A method for preparing 2,4-dichloro-6-(methylthio)-1,3,5-triazine
By controlling the reaction conditions of 2,4,6-trichloro-1,3,5-triazine with carbonates and methanethiol, the problems of numerous byproducts and low purity in existing technologies were solved, and 2,4-dichloro-6-(methylthio)-1,3,5-triazine was prepared with high yield and high purity.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2023-06-28
- Publication Date
- 2026-03-13
AI Technical Summary
Existing methods for synthesizing 2,4-dichloro-6-(methylthio)-1,3,5-triazine are prone to generating byproducts, resulting in low purity, and the synthesis temperature is too low and the conditions are harsh.
The synthesis was carried out by reacting 2,4,6-trichloro-1,3,5-triazine with carbonate and methanethiol under an inert gas atmosphere, controlling the molar ratio and temperature, and by adding a propylene glycol solution of methanethiol dropwise. Post-treatment included crystallization, washing and rotary evaporation.
It effectively reduces the generation of by-products, achieves a yield of 89%, a purity of 98-99%, and uses mild synthesis conditions, making it suitable for large-scale production.
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Figure CN116768809B_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for preparing 2,4-dichloro-6-(methylthio)-1,3,5-triazine. Background Technology
[0002] The general method for synthesizing 2,4-dichloro-6-(methylthio)-1,3,5-triazine involves adding methanethiol to an acetone solution of 2,4,6-trichloro-1,3,5-triazine at a temperature of -25 to -30°C, slowly adding trimethylpyridine, adding hydrochloric acid to initiate precipitation, allowing the mixture to stand at 0°C for one hour, pouring the mixture onto ice, and precipitating a white crystalline substance. The precipitate is then washed with water and dried in a desiccator to obtain the product. The low temperatures at which methanethiol is added and the relatively low reaction temperature, combined with the fact that 2,4,6-trichloro-1,3,5-triazine has three identical sites, readily generates byproducts containing two methylthio groups.
[0003] Existing methods for synthesizing 2,4-dichloro-6-(methylthio)-1,3,5-triazine suffer from problems such as the easy formation of byproducts leading to low purity, excessively low synthesis temperatures, and stringent synthesis conditions. Therefore, developing a method for preparing 2,4-dichloro-6-(methylthio)-1,3,5-triazine with fewer byproducts, higher purity, higher yield, and milder synthesis conditions is a pressing issue in this field. Summary of the Invention
[0004] In view of the shortcomings of the prior art, the present invention aims to provide a method for preparing 2,4-dichloro-6-(methylthio)-1,3,5-triazine. The preparation method generates few by-products, obtains products with high yield and purity, and uses relatively mild synthesis conditions. It can be used for the large-scale preparation of 2,4-dichloro-6-(methylthio)-1,3,5-triazine.
[0005] To achieve this objective, the present invention adopts the following technical solution:
[0006] In a first aspect, the present invention provides a method for preparing 2,4-dichloro-6-(methylthio)-1,3,5-triazine, the method comprising: reacting 2,4,6-trichloro-1,3,5-triazine, carbonate and methanethiol to obtain the 2,4-dichloro-6-(methylthio)-1,3,5-triazine.
[0007] Preferably, the preparation method is as follows:
[0008]
[0009] Preferably, the carbonate is a soluble carbonate.
[0010] Preferably, the carbonate is any one or a combination of at least two of sodium carbonate, potassium carbonate, sodium bicarbonate, or potassium bicarbonate.
[0011] In this invention, 2,4,6-trichloro-1,3,5-triazine is added to acetone to dissolve, and the phenomenon is that the original clear liquid becomes an emulsion, and then becomes clear again. Then carbonate is added, and the phenomenon is that the reaction solution becomes turbid again because the carbonate is insoluble, and there are transparent crystals on the bottle wall. A propylene glycol solution of methanethiol is slowly added dropwise, and after the addition is completed, the mixture is stirred at room temperature for 2 hours. The phenomenon is that the solution is still an emulsion.
[0012] Preferably, the molar ratio of 2,4,6-trichloro-1,3,5-triazine to carbonate is 1:(1.8-2.5), for example, it can be 1:1.8, 1:1.9, 1:2, 1:2.1, 1:2.2, 1:2.5, and specific values between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values included in the range.
[0013] Preferably, the molar ratio of 2,4,6-trichloro-1,3,5-triazine to methanethiol is 1:(1.1-1.5), for example, it can be 1:1.1, 1:1.2, 1:1.3, 1:1.5, and specific values between the above points. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values included in the range.
[0014] Preferably, the methanethiol is a propylene glycol solution of methanethiol.
[0015] Preferably, the mass concentration of methanethiol in the propylene glycol solution is 5-15%, for example, it can be 5%, 7%, 9%, 10%, 12%, 14%, 15%, and specific values between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values included in the range.
[0016] Preferably, the reaction is carried out in the presence of a solvent.
[0017] Preferably, the solvent includes acetone.
[0018] Preferably, the reaction is carried out under conditions of inert gas protection.
[0019] Preferably, the inert gas protection includes nitrogen protection.
[0020] Preferably, after mixing the 2,4,6-trichloro-1,3,5-triazine with a solvent, carbonate is added, followed by the addition of methanethiol to react and obtain the 2,4-dichloro-6-(methylthio)-1,3,5-triazine.
[0021] Preferably, the temperature at which methanethiol is added is between -5°C and 0°C, for example, it can be -5°C, -4°C, -3°C, -2°C, -1°C, 0°C, and specific values between the above values. Due to space limitations and for the sake of brevity, this invention will not exhaustively list all the specific values included in the range.
[0022] Preferably, the time for adding methanethiol is 10-15 minutes, for example, 10 minutes, 11 minutes, 12 minutes, 13 minutes, 14 minutes, 15 minutes, and specific values between the above values. Due to space limitations and for the sake of brevity, this invention will not exhaustively list all the specific values included in the range.
[0023] Preferably, the reaction temperature is 20-30℃, for example, it can be 20℃, 22℃, 24℃, 25℃, 26℃, 28℃, 30℃, and specific values between the above points. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values included in the range.
[0024] Preferably, the reaction time is 1-3 hours, for example, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, and specific values between the above values. Due to space limitations and for the sake of brevity, this invention will not exhaustively list all the specific values included in the range.
[0025] Detection reaction: Thin-layer chromatography analysis was performed using petroleum ether and ethyl acetate in a volume ratio of 10:1.
[0026] Preferably, the preparation method specifically includes the following steps:
[0027] 2,4,6-trichloro-1,3,5-triazine and a solvent were mixed, and then carbonate was added to obtain a mixture. A propylene glycol solution of methanethiol was added dropwise to the mixture at a temperature of -5 to 0°C for 10 to 15 minutes. The molar ratio of 2,4,6-trichloro-1,3,5-triazine, carbonate, and methanethiol was 1:(1.8-2.5):(1.1-1.5). After the addition was completed, the temperature was raised to 20 to 30°C and the reaction was carried out in an inert atmosphere for 1 to 3 hours to obtain 2,4-dichloro-6-(methylthio)-1,3,5-triazine.
[0028] Preferably, the molar ratio of the 2,4,6-trichloro-1,3,5-triazine, carbonate, and methanethiol is 1:2.0:1.5.
[0029] Preferably, the reaction further includes post-processing.
[0030] Preferably, the post-processing includes crystallization, first washing, first filtration, rotary evaporation, pulping, second filtration, and second washing.
[0031] Preferably, the crystallization process involves adding 400-600 mL of ice water and letting it stand for 5-15 minutes.
[0032] Preferably, the first wash includes an ice water wash.
[0033] Preferably, the rotary evaporation includes vacuum rotary drying at 25-40°C.
[0034] Preferably, the pulping process involves a water-to-petroleum ether volume ratio of (80-150):1.
[0035] Preferably, the second washing includes petroleum ether washing and / or diethyl ether washing.
[0036] Compared with the prior art, the present invention has the following beneficial effects:
[0037] This invention provides a method for preparing 2,4-dichloro-6-(methylthio)-1,3,5-triazine. Through the interaction of 2,4,6-trichloro-1,3,5-triazine, methanethiol, and carbonate, 2,4-dichloro-6-(methylthio)-1,3,5-triazine can be effectively synthesized, reducing the formation of by-products. The yield of the obtained product can reach 89%, and the purity can reach 98-99%. The preparation conditions are mild and can be applied to the large-scale production of 2,4-dichloro-6-(methylthio)-1,3,5-triazine. Attached Figure Description
[0038] Figure 1 The 1H NMR spectrum of 2,4-dichloro-6-(methylthio)-1,3,5-triazine obtained in Example 1 of this invention;
[0039] Figure 2 The image shows the gas chromatogram-mass spectrum of 2,4-dichloro-6-(methylthio)-1,3,5-triazine obtained in Example 1 of this invention. Detailed Implementation
[0040] The technical solution of the present invention will be further illustrated below through specific embodiments. Those skilled in the art should understand that the embodiments described are merely illustrative of the present invention and should not be construed as limiting the invention in any way.
[0041] Example 1
[0042] This embodiment provides a method for preparing 2,4-dichloro-6-(methylthio)-1,3,5-triazine. The specific preparation method is as follows: Under anhydrous and oxygen-free conditions and nitrogen protection, 2,4,6-trichloro-1,3,5-triazine (5g, 27.11mmol) was added to a 500ml three-necked flask containing 50ml acetone to dissolve. The solution changed from clear to emulsion, then became clear again. Then, anhydrous sodium bicarbonate (4.56g, 54.23mmol) was added. The solution became cloudy again because sodium bicarbonate is insoluble, and transparent crystals appeared on the flask wall. The reaction system was cooled to -5℃, and methanethiol (a 10% methanethiol solution in propylene glycol) (14.51g, 30.165mmol) was slowly added dropwise. After the addition was complete, the mixture was stirred at room temperature for 2 hours. The solution remained an emulsion. After the reaction was completed, 450 ml of ice water was added, and the mixture was allowed to stand for 10 minutes. The observed phenomenon was that a pale yellow solid began to precipitate from the emulsion, with a solid layer on top and a clear liquid layer below. After filtration, a layer of crushed ice remained on the filter paper. The mixture was washed repeatedly with ice water to obtain a pure white solid. The water was then removed, and the solid was evaporated under vacuum at 30°C to remove any remaining methanethiol and water. The measured 1H NMR spectrum is shown below. Figure 1 As shown, the gas chromatography-mass spectrum of the test is as follows. Figure 2 The result shows that the product obtained is 2,4-dichloro-6-(methylthio)-1,3,5-triazine, with a product weight of 4.74 g, a yield of 89.16%, and a purity of 99%. + % 1 H NMR (400MHz, CDCl3) δ2.63 (s, 3H); GCMS ACN 99 + %.
[0043] Example 2
[0044] This embodiment provides a method for preparing 2,4-dichloro-6-(methylthio)-1,3,5-triazine. The specific preparation method is as follows: Under anhydrous and oxygen-free conditions and nitrogen protection, 5 g of 2,4,6-trichloro-1,3,5-triazine (27.11 mmol) was added to a 500 ml three-necked flask containing 50 ml of acetone to dissolve. The solution changed from clear to emulsion, then became clear again. Then, anhydrous sodium bicarbonate (4.56 g, 54.23 mmol) was added. The solution became cloudy again because sodium bicarbonate is insoluble, and transparent crystals appeared on the flask wall. The reaction system was cooled to -5°C, and 14.51 g of methanethiol (a 10% methanethiol solution in propylene glycol) (30.165 mmol) was slowly added dropwise. After the addition was complete, the mixture was stirred at room temperature for 5 hours. The solution remained an emulsion. After the reaction was complete, 450 ml of ice water was added, and the mixture was allowed to stand for 10 minutes. The following observations were observed: a pale yellow solid began to precipitate from the emulsion, with a solid layer on top and a clear liquid layer at the bottom. After filtration, a layer of crushed ice remained on the filter paper. The mixture was washed repeatedly with ice water to obtain a pure white solid. The water was then removed by vacuum drying at 30°C to remove any remaining methanethiol and water. 1 HNMR and GCMS results indicate that the product contains 84% of the target product, with 15% being 2-chloro-4,6-di(methylthio)-1,3,5-triazine.
[0045] Example 3
[0046] This embodiment provides a method for preparing 2,4-dichloro-6-(methylthio)-1,3,5-triazine. The specific preparation method is as follows: Under anhydrous and oxygen-free conditions and nitrogen protection, 2,4,6-trichloro-1,3,5-triazine (5g, 27.11mmol) was added to a 500ml three-necked flask containing 50ml acetone to dissolve. The solution changed from clear to emulsion, then became clear again. Then, anhydrous sodium bicarbonate (4.56g, 54.23mmol) was added. The solution became cloudy again because sodium bicarbonate is insoluble, and transparent crystals appeared on the flask wall. Methanethiol (10% propylene glycol solution) (14.51g, 30.165mmol) was slowly added dropwise at room temperature. After the addition was complete, the solution was stirred at room temperature for 2 hours. The solution remained an emulsion. After the reaction was complete, 450 ml of ice water was added, and the mixture was allowed to stand for 10 minutes. The following observations were observed: a pale yellow solid began to precipitate from the emulsion, with a solid layer on top and a clear liquid layer at the bottom. After filtration, a layer of crushed ice remained on the filter paper. The mixture was washed repeatedly with ice water to obtain a pure white solid. The water was then removed by vacuum drying at 30°C to remove any remaining methanethiol and water. 1 HNMR and GCMS results showed that the target product accounted for 37% of the filter cake, with the remainder being raw material. The reaction at room temperature would cause the volatilization of methanethiol (the boiling point of methanethiol is 6℃ (lit)).
[0047] Example 4
[0048] This embodiment provides a method for preparing 2,4-dichloro-6-(methylthio)-1,3,5-triazine. The only difference between this method and Example 1 is the amount of anhydrous sodium bicarbonate used (5.47 g, 65.08 mmol); all other raw materials, amounts, and preparation methods are the same as in Example 1. The product weight is 4.44 g, and the yield is 82.48%. 1 HNMR and GCMS analysis results indicate a purity of 99%. + % 1 H NMR (400MHz, CDCl3) δ2.63 (s, 3H); GCMS ACN 99 + %.
[0049] Example 5
[0050] This embodiment provides a method for preparing 2,4-dichloro-6-(methylthio)-1,3,5-triazine. The only difference between this method and Example 1 is that anhydrous sodium carbonate is used instead of anhydrous sodium bicarbonate; all other raw materials, amounts, and preparation methods are the same as in Example 1. 1 HNMR and GCMS results showed that 45% was the target product and the remainder was the raw material.
[0051] Example 6
[0052] This embodiment provides a method for preparing 2,4-dichloro-6-(methylthio)-1,3,5-triazine. The only difference between this method and Example 1 is that the time for adding methanethiol is 1 minute; all other raw materials, amounts, and preparation methods are the same as in Example 1. 1 HNMR and GCMS results showed that 66.7% of the product was 2-chloro-4,6-di(methylthio)-1,3,5-triazine, 10% was the raw material, 20% was the target product, and the remainder was an unknown impurity.
[0053] Comparative Example 1
[0054] This comparative example provides a method for preparing 2,4-dichloro-6-(methylthio)-1,3,5-triazine. The only difference between this method and Example 1 is that the amount of methanethiol used is 65.21 g and 135.57 mmol; the other raw materials, amounts, and preparation methods are the same as in Example 1. 1 HNMR and GCMS results showed that the filter cake contained 74.23% 2-chloro-4,6-di(methylthio)-1,3,5-triazine, with the remainder being unreacted raw materials.
[0055] Comparative Example 2
[0056] This comparative example provides a method for preparing 2,4-dichloro-6-(methylthio)-1,3,5-triazine. The only difference between this method and Example 1 is that the amount of anhydrous sodium bicarbonate used is 5.16 g and 61.46 mmol; all other raw materials, amounts, and preparation methods are the same as in Example 1. 1 ¹H NMR and GC MS results showed that the filter cake contained 74.23% 2-chloro-4,6-di(methylthio)-1,3,5-triazine, with the remainder being unreacted starting material. The yield was 2 g of 2,4-dichloro-6-(methylthio)-1,3,5-triazine, with a yield of 37.55% and a purity of 75%. + %.
[0057] Comparative Example 3
[0058] This comparative example provides a method for preparing 2,4-dichloro-6-(methylthio)-1,3,5-triazine. The only difference between this method and Example 1 is that anhydrous sodium bicarbonate is not added, and trimethylpyridine (6.56 g, 54.23 mmol) is used instead. All other raw materials, amounts, and preparation methods are the same as in Example 1. 1 ¹H NMR and GC MS results showed that the filter cake contained 74.23% 2-chloro-4,6-di(methylthio)-1,3,5-triazine, with the remainder being unreacted raw materials. Detection indicated that the reaction contained numerous impurities and no target product was found.
[0059] This invention provides a method for preparing 2,4-dichloro-6-(methylthio)-1,3,5-triazine. Through the interaction between raw materials and the control of the feed ratio, 2,4-dichloro-6-(methylthio)-1,3,5-triazine can be effectively synthesized. Example 1 shows the preparation of 2,4-dichloro-6-(methylthio)-1,3,5-triazine, with a mild preparation process and high product purity and yield. In contrast, Comparative Examples 1-2 showed low yields, and Comparative Example 3 showed no formation of the target product.
[0060] The applicant declares that the present invention is illustrated by the above embodiments, but the present invention is not limited to the above process steps, that is, it does not mean that the present invention must rely on the above process steps to be implemented. Those skilled in the art should understand that any improvements to the present invention, equivalent substitutions of the raw materials used in the present invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.
Claims
1. A method for preparing 2,4-dichloro-6-(methylthio)-1,3,5-triazine, characterized in that, The preparation method includes: 2,4,6-Trichloro-1,3,5-triazine After mixing with a solvent, bicarbonate is added, followed by the addition of methanethiol to react and obtain the 2,4-dichloro-6-(methylthio)-1,3,5-triazine. The temperature for adding methanethiol is -5 to 0°C, and the temperature for the reaction is 20-30°C. The bicarbonate is sodium bicarbonate.
2. The preparation method according to claim 1, characterized in that, The molar ratio of 2,4,6-trichloro-1,3,5-triazine to methanethiol is 1:(1.1-1.5).
3. The preparation method according to claim 1, characterized in that, The methanethiol is a propylene glycol solution of methanethiol.
4. The preparation method according to claim 3, characterized in that, The mass concentration of methanethiol in the propylene glycol solution is 5-15%.
5. The preparation method according to claim 1, characterized in that, The solvent is acetone.
6. The preparation method according to claim 1, characterized in that, The reaction is carried out under inert gas protection.
7. The preparation method according to claim 6, characterized in that, The inert gas protection is nitrogen protection.
8. The preparation method according to claim 1, characterized in that, The time for adding methanethiol is 10-15 minutes.
9. The preparation method according to claim 1, characterized in that, The reaction time is 1-3 h.
10. The preparation method according to claim 1, characterized in that, The preparation method specifically includes the following steps: 2,4,6-trichloro-1,3,5-triazine and a solvent were mixed, and then a bicarbonate was added to obtain a mixture; the bicarbonate was sodium bicarbonate. A propylene glycol solution of methanethiol is added dropwise to the mixture at a temperature of -5 to 0°C for 10-15 minutes. The molar ratio of 2,4,6-trichloro-1,3,5-triazine, bicarbonate, and methanethiol is 1:(1.8-2.5):(1.1-1.5). After the addition is complete, the temperature is raised to 20-30℃ and reacted in an inert protective atmosphere for 1-3 h to obtain the 2,4-dichloro-6-(methylthio)-1,3,5-triazine.