A method for preparing a key intermediate of prothioconazole using a fixed bed reactor
By using an activated catalyst and optimizing reaction conditions in a fixed-bed reactor, a key intermediate of prothioconazole was prepared, solving the problems of poor reaction selectivity and environmental unfriendliness in existing technologies, and achieving high yield and high purity preparation results.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- QIZHOU GREEN CHEM (JINING) CO LTD
- Filing Date
- 2024-12-05
- Publication Date
- 2026-06-05
AI Technical Summary
Existing technologies for preparing key intermediates of prothioconazole suffer from problems such as poor reaction selectivity, unsatisfactory yield, complex operation, environmental unfriendliness, and high equipment costs.
A fixed-bed reactor was used to carry out the reaction under a protective atmosphere with activated catalyst. The activation temperature and time were controlled, the catalyst loading was optimized, and a suitable solvent was selected to be mixed with chlorine gas before the reaction to generate the key intermediate of prothioconazole.
This invention enables the preparation of key intermediates for prothioconazole under mild reaction conditions, with simple operation, environmental friendliness, high yield, and high purity, thus overcoming the shortcomings of existing technologies.
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Figure CN122145287A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for preparing a key intermediate of prothioconazole using a fixed-bed reactor. Background Technology
[0002] Prothioconazole is a highly effective, broad-spectrum triazole thione fungicide, mainly used to control numerous diseases in cereals, wheat, and legumes. Prothioconazole has low toxicity, no teratogenic or mutagenic effects, is non-embryonic, and safe for humans and the environment. Its mechanism of action involves inhibiting the demethylation of lanosterol or 2,4-methylenedihydrolanosterol at the 14-position, a precursor of sterols in fungi, thereby affecting ergosterol biosynthesis and ultimately influencing normal fungal physiological processes.
[0003] 2-Chloro-1-(1-Chlorocyclopropyl)acetone (CAS No.: 120983-72-4) is a key intermediate in the synthesis of the pesticide prothioconazole, and its structural formula is as follows:
[0004]
[0005] The mainstream synthesis process for this compound involves using sulfonyl chloride as the chlorinating agent to react with 1-chloro-1-acetylcyclopropane in a synthesis flask. This reaction is highly exothermic, leading to severe localized overheating and heat exchange issues within the reaction system, resulting in poor selectivity and unsatisfactory yields. Furthermore, the reaction is time-consuming and generates large amounts of sulfur dioxide waste gas, which is environmentally unfriendly. Some researchers have used chlorine as the chlorinating agent in a microchannel reactor; however, this method requires sophisticated equipment, is expensive, and is difficult to scale up. It also suffers from low yields, high impurities, and complex operation. Summary of the Invention
[0006] The purpose of this invention is to provide a method for preparing key intermediates of prothioconazole using a fixed-bed reactor. This method has mild reaction conditions, is environmentally friendly, easy to operate, and has a high yield.
[0007] To achieve the above objectives, the technical solution adopted by the present invention is as follows:
[0008] A method for preparing a key intermediate of prothioconazole using a fixed-bed reactor includes reacting a compound of Formula 1 with chlorine gas in a fixed-bed reactor to generate the key intermediate, wherein Formula 1 is... The structural formula of the key intermediate is as follows: The fixed-bed reactor is filled with an activated catalyst. The method for preparing the activated catalyst includes activating the catalyst under a protective atmosphere, controlling the activation temperature to be no less than 300°C and the activation time to be no less than 24 hours.
[0009] This invention uses a fixed-bed reactor to prepare the above-mentioned key intermediates. The reaction conditions are mild, the operation is simple, the reaction rate is fast and the continuity is good. By optimizing the catalyst packed in the fixed-bed reactor, the yield and purity of the target product are improved.
[0010] Preferably, the activation temperature is controlled at 450–700°C and the activation time is controlled at 48–96 hours. If the activation temperature is too low, the improvement in product quality is limited; if the activation temperature is too high, it will negatively affect the catalytic reaction. Therefore, the temperature cannot be too high or too low. Similarly, the activation time should also be carefully controlled.
[0011] More preferably, the activation temperature is controlled at 550–650°C and the activation time is controlled at 56–80 h.
[0012] More preferably, the activation time is controlled to be 65-75 hours.
[0013] Preferably, the protective atmosphere includes one or more of nitrogen, argon, and Freon atmospheres.
[0014] Preferably, the catalyst comprises one or more of activated carbon, alumina, zeolite, ceramic powder, and molecular sieve.
[0015] Preferably, the molar ratio of the compound shown in Formula 1 to chlorine is 1:(0.95-2), more preferably 1:(0.95-1.5), even more preferably 1:(1.1-1.5), and still more preferably 1:(1.2-1.5), for example 1:1.2, 1:1.3, 1:1.4, and 1:1.5.
[0016] In some embodiments, the feed flow rate of the compound represented by Formula 1 is 20–30 g / min, more preferably 23–28 g / min, and even more preferably 24–26 g / min.
[0017] In some embodiments, the chlorine gas feed flow rate is 15-30 g / min, more preferably 18-25 g / min, and even more preferably 20-25 g / min.
[0018] Preferably, the preparation method further includes selectively mixing the compound shown in Formula 1 with an organic solvent, then mixing it together with the chlorine gas in a mixer and preheating it to the reaction temperature before introducing it into the fixed-bed reactor for reaction.
[0019] More preferably, the organic solvent is selected from one or more of methanol, ethanol, toluene, xylene, dichloromethane, dichloroethane, chloroform, and carbon tetrachloride.
[0020] Preferably, when the compound shown in Formula 1 is mixed with an organic solvent, the mass ratio of the compound shown in Formula 1 to the organic solvent is 1:(0.5 to 1.5), more preferably 1:(0.8 to 1.2), and even more preferably 1:(0.9 to 1.1).
[0021] Preferably, the temperature of the reaction is controlled at 0–20°C, more preferably 5–15°C, and even more preferably 8–12°C.
[0022] Preferably, the preparation method further includes the step of washing and desolvating the reaction system with a saturated sodium carbonate aqueous solution after the reaction is completed.
[0023] Due to the application of the above technical solution, the present invention has the following advantages compared with the prior art:
[0024] This invention uses a fixed-bed reactor to prepare the key intermediate 2-chloro-1-(1-chlorocyclopropyl)ethyl ketone. The reaction conditions are mild, the operation is simple, the reaction rate is fast, the reaction is continuous, and the environment is friendly. By optimizing the catalyst packed in the fixed-bed reactor, the resulting product has high purity and high yield. Attached Figure Description
[0025] Figure 1 This is a simplified structural diagram of a fixed-bed reactor according to the present invention;
[0026] The components include: 1. Reactor; 2. Mixer; 3. Cooling device; 4. Material collection device; 5. Insulation jacket; 6. Liquid feed pipe; 61. Metering pump; 7. Gas feed pipe; 71. Flow meter; 8. 1-Chloro-1-acetylcyclopropane storage tank; 9. Chlorine tank. Detailed Implementation
[0027] In previous studies, the applicant carried out a chlorination reaction by introducing the compound shown in Formula 1 and chlorine gas into a chlorination tower from the top and middle of the tower, respectively, as detailed in patent CN 117105759 B. However, the production efficiency, product yield, and purity of this method still need improvement. Based on previous research, the applicant has conducted extensive studies and proposed the technical method of this invention. The following provides a further explanation of the technical solution, implementation process, and principles of this invention.
[0028] This invention provides a method for preparing a key intermediate of prothioconazole using a fixed-bed reactor, comprising the following steps:
[0029] (1) Activate the catalyst under a protective atmosphere, control the activation temperature to be no less than 300℃ and the time to be no less than 24h, and then load the activated catalyst into the reactor of the fixed bed reactor.
[0030] (2) The compound shown in Formula 1 is selectively mixed with an organic solvent, then mixed with chlorine gas in a mixer and preheated to the reaction temperature, and finally introduced into a reactor for reaction. The reaction equation is as follows:
[0031]
[0032] The compound shown in Formula 2 is the key intermediate.
[0033] In some preferred embodiments, the preparation method of the key intermediate specifically includes the following steps:
[0034] (1) The catalyst is activated under a protective atmosphere, and the activation temperature is controlled at 550-650℃ and the time is 65-75h. The activated catalyst is then loaded into the reactor of the fixed bed reactor. The catalyst includes one or more of activated carbon, alumina, zeolite, ceramic powder, and molecular sieve. The protective atmosphere includes one or more of nitrogen, argon, and Freon atmosphere.
[0035] (2) Selectively mix the compound shown in Formula 1 with an organic solvent, then pass it into a mixer together with chlorine gas for mixing and preheating to the reaction temperature, and finally pass it into the reactor from the top of the reactor for reaction. Control the feed flow rate of the compound shown in Formula 1 to be 20-30 g / min, the feed flow rate of chlorine gas to be 15-30 g / min, and the reaction temperature to be 0-20℃.
[0036] like Figure 1 As shown, the fixed-bed reactor includes: a reactor 1 filled with activated catalyst, an insulation jacket 5 surrounding the reactor 1, a mixer 2 located at the feed end of the reactor 1, a cooling device 3 located at the discharge end of the reactor 1, a material collection device 4 connected to the discharge end of the cooling device 3, and a feed pipe connected to the feed end of the mixer 2. The feed end and discharge end of the reactor 1 are located on the upper and lower sides of the reactor 1, respectively. The feed pipe includes a liquid feed pipe 6 and a gas feed pipe 7. The liquid feed pipe 6 is equipped with a metering pump 61, which is connected to a 1-chloro-1-acetylcyclopropane (i.e., the compound shown in Formula 1, CAS No.: 63141-09-3) storage tank 8 for introducing 1-chloro-1-acetylcyclopropane; the gas feed pipe 7 is equipped with a flow meter 71, which is connected to a chlorine tank 9 for introducing chlorine gas.
[0037] The present invention will be further described below with reference to embodiments. However, the present invention is not limited to the following embodiments. The implementation conditions used in the embodiments can be further adjusted according to different requirements of specific applications, and the implementation conditions not specified are conventional conditions in the industry. The technical features involved in the various embodiments of the present invention can be combined with each other as long as they do not conflict with each other.
[0038] Unless otherwise specified, all raw materials mentioned below are commercially available products or can be prepared using existing methods.
[0039] Unless otherwise specified, the following text uses... Figure 1 The fixed-bed reactor shown is controlled at a reaction pressure of 1-3 atm.
[0040] Example 1
[0041] A method for preparing 2-chloro-1-(1-chlorocyclopropyl)ethyl ketone includes the following steps:
[0042] (1) The catalyst zeolite was activated at 600°C for 72 hours under nitrogen protection, and the activated catalyst was then filled into reactor 1.
[0043] (2) Use metering pump 61 to feed raw material 1-chloro-1-acetylcyclopropane into mixer 2, control the flow rate to 25 g / min, and at the same time, use flow meter 71 to feed chlorine into mixer 2, control the flow rate to 22.4 g / min. The material passes through mixer 2 and the temperature is controlled at 10±2℃. After mixing, it is fed into reactor 1 and reacted at 10℃.
[0044] (3) Material collection device 4 sampling control, feeding for 20 minutes, collecting liquid to detect complete reaction;
[0045] (4) The organic layer was washed with saturated sodium carbonate aqueous solution, separated and desolventized to obtain the product. The product was a pale yellow liquid with a weight of 659.1g, a purity of 95%, and a yield of 97%.
[0046] Example 2
[0047] A method for preparing 2-chloro-1-(1-chlorocyclopropyl)ethyl ketone includes the following steps:
[0048] (1) The catalyst zeolite was activated at 600℃ for 72 hours under argon protection, and the activated catalyst was filled into a fixed bed reactor.
[0049] (2) Use metering pump 61 to feed raw material 1-chloro-1-acetylcyclopropane into mixer 2, control the flow rate to 25 g / min, and at the same time, use flow meter 71 to feed chlorine into mixer 2, control the flow rate to 22.4 g / min. The material passes through mixer 2 and the temperature is controlled at 10±2℃. After mixing, it is fed into reactor 1 and reacted at 10℃.
[0050] (3) Material collection device 4 sampling control, feeding for 20 minutes, collecting liquid to detect complete reaction;
[0051] (4) The organic layer was washed with saturated sodium carbonate aqueous solution, separated and desolventized to obtain the product. The product was a pale yellow liquid with a weight of 625.1 g, a purity of 95%, and a yield of 92%.
[0052] Example 3
[0053] A method for preparing 2-chloro-1-(1-chlorocyclopropyl)ethyl ketone includes the following steps:
[0054] (1) The catalyst zeolite was activated at 600°C for 72 hours under Freon protection, and the activated catalyst was then packed into a fixed-bed reactor.
[0055] (2) Use metering pump 61 to feed raw material 1-chloro-1-acetylcyclopropane into mixer 2, control the flow rate to 25 g / min, and at the same time, use flow meter 71 to feed chlorine into mixer 2, control the flow rate to 22.4 g / min. The material passes through mixer 2 and the temperature is controlled at 10±2℃. After mixing, it is fed into reactor 1 and reacted at 10℃.
[0056] (3) Material collection device 4 sampling control, feeding for 20 minutes, collecting liquid to detect complete reaction;
[0057] (4) The organic layer was washed with saturated sodium carbonate aqueous solution, separated and desolventized to obtain the product. The product was a pale yellow liquid with a weight of 638.7g, a purity of 95%, and a yield of 94%.
[0058] Example 4
[0059] A method for preparing 2-chloro-1-(1-chlorocyclopropyl)ethyl ketone includes the following steps:
[0060] (1) The catalyst zeolite was activated at 450°C for 72 hours under nitrogen protection, and the activated catalyst was then packed into a fixed-bed reactor.
[0061] (2) Use metering pump 61 to feed raw material 1-chloro-1-acetylcyclopropane into mixer 2, control the flow rate to 25 g / min, and at the same time, use flow meter 71 to feed chlorine into mixer 2, control the flow rate to 22.4 g / min. The material passes through mixer 2 and the temperature is controlled at 10±2℃. After mixing, it is fed into reactor 1 and reacted at 10℃.
[0062] (3) Material collection device 4 sampling control, feeding for 20 minutes, collecting liquid to detect complete reaction;
[0063] (4) The organic layer was washed with saturated sodium carbonate aqueous solution, separated and desolventized to obtain the product, which was a pale yellow liquid with a weight of 625g, a purity of 90%, and a yield of 87%.
[0064] Example 5
[0065] A method for preparing 2-chloro-1-(1-chlorocyclopropyl)ethyl ketone includes the following steps:
[0066] (1) The catalyst zeolite was activated at 300°C for 72 hours under nitrogen protection, and the activated catalyst was filled into a fixed bed reactor.
[0067] (2) Use metering pump 61 to feed raw material 1-chloro-1-acetylcyclopropane into mixer 2, control the flow rate to 25 g / min, and at the same time, use flow meter 71 to feed chlorine into mixer 2, control the flow rate to 22.4 g / min. The material passes through mixer 2 and the temperature is controlled at 10±2℃. After mixing, it is fed into reactor 1 and reacted at 10℃.
[0068] (3) Material collection device 4 sampling control, feeding for 20 minutes, collecting liquid to detect complete reaction;
[0069] (4) The organic layer was washed with saturated sodium carbonate aqueous solution, separated and desolventized to obtain the product, which was a pale yellow liquid with a weight of 615g, a purity of 88%, and a yield of 84%.
[0070] Example 6
[0071] A method for preparing 2-chloro-1-(1-chlorocyclopropyl)ethyl ketone includes the following steps:
[0072] (1) The catalyst zeolite was activated at 600°C for 48 hours under nitrogen protection, and the activated catalyst was then packed into a fixed-bed reactor.
[0073] (2) The raw material 1-chloro-1-acetylcyclopropane is fed into the mixer 2 using the metering pump 61, and the flow rate is controlled at 25 g / min. At the same time, chlorine gas is fed into the mixer 2 through the flow meter 71, and the flow rate is controlled at 22.4 g / min. The material reacts in the mixer 2 at a controlled temperature of 10 ± 2 °C. After mixing, it is fed into the reactor 1 and reacted at 10 °C.
[0074] (3) Material collection device 4 sampling control, feeding for 20 minutes, collecting liquid to detect complete reaction;
[0075] (4) The organic layer was washed with saturated sodium carbonate aqueous solution, separated and desolventized to obtain the product. The product was a pale yellow liquid with a weight of 633.6 g, a purity of 92%, and a yield of 90%.
[0076] Example 7
[0077] A method for preparing 2-chloro-1-(1-chlorocyclopropyl)ethyl ketone includes the following steps:
[0078] (1) The catalyst zeolite was activated at 600°C for 72 hours under nitrogen protection, and the activated catalyst was filled into a fixed bed reactor.
[0079] (2) The raw material 1-chloro-1-acetylcyclopropane is fed into the mixer 2 using metering pump 61, and the flow rate is controlled at 25 g / min. At the same time, chlorine gas is fed into the mixer 2 through flow meter 71, and the flow rate is controlled at 22.4 g / min. The material reacts in the mixer 2 at a controlled temperature of 5±2℃. After mixing, it is fed into the reactor 1 and reacted at 5℃.
[0080] (3) Material collection device 4 sampling control, feeding for 20 minutes, collecting liquid to detect complete reaction;
[0081] (4) The organic layer was washed with saturated sodium carbonate aqueous solution, separated and desolventized to obtain the product. The product was a pale yellow liquid with a weight of 652.3g, a purity of 95%, and a yield of 96%.
[0082] Example 8
[0083] A method for preparing 2-chloro-1-(1-chlorocyclopropyl)ethyl ketone includes the following steps:
[0084] (1) The activated carbon catalyst was activated at 600°C for 72 hours under nitrogen protection, and the activated catalyst was then packed into a fixed-bed reactor.
[0085] (2) The raw material 1-chloro-1-acetylcyclopropane is fed into the mixer 2 using the metering pump 61, and the flow rate is controlled at 25 g / min. At the same time, chlorine gas is fed into the mixer 2 through the flow meter 71, and the flow rate is controlled at 22.4 g / min. The material reacts in the mixer 2 at a controlled temperature of 10 ± 2 °C. After mixing, it is fed into the reactor 1 and reacted at 10 °C.
[0086] (3) Material collection device 4 sampling control, feeding for 20 minutes, collecting liquid to detect complete reaction;
[0087] (4) The organic layer was washed with saturated sodium carbonate aqueous solution, separated and desolventized to obtain the product. The product was a pale yellow liquid with a weight of 631.9 g, a purity of 93%, and a yield of 91%.
[0088] Example 9
[0089] A method for preparing 2-chloro-1-(1-chlorocyclopropyl)ethyl ketone includes the following steps:
[0090] (1) The catalyst alumina was activated at 600°C for 72 hours under nitrogen protection, and the activated catalyst was then packed into a fixed-bed reactor.
[0091] (2) The raw material 1-chloro-1-acetylcyclopropane is fed into the mixer 2 using the metering pump 61, and the flow rate is controlled at 25 g / min. At the same time, chlorine gas is fed into the mixer 2 through the flow meter 71, and the flow rate is controlled at 22.4 g / min. The material reacts in the mixer 2 at a controlled temperature of 10 ± 2 °C. After mixing, it is fed into the reactor 1 and reacted at 10 °C.
[0092] (3) Material collection device 4 sampling control, feeding for 20 minutes, collecting liquid to detect complete reaction;
[0093] (4) The organic layer was washed with saturated sodium carbonate aqueous solution, separated and desolventized to obtain the product. The product was a pale yellow liquid with a weight of 622.7g, a purity of 95%, and a yield of 92%.
[0094] Example 10
[0095] A method for preparing 2-chloro-1-(1-chlorocyclopropyl)ethyl ketone includes the following steps:
[0096] (1) The catalyst ceramic powder was activated at 600°C for 72 hours under nitrogen protection, and the activated catalyst was filled into a fixed bed reactor.
[0097] (2) The raw material 1-chloro-1-acetylcyclopropane is fed into the mixer 2 using the metering pump 61, and the flow rate is controlled at 25 g / min. At the same time, chlorine gas is fed into the mixer 2 through the flow meter 71, and the flow rate is controlled at 22.4 g / min. The material reacts in the mixer 2 at a controlled temperature of 10 ± 2 °C. After mixing, it is fed into the reactor 1 and reacted at 10 °C.
[0098] (3) Material collection device 4 sampling control, feeding for 20 minutes, collecting liquid to detect complete reaction;
[0099] (4) The organic layer was washed with saturated sodium carbonate aqueous solution, separated and desolventized to obtain the product. The product was a pale yellow liquid with a weight of 636.4 g, a purity of 95%, and a yield of 94%.
[0100] Example 11
[0101] A method for preparing 2-chloro-1-(1-chlorocyclopropyl)ethyl ketone includes the following steps:
[0102] (1) The catalyst molecular sieve was activated at 600℃ for 72 hours under nitrogen protection, and the activated catalyst was filled into a fixed bed reactor.
[0103] (2) The raw material 1-chloro-1-acetylcyclopropane is fed into the mixer 2 using the metering pump 61, and the flow rate is controlled at 25 g / min. At the same time, chlorine gas is fed into the mixer 2 through the flow meter 71, and the flow rate is controlled at 22.4 g / min. The material reacts in the mixer 2 at a controlled temperature of 10 ± 2 °C. After mixing, it is fed into the reactor 1 and reacted at 10 °C.
[0104] (3) Material collection device 4 sampling control, feeding for 20 minutes, collecting liquid to detect complete reaction;
[0105] (4) The organic layer was washed with saturated sodium carbonate aqueous solution, separated and desolventized to obtain the product. The product was a pale yellow liquid with a weight of 650.1g, a purity of 95%, and a yield of 96%.
[0106] Example 12
[0107] A method for preparing 2-chloro-1-(1-chlorocyclopropyl)ethyl ketone includes the following steps:
[0108] (1) The catalyst molecular sieve was activated at 600℃ for 72 hours under nitrogen protection, and the activated catalyst was filled into a fixed bed reactor.
[0109] (2) Mix 1-chloro-1-acetylcyclopropane and dichloromethane at a mass ratio of 1:1 to obtain a 1-chloro-1-acetylcyclopropane solution. Use metering pump 61 to pass the 1-chloro-1-acetylcyclopropane solution into mixer 2 and control the flow rate to 50 g / min. At the same time, chlorine gas is passed into mixer 2 through flow meter 71 and the flow rate is controlled to 22.4 g / min. The material reacts in mixer 2 at a controlled temperature of 10 ± 2 °C. After mixing, it is passed into reactor 1 and reacted at 10 °C.
[0110] (3) Material collection device 4 sampling control, feeding for 20 minutes, collecting liquid to detect complete reaction;
[0111] (4) The organic layer was washed with saturated sodium carbonate aqueous solution, separated and desolventized to obtain the product. The product was a pale yellow liquid with a weight of 660.0 g, a purity of 96%, and a yield of 98%.
[0112] Example 13
[0113] A method for preparing 2-chloro-1-(1-chlorocyclopropyl)ethyl ketone includes the following steps:
[0114] (1) The catalyst molecular sieve was activated at 600℃ for 72 hours under nitrogen protection, and the activated catalyst was filled into a fixed bed reactor.
[0115] (2) Mix 1-chloro-1-acetylcyclopropane and chloroform at a mass ratio of 1:1 to obtain a 1-chloro-1-acetylcyclopropane solution. Use metering pump 61 to pass the 1-chloro-1-acetylcyclopropane solution into mixer 2 and control the flow rate to 50 g / min. At the same time, chlorine gas is passed into mixer 2 through flow meter 71 and the flow rate is controlled to 22.4 g / min. The material reacts in mixer 2 at a controlled temperature of 10 ± 2 °C. After mixing, it is passed into reactor 1 and reacted at 10 °C.
[0116] (3) Material collection device 4 sampling control, feeding for 20 minutes, collecting material to test the liquid to determine if the reaction has been completed;
[0117] (4) The organic layer was washed with saturated sodium carbonate aqueous solution, separated and desolventized to obtain the product, which was a pale yellow liquid with a weight of 665.0 g, a purity of 97%, and a yield of 99.9%.
[0118] Example 14
[0119] A method for preparing 2-chloro-1-(1-chlorocyclopropyl)ethyl ketone includes the following steps:
[0120] (1) The catalyst molecular sieve was activated at 600℃ for 72 hours under nitrogen protection, and the activated catalyst was filled into a fixed bed reactor.
[0121] (2) Mix 1-chloro-1-acetylcyclopropane and methanol at a mass ratio of 1:1 to obtain a 1-chloro-1-acetylcyclopropane solution. Use metering pump 61 to pass the 1-chloro-1-acetylcyclopropane solution into mixer 2 and control the flow rate to 50 g / min. At the same time, chlorine gas is passed into mixer 2 through flow meter 71 and the flow rate is controlled to 18.0 g / min. The material reacts in mixer 2 at a controlled temperature of 10 ± 2 °C. After mixing, it is passed into reactor 1 and reacted at 10 °C.
[0122] (3) Material collection device 4 sampling control, feeding for 20 minutes, collecting material to test the liquid to determine if the reaction has been completed;
[0123] (4) The organic layer was washed with saturated sodium carbonate aqueous solution, separated and desolventized to obtain the product. The product was a pale yellow liquid with a weight of 650.1g, a purity of 95%, and a yield of 96%.
[0124] Example 15
[0125] A method for preparing 2-chloro-1-(1-chlorocyclopropyl)ethyl ketone includes the following steps:
[0126] (1) The catalyst molecular sieve was activated at 600℃ for 72 hours under nitrogen protection, and the activated catalyst was filled into a fixed bed reactor.
[0127] (2) Mix 1-chloro-1-acetylcyclopropane and toluene at a mass ratio of 1:1 to obtain a 1-chloro-1-acetylcyclopropane solution. Use metering pump 61 to pass the 1-chloro-1-acetylcyclopropane solution into mixer 2 and control the flow rate to 50 g / min. At the same time, chlorine gas is passed into mixer 2 through flow meter 71 and the flow rate is controlled to 18.0 g / min. The material reacts in mixer 2 at a controlled temperature of 10 ± 2 °C. After mixing, it is passed into reactor 1 and reacted at 10 °C.
[0128] (3) Material collection device 4 sampling control, feeding for 20 minutes, collecting material to test the liquid to determine if the reaction has been completed;
[0129] (4) The organic layer was washed with saturated sodium carbonate aqueous solution, separated and desolventized to obtain the product. The product was a pale yellow liquid with a weight of 622.7g, a purity of 95%, and a yield of 92%.
[0130] Example 16
[0131] A method for preparing 2-chloro-1-(1-chlorocyclopropyl)ethyl ketone includes the following steps:
[0132] (1) The catalyst molecular sieve was activated at 600℃ for 72 hours under nitrogen protection, and the activated catalyst was filled into a fixed bed reactor.
[0133] (2) Mix 1-chloro-1-acetylcyclopropane and dichloroethane at a mass ratio of 1:1 to obtain a 1-chloro-1-acetylcyclopropane solution. Use metering pump 61 to pass the 1-chloro-1-acetylcyclopropane solution into mixer 2 and control the flow rate to 50 g / min. At the same time, chlorine gas is passed into mixer 2 through flow meter 71 and the flow rate is controlled to 18.0 g / min. The material reacts in mixer 2 at a controlled temperature of 10 ± 2 °C. After mixing, it is passed into reactor 1 and reacted at 10 °C.
[0134] (3) Material collection device 4 sampling control, feeding for 20 minutes, collecting material to test the liquid to determine if the reaction has been completed;
[0135] (4) The organic layer was washed with saturated sodium carbonate aqueous solution, separated and desolventized to obtain the product. The product was a pale yellow liquid with a weight of 641.3g, a purity of 96%, and a yield of 95%.
[0136] Example 17
[0137] A method for preparing 2-chloro-1-(1-chlorocyclopropyl)ethyl ketone includes the following steps:
[0138] (1) The catalyst molecular sieve was activated at 600℃ for 72 hours under nitrogen protection, and the activated catalyst was filled into a fixed bed reactor.
[0139] (2) Mix 1-chloro-1-acetylcyclopropane and chloroform at a mass ratio of 1:1 to obtain a 1-chloro-1-acetylcyclopropane solution. Use metering pump 61 to pass the 1-chloro-1-acetylcyclopropane solution into mixer 2 and control the flow rate to 50 g / min. At the same time, chlorine gas is passed into mixer 2 through flow meter 71 and the flow rate is controlled to 18.0 g / min. The material reacts in mixer 2 at a controlled temperature of 10 ± 2 °C. After mixing, it is passed into reactor 1 and reacted at 10 °C.
[0140] (3) Material collection device 4 sampling control, feeding for 20 minutes, collecting material to test the liquid to determine if the reaction has been completed;
[0141] (4) The organic layer was washed with saturated sodium carbonate aqueous solution, separated and desolventized to obtain the product. The product was a pale yellow liquid with a weight of 655.0 g, a purity of 96%, and a yield of 97%.
[0142] Comparative Example 1
[0143] A method for preparing 2-chloro-1-(1-chlorocyclopropyl)ethyl ketone includes the following steps:
[0144] (1) Unactivated catalyst zeolite is packed into a fixed-bed reactor;
[0145] (2) The raw material 1-chloro-1-acetylcyclopropane is fed into the mixer 2 using the metering pump 61, and the flow rate is controlled at 25 g / min. At the same time, chlorine gas is fed into the mixer 2 through the flow meter 71, and the flow rate is controlled at 22.4 g / min. The material reacts in the mixer 2 at a controlled temperature of 10 ± 2 °C. After mixing, it is fed into the reactor 1 and reacted at 10 °C.
[0146] (3) Material collection device 4 sampling control, feeding for 20 minutes, collecting liquid to detect complete reaction;
[0147] (4) The organic layer was washed with saturated sodium carbonate aqueous solution, separated and desolventized to obtain the product, which was a pale yellow liquid with a weight of 640g, a purity of 75%, and a yield of 74%.
[0148] Comparative Example 2
[0149] A method for preparing 2-chloro-1-(1-chlorocyclopropyl)ethyl ketone includes the following steps:
[0150] (1) The catalyst zeolite was activated at 600℃ for 72 hours in an atmospheric environment, and the activated catalyst was then packed into a fixed-bed reactor.
[0151] (2) Use metering pump 61 to feed raw material 1-chloro-1-acetylcyclopropane into mixer 2, control the flow rate to 25 g / min, and at the same time, use flow meter 71 to feed chlorine into mixer 2, control the flow rate to 22.4 g / min. The material passes through mixer 2 and the temperature is controlled at 10±2℃. After mixing, it is fed into reactor 1 and reacted at 10℃.
[0152] (3) Material collection device 4 sampling control, feeding for 20 minutes, collecting liquid to detect complete reaction;
[0153] (4) The organic layer was washed with saturated sodium carbonate aqueous solution, separated and desolventized to obtain the product, which was a pale yellow liquid with a weight of 600g, a purity of 55%, and a yield of 51%.
[0154] Comparative Example 3
[0155] A method for preparing 2-chloro-1-(1-chlorocyclopropyl)ethyl ketone includes: introducing 1-chloro-1-acetylcyclopropane and chlorine gas into a chlorination tower from the top and middle of the tower, respectively, and reacting them at 10°C. The chlorination tower is the same as the one used in Example 1 of CN 117105759 B, with a flow rate of 25 g / min for 1-chloro-1-acetylcyclopropane and a flow rate of 22.4 g / min for chlorine gas.
[0156] The organic layer was washed with a saturated sodium carbonate aqueous solution, separated, and desolventized to obtain the product, a pale yellow liquid weighing 600g, with a purity of 15% and a yield of 14%. Due to changes in reaction conditions and incompatibility with the chlorination tower, the product purity and yield decreased.
[0157] Comparative Example 4
[0158] 200g of dichloromethane and 100g of 1-chloro-1-acetylcyclopropane were added to a round-bottom flask. 401.2g of sulfonyl chloride was added dropwise with stirring at 10-20℃. After the addition was complete, the mixture was kept at this temperature and stirred for 4 hours. A controlled sample was taken to ensure the reaction was complete. 400g of water was added dropwise to quench the reaction, maintaining the temperature below 30℃ throughout the process. After the addition was complete, stirring was continued for 0.5 hours. The mixture was allowed to stand and separate into layers. The organic layer was washed with a saturated sodium bicarbonate aqueous solution and separated. The organic phase was desolvated under negative pressure to obtain 139.3g of a colorless product with a purity of 81% and a yield of 88%.
[0159] By comparing the above comparative examples and embodiments, it was found that the fixed-bed reactor has good continuity. However, when the catalyst in reactor 1 is not used properly, it will affect the product quality. In particular, when the catalyst is not activated at high temperature, the yield and purity of the product are greatly reduced.
[0160] Furthermore, higher product yields and purity are obtained when activation is performed at high temperatures in a protective atmosphere such as nitrogen, argon, or Freon. In addition, activation temperature and activation time also affect product quality; optimal activation is at 600°C for 72 hours.
[0161] Compared to existing technologies, this invention enables the direct feeding of 1-chloro-1-acetylcyclopropane without the need for solvents, making it more environmentally friendly. When 1-chloro-1-acetylcyclopropane is mixed with a solvent to form a solution for feeding, the choice of solvent also affects product quality, with chloroform being the best and dichloromethane the next best.
[0162] The present invention has been described in detail above, with the aim of enabling those skilled in the art to understand and implement the invention. However, this description should not be construed as limiting the scope of protection of the invention. All equivalent changes or modifications made in accordance with the spirit and essence of the invention should be included within the scope of protection of the invention.
Claims
1. A method for preparing a key intermediate of prothioconazole using a fixed-bed reactor, characterized in that, The preparation method includes reacting the compound shown in Formula 1 and chlorine gas in a fixed-bed reactor to generate the key intermediate, wherein Formula 1 is... The structural formula of the key intermediate is as follows: The fixed-bed reactor is filled with an activated catalyst. The method for preparing the activated catalyst includes activating the catalyst under a protective atmosphere, controlling the activation temperature to be no less than 300°C and the activation time to be no less than 24 hours.
2. The method for preparing key intermediates of prothioconazole using a fixed-bed reactor according to claim 1, characterized in that, The activation temperature is controlled at 450–700°C and the activation time is controlled at 48–96 h.
3. The method for preparing key intermediates of prothioconazole using a fixed-bed reactor according to claim 2, characterized in that, The activation temperature is controlled at 550–650°C and the activation time is controlled at 56–80 h.
4. The method for preparing key intermediates of prothioconazole using a fixed-bed reactor according to claim 1, characterized in that, The protective atmosphere includes one or more of nitrogen, argon, and Freon atmospheres.
5. The method for preparing key intermediates of prothioconazole using a fixed-bed reactor according to claim 1, characterized in that, The catalyst includes one or more of activated carbon, alumina, zeolite, ceramic powder, and molecular sieve.
6. The method for preparing key intermediates of prothioconazole using a fixed-bed reactor according to claim 1, characterized in that, The molar ratio of the compound shown in Formula 1 to chlorine gas is 1:(0.95~2); and / or, The feed flow rate of the compound represented by Formula 1 is 20–30 g / min; and / or, The chlorine gas feed flow rate is 15-30 g / min.
7. The method for preparing key intermediates of prothioconazole using a fixed-bed reactor according to claim 1, characterized in that, The preparation method further includes selectively mixing the compound shown in Formula 1 with an organic solvent, then mixing it together with the chlorine gas in a mixer and preheating it to the reaction temperature before introducing it into the fixed-bed reactor for reaction.
8. The method for preparing key intermediates of prothioconazole using a fixed-bed reactor according to claim 7, characterized in that, The organic solvent is selected from one or more of methanol, ethanol, toluene, xylene, dichloromethane, dichloroethane, chloroform, and carbon tetrachloride; and / or, When the compound shown in Formula 1 is mixed with an organic solvent, the mass ratio of the compound shown in Formula 1 to the organic solvent is 1:(0.5 to 1.5).
9. The method for preparing a key intermediate of prothioconazole using a fixed-bed reactor according to claim 1 or 7, characterized in that, The temperature of the reaction is controlled to be between 0 and 20°C.
10. The method for preparing a key intermediate of prothioconazole using a fixed-bed reactor according to claim 1, characterized in that, The preparation method further includes the steps of washing and desolvating the reaction system with a saturated sodium carbonate aqueous solution after the reaction is completed.