Preparation method of mesotrione

Abstract

The invention provides a preparation method of mesotrione, and belongs to the technical field of herbicide preparation. The preparation method comprises the following steps: firstly, carrying out acylating chlorination reaction on 2-nitro-4-methylsulfonylbenzoic acid in the presence of a catalyst to obtain 2-nitro-4-methylsulfonylbenzoyl chloride; 2-nitro-4-methylsulfonyl benzoyl chloride and 1, 3-cyclohexanone are subjected to an esterification reaction in the presence of an acid-binding agent, and an enol ester reaction solution is obtained; finally, a rearrangement agent is added into the enol ester reaction liquid for a rearrangement reaction, mesotrione is obtained, and the rearrangement agent is triethylene diamine and inorganic base. By adjusting process parameters and selecting proper types of rearrangement agents for combination, the purity and the yield of the prepared mesotrione are remarkably improved, and the use of rearrangement agents with strong toxicity is avoided.

Description

Technical Field

[0001] The invention relates to the technical field of herbicide preparation, and in particular to a method for preparing mesotrione. Background Art

[0002] Mesotrione is an organic compound with the molecular formula C 14 H 13 NO7S belongs to the benzoylcyclohexanedione herbicide. It is an effective competitive hydroxyphenylpyruvate dioxygenase (HPPD) enzyme inhibitor that is selective for corn crops. The herbicidal activity of mesotrione is manifested by the inhibition of HPPD, which results in the inhibition of HPPD in the weeds, which in turn blocks the process of converting para-hydroxyphenylpyruvate into homogentisate, thereby affecting the biosynthesis of carotenoids in the target body, and ultimately causing the weeds to turn white and die. Mesotrione is a broad-spectrum, systemic, selective, contact herbicide that can be used to control annual broadleaf weeds and some grass weeds in corn fields before or after germination. In addition, mesotrione has a fast metabolism rate in susceptible crops and high tolerance, making it a safe and effective herbicide.

[0003] Many preparation methods of mesotrione are disclosed in the prior art, such as: Patent No. CN105254543A discloses a synthesis method of mesotrione, using 6-chloropurine, mercaptopurine, sodium sulfathiopurine, thioguanine, 2,6-dichloropurine, and 6-aminopurine as rearrangement agents to replace the highly toxic cyanide of the traditional process, and the yield of mesotrione can reach 92.3%. Patent No. CN108440352A discloses a preparation method of mesotrione, and the yield of the product obtained under the optimal process conditions can reach 95%, and the content is 98.5%. Therefore, it is of great significance to study a preparation method of mesotrione to improve the purity and yield of the product. Summary of the invention

[0004] The object of the present invention is to provide a method for preparing mesotrione to solve the problems of low purity and yield of mesotrione in the prior art.

[0005] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0006] The present invention provides a method for preparing mesotrione, comprising the following steps:

[0007] (1) subjecting 2-nitro-4-methylsulfonylbenzoic acid to an acyl chlorination reaction in the presence of a catalyst to obtain 2-nitro-4-methylsulfonylbenzoyl chloride;

[0008] (2) subjecting 2-nitro-4-methylsulfonylbenzoyl chloride and 1,3-cyclohexanone to an esterification reaction in the presence of an acid binding agent to obtain an enol ester reaction solution;

[0009] (3) adding a rearrangement agent to the enol ester reaction solution to carry out a rearrangement reaction to obtain mesotrione;

[0010] The rearrangement agent is triethylenediamine and an inorganic base.

[0011] Preferably, in the step (1), the chlorination agent for the chlorination reaction is phosphorus oxychloride, phosphorus pentachloride, phosphorus trichloride or thionyl chloride; the catalyst is N,N-dimethylformamide; and the chlorination reaction is carried out in an organic solvent.

[0012] Preferably, in step (1), the amount of catalyst added is 0.05 to 1.0% by weight of 2-nitro-4-methylsulfonylbenzoic acid.

[0013] Preferably, the temperature of the acyl chlorination reaction is 40-60° C. and the time is 1-3 hours.

[0014] Preferably, the acid binding agent is triethylamine or pyridine; the molar ratio of the acid binding agent to 2-nitro-4-methylsulfonylbenzoic acid is 0.8-1.5:1.

[0015] Preferably, in step (2), the reaction temperature is 30-40° C., and the reaction time is 1-2 h.

[0016] Preferably, the molar ratio of triethylenediamine to inorganic base is 1:5-10; the molar ratio of triethylenediamine to 2-nitro-4-methylsulfonylbenzoic acid is 0.3-0.6:1.

[0017] Preferably, in step (3), the temperature of the rearrangement reaction is 35-45° C., and the reaction time is 1-2 h.

[0018] Beneficial effects of the present invention:

[0019] (1) The present invention performs a rearrangement reaction on the prepared enol ester reaction solution under the combined action of an inorganic base and triethylenediamine, thereby avoiding the use of a toxic rearrangement agent and improving the purity of mesotrione.

[0020] (2) The present invention can significantly improve the yield of mesotrione by adjusting the process parameters. DETAILED DESCRIPTION

[0021] The present invention provides a method for preparing mesotrione, comprising the following steps:

[0022] (1) subjecting 2-nitro-4-methylsulfonylbenzoic acid to an acyl chlorination reaction in the presence of a catalyst to obtain 2-nitro-4-methylsulfonylbenzoyl chloride;

[0023] (2) subjecting 2-nitro-4-methylsulfonylbenzoyl chloride and 1,3-cyclohexanone to an esterification reaction in the presence of an acid binding agent to obtain an enol ester reaction solution;

[0024] (3) adding a rearrangement agent to the enol ester reaction solution to carry out a rearrangement reaction to obtain mesotrione;

[0025] The rearrangement agent is triethylenediamine and an inorganic base.

[0026] In the present invention, in the step (1), the chlorination agent for the chlorination reaction is phosphorus oxychloride, phosphorus pentachloride, phosphorus trichloride or thionyl chloride, preferably phosphorus pentachloride, phosphorus trichloride or thionyl chloride, further preferably thionyl chloride; the catalyst is N,N-dimethylformamide; and the chlorination reaction is carried out in an organic solvent.

[0027] In the present invention, N,N-dimethylformamide is used as a catalyst, which can not only greatly shorten the reaction time, but also improve the conversion rate of 2-nitro-4-methylsulfonylbenzoic acid.

[0028] In the present invention, the organic solvent comprises one or more of dichloroethane, dichloromethane, cyclohexane and chloroform. In the embodiment of the present invention, dichloroethane is preferably used.

[0029] In the present invention, in the step (1), the amount of catalyst added is 0.05 to 1.0% by weight of 2-nitro-4-methylsulfonylbenzoic acid, preferably 0.2 to 0.9%, and more preferably 0.40 to 0.78%.

[0030] In the present invention, the temperature of the acyl chlorination reaction is 40 to 60° C., preferably 45 to 55° C., more preferably 50° C., and the time is 1 to 3 hours, preferably 1 hour.

[0031] In the present invention, the acid binding agent is triethylamine or pyridine, preferably triethylamine; the molar ratio of the acid binding agent to 2-nitro-4-methylsulfonylbenzoic acid is 0.8-1.5:1, preferably 1.0-1.3:1, and more preferably 1.2:1.

[0032] In the present invention, in the step (2), the reaction temperature is 30-40°C, preferably 30°C, and the reaction time is 1-2h, preferably 2h.

[0033] In the present invention, the molar ratio of triethylenediamine to inorganic base is 1:5-10, preferably 1:5 or 1:10; the molar ratio of triethylenediamine to 2-nitro-4-methylsulfonylbenzoic acid is 0.3-0.6:1, preferably 0.4-0.5:1.

[0034] In the present invention, in step (3), the temperature of the rearrangement reaction is 35-45°C, preferably 40°C, and the reaction time is 1-2h, preferably 1h.

[0035] The technical solutions provided by the present invention are described in detail below in conjunction with the embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0036] Example 1

[0037] 19.12 g (0.078 mol) of 2-nitro-4-methylsulfonylbenzoic acid, 140 g of dichloroethane and 0.15 g of N,N-dimethylformamide were placed in a reaction bottle, stirred and heated to 50°C, 13.92 g (0.117 mol) of thionyl chloride was added dropwise, and after the addition was completed, the temperature was kept constant and refluxed for 1 hour, and the solvent was evaporated under reduced pressure to obtain 2-nitro-4-methylsulfonylbenzoyl chloride.

[0038] Add 140 g of ethylene dichloride and 9.19 g (0.082 mol) of 1,3-cyclohexanedione to the above-mentioned 2-nitro-4-methylsulfonylbenzoyl chloride, control the temperature in the range of 3 to 8°C, add 9.51 g (0.094 mol) of triethylamine dropwise within 2 hours, and then raise the temperature to 30°C for esterification reaction. The esterification reaction time is 2 hours to obtain an enol ester reaction solution.

[0039] 5.4 g (0.135 mol) of sodium hydroxide and 3.03 g (0.027 mol) of triethylenediamine were added to the enol ester reaction solution, and the mixture was reacted at 40° C. for 2 h. The solvent was evaporated under reduced pressure, 30 g of water was added, the mixture was acidified with hydrochloric acid, extracted with dichloroethane, and dried to obtain mesotrione with a purity of 98.6% and a yield of 98.6%.

[0040] Example 2

[0041] The difference from Example 1 is that the added amount of sodium hydroxide is 6.24 g (0.156 mol), the added amount of triethylenediamine is 3.5 g (0.0312 mol), and other conditions are the same, and mesotrione is obtained with a purity of 99.3% and a yield of 99.0%.

[0042] Example 3

[0043] The difference from Example 1 is that the added amount of sodium hydroxide is 15.6 g (0.39 mol), the added amount of triethylenediamine is 4.37 g (0.039 mol), and other conditions are the same, and mesotrione is obtained with a purity of 98.7% and a yield of 98.4%.

[0044] Comparative Example 1

[0045] The difference from Example 1 is that triethylenediamine is not added, and only sodium hydroxide is used as a rearrangement agent. Other conditions are the same, and mesotrione is obtained with a purity of 96.5% and a yield of 93.2%.

[0046] Comparative Example 2

[0047] The difference from Example 1 is that the added amount of triethylenediamine is 1.75 g (0.0156 mol), and other conditions are the same, and mesotrione is obtained with a purity of 97.2% and a yield of 94.4%.

[0048] Comparative Example 3

[0049] The difference from Example 1 is that the added amount of triethylenediamine is 6.125 g (0.0546 mol), and other conditions are the same, and mesotrione is obtained with a purity of 97.0% and a yield of 95.1%.

[0050] By comparing the purity and yield of mesotrione obtained in Examples 1 to 3 and Comparative Examples 1 to 3, it can be seen that the purity and yield of the product can be significantly improved by compounding the rearrangement agent and adding it in an appropriate amount.

[0051] From the above embodiments, the present invention provides a method for preparing mesotrione, and the specific steps are: first, 2-nitro-4-methylsulfonylbenzoic acid is subjected to chlorination reaction in the presence of a catalyst to obtain 2-nitro-4-methylsulfonylbenzoyl chloride; then, 2-nitro-4-methylsulfonylbenzoyl chloride and 1,3-cyclohexanone are subjected to esterification reaction in the presence of an acid binding agent to obtain an enol ester reaction liquid; finally, a rearrangement agent is added to the enol ester reaction liquid for rearrangement reaction to obtain mesotrione; wherein the rearrangement agent is triethylenediamine and an inorganic base. The present invention significantly improves the purity and yield of the obtained mesotrione by adjusting the process parameters and selecting the appropriate type of rearrangement agent for combination.

[0052] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for preparing mesotrione, characterized in that: The steps include: (1) subjecting 2-nitro-4-methylsulfonylbenzoic acid to an acyl chlorination reaction in the presence of a catalyst to obtain 2-nitro-4-methylsulfonylbenzoyl chloride; (2) subjecting 2-nitro-4-methylsulfonylbenzoyl chloride and 1,3-cyclohexanone to an esterification reaction in the presence of an acid binding agent to obtain an enol ester reaction solution; (3) adding a rearrangement agent to the enol ester reaction solution to carry out a rearrangement reaction to obtain mesotrione; The rearrangement agent is triethylenediamine and an inorganic base.

2. The method for preparing mesotrione according to claim 1, characterized in that: In the step (1), the chlorination agent for the chlorination reaction is phosphorus oxychloride, phosphorus pentachloride, phosphorus trichloride or thionyl chloride; the catalyst is N,N-dimethylformamide; and the chlorination reaction is carried out in an organic solvent.

3. The method for preparing mesotrione according to claim 2, characterized in that: In the step (1), the amount of catalyst added is 0.05 to 1.0% of the weight of 2-nitro-4-methylsulfonylbenzoic acid.

4. The method for preparing mesotrione according to any one of claims 1 to 3, characterized in that: The temperature of the acyl chlorination reaction is 40-60° C. and the time is 1-3 hours.

5. The method for preparing mesotrione according to claim 4, characterized in that: The acid binding agent is triethylamine or pyridine; the molar ratio of the acid binding agent to 2-nitro-4-methylsulfonylbenzoic acid is 0.8-1.5:

1.

6. The method for preparing mesotrione according to claim 3 or 5, characterized in that: In the step (2), the reaction temperature is 30-40° C. and the reaction time is 1-2 h.

7. The method for preparing mesotrione according to claim 6, characterized in that: The molar ratio of the triethylenediamine to the inorganic base is 1:5-10; the molar ratio of the triethylenediamine to 2-nitro-4-methylsulfonylbenzoic acid is 0.3-0.6:

1.

8. The method for preparing mesotrione according to claim 5 or 7, characterized in that: In the step (3), the temperature of the rearrangement reaction is 35 to 45° C., and the reaction time is 1 to 2 hours.