阅读说明：本技术 一种丙环唑的制备方法 (Preparation method of propiconazole ) 是由 李超 朱振亚 何永利 于 2021-09-18 设计创作，主要内容包括：本发明涉及一种丙环唑的制备方法。为了解决现有技术中涉及高危的溴化反应,会产生大量含溴副产品,单耗和成本高,缩合反应温度高,时间长,溶剂回收困难,废水难处理等明显不足,本发明的制备方法包括使用中间体3与三氮唑或其盐缩合反应生成丙环唑的步骤,所述的中间体3的结构式为：本发明的丙环唑的制备方法避开了传统合成方法中高危险性的溴代反应,避免含溴副产品的产生,并减少环境污染；本发明的丙环唑的制备方法具有优异的原料转化率和收率,产品纯度较高。进一步地,可使用低毒、低成本的反应溶剂代替传统工艺中的高毒DMSO和N,N-二甲基甲酰胺溶剂,反应更加温和,后处理简化,更加便于操作,且能耗显著降低,更适合工业化生产。(The invention relates to a preparation method of propiconazole. In order to solve the obvious defects of high-risk bromination reaction, generation of a large amount of bromine-containing byproducts, high unit consumption and cost, high condensation reaction temperature, long time, difficult solvent recovery, difficult wastewater treatment and the like in the prior art, the preparation method comprises the step of generating propiconazole by using an intermediate 3 and triazole or a salt thereof through condensation reaction, wherein the intermediate 3 has the structural formula:)

1. The preparation method of the propiconazole is characterized by comprising the step of carrying out condensation reaction on an intermediate 3 and triazole or a salt thereof to generate the propiconazole, wherein the intermediate 3 has a structural formula as follows:

2. the preparation method according to claim 1, characterized in that the intermediate 3 and triazole or a salt thereof react at 30-150 ℃ in the presence of the first solvent to form propiconazole.

3. The method according to claim 2, wherein the first solvent is one or more of toluene, chlorobenzene, cyclohexane, methylcyclohexane, dimethylsulfoxide, and N, N-dimethylformamide.

4. The process of claim 1, further comprising the step of reacting intermediate 2 with p-toluenesulfonyl chloride in the presence of a second solvent and an organic base catalyst to form intermediate 3, wherein intermediate 2 has the formula:

5. the preparation method according to claim 4, wherein the organic base catalyst is one or more of triethylamine, piperidine and pyridine; and/or the second solvent is one or more of toluene, chlorobenzene, cyclohexane, methylcyclohexane, dimethyl sulfoxide and N, N-dimethylformamide; and/or, the first solvent comes from the second solvent added in the reaction system of the intermediate 2 and the paratoluensulfonyl chloride; and/or the reaction temperature of the intermediate 2 and the p-toluenesulfonyl chloride is 20-100 ℃.

6. The preparation method according to claim 4, wherein the feeding mass ratio of the intermediate 2 to the tosyl chloride is 1-2: 1; and/or the feeding mass ratio of the intermediate 2 to the organic base catalyst is 1.5-3: 1; and/or the feeding molar weight ratio of the intermediate 2 to the triazole or the salt thereof is 0.9-1.2: 1; and/or the sum of the mass of the first solvent and the second solvent is 1-3.5 times of the feeding mass of the intermediate 2; and/or the tosyl chloride is fed in a dropwise manner.

7. The method of claim 1, comprising the steps of:

(1) reacting the intermediate 2 with tosyl chloride in the presence of an organic base catalyst and a second solvent at 20-100 ℃ to obtain a primary reaction solution;

(2) purifying the primary reaction liquid obtained in the step (1) by adopting a water washing liquid separation method, wherein an organic phase is the purified primary reaction liquid,

or, purifying the primary reaction liquid obtained in the step (1) by adopting a water washing liquid separation method, collecting an organic phase, and removing the solvent to obtain a primary reaction product;

(3) mixing the purified primary reaction liquid obtained in the step (2) with triazole or a salt thereof, reacting at 30-150 ℃ to generate a secondary reaction liquid,

or mixing the primary reaction product obtained in the step (2), triazole or a salt thereof and a first solvent, and reacting at 30-150 ℃ to generate a second-step reaction solution;

(4) and (4) purifying the two-step reaction solution obtained in the step (3) by adopting a water washing liquid separation method, and removing the solvent from an organic phase to obtain the propiconazole.

8. The preparation method of claim 7, wherein the tosyl chloride in the step (1) is fed in a dropwise manner, the dropwise addition time of the tosyl chloride is controlled to be 1-3 hours, and the reaction time after the dropwise addition is 1-6 hours; and/or, the reaction time of the step (3) is 1-24 hours.

9. The method of claim 4 or 7, further comprising the step of using a condensation reaction of starting material 1 and 1, 2-pentanediol to form intermediate 2, wherein the starting material 1 has the formula:

10. a propiconazole intermediate, which is characterized in that the structural formula is shown as 3:

Technical Field

The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of propiconazole.

Background

Propiconazole is a triazole bactericide with protection and treatment effects, broad spectrum and systemic property. The bactericidal composition has good control effects on banana leaf spot, wheat powdery mildew, leaf blight, grape powdery mildew, rice bakanae disease and the like, and the lasting period reaches 3-5 weeks.

The domestic report of the product is mainly after 2000 years, for example, the industrial production process of propiconazole is introduced in the domestic journal for the first time in 2001 by cinnabar and the like, a method of bromination firstly and cyclization secondly is adopted, and a substance shown as an intermediate 5 is involved in the preparation method:

chinese patent CN101781290A discloses a method for producing propiconazole, which also adopts intermediate 5 as raw material to perform condensation reaction with triazole potassium under alkaline condition to prepare the propiconazole.

Chinese patent CN102225935A discloses a method for producing propiconazole, which also adopts intermediate 5 as raw material to carry out condensation reaction with triazole and potassium carbonate to prepare the propiconazole product.

Chinese patent CN110105322A also discloses a process for synthesizing propiconazole by using the intermediate 5 as a raw material.

Researches show that when the intermediate 5 is synthesized, brominating reagents such as bromine and the like are needed, the method belongs to a high-risk process, a large amount of bromine-containing byproducts are generated, and the unit consumption and the cost are high. In the condensation reaction process, the intermediate 5 is used as a raw material, a large amount of DMSO or N, N-dimethylformamide is used as a solvent, the reaction temperature is high, the time is long, the solvent is difficult to recover, the wastewater is difficult to treat, and the like.

Disclosure of Invention

The invention aims to provide a novel preparation method of propiconazole, which avoids an intermediate 5 on the premise of ensuring higher yield, does not generate a bromine-containing byproduct, and has the advantages of less three wastes, higher safety and lower cost.

In order to achieve the purpose, the invention adopts the technical scheme that:

the invention provides a preparation method of propiconazole, which comprises the step of generating propiconazole by using an intermediate 3 and triazole or a salt thereof through a condensation reaction, wherein the intermediate 3 has a structural formula as follows:

preferably, the intermediate 3 and triazole or a salt thereof react at 30-150 ℃ in the presence of a first solvent to generate the propiconazole.

Further preferably, the intermediate 3 and triazole or a salt thereof react at 50-120 ℃ in the presence of the first solvent to generate propiconazole.

Still more preferably, the intermediate 3 and triazole or a salt thereof react at 50-90 ℃ in the presence of the first solvent to generate propiconazole.

Preferably, the reaction time of the intermediate 3 and triazole or a salt thereof is 1 to 24 hours, more preferably 2 to 10 hours, and even more preferably 3 to 5 hours.

Further preferably, the first solvent is one or more of toluene, chlorobenzene, cyclohexane, methylcyclohexane, dimethyl sulfoxide and N, N-dimethylformamide.

Further preferably, the triazole salt is sodium triazole.

Still further preferably, the first solvent is one or more of toluene, methylcyclohexane or N, N-dimethylformamide.

Still further preferably, the first solvent is toluene and/or N, N-dimethylformamide.

Still more preferably, the first solvent is toluene.

Preferably, the preparation method further comprises the step of reacting the intermediate 3 with the intermediate 2 and p-toluenesulfonyl chloride in the presence of a second solvent and an organic base catalyst, wherein the structural formula of the intermediate 2 is as follows:

further preferably, the organic base catalyst is one or more of triethylamine, piperidine and pyridine.

Still more preferably, the organic base catalyst is triethylamine.

Further preferably, the second solvent is one or more of toluene, chlorobenzene, cyclohexane, methylcyclohexane, dimethyl sulfoxide and N, N-dimethylformamide.

Still more preferably, the second solvent is toluene and/or methylcyclohexane.

According to a particular and preferred embodiment, said first solvent and said second solvent are the same.

Further preferably, the first solvent and the second solvent are both toluene.

Further preferably, the first solvent is the second solvent added in the reaction system of the intermediate 2 and the paratoluensulfonyl chloride. The reaction liquid obtained after the reaction of the intermediate 2 and the p-toluenesulfonyl chloride can be used for condensation reaction, and a second solvent is not added, namely, only one solvent is added in the two-step reaction, so that the operation is simpler and more convenient, and the solvent utilization rate is higher.

Further preferably, the temperature of the reaction between the intermediate 2 and the p-toluenesulfonyl chloride is 20-100 ℃.

Still further preferably, the reaction temperature of the intermediate 2 and the p-toluenesulfonyl chloride is 20-80 ℃.

Still more preferably, the temperature of the reaction between the intermediate 2 and the paratoluensulfonyl chloride is 30-60 ℃.

Further preferably, the feeding mass ratio of the intermediate 2 to the tosyl chloride is 1-2: 1.

Further preferably, the feeding mass ratio of the intermediate 2 to the organic base catalyst is 1.5-3: 1.

More preferably, the feeding molar weight ratio of the intermediate 2 to the triazole or the salt thereof is 0.9-1.2: 1, and still more preferably 0.9-1.1: 1.

More preferably, the sum of the mass of the first solvent and the mass of the second solvent is 1 to 3.5 times of the feeding mass of the intermediate 2.

Still more preferably, the sum of the mass of the first solvent and the second solvent is 1 to 3 times of the charged mass of the intermediate 2.

More preferably, the sum of the mass of the first solvent and the second solvent is 1-2 times of the charged mass of the intermediate 2.

Still more preferably, the sum of the mass of the first solvent and the second solvent is 1 to 1.8 times of the mass of the intermediate 2.

Further preferably, the tosyl chloride is fed in a dropwise manner.

According to some embodiments, the dropping time of the tosyl chloride is controlled to be 1 to 3 hours.

According to some embodiments, the reaction is carried out for 1-6 hours under heat preservation after the dropwise addition.

Preferably, after the dropwise addition, the reaction is carried out for 1-3 hours in a heat preservation manner.

According to some embodiments, the preparation method comprises the following steps:

(1) reacting the intermediate 2 with tosyl chloride in the presence of an organic base catalyst and a second solvent at 20-100 ℃ to obtain a primary reaction solution;

(2) purifying the primary reaction liquid obtained in the step (1) by adopting a water washing liquid separation method, wherein an organic phase is the purified primary reaction liquid,

or, purifying the primary reaction liquid obtained in the step (1) by adopting a water washing liquid separation method, collecting an organic phase, and removing the solvent to obtain a primary reaction product;

(3) mixing the purified primary reaction liquid obtained in the step (2) with triazole or a salt thereof, reacting at 30-150 ℃ to generate a secondary reaction liquid,

or mixing the primary reaction product obtained in the step (2), triazole or a salt thereof and a first solvent, and reacting at 30-150 ℃ to generate a second-step reaction solution;

(4) and (4) purifying the two-step reaction solution obtained in the step (3) by adopting a water washing liquid separation method, and removing the solvent from an organic phase to obtain the propiconazole.

Preferably, the tosyl chloride in the step (1) is fed in a dropwise adding manner, the dropwise adding time of the tosyl chloride is controlled to be 1-3 hours, and the reaction time after the dropwise adding is 1-6 hours, and further preferably 1-3 hours.

Preferably, the reaction time of the step (3) is 1 to 24 hours, more preferably 2 to 10 hours, and still more preferably 3 to 5 hours.

More specifically, the preparation method comprises the following steps:

(1) mixing the intermediate 2, an organic base catalyst and a second solvent, dropwise adding p-toluenesulfonyl chloride at 20-100 ℃, and after dropwise adding, keeping the temperature at 20-100 ℃ for reaction until the reaction is finished to obtain a primary reaction solution;

(2) mixing the primary reaction liquid obtained in the step (1) with water, carrying out organic phase reflux water cutting after liquid separation, heating to 115-120 ℃, finishing water cutting to obtain purified primary reaction liquid,

or mixing the preliminary reaction liquid obtained in the step (1) with water, separating the liquid, collecting an organic phase, and removing the solvent to obtain a preliminary reaction product;

(3) cooling the purified primary reaction liquid obtained in the step (2) to 20-60 ℃, mixing triazole or salt thereof, reacting at 30-150 ℃ until the sampling central control raw material is less than 0.8%, stopping the reaction to obtain a secondary reaction liquid,

or mixing the primary reaction product obtained in the step (2), triazole or salt thereof and a first solvent, reacting at 30-150 ℃ until the sampling central control raw material is less than 0.8%, and stopping the reaction to obtain a second-step reaction solution;

(4) and (4) mixing the reaction liquid obtained in the step (3) with water at 50-100 ℃ for 0.5-2 hours in a heat preservation manner, separating the liquid, taking an organic phase, and removing the organic solvent under reduced pressure to obtain the propiconazole.

In the present invention, the intermediate 2 may be commercially available, or the preparation method may further comprise a step of producing the intermediate 2 by condensation reaction of the starting material 1 with 1, 2-pentanediol.

Specifically, the intermediate 2 is generated by reacting alpha-hydroxy (2 ', 4' -dichloro) acetophenone and 1, 2-pentanediol in the presence of a catalyst and a solvent.

Further, the solvent is cyclohexane, and the catalyst is sulfuric acid.

The invention also provides a propiconazole intermediate, the structural formula of which is shown in the specification of 3:

due to the application of the technical scheme, compared with the prior art, the invention has the following advantages:

the preparation method of propiconazole avoids the technical process of preparing the intermediate 5 by high-risk bromination reaction in the traditional synthetic method, avoids the generation of bromine-containing byproducts and reduces environmental pollution; the preparation method of propiconazole has excellent raw material conversion rate and yield and higher product purity. Furthermore, a reaction solvent with low toxicity and low cost can be used for replacing a high-toxicity DMSO solvent and an N, N-dimethylformamide solvent in the traditional process, the reaction is milder, the post-treatment is simplified, the operation is more convenient, the energy consumption is obviously reduced, and the method is more suitable for industrial production.

Detailed Description

All of the features disclosed in this specification, or all of the steps in any method or process so disclosed, may be combined in any combination, except combinations where mutually exclusive features or steps are expressly stated. The invention will now be further described with reference to specific examples, but the invention should not be limited to these examples, but may be substituted by other equivalent or similarly purposed alternative features unless specifically stated. Unless expressly stated otherwise, each feature is only an example of a generic series of equivalent or similar features. Terms used in the present invention generally have meanings commonly understood by those of ordinary skill in the art, unless otherwise specified.

The synthesis routes disclosed by the prior art all comprise preparation of the intermediate 5, and bromine and other brominating reagents are needed, so that the method belongs to a high-risk process, a large amount of bromine-containing byproducts are generated, and the unit consumption and the cost are high. Further, in the condensation reaction process, the intermediate 5 is used as a raw material, a large amount of DMSO or N, N-dimethylformamide is used as a solvent, the reaction temperature is high, the reaction time is long, the solvent is difficult to recover, the wastewater is difficult to treat, and the like.

In view of the deficiencies in the prior art, the inventors of the present invention have made extensive studies and extensive practices to provide technical solutions of the present invention. The technical solution, its implementation and principles, etc. will be further explained as follows.

The embodiment of the invention provides a propiconazole intermediate, the structural formula of which is shown as 3:

the embodiment of the invention provides a synthetic route of propiconazole as follows:

specifically, in the embodiment, the intermediate 2 reacts with tosyl chloride to obtain an intermediate, the intermediate 3 reacts with sodium triazole through condensation reaction to generate a compound 4, the compound 4 is propiconazole, and the improved route does not need to use a bromo compound under the condition of ensuring that the yield and purity of the product are acceptable:the method has the advantages of avoiding bromination reaction, discharging no hydrogen bromide gas, generating no bromine-containing byproducts, simple post-treatment, less three wastes, improving production safety and reducing environmental pollution.

Specifically, the reaction of the intermediate 2 with tosyl chloride uses an organic base catalyst, and one or more of toluene, chlorobenzene, cyclohexane, methylcyclohexane, dimethyl sulfoxide, and N, N-dimethylformamide may be used as a reaction solvent. The reaction of the intermediate 3 and the sodium triazole can also use one or more of toluene, chlorobenzene, cyclohexane, methylcyclohexane, dimethyl sulfoxide and N, N-dimethylformamide as a reaction solvent.

Because the reaction temperature of the condensation reaction between the intermediate 3 and the triazole sodium is lower than that of the condensation reaction between the intermediate 5 and the triazole, the solvent of the condensation reaction between the intermediate 3 and the triazole does not necessarily need DMSO and/or N, N-dimethylformamide, and the solvent preferably adopts toluene which is lower in toxicity, easier to recycle and lower in cost. And the solvent in the condensation reaction of the intermediate 3 and the sodium triazole can be a solvent added in a reaction system of the intermediate 2 and the p-toluenesulfonyl chloride, namely, a reaction solution obtained after the reaction of the intermediate 2 and the p-toluenesulfonyl chloride can be used for the condensation reaction, no additional solvent is added, the solvent is only added once in the two-step reaction, the operation is simpler and more convenient, and the solvent cost is further reduced.

The organic base catalyst used in the reaction of the intermediate 2 and the tosyl chloride is one or more of triethylamine, piperidine and pyridine. Under the condition of a proper organic base catalyst and a proper solvent, the reaction temperature of the intermediate 2 and the paratoluensulfonyl chloride is milder, and the reaction time is shorter.

Specifically, in the embodiment, the organic base catalyst is triethylamine, the reaction temperature is preferably 30-60 ℃, the tosyl chloride is added in a dropwise manner, the dropwise addition time is 1-3 hours, and the reaction time is 1-3 hours after the dropwise addition. The reaction temperature of the intermediate 3 and sodium triazole is 30-150 ℃, preferably 50-120 ℃, and further preferably 50-90 ℃; the reaction time of the intermediate 3 and the sodium triazole is preferably 1-24 hours, more preferably 2-10 hours, and even more preferably 3-5 hours.

Further, the reaction liquid obtained after the reaction of the intermediate 2 and tosyl chloride can be simply purified, and the reaction liquid obtained after the condensation reaction of the intermediate 3 and sodium triazole can be simply purified, so that the purity of the obtained propiconazole can be over 85 percent.

Specifically, in some embodiments, a reaction solution obtained after reaction of the intermediate 2 and tosyl chloride is mixed with water, an organic phase is refluxed and water is cut after liquid separation, and the water is cut after the temperature is raised to 115-120 ℃ to obtain a purified primary reaction solution; and (3) cooling the purified primary reaction liquid to 20-60 ℃, mixing with sodium triazole, reacting at 30-150 ℃ until the sampling central control raw material is less than 0.8%, and stopping the reaction to obtain a secondary reaction liquid.

In other embodiments, the reaction solution obtained after the reaction of the intermediate 2 and tosyl chloride is mixed with water, and the organic phase is collected after liquid separation, and the solvent is removed to obtain a primary reaction product; and mixing the primary reaction product with sodium triazole and a first solvent, reacting at 30-150 ℃ until the sampling central control raw material is less than 0.8%, and stopping the reaction to obtain a second-step reaction solution.

In the embodiment, the reaction liquid in the second step and water are mixed at 50-100 ℃ for 0.5-2 hours under heat preservation, an organic phase is taken after liquid separation, and the organic solvent is removed under reduced pressure to obtain the propiconazole.

After route improvement and reaction condition optimization, in the embodiment, the feeding mass ratio of the intermediate 2 to tosyl chloride is 1-2: 1, the feeding mass ratio of the intermediate 2 to the organic base catalyst is 1.5-3: 1, the feeding mass ratio of the intermediate 2 to triazole sodium is 4-6: 1, the using amount of the solvent is 1-3.5 times of that of the intermediate 2, the reaction temperature can be adjusted to be below 90 ℃, the total reaction time is reduced to be within 9 hours, and the yield and the purity can reach more than 85% at most.

In conclusion, the embodiment shows that the intermediate 5 is avoided being used by improving the traditional synthetic route of the propiconazole, so that the bromination reaction is not involved, the high-risk process is avoided, the generation of bromine-containing byproducts is avoided, and the environmental pollution is reduced. Furthermore, in the step of carrying out the condensation reaction by using the compound 3, the reaction temperature is relatively milder, and a reaction solvent (preferably toluene) with low toxicity and low cost can be used for replacing high-toxicity DMSO and N, N-dimethylformamide as solvents, so that the unit consumption of the solvents is reduced. Wastewater containing DMSO is difficult to treat, and after optimization, the generation of the wastewater difficult to treat is avoided. The preparation process has the advantages of milder reaction, simplified post-treatment, convenient operation, obviously reduced energy consumption, short reaction time and high yield and purity which can reach more than 85%.

The present invention will be further described with reference to the following examples. However, the present invention is not limited to the following examples. The implementation conditions adopted in the embodiments can be further adjusted according to different requirements of specific use, and the implementation conditions not mentioned are conventional conditions in the industry. The technical features of the embodiments of the present invention may be combined with each other as long as they do not conflict with each other.

In the following examples, various procedures and methods not described in detail are conventional methods well known in the art. The raw materials and reagents used are commercially available.

Example 1

Preparation of intermediate 2

Taking 200g of alpha-hydroxy (2 ', 4' -dichloro) acetophenone, adding 200g of cyclohexane, adding 110g of 1, 2-pentanediol, adding 1g of sulfuric acid, heating to reflux, cutting water for 10-12h, and controlling the reaction to end when the content of the alpha-hydroxy (2 ', 4' -dichloro) acetophenone is less than 1%. Cooling to 50 ℃, adding 100g of water, stirring, adjusting the pH to 7-8, and removing the solvent by an organic phase rotary evaporator to obtain the intermediate 2 with the content of more than 98% and the yield of 95%.

Example 2

290g of intermediate 2 is taken, 500g of toluene is added, 120g of triethylamine is added, 195g of paratoluensulfonyl chloride is added dropwise, the temperature is controlled to be 40-45 ℃, the dropping time is controlled to be 2h, the temperature is kept for 2h after the dropping is finished, 100g of water is added to wash a toluene phase after the reaction is finished, the toluene phase flows back and is cut into water after the liquid separation, the temperature is increased to 117 ℃, the water is cut out, the temperature is reduced to 40 ℃, 91g of sodium triazole is added, the temperature is increased to 70-80 ℃, the temperature is kept for 5h, the central control raw material is sampled and is less than 0.8%, 100g of water is added, the temperature is kept for 1h, standing and layering are carried out, the toluene is removed under reduced pressure, and a propiconazole crude product is obtained, the content is 85.9%, and the yield is 86.5%.

Example 3

290g of intermediate 2 is taken, 500g of toluene is added, 120g of triethylamine is added, 195g of paratoluensulfonyl chloride is added dropwise, the temperature is controlled to be 40-45 ℃, the dropping time is controlled to be 2h, the temperature is kept for 2h after the dropping is finished, 100g of water is added to wash a toluene phase after the reaction is finished, the toluene phase flows back and is cut into water after the liquid separation, the temperature is increased to 117 ℃, the water is cut out, the temperature is reduced to 40 ℃, 91g of sodium triazole is added, the temperature is increased to 120 ℃ of reflux temperature, the temperature is kept for 3h, the sampling central control raw material is less than 0.8 percent, 100g of water is added, the temperature is kept for 1h at 70-80 ℃, standing and layering are carried out, the toluene is removed under reduced pressure, and a propiconazole crude product is obtained, the content is 84.6%, and the yield is 84.1%.

Example 4

290g of intermediate 2 is taken, 500g of toluene is added, 120g of triethylamine is added, 195g of paratoluensulfonyl chloride is added dropwise, the temperature is controlled to be 40-45 ℃, the dropping time is controlled to be 2h, the temperature is kept for 2h after the dropping is finished, 100g of water is added to wash a toluene phase after the reaction is finished, the toluene phase is taken after the liquid separation, the toluene is removed to obtain an intermediate 3(HPLC-MS:444.12, melting point 124 and melting point 126 ℃), the temperature is reduced to 80 ℃, 91g of sodium triazole and 500g of N, N-dimethylformamide are added, the temperature is raised to the reflux temperature 153 ℃, the temperature is kept for 2h, the sampling central control raw material is less than 0.8 percent, 100g of water is added, the temperature is kept for 1h at 70-80 ℃, standing and layering is carried out, the toluene is removed under reduced pressure, and a propiconazole crude product is obtained, the content is 84.6%, and the yield is 84.1%.

Example 5

290g of intermediate 2 is taken, 300g of toluene is added, 120g of triethylamine is added, 195g of paratoluensulfonyl chloride is added dropwise, the temperature is controlled to be 40-45 ℃, the dropping time is controlled to be 2h, the temperature is kept for 2h after the dropping is finished, 100g of water is added to wash a toluene phase after the reaction is finished, the toluene phase flows back and is cut into water after the liquid separation, the temperature is increased to 117 ℃, the water is cut out, the temperature is reduced to 40 ℃, 91g of sodium triazole is added, the temperature is raised to 70-80 ℃, the temperature is kept for 5h, the central control raw material in sampling is less than 0.8%, water is added for 100g, the temperature is kept for 1h at 70-80 ℃, standing and layering are carried out, the toluene is removed under reduced pressure, and a propiconazole crude product is obtained, the content is 81.9%, and the yield is 82.5%.

Example 6

290g of intermediate 2 is taken, 500g of methylcyclohexane is added, 120g of triethylamine is added, 195g of paratoluensulfonyl chloride is added dropwise, the temperature is controlled to be 40-45 ℃, the dropping time is controlled to be 2h, the temperature is kept for 5h after the dropping is finished, 100g of water washing organic phase is added after the reaction is finished, the methylcyclohexane phase flows back and cuts water after the liquid separation, the temperature is raised to 98 ℃, the water cutting is finished, the temperature is reduced to 40 ℃, 91g of sodium triazole is added, the temperature is raised to 100-102 ℃ of reflux temperature, the temperature is kept for 5h, the sampling central control raw material is less than 0.8 percent, 100g of water is added, the temperature is kept for 1h at 70-80 ℃, standing and layering are carried out, the methylcyclohexane is removed under reduced pressure, and a crude product of propiconazole with the content of 78.5 percent and the yield of 76.3 percent is obtained.

Example 7

290g of intermediate 2 is taken, 500g of toluene is added, 120g of triethylamine is added, 195g of paratoluensulfonyl chloride is added dropwise, the temperature is controlled to be 40-45 ℃, the dropping time is controlled to be 2h, the temperature is kept for 2h after the dropping is finished, 100g of water-washed toluene phase is added after the reaction is finished, 91g of triazole sodium is directly added without cutting water, the water is cut during the heating process to the reflux temperature of 110 and 120 ℃, the sampling central control raw material is less than 2 percent after the temperature is kept for 10h, 100g of water is added, the temperature is kept for 1h at 70-80 ℃, standing and layering are carried out, the toluene is removed under reduced pressure, and the crude propiconazole product with the content of 81.2 percent and the yield of 78.6 percent is obtained.

Example 8

290g of intermediate 2 is taken, 500g of toluene is added, 30g of triethylamine is added, 195g of paratoluensulfonyl chloride is added dropwise, the temperature is controlled to be 40-45 ℃, the dropping time is controlled to be 2h, the temperature is kept for 2h after the dropping is finished, 100g of water is added to wash a toluene phase after the reaction is finished, the toluene phase flows back and is cut into water after the liquid separation, the temperature is increased to 117 ℃, the water is cut out, the temperature is reduced to 40 ℃, 91g of sodium triazole is added, the temperature is increased to 120 ℃ of reflux temperature, the temperature is kept for 2h, the sampling central control raw material is less than 0.5 percent, 100g of water is added, the temperature is kept for 1h at 70-80 ℃, standing and layering are carried out, the toluene is removed under reduced pressure, and a propiconazole crude product is obtained, the content is 83.2 percent, and the yield is 54.8 percent.

The above embodiments are merely illustrative of the technical ideas and features of the present invention, and the purpose thereof is to enable those skilled in the art to understand the contents of the present invention and implement the present invention, and not to limit the protection scope of the present invention. All equivalent changes and modifications made according to the spirit of the present invention should be covered within the protection scope of the present invention.