A kind of preparation method of 2-chloro-6-methylthiotoluene

Abstract

The invention belongs to the technical field of organic compound synthesis, and is specifically a method for preparing 2-chloro-6-methylthiotoluene. The present invention uses 2,6-dichlorotoluene, dimethyl disulfide and active alkali metal as raw materials, and obtains 2-chloro-6-methylthiotoluene by one-step reaction in a polar aprotic solvent or solvent-free condition. The reaction process is simple, the reaction speed is fast, and the product can be obtained by simple post-processing through rectification; the problems that the raw material anhydrous sodium methyl mercaptan is difficult to obtain, the post-reaction processing process is complicated, the solvent recovery is difficult, and the diazotization process has high safety risks and a large amount of three wastes are overcome.

Description

Technical Field

[0001] The invention belongs to the technical field of organic compound synthesis, and specifically relates to a method for preparing 2-chloro-6-methylthiotoluene. Background Art

[0002] 2-Chloro-6-methylthiotoluene is an important organic synthetic building block, widely used in organic synthesis fields such as medicine and pesticides, such as the preparation of pesticide herbicides such as cypermethrin, fluazifop, and triazosulfuron. Cypermethrin is a triketone cornfield herbicide developed by Bayer. Since its launch in 2007, its global sales have maintained a high growth rate, showing a good development trend and ranking at the forefront of the corn herbicide market. In view of the growing market demand for cypermethrin, coupled with the gradual launch of new herbicides such as fluazifop and triazosulfuron, the demand for 2-chloro-6-methylthiotoluene continues to expand, and it is expected that the annual demand will reach thousands of tons in the future.

[0003] At present, there are two main methods for the synthesis of 2-chloro-6-methylthiotoluene. One method is as reported in the patents of CN1793118A, CN109053511A, CN105601548 or CN109053511, using 3-chloro-2-methylaniline as raw material, through diazotization reaction, and sodium methyl mercaptide aqueous solution reaction preparation; the diazotization reaction, a large amount of high-salt wastewater will be produced, and the ortho-position of the diazonium salt has a methyl electron-donating effect, which causes the diazonium salt to be unstable, and the diazonium salt is easy to decompose and explode and release a large amount of heat, and there are major problems in process safety and environmental protection, which is not suitable for large-scale production, and the 3-chloro-2-methylaniline manufacturer is less, and the market supply is limited. Another method is reported in patents such as US Patent Publication No. US6211216, Chinese Patent Publication No. CN1323292A, CN1364160A, CN106008295A, CN111233721A, etc., using 2,6-dichlorotoluene as a raw material, and obtaining it through anhydrous sodium methyl mercaptan sulfidation reaction; this route requires the use of anhydrous sodium methyl mercaptan, which is difficult to obtain because it is easily oxidized and decomposed, resulting in its own unstable structure. There is no commercial production and supply on the market so far; Chinese Patent Publication No. CN106008295A and CN111233721A attempt to prepare anhydrous sodium methyl mercaptan from an aqueous solution of sodium methyl mercaptan by evaporation and dehydration. After the inventors verified the process, it was found that during the evaporation and dehydration, a large amount of methyl mercaptan volatilized and escaped, causing serious material loss, and the purpose of preparing anhydrous sodium methyl mercaptan by evaporation and dehydration was difficult to achieve. The Chinese patent publication number CN108947878A generates methyl mercaptan by reacting sulphuric acid with sodium methyl mercaptan aqueous solution, and then converts it into an organic solution of anhydrous sodium methyl mercaptan by absorption in potassium hydroxide organic solvent; the process steps are cumbersome, and the reaction process produces highly toxic methyl mercaptan gas, which has a large potential safety hazard. The method uses hexamethylphosphoric triamide or DMSO or ionic liquid as solvent, and hexamethylphosphoric triamide is a strong carcinogen and is restricted for use, and the method also has problems such as large wastewater volume and complex post-processing; in addition, the method uses anhydrous sodium methyl mercaptan to be added to the reaction at one time, resulting in excessive concentration of sodium methyl mercaptan in the system, and demethylation side reactions will also occur with the target product, causing the target product to be difficult to separate and generate dangerous and smelly dimethyl sulfide byproducts, which are difficult to handle.

[0004] The above two synthesis methods have many problems such as difficulty in obtaining raw materials, complex post-treatment process, large amount of three wastes, and difficulty in solvent recovery, which make the commercial production of 2-chloro-6-methylthiotoluene difficult, increase product costs, and limit the large-scale promotion and application of new herbicides such as tembotrione. Therefore, a synthesis method is urgently needed to overcome these technical problems. Summary of the invention

[0005] In order to overcome the problems of the prior art that the raw material anhydrous sodium methyl mercaptan is difficult to obtain, the post-reaction treatment process is complicated, the solvent recovery is difficult, and the diazotization process has high safety risks and a large amount of three wastes, the present invention proposes a preparation method of 2-chloro-6-methylthiotoluene. The method uses 2,6-dichlorotoluene, dimethyl disulfide and active alkali metal as raw materials, and obtains 2-chloro-6-methylthiotoluene by a one-step reaction in a polar aprotic solvent or without solvent; the reaction process is simple, the reaction speed is fast, and the product can be obtained by simple post-treatment and distillation.

[0006] A method for preparing 2-chloro-6-methylthiotoluene comprises the following specific steps:

[0007] Step 1, adding 2,6-dichlorotoluene, aprotic polar solvent and dimethyl disulfide into a reaction container at room temperature, and performing nitrogen inertization replacement; starting stirring, heating to the reaction temperature, dropping liquid active metal M, and keeping the temperature for 2 hours after the dropping, sampling and testing until the reaction is complete, and distilling off most of the solvent under reduced pressure;

[0008] Step 2, after distilling off most of the solvent under reduced pressure, cool to 40°C~60°C, slowly drop 5%~7% water relative to the mass of 2,6-dichlorotoluene to quench the reaction, then slowly add the oxidant, react for 1h, raise the temperature to 100~110°C, distill the product, collect it after condensation to obtain a light yellow oily compound, and then perform conventional vacuum distillation (110~120°C / 1.0~2.0kPa) to obtain the target compound 2-chloro-6-methylthiotoluene.

[0009] Furthermore, in step 1, the aprotic polar solvent is one of DMF, DMAC, DMSO, sulfolane, NMP or diethylene glycol dimethyl ether.

[0010] Furthermore, in step 1, the mass of the aprotic solvent is 0 to 4 times the mass of 2,6-dichlorotoluene.

[0011] Furthermore, in step 1, the molar ratio of dimethyl disulfide to 2,6-dichlorotoluene is 0.45-0.6:1.

[0012] Furthermore, in step 1, the reaction temperature is 100-130°C.

[0013] Furthermore, in step 1, the active metal M is metallic potassium or metallic sodium.

[0014] Furthermore, in step 1, the molar ratio of the active metal M to dimethyl disulfide is 1.8-2.1:1.

[0015] Furthermore, in step 2, the oxidant is one of conventional oxidants such as hydrogen peroxide, sodium hypochlorite, oxygen or air.

[0016] Furthermore, in step 2, the hydrogen peroxide is commercially available 27.5% hydrogen peroxide, and the sodium hypochlorite is commercially available 10% sodium hypochlorite.

[0017] Furthermore, in step 2, the molar ratio of the oxidant to 2,6-dichlorotoluene is 0.1-0.3:1.

[0018] Furthermore, in step 2, the distillation is steam distillation or reduced pressure distillation.

[0019] Furthermore, step 1 and step 2 can be carried out in either an intermittent manner or a continuous reaction manner; the reaction mode does not affect the effectiveness of the process of the present invention.

[0020] Compared with the prior art, the beneficial effects of the present invention are as follows.

[0021] (1) Using cheap and readily available dimethyl disulfide as a raw material, metal methyl mercaptan salt is produced in situ with an active alkali metal, and then reacted with 2,6-dichlorotoluene to generate the target product, effectively solving the problem of the difficulty in supplying anhydrous sodium methyl mercaptan raw materials.

[0022] (2) The concentration of methyl mercaptan metal salt in the reaction system is controlled by using active alkali metal with low melting point and adopting liquid closed dropwise addition method, which effectively reduces the occurrence of demethylation side reaction and improves process safety.

[0023] (3) Post-treatment uses an oxidant to convert a small amount of by-product thiophenol into a high-boiling disulfide, which forms a boiling point difference of more than 100°C with the target product. Therefore, simple distillation such as steam distillation or vacuum distillation can achieve efficient separation of the product and the by-product.

[0024] (4) The preparation process of the product of the present invention is simple, with only one step of synthesis reaction and mild reaction conditions; the raw materials are cheap and easily available, and the raw materials used are basic chemicals that are produced and supplied on a large scale in the market; there are few side reactions, and the yield is comparable to that of the existing diazotization reaction, which is suitable for large-scale production.

[0025] (5) The present invention avoids the use of dangerous processes such as diazotization, avoids the use of dangerous substances such as anhydrous methyl mercaptan, reduces the generation and discharge of high-salt wastewater, and the reaction solvent can be distilled and recovered, reducing safety and environmental risks. DETAILED DESCRIPTION

[0026] The technical solution of the present invention is described below by specific embodiments. Those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. The implementation conditions used in the embodiments can be further adjusted according to the different requirements of specific use, and the implementation conditions not specified are the conventional conditions of the industry.

[0027] A method for preparing 2-chloro-6-methylthiotoluene comprises the following specific steps:

[0028] Step 1, adding 2,6-dichlorotoluene, aprotic polar solvent and dimethyl disulfide into a reaction container at room temperature, and performing nitrogen inertization replacement; starting stirring, heating to the reaction temperature, dropping liquid active metal M, and keeping the temperature for 2 hours after the dropping, sampling and testing until the reaction is complete, and distilling off most of the solvent under reduced pressure;

[0029] Step 2, after distilling off most of the solvent under reduced pressure, cool to 40°C~60°C, slowly drop 5%~7% water relative to the mass of 2,6-dichlorotoluene to quench the reaction, then slowly add the oxidant, react for 1h, raise the temperature to 100~110°C, distill the product, collect it after condensation to obtain a light yellow oily compound, and then perform conventional vacuum distillation (110~120°C / 1.0~2.0kPa) to obtain the target compound 2-chloro-6-methylthiotoluene.

[0030] Furthermore, in step 1, the aprotic polar solvent is one of DMF, DMAC, DMSO, sulfolane, NMP, diethylene glycol dimethyl ether, etc.; preferably DMSO or DMAC.

[0031] Furthermore, in step 1, the mass of the aprotic solvent is 0 to 4 times the mass of 2,6-dichlorotoluene; preferably 2 times.

[0032] Furthermore, in step 1, the molar ratio of dimethyl disulfide to 2,6-dichlorotoluene is 0.45-0.6:1; preferably 0.5-0.55:1.

[0033] Furthermore, in step 1, the reaction temperature is 100-130°C; preferably 100-110°C.

[0034] Furthermore, in step 1, the active metal M is metallic potassium or metallic sodium.

[0035] Furthermore, in step 1, the molar ratio of the active metal M to dimethyl disulfide is 1.8-2.1:1; preferably 1.9-2.0:1.

[0036] Furthermore, in step 2, the oxidant is one of conventional oxidants such as hydrogen peroxide, sodium hypochlorite, oxygen or air; preferably hydrogen peroxide or air.

[0037] Furthermore, in step 2, the hydrogen peroxide is commercially available 27.5% hydrogen peroxide, and the sodium hypochlorite is commercially available 10% sodium hypochlorite.

[0038] Furthermore, in step 2, the molar ratio of the oxidant to 2,6-dichlorotoluene is 0.1-0.3:1; preferably 0.15-0.20:1.

[0039] Furthermore, in step 2, the distillation is steam distillation or reduced pressure distillation.

[0040] Furthermore, step 1 and step 2 can be carried out in either an intermittent manner or a continuous reaction manner; the reaction mode does not affect the effectiveness of the process of the present invention.

[0041] The synthetic route is as follows:

[0042] .

[0043] Raw material description: All raw materials in the present invention are purchased from the market in bulk, and the purity is above 99.5%.

[0044] Liquid metal sodium / potassium: Since metal sodium / potassium is solid at room temperature, for the purpose of conducting the experiment, the present invention heats and melts the commercially available solid metal sodium / potassium into liquid state. The specific operation is as follows:

[0045] (1) Preparation of liquid sodium metal: Add xylene and sodium metal block to a reaction flask, heat to 100-110°C, and let stand under heat preservation to separate into layers. The lower layer is the alkali metal sodium liquid, and the upper layer is xylene (which serves as an isolation and protection). When in use, add it dropwise into the reaction flask through a heating pipeline.

[0046] (2) Preparation of liquid potassium metal: Add n-heptane and potassium metal block to a reaction flask and heat to 70-80°C until the alkali metal is completely melted. Then let it stand and separate into layers under insulation. The lower layer is the alkali metal liquid and the upper layer is n-heptane (which serves as an isolation and protection). When in use, add it dropwise to the reaction flask through a heating pipeline.

[0047] It should be noted that liquid metallic sodium or liquid metallic potassium is a raw material supplied on a large scale commercially and can be purchased directly or prepared by oneself as described above.

[0048] The present invention is further described below by way of examples, but the scope of the present invention is not limited thereto.

[0049] Example 1.

[0050] (1) 160 g 2,6-dichlorotoluene (1.0 mol), 480 g N,N-dimethylacetamide DMAC (3 M), and 42 g dimethyl disulfide (0.45 mol) were added to a 1 L glass reaction container at room temperature and replaced with nitrogen for inertization; stirring was started, and the temperature was raised to 110°C. 19 g (0.85 mol) of liquid metal sodium was added dropwise under temperature control. After the addition was completed, the temperature was kept constant for 2 h, and samples were taken for testing until the reaction was complete. Most of the solvent was distilled off under reduced pressure;

[0051] (2) The system was cooled to 45°C, 10 g of water was dripped in to quench the reaction, 12 g (0.1 mol) of 27.5% hydrogen peroxide was slowly dripped in, and the reaction was allowed to react for 1 h. The reaction system was heated to 110°C again, and steam distillation was started to evaporate the product until almost no product was distilled out. A light yellow oily compound was obtained by condensation and collection, and conventional vacuum distillation (120°C / 2 kPa) was performed to obtain the target compound 2-chloro-6-methylthiotoluene.

[0052] 131 g of 2-chloro-6-methylthiotoluene, purity 99%, yield 76%.

[0053] Example 2.

[0054] (1) 160 g 2,6-dichlorotoluene (1.0 mol), 480 g dimethyl sulfoxide (DMSO) (3 M), and 51 g dimethyl disulfide (0.54 mol) were added to a 1 L glass reaction container at room temperature, and nitrogen was replaced by inertization; stirring was started, and the temperature was raised to 120°C, and 25 g (1.09 mol) of liquid metal sodium was added dropwise under temperature control. After the addition was completed, the temperature was kept constant for 3 h, and samples were taken for testing until the reaction was complete, and most of the solvent was distilled off under reduced pressure;

[0055] (2) The system was cooled to 50°C, 10 g of water was added dropwise to quench the reaction, 19 g (0.14 mol) of 27.5% hydrogen peroxide was slowly added dropwise, the reaction was continued for 1 h, the temperature was raised to 105°C, and steam distillation was started to evaporate the product until almost no product was distilled out. A light yellow oily compound was obtained by condensation and collection, and conventional vacuum distillation (120°C / 2 kPa) was performed to obtain the target compound 2-chloro-6-methylthiotoluene.

[0056] 140.1 g of 2-chloro-6-methylthiotoluene, purity 99%, yield 82%.

[0057] Example 3.

[0058] (1) 160 g 2,6-dichlorotoluene (1.0 mol), 320 g dimethyl sulfoxide (DMSO) (2 M), and 45 g dimethyl disulfide (0.48 mol) were added to a 1 L glass reaction container at room temperature, and nitrogen was replaced for inertization; stirring was started, the temperature was raised to 100 °C, and 20 g (0.87 mol) of liquid metal sodium was added dropwise under temperature control. After the addition was completed, the temperature was kept constant for 2 h, and samples were taken for testing until the reaction was complete, and most of the solvent was distilled off under reduced pressure;

[0059] (2) The system was cooled to 50°C, 10 g of water was added dropwise to quench the reaction, 100 g (0.14 mol) of 10% sodium hypochlorite solution was slowly added dropwise, the reaction was continued for 1 h, the temperature was raised to 110°C, and steam distillation was started to evaporate the product until almost no product was distilled out. A light yellow oily compound was obtained by condensation and collection, and conventional vacuum distillation (120°C / 2 kPa) was performed to obtain the target compound 2-chloro-6-methylthiotoluene.

[0060] 134.6 g of 2-chloro-6-methylthiotoluene, purity 99%, yield 78%.

[0061] Example 4.

[0062] (1) 160 g 2,6-dichlorotoluene (1.0 mol), 320 g cyclopentane sulfone (4 M), and 47 g dimethyl disulfide (0.5 mol) were added to a 1 L glass reaction container at room temperature, and nitrogen was replaced for inertization; stirring was started, the temperature was raised to 110°C, and 39 g (1.0 mol) of liquid potassium metal was added dropwise under temperature control. After the addition was completed, the temperature was kept constant for 2 h, and samples were taken for testing until the reaction was complete, and most of the solvent was distilled off under reduced pressure;

[0063] (2) The system was cooled to 50°C, 10 g of water was added dropwise to quench the reaction, 100 g (0.14 mol) of 10% sodium hypochlorite solution was slowly added dropwise, the reaction was continued for 1 h, the temperature was raised to 100°C, the vacuum pump system was turned on and the pressure was reduced to 1 kPa to evaporate the product until almost no product was distilled out, and a yellow oily compound was obtained by condensation and collection, and conventional vacuum distillation (120°C / 2 kPa) was performed to obtain the target compound 2-chloro-6-methylthiotoluene.

[0064] 2-Chloro-6-methylthiotoluene 135.2 g, purity 99%, yield 79%.

[0065] Example 5.

[0066] (1) At room temperature, 160 g (1.0 mol) of 2,6-dichlorotoluene and 47 g (0.5 mol) of dimethyl disulfide were added to a 1 L glass reaction container in sequence to replace the inert gas with nitrogen; stirring was started, the temperature was raised to 120°C, and 39 g (1.0 mol) of liquid potassium metal was added dropwise under temperature control. After the addition was completed, the temperature was kept constant for 2 h, and then sampling was performed for detection until the reaction was complete;

[0067] (2) The system was cooled to 50°C, 10 g of water was added dropwise to quench the reaction, 30 ml (0.16 mol) of air was slowly introduced, the reaction was allowed to proceed for 1 h, the temperature was raised to 110°C, and steam distillation was started to evaporate the product until almost no product was distilled out. A light yellow oily compound was obtained by condensation and collection, and conventional vacuum distillation (120°C / 2 kPa) was performed to obtain the target compound 2-chloro-6-methylthiotoluene.

[0068] 2-Chloro-6-methylthiotoluene 118.5 g, purity 98%, yield 69%.

[0069] The above embodiments are only for illustrating the technical concept and features of the present invention, and their purpose is to enable people familiar with the technology to understand the content of the present invention and implement it accordingly, and they cannot limit the protection scope of the present invention. Therefore, all equivalent modifications or changes made by those with ordinary knowledge in the technical field without departing from the spirit and technical ideas disclosed by the present invention should still be covered by the claims of the present invention.

Claims

1. A method for preparing 2-chloro-6-methylthiotoluene, characterized in that: The specific steps include: Step 1, adding 2,6-dichlorotoluene, aprotic polar solvent and dimethyl disulfide into a reaction container at room temperature, and performing nitrogen inertization replacement; starting stirring, heating to a reaction temperature of 100-130° C., dripping liquid active metal M through a heating pipeline, and keeping the temperature for 2 hours after dripping, sampling and testing until the reaction is complete, and distilling off most of the solvent under reduced pressure; the active metal M is potassium metal or sodium metal; Step 2: After distilling off most of the solvent under reduced pressure, cool to 40°C~60°C, slowly drop 5%~7% water relative to the mass of 2,6-dichlorotoluene to quench the reaction, then slowly add the oxidant, react for 1 hour, raise the temperature to 100~110°C, distill the product, collect after condensation to obtain a light yellow oily compound, and then perform conventional vacuum distillation to obtain the target compound 2-chloro-6-methylthiotoluene.

2. The method for preparing 2-chloro-6-methylthiotoluene according to claim 1, wherein In the step 1, the aprotic polar solvent is one of DMF, DMAC, DMSO, sulfolane, NMP or diethylene glycol dimethyl ether.

3. The method for preparing 2-chloro-6-methylthiotoluene according to claim 1, characterized in that: In the step 1, the mass of the aprotic polar solvent is 0 to 4 times the mass of 2,6-dichlorotoluene.

4. The method for preparing 2-chloro-6-methylthiotoluene according to claim 1, characterized in that: In the step 1, the molar ratio of dimethyl disulfide to 2,6-dichlorotoluene is 0.45-0.6:

1.

5. The method for preparing 2-chloro-6-methylthiotoluene according to claim 1, characterized in that: In the step 1, the molar ratio of the active metal M to dimethyl disulfide is 1.8-2.1:

1.

6. The method for preparing 2-chloro-6-methylthiotoluene according to claim 1, characterized in that: In step 2, the oxidant is one of hydrogen peroxide, sodium hypochlorite, oxygen or air.

7. The method for preparing 2-chloro-6-methylthiotoluene according to claim 1, characterized in that: In the step 2, the hydrogen peroxide is commercially available with a concentration of 27.5%, and the sodium hypochlorite is commercially available with a concentration of 10%.

8. The method for preparing 2-chloro-6-methylthiotoluene according to claim 1, characterized in that: In the step 2, the molar ratio of the oxidant to 2,6-dichlorotoluene is 0.1-0.3:1.