System and method for continuous preparation of 3,4-dichlorophenylboronic acid

Abstract

The present invention provides a system and method for continuously preparing 3,4-dichlorophenylboronic acid. The system includes: a bromination reaction unit, which is composed of a first feed module, a first reaction module and a first quenching module connected in sequence; a Grignard reagent preparation unit, which is composed of a second feed module and a second reaction module connected in sequence; and a Grignard reaction unit, which is composed of a third feed module, a third reaction module and a second quenching module connected in sequence; the bromination reaction unit, the Grignard reagent preparation unit and the Grignard reaction unit are connected in sequence. The use of the above-mentioned continuous synthesis system to prepare 3,4-dichlorophenylboronic acid can improve production efficiency and product yield.

Description

Technical Field

[0001] The invention relates to the technical field of chemical synthesis, and in particular to a system and method for continuously preparing 3,4-dichlorophenylboronic acid. Background Art

[0002] 3,4-Dichlorophenylboronic acid, molecular formula C6H5BCl2O2, CAS: 151169-75-4. 3,4-Dichlorophenylboronic acid is a solid, white crystals at room temperature. It is slightly soluble in water and has a low solubility. It can be dissolved in many organic solvents, such as ethers, ketones and alcohols. This compound has a certain stability, but it will decompose under high temperature or high pressure. 3,4-Dichlorophenylboronic acid is an important organic synthesis intermediate. It can be used to synthesize various organoboron compounds, such as organopalladium catalysts, organophosphorus-boron ligands, etc. These organoboron compounds have important applications in organic synthesis. 3,4-Dichlorophenylboronic acid can also be used as a catalyst and raw material for catalytic reactions, and is widely used in chemical research and industrial production.

[0003] .

[0004] The synthetic route of 3,4-dichlorophenylboronic acid is shown in the above chemical equation. It is mostly prepared with o-dichlorobenzene as raw material, prepared by bromination reaction, Grignard reagent, and synthesized into a final product by nucleophilic addition reaction. Among them, the bromination reaction is highly exothermic, bromine is highly toxic, corrosive, and easily volatile, which is a big risk problem, and the preparation of Grignard reagent needs to be carried out under anhydrous and oxygen-free conditions. The existing production of 3,4-dichlorophenylboronic acid mostly adopts an intermittent operation mode, which has high labor intensity, low production efficiency, poor heat exchange, many side reactions, and high risk factors. Therefore, how to provide an efficient solution that can carry out the continuous reaction of 3,4-dichlorophenylboronic acid is of great significance for the industrial production and application of this compound. Summary of the invention

[0005] The main purpose of the present invention is to provide a system and method for continuously preparing 3,4-dichlorophenylboronic acid, so as to solve the problem of low product yield of 3,4-dichlorophenylboronic acid in the prior art.

[0006] To achieve the above-mentioned object, according to a first aspect of the present invention, a system for continuously preparing 3,4-dichlorophenylboronic acid is provided, comprising: a bromination reaction unit, which is composed of a first feeding module, a first reaction module and a first quenching module connected in sequence; a Grignard reagent preparation unit, which is composed of a second feeding module and a second reaction module connected in sequence; and a Grignard reaction unit, which is composed of a third feeding module, a third reaction module and a second quenching module connected in sequence; the bromination reaction unit, the Grignard reagent preparation unit and the Grignard reaction unit are connected in sequence.

[0007] Furthermore, the first reaction module includes: a first main reactor, a first temperature control device, a first tail gas absorption device and a first explosion relief device; the first temperature control device is connected to the first main reactor through a public engineering pipeline, and the reaction temperature in the first main reactor is controlled by negative feedback regulation; the first tail gas absorption device and the first explosion relief device are connected to the first main reactor through the first tail gas absorption pipeline and the first explosion relief pipeline respectively; the feed inlet of the first main reactor is connected to the feed outlet of the first feeding module.

[0008] Furthermore, the first main reactor comprises a mixer and a first reactor connected in sequence; preferably, the type of the first reactor is selected from any one of the following: a microchannel tubular reactor, a continuous overflow reactor, a dynamic tubular reactor, a vertical tube reactor, a tube-in-tube reactor, a coil reactor, a U-shaped tubular reactor and a horizontal tubular reactor.

[0009] Furthermore, the second reaction module includes: a second main reactor, a second temperature control device, a second tail gas absorption device and a first nitrogen protection device; the second temperature control device is connected to the second main reactor through a public engineering pipeline, and the reaction temperature in the second main reactor is controlled by negative feedback regulation; the second tail gas absorption device and the first nitrogen protection device are connected to the second main reactor through a second tail gas absorption pipeline and a first nitrogen pipeline respectively; the feed inlet of the second main reactor is connected to the feed outlet of the second feed module.

[0010] Furthermore, the second main reactor includes a second reactor and a first agitator arranged in the second reactor; preferably, the type of the second reactor is selected from any one of the following: a slurry bed reactor, a trickle bed reactor, a suspended bed reactor and an internal loop reactor with a guide tube.

[0011] Furthermore, the third reaction module includes: a third main reactor, a third temperature control device, a third tail gas absorption device and a second nitrogen protection device; the third temperature control device is connected to the third main reactor through a public engineering pipeline, and the reaction temperature in the third main reactor is controlled by negative feedback regulation; the third tail gas absorption device and the second nitrogen protection device are connected to the third main reactor through a third tail gas absorption pipeline and a second nitrogen pipeline, respectively; the feed inlet of the third main reactor is connected to the feed outlet of the third feed module.

[0012] Furthermore, the third main reactor includes a third reactor and a second agitator arranged in the third reactor; preferably, the type of the third reactor is selected from any one of the following: a continuous overflow reactor, an internal loop reactor with a guide tube, a vertical tube reactor and a shell and tube reactor.

[0013] In order to achieve the above-mentioned object, according to a second aspect of the present invention, a method for continuously preparing 3,4-dichlorophenylboronic acid is provided. The system for continuously preparing 3,4-dichlorophenylboronic acid is used to continuously synthesize 3,4-dichlorophenylboronic acid. The method comprises: adding o-dichlorobenzene, bromine and ferric bromide into a first reaction module through a first feeding module for bromination reaction, and the product of the bromination reaction enters a first quenching module for a first quenching treatment to obtain 3,4-dichlorobromobenzene; adding 3,4-dichlorobromobenzene, magnesium powder and tetrahydrofuran into a second reaction module through a second feeding module for Grignard reagent preparation to obtain a Grignard reagent; adding the Grignard reagent and trimethyl borate into a third reaction module through a third feeding module for Grignard reaction, and the product of the Grignard reaction enters a second quenching module for a second quenching treatment to obtain 3,4-dichlorophenylboronic acid.

[0014] Furthermore, in the bromination reaction, the mass ratio of o-dichlorobenzene, bromine and ferric bromide is 1.0:1.0~3.0:0.1~2.0; preferably, the temperature of the bromination reaction is 0-60°C, and preferably, the time of the bromination reaction is 20-150min.

[0015] Furthermore, in the reaction of preparing the Grignard reagent, the mass ratio of 3,4-dichlorobromobenzene, magnesium powder and tetrahydrofuran is 1.0:1.0~3.0:0.50~5; preferably, the temperature of the reaction of preparing the Grignard reagent is 20~70°C, and preferably, the reaction time of the Grignard reagent is 20~200min.

[0016] Furthermore, in the Grignard reaction, the mass ratio of the Grignard reagent to trimethyl borate is 1.0:0.1-4.0; preferably, the temperature of the Grignard reaction is 0-40° C., and preferably, the time of the Grignard reaction is 30-150 min.

[0017] By applying the technical solution of the present invention, the above-mentioned continuous synthesis system is used to prepare 3,4-dichlorophenylboronic acid, which can realize automatic control, save labor, save production time, and effectively reduce production costs; at the same time, it can improve production efficiency and product yield; the above-mentioned continuous synthesis process is used to prepare 3,4-dichlorophenylboronic acid, and online quenching can be realized, avoiding the danger caused by long-term storage of a large amount of highly reactive materials, thereby greatly improving process safety. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] The drawings constituting a part of the present application are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation of the present invention. In the drawings:

[0019] Figure 1 A schematic diagram of a system for continuous preparation of 3,4-dichlorophenylboronic acid in an embodiment of the present application is shown;

[0020] The above drawings include the following reference numerals:

[0021] 101: first reaction module; 102: first quenching module; 103: first liquid separation module; 104: first concentration module; 201: second reaction module; 301: third reaction module; 302: second quenching module; 303: second concentration module; 304: first crystallization module. DETAILED DESCRIPTION

[0022] It should be noted that, in the absence of conflict, the embodiments and features in the embodiments of the present application can be combined with each other. The present invention will be described in detail below with reference to the accompanying drawings and in combination with the embodiments.

[0023] The present application is further described in detail below in conjunction with specific embodiments. These embodiments should not be construed as limiting the scope of protection claimed in the present application.

[0024] As described in the background technology, the existing production of 3,4-dichlorophenylboronic acid mostly adopts an intermittent operation mode, which has the problems of high labor intensity, low production efficiency, poor heat exchange, many side reactions, high risk factor, etc. Therefore, in the first typical embodiment of the present application, a system for continuously preparing 3,4-dichlorophenylboronic acid is provided, including: a bromination reaction unit, the bromination reaction unit is composed of a first feed module, a first reaction module 101 and a first quenching module 102 connected in sequence; a Grignard reagent preparation unit, the Grignard reagent preparation unit is composed of a second feed module and a second reaction module 201 connected in sequence; and a Grignard reaction unit, the Grignard reaction unit is composed of a third feed module, a third reaction module 301 and a second quenching module 302 connected in sequence; the bromination reaction unit, the Grignard reagent preparation unit and the Grignard reaction unit are connected in sequence.

[0025] Using the above continuous system (such as Figure 1 As shown in the figure, the bromination reaction, the preparation of the Grignard reagent and the Grignard reaction can be completed continuously and efficiently in a controllable manner to obtain 3,4-dichlorophenylboronic acid. The continuous bromination reaction system reduces the multi-substituted impurities and improves the reaction yield by screening the retention time and equivalent of the bromination reagent in the continuous reactor; at the same time, the excellent heat exchange efficiency of the continuous reactor can more accurately control the reaction temperature to remove the generated heat and reduce the thermal risk. In the continuous Grignard reagent preparation and Grignard reaction stage, the prepared high-activity Grignard reagent quickly enters the next stage through the continuous reaction system to mix with the addition substrate to quickly generate the product, which greatly reduces the generation of coupling impurities and dehalogenation impurities of the Grignard reagent and improves the yield.

[0026] In order to further efficiently control the feeding efficiency of the bromination reaction, in a preferred embodiment, the first feeding module includes a continuous bromine feeding device, a continuous ferric bromide solution feeding device, a continuous o-dichlorobenzene feeding device, a continuous sodium hydroxide solution feeding device and a control system; the discharge ports of the continuous bromine feeding device, the continuous ferric bromide solution feeding device and the continuous o-dichlorobenzene feeding device are connected to the feed port of the first reaction module 101, and the discharge port of the continuous sodium hydroxide solution feeding device is connected to the feed port of the first quenching module 102. The control system is connected to the continuous bromine feeding device, the continuous ferric bromide solution feeding device, the continuous o-dichlorobenzene feeding device and the continuous sodium hydroxide solution feeding device through explosion-proof cables, respectively, and the accurate feed amount of the above devices is controlled according to the control logic of negative feedback regulation.

[0027] In order to further accurately control the progress of the bromination reaction in the first reaction module 101, in a preferred embodiment, the first reaction module 101 includes: a first main reactor, a first temperature control device, a first tail gas absorption device and a first explosion relief device; the first temperature control device is connected to the first main reactor through a public engineering pipeline, and the reaction temperature in the first main reactor is controlled by negative feedback regulation; the first tail gas absorption device and the first explosion relief device are connected to the first main reactor through the first tail gas absorption pipeline and the first explosion relief pipeline respectively. Among them, the discharge ports of the continuous bromine feeding device, the continuous ferric bromide solution feeding device and the continuous o-dichlorobenzene feeding device are connected to the feed port of the first main reactor through a pipeline; the feed port of the first main reactor is connected to the discharge port of the first feeding module.

[0028] In order to further control the reaction environment of the bromination reaction at a more appropriate level, in a preferred embodiment, the first main reactor includes a mixer and a first reactor connected in sequence; preferably, the type of the first reactor is selected from any one of the following: a microchannel tubular reactor, a continuous overflow reactor, a dynamic tubular reactor, a vertical tube reactor, a tube reactor, a coil reactor, a U-shaped tubular reactor and a horizontal tubular reactor. Different types of reactors have different control over the temperature of the reaction and the degree of contact of the reactants. In a preferred embodiment, the type of the first reactor is a horizontal tubular reactor. In a preferred embodiment, the material of the first reactor is selected from any one of the following: Hastelloy A, Hastelloy B, Hastelloy C, nickel, monel, polytetrafluoroethylene and Stellite 19-P, preferably nickel.

[0029] In order to reduce the occurrence of side reactions in subsequent reactions, the material discharged from the first reaction module 101 needs to pass through the first quenching module 102 to stop the reaction and perform preliminary separation and concentration on the output material. In a preferred embodiment, the first quenching module 102 also includes a first liquid separation module 103 and a first concentration module 104 connected in series, which can sequentially quench, separate and concentrate the material discharged from the first reaction module 101. In a preferred embodiment, the 3,4-dichlorobromobenzene solution obtained by the bromination reaction unit is discharged from the discharge port of the first concentration module 104 and then passed into the second feed module in the Grignard reagent preparation unit.

[0030] In order to further efficiently control the feeding efficiency of the Grignard reagent preparation, in a preferred embodiment, the second feeding module includes a continuous 3,4-dichlorobromobenzene feeding device, a continuous tetrahydrofuran feeding device, a continuous magnesium powder feeding device, a mixing device and a control system; the inlet of the continuous 3,4-dichlorobromobenzene feeding device is connected to the outlet of the first concentration module 104, the outlets of the 3,4-dichlorobromobenzene feeding device and the continuous tetrahydrofuran feeding device are connected to the inlet of the mixing device, 3,4-dichlorobromobenzene and tetrahydrofuran enter the mixing device for mixing to obtain a tetrahydrofuran solution of 3,4-dichlorobromobenzene, the outlets of the mixing device and the continuous magnesium powder feeding device are respectively connected to the inlet of the second reaction module 201, the control system is respectively connected to the continuous 3,4-dichlorobromobenzene feeding device, the continuous tetrahydrofuran feeding device, the continuous magnesium powder feeding device, and the mixing device through explosion-proof cables, and the accurate feeding amount of the above devices is controlled according to the control logic of negative feedback regulation.

[0031] In order to further accurately control the preparation of the Grignard reagent in the second reaction module 201, in a preferred embodiment, the second reaction module 201 includes: a second main reactor, a second temperature control device, a second tail gas absorption device and a first nitrogen protection device; the second temperature control device is connected to the second main reactor through a public engineering pipeline, and the reaction temperature in the second main reactor is controlled by negative feedback regulation; the second tail gas absorption device and the first nitrogen protection device are connected to the second main reactor through the second tail gas absorption pipeline and the first nitrogen pipeline respectively; the feed inlet of the second main reactor is connected to the feed outlet of the second feed module.

[0032] In order to further control the reaction environment of the Grignard reagent preparation at a more appropriate level, in a preferred embodiment, the second main reactor includes a second reactor and a first agitator arranged in the second reactor; in a preferred embodiment, the type of the second reactor is selected from any one of the following: a slurry bed reactor, a trickle bed reactor, a suspended bed reactor and an inner loop reactor with a guide tube, and when the type of the second reactor is one of a slurry bed reactor, a trickle bed reactor or a suspended bed reactor, a first guide structure is also provided in the second reactor. More preferably, the type of the second reactor is a suspended bed reactor. In a preferred embodiment, the material of the first reactor is selected from any one of the following: high carbon steel, 304 stainless steel, 316L stainless steel and Hastelloy, preferably 304 stainless steel.

[0033] In order to further efficiently control the feeding efficiency of the Grignard reaction, in a preferred embodiment, the third feeding module includes a continuous Grignard reagent feeding device, a continuous trimethyl borate solution feeding device, a continuous hydrochloric acid solution feeding device and a control system; the inlet of the continuous Grignard reagent feeding device is connected to the outlet of the second reactor, the outlet of the continuous trimethyl borate solution feeding device is connected to the inlet of the third reaction module 301, and the outlet of the continuous hydrochloric acid solution feeding device is connected to the inlet of the second quenching module 302. The control system is connected to the continuous Grignard reagent feeding device, the continuous trimethyl borate solution feeding device and the continuous hydrochloric acid solution feeding device through explosion-proof cables, respectively, and the accurate feeding amount of the above devices is controlled according to the control logic of negative feedback regulation.

[0034] In order to further accurately control the progress of the Grignard reaction in the third reaction module 301, in a preferred embodiment, the third reaction module 301 includes: a third main reactor, a third temperature control device, a third tail gas absorption device and a second nitrogen protection device; the third temperature control device is connected to the third main reactor through a public engineering pipeline, and the reaction temperature in the third main reactor is controlled by negative feedback regulation; the third tail gas absorption device and the second nitrogen protection device are connected to the third main reactor through a third tail gas absorption pipeline and a second nitrogen pipeline respectively; the feed inlet of the third main reactor is connected to the feed outlet of the third feed module.

[0035] In order to further control the Grignard reaction to be carried out under a more suitable environment, in a preferred embodiment, the third main reactor includes a third reactor and a second agitator arranged in the third reactor; preferably, the type of the third reactor is selected from any one of the following: a continuous overflow reactor, an internal loop reactor with a guide tube, a vertical tube reactor and a tube reactor, and when the type of the third reactor is one of a continuous overflow reactor, a vertical tube reactor or a tube reactor, a second guide structure is also arranged in the third reactor. In a preferred embodiment, the type of the third reactor is an internal loop reactor with a guide tube.

[0036] In order to reduce the occurrence of side reactions and further obtain a purer product 3,4-dichlorophenylboronic acid, the material discharged from the third reaction module 301 needs to pass through the second quenching module 302 to stop the reaction and perform preliminary separation and concentration on the output material. In a preferred embodiment, the second quenching module 302 also includes a second concentration module 303 and a first crystallization module 304 which are connected in series in sequence, which can sequentially quench, concentrate and crystallize the material discharged from the third reaction module 301.

[0037] In order to further accurately control the liquid reactants entering each reaction module, in a preferred embodiment, the continuous bromine feeding device, the continuous ferric bromide solution feeding device, the continuous o-dichlorobenzene feeding device, the continuous sodium hydroxide solution feeding device, the continuous 3,4-dichlorobromobenzene feeding device, the continuous tetrahydrofuran feeding device, the mixing device, the continuous Grignard reagent feeding device, the continuous trimethyl borate solution feeding device and the continuous hydrochloric acid solution feeding device also include: a delivery pump, a metering system and a liquid feeding control system. The discharge port of each continuous liquid feeding device is connected to the inlet of the corresponding reactor through a delivery pump, and the metering system is connected to each continuous liquid feeding device and the control system respectively. The metering system feeds back the feed amount of each continuous liquid feeding device to the control system, and the control system sends a flow adjustment instruction to the delivery pump according to the control logic of negative feedback regulation to ensure the accuracy of the feed amount.

[0038] In a second typical embodiment of the present application, a method for continuously preparing 3,4-dichlorophenylboronic acid is provided, and the above-mentioned system for continuously preparing 3,4-dichlorophenylboronic acid is used to continuously synthesize 3,4-dichlorophenylboronic acid, and the method comprises: adding o-dichlorobenzene, bromine and ferric bromide to a first reaction module 101 through a first feeding module for bromination reaction, and the product of the bromination reaction enters a first quenching module 102 for a first quenching treatment to obtain 3,4-dichlorobromobenzene; adding 3,4-dichlorobromobenzene, magnesium powder and tetrahydrofuran to a second reaction module 201 through a second feeding module for Grignard reagent preparation to obtain a Grignard reagent; adding the Grignard reagent and trimethyl borate to a third reaction module 301 through a third feeding module for Grignard reaction, and the product of the Grignard reaction enters a second quenching module 302 for a second quenching treatment to obtain 3,4-dichlorophenylboronic acid.

[0039] In a preferred embodiment, orthodichlorobenzene, bromine and ferric bromide are added to the first main reactor of the first reaction module 101 respectively through the continuous bromine feeding device, the continuous ferric bromide solution feeding device and the continuous orthodichlorobenzene feeding device in the first feeding module, and the accurate feeding amount of the above devices is controlled by the control system according to the control logic of negative feedback regulation. The bromination reaction is carried out in the first main reactor, and the temperature and by-products of the reaction are controlled by the first temperature control device, the first tail gas absorption device and the first explosion relief device during the bromination reaction. The material discharged from the first main reactor in the first reaction module 101 needs to pass through the first quenching module 102, stop the reaction with sodium hydroxide and perform preliminary separation and concentration of the output material through the first liquid separation module 103 and the first concentration module 104 to obtain 3,4-dichlorobromobenzene solution.

[0040] In a preferred embodiment, in the bromination reaction, the mass ratio of o-dichlorobenzene, bromine and ferric bromide is 1.0:1.0~3.0:0.1~2.0; the temperature of the bromination reaction is 0-60°C, and the time of the bromination reaction is 20-150min.

[0041] In a preferred embodiment, the 3,4-dichlorobromobenzene solution enters the continuous 3,4-dichlorobromobenzene feeding device from the first concentration module 104, and the 3,4-dichlorobromobenzene and tetrahydrofuran are added to the mixing device through the continuous 3,4-dichlorobromobenzene feeding device and the continuous tetrahydrofuran feeding device in the second feeding module, respectively, to obtain the tetrahydrofuran solution of 3,4-dichlorobromobenzene, and the mixing device and the continuous magnesium powder feeding device respectively add the tetrahydrofuran solution of 3,4-dichlorobromobenzene and magnesium powder to the second main reactor of the second reaction module 201, and the control system controls the accurate feeding amount of the above devices according to the control logic of negative feedback regulation. The reaction of the Grignard reagent preparation is carried out in the second main reactor, and the reaction temperature, reaction environment gas and by-products are controlled by the second temperature control device, the second tail gas absorption device and the first nitrogen protection device during the Grignard reagent preparation process.

[0042] In a preferred embodiment, in the reaction of preparing the Grignard reagent, the mass ratio of 3,4-dichlorobromobenzene, magnesium powder and tetrahydrofuran is 1.0:1.0~3.0:0.50~5; the temperature of the reaction of preparing the Grignard reagent is 20~70°C, and the time of the reaction of preparing the Grignard reagent is 20~200 min.

[0043] In a preferred embodiment, the Grignard reagent enters the continuous Grignard reagent feeding device from the second reaction module 201, and the Grignard reagent and trimethyl borate are added to the first main reactor of the third reaction module 301 by the continuous Grignard reagent feeding device and the continuous trimethyl borate solution feeding device in the third feeding module, respectively, and the accurate feed amount of the above-mentioned device is controlled by the control system according to the control logic of negative feedback regulation. The Grignard reaction is carried out in the third main reactor, and the temperature, reaction environment gas and by-product of the reaction are controlled by the third temperature control device, the third tail gas absorption device and the second nitrogen protection device during the Grignard reaction. The material discharged from the third main reactor in the third reaction module 301 needs to pass through the second quenching module 302, and the reaction is stopped by hydrochloric acid and the output material is concentrated and crystallized by the second concentration module 303 and the first crystallization module 304 to obtain 3,4-dichlorophenylboronic acid.

[0044] In a preferred embodiment, in the Grignard reaction, the mass ratio of the Grignard reagent to trimethyl borate is 1.0:0.5-2.0; the temperature of the Grignard reaction is 0-40° C., and the time of the Grignard reaction is 30-150 min.

[0045] The beneficial effects of the present application will be further described below in conjunction with specific embodiments. It should be noted that the equipment used in the following embodiments is as follows: Figure 1 shown.

[0046] Example 1 Effects of different types of first reactors on bromination reaction

[0047] Ortho-dichlorobenzene, bromine and ferric bromide are respectively added to the first main reactor of the first reaction module 101 through the continuous bromine feeding device, the continuous ferric bromide solution feeding device and the continuous ortho-dichlorobenzene feeding device in the first feeding module. The accurate feeding amount of the above devices is controlled by the control system according to the control logic of negative feedback regulation, wherein ortho-dichlorobenzene, bromine and ferric bromide are added to the first main reactor at mass flow rates of 1.00 kg / h, 1.50 kg / h and 0.1 kg / h, respectively.

[0048] The bromination reaction is carried out in the first main reactor, wherein the type of the first reactor in the first main reactor is shown in Table 1 below, and the material is nickel. The temperature of the reaction and the by-product gas content are controlled by the first temperature control device, the first tail gas absorption device and the first explosion relief device. Among them, the temperature of the bromination reaction is 50°C and the time is 130min. The material discharged from the first main reactor in the first reaction module 101 needs to pass through the first quenching module 102, stop the reaction with sodium hydroxide, and perform preliminary separation and concentration of the output material through the first liquid separation module 103 and the first concentration module 104 to obtain the bromination reaction material. The o-dichlorobenzene residue, reaction molar yield, product separation yield and product purity of the bromination reaction material are shown in Table 1 below.

[0049] In addition, except for the different types of the first reactor in the first main reactor, the other bromination reaction conditions and parameters are the same as above, and the different types of first reactors and the corresponding parameters of the products are shown in Table 1 below. Among them, the calculation method of the remaining o-dichlorobenzene is the ratio of the mass of o-dichlorobenzene in the total product of the first reaction to the mass of the added o-dichlorobenzene reactant; the calculation method of the reaction molar yield is the ratio of the mass of the total product in the system after the reaction to the mass of the reactant; the calculation method of the product separation yield is the ratio of the mass of the total product of the reaction after post-treatment (i.e., the material discharged from the first concentration module 104) to the mass of the reactant; the product separation yield removes some impurities compared to the reaction molar yield, and loses some yield in the process of removing impurities. It can be seen that when the first reactor is a horizontal tubular reactor, the product separation yield of the bromination reaction is higher.

[0050] Table 1:

[0051]

[0052] Example 2 Effect of different mass ratios of reactants on bromination reaction

[0053] The first reactor in this embodiment is a horizontal tubular reactor made of nickel. Except that the mass ratio of the reactants o-dichlorobenzene, bromine and ferric bromide is different from that in Example 1, the other reaction conditions and parameters are the same as those in Example 1. The parameters of the reactants in different mass ratios and the corresponding products are shown in Table 2 below.

[0054] Table 2:

[0055]

[0056] Example 3 Effect of different types of second reactors on the preparation of Grignard reagents

[0057] The 3,4-dichlorobromobenzene solution enters the continuous 3,4-dichlorobromobenzene feeding device from the first concentration module 104, and is mixed in the mixing device through the continuous 3,4-dichlorobromobenzene feeding device in the second feeding module and the tetrahydrofuran in the continuous tetrahydrofuran feeding device to obtain the tetrahydrofuran solution of 3,4-dichlorobromobenzene. The mixing device and the continuous magnesium powder feeding device respectively add the tetrahydrofuran solution of 3,4-dichlorobromobenzene and magnesium powder into the second main reactor of the second reaction module 201. The control system is used to control the accurate feeding amount of the above devices according to the control logic of negative feedback regulation, wherein 3,4-dichlorobromobenzene, magnesium powder, and tetrahydrofuran participate in the preparation of Grignard reagent at mass flow rates of 1.00 kg / h, 1.00 kg / h, and 3.00 kg / h, respectively.

[0058] The preparation of Grignard reagent is carried out in the second main reactor, wherein the type of the second reactor in the second main reactor is shown in Table 3 below, and the material is 304 stainless steel. The reaction temperature, reaction environment gas and by-product gas content are controlled by the second temperature control device, the second tail gas absorption device and the first nitrogen protection device. Among them, the temperature of the reaction for preparing the Grignard reagent is 55°C, the time is 90min, the Grignard reagent is obtained, and the material in the second reactor is tested to obtain the residual content of 3,4-dichlorobromobenzene. The influence of different types of second reactors on the preparation of Grignard reagent, that is, the influence of the residual content of the product 3,4-dichlorobromobenzene is shown in Table 3. It can be seen that when the second reactor is a suspended bed reactor, the residual content of 3,4-dichlorobromobenzene in the Grignard reagent preparation reaction is lower. Among them, the calculation method of the remaining 3,4-dichlorobromobenzene is the ratio of the mass of 3,4-dichlorobromobenzene in the total product of the second reaction to the mass of the added 3,4-dichlorobromobenzene reactant;

[0059] Table 3:

[0060]

[0061] Example 4

[0062] The second reactor in this embodiment is a suspended bed reactor made of 304 stainless steel. Except that the mass ratio of the reactants 3,4-dichlorobromobenzene, magnesium powder, and tetrahydrofuran is different from that in Example 3, the other reaction conditions and parameters are the same as those in Example 3. The parameters of the reactants with different mass ratios and the corresponding residual content of 3,4-dichlorobromobenzene are shown in Table 4 below.

[0063] Table 4:

[0064]

[0065] Example 5

[0066] The Grignard reagent enters the continuous Grignard reagent feeding device from the second reaction module 201, and the Grignard reagent and trimethyl borate are respectively added to the third main reactor of the third reaction module 301 through the continuous Grignard reagent feeding device and the continuous trimethyl borate solution feeding device in the third feeding module. The accurate feeding amount of the above devices is controlled by the control system according to the control logic of negative feedback regulation, wherein the Grignard reagent and trimethyl borate are added to the third main reactor at mass flow rates of 1.00 kg / h and 0.5 kg / h, respectively.

[0067] The Grignard reaction is carried out in the third main reactor, wherein the type of the third reactor in the third main reactor is shown in Table 5 below, and the material is 304 stainless steel. The temperature of the reaction, the reaction environment gas and the by-product gas content are controlled by the third temperature control device, the third tail gas absorption device and the second nitrogen protection device. Among them, the temperature of the Grignard reaction is 35°C and the time is 60 min. The material discharged from the third main reactor in the third reaction module 301 needs to pass through the second quenching module 302, stop the reaction with hydrochloric acid and concentrate and crystallize the output material through the second concentration module 303 and the first crystallization module 304 to obtain 3,4-dichlorophenylboronic acid. Different types of third reactors and corresponding parameters of the products are shown in Table 5 below. It can be seen that when the third reactor is a continuous overflow reactor, the product separation yield of the Grignard reaction is higher.

[0068] Among them, o-dichlorobenzene is a substance produced by quenching the Grignard reagent, and the calculation method of the remaining o-dichlorobenzene is the ratio of the mass of o-dichlorobenzene in the total product of the third reaction to the mass of the added Grignard reagent reactant; the calculation method of the reaction molar yield is the ratio of the mass of the total product in the system after the reaction to the mass of the reactant; the calculation method of the product separation yield is the ratio of the mass of the total reaction product after post-treatment (i.e., the material discharged from the first concentration module 104) to the mass of the reactant;

[0069] Table 5:

[0070]

[0071] Example 6

[0072] The third reactor in this embodiment is a continuous overflow reactor made of 304 stainless steel. Except that the mass ratio of the reactants Grignard reagent and trimethyl borate is different from that in Example 5, the other reaction conditions and parameters are the same as those in Example 5. The parameters of the reactants in different mass ratios and the corresponding products are shown in Table 6 below.

[0073] Table 6:

[0074]

[0075] Comparative Example 1 (Batch Reaction)

[0076] Add 5g of o-dichlorobenzene into a 250ml four-necked bottle, then add 0.1g of ferric bromide, and finally slowly drop 7.5g of bromine. At the same time, raise the temperature to 60°C for reaction. After reacting for 140 minutes, the remaining o-dichlorobenzene is 5%, the reaction molar yield is 91%, the product separation yield is 85%, and the product purity is 95%.

[0077] In a 250ml four-necked bottle, add 75g 3,4-dichlorobromobenzene, then add 25g magnesium powder and 0.5g iodine, control the temperature at 60°C, reflux, and finally slowly drop 25g 3,4-dichlorobromobenzene. At the same time, raise the temperature to 80°C for reaction. After reacting for 140 minutes, 3,4-dichlorobromobenzene remains 3%. After delaying the reaction for 40 minutes, 3,4-dichlorobromobenzene remains 0%. Lower the temperature to 20°C, slowly drop 12.5g trimethyl borate, react for 130 minutes, and the product 3,4-dichlorobenzene boronic acid has a separation yield of 92%.

[0078] It can be seen that although Comparative Example 1 can obtain a product with a yield not much different from that of the embodiment, the total reaction time is relatively long. It takes 450 minutes to complete the production of 3,4-dichlorophenylboronic acid using the method of Comparative Example 1, while it takes about 280 minutes to complete the production using the scheme of the present application, which greatly improves the production efficiency compared with Comparative Example 1.

[0079] It can be seen from the above description that the above embodiments of the present invention achieve the following technical effects: the preparation of 3,4-dichlorophenylboronic acid by the above continuous synthesis system can realize automatic control, and each reactor has a large heat exchange specific surface area and a strong heat exchange capacity, which is beneficial to the control of the reaction temperature, and can also save labor, save production time, and effectively reduce production costs; at the same time, it can improve production efficiency and product yield; the preparation of 3,4-dichlorophenylboronic acid by the above continuous synthesis process can also realize online quenching, avoiding the danger caused by long-term storage of a large amount of highly reactive materials, and greatly improving the process safety.

[0080] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for continuously preparing 3,4-dichlorophenylboronic acid, characterized in that: The continuous synthesis of 3,4-dichlorophenylboronic acid is carried out by using a continuous preparation system of 3,4-dichlorophenylboronic acid. Wherein, the system for continuously preparing 3,4-dichlorophenylboronic acid comprises: A bromination reaction unit, the bromination reaction unit comprising a first feed module, a first reaction module (101) and a first quenching module (102) connected in sequence; A Grignard reagent preparation unit, the Grignard reagent preparation unit comprising a second feed module and a second reaction module (201) connected in sequence; and A Grignard reaction unit, the Grignard reaction unit comprising a third feeding module, a third reaction module (301) and a second quenching module (302) connected in sequence; The bromination reaction unit, the Grignard reagent preparation unit and the Grignard reaction unit are connected in sequence; The first reaction module (101) comprises: a first main reactor, the first main reactor comprising a mixer and a first reactor connected in sequence; The first reactor is a horizontal tubular reactor; The second reaction module (201) further comprises: a second main reactor, the second main reactor comprising a second reactor and a first agitator arranged in the second reactor; The second reactor is a suspended bed reactor; The third reaction module (301) comprises: a third main reactor, the third main reactor comprising a third reactor and a second agitator arranged in the third reactor; The third reactor is a continuous overflow reactor; The method comprises: Adding o-dichlorobenzene, bromine and ferric bromide into the first reaction module (101) through the first feed module for a bromination reaction, and the product of the bromination reaction enters the first quenching module (102) for a first quenching treatment to obtain 3,4-dichlorobromobenzene; Adding the 3,4-dichlorobromobenzene, magnesium powder and tetrahydrofuran into the second reaction module (201) through the second feed module to prepare a Grignard reagent, thereby obtaining a Grignard reagent; The Grignard reagent and trimethyl borate are added to the third reaction module (301) through the third feed module to perform a Grignard reaction, and the product of the Grignard reaction enters the second quenching module (302) for a second quenching treatment to obtain 3,4-dichlorophenylboronic acid; In the bromination reaction, the mass ratio of the o-dichlorobenzene, the bromine and the ferric bromide is 1.0:2.0-2.5:0.1; In the reaction of preparing the Grignard reagent, the mass ratio of the 3,4-dichlorobromobenzene, the magnesium powder and the tetrahydrofuran is 1.0:2.0~3.0:4.0~5.0; In the Grignard reaction, the mass ratio of the Grignard reagent to the trimethyl borate is 1.0:2.0-3.

0.

2. The method according to claim 1, characterized in that: The first reaction module (101) further comprises: a first temperature control device, a first tail gas absorption device and a first explosion relief device; The first temperature control device is connected to the first main reactor through a public engineering pipeline, and controls the reaction temperature in the first main reactor through negative feedback regulation; The first tail gas absorption device and the first explosion relief device are connected to the first main reactor through a first tail gas absorption pipeline and a first explosion relief pipeline respectively; The feed inlet of the first main reactor is connected to the feed outlet of the first feed module.

3. The method according to claim 1, characterized in that The second reaction module (201) further comprises: a second temperature control device, a second tail gas absorption device and a first nitrogen protection device; The second temperature control device is connected to the second main reactor through a utility pipeline, and controls the reaction temperature in the second main reactor through negative feedback regulation; The second tail gas absorption device and the first nitrogen protection device are connected to the second main reactor through a second tail gas absorption pipeline and a first nitrogen pipeline respectively; The feed inlet of the second main reactor is connected to the feed outlet of the second feed module.

4. The method according to claim 1, characterized in that: The third reaction module (301) further comprises: a third temperature control device, a third tail gas absorption device and a second nitrogen protection device; The third temperature control device is connected to the third main reactor through a public engineering pipeline, and controls the reaction temperature in the third main reactor through negative feedback regulation; The third tail gas absorption device and the second nitrogen protection device are connected to the third main reactor through a third tail gas absorption pipeline and a second nitrogen pipeline respectively; The feed inlet of the third main reactor is connected to the feed outlet of the third feed module.

5. The method according to claim 1, characterized in that The temperature of the bromination reaction is 0-60° C., and the time of the bromination reaction is 20-150 min.

6. The method according to claim 1, characterized in that The reaction temperature of the Grignard reagent preparation is 20-70° C., and the reaction time of the Grignard reagent preparation is 20-200 min.

7. The method according to claim 1, characterized in that The temperature of the Grignard reaction is 0-40° C., and the time of the Grignard reaction is 30-150 min.

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