CN111100081A - Continuous preparation method of prothioconazole - Google Patents
Continuous preparation method of prothioconazole Download PDFInfo
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- CN111100081A CN111100081A CN201811255991.2A CN201811255991A CN111100081A CN 111100081 A CN111100081 A CN 111100081A CN 201811255991 A CN201811255991 A CN 201811255991A CN 111100081 A CN111100081 A CN 111100081A
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- propane
- hydroxy
- prothioconazole
- triazolidine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D249/12—Oxygen or sulfur atoms
Abstract
The invention relates to a continuous preparation method of prothioconazole, which comprises the step of reacting 2- (1-chloro-cyclopropyl-1-yl) -1- (2-chlorphenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thion-1-yl) -propane in the presence of an oxidant to prepare the prothioconazole, wherein the reaction is carried out in a micro-channel continuous flow reactor. The preparation raw materials are cheap and easy to obtain, the microchannel continuous flow reactor is adopted to accelerate the reaction speed, reduce the use of the oxidant and improve the reaction safety, the three wastes are less polluted, the preparation method is clean and environment-friendly, and is suitable for industrial production, and the yield and the content of the final product are high.
Description
Technical Field
The invention particularly relates to a continuous preparation method of prothioconazole.
Background
Prothioconazole (prothioconazole) is a low-toxicity, high-efficiency and broad-spectrum triazolethione bactericide developed by Bayer companies, and is mainly used for preventing and treating a plurality of diseases of cereals, wheat and bean crops and the like. The prothioconazole is synthesized by 2- (1-chloro-cyclopropan-1-yl) -1- (2-chlorphenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thion-1-yl) -propane, so that the generation of isomeric solid wastes can be avoided from the source, and a series of reaction conditions which are not suitable for industrial production, such as dangerous chemicals, high temperature and the like can be avoided. At present, a method for preparing prothioconazole by oxidizing 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane has been reported, for example: US6201128, US6559317, pctint. appl.2001046158, and the like. However, the existing method has the problems that the reaction conditions are not easy to control, the solid waste is more, the green environmental protection requirement is not met, and the industrial production is not facilitated.
For example:
in the synthesis route of US6201128, air/catalytic amount of sulfur powder or excess sulfur powder is required as a reaction reagent, and the reaction is carried out at a higher temperature, so that by-products with peculiar smell are generated, and the synthesis yield is not high.
In the synthetic route of US6559317, an excess of ferric chloride is used as a reagent, resulting in the reaction generating a large amount of solid waste.
Disclosure of Invention
The invention aims to provide an economical, green and environment-friendly preparation method of prothioconazole suitable for industrial production.
In order to solve the technical problems, the invention adopts the following technical scheme:
a continuous preparation method of prothioconazole, 2- (1-chloro-cyclopropyl-1-yl) -1- (2-chlorphenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thion-1-yl) -propane (formula I) is reacted in the presence of an oxidizing agent to prepare the prothioconazole (formula II), and the reaction is carried out in a micro-channel continuous flow reactor.
Reaction formula is
Preferably, the microchannel continuous flow reactor is a high-flux microchannel continuous flow reactor of corning, usa.
Preferably, the oxidant is ferric trichloride and/or oxygen.
According to one embodiment, the oxidant is ferric trichloride or oxygen, and the molar ratio of the 2- (1-chloro-cyclopropane-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane to the oxidant is 1: 0.01-6.
Preferably, the feeding molar ratio of the 2- (1-chloro-cyclopropane-1-yl) -1- (2-chlorphenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thion-1-yl) -propane to the oxidant is 1: 0.01-3.
According to a specific embodiment, when the oxidant is ferric trichloride, the feeding molar ratio of the 2- (1-chloro-cyclopropane-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane to the ferric trichloride is 1: 1-2.5.
According to another specific embodiment, when the oxidant is oxygen, the feeding molar ratio of the 2- (1-chloro-cyclopropane-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane to the oxygen is 1: 0.5-2.
According to another embodiment, the oxidant is ferric chloride and oxygen, and the molar ratio of the 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidin-5-thione-1-yl) -propane to the iron trichloride to the oxygen is 1: 0.01-3: 0.1-3.
Preferably, the feeding molar ratio of the 2- (1-chloro-cyclopropane-1-yl) -1- (2-chlorphenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thion-1-yl) -propane, the ferric trichloride and the oxygen is 1: 0.01-2.8: 0.2-2.8.
More preferably, the feeding molar ratio of the 2- (1-chloro-cyclopropane-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thion-1-yl) -propane to the ferric trichloride to the oxygen is 1: 0.02-2.5: 0.5-2.8.
In the present invention, said microchannel continuous flow reactor comprises a plurality of heating zones connected in series, and according to one embodiment, when said oxidizing agent is ferric chloride, said 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidin-5-thione-1-yl) -propane and said oxidizing agent are introduced from the first of said heating zones; according to another embodiment, when said oxidizing agent is oxygen, said 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidin-5-thione-1-yl) -propane is introduced into a first of said heating zones and said oxidizing agent is introduced into a second of said heating zones; according to still another embodiment, when said oxidizing agent is ferric chloride and oxygen, said 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidin-5-thione-1-yl) -propane and said ferric chloride are introduced from the first said heating zone, said oxygen is introduced from the second said heating zone, and if oxygen is also added from the first said heating zone, it is not favorable for the uniform mixing of oxygen and 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidin-5-thione-1-yl) -propane and the stabilization of the reaction temperature, if oxygen is introduced from the third or later heating zone, the contact time of oxygen with 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidin-5-thione-1-yl) -propane is short, which is not favorable for the reaction.
Preferably, said 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazol-ane-5-thione-1-yl) -propane and said iron trichloride are passed into said heating zone in the form of a solution.
Preferably, said 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazol-5-thione-1-yl) -propane is dissolved in a solvent to form a solution of 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazol-5-thione-1-yl) -propane, said 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, the mass concentration of the 2, 4-triazolidine-5-thione-1-yl) -propane solution is 5-50%, more preferably 5-40%, still more preferably 5-20%, and more preferably 5-10%; the feeding rate is 10mL/min to 150mL/min, more preferably 20mL/min to 120mL/min, and still more preferably 20mL/min to 100 mL/min.
Further preferably, the solvent is one or more of acetonitrile, tetrahydrofuran, acetone, dimethyl sulfoxide, N-dimethylformamide, N-methylpyrrolidone, methanol, ethanol, N-butanol, tert-butanol, toluene, water and dichloromethane.
Preferably, the ferric trichloride is dissolved in a solvent to form a ferric trichloride solution, and the mass concentration of the ferric trichloride solution is 0.1-50%, more preferably 0.1-30%, still more preferably 0.1-20%, and more preferably 0.1-10%; the feeding speed of the ferric trichloride solution is 1 mL/min-130 mL/min, and more preferably 1 mL/min-80 mL/min; more preferably 1 to 30 mL/min.
Further preferably, the solvent is one or more of acetonitrile, tetrahydrofuran, acetone, dimethyl sulfoxide, N-dimethylformamide, N-methylpyrrolidone, methanol, ethanol, N-butanol, tert-butanol, toluene, water and dichloromethane.
In the present invention, the oxygen is fed in the form of pure oxygen, or in the form of other gases containing oxygen, for example, in the form of air.
Preferably, the oxygen is fed at a rate of 50mL/min to 800mL/min, more preferably 100mL/min to 650mL/min, and still more preferably 100mL/min to 450 mL/min.
Further preferably, said 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidin-5-thione-1-yl) -propane is fed from a first inlet port of a first of said heating zones and said ferric chloride is fed from a second inlet port of a first of said heating zones.
Further preferably, said 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane and said iron trichloride are added to said microchannel continuous flow reactor by means of a polytetrafluoroethylene pump or a stainless steel pump, respectively.
Preferably, the reaction is carried out at 0-160 ℃, more preferably at 20-100 ℃, and even more preferably at 90-100 ℃.
Preferably, the residence time of the 2- (1-chloro-cyclopropan-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane and the oxidant in the micro-channel continuous flow reactor is 0.1-6 min.
Preferably, the continuous preparation method further comprises the steps of concentrating the reaction liquid from the micro-channel continuous flow reactor, extracting, layering, concentrating and recrystallizing to obtain the prothioconazole.
In the present invention, the molar ratio of 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazol-5-thione-1-yl) -propane to the oxidant is the ratio of the molar amount of 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazol-5-thione-1-yl) -propane and the oxidant introduced into the microchannel continuous flow reactor per minute.
The invention adopts the flow chart of the micro-channel continuous flow reactor for reaction, and refers to a figure 1, wherein a raw material solution is a 2- (1-chloro-cyclopropyl-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thion-1-yl) -propane solution, an oxidant 1 solution is an iron trichloride solution, and an oxidant 2 is air or oxygen.
Due to the implementation of the technical scheme, compared with the prior art, the invention has the following advantages:
the preparation raw materials are cheap and easy to obtain, the microchannel continuous flow reactor is adopted to accelerate the reaction speed, reduce the use of the oxidant and improve the reaction safety, the three wastes are less polluted, the preparation method is clean and environment-friendly, and is suitable for industrial production, and the yield and the content of the final product are high.
Drawings
FIG. 1 is a flow diagram of a reaction carried out using the microchannel continuous flow reactor.
Detailed Description
The present invention will be described in further detail with reference to specific examples. It is to be understood that these embodiments are provided to illustrate the basic principles, essential features and advantages of the present invention, and the present invention is not limited by the following embodiments. The implementation conditions used in the examples can be further adjusted according to specific requirements, and the implementation conditions not indicated are generally the conditions in routine experiments.
Example one
The preparation method of prothioconazole of the embodiment comprises the following steps:
2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidin-5-thione-1-yl) -propane I (90g,0.25mol) was dissolved in a mixed solution of toluene and ethanol (1068mL, wherein the volume ratio of toluene to ethanol was 4.4:1), iron trichloride (90g,0.54mol) was dissolved in water (900mL), and the mixed solution was placed in raw material bottles, respectively. And (3) starting a temperature control system, keeping the temperature of the micro-channel continuous flow reactor at 30 ℃, and pumping a 2- (1-chloro-cyclopropan-1-yl) -1- (2-chlorphenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thion-1-yl) -propane I solution (21mL/min) and an iron trichloride aqueous solution (16mL/min) into a first heating zone of the micro-channel continuous flow reactor for 2.1 min. The reaction liquid is cooled and then received at the outlet section of the micro-channel continuous flow reactor. The raw material content in the reaction solution was 63.1%, the prothioconazole content was 36.9%, and 90g of the reaction solution obtained by introducing 2- (1-chloro-cyclopropan-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane I was collected and treated to obtain prothioconazole II (32.0g), white solid, content 98%, yield 37%.
Example two
The preparation method of prothioconazole of the embodiment comprises the following steps:
2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidin-5-thione-1-yl) -propane I (90g,0.25mol) was dissolved in a mixed solution of toluene and ethanol (1068mL, wherein the volume ratio of toluene to ethanol was 4.4:1), iron trichloride (90g,0.54mol) was dissolved in water (900mL), and the mixed solution was placed in raw material bottles, respectively. Starting a temperature control system, keeping the temperature of the microchannel continuous flow reactor constant at 90 ℃, pumping a 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorphenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane I solution (23mL/min) and an iron trichloride aqueous solution (4.0mL/min) into a first heating zone of the microchannel continuous flow reactor, and simultaneously injecting oxygen (10.2g, 0.32mol) into a second heating zone of the microchannel continuous flow reactor at a feeding speed of 110 mL/min. The residence time was 2.2 min. The reaction liquid is cooled and then received at the outlet section of the micro-channel continuous flow reactor. The raw material content in the reaction solution is 0.7%, the prothioconazole content is 98.1%, the reaction solution obtained by introducing 90g of 2- (1-chloro-cyclopropyl-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane I is collected, and prothioconazole II (83.4g) is obtained after treatment, the white solid content is 98%, and the yield is 96%.
EXAMPLE III
The preparation method of prothioconazole of the embodiment comprises the following steps:
2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidin-5-thione-1-yl) -propane I (90g,0.25mol) was dissolved in a mixed solution of toluene and ethanol (1068mL, wherein the volume ratio of toluene to ethanol was 4.4:1), iron trichloride (90g,0.54mol) was dissolved in water (900mL), and the mixed solution was placed in raw material bottles, respectively. Starting a temperature control system, keeping the temperature of the microchannel continuous flow reactor constant at 96-100 ℃, pumping a 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorphenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane I solution (23mL/min) and an iron trichloride aqueous solution (4.0mL/min) into a first heating zone of the microchannel continuous flow reactor, and simultaneously directly injecting oxygen (20.5g, 0.64mol) into a second heating zone of the microchannel continuous flow reactor at a feeding speed of 220 mL/min. The residence time was 1.6 min. The reaction liquid is cooled and then received at the outlet section of the micro-channel continuous flow reactor. The raw material content in the reaction solution is 0.2%, the prothioconazole content is 99.1%, the reaction solution obtained by introducing 90g of 2- (1-chloro-cyclopropyl-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane I is collected, and prothioconazole II (85.1g) is obtained after treatment, the white solid content is 98%, and the yield is 98%.
Example four
The preparation method of prothioconazole of the embodiment comprises the following steps:
2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidin-5-thione-1-yl) -propane I (90g,0.25mol) was dissolved in a mixed solution of toluene and ethanol (1068mL, wherein the volume ratio of toluene to ethanol was 4.4:1), iron trichloride (18g,0.11mol) was dissolved in water (900mL), and the mixed solution was placed in raw material bottles, respectively. Starting a temperature control system, keeping the temperature of the microchannel continuous flow reactor constant at 90 ℃, pumping a 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorphenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane I solution (23mL/min) and an iron trichloride aqueous solution (4.0mL/min) into a first heating zone of the microchannel continuous flow reactor, and simultaneously injecting oxygen (10.2g, 0.32mol) into a second heating zone of the microchannel continuous flow reactor at a feeding speed of 110 mL/min. The residence time was 2.2 min. The reaction liquid is cooled and then received at the outlet section of the micro-channel continuous flow reactor. The reaction solution had no raw material left, the prothioconazole content was 97.1%, the reaction solution obtained by introducing 90g of 2- (1-chloro-cyclopropan-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane I was collected and treated to give prothioconazole II (82.9g), white solid, content 98%, yield 96%.
EXAMPLE five
The preparation method of prothioconazole of the embodiment comprises the following steps:
2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidin-5-thione-1-yl) -propane I (90g,0.25mol) was dissolved in a mixed solution of toluene and ethanol (1068mL, wherein the volume ratio of toluene to ethanol was 4.4:1), iron trichloride (3.6g,0.02mol) was dissolved in water (900mL), and the mixed solution was placed in raw material bottles, respectively. Starting a temperature control system, keeping the temperature of the microchannel continuous flow reactor constant at 90 ℃, pumping a 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorphenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane I solution (23mL/min) and an iron trichloride aqueous solution (4.0mL/min) into a first heating zone of the microchannel continuous flow reactor, and simultaneously injecting oxygen (10.2g, 0.32mol) into a second heating zone of the microchannel continuous flow reactor at a feeding speed of 110 mL/min. The residence time was 2.2 min. The reaction liquid is cooled and then received at the outlet section of the micro-channel continuous flow reactor. The content of the raw material in the reaction liquid is 0.2%, the content of prothioconazole is 97.5%, 90g of reaction liquid obtained by introducing 2- (1-chloro-cyclopropyl-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane I is collected and treated to obtain prothioconazole II (81.5g), white solid, the content of the white solid is 97%, and the yield is 93%.
EXAMPLE six
The preparation method of prothioconazole of the embodiment comprises the following steps:
2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidin-5-thione-1-yl) -propane I (90g,0.25mol) was dissolved in a mixed solution of toluene and ethanol (1068mL, wherein the volume ratio of toluene to ethanol was 4.4:1), iron trichloride (3.6g,0.02mol) was dissolved in water (900mL), and the mixed solution was placed in raw material bottles, respectively. Starting a temperature control system, keeping the temperature of the micro-channel continuous flow reactor constant at 90 ℃, pumping a 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorphenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane I solution (92mL/min) and an iron trichloride aqueous solution (16mL/min) into a first heating zone of the micro-channel continuous flow reactor, and simultaneously injecting oxygen (10.2g, 0.32mol) into a second heating zone of the micro-channel continuous flow reactor at a feeding speed of 440 mL/min. The residence time was 0.5 min. The reaction liquid is cooled and then received at the outlet section of the micro-channel continuous flow reactor. The raw material content in the reaction solution is 1.0%, the prothioconazole content is 97.5%, the reaction solution obtained by introducing 90g of 2- (1-chloro-cyclopropane-1-yl) -1- (2-chlorphenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane I is collected and treated to obtain prothioconazole II (80.6g), white solid, the content of 97% and the yield of 92%.
EXAMPLE seven
The preparation method of prothioconazole of the embodiment comprises the following steps:
2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidin-5-thione-1-yl) -propane I (90g,0.25mol) was dissolved in a mixed solution of toluene and ethanol (1068mL, wherein the volume ratio of toluene to ethanol was 4.4:1), and placed in a raw material bottle. The temperature control system was turned on, the microchannel continuous flow reactor was thermostated at 90 ℃, and 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidin-5-thione-1-yl) -propane I solution (23mL/min) was pumped into the first heating zone of the microchannel continuous flow reactor while oxygen (10.2g, 0.32mol) was injected directly into the second heating zone of the microchannel continuous flow reactor at a feed rate of 110 mL/min. The residence time was 2.2 min. The reaction liquid is cooled and then received at the outlet section of the micro-channel continuous flow reactor. The raw material content in the reaction solution is 0.6%, the prothioconazole content is 94.2%, the reaction solution obtained by introducing 90g of 2- (1-chloro-cyclopropyl-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane I is collected, and the reaction solution is recrystallized to obtain prothioconazole II (78.9g), white solid with the content of 97% and the yield of 90%.
Example eight
The preparation method of prothioconazole of the embodiment comprises the following steps:
2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidin-5-thione-1-yl) -propane I (90g,0.25mol) was dissolved in a mixed solution of toluene and ethanol (1068mL, wherein the volume ratio of toluene to ethanol was 4.4:1), iron trichloride (90g,0.54mol) was dissolved in water (900mL), and the mixed solution was placed in raw material bottles, respectively. Starting a temperature control system, keeping the temperature of the microchannel continuous flow reactor constant at 96-100 ℃, simultaneously pumping a 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorphenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane I solution (23mL/min), an iron trichloride aqueous solution (4.0mL/min) and oxygen (20.5g, 0.64mol, 220mL/min) into a first heating zone of the microchannel continuous flow, and simultaneously directly injecting the mixture into the microchannel continuous flow reactor. The residence time was 1.6 min. The reaction liquid is cooled and then received at the outlet section of the micro-channel continuous flow reactor. The raw material content in the reaction liquid is 1%, the prothioconazole content is 97%, the reaction liquid obtained by introducing 90g of 2- (1-chloro-cyclopropane-1-yl) -1- (2-chlorphenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thion-1-yl) -propane I is collected, and prothioconazole II (78.9g) is obtained after treatment, the content of white solid is 97%, and the yield is 90%.
The above embodiments are merely illustrative of the technical concept and features of the present invention, and the purpose thereof is to enable those skilled in the art to understand the content of the present invention and implement the invention, and not to limit the scope of the invention, and all equivalent changes or modifications made according to the spirit of the present invention should be covered by the scope of the present invention.
Claims (19)
1. A continuous process for the preparation of prothioconazole by reacting 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane in the presence of an oxidizing agent, characterized in that: the reaction is carried out in a microchannel continuous flow reactor.
2. The continuous process for producing prothioconazole according to claim 1, wherein: the micro-channel continuous flow reactor is a high-flux micro-channel continuous flow reactor of Corning, USA.
3. The continuous process for producing prothioconazole according to claim 1, wherein: the oxidant is ferric trichloride and/or oxygen.
4. The continuous production method of prothioconazole according to claim 3, wherein the reaction time is: the feeding molar ratio of the 2- (1-chloro-cyclopropane-1-yl) -1- (2-chlorphenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thion-1-yl) -propane to the oxidant is 1: 0.01-6.
5. The continuous process for producing prothioconazole according to claim 4, wherein: the feeding molar ratio of the 2- (1-chloro-cyclopropane-1-yl) -1- (2-chlorphenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thion-1-yl) -propane to the oxidant is 1: 0.01-3.
6. The continuous production method of prothioconazole according to claim 3, wherein the reaction time is: the feeding molar ratio of the 2- (1-chloro-cyclopropane-1-yl) -1- (2-chlorphenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thion-1-yl) -propane, the ferric trichloride and the oxygen is 1: 0.01-3: 0.1-3.
7. The continuous process for producing prothioconazole according to claim 6, wherein: the feeding molar ratio of the 2- (1-chloro-cyclopropane-1-yl) -1- (2-chlorphenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thion-1-yl) -propane, the ferric trichloride and the oxygen is 1: 0.02-2.5: 0.5-2.8.
8. The continuous production method of prothioconazole according to claim 3, wherein the reaction time is: said microchannel continuous flow reactor comprising a plurality of heating zones connected in series, said 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane and said oxidant being passed from a first of said heating zones when said oxidant is ferric trichloride; when said oxidizing agent is oxygen, said 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane is introduced into a first of said heating zones, and said oxidizing agent is introduced into a second of said heating zones; when the oxidant is ferric trichloride and oxygen, the 2- (1-chloro-cyclopropyl-1-yl) -1- (2-chlorphenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thion-1-yl) -propane and the ferric trichloride are introduced from the first heating zone, and the oxygen is introduced from the second heating zone.
9. The continuous production method of prothioconazole according to claim 8, wherein the reaction time is: said 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane and said ferric chloride are introduced into said heating zone in the form of a solution.
10. The continuous production method of prothioconazole according to claim 1 or 9, wherein: dissolving the 2- (1-chloro-cyclopropane-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane in a solvent to form a 2- (1-chloro-cyclopropane-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane solution, wherein the mass concentration of the 2- (1-chloro-cyclopropane-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane solution is 5-50%; the feeding speed is 10 mL/min-150 mL/min.
11. The continuous production method of prothioconazole according to claim 10, wherein the reaction time is: the solvent is one or more of acetonitrile, tetrahydrofuran, acetone, dimethyl sulfoxide, N-dimethylformamide, N-methylpyrrolidone, methanol, ethanol, N-butanol, tert-butanol, toluene, water and dichloromethane.
12. The continuous production method of prothioconazole according to claim 9, wherein the reaction time is: the ferric trichloride is dissolved in a solvent to form a ferric trichloride solution, and the mass concentration of the ferric trichloride solution is 0.1-50%; the feeding speed of the ferric trichloride solution is 1 mL/min-130 mL/min.
13. The continuous production method of prothioconazole according to claim 12, wherein the reaction time of the prothioconazole is set to the following reaction time: the solvent is one or more of acetonitrile, tetrahydrofuran, acetone, dimethyl sulfoxide, N-dimethylformamide, N-methylpyrrolidone, methanol, ethanol, N-butanol, tert-butanol, toluene, water and dichloromethane.
14. The continuous production method of prothioconazole according to claim 8, wherein the reaction time is: the feeding speed of the oxygen is 50 mL/min-800 mL/min.
15. The continuous production method of prothioconazole according to claim 8, wherein the reaction time is: said 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidin-5-thione-1-yl) -propane is fed from a first inlet port of a first of said heating zones, and said ferric chloride is fed from a second inlet port of a first of said heating zones.
16. The continuous production method of prothioconazole according to claim 8, wherein the reaction time is: the 2- (1-chloro-cyclopropan-1-yl) -1- (2-chlorphenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thion-1-yl) -propane and the ferric trichloride are respectively added into the micro-channel continuous flow reactor through a polytetrafluoroethylene or stainless steel pump.
17. The continuous process for producing prothioconazole according to claim 1, wherein: the reaction is carried out at 0-160 ℃.
18. The continuous process for producing prothioconazole according to claim 1, wherein: the residence time of the 2- (1-chloro-cyclopropan-1-yl) -1- (2-chlorphenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thioketone-1-yl) -propane and the oxidant in the micro-channel continuous flow reactor is 0.1-6 min.
19. The continuous process for producing prothioconazole according to claim 1, wherein: the continuous preparation method also comprises the steps of concentrating the reaction liquid from the micro-channel continuous flow reactor, extracting, layering, concentrating and recrystallizing to obtain the prothioconazole.
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| CN116162067A (en) * | 2023-04-21 | 2023-05-26 | 江苏七洲绿色科技研究院有限公司 | Preparation method of prothioconazole |
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| CN114773280A (en) * | 2022-04-28 | 2022-07-22 | 安徽久易农业股份有限公司 | Method for continuously synthesizing prothioconazole by utilizing tubular reactor |
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