A method for synthesizing 2-chloro-6-nitrotoluene

Abstract

The present invention relates to the field of organic synthesis, and particularly relates to a new method for synthesizing 2-chloro-6-nitrotoluene. The synthesis method of 2-chloro-6-nitrotoluene provided by the present invention uses 2,3-dichloronitrobenzene (Compound 1) as a raw material, reacts with methyl cyanoacetate or dimethyl malonate under the action of a reaction solvent and an acid-binding agent to form Compound 2, and after filtration and decolorization, a dilute acid solution is added for de-esterification reaction to obtain Compound 3. Finally, the R group is removed in a dilute acid solution to obtain the final product 2-chloro-6-nitrotoluene (Compound 4). The synthesis method of 2-chloro-6-nitrotoluene described in the present invention has the advantages of simple operation, safety, economy, environmental friendliness, and low cost.

Description

Technical Field

[0001] The present invention relates to the field of organic synthesis, and particularly to a method for synthesizing 2-chloro-6-nitrotoluene. Background Art

[0002] 2-Chloro-6-nitrotoluene is an important intermediate for pharmaceuticals, pesticides, and dyes, and belongs to high-value-added fine chemical products.

[0003] Currently, the main preparation process routes of 2-chloro-6-nitrotoluene are as follows: (1) Using o-nitrotoluene as a raw material, under the action of a catalyst, chlorine gas is introduced for chlorination to obtain a mixture containing 65% of 2-chloro-6-nitrotoluene, 24% of 4-chloro-2-nitrotoluene, 1% of dichloronitrotoluene, and 10% of o-nitrotoluene. After rectification, 2-chloro-6-nitrotoluene is obtained (References: CN101985425A, CN107473973A); (2) Using o-chlorotoluene as a raw material, nitration is carried out under the action of a catalyst to obtain a mixture containing 11% of 2-chloro-6-nitrotoluene, 19% of 2-chloro-4-nitrotoluene, 13% of 2-chloro-3-nitrotoluene, and 40% of 2-chloro-5-nitrotoluene. After rectification, 2-chloro-6-nitrotoluene is obtained (Reference: Nitration of deactivated aromatic compounds via mechanochemical reaction, By: Wu, Jian-Wei; Zhang, Pu; Guo, Zhi-Xin, Tetrahedron Letters (2021), 72, 153087).

[0004] Upon analysis, both of the above two methods have serious deficiencies. The first method uses chlorine gas as a toxic gas, posing a safety hazard; the catalyst used is expensive and cannot be recycled, resulting in extremely high production costs; the mixture obtained is prone to explosion hazards during rectification at high temperatures. The second method has the problems that the waste acid solution obtained by nitration with nitric acid is difficult to treat, and poly-nitro compounds are obtained during the nitration process, posing a safety hazard and being prone to accidents, which is not conducive to large-scale industrial production and other defects. Summary of the Invention

[0005] In view of the above-mentioned defects existing in the existing preparation methods of 2-chloro-6-nitrotoluene, the present invention provides a new method for synthesizing 2-chloro-6-nitrotoluene. This method has mild reaction conditions, higher production safety, and the raw materials are cheap and easily available. The reaction solvent and dilute acid solution can be recycled and reused multiple times, which can significantly reduce the production cost. Therefore, this method is more suitable for large-scale industrial production.

[0006] The method for synthesizing 2-chloro-6-nitrotoluene provided by the present invention includes:

[0007] (1) Under the action of a reaction solvent and an acid-binding agent, 2,3-dichloronitrobenzene (Compound 1) reacts with Compound A to form Compound 2

[0008] Compound A is methyl cyanoacetate, and R is -CN,

[0009] Compound A is dimethyl malonate, and R is -COOCH3;

[0010] (2) The obtained Compound 2 is de-esterified to obtain Compound 3

[0011] (3) The obtained Compound 3 is de-R group to obtain 2-chloro-6-nitrotoluene (Compound 4)

[0012] The synthesis method of 2-chloro-6-nitrotoluene described in the present invention has the advantages of simple operation, safety, economy, environmental protection, and low cost.

[0013] The synthesis route of the said synthesis method is as follows:

[0014]

[0015] In the above step (1), the reaction temperature is 70 - 180 °C, preferably 100 - 110 °C. Within this temperature range, it can not only ensure the full progress of the reaction, but also avoid the increase of side reactions caused by higher temperature, which is more conducive to improving the product purity and yield.

[0016] In the above step (1), the molar ratio of the feed of 2,3-dichloronitrobenzene (Compound 1) to Compound A is between 1:1.0 - 1.5, preferably 1:1.1 - 1.2. The appropriate excess of Compound A is beneficial to the full reaction of Compound 1 to improve the yield, while avoiding the waste of raw materials.

[0017] In the above step (1), the reaction solvent is selected from one or more of dichloroethane, toluene, 1,3-dimethyl-2-imidazolidinone (DMI), N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), or dimethyl sulfoxide (DMSO); preferably N,N-dimethylformamide (DMF), which has the advantages of low boiling point, easy distillation, low price, and simple post-treatment.

[0018] In the above step (1), the weight ratio of the feed of 2,3-dichloronitrobenzene (Compound 1) to the reaction solvent is between 1:3.0 - 5.0, preferably 1:4.0 - 4.5.

[0019] In the above step (1), the acid-binding agent is selected from one or a mixture of anhydrous sodium carbonate, anhydrous potassium carbonate, triethylamine, pyridine, solid sodium methoxide, solid sodium ethoxide, sodium acetate or potassium acetate. Anhydrous potassium carbonate is preferably selected, which has the advantages of high efficiency, low price and easy storage.

[0020] In the above step (1), the molar ratio of the feed of 2,3-dichloronitrobenzene (Compound 1) to the acid-binding agent is between 1:1.0 and 1.5. It is preferably controlled between 1:1.2 and 1.4, which is more conducive to the full reaction of the raw materials and thus improves the yield. At the same time, it avoids waste of raw materials and reduces costs.

[0021] In the above step (1), the feeding sequence is as follows: 2,3-dichloronitrobenzene is added to the reaction solvent to dissolve, then the acid-binding agent is added, and the temperature is raised to 100-110°C, and then Compound A is slowly added dropwise. By adopting the above feeding method, the influence of the acid-binding agent on the raw material 2,3-dichloronitrobenzene can be avoided, so that 2,3-dichloronitrobenzene can be fully dissolved in the solvent and react fully with Compound A, improving the yield.

[0022] In the above step (1), after the reaction is completed, the temperature is lowered to room temperature, and after filtration and decolorization, degreasing is carried out; the purpose of filtration and decolorization is to remove the remaining acid-binding agent, the generated salts and by-products, and improve the product purity.

[0023] In the above step (2), the reaction temperature for degreasing is 60-120°C, and 80-90°C is preferably selected. Within this temperature range, both the full progress of the reaction can be ensured and the increase in side reactions caused by too high a temperature can be avoided, which is more conducive to improving the product purity and yield.

[0024] In the above step (2), the degreasing is carried out in a dilute acid solution; the acid is one or more of hydrochloric acid, sulfuric acid, acetic acid or formic acid, and dilute sulfuric acid is preferably selected; the mass concentration of the dilute sulfuric acid solution is between 50-95%, and 60-70% is preferably selected. Research shows that by reasonably controlling the mass concentration of the dilute acid solution, it is beneficial to shorten the reaction time, reduce the generation of by-products, and thus improve the product purity and yield, and at the same time improve the production efficiency.

[0025] In the above step (2), the molar ratio of the feed of Compound 2 to the dilute sulfuric acid is between 1:1.0 and 1.5, and 1:1.2-1.3 is preferably selected.

[0026] In the above step (3), the reaction temperature for removing the R group is 60-120°C, and 95-105°C is preferably selected. Within this temperature range, both the full progress of the reaction can be ensured and the increase in side reactions caused by too high a temperature can be avoided, which is more conducive to improving the product purity and yield.

[0027] In the above step (3), the de-R group reaction is carried out in a dilute acid solution; the acid is one or more of hydrochloric acid, sulfuric acid, acetic acid or formic acid, and dilute sulfuric acid is preferably selected, and the mass concentration of the dilute sulfuric acid solution is between 50% and 95%, and preferably 85% - 90%. Research shows that by reasonably controlling the mass concentration of the dilute acid solution, it is beneficial to reduce the reaction time, reduce the generation of by-products, and improve the purity and yield of the product.

[0028] In the above step (3), the feeding molar ratio of the compound 3 to the dilute sulfuric acid solution is between 1:1.2 and 1.8, and preferably 1:1.3 - 1.5.

[0029] As one of the specific embodiments of the present invention, the synthesis method of 2-chloro-6-nitrotoluene includes:

[0030] S1. Add 2,3-dichloronitrobenzene to a reaction solvent, dissolve it, add an acid-binding agent, heat up to 100 - 110 °C, and slowly dropwise add compound A to react to form compound 2; after the reaction is completed, cool down to room temperature, and obtain a mother liquor containing compound 2 after filtration and decolorization treatment;

[0031] S2. Slowly add a dilute acid solution with a mass concentration of 60 - 70% to the obtained mother liquor containing compound 2 under stirring, and slowly heat up to 80 - 90 °C for the de-esterification reaction; after the reaction is completed, distill off the reaction solvent under reduced pressure to obtain a reaction solution containing compound 3;

[0032] S3. Slowly add a dilute acid solution with a mass concentration of 85 - 90% to the reaction solution containing compound 3 after removing the reaction solvent under stirring, and heat up to 95 - 105 °C for the de-R group reaction to obtain the final product.

[0033] The beneficial effects of the present invention are as follows:

[0034] The new method for synthesizing 2-chloro-6-nitrotoluene provided by the present invention has mild reaction conditions, higher production safety, and inexpensive and easily available raw materials. The reaction solvent and dilute acid solution can be recycled and reused multiple times, which can significantly reduce the production cost. Therefore, this method is more suitable for large-scale industrial production. The specific manifestations are as follows:

[0035] (1) During the synthesis process, no toxic gases such as chlorine are used, and the operating temperatures of each reaction treatment are relatively low, and no explosive substances such as polynitro compounds are generated. Therefore, the production process is relatively safer.

[0036] (2) All raw material reagents used in the synthesis process are conventional reagents, no expensive and non-recyclable catalysts are used. At the same time, the acid solution used is dilute acid, and the dosage is relatively small, and it can be recycled and reused multiple times, so the overall production cost is greatly reduced.

[0037] (3) The product obtained by the synthesis method of the present invention has a high yield and purity, meeting the requirements of industrial production. Specific Embodiments

[0038] The following examples are used to illustrate the present invention, but do not limit the scope of the present invention.

[0039] Example 1

[0040] This example provides a synthesis method of 2-chloro-6-nitrotoluene, and the specific steps are as follows:

[0041] (1) In a 2000 ml four-necked flask equipped with a mechanical stirrer, a thermometer, and a condenser, add 192 g (1.0 mol) of 2,3-dichloronitrobenzene and 864 g (4.5 eq) of DMF. After stirring and dissolving, slowly add 193.49 g (1.4 mol) of anhydrous potassium carbonate powder. Heat up to 100 - 110 °C, and slowly dropwise add 118.91 g (1.2 mol) of methyl cyanoacetate. After the addition is complete, keep the temperature for reaction for 2.0 - 3.0 h; after sampling and analyzing that the reaction is complete, cool down to room temperature and filter to obtain the DMF mother liquor;

[0042] (2) Slowly add 182.13 g (1.30 mol) of 70% sulfuric acid solution under stirring, heat up to 80 - 90 °C and keep the temperature for reaction for 2.0 - 3.0 h; after sampling and analyzing that the reaction is complete, cool down to 30 - 40 °C and distill off DMF under reduced pressure;

[0043] (3) Slowly add 163.45 g (1.5 mol) of 90% sulfuric acid solution, heat up to 95 - 105 °C, and keep the temperature for reaction for 5.0 - 6.0 h; after sampling and analyzing that the reaction is complete, dilute to 20% sulfuric acid solution, extract with ethyl acetate, and after decolorization and purification, obtain 170.65 g of a light yellow solid, with a content of 94.26% and a yield of 93.75%.

[0044] Example 2

[0045] This example provides a synthesis method of 2-chloro-6-nitrotoluene, and the specific steps are as follows:

[0046] (1) In a 2000 ml four-necked flask equipped with a mechanical stirrer, a thermometer, and a condenser, add 192 g (1.0 mol) of 2,3-dichloronitrobenzene and 768 g (4.0 eq) of DMF. After stirring and dissolving, slowly add 165.85 g (1.2 mol) of anhydrous potassium carbonate powder. Heat up to 100 - 110 °C, and slowly dropwise add 109.00 g (1.1 mol) of methyl cyanoacetate. After the addition is complete, keep the temperature for reaction for 2.0 - 3.0 h. After sampling and analyzing that the reaction is complete, cool down to room temperature and filter to obtain the DMF mother liquor;

[0047] (2) Slowly add 196.14 g (1.20 mol) of 60% sulfuric acid solution under stirring, heat up to 80 - 90 °C and keep the reaction for 2.0 - 3.0 h. After sampling and analyzing that the reaction is completed, cool down to 30 - 40 °C and remove DMF by vacuum distillation;

[0048] (3) Slowly add 150 g (1.3 mol) of 90% sulfuric acid solution, heat up to 95 - 105 °C, keep the reaction for 5.0 - 6.0 h. After sampling and analyzing that the reaction is completed, dilute it to 20% sulfuric acid solution, extract with ethyl acetate, and after decolorization and purification, obtain 167.89 g of light yellow solid, with a content of 93.69% and a yield of 91.51%.

[0049] Compared with Example 1, in Example 2, due to the relatively small amounts of solvent, acid-binding agent and methyl cyanoacetate in step (1), and the relatively low sulfuric acid concentration and small amount in step (2), the content and yield of the obtained product are reduced to a certain extent.

[0050] Example 3

[0051] This example provides a method for synthesizing 2-chloro-6-nitrotoluene, and the specific steps are as follows:

[0052] (1) In a 2000 ml four-necked flask equipped with a mechanical stirrer, thermometer and condenser, add 192 g (1.0 mol) of 2,3-dichloronitrobenzene and 864 g (4.5 eq) of DMF. After stirring and dissolving, slowly add 148.38 g (1.4 mol) of anhydrous sodium carbonate powder. Heat up to 100 - 110 °C, and slowly dropwise add 118.91 g (1.2 mol) of methyl cyanoacetate. After the addition is completed, keep the reaction for 2.0 - 3.0 h. After sampling and analyzing that the reaction is completed, cool down to room temperature and filter to obtain the DMF mother liquor;

[0053] (2) Slowly add 182.13 g (1.30 mol) of 70% sulfuric acid solution under stirring, heat up to 80 - 90 °C and keep the reaction for 2.0 - 3.0 h. After sampling and analyzing that the reaction is completed, cool down to 30 - 40 °C and remove DMF by vacuum distillation;

[0054] (3) Slowly add 163.45 g (1.5 mol) of 90% sulfuric acid solution, heat up to 95 - 105 °C, keep the reaction for 5.0 - 6.0 h. After sampling and analyzing that the reaction is completed, dilute it to 20% sulfuric acid solution, extract with ethyl acetate, and after decolorization and purification, obtain 165.86 g of light yellow solid, with a content of 92.35% and a yield of 89.27%.

[0055] Compared with Example 1, in step (1) of Example 3, anhydrous sodium carbonate powder is used as the acid-binding agent, and the content and yield of the obtained product are reduced to a certain extent. The reaction effect of sodium carbonate is not as good as that of potassium carbonate, so the content and yield will decrease.

[0056] Example 4

[0057] This example provides a method for synthesizing 2-chloro-6-nitrotoluene, and the specific steps are as follows:

[0058] (1) In a 2000 ml four-necked flask equipped with a mechanical stirrer, a thermometer, and a condenser, add 192 g (1.0 mol) of 2,3-dichloronitrobenzene and 864 g (4.5 eq) of DMF. After stirring and dissolving, slowly add 193.49 g (1.4 mol) of anhydrous potassium carbonate powder. Heat up to 90 - 100 °C, and slowly dropwise add 118.91 g (1.2 mol) of methyl cyanoacetate. After the addition is complete, keep the temperature for reaction for 5.0 - 6.0 h. After sampling and analyzing that the reaction is complete, cool down to room temperature, and perform suction filtration to obtain the DMF mother liquor;

[0059] (2) Slowly add 141.66 g (1.30 mol) of 90% sulfuric acid solution under stirring, heat up to 90 - 100 °C, and keep the temperature for reaction for 2.0 - 3.0 h. After sampling and analyzing that the reaction is complete, cool down to 30 - 40 °C, and perform vacuum distillation to remove DMF;

[0060] (3) Slowly add 141.66 g (1.3 mol) of 90% sulfuric acid solution, heat up to 105 - 115 °C, and keep the temperature for reaction for 4.0 - 5.0 h. After sampling and analyzing that the reaction is complete, dilute it to a 20% sulfuric acid solution, extract with ethyl acetate, and after decolorization and purification, obtain 161.80 g of a light yellow solid, with a content of 85.46% and a yield of 80.59%.

[0061] Compared with Example 1, in Example 4, due to the lower reaction temperature in step (1), the higher sulfuric acid concentration in step (2), and the higher reaction temperature in step (3), the content and yield of the obtained product are significantly reduced.

[0062] Comparative Example

[0063] The process route for producing 2-chloro-6-nitrotoluene according to the existing technology is as follows:

[0064]

[0065] The specific scheme is as follows:

[0066] Comparative Example 1

[0067] In a 100 ml four-necked flask equipped with a mechanical stirrer, a thermometer, and a condenser, 68.57 g (0.5 mol) of o-nitrotoluene was added successively. While stirring, the temperature was slowly raised to between 65 - 70 °C, and 1.37 g (2% of the mass of o-nitrotoluene) of tin oxide was added. Chlorine gas was introduced at a rate of 3.43 g / h (5% of the mass of o-nitrotoluene). When the content of o-nitrotoluene was detected to be around 10%, the reaction was terminated, cooled, quenched with water, and subjected to rectification operation.

[0068] Sampling analysis: 2-chloro-6-nitrotoluene 63.57%, 4-chloro-2-nitrotoluene 23.19%, dichloronitrotoluene 2.53%, o-nitrotoluene 10.05%.

[0069] Comparative Example 2

[0070] In a 100 ml four-necked flask equipped with a mechanical stirrer, a thermometer, and a condenser, 68.57 g (0.5 mol) of o-nitrotoluene and 6.86 g of thionyl chloride (10% of the mass of o-nitrotoluene) were added successively. While stirring, the temperature was slowly raised to between 65 - 70 °C, and 1.37 g (2% of the mass of o-nitrotoluene) of tin oxide was added. Chlorine gas was introduced at a rate of 3.43 g / h (5% of the mass of o-nitrotoluene). When the content of o-nitrotoluene was detected to be around 10%, the reaction was terminated, cooled, quenched with water, and subjected to rectification operation.

[0071] Sampling analysis: 2-chloro-6-nitrotoluene 65.41%, 4-chloro-2-nitrotoluene 22.76%, dichloronitrotoluene 3.97%, o-nitrotoluene 7.50%.

[0072] It can be seen from the experimental operation processes of Comparative Examples 1 and 2 that:

[0073] Although there is a tail gas absorption device, there is still a faint smell of chlorine in the air; the introduction rate of chlorine gas decreases with the increase of reaction time, and it is not easy to control the introduction rate, and thus it is not easy to control the content of dichloro compounds; a large amount of acid-containing wastewater that is difficult to treat will be obtained during the post-treatment quenching and washing with water; therefore, the existing technical process route causes great pressure on environmental protection, production safety, and production cost.

[0074] Compared with the existing technical process route, the present invention overcomes the above defects, has mild reaction conditions, cheap and easily available raw materials, simple operation, and the reaction solvent and dilute acid solution can be recycled and reused multiple times, with low cost, easy environmental protection, and is more suitable for large-scale industrial production.

[0075] Although the present invention has been described in detail above with general descriptions and specific embodiments, modifications or improvements can be made thereto based on the present invention, which will be obvious to those skilled in the art. Therefore, these modifications or improvements made without departing from the spirit of the present invention all fall within the scope of protection claimed by the present invention.

Claims

1. A method for synthesizing 2-chloro-6-nitrotoluene, characterized in that, Comprising: (1) Under the action of a reaction solvent and an acid-binding agent, 2,3-dichloronitrobenzene reacts with compound A to form compound 2 The compound A is methyl cyanoacetate. When the compound A is methyl cyanoacetate, R is -CN. Or the compound A is dimethyl malonate. When the compound A is dimethyl malonate, R is -COOCH3. (2) The obtained compound 2 is de-esterified to obtain compound 3 (3) The resulting compound 3 is de-R-grouped to obtain 2-chloro-6-nitrotoluene 2. The synthesis method according to claim 1, characterized in that, In step (1), the reaction temperature is 70 - 180 °C.

3. The synthesis method according to claim 1, characterized in that, In step (1), the reaction temperature is 100 - 110 °C.

4. The synthesis method according to claim 3, characterized in that, In step (1), the molar ratio of the feed of 2,3 - dichloronitrobenzene to the compound A is 1:1.0 - 1.

5.

5. The synthesis method according to claim 4, characterized in that, In step (1), the molar ratio of the feed of 2,3 - dichloronitrobenzene to the compound A is 1:1.1 - 1.

2.

6. The synthesis method according to claim 5, wherein In step (1), the reaction solvent is selected from one or more mixtures of dichloroethane, toluene, 1,3 - dimethyl - 2 - imidazolidinone, N,N - dimethylformamide, N,N - dimethylacetamide, or dimethyl sulfoxide. The weight ratio of the feed of 2,3 - dichloronitrobenzene to the reaction solvent is 1:3.0 - 5.

0.

7. The synthesis method according to claim 6, characterized in that, In step (1), the reaction solvent is N,N - dimethylformamide. The weight ratio of the feed of 2,3 - dichloronitrobenzene to the reaction solvent is 1:4.0 - 4.

5.

8. The synthesis method according to claim 7, characterized in that, In step (1), the acid - binding agent is selected from one or more mixtures of anhydrous sodium carbonate, anhydrous potassium carbonate, triethylamine, pyridine, solid sodium methoxide, solid sodium ethoxide, sodium acetate, or potassium acetate. The molar ratio of the feed of 2,3 - dichloronitrobenzene to the acid - binding agent is 1:1.0 - 1.

5.

9. The synthesis method according to claim 8, wherein In step (1), the acid - binding agent is anhydrous potassium carbonate. The molar ratio of the feed of 2,3 - dichloronitrobenzene to the acid - binding agent is 1:1.2 - 1.

4.

10. The synthesis method according to claim 9, wherein, In step (2), the reaction temperature for de - esterification is 60 - 120 °C.

11. The synthesis method according to claim 10, characterized in that, In step (2), the reaction temperature for de - esterification is 80 - 90 °C.

12. The synthesis method according to claim 11, characterized in that, In step (2), the de - esterification is carried out in a dilute acid solution. The acid is one or more of hydrochloric acid, sulfuric acid, acetic acid, or formic acid.

13. The synthesis method according to claim 12, wherein The dilute acid solution is a dilute sulfuric acid solution, and the mass concentration of the dilute sulfuric acid solution is 50 - 95%. The molar ratio of the feed of compound 2 to the dilute sulfuric acid is 1:1.0 - 1.

5.

14. The synthesis method according to claim 13, characterized in that, The acid is dilute sulfuric acid, and the mass concentration of its dilute sulfuric acid solution is 60 - 70%. The molar ratio of the feed of compound 2 to the dilute sulfuric acid is 1:1.2 - 1.

3.

15. The synthesis method according to claim 14, wherein In step (3), the reaction temperature for removing the R group is 60 - 120 °C.

16. The synthesis method according to claim 15, characterized in that, In step (3), the reaction temperature for removing the R group is 95 - 105 °C.

17. The synthesis method according to claim 16, wherein In step (3), the removal of the R group from the obtained compound 3 is carried out in a dilute acid solution. The acid is one or more of hydrochloric acid, sulfuric acid, acetic acid, or formic acid.

18. The synthesis method according to claim 17, characterized in that, The dilute acid solution is a dilute sulfuric acid solution, and the mass concentration of the dilute sulfuric acid solution is 50 - 95%. The molar ratio of the feed of compound 3 to the dilute sulfuric acid solution is 1:1.2 - 1.

8.

19. The synthesis method according to claim 18, characterized in that, The acid is dilute sulfuric acid, and the mass concentration of its dilute sulfuric acid solution is 85 - 90%. The molar ratio of the feed of compound 3 to the dilute sulfuric acid solution is 1:1.3 - 1.

5.

20. According to the synthesis method described in claim 1, characterized in that, S1. Add 2,3-dichloronitrobenzene into a reaction solvent. After dissolution, add an acid-binding agent, heat up to 100 - 110 °C, and slowly dropwise add compound A to react to form compound 2. After the reaction is completed, cool down to room temperature, and obtain the mother liquor containing compound 2 after filtration and decolorization treatment. S2. Slowly add a dilute acid solution with a mass concentration of 60 - 70% to the obtained mother liquor containing compound 2 under stirring, and slowly heat up to 80 - 90 °C for an esterification removal reaction. After the reaction is completed, remove the reaction solvent by distillation under reduced pressure to obtain a reaction solution containing compound 3. S3. Slowly add a dilute acid solution with a mass concentration of 85 - 90% to the reaction solution containing compound 3 after removing the reaction solvent under stirring, heat up to 95 - 105 °C for an R-group removal reaction to obtain the final product.

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