A process for the preparation of 2-methylamino-5-tert-butyl-1,3,4-thiadiazole

Abstract

The application discloses a preparation method of 2-methylamino-5-tert-butyl-1,3,4-thiadiazole, which comprises the following steps: under water bath cooling, first toluene solvent, 4-methylaminothiourea, a dehydration reaction catalyst and pivaloyl chloride are sequentially added into a reaction bottle and stirred, the temperature is increased to 60-100 DEG C for reaction, after the reaction is completed, cooling and filtering are carried out, the filter cake is added into second toluene solvent, the temperature is increased to 50-80 DEG C, then the filter cake is neutralized by liquid alkali, the water phase is separated, the organic phase is refluxed to remove water and dissolve, and 2-methylamino-5-tert-butyl-1,3,4-thiadiazole is obtained. The preparation method can avoid the phenomena of stirring failure and flying temperature, has high yield, is safe and simple to operate, and is low in cost.

Description

Technical Field

[0001] This invention relates to the field of organic chemical technology, specifically to a method for preparing 2-methylamino-5-tert-butyl-1,3,4-thiadiazole. Background Technology

[0002] 2-Methylamino-5-tert-butyl-1,3,4-thiadiazole (MTBA) is an important intermediate of terbuthiuron. Terbuthiuron, also known as terbuthiuron, is a photosynthesis inhibitor, a systemic broad-spectrum soil herbicide that is mainly absorbed through plant roots and inhibits electron transport during photosynthesis. It has attracted much attention due to its low toxicity, low dosage, broad spectrum of weed control, and long residual effect. It can be used to control annual weeds in forests (firebreaks), as well as to control the growth of various plants in non-planting areas and to selectively control weeds in sugarcane fields.

[0003] There are several methods for synthesizing MTBA, the main one being the condensation of methylaminothiourea (MTSC) with pivalic acid or pivaloyl chloride to form 4-methyl-pivaloylaminothiourea, followed by cyclization with a dehydrating agent to obtain MTBA hydrochloride, and then alkalization to obtain MTBA. Depending on the reactants with MTSC, these methods can be categorized into the pivalic acid method, the pivaloyl chloride method, and other synthetic methods.

[0004] 1. Synthesis of MTBA via the pentovalinic acid method

[0005] TAO [US3887572A, publication date 1975-06-03] added MTSC and pivalic acid sequentially to a mixture of polyphosphoric acid and sulfuric acid at low temperature, then heated to 105°C and reacted for 3 hours to obtain MTBA, with a yield of 93.0%. David et al. [US4283543A, publication date 1981-08-11] used MTSC and pivalic acid as raw materials and dehydrated and condensed them with polyphosphoric acid and concentrated sulfuric acid at 70-80°C to obtain MTBA, with a yield of 98.0%.

[0006]

[0007] This method has a high yield of MTBA and low consumption of pentylene acid, but it requires a large amount of acid and generates a large amount of waste acid during the post-processing, resulting in high treatment costs.

[0008] 2. Synthesis of MTBA via pentanoyl chloride method

[0009] The synthesis of MTBA via the pentoval acyl chloride method can be further subdivided into two steps: first, pentoval acyl chloride reacts with MTSC to generate 4-methyl-1-trimethylacetyl-3-aminothiourea (abbreviated as "acyl hydrazine"), and then dehydrates with other dehydrating agents to obtain MTBA; or, pentoval acyl chloride is used as a dehydrating agent to continue dehydration to obtain MTBA.

[0010] (1) MTBA was obtained by dehydration with other dehydrating agents.

[0011] Ling Gang et al. [Pesticides, 2012, 51(10):715-716] mixed MTSC with excess pentanoyl chloride and toluene, heated the mixture, added phosphorus oxychloride dropwise at 100℃, and kept the reaction at this temperature for 4 hours to obtain MTBA. This was then reacted with MCC to synthesize terbutaline, with a total yield of 95.0% in both steps. Wang Huizhen et al. [CN104610250B, Publication Date 2017-03-22] also used phosphorus oxychloride as a dehydrating agent to synthesize MTBA, with a yield of 70.7%. Wang Lei et al. [Pesticides, 2019, 58(3):180-182] mixed 1.2 molar amounts of pentanoyl chloride with MTSC and toluene, stirred at room temperature for 1 hour, then added phosphorus oxychloride and refluxed for 3 hours to obtain MTBA with a purity of 90.5% and a yield of 85.2%. Zhu Yan et al. [CN103288777A, Publication Date 2013-09-11] used 1,2-dichloroethane as solvent to react 1.5 molar amounts of pivaloyl chloride with MTSC under reflux to generate 4-methyl-pivaloylaminothiourea. Then, MTBA was synthesized by cyclization using chlorosulfonic acid, acetic anhydride, acetyl chloride, etc. as dehydrating agents, with a yield of 94.1%-95.6%.

[0012] The above method has a relatively high yield of MTBA, but using phosphorus oxychloride as a dehydrating agent will generate a large amount of phosphorus- and acid-containing wastewater. Other dehydrating agents will also introduce new substances into the reaction system, resulting in high post-treatment costs.

[0013] (2) Continue dehydration using tervastatin chloride as a dehydrating agent to obtain MTBA.

[0014]

[0015] Li Jun [CN105524017B, Publication Date 2017-06-30] first synthesized pivaloyl chloride from pentivalic acid with triphosgene (or diphosgene, phosgene), and then used triethylamine as an acid-binding agent to react pentivaloyl chloride with MTSC to synthesize MTBA, with a yield of 97.1%-98.9%. This method generates a large amount of triethylamine hydrochloride, which typically requires alkalization, dehydration, and distillation to recover anhydrous triethylamine, resulting in high post-processing costs. Furthermore, triethylamine pentivalate is also generated during the formation of triethylamine hydrochloride, and this salt enters the triethylamine recovery system along with the triethylamine hydrochloride, making it impossible to recover pentivalic acid, thus increasing production costs and making the treatment of "three wastes" (waste gas, wastewater, and solid waste) more difficult. In addition, the MTBA obtained by this method is obtained by desolvation from the organic phase, which contains not only toluene but also high-boiling-point substances such as pentivalic acid, requiring high temperatures for removal. MTBA molecules contain a high amount of nitrogen and sulfur, which makes them thermosensitive. Therefore, there are safety risks in the process of obtaining MTBA by this method.

[0016] Shi Rongchao et al. [Chemical World, 2019, 60(10):706-710] used 2.2 molar amounts of pivaloyl chloride as both a reaction reagent and a dehydrating agent to synthesize MTBA by reflux reaction with MTSC. The product purity was 97.0% and the yield was 93.6%. This method has a major drawback in actual operation: during the process of adding pivaloyl chloride dropwise to the mixture of MTSC and toluene, the reaction solution gradually becomes a paste, the mass and heat transfer effects deteriorate, and the phenomena of stirring failure and temperature runaway occur. If this method is applied to industrial production, it will cause safety accidents such as material spillage and explosion. Therefore, Gao Zhongliang et al. [CN109251188A, Publication Date 2019-01-22] added pivaloyl chloride to the reactor in two batches: pivaloyl chloride first reacted with MTSC to generate 4-methyl-pivaloylaminothiourea, and then pivaloyl chloride was used to dehydrate and cyclize to obtain MTBA, with a yield of 92.0%-97.3%. However, during the experimental verification process, there were still phenomena such as stirring failure and temperature runaway.

[0017] 3. Other methods

[0018] Chen Jianlong et al. [CN110372634 B, Publication Date 2021-03-19] used tervaline (I) and hydrazine hydrate as raw materials, and obtained intermediate (II) through condensation reaction, obtained intermediate (III) through sulfidation reaction with sulfiding agent, then obtained intermediate (IV) through dehydration and cyclization, obtained intermediate (V) through condensation reaction with paraformaldehyde, and finally obtained MTBA (VI) through hydrogenation reduction reaction.

[0019]

[0020] This method provides a new approach to synthesizing MTBA, but it involves many reaction steps and has a low yield, making it unsuitable for industrial application.

[0021] With the increasing market demand for terbutaline and the ever-increasing environmental protection requirements, it is necessary to optimize the production process of 2-methylamino-5-tert-butyl-1,3,4-thiadiazole to improve reaction yield, reduce production waste, and ultimately enhance the economic and social benefits of enterprises. Continuing to use pentovaleryl chloride as a dehydrating agent to obtain MTBA yields a higher rate. Although using pentovaleryl chloride as a dehydrating agent requires its consumption, the pentovaleryl chloride used as a dehydrating agent generates pentovaleric acid, which can then be chlorinated to obtain pentovaleryl chloride again, making it a synthesis method with minimal waste. Therefore, it is essential to address the issues of stirring failure and temperature runaway. Summary of the Invention

[0022] The technical problem to be solved by the present invention is to overcome the shortcomings of the prior art and provide a method for preparing 2-methylamino-5-tert-butyl-1,3,4-thiadiazole that avoids stirring failure and temperature runaway, has a high yield, is safe and easy to operate, has low cost and produces less waste.

[0023] To solve the above-mentioned technical problems, the present invention adopts the following technical solution.

[0024] A method for preparing 2-methylamino-5-tert-butyl-1,3,4-thiadiazole includes the following steps: Under water bath cooling, a first toluene-based solvent, 4-methylaminothiourea, a dehydration reaction catalyst, and tertivalyl chloride are added to a reaction flask and stirred. The mixture is then heated to 60℃~100℃ for reaction. After the reaction is completed, the mixture is cooled and filtered. The filter cake is added to a second toluene-based solvent, heated to 50℃~80℃, neutralized with liquid alkali, and the aqueous phase is separated. The resulting organic phase is refluxed to separate water and solvent to obtain 2-methylamino-5-tert-butyl-1,3,4-thiadiazole. The molar ratio of tertivalyl chloride to 4-methylaminothiourea is 2.1~2.5∶1, and the dehydration reaction catalyst is a vanadium pentoxide-containing dehydration reaction catalyst.

[0025] The chemical reaction formula of this invention is as follows:

[0026]

[0027] In the above-mentioned method for preparing 2-methylamino-5-tert-butyl-1,3,4-thiadiazole, preferably, the dehydration reaction catalyst is a composite catalyst of vanadium pentoxide and silicon dioxide, a composite catalyst of vanadium pentoxide and aluminum oxide, a composite catalyst of vanadium pentoxide and titanium dioxide, or vanadium pentoxide, wherein the mass fraction of vanadium pentoxide in each composite catalyst is in the range of 5% to 95%.

[0028] In the above-mentioned method for preparing 2-methylamino-5-tert-butyl-1,3,4-thiadiazole, preferably, the mass ratio of the dehydration reaction catalyst to the 4-methylaminothiourea is 0.001 to 0.01:1.

[0029] In the above-mentioned method for preparing 2-methylamino-5-tert-butyl-1,3,4-thiadiazole, preferably, the first toluene solvent is toluene or xylene, and the second toluene solvent is the same as the first toluene solvent.

[0030] In the above-mentioned method for preparing 2-methylamino-5-tert-butyl-1,3,4-thiadiazole, preferably, the mass ratio of the first toluene solvent to the 4-methylaminothiourea is 3 to 7:1.

[0031] In the above-mentioned method for preparing 2-methylamino-5-tert-butyl-1,3,4-thiadiazole, preferably, the mass ratio of the second toluene solvent to the 4-methylaminothiourea is 2 to 5:1.

[0032] In the preferred method for preparing 2-methylamino-5-tert-butyl-1,3,4-thiadiazole, the water bath cooling temperature is 10℃~30℃, and the reaction time is 2h~6h.

[0033] The method for preparing MTBA in this invention can be divided into the synthesis and post-processing of MTBA. The main principle of MTBA synthesis is as follows: the reaction of MTSC with pivaloyl chloride to synthesize MTBA is divided into two stages. The first stage involves a nucleophilic substitution reaction between MTSC and pivaloyl chloride to generate 4-methyl-1-trimethylacetyl-3-aminothiourea (referred to as "acylhydrazine"). The second stage involves the dehydration and cyclization of the acylhydrazine under the action of pivaloyl chloride to generate 2-methylamino-5-tert-butyl-1,3,4-thiadiazole hydrochloride (referred to as "thiadiazole hydrochloride"). The post-processing of MTBA involves cooling and filtering the thiadiazole hydrochloride solution. The filter cake is added to a toluene-based solvent, heated to 50℃~80℃, neutralized with liquid alkali, and the aqueous phase is separated. The organic phase is refluxed, dehydrated, and desolventized to obtain 2-methylamino-5-tert-butyl-1,3,4-thiadiazole.

[0034] The synthesis of MTBA involves the conversion of three substances: thiourea-acylhydrazine-thiadiazole hydrochloride, and has the following characteristics: ① Thiourea particles are large, acylhydrazine is a loose, lightweight (cotton-like) substance, and thiadiazole hydrochloride is a fine-particle substance; ② The rate of the first-stage reaction (formation of acylhydrazine) is greater than the rate of the second-stage reaction (formation of thiadiazole hydrochloride); ③ Thiourea, acylhydrazine, and thiadiazole hydrochloride have poor solubility in organic solvents. Therefore, as the reaction proceeds, the reaction system becomes increasingly viscous, eventually leading to poor mass and heat transfer, resulting in stirring failure and temperature runaway. If applied to industrial production, this could cause safety accidents such as material spillage and explosions. This invention accelerates the second-stage reaction by adding a dehydration catalyst, reducing the amount of acylhydrazine in the reaction system. Simultaneously, by adding a sufficient amount of pentanoyl chloride in a single step, the second-stage reaction proceeds smoothly after the first stage, thus avoiding the increasingly viscous reaction system and preventing stirring failure and temperature runaway.

[0035] Compared with the prior art, the advantages of the present invention are as follows:

[0036] (1) The method of the present invention is safe, smooth, simple to operate, and effective. By adding a dehydration reaction catalyst, the second stage reaction is accelerated, reducing the amount of hydrazide in the reaction system. At the same time, by adding sufficient pentanoyl chloride at one time, the second stage reaction is ensured to proceed smoothly after the first stage, thereby avoiding the reaction system from becoming increasingly viscous and preventing the phenomena of stirring failure and temperature runaway.

[0037] (2) The present invention uses pentanoyl chloride as a dehydrating agent, which reduces the amount of wastewater, increases the yield to 98.13% to 99.26%, and reduces production costs, thereby achieving the goal of improving the economic and social benefits of enterprises.

[0038] (3) In this invention, toluene-based solvents are used as reaction solvents and post-treatment solvents. The organic phase in the post-treatment process is refluxed to separate water and desolvent to obtain MTBA. In actual production, the MTBA solution after refluxing to separate water in the organic phase does not need to be desolventized and can be directly used for the synthesis of butylthiazoline technical. Detailed Implementation

[0039] The present invention will be further described below with reference to specific preferred embodiments, but this does not limit the scope of protection of the present invention. All materials and instruments used in the following embodiments are commercially available.

[0040] Example 1

[0041] A method for preparing 2-methylamino-5-tert-butyl-1,3,4-thiadiazole according to the present invention includes the following steps:

[0042] Under a water bath cooling at 20℃, 327.54 g of toluene, 109.18 g (96.32%, 1 mol) of 4-methylaminothiourea, 0.11 g of vanadium pentoxide, and 255.78 g (99%, 2.1 mol) of tert-valerate chloride were added to a 2000 mL three-necked flask. After stirring until homogeneous, the mixture was heated to 60℃ and reacted for 6 h. No stirring failure or temperature runaway occurred during the reaction. After the reaction was completed, the mixture was cooled and filtered. The filter cake was added to 218.36 g of toluene, heated to 50℃, neutralized with liquid alkali, and the aqueous phase was separated. The organic phase was refluxed, dehydrated, and dissolved to obtain 169.12 g of white solid, which was 2-methylamino-5-tert-butyl-1,3,4-thiadiazole. Liquid chromatography with external standard method analysis showed that the MTBA content in the white solid was 99.37%, and the calculated yield was 98.13%.

[0043] Example 2:

[0044] A method for preparing 2-methylamino-5-tert-butyl-1,3,4-thiadiazole according to the present invention includes the following steps:

[0045] Under 10℃ water bath cooling, 436.72 g of toluene, 109.18 g (96.32%, 1 mol) of 4-methylaminothiourea, 0.33 g of vanadium pentoxide, and 267.96 g (99%, 2.2 mol) of tert-valerate chloride were added to a 2000 mL three-necked flask. After stirring evenly, the mixture was heated to 70℃ and reacted for 5 h. No stirring failure or temperature runaway occurred during the reaction. After the reaction was completed, the mixture was cooled and filtered. The filter cake was added to 327.54 g of toluene, heated to 60℃, neutralized with liquid alkali, and the aqueous phase was separated. The organic phase was refluxed, dehydrated, and dissolved to obtain 170.40 g of white solid, which was 2-methylamino-5-tert-butyl-1,3,4-thiadiazole. The MTBA content in the white solid was 99.06% by external standard liquid chromatography, and the calculated yield was 98.56%.

[0046] Example 3:

[0047] A method for preparing 2-methylamino-5-tert-butyl-1,3,4-thiadiazole according to the present invention includes the following steps:

[0048] Under a 30℃ water bath cooling environment, 545.9 g of toluene, 109.18 g (96.32%, 1 mol) of 4-methylaminothiourea, 0.55 g of a vanadium pentoxide and silica composite catalyst (vanadium pentoxide mass fraction 95%), and 280.14 g (99%, 2.3 mol) of pentanoyl chloride were added to a 2000 mL three-necked flask. After stirring thoroughly, the mixture was heated to 80℃ and reacted for 4 h. No stirring failure or temperature runaway occurred during the reaction. After the reaction was completed, the mixture was cooled and filtered. The filter cake was added to 436.72 g of toluene, heated to 70℃, neutralized with liquid alkali, and the aqueous phase was separated. The organic phase was refluxed, dehydrated, and dissolved to obtain 171.97 g of a white solid, namely 2-methylamino-5-tert-butyl-1,3,4-thiadiazole. The MTBA content in the white solid was 98.85% by external standard liquid chromatography, and the calculated yield was 99.26%.

[0049] Example 4:

[0050] A method for preparing 2-methylamino-5-tert-butyl-1,3,4-thiadiazole according to the present invention includes the following steps:

[0051] Under a 2000 mL three-necked flask cooled in a 20℃ water bath, 655.08 g of xylene, 109.18 g (96.32%, 1 mol) of 4-methylaminothiourea, 0.76 g of a vanadium pentoxide / alumina composite catalyst (vanadium pentoxide mass fraction 50%), and 292.32 g (99%, 2.4 mol) of pentanoyl chloride were added. After stirring thoroughly, the mixture was heated to 90℃ and reacted for 3 h. No stirring failure or temperature runaway occurred during the reaction. After the reaction was completed, the mixture was cooled and filtered. The filter cake was added to 545.9 g of xylene, heated to 80℃, neutralized with liquid alkali, and the aqueous phase was separated. The organic phase was refluxed, dehydrated, and dissolved to obtain 171.12 g of white solid, which was 2-methylamino-5-tert-butyl-1,3,4-thiadiazole. Liquid chromatography with external standard method analysis showed that the MTBA content in the white solid was 99.13%, and the calculated yield was 99.05%.

[0052] Example 5:

[0053] A method for preparing 2-methylamino-5-tert-butyl-1,3,4-thiadiazole according to the present invention includes the following steps:

[0054] Under a 25°C water bath cooling environment, 764.26 g of xylene, 109.18 g (96.32%, 1 mol) of 4-methylaminothiourea, 1.09 g of a vanadium pentoxide and titanium dioxide composite catalyst (vanadium pentoxide mass fraction 5%), and 304.49 g (99%, 2.5 mol) of pentanoyl chloride were added to a 2000 mL three-necked flask. After stirring thoroughly, the mixture was heated to 100°C and reacted for 2 h. No stirring failure or temperature runaway occurred during the reaction. After the reaction was completed, the mixture was cooled and filtered. The filter cake was added to 436.72 g of xylene, heated to 60°C, neutralized with liquid alkali, and the aqueous phase was separated. The organic phase was refluxed, dehydrated, and dissolved to obtain 170.36 g of a white solid, namely 2-methylamino-5-tert-butyl-1,3,4-thiadiazole. Liquid chromatography with external standard method analysis showed that the MTBA content in the white solid was 99.25%, and the calculated yield was 98.73%.

[0055] Comparative Example 1

[0056] A method for preparing 2-methylamino-5-tert-butyl-1,3,4-thiadiazole according to the present invention includes the following steps:

[0057] 600 mL of toluene and 109.18 g (96.32%, 1 mol) of 4-methylaminothiourea were added to a 2000 mL four-necked flask. After stirring evenly, the temperature was raised to 100 °C, and pentanoyl chloride was added dropwise. 267.96 g (99%, 2.2 mol) of pentanoyl chloride was placed in a constant pressure dropping funnel. The temperature was gradually raised to reflux, and the reaction solution gradually became viscous. After adding 182 g of pentanoyl chloride (over 0.5 h), the stirring stopped working. The addition of pentanoyl chloride continued. After 5 min, the viscosity of the reaction material decreased, and heat and gas were released violently. The material was ejected from the reflux condenser, and the experiment failed.

[0058] Comparative Example 2

[0059] A method for preparing 2-methylamino-5-tert-butyl-1,3,4-thiadiazole according to the present invention includes the following steps:

[0060] 600 mL of toluene and 109.18 g (96.32%, 1 mol) of 4-methylaminothiourea were added to a 2000 mL four-necked flask. After stirring evenly, the temperature was raised to 100 °C, and pentanoyl chloride was added dropwise. 267.96 g (99%, 2.2 mol) of pentanoyl chloride was placed in a constant pressure dropping funnel. The temperature was gradually raised to reflux, and the reaction solution gradually became viscous. After adding 191 g of pentanoyl chloride (over 1.5 h), the stirring stopped working. The addition of pentanoyl chloride continued. After 5 min, the viscosity of the reaction material decreased, and heat and gas were released violently. The material was ejected from the reflux condenser, and the experiment failed.

[0061] Comparative Example 3

[0062] A method for preparing 2-methylamino-5-tert-butyl-1,3,4-thiadiazole according to the present invention includes the following steps:

[0063] 1000 mL of toluene and 109.18 g (96.32%, 1 mol) of 4-methylaminothiourea were added to a 2000 mL four-necked flask. After stirring, 121.8 g (99%, 1 mol) of pentanoyl chloride was added, and the temperature was raised to 70 °C. The reaction solution gradually became viscous, but stirring was still effective. After maintaining the temperature for 1.5 h, pentanoyl chloride was added dropwise. The constant pressure dropping funnel contained 146.16 g (99%, 1.2 mol) of pentanoyl chloride. The temperature gradually rose, and the reaction solution became more viscous. After adding 92 g of pentanoyl chloride (over 0.5 h), stirring became ineffective. The addition of pentanoyl chloride continued. After 5 min, the viscosity of the reaction material decreased, and heat and gas were released violently. The material was ejected from the reflux condenser, and the experiment failed.

[0064] Comparative Example 4

[0065] A method for preparing 2-methylamino-5-tert-butyl-1,3,4-thiadiazole according to the present invention includes the following steps:

[0066] 1000 mL of toluene and 109.18 g (96.32%, 1 mol) of 4-methylaminothiourea were added to a 3000 mL four-necked flask. After stirring, 121.8 g (99%, 1 mol) of pentanoyl chloride was added, and the temperature was raised to 70 °C. The reaction solution gradually became viscous, but stirring was still effective. After maintaining the temperature for 1.5 h, pentanoyl chloride was added dropwise. The constant pressure dropping funnel contained 146.16 g (99%, 1.2 mol) of pentanoyl chloride. The temperature gradually rose, and the reaction solution became more viscous. After adding 90 g of pentanoyl chloride (approximately 0.5 h), stirring became ineffective. The addition of pentanoyl chloride continued. After 5 min, the viscosity of the reaction material decreased, and heat and gas were released violently. The reaction temperature rose from 90 °C to 112 °C (violent reflux; after enlarging the reaction flask, no further reflux was performed, but solvent was clearly carried out by the gas). After the addition of tervaline chloride was complete, the reaction was maintained at 90°C for 1 hour, then cooled to room temperature. The mixture was filtered, and the pH was adjusted to 7-8 with ammonia (stirring was difficult). 700 mL of toluene was added, and the product was back-extracted into the toluene (the product did not completely dissolve at room temperature; it only dissolved completely upon heating to 60°C). The mixture was separated while hot, and the organic phase was desolvated to give 162.58 g of a white solid. Liquid chromatography with external standard analysis showed that the MTBA content in the white solid was 96.7%, and the calculated yield was 91.8%.

[0067] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make many possible variations and modifications to the technical solutions of the present invention using the methods and techniques disclosed above, or modify them into equivalent embodiments with equivalent changes, without departing from the spirit and technical essence of the present invention. Therefore, any simple modifications, equivalent substitutions, equivalent changes, and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solutions of the present invention shall still fall within the protection scope of the technical solutions of the present invention.

Claims

1. A method for preparing 2-methylamino-5-tert-butyl-1,3,4-thiadiazole, characterized in that, The process includes the following steps: Under water bath cooling, a first toluene-based solvent, 4-methylaminothiourea, a dehydration reaction catalyst, and tertivalyl chloride are added to a reaction flask and stirred. The mixture is then heated to 60℃~100℃ for reaction. After the reaction is complete, the mixture is cooled and filtered. The filter cake is added to a second toluene-based solvent, heated to 50℃~80℃, neutralized with liquid alkali, and the aqueous phase is separated. The resulting organic phase is refluxed to separate water and remove solvent to obtain 2-methylamino-5-tert-butyl-1,3,4-thiadiazole. The molar ratio of tertivalyl chloride to 4-methylaminothiourea is 2.1~2.5∶1, and the dehydration reaction catalyst is a vanadium pentoxide-containing dehydration reaction catalyst.

2. The method for preparing 2-methylamino-5-tert-butyl-1,3,4-thiadiazole according to claim 1, characterized in that, The dehydration reaction catalyst is a composite catalyst of vanadium pentoxide and silicon dioxide, a composite catalyst of vanadium pentoxide and aluminum oxide, a composite catalyst of vanadium pentoxide and titanium dioxide, or vanadium pentoxide, and the mass fraction of vanadium pentoxide in each composite catalyst is in the range of 5% to 95%.

3. The method for preparing 2-methylamino-5-tert-butyl-1,3,4-thiadiazole according to claim 1, characterized in that, The mass ratio of the dehydration reaction catalyst to the 4-methylaminothiourea is 0.001 to 0.01:

1.

4. The method for preparing 2-methylamino-5-tert-butyl-1,3,4-thiadiazole according to any one of claims 1 to 3, characterized in that, The first toluene-based solvent is toluene or xylene, and the second toluene-based solvent is the same as the first toluene-based solvent.

5. The method for preparing 2-methylamino-5-tert-butyl-1,3,4-thiadiazole according to any one of claims 1 to 3, characterized in that, The mass ratio of the first toluene solvent to the 4-methylaminothiourea is 3 to 7:

1.

6. The method for preparing 2-methylamino-5-tert-butyl-1,3,4-thiadiazole according to any one of claims 1 to 3, characterized in that, The mass ratio of the second toluene solvent to the 4-methylaminothiourea is 2 to 5:

1.

7. The method for preparing 2-methylamino-5-tert-butyl-1,3,4-thiadiazole according to any one of claims 1 to 3, characterized in that, The water bath cooling temperature is 10℃~30℃, and the reaction time is 2h~6h.

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