阅读说明：本技术 一种反应-精馏技术合成苯基丙二酸二乙酯的工艺方法 (Process method for synthesizing diethyl phenylmalonate by reaction-rectification technology ) 是由 牛磊磊 张朋 杨文兵 郭云山 于 2021-08-17 设计创作，主要内容包括：本发明公开了通过反应-精馏技术合成苯基丙二酸酯的工艺方法,将含有苯乙酸乙酯和碳酸二乙酯的原料与催化剂接触,经过反应、分离、结晶,制备得到所述的苯基丙二酸酯；所述催化剂为碱金属醇盐和/或碱金属醇盐的醇溶液；所述反应在精馏塔中进行,精馏塔塔顶温度40℃～50℃,精馏塔塔釜温度60℃～100℃；精馏塔塔内表压力-0.05MPa～-0.08MPa；塔顶回流比1:1～5:1。与传统工艺相比,产品无需精馏提纯,能耗明显降低,工艺简单,且可反应精馏塔可连续使塔顶乙醇含量稳定,副产乙醇无需再次精馏提纯。(The invention discloses a process method for synthesizing phenyl malonate by reaction-rectification technology, comprising the steps of contacting raw materials containing ethyl phenylacetate and diethyl carbonate with a catalyst, and preparing the phenyl malonate through reaction, separation and crystallization; the catalyst is alkali metal alkoxide and/or alcohol solution of alkali metal alkoxide; the reaction is carried out in a rectifying tower, the temperature of the top of the rectifying tower is 40-50 ℃, and the temperature of the bottom of the rectifying tower is 60-100 ℃; the pressure in the rectifying tower is-0.05 MPa to-0.08 MPa; the reflux ratio of the tower top is 1: 1-5: 1. Compared with the traditional process, the product does not need rectification and purification, the energy consumption is obviously reduced, the process is simple, the reactive rectifying tower can continuously stabilize the ethanol content at the tower top, and the secondary rectification and purification of the byproduct ethanol are not needed.)

1. A process for synthesizing phenyl malonate comprises contacting raw materials containing ethyl phenylacetate and diethyl carbonate with a catalyst, and reacting, separating and crystallizing to obtain the phenyl malonate; the catalyst is alkali metal alkoxide and/or alcohol solution of alkali metal alkoxide; the reaction is carried out in a rectifying tower, the temperature of the top of the rectifying tower is 40-50 ℃, and the temperature of the bottom of the rectifying tower is 60-100 ℃; the pressure in the rectifying tower is-0.05 MPa to-0.08 MPa; the reflux ratio of the tower top is 1: 1-5: 1.

2. The process for synthesizing diethyl phenylmalonate according to claim 1, wherein the diethyl phenylmalonate,

in the method, the temperature of the top of the rectifying tower is 43-45 ℃; the temperature of a tower kettle of the rectifying tower is 70-90 ℃, and preferably 65-80 ℃; the inner surface pressure of the rectifying tower is-0.06 MPa to-0.07 MPa; the reflux ratio of the tower top is 1: 1-3: 1.

3. The process for synthesizing diethyl phenylmalonate according to claim 1, wherein the molar ratio of ethyl phenylacetate to diethyl carbonate to the catalyst is 2-10: 1: 1-2, preferably 4-6: 1: 1-1.5.

4. The process for synthesizing diethyl phenylmalonate according to claim 1, wherein the alkali metal alkoxide is at least one selected from potassium ethoxide, sodium ethoxide, and potassium tert-butoxide; preferably, the alcohol solution in the alcohol solution of the alkali metal alkoxide is an ethanol solution.

5. The process for synthesizing diethyl phenylmalonate according to claim 1, wherein the ethyl phenylacetate is added into the rectifying tower dropwise.

6. The process for synthesizing diethyl phenylmalonate according to claim 1, wherein the separation is performed by using a layering kettle, and the effluent liquid phase is subjected to acid washing and then enters the layering kettle after the raw materials in the rectifying tower react.

7. The process for synthesizing diethyl phenylmalonate according to claim 1, wherein the aqueous phase separated by the layering kettle is purified in an evaporation crystallizer, and the organic phase is purified in a static crystallizer or a dynamic crystallizer.

8. The process for synthesizing diethyl phenylmalonate according to claim 7, wherein the dynamic crystallizer is a tower dynamic crystallizer.

9. The process method for synthesizing diethyl phenylmalonate according to claim 1, wherein the mother liquor is returned to the rectifying tower for recycling after the organic phase is crystallized.

10. The process method for synthesizing diethyl phenylmalonate according to claim 1, wherein the number of theoretical plates of the rectifying tower is 20-30.

Technical Field

The invention relates to a method for synthesizing diethyl phenylmalonate, in particular to a process method for synthesizing diethyl phenylmalonate through reaction-rectification.

Background

Diethyl phenylmalonate is an important medical intermediate and is mainly used for preparing phenobarbital and cephalosporins. The traditional process adopts a claisen condensation method, sodium ethoxide is taken as a catalyst, and diethyl carbonate or diethyl oxalate and ethyl phenylacetate are taken as raw materials to carry out ester condensation reaction to prepare the compound. The process comprises the steps of firstly concentrating sodium ethoxide, concentrating a commercially available 20% sodium ethoxide ethanol solution to about 50%, and then mixing the raw materials for reaction. The reaction process consumes long time, and the energy consumption of the product is high by the purification in a rectification mode.

Disclosure of Invention

The invention aims to provide a process method for synthesizing diethyl phenylmalonate by a reaction-rectification technology, wherein ethyl phenylacetate and diethyl carbonate are used as raw materials, sodium ethoxide, potassium ethoxide and the like are used as catalysts, and the diethyl phenylmalonate is obtained through the processes of reaction rectification, crystallization separation and the like. The process comprises key equipment such as a rectifying tower, a layering kettle, a crystallizer and the like. Raw materials of ethyl phenylacetate, an alcohol solution of alkali metal alkoxide and diethyl carbonate are fed from the bottom of a reaction rectifying tower, the ethyl phenylacetate, the alcohol solution of alkali metal alkoxide and the diethyl carbonate are mixed and contacted in a tower kettle of the rectifying tower, and react under the action of a catalyst, and a generated alcohol substance is extracted from the top of the tower; after the tower kettle is subjected to acid washing and layering, the organic layer is crystallized and purified to obtain a qualified diethyl phenylmalonate product.

The purpose of the invention is realized by the following technical scheme:

a process for synthesizing phenyl malonate comprises contacting raw materials containing ethyl phenylacetate and diethyl carbonate with a catalyst, and reacting, separating and crystallizing to obtain the phenyl malonate; the catalyst is alkali metal alkoxide and/or alcohol solution of alkali metal alkoxide; the reaction is carried out in a rectifying tower, the temperature of the top of the rectifying tower is 40-50 ℃, and the temperature of the bottom of the rectifying tower is 60-100 ℃; the pressure in the rectifying tower is-0.05 MPa to-0.08 MPa, preferably-0.069 MPa or-0.06 MPa; the reflux ratio of the tower top is 1: 1-5: 1.

In the method, the tower top temperature of the rectifying tower is 43-45, preferably 40-43 ℃ or 48-50 ℃; the temperature of the tower kettle of the rectifying tower is 70-90 ℃, preferably 65-80 ℃ or 70-100 ℃; the inner surface pressure of the rectifying tower is-0.06 MPa to-0.07 MPa; the reflux ratio of the tower top is 1: 1-3: 1.

As a preferable scheme, the rectifying tower is provided with two tower kettles, and after one of the two towers finishes the reaction, the rectifying tower is subjected to post-treatment; the other tower kettle starts to react, and the two tower kettles are alternately recycled.

Preferably, the molar ratio of the ethyl phenylacetate to the diethyl carbonate to the catalyst is 2-10: 1: 1-2, preferably 4-6: 1: 1-1.5, more preferably 5:1:1.05 or 4:1: 1.3.

Preferably, the alkali metal alkoxide is at least one selected from potassium ethoxide, sodium ethoxide and potassium tert-butoxide; preferably, the alcohol solution in the alcohol solution of the alkali metal alkoxide is an ethanol solution.

Preferably, the ethyl phenylacetate is added into the rectifying tower in a dropwise adding manner, the dropwise adding speed is not specifically required, and the ethyl phenylacetate is controlled to be dropwise added at a uniform speed within a specified time according to the total feeding amount of the ethyl phenylacetate, for example, when the total feeding amount is 12Kg (the molar ratio of diethyl carbonate to ethyl phenylacetate to sodium ethoxide ethanol solution is 5.94: 1: 1.06), 6.978Kg of diethyl carbonate and 3.389Kg of sodium ethoxide ethanol solution are firstly pumped into the tower bottom of the rectifying tower, 1.632Kg of ethyl phenylacetate is dropwise added, and the dropwise adding time is controlled to be 2-8 hours, preferably 4-6 hours; namely, 0.029-0.117 g of ethyl phenylacetate is dropwise added into 1Kg of diethyl carbonate within 1 hour; preferably 0.039-0.058 g.

As a preferable scheme, the separation adopts a layering kettle, and after raw materials in the rectifying tower react, an effluent liquid phase enters the layering kettle after being subjected to acid washing.

Preferably, the water phase separated by the layering kettle enters an evaporation crystallizer for purification, and the organic phase enters a static crystallizer or a dynamic crystallizer for purification.

Preferably, the dynamic crystallizer is a tower-type dynamic crystallizer, and the product is obtained after cooling crystallization, mother liquor discharge, temperature rise sweating and sweat discharge, and the product purity is over 99.5%.

The product is obtained by the static crystallizer after cooling crystallization, mother liquor discharge, temperature rise sweating and sweat discharge, and the product purity is more than 99.5 percent.

Preferably, after the organic phase is crystallized, the mother liquor returns to the rectifying tower for recycling.

Preferably, the number of theoretical plates of the rectifying tower is 20-30.

The method comprises the following process steps:

(1) raw materials of ethyl phenylacetate, alkali metal alcohol solution and diethyl carbonate are fed from the bottom of the reaction rectifying tower; preferably, the rectifying tower is provided with a plurality of tower kettles;

(2) the gas-phase extract at the top of the tower is ethanol, and the extraction amount of diethyl carbonate is controlled to be below 1 percent by virtue of rectification;

(3) directly selling the extracted substances at the tower top; pickling the tower kettle liquid phase, and then entering a layering kettle for layering;

(4) the lower water phase in the layered kettle is sent to an evaporation crystallizer, and the organic phase is sent to the crystallizer for product purification;

(5) the crystallizer obtains a qualified diethyl phenylmalonate product, and the mother liquor returns to the rectifying tower to continuously participate in the reaction.

According to the process method for synthesizing the diethyl phenylmalonate, the sodium ethoxide ethanol solution can be directly added into a reaction system without concentration.

The invention has the advantages and effects that:

(1) more than 99 percent of ethanol is extracted from the top of the tower through reactive distillation without rectification and purification again;

(2) the product is not required to be purified by a rectification method, and the energy consumption is obviously reduced by a crystallization mode;

(3) the two tower kettles arranged by the rectifying tower are alternately recycled, the product quality is stable, and the yield of the diethyl phenylmalonate is high.

Drawings

FIG. 1 is a schematic view of an embodiment of the process of the present invention;

in the figure, 1 a rectifying column; 2, layering a kettle; 3, a static crystallizer; 4 an evaporative crystallizer.

Detailed Description

The present invention will be described in detail with reference to the embodiments shown in the drawings.

The method takes ethyl phenylacetate (with the purity of more than 99%) and diethyl carbonate (with the purity of more than 99%) as raw materials, and the feeding molar ratio is 2-10: 1: 1-2, preferably 4-6: 1: 1-1.5.

Taking various alkali metal alkoxides or alcoholic solutions thereof (such as sodium ethoxide, potassium tert-butoxide and the like) as catalysts, and obtaining the product diethyl phenylmalonate through the processes of reaction-rectification, crystallization separation and the like.

The specific process of the invention comprises the following steps:

raw material diethyl carbonate carries a certain amount of homogeneous catalyst and is fed from the reaction kettle, and ethyl phenylacetate raw material is fed from the upper part of the reaction kettle. The temperature of the top of the rectifying tower is controlled to be between 40 and 50 ℃, and the temperature of the bottom of the rectifying tower is controlled to be between 60 and 100 ℃. Stirring diethyl carbonate and a catalyst liquid phase in a reaction kettle, continuously adding ethyl phenylacetate from the upper part of the reaction kettle in a liquid phase state, and contacting the ethyl phenylacetate, a large amount of diethyl carbonate and the catalyst in the reaction kettle to react. The generated ethanol moves to the top of the tower in a gas phase, the closer to the top of the tower, the higher the ethanol content is, the extracted substances at the top of the tower are ethanol and diethyl carbonate, the diethyl carbonate content is lower than 1%, and the high-boiling point diethyl carbonate is remained in the reaction kettle by means of rectification. The tower bottom is excessive diethyl carbonate, sodium salt and sodium ethoxide, and the excessive diethyl carbonate, the sodium salt and the sodium ethoxide directly enter the layering kettle after acid washing and neutralization in the kettle. The water phase in the layering kettle enters an evaporation crystallizer to obtain sodium sulfate; the organic phase enters a crystallizer to obtain a product of diethyl phenylmalonate, and the mother liquor returns to the reaction kettle to continue to react.

The yield of diethyl phenylmalonate is calculated by the following formula:

when the ethyl phenylacetate in the starting material was completely reacted, the mass of the produced diethyl phenylmalonate means the mass of the product obtainable when the starting material was completely reacted theoretically, i.e. the mass of ethyl phenylacetate in the starting material/164.2 × 236.26.

Example 1

As shown in fig. 1, diethyl phenylmalonate is prepared from diethyl carbonate and ethyl phenylacetate as raw materials, the feeding molar ratio of the raw materials diethyl carbonate and diethyl phenylmalonate to the catalyst is 5:1:1.05, the diethyl carbonate and the catalyst are fed from the upper part of a reaction kettle, and the catalyst adopts sodium ethoxide ethanol solution (omega ═ 21%) and can be completely dissolved in the diethyl carbonate. And adding the ethyl phenylacetate into the reaction kettle in one step, and contacting and reacting in the reaction kettle. The theoretical plate number of the rectifying tower is 20-30, metal theta ring is filled, the height of the filler is 1m, the reflux ratio of the tower top is controlled to be 1: 1-5: 1, the surface pressure is controlled to be-0.069 MPa, the temperature of the tower top is stabilized to be 40-43 ℃, the temperature of the tower bottom is gradually increased to be 65-80 ℃, and the components of the tower top are measured to be about 99.2% of ethanol and 0.8% of diethyl carbonate. Diethyl carbonate and a product sodium salt in a tower kettle are subjected to sulfuric acid pickling and then are layered, a water phase enters an evaporative crystallization kettle for crystallization to obtain white sodium sulfate crystals, an organic layer is washed by sodium sulfate brine and then enters a static crystallizer, the temperature of a refrigerant is gradually reduced to 16 ℃ so as to be preliminarily pre-cooled, the temperature of the refrigerant is further slowly reduced to-5 ℃ at the cooling rate of 2 ℃/h, mother liquor is discharged, the temperature of the refrigerant is gradually increased, sweating operation is carried out on the refrigerant until the content of diethyl phenylmalonate reaches 98.5%, the temperature is rapidly increased to obtain a qualified product, and the yield of diethyl phenylmalonate can approach 95%.

Example 2

As shown in fig. 1, diethyl phenylmalonate is prepared from diethyl carbonate and ethyl phenylacetate as raw materials, the feeding molar ratio of the raw materials diethyl carbonate and diethyl phenylmalonate to the catalyst is 4:1:1.3, the diethyl carbonate and the catalyst are fed from the upper part of a reaction kettle, and the catalyst adopts sodium ethoxide solid (omega 96 percent) which can be partially dissolved in the diethyl carbonate. The ethyl phenylacetate is slowly fed from the upper part of the reaction kettle in a dropwise manner, the total feeding time is controlled to be 2 hours, and the ethyl phenylacetate is contacted and reacted in the reaction kettle. The theoretical plate number of the rectifying tower is 20-30, metal theta ring is filled, the height of the filler is 1m, the reflux ratio of the tower top is controlled to be 1: 1-3: 1, the pressure of the gauge pressure is controlled to be-0.06 MPa, the temperature of the tower top is stabilized to be 48-50 ℃, the temperature of the tower bottom is 70-100 ℃, and the compositions of the tower top are determined to be about 98.5% of ethanol and 1.5% of diethyl carbonate. Acid-washing diethyl carbonate and a product sodium salt in a tower-I kettle, standing and layering, allowing a water phase to enter an evaporative crystallization kettle for crystallization to obtain white sodium sulfate crystals, allowing an organic layer to enter a dynamic crystallizer, gradually reducing the temperature of a refrigerant to 16 ℃ for preliminary precooling, further slowly reducing the temperature of the refrigerant to-10 ℃ at a cooling rate of 2 ℃/h, stably running for 5h, discharging a mother solution, gradually increasing the temperature of the refrigerant, performing sweating operation on the refrigerant, and quickly heating to obtain a qualified product after the content of diethyl phenylmalonate reaches 98.5%, wherein the yield of diethyl phenylmalonate can approach 90%.

A process for synthesizing diethyl phenylmalonate by reaction-rectification technology includes feeding raw materials of ethyl phenylacetate, alkali metal alcohol solution and diethyl carbonate from the bottom of a reaction rectification tower, mixing and contacting the raw materials in the tower kettle of the rectification tower, reacting under the action of a catalyst, and collecting generated alcohol substances from the top of the tower; after the tower kettle is subjected to acid washing and layering, the organic layer is crystallized and purified to obtain a qualified diethyl phenylmalonate product. Compared with the traditional process, the product does not need rectification and purification, the energy consumption is obviously reduced, the process is simple, the reactive rectifying tower can continuously stabilize the ethanol content at the tower top, and the secondary rectification and purification of the byproduct ethanol are not needed.