阅读说明：本技术 三苯基磷中间体苯基氯化镁的连续合成装置及方法 (Continuous synthesis device and method of triphenylphosphine intermediate phenylmagnesium chloride ) 是由 周留扣 杨智深 徐小海 蔡继元 于 2020-05-27 设计创作，主要内容包括：本发明公开了三苯基磷中间体苯基氯化镁的连续合成装置及方法,属于医药中间体合成领域。三苯基磷中间体苯基氯化镁的连续合成装置,包括干燥器、溶剂混合釜、混合溶剂储罐、镁屑加料器、冷凝器、一级反应釜、二级反应釜、反应液降温釜、苯基氯化镁储存罐和氯苯添加通道；本发明一级反应釜反应完成后的试剂反应液中无镁屑残存,降低了下一步产生氢气的风险,整个过程,缩短反应流程,降低设备投资,能耗有效降低,降低风险,提高安全系数,形成一种高效的绿色工艺。(The invention discloses a continuous synthesis device and method of triphenylphosphine intermediate phenylmagnesium chloride, belonging to the field of synthesis of medical intermediates. The continuous synthesis device of the triphenylphosphine intermediate phenylmagnesium chloride comprises a dryer, a solvent mixing kettle, a mixed solvent storage tank, a magnesium scrap feeder, a condenser, a primary reaction kettle, a secondary reaction kettle, a reaction liquid cooling kettle, a phenylmagnesium chloride storage tank and a chlorobenzene adding channel; according to the invention, no magnesium chips remain in the reagent reaction solution after the reaction of the first-stage reaction kettle is completed, the risk of generating hydrogen in the next step is reduced, the whole process is shortened, the equipment investment is reduced, the energy consumption is effectively reduced, the risk is reduced, the safety coefficient is improved, and an efficient green process is formed.)

1. Continuous synthesis device of triphenyl phosphine midbody phenyl magnesium chloride, its characterized in that: including desicator (1), solvent mixing kettle (2), mixed solvent storage tank (3), magnesium bits charging means (4), condenser (5), one-level reation kettle (6), second grade reation kettle (7), reaction liquid cooling cauldron (8), phenyl magnesium chloride holding vessel (9) and chlorobenzene add passageway (10), desicator (1), solvent mixing kettle (2), mixed solvent storage tank (3), one-level reation kettle (6), second grade reation kettle (7), reaction liquid cooling cauldron (8), phenyl magnesium chloride holding vessel (9) link to each other in proper order through the pipeline, magnesium bits charging means (4) discharge gate is connected on the feed inlet of one-level reation kettle (6), chlorobenzene adds passageway (10) discharge gate and connects on the feed inlet of one-level reation kettle (6).

2. The continuous synthesis device of triphenylphosphine intermediate phenylmagnesium chloride according to claim 1, wherein: and the first-stage reaction kettle (6), the second-stage reaction kettle (7) and the reaction liquid cooling kettle (8) are all connected with a condenser (5).

3. The continuous synthesis device of triphenylphosphine intermediate phenylmagnesium chloride according to claim 1, wherein: stirrers are arranged in the solvent mixing kettle (2), the first-stage reaction kettle (6), the second-stage reaction kettle (7) and the reaction liquid cooling kettle (8).

4. The continuous synthesis device of triphenylphosphine intermediate phenylmagnesium chloride according to claim 1, wherein: the solvent in the mixed solvent storage tank (3) is a mixed solvent of toluene and tetrahydrofuran with the volume of 1: 1.

5. The continuous synthesis device of triphenylphosphine intermediate phenylmagnesium chloride according to any one of claims 1-4, wherein the reaction temperature of the primary reaction kettle (6) is 95-100 ℃.

6. A method for preparing triphenylphosphine intermediate phenylmagnesium chloride by using the device of any one of claims 1-4, comprising the following operations:

1) mixing toluene and tetrahydrofuran in a solvent mixing kettle (2), and then entering a mixed solvent storage tank (3);

2) mixing toluene and tetrahydrofuran: chlorobenzene: the magnesium chips are respectively fed from a mixed solvent storage tank (3), a chlorobenzene adding channel (10) and a magnesium chip feeder (4) in a mixed mode;

3) controlling the reaction temperature of the mixed feed in the first-stage reaction kettle (6) and the second-stage reaction kettle (7) to be 95-100 ℃;

4) and discharging the reaction liquid from the secondary reaction kettle, feeding the reaction liquid into a cooling kettle (8) to obtain a phenylmagnesium chloride solution, and transferring the phenylmagnesium chloride solution into a phenylmagnesium chloride storage tank (9).

7. The method for preparing triphenylphosphine intermediate phenylmagnesium chloride according to claim 6, wherein: the volume ratio of the toluene and tetrahydrofuran mixed solvent is 1:1, and the water content is lower than 0.2%.

8. The method for preparing triphenylphosphine intermediate phenylmagnesium chloride according to claim 6, wherein: the toluene and tetrahydrofuran mixed solvent: chlorobenzene: the proportion of the magnesium chips is 1200L: 300L: 75 kg.

Technical Field

The invention relates to the technical field of synthesis of medical intermediates, in particular to a continuous synthesis device and a continuous synthesis method of triphenylphosphine intermediate phenylmagnesium chloride.

Background

At present, phenylmagnesium chloride is a key raw material for synthesizing triphenylphosphine, and the method mainly adopts intermittent production, has low efficiency, large equipment investment, high production risk and complex process.

In the actual production, the mixed solution of half toluene and tetrahydrofuran is firstly added at low temperature, then magnesium chips are added, the temperature is controlled to be about 60 ℃, chlorobenzene is slowly dripped to initiate reaction, the risk of the stage is high, and the material is easily flushed due to improper control. After the reaction is initiated, adding the other half of the mixed solution, continuously dropwise adding chlorobenzene for reaction, finishing the addition of the chlorobenzene, slowly raising the temperature to 90 ℃, and then preserving the temperature for reaction for 2 hours until the reaction is finished.

After the reaction is finished, standing to settle magnesium chip solids, transferring the magnesium chip solids to a reaction liquid to react with phosphorus trichloride in the next step, and introducing unreacted magnesium chips in the process can easily generate hydrogen to easily cause fire, so that the disadvantages of long reaction time, low equipment utilization rate and the like can be caused by slow dropwise addition at low temperature, solvent adding in times, low-temperature reaction sections and the like.

Disclosure of Invention

The invention aims to solve the problems in the prior art and provides a continuous synthesis device of triphenylphosphine intermediate phenylmagnesium chloride.

In order to achieve the purpose, the invention adopts the following technical scheme:

continuous synthesizer of triphenyl phosphorus midbody phenyl magnesium chloride, add the passageway including desicator, solvent mixing kettle, mixed solvent storage tank, magnesium bits charging means, condenser, one-level reation kettle, second grade reation kettle, reaction liquid cooling cauldron, phenyl magnesium chloride holding vessel and chlorobenzene, desicator, solvent mixing kettle, mixed solvent storage tank, one-level reation kettle, second grade reation kettle, reaction liquid cooling cauldron, phenyl magnesium chloride holding vessel pass through the pipeline and link to each other in proper order, magnesium bits charging means discharge gate is connected on one-level reation kettle's feed inlet, the chlorobenzene adds the passageway discharge gate and connects on one-level reation kettle's feed inlet.

Further, in the above technical scheme, condensers are connected to the primary reaction kettle, the secondary reaction kettle and the reaction liquid cooling kettle.

Further, in the above technical scheme, stirrers are arranged in the solvent mixing kettle, the primary reaction kettle, the secondary reaction kettle and the reaction liquid cooling kettle.

Further, in the above technical scheme, the solvent in the mixed solvent storage tank is a mixed solvent of toluene and tetrahydrofuran in a volume ratio of 1: 1.

Further, in the technical scheme, the reaction temperature of the primary reaction kettle is 95-100 ℃.

A method for preparing triphenylphosphine intermediate phenylmagnesium chloride by adopting the device comprises the following operations:

1) mixing toluene and tetrahydrofuran in a solvent mixing kettle, and then entering a mixed solvent storage tank;

2) mixing toluene and tetrahydrofuran: chlorobenzene: the magnesium chips are respectively fed from a mixed solvent storage tank, a chlorobenzene adding channel and a magnesium chip feeder in a mixed mode;

3) controlling the reaction temperature of the mixed feed in the first-stage reaction kettle and the second-stage reaction kettle to be 95-100 ℃;

4) and discharging the reaction liquid from the secondary reaction kettle, feeding the reaction liquid into a cooling kettle to obtain a phenylmagnesium chloride solution, and transferring the phenylmagnesium chloride solution into a phenylmagnesium chloride storage tank.

Further, in the above technical scheme, the volume ratio of the toluene and tetrahydrofuran mixed solvent is 1:1, and the water content is lower than 0.2%.

Further, in the above technical solution, the toluene and tetrahydrofuran mixed solvent: chlorobenzene: the proportion of the magnesium chips is 1200L: 300L: 75 kg.

Compared with the prior art, the invention provides a continuous synthesis device and a continuous synthesis method of triphenylphosphine intermediate phenylmagnesium chloride, which have the following beneficial effects:

1. according to the continuous synthesis device of the triphenylphosphine intermediate phenylmagnesium chloride, uninterrupted feeding reaction is carried out by utilizing continuous reaction equipment and design, so that each batch of initiation section and batch feeding process are omitted, and the reaction temperature is increased;

2. the invention adds a dryer to the mixed solvent for dehydration, ensures that the water content of the solvent is below 0.2 percent, and is simple and efficient; the dosage of the magnesium chips is reduced from 1.15 equivalent to 1.04 equivalent by 10 percent;

3. the process simplifies the reaction flow, shortens the reaction time, improves the utilization rate of equipment, and has the production capacity 3.6 times of that of batch reaction under the same condition of continuous operation; meanwhile, the process safety is improved; magnesium chips are not left in the reaction liquid after the reaction of the first-stage reaction kettle is finished, so that the risk of generating hydrogen in the next step is reduced.

4. The invention shortens the reaction flow, reduces the equipment investment, effectively reduces the energy consumption, improves the safety coefficient and is an efficient green process.

Drawings

FIG. 1 is a partial system diagram of a continuous synthesis apparatus for triphenylphosphine intermediate phenylmagnesium chloride;

FIG. 2 is a partial system schematic diagram of a continuous synthesis device of triphenylphosphine intermediate phenylmagnesium chloride provided by the invention.

1. A dryer; 2. a solvent mixing kettle; 3. a mixed solvent storage tank; 4. a magnesium scrap feeder; 5. a condenser; 6. a first-stage reaction kettle; 7. a second-stage reaction kettle; 8. cooling the reaction solution in a kettle; 9. a phenylmagnesium chloride storage tank; 10. chlorobenzene addition channel.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments.

In the description of the present invention, it is to be understood that the terms "upper", "lower", "front", "rear", "left", "right", "top", "bottom", "inner", "outer", and the like, indicate orientations or positional relationships based on the orientations or positional relationships shown in the drawings, are merely for convenience in describing the present invention and simplifying the description, and do not indicate or imply that the device or element being referred to must have a particular orientation, be constructed and operated in a particular orientation, and thus, should not be construed as limiting the present invention.

Referring to fig. 1-2, a continuous synthesis device of triphenylphosphine intermediate phenylmagnesium chloride comprises a dryer 1, a solvent mixing kettle 2, a mixed solvent storage tank 3, a magnesium scrap feeder 4, a condenser 5, a primary reaction kettle 6, a secondary reaction kettle 7, a reaction liquid cooling kettle 8, a phenylmagnesium chloride storage tank 9 and a chlorobenzene adding channel 10, wherein the dryer 1, the solvent mixing kettle 2, the mixed solvent storage tank 3, the primary reaction kettle 6, the secondary reaction kettle 7, the reaction liquid cooling kettle 8 and the phenylmagnesium chloride storage tank 9 are sequentially connected through a pipeline, a discharge hole of the magnesium scrap feeder 4 is connected to a feed inlet of the primary reaction kettle 6, and a discharge hole of the chlorobenzene adding channel 10 is connected to a feed inlet of the primary reaction kettle 6;

by utilizing continuous reaction equipment and design, the invention carries out uninterrupted feeding reaction, saves the initiation working section of each batch and the batch feeding process, and improves the reaction temperature; meanwhile, the dryer 1 is added for dehydrating the mixed solvent, so that the moisture of the solvent is ensured to be below 0.2 percent, and the method is simple and efficient; the consumption of the magnesium chips is reduced from the original 1.15 equivalent to 1.04 equivalent by 10 percent; the process simplifies the reaction flow, shortens the reaction time, improves the utilization rate of equipment, and has the continuous production capacity 3.6 times of the production capacity of the batch reaction under the same condition; meanwhile, the process safety is improved; magnesium chips in a reagent reaction solution after the reaction of the first-stage reaction kettle 6 is completed are basically not contained, the risk of hydrogen generation in the next step is reduced, the whole process is shortened, the equipment investment is reduced, the energy consumption is effectively reduced, the risk is reduced, the safety coefficient is improved, and an efficient green process is formed.

The first-stage reaction kettle 6, the second-stage reaction kettle 7 and the reaction liquid cooling kettle 8 are all connected with a condenser 5 for controlling the temperature.

The solvent mixing kettle 2, the first-stage reaction kettle 6, the second-stage reaction kettle 7 and the reaction liquid cooling kettle 8 are all provided with stirrers, so that the uniform mixing and stirring reaction is ensured.

The solvent in the mixed solvent storage tank 3 is a mixed solvent of toluene and tetrahydrofuran with the volume of 1: 1; the reaction temperature of the first-stage reaction kettle 6 is 95-100 ℃.

Comparative example 1:

putting 2600L of toluene and tetrahydrofuran mixed solvent (the volume ratio is 1:1, the water content is lower than 0.2%) into a 10000L reaction kettle, then putting 360 kg of magnesium chips, heating to 60 ℃, slowly dropwise adding (according to chlorobenzene 250L/h) for initiating reaction, dropwise adding 1 h for initiating normally, then putting the rest 2600L of toluene and tetrahydrofuran mixed solvent into the reaction kettle, dropwise adding chlorobenzene (according to 300L/h) into the reaction kettle, completely adding 1300L of chlorobenzene for 4-5 h, simultaneously controlling the temperature to slowly rise to 90-93 ℃, keeping the temperature for 2 h, sampling and analyzing that the chlorobenzene content is lower than 1%, finishing the reaction, cooling to 30 ℃, stopping stirring, standing and settling magnesium chips, and transferring from the upper part to the next step; the whole batch takes 12 hours from the feeding to the end of the transferring.