A preparation method of 2-trifluoromethyl-4-aminobenzoic acid

Abstract

The present invention provides a method for preparing 2-trifluoromethyl-4-aminobenzoic acid, belonging to the field of pharmaceutical chemical technology. The preparation method uses a mixed reagent of N,N-dimethylformamide and ethylene glycol in a set ratio as an organic solvent, uses 2-trifluoromethyl-4-amino-benzonitrile and caustic soda as raw materials, and heats the mixture to undergo an alcoholysis reaction to generate 2-trifluoromethyl-4-aminobenzoic acid. The present invention provides a mixed organic solvent of DMF-ethylene glycol, which increases the reaction rate of the alcoholysis of 2-trifluoromethyl-4-amino-benzonitrile to 2-trifluoromethyl-4-aminobenzoic acid, while allowing the intermediate state (amide) produced by the reaction to be more thoroughly converted into the target product, 2-trifluoromethyl-4-aminobenzoic acid.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical chemical industry, and particularly relates to a method for preparing 2-trifluoromethyl-4-aminobenzoic acid. Background Art

[0002] Aromatic carboxylic acid compounds play a very important role in the fields of chemistry and biology. For example, 2-trifluoromethyl-4-aminobenzoic acid is widely used in the preparation of medicines, dyes, agricultural pesticides and fungicides.

[0003] The hydrolysis of cyano groups is an important route for preparing amides or carboxylic acids. However, in both acidic and alkaline environments, the hydrolysis product of cyano groups is often a mixture of amides and carboxylic acids, resulting in poor selectivity and slow hydrolysis. To improve the selectivity and reaction rate of cyano group hydrolysis, more stringent hydrolysis conditions are required, such as high concentrations of strong bases, strong acids, high temperatures, or the addition of catalysts. Summary of the Invention

[0004] In view of this, the object of the present invention is to provide a method for preparing 2-trifluoromethyl-4-aminobenzoic acid, aiming to solve at least one technical problem among the background technology.

[0005] The present invention is achieved by: a method for preparing 2-trifluoromethyl-4-aminobenzoic acid, wherein a mixture of N,N-dimethylformamide and ethylene glycol in a predetermined ratio is used as an organic solvent, 2-trifluoromethyl-4-amino-benzonitrile and caustic soda are used as raw materials, and an alcoholysis reaction is performed under alkaline conditions to generate 2-trifluoromethyl-4-aminobenzoic acid. The synthesis route is as follows:

[0006]

[0007] Furthermore, the weight ratio of N,N-dimethylformamide to 2-trifluoromethyl-4-amino-benzonitrile is 2 to 3:1; the weight ratio of ethylene glycol to 2-trifluoromethyl-4-amino-benzonitrile is 0.2 to 0.5:1.

[0008] Furthermore, the weight ratio of N,N-dimethylformamide to 2-trifluoromethyl-4-amino-benzonitrile is 3:1; the weight ratio of ethylene glycol to 2-trifluoromethyl-4-amino-benzonitrile is 0.5:1.

[0009] Furthermore, the reaction temperature of the alcoholysis is 140-150°C.

[0010] Furthermore, the alcoholysis reaction is carried out under anhydrous conditions, and the molar ratio of the 2-trifluoromethyl-4-amino-benzonitrile to the caustic soda (sodium hydroxide) is 1:2.2-3.0, more preferably 1:2.5-3.0.

[0011] Furthermore, the reaction time of the alcoholysis is 5 to 10 hours.

[0012] Furthermore, the preparation method also includes a step of separating 2-trifluoromethyl-4-aminobenzoic acid, specifically: after the reaction is completed, the reaction system is cooled to 30-35°C, diluted with water, and hydrochloric acid is added to adjust the pH to 1-2 to precipitate crystals, which are filtered and dried to obtain the target product 2-trifluoromethyl-4-aminobenzoic acid.

[0013] Compared with the prior art, the present invention has the following beneficial effects:

[0014] 1. The present invention provides N,N-dimethylformamide (DMF)-ethylene glycol as a mixed organic solvent in the cyano substitution reaction, thereby increasing the reaction rate of the alcoholysis of 2-trifluoromethyl-4-amino-benzonitrile to 2-trifluoromethyl-4-aminobenzoic acid, while enabling the intermediate (amide) produced by the reaction to be more thoroughly converted into the target product, 2-trifluoromethyl-4-aminobenzoic acid.

[0015] 2. The method of the present invention has a mild reaction, short time consumption, does not require high temperature or addition of catalyst, is low in cost and has a simple process. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 This is a purity spectrum of 2-trifluoromethyl-4-aminobenzoic acid prepared in the present invention;

[0017] Figure 2 The HNMR spectrum of 2-trifluoromethyl-4-aminobenzoic acid prepared in the present invention is shown in FIG. DETAILED DESCRIPTION

[0018] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific implementation cases described herein are only used to explain the present invention and are not intended to limit the present invention.

[0019] Example 1

[0020] The preparation method of 2-trifluoromethyl-4-aminobenzoic acid comprises the following steps:

[0021] (1) 100 g (0.537 mol) of 2-trifluoromethyl-4-amino-benzonitrile, 53.7 g (1.34 mol, 2.5 eq.) of caustic soda, and 300 g of DMF were placed in a reaction kettle. 50 g of ethylene glycol was then added under stirring. The temperature was raised to 150° C. and the mixture was kept warm for 7 hours.

[0022] (2) After TLC detection, the starting material was almost gone, and the temperature was lowered to 30-35°C, diluted with water, and adjusted to pH 1-2 with hydrochloric acid. The mixture was filtered and dried to obtain the target product, 2-trifluoromethyl-4-aminobenzoic acid, with a yield of 93.2% and a purity of ≥99.5%.

[0023] The purity spectrum and HNMR spectrum of the target product 2-trifluoromethyl-4-aminobenzoic acid are as follows: Figure 1 and Figure 2 shown.

[0024] Example 2

[0025] The preparation method of 2-trifluoromethyl-4-aminobenzoic acid comprises the following steps:

[0026] (1) 100 g (0.537 mol) of 2-trifluoromethyl-4-amino-benzonitrile, 53.7 g (1.34 mol, 2.5 eq.) of caustic soda, and 300 g of DMF were placed in a reaction kettle. 40 g of ethylene glycol was then added under stirring. The temperature was raised to 150° C. and the reaction was maintained at this temperature for 7 hours. TLC detection revealed a small amount of unreacted intermediate.

[0027] (2) Cooling to 30-35°C, adding water to dilute, adding hydrochloric acid to adjust the pH to 1-2, filtering, and drying to obtain the dry product, which is the target product 2-trifluoromethyl-4-aminobenzoic acid, with a yield of 94.1% and a purity of ≥97.5%.

[0028] If the insulation reaction in step (1) of this embodiment is extended to 8 hours and step (2) is repeated, the target product 2-trifluoromethyl-4-aminobenzoic acid has a yield of 93.8% and a purity of ≥98.8%.

[0029] Example 3

[0030] The preparation method of 2-trifluoromethyl-4-aminobenzoic acid comprises the following steps:

[0031] (1) 100 g (0.537 mol) of 2-trifluoromethyl-4-amino-benzonitrile, 53.7 g (1.34 mol, 2.5 eq.) of caustic soda and 300 g of DMF were placed in a reaction kettle. 30 g of ethylene glycol was then added under stirring. The temperature was raised to 150° C. and the mixture was kept warm for 7 hours. TLC analysis revealed that an intermediate state had not been completely reacted.

[0032] (2) Cooling to 30-35°C, adding water to dilute, adding hydrochloric acid to adjust the pH to 1-2, filtering, and drying to obtain the dry product, which is the target product 2-trifluoromethyl-4-aminobenzoic acid, with a yield of 94.8% and a purity of ≥94.7%.

[0033] If the insulation reaction in step (1) of this embodiment is increased to 9 hours and step (2) is repeated, the target product 2-trifluoromethyl-4-aminobenzoic acid has a yield of 93.1% and a purity of ≥99.3%.

[0034] Example 4

[0035] The preparation method of 2-trifluoromethyl-4-aminobenzoic acid comprises the following steps:

[0036] (1) 100 g (0.537 mol) of 2-trifluoromethyl-4-amino-benzonitrile, 53.7 g (1.34 mol, 2.5 eq.) of caustic soda and 300 g of DMF were placed in a reaction kettle. 20 g of ethylene glycol was then added under stirring. The temperature was raised to 150° C. and the mixture was kept warm for 7 hours. TLC analysis revealed that an intermediate state had not been completely reacted.

[0037] (2) Cooling to 30-35°C, adding water to dilute, adding hydrochloric acid to adjust the pH to 1-2, filtering, and drying to obtain the dry product, which is the target product 2-trifluoromethyl-4-aminobenzoic acid, with a yield of 95.2% and a purity of ≥91.7%.

[0038] If the insulation reaction in step (1) of this embodiment is extended to 10 hours and step (2) is repeated, the target product 2-trifluoromethyl-4-aminobenzoic acid has a yield of 93.3% and a purity of ≥99.1%.

[0039] Example 5

[0040] The preparation method of 2-trifluoromethyl-4-aminobenzoic acid comprises the following steps:

[0041] (1) 100 g (0.537 mol) of 2-trifluoromethyl-4-amino-benzonitrile, 53.7 g (1.34 mol, 2.5 eq.) of caustic soda, and 300 g of DMF were placed in a reaction kettle. 60 g of ethylene glycol was then added under stirring. The temperature was raised to 150° C. and the mixture was kept warm for 7 hours.

[0042] (2) After TLC detection, the starting material was almost gone, and the temperature was lowered to 30-35°C, diluted with water, and adjusted to pH 1-2 with hydrochloric acid. The mixture was filtered and dried to obtain the target product, 2-trifluoromethyl-4-aminobenzoic acid, with a yield of 93.4% and a purity of ≥99.6%.

[0043] Example 6

[0044] The preparation method of 2-trifluoromethyl-4-aminobenzoic acid comprises the following steps:

[0045] (1) 100 g (0.537 mol) of 2-trifluoromethyl-4-amino-benzonitrile, 53.7 g (1.34 mol, 2.5 eq.) of caustic soda, and 250 g of DMF were placed in a reactor. 50 g of ethylene glycol was then added under stirring. The temperature was raised to 150° C. and the reaction was maintained at this temperature for 7 hours. TLC detection revealed a small amount of unreacted intermediate.

[0046] (2) Cool to 30-35°C, add water to dilute, add hydrochloric acid to adjust the pH to 1-2, filter, and dry to obtain the target product, 2-trifluoromethyl-4-aminobenzoic acid, with a yield of 92.8% and a purity of ≥97.8%.

[0047] If the insulation reaction in step (1) of this embodiment is increased to 8.5 hours and step (2) is repeated, the target product 2-trifluoromethyl-4-aminobenzoic acid has a yield of 93.2% and a purity of ≥99.3%.

[0048] Example 7

[0049] The preparation method of 2-trifluoromethyl-4-aminobenzoic acid comprises the following steps:

[0050] (1) 100 g (0.537 mol) of 2-trifluoromethyl-4-amino-benzonitrile, 53.7 g (1.34 mol, 2.5 eq.) of caustic soda, and 200 g of DMF were placed in a reaction kettle. 50 g of ethylene glycol was then added under stirring. The temperature was raised to 150° C. and the reaction was maintained at this temperature for 7 hours. TLC detection revealed a small amount of unreacted intermediate.

[0051] (2) Cooling to 30-35°C, adding water to dilute, adding hydrochloric acid to adjust the pH to 1-2, filtering, and drying to obtain the dry product, which is the target product 2-trifluoromethyl-4-aminobenzoic acid, with a yield of 92.2% and a purity of ≥97.5%.

[0052] If the insulation reaction in step (1) of this embodiment is extended to 10 hours and step (2) is repeated, the target product 2-trifluoromethyl-4-aminobenzoic acid has a yield of 93.0% and a purity of ≥99.1%.

[0053] Example 8

[0054] The preparation method of 2-trifluoromethyl-4-aminobenzoic acid comprises the following steps:

[0055] (1) 100 g (0.537 mol) of 2-trifluoromethyl-4-amino-benzonitrile, 53.7 g (1.34 mol, 2.5 eq.) of caustic soda, and 350 g of DMF were placed in a reaction kettle. 50 g of ethylene glycol was then added under stirring. The temperature was raised to 150° C. and the mixture was kept warm for 7 hours.

[0056] (2) After TLC detection, the starting material was almost gone, and the temperature was lowered to 30-35°C, diluted with water, and adjusted to pH 1-2 with hydrochloric acid. The mixture was filtered and dried to obtain the target product, 2-trifluoromethyl-4-aminobenzoic acid, with a yield of 93.3% and a purity of ≥99.7%.

[0057] Example 9

[0058] The preparation method of 2-trifluoromethyl-4-aminobenzoic acid comprises the following steps:

[0059] (1) 100 g (0.537 mol) of 2-trifluoromethyl-4-amino-benzonitrile, 43.0 g (1.07 mol, 2.0 eq.) of caustic soda, and 300 g of DMF were placed in a reaction kettle. 50 g of ethylene glycol was then added under stirring. The temperature was raised to 150° C. and the mixture was kept warm for 7 hours.

[0060] (2) After TLC detection, the starting material was almost gone, and the temperature was lowered to 30-35°C, diluted with water, and adjusted to pH 1-2 with hydrochloric acid. The mixture was filtered and dried to obtain the target product, 2-trifluoromethyl-4-aminobenzoic acid, with a yield of 90.5% and a purity of ≥99.7%.

[0061] Example 10

[0062] The preparation method of 2-trifluoromethyl-4-aminobenzoic acid comprises the following steps:

[0063] (1) 100 g (0.537 mol) of 2-trifluoromethyl-4-amino-benzonitrile, 47.3 g (1.18 mol, 2.2 eq.) of caustic soda flakes, and 300 g of DMF were placed in a reaction kettle. 50 g of ethylene glycol was then added under stirring. The temperature was raised to 150° C. and the mixture was kept warm for 7 hours.

[0064] (2) After TLC detection, the starting material was almost gone, and the temperature was lowered to 30-35°C, diluted with water, and adjusted to pH 1-2 with hydrochloric acid. The mixture was filtered and dried to obtain the target product, 2-trifluoromethyl-4-aminobenzoic acid, with a yield of 92.6% and a purity of ≥99.6%.

[0065] Example 11

[0066] The preparation method of 2-trifluoromethyl-4-aminobenzoic acid comprises the following steps:

[0067] (1) 100 g (0.537 mol) of 2-trifluoromethyl-4-amino-benzonitrile, 64.5 g (1.34 mol, 3.0 eq.) of caustic soda, and 300 g of DMF were placed in a reaction kettle. 50 g of ethylene glycol was then added under stirring. The temperature was raised to 150° C. and the mixture was kept warm for 7 hours.

[0068] (2) After TLC detection, the starting material was almost gone, and the temperature was lowered to 30-35°C, diluted with water, and adjusted to pH 1-2 with hydrochloric acid. The mixture was filtered and dried to obtain the target product, 2-trifluoromethyl-4-aminobenzoic acid, with a yield of 93.5% and a purity of ≥99.1%.

[0069] Example 12

[0070] The preparation method of 2-trifluoromethyl-4-aminobenzoic acid comprises the following steps:

[0071] (1) 100 g (0.537 mol) of 2-trifluoromethyl-4-amino-benzonitrile, 66.6 g (1.66 mol, 3.1 eq.) of caustic soda flakes, and 300 g of DMF were placed in a reaction kettle. 50 g of ethylene glycol was then added under stirring. The temperature was raised to 150° C. and the mixture was kept warm for 7 hours.

[0072] (2) After TLC detection, the starting material was almost gone, and the temperature was lowered to 30-35°C, diluted with water, and adjusted to pH 1-2 with hydrochloric acid. The mixture was filtered and dried to obtain the target product, 2-trifluoromethyl-4-aminobenzoic acid, with a yield of 93.5% and a purity of ≥98.4%.

[0073] Example 13

[0074] The preparation method of 2-trifluoromethyl-4-aminobenzoic acid comprises the following steps:

[0075] (1) 100 g (0.537 mol) of 2-trifluoromethyl-4-amino-benzonitrile, 66.6 g (1.66 mol, 3.1 eq.) of caustic soda flakes, and 300 g of DMF were placed in a reaction kettle. 50 g of ethylene glycol was then added under stirring. The temperature was raised to 145° C. and the mixture was kept warm for 7 hours.

[0076] (2) After TLC detection, the starting material was almost gone, and the temperature was lowered to 30-35°C, diluted with water, and the pH was adjusted to 1-2 with hydrochloric acid. The mixture was filtered and dried to obtain the target product, 2-trifluoromethyl-4-aminobenzoic acid, with a yield of 92.9% and a purity of ≥99.1%.

[0077] Example 14

[0078] The preparation method of 2-trifluoromethyl-4-aminobenzoic acid comprises the following steps:

[0079] (1) 100 g (0.537 mol) of 2-trifluoromethyl-4-amino-benzonitrile, 66.6 g (1.66 mol, 3.1 eq.) of caustic soda, and 300 g of DMF were placed in a reaction kettle. 50 g of ethylene glycol was then added under stirring. The temperature was raised to 140° C. and the mixture was kept warm for 7 hours.

[0080] (2) After TLC detection, the starting material was almost gone, and the temperature was lowered to 30-35°C, diluted with water, and adjusted to pH 1-2 with hydrochloric acid. The mixture was filtered and dried to obtain the target product, 2-trifluoromethyl-4-aminobenzoic acid, with a yield of 92.5% and a purity of ≥98.5%.

[0081] Example 15

[0082] The preparation method of 2-trifluoromethyl-4-aminobenzoic acid comprises the following steps:

[0083] (1) 100 g (0.537 mol) of 2-trifluoromethyl-4-amino-benzonitrile, 66.6 g (1.66 mol, 3.1 eq.) of caustic soda flakes, and 300 g of DMF were placed in a reaction kettle. 50 g of ethylene glycol was then added under stirring. The temperature was raised to 130° C. and the mixture was kept warm for 7 hours.

[0084] (2) After TLC detection, the starting material was almost gone, and the temperature was lowered to 30-35°C, diluted with water, and adjusted to pH 1-2 with hydrochloric acid. The mixture was filtered and dried to obtain the target product, 2-trifluoromethyl-4-aminobenzoic acid, with a yield of 90.5% and a purity of ≥96.6%.

[0085] Example 16

[0086] The preparation method of 2-trifluoromethyl-4-aminobenzoic acid comprises the following steps:

[0087] (1) 100 g (0.537 mol) of 2-trifluoromethyl-4-amino-benzonitrile, 66.6 g (1.66 mol, 3.1 eq.) of caustic soda flakes, and 300 g of DMF were placed in a reaction kettle. 50 g of ethylene glycol was then added under stirring. The temperature was raised to 155° C. and the mixture was kept warm for 7 hours.

[0088] (2) After TLC detection, the starting material was almost gone, and the temperature was lowered to 30-35°C, diluted with water, and adjusted to pH 1-2 with hydrochloric acid. The mixture was filtered and dried to obtain the target product, 2-trifluoromethyl-4-aminobenzoic acid, with a yield of 93.2% and a purity of ≥99.6%.

[0089] Comparative Example 1

[0090] The preparation method of 2-trifluoromethyl-4-aminobenzoic acid comprises the following steps:

[0091] 100 g (0.537 mol) of 2-trifluoromethyl-4-amino-benzonitrile, 54 g (1.35 mol, 2.5 eq.) of caustic soda and 300 g of DMF were added to a reaction kettle, the temperature was raised to 150° C., and the mixture was kept at this temperature for 10 hours.

[0092] TLC detection showed that the raw material and intermediates were not completely reacted. The temperature was lowered to 30-35° C., diluted with water, and adjusted to pH 1-2 with hydrochloric acid. The mixture was filtered and dried to obtain the target product, 2-trifluoromethyl-4-aminobenzoic acid. The yield was 90.2% and the purity was ≥85.5%.

[0093] Comparative Example 2

[0094] The preparation method of 2-trifluoromethyl-4-aminobenzoic acid comprises the following steps:

[0095] 100 g (0.537 mol) of 2-trifluoromethyl-4-amino-benzonitrile, 54 g (1.35 mol, 2.5 eq.) of caustic soda and 300 g of DMF were added to a reaction kettle, the temperature was raised to 160° C., and the mixture was kept warm for 10 hours.

[0096] TLC detection showed that the raw material and intermediates were not completely reacted. The temperature was lowered to 30-35° C., diluted with water, and adjusted to pH 1-2 with hydrochloric acid. The mixture was filtered and dried to obtain the target product, 2-trifluoromethyl-4-aminobenzoic acid. The yield was 90.8% and the purity was ≥88.5%.

[0097] Comparative Example 3

[0098] The preparation method of 2-trifluoromethyl-4-aminobenzoic acid comprises the following steps:

[0099] 100 g (0.537 mol) of 2-trifluoromethyl-4-amino-benzonitrile, 54 g (1.35 mol, 2.5 eq.) of caustic soda and 300 g of ethylene glycol were added to the reaction kettle, the temperature was raised to 150° C., and the reaction was carried out at this temperature for 10 hours.

[0100] TLC detection showed that there were unreacted raw materials and intermediates. The temperature was lowered to 30-35° C., diluted with water, and adjusted to pH 1-2 with hydrochloric acid. The mixture was filtered and dried to obtain the target product, 2-trifluoromethyl-4-aminobenzoic acid. The yield was 90.8% and the purity was ≥93.5%.

[0101] Comparative Example 4

[0102] The preparation method of 2-trifluoromethyl-4-aminobenzoic acid comprises the following steps:

[0103] 100 g (0.537 mol) of 2-trifluoromethyl-4-amino-benzonitrile, 54 g (1.35 mol, 2.5 eq.) of caustic soda and 300 g of water were added to the reactor, the temperature was raised to 200° C., and the reaction was carried out at this temperature for 12 hours.

[0104] TLC detection showed that a large amount of raw materials and intermediates had not reacted completely. The temperature was lowered to 30-35° C., diluted with water, and adjusted to pH 1-2 with hydrochloric acid. The mixture was filtered and dried to obtain the target product, 2-trifluoromethyl-4-aminobenzoic acid. The yield was 72.2% and the purity was ≥76.5%.

[0105] The reaction parameters and product characterizations of Examples 1 to 16 and Comparative Examples 1 to 4 are shown in Table 1 below.

[0106] Table 1 Reaction parameters and product characterization

[0107]

[0108]

[0109] Comparison of Examples 1 to 5 shows that in a DMF-ethylene glycol mixed solvent, ethylene glycol can promote the conversion of the intermediate to the target product. As the ethylene glycol content increases, the reaction rate of the alcoholysis of the cyano group to the carboxylic acid increases. When the ethylene glycol content increases above 0.5 W, its promoting effect on the reaction rate does not significantly increase. Therefore, the ethylene glycol content is set to 0.2 W to 0.5 W (based on the mass of the raw material 2-trifluoromethyl-4-amino-benzonitrile). When the ethylene glycol content is low, the reaction time needs to be increased to facilitate the conversion of the intermediate to the target product.

[0110] From the comparison of Example 1 and Examples 5 to 8, it can be seen that the alcoholysis efficiency of 2-trifluoromethyl-4-amino-benzonitrile can be promoted in the DMF-ethylene glycol mixed solvent because it has good solubility in DMF; as the DMF content increases, the solubility of 2-trifluoromethyl-4-amino-benzonitrile increases, promoting the alcoholysis of cyano group to carboxylic acid. When the DMF content increases to more than 3W, its promoting effect on the alcoholysis reaction does not increase significantly, so the DMF content is set to 2W~3W (based on the mass of the raw material 2-trifluoromethyl-4-amino-benzonitrile).

[0111] From the comparison of Example 1 and Examples 9 to 12, it can be seen that the change in the dosage of caustic soda affects the yield and purity of the target product. The theoretical amount of caustic soda is 2 times the molar number of 2-trifluoromethyl-4-amino-benzonitrile. In practical applications, the amount of caustic soda added should be higher than the theoretical amount, at least 2.2 times or more. As the amount of caustic soda increases, the yield of the target product increases; however, when the amount of caustic soda increases to three times the molar number of 2-trifluoromethyl-4-amino-benzonitrile, it continues to increase and the yield remains basically unchanged.

[0112] From the comparison of Example 1 and Examples 13 to 16, it can be seen that the change in reaction temperature affects the yield and purity of the target product. As the reaction temperature increases, the yield and purity of the target product increase; however, when the reaction temperature reaches 150°C, continuing to increase the reaction temperature, the yield and purity remain basically unchanged, but the energy consumption cost increases.

[0113] Comparison of Example 1 with Comparative Examples 1 to 4 shows that although using DMF or ethylene glycol alone as an organic solvent has a certain promoting effect on the alcoholysis efficiency, the effect is not obvious, and the purity of the target product is less than 90%.

[0114] The above-described embodiments merely illustrate several implementations of the present invention, and while their descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that a person skilled in the art would be able to make numerous variations and improvements without departing from the spirit of the present invention, all of which fall within the scope of protection of the present invention. Therefore, the scope of protection of the present invention shall be determined by the appended claims.

Claims

1. A method for preparing 2-trifluoromethyl-4-aminobenzoic acid, characterized in that: The preparation method uses a mixed reagent of N,N-dimethylformamide and ethylene glycol in a set ratio as an organic solvent, 2-trifluoromethyl-4-amino-benzonitrile and caustic soda as raw materials, and heats the mixture to undergo an alcoholysis reaction to produce 2-trifluoromethyl-4-aminobenzoic acid; the alcoholysis reaction is carried out under anhydrous conditions; The weight ratio of N,N-dimethylformamide to 2-trifluoromethyl-4-amino-benzonitrile is 2 to 3:1; the weight ratio of ethylene glycol to 2-trifluoromethyl-4-amino-benzonitrile is 0.2 to 0.5:1; The molar ratio of the 2-trifluoromethyl-4-amino-benzonitrile to the caustic soda is 1:2.2-3.

0.

2. The method for preparing 2-trifluoromethyl-4-aminobenzoic acid according to claim 1, wherein The weight ratio of N,N-dimethylformamide to 2-trifluoromethyl-4-amino-benzonitrile is 3:1; the weight ratio of ethylene glycol to 2-trifluoromethyl-4-amino-benzonitrile is 0.5:

1.

3. The method for preparing 2-trifluoromethyl-4-aminobenzoic acid according to claim 1, wherein The reaction temperature of the alcoholysis is 140-150°C.

4. The method for preparing 2-trifluoromethyl-4-aminobenzoic acid according to claim 1, wherein The molar ratio of the 2-trifluoromethyl-4-amino-benzonitrile to the caustic soda is 1:2.5-3.

0.

5. The method for preparing 2-trifluoromethyl-4-aminobenzoic acid according to claim 1, wherein The reaction time of the alcoholysis is 5 to 10 hours.

6. The method for preparing 2-trifluoromethyl-4-aminobenzoic acid according to claim 1, wherein The preparation method also includes a step of separating 2-trifluoromethyl-4-aminobenzoic acid, specifically, after the reaction is completed, cooling the reaction system to 30-35° C., adding water to dilute, adding hydrochloric acid to adjust the pH to 1-2 to precipitate crystals, filtering and drying to obtain the target product 2-trifluoromethyl-4-aminobenzoic acid.

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