoic acid was obtained. Recrystallization from water yielded 2,4-dimethoxybenzoic acid with a yield of 94.9% and a purity of 99.5%.

[0033] This invention is not limited to the above embodiments. Those skilled in the art will understand that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and spirit of this invention. The scope of this invention is defined by the claims and their equivalents.

Claims

1. A process for the synthesis of 2,4-dimethoxybenzoyl chloride, characterized in that, The operation steps are: taking m-dimethoxybenzene into a reaction container, stirring, adding part of the catalyst, heating to 50-60℃, adding dropwise a mixed solution of oxalyl chloride and an organic solvent, controlling the temperature at 70-90℃ after dropwise addition, adding the remaining catalyst in batches during the dropwise addition and the reaction, removing the organic solvent by distillation under reduced pressure after the reaction is completed to obtain 2,4-dimethoxybenzoyl chloride, The catalyst is azobisdimethyl valeronitrile or benzoyl peroxide; The amount of the catalyst is 1%-2% of the mass of m-dimethoxybenzene; The organic solvent is one of toluene, xylene, 1,2-dichloroethane, carbon tetrachloride, chloroform, dichlorobenzene and petroleum ether; The molar ratio of m-dimethoxybenzene to oxalyl chloride is 1:1-1:1.

2.

2. A method of synthesizing 2,4-dimethoxybenzoic acid, characterized by: The method according to any one of claim 1 is used to prepare 2,4-dimethoxybenzoyl chloride first, and then 2,4-dimethoxybenzoic acid is obtained by hydrolysis and recrystallization.

3. The process for synthesis of 2,4-dimethoxybenzoic acid as claimed in claim 2, wherein: The solvent used for recrystallization is water.

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