Method for synthesizing thiazole derivative by taking carbon disulfide, ammonia gas and monochloroacetone as raw materials

Abstract

The invention relates to a method for synthesizing 4-methylthiazole by using carbon disulfide, ammonia gas and monochloroacetone as raw materials. The method comprises the following step: synthesizing 4-methylthiazole in a water phase in the presence of a catalyst by using carbon disulfide, ammonia gas, oxygen and monochloroacetone as raw materials, the catalyst is one or a combination of more than two of polyethylene glycol, crown ether, heteropoly acid, quaternary ammonium salt and 4-dimethylaminopyridine and contains at least one phase transfer catalyst. 4-cyanothiazole, thiabendazole and the like can be further prepared by taking the synthesized 4-methylthiazole as a mother nucleus. The five-membered heterocyclic thiazole derivative can be prepared by taking simple small molecular compounds such as carbon disulfide, ammonia gas and monochloroacetone as raw materials, and has the characteristics that the raw materials are cheap and easy to obtain, the synthesis process is simple, the reaction conditions of the whole process are relatively mild, no harsh requirements on a reaction equipment system exist, the process cost is low, and the method is green and environment-friendly.

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 taking carbon disulfide, ammonia and monochloroacetone as raw materials. Background Art

[0002] Thiabendazole is a fungicide with systemic apical conduction, long lasting effect, and inhibitory activity against ascomycetes, basidiomycetes and deuteromycetes. It can be used to prevent and control fungal diseases of various crops and preserve fruits and vegetables. Thiabendazole can be processed into 42% thiabendazole suspension, 60% thiabendazole wettable powder, 3% thiabendazole smoke agent, fruit cling film, etc.

[0003] At present, many literature patents have also publicly reported the synthesis method of thiabendazole. For example, the synthesis route disclosed in Chinese patent application CN101712677A is: using lactic acid and o-phenylenediamine as starting materials, first generating 2-hydroxyethylbenzimidazole (compound 1), compound 1 is oxidized to benzimidazolone (compound 2) by potassium permanganate, compound 2 is brominated to obtain dibromobenzimidazolone (compound 3), and compound 3 is finally reacted with phosphorus pentasulfide and formamide to obtain thiabendazole (compound 4), and the synthesis route is as follows. The process steps are simple, but phosphorus pentasulfide and o-phenylenediamine are needed, and these compounds cause great pollution to the environment, phosphorus-containing wastewater is not easy to treat, and the cost of industrial production is high.

[0004]

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

[0006]

[0007] For another example, the synthesis route disclosed in Chinese patent application CN1042150A is: pyruvic acid is prepared by cracking tartaric acid, and pyruvic acid is brominated to form bromopyruvic acid; thioformamide is prepared by reacting phosphorus pentasulfide with formamide; bromopyruvic acid and thioformamide are reacted to form thiazolecarboxylic acid hydrobromide, and thiazolecarboxylic acid hydrobromide is reacted with o-phenylenediamine to form thiabendazole (the synthesis route is as follows): this process still uses bromine and phosphorus pentasulfide, and the first step reaction yield is low, the production cost is high and it is not environmentally friendly.

[0008]

[0009] For another example, the synthesis route disclosed in Chinese patent application CN104557902A is: 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, and then the amino group is removed by diazotization to obtain 4-methylthiazole, which is oxidized to generate thiazole-4-carboxylic acid, and finally thiazole-4-carboxylic acid is reacted with o-phenylenediamine to obtain thiabendazole (the synthesis route is 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 used, and the wastewater treatment is 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 resolved

[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, green and environmental protection, etc., and can provide technical support for the industrial production of thiabendazole technical.

[0014] (II) 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; 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.), and the pressure is maintained by introducing oxygen, and the pressure is maintained at 0.4-0.8MPa, and the temperature is kept for 1-3h (at this time, a 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 a cyclization reaction, and the dropping time of monochloroacetone is 1.5-3h; after the dropwise addition is completed, the temperature is kept at 40-60° C. for 3-7h, and after the reaction is completed, the reaction system is transferred to a separating funnel for standing and stratification, and washed with water (washed with water twice or more times), 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, i.e. 4-methylthiazole. Wherein, the desiccant is anhydrous magnesium sulfate or anhydrous sodium sulfate or the like.

[0022] According to a preferred embodiment of the present invention, the process of synthesizing 4-methylthiazole is carried out in a reactor of kettle type, tower type, 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, which comprises:

[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 generate 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 also contains a non-transition metal, and the non-transition metal 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, the transition metal oxide catalyst is loaded in the tubular fixed bed reactor; 4-methylthiazole, ammonia and air are continuously introduced into the preheating chamber of the tubular fixed bed reactor respectively, the preheating chamber preheats 4-methylthiazole, ammonia and air to 250-300° C., and vaporizes 4-methylthiazole, and 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., preferably 310° C.; the material is discharged from the bottom opening of the tubular fixed bed reactor to obtain 4-cyanothiazole; wherein the flow rate ratio of ammonia to air is 1:(10-20), preferably 1:12; for every 1 g of 4-methylthiazole introduced, 500-550 ml of ammonia is introduced.

[0030] Preferably, the operation method is: 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 to 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; the air is continued to be introduced for 8-15 minutes and then the air is turned off, and the product 4-cyanothiazole is received 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, making 4-cyanothiazole and aniline 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, transfer the aqueous solution of 4-(N-phenyl-amidino)thiazole hydrochloride into a cyclization reaction kettle, adjust the pH to 8-10, dropwise add sodium hypochlorite to catalyze the cyclization of 4-(N-phenyl-amidino)thiazole, filter, and obtain a crude product of thiabendazole;

[0035] S4. Dissolve the crude thiabendazole in water and hydrochloric acid, add activated carbon for decolorization, filter, wash with water, alkalize 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 in an amount 2-5 times (preferably 3 times) the mass of 4-cyanothiazole is added into a reaction container, and then 4-cyanothiazole and aniline are added. 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 the temperature is kept for 2-4 hours to terminate the reaction. The temperature is lowered to 60-80° C., water is added, and the mixture is stirred for 15-40 minutes and then allowed to stand for stratification to separate the dichlorobenzene and retain the aqueous phase, which is a 4-(N-phenyl-amidino)thiazole hydrochloride aqueous solution. Activated carbon in an amount of 0.1-5.0% (preferably 0.5%) of the mass of 4-cyanothiazole is added for decolorization, and 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 add sodium carbonate to the aqueous solution of 4-(N-phenyl-amidino)thiazole hydrochloride, adjust the pH to 8-10 (preferably pH=9), heat the aqueous solution of 4-(N-phenyl-amidino)thiazole hydrochloride to 30-40°C, add aqueous sodium hypochlorite 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 product of 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] (III) Beneficial effects

[0043] The beneficial technical effects of the present invention are mainly as follows: the present invention uses simple small molecular 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 the basic mother nucleus, and then catalytic reaction is used to obtain 4-cyanothiazole, and 4-cyanothiazole is then reacted with aniline to generate 4-(N-phenyl-amidino)thiazole, and further cyclization reaction is performed to obtain 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, and has the characteristics of cheap and easily available raw materials, simple synthesis process, mild reaction conditions in the whole process, no strict requirements on the reaction equipment system, low process cost, green and environmental protection, etc.; More importantly, the present invention has high yield and purity when preparing 4-methylthiazole, 4-cyanothiazole and thiabendazole, and the purity of the 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 implementation methods.

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

[0047] (1) 4-Methylthiazole is synthesized in water 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 monochloroacetone; and the mass of water is 2-8 times the mass of 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, and the mass ratio of the two is 1-5:5-1. TBAB is tetrabutylammonium bromide, which is a quaternary ammonium salt phase transfer catalyst, which can help hydrophobic substrates or reagents transfer from the organic phase to the aqueous phase to complete the reaction; DMAP refers to 4-dimethylaminopyridine, which is not a conventional phase transfer catalyst, but 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 transformation.

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

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

[0053] Preferably, the operation process of the method is 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, the total amount of ammonia introduced is monitored during the introduction process, oxygen is introduced after the ammonia is introduced, and the temperature is raised to 90-120° C. (preferably 100° C.), and the pressure is maintained by introducing oxygen, and the pressure is maintained at 0.4-0.8 MPa, and the temperature is kept for 1-3 hours, at which time an intermediate complex CN-SH·NH3 is generated. Then, exhaust to normal pressure, cool to 30-60℃, slowly drop monochloroacetone to carry out cyclization reaction, the drop time of monochloroacetone is 1.5-3h; after the drop addition, keep warm at 40-60℃ for 3-7h, after the reaction is over, transfer the reaction system to a separatory funnel, let it stand for stratification, and wash with water (wash twice or more), separate the light yellow oil phase, dry the oil phase with anhydrous magnesium sulfate or anhydrous sodium sulfate, and obtain a light yellow clear and transparent liquid, which is 4-methylthiazole. The high-pressure reaction vessel is a reactor such as kettle, tower or tubular. Among them, 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 also contains a non-transition metal, and the non-transition metal 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, the transition metal oxide catalyst is loaded in the tubular fixed bed reactor; 4-methylthiazole, ammonia and air are continuously introduced into the preheating chamber of the tubular fixed bed reactor respectively, the preheating chamber preheats 4-methylthiazole, ammonia and air to 250-300° C., and vaporizes 4-methylthiazole, and 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., preferably 310° C.; the material is discharged from the bottom opening of the tubular fixed bed reactor to obtain 4-cyanothiazole; wherein the flow rate ratio of ammonia to air is 1:(10-20), preferably 1:12; for every 1 g of 4-methylthiazole introduced, 500-550 ml of ammonia is introduced.

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

[0062]

[0063] (3) 4-(N-phenyl-amidino)thiazole hydrochloride is obtained by catalytic addition reaction 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, and dichlorobenzene is removed. The aqueous phase is decolorized by adding 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. Further, the reaction is carried out in o-dichlorobenzene.

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

[0066] First, o-dichlorobenzene in an amount 2-5 times (preferably 3 times) of the mass of 4-cyanothiazole is added into a reaction container, and then 4-cyanothiazole and aniline are added. 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 the temperature is kept for 2-4 hours to terminate the reaction. The temperature is lowered to 60-80° C., water is added, and the mixture is stirred for 15-40 minutes, and then the mixture is allowed to stand for stratification to remove the oil phase of dichlorobenzene and retain the aqueous phase, which is a 4-(N-phenyl-amidino)thiazole hydrochloride aqueous solution. Activated carbon in an amount of 0.1-5.0% (preferably 0.5%) of the mass of 4-cyanothiazole is added for decolorization, and the mixture is filtered and washed with water for more than two times to obtain a light yellow transparent aqueous solution, i.e., a 4-(N-phenyl-amidino)thiazole hydrochloride aqueous solution.

[0067] Among them, the main chemical reactions that occur 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, and 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 6-8h, preferably 6h.

[0071] Further, the specific operation of this step is as follows: first prepare a 10% sodium hypochlorite solution, first cool the 4-(N-phenyl-amidino)thiazole hydrochloride aqueous solution to below 25°C, then slowly add sodium carbonate, adjust the pH to 8-10 (preferably pH=9), heat the 4-(N-phenyl-amidino)thiazole hydrochloride aqueous solution to 30-40°C, dropwise add 10% (mass concentration) sodium hypochlorite aqueous solution, 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. Among them, the main chemical reactions that occur are as follows:

[0072]

[0073] (5) Add water and hydrochloric acid to the crude thiabendazole product 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: dissolve the crude thiabendazole in 3-5 times the mass of water (preferably 3 times), adjust the pH to 1-3 with concentrated hydrochloric acid, heat to 45-55°C, so that thiabendazole is dissolved in water in the form of salt, add 0.1-5.0% (preferably 0.5%) of the mass of the crude thiabendazole activated carbon for decolorization, decolorize for 0.5-2h (preferably 1h), filter while hot, wash twice with 45-60°C hot water, add sodium carbonate to the filtrate for alkalization, filter, wash the filter cake with 45-60°C hot water three times, and dry to obtain purified thiabendazole.

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

[0076]

[0077] The scheme of the present invention is described below in conjunction with the 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 prepares thiabendazole. The synthesis method is as follows:

[0080] Step 1: Synthesize 4-methylthiazole in water phase with 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, and then the temperature was raised and pure oxygen was introduced, while maintaining the pressure at 0.5 MPa. When the temperature reached 100°C, the reaction was kept warm for 2 h, at which time an intermediate complex CN-SH·NH3 was generated.

[0082] (2) The high-pressure reaction vessel was depressurized to normal pressure, 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 reaction system was washed with water twice, and a light yellow oil phase was separated. The oil phase was dried with 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 pure substances 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 monochloroacetone. The mass of water is 3 times the mass of 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) 30Loaded in a tubular fixed bed reactor. 75g of 4-methylthiazole (content of 97%, about 0.73mol) was vaporized in the preheating chamber of the tubular fixed bed reactor through a peristaltic pump, with a feed rate of 0.5g / min; at the same time, 18.7g (1.1mol) of ammonia was introduced into the preheating chamber through an ammonia cylinder, a pressure reducing valve, and a flow meter, and the ammonia flow rate was controlled at 260ml / min; compressed air entered the preheating chamber through a pressure reducing valve and a flow meter, and the flow rate ratio of ammonia to air was 1:12. The temperature of the preheating chamber was 280°C. Among them, the molar ratio of 4-methylthiazole to ammonia was 1:1.5. The vaporized 4-methylthiazole, ammonia and air formed a mixed gas; the mixed gas entered the tubular fixed bed reactor from the upper inlet, and the reactor temperature was controlled at 310°C. After the raw materials were introduced and the reaction lasted for about 150min according to the above mode, the introduction of 4-methylthiazole and ammonia was turned off, and the compressed air was also turned off after continuing for 10min. The material was discharged from the bottom opening of the tubular fixed bed reactor, and 72 g of 4-cyanothiazole was collected. The yield based on 4-methylthiazole was 89.7%, the purity was 98%, and the yield of pure substances was 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] Add 210g of o-dichlorobenzene, 70g of 4-cyanothiazole (purity 98%, about 0.624mol), and 61.6g (0.655mol) of 99% aniline to a 1000ml four-necked flask, stir and heat to 110℃, and slowly introduce 27.4g (0.749mol) of dry HCl gas through a pressure reducing valve and a gas flow meter, and the ventilation time is controlled to be 2h. After the ventilation is completed, the temperature is raised to 135℃ and kept for 3h, then cooled to 60℃, and 280g of 50℃ hot water is added for water washing. After stirring for 30min, the mixture is allowed to stand and the oil phase dichlorobenzene is separated. The remaining aqueous phase is an aqueous solution of 4-(N-phenyl-amidino)thiazole hydrochloride, which is decolorized by adding 0.35g of activated carbon, filtered, and washed twice to obtain a light yellow transparent aqueous solution. Among them, 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 the 4-(N-phenyl-amidino)thiazole hydrochloride aqueous solution was 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 10% sodium hypochlorite (0.75mol) aqueous solution was added dropwise, and the dropping time was controlled to be 2h. After the dropwise addition was completed, the temperature was kept at 45°C for 6h, and the crude product 105.5g of thiabendazole was directly separated by filtration without cooling. The yield was 84% ​​based on 4-cyanothiazole, the purity was 96.8%, and the yield of pure substances was 81.3%. Among them, 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, then 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% crude thiabendazole into 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 50°C hot water, add sodium carbonate powder to the filtrate for alkalization, adjust the pH to 7.5, filter, wash the filter cake three times with 50°C hot water, 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 prepares thiabendazole. The synthesis method is as follows:

[0097] Step 1: Synthesize 4-methylthiazole in water phase with 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 changed to: pure oxygen was introduced to maintain the pressure at 0.4 MPa, and when the temperature reached 90° C., the reaction was kept warm for 3 h, at which time an intermediate complex CN-SH·NH3 was generated. The other conditions were the same as those 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 h. After the addition was completed, the mixture was kept at 48° C. for 4 h. 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 pure substances 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 Loaded in a tubular fixed bed reactor. 75.2g of 4-methylthiazole (content of 95.8%, about 0.728mol) was vaporized in the preheating chamber of the tubular fixed bed reactor through a peristaltic pump, with a feed rate of 0.5g / min; at the same time, 18.7g (1.1mol) of ammonia was introduced into the preheating chamber through an ammonia cylinder, a pressure reducing valve, and a flow meter, and the ammonia flow rate was controlled at 260ml / min; compressed air entered the preheating chamber through a pressure reducing valve and a flow meter, and the flow rate ratio of ammonia to air was 1:10. The temperature of the preheating chamber was 285°C. Among them, the molar ratio of 4-methylthiazole to ammonia was 1:1.51. The vaporized 4-methylthiazole, ammonia and air formed a mixed gas; the mixed gas entered the tubular fixed bed reactor from the upper inlet, and the reactor temperature was controlled at 315°C. After the raw materials were introduced and the reaction lasted for about 150min according to the above mode, the introduction of 4-methylthiazole and ammonia was turned off, and the compressed air was also turned off after continuing for 12min. The material was discharged from the bottom opening of the tubular fixed bed reactor, and 71.4 g of 4-cyanothiazole was collected. The yield based on 4-methylthiazole was 89.16%, the purity was 97.2%, and the yield of pure substances was 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] Add 210g of o-dichlorobenzene, 70g of 4-cyanothiazole (purity 97.2%, about 0.618mol), and 61.6g (0.655mol) of 99% aniline to a 1000ml four-necked flask, stir and heat to 112℃, and slowly introduce 27.4g (0.749mol) of dry HCl gas through a pressure reducing valve and a gas flow meter, and the ventilation time is controlled to be 2h. After the ventilation is completed, the temperature is raised to 140℃ and kept for 2h, then cooled to 60℃, and 280g of 55℃ hot water is added for water washing. After stirring for 40min, the mixture is allowed to stand and the oil phase dichlorobenzene is separated. The remaining aqueous phase is an aqueous solution of 4-(N-phenyl-amidino)thiazole hydrochloride, which is decolorized by adding 0.35g of activated carbon, filtered, and washed twice to obtain a light yellow transparent aqueous solution. Among them, 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 the 4-(N-phenyl-amidino)thiazole hydrochloride aqueous solution was 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 10% sodium hypochlorite (0.686mol) aqueous solution was added dropwise, and the dropping time was controlled to be 2.5h. After the dropwise addition was completed, the temperature was kept at 40°C for 8h, and the crude product 105.8g of thiabendazole was directly separated by filtration without cooling. The yield was 85.1% based on 4-cyanothiazole, the purity was 95.4%, and the yield of pure substances was 81.15%. Among them, 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, then 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 into 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 50°C hot water, add sodium carbonate powder to the filtrate for alkalization, adjust the pH to 8, filter, wash the filter cake with 50°C hot water 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 prepares thiabendazole. The synthesis method is as follows:

[0109] Step 1: Synthesize 4-methylthiazole in water phase with 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 changed to: when the temperature reached 120° C., the reaction was kept warm for 2 h, at which time an intermediate complex CN-SH·NH3 was generated. The other conditions were the same as those 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 reaction system 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 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., 70.5 g of 4-methylthiazole. The yield based on monochloroacetone was 85.8%, the purity was 94.3%, and the yield of pure substances 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] The catalyst V 10 P 10 Zn1O 53 (SiO2) 40Loaded in a tubular fixed bed reactor. 60g of 4-methylthiazole (content of 94.3%, about 0.571mol) was vaporized in the preheating chamber of the tubular fixed bed reactor through a peristaltic pump, with a feed rate of 0.5g / min; at the same time, 14.6g of ammonia (0.859mol) was introduced into the preheating chamber through an ammonia cylinder, a pressure reducing valve, and a flow meter, and the ammonia flow rate was controlled at 260ml / min; compressed air entered the preheating chamber through a pressure reducing valve and a flow meter, and the flow rate ratio of ammonia to air was 1:12. The temperature of the preheating chamber was 280℃. Among them, the molar ratio of 4-methylthiazole to ammonia was 1:1.50. The vaporized 4-methylthiazole, ammonia and air formed a mixed gas; the mixed gas entered the tubular fixed bed reactor from the upper inlet, and the reactor temperature was controlled at 310℃. After the raw materials were introduced and the reaction was about 120min according to the above mode, the introduction of 4-methylthiazole and ammonia was turned off, and the compressed air was also turned off after continuing for 15min. The material was discharged from the bottom opening of the tubular fixed bed reactor, and 57.2 g of 4-cyanothiazole was collected, with a yield of 91.07% based on 4-methylthiazole, a purity of 92.1%, and a pure material 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] Add 150g of o-dichlorobenzene, 50g of 4-cyanothiazole (purity 92.1%, about 0.418mol), and 41.0g (0.436mol) of 99% aniline to a 1000ml four-necked flask, stir and heat to 110℃, and slowly introduce 18.3g (0.5mol) of dry HCl gas through a pressure reducing valve and a gas flow meter, and the ventilation time is controlled to be 2h. After the ventilation is completed, heat to 135℃ and keep warm for 3h, then cool to 60℃, add 200g of 50℃ hot water for water washing, stir for 30min, stand and separate, remove the oil phase dichlorobenzene, and the retained water phase is 4-(N-phenyl-amidino)thiazole hydrochloride aqueous solution, add 0.25g of activated carbon for decolorization, filter, and wash twice to obtain a light yellow transparent aqueous solution. Among them, 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 the 4-(N-phenyl-amidino)thiazole hydrochloride aqueous solution was 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 10% sodium hypochlorite (0.501mol) aqueous solution was added dropwise, and the dropping time was controlled to be 2.0h. After the dropwise addition was completed, the temperature was kept at 45°C for 6h, and the crude product 70.3g of thiabendazole was directly filtered and separated without cooling. The yield was 83.57% based on 4-cyanothiazole, the purity was 94.5%, and the yield of pure substances was 78.97%. Among them, 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, then 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 into a 500mL four-necked flask, add 30% hydrochloric acid while stirring to adjust the pH to 1, 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 50°C hot water, add sodium carbonate powder to the filtrate for alkalization, adjust the pH to 7.5, filter, wash the filter cake with 50°C hot water 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-metal element in the transition metal oxide catalyst, and then adopting any conventional method or a combination of multiple conventional methods including 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 by ball milling or the like), hydrothermal / solvothermal synthesis (synthesizing a catalyst of a specific form under high temperature and high pressure conditions in an autoclave).

[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 ratios of the metal elements and non-metal elements. Vanadium can be provided by V2O5, zinc can be provided by Zn(NO3)2, and phosphorus can be provided by phosphoric acid.

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

[0125] The slurry is spray dried with a rotary spray dryer to obtain solid particles, which are 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 ratios of the metal elements and non-metal elements. 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 into 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 solid content is 20.4wt% or other commercial 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 slurry, spray dry the slurry with a rotary spray dryer to obtain solid particles, roast at 380-450°C (preferably 400°C) for 1.5-4h (preferably 2h), then heat to 520-580°C (preferably 550°C) and continue roasting for 1.5-4h (preferably 2h).

[0129] The preparation methods of the above two catalysts are a combination of coprecipitation and sol (commercially available silica sol) gel method, and both use silicon dioxide as a carrier of metal oxide. Among them, the drying method is not limited to spray drying, and conventional drying methods can be used to obtain solids, which are then ground after roasting to obtain transition metal oxide catalysts with larger 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 aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned 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 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; the mass of water is 2-8 times the mass of monochloroacetone.

2. The method according to claim 1, characterized in that The catalyst is a combination of TBAB and DMAP.

3. The method according to claim 1, characterized in that The operation process of the method is as follows: water, carbon disulfide and a catalyst are added to a high-pressure reaction container, ammonia is slowly introduced into the high-pressure reaction container, the total amount of ammonia introduced is monitored during the introduction process, oxygen is introduced after the ammonia is introduced, the temperature is raised to 90-120° C., the pressure is maintained by introducing oxygen, the pressure is maintained at 0.4-0.8MPa, and the temperature is kept for 1-3h; then, the air is exhausted to normal pressure, the temperature is lowered to 30-60° C., monochloroacetone is slowly added dropwise to carry out a cyclization reaction, and the monochloroacetone is added dropwise for 1.5-3h; after the addition is completed, the temperature is kept at 40-60° C. for 3-7h, and after the reaction is completed, the reaction system is transferred to a separating funnel for standing and stratification, and washed with water, a light yellow oil phase is separated, and the oil phase is dried with a desiccant to obtain a light yellow clear and transparent liquid, namely 4-methylthiazole.

4. 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 according to any one of claims 1 to 3; (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 generate 4-cyanothiazole; 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 also contains a non-transition metal, and the non-transition metal is at least one of Zn, Na, K, Mg, Ca, Al, Ge, La, Sn, Sb, Te, Bi, Pb and Ce.

5. The method according to claim 4, characterized in that 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 .

6. The method according to claim 4, 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 in 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 500-550 ml of ammonia is introduced for every 1 g of 4-methylthiazole introduced; The preheating chamber preheats 4-methylthiazole, ammonia and air to 250-300°C, and vaporizes 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.

7. A method for synthesizing thiabendazole using carbon disulfide, ammonia and monochloroacetone as raw materials, characterized in that: include: S1. Synthesizing 4-cyanothiazole according to the method described in any one of claims 4 to 6; S2, dispersing 4-cyanothiazole and aniline in o-dichlorobenzene, passing dry HCl gas, making 4-cyanothiazole and aniline 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, transfer the aqueous solution of 4-(N-phenyl-amidino)thiazole hydrochloride into a cyclization reaction kettle, adjust the pH to 8-10, dropwise add sodium hypochlorite to catalyze the cyclization of 4-(N-phenyl-amidino)thiazole, filter, and obtain a crude product of thiabendazole; S4. Dissolve the crude thiabendazole in water and hydrochloric acid, add activated carbon for decolorization, filter, wash with water, alkalize the filtrate, filter, wash the filter cake with water, and dry to obtain purified thiabendazole.

8. The method according to claim 7, 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: firstly, o-dichlorobenzene 2-5 times the mass of 4-cyanothiazole is added into the reaction container, and then 4-cyanothiazole and aniline are added, and after the temperature is raised to 100-120°C, dry HCl gas is slowly introduced, and after the ventilation is completed, the temperature is raised to 130 -140°C, keep warm for 2-4h, the reaction is finished; cool to 60-80°C, add water, stir for 15-40min and then stand for stratification, remove dichlorobenzene, retain the aqueous phase, the aqueous phase is a 4-(N-phenyl-amidino)thiazole hydrochloride aqueous solution, add 0.1-5.0% activated carbon by mass of 4-cyanothiazole for decolorization, filter, wash with water to obtain a light yellow transparent aqueous solution, that is, a 4-(N-phenyl-amidino)thiazole hydrochloride aqueous solution.

9. The method according to claim 7, 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, dropwise add aqueous sodium hypochlorite solution, and after the dropwise addition is completed, keep warm at 40-50°C for 6-8h, without cooling, directly filter to separate the crude product of thiabendazole.

10. The method according to claim 7, characterized in that The operation process of S4 is: dissolve the crude thiabendazole in 3-5 times the mass of water, adjust the pH to 1-3 with concentrated hydrochloric acid, heat to 45-55°C, so that thiabendazole is dissolved in the water in the form of salt, add 0.1-5.0% of the mass of the crude thiabendazole activated carbon for decolorization, decolorize for 0.5-2h, filter while hot, wash with 45-60°C hot water, add sodium carbonate to the filtrate for alkalization, filter, wash the filter cake with 45-60°C hot water and then dry to obtain purified thiabendazole.

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