CN113603569B - Method for preparing 4-chloro-3, 5-dimethylphenol by low-temperature chlorination - Google Patents
Method for preparing 4-chloro-3, 5-dimethylphenol by low-temperature chlorination Download PDFInfo
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Abstract
The invention discloses a method for preparing 4-chloro-3, 5-dimethylphenol by low-temperature chlorination, which comprises the following steps: (1) 3, carrying out chlorination reaction on 5-dimethylphenol and a chlorinating agent at low temperature until solid is separated out, and carrying out solid-liquid separation to obtain a solid crude product 1 and an intermediate mother liquor; (2) The intermediate mother liquor is further subjected to chlorination reaction at low temperature, and the final solid-liquid separation is carried out after the reaction is finished to obtain a solid crude product 2 and a final mother liquor; and carrying out post-treatment on the solid crude product 1 and the solid crude product 2 to obtain the 4-chloro-3, 5-dimethylphenol. The invention separates the precipitated crystals in time in the reaction process, thereby reducing the wrapping of the raw materials and improving the conversion rate on the one hand.
Description
Technical Field
The invention belongs to the field of fine chemical engineering, and particularly relates to a method for preparing 4-chloro-3, 5-dimethylphenol by low-temperature chlorination.
Background
The 4-chloro-3, 5-dimethylphenol has a structure shown in a formula (I), is a broad-spectrum mildew-proof antibacterial agent, has a killing effect on most gram-positive and gram-negative bacteria, fungi and mould, and can be widely applied to disinfection or personal care products, such as anti-dandruff shampoos, hand sanitizers, soaps, other sanitary products and other antibacterial detergents as the mildew-proof antibacterial agent. Can also be used as a preservative and a mildew preventive in the industrial fields of glue, coating, paint, textile, leather, paper making and the like. 4-chloro-3, 5-dimethylphenol has good development prospect due to excellent sterilization and anticorrosion functions, and is accepted by wide consumers.
4-chloro-3, 5-dimethylphenol is generally obtained by industrially carrying out chlorination reaction on 3, 5-dimethylphenol serving as a raw material under the action of a chlorinating agent, wherein the chlorinating agent can be sulfuryl chloride or chlorine. In patent CN104326881A, a method is proposed for synthesizing 4-chloro-3, 5-dimethylphenol by performing directional chlorination reaction in two stages of low-temperature chlorination and high-temperature chlorination by using tetrachloroethylene as a solvent, benzylthiophenol and aluminum chloride as co-catalysts and sulfuryl chloride as a chlorinating agent. The method utilizes low-temperature chlorination to maintain the selectivity of the product 4-chloro-3, 5-dimethylphenol, and high-temperature chlorination to improve the conversion rate of a substrate, thereby achieving the purpose of improving the product yield. However, in the high-temperature chlorination (50-65 ℃), the selectivity of the product is reduced, and the catalyst recovery of the method is difficult, so that the method has serious environmental pollution.
Patent CN102675055B discloses a new method for producing p-chloro-m-xylenol by high-temperature chlorination, comprising gasifying sulfuryl chloride, feeding the gasified sulfuryl chloride into the lower part of a chlorination tower, preheating and heating liquid raw materials, feeding the liquid raw materials into the upper part of the chlorination tower, contacting the raw materials with gaseous sulfuryl chloride in the chlorination tower for reaction, forcing the materials to circulate externally by a circulating pump, and arranging a heat exchanger at the outlet of the circulating pump to adjust the temperature in the chlorination tower. The method can realize automatic control, has high continuous degree, but has higher reaction temperature and poorer product selectivity.
Patent CN 103351282B discloses a preparation method of 4-chloro-3, 5-dimethylphenol, which comprises using cupric salt as catalyst, 3, 5-dimethylphenol as raw material, oxygen as oxidant, hydrochloric acid as chlorinating agent, reacting at 90-98 ℃ to synthesize 3, 5-dimethyl-4-chlorophenol. When the actual conversion rate of the 3, 5-dimethylphenol reaches 99 percent, the selectivity of the product only reaches 80 percent, the selectivity of the product is low, and the separation difficulty of the product is increased.
In patent CN101823941B, a green industrial preparation method of 4-chloro-3, 5-dimethylphenol is disclosed, wherein water is used as a solvent, sulfuryl chloride or chlorine is used as a chlorinating agent, and a substrate 3, 5-dimethylphenol is subjected to chlorination reaction in a multi-stage temperature control manner. The method is complicated in operation and difficult to industrially apply on a large scale, the reaction selectivity is reduced due to high temperature in the reaction process, and more than 10% of o-chloro byproducts and dichloro byproducts are generated in the reaction process.
Patent CN102659528A discloses a continuous tank type chlorination process, in which a chlorinating agent is added in batches, so as to improve the conversion rate of the reaction and reduce the occurrence of side reactions to a certain extent, but the present inventors found that there are problems of crystal precipitation in the chlorination process, such as crystal precipitation in chlorination tank B and chlorination tank C, especially more crystal precipitation in chlorination tank C, more crystal precipitation, and wrapping of raw material 3, 5-dimethylphenol, which affects the conversion rate of the reaction.
Disclosure of Invention
The invention aims to solve the technical problem of providing a method for preparing 4-chloro-3, 5-dimethylphenol by low-temperature chlorination, which can overcome the problem of low conversion rate caused by wrapping raw materials by product crystals in low-temperature chlorination in the prior art.
A method for preparing 4-chloro-3, 5-dimethylphenol by low-temperature chlorination comprises the following steps:
(1) 3, carrying out chlorination reaction on 5-dimethylphenol and a chlorinating agent at low temperature until solid is separated out, and carrying out solid-liquid separation to obtain a solid crude product 1 and an intermediate mother liquor;
(2) The intermediate mother liquor is further subjected to chlorination reaction at low temperature, and the final solid-liquid separation is carried out after the reaction is finished to obtain a solid crude product 2 and a final mother liquor;
and carrying out post-treatment on the solid crude product 1 and the solid crude product 2 to obtain the 4-chloro-3, 5-dimethylphenol.
The inventor finds that the low-temperature chlorination causes the reduction of the conversion rate of the raw materials by two reasons: (1) The density of the precipitated crystals is less than that of the solvent, the precipitated crystals suspend on the surface layer of the solvent, the crystals are aggregated and agglomerated on the surface layer of the solvent, the reaction between the chlorinating agent and the substrate is blocked, and the larger the reaction device is, the more obvious the blocking phenomenon is, and the lower the substrate conversion rate is; (2) The crystals agglomerate, which can wrap the raw materials and can cause part of the raw materials to be unable to participate in the reaction. The above two factors affect the low conversion rate of 3, 5-dimethylphenol under low temperature conditions. The invention can avoid the crystal from caking in large area and wrapping the raw material and prevent the precipitated crystal from blocking the reaction of the chlorinating agent and the substrate by separating the precipitated crystal from the reaction liquid in time, and is particularly suitable for large-scale production process. In addition, the precipitated crystals are purified to obtain qualified products, and the residual raw materials are accumulated for multiple times and recovered for preparing 4-chloro-3, 5-dimethylphenol, so that the residual raw materials are completely converted.
Preferably, in the step (1), the temperature of the chlorination reaction is 25-35 ℃, the reaction time is 5-8 hours, and the lower reaction temperature is favorable for improving the conversion rate of the product because the solid product is separated from the reaction liquid in time.
In the present invention, the chlorinating agent may be a reagent commonly used in the prior art for chlorination of benzene ring, and preferably, in the step (1), the chlorinating agent is one or two of sulfuryl chloride and chlorine.
Preferably, in the step (1), the chlorination reaction is carried out in a halogenated hydrocarbon solvent; the halogenated hydrocarbon solvent is preferably a chlorine-substituted C1-C3 hydrocarbon compound; more preferably one or more of methylene chloride, chloroform, carbon tetrachloride, trichloroethylene, tetrachloroethylene, and most preferably in tetrachloroethylene.
Preferably, the chlorinating agent is sulfuryl chloride, the sulfuryl chloride is added in batches, and in the step (1), the mass ratio of 3, 5-dimethylphenol: sulfuryl chloride = 1;
in the step (2), by mass, 3, 5-dimethylphenol: sulfuryl chloride =1, 0.3-0.8.
In the step (1) and the step (2), the adding manner of the chlorinating agent twice is not limited, and the chlorinating agent twice can be added in a dropwise manner, can be transferred by a metering pump, can be sprayed by an injector to feed (increase the contact area), can also be fed by inserting a feeding pipe below the liquid level (gas feeding), and the like, preferably, when the chlorinating agent is sulfuryl chloride, the sulfuryl chloride is added in the dropwise manner in the step (1) and the step (2).
Preferably, in the step (2), the temperature of the chlorination reaction is 30 to 35 ℃ and the reaction time is 2 to 5 hours. The reaction in step (2) may be carried out at a slightly higher temperature than that in step (1) to promote the reaction in the later stage.
Preferably, in the steps (1) and (2), the solid-liquid separation is performed by centrifugation or filtration;
and cooling and crystallizing the solid crude product 1 and the solid crude product 2 to obtain the 4-chloro-3, 5-dimethylphenol. Wherein, the specific process of cooling crystallization is as follows: mixing the solid crude product 1 and the solid crude product 2, adding 1.5-2.0 times of solvent (preferably tetrachloroethylene based on the mass of the mixed solid), heating to 75-85 ℃, stirring for dissolving, then cooling at the speed of 3-8 ℃/h, controlling the final temperature to be 25-30 ℃, and obtaining the product 4-chloro-3, 5-dimethylphenol and crystallization mother liquor by centrifugation.
Preferably, the mother liquor obtained by solid-liquid separation and the crystallization mother liquor obtained by cooling crystallization are added into the chlorination reaction of the next batch for reuse. By the operation, the utilization rate of raw materials can be further improved, and the discharge treatment of waste liquid is reduced.
Preferably, the off gas generated by the low-temperature chlorination reaction is condensed and recovered.
In the step (1), the number of times of solid-liquid separation is not particularly limited, and may be one or more, preferably, the number of times of solid-liquid separation is one, and the solid-liquid separation is performed when the conversion rate reaches 40 to 70%, and in this case, the purposes of convenient operation and reaction yield can be both considered; further preferably, the number of solid-liquid separations is plural, the solids obtained by each solid-liquid separation are combined to form a solid crude product 1, and the reaction is continued with the intermediate mother liquor obtained by each solid-liquid separation. The increase of the number of separation can transfer the precipitated solid in time, which is favorable for the reaction, but the operation is complicated due to the excessive number of separation, and the number of separation is more preferably 2 to 4.
Compared with the prior art, the invention has the beneficial effects that:
(1) The invention separates the precipitated crystal in time in the reaction process, thereby reducing the wrapping of raw materials, improving the conversion rate, reducing the obstruction of the crystal to the reaction and increasing the reaction rate;
(2) The low-temperature chlorination can improve the selectivity of the product and reduce the generation of byproducts, so that the treatment capacity of the waste liquid can be greatly reduced, and the method is beneficial to environmental protection.
Drawings
FIG. 1 is a flow diagram of a process for the preparation of 4-chloro-3, 5-dimethylphenol of the present invention (with one separation as an example).
Detailed Description
The invention is further described below with reference to specific examples, wherein the purity of the products obtained in the examples, if not specified in particular, is HPLC purity.
Example 1
Chlorination 1: 61g of 3, 5-dimethylphenol and 122g of tetrachloroethylene are added into a 500mL four-neck flask, a stirring device is started, the temperature is kept between 25 and 35 ℃, 33.6g of sulfuryl chloride is dropwise added at constant speed at the temperature for 5 hours, and after the dropwise addition is finished, sampling analysis shows that the one-time conversion rate of the 3, 5-dimethylphenol is 48.78 percent. Separating the precipitated solid 1 from the mother liquor 1 by cooling centrifugation, and controlling the temperature to be 20-25 ℃.
Chlorination 2: and (3) adding the mother solution 1 into the four-neck flask again, starting a stirring device, keeping the temperature at 30-35 ℃, continuously dropwise adding 33.6g of sulfuryl chloride at the temperature, wherein the dropwise adding time is 3 hours, and after the dropwise adding is finished, sampling and analyzing, wherein the secondary conversion rate of the 3, 5-dimethylphenol is 47.78%. Separating the precipitated solid 2 from the mother liquor 2 by cooling centrifugation, and controlling the temperature to be 20-25 ℃.
And (3) combining the solid 1 and the solid 2, adding 105.0g of tetrachloroethylene, heating to 80 ℃, stirring for dissolving, slowly cooling to 25-30 ℃, centrifuging, and drying to obtain a white acicular crystal product 4-chloro-3, 5-dimethylphenol (69.97g, 99.28%), wherein the sum of the two conversion rates of the raw materials is 96.56%, the product yield is 88.84%, the product selectivity is 92.01%, and the crystallization centrifugal mother liquor is used as the raw material for the next reaction.
Example 2
Chlorination 1: 61g of 3, 5-dimethylphenol and 183g of tetrachloroethylene are added into a 500mL four-neck flask, a stirring device is started, the temperature is kept between 25 ℃ and 35 ℃, 40.3g of sulfuryl chloride is dropwise added at constant speed at the temperature for 6 hours, and after the dropwise addition is finished, sampling analysis shows that the one-time conversion rate of the 3, 5-dimethylphenol is 58.50 percent. And separating the precipitated solid 1 from the mother liquor 1 by cooling and centrifuging, wherein the temperature is controlled to be 20-25 ℃.
And (2) chlorination: and (3) adding the mother solution 1 into the four-neck flask again, starting a stirring device, keeping the temperature at 30-35 ℃, continuously dropwise adding 29.9g of sulfuryl chloride at the temperature, wherein the dropwise adding time is 4 hours, and after the dropwise adding is finished, sampling and analyzing, wherein the secondary conversion rate of the 3, 5-dimethylphenol is 38.47%. Separating the precipitated solid 2 from the mother liquor 2 by cooling centrifugation, and controlling the temperature to be 20-25 ℃.
And (3) combining the solid 1 and the solid 2, adding 105.0g of tetrachloroethylene, heating to 80 ℃, stirring for dissolving, slowly cooling to 25-30 ℃, centrifuging, and drying to obtain a white acicular crystal product 4-chloro-3, 5-dimethylphenol (69.62g, 99.42%), wherein the sum of the two conversion rates of the raw materials is 96.97%, the product yield is 88.52%, the product selectivity is 91.29%, and the crystallization centrifugal mother liquor is used as the raw material for the next reaction.
Example 3
Chlorination 1: 61g of 3, 5-dimethylphenol and 305g of tetrachloroethylene are added into a 500mL four-neck flask, a stirring device is started, the temperature is kept between 25 and 35 ℃, 46.9g of sulfuryl chloride is dropwise added at a constant speed at the temperature for 8 hours, and after the dropwise addition is finished, sampling analysis shows that the one-time conversion rate of the 3, 5-dimethylphenol is 68.09 percent. And separating the precipitated solid 1 from the mother liquor 1 by cooling and centrifuging, wherein the temperature is controlled to be 20-25 ℃.
Chlorination 2: and (3) adding the mother solution 1 into the four-neck flask again, starting a stirring device, keeping the temperature at 30-35 ℃, continuously dropwise adding 26.3g of sulfuryl chloride at the temperature, wherein the dropwise adding time is 2 hours, and after the dropwise adding is finished, sampling and analyzing, wherein the secondary conversion rate of the 3, 5-dimethylphenol is 29.32%. Separating the precipitated solid 2 from the mother liquor 2 by cooling and centrifuging, and controlling the temperature to be 20-25 ℃.
And (3) combining the solid 1 and the solid 2, adding 108.0g of tetrachloroethylene, heating to 80 ℃, stirring for dissolving, slowly cooling to 25-30 ℃, centrifuging, and drying to obtain a white acicular crystal product 4-chloro-3, 5-dimethylphenol (71.10 g, 99.35%), wherein the sum of the two conversion rates of the raw materials is 97.41%, the product yield is 90.33%, the product selectivity is 92.73%, and the crystallization centrifugal mother liquor is used as the raw material for the next reaction.
Example 4
Chlorination 1: 61g of 3, 5-dimethylphenol and 305g of tetrachloroethylene are added into a 500mL four-neck flask, a stirring device is started, the temperature is kept between 25 ℃ and 35 ℃, 44.0g of sulfuryl chloride is dropwise added at constant speed at the temperature for 7 hours, and after the dropwise addition is finished, the sampling analysis shows that the one-time conversion rate of the 3, 5-dimethylphenol is 64.81 percent. And separating the precipitated solid 1 from the mother liquor 1 by cooling and centrifuging, wherein the temperature is controlled to be 20-25 ℃.
Chlorination 2: and (3) adding the mother solution 1 into the four-neck flask again, starting a stirring device, keeping the temperature at 30-35 ℃, continuously dropwise adding 29.2g of sulfuryl chloride at the temperature, wherein the dropwise adding time is 3 hours, and after the dropwise adding is finished, sampling and analyzing, wherein the secondary conversion rate of the 3, 5-dimethylphenol is 32.93%. Separating the precipitated solid 2 from the mother liquor 2 by cooling centrifugation, and controlling the temperature to be 20-25 ℃.
And (3) combining the solid 1 and the solid 2, adding 110.0g of tetrachloroethylene, heating to 80 ℃, stirring for dissolving, slowly cooling to 25-30 ℃, centrifuging, and drying to obtain a white acicular crystal product 4-chloro-3, 5-dimethylphenol (72.61g, 99.41%), wherein the sum of the two conversion rates of the raw materials is 97.74%, the product yield is 92.31%, the product selectivity is 94.44%, and the crystallization centrifugal mother liquor is used as the raw material for the next reaction.
Example 5
Chlorination 1: 61g of 3, 5-dimethylphenol and 305g of tetrachloroethylene are added into a 500mL four-neck flask, a stirring device is started, the temperature is kept between 25 and 35 ℃, 51.2g of sulfuryl chloride is dropwise added at constant speed at the temperature for 8 hours, and after the dropwise addition is finished, sampling analysis shows that the one-time conversion rate of the 3, 5-dimethylphenol is 72.32 percent. Separating the precipitated solid 1 from the mother liquor 1 by cooling centrifugation, and controlling the temperature to be 20-25 ℃.
And (2) chlorination: and (3) adding the mother solution 1 into the four-neck flask again, starting a stirring device, keeping the temperature at 30-35 ℃, continuously dropwise adding 22.0g of sulfuryl chloride at the temperature, wherein the dropwise adding time is 2 hours, and after the dropwise adding is finished, sampling and analyzing, wherein the secondary conversion rate of the 3, 5-dimethylphenol is 23.08%. Separating the precipitated solid 2 from the mother liquor 2 by cooling and centrifuging, and controlling the temperature to be 20-25 ℃.
And (3) combining the solid 1 and the solid 2, adding 108.0g of tetrachloroethylene, heating to 80 ℃, stirring for dissolving, slowly cooling to 25-30 ℃, centrifuging, and drying to obtain a white acicular crystal product 4-chloro-3, 5-dimethylphenol (68.48g, 99.29%), wherein the sum of the two conversion rates of the raw materials is 95.40%, the product yield is 86.95%, the product selectivity is 91.14%, and the crystallization centrifugal mother liquor is used as the raw material for the next reaction.
Example 6 (applied experiment)
Chlorination 1: mixing the mother liquor 1 and 2 in the example 1 with the crystallization mother liquor generated in the process of preparing 4-chloro-3, 5-dimethylphenol by solid temperature reduction crystallization, adding the mixture into a 500mL four-neck flask, supplementing 59.5g of 3, 5-dimethylphenol and 20g of tetrachloroethylene, starting a stirring device, keeping the temperature at 25-35 ℃, dropwise adding 33.6g of sulfuryl chloride at constant speed at the temperature for 5 hours, sampling and analyzing after dropwise adding, wherein the primary conversion rate of the 3, 5-dimethylphenol is 47.29 percent. Separating the precipitated solid 1 from the mother liquor 1 by cooling centrifugation, and controlling the temperature to be 20-25 ℃.
Chlorination 2: and (3) adding the mother solution 1 into the four-neck flask again, starting a stirring device, keeping the temperature at 30-35 ℃, continuously dropwise adding 33.6g of sulfuryl chloride at the temperature, wherein the dropwise adding time is 2 hours, and after the dropwise adding is finished, sampling and analyzing to obtain that the secondary conversion rate of the 3, 5-dimethylphenol is 48.20%. Separating the precipitated solid 2 from the mother liquor 2 by cooling centrifugation, and controlling the temperature to be 20-25 ℃.
And (3) combining the solid 1 and the solid 2, adding 105.0g of tetrachloroethylene, heating to 80 ℃, stirring for dissolving, slowly cooling to 25-30 ℃, centrifuging, and drying to obtain a white acicular crystal product 4-chloro-3, 5-dimethylphenol (70.12g, 99.29%), wherein the sum of the two conversion rates of the raw materials is 96.49%, the product yield is 89.03%, the product selectivity is 92.27%, and the crystallization centrifugal mother liquor is used as the raw material for the next reaction.
Example 7:
chlorination 1: 61g of 3, 5-dimethylphenol and 305g of dichloromethane are added into a 500mL four-neck flask, a stirring device is started, the temperature is kept between 25 and 35 ℃, chlorine is introduced into the solution at a constant speed at the temperature, the chlorine flow is 1.5L/h, the reaction time is 6 hours, after the dropwise addition, the sampling analysis is carried out, and the primary conversion rate of the 3, 5-dimethylphenol is 63.28 percent. And separating the precipitated solid 1 from the mother liquor 1 by cooling and centrifuging, wherein the temperature is controlled to be 20-25 ℃.
Chlorination 2: and (2) adding the mother liquor 1 into the four-neck flask again, starting a stirring device, keeping the temperature at 30-35 ℃, continuously introducing chlorine into the mother liquor 1 at a constant speed at the temperature, wherein the chlorine flow is 1.2L/h, the reaction time is 4 hours, and after the dropwise addition, sampling and analyzing, wherein the secondary conversion rate of the 3, 5-dimethylphenol is 32.95%. Separating the precipitated solid 2 from the mother liquor 2 by cooling centrifugation, and controlling the temperature to be 20-25 ℃.
And (3) combining the solid 1 and the solid 2, adding 150.0g of dichloromethane, heating to 80 ℃, stirring for dissolving, slowly cooling to 25-30 ℃, centrifuging, and drying to obtain a white acicular crystal product 4-chloro-3, 5-dimethylphenol (68.93g, 99.32%), wherein the sum of the two conversion rates of the raw materials is 96.23%, the product yield is 87.52%, the product selectivity is 90.95%, and the crystallization centrifugal mother liquor is used as the raw material for the next batch of reaction.
Example 8
Chlorination 1: 61g of 3, 5-dimethylphenol and 305g of tetrachloroethylene are added into a 500mL four-neck flask, a stirring device is started, the temperature is kept between 25 and 35 ℃, 30.0g of sulfuryl chloride is dropwise added at constant speed at the temperature for 4 hours, and after the dropwise addition is finished, sampling analysis shows that the one-time conversion rate of the 3, 5-dimethylphenol is 39.63 percent. Separating the precipitated solid 1 from the mother liquor 1 by cooling centrifugation, and controlling the temperature to be 20-25 ℃.
And (2) chlorination: and (3) adding the mother solution 1 into the four-neck flask again, starting a stirring device, keeping the temperature at 30-35 ℃, continuously dropwise adding 22.0g of sulfuryl chloride at the temperature, wherein the dropwise adding time is 2 hours, and after the dropwise adding is finished, sampling and analyzing, wherein the secondary conversion rate of the 3, 5-dimethylphenol is 29.51%. Separating the precipitated solid 2 from the mother liquor 2 by cooling and centrifuging, and controlling the temperature to be 20-25 ℃.
Chlorination 3: and (3) adding the mother solution 2 into the four-neck flask again, starting a stirring device, keeping the temperature at 30-35 ℃, continuously dropwise adding 21.2g of sulfuryl chloride at the temperature for 2 hours, and sampling and analyzing after the dropwise adding is finished, wherein the tertiary conversion rate of the 3, 5-dimethylphenol is 29.32%. Separating the precipitated solid 3 from the mother liquor 3 by cooling and centrifuging, and controlling the temperature to be 20-25 ℃.
And combining the solid 1, the solid 2 and the solid 3, adding 108.0g of tetrachloroethylene, heating to 80 ℃, stirring for dissolving, slowly cooling to 25-30 ℃, centrifuging, and drying to obtain a white needle-shaped crystal product 4-chloro-3, 5-dimethylphenol (72.73g, 99.37%), wherein the sum of the three conversion rates of the raw materials is 98.46%, the product yield is 92.43%, the product selectivity is 93.87%, and the crystallization centrifugal mother liquor is used as the raw material for the next batch of reaction.
Comparative example 1
61g of 3, 5-dimethylphenol and 305g of carbon tetrachloride are added into a 500mL four-neck flask, then a stirring device is started, the temperature is kept between 25 ℃ and 35 ℃, 67.1g of sulfuryl chloride is dropwise added at constant speed at the temperature for 8 hours, and after the dropwise addition is finished, the conversion rate of the 3, 5-dimethylphenol is 88.42 percent by sampling analysis.
The reaction solution was then crystallized, centrifuged and dried to obtain 4-chloro-3, 5-dimethylphenol (63.9 g, 99.64%) as a white needle-like crystalline product with a yield of 81.43% and a selectivity of 92.10%.
Comparative example 2
61g of 3, 5-dimethylphenol and 305g of carbon tetrachloride are added into a 500mL four-neck flask, then a stirring device is started, and 33.6g of sulfuryl chloride is dropwise added at a constant speed at 25-35 ℃ for 4 hours. Then, the reaction temperature is raised to 60-65 ℃, 16.8g of sulfuryl chloride is dropwise added at the temperature at a constant speed for 2 hours. And finally, raising the reaction temperature to 80-85 ℃, and continuously dropwise adding 16.8g of sulfuryl chloride at a constant speed for 2 hours at the temperature. After the completion of the dropwise addition, a sample was taken and analyzed, and the conversion of 3, 5-dimethylphenol was 99.15%.
The reaction solution was crystallized, centrifuged and dried to obtain 4-chloro-3, 5-dimethylphenol as a white needle-like crystalline product (65.6 g, 99.58%), yield of 83.62% and selectivity of 84.34%.
Comparative example 3
61g of 3, 5-dimethylphenol and 95.8g of tetrachloroethylene are added into a 500mL four-neck flask, then a stirring device is started, a sulfuryl chloride injection port extends to the position below the liquid level and is positioned above a stirring paddle, the temperature is kept between 35 and 40 ℃, 45.8g of sulfuryl chloride is fed at the temperature, the feeding time is 5 hours, and a small amount of solid is separated out; controlling the reaction temperature to be 30-35 ℃, continuously feeding 19.6g of sulfuryl chloride at the temperature, wherein the feeding time is 2 hours, and the solid precipitation amount is increased; controlling the reaction temperature at 20-25 ℃, feeding 8.0g of sulfuryl chloride at the temperature, wherein the feeding time is 1 hour, the solid precipitation amount is greatly increased, and the sulfuryl chloride is suspended above the liquid level; when the sulfuryl chloride feed was completed, a sample was taken for analysis, and the conversion of 3, 5-dimethylphenol was 88.74%.
The reaction solution was crystallized, centrifuged and dried to obtain white needle-like crystalline product 4-chloro-3, 5-dimethylphenol (63.9 g, 99.47%), yield 81.36% and selectivity 91.68%.
The results of comparative example 3 show that if the reaction is carried out in stages with varying temperature, but the product is not separated from the mother liquor in the middle of the reaction, it also results in crystals wrapping the starting material, isolating the reaction and reducing the overall conversion and yield.
Claims (5)
1. A method for preparing 4-chloro-3, 5-dimethylphenol by low-temperature chlorination is characterized by comprising the following steps:
(1) 3, carrying out chlorination reaction on the 5-dimethylphenol and a chlorinating agent at a low temperature until the conversion rate reaches 40 to 70 percent, and carrying out solid-liquid separation to obtain a solid crude product 1 and an intermediate mother liquor;
(2) The intermediate mother liquor is further subjected to chlorination reaction at low temperature, and the final solid-liquid separation is carried out after the reaction is finished to obtain a solid crude product 2 and a final mother liquor;
carrying out post-treatment on the solid crude product 1 and the solid crude product 2 to obtain the 4-chloro-3, 5-dimethylphenol;
in the step (1), the chlorination reaction temperature is 25 to 35 ℃, and the reaction time is 5 to 8 hours;
in the step (2), the temperature of the chlorination reaction is 30 to 35 ℃, and the reaction time is 2 to 5 hours;
the solid-liquid separation is carried out once;
in the step (1), the halogenated hydrocarbon solvent is one or a combination of dichloromethane and tetrachloroethylene;
the chlorinating agent is sulfuryl chloride, the sulfuryl chloride is added in batches, and in the step (1), by mass, the reaction product of 3, 5-dimethylphenol: sulfuryl chloride =1, 0.5 to 0.8;
in the step (2), 3, 5-dimethylphenol by mass: sulfuryl chloride =1, 0.3 to 0.8.
2. 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 solid-liquid separation is carried out by centrifugation or filtration;
and cooling and crystallizing the solid crude product 1 and the solid crude product 2 to obtain the 4-chloro-3, 5-dimethylphenol.
3. The method for preparing 4-chloro-3, 5-dimethylphenol by low-temperature chlorination according to claim 2, wherein the mother liquor obtained by solid-liquid separation and the crystallization mother liquor obtained by cooling crystallization are added to the chlorination reaction of the next batch for reuse.
4. The method for preparing 4-chloro-3, 5-dimethylphenol by low-temperature chlorination according to claim 2, wherein off-gas generated by the low-temperature chlorination is condensed and recovered.
5. A method for preparing 4-chloro-3, 5-dimethylphenol by low-temperature chlorination is characterized by comprising the following steps: (1) Adding 61g of 3, 5-dimethylphenol and 305g of dichloromethane into a 500mL four-neck flask, starting a stirring device, keeping the temperature at 25-35 ℃, introducing chlorine into the solution at a constant speed at the temperature, wherein the chlorine flow is 1.5L/h, the reaction time is 6 hours, sampling and analyzing after the dropwise addition, the primary conversion rate of the 3, 5-dimethylphenol is 63.28%, separating the precipitated solid 1 from the mother solution 1 by cooling and centrifuging, and controlling the temperature at 20-25 ℃;
(2) Adding the mother liquor 1 into a four-neck flask again, starting a stirring device, keeping the temperature at 30-35 ℃, continuously introducing chlorine into the mother liquor 1 at a constant speed at the temperature, wherein the chlorine flow is 1.2L/h, the reaction time is 4 hours, after the dropwise addition, sampling and analyzing, wherein the secondary conversion rate of 3, 5-dimethylphenol is 32.95%, separating the precipitated solid 2 from the mother liquor 2 by cooling and centrifuging, and controlling the temperature at 20-25 ℃;
(3) And (3) combining the solid 1 and the solid 2, adding 150.0g of dichloromethane, heating to 80 ℃, stirring for dissolving, slowly cooling to 25-30 ℃, centrifuging, drying to obtain 68.93g of white acicular crystal product 4-chloro-3, 5-dimethylphenol, and mechanically using the centrifugal mother liquor of the crystals as a raw material for the next batch of reaction.
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| PCT/CN2022/101130 WO2023284525A1 (en) | 2021-07-13 | 2022-06-24 | Method for preparing 4-chloro-3,5-dimethylphenol by means of low-temperature chlorination |
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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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| GB529070A (en) * | 1939-05-20 | 1940-11-13 | George William Gladden | Improvements in preparation of 2-chlor-meta-5-xylenol |
| GB1522271A (en) * | 1976-06-18 | 1978-08-23 | Lankro Chem Ltd | Processes for the preparation of chlorinated phenols |
| CN100560554C (en) * | 2007-01-10 | 2009-11-18 | 胡汉忠 | Industrialized process for preparing to the chloro alkylphenol |
| CN101823941B (en) * | 2010-05-21 | 2012-12-12 | 湖南利洁生物化工有限公司 | Green industrialized preparation method for 1-hydroxy-3,5-dimethyl-chlorobenzene |
| CN102659528B (en) * | 2012-04-01 | 2014-09-17 | 江苏焕鑫新材料股份有限公司 | Continuous kettle type chlorination technology |
| CN104326881A (en) * | 2014-10-16 | 2015-02-04 | 荣成青木高新材料有限公司 | Preparation method of 3,5-dimethyl-4-chlorophenol |
| CN111574329B (en) * | 2020-05-18 | 2022-09-20 | 万华化学集团股份有限公司 | Reactive distillation device and method for producing 4-chloro-3, 5-dimethylphenol |
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| CN113603569B (en) * | 2021-07-13 | 2022-12-06 | 山东新和成维生素有限公司 | Method for preparing 4-chloro-3, 5-dimethylphenol by low-temperature chlorination |
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