Synthesis of 2-chloro-3-methyl-4-methylsulfonylbenzoic acid

Abstract

The application discloses a synthesis method of 2-chloro-3-methyl-4-methylsulfonylbenzoic acid, which is obtained by one-step oxidation of 2-chloro-3-methyl-4-methylsulfanyl acetophenone with freshly prepared hypochlorite, and the freshly prepared hypochlorite is prepared by passing chlorine into a strong alkaline aqueous solution. It is found through a large number of tests that the freshly prepared sodium hypochlorite can simultaneously oxidize acetyl and methylthio, while the conventional industrial sodium hypochlorite can only oxidize acetyl and cannot oxidize methylthio. Therefore, compared with the prior art, the method disclosed by the application has fewer reaction steps, avoids the use of expensive sodium tungstate catalyst, greatly reduces the production cost, and in particular, the reaction yield of the application is obviously higher than the two-step reaction yield of less than 50% in the prior art.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of herbicide intermediate synthesis, and particularly relates to a synthesis method of a key intermediate 2-chloro-3-methyl-4-methylsulfonylbenzoic acid of tembotrione and furametpyr. BACKGROUND

[0002] 2-chloro-3-methyl-4-methylsulfonylbenzoic acid is a key intermediate of tembotrione and furametpyr.

[0003] The existing preparation method of 2-chloro-3-methyl-4-methylsulfonylbenzoic acid is basically as follows: 2,6-dichlorotoluene is used as a starting material, 2-chloro-6-methylthiotoluene is obtained by reacting with sodium thiomethoxide (also known as sodium methyl mercaptide), 2-chloro-3-methyl-4-methylthiotoluene is obtained by reacting with acetyl chloride, 2-chloro-3-methyl-4-methylsulfonylphenylacetone is obtained by oxidizing with hydrogen peroxide under the catalysis of sodium tungstate, and 2-chloro-3-methyl-4-methylsulfonylbenzoic acid is obtained by oxidizing with sodium hypochlorite again

see Chinese patent documents CN1323292A and CN1364160A

[0004] The last two reaction steps are as follows:

[0005] .

[0006] The last two reaction steps have the following disadvantages: (1) two reaction steps are needed, and the reaction steps are more; (2) the yield of catalytic oxidation reaction is only 48%, and the yield is low, which is not suitable for industrial mass production; (3) the catalytic oxidation needs to use expensive sodium tungstate, which leads to high production cost, and is also not suitable for industrial mass production. SUMMARY

[0007] The present application aims to solve the above problems, and provides a preparation method of 2-chloro-3-methyl-4-methylsulfonylbenzoic acid, which has fewer reaction steps, higher reaction yield, lower production cost, and is suitable for industrial mass production.

[0008] The technical scheme for achieving the present application is as follows: a synthesis method of 2-chloro-3-methyl-4-methylsulfonylbenzoic acid, which is obtained by one-step oxidation of 2-chloro-3-methyl-4-methylthiotoluene with freshly prepared hypochlorite.

[0009] The reaction formula is as follows:

[0010] .

[0011] The one-step oxidation reaction is carried out in the presence of an organic solvent; the organic solvent is 1,4-dioxane, 2-methyltetrahydrofuran, tetrahydrofuran, diethoxymethane or propyl ether; in order to obtain higher reaction yield and product purity, the organic solvent is preferably 1,4-dioxane, 2-methyltetrahydrofuran, tetrahydrofuran, and more preferably 1,4-dioxane.

[0012] The weight ratio of the 2-chloro-3-methyl-4-methylsulfanyl acetophenone to the organic solvent is 1:3 to 1:8.

[0013] The one-step oxidation reaction temperature is 20 to 30℃, and the reaction time is 6 to 15h.

[0014] The freshly prepared sodium hypochlorite is prepared by passing chlorine into a strong alkali aqueous solution.

[0015] The strong alkali is sodium hydroxide or potassium hydroxide, and preferably sodium hydroxide.

[0016] The molar ratio of the 2-chloro-3-methyl-4-methylsulfanyl acetophenone to the strong alkali is 1:10 to 1:30, and preferably 1:15 to 1:20.

[0017] The molar ratio of the chlorine to the strong alkali is 1:2 to 1:3.

[0018] Taking the sodium hydroxide aqueous solution as an example, the above reaction equation is as follows:

[0019] .

[0020] The present application has the following positive effects: through a large number of experiments, it is found that the freshly prepared sodium hypochlorite can simultaneously oxidize the acetyl group and the methylthio group, while the conventional industrial sodium hypochlorite can only oxidize the acetyl group and cannot oxidize the methylthio group, therefore, the method of the present application not only has fewer reaction steps compared with the prior art, but also avoids the use of expensive sodium tungstate catalyst, greatly reducing the production cost, and in particular, the reaction yield of the present application is significantly higher than the two-step reaction yield of 50% or less in the prior art. BRIEF DESCRIPTION OF DRAWINGS

[0021] Figure 1 The nuclear magnetic resonance spectrum of the target product prepared in Example 1.

[0022] Figure 2 The high performance liquid chromatogram of the target product prepared in Example 1. DETAILED DESCRIPTION

[0023] (Example 1)

[0024] The synthesis method of 2-chloro-3-methyl-4-methylsulfonyl benzoic acid in this example has the following steps:

[0025] ① In a 300 mL beaker, 21.5 g of 2-chloro-3-methyl-4-methylsulfanyl acetophenone (0.1 mol) and 90 g of 1,4-dioxane were added and stirred to dissolve, ready for use.

[0026] ② In a 1000 mL four-necked flask, 70 g of sodium hydroxide (1.75 mol) and 450 g of water were added, and then 54 g of chlorine gas (0.76 mol) was bubbled in at a temperature of 5-10°C to obtain a freshly prepared sodium hypochlorite solution.

[0027] ③ The 1,4-dioxane solution of 2-chloro-3-methyl-4-methylsulfanyl acetophenone obtained in step ① was added dropwise to the freshly prepared sodium hypochlorite solution obtained in step ② at a temperature of 20-30°C, and the dropping was completed in about half an hour. At this time, the reaction solution was turbid, and the reaction was maintained at a temperature of 20-30°C for 8 h. The content of 2-chloro-3-methyl-4-methylsulfanyl acetophenone was controlled to be <0.1% by HPLC, and the reaction was terminated.

[0028] ④ After the reaction was terminated, the layers were separated by standing, and the small amount of organic layer in the lower layer was discarded. The upper aqueous layer was acidified to strong acidity (pH = 1.0 in this example) at a temperature of 25-30°C using industrial hydrochloric acid, and then filtered. The filter cake was washed with water and dried to obtain 21.2 g of 2-chloro-3-methyl-4-methylsulfonyl benzoic acid, with a yield of 85.1% and a purity of 98.9% by HPLC.

[0029] The nuclear magnetic resonance spectrum of the target product obtained in this example is shown in Figure 1 .

[0030] The high performance liquid chromatogram of the target product obtained in this example is shown in Figure 2 .

[0031] (Examples 2-3)

[0032] The methods of Examples 2 and 3 were basically the same as those of Example 1, except for the type of organic solvent, as shown in Table 1.

[0033] (Comparative Examples 1-2)

[0034] The methods of Comparative Examples 1 and 2 were basically the same as those of Example 1, except for the type of organic solvent, as shown in Table 1.

[0035] Table 1

[0036] Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Organic solvent 1,4-dioxane 2-methyltetrahydrofuran tetrahydrofuran diethoxymethane propyl ether Product 21.2g 20.0g 19.8g 17.0g 11.1g Yield 85.1% 80.3% 79.5% 68.3% 44.6% Purity 98.9% 98.1% 97.8% 76.9% 92.1%

[0037] (Examples 4-6)

[0038] The method of Examples 4 to 7 is substantially the same as that of Example 1, except for the type and amount of strong base, as shown in Table 2.

[0039] Table 2

[0040] Example 1 Example 4 Example 5 Example 6 Strong base 70 g sodium hydroxide (1.75 mol) 80 g sodium hydroxide (2.00 mol) 98 g potassium hydroxide (1.75 mol) 112 g potassium hydroxide (2.00 mol) Product 21.2g 21.1g 17.8g 17.6g Yield 85.1% 84.7% 71.5% 70.7% Purity 98.9% 98.6% 95.4% 95.2%

[0041] (Comparative Example 3)

[0042] This comparative example is the oxidation of 2-chloro-3-methyl-4-methylthioacetophenone using conventional industrial sodium hypochlorite, according to the following method:

[0043] Into a 1000 mL four-necked flask was added 21.5 g of 2-chloro-3-methyl-4-methylthioacetophenone (0.1 mol) and 90 g of 1,4-dioxane, and the mixture was stirred until dissolved, then 400 g of 13 wt% industrial sodium hypochlorite solution was added dropwise at a temperature of 20-30°C, and the dropwise addition was completed in about half an hour. The reaction was carried out at a temperature of 20-30°C after the dropwise addition was completed, and the HPLC control of 2-chloro-3-methyl-4-methylthioacetophenone was <5%, and the reaction was completed.

[0044] After the reaction was completed, the layers were allowed to separate, and the lower organic layer was discarded. The upper aqueous layer was acidified with industrial hydrochloric acid at a temperature of 25-30°C until the pH was 1.0, and the mixture was filtered, and the filter cake was washed with water and dried. As a result, 19.4 g of white solid 2-chloro-3-methyl-4-methylthio benzoic acid was obtained.

Claims

1. A method for the synthesis of 2-chloro-3-methyl-4-methylsulfonylbenzoic acid, characterized by: It is obtained by one-step oxidation of 2-chloro-3-methyl-4-methylsulfanyl-acetophenone with freshly prepared hypochlorite; The freshly prepared hypochlorite is prepared by passing chlorine into strong alkali aqueous solution; the strong alkali is sodium hydroxide; the molar ratio of 2-chloro-3-methyl-4-methylsulfanyl-acetophenone to the strong alkali is 1:15-1:20; The one-step oxidation reaction is carried out in the presence of an organic solvent; the weight ratio of 2-chloro-3-methyl-4-methylsulfanyl-acetophenone to the organic solvent is 1:3-1:8; the organic solvent is 1,4-dioxane, 2-methyltetrahydrofuran or tetrahydrofuran.

2. The process for the synthesis of 2-chloro-3-methyl-4-methylsulfonylbenzoic acid according to claim 1, characterized by: The molar ratio of chlorine to the strong alkali is 1:2-1:

3.

3. The method of synthesis of 2-chloro-3-methyl-4-methylsulfonylbenzoic acid according to claim 1, characterized by that: The organic solvent is 1,4-dioxane.

4. The method of synthesis of 2-chloro-3-methyl-4-methylsulfonylbenzoic acid according to claim 1, characterized by that: The one-step oxidation reaction temperature is 20-30℃, and the reaction time is 6-15h.

Images