A method for synthesizing thiazole derivatives using carbon disulfide, ammonia and monochloroacetone as raw materials

Abstract

The present invention relates to a method for synthesizing 4-methylthiazole using carbon disulfide, ammonia and monochloroacetone as raw materials, comprising: synthesizing 4-methylthiazole in an aqueous phase in the presence of a catalyst using carbon disulfide, ammonia, oxygen and monochloroacetone as raw materials; the catalyst is a combination of one or more of polyethylene glycol, crown ether, heteropoly acid, quaternary ammonium salt and 4-dimethylaminopyridine and contains at least one phase transfer catalyst. Using the synthesized 4-methylthiazole as a parent nucleus, 4-cyanothiazole, thiabendazole and the like can be further obtained. The present invention can prepare five-membered heterocyclic thiazole derivatives using simple small molecule compounds such as carbon disulfide, ammonia and monochloroacetone as raw materials, with cheap raw materials, simple synthesis process, relatively mild reaction conditions of the whole process, no harsh requirements on the reaction equipment system, low process cost, and the characteristics of green environmental protection.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing thiazole derivatives by using carbon disulfide, ammonia and monochloroacetone as raw materials. Background Art

[0002] Thiabendazole is a fungicide with systemic, apically conductive properties and a long-lasting effect. It exhibits inhibitory activity against Ascomycetes, Basidiomycetes, and Deuteromycetes. It is used to control a variety of crop fungal diseases and preserve fruits and vegetables. Thiabendazole can be processed into 42% thiabendazole suspension concentrate, 60% thiabendazole wettable powder, 3% thiabendazole smoke spray, and fruit wrap.

[0003] Currently, many patents and publications have publicly reported methods for synthesizing thiabendazole. For example, Chinese patent application CN101712677A discloses a synthetic route that uses lactic acid and o-phenylenediamine as starting materials to generate 2-hydroxyethylbenzimidazole (Compound 1). Compound 1 is oxidized with potassium permanganate to benzimidazolone (Compound 2). Compound 2 undergoes a bromination reaction to obtain dibromobenzimidazolone (Compound 3). Compound 3 is finally reacted with phosphorus pentasulfide and formamide to obtain thiabendazole (Compound 4). The synthetic route is as follows. This process is simple, but requires phosphorus pentasulfide and o-phenylenediamine, which are significant environmental pollutants, making phosphorus-containing wastewater difficult to manage and resulting in high industrial production costs.

[0004]

[0005] For example, the synthesis route disclosed in Chinese patent application CN1121516A is as follows: pyruvic acid is subjected to a bromination reaction to obtain bromopyruvic acid, which is then subjected to a cyclization reaction in a tetrahydrofuran solution to obtain thiazole-4-carboxylic acid, followed by a condensation reaction in the presence of formamide and phosphorus pentoxide at 220-230° C. to obtain thiabendazole (synthesis route as follows). Although this route has simple steps, the raw material pyruvic acid used has poor stability and is difficult to store (which is not conducive to industrial production). In addition, the prices of pyruvic acid, tetrahydrofuran, and bromine are relatively high, resulting in high industrial production costs. In addition, phosphorus pentasulfide is also used, which is not environmentally friendly.

[0006]

[0007] For example, the synthesis route disclosed in Chinese patent application CN1042150A is as follows: tartaric acid is cracked to produce pyruvic acid, which is then brominated to produce bromopyruvic acid; thioformamide is prepared by reacting phosphorus pentasulfide with formamide; bromopyruvic acid and thioformamide react to produce thiazolecarboxylic acid hydrobromide, which is then reacted with o-phenylenediamine to produce thiabendazole (synthesis route as follows): This process still uses bromine and phosphorus pentasulfide, and the yield of the first step reaction is low, resulting in high production costs and environmental concerns.

[0008]

[0009] For example, the synthesis route disclosed in Chinese patent application CN104557902A is as follows: acetone and chlorine are used as starting materials to synthesize monochloroacetone, which can be directly reacted with thiourea without separation to obtain 2-amino-4-methylthiazole, which is then deamined through a diazotization reaction to obtain 4-methylthiazole, which is oxidized to produce thiazole-4-carboxylic acid. Finally, thiazole-4-carboxylic acid is reacted with o-phenylenediamine to obtain thiabendazole (synthesis route as follows): This process uses thiourea and o-phenylenediamine, and the production cost is high; the diazotization reaction produces a lot of wastewater, the yield is only 72%, and sodium hypophosphite, potassium permanganate, nitric acid, etc. are still required, making wastewater treatment difficult.

[0010]

[0011] In summary, it is necessary to find a lower-cost, more economical, more readily available starting material, and environmentally friendly synthetic process route to produce thiabendazole. Summary of the Invention

[0012] (1) Technical issues to be solved

[0013] In view of the above-mentioned shortcomings and deficiencies of the prior art, the present invention provides a method for synthesizing thiazole derivatives using carbon disulfide, ammonia and monochloroacetone as raw materials. The method can use cheap and readily available raw materials to synthesize thiazole derivatives such as 4-methylthiazole, 4-cyanothiazole and thiabendazole. The method has the characteristics of cheap and readily available raw materials, simple synthesis process, low process cost, and green environmental protection. It can provide technical support for the industrial production of thiabendazole technical.

[0014] (2) Technical solution

[0015] In a first aspect, the present invention provides a method for synthesizing 4-methylthiazole using carbon disulfide, ammonia and monochloroacetone as raw materials, comprising:

[0016] 4-Methylthiazole is synthesized in an aqueous phase using carbon disulfide, ammonia, oxygen, and monochloroacetone as raw materials in the presence of a catalyst; wherein the molar ratio of monochloroacetone, carbon disulfide, and ammonia is 1:1-1.5:2-3;

[0017] The catalyst is one or a combination of two or more of polyethylene glycol, crown ether, heteropoly acid, quaternary ammonium salt and 4-dimethylaminopyridine and contains at least one phase transfer catalyst; the mass of the catalyst is 0.1-2% of the mass of monochloroacetone; and the mass of water is 2-8 times the mass of monochloroacetone.

[0018] According to a preferred embodiment of the present invention, the molar ratio of monochloroacetone, carbon disulfide, and ammonia is 1:1.2:2.5.

[0019] According to a preferred embodiment of the present invention, the catalyst is a combination of TBAB and DMAP.

[0020] According to a preferred embodiment of the present invention, the mass of the catalyst is 0.5% of the mass of monochloroacetone; the mass of water is 3 times the mass of monochloroacetone.

[0021] According to a preferred embodiment of the present invention, the operation process of the method is as follows: water, carbon disulfide, and a catalyst are added to a high-pressure reaction vessel, ammonia is slowly introduced into the high-pressure reaction vessel, the total amount of ammonia introduced is monitored during the introduction process, oxygen is introduced after the ammonia is completed, and the temperature is raised to 90-120° C. (preferably 100° C.), the pressure is maintained by introducing oxygen, the pressure is maintained at 0.4-0.8 MPa, and the temperature is kept for 1-3 hours (a complex CN-SH·NH3 is generated at this time); then the pressure is exhausted to normal pressure, the temperature is lowered to 30-60° C., and monochloroacetone is slowly added dropwise to carry out a cyclization reaction, and the addition time of monochloroacetone is 1.5-3 hours; after the addition is completed, the temperature is kept at 40-60° C. for 3-7 hours. After the reaction is completed, the reaction system is transferred to a separating funnel and allowed to stand for stratification, and washed with water (washed twice or more), the light yellow oil phase is separated, and the oil phase is dried with a desiccant to obtain a light yellow clear and transparent liquid, which is 4-methylthiazole. Wherein, the desiccant is anhydrous magnesium sulfate or anhydrous sodium sulfate.

[0022] According to a preferred embodiment of the present invention, the process of synthesizing 4-methylthiazole is carried out in a reactor of a kettle type, a tower type, a tubular type, etc., and the reaction process can be a liquid phase reaction or a gas phase reaction.

[0023] In a second aspect, the present invention provides a method for synthesizing 4-cyanothiazole using carbon disulfide, ammonia and monochloroacetone as raw materials, comprising:

[0024] 4-Methylthiazole was synthesized according to the above method;

[0025] 4-Methylthiazole, ammonia and oxygen are used as raw materials to react in a fixed bed reactor in the presence of a transition metal oxide catalyst to produce 4-cyanothiazole;

[0026] The transition metal in the transition metal oxide catalyst is at least one of Ti, Zr, Nb, Ta, Cr, W, Mn, Re, Fe, Co, Ni, Cu, Ag and Te; the transition metal oxide catalyst further comprises a non-transition metal, which is at least one of Zn, Na, K, Mg, Ca, Al, Ge, La, Sn, Sb, Te, Bi, Pb and Ce. Preferably, the transition metal oxide catalyst is Mo 15 Fe 10 NiO 0.5 K 0.2 O 60.6 (SiO2) 30or V 10 P 10 ZnO 53 (SiO2) 40 .

[0027] According to a preferred embodiment of the present invention, the molar ratio of 4-methylthiazole to ammonia is 1:(1-3), preferably 1:1.5.

[0028] Preferably, the method for synthesizing 4-cyanothiazole comprises:

[0029] The fixed bed reactor is a tubular fixed bed reactor, in which the transition metal oxide catalyst is loaded; 4-methylthiazole, ammonia, and air are continuously introduced into a preheating chamber of the tubular fixed bed reactor, respectively, and the preheating chamber preheats the 4-methylthiazole, ammonia, and air to 250-300° C., vaporizing the 4-methylthiazole. The vaporized 4-methylthiazole forms a mixed gas with ammonia and air; the mixed gas enters the tubular fixed bed reactor from an upper inlet, and the reaction temperature is controlled at 300-350° C., preferably 310° C.; and 4-cyanothiazole is discharged from a bottom opening of the tubular fixed bed reactor. The flow rate ratio of ammonia to air is 1:(10-20), preferably 1:12; and 500-550 ml of ammonia is introduced for every 1 g of 4-methylthiazole introduced.

[0030] Preferably, the operation method is as follows: controlling the temperature of the preheating chamber to 275-285°C; feeding the preheated material from the upper inlet of the tubular fixed bed reactor, reacting under the action of the catalyst, and controlling the temperature in the tubular fixed bed reactor at 305-315°C; after the raw materials are introduced as described above for 120-180 minutes, stopping the introduction of 4-methylthiazole and ammonia; continuing to introduce air for 8-15 minutes, then turning off the air introduction, and collecting the product 4-cyanothiazole from the bottom outlet of the tubular fixed bed reactor.

[0031] In a third aspect, the present invention provides a method for synthesizing thiabendazole using carbon disulfide, ammonia and monochloroacetone as raw materials, comprising:

[0032] S1, synthesizing 4-cyanothiazole according to the above method;

[0033] S2, dispersing 4-cyanothiazole and aniline in o-dichlorobenzene, passing dry HCl gas, causing 4-cyanothiazole and aniline to undergo addition reaction to generate 4-(N-phenyl-amidino)thiazole hydrochloride; after the reaction is completed, adding water to dissolve, separating the dichlorobenzene of the oil phase, retaining the aqueous phase, adding activated carbon to the aqueous phase for decolorization, filtering, and washing with water to obtain an aqueous solution of 4-(N-phenyl-amidino)thiazole hydrochloride;

[0034] S3, transferring the aqueous solution of 4-(N-phenyl-amidino)thiazole hydrochloride into a cyclization reaction kettle, adjusting the pH to 8-10, adding sodium hypochlorite dropwise to catalyze the cyclization of 4-(N-phenyl-amidino)thiazole, filtering, and obtaining a crude product of thiabendazole;

[0035] S4. Dissolve the crude thiabendazole in water and hydrochloric acid, add activated carbon for decolorization, filter, and wash with water. Alkalinize the filtrate, filter, wash the filter cake with water, and dry to obtain purified thiabendazole.

[0036] According to a preferred embodiment of the present invention, in S2, the molar ratio of 4-cyanothiazole, HCl and aniline is 1:1-2:1-1.5, preferably 1:1.2:1.05; the reaction temperature is 130-140°C, and the reaction time is 2-4h.

[0037] According to a preferred embodiment of the present invention, the operation process of S2 is:

[0038] First, o-dichlorobenzene (2-5 times (preferably 3 times) the mass of 4-cyanothiazole) is added to a reaction container, followed by 4-cyanothiazole and aniline. After the temperature is raised to 100-120° C., dry HCl gas is slowly introduced. After the ventilation is completed, the temperature is raised to 130-140° C. and kept warm for 2-4 hours to terminate the reaction. The temperature is then lowered to 60-80° C., water is added, and the mixture is stirred for 15-40 minutes. After standing to separate the layers, the dichlorobenzene is removed and the aqueous phase is retained. The aqueous phase is a 4-(N-phenyl-amidino)thiazole hydrochloride aqueous solution. Activated carbon (0.1-5.0% (preferably 0.5%) by mass of 4-cyanothiazole) is added for decolorization. The mixture is filtered and washed with water to obtain a light yellow transparent aqueous solution, i.e., a 4-(N-phenyl-amidino)thiazole hydrochloride aqueous solution.

[0039] According to a preferred embodiment of the present invention, in S3, the molar ratio of 4-cyanothiazole to sodium hypochlorite is 1:1-2, preferably 1:1.2, the reaction temperature is 40-50°C, and the reaction time is 6-8h, preferably 6h.

[0040] According to a preferred embodiment of the present invention, the operation process of S3 is: slowly adding sodium carbonate to the aqueous solution of 4-(N-phenyl-amidino)thiazole hydrochloride, adjusting the pH to 8-10 (preferably pH = 9), heating the aqueous solution of 4-(N-phenyl-amidino)thiazole hydrochloride to 30-40°C, adding a sodium hypochlorite aqueous solution dropwise, and after the addition is completed, keeping warm at 40-50°C for 6-8h (preferably 6h), without cooling, directly filtering to separate the crude thiabendazole.

[0041] According to a preferred embodiment of the present invention, the operating process of S4 is: dissolving the crude thiabendazole into 3-5 times the mass of water (preferably 3 times), adjusting the pH to 1-3 with concentrated hydrochloric acid, heating to 45-55°C, thereby dissolving thiabendazole in the water in the form of salt, adding 0.1-5.0% (preferably 0.5%) of the mass of the crude thiabendazole activated carbon for decolorization, decolorizing for 0.5-2h (preferably 1h), filtering while hot, washing with 45-60°C hot water, alkalizing the filtrate with sodium carbonate, filtering, washing the filter cake with 45-60°C hot water and drying to obtain purified thiabendazole.

[0042] (3) Beneficial effects

[0043] The beneficial technical effects of the present invention are mainly as follows: the present invention uses simple small molecule compounds such as carbon disulfide, ammonia and monochloroacetone as raw materials to prepare five-membered heterocyclic thiazole derivatives, including 4-methylthiazole, 4-cyanothiazole, thiabendazole, etc.; the most important of which is the method for synthesizing 4-methylthiazole, and the 4-methylthiazole that can be synthesized later is used as the basic parent nucleus, and then catalytic reaction is used to prepare 4-cyanothiazole, which is then reacted with aniline to generate 4-(N-phenyl-amidino)thiazole, and further cyclization reaction is performed to prepare thiabendazole, etc. Among them, the process of synthesizing 4-methylthiazole can be carried out continuously, thereby continuously providing 4-methylthiazole raw materials for subsequent steps.

[0044] The most important feature of the present invention is that it can use cheap and easily available simple small molecule raw materials (carbon disulfide, ammonia and monochloroacetone) to synthesize thiazole derivatives such as 4-methylthiazole, 4-cyanothiazole and thiabendazole. It has the characteristics of cheap and easily available raw materials, simple synthesis process, relatively mild reaction conditions in the entire process, no stringent requirements on the reaction equipment system, low process cost, and green environmental protection. More importantly, the present invention has high yield and purity when preparing 4-methylthiazole, 4-cyanothiazole and thiabendazole, and the purity of the final refined thiabendazole technical reaches more than 99%. These excellent recovery rates and purity can provide technical support for the industrial production of thiabendazole and downstream products. DETAILED DESCRIPTION

[0045] In order to better explain the present invention and facilitate understanding, the present invention is described in detail below in conjunction with specific embodiments.

[0046] The novel process for synthesizing the technical substance of thiabendazole of the present invention comprises the following steps:

[0047] (1) 4-Methylthiazole was synthesized in aqueous phase using carbon disulfide, ammonia, oxygen and monochloroacetone as raw materials in the presence of a catalyst.

[0048] The molar ratio of monochloroacetone, carbon disulfide and ammonia is 1:1-1.5:2-3; the catalyst is one or a combination of two or more of polyethylene glycol, crown ether, heteropoly acid, quaternary ammonium salt and 4-dimethylaminopyridine and contains at least one phase transfer catalyst; the total mass of the catalyst is 0.1-2% of the mass of the monochloroacetone; and the mass of water is 2-8 times the mass of the monochloroacetone.

[0049] Furthermore, the molar ratio of monochloroacetone, carbon disulfide and ammonia is 1:1.2:2.5.

[0050] Furthermore, the catalyst is TBAB / DMAP, with a mass ratio of 1-5:5-1. TBAB is tetrabutylammonium bromide, a quaternary ammonium salt phase transfer catalyst that helps transfer hydrophobic substrates or reagents from the organic phase to the aqueous phase, thereby completing the reaction. DMAP refers to 4-dimethylaminopyridine. Although not a conventional phase transfer catalyst, it can promote the transfer of substances between phases and can form stable intermediates soluble in different phases with the reaction raw materials to promote chemical transformations.

[0051] Preferably, the mass of the catalyst accounts for 0.5% of the mass of the monochloroacetone.

[0052] Preferably, the amount of water added is 3 times the mass of monochloroacetone. In the solution of the present invention, water is both a polar solvent that can dissolve ammonia and a reaction raw material. Water itself also participates in the synthesis reaction.

[0053] Preferably, the method is operated as follows: water, carbon disulfide, and a catalyst (preferably TBAB / DMAP) are added to a high-pressure reaction vessel, ammonia is slowly introduced into the high-pressure reaction vessel, and the total amount of ammonia introduced is monitored during the introduction process. After the ammonia introduction is completed, oxygen is introduced and the temperature is raised to 90-120°C (preferably 100°C). The pressure is maintained at 0.4-0.8 MPa by introducing oxygen, and the temperature is maintained for 1-3 hours, at which time the intermediate complex CN-SH·NH3 is generated. Then, the air is exhausted to normal pressure, the temperature is lowered to 30-60°C, and monochloroacetone is slowly added dropwise to carry out the cyclization reaction. The addition time of monochloroacetone is 1.5-3 hours. After the addition is completed, the temperature is kept at 40-60°C for 3-7 hours. After the reaction is completed, the reaction system is transferred to a separatory funnel and allowed to stand for stratification, and washed with water (washed with water twice or more times). The light yellow oil phase is separated and dried with a desiccant such as anhydrous magnesium sulfate or anhydrous sodium sulfate to obtain a light yellow clear and transparent liquid, which is 4-methylthiazole. The high-pressure reaction vessel is a reactor such as a kettle, tower or tubular reactor. The main chemical reactions that occur are as follows:

[0054]

[0055] (2) 4-Methylthiazole, ammonia and oxygen are used as raw materials to react in a fixed bed reactor in the presence of a transition metal catalyst to produce 4-cyanothiazole.

[0056] The transition metal in the transition metal oxide catalyst is at least one of Ti, Zr, Nb, Ta, Cr, W, Mn, Re, Fe, Co, Ni, Cu, Ag and Te; the transition metal oxide catalyst further comprises a non-transition metal, which is at least one of Zn, Na, K, Mg, Ca, Al, Ge, La, Sn, Sb, Te, Bi, Pb and Ce. Preferably, the transition metal oxide catalyst is Mo 15 Fe 10 NiO 0.5 K 0.2 O 60.6 (SiO2) 30 or V 10 P 10 ZnO 53 (SiO2) 40 .

[0057] Mo, Fe, and Ni oxides are the main catalytic active components, SiO2 is the carrier, and the carrier can also be replaced by porous alumina. The catalytic active components can be replaced by Fe, Sb or V oxides, such as V 10 P 10 ZnO 53 (SiO2) 40 It can also serve as a catalyst in this step.

[0058] Preferably, the molar ratio of 4-methylthiazole to ammonia is 1:1-3, preferably 1:1.5.

[0059] Preferably, the method for synthesizing 4-cyanothiazole comprises:

[0060] The fixed bed reactor is a tubular fixed bed reactor, in which the transition metal oxide catalyst is loaded; 4-methylthiazole, ammonia, and air are continuously introduced into a preheating chamber of the tubular fixed bed reactor, respectively, and the preheating chamber preheats the 4-methylthiazole, ammonia, and air to 250-300° C., vaporizing the 4-methylthiazole. The vaporized 4-methylthiazole forms a mixed gas with ammonia and air; the mixed gas enters the tubular fixed bed reactor from an upper inlet, and the reaction temperature is controlled at 300-350° C., preferably 310° C.; and 4-cyanothiazole is discharged from a bottom opening of the tubular fixed bed reactor. The flow rate ratio of ammonia to air is 1:(10-20), preferably 1:12; and 500-550 ml of ammonia is introduced for every 1 g of 4-methylthiazole introduced.

[0061] Preferably, the temperature of the preheating chamber is controlled at 275-285°C; the preheated materials are fed from the upper inlet of the tubular fixed-bed reactor, reacting under the action of the catalyst, and the temperature inside the tubular fixed-bed reactor is controlled at 305-315°C; after the raw materials are introduced as described above for 120-180 minutes, the introduction of 4-methylthiazole and ammonia is stopped; air is continued to be introduced for 8-15 minutes, and then the air is turned off, and the product 4-cyanothiazole is collected from the bottom outlet of the tubular fixed-bed reactor. The main chemical reactions that occur are as follows:

[0062]

[0063] (3) 4-(N-phenyl-amidino)thiazole hydrochloride is obtained by catalytic addition of 4-cyanothiazole, dry HCl, and aniline as raw materials in o-dichlorobenzene solution. After the reaction is completed, water is added to dissolve the mixture, dichlorobenzene is removed, and the aqueous phase is decolorized with activated carbon, filtered, and washed with water twice to obtain an aqueous solution of 4-(N-phenyl-amidino)thiazole hydrochloride.

[0064] Preferably, the molar ratio of 4-cyanothiazole, dry HCl, and aniline as raw materials is 1:(1-2):(1-1.5), preferably 1:1.2:1.05. Furthermore, the reaction is carried out in o-dichlorobenzene.

[0065] Furthermore, the specific operations of this step are as follows:

[0066] First, o-dichlorobenzene (2-5 times (preferably 3 times) the mass of 4-cyanothiazole) is added to a reaction container, followed by 4-cyanothiazole and aniline. After the temperature is raised to 100-120° C., dry HCl gas is slowly introduced. After the ventilation is completed, the temperature is raised to 130-140° C. and kept warm for 2-4 hours to terminate the reaction. The temperature is then lowered to 60-80° C., water is added, and the mixture is stirred for 15-40 minutes. The mixture is allowed to stand for stratification, the oil phase (dichlorobenzene) is removed, and the aqueous phase (4-(N-phenyl-amidino)thiazole hydrochloride aqueous solution) is retained. Activated carbon (0.1-5.0% (preferably 0.5%) of the mass of 4-cyanothiazole) is added for decolorization. The mixture is filtered and washed with water twice or more to obtain a light yellow transparent aqueous solution, i.e., the 4-(N-phenyl-amidino)thiazole hydrochloride aqueous solution.

[0067] Among them, the main chemical reactions are as follows:

[0068]

[0069] (4) The aqueous solution of 4-(N-phenyl-amidino)thiazole hydrochloride was transferred into a reaction kettle, and sodium carbonate was added to neutralize and adjust the pH to 8-10. Sodium hypochlorite solution was added dropwise for cyclization, and the crude product of thiabendazole was obtained by filtration.

[0070] Preferably, the molar ratio of 4-cyanothiazole to sodium hypochlorite is 1:1-2, preferably 1:1.2, the reaction temperature is 40-50° C., and the reaction time is 6-8 h, preferably 6 h.

[0071] Furthermore, the specific operation of this step is as follows: first prepare a 10% sodium hypochlorite solution, cool the 4-(N-phenyl-amidino)thiazole hydrochloride aqueous solution to below 25°C, then slowly add sodium carbonate to adjust the pH to 8-10 (preferably pH = 9), heat the 4-(N-phenyl-amidino)thiazole hydrochloride aqueous solution to 30-40°C, add 10% (mass concentration) sodium hypochlorite aqueous solution dropwise, and after the addition is completed, keep warm at 40-50°C for 6-8h (preferably 6h), without cooling, directly filter, and separate the crude thiabendazole. The main chemical reactions that occur are as follows:

[0072]

[0073] (5) Add water and hydrochloric acid to the crude product of thiabendazole in the previous step, dissolve it, add activated carbon for decolorization, filter it, wash it with water, alkalize the filtrate, filter it, wash it with water, and dry it to obtain the fine thiabendazole technical.

[0074] Furthermore, the specific operation of this step is as follows: dissolving the crude thiabendazole in 3-5 times the mass of water (preferably 3 times), adjusting the pH to 1-3 with concentrated hydrochloric acid, heating to 45-55°C, thereby dissolving thiabendazole in the water in the form of salt, adding 0.1-5.0% (preferably 0.5%) of the mass of the crude thiabendazole activated carbon for decolorization, decolorizing for 0.5-2h (preferably 1h), filtering while hot, washing twice with 45-60°C hot water, alkalizing the filtrate with sodium carbonate, filtering, washing the filter cake with 45-60°C hot water three times, and drying to obtain purified thiabendazole.

[0075] The synthetic route of the synthetic thiabendazole designed by the present invention is as follows:

[0076]

[0077] The present invention is described below in conjunction with preferred embodiments of the present invention.

[0078] Example 1

[0079] This example uses monochloroacetone, ammonia, and carbon disulfide as starting materials to synthesize 4-methylthiazole and further prepare thiabendazole. The synthesis method is as follows:

[0080] Step 1: Synthesize 4-methylthiazole in an aqueous phase using carbon disulfide, ammonia, oxygen, and monochloroacetone as raw materials in the presence of a catalyst. The operation method is as follows:

[0081] (1) 231 g of water, 76 g (1.0 mol) of carbon disulfide, and a composite catalyst (0.2 g of TBAB + 0.3 g of DMAP) were added to a 500 ml high-pressure reaction vessel. 42.5 g (2.5 mol) of ammonia was slowly introduced. The temperature was then raised and pure oxygen was introduced, maintaining the pressure at 0.5 MPa. When the temperature reached 100°C, the reaction was maintained at this temperature for 2 h, at which point the intermediate complex CN-SH·NH3 was generated.

[0082] (2) The high-pressure reaction vessel was depressurized to normal pressure and cooled to 30° C., and 77 g (0.83 mol) of monochloroacetone was slowly added dropwise to carry out a cyclization reaction. The monochloroacetone was added dropwise for 2 h. After the addition was completed, the mixture was kept at 45° C. for 5 h. After the reaction was completed, the reaction system was transferred to a separating funnel and allowed to stand for stratification. The mixture was washed with water twice, and a light yellow oil phase was separated. The oil phase was dried over anhydrous magnesium sulfate to obtain a light yellow clear and transparent liquid, i.e., 78 g of 4-methylthiazole. The yield based on monochloroacetone was 94.9%, the purity was 97%, and the yield of the pure substance was 92.1%.

[0083] The molar ratio of monochloroacetone, carbon disulfide, and ammonia is 1:1.2:3.0. The mass of the catalyst accounts for 0.65% of the mass of the monochloroacetone. The mass of water is three times the mass of the monochloroacetone.

[0084] Step 2: Using 4-methylthiazole, ammonia, and oxygen as raw materials, react in a fixed bed reactor in the presence of a transition metal catalyst to generate 4-cyanothiazole. The operation method is as follows:

[0085] The catalyst Mo 15 Fe 10 NiO 0.5 K 0.2 O 60.6 (SiO2) 30A tubular fixed-bed reactor was loaded. 75 g of 4-methylthiazole (97% content, approximately 0.73 mol) was introduced into the preheating chamber of the tubular fixed-bed reactor via a peristaltic pump for vaporization at a feed rate of 0.5 g / min. Simultaneously, 18.7 g (1.1 mol) of ammonia was introduced into the preheating chamber via an ammonia cylinder, a pressure reducing valve, and a flowmeter, with the ammonia flow rate controlled at 260 ml / min. Compressed air was introduced into the preheating chamber via a pressure reducing valve and a flowmeter, with an ammonia to air flow ratio of 1:12. The preheating chamber temperature was 280°C. The molar ratio of 4-methylthiazole to ammonia was 1:1.5. The vaporized 4-methylthiazole, ammonia, and air were mixed to form a gas, which was then introduced into the tubular fixed-bed reactor through the upper inlet. The reactor temperature was controlled at 310°C. Following the aforementioned process, the raw materials were introduced and reacted for approximately 150 minutes. The 4-methylthiazole and ammonia feeds were then shut off, and the compressed air flow continued for 10 minutes before being shut off. The material was discharged from the bottom opening of the tubular fixed-bed reactor to collect 72 g of 4-cyanothiazole, with a yield of 89.7% based on 4-methylthiazole, a purity of 98%, and a pure substance yield of 87.8%.

[0086] Step 3: Prepare 4-(N-phenyl-amidino)thiazole hydrochloride by addition reaction of 4-cyanothiazole and aniline, and further cyclize to generate thiabendazole. The operation method is as follows:

[0087] To a 1000ml four-necked flask, add 210g of o-dichlorobenzene, 70g of 4-cyanothiazole (98% purity, approximately 0.624 mol), and 61.6g (0.655 mol) of 99% aniline. With stirring, heat to 110°C, and slowly introduce 27.4g (0.749 mol) of dry HCl gas through a pressure-reducing valve and a gas flowmeter for 2 hours. After completion of the aeration, heat the mixture to 135°C and maintain for 3 hours, then cool to 60°C and wash with 280g of 50°C hot water. After stirring for 30 minutes, allow the mixture to stand and separate. The oily dichlorobenzene phase is removed, leaving the remaining aqueous phase as an aqueous solution of 4-(N-phenyl-amidino)thiazole hydrochloride. Add 0.35g of activated carbon for decolorization, filter, and wash twice with water to obtain a light yellow, transparent aqueous solution. The molar ratio of 4-cyanothiazole, HCl, and aniline is 1:1.2:1.05. The amount of activated carbon used was 0.5% of 4-cyanothiazole.

[0088] Next, the 4-(N-phenyl-amidino)thiazole hydrochloride aqueous solution was cooled to below 25°C and transferred to a 1000ml flask. Solid sodium carbonate was added to adjust the pH to 9.0. The temperature was raised to 35°C, and 558g of a 10% aqueous sodium hypochlorite solution (0.75mol) was added dropwise over a 2h period. After the addition, the solution was kept at 45°C for 6h without cooling, and 105.5g of crude thiabendazole was directly isolated by filtration. The yield, based on 4-cyanothiazole, was 84%, the purity was 96.8%, and the yield of the pure substance was 81.3%. The molar ratio of 4-cyanothiazole to sodium hypochlorite was 1:1.2.

[0089] The melting point and spectral data of the product are as follows:

[0090] Mp:304-305℃

[0091] μν: 298nm, IR:cm -1 (KBr tablets) 3100, 3056, 2937, 2794, 2665, 1621, 1576, 1492, 1453, 1414, 1367, 1304, 1278, 1231, 1198, 1094, 986, 884, 827, 745.

[0092] HNMR (MeoD): δ 3.04 (singlet, 1H); δ 8.05 (singlet, 5H); δ 8.83 (singlet, 2H).

[0093] Step 4: Add water and hydrochloric acid to the crude thiabendazole product in the previous step, dissolve it, add activated carbon for decolorization, filter, wash with water, alkalize the filtrate, filter, wash with water, and dry to obtain the fine thiabendazole technical.

[0094] The specific operation of this step is as follows: add 300g of water and 100g (0.481mol) of 96.8% thiabendazole crude product to a 500mL four-necked flask, add 30% hydrochloric acid to adjust the pH to 2 while stirring, raise the temperature to 50°C, stir thoroughly to dissolve thiabendazole in the water in the form of salt, add 0.5g of activated carbon for decolorization for 60min, filter while hot, wash twice with hot water at 50°C, alkalize the filtrate with sodium carbonate powder, adjust the pH to 7.5, filter, wash the filter cake three times with hot water at 50°C, and dry to obtain 95g of white fine thiabendazole with a content of 99.4% and a pure substance yield of 97.55%.

[0095] Example 2

[0096] This example uses monochloroacetone, ammonia, and carbon disulfide as starting materials to synthesize 4-methylthiazole and further prepare thiabendazole. The synthesis method is as follows:

[0097] Step 1: Synthesize 4-methylthiazole in an aqueous phase using carbon disulfide, ammonia, oxygen, and monochloroacetone as raw materials in the presence of a catalyst. The operation method is as follows:

[0098] (1) The reaction conditions of step (1) in the first step of Example 1 were modified as follows: pure oxygen was introduced to maintain the pressure at 0.4 MPa, and when the temperature reached 90° C., the reaction was kept at this temperature for 3 h, at which time the intermediate complex CN-SH·NH 3 was generated. Other conditions were as in Example 1.

[0099] (2) The high-pressure reaction vessel was depressurized to normal pressure, cooled to 40°C, and 77 g (0.83 mol) of monochloroacetone was slowly added dropwise to carry out a cyclization reaction. The monochloroacetone was added dropwise for 3 hours. After the addition was completed, the mixture was kept at 48°C for 4 hours. After the reaction was completed, the reaction system was transferred to a separating funnel and allowed to stand for stratification. The reaction system was washed with water three times, and a light yellow oil phase was separated. The oil phase was dried with anhydrous sodium sulfate to obtain a light yellow clear and transparent liquid, i.e., 75.2 g of 4-methylthiazole. The yield based on monochloroacetone was 91.5%, the purity was 95.8%, and the yield of the pure substance was 87.67%.

[0100] Step 2: Using 4-methylthiazole, ammonia, and oxygen as raw materials, react in a fixed bed reactor in the presence of a transition metal catalyst to generate 4-cyanothiazole. The operation method is as follows:

[0101] The catalyst Mo 15 Fe 10 NiO 0.5 K 0.2 O 60.6 (SiO2) 30 A tubular fixed-bed reactor was loaded. 75.2 g of 4-methylthiazole (95.8% content, approximately 0.728 mol) was vaporized in the preheating chamber of the tubular fixed-bed reactor via a peristaltic pump at a feed rate of 0.5 g / min. Simultaneously, 18.7 g (1.1 mol) of ammonia was introduced into the preheating chamber via an ammonia cylinder, a pressure reducing valve, and a flowmeter, with the ammonia flow rate controlled at 260 ml / min. Compressed air was introduced into the preheating chamber via a pressure reducing valve and a flowmeter, with an ammonia to air flow ratio of 1:10. The preheating chamber temperature was 285°C. The molar ratio of 4-methylthiazole to ammonia was 1:1.51. The vaporized 4-methylthiazole, ammonia, and air were mixed to form a gas, which was then introduced into the tubular fixed-bed reactor through the upper inlet. The reactor temperature was controlled at 315°C. Following the aforementioned process, the raw materials were introduced and reacted for approximately 150 minutes. The 4-methylthiazole and ammonia feeds were then shut off, and the compressed air flow continued for 12 minutes before being shut off. The material was discharged from the bottom opening of the tubular fixed-bed reactor to collect 71.4 g of 4-cyanothiazole, with a yield of 89.16% based on 4-methylthiazole, a purity of 97.2%, and a pure substance yield of 86.66%.

[0102] Step 3: Prepare 4-(N-phenyl-amidino)thiazole hydrochloride by addition reaction of 4-cyanothiazole and aniline, and further cyclize to generate thiabendazole. The operation method is as follows:

[0103] To a 1000ml four-necked flask, add 210g of o-dichlorobenzene, 70g of 4-cyanothiazole (97.2% purity, approximately 0.618 mol), and 61.6g of 99% aniline (0.655 mol). With stirring, heat to 112°C, and slowly introduce 27.4g of dry HCl gas (0.749 mol) through a pressure-reducing valve and a gas flowmeter for 2 hours. After completion of the aeration, heat the mixture to 140°C and maintain for 2 hours, then cool to 60°C and wash with 280g of 55°C hot water. After stirring for 40 minutes, allow the mixture to stand and separate. The oily dichlorobenzene phase is removed, leaving the remaining aqueous phase as an aqueous solution of 4-(N-phenyl-amidino)thiazole hydrochloride. Add 0.35g of activated carbon for decolorization, filter, and wash twice with water to obtain a light yellow, transparent aqueous solution. The molar ratio of 4-cyanothiazole, HCl, and aniline is 1:1.21:1.06. The amount of activated carbon used was 0.5% of 4-cyanothiazole.

[0104] Next, the 4-(N-phenyl-amidino)thiazole hydrochloride aqueous solution was cooled to below 25°C and transferred to a 1000ml flask. Solid sodium carbonate was added to adjust the pH to 10. The temperature was raised to 40°C, and 511g of a 10% aqueous sodium hypochlorite solution (0.686mol) was added dropwise over 2.5 hours. After the addition, the solution was kept at 40°C for 8 hours without cooling. The crude product, 105.8g of thiabendazole, was directly isolated by filtration, yielding 85.1% and 95.4% purity based on 4-cyanothiazole. The yield of the pure substance was 81.15%. The molar ratio of 4-cyanothiazole to sodium hypochlorite was 1:1.11.

[0105] Step 4: Add water and hydrochloric acid to the crude thiabendazole product in the previous step, dissolve it, add activated carbon for decolorization, filter, wash with water, alkalize the filtrate, filter, wash with water, and dry to obtain the fine thiabendazole technical.

[0106] The specific operation of this step is as follows: add 300g of water and 100g (0.474mol) of 95.4% crude thiabendazole to a 500mL four-necked flask, add 30% hydrochloric acid to adjust the pH to 3 while stirring, raise the temperature to 50°C, stir thoroughly to dissolve thiabendazole in the water in the form of salt, add 0.5g of activated carbon for decolorization for 60min, filter while hot, wash twice with hot water at 50°C, add sodium carbonate powder to the filtrate to alkalize, adjust the pH to 8, filter, wash the filter cake with hot water at 50°C three times, and dry to obtain 93.4g of white fine thiabendazole with a content of 99.2% and a pure substance yield of 97.12%.

[0107] Example 3

[0108] This example uses monochloroacetone, ammonia, and carbon disulfide as starting materials to synthesize 4-methylthiazole and further prepare thiabendazole. The synthesis method is as follows:

[0109] Step 1: Synthesize 4-methylthiazole in an aqueous phase using carbon disulfide, ammonia, oxygen, and monochloroacetone as raw materials in the presence of a catalyst. The operation method is as follows:

[0110] (1) The reaction conditions of step (1) in the first step of Example 1 were modified as follows: after the temperature reached 120° C., the reaction was kept at this temperature for 2 h, at which time the intermediate complex CN-SH·NH 3 was generated. Other conditions were as in Example 1.

[0111] (2) The high-pressure reaction vessel was depressurized to normal pressure, cooled to 60° C., and 77 g (0.83 mol) of monochloroacetone was slowly added dropwise to carry out a cyclization reaction. The monochloroacetone was added dropwise for 2 h. After the addition was completed, the mixture was kept at 60° C. for 3 h. After the reaction was completed, the reaction system was transferred to a separating funnel and allowed to stand for stratification. The mixture was washed with water three times, and a light yellow oil phase was separated. The oil phase was dried over anhydrous sodium sulfate to obtain a light yellow clear and transparent liquid, i.e., 70.5 g of 4-methylthiazole. The yield based on monochloroacetone was 85.8%, the purity was 94.3%, and the yield of the pure substance was 80.9%.

[0112] Step 2: Using 4-methylthiazole, ammonia, and oxygen as raw materials, react in a fixed bed reactor in the presence of a transition metal catalyst to generate 4-cyanothiazole. The operation method is as follows:

[0113] Catalyst V 10 P 10 Zn1O 53 (SiO2) 40A tubular fixed-bed reactor was loaded. 60 g of 4-methylthiazole (94.3% content, approximately 0.571 mol) was introduced into the preheating chamber of the tubular fixed-bed reactor via a peristaltic pump for vaporization at a feed rate of 0.5 g / min. Simultaneously, 14.6 g of ammonia (0.859 mol) was introduced into the preheating chamber via an ammonia cylinder, a pressure reducing valve, and a flowmeter, with the ammonia flow rate controlled at 260 ml / min. Compressed air was introduced into the preheating chamber via a pressure reducing valve and a flowmeter, with an ammonia to air flow ratio of 1:12. The preheating chamber temperature was 280°C. The molar ratio of 4-methylthiazole to ammonia was 1:1.50. The vaporized 4-methylthiazole, ammonia, and air were mixed to form a gas, which was then introduced into the tubular fixed-bed reactor through the upper inlet. The reactor temperature was controlled at 310°C. Following the aforementioned process, the raw materials were introduced and reacted for approximately 120 minutes. The 4-methylthiazole and ammonia feeds were then shut off, and the compressed air flow continued for 15 minutes before being shut off. The material was discharged from the bottom opening of the tubular fixed bed reactor to obtain 57.2 g of 4-cyanothiazole, with a yield of 91.07% based on 4-methylthiazole, a purity of 92.1%, and a pure substance yield of 83.9%. The reaction in this step can be carried out continuously.

[0114] Step 3: Prepare 4-(N-phenyl-amidino)thiazole hydrochloride by addition reaction of 4-cyanothiazole and aniline, and further cyclize to generate thiabendazole. The operation method is as follows:

[0115] To a 1000ml four-necked flask, add 150g of o-dichlorobenzene, 50g of 4-cyanothiazole (92.1% purity, approximately 0.418 mol), and 41.0g of 99% aniline (0.436 mol). With stirring, heat the mixture to 110°C and slowly introduce 18.3g (0.5 mol) of dry HCl gas through a pressure reducing valve and a gas flowmeter for 2 hours. After the evaporation period, heat the mixture to 135°C and maintain for 3 hours. Then cool the mixture to 60°C and wash with 200g of 50°C hot water. After stirring for 30 minutes, allow the mixture to stand and separate. The oily dichlorobenzene phase is removed, leaving the remaining aqueous phase as an aqueous solution of 4-(N-phenyl-amidino)thiazole hydrochloride. Add 0.25g of activated carbon for decolorization, filter, and wash twice with water to obtain a light yellow, transparent aqueous solution. The molar ratio of 4-cyanothiazole, HCl, and aniline is 1:1.2:1.04. The amount of activated carbon used was 0.5% of 4-cyanothiazole.

[0116] Next, the 4-(N-phenyl-amidino)thiazole hydrochloride aqueous solution was cooled to below 25°C and transferred to a 1000ml flask. Solid sodium carbonate was added to adjust the pH to 9.5. The temperature was raised to 35°C, and 373g of a 10% aqueous sodium hypochlorite solution (0.501mol) was added dropwise over a 2.0h period. After the addition, the solution was kept at 45°C for 6h without cooling, and 70.3g of crude thiabendazole was directly isolated by filtration. The yield, based on 4-cyanothiazole, was 83.57%, the purity was 94.5%, and the yield of the pure substance was 78.97%. The molar ratio of 4-cyanothiazole to sodium hypochlorite was 1:1.2.

[0117] Step 4: Add water and hydrochloric acid to the crude thiabendazole product in the previous step, dissolve it, add activated carbon for decolorization, filter, wash with water, alkalize the filtrate, filter, wash with water, and dry to obtain the fine thiabendazole technical.

[0118] The specific operation of this step is as follows: add 200g of water and 50g of 94.5% crude thiabendazole to a 500mL four-necked flask, add 30% hydrochloric acid to adjust the pH to 1 while stirring, raise the temperature to 50°C, stir thoroughly to dissolve thiabendazole in the water in the form of salt, add 0.25g of activated carbon for decolorization for 60min, filter while hot, wash twice with hot water at 50°C, add sodium carbonate powder to the filtrate to alkalize, adjust the pH to 7.5, filter, wash the filter cake with hot water at 50°C three times, and dry to obtain 46.2g of white fine thiabendazole with a content of 99.1% and a pure substance yield of 96.9%.

[0119] In the above examples, the transition metal oxide catalyst used in Examples 1-2 is Mo 15 Fe 10 NiO 0.5 K 0.2 O 60.6 (SiO2) 30 The transition metal oxide catalyst used in Example 3 is V 10 P 10 ZnO 53 (SiO2) 40 .

[0120] These transition metal oxide catalysts can be prepared by weighing the raw materials according to the stoichiometric ratio of each metal element and non-metallic element in the transition metal oxide catalyst, and then using any one of the conventional methods or a combination of multiple conventional methods: sol-gel method, co-precipitation method (precipitating metal ions from the solution by adding a precipitant to form a catalyst precursor), impregnation method (impregnating silica into a solution containing an active metal salt, and then drying and calcining to fix the metal component), mechanical alloying (directly mixing and alloying metal powders using ball milling or other methods), hydrothermal / solvothermal synthesis (synthesizing a specific form of catalyst in an autoclave under high temperature and high pressure conditions).

[0121] In the present invention, the preparation method of the transition metal oxide catalyst is as follows:

[0122] (1) Catalyst V 10 P 10 ZnO 53 (SiO2) 40 The preparation process is as follows:

[0123] According to V 10 P 10 ZnO 53 (SiO2) 40 The raw materials are weighed according to the stoichiometric ratio of each metal element and non-metal element. Vanadium can be provided by V2O5, zinc can be provided by Zn(NO3)2, and phosphorus can be provided by phosphoric acid.

[0124] Add sufficient oxalic acid to deionized water to prepare an oxalic acid solution, dissolve V2O5 therein to obtain a clear, transparent solution. Dissolve Zn(NO3)2 in deionized water to obtain a clear, transparent solution. Mix the V2O5 solution and the Zn(NO3)2 solution, and add phosphoric acid (85.3% phosphoric acid concentration, other concentrations are acceptable). Heat the solution containing phosphoric acid at 90-110°C (preferably 100°C) for 2-4 hours (preferably 3 hours), then add silica sol (silica sol with a solid content of 20.4wt% or other commercially available silica sol products of other specifications) and stir thoroughly to obtain a slurry.

[0125] The slurry is spray-dried using a rotary disk spray dryer to obtain solid particles, which are then calcined at 220-280°C (preferably 240-250°C) for 3-6h (preferably 3h), and then heated to 700-800°C (preferably 750-760°C) and continued to be calcined for 1.5-4h (preferably 2h).

[0126] (2) Catalyst Mo 15 Fe 10 NiO 0.5 K 0.2 O 60.6 (SiO2) 30 The preparation process is as follows:

[0127] According to Mo 15 Fe 10 NiO 0.5 K 0.2 O 60.6 (SiO2) 30 The raw materials are weighed according to the stoichiometric ratio of each metal element and non-metal element. Iron can be provided by ferric nitrate, nickel can be provided by nickel nitrate, molybdenum can be provided by ammonium molybdate, and potassium can be provided by potassium nitrate.

[0128] Add ferric nitrate, nickel nitrate and potassium nitrate to deionized water, stir and dissolve into a clear and transparent solution. Dissolve ammonium molybdate tetrahydrate in deionized water to obtain a clear and transparent ammonium molybdate solution. Mix the nitrate solution containing iron, nickel and potassium with the ammonium molybdate solution, add silica sol (silica sol with a solid content of 20.4wt% or other commercially available silica sol products of other specifications), stir and mix thoroughly, heat at 90-110°C (preferably 100°C) for 2-4h (preferably 2h) to obtain a slurry, spray dry the slurry using a rotary disk spray dryer to obtain solid particles, and calcine at 380-450°C (preferably 400°C) for 1.5-4h (preferably 2h), then raise the temperature to 520-580°C (preferably 550°C) and continue calcining for 1.5-4h (preferably 2h).

[0129] Both catalysts are prepared by a combination of coprecipitation and sol-gel (commercially available silica sol) methods, using silica as the metal oxide carrier. Drying methods are not limited to spray drying; conventional drying methods can be employed to obtain a solid, which is then calcined and ground to yield a transition metal oxide catalyst with a large specific surface area.

[0130] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the above embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for synthesizing 4-methylthiazole using carbon disulfide, ammonia and monochloroacetone as raw materials, characterized in that: It includes: 4-Methylthiazole is synthesized in an aqueous phase using carbon disulfide, ammonia, oxygen, and monochloroacetone as raw materials in the presence of a catalyst; wherein the molar ratio of monochloroacetone, carbon disulfide, and ammonia is 1:1-1.5:2-3; The catalyst is a combination of TBAB and DMAP; the mass of the catalyst is 0.1-2% of the mass of monochloroacetone; the mass of water is 2-8 times the mass of monochloroacetone; The method comprises the following steps: adding water, carbon disulfide and a catalyst into a high-pressure reaction vessel, slowly introducing ammonia into the high-pressure reaction vessel, monitoring the total amount of ammonia introduced during the introduction process, introducing oxygen after the completion of the introduction of ammonia, heating the reaction vessel to 90-120° C., maintaining the pressure at 0.4-0.8 MPa by introducing oxygen, and maintaining the temperature for 1-3 hours; then venting the reaction vessel to normal pressure, cooling the temperature to 30-60° C., slowly adding monochloroacetone dropwise to carry out a cyclization reaction, and maintaining the monochloroacetone dropwise for 1.5-3 hours; after the completion of the dropwise addition, maintaining the temperature at 40-60° C. for 3-7 hours, and after the reaction is completed, transferring the reaction system to a separating funnel, standing and separating the layers, washing with water, separating a light yellow oil phase, and drying the oil phase with a desiccant to obtain a light yellow clear and transparent liquid, namely 4-methylthiazole.

2. A method for synthesizing 4-cyanothiazole using carbon disulfide, ammonia and monochloroacetone as raw materials, characterized in that: It includes the following steps: (1) synthesizing 4-methylthiazole according to the method of claim 1; (2) using 4-methylthiazole, ammonia, and oxygen as raw materials to react in a fixed bed reactor in the presence of a transition metal oxide catalyst to produce 4-cyanothiazole; The transition metal oxide catalyst is Mo 15 Fe 10 NiO 0.5 K 0.2 O 60.6 (SiO2) 30 or V 10 P 10 ZnO 53 (SiO2) 40 .

3. The method according to claim 2, characterized in that The molar ratio of 4-methylthiazole to ammonia is 1:1-3; the fixed bed reactor is a tubular fixed bed reactor, and the transition metal oxide catalyst is loaded into the tubular fixed bed reactor; The method for synthesizing 4-cyanothiazole comprises: continuously introducing 4-methylthiazole, ammonia, and air into a preheating chamber of a tubular fixed-bed reactor, wherein the flow rate ratio of ammonia to air is 1:10-20; and for every 1g of 4-methylthiazole introduced, 500-550ml of ammonia is introduced; The preheating chamber preheats 4-methylthiazole, ammonia, and air to 250-300°C, vaporizing the 4-methylthiazole. The vaporized 4-methylthiazole, ammonia, and air form a mixed gas. The mixed gas enters the tubular fixed-bed reactor from the upper inlet, and the reaction temperature is controlled at 300-350°C. The material is discharged from the bottom opening of the tubular fixed-bed reactor to obtain 4-cyanothiazole.

4. A method for synthesizing thiabendazole using carbon disulfide, ammonia and monochloroacetone as raw materials, characterized in that: include: S1. Synthesize 4-cyanothiazole according to the method according to any one of claims 2 to 3; S2, dispersing 4-cyanothiazole and aniline in o-dichlorobenzene, passing dry HCl gas, causing 4-cyanothiazole and aniline to undergo addition reaction to generate 4-(N-phenyl-amidino)thiazole hydrochloride; after the reaction is completed, adding water to dissolve, separating the dichlorobenzene of the oil phase, retaining the aqueous phase, adding activated carbon to the aqueous phase for decolorization, filtering, and washing with water to obtain an aqueous solution of 4-(N-phenyl-amidino)thiazole hydrochloride; S3, transferring the aqueous solution of 4-(N-phenyl-amidino)thiazole hydrochloride into a cyclization reaction kettle, adjusting the pH to 8-10, adding sodium hypochlorite dropwise to catalyze the cyclization of 4-(N-phenyl-amidino)thiazole, filtering, and obtaining a crude product of thiabendazole; S4. Dissolve the crude thiabendazole in water and hydrochloric acid, add activated carbon for decolorization, filter, and wash with water. Alkalinize the filtrate, filter, wash the filter cake with water, and dry to obtain purified thiabendazole.

5. The method according to claim 4, characterized in that In S2, the molar ratio of 4-cyanothiazole, HCl and aniline is 1:1-2:1-1.5; the reaction temperature is 130-140°C, and the reaction time is 2-4h; the operation process of S2 is: first, o-dichlorobenzene 2-5 times the mass of 4-cyanothiazole is added to the reaction vessel, then 4-cyanothiazole and aniline are added, and after heating to 100-120°C, dry HCl gas is slowly introduced. After the ventilation is completed, the temperature is raised to 130 -140°C, keep warm for 2-4 hours to complete the reaction; cool to 60-80°C, add water, stir for 15-40 minutes, then stand and separate the layers, remove dichlorobenzene, retain the aqueous phase, which is a 4-(N-phenyl-amidino)thiazole hydrochloride aqueous solution, add activated carbon with a mass fraction of 0.1-5.0% of 4-cyanothiazole for decolorization, filter, and wash with water to obtain a light yellow transparent aqueous solution, i.e., a 4-(N-phenyl-amidino)thiazole hydrochloride aqueous solution.

6. The method according to claim 4, characterized in that In S3, the molar ratio of 4-cyanothiazole to sodium hypochlorite is 1:1-2, the reaction temperature is 40-50°C, and the reaction time is 6-8h; The operation process of S3 is: slowly add sodium carbonate to the aqueous solution of 4-(N-phenyl-amidino)thiazole hydrochloride, adjust the pH to 8-10, heat the aqueous solution of 4-(N-phenyl-amidino)thiazole hydrochloride to 30-40°C, add sodium hypochlorite aqueous solution dropwise, and after the addition is completed, keep it at 40-50°C for 6-8h, without cooling, directly filter and separate the crude product of thiabendazole.

7. The method according to claim 4, characterized in that The operation process of S4 is as follows: dissolving the crude thiabendazole in 3-5 times the mass of water, adjusting the pH to 1-3 with concentrated hydrochloric acid, heating to 45-55°C to dissolve the thiabendazole in the water in the form of salt, adding 0.1-5.0% of the mass of the crude thiabendazole activated carbon for decolorization, decolorizing for 0.5-2h, filtering while hot, washing with 45-60°C hot water, alkalizing the filtrate with sodium carbonate, filtering, washing the filter cake with 45-60°C hot water and drying to obtain purified thiabendazole.

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