WO2023284525A1 - Method for preparing 4-chloro-3,5-dimethylphenol by means of low-temperature chlorination - Google Patents

Method for preparing 4-chloro-3,5-dimethylphenol by means of low-temperature chlorination Download PDF

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WO2023284525A1
WO2023284525A1 PCT/CN2022/101130 CN2022101130W WO2023284525A1 WO 2023284525 A1 WO2023284525 A1 WO 2023284525A1 CN 2022101130 W CN2022101130 W CN 2022101130W WO 2023284525 A1 WO2023284525 A1 WO 2023284525A1
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dimethylphenol
chloro
temperature
solid
low
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PCT/CN2022/101130
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French (fr)
Chinese (zh)
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毛建拥
李泉
胡鹏翔
王会
王丰阳
龚琴琴
李聪
潘洪
王盛文
俞宏伟
胡柏剡
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山东新和成维生素有限公司
浙江新和成股份有限公司
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
    • C07C37/62—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by introduction of halogen; by substitution of halogen atoms by other halogen atoms

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  • the invention belongs to the field of fine chemicals, and in particular relates to a method for preparing 4-chloro-3,5-dimethylphenol by low-temperature chlorination.
  • 4-Chloro-3,5-dimethylphenol whose structure is shown in formula (I), is a broad-spectrum antifungal and antibacterial agent, which can kill most Gram-positive and negative bacteria, fungi, and molds Efficacy, it can be widely used as an anti-mildew and anti-bacterial agent in disinfection or personal care products, such as anti-dandruff shampoo, anti-bacterial detergent such as hand sanitizer, soap and other hygiene products. It can also be used as a preservative and antifungal agent in glue, paint, paint, textile, leather, paper and other industrial fields. 4-Chloro-3,5-dimethylphenol has a good development prospect due to its excellent bactericidal and antiseptic functions, and has been recognized by consumers.
  • 4-Chloro-3,5-dimethylphenol is generally obtained from 3,5-dimethylphenol in industry by chlorination under the action of a chlorinating agent.
  • the chlorinating agent used can be sulfuryl chloride or chlorine gas.
  • Patent CN104326881A mentions a kind of using tetrachlorethylene as solvent, benzylthiophenol and aluminum chloride as co-catalyst, sulfuryl chloride as chlorinating agent, and synthesizes 4- Chloro-3,5-dimethylphenol method.
  • the method utilizes low-temperature chlorination to maintain the selectivity of the product 4-chloro-3,5-dimethylphenol, and high-temperature chlorination to increase the conversion rate of the substrate, thereby achieving the purpose of increasing product yield.
  • the selectivity of the product will still be reduced, and the recovery of the catalyst in this method is difficult, causing serious environmental pollution.
  • Patent CN102675055B discloses a new method for producing p-chloro-m-xylenol by high-temperature chlorination. After sulfuryl chloride is vaporized, it is sent to the lower part of the chlorination tower, and the liquid raw material is preheated and then sent to the upper part of the chlorination tower. Contact with gaseous sulfuryl chloride in the chlorination tower to react, the material is forced to circulate externally through the circulation pump, and a heat exchanger is installed at the outlet of the circulation pump to adjust the temperature in the chlorination tower. This method can realize automatic control, and continuous degree is high, but reaction temperature is higher, and product selectivity is poorer.
  • Patent CN103351282B discloses a preparation method of 4-chloro-3,5-dimethylphenol, using divalent copper salt as catalyst, 3,5-dimethylphenol as raw material, oxygen as oxidant, hydrochloric acid as chlorination Reagent, react at 90-98°C to synthesize 3,5-dimethyl-4-chlorophenol.
  • the product selectivity only reaches 80%, the product selectivity is low, and the difficulty of product separation increases.
  • Patent CN101823941B discloses a green industrialized preparation method of 4-chloro-3,5-dimethylphenol, using water as a solvent, sulfuryl chloride or chlorine as a chlorinating agent, and the substrate 3,5-dimethylphenol
  • the chlorination reaction is carried out by means of multi-stage temperature control.
  • the operation of the method is cumbersome, it is difficult to be applied on a large scale in industry, and the temperature in the reaction process is high, resulting in a decrease in reaction selectivity, and more than 10% of ortho-chlorinated by-products and di-chlorinated by-products are generated in the reaction process.
  • Patent CN102659528A discloses a continuous tank type chlorination process.
  • the chlorination process chlorination agent is added in batches, which improves the conversion rate of the reaction and reduces the occurrence of side reactions to a certain extent.
  • the inventors found that in There is the crystallization problem in this chlorination process, as chlorination still B and chlorination still C have crystallization and separate out, especially the crystallization that separates out in chlorination still C is more, and the crystallization of precipitation is many, causes raw material 3,5 -Xylenol is wrapped, which affects the conversion rate of the reaction.
  • the patent only analyzes the composition of the outlet of the chlorination kettle C, without considering the wrapping of raw materials. The analysis results are somewhat different from the actual reaction process. deviation.
  • the technical problem to be solved by the present invention is to provide a method for preparing 4-chloro-3,5-dimethylphenol by low-temperature chlorination, which can overcome the reduction in conversion rate caused by product crystallization and encapsulation of raw materials in low-temperature chlorination in the prior art The problem.
  • a method for preparing 4-chloro-3,5-dimethylphenol by low-temperature chlorination comprising:
  • the solid crude product 1 and the solid crude product 2 were post-processed to obtain the 4-chloro-3,5-dimethylphenol.
  • the inventors have found through research that there are two reasons why the low-temperature chlorination causes the conversion rate of raw materials to decrease: (1) the density of the precipitated crystals is less than that of the solvent, suspended on the surface of the solvent, and agglomerated on the surface of the solvent to prevent the chlorination agent from contacting the bottom. And the larger the reaction device, the more obvious the hindrance phenomenon and the lower the conversion rate of the substrate; (2) The crystal agglomeration will wrap the raw materials and cause some raw materials to fail to participate in the reaction. The above two points are the main reasons for the low conversion rate of 3,5-dimethylphenol under low temperature conditions.
  • the present invention can not only avoid large-area agglomeration of the crystals and wrap the raw materials, but also prevent the precipitated crystals from blocking the reaction between the chlorinating agent and the substrate, and is especially suitable for large-scale production processes.
  • the precipitated crystals are purified to obtain qualified products, and the remaining raw materials are accumulated multiple times and recovered for the preparation of 4-chloro-3,5-dimethylphenol, so that the remaining raw materials are completely converted.
  • the temperature of the chlorination reaction is 25 to 35°C, and the reaction time is 5 to 8 hours. Since the solid product is separated from the reaction solution in time, a lower reaction temperature is conducive to the improvement of the product conversion rate. .
  • described chlorination agent can adopt the reagent that chlorination reaction is carried out to benzene ring commonly used in the prior art, as preferably, in step (1), described chlorination agent is sulfuryl chloride, chlorine in One or two.
  • the chlorination reaction is carried out in a halogenated hydrocarbon solvent;
  • the halogenated hydrocarbon solvent is preferably chlorine-substituted C 1 -C 3 hydrocarbon compounds; more preferably dichloromethane,
  • chloroform, carbon tetrachloride, trichloroethylene, and tetrachloroethylene are most preferably carried out in tetrachloroethylene.
  • step (1) and step (2) of the present invention when the chlorinating agent is sulfuryl chloride, the mass ratio of 3,5-dimethylphenol to the total amount of sulfuryl chloride is 1:1.1-1.5;
  • the above-mentioned chlorinating agent is chlorine gas, the flow range of chlorine gas is 1-2 L/h.
  • the chlorinating agent is sulfuryl chloride, and sulfuryl chloride is added in batches.
  • step (1) and step (2) the way of adding chlorinating agent for two times is not limited, it can be dripping, it can be metering pump transfer, it can be injector injection feeding (increase contact area), it can also be Feed pipe is inserted below the liquid surface feed (gas feed) etc., as preferably, when chlorinating agent is sulfuryl chloride, in step (1) and step (2), sulfuryl chloride adopts the mode of dripping to add.
  • step (2) the temperature of the chlorination reaction is 30-35° C., and the reaction time is 2-5 hours.
  • the reaction of step (2) can be slightly higher than step (1) temperature of reaction, to promote the carrying out of later stage reaction.
  • the operation mode of the solid-liquid separation is centrifugation or filtration
  • the solid crude product 1 and the solid crude product 2 were crystallized by cooling down to obtain 4-chloro-3,5-dimethylphenol.
  • the specific process of cooling crystallization is as follows: mix the solid crude product 1 and the solid crude product 2, add 1.5 to 2.0 times the solvent (based on the mass of the mixed solid, preferably tetrachloroethylene), heat up to 75 to 85 ° C and stir to dissolve, Then the temperature is lowered at a rate of 3-8°C/h, the final temperature is controlled at 25-30°C, and the product 4-chloro-3,5-dimethylphenol and crystallization mother liquor are obtained by centrifugation.
  • the mother liquor obtained by solid-liquid separation and the crystallization mother liquor obtained by cooling crystallization are added to the next batch of chlorination reaction and applied mechanically. Through this applied operation, the utilization rate of raw materials can be further improved, and the discharge and treatment of waste liquid can be reduced.
  • the tail gas produced by the low-temperature chlorination reaction is condensed and recovered.
  • the number of solid-liquid separations is not particularly limited, and may be one or more times.
  • the number of solid-liquid separations is one time, and is carried out when the conversion rate reaches 40-70%. At this time The purpose of easy operation and reaction yield can be taken into account; as another preference, the number of solid-liquid separations is multiple times, and the solids obtained by solid-liquid separations are combined into solid crude product 1, and the intermediate obtained by solid-liquid separations each time is The mother liquor continues to react.
  • An increase in the number of separations can transfer the precipitated solids in time, which is beneficial to the occurrence of the reaction, but too many separation times will also cause complicated operations, and the number of separations is further preferably 2 to 4 times.
  • the present invention separates the precipitated crystals in time during the reaction process, which reduces the wrapping of raw materials on the one hand, improves the conversion rate, reduces the hindrance of the crystallization to the reaction on the other hand, and increases the reaction rate;
  • Fig. 1 is a process flow diagram of a specific embodiment for preparing 4-chloro-3,5-dimethylphenol of the present invention.
  • Fig. 1 is the process flow diagram of a specific embodiment of preparing 4-chloro-3,5-dimethylphenol of the present invention, as shown in Fig. 1, the preparation method specifically includes the following steps:
  • mother liquor 1 further carries out chlorination reaction 2 with chlorinating agent, centrifuges after completion of the reaction to obtain solid crude product 2 and mother liquor 2, and mother liquor 2 is applied mechanically to the next batch of chlorination reactions;
  • the solid crude product 1 and the solid crude product 2 are combined and then crystallized to obtain the 4-chloro-3,5-dimethylphenol product and crystallization mother liquor, and the crystallization mother liquor is also applied to the next batch of chlorination reaction.
  • the chlorination tail gas produced by chlorination reaction 1 and chlorination reaction 2 is post-treated.
  • Chlorination 1 Add 61g of 3,5-dimethylphenol and 122g of tetrachlorethylene into a 500mL four-neck flask, start the stirring device, keep warm at 25-35°C, and add 33.6g of sulfur dropwise at a constant speed at this temperature The acid chloride was added dropwise for 5 hours. After the dropwise addition was completed, sampling and analysis showed that the primary conversion rate of 3,5-dimethylphenol was 48.78%. The precipitated solid crude product 1 was separated from the mother liquor 1 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
  • Chlorination 2 re-add the mother liquor 1 into the four-necked flask, then start the stirring device, keep the temperature between 30 and 35°C, continue to add 33.6g of sulfuryl chloride dropwise at this temperature, and the dropping time is 3 hours, and the dropping is completed , sampling analysis, the secondary conversion rate of 3,5-dimethylphenol was 47.78%.
  • the precipitated solid crude product 2 was separated from the mother liquor 2 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
  • Chlorination 1 Add 61g of 3,5-dimethylphenol and 183g of tetrachlorethylene into a 500mL four-necked flask, start the stirring device, keep warm at 25-35°C, and add 40.3g of sulfur dropwise at a constant speed at this temperature The acid chloride was added dropwise for 6 hours. After the dropwise addition was completed, sampling and analysis showed that the primary conversion rate of 3,5-dimethylphenol was 58.50%. The precipitated solid crude product 1 was separated from the mother liquor 1 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
  • Chlorination 2 re-add the mother liquor 1 into the four-necked flask, then start the stirring device, keep it warm at 30-35°C, continue to add 29.9g of sulfuryl chloride dropwise at this temperature, and the dropping time is 4 hours, and the dropping is completed , sampling analysis, the secondary conversion rate of 3,5-dimethylphenol was 38.47%.
  • the precipitated solid crude product 2 was separated from the mother liquor 2 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
  • Chlorination 1 Add 61g of 3,5-dimethylphenol and 305g of tetrachlorethylene into a 500mL four-neck flask, start the stirring device, keep warm at 25-35°C, and add 46.9g of sulfur dropwise at a constant speed at this temperature The acid chloride was added dropwise for 8 hours. After the dropwise addition was completed, sampling and analysis showed that the primary conversion rate of 3,5-dimethylphenol was 68.09%. The precipitated solid crude product 1 was separated from the mother liquor 1 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
  • Chlorination 2 re-add the mother liquor 1 into the four-necked flask, then start the stirring device, keep it warm at 30-35°C, continue to add 26.3g of sulfuryl chloride dropwise at this temperature, and the dropping time is 2 hours, and the dropping is completed , sampling analysis, the secondary conversion rate of 3,5-dimethylphenol was 29.32%.
  • the precipitated solid crude product 2 was separated from the mother liquor 2 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
  • Chlorination 1 Add 61g of 3,5-dimethylphenol and 305g of tetrachlorethylene into a 500mL four-neck flask, start the stirring device, keep warm at 25-35°C, and add 44.0g of sulfur dropwise at a constant speed at this temperature The acid chloride was added dropwise for 7 hours. After the dropwise addition was completed, sampling and analysis showed that the primary conversion rate of 3,5-dimethylphenol was 64.81%. The precipitated solid crude product 1 was separated from the mother liquor 1 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
  • Chlorination 2 re-add the mother liquor 1 into the four-necked flask, then start the stirring device, keep it warm at 30-35°C, continue to add 29.2g of sulfuryl chloride dropwise at this temperature, and the dropping time is 3 hours, and the dropping is completed , sampling analysis, the secondary conversion rate of 3,5-dimethylphenol was 32.93%.
  • the precipitated solid crude product 2 was separated from the mother liquor 2 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
  • Chlorination 1 Add 61g of 3,5-dimethylphenol and 305g of tetrachlorethylene into a 500mL four-neck flask, start the stirring device, keep warm at 25-35°C, and add 51.2g of sulfur dropwise at a constant speed at this temperature The acid chloride was added dropwise for 8 hours. After the dropwise addition was completed, sampling and analysis showed that the primary conversion rate of 3,5-dimethylphenol was 72.32%. The precipitated solid crude product 1 was separated from the mother liquor 1 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
  • Chlorination 2 re-add the mother liquor 1 into the four-necked flask, then start the stirring device, keep it warm at 30-35°C, continue to add 22.0g of sulfuryl chloride dropwise at this temperature, and the dropping time is 2 hours, and the dropping is completed , sampling analysis, the secondary conversion rate of 3,5-dimethylphenol was 23.08%.
  • the precipitated solid crude product 2 was separated from the mother liquor 2 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
  • Embodiment 6 (experiment applied mechanically)
  • Chlorination 1 Mix the mother liquor 1 and 2 in Example 1 with the crystallization mother liquor produced in the process of preparing 4-chloro-3,5-dimethylphenol by solid cooling and crystallization, add it to a 500mL four-necked flask, and add 59.5g of 3,5-dimethylphenol, 20g of tetrachlorethylene, start the stirring device, keep warm at 25-35°C, add 33.6g of sulfuryl chloride dropwise at a constant speed at this temperature, the dropping time is 5 hours, dropwise After completion, sampling analysis showed that the primary conversion rate of 3,5-dimethylphenol was 47.29%.
  • the precipitated solid crude product 1 was separated from the mother liquor 1 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
  • Chlorination 2 re-add the mother liquor 1 into the four-necked flask, then start the stirring device, keep it warm at 30-35°C, continue to add 33.6g of sulfuryl chloride dropwise at this temperature, and the dropping time is 2 hours, and the dropping is completed , sampling analysis, the secondary conversion rate of 3,5-dimethylphenol was 48.20%.
  • the precipitated solid crude product 2 was separated from the mother liquor 2 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
  • Embodiment 7 is a diagrammatic representation of Embodiment 7:
  • Chlorination 1 Add 61g of 3,5-dimethylphenol and 305g of dichloromethane into a 500mL four-neck flask, start the stirring device, keep warm at 25-35°C, and pour into the solution at a uniform speed at this temperature Chlorine gas, the flow rate of chlorine gas is 1.5L/h, the reaction time is 6 hours, the dropwise addition is completed, and the sampling analysis shows that the primary conversion rate of 3,5-dimethylphenol is 63.28%.
  • the precipitated solid crude product 1 was separated from the mother liquor 1 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
  • Chlorination 2 re-add the mother liquor 1 into the four-neck flask, then start the stirring device, keep it warm at 30-35°C, and continue to feed chlorine gas into the mother liquor 1 at a constant speed at this temperature, the flow rate of chlorine gas is 1.2L/h, The reaction time was 4 hours. After the dropwise addition was completed, sampling and analysis showed that the secondary conversion rate of 3,5-dimethylphenol was 32.95%.
  • the precipitated solid crude product 2 was separated from the mother liquor 2 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
  • Chlorination 1 Add 61g of 3,5-dimethylphenol and 305g of tetrachlorethylene into a 500mL four-neck flask, start the stirring device, keep warm at 25-35°C, and add 30.0g of sulfur dropwise at a constant speed at this temperature The acid chloride was added dropwise for 4 hours. After the dropwise addition was completed, sampling and analysis showed that the primary conversion rate of 3,5-dimethylphenol was 39.63%. The precipitated solid crude product 1 was separated from the mother liquor 1 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
  • Chlorination 2 re-add the mother liquor 1 into the four-necked flask, then start the stirring device, keep it warm at 30-35°C, continue to add 22.0g of sulfuryl chloride dropwise at this temperature, and the dropping time is 2 hours, and the dropping is completed , sampling analysis, the secondary conversion rate of 3,5-dimethylphenol was 29.51%.
  • the precipitated solid crude product 2 was separated from the mother liquor 2 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
  • Chlorination 3 re-add the mother liquor 2 into the four-necked flask, then start the stirring device, keep it warm at 30-35°C, continue to add 21.2g of sulfuryl chloride dropwise at this temperature, and the dropping time is 2 hours, and the dropping is completed , sampling analysis, 3,5-xylenol three times conversion rate of 29.32%.
  • the precipitated solid crude product 3 was separated from the mother liquor 3 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
  • the reaction solution was crystallized, centrifuged and dried to obtain white needle-like crystal product 4-chloro-3,5-dimethylphenol (63.9g, 99.64%), the product yield was 81.43%, and the product selectivity was 92.10%.
  • the reaction solution was crystallized, centrifuged, and dried to obtain the white needle-like crystal product 4-chloro-3,5-dimethylphenol (65.6g, 99.58%), the product yield was 83.62%, and the product selectivity was 84.34%.
  • the reaction solution was crystallized, centrifuged and dried to obtain the white needle crystal product 4-chloro-3,5-dimethylphenol (63.9g, 99.47%), the product yield was 81.36%, and the product selectivity was 91.68%.

Abstract

Disclosed in the present invention is a method for preparing 4-chloro-3,5-dimethylphenol by means of low-temperature chlorination. The method comprises: (1) subjecting 3,5-dimethylphenol and a chlorinating agent to a chlorination reaction at a low temperature until a solid is precipitated, and carrying out solid-liquid separation to obtain a solid crude product 1 and an intermediate mother solution; (2) further subjecting the intermediate mother solution to a chlorination reaction at a low temperature, and after the reaction is finished, carrying out final solid-liquid separation to obtain a solid crude product 2 and a final mother solution; and subjecting the solid crude product 1 and the solid crude product 2 to a post-treatment to obtain 4-chloro-3,5-dimethylphenol. By means of the present invention, by separating precipitated crystals in a timely manner during the reaction process, the wrapping of raw materials is reduced, and the conversion rate is improved.

Description

一种低温氯化制备4-氯-3,5-二甲基苯酚的方法A method for preparing 4-chloro-3,5-dimethylphenol by low-temperature chlorination 技术领域technical field
本发明属于精细化工领域，具体涉及一种低温氯化制备4-氯-3,5-二甲基苯酚的方法。The invention belongs to the field of fine chemicals, and in particular relates to a method for preparing 4-chloro-3,5-dimethylphenol by low-temperature chlorination.
背景技术Background technique
4-氯-3,5-二甲基苯酚，结构如式(I)所示，是一种广谱的防霉抗菌剂，对多数革兰氏阳性、阴性菌、真菌、霉菌都有杀灭功效，它可作为防霉抗菌剂广泛应用于消毒或个人护理用品，如去屑香波，洗手液、肥皂和其它卫生用品等抗菌洗涤剂中。也可以作为防腐剂和防霉剂用于胶水、涂料、油漆、纺织、皮革、造纸等工业领域。4-氯-3,5-二甲基苯酚由于其优异的杀菌和防腐功能，发展前景看好，已被广大消费者认可。4-Chloro-3,5-dimethylphenol, whose structure is shown in formula (I), is a broad-spectrum antifungal and antibacterial agent, which can kill most Gram-positive and negative bacteria, fungi, and molds Efficacy, it can be widely used as an anti-mildew and anti-bacterial agent in disinfection or personal care products, such as anti-dandruff shampoo, anti-bacterial detergent such as hand sanitizer, soap and other hygiene products. It can also be used as a preservative and antifungal agent in glue, paint, paint, textile, leather, paper and other industrial fields. 4-Chloro-3,5-dimethylphenol has a good development prospect due to its excellent bactericidal and antiseptic functions, and has been recognized by consumers.
Figure PCTCN2022101130-appb-000001
Figure PCTCN2022101130-appb-000001
4-氯-3,5-二甲基苯酚在工业上一般以3,5-二甲基苯酚为原料，在氯化剂的作用下进行氯化反应得到，所用的氯化剂可以为硫酰氯或氯气。专利CN104326881A中提到一种以四氯乙烯为溶剂，苄硫酚和氯化铝为共催化剂，硫酰氯为氯化剂，通过低温氯化、高温氯化两阶段进行定向氯化反应合成4-氯-3,5-二甲基苯酚的方法。该方法利用低温氯化保持产品4-氯-3,5-二甲基苯酚的选择性，高温氯化提高底物的转化率，从而实现提高产品收率的目的。但是，在高温氯化(50～65℃)阶段，还是会导致产品的选择性降低，并且该方法的催化剂回收困难，对环境污染严重。4-Chloro-3,5-dimethylphenol is generally obtained from 3,5-dimethylphenol in industry by chlorination under the action of a chlorinating agent. The chlorinating agent used can be sulfuryl chloride or chlorine gas. Patent CN104326881A mentions a kind of using tetrachlorethylene as solvent, benzylthiophenol and aluminum chloride as co-catalyst, sulfuryl chloride as chlorinating agent, and synthesizes 4- Chloro-3,5-dimethylphenol method. The method utilizes low-temperature chlorination to maintain the selectivity of the product 4-chloro-3,5-dimethylphenol, and high-temperature chlorination to increase the conversion rate of the substrate, thereby achieving the purpose of increasing product yield. However, in the high-temperature chlorination (50-65° C.) stage, the selectivity of the product will still be reduced, and the recovery of the catalyst in this method is difficult, causing serious environmental pollution.
专利CN102675055B中公开了一种高温氯化生产对氯间二甲苯酚的新方法，将硫酰氯气化后送入氯化塔下部，将液态原料进行预热升温后送入氯化塔上部，原料与气态硫酰氯在氯化塔内接触发生反应，物料通过循环泵强制外循环，循环泵出口设置换热器调节氯化塔内的温度。该方法可实 现自动控制，连续化程度高，但是反应温度较高，产品选择性较差。Patent CN102675055B discloses a new method for producing p-chloro-m-xylenol by high-temperature chlorination. After sulfuryl chloride is vaporized, it is sent to the lower part of the chlorination tower, and the liquid raw material is preheated and then sent to the upper part of the chlorination tower. Contact with gaseous sulfuryl chloride in the chlorination tower to react, the material is forced to circulate externally through the circulation pump, and a heat exchanger is installed at the outlet of the circulation pump to adjust the temperature in the chlorination tower. This method can realize automatic control, and continuous degree is high, but reaction temperature is higher, and product selectivity is poorer.
专利CN103351282B公开了一种4-氯-3,5-二甲基苯酚的制备方法，由二价铜盐作催化剂，以3,5-二甲基苯酚为原料，氧气为氧化剂，盐酸为氯化剂，在90～98℃下进行反应合成3,5-二甲基-4-氯苯酚。该方法实际的3,5-二甲基苯酚转化率达到99％时，产品的选择性仅达到80％，产品选择性低，产物分离难度增加。Patent CN103351282B discloses a preparation method of 4-chloro-3,5-dimethylphenol, using divalent copper salt as catalyst, 3,5-dimethylphenol as raw material, oxygen as oxidant, hydrochloric acid as chlorination Reagent, react at 90-98°C to synthesize 3,5-dimethyl-4-chlorophenol. When the actual conversion rate of 3,5-dimethylphenol in this method reaches 99%, the product selectivity only reaches 80%, the product selectivity is low, and the difficulty of product separation increases.
专利CN101823941B中公开了一种4-氯-3,5-二甲基苯酚的绿色工业化制备方法，以水为溶剂，硫酰氯或氯气为氯化剂，将底物3,5-二甲基苯酚通过多段控温的方式进行氯化反应。该方法的操作较为繁琐，难以在工业上大规模应用，而且反应过程中温度较高，导致反应选择性降低，反应过程生成的邻氯代副产物和二氯代副产物有10％以上。Patent CN101823941B discloses a green industrialized preparation method of 4-chloro-3,5-dimethylphenol, using water as a solvent, sulfuryl chloride or chlorine as a chlorinating agent, and the substrate 3,5-dimethylphenol The chlorination reaction is carried out by means of multi-stage temperature control. The operation of the method is cumbersome, it is difficult to be applied on a large scale in industry, and the temperature in the reaction process is high, resulting in a decrease in reaction selectivity, and more than 10% of ortho-chlorinated by-products and di-chlorinated by-products are generated in the reaction process.
专利CN102659528A公开了连续釜式氯化工艺，该氯化工艺氯化剂通过分批次进行加入，在一定程度上提高了反应的转化率和降低了副反应的发生，但是本发明人发现，在该氯化工艺中存在着晶体析出的问题，如氯化釜B和氯化釜C会有晶体析出，尤其是氯化釜C中析出的晶体更多，析出的晶体多，导致原料3,5-二甲基苯酚发生包裹，影响了反应的转化率，该专利最后仅仅分析了氯化釜C的出料口的组分组成，未考虑原料的包裹问题，其分析结果与实际反应过程有一定的偏差。Patent CN102659528A discloses a continuous tank type chlorination process. The chlorination process chlorination agent is added in batches, which improves the conversion rate of the reaction and reduces the occurrence of side reactions to a certain extent. However, the inventors found that in There is the crystallization problem in this chlorination process, as chlorination still B and chlorination still C have crystallization and separate out, especially the crystallization that separates out in chlorination still C is more, and the crystallization of precipitation is many, causes raw material 3,5 -Xylenol is wrapped, which affects the conversion rate of the reaction. In the end, the patent only analyzes the composition of the outlet of the chlorination kettle C, without considering the wrapping of raw materials. The analysis results are somewhat different from the actual reaction process. deviation.
发明内容Contents of the invention
本发明所要解决的技术问题在于提供一种低温氯化制备4-氯-3,5-二甲基苯酚的方法，可以克服现有技术中低温氯化中产品结晶包裹原料所导致的转化率降低的问题。The technical problem to be solved by the present invention is to provide a method for preparing 4-chloro-3,5-dimethylphenol by low-temperature chlorination, which can overcome the reduction in conversion rate caused by product crystallization and encapsulation of raw materials in low-temperature chlorination in the prior art The problem.
一种低温氯化制备4-氯-3,5-二甲基苯酚的方法，包括：A method for preparing 4-chloro-3,5-dimethylphenol by low-temperature chlorination, comprising:
(1)3,5-二甲基苯酚和氯化剂在低温下进行氯化反应，反应进行至有固体析出，进行固液分离，得到固体粗产物1与中间母液；(1) 3,5-dimethylphenol and a chlorinating agent are chlorinated at a low temperature, and the reaction is carried out until a solid is precipitated, and the solid-liquid separation is carried out to obtain a solid crude product 1 and an intermediate mother liquor;
(2)中间母液进一步在低温下进行氯化反应，反应完成后进行末次固液分离，得到固体粗产物2和最终母液；(2) The intermediate mother liquor is further chlorinated at a low temperature, and the final solid-liquid separation is carried out after the reaction is completed to obtain the solid crude product 2 and the final mother liquor;
固体粗产物1和固体粗产物2经过后处理得到所述的4-氯-3,5-二甲基苯酚。The solid crude product 1 and the solid crude product 2 were post-processed to obtain the 4-chloro-3,5-dimethylphenol.
本发明人经过研究发现，低温氯化导致原料转化率降低的原因有两 点：(1)析出的晶体密度小于溶剂密度，悬浮于溶剂表层，在溶剂表层聚集结块，阻挡氯化剂与底物的反应，而且反应装置越大，这种阻碍现象越明显，底物转化率越低；(2)晶体结块，会包裹原料，又会造成部分原料无法参与反应。以上两点是影响3,5-二甲基苯酚在低温条件下转化率低的主要原因。本发明通过将析出的晶体及时与反应液分离，既可以避免晶体大面积结块，包裹原料，又可以避免析出的晶体阻挡氯化剂与底物的反应，特别适应于大生产工艺。此外，析出的晶体通过纯化处理，得到合格的产品，剩余的原料通过多次累积，回收后用于制备4-氯-3,5-二甲基苯酚，使得剩余的原料转化完全。The inventors have found through research that there are two reasons why the low-temperature chlorination causes the conversion rate of raw materials to decrease: (1) the density of the precipitated crystals is less than that of the solvent, suspended on the surface of the solvent, and agglomerated on the surface of the solvent to prevent the chlorination agent from contacting the bottom. And the larger the reaction device, the more obvious the hindrance phenomenon and the lower the conversion rate of the substrate; (2) The crystal agglomeration will wrap the raw materials and cause some raw materials to fail to participate in the reaction. The above two points are the main reasons for the low conversion rate of 3,5-dimethylphenol under low temperature conditions. By separating the precipitated crystals from the reaction liquid in time, the present invention can not only avoid large-area agglomeration of the crystals and wrap the raw materials, but also prevent the precipitated crystals from blocking the reaction between the chlorinating agent and the substrate, and is especially suitable for large-scale production processes. In addition, the precipitated crystals are purified to obtain qualified products, and the remaining raw materials are accumulated multiple times and recovered for the preparation of 4-chloro-3,5-dimethylphenol, so that the remaining raw materials are completely converted.
作为优选，步骤(1)中，氯化反应的温度为25～35℃，反应时间为5～8小时，由于固体产物及时从反应液中分离，较低的反应温度有利于产物转化率的提高。As preferably, in step (1), the temperature of the chlorination reaction is 25 to 35°C, and the reaction time is 5 to 8 hours. Since the solid product is separated from the reaction solution in time, a lower reaction temperature is conducive to the improvement of the product conversion rate. .
本发明中，所述的氯化剂可以采用现有技术中常用的对苯环进行氯化反应的试剂，作为优选，步骤(1)中，所述的氯化剂为硫酰氯、氯气中的一种或者两种。Among the present invention, described chlorination agent can adopt the reagent that chlorination reaction is carried out to benzene ring commonly used in the prior art, as preferably, in step (1), described chlorination agent is sulfuryl chloride, chlorine in One or two.
作为优选，步骤(1)中，氯化反应在卤代烃类溶剂中进行；所述的卤代烃类溶剂优选为氯取代的C 1～C 3烃类化合物；更优选为二氯甲烷、三氯甲烷、四氯化碳、三氯乙烯、四氯乙烯中的一种或多种组合，最优选为在四氯乙烯中进行。 As a preference, in step (1), the chlorination reaction is carried out in a halogenated hydrocarbon solvent; the halogenated hydrocarbon solvent is preferably chlorine-substituted C 1 -C 3 hydrocarbon compounds; more preferably dichloromethane, One or more combinations of chloroform, carbon tetrachloride, trichloroethylene, and tetrachloroethylene are most preferably carried out in tetrachloroethylene.
本发明的步骤(1)和步骤(2)中，当所述的氯化剂为硫酰氯，3,5-二甲基苯酚与硫酰氯总量的质量比为1：1.1～1.5；当所述的氯化剂为氯气时，氯气的流量范围为1～2L/h。In step (1) and step (2) of the present invention, when the chlorinating agent is sulfuryl chloride, the mass ratio of 3,5-dimethylphenol to the total amount of sulfuryl chloride is 1:1.1-1.5; When the above-mentioned chlorinating agent is chlorine gas, the flow range of chlorine gas is 1-2 L/h.
作为优选，所述的氯化剂为硫酰氯，硫酰氯分批加入，步骤(1)中，以质量计，3,5-二甲基苯酚：硫酰氯＝1:0.5～0.8；As a preference, the chlorinating agent is sulfuryl chloride, and sulfuryl chloride is added in batches. In step (1), by mass, 3,5-dimethylphenol:sulfuryl chloride=1:0.5～0.8;
步骤(2)中，以质量计，3,5-二甲基苯酚：硫酰氯＝1:0.3～0.8。In step (2), by mass, 3,5-dimethylphenol:sulfuryl chloride=1:0.3-0.8.
步骤(1)和步骤(2)中，两次氯化剂加入方式不限，可以是滴加，可以是计量泵转料，可以是喷射器喷射进料(增大接触面积)，也可以是进料管插入液面以下进料(气体进料)等，作为优选，当氯化剂为硫酰氯时，步骤(1)和步骤(2)中，硫酰氯采用滴加的方式加入。In step (1) and step (2), the way of adding chlorinating agent for two times is not limited, it can be dripping, it can be metering pump transfer, it can be injector injection feeding (increase contact area), it can also be Feed pipe is inserted below the liquid surface feed (gas feed) etc., as preferably, when chlorinating agent is sulfuryl chloride, in step (1) and step (2), sulfuryl chloride adopts the mode of dripping to add.
作为优选，步骤(2)中，所述氯化反应的温度为30～35℃，反应时间为2～5小时。步骤(2)的反应可以比步骤(1)反应温度略高，以促进 后期反应的进行。Preferably, in step (2), the temperature of the chlorination reaction is 30-35° C., and the reaction time is 2-5 hours. The reaction of step (2) can be slightly higher than step (1) temperature of reaction, to promote the carrying out of later stage reaction.
作为优选，步骤(1)和(2)中，所述固液分离的操作方式为离心或者过滤；As a preference, in steps (1) and (2), the operation mode of the solid-liquid separation is centrifugation or filtration;
所述固体粗产物1和固体粗产物2通过降温结晶得到4-氯-3,5-二甲基苯酚。其中，降温结晶的具体过程如下：将固体粗产物1和固体粗产物2混合，加入1.5～2.0倍的溶剂(以混合固体质量计，优选为四氯乙烯)，升温75～85℃搅拌溶解，然后以3～8℃/h的速率降温，最终温度控制在25～30℃，通过离心获得产品4-氯-3,5-二甲基苯酚和结晶母液。The solid crude product 1 and the solid crude product 2 were crystallized by cooling down to obtain 4-chloro-3,5-dimethylphenol. Among them, the specific process of cooling crystallization is as follows: mix the solid crude product 1 and the solid crude product 2, add 1.5 to 2.0 times the solvent (based on the mass of the mixed solid, preferably tetrachloroethylene), heat up to 75 to 85 ° C and stir to dissolve, Then the temperature is lowered at a rate of 3-8°C/h, the final temperature is controlled at 25-30°C, and the product 4-chloro-3,5-dimethylphenol and crystallization mother liquor are obtained by centrifugation.
作为优选，固液分离得到的母液、降温结晶得到的结晶母液加入到下一批次的氯化反应中进行套用。通过该套用操作，可以进一步提高原料的利用率，减少废液的排放处理。As a preference, the mother liquor obtained by solid-liquid separation and the crystallization mother liquor obtained by cooling crystallization are added to the next batch of chlorination reaction and applied mechanically. Through this applied operation, the utilization rate of raw materials can be further improved, and the discharge and treatment of waste liquid can be reduced.
作为优选，低温氯化反应产生的尾气经过冷凝，进行回收。Preferably, the tail gas produced by the low-temperature chlorination reaction is condensed and recovered.
步骤(1)中，其中固液分离的次数无特别的限定，可以为一次或者多次，作为优选，所述固液分离的次数为一次，在转化率达到40～70％时进行，此时可以兼顾操作方便和反应收率的目的；作为另外的优选，所述固液分离的次数为多次，每次固液分离得到的固体合并为固体粗产物1，每次固液分离得到的中间母液继续进行反应。分离次数的增加可以及时转移析出的固体，有利于反应的发生，但是分离次数过多也会造成操作复杂，分离次数进一步优选为2～4次。In step (1), the number of solid-liquid separations is not particularly limited, and may be one or more times. Preferably, the number of solid-liquid separations is one time, and is carried out when the conversion rate reaches 40-70%. At this time The purpose of easy operation and reaction yield can be taken into account; as another preference, the number of solid-liquid separations is multiple times, and the solids obtained by solid-liquid separations are combined into solid crude product 1, and the intermediate obtained by solid-liquid separations each time is The mother liquor continues to react. An increase in the number of separations can transfer the precipitated solids in time, which is beneficial to the occurrence of the reaction, but too many separation times will also cause complicated operations, and the number of separations is further preferably 2 to 4 times.
同现有技术相比，本发明的有益效果体现在：Compared with the prior art, the beneficial effects of the present invention are reflected in:
(1)本发明在反应过程中及时将析出的晶体分离出来，一方面减少了原料的包裹，提高了转化率，另一方面减少了结晶物对反应的阻碍，增加了反应速率；(1) The present invention separates the precipitated crystals in time during the reaction process, which reduces the wrapping of raw materials on the one hand, improves the conversion rate, reduces the hindrance of the crystallization to the reaction on the other hand, and increases the reaction rate;
(2)低温氯化能够提高产品的选择性，减少副产物的生成，因此废液处理量也会大幅度降低，有利于环保。(2) Low-temperature chlorination can improve the selectivity of products and reduce the generation of by-products, so the amount of waste liquid treatment will also be greatly reduced, which is conducive to environmental protection.
附图说明Description of drawings
图1为本发明的制备4-氯-3,5-二甲基苯酚的一种具体实施方式的工艺流程图。Fig. 1 is a process flow diagram of a specific embodiment for preparing 4-chloro-3,5-dimethylphenol of the present invention.
具体实施方式detailed description
图1为本发明的制备4-氯-3,5-二甲基苯酚的一种具体实施方式的工艺流程图，如图1所示，该制备方法具体包括以下步骤：Fig. 1 is the process flow diagram of a specific embodiment of preparing 4-chloro-3,5-dimethylphenol of the present invention, as shown in Fig. 1, the preparation method specifically includes the following steps:
(1)3,5-二甲基苯酚和氯化剂在溶剂中进行氯化反应1，氯化反应1进行至有固体析出，进行离心分离，得到固体粗产物1与母液1；(1) 3,5-dimethylphenol and a chlorination agent are carried out in a solvent for a chlorination reaction 1, and the chlorination reaction 1 is carried out until a solid is precipitated, and centrifuged to obtain a solid crude product 1 and a mother liquor 1;
(2)母液1进一步与氯化剂进行氯化反应2，反应完成后进行离心分离，得到固体粗产物2和母液2，母液2套用至下一批次氯化反应；(2) mother liquor 1 further carries out chlorination reaction 2 with chlorinating agent, centrifuges after completion of the reaction to obtain solid crude product 2 and mother liquor 2, and mother liquor 2 is applied mechanically to the next batch of chlorination reactions;
固体粗产品1和固体粗产物2合并后进行结晶，得到的4-氯-3,5-二甲基苯酚产品和结晶母液，结晶母液也套用至下一批次氯化反应。The solid crude product 1 and the solid crude product 2 are combined and then crystallized to obtain the 4-chloro-3,5-dimethylphenol product and crystallization mother liquor, and the crystallization mother liquor is also applied to the next batch of chlorination reaction.
氯化反应1和氯化反应2产生的氯化尾气进行后处理。The chlorination tail gas produced by chlorination reaction 1 and chlorination reaction 2 is post-treated.
以下结合具体实施例对本发明作进一步的描述，实施例中得到的产物的纯度，如无特别说明为HPLC纯度。The present invention will be further described below in conjunction with specific examples, and the purity of the product obtained in the examples is HPLC purity unless otherwise specified.
实施例1Example 1
氯化1：在500mL的四口烧瓶中加入61g 3,5-二甲基苯酚，四氯乙烯122g，启动搅拌装置，保温在25～35℃之间，在此温度下匀速滴加33.6g硫酰氯，滴加时间为5小时，滴加完毕，取样分析，3,5-二甲基苯酚一次转化率为48.78％。通过降温离心将析出的固体粗产物1与母液1分离，温度控制在20～25℃。Chlorination 1: Add 61g of 3,5-dimethylphenol and 122g of tetrachlorethylene into a 500mL four-neck flask, start the stirring device, keep warm at 25-35°C, and add 33.6g of sulfur dropwise at a constant speed at this temperature The acid chloride was added dropwise for 5 hours. After the dropwise addition was completed, sampling and analysis showed that the primary conversion rate of 3,5-dimethylphenol was 48.78%. The precipitated solid crude product 1 was separated from the mother liquor 1 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
氯化2：母液1重新加入到四口烧瓶中，然后启动搅拌装置，保温在30～35℃之间，在此温度下继续滴加33.6g硫酰氯，滴加时间为3小时，滴加完毕，取样分析，3,5-二甲基苯酚二次转化率为47.78％。通过降温离心将析出的固体粗产物2与母液2分离，温度控制在20～25℃。Chlorination 2: re-add the mother liquor 1 into the four-necked flask, then start the stirring device, keep the temperature between 30 and 35°C, continue to add 33.6g of sulfuryl chloride dropwise at this temperature, and the dropping time is 3 hours, and the dropping is completed , sampling analysis, the secondary conversion rate of 3,5-dimethylphenol was 47.78%. The precipitated solid crude product 2 was separated from the mother liquor 2 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
将固体粗产物1与固体粗产物2合并处理，加入105.0g四氯乙烯，升温至80℃搅拌溶解，缓慢降温至25～30℃，经过离心、干燥后得到白色针状结晶产物4-氯-3,5-二甲基苯酚(69.97g，99.28％)，原料的两次转化率之和为96.56％，产品收率88.84％，产品选择性92.01％，结晶母液作为原料套用至下一批反应。Combine the solid crude product 1 and the solid crude product 2, add 105.0g of tetrachloroethylene, heat up to 80°C and stir to dissolve, slowly cool down to 25-30°C, centrifuge and dry to obtain the white needle crystal product 4-chloro- 3,5-Xylenol (69.97g, 99.28%), the sum of the two conversions of raw materials is 96.56%, the product yield is 88.84%, and the product selectivity is 92.01%. The crystallized mother liquor is used as a raw material for the next batch of reactions .
实施例2Example 2
氯化1：在500mL的四口烧瓶中加入61g 3,5-二甲基苯酚，四氯乙烯183g，启动搅拌装置，保温在25～35℃之间，在此温度下匀速滴加40.3g 硫酰氯，滴加时间为6小时，滴加完毕，取样分析，3,5-二甲基苯酚一次转化率为58.50％。通过降温离心将析出的固体粗产物1与母液1分离，温度控制在20～25℃。Chlorination 1: Add 61g of 3,5-dimethylphenol and 183g of tetrachlorethylene into a 500mL four-necked flask, start the stirring device, keep warm at 25-35°C, and add 40.3g of sulfur dropwise at a constant speed at this temperature The acid chloride was added dropwise for 6 hours. After the dropwise addition was completed, sampling and analysis showed that the primary conversion rate of 3,5-dimethylphenol was 58.50%. The precipitated solid crude product 1 was separated from the mother liquor 1 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
氯化2：母液1重新加入到四口烧瓶中，然后启动搅拌装置，保温在30～35℃之间，在此温度下继续滴加29.9g硫酰氯，滴加时间为4小时，滴加完毕，取样分析，3,5-二甲基苯酚二次转化率为38.47％。通过降温离心将析出的固体粗产物2与母液2分离，温度控制在20～25℃。Chlorination 2: re-add the mother liquor 1 into the four-necked flask, then start the stirring device, keep it warm at 30-35°C, continue to add 29.9g of sulfuryl chloride dropwise at this temperature, and the dropping time is 4 hours, and the dropping is completed , sampling analysis, the secondary conversion rate of 3,5-dimethylphenol was 38.47%. The precipitated solid crude product 2 was separated from the mother liquor 2 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
将固体粗产物1与固体粗产物2合并处理，加入105.0g四氯乙烯，升温至80℃搅拌溶解，缓慢降温至25～30℃，经过离心、干燥后得到白色针状结晶产物4-氯-3,5-二甲基苯酚(69.62g，99.42％)，原料的两次转化率之和为96.97％，产品收率88.52％，产品选择性91.29％，结晶母液作为原料套用至下一批反应。Combine the solid crude product 1 and the solid crude product 2, add 105.0g of tetrachloroethylene, heat up to 80°C and stir to dissolve, slowly cool down to 25-30°C, centrifuge and dry to obtain the white needle crystal product 4-chloro- 3,5-Xylenol (69.62g, 99.42%), the sum of the two conversions of raw materials is 96.97%, the product yield is 88.52%, and the product selectivity is 91.29%. The crystallized mother liquor is used as a raw material for the next batch of reactions .
实施例3Example 3
氯化1：在500mL的四口烧瓶中加入61g 3,5-二甲基苯酚，四氯乙烯305g，启动搅拌装置，保温在25～35℃之间，在此温度下匀速滴加46.9g硫酰氯，滴加时间为8小时，滴加完毕，取样分析，3,5-二甲基苯酚一次转化率为68.09％。通过降温离心将析出的固体粗产物1与母液1分离，温度控制在20～25℃。Chlorination 1: Add 61g of 3,5-dimethylphenol and 305g of tetrachlorethylene into a 500mL four-neck flask, start the stirring device, keep warm at 25-35°C, and add 46.9g of sulfur dropwise at a constant speed at this temperature The acid chloride was added dropwise for 8 hours. After the dropwise addition was completed, sampling and analysis showed that the primary conversion rate of 3,5-dimethylphenol was 68.09%. The precipitated solid crude product 1 was separated from the mother liquor 1 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
氯化2：母液1重新加入到四口烧瓶中，然后启动搅拌装置，保温在30～35℃之间，在此温度下继续滴加26.3g硫酰氯，滴加时间为2小时，滴加完毕，取样分析，3,5-二甲基苯酚二次转化率为29.32％。通过降温离心将析出的固体粗产物2与母液2分离，温度控制在20～25℃。Chlorination 2: re-add the mother liquor 1 into the four-necked flask, then start the stirring device, keep it warm at 30-35°C, continue to add 26.3g of sulfuryl chloride dropwise at this temperature, and the dropping time is 2 hours, and the dropping is completed , sampling analysis, the secondary conversion rate of 3,5-dimethylphenol was 29.32%. The precipitated solid crude product 2 was separated from the mother liquor 2 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
将固体粗产物1与固体粗产物2合并处理，加入108.0g四氯乙烯，升温至80℃搅拌溶解，缓慢降温至25～30℃，经过离心、干燥后得到白色针状结晶产物4-氯-3,5-二甲基苯酚(71.10g，99.35％)，原料的两次转化率之和为97.41％，产品收率90.33％，产品选择性92.73％，结晶母液作为原料套用至下一批反应。Combine the solid crude product 1 and the solid crude product 2, add 108.0g of tetrachlorethylene, heat up to 80°C and stir to dissolve, slowly cool down to 25-30°C, centrifuge and dry to obtain the white needle crystal product 4-chloro- 3,5-Xylenol (71.10g, 99.35%), the sum of the two conversions of raw materials is 97.41%, the product yield is 90.33%, and the product selectivity is 92.73%. The crystallized mother liquor is used as a raw material for the next batch of reactions .
实施例4Example 4
氯化1：在500mL的四口烧瓶中加入61g 3,5-二甲基苯酚，四氯乙烯 305g，启动搅拌装置，保温在25～35℃之间，在此温度下匀速滴加44.0g硫酰氯，滴加时间为7小时，滴加完毕，取样分析，3,5-二甲基苯酚一次转化率为64.81％。通过降温离心将析出的固体粗产物1与母液1分离，温度控制在20～25℃。Chlorination 1: Add 61g of 3,5-dimethylphenol and 305g of tetrachlorethylene into a 500mL four-neck flask, start the stirring device, keep warm at 25-35°C, and add 44.0g of sulfur dropwise at a constant speed at this temperature The acid chloride was added dropwise for 7 hours. After the dropwise addition was completed, sampling and analysis showed that the primary conversion rate of 3,5-dimethylphenol was 64.81%. The precipitated solid crude product 1 was separated from the mother liquor 1 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
氯化2：母液1重新加入到四口烧瓶中，然后启动搅拌装置，保温在30～35℃之间，在此温度下继续滴加29.2g硫酰氯，滴加时间为3小时，滴加完毕，取样分析，3,5-二甲基苯酚二次转化率为32.93％。通过降温离心将析出的固体粗产物2与母液2分离，温度控制在20～25℃。Chlorination 2: re-add the mother liquor 1 into the four-necked flask, then start the stirring device, keep it warm at 30-35°C, continue to add 29.2g of sulfuryl chloride dropwise at this temperature, and the dropping time is 3 hours, and the dropping is completed , sampling analysis, the secondary conversion rate of 3,5-dimethylphenol was 32.93%. The precipitated solid crude product 2 was separated from the mother liquor 2 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
将固体粗产物1与固体粗产物2合并处理，加入110.0g四氯乙烯，升温至80℃搅拌溶解，缓慢降温至25～30℃，经过离心、干燥后得到白色针状结晶产物4-氯-3,5-二甲基苯酚(72.61g，99.41％)，原料的两次转化率之和为97.74％，产品收率92.31％，产品选择性94.44％，结晶母液作为原料套用至下一批反应。Combine the solid crude product 1 and the solid crude product 2, add 110.0g of tetrachlorethylene, heat up to 80°C and stir to dissolve, slowly cool down to 25-30°C, centrifuge and dry to obtain the white needle crystal product 4-chloro- 3,5-Xylenol (72.61g, 99.41%), the sum of the two conversions of raw materials is 97.74%, the product yield is 92.31%, and the product selectivity is 94.44%. The crystallized mother liquor is used as a raw material for the next batch of reactions .
实施例5Example 5
氯化1：在500mL的四口烧瓶中加入61g 3,5-二甲基苯酚，四氯乙烯305g，启动搅拌装置，保温在25～35℃之间，在此温度下匀速滴加51.2g硫酰氯，滴加时间为8小时，滴加完毕，取样分析，3,5-二甲基苯酚一次转化率为72.32％。通过降温离心将析出的固体粗产物1与母液1分离，温度控制在20～25℃。Chlorination 1: Add 61g of 3,5-dimethylphenol and 305g of tetrachlorethylene into a 500mL four-neck flask, start the stirring device, keep warm at 25-35°C, and add 51.2g of sulfur dropwise at a constant speed at this temperature The acid chloride was added dropwise for 8 hours. After the dropwise addition was completed, sampling and analysis showed that the primary conversion rate of 3,5-dimethylphenol was 72.32%. The precipitated solid crude product 1 was separated from the mother liquor 1 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
氯化2：母液1重新加入到四口烧瓶中，然后启动搅拌装置，保温在30～35℃之间，在此温度下继续滴加22.0g硫酰氯，滴加时间为2小时，滴加完毕，取样分析，3,5-二甲基苯酚二次转化率为23.08％。通过降温离心将析出的固体粗产物2与母液2分离，温度控制在20～25℃。Chlorination 2: re-add the mother liquor 1 into the four-necked flask, then start the stirring device, keep it warm at 30-35°C, continue to add 22.0g of sulfuryl chloride dropwise at this temperature, and the dropping time is 2 hours, and the dropping is completed , sampling analysis, the secondary conversion rate of 3,5-dimethylphenol was 23.08%. The precipitated solid crude product 2 was separated from the mother liquor 2 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
将固体粗产物1与固体粗产物2合并处理，加入108.0g四氯乙烯，升温至80℃搅拌溶解，缓慢降温至25～30℃，经过离心、干燥后得到白色针状结晶产物4-氯-3,5-二甲基苯酚(68.48g，99.29％)，原料的两次转化率之和为95.40％，产品收率86.95％，产品选择性91.14％，结晶母液作为原料套用至下一批反应。Combine the solid crude product 1 and the solid crude product 2, add 108.0g of tetrachlorethylene, heat up to 80°C and stir to dissolve, slowly cool down to 25-30°C, centrifuge and dry to obtain the white needle crystal product 4-chloro- 3,5-Xylenol (68.48g, 99.29%), the sum of the two conversions of raw materials is 95.40%, the product yield is 86.95%, and the product selectivity is 91.14%. The crystallized mother liquor is used as a raw material for the next batch of reactions .
实施例6(套用实验)Embodiment 6 (experiment applied mechanically)
氯化1：将实施例1中的母液1、2与固体降温结晶制备4-氯-3,5-二甲基苯酚过程中产生的结晶母液混合，加入到在500mL的四口烧瓶中，补充59.5g 3,5-二甲基苯酚，四氯乙烯20g，启动搅拌装置，保温在25～35℃之间，在此温度下匀速滴加33.6g硫酰氯，滴加时间为5小时，滴加完毕，取样分析，3,5-二甲基苯酚一次转化率为47.29％。通过降温离心将析出的固体粗产物1与母液1分离，温度控制在20～25℃。Chlorination 1: Mix the mother liquor 1 and 2 in Example 1 with the crystallization mother liquor produced in the process of preparing 4-chloro-3,5-dimethylphenol by solid cooling and crystallization, add it to a 500mL four-necked flask, and add 59.5g of 3,5-dimethylphenol, 20g of tetrachlorethylene, start the stirring device, keep warm at 25-35°C, add 33.6g of sulfuryl chloride dropwise at a constant speed at this temperature, the dropping time is 5 hours, dropwise After completion, sampling analysis showed that the primary conversion rate of 3,5-dimethylphenol was 47.29%. The precipitated solid crude product 1 was separated from the mother liquor 1 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
氯化2：母液1重新加入到四口烧瓶中，然后启动搅拌装置，保温在30～35℃之间，在此温度下继续滴加33.6g硫酰氯，滴加时间为2小时，滴加完毕，取样分析，3,5-二甲基苯酚二次转化率为48.20％。通过降温离心将析出的固体粗产物2与母液2分离，温度控制在20～25℃。Chlorination 2: re-add the mother liquor 1 into the four-necked flask, then start the stirring device, keep it warm at 30-35°C, continue to add 33.6g of sulfuryl chloride dropwise at this temperature, and the dropping time is 2 hours, and the dropping is completed , sampling analysis, the secondary conversion rate of 3,5-dimethylphenol was 48.20%. The precipitated solid crude product 2 was separated from the mother liquor 2 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
将固体粗产物1与固体粗产物2合并处理，加入105.0g四氯乙烯，升温至80℃搅拌溶解，缓慢降温至25～30℃，经过离心、干燥后得到白色针状结晶产物4-氯-3,5-二甲基苯酚(70.12g，99.29％)，原料的两次转化率之和为96.49％，产品收率89.03％，产品选择性92.27％，结晶母液作为原料套用至下一批反应。Combine the solid crude product 1 and the solid crude product 2, add 105.0g of tetrachloroethylene, heat up to 80°C and stir to dissolve, slowly cool down to 25-30°C, centrifuge and dry to obtain the white needle crystal product 4-chloro- 3,5-Xylenol (70.12g, 99.29%), the sum of the two conversions of raw materials is 96.49%, the product yield is 89.03%, and the product selectivity is 92.27%. The crystallized mother liquor is used as a raw material for the next batch of reactions .
实施例7：Embodiment 7:
氯化1：在500mL的四口烧瓶中加入61g 3,5-二甲基苯酚，二氯甲烷305g，启动搅拌装置，保温在25～35℃之间，在此温度下向溶液中匀速通入氯气，氯气流量为1.5L/h，反应时间为6小时，滴加完毕，取样分析，3,5-二甲基苯酚一次转化率为63.28％。通过降温离心将析出的固体粗产物1与母液1分离，温度控制在20～25℃。Chlorination 1: Add 61g of 3,5-dimethylphenol and 305g of dichloromethane into a 500mL four-neck flask, start the stirring device, keep warm at 25-35°C, and pour into the solution at a uniform speed at this temperature Chlorine gas, the flow rate of chlorine gas is 1.5L/h, the reaction time is 6 hours, the dropwise addition is completed, and the sampling analysis shows that the primary conversion rate of 3,5-dimethylphenol is 63.28%. The precipitated solid crude product 1 was separated from the mother liquor 1 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
氯化2：母液1重新加入到四口烧瓶中，然后启动搅拌装置，保温在30～35℃之间，在此温度下向母液1中继续匀速通入氯气，氯气流量为1.2L/h，反应时间为4小时，滴加完毕，取样分析，3,5-二甲基苯酚二次转化率为32.95％。通过降温离心将析出的固体粗产物2与母液2分离，温度控制在20～25℃。Chlorination 2: re-add the mother liquor 1 into the four-neck flask, then start the stirring device, keep it warm at 30-35°C, and continue to feed chlorine gas into the mother liquor 1 at a constant speed at this temperature, the flow rate of chlorine gas is 1.2L/h, The reaction time was 4 hours. After the dropwise addition was completed, sampling and analysis showed that the secondary conversion rate of 3,5-dimethylphenol was 32.95%. The precipitated solid crude product 2 was separated from the mother liquor 2 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
将固体粗产物1与固体粗产物2合并处理，加入150.0g二氯甲烷，升温至80℃搅拌溶解，缓慢降温至25～30℃，经过离心、干燥后得到白色针状结晶产物4-氯-3,5-二甲基苯酚(68.93g，99.32％)，原料的两次转化率之和为96.23％，产品收率87.52％，产品选择性90.95％，结晶母液作为原 料套用至下一批反应。Combine the solid crude product 1 and the solid crude product 2, add 150.0g of dichloromethane, heat up to 80°C and stir to dissolve, slowly cool down to 25-30°C, centrifuge and dry to obtain the white needle crystal product 4-chloro- 3,5-Xylenol (68.93g, 99.32%), the sum of the two conversions of raw materials is 96.23%, the product yield is 87.52%, and the product selectivity is 90.95%. The crystallized mother liquor is used as a raw material for the next batch of reactions .
实施例8Example 8
氯化1：在500mL的四口烧瓶中加入61g 3,5-二甲基苯酚，四氯乙烯305g，启动搅拌装置，保温在25～35℃之间，在此温度下匀速滴加30.0g硫酰氯，滴加时间为4小时，滴加完毕，取样分析，3,5-二甲基苯酚一次转化率为39.63％。通过降温离心将析出的固体粗产物1与母液1分离，温度控制在20～25℃。Chlorination 1: Add 61g of 3,5-dimethylphenol and 305g of tetrachlorethylene into a 500mL four-neck flask, start the stirring device, keep warm at 25-35°C, and add 30.0g of sulfur dropwise at a constant speed at this temperature The acid chloride was added dropwise for 4 hours. After the dropwise addition was completed, sampling and analysis showed that the primary conversion rate of 3,5-dimethylphenol was 39.63%. The precipitated solid crude product 1 was separated from the mother liquor 1 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
氯化2：母液1重新加入到四口烧瓶中，然后启动搅拌装置，保温在30～35℃之间，在此温度下继续滴加22.0g硫酰氯，滴加时间为2小时，滴加完毕，取样分析，3,5-二甲基苯酚二次转化率为29.51％。通过降温离心将析出的固体粗产物2与母液2分离，温度控制在20～25℃。Chlorination 2: re-add the mother liquor 1 into the four-necked flask, then start the stirring device, keep it warm at 30-35°C, continue to add 22.0g of sulfuryl chloride dropwise at this temperature, and the dropping time is 2 hours, and the dropping is completed , sampling analysis, the secondary conversion rate of 3,5-dimethylphenol was 29.51%. The precipitated solid crude product 2 was separated from the mother liquor 2 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
氯化3：母液2重新加入到四口烧瓶中，然后启动搅拌装置，保温在30～35℃之间，在此温度下继续滴加21.2g硫酰氯，滴加时间为2小时，滴加完毕，取样分析，3,5-二甲基苯酚三次转化率为29.32％。通过降温离心将析出的固体粗产物3与母液3分离，温度控制在20～25℃。Chlorination 3: re-add the mother liquor 2 into the four-necked flask, then start the stirring device, keep it warm at 30-35°C, continue to add 21.2g of sulfuryl chloride dropwise at this temperature, and the dropping time is 2 hours, and the dropping is completed , sampling analysis, 3,5-xylenol three times conversion rate of 29.32%. The precipitated solid crude product 3 was separated from the mother liquor 3 by cooling and centrifuging, and the temperature was controlled at 20-25°C.
将固体粗产物1、固体粗产物2与固体粗产物3合并处理，加入108.0g四氯乙烯，升温至80℃搅拌溶解，缓慢降温至25～30℃，经过离心、干燥后得到白色针状结晶产物4-氯-3,5-二甲基苯酚(72.73g，99.37％)，原料的三次转化率之和为98.46％，产品收率92.43％，产品选择性93.87％，结晶母液作为原料套用至下一批反应。Combine solid crude product 1, solid crude product 2 and solid crude product 3, add 108.0 g of tetrachlorethylene, heat up to 80°C and stir to dissolve, slowly cool down to 25-30°C, centrifuge and dry to obtain white needle crystals The product 4-chloro-3,5-dimethylphenol (72.73g, 99.37%), the sum of the three conversions of raw materials is 98.46%, the product yield is 92.43%, and the product selectivity is 93.87%. The crystallization mother liquor is used as a raw material to Next batch of responses.
对比例1Comparative example 1
在500mL的四口烧瓶中加入61g 3,5-二甲基苯酚，四氯化碳305g，然后启动搅拌装置，保温在25-35℃之间，在此温度下匀速滴加67.1g硫酰氯，滴加时间为8小时，滴加完毕，取样分析，3，5-二甲基苯酚转化率为88.42％。Add 61g of 3,5-dimethylphenol and 305g of carbon tetrachloride into a 500mL four-neck flask, then start the stirring device, keep it warm at 25-35°C, and add 67.1g of sulfuryl chloride dropwise at a constant speed at this temperature, The dropping time was 8 hours. After the dropping was completed, sampling and analysis showed that the conversion rate of 3,5-dimethylphenol was 88.42%.
反应液再分别经结晶、离心、干燥得到白色针状结晶产物4-氯-3,5-二甲基苯酚(63.9g，99.64％)，产品收率81.43％，产品选择性92.10％。The reaction solution was crystallized, centrifuged and dried to obtain white needle-like crystal product 4-chloro-3,5-dimethylphenol (63.9g, 99.64%), the product yield was 81.43%, and the product selectivity was 92.10%.
对比例2Comparative example 2
在500mL的四口烧瓶中加入61g 3,5-二甲基苯酚，四氯化碳305g，然后启动搅拌装置，在25-35℃匀速滴加33.6g硫酰氯，滴加时间为4小时。然后，将反应温度升至60～65℃，在此温度下匀速滴加16.8g硫酰氯，滴加时间为2小时。最后，将反应温度升至80～85℃，在此温度下继续匀速滴加16.8g硫酰氯，滴加时间为2小时。滴加完毕，取样分析，3，5-二甲基苯酚转化率为99.15％。Add 61g of 3,5-dimethylphenol and 305g of carbon tetrachloride into a 500mL four-neck flask, then start the stirring device, and add 33.6g of sulfuryl chloride dropwise at a constant speed at 25-35°C for 4 hours. Then, the reaction temperature was raised to 60-65° C., and 16.8 g of sulfuryl chloride was added dropwise at a constant speed at this temperature for 2 hours. Finally, the reaction temperature was raised to 80-85° C., and 16.8 g of sulfuryl chloride was continuously added dropwise at this temperature for 2 hours. After the dropwise addition, sampling and analysis showed that the conversion rate of 3,5-dimethylphenol was 99.15%.
反应液分别经结晶、离心、干燥得到白色针状结晶产物4-氯-3,5-二甲基苯酚(65.6g，99.58％)，产品收率83.62％，产品选择性84.34％。The reaction solution was crystallized, centrifuged, and dried to obtain the white needle-like crystal product 4-chloro-3,5-dimethylphenol (65.6g, 99.58%), the product yield was 83.62%, and the product selectivity was 84.34%.
对比例3Comparative example 3
在500mL的四口烧瓶中加入61g 3,5-二甲基苯酚，四氯乙烯95.8g，然后启动搅拌装置，硫酰氯进样口延伸到液面以下，位于搅拌桨上方，保温在35～40℃之间，在此温度下硫酰氯进料45.8g，进料时间为5小时，有少量固体析出；将反应温度控制在30～35℃，在此温度下硫酰氯继续进料19.6g，进料时间为2小时，固体析出量增加；将反应温度控制在20～25℃，在此温度下硫酰氯再进料8.0g，进料时间为1小时，固体析出量大大增加，悬浮于液面之上；硫酰氯进料完毕，取样分析，3,5-二甲基苯酚转化率为88.74％。Add 61g of 3,5-dimethylphenol and 95.8g of tetrachlorethylene into a 500mL four-neck flask, then start the stirring device, the sulfuryl chloride injection port extends below the liquid level and is located above the stirring paddle, and keep warm at 35-40 Between ℃, at this temperature sulfuryl chloride feed 45.8g, feed time is 5 hours, and a small amount of solid is separated out; Reaction temperature is controlled at 30～35 ℃, under this temperature sulfuryl chloride continues to feed 19.6g, enters The feeding time is 2 hours, and the amount of solid precipitation increases; the reaction temperature is controlled at 20-25 ° C, and at this temperature, 8.0 g of sulfuryl chloride is fed again, and the feeding time is 1 hour, the amount of solid precipitation increases greatly, and it is suspended on the liquid surface Above; sulfuryl chloride feeding is completed, sampling analysis shows that the conversion rate of 3,5-dimethylphenol is 88.74%.
反应液再分别经结晶、离心、干燥得到白色针状结晶产物4-氯-3,5-二甲基苯酚(63.9g，99.47％)，产品收率81.36％，产品选择性91.68％。The reaction solution was crystallized, centrifuged and dried to obtain the white needle crystal product 4-chloro-3,5-dimethylphenol (63.9g, 99.47%), the product yield was 81.36%, and the product selectivity was 91.68%.
对比例3的结果表明，如果采用改变温度分段进行反应，但是反应中间不将产物与母液进行分离，也会导致晶体包裹原料，隔绝反应，降低总的转化率和收率。The results of comparative example 3 show that if the reaction is carried out in stages by changing the temperature, but the product is not separated from the mother liquor in the middle of the reaction, it will also cause crystals to wrap the raw materials, isolate the reaction, and reduce the overall conversion rate and yield.

Claims (14)

  1. 一种低温氯化制备4-氯-3,5-二甲基苯酚的方法，其特征在于，包括：A method for preparing 4-chloro-3,5-dimethylphenol by low-temperature chlorination, characterized in that it comprises:
    (1)3,5-二甲基苯酚和氯化剂在低温下进行氯化反应，反应进行至有固体析出，进行固液分离，得到固体粗产物1与中间母液；(1) 3,5-dimethylphenol and a chlorinating agent are chlorinated at a low temperature, and the reaction is carried out until a solid is precipitated, and the solid-liquid separation is carried out to obtain a solid crude product 1 and an intermediate mother liquor;
    (2)中间母液进一步在低温下进行氯化反应，反应完成后进行末次固液分离，得到固体粗产物2和最终母液；(2) The intermediate mother liquor is further chlorinated at a low temperature, and the final solid-liquid separation is carried out after the reaction is completed to obtain the solid crude product 2 and the final mother liquor;
    固体粗产物1和固体粗产物2经过后处理得到所述的4-氯-3,5-二甲基苯酚。The solid crude product 1 and the solid crude product 2 were post-processed to obtain the 4-chloro-3,5-dimethylphenol.
  2. 根据权利要求1所述的低温氯化制备4-氯-3,5-二甲基苯酚的方法，其特征在于，步骤(1)中，氯化反应的温度为25～35℃，反应时间为5～8小时。The method for preparing 4-chloro-3,5-xylenol by low-temperature chlorination according to claim 1, characterized in that, in step (1), the temperature of the chlorination reaction is 25 to 35° C., and the reaction time is 5-8 hours.
  3. 根据权利要求1所述的低温氯化制备4-氯-3,5-二甲基苯酚的方法，其特征在于，步骤(1)中，所述的氯化剂为硫酰氯、氯气中的一种或者两种。The method for preparing 4-chloro-3,5-xylenol by low-temperature chlorination according to claim 1 is characterized in that, in step (1), the chlorinating agent is one of sulfuryl chloride and chlorine one or two.
  4. 根据权利要求1所述的低温氯化制备4-氯-3,5-二甲基苯酚的方法，其特征在于，步骤(1)中，氯化反应在卤代烃类溶剂中进行。The method for preparing 4-chloro-3,5-dimethylphenol by low-temperature chlorination according to claim 1, characterized in that, in step (1), the chlorination reaction is carried out in a halogenated hydrocarbon solvent.
  5. 根据权利要求4所述的低温氯化制备4-氯-3,5-二甲基苯酚的方法，其特征在于，步骤(1)中，所述的卤代烃类溶剂为氯取代的C 1～C 3烃类化合物。 The method for preparing 4-chloro-3,5-dimethylphenol by low-temperature chlorination according to claim 4, characterized in that, in step (1), the halogenated hydrocarbon solvent is chlorine-substituted C1 ~ C3 hydrocarbons.
  6. 根据权利要求5所述的低温氯化制备4-氯-3,5-二甲基苯酚的方法，其特征在于，步骤(1)中，所述的卤代烃类溶剂为二氯甲烷、三氯甲烷、四氯化碳、三氯乙烯、四氯乙烯中的一种或多种组合。The method for preparing 4-chloro-3,5-dimethylphenol by low-temperature chlorination according to claim 5, characterized in that, in step (1), the halogenated hydrocarbon solvent is dichloromethane, tris One or more combinations of methyl chloride, carbon tetrachloride, trichloroethylene, and tetrachloroethylene.
  7. 根据权利要求3所述的低温氯化制备4-氯-3,5-二甲基苯酚的方法，其特征在于，所述的氯化剂为硫酰氯，硫酰氯分批加入，步骤(1)中，以质量计，3,5-二甲基苯酚：硫酰氯＝1:0.5～0.8；The method for preparing 4-chloro-3,5-xylenol by low-temperature chlorination according to claim 3, is characterized in that, described chlorination agent is sulfuryl chloride, and sulfuryl chloride is added in batches, step (1) Among them, by mass, 3,5-dimethylphenol:sulfuryl chloride=1:0.5～0.8;
    步骤(2)中，以质量计，3,5-二甲基苯酚：硫酰氯＝1:0.3～0.8。In step (2), by mass, 3,5-dimethylphenol:sulfuryl chloride=1:0.3-0.8.
  8. 根据权利要求1所述的所述的低温氯化制备4-氯-3,5-二甲基苯酚的方法，其特征在于，步骤(2)中，所述氯化反应的温度为30～35℃，反应时间为2～5小时。The method for preparing 4-chloro-3,5-dimethylphenol according to the described low-temperature chlorination of claim 1, characterized in that, in step (2), the temperature of the chlorination reaction is 30 to 35 °C, the reaction time is 2 to 5 hours.
  9. 根据权利要求1所述的低温氯化制备4-氯-3,5-二甲基苯酚的方法，其特征在于，步骤(1)和(2)中，所述固液分离的操作方式为离心或者过滤；The method for preparing 4-chloro-3,5-dimethylphenol by low-temperature chlorination according to claim 1, characterized in that, in steps (1) and (2), the operation mode of the solid-liquid separation is centrifugation or filter;
    所述固体粗产物1和固体粗产物2通过降温结晶得到4-氯-3,5-二甲基苯酚。The solid crude product 1 and the solid crude product 2 were crystallized by cooling down to obtain 4-chloro-3,5-dimethylphenol.
  10. 根据权利要求9所述的低温氯化制备4-氯-3,5-二甲基苯酚的方法，其特征在于，固液分离得到的母液、降温结晶得到的结晶母液加入到下一批次的氯化反应中进行套用。The method for preparing 4-chloro-3,5-xylenol by low-temperature chlorination according to claim 9, characterized in that the mother liquor obtained by solid-liquid separation and the crystallized mother liquor obtained by cooling crystallization are added to the next batch of Apply mechanically in the chlorination reaction.
  11. 根据权利要求9所述的低温氯化制备4-氯-3,5-二甲基苯酚的方法，其特征在于，低温氯化反应产生的尾气经过冷凝，进行回收。The method for preparing 4-chloro-3,5-dimethylphenol by low-temperature chlorination according to claim 9, characterized in that the tail gas generated by the low-temperature chlorination reaction is condensed and recovered.
  12. 根据权利要求1～11任一项所述的低温氯化制备4-氯-3,5-二甲基苯酚的方法，其特征在于，步骤(1)中，固液分离的次数为一次或者多次。According to the method for preparing 4-chloro-3,5-dimethylphenol by low-temperature chlorination according to any one of claims 1 to 11, it is characterized in that, in step (1), the number of times of solid-liquid separation is one or more Second-rate.
  13. 根据权利要求12所述的低温氯化制备4-氯-3,5-二甲基苯酚的方法，其特征在于，所述固液分离的次数为一次，在转化率达到40～70％时进行。The method for preparing 4-chloro-3,5-xylenol by low-temperature chlorination according to claim 12, characterized in that, the number of solid-liquid separations is once, and is carried out when the conversion rate reaches 40-70%. .
  14. 根据权利要求12所述的低温氯化制备4-氯-3,5-二甲基苯酚的方法，其特征在于，所述固液分离的次数为多次，每次固液分离得到的固体合并为固体粗产物1，每次固液分离得到的中间母液继续进行反应。The method for preparing 4-chloro-3,5-xylenol by low-temperature chlorination according to claim 12, characterized in that, the number of solid-liquid separations is multiple times, and the solids obtained by solid-liquid separation are merged each time It is the solid crude product 1, and the intermediate mother liquor obtained by each solid-liquid separation continues to react.
PCT/CN2022/101130 2021-07-13 2022-06-24 Method for preparing 4-chloro-3,5-dimethylphenol by means of low-temperature chlorination WO2023284525A1 (en)

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CN115466166B (en) * 2022-10-31 2023-02-03 山东新和成维生素有限公司 Method for synthesizing 4-chloro-3, 5-dimethylphenol at low temperature

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