Method for synthesizing methyl anisate through tandem methylation reaction with participation of dimethyl carbonate

Abstract

The invention discloses a method for synthesizing methyl anisate through a tandem methylation reaction with participation of dimethyl carbonate, and belongs to the technical field of organic synthesis catalysis. The method comprises the following steps: reacting p-hydroxybenzoic acid and dimethyl carbonate under the action of a composite catalytic system consisting of organic amine, alkyl halide and a stabilizer to obtain methyl anisate; and carrying out methylation reaction and methyl esterification reaction to generate methyl anisate. According to the method, an environment-friendly emerging green chemical raw material dimethyl carbonate is adopted as a methylation reagent, so that the generation of three wastes is reduced, the efficiency of a catalytic system is high, the atom utilization rate of dimethyl carbonate is effectively improved, and one-step synthesis of methyl anisate can be efficiently realized.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis catalysis, and specifically relates to a method for synthesizing methyl anisate by a tandem methylation reaction involving dimethyl carbonate. Background Art

[0002] Methyl anisate (or methyl p-methoxybenzoate) is a commonly used food flavor and an important pharmaceutical intermediate. Traditional synthesis methods mostly use dimethyl sulfate as the methylation reagent to synthesize methyl anisate. In this process, a large amount of strong base substances such as sodium hydroxide are used, and high-salt wastewater will be generated. There are defects such as equipment corrosion, high three wastes, complex process, poor safety, and low efficiency. It is urgent to develop a safe, green and efficient process to solve the existing problems.

[0003] Dimethyl carbonate is a new type of green chemical raw material with low pollution and environmental friendliness. During the process of using it as a methylation reagent to react with p-hydroxybenzoic acid to synthesize methyl anisate, no wastewater is generated, equipment corrosion can be avoided, it conforms to atom economy, is harmless to the environment, non-toxic and pollution-free, so it has received wide attention. However, the reaction conditions of using dimethyl carbonate as a methylation reagent are harsh and often need to be carried out under high temperature and high pressure. Moreover, due to the special nature of the p-hydroxybenzoic acid substrate, it is extremely easy to decarboxylate at high temperature to produce a large amount of phenol by-products, resulting in a significant decrease in reaction efficiency and an increase in subsequent separation difficulty. Therefore, developing a medium and low temperature catalytic system for synthesizing methyl anisate using dimethyl carbonate as a methylation reagent has important industrial application significance. Summary of the Invention

[0004] To overcome the problem that the reaction system temperature is relatively high when using dimethyl carbonate as a methylation reagent in the prior art, which will cause irreversible decarboxylation of the raw material p-hydroxybenzoic acid to generate a large amount of phenol by-products during the synthesis of methyl anisate, the purpose of the present invention is to provide a method for synthesizing methyl anisate by a tandem methylation reaction involving dimethyl carbonate. Under the catalytic system, using dimethyl carbonate as a methylation reagent, two tandem methylation reactions of p-hydroxybenzoic acid are efficiently completed to synthesize methyl anisate. This catalytic system has high catalytic efficiency and high atom utilization rate, can simplify the production process of methyl anisate, and significantly reduce the generation of three wastes, having the prospect of large-scale application in industry.

[0005] To achieve the above purpose, the present invention is realized through the following technical solutions: A method for synthesizing methyl anisate by a tandem methylation reaction involving dimethyl carbonate, comprising the following steps: Subject p-hydroxybenzoic acid and dimethyl carbonate to a combined catalytic system composed of an organic amine, an alkyl halide, and a stabilizer to carry out a methylation reaction and a methyl esterification reaction to generate methyl anisate.

[0006] A further improvement of the present invention lies in that the organic amine includes one of 1,8-diazabicyclo[5,4,0]undec-7-ene, 1,4-diazabicyclo[2.2.2]octane, 4-dimethylaminopyridine, DBN (1,5-diazabicyclo[4.3.0]-5-nonene, 1,5,7-triazabicyclo[4.4.0]dec-5-ene, N,N-dimethylbenzylamine, 4-tert-butylpyridine, 2,2'-bipyridine, 4,4'-di-tert-butyl-2,2'-bipyridine, 5,5'-diamino-2,2'-bipyridine, 1,10-phenanthroline and 2,9-dimethyl-1,10-phenanthroline).

[0007] A further improvement of the present invention lies in that the alkyl halide includes one of 1-bromobutane, 1-bromopentane, 1-bromohexane, 1-bromododecane, 1-bromohexadecane, 1-chlorobutane, 1-chloropentane, 1-chlorohexane, 1-chlorododecane and 1-chlorohexadecane.

[0008] A further improvement of the present invention lies in that the stabilizer includes one or more of 2,2,6,6-tetramethylpiperidine-n-oxide, 4-hydroxy-2,2,6,6-tetramethylpiperidine-n-oxide, 1,1-diphenyl-2-trinitrophenylhydrazine, 2,6-di-tert-butyl-p-cresol and p-benzoquinone.

[0009] A further improvement of the present invention lies in that the molar ratio of dimethyl carbonate to p-hydroxybenzoic acid is 1.0 - 5.0:1.0.

[0010] A further improvement of the present invention lies in that the molar ratio of the organic amine to the p-hydroxybenzoic acid is 0.01 - 0.5:1.0.

[0011] A further improvement of the present invention lies in that the molar ratio of the alkyl halide to the p-hydroxybenzoic acid is 0.01 - 1.0:1.0.

[0012] A further improvement of the present invention lies in that the molar ratio of the stabilizer to the p-hydroxybenzoic acid is 0.005 - 0.05:1.0.

[0013] A further improvement of the present invention lies in that the temperature of the methyl etherification reaction is 80°C - 130°C, the time is 1 - 5 h, and the pressure is 3.0 - 5.0 MPa.

[0014] A further improvement of the present invention lies in that the temperature of the methyl esterification reaction is 130°C - 180°C, the time is 1 - 10 h, and the pressure is 3.0 - 5.0 MPa.

[0015] The beneficial effects of the present invention compared with the prior art are as follows: In the present invention, a method for synthesizing methyl anisate by a one-step method using p-hydroxybenzoic acid and dimethyl carbonate as raw materials. Dimethyl carbonate is used as a methylation reagent to replace the traditional dimethyl sulfate. Dimethyl carbonate serves as both a reactant and a solvent, reducing the raw material cost from the source and eliminating the generation of three wastes. On the other hand, the present invention changes the traditional basic reaction system of methylation reaction. A sterically hindered organic amine and an alkyl halide are used to in-situ react to generate a predominantly neutral organic amine salt as the main catalyst, changing the activation mode of substrate functional groups, enhancing the reaction selectivity and adaptability of the substrate. At the same time, a stabilizer represented by a radical blocker is used as a co-catalyst to further enhance the reaction stability of the substrate. The neutral reaction environment, medium and low temperature reaction system, and catalytic amount of stabilizer jointly enhance the reaction stability of the substrate, solving the problem of substrate decarboxylation. Under the action of this catalytic system, p-hydroxybenzoic acid and dimethyl carbonate continuously undergo two methylation reactions to generate methyl anisate. The reaction conditions are mild, the catalytic system has excellent performance, and the atom utilization rate is high. It is a green, safe and efficient method for synthesizing methyl anisate. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 It is a reaction mechanism diagram speculated based on reaction raw materials and products (the organic amine is taken as DBU for example). DETAILED DESCRIPTION OF THE INVENTION

[0017] To facilitate the understanding of the present invention, the present invention will be described more comprehensively below with reference to the relevant drawings. The preferred embodiments of the present invention are shown in the drawings. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the disclosure of the present invention more thorough and comprehensive.

[0018] A method for synthesizing methyl anisate by a tandem methylation reaction involving dimethyl carbonate provided by the present invention uses p-hydroxybenzoic acid as a raw material and dimethyl carbonate as a methylation reagent and a solvent. Through the action of a composite catalytic system composed of a sterically hindered organic amine, an alkyl halide and a stabilizer, and under the condition of segmented heating, two tandem methylation reactions of methoxylation and methylation occur by a "one-pot method" to generate methyl anisate. The reaction is carried out in a high-pressure reaction kettle equipped with a coil heat exchanger, a back pressure valve and an exhaust port. The specific steps are as follows: Steps such as ingredient preparation, inert gas replacement, stepwise temperature rise reaction, and cooling detection are as follows: First, under stirring, dimethyl carbonate, a large steric hindrance amine (i.e., organic amine), alkyl halide, stabilizer, and p-hydroxybenzoic acid in a quantitative ratio are successively added to the reaction kettle. Subsequently, the reaction kettle is closed. After nitrogen replacement, the cooling water is turned on. The reaction temperature is selected for two-stage temperature rise heating reaction. The gas generated during the reaction is discharged through the condenser and back pressure valve. After the reaction is completed, the residual gas in the kettle is discharged. Finally, the liquid chromatography is used to detect the content of each component, and the conversion rate of p-hydroxybenzoic acid and the selectivity of methyl anisate are calculated.

[0019] The large steric hindrance organic amine compounds include one of DBU (1,8-diazabicyclo[5,4,0]undec-7-ene), DABCO (1,4-diazabicyclo[2.2.2]octane), DMAP (4-dimethylaminopyridine), DBN (1,5-diazabicyclo[4.3.0]-5-nonene), TBD (1,5,7-triazabicyclo[4.4.0]dec-5-ene), BDMA (N,N-dimethylbenzylamine), 4-tert-butylpyridine, 2,2'-bipyridine, 4,4'-di-tert-butyl-2,2'-bipyridine, 5,5'-diamino-2,2'-bipyridine, 1,10-phenanthroline, and 2,9-dimethyl-1,10-phenanthroline.

[0020] The alkyl halide includes one of 1-bromobutane, 1-bromopentane, 1-bromohexane, 1-bromododecane, 1-bromohexadecane, 1-chlorobutane, 1-chloropentane, 1-chlorohexane, 1-chlorododecane, and 1-chlorohexadecane.

[0021] The stabilizer includes one or several of TEMPO (2,2,6,6-tetramethylpiperidine-n-oxide), 4-hydroxy-TEMPO (4-hydroxy-2,2,6,6-tetramethylpiperidine-n-oxide), DPPH (1,1-diphenyl-2-picrylhydrazyl), BHT (2,6-di-tert-butyl-p-cresol), and PBQ (p-benzoquinone).

[0022] p-Hydroxybenzoic acid, dimethyl carbonate, and the composite catalyst are fed in a quantitative ratio. The molar ratio of dimethyl carbonate to p-hydroxybenzoic acid in the feed is 1.0 - 5.0:1.0; the molar ratio of the large steric hindrance organic amine to p-hydroxybenzoic acid is 0.01 - 0.5:1.0; the molar ratio of the alkyl halide to p-hydroxybenzoic acid is 0.01 - 1.0:1.0; the molar ratio of the stabilizer to p-hydroxybenzoic acid is 0.005 - 0.05:1.0.

[0023] The reaction is carried out by staged heating. The reaction temperature in the first stage is 80°C to 130°C, and the reaction temperature in the second stage is 130°C to 180°C; the reaction time in the first stage is 1 to 5 h, and the reaction time in the second stage is 1 to 10 h.

[0024] The reaction is carried out under constant pressure, and the constant pressure is 3.0 to 5.0 MPa.

[0025] See Figure 1 , the reaction mechanism of the present invention is as follows: Based on the speculation of the reaction raw materials, products and some intermediates, the reaction involved in the present invention may experience a process such as Figure 1 . Specifically, it undergoes 5 basic steps: The first step is that an organic amine (taking DBU as an example) and an alkyl halide in-situ generate an organic amine salt under heating conditions; the second step is that the phenolic hydroxyl group of the organic amine salt activates the phenolic hydroxyl group of p-hydroxybenzoic acid, promoting the phenolic hydroxyl group of the chelate intermediate to undergo a nucleophilic attack on the terminal methyl group of dimethyl carbonate; the third step is that after the nucleophilic attack, p-methoxybenzoic acid is generated while the organic amine salt dissociates, and then it interacts with the monomethyl carbonate that has lost a methyl group; the fourth step is that the activated monomethyl carbonate generates carbon dioxide and methanol under catalysis, and the organic amine salt dissociates; the fifth step is that p-methoxybenzoic acid and methanol undergo Fischer esterification to form methyl anisate under the action of the organic amine salt, and the organic amine salt dissociates and then continues to enter the next round of catalytic cycle.

[0026] The following are specific examples.

[0027] Example 1 Weigh 39.1 g of dimethyl carbonate and add it to a 100 mL high-pressure reactor. While stirring, successively add the organic amine DBU (1,8-diazabicyclo[5,4,0]undec-7-ene), alkyl halide 1-chlorobutane, and stabilizer BHT (2,6-di-tert-butyl-p-cresol). Then weigh 20.0 g of p-hydroxybenzoic acid and add it to the reactor. The overall molar ratio of the feed is (n 对羟基苯甲酸 :n 碳酸二甲酯 :n 烷基有机胺 :n 烷基卤代烷 :n 稳定剂 = 1.0:3.0:0.01:0.01:0.005). Close the reactor, displace with nitrogen, set the back pressure to 4.0 MPa with a back pressure valve, and then start heating and reacting. Keep the temperature at 120°C for 2.0 h in the first stage and 150°C for 4.0 h in the second stage. After the reaction, analyze and detect by liquid chromatography. The result shows that the conversion rate of p-hydroxybenzoic acid is 63.3%, and the selectivity of methyl anisate product is 89.6%.

[0028] Example 2 Differing from Example 1, the feeding amounts of raw materials p-hydroxybenzoic acid and dimethyl carbonate remain unchanged, only the feeding amount of the catalyst system is changed, and other conditions remain unchanged. That is, the molar ratio of the total feed is (n 对羟基苯甲酸 : n 碳酸二甲酯 : n 有机胺 : n 烷基卤代烷 : n 稳定剂 = 1.0: 3.0: 0.02: 0.02: 0.01). After the reaction, liquid chromatography analysis shows that the conversion rate of p-hydroxybenzoic acid is 90.2%, and the selectivity of methyl anisate product is 87.0%.

[0029] Example 3 Differing from Example 2, only the feeding amount of dimethyl carbonate is changed, and other conditions remain unchanged, that is, 52.2 g of dimethyl carbonate is fed. The molar ratio of the total feed is (n 对羟基苯甲酸 : n 碳酸二甲酯 : n 有机胺 : n 烷基卤代烷 : n 稳定剂 = 1.0: 4.0: 0.02: 0.02: 0.01). After the reaction, liquid chromatography analysis shows that the conversion rate of p-hydroxybenzoic acid is 94.5%, and the selectivity of methyl anisate product is 87.3%.

[0030] Example 4 Weigh 52.2 g of dimethyl carbonate and add it to a 100 mL high-pressure reactor. While stirring, sequentially add organic amine DBU (1,8-diazabicyclo[5,4,0]undec-7-ene), alkyl halide 1-chlorobutane, and stabilizer TEMPO (2,2,6,6-tetramethylpiperidine-n-oxide). Then weigh 20.0 g of p-hydroxybenzoic acid and add it to the reactor. The molar ratio of the total feed is (n 对羟基苯甲酸 : n 碳酸二甲酯 : n 有机胺 : n 烷基卤代烷 : n 稳定剂 = 1.0: 4.0: 0.02: 0.02: 0.01). Close the reactor, displace with nitrogen, set the back pressure valve to a back pressure of 4.0 MPa, and then start heating the reaction. Keep the temperature at 120 °C for 2.0 h in the first stage and keep it at 150 °C for 4.0 h in the second stage. After the reaction, use liquid chromatography analysis for detection. The results show that the conversion rate of p-hydroxybenzoic acid is 95.0%, and the selectivity of methyl anisate product is 97.1%.

[0031] Example 5 Weigh 52.2 g of dimethyl carbonate and add it to a 100 mL high-pressure reactor. While stirring, successively add the organic amine DBU (1,8-diazabicyclo[5,4,0]undec-7-ene), the alkyl halide 1-chlorohexadecane, and the stabilizer TEMPO (2,2,6,6-tetramethylpiperidine-n-oxide). Subsequently, weigh 20.0 g of p-hydroxybenzoic acid and add it to the reactor. The overall molar ratio of the feed materials is (n 对羟基苯甲酸 : n 碳酸二甲酯 : n 有机胺 : n 烷基卤代烷 : n 稳定剂 = 1.0:4.0:0.02:0.02:0.01). Close the reactor, displace the air with nitrogen, set the back pressure valve to a back pressure of 4.0 MPa, and then start heating the reaction. In the first stage, maintain the temperature at 120 °C for 2.0 h, and in the second stage, maintain the temperature at 150 °C for 4.0 h. After the reaction is completed, analyze and detect using liquid chromatography. The result shows that the conversion rate of p-hydroxybenzoic acid is 96.5%, and the selectivity of methyl anisate product is 97.5%.

[0032] Example 6 Weigh 52.2 g of dimethyl carbonate and add it to a 100 mL high-pressure reactor. While stirring, successively add the organic amine BABCO (1,4-diazabicyclo[2.2.2]octane), the alkyl halide 1-chlorohexadecane, and the stabilizer TEMPO (2,2,6,6-tetramethylpiperidine-n-oxide). Subsequently, weigh 20.0 g of p-hydroxybenzoic acid and add it to the reactor. The overall molar ratio of the feed materials is (n 对羟基苯甲酸 : n 碳酸二甲酯 : n 有机胺 : n 烷基卤代烷 : n 稳定剂 = 1.0:4.0:0.02:0.02:0.01). Close the reactor, displace the air with nitrogen, set the back pressure valve to a back pressure of 4.0 MPa, and then start heating the reaction. In the first stage, maintain the temperature at 120 °C for 2.0 h, and in the second stage, maintain the temperature at 150 °C for 4.0 h. After the reaction is completed, analyze and detect using liquid chromatography. The result shows that the conversion rate of p-hydroxybenzoic acid is 98.5%, and the selectivity of methyl anisate product is 98.2%.

[0033] Example 7 The difference from Example 5 is that only the reaction temperature and time are changed, and the feed amounts of other substances and the reaction conditions remain unchanged. That is, in the first stage, maintain the temperature at 130 °C for 1.0 h, and in the second stage, maintain the temperature at 170 °C for 2.5 h. After the reaction is completed, analyze and detect using liquid chromatography. The result shows that the conversion rate of p-hydroxybenzoic acid is 98.7%, and the selectivity of methyl anisate product is 98.0%.

[0034] Example 8 Weigh 65.2 g of dimethyl carbonate and add it to a 100 mL high-pressure reactor. While stirring, successively add the organic amine DMAP, the alkyl halide 1-bromobutane, and the stabilizer 4-hydroxy-TEMPO. Then weigh 20.0 g of p-hydroxybenzoic acid and add it to the reactor. The overall molar ratio of the feed materials is (n 对羟基苯甲酸 : n 碳酸二甲酯 : n 烷基有机胺 : n 烷基卤代烷 : n 稳定剂 = 1:5:0.5:1:0.05). Close the reactor, replace the air with nitrogen, set the back pressure valve to a back pressure of 3.0 MPa, and then start heating and reacting. Keep the temperature at 130 °C for 1.0 h in the first stage and at 130 °C for 10.0 h in the second stage. After the reaction is completed, perform liquid chromatography analysis and detection. The results show that the conversion rate of p-hydroxybenzoic acid is 97.3%, and the selectivity of methyl anisate product is 95.1%.

[0035] Example 9 Weigh 39.1 g of dimethyl carbonate and add it to a 100 mL high-pressure reactor. While stirring, successively add the organic amine DBN, the alkyl halide 1-bromopentane, and the stabilizer DPPH. Then weigh 20.0 g of p-hydroxybenzoic acid and add it to the reactor. The overall molar ratio of the feed materials is (n 对羟基苯甲酸 : n 碳酸二甲酯 : n 烷基有机胺 : n 烷基卤代烷 : n 稳定剂 = 1:3:0.1:0.06:0.02). Close the reactor, replace the air with nitrogen, set the back pressure valve to a back pressure of 4.0 MPa, and then start heating and reacting. Keep the temperature at 80 °C for 5.0 h in the first stage and at 180 °C for 1.0 h in the second stage. After the reaction is completed, perform liquid chromatography analysis and detection. The results show that the conversion rate of p-hydroxybenzoic acid is 78.8%, and the selectivity of methyl anisate product is 96.4%.

[0036] Example 10 Weigh 52.2 g of dimethyl carbonate and add it to a 100 mL high-pressure reactor. While stirring, successively add the organic amine BDMA, the alkyl halide 1-bromohexadecane, and the stabilizer (a mixture of BHT and PBQ with a molar ratio of 1:1). Then weigh 20.0 g of p-hydroxybenzoic acid and add it to the reactor. The overall molar ratio of the feed materials is (n 对羟基苯甲酸 : n 碳酸二甲酯 : n 烷基有机胺 : n 烷基卤代烷 : n 稳定剂= 1:4:0.06:1:0.03). The reactor was closed, purged with nitrogen, and after setting the back pressure of the back pressure valve to 5.0 MPa, the reaction was started by heating. The temperature was maintained at 100 °C for 3.0 h in the first stage and at 140 °C for 5.0 h in the second stage. After the reaction, liquid chromatography analysis was used for detection. The results showed that the conversion rate of p-hydroxybenzoic acid was 93%, and the selectivity of methyl anisate product was 97.1%.

[0037] Comparative Example 1 It was different from Example 6 in that the stabilizer TEMPO (2,2,6,6-tetramethylpiperidine-n-oxide) was not added during the reaction, and the other feeding amounts and reaction conditions remained unchanged. After the reaction, liquid chromatography analysis was used for detection. The results showed that the conversion rate of p-hydroxybenzoic acid was 92.6%, and the selectivity of methyl anisate product was 43.1%.

[0038] Comparative Example 2 It was different from Example 6 in that the organic amine BABCO (1,4-diazabicyclo[2.2.2]octane) was not added during the reaction, and the feeding amounts of other substances and the reaction conditions remained unchanged. After the reaction, liquid chromatography analysis was used for detection. The result showed that there was no obvious reaction of p-hydroxybenzoic acid.

[0039] Comparative Example 3 It was different from Example 6 in that the alkyl halide 1-chlorohexadecane was not added during the reaction, and the feeding amounts of other substances and the reaction conditions remained unchanged. After the reaction, liquid chromatography analysis was used for detection. The result showed that there was no obvious reaction of p-hydroxybenzoic acid.

[0040] Comparing Example 1 and Example 2, it can be seen that increasing the feeding amount of the composite catalyst can promote the reaction conversion; comparing Example 2 and Example 3, it can be seen that increasing the feeding amount of dimethyl carbonate can further promote the reaction; comparing Example 6 with Comparative Example 1, Comparative Example 2, and Comparative Example 3, it can be seen that the composite catalytic system plays a major role in the reaction. From the above experimental results, it can be known that the method for synthesizing methyl anisate by a tandem methylation reaction involving dimethyl carbonate provided by the present invention has strong operability, no three-waste discharge, and a relatively high overall catalytic efficiency of the composite catalytic system, and is a green and efficient method for synthesizing methyl anisate.

[0041] The sterically hindered organic amine compound in the present invention can also be one of 4-tert-butylpyridine, 2,2'-bipyridine, 4,4'-di-tert-butyl-2,2'-bipyridine, 5,5'-diamino-2,2'-bipyridine, 1,10-phenanthroline, and 2,9-dimethyl-1,10-phenanthroline.

[0042] The alkyl halide can also be one of 1-bromohexane, 1-bromododecane, 1-chloropentane, 1-chlorohexane, and 1-chlorododecane.

[0043] The above description is only for the best embodiments of the present invention, but it should not be construed as a limitation to the claims. The present invention is not limited to the above embodiments, and its specific structure is allowed to vary. Any variations made within the scope of protection of the independent claims of the present invention are within the scope of protection of the present invention.

[0044] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the technical field to which this invention belongs. The terms used in the description of the present invention herein are for the purpose of describing specific embodiments only and are not intended to limit the present invention. The term "and / or" used herein includes any and all combinations of one or more of the associated listed items.

Claims

1. A method for synthesizing methyl anisate by a tandem methylation reaction involving dimethyl carbonate, characterized in that, It includes the following steps: React p-hydroxybenzoic acid with dimethyl carbonate under the action of a composite catalyst system composed of an organic amine, an alkyl halide and a stabilizer to carry out the methyl etherification reaction and the methyl esterification reaction to produce methyl anisate.

2. The method for synthesizing methyl anisate by the tandem methylation reaction involving dimethyl carbonate according to claim 1, characterized in that, The organic amine includes one of 1,8-diazabicyclo[5,4,0]undec-7-ene, 1,4-diazabicyclo[2.2.2]octane, 4-dimethylaminopyridine, DBN (1,5-diazabicyclo[4.3.0]-5-nonene, 1,5,7-triazabicyclo[4.4.0]dec-5-ene), N,N-dimethylbenzylamine, 4-tert-butylpyridine, 2,2'-bipyridine, 4,4'-di-tert-butyl-2,2'-bipyridine, 5,5'-diamino-2,2'-bipyridine, 1,10-phenanthroline and 2,9-dimethyl-1,10-phenanthroline.

3. The method for synthesizing methyl anisate by the tandem methylation reaction involving dimethyl carbonate according to claim 1, characterized in that, The alkyl halide includes one of 1-bromobutane, 1-bromopentane, 1-bromohexane, 1-bromododecane, 1-bromohexadecane, 1-chlorobutane, 1-chloropentane, 1-chlorohexane, 1-chlorododecane and 1-chlorohexadecane.

4. The method for synthesizing methyl anisate by the tandem methylation reaction involving dimethyl carbonate according to claim 1, characterized in that, The stabilizer includes one or more of 2,2,6,6-tetramethylpiperidine-N-oxide, 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxide, 1,1-diphenyl-2-picrylhydrazyl, 2,6-di-tert-butyl-p-cresol and p-benzoquinone.

5. The method for synthesizing methyl anisate by the tandem methylation reaction involving dimethyl carbonate according to claim 1, characterized in that, The molar ratio of dimethyl carbonate to p-hydroxybenzoic acid is 1.0 - 5.0:1.

0.

6. The method for synthesizing methyl anisate by the tandem methylation reaction involving dimethyl carbonate according to claim 1, characterized in that, The molar ratio of the organic amine to p-hydroxybenzoic acid is 0.01 - 0.5:1.

0.

7. The method for synthesizing methyl anisate by the tandem methylation reaction involving dimethyl carbonate according to claim 1, characterized in that, The molar ratio of the alkyl halide to p-hydroxybenzoic acid is 0.01 - 1.0:1.

0.

8. The method for synthesizing methyl anisate by the tandem methylation reaction involving dimethyl carbonate according to claim 1, characterized in that, The molar ratio of the stabilizer to p-hydroxybenzoic acid is 0.005 - 0.05:1.

0.

9. The method for synthesizing methyl anisate by the tandem methylation reaction involving dimethyl carbonate according to claim 1, characterized in that, The temperature of the methyl etherification reaction is 80°C - 130°C, the time is 1 - 5 h, and the pressure is 3.0 - 5.0 MPa.

10. The method for synthesizing methyl anisate by the tandem methylation reaction involving dimethyl carbonate according to claim 1, characterized in that, The temperature of the methyl esterification reaction is 130°C - 180°C, the time is 1 - 10 h, and the pressure is 3.0 - 5.0 MPa.

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