A method for preparing prometryn

Abstract

The application discloses a preparation method of terbucarb, which comprises the following steps: taking 2-methylamino-5-tert-butyl-1,3,4-thiadiazole hydrochloride as raw material, reacting with methyl isocyanate in water under the action of a phase transfer catalyst, adjusting the reaction solution to be neutral after the reaction is completed and the temperature is increased to 50-60 DEG C, cooling and crystallizing, filtering, washing and drying the filter cake, and obtaining terbucarb products. The preparation method has the advantages of high yield, less waste, low cost, simple operation and the like.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of organic chemical industry, in particular to a preparation method of tebutam. BACKGROUND

[0002] Tebuthiuron, also known as buthiuron, diazuron and tebuturon, is commonly known as Tebuthiuron. It is a photosynthesis inhibitor and a broad-spectrum herbicide for soil application. It is mainly absorbed by the roots of plants and inhibits photosynthesis electron transfer. Due to its low toxicity, small dosage, wide spectrum of weeds, and long residual period, it has attracted much attention and can be used to prevent and control annual weeds in forests (firebreaks), and can also be used to prevent and control the growth of various plants in non-cultivated areas and selectively control weeds in sugarcane fields.

[0003] Tebuthiuron was first developed by Eillilly (now Dow) and introduced into Brazil in 1974. It is an early variety on the market. Tebuthiuron did not pass the EU re-evaluation and was withdrawn from the market in July 2003. In the Brazilian market, tebuthiuron is one of the most important herbicides. In 2005, Andermatt was the first to complete the registration of tebuthiuron imitation in Brazil, and other domestic companies also followed suit. In 2022, due to the successful promotion of the mefenacet + tebuthiuron mixture of FMC and Andermatt in Brazil, the demand for tebuthiuron in the market increased significantly.

[0004] There are many synthesis routes for tebuthiuron. According to the different reaction materials of the key intermediate 2-methylamino-5-tert-butyl-1,3,4-thiadiazole (MTBA), it can be divided into methyl isocyanate (MIC) route, methylamino carbonyl chloride (MCC) route, phosgene (double phosgene, solid phosgene)-methylamine route and other synthesis routes.

[0005] Tao et al. [Synthesis of 1-(5-t-butyl-1,3,4-thiadiazol-2-yl)-1,3-dimethylurea. Synthetic Communications, 1974, 4(4):249-250] used 1-pivaloyl-4-methyl-3- aminothiourea as raw material, dehydrated with concentrated sulfuric acid at 50-55 ℃ to obtain MTBA, extracted with toluene, and reacted with MIC at 85-90 ℃ for 1.5 h to obtain terbumeton, with a total yield of 88.5%. David et al. [Process for preparing compound 5-t-butyl-2-methylamino-1,3,4-triadiazole. US, 4283543, 1981-08-11] used methylthiosemicarbazide (MTSC) and pivalic acid as raw materials, dehydrated and condensed with polyphosphoric acid and concentrated sulfuric acid at 70-80 ℃ to obtain MTBA, which was extracted with toluene and reacted with MIC to obtain terbumeton, with a total yield of 90.8%, and the yield of MTBA and MIC reaction was 92.65%. MIC is a highly toxic chemical, with a boiling point of 39.1 ℃, and high-temperature reaction may cause MIC to escape, causing safety accidents.

[0006] Shi et al. [Study on the synthesis process of tebutam, Chemical World, 2019, 60(10):706-710] used methylcarbamoyl chloride (MCC) route to synthesize terbumeton. The MCC used in this method can be synthesized from methylamine and phosgene, bis-phosgene or tris-phosgene, and can be transported and stored, avoiding the use of MIC which is only owned by phosgene production enterprises. However, this process uses a large amount of acid-binding agent, increasing the cost of raw materials and "three wastes" treatment, which is the only choice for non-phosgene production enterprises to produce terbumeton.

[0007] Chinese patent document CN101157665A discloses a method for preparing terbumeton, which uses phosgene (bis-phosgene, solid phosgene)-methylamine route to synthesize terbumeton. In the process of acyl chloride reaction of MTBA, symmetrical urea is easily generated, making the product difficult to refine. In addition, the acyl chloride reaction of MTBA requires excess phosgene (bis-phosgene or tris-phosgene), and the amidation reaction requires excess methylamine. Therefore, the raw materials and "three wastes" treatment cost of this method for producing terbumeton is high.

[0008] Chinese patent document CN105669592A discloses a synthetic method of terbumeton, which is obtained by reacting 1,3-dimethylurea and a derivative of 5-tert-butyl-1,3,4-thiadiazole in an excess amount under alkaline conditions, with a yield of 88%-94.4%. This method avoids the use of MIC, MCC, phosgene (bis-phosgene, solid light) and methylamine which are relatively toxic, but the raw materials 1,3-dimethylurea and the derivative of 5-tert-butyl-1,3,4-thiadiazole are high in cost, so this method is not suitable for large-scale industrial production. Liu Huihua et al. [CN 101157665.2008-04-09] reacted chloroformate compounds with MTBA to obtain N-(5-(tert-butyl)-1,3,4-thiadiazol-2-yl)-N-methyl carbamate compounds, and then used aqueous methylamine solution to carry out ammonolysis to obtain terbumeton, with a yield of 63.7%. This method needs to use an excess of chloroformate compounds to react with MTBA and an excess of aqueous methylamine solution for ammonolysis, so the yield is low, the raw materials and the treatment cost of "three wastes" are high, and this method is not suitable for large-scale industrial production.

[0009] Green chemistry is "aiming to imitate nature, focusing on reducing downstream chemical waste", and water cannot be used to dissolve many organic compounds, resulting in the use of a large amount of organic solvents harmful to the environment in many industries, and no better way can be found to solve the problem.

[0010] With the increasing market demand for terbumeton and the increasing requirements for environmental protection, it is necessary to develop a new production process of terbumeton to improve the reaction yield, reduce the production of "three wastes", and achieve the goal of improving the economic and social benefits of enterprises. SUMMARY

[0011] The technical problem to be solved by the present application is to overcome the shortcomings of the prior art and provide a preparation method of terbumeton, which has high reaction yield, low cost, simple operation and less "three wastes".

[0012] To solve the above technical problems, the following technical solutions are adopted in the present application.

[0013] A preparation method of terbumeton, which uses 2-methylamino-5-tert-butyl-1,3,4-thiadiazole hydrochloride as a raw material, reacts with methyl isocyanate in water under the action of a phase transfer catalyst, warms up to 50-60℃ after the reaction is completed, makes the obtained reaction liquid fully dissolved, adjusts the reaction liquid to be neutral, cools and crystallizes, filters, and then washes and dries the filter cake to obtain terbumeton product.

[0014] The chemical reaction formula of the present application is as follows:

[0015]

[0016] The preparation method of the above-mentioned terbuthylazine, preferably, the temperature of the reaction is 15-25℃.

[0017] The preparation method of the above-mentioned terbuthylazine, preferably, the phase transfer catalyst is one or more of tetrabutylammonium bromide, tetrabutylammonium chloride and tetrabutylammonium hydrogen sulfate.

[0018] The preparation method of the above-mentioned terbuthylazine, preferably, the molar amount of the phase transfer catalyst is 0.05-0.5% of the molar amount of 2-methylamino-5-tert-butyl-1,3,4-thiadiazole hydrochloride.

[0019] The preparation method of the above-mentioned terbuthylazine, preferably, the molar ratio of 2-methylamino-5-tert-butyl-1,3,4-thiadiazole hydrochloride to methyl isocyanate is 1:1.02-1.06.

[0020] The preparation method of the above-mentioned terbuthylazine, preferably, the mass ratio of water to 2-methylamino-5-tert-butyl-1,3,4-thiadiazole hydrochloride is 2-4:1.

[0021] The preparation method of the above-mentioned terbuthylazine, preferably, the reaction product is adjusted to neutral by adding sodium hydroxide solution.

[0022] The preparation method of the above-mentioned terbuthylazine, preferably, the filter cake is washed with water.

[0023] The preparation method of the above-mentioned terbuthylazine, preferably, in the preparation method, the 2-methylamino-5-tert-butyl-1,3,4-thiadiazole hydrochloride, the phase transfer catalyst and the water are mixed first, then the methyl isocyanate is added dropwise at the reaction temperature, and after the dropwise addition is completed, the reaction is kept for a certain time until the reaction is finished.

[0024] The preparation method of the above-mentioned terbuthylazine, preferably, the keeping time of the reaction is 0.5-3h.

[0025] The main principle of the present application is:

[0026] The phase transfer catalyst is added to make the methyl isocyanate contact more fully with the 2-methylamino-5-tert-butyl-1,3,4-thiadiazole hydrochloride in the water phase, improve the mass transfer efficiency, enable the reaction to be completed rapidly in the water at a lower temperature, reduce the hydrolysis of the methyl isocyanate and the occurrence of other side reactions, improve the yield of the terbuthylazine product, reduce the consumption of the methyl isocyanate and the difficulty of wastewater treatment, and reduce the production cost.

[0027] Compared with the prior art, the present application has the following advantages:

[0028] The method of the present application has simple process and obvious effect. By adding the phase transfer catalyst, the reaction of methyl isocyanate and 2-methylamino-5-tert-butyl-1, 3, 4-thiadiazole hydrochloride in water phase is rapid and sufficient, the mass transfer efficiency is high, compared with the prior art, the method of the present application obviously improves the reaction yield, the yield is 97.5% to 98.3% (content 98.0% to 98.5%). The present application uses water as the solvent, avoids the use of toxic solvents, and is friendly to the environment. At the same time, low temperature reaction reduces the hydrolysis of methyl isocyanate and the occurrence of other side reactions, reduces the consumption of methyl isocyanate, reduces the production cost, and achieves the goal of improving the economic benefit and social benefit of enterprises. DETAILED DESCRIPTION

[0029] The present application is further described below in combination with specific preferred embodiments, but does not limit the protection scope of the present application. The materials and instruments used in the following examples are commercially available.

[0030] Example 1

[0031] A preparation method of the terbumeton of the present application, comprising the following steps:

[0032] 2000mL three-necked flask was sequentially added 211.45g (98.13%, 1mol) 2-methylamino-5-tert-butyl-1, 3, 4-thiadiazole hydrochloride, 0.33g (99%, 0.001mol) tetrabutylammonium bromide and 422.9g water, and then 58.39g (99.64%, 1.02mol) methyl isocyanate was added dropwise after cooling to 15℃, and the reaction was maintained for 0.5h after the dropwise addition was completed. After the reaction was completed, the temperature was increased to 50℃ to 60℃, the material was fully dissolved, and then a 40% sodium hydroxide solution was added to adjust the reaction system to neutral, and then cooled and crystallized, filtered, the filter cake was washed with water, and dried to obtain 225.99g white crystal terbumeton product, content 98.5%, yield 97.5%.

[0033] Example 2

[0034] A preparation method of the terbumeton of the present application, comprising the following steps:

[0035] Into a 2000ml three-necked flask, 211.45g (98.13%, 1mol) 2-methylamino-5-tert-butyl-1, 3, 4-thiadiazole hydrochloride, 1.42g (98%, 0.005mol) tetrabutylammonium chloride and 634.35g water were sequentially added, and then the temperature was lowered to 25°C. After that, 59.54g (99.64%, 1.04mol) methyl isocyanate was added dropwise, and the reaction was allowed to proceed for 1h after the addition was completed. After the reaction was completed, the temperature was raised to 50-60°C, and then a 40% sodium hydroxide solution was added to adjust the reaction system to neutral. After the reaction system was cooled and crystallized, the product was filtered and washed with water, and then dried to obtain 227.12g of white crystal of terbumeton product, with a content of 98.21% and a yield of 97.7%.

[0036] Example 3

[0037] A method for preparing terbumeton according to the present application comprises the following steps:

[0038] Into a 2000ml three-necked flask, 211.45g (98.13%, 1mol) 2-methylamino-5-tert-butyl-1, 3, 4-thiadiazole hydrochloride, 0.17g (99%, 0.0005mol) tetrabutylammonium hydrogen sulfate and 845.8g water were sequentially added, and then the temperature was lowered to 18°C. After that, 60.68g (99.64%, 1.06mol) methyl isocyanate was added dropwise, and the reaction was allowed to proceed for 2h after the addition was completed. After the reaction was completed, the temperature was raised to 50-60°C, and then a 40% sodium hydroxide solution was added to adjust the reaction system to neutral. After the reaction system was cooled and crystallized, the product was filtered and washed with water, and then dried to obtain 229.01g of white crystal of terbumeton product, with a content of 98% and a yield of 98.3%.

[0039] Example 4

[0040] A method for preparing terbumeton according to the present application comprises the following steps:

[0041] Into a 2000ml three-necked flask, 211.45g (98.13%, 1mol) 2-methylamino-5-tert-butyl-1, 3, 4-thiadiazole hydrochloride, 0.65g (99%, 0.002mol) tetrabutylammonium bromide and 634.35g water were sequentially added, and then the temperature was lowered to 15°C. After that, 59.96g (99.64%, 1.03mol) methyl isocyanate was added dropwise, and the reaction was allowed to proceed for 2h after the addition was completed. After the reaction was completed, the temperature was raised to 50-60°C, and then a 40% sodium hydroxide solution was added to adjust the reaction system to neutral. After the reaction system was cooled and crystallized, the product was filtered and washed with water, and then dried to obtain 227.66g of white crystal of terbumeton product, with a content of 98.18% and a yield of 97.9%.

[0042] Example 5

[0043] A preparation method of the terbuthylazine of the present application, comprising the following steps:

[0044] In a 2000 mL three-necked flask, 211.45 g (98.13%, 1 mol) of 2-methylamino-5-tert-butyl-1,3,4-thiadiazole hydrochloride, 0.98 g (99%, 0.003 mol) of tetrabutylammonium bromide and 528.63 g of water were sequentially added, and then 58.39 g (99.64%, 1.02 mol) of methyl isocyanate was added dropwise after cooling to 15°C. After the dropwise addition was completed, the reaction was maintained for 3 h. After the reaction was completed, the temperature was increased to 50-60°C, and then a 40% sodium hydroxide solution was added to adjust the reaction system to neutral. After cooling and crystallization, the filter cake was washed with water, and then dried to obtain 228.26 g of white crystalline terbuthylazine product with a content of 98.22% and a yield of 98.2%.

[0045] Example 6

[0046] A preparation method of the terbuthylazine of the present application, comprising the following steps:

[0047] In a 2000 mL three-necked flask, 211.45 g (98.13%, 1 mol) of 2-methylamino-5-tert-butyl-1,3,4-thiadiazole hydrochloride, 0.98 g (99%, 0.003 mol) of tetrabutylammonium bromide and 528.63 g of water were sequentially added, and then 58.39 g (99.64%, 1.02 mol) of methyl isocyanate was added dropwise after cooling to 15°C. After the dropwise addition was completed, the reaction was maintained for 3 h. After the reaction was completed, the temperature was increased to 50-60°C, and then a 40% sodium hydroxide solution was added to adjust the reaction system to neutral. After cooling and crystallization, the filter cake was washed with water, and then dried to obtain 228.26 g of white crystalline terbuthylazine product with a content of 98.22% and a yield of 98.2%.

[0048] Example 7

[0049] A preparation method of the terbuthylazine of the present application, comprising the following steps:

[0050] Into a 2000ml three-necked flask, 211.45g (98.13%, 1mol) 2-methylamino-5-tert-butyl-1,3,4-thiadiazole hydrochloride, 0.27g (99%, 0.0008mol) tetrabutylammonium hydrogen sulfate and 740.08g water were added successively, and then the temperature was lowered to 15°C. After that, 58.39g (99.64%, 1.02mol) methyl isocyanate was added dropwise. After the addition was completed, the reaction was allowed to proceed for 2h. After the reaction was completed, the temperature was raised to 50-60°C. After the material was completely dissolved, 40% sodium hydroxide solution was added to adjust the reaction system to neutral. After cooling and crystallization, the product was filtered and washed with water. After drying, 227.77g white crystal of terbumeton was obtained, with a content of 98.13% and a yield of 97.9%.

[0051] The above description is only the preferred embodiment of the present application, and does not limit the present application in any form. Although the present application has been disclosed as above with the preferred embodiment, it is not intended to limit the present application. Any person skilled in the art can make many possible changes and modifications to the technical solution of the present application, or modify equivalent embodiments with the above disclosed methods and technical contents without departing from the spirit and technical solution of the present application. Therefore, any simple modification, equivalent replacement, equivalent change and modification made to the above embodiments according to the technical essence of the present application, which does not depart from the content of the technical solution of the present application, still belongs to the protection scope of the technical solution of the present application.

Claims

1. A process for the preparation of tetbutylthidiazole, characterized in that, The 2-methylamino-5-tert-butyl-1,3,4-thiadiazole hydrochloride is used as raw material, and reacts with methyl isocyanate in water under the action of phase transfer catalyst, the reaction product is heated to 50-60 DEG C after the reaction, the material in the reaction liquid is dissolved, the reaction liquid is adjusted to neutral, and the product is obtained by cooling and crystallization, filtration, washing and drying of the filter cake. The phase transfer catalyst is one or more of tetrabutylammonium bromide, tetrabutylammonium chloride and tetrabutylammonium hydrogen sulfate.

2. The process for preparing the tebtuthion according to claim 1, characterized in that, The reaction temperature is 15-25 DEG C.

3. The process for the preparation of tebtine according to claim 1 or 2, characterized in that, The molar amount of the phase transfer catalyst is 0.05-0.5% of the molar amount of 2-methylamino-5-tert-butyl-1,3,4-thiadiazole hydrochloride.

4. The process for the preparation of tebtine according to claim 1 or 2, characterized in that, The molar ratio of 2-methylamino-5-tert-butyl-1,3,4-thiadiazole hydrochloride to methyl isocyanate is 1:1.02-1.

06.

5. The process for the preparation of tebtine according to claim 1 or 2, characterized in that, The mass ratio of water to 2-methylamino-5-tert-butyl-1,3,4-thiadiazole hydrochloride is 2-4:

1.

6. The method of preparing tebtuthion according to claim 1 or 2, characterized in that, The reaction product is adjusted to neutral by adding sodium hydroxide solution.

7. The method of preparing tebtuthion according to claim 1 or 2, characterized in that, The filter cake is washed with water.

8. The process for preparing tebtuthion according to claim 1 or 2, characterized by, In the preparation method, the 2-methylamino-5-tert-butyl-1,3,4-thiadiazole hydrochloride, phase transfer catalyst and water are mixed first, then methyl isocyanate is added dropwise at the reaction temperature, and the reaction is kept until the reaction is completed after the dropwise addition is completed.

9. The process for the preparation of tebtine according to claim 8, characterized in that, The keeping reaction time is 0.5-3h.

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