A method for preparing 2,5-dimethylphenylacetic acid

Abstract

The invention discloses a method for preparing 2,5-dimethylphenylacetic acid, and belongs to the technical field of fine chemicals. 2,5-dimethylbenzoyl chloride is used as a raw material, reacts with sodium cyanide in an acetonitrile solution to obtain 2,5-dimethylbenzoyl nitrile; then 2,5-dimethylbenzoyl nitrile is subjected to a reduction hydrolysis reaction with hydrazine hydrate and potassium hydroxide in a 1,3-propylene glycol solution, and 2,5-dimethylphenylacetic acid is obtained by acidification and filtration. The method has short reaction steps, simple operation, mild reaction conditions, high yield and product purity, and is very easy to realize industrial production.

Description

Technical Field

[0001] The invention belongs to the technical field of fine chemicals and relates to a method for preparing 2,5-dimethylphenylacetic acid, and more specifically to a method for preparing 2,5-dimethylphenylacetic acid by using 2,5-dimethylbenzoyl chloride as a raw material. Technical Background

[0002] Spirotetramat is a new tetronic acid insecticide developed by Bayer. Its mechanism of action is different from that of existing insecticides. It interferes with the fat biosynthesis of insects, causing the death of larvae and reducing the reproductive capacity of adults. It has good systemic properties and can be transmitted through the xylem and top (upward) of plants. It has a wide insecticide spectrum and a long lasting effect. It is also the only insecticide with bidirectional systemic transmission properties. 2,5-Dimethylphenylacetyl chloride is an important intermediate for the synthesis of spirotetramat, and 2,5-Dimethylphenylacetic acid is an indispensable raw material for the synthesis of 2,5-Dimethylphenylacetyl chloride.

[0003] Patent CN1918103 uses xylene and chloroacetyl chloride to undergo Friedel-Crafts acylation, followed by condensation with neopentyl glycol, followed by high-temperature rearrangement, hydrolysis and neutralization to obtain 2,5-dimethylphenylacetic acid. In this process, water is added after the Friedel-Crafts acylation reaction to quench a large amount of heat release, which can easily cause safety accidents if not properly controlled, and produces a large amount of acidic wastewater containing aluminum salts. The rearrangement reaction temperature requires 180°C, which is a relatively high reaction temperature.

[0004] [Bulltetin of chemical society of Japan 1975, 48, 497-502] Using p-xylene as raw material, it reacts with sodium cyanide after chloromethylation, and then hydrolyzes to obtain 2,5-dimethylphenylacetic acid. This method has easy-to-obtain raw materials and is easy to operate. The disadvantage is that there is a lot of acidic wastewater, sodium cyanide is a controlled product, and strict requirements are placed on workers during workshop production. The reaction route is as follows:

[0005]

[0006] CN201110060598 uses 2,5-dimethylbenzyl chloride and CO gas to react in the presence of a palladium catalyst, and then treats them with 30% liquid alkali, and neutralizes the water layer with concentrated hydrochloric acid to obtain 2,5-dimethylphenylacetic acid. In this method, the CO raw material is easy to obtain and the method is simple, but the technology and equipment requirements are high, and the use of precious metal catalysts increases the cost. The reaction route is as follows:

[0007]

[0008] JP2008291008 reported that 2,5-dimethylphenylacetic acid was synthesized from 2,5-dimethylacetophenone as the initial raw material through coupling and hydrolysis reactions. The method is simple to operate, but the coupling yield is low at 66%. Elemental sulfur is used in the reaction, and the sulfur-containing waste gas during hydrolysis has a great impact on the environment. The reaction route is as follows:

[0009] Summary of the invention

[0010] In order to solve the problems existing in the prior art, the present invention provides a method for preparing 2,5-dimethylphenylacetic acid. 2,5-dimethylbenzoyl chloride is used as a raw material, and 2,5-dimethylphenylacetic acid is prepared by two-step reaction. The method has the advantages of short reaction steps, high yield, stable quality, simple operation, etc., and is easy to industrialize and produce.

[0011] The method for preparing 2,5-dimethylphenylacetic acid of the present invention comprises the following steps: 2,5-dimethylbenzoyl chloride is used as a starting material, and 2,5-dimethylphenylacetic acid is obtained by two steps of cyanation and reduction hydrolysis. The reaction equation is as follows:

[0012]

[0013] Furthermore, in the above technical solution, the cyanation reaction is that 2,5-dimethylbenzoyl chloride and sodium cyanide react in an organic solvent to obtain 2,5-dimethylbenzoyl nitrile.

[0014] Furthermore, in the above technical solution, in the cyanation reaction, the molar ratio of 2,5-dimethylbenzoyl chloride to sodium cyanide is 1:1.0-1.5.

[0015] Furthermore, in the above technical solution, in the cyanation reaction, the reaction temperature is 50-100°C.

[0016] Furthermore, in the above technical solution, the organic solvent is one or a mixture of acetonitrile, DMF, chloroform, toluene, chlorobenzene, etc.

[0017] Furthermore, in the above technical scheme, in the reduction hydrolysis reaction, 2,5-dimethylbenzoyl nitrile, hydrazine hydrate and base are reacted in an organic solvent, and after the reaction is completed, acid is added to adjust the pH, and 2,5-dimethylphenylacetic acid is obtained after treatment.

[0018] Furthermore, in the above technical solution, in the reduction hydrolysis reaction, the reaction temperature is 80-130°C.

[0019] Furthermore, in the above technical solution, in the reduction hydrolysis reaction, the molar ratio of 2,5-dimethylbenzoyl nitrile to hydrazine hydrate is 1:1.0-2.0, and the molar ratio of 2,5-dimethylbenzoyl nitrile to the base is 1:5.

[0020] Furthermore, in the above technical solution, in the reduction hydrolysis reaction, the organic solvent is selected from one or a mixture of 1,3-propylene glycol, 1,2-ethylene glycol, ethylene glycol monoacetate, and diethylene glycol acetate.

[0021] Furthermore, in the above technical solution, in the reduction hydrolysis reaction, the base is one or a mixture of sodium hydroxide, potassium hydroxide and lithium hydroxide.

[0022] Furthermore, in the above technical solution, after the reduction hydrolysis reaction is completed, the acid used to adjust the pH value is hydrochloric acid or sulfuric acid.

[0023] Furthermore, in the above technical scheme, a typical operation of the technical scheme of the present invention is as follows: 2,5-dimethylbenzoyl chloride is used as a raw material to react with sodium cyanide in an acetonitrile solution to obtain 2,5-dimethylbenzoyl nitrile; then 2,5-dimethylbenzoyl nitrile is subjected to a reduction hydrolysis reaction with hydrazine hydrate and potassium hydroxide in a 1,3-propylene glycol solution, and 2,5-dimethylphenylacetic acid is obtained after acidification and filtration.

[0024] Beneficial effects of the invention:

[0025] A. Using 2,5-dimethylbenzoyl chloride as the starting material, the final product is obtained through two steps of cyanation and reduction hydrolysis. The reaction steps are short, the purity is high, and the two-step yield is more than 90%.

[0026] B. Using hydrazine hydrate and potassium hydroxide in 1,3-propylene glycol solvent, the carbonyl group of 2,5-dimethylbenzoyl nitrile is reduced to methylene. At the same time, under alkaline conditions, the cyano group is hydrolyzed to carboxylate. Hydrochloric acid is used to adjust the pH to below 2 to obtain the target compound.

[0027] C. The whole reaction process is simple to operate and the reaction conditions are mild, which is suitable for industrial production. The reduction and hydrolysis reactions are completed in one pot, which also provides a useful idea for the synthesis of compounds with similar structures. Specific implementation plan

[0028] The present invention will be described in more detail below in conjunction with specific embodiments, but the protection scope of the present invention is not limited thereto.

[0029] Embodiment 1:

[0030] Cyanation reaction: preparation of 2,5-dimethylbenzoylnitrile

[0031] In a 2L four-necked flask equipped with a condenser, a thermometer and a dropping funnel, add 500g of chloroform and 49g (1.0mol) of sodium cyanide in sequence, heat to 50°C with stirring, drop 168.6g (1.0mol) of 2,5-dimethylbenzoyl chloride solution, raise the temperature to reflux after the dropwise addition, and keep the temperature to react for 10h. Cool to room temperature, add water, wash the organic layer with water until it is neutral, and concentrate to obtain 148.4g of oily substance with a purity of 97.8% (GC, A / A%) and a yield of 93.2%.

[0032] Embodiment 2:

[0033] Cyanation reaction: preparation of 2,5-dimethylbenzoylnitrile

[0034] In a 2L four-necked flask equipped with a condenser, a thermometer and a dropping funnel, 500 g of acetonitrile and 54 g (1.1 mol) of sodium cyanide were added in sequence, heated to 50°C with stirring, and 168.6 g (1.0 mol) of 2,5-dimethylbenzoyl chloride solution was added dropwise. After the addition was completed, the temperature was raised to 75°C and the reaction was kept at this temperature for 10 hours. The temperature was lowered to room temperature, water was added to separate the organic layer, and the organic layer was washed with water until it was neutral, and concentrated to obtain 155.1 g of an oily substance with a purity of 98.2% (GC, A / A%) and a yield of 97.4%.

[0035] Embodiment 3:

[0036] Cyanation reaction: preparation of 2,5-dimethylbenzoylnitrile

[0037] In a 2L four-necked flask equipped with a condenser, a thermometer and a dropping funnel, 500 g of toluene and 64 g (1.3 mol) of sodium cyanide were added in sequence, heated to 50°C with stirring, and 168.6 g (1.0 mol) of 2,5-dimethylbenzoyl chloride solution was added dropwise. After the addition was completed, the temperature was raised to 100°C and the reaction was kept at this temperature for 10 hours. The temperature was lowered to room temperature, water was added and the organic layer was washed with water until it was neutral, and concentrated to obtain 130.5 g of an oily substance with a purity of 97.6% (GC, A / A%) and a yield of 82%.

[0038] Embodiment 4:

[0039] Cyanation reaction: preparation of 2,5-dimethylbenzoylnitrile

[0040] In a 2L four-necked flask equipped with a condenser, a thermometer and a dropping funnel, add 500 g of chlorobenzene and 44 g (0.9 mol) of sodium cyanide in sequence, heat to 50°C with stirring, drop 168.6 g (1.0 mol) of 2,5-dimethylbenzoyl chloride solution, raise the temperature to 110°C after the dropwise addition, and keep the temperature for 10 hours. Cool to room temperature, add water, wash the organic layer with water until it is neutral, and concentrate to obtain 124.5 g of oily substance with a purity of 96.8% (GC, A / A%) and a yield of 78.2%.

[0041] Embodiment 5:

[0042] Cyanation reaction: preparation of 2,5-dimethylbenzoylnitrile

[0043] In a 2L four-necked flask equipped with a condenser, a thermometer and a dropping funnel, 500 g of DMF and 54 g (1.1 mol) of sodium cyanide were added in sequence, heated to 50°C with stirring, and 168.6 g (1.0 mol) of 2,5-dimethylbenzoyl chloride solution was added dropwise. After the addition was completed, the temperature was raised to 100°C and the reaction was kept at this temperature for 10 hours. The temperature was lowered to room temperature, water was added and the organic layer was washed with water until neutral, and concentrated to obtain 143.3 g of an oily substance with a purity of 98.0% (GC, A / A%) and a yield of 90%.

[0044] Embodiment 6:

[0045] Reductive hydrolysis reaction: preparation of 2,5-dimethylphenylacetic acid

[0046] 127 g (0.8 mol) of 2,5-dimethylbenzoyl nitrile oily substance obtained by cyanation reaction, 75 g (80% content, 1.2 mol) of hydrazine hydrate, 134 g (2.4 mol) of potassium hydroxide and 500 g of 1.3-propylene glycol were added into a 2000 mL four-necked bottle in sequence, first heated to 80°C, kept warm for 2 hours, then continued to heat to 130°C, kept warm for 10 hours, and GC detected that 2,5-dimethylbenzoyl nitrile (<0.1%) was completely reacted. After the reaction was completed, the temperature was lowered to 50°C, 500 g of water was added for quenching, 316 g (2.6 mol) of 30% hydrochloric acid was used to adjust the solution pH to less than 2, the temperature was lowered to below 20°C, filtered and dried to obtain 122.7 g of 2,5-dimethylbenzoic acid white solid, with a content of 98.5% (GC, A / A%), and a yield of 93.4%.

[0047] Embodiment 7:

[0048] Reductive hydrolysis reaction: preparation of 2,5-dimethylphenylacetic acid

[0049] 127 g (0.8 mol) of 2,5-dimethylbenzoyl nitrile oily substance, 94 g (80% content, 1.5 mol) of hydrazine hydrate, 96 g (2.4 mol) of sodium hydroxide and 500 g of 1.2-ethylene glycol obtained by cyanation reaction were added into a 2000 mL four-necked bottle in sequence, first heated to 50° C., kept warm for 2 h, then continued to heat to 150° C., kept warm for 10 h, and GC detected that 2,5-dimethylbenzoyl nitrile (<0.1%) was completely reacted. After the reaction was completed, the temperature was lowered to 50° C., 500 g of water was added for quenching, 316 g (2.6 mol) of 30% hydrochloric acid was used to adjust the solution pH to less than 2, the temperature was lowered to below 20° C., filtered and dried to obtain 117 g of 2,5-dimethylbenzoic acid white solid, with a content of 98.2% (GC, A / A%), and a yield of 89.1%.

[0050] Embodiment 8:

[0051] Reductive hydrolysis reaction: preparation of 2,5-dimethylphenylacetic acid

[0052] The cyanation reaction obtained 2,5-dimethylbenzoyl nitrile oily substance 127 g (0.8 mol), hydrazine hydrate 60 g (content 80%, 1.2 mol), lithium hydroxide 19.2 g (0.8 mol), sodium hydroxide 32 g (0.8 mol), potassium hydroxide 45 g (0.8 mol) and ethylene glycol monoacetate 500 g, were added into a 2000 mL four-necked bottle in sequence, first heated to 100 ° C, kept warm for 2 h, then continued to heat to 180 ° C, kept warm for 10 h, GC detection 2,5-dimethylbenzoyl nitrile (<0.1%) reaction was complete. After the reaction, the temperature was lowered to 50°C, 500 g of water was added to quench, 316 g (2.6 mol) of 30% hydrochloric acid was used to adjust the pH value of the solution to less than 2, the temperature was lowered to below 20°C, filtered and dried to obtain 106.4 g of 2,5-dimethylbenzoic acid as a white solid with a content of 96.8% (GC, A / A%) and a yield of 81.0%.

[0053] Embodiment 9:

[0054] Reductive hydrolysis reaction: preparation of 2,5-dimethylphenylacetic acid

[0055] The cyanation reaction obtained 2,5-dimethylbenzoyl nitrile oily substance 127 grams (0.8 mol), hydrazine hydrate 62.5 grams (content 80%, 1.0 mol), potassium hydroxide 89.6 grams (1.6 mol) and diethylene glycol 500 grams, added into a 2000 mL four-necked bottle in sequence, first heated to 70 ° C, kept warm for 2 hours, then continued to heat to 100 ° C, kept warm for 10 hours, GC detected 2,5-dimethylbenzoyl nitrile (<0.1%) reaction was complete. After the reaction, the temperature was lowered to 50 ° C, quenched with 500 grams of water, 50% sulfuric acid 510 grams (2.6 mol) was used to adjust the solution pH value to less than 2, the temperature was lowered to below 20 ° C, filtered and dried to obtain 2,5-dimethylbenzoic acid white solid 111.7 grams, content 97.8% (GC, A / A%), yield 85.0%.

[0056] Embodiment 10:

[0057] Reductive hydrolysis reaction: preparation of 2,5-dimethylphenylacetic acid

[0058] 127 g (0.8 mol) of 2,5-dimethylbenzoyl nitrile oily substance, 125 g (80% content, 2.0 mol) of hydrazine hydrate, 57.5 g (2.4 mol) of lithium hydroxide and 500 g of 1.3-propylene glycol obtained by cyanation reaction were added into a 2000 mL four-necked bottle in sequence, first heated to 80°C, kept warm for 2 hours, then continued to heat to 170°C, kept warm for 10 hours, and GC detected that 2,5-dimethylbenzoyl nitrile (<0.1%) was completely reacted. After the reaction was completed, the temperature was lowered to 50°C, 500 g of water was added for quenching, 510 g (2.6 mol) of 50% sulfuric acid was used to adjust the solution pH to less than 2, the temperature was lowered to below 20°C, filtered and dried to obtain 119.2 g of 2,5-dimethylbenzoic acid white solid, with a content of 98.0% (GC, A / A%), and a yield of 90.7%.

[0059] The above are only preferred embodiments of the present invention. It should be noted that the above preferred embodiments should not be regarded as limiting the present invention, and the protection scope of the present invention should be based on the scope defined by the claims. For ordinary technicians in this technical field, several improvements and modifications can be made without departing from the spirit and scope of the present invention, and these improvements and modifications should also be regarded as the protection scope of the present invention.

Claims

1. A method for preparing 2,5-dimethylphenylacetic acid, characterized in that: The method comprises the following steps: 2,5-dimethylbenzoyl chloride is used as a starting material, and 2,5-dimethylphenylacetic acid is obtained through two steps of cyanation and reduction hydrolysis. The reaction equation is as follows: ； In the reduction hydrolysis reaction, 2,5-dimethylbenzoyl nitrile, hydrazine hydrate and a base are reacted in an organic solvent. After the reaction is completed, an acid is added to adjust the pH, and 2,5-dimethylphenylacetic acid is obtained after treatment. In the reduction hydrolysis reaction, the organic solvent is selected from one or a mixture of 1,3-propylene glycol, 1,2-ethylene glycol, monoethylene glycol and diethylene glycol. In the reduction hydrolysis reaction, the base is one or a mixture of sodium hydroxide, potassium hydroxide and lithium hydroxide.

2. The method for preparing 2,5-dimethylphenylacetic acid according to claim 1, characterized in that: The cyanation reaction is that 2,5-dimethylbenzoyl chloride and sodium cyanide react in an organic solvent to obtain 2,5-dimethylbenzoyl nitrile.

3. The method for preparing 2,5-dimethylphenylacetic acid according to claim 2, characterized in that: In the cyanation reaction, the molar ratio of 2,5-dimethylbenzoyl chloride to sodium cyanide is 1:1.0-1.

5.

4. The method for preparing 2,5-dimethylphenylacetic acid according to claim 2, characterized in that: In the cyanation reaction, the reaction temperature is 50-100°C.

5. The method for preparing 2,5-dimethylphenylacetic acid according to claim 2, characterized in that: The organic solvent is one or a mixture of acetonitrile, DMF, chloroform, toluene, chlorobenzene, etc.

6. The method for preparing 2,5-dimethylphenylacetic acid according to claim 1, characterized in that: In the reduction hydrolysis reaction, the reaction temperature is 80-130°C.

7. The method for preparing 2,5-dimethylphenylacetic acid according to claim 1, characterized in that: In the reduction hydrolysis reaction, the molar ratio of 2,5-dimethylbenzoyl nitrile to hydrazine hydrate is 1:1.0-2.0, and the molar ratio of 2,5-dimethylbenzoyl nitrile to the base is 1:5.

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