CN111100081B - Continuous preparation method of prothioconazole - Google Patents
Continuous preparation method of prothioconazole Download PDFInfo
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- CN111100081B CN111100081B CN201811255991.2A CN201811255991A CN111100081B CN 111100081 B CN111100081 B CN 111100081B CN 201811255991 A CN201811255991 A CN 201811255991A CN 111100081 B CN111100081 B CN 111100081B
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- 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
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Abstract
The invention relates to a continuous preparation method of prothioconazole, which is prepared by 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, 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 crops, 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. 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.
The 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 chloride or oxygen, and the molar ratio of 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane to oxidant is 1.
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.
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.
According to another embodiment, when the oxidant is oxygen, 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 oxygen is 1.
According to another embodiment, the oxidizing agent 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 ferric chloride to the oxygen is 1: 0.01-3.
Preferably, the feeding molar ratio of the 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane to the ferric trichloride to the oxygen is 1.
Further preferably, the feeding molar ratio of the 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane, the ferric trichloride and the oxygen is 1.
In the present invention, said microchannel continuous flow reactor comprises a plurality of heating zones in series, and when said oxidizing agent is ferric trichloride, according to one embodiment, said 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane and said oxidizing agent are passed into 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-triazol-5-thione-1-yl) -propane is passed into a first of said heated zones, and said oxidizing agent is passed into a second of said heated zones; according to yet another embodiment, when said oxidizing agent is iron trichloride 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 iron trichloride are introduced from the first said heating zone, said oxygen is introduced from the second said heating zone, if oxygen is also added from the first said heating zone, it is not favorable for the oxygen to be uniformly mixed with 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidin-5-thione-1-yl) -propane and for the reaction temperature to be stable, and if oxygen is introduced from the third or later heating zone, the oxygen is not favorable for the reaction to proceed for a short time.
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, the 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazol-e-5-thione-1-yl) -propane is dissolved in a solvent to form a 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazol-e-5-thione-1-yl) -propane solution, and the mass concentration of the 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazol-e-5-thione-1-yl) -propane solution is 5 to 50 percent, more preferably 5 to 40 percent, still more preferably 5 to 20 percent, and more preferably 5 to 10 percent; the feeding rate is 10mL/min to 150mL/min, more preferably 20mL/min to 120mL/min, and still more preferably 20mL/min to 100mL/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 30mL/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 450mL/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 to 160 ℃, more preferably 20 to 100 ℃, and even more preferably 90 to 100 ℃.
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 oxidizing agent are maintained in said microchannel continuous flow reactor for a residence time of 0.1 to 6min.
Preferably, the continuous preparation method further comprises the steps of concentrating the reaction liquid from the micro-channel continuous flow reactor, extracting and layering, concentrating and recrystallizing to obtain the prothioconazole.
In the present invention, the molar ratio of the 2- (1-chloro-cycloprop-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazol-idin-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-idin-5-thione-1-yl) -propane and the oxidant introduced into the microchannel continuous flow reactor per minute.
The flow chart of the reaction carried out by adopting the micro-channel continuous flow reactor is shown in 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, reactants in the invention are continuously introduced into the micro-channel continuous flow reactor, and are continuously discharged from a cooling zone to be collected to obtain a reaction liquid after passing through a plurality of heating zones, and the reaction liquid is subjected to post-treatment to obtain prothioconazole.
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 illustrative of the principles, essential features and advantages of the present invention, and that the invention is not limited to the following embodiments. The implementation conditions used in the examples can be further adjusted according to specific requirements, and the implementation conditions not noted are generally those 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 (1068 mL, wherein the volume ratio of toluene to ethanol was 4.4. Starting a temperature control system, keeping the temperature of the micro-channel continuous flow reactor constant at 30 ℃, and pumping 2- (1-chloro-cyclopropan-1-yl) -1- (2-chlorphenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thion-1-yl) -propane I solution (21 mL/min) and ferric trichloride aqueous solution (16 mL/min) into a first heating zone of the micro-channel continuous flow reactor for 2.1min. And 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 63.1%, the prothioconazole content is 36.9%, 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 (32.0 g) is obtained after treatment, the white solid content is 98%, and the yield is 37%.
Example two
The preparation method of prothioconazole in the embodiment has 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 (1068 mL, wherein the volume ratio of toluene to ethanol was 4.4. Starting a temperature control system, keeping the temperature of the microchannel continuous flow reactor constant at 90 ℃, pumping a 2- (1-chloro-cyclopropyl-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane I solution (23 mL/min) and an iron trichloride aqueous solution (4.0 mL/min) into a first heating zone of the microchannel continuous flow reactor, and simultaneously injecting oxygen (10.2 g, 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 2.2min. And 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 0.7%, the prothioconazole content is 98.1%, the reaction liquid 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 (83.4 g) 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 (1068 mL, wherein the volume ratio of toluene to ethanol was 4.4. 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 (23 mL/min) and an iron trichloride aqueous solution (4.0 mL/min) into a first heating zone of the microchannel continuous flow reactor, and simultaneously directly injecting oxygen (20.5 g, 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 1.6min. And 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 0.2%, the prothioconazole content is 99.1%, the reaction liquid 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 (85.1 g) 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 (1068 mL, wherein the volume ratio of toluene to ethanol was 4.4. Starting a temperature control system, keeping the temperature of the microchannel continuous flow reactor constant at 90 ℃, pumping a 2- (1-chloro-cyclopropyl-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane I solution (23 mL/min) and an iron trichloride aqueous solution (4.0 mL/min) into a first heating zone of the microchannel continuous flow reactor, and simultaneously injecting oxygen (10.2 g, 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 2.2min. The reaction liquid is cooled and then received at the outlet section of the micro-channel continuous flow reactor. The reaction solution has no raw material residue, the content of prothioconazole is 97.1 percent, 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 treated to obtain prothioconazole II (82.9 g), white solid with the content of 98 percent and the yield of 96 percent.
EXAMPLE five
The preparation method of prothioconazole in the embodiment has 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 (1068 mL, wherein the volume ratio of toluene to ethanol was 4.4. Starting a temperature control system, keeping the temperature of the microchannel continuous flow reactor constant at 90 ℃, pumping a 2- (1-chloro-cyclopropyl-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane I solution (23 mL/min) and an iron trichloride aqueous solution (4.0 mL/min) into a first heating zone of the microchannel continuous flow reactor, and simultaneously injecting oxygen (10.2 g, 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 2.2min. And 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 the 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 prothioconazole II (81.5 g) is obtained after treatment, wherein the content of 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 (1068 mL, wherein the volume ratio of toluene to ethanol was 4.4. Starting a temperature control system, keeping the temperature of the microchannel continuous flow reactor constant at 90 ℃, pumping a 2- (1-chloro-cyclopropan-1-yl) -1- (2-chlorphenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane I solution (92 mL/min) and an iron trichloride aqueous solution (16 mL/min) into a first heating zone of the microchannel continuous flow reactor, and simultaneously injecting oxygen (10.2 g, 0.32mol) into a second heating zone of the microchannel continuous flow reactor at a feeding speed of 440 mL/min. The residence time was 0.5min. 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-cyclopropyl-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane I is collected, and prothioconazole II (80.6 g) is obtained after treatment, the white solid content is 97%, and the yield is 92%.
EXAMPLE seven
The preparation method of prothioconazole in the embodiment has 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 (1068 mL, wherein the volume ratio of toluene to ethanol was 4.4. 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-triazolidine-5-thione-1-yl) -propane I solution (23 mL/min) was pumped into the first heating zone of the microchannel continuous flow reactor while oxygen (10.2 g, 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 2.2min. 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 0.6%, the content of prothioconazole is 94.2%, the reaction liquid 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 liquid is recrystallized to obtain prothioconazole II (78.9 g), white solid with the content of 97% and the yield of 90%.
Example eight
The preparation method of prothioconazole in the embodiment has 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 (1068 mL, wherein the volume ratio of toluene to ethanol was 4.4. Starting a temperature control system, keeping the temperature of the micro-channel 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 (23 mL/min), an iron trichloride aqueous solution (4.0 mL/min) and oxygen (20.5 g,0.64mol, 220mL/min) into a first heating zone of the micro-channel continuous flow, and simultaneously injecting the mixture into the micro-channel continuous flow reactor. The residence time was 1.6min. 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-cyclopropyl-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thion-1-yl) -propane I is collected, and prothioconazole II (78.9 g) 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 (12)
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 micro-channel continuous flow reactor, and the oxidant is oxygen or the combination of ferric trichloride and oxygen;
the feeding molar ratio of the 2- (1-chloro-cyclopropyl-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane to the oxidant is 1;
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 passed into said micro-channel continuous flow reactor in the form of a solution;
dissolving the 2- (1-chloro-cyclopropan-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-cyclopropan-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-cyclopropan-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;
dissolving ferric trichloride in a solvent to form a ferric trichloride solution, wherein 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;
the feeding speed of the oxygen is 50 mL/min-800 mL/min;
the reaction is carried out at 90 to 100 ℃.
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 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.
4. The continuous process for producing prothioconazole according to claim 1, wherein: the feeding molar ratio of the 2- (1-chloro-cyclopropan-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.
5. The continuous process for producing prothioconazole according to claim 4, wherein: the molar ratio of the 2- (1-chloro-cyclopropan-1-yl) -1- (2-chlorophenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thione-1-yl) -propane to the ferric trichloride to the oxygen is 1.
6. The continuous process for producing prothioconazole according to claim 1, wherein: 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 being passed through a first of said heating zones and said oxidant being passed through a second of said heating zones when said oxidant is oxygen; 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.
7. The continuous process for producing prothioconazole according to claim 1, wherein: the solvent of the 2- (1-chloro-cyclopropan-1-yl) -1- (2-chlorphenyl) -2-hydroxy-3- (1, 2, 4-triazolidine-5-thion-1-yl) -propane solution is one or more of acetonitrile, tetrahydrofuran, acetone, dimethyl sulfoxide, N-dimethylformamide, N-methylpyrrolidone, methanol, ethanol, N-butanol, tert-butanol, toluene, water and dichloromethane.
8. The continuous process for producing prothioconazole according to claim 1, wherein: the solvent of the ferric trichloride is one or more of acetonitrile, tetrahydrofuran, acetone, dimethyl sulfoxide, N-dimethylformamide, N-methylpyrrolidone, methanol, ethanol, N-butanol, tert-butanol, toluene, water and dichloromethane.
9. The continuous process for producing prothioconazole according to claim 6, wherein: 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.
10. The continuous process for producing prothioconazole according to claim 1, wherein: 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.
11. 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-thion-1-yl) -propane and the oxidant in the micro-channel continuous flow reactor is 0.1 to 6min.
12. 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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