A method for continuous preparation of a prothioconazole intermediate and a production system thereof

Abstract

The present application relates to the technical fields of organic chemical synthesis, and discloses a continuous preparation method of a prothioconazole intermediate and a production system thereof. The continuous preparation method of the prothioconazole intermediate is characterized in that a plurality of spherical mixing structures inside a mixer are used to sufficiently mix materials, so as to avoid the materials from being separated again in a short time; and a plurality of guide vanes between any two adjacent spherical cavities can enhance the turbulence degree of the materials, so as to play a role of secondary mixing of the materials and further improve the mixing effect. The unique mixer structure is used to make the subsequent reaction sufficiently react without using any auxiliary agent or catalyst, so that the yield can reach more than 91.5%, the purity can reach more than 97.5%, the yield of the final product is improved, and the quality is stable; the reaction is carried out in a tubular reactor, the reaction amount is small and the reaction is fast, the risk of explosion of hydrazine hydrate is effectively avoided, and the method is suitable for large-scale production.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of organic chemical synthesis, in particular to a continuous preparation method of a prothioconazole intermediate and a production system thereof. BACKGROUND

[0002] Prothioconazole is a new broad-spectrum fungicide developed by Bayer Company, which is mainly used for preventing and treating crop diseases such as cereals, wheat and legumes. It has good safety, good control effect, long effective period and obvious yield increase. 2-(1-chloro-cyclopropyl-1-yl)-3-(2-chlorophenyl)-2-hydroxypropyl-1-hydrazine is one of the important intermediates of prothioconazole, and its molecular formula is C 12 H 16 Cl2N2O, and its structural formula is shown in formula I. 2-(1-chloro-cyclopropyl-1-yl)-3-(2-chlorophenyl)-2-hydroxypropyl-1-hydrazine is unstable in air, and is usually prepared into hydrochloride (see formula II) for transfer or sale.

[0003]

[0004] The existing production method of 2-(1-chloro-cyclopropyl-1-yl)-3-(2-chlorophenyl)-2-hydroxypropyl-1-hydrazine is mainly intermittent reaction. 1-(2-chlorophenyl)-2-(1-chlorocyclopropyl)-3-chloro-2-propanol (structural formula shown in formula III) is used as raw material, and reacts with hydrazine hydrate in the presence of inert organic solvent; or 2-(2-chlorobenzyl)-2-(1-chloromethyl)oxirane (structural formula shown in formula IV) is used as raw material, and reacts with hydrazine hydrate in the presence of a specific solvent, and then introduces hydrogen chloride or uses hydrochloric acid solution to stabilize the hydrazine intermediate compound in the form of salt, to obtain the corresponding hydrochloride of hydrazine, and then adds a base to free the hydrazine. In the reaction process of the existing preparation method, a large amount of toxic reagent hydrazine hydrate solution is used, the reaction time is more than 3h, and there is an explosion risk; the hydrochloride of hydrazine needs to be added with a base to free it in the subsequent reaction, and the use of the salting-free method brings the problem of salt-containing wastewater treatment, and the post-treatment steps are complicated; the hydrazine hydrochloride mother liquor has high acidity, which seriously corrodes the equipment, and there are more wastes, which is not conducive to industrial production. The product yield and quality of intermittent reaction fluctuate greatly, which seriously restricts the quality and cost of prothioconazole, and therefore it is urgent to find a continuous green and safe preparation method.

[0005] SUMMARY

[0006] In view of the above problems, the present application provides a continuous preparation method of a prothioconazole intermediate and a production system thereof, so as to obtain 2-(1-chloro-cyclopropyl-1-yl)-3-(2-chlorophenyl)-2-hydroxypropyl-1-hydrazine which is environmentally friendly, low in energy consumption, low in cost, high in yield and stable in quality.

[0007] To solve the above technical problems, the technical scheme provided by the present application is:

[0008] A continuous preparation method of a prothioconazole intermediate, comprising the following steps:

[0009] S1, methanol, 2-(2-chlorobenzyl)-2-(1-chloromethyl)oxirane and hydrazine hydrate are mixed, and the mixture is reacted at 80-180 DEG C under an inert atmosphere for 1-30 min to obtain a reaction liquid;

[0010] S2, the reaction liquid is distilled under reduced pressure to remove methanol, toluene is added, and the mixture is warmed to dissolve, separated into two phases, and a toluene oil phase containing 2-(1-chloro-cyclopropyl-1-yl)-3-(2-chlorophenyl)-2-hydroxypropyl-1-hydrazine is obtained;

[0011] S3, the toluene oil phase is cooled to -30-20 DEG C to precipitate crystals, and solid-liquid separation is performed to obtain 2-(1-chloro-cyclopropyl-1-yl)-3-(2-chlorophenyl)-2-hydroxypropyl-1-hydrazine;

[0012] In step S1, the mixing is carried out in a mixer; wherein the interior of the mixer has a plurality of spherical cavities arranged in sequence, each of which is provided with a spherical mixing structure, and a connecting channel is arranged between any two adjacent spherical cavities, and a plurality of guide vanes are arranged in any connecting channel; in step S1, the reaction is carried out in a tubular reactor.

[0013] Compared with the prior art, the continuous preparation method of the prothioconazole intermediate provided by the present application (reaction formula V) uses a plurality of spherical mixing structures in the interior of the mixer to fully mix the materials, avoiding the materials from being separated again in a short time; the plurality of guide vanes between any two adjacent spherical cavities can enhance the degree of turbulence of the materials, play the role of secondary mixing of the materials, and further improve the mixing effect. The unique mixer structure used in the present application enables the subsequent reaction to be fully carried out without using any auxiliary agent or catalyst, thereby improving the yield of the final product; the reaction is carried out in a tubular reactor, the reaction amount is small and the reaction is fast, and the risk of explosion of hydrazine hydrate is effectively avoided.

[0014]

[0015] The reaction solution of the present application contains 2-(1-chloro-cycloprop-1-yl)-3-(2-chlorophenyl)-2-hydroxypropyl-1-hydrazine, residual hydrazine hydrate and solvent methanol, the methanol is first distilled out under reduced pressure, then toluene is added to purify the 2-(1-chloro-cycloprop-1-yl)-3-(2-chlorophenyl)-2-hydroxypropyl-1-hydrazine containing hydrazine hydrate, remove the hydrazine hydrate aqueous phase, finally the 2-(1-chloro-cycloprop-1-yl)-3-(2-chlorophenyl)-2-hydroxypropyl-1-hydrazine in the toluene oil phase is separated out by cooling crystallization, and the final product is obtained. The results of the examples show that the yield of the 2-(1-chloro-cycloprop-1-yl)-3-(2-chlorophenyl)-2-hydroxypropyl-1-hydrazine prepared by the present application can reach more than 91.5%, and the purity can reach more than 97.5%, which is suitable for large-scale production and has high market application value.

[0016] In addition, the continuous preparation method of the propiconazole intermediate provided by the present application is simple, safe, low in cost, pollution-free, and can continuously produce 2-(1-chloro-cycloprop-1-yl)-3-(2-chlorophenyl)-2-hydroxypropyl-1-hydrazine. The present application does not use hydrochloric acid or hydrogen chloride to form a salt, avoids the generation of acidic waste liquid, and when used subsequently, liquid alkali does not need to be added again, thereby avoiding the generation of brine and solving the environmental protection problem of handling a large amount of acidic waste water.

[0017] It should be noted that in step S2 of the present application, the distilled methanol can be recycled and used in step S1. In step S2, toluene is added to the reaction solution from which methanol has been removed, and after phase separation, toluene oil phase containing 2-(1-chloro-cycloprop-1-yl)-3-(2-chlorophenyl)-2-hydroxypropyl-1-hydrazine and hydrazine hydrate aqueous phase can be obtained. For the hydrazine hydrate aqueous phase, methods such as toluene extraction, resin adsorption decolorization, concentration or neutralization can be used for treatment, and then recycled and used in step S1. In step S3, solid-liquid separation can obtain the final product and 2-(1-chloro-cycloprop-1-yl)-3-(2-chlorophenyl)-2-hydroxypropyl-1-hydrazine and toluene mother liquor, and the toluene mother liquor can be repeatedly used in step S2 after distillation.

[0018] Preferably, the spherical mixed structure is a regular honeycomb structure, an irregular honeycomb structure, a multi-layer corrugated microporous mesh structure, or a combination of two or three of the regular honeycomb structure, the irregular honeycomb structure and the multi-layer corrugated microporous mesh structure.

[0019] The present application limits the spherical mixed structure, so that the material can be optimally mixed in a trace state, even to the level of molecular flow mixing, providing an excellent prerequisite for the subsequent chlorination reaction or decarboxylation reaction; at the same time, the degree of automation is further improved, labor is saved, and good economic and social benefits are obtained.

[0020] Preferably, the material of the spherical mixing structure is at least one of ceramic, silicon carbide, polytetrafluoroethylene or stainless steel alloy.

[0021] Preferably, the stainless steel alloy includes at least one of HC267, 304, 316L, 321, 2205 or titanium alloy.

[0022] Preferably, the guide vanes are evenly divided into multiple layers along the length direction of the connecting channel, each layer of the guide vanes includes multiple vane bodies arranged annularly and spaced apart around the central axis of the connecting channel, and each vane body in the multiple layers of the guide vanes is arranged in a staggered manner.

[0023] Preferably, the guide vanes are evenly divided into three layers along the length direction of the connecting channel, each layer of the guide vanes includes three vane bodies arranged annularly and spaced apart around the central axis of the connecting channel, and the included angle of each vane body in each layer of the guide vanes is 120°, and each vane body in adjacent two layers of the guide vanes is arranged in a staggered manner with an angle of 40°, that is, each vane body in the multiple layers of the guide vanes is arranged in a staggered manner with an angle of 40°.

[0024] The multiple guide vanes are evenly distributed, the degree of material turbulence is enhanced, the mixing state between materials can be further ensured, and the overall mixing effect is improved.

[0025] Preferably, the number of the spherical cavities is 5-30.

[0026] In the application, the material passes through the combination of multiple spherical mixing structures and guide vanes, so that the material continuously experiences the processes of micro-mixing, overall mixing and re-distribution of micro-mixing, and the mixing effect is further improved.

[0027] It should be noted that the application does not have any requirements for the mixing order of methanol, 2-(2-chlorobenzyl)-2-(1-chloromethyl)oxirane and hydrazine hydrate, and any two substances can be mixed first and then mixed with the other substance.

[0028] Preferably, in step S1, the mixing includes: first mixing methanol and 2-(2-chlorobenzyl)-2-(1-chloromethyl)oxirane, and second mixing by adding hydrazine hydrate.

[0029] Preferably, the mixing step can make the mixing effect of the reaction raw materials reach the optimal state.

[0030] Preferably, in step S1, the temperature of the mixing is 80-150℃.

[0031] Further preferably, in step S1, the first mixture is preheated to a temperature of 85-160°C before the second mixing, and the hydrazine hydrate is preheated to a temperature of 80-150°C, more preferably 80-120°C.

[0032] Preferably, in step S1, the flow rate of the methanol is 400-2600 kg / h, the flow rate of the 2-(2-chlorobenzyl)-2-(1-chloromethyl)oxirane is 300-1500 kg / h, and the flow rate of the hydrazine hydrate is 350-2600 kg / h.

[0033] Preferably, in step S1, the mass ratio of the methanol to the 2-(2-chlorobenzyl)-2-(1-chloromethyl)oxirane is (1-5):1.

[0034] Preferably, in step S1, the molar ratio of the 2-(2-chlorobenzyl)-2-(1-chloromethyl)oxirane to the hydrazine hydrate is 1:(5-10).

[0035] Preferably, in step S1, the reaction pressure is 0.2-2.0 MPa.

[0036] The present application can ensure that the reaction is more complete and further improve the yield and purity of the final product by controlling the amount of each raw material and the reaction conditions.

[0037] For example, in step S1, the end point of the reaction is controlled so that the content of the 2-(2-chlorobenzyl)-2-(1-chloromethyl)oxirane is ≤0.5 wt%.

[0038] For example, in step S2, the pressure of the vacuum distillation is 0.1-101 kPa.

[0039] Preferably, in step S2, the amount of the toluene added is 1-3 times the mass of the 2-(2-chlorobenzyl)-2-(1-chloromethyl)oxirane.

[0040] Preferably, in step S2, the toluene is preheated to a temperature of 50-70°C.

[0041] Preferably, in step S2, the temperature of the warming and dissolving is 40-80°C.

[0042] For example, in step S2, the phase separation is by standing or centrifugal extraction.

[0043] Preferably, in step S3, the crystallization time is 0.5-4 h.

[0044] The application further provides a continuous production system of prothioconazole intermediate, which comprises a mixer, a tubular reactor, a scraped evaporator, a dissolving tank, a pipeline centrifuge, a crystallization tank and a centrifuge which are connected by pipelines in sequence.

[0045] The mixer is used for mixing methanol, 2-(2-chlorobenzyl)-2-(1-chloromethyl)oxirane and hydrazine hydrate.

[0046] The tubular reactor is connected with the outlet of the mixer and is used for reaction.

[0047] The scraped evaporator is connected with the outlet of the tubular reactor and is used for vacuum distillation of the reaction liquid.

[0048] The dissolving tank is connected with the outlet of the scraped evaporator, is provided with an inlet for adding toluene, and is used for mixing and warming the reaction liquid from which methanol is removed with toluene.

[0049] The pipeline centrifuge is connected with the outlet of the dissolving tank and is used for separating the reaction liquid after warming.

[0050] The crystallization tank is connected with the outlet of the pipeline centrifuge and is used for cooling and crystallizing the toluene oil phase.

[0051] The centrifuge is connected with the outlet of the crystallization tank and is used for separating the toluene oil phase after crystallization.

[0052] The continuous production system of prothioconazole intermediate has high selectivity for 2-(1-chloro-cyclopropyl-1-yl)-3-(2-chlorophenyl)-2-hydroxypropyl-1-hydrazine, short overall reaction time, high yield of end product, stable quality, low cost, no pollution, high automation, and can realize continuous production of 2-(1-chloro-cyclopropyl-1-yl)-3-(2-chlorophenyl)-2-hydroxypropyl-1-hydrazine, has good economic and social benefits, and is suitable for large-scale production.

[0053] Preferably, the number of the spherical cavities is 5-30.

[0054] Preferably, the spherical mixing structure is a regular honeycomb structure, an irregular honeycomb structure, a multi-layer corrugated microporous mesh structure, or a combination of two or three of the regular honeycomb structure, the irregular honeycomb structure and the multi-layer corrugated microporous mesh structure.

[0055] Preferably, the material of the spherical mixed structure is at least one of ceramic, silicon carbide, polytetrafluoroethylene or stainless steel alloy.

[0056] Illustratively, the stainless steel alloy includes at least one of HC276, 2205 or titanium alloy.

[0057] Preferably, the guide vanes are uniformly divided into multiple layers along the length direction of the connecting channel; each layer of the guide vanes includes multiple vane bodies arranged annularly and spaced apart around the central axis of the connecting channel; and each of the vane bodies in the multiple layers of the guide vanes is arranged in a staggered manner.

[0058] Preferably, the mixer includes a mixer I and a mixer II; the mixer I is provided with two feed ports for first mixing of methanol and 2-(2-chlorobenzyl)-2-(1-chloromethyl)oxirane; and the mixer II is provided with two feed ports for second mixing of the mixed raw materials obtained by the first mixing and hydrazine hydrate.

[0059] Illustratively, the mixer I and the mixer II are fastened by bolts through flanges 1 and 2; the sealing surfaces of the flanges 1 and 2 are concave and convex respectively, and a Teflon rubber ring is arranged therebetween for sealing.

[0060] Preferably, the tubular reactor is of a tube plate full immersion structure, and a spiral flow mixer is arranged in each tube.

[0061] The present application adopts the tube plate full immersion structure to immerse the tubular reactor completely in the fluid outside the tube, facilitates the control of the temperature in the tube, and effectively reduces the energy consumption and saves the manufacturing cost of the equipment; the spiral flow mixer is used as a static mixer to keep the material in a uniformly mixed state during the reaction, effectively avoids the phase separation of the material, and thus improves the degree and efficiency of the reaction and increases the yield and purity of the final product.

[0062] Illustratively, the material of the tubular reactor is a stainless steel alloy, which includes at least one of HC267, 304, 316L, 321, 2205 or titanium alloy.

[0063] Preferably, the two feed ports of the mixer I are connected with a storage tank 1 connected with a metering pump 1 and a storage tank 2 connected with a metering pump 2 respectively; the two feed ports of the mixer II are connected with the outlet of the mixer I and a storage tank 3 connected with a metering pump 3 respectively; the gas phase outlet of the scraper evaporator is connected with a storage tank 4; the inlet of the dissolving pipe is connected with a storage tank 5 connected with a metering pump 4; the outlet of the pipeline centrifuge is further connected with a storage tank 6; the two outlets of the centrifuge are connected with a storage tank 7 and a storage tank 8 respectively; and

[0064] The storage tank 1 is used for storing methanol;

[0065] The storage tank 2 is used for storing 2-(2-chlorobenzyl)-2-(1-chloromethyl)oxirane;

[0066] The storage tank 3 is used for storing hydrazine hydrate;

[0067] The metering pump 1-3 are all used for controlling the metering of the feed;

[0068] The storage tank 4 is used for receiving methanol;

[0069] The storage tank 5 is used for storing toluene;

[0070] The storage tank 6 is used for receiving hydrazine hydrate aqueous phase;

[0071] The storage tank 7 is used for receiving toluene mother liquor;

[0072] The storage tank 8 is used for receiving 2-(1-chloro-cyclopropyl-1-yl)-3-(2-chlorophenyl)-2-hydroxypropyl-1-hydrazine.

[0073] It should be noted that the mixing order of the methanol, 2-(2-chlorobenzyl)-2-(1-chloromethyl)oxirane and hydrazine hydrate can not be required in the present application, and the methanol, 2-(2-chlorobenzyl)-2-(1-chloromethyl)oxirane and hydrazine hydrate can be stored in the storage tank 1-3 in any order.

[0074] For example, the metering pump 1 and the mixer I are connected with a mass flow regulator MFC1;

[0075] The metering pump 2 and the mixer I are connected with a mass flow regulator MFC2;

[0076] The metering pump 3 and the mixer II are connected with a mass flow regulator MFC3;

[0077] The metering pump 4 and the dissolving tank are connected with a mass flow regulator MFC4.

[0078] Preferably, the two feed inlets of the mixer II are respectively connected with heat exchangers 1 and 2 for controlling the temperature of the feed; and the inlet of the dissolving tank is connected with a heat exchanger 3 for controlling the temperature of the feed.

[0079] Further preferably, the gas phase outlet of the wiped film evaporator is connected with a heat exchanger 4 for controlling the temperature of the outlet, and the liquid phase outlet of the wiped film evaporator is connected with a circulating tank.

[0080] For example, the circulating tank and the storage tank 4 are connected with a vacuum system for performing vacuum distillation on the reaction feed liquid.

[0081] The circulating tank and the storage tank 4 of the scraper evaporator are placed in a vacuum environment, so that the boiling point of the reaction liquid can be effectively reduced, and the methanol can be evaporated.

[0082] The heat exchanger 1 is connected with the temperature regulator T1 between the mixer II;

[0083] The heat exchanger 2 is connected with the temperature regulator T2 between the mixer II;

[0084] The mixer II is connected with the temperature regulator T3 between the tubular reactor;

[0085] The tubular reactor is connected with the temperature regulator T4 and the pressure regulator P1 between the scraper evaporator;

[0086] The heat exchanger 3 is connected with the temperature regulator T5 between the dissolving tank;

[0087] The circulating tank is connected with the temperature regulator T6 and the pressure regulator P2;

[0088] The dissolving tank is connected with the temperature regulator T7;

[0089] The crystallization tank is connected with the temperature regulator T8 between the centrifugal machine.

[0090] The temperature and pressure in each process step of the continuous production system of the prothioconazole intermediate can be monitored in real time according to the data change trend through the temperature regulator and the pressure regulator, the degree of automation is further improved, the operation cost is reduced, and good economic and social benefits are obtained. BRIEF DESCRIPTION OF DRAWINGS

[0091] Figure 1 The flowchart of the continuous production system of the prothioconazole intermediate provided by the embodiment of the present application is shown;

[0092] Figure 2 The external structure diagram of the mixer I or the mixer II in the embodiment of the present application is shown;

[0093] Figure 3 The internal structure diagram of the mixer I or the mixer II in the embodiment of the present application is shown;

[0094] Figure 4 The cross-sectional structure diagram of the mixer I or the mixer II in the embodiment of the present application is shown;

[0095] Figure 5 The three structure diagrams of the spherical mixing structure in the mixer I or the mixer II in the embodiment of the present application are shown;

[0096] Figure 6Two structure diagrams of the tube plate full immersion structure of the embodiment of the present application;

[0097] Figure 7 The structure diagram of the baffle of the embodiment of the present application. DETAILED DESCRIPTION

[0098] In order to make the purpose, technical scheme and advantages of the present application more clear, the present application is further described in detail below in combination with embodiments. It should be understood that the specific embodiments described herein are only used to explain the present application and do not limit the present application.

[0099] Please refer to Figure 1 and Figure 3 , the continuous production system of the prothioconazole intermediate provided by the present application will be described. A continuous production system of a prothioconazole intermediate, comprising a mixer I, a mixer II, a tubular reactor, a scraped evaporator, a dissolving tank, a pipeline centrifuge, a crystallization tank and a centrifuge connected by pipelines in sequence; wherein,

[0100] The mixer I is provided with two feed ports for first mixing of methanol and 2-(2-chlorobenzyl)-2-(1-chloromethyl)oxirane;

[0101] The mixer II is provided with two feed ports for second mixing of the mixed raw materials obtained by the first mixing and hydrazine hydrate;

[0102] The tubular reactor is connected with the outlet of the mixer II for reaction;

[0103] The scraped evaporator is connected with the outlet of the tubular reactor for vacuum distillation of the reaction liquid;

[0104] The dissolving tank is connected with the outlet of the scraped evaporator and is provided with an inlet for adding toluene, for mixing and warming the reaction liquid from which methanol is removed with toluene;

[0105] The pipeline centrifuge is connected with the outlet of the dissolving tank for separation of the reaction liquid after warming and dissolving;

[0106] The crystallization tank is connected with the outlet of the pipeline centrifuge for cooling and crystallization of the toluene oil phase;

[0107] The centrifuge is connected with the outlet of the crystallization tank for separation of the toluene oil phase after crystallization;

[0108] The interior of the mixer I and the mixer II each has a plurality of spherical cavities arranged in sequence, each of which is provided with a spherical mixing structure, and each of any two adjacent spherical cavities is provided with a connecting channel, and each of any connecting channel is provided with a plurality of guide vanes.

[0109] The continuous production system of the prothioconazole intermediate provided in the embodiment has the working principle that: methanol and 2-(2-chlorobenzyl)-2-(1-chloromethyl)oxirane are first mixed in the mixer I; the mixed raw materials obtained through the first mixing and hydrazine hydrate are second mixed in the mixer II; the reaction occurs in the tubular reactor; the obtained reaction liquid is subjected to vacuum distillation to remove methanol in the scraped plate evaporator; the reaction liquid from which the methanol is removed is mixed with toluene in the dissolving tank, and is warmed and dissolved; the reaction liquid after being warmed and dissolved is separated in the pipeline centrifuge; the obtained toluene oil phase containing 2-(1-chloro-cycloprop-1-yl)-3-(2-chlorophenyl)-2-hydroxypropyl-1-hydrazine is cooled and crystallized in the crystallization tank; finally, 2-(1-chloro-cycloprop-1-yl)-3-(2-chlorophenyl)-2-hydroxypropyl-1-hydrazine is separated out through the centrifuge to obtain the final product. The plurality of spherical mixing structures in the interior of the mixer are used to mix the materials sufficiently, so that the materials are prevented from being separated again in a short time; the plurality of guide vanes between any two adjacent spherical cavities can enhance the turbulence degree of the materials, so that the materials are mixed twice.

[0110] In some embodiments, the number of the spherical cavities is 5-15.

[0111] Please refer to Figures 4-5 In some embodiments, the spherical mixing structure is a regular honeycomb structure, an irregular honeycomb structure, a multi-layer corrugated microporous mesh structure, or a combination of two or three of the regular honeycomb structure, the irregular honeycomb structure and the multi-layer corrugated microporous mesh structure.

[0112] In some embodiments, the material of the spherical mixing structure is at least one of ceramic, silicon carbide, polytetrafluoroethylene or stainless steel alloy.

[0113] In the embodiment, the stainless steel alloy includes at least one of HC267, 304, 316L, 321, 2205 or titanium alloy.

[0114] In some embodiments, the guide vanes are uniformly divided into multiple layers along the length direction of the connecting channel; each layer of the guide vanes includes a plurality of vane bodies arranged annularly and spaced apart around the central axis of the connecting channel; and each of the vane bodies in the multiple layers of the guide vanes is arranged in a staggered manner.

[0115] In the embodiment, the guide vanes are evenly divided into three layers along the length direction of the connecting channel. Each layer of the guide vanes comprises three vane bodies arranged annularly and spaced apart around the central axis of the connecting channel. The included angle of each vane body in each layer of the guide vanes is 120°. The vane bodies in the multiple layers of the guide vanes are arranged with a 40° stagger.

[0116] Referring to Figure 2 and Figure 4 In some embodiments, the mixer I and the mixer II are fastened by the flange 1 and the flange 2 by bolts. The sealing surfaces of the flange 1 and the flange 2 are concave and convex respectively, and a Teflon rubber ring is arranged therebetween for sealing.

[0117] Referring to Figure 6 In some embodiments, the tubular reactor is of a tube plate full immersion structure, and each of the tubes is provided with a helical flow mixer.

[0118] In the embodiment, the tubular reactor comprises a tank body having a cavity, a plurality of straight tubes and a plurality of bent tubes. Referring to Figure 6 , the tank body is provided with two inlets and outlets respectively communicating with the cavity and having a height difference. The plurality of straight tubes and the plurality of bent tubes are combined to form a serpentine reaction tube body having a height difference at two ends and extending out of the tank body. The tube plate full immersion structure refers to that the plurality of straight tubes are arranged in the closed cavity. The cavity is used to contain fluid, and the temperature of the material in the serpentine reaction tube body is controlled by controlling the temperature of the fluid in the cavity.

[0119] For example, the length of each straight tube is 30 m.

[0120] It should be noted that the helical flow mixer comprises an axis equal in length to the straight tube and helical vanes distributed on the axis. The axis coincides with the central axis of the straight tube, and the two ends of the axis are fixed on the straight tube. The specific function is to enhance the turbulent degree of the reaction material and avoid phase separation of the material. The helical flow mixer is a prior art, and will not be described here.

[0121] Referring to Figure 6 In some embodiments, the length of the tube of the tubular reactor is adjusted according to the corresponding reaction time.

[0122] Referring to Figure 6 and Figure 7 In some embodiments, each tank body is provided with a plurality of baffle plates vertically distributed with the straight tubes. Each baffle plate is provided with a hole through which the serpentine reaction tube body passes. The baffle plate can be arc-shaped to separate the cavity to form a serpentine channel.

[0123] In this embodiment, the baffle plate not only prevents fluid short circuiting and increases fluid velocity, but also forces the fluid to pass through the tube bundle multiple times in a prescribed path, greatly increasing the degree of fluid turbulence to improve the fluid heat transfer coefficient.

[0124] In some embodiments, the two feed ports of the mixer I are respectively connected with a storage tank 1 connected with a metering pump 1 and a storage tank 2 connected with a metering pump 2; the two feed ports of the mixer II are respectively connected with the outlet of the mixer I and a storage tank 3 connected with a metering pump 3; the gas phase outlet of the wiped evaporator is connected with a storage tank 4; the inlet of the dissolving pipe is connected with a storage tank 5 connected with a metering pump 4; the outlet of the pipe centrifuge is also connected with a storage tank 6; the two outlets of the centrifuge are respectively connected with a storage tank 7 and a storage tank 8; wherein,

[0125] The storage tank 1 is used for storing methanol;

[0126] The storage tank 2 is used for storing 2-(2-chlorobenzyl)-2-(1-chloromethyl)oxirane;

[0127] The storage tank 3 is used for storing hydrazine hydrate;

[0128] The metering pumps 1-3 are all used for controlling the metering of feed;

[0129] The storage tank 4 is used for receiving methanol and can be directly used for the storage tank 1;

[0130] The storage tank 5 is used for storing toluene;

[0131] The storage tank 6 is used for receiving hydrazine hydrate aqueous phase;

[0132] The storage tank 7 is used for receiving toluene mother liquor;

[0133] The storage tank 8 is used for receiving 2-(1-chloro-cyclopropyl-1-yl)-3-(2-chlorophenyl)-2-hydroxypropyl-1-hydrazine.

[0134] In some embodiments, a mass flow regulator MFC1 is connected between the metering pump 1 and the mixer I;

[0135] A mass flow regulator MFC2 is connected between the metering pump 2 and the mixer I;

[0136] A mass flow regulator MFC3 is connected between the metering pump 3 and the mixer II;

[0137] A mass flow regulator MFC4 is connected between the metering pump 4 and the dissolving tank.

[0138] In some embodiments, heat exchanger 1 and heat exchanger 2 are respectively connected to the two feed ports of the mixer II for controlling the temperature of the feed; heat exchanger 3 is connected to the inlet of the dissolving tank for controlling the temperature of the feed.

[0139] In some embodiments, heat exchanger 4 is connected to the gas phase outlet of the wiped evaporator for controlling the temperature of the outlet; the liquid phase outlet of the wiped evaporator is connected to a circulating tank.

[0140] In some embodiments, a vacuum system is connected to the circulating tank and the storage tank 4.

[0141] In some embodiments, temperature regulator T1 is connected between heat exchanger 1 and the mixer II;

[0142] Temperature regulator T2 is connected between heat exchanger 2 and the mixer II;

[0143] Temperature regulator T3 is connected between the mixer II and the tubular reactor;

[0144] Temperature regulator T4 and pressure regulator P1 are connected between the tubular reactor and the wiped evaporator;

[0145] Temperature regulator T5 is connected between heat exchanger 3 and the dissolving tank;

[0146] Temperature regulator T6 and pressure regulator P2 are connected to the circulating tank;

[0147] Temperature regulator T7 is connected to the dissolving tank;

[0148] Temperature regulator T8 is connected between the crystallization tank and the centrifuge.

[0149] In order to better illustrate the present application, the following examples are further illustrated.

[0150] Example 1

[0151] The present embodiment provides a continuous preparation method of prothioconazole intermediate, using a continuous production system of prothioconazole intermediate, and the specific steps are as follows:

[0152] S1, methanol is put into storage tank 1, and metering pump 1 is used to enter mixer I at a mass flow rate of 1000 kg / h through mass flow rate regulator MFC1; at the same time, 2-(2-chlorobenzyl)-2-(1-chloromethyl)oxirane is put into storage tank 2, and metering pump 2 is used to enter mixer I at a mass flow rate of 500 kg / h through mass flow rate regulator MFC2; that is, the mass ratio of methanol and 2-(2-chlorobenzyl)-2-(1-chloromethyl)oxirane is 2:1.

[0153] S2, the methanol and 2-(2-chlorobenzyl)-2-(1-chloromethyl)oxirane are mixed by 11 regular honeycomb spherical mixing structure made of silicon carbide, and then enter the mixer II through the heat exchanger 1 (the outlet temperature is 90℃); at the same time, the hydrazine hydrate is put into the storage tank 3, and is introduced into the mixer II through the heat exchanger 2 (the outlet temperature is 80℃) by using the metering pump 3 and the mass flow regulator MFC3 at a rate of 8750 kg / h; that is, the molar ratio of the hydrazine hydrate to 2-(2-chlorobenzyl)-2-(1-chloromethyl)oxirane is 8:1.

[0154] S3, the above raw materials are fully mixed by 10 irregular honeycomb spherical mixing structure made of ceramic (the outlet temperature of the mixer II is 86℃), and then enter the tubular reactor, and the reaction is carried out at 125℃ for 8 min under the nitrogen atmosphere, the reaction pressure is 0.7 MPa, and when the content of 2-(2-chlorobenzyl)-2-(1-chloromethyl)oxirane is 0.17wt%, the reaction is ended, and the reaction liquid is obtained.

[0155] S4, the above reaction liquid is continuously introduced into the wiped evaporator, and the methanol is removed by distillation under the reduced pressure of 101 kPa, and the evaporated methanol can be directly used in the above storage tank 1.

[0156] S5, the reaction liquid from which the methanol is removed is continuously punched into the dissolving tank, at the same time, the toluene is put into the storage tank 5, and is continuously introduced into the dissolving tank by using the metering pump 4 and the mass flow regulator MFC4 through the heat exchanger 3 (the outlet temperature is 50℃) at a rate of 950 kg / h (that is, the mass ratio of the toluene to 2-(2-chlorobenzyl)-2-(1-chloromethyl)oxirane is 1.9:1); the temperature is increased to 48℃ for dissolving. The reaction liquid after being dissolved by increasing the temperature is continuously punched into the pipeline centrifuge for phase separation, and the toluene oil phase containing 2-(1-chloro-cyclopropyl-1-yl)-3-(2-chlorophenyl)-2-hydroxypropyl-1-hydrazine is obtained.

[0157] S6, the above toluene oil phase is introduced into the crystallization tank, the temperature is decreased to 10℃ for crystallization, and the centrifugal filtration is carried out, and the filter cake and the toluene mother liquor are obtained, and the filter cake is 2-(1-chloro-cyclopropyl-1-yl)-3-(2-chlorophenyl)-2-hydroxypropyl-1-hydrazine.

[0158] It should be noted that the filter cake is directly used in the subsequent production of prothioconazole; the toluene mother liquor is punched into the storage tank 5 after being distilled; and the hydrazine hydrate aqueous phase obtained by phase separation is punched into the storage tank 3 after being treated.

[0159] Examples 2-9

[0160] Examples 2-9 all provide a continuous preparation method of prothioconazole intermediate, and a continuous production system of prothioconazole intermediate is used, the specific steps are similar to those of Example 1, and the different reaction conditions are shown in Table 1.

[0161] The yield and purity of 2-(1-chloro-cyclopropyl-1-yl)-3-(2-chlorophenyl)-2-hydroxypropyl-1-hydrazine prepared by the continuous preparation method of propiconazole intermediate according to examples 1-9 were calculated and detected, and the results are shown in Table 1. As can be seen from Table 1, the yield of 2-(1-chloro-cyclopropyl-1-yl)-3-(2-chlorophenyl)-2-hydroxypropyl-1-hydrazine prepared by the continuous preparation method of propiconazole intermediate and the production system provided by the present application can reach more than 91.5%, and the purity can reach more than 97.5%, which is much higher than the yield (79%-84%) and purity (94%-96.5%) of the batch reaction in the prior art, and is suitable for large-scale production and has high market application value.

[0162] Table 1 Reaction conditions, yield and purity of the final product of the continuous preparation method of propiconazole intermediate according to examples

[0163]

[0164]

[0165] The above only describes the preferred embodiments of the present application and is not intended to limit the present application. Any modification, equivalent replacement or improvement made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A continuous preparation method for a prothioconazole intermediate, characterized in that, Includes the following steps: S1, methanol, 2-(2-chlorobenzyl)-2-(1-chloromethyl)ethylene oxide and hydrazine hydrate are mixed and reacted at 80~180℃ for 1~30 min under an inert atmosphere and at a reaction pressure of 0.2~2.0 MPa to obtain a reaction solution; S2, the reaction solution is subjected to vacuum distillation to remove methanol, toluene is added, the solution is heated to dissolve and separate the phases to obtain a toluene oil phase containing 2-(1-chloro-cyclopropyl-1-yl)-3-(2-chlorophenyl)-2-hydroxypropyl-1-hydrazine; S3, the toluene oil phase is cooled to -30~20℃ to crystallize, and the solid and liquid phases are separated to obtain 2-(1-chloro-cyclopropyl-1-yl)-3-(2-chlorophenyl)-2-hydroxypropyl-1-hydrazine; In step S1, the mixing is carried out in a mixer; wherein, the mixer has a plurality of spherical cavities arranged sequentially at intervals, each spherical cavity is provided with a spherical mixing structure, and a connecting channel is provided between any two adjacent spherical cavities, and a plurality of guide vanes are provided in any connecting channel; in step S1, the reaction is carried out in a tubular reactor.

2. The continuous preparation method of the prothioconazole intermediate as described in claim 1, characterized in that, The spherical hybrid structure is a regular honeycomb structure, or an irregular honeycomb structure, or a multi-layer corrugated microporous mesh structure, or a combination of two or three of the following: regular honeycomb structure, irregular honeycomb structure, and multi-layer corrugated microporous mesh structure.

3. The continuous preparation method of the prothioconazole intermediate as described in claim 1, characterized in that, The guide vane is evenly divided into multiple layers along the length of the connecting channel. Each layer of the guide vane includes multiple pieces of vane arranged in a ring around the central axis of the connecting channel. The pieces of vane in the multiple layers of the guide vane are staggered.

4. The continuous preparation method of the prothioconazole intermediate as described in claim 1, characterized in that, The spherical hybrid structure is made of at least one of ceramic, silicon carbide, polytetrafluoroethylene, or stainless steel alloy; and / or The number of spherical cavities is 5 to 30.

5. The continuous preparation method of the prothioconazole intermediate as described in claim 1, characterized in that, In step S1, the specific steps of mixing include: first mixing methanol and 2-(2-chlorobenzyl)-2-(1-chloromethyl)ethylene oxide, and second mixing by adding hydrazine hydrate.

6. The continuous preparation method of the prothioconazole intermediate as described in claim 1, characterized in that, In step S1, the mixing temperature is 80~150℃; and / or In step S2, the toluene is preheated to a temperature of 50-70°C; and / or In step S2, the temperature of the heated solvent is 40~80℃; and / or In step S3, the crystallization time is 0.5~4h.

7. The continuous preparation method of the prothioconazole intermediate as described in claim 1, characterized in that, In step S1, the mass ratio of methanol to 2-(2-chlorobenzyl)-2-(1-chloromethyl)ethylene oxide is (1~5):1; and / or In step S1, the molar ratio of 2-(2-chlorobenzyl)-2-(1-chloromethyl)ethylene oxide to hydrazine hydrate is 1:(5~10); and / or In step S2, the amount of toluene added is 1 to 3 times the mass of 2-(2-chlorobenzyl)-2-(1-chloromethyl)ethylene oxide.

8. A continuous production system for a prothioconazole intermediate, characterized in that, It includes a mixer, a tubular reactor, a scraped evaporator, a dissolving tank, a tubular centrifuge, a crystallizing tank, and a centrifuge connected in sequence by pipes; among which, The mixer is used to mix methanol, 2-(2-chlorobenzyl)-2-(1-chloromethyl)ethylene oxide and hydrazine hydrate; The mixer has multiple spherical cavities arranged at intervals in sequence. Each spherical cavity is provided with a spherical mixing structure. A connecting channel is provided between any two adjacent spherical cavities. Multiple guide vanes are provided in any connecting channel. The tubular reactor is connected to the outlet of the mixer and is used to carry out the reaction. The scraped evaporator is connected to the outlet of the tubular reactor and is used for vacuum distillation of the reaction liquid. The dissolving tank is connected to the outlet of the scraped evaporator and is equipped with an inlet for adding toluene, which is used to remove the methanol reaction solution from the mixing of toluene and to heat and dissolve the solution. The pipeline centrifuge is connected to the outlet of the dissolving tank and is used to separate the reaction liquid after heating and dissolving. The crystallization tank is connected to the outlet of the pipeline centrifuge and is used to cool and crystallize the toluene oil phase. The centrifuge is connected to the outlet of the crystallization tank and is used to separate the toluene oil phase after crystallization.

9. The continuous production system for the prothioconazole intermediate as described in claim 8, characterized in that, The number of spherical cavities is 5 to 30; and / or The spherical hybrid structure is a regular honeycomb structure, or an irregular honeycomb structure, or a multi-layer corrugated microporous mesh structure, or a combination of two or three of the following: regular honeycomb structure, irregular honeycomb structure, and multi-layer corrugated microporous mesh structure; and / or The spherical hybrid structure is made of at least one of ceramic, silicon carbide, polytetrafluoroethylene, or stainless steel alloy; and / or The guide vanes are uniformly divided into multiple layers along the length of the connecting channel; each layer of the guide vanes includes multiple pieces of vane spaced annularly around the central axis of the connecting channel; the pieces of vane in the multiple layers of the guide vanes are staggered; and / or The mixer includes mixer I and mixer II; wherein, mixer I is provided with two feed ports for first mixing methanol and 2-(2-chlorobenzyl)-2-(1-chloromethyl)ethylene oxide; mixer II is provided with two feed ports for second mixing the mixed raw materials obtained from the first mixing with hydrazine hydrate.

10. The continuous production system for the prothioconazole intermediate as described in claim 9, characterized in that, The tubular reactor has a fully submerged tube sheet structure, and each tube is equipped with a spiral mixer; and / or The mixer II has two feed inlets connected to heat exchangers 1 and 2 for controlling the feed temperature, respectively; the dissolving tank has a heat exchanger 3 connected to its inlet for controlling the feed temperature.

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