Method for producing organic synthesis intermediate diethyl maleate through continuous catalysis of solid salt

Abstract

The invention relates to the technical field of fine chemical production, and discloses a method for producing an organic synthesis intermediate diethyl maleate through continuous catalysis of solid salt, which comprises the following steps: S1, a reaction stage: adding maleic anhydride, ethanol, a water-carrying agent A and a solid salt catalyst B into a reaction kettle, then adding a proper amount of ethanol into a water segregator, and reacting at the temperature C, the reaction is qualified; the catalyst B is solid salt; s2, a reaction post-treatment stage: after the reaction is finished, centrifuging or carrying out suction filtration to recover the catalyst, and then distilling or rectifying to recover the ethanol and the water-carrying agent; and stirring and washing the residual liquid with an alkali solution D, separating into an organic phase and a water phase, and rectifying the organic phase to obtain a diethyl maleate product. According to the scheme, the diethyl maleate can be catalytically synthesized by adopting the conventional solid salt, so that not only is the product yield effectively improved, but also part of the raw materials (including the water-carrying agent, the ethanol, the catalyst and the like) can be recycled, the production cost is reduced, and the production benefit is improved.

Description

Technical Field

[0001] The invention relates to the technical field of fine chemical production, and in particular to a method for producing organic synthesis intermediate diethyl maleate by continuous catalysis of solid salt. Background Art

[0002] Diethyl maleate, also known as diethyl maleate, is widely used in organic synthesis. It is an important intermediate in the synthesis of medicines, spices, water stabilizers, pesticides, and polymer monomers. Therefore, it is very important to synthesize diethyl maleate using a green, simple, and efficient method. The traditional synthesis method is to use maleic acid or maleic anhydride and ethanol to undergo an esterification reaction under the catalysis of sulfuric acid. Although this process has the advantages of "cheap and easy to obtain sulfuric acid, good catalytic effect, and mature process", it will cause slow corrosion to the equipment, and the solubility of sodium sulfate is greatly affected by temperature, resulting in difficulty in post-processing of the alkaline washing solution, so this process has been gradually eliminated.

[0003] In recent years, some novel methods for synthesizing diethyl maleate have been gradually reported in the literature, such as supported ionic liquid catalysis reported by Zhao Dishun, acidic functionalized ionic liquid catalysis reported by Guo Hongyun, tetraethyl titanate catalysis reported by Song Guixian, sodium bisulfate catalysis and ammonium ferric sulfate dodecahydrate catalysis reported by Guan Shibin, hydrated ferric sulfate catalysis reported by Xin Hong, and strong acid ion exchange resin catalysis reported by Liu Xiao. However, most of these methods have the disadvantages of "high catalyst cost, poor repeated catalytic performance, large amount of reaction solvent, difficult post-reaction treatment, and low reaction yield".

[0004] In view of this, the development of a method for continuously catalyzing the production of diethyl maleate, an organic synthesis intermediate, using a conventional solid salt catalyst not only effectively makes up for the deficiencies of the prior art, but also effectively reduces catalyst requirements and costs, which is of great significance for improving the production efficiency of diethyl maleate. Summary of the invention

[0005] The present invention aims to provide a method for producing diethyl maleate, an organic synthesis intermediate, by continuous catalysis of solid salt, so as to solve the technical problem that the catalyst cost of producing diethyl maleate in the prior art is high and the catalytic performance is poor, thereby reducing the production efficiency.

[0006] To achieve the above object, the present invention adopts the following technical scheme: a method for producing diethyl maleate, an organic synthesis intermediate, by continuous catalysis of a solid salt, comprising the following steps:

[0007] S1, reaction stage: maleic anhydride, ethanol, water-carrying agent A, solid salt catalyst B are added to the reactor, and then a proper amount of ethanol is added to the water separator and reacted at temperature C until the reaction is qualified; the catalyst B is a solid salt;

[0008] S2, post-reaction treatment stage: after the reaction is completed, the catalyst is recovered by centrifugation or filtration, and then the ethanol and water-carrying agent are recovered by distillation or rectification; the remaining residual liquid is stirred and washed with alkaline solution D and then separated into an organic phase and an aqueous phase, and the organic phase is rectified to obtain the diethyl maleate product.

[0009] The principles and advantages of this solution are:

[0010] 1. Compared with the high cost and poor catalytic effect of the catalyst used in the production of diethyl maleate in the prior art, this scheme optimizes the types of auxiliary materials added in the reaction process, and uses conventional solid salts to catalyze the synthesis of diethyl maleate, effectively reducing production costs and improving production efficiency. Specifically, since most solid salts have the advantages of "easy to store and transport, not easy to absorb moisture, low corrosion to equipment, insoluble in organic reaction systems, and good repeated catalytic performance", they are an environmentally friendly catalyst in the synthesis reaction of diethyl maleate and a better catalyst to replace sulfuric acid, supported ionic liquids, and ion exchange resins.

[0011] 2. This scheme uses solid salt as a catalyst for synthesizing diethyl maleate, and the solid salt has low solubility in organic solvents. After the esterification reaction is completed, it can be directly filtered and then used again for the second esterification reaction, further reducing the catalyst cost and improving the production efficiency of diethyl maleate.

[0012] 3. In addition to the catalyst, the reaction solvent, water-carrying agent, process water, etc. in this scheme can be reused, and the yield of diethyl maleate produced by reuse is still high, which not only effectively reduces the production cost, but also reduces the amount of industrial wastewater generated, thereby effectively reducing its pollution to the environment and the cost of wastewater treatment, and further improving production efficiency.

[0013] Preferably, as an improvement, the solid salt includes one or any combination of disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, ammonium dihydrogen phosphate, sodium bicarbonate, potassium bicarbonate, sodium bisulfite, potassium bisulfite, sodium bisulfate, potassium bisulfate, ammonium ferric sulfate, and potassium aluminum sulfate.

[0014] Technical effect: The above-mentioned setting is adopted in this scheme to facilitate the catalytic synthesis of diethyl maleate from maleic anhydride. Solid salt has the following advantages as a catalyst: (1) Easy to separate, recycle and reuse: There is an obvious phase difference (solid-liquid or solid-gas) between the solid salt catalyst and the reactants and products, so it can be easily separated by simple physical methods such as filtration, centrifugation or sedimentation, avoiding complicated post-processing steps. Solid salt catalysts have high stability and can be reused many times after proper cleaning and regeneration, which reduces the cost of the catalyst and the risk of catalyst loss to the environment, conforms to the principle of green chemistry, and helps to reduce the impact on the environment. (2) High selectivity: Solid salt catalysts usually have specific active sites that can selectively activate certain functional groups or reaction pathways, thereby improving the selectivity of the target product. For example, some metal salts can selectively promote the breaking or formation of specific types of chemical bonds. By rationally designing the structure of solid salts, stereoselective control of the reaction can be achieved. For example, chiral metal salt catalysts can induce specific chiral products in asymmetric synthesis. (3) Good stability: Many solid salt catalysts have high thermal stability and can maintain activity over a wide range of temperature and pH. Solid salt catalysts have good mechanical strength and are not easy to break or wear, making them suitable for use in continuous flow reactors or fixed bed reactors. (4) Low cost: The raw materials of solid salt catalysts are widely available and inexpensive, which reduces the cost of preparing the catalysts. They are also stable and recyclable, and they can remain active for a long time, reducing the need for frequent catalyst replacement and long-term operating costs. The preparation process of solid salt catalysts is relatively simple, suitable for large-scale industrial production, and can meet the production needs of different scales.

[0015] Preferably, as an improvement, the amount of the catalyst B is 1% to 100%, preferably 10 to 30%, of the amount of maleic anhydride.

[0016] Technical effect: This scheme adopts the above-mentioned setting to improve the product yield of diethyl maleate. The applicant has found through long-term experiments that if the amount of catalyst D is too small, the reaction yield will be significantly reduced due to catalyst loss; if the amount of catalyst D is too large, it will lead to catalyst waste and side reactions, and the reaction yield will not be significantly improved.

[0017] Preferably, as an improvement, the water-carrying agent A is one of toluene, benzene, xylene, n-hexane, petroleum ether, dichloromethane, chloroform, and carbon tetrachloride.

[0018] Technical effect: This scheme adopts the above-mentioned setting, which makes it easy to quickly remove the water produced by the reaction, thereby promoting the forward reaction and increasing the reaction speed.

[0019] Preferably, as an improvement, the amount of the water-carrying agent A is 10% to 500%, preferably 100 to 300%, of the amount of maleic anhydride.

[0020] Technical effect: This scheme adopts the above-mentioned setting, which is convenient for quickly taking out the water produced by the reaction, thereby promoting the forward reaction and increasing the reaction speed. The applicant has found through long-term experiments that if the amount of water-carrying agent A is too small, the water-carrying agent cannot effectively form a ternary azeotrope with anhydrous ethanol and water to take water out of the reaction system, resulting in the esterification reaction not being able to proceed in a better forward direction, thereby causing the reaction yield to be lower; and if the amount of water-carrying agent A is too much, it will lead to a decrease in the concentration of the reactants maleic anhydride and ethanol, and will also reduce the boiling point of the azeotrope, so that the temperature of the reaction system is reduced, which is not conducive to the forward progress of the esterification reaction.

[0021] Preferably, as an improvement, the molar ratio of maleic anhydride to ethanol is 1:2 to 1:5.

[0022] Technical effect: This scheme adopts the above-mentioned setting, and the excess ethanol facilitates the formation of diethyl maleate and ensures that maleic anhydride is fully converted. The applicant has found through long-term experiments that if the amount of ethanol used is too little, the material ratio of the esterification equilibrium reaction will be reduced, and the azeotropic dehydration will also bring out a small amount of ethanol, causing the esterification reaction to mostly stay at the intermediate monoethyl maleate stage, thereby causing the yield of diethyl maleate to decrease; and if the amount of ethanol used is too much, the reaction yield will not be significantly improved due to the decrease in the concentration of maleic anhydride in the reaction system, and there will be more residual raw materials, increasing the cost of raw material recovery in the later stage.

[0023] Preferably, as an improvement, the temperature C is room temperature to 100°C, preferably 60 to 90°C.

[0024] Technical effect: This scheme adopts the above-mentioned setting to accelerate the reaction speed and improve the reaction efficiency. The applicant has found through long-term experiments that if the temperature is too high, the ethanol reflux rate will increase, and more ethanol will be brought out by azeotropy, resulting in a decrease in the ethanol content of the reaction system, which will slow down the reaction and reduce the yield; if the temperature is too low, the random collisions between the raw material molecules will be reduced, resulting in a large amount of raw materials remaining and not participating in the reaction.

[0025] Preferably, as an improvement, the base D is one or any combination of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, ammonia water, and ammonia gas.

[0026] Technical effect: This scheme adopts the above-mentioned setting, which is convenient for quickly separating the product diethyl maleate and neutralizing the remaining small amount of maleic anhydride and the intermediate monoethyl maleate. The applicant has found through long-term experiments that if the base D is not used, the remaining raw material maleic anhydride and the intermediate monoethyl maleate cannot be neutralized, resulting in a small amount of maleic anhydride and intermediates being taken out during distillation, affecting the purity of the product.

[0027] Preferably, as an improvement, the amount of the base D used is 1.25-25% of the amount of maleic anhydride used.

[0028] Technical effect: This scheme adopts the above-mentioned setting, which is convenient for effectively separating the product diethyl maleate and neutralizing the remaining small amount of maleic anhydride and the intermediate monoethyl maleate.

[0029] Preferably, as an improvement, it also includes S3, application stage: detecting the quality and content of the recovered ethanol, water-carrying agent and catalyst, adding fresh ethanol, water-carrying agent and catalyst to within the qualified range and applying them to the next esterification reaction.

[0030] Technical effect: This scheme adopts the above-mentioned setting, which is convenient for the repeated use of recycled reagents for the continuous production of diethyl maleate, reducing costs while improving production efficiency.

[0031] This scheme uses a suitable catalyst to synthesize diethyl maleate simply and efficiently, and optimizes various reaction parameters such as solvents, catalysts, and water-carrying agents, so as to minimize the water content in the reaction system and make the reaction more inclined to positive completion. And by treating the bottom liquid of the kettle with alkali D, the post-processing scheme is optimized, and the finished product diethyl maleate is easier to obtain. Compared with the prior art, it also makes the recycling of solvents, catalysts, water-carrying agents, and process water simpler, simplifies the process and improves production efficiency. In addition, this scheme realizes the long-term recycling of solvents, catalysts, water-carrying agents, and process water, which not only realizes the continuous production of diethyl maleate, but also produces very little three wastes, realizes the unity of economic benefits and environmental benefits, and is convenient for promoting production. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 This is the central control detection spectrum of the continuous catalytic production of organic synthesis intermediate diethyl maleate by solid salt in Example 3 of the present invention.

[0033] Figure 2 This is the finished product detection spectrum of the solid salt continuous catalytic production of organic synthesis intermediate diethyl maleate in Example 3 of the present invention. DETAILED DESCRIPTION

[0034] The present invention is further described in detail below in conjunction with examples, but the embodiments of the present invention are not limited thereto. Unless otherwise specified, the technical means used in the following examples and experimental examples are conventional means well known to those skilled in the art, and the materials, reagents, etc. used can be obtained from commercial sources.

[0035] Program Overview

[0036] This scheme provides a method for continuously catalyzing the production of diethyl maleate, an organic synthesis intermediate, by solid salt, comprising the following steps:

[0037] (1) Reaction stage

[0038] Add maleic anhydride, ethanol, water-carrying agent and catalyst into the reactor, then add appropriate amount of ethanol into the water separator and heat the reaction until the maleic anhydride is consumed. Take samples during the reaction for gas chromatography detection. For details of the central control detection spectrum, see Figure 1 , the finished product test spectrum is shown in Figure 2 .

[0039] As a reference, the water-carrying agent is one of toluene, benzene, xylene, n-hexane, petroleum ether, dichloromethane, chloroform, and carbon tetrachloride; the catalyst is disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, ammonium dihydrogen phosphate, sodium bicarbonate, potassium bicarbonate, sodium bisulfite, potassium bisulfite, sodium bisulfate, potassium bisulfate, ammonium ferric sulfate, and potassium aluminum sulfate.

[0040] As a reference, based on the amount of raw material maleic anhydride, the amount of ethanol used is between 2 and 5 times that of maleic anhydride, the amount of water-carrying agent used is between 10% and 500% of maleic anhydride (preferably 100 to 300%), and the amount of catalyst used is between 1% and 100% of maleic anhydride (preferably 10 to 30%) (the amount ratios of other raw materials to maleic anhydride in this scheme are all molar ratios).

[0041] As a reference, the reaction temperature is a value between room temperature and 100° C. (preferably 60 to 90° C.), and the raw material maleic anhydride can be consumed in 2 to 2.5 hours of reaction in this scheme.

[0042] The reaction equation in this stage is as follows:

[0043]

[0044] The reaction is specifically divided into two steps:

[0045] 1. First, the oxygen atom in ethanol nucleophilically attacks the carbonyl carbon atom in maleic anhydride to form an oxygen anion, and then the five-membered ring opens to form monoethyl maleate intermediate.

[0046] 2. Then the monoethyl maleate intermediate undergoes an esterification reaction with one molecule of ethanol to generate the product diethyl maleate and produce one molecule of water.

[0047] Since the esterification reaction is a reversible reaction, adding excess ethanol to the reaction environment and separating the produced water by distillation or other methods can effectively promote the reaction to the right direction.

[0048] (2) Post-reaction treatment stage

[0049] After the reaction is finished, the catalyst is recovered by centrifugation or filtration, and the filtrate is distilled to recover ethanol and water-carrying agent. Finally, the kettle residue is stirred and washed with an alkali solution and then separated. The organic phase is distilled to obtain diethyl maleate product, and the aqueous phase is distilled to obtain process water. The alkali is one of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, ammonia water, and ammonia gas.

[0050] (3) Application stage

[0051] The quality and content of the recovered ethanol, water-carrying agent, and catalyst are tested, and then fresh ethanol, water-carrying agent, and catalyst are added to the qualified range for use in the first step of esterification reaction. The lower aqueous phase obtained by separation is distilled, and the process water fraction is collected and then used for the preparation of the next alkaline solution.

[0052] Table 1 shows the efficient synthesis method of diethyl maleate in this scheme with different parameter combinations, mainly including specific experimental data and experimental results of condition screening and amplification experiments.

[0053] Table 1 Production results under different experimental conditions

[0054]

[0055]

[0056] Experimental data show that this scheme can catalyze the synthesis of diethyl maleate using conventional solid salts, which not only effectively improves the product yield, but also some raw materials (including water-carrying agent, ethanol, catalyst, etc.) can be recycled and reused, reducing production costs and improving production efficiency. The applicant has found in long-term research and development that factors such as catalyst type and dosage, water-carrying agent type, and ethanol dosage will affect the product yield. Specifically, when catalyst D is replaced by ferric sulfate (such as comparative example 1), its product is selectively reduced, thereby causing the product yield to be significantly reduced. The applicant analyzes the reason because: ferric sulfate is a Lewis acid, and the catalytic mechanism may be different from other catalysts, so the reaction yield is slightly low. If the water-carrying agent is replaced by cyclohexane, whether the catalyst is sodium dihydrogen phosphate or ammonium ferric sulfate (Comparative Example 2 and Comparative Example 8, respectively), the product yield will be reduced. The applicant analyzed the reason because: the boiling point of the ternary azeotrope formed by cyclohexane, ethanol and water is somewhat different from that of other water-carrying agents, resulting in less byproduct water separated from the reaction system, and then the degree to which the reaction tends to be positive is reduced, so the product yield is slightly reduced. If the amount of catalyst is too little (such as Comparative Example 3), the reaction will slow down and the product will be reduced due to the insufficient amount of catalyst participating in the reaction cycle, thereby reducing the product yield. If the amount of catalyst is too high (such as Comparative Example 4), the product yield will not continue to be improved, but the catalyst cost will be increased and the production efficiency will be reduced. If the amount of ethanol is too much (such as Comparative Examples 5 and 6), the product yield will not continue to be improved, but the ethanol cost will be increased.

[0057] The applicant increased the amount of raw materials in equal proportion (Example 7 and Example 8) and found that the product yields were all high. It can be seen that this solution still has a high product yield after expanding production, which is convenient for promotion and application to large-scale production of diethyl maleate, reducing production costs and improving benefits.

[0058] In summary, this program is used for the simple and efficient synthesis of diethyl maleate by finding a suitable catalyst, and optimizes each reaction parameter such as solvent, catalyst, water-carrying agent, minimizes the content of water in the reaction system, and allows the reaction to be more tended to positive completion. And the bottom liquid of the kettle is processed by alkali D, and the post-processing scheme is optimized, and the finished product diethyl maleate is easier to obtain, and compared to the prior art, the recycling of solvent, catalyst, water-carrying agent, and process water is also made simpler, and the simplified process improves production efficiency. In addition, this program realizes the long-term recycling of solvent, catalyst, water-carrying agent, and process water, not only realizes the continuous production of diethyl maleate, and the three wastes produced are very few, realize the unification of economic benefit and environmental benefit, and are convenient to promote production. If alkali D (such as comparative example 7) is not used, then because the remaining raw material maleic anhydride and the intermediate monoethyl maleate cannot be neutralized, a small amount of by-products will be taken out during distillation, and then product purity and yield are affected.

[0059] The above is only an embodiment of the present invention, and the common knowledge such as the known specific technical solutions and / or characteristics in the solution is not described in detail here. It should be pointed out that for those skilled in the art, without departing from the technical solution of the present invention, several modifications and improvements can be made, which should also be regarded as the protection scope of the present invention, and these will not affect the effect of the implementation of the present invention and the practicality of the patent. The scope of protection required by this application shall be based on the content of its claims, and the specific implementation methods and other records in the specification can be used to interpret the content of the claims.

Claims

1. A method for producing diethyl maleate, an organic synthesis intermediate, by continuous catalysis of solid salts, characterized in that: The steps include: S1, reaction stage: maleic anhydride, ethanol, water-carrying agent A, solid salt catalyst B are added to the reactor, and then a proper amount of ethanol is added to the water separator and reacted at temperature C until the reaction is qualified; the catalyst B is a solid salt; S2, post-reaction treatment stage: after the reaction is completed, the catalyst is recovered by centrifugation or filtration, and then the ethanol and water-carrying agent are recovered by distillation or rectification; the remaining residual liquid is stirred and washed with alkaline solution D and then separated into an organic phase and an aqueous phase, and the organic phase is rectified to obtain the diethyl maleate product.

2. The method for producing diethyl maleate as an organic synthesis intermediate by continuous catalysis of a solid salt according to claim 1, characterized in that: The solid salt includes one or any combination of disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, ammonium dihydrogen phosphate, sodium bicarbonate, potassium bicarbonate, sodium bisulfite, potassium bisulfite, sodium bisulfate, potassium bisulfate, ammonium ferric sulfate, and potassium aluminum sulfate.

3. The method for producing diethyl maleate as an organic synthesis intermediate by continuous catalysis of a solid salt according to claim 1, characterized in that: The amount of the catalyst B is 10-30% of the amount of maleic anhydride.

4. The method for producing diethyl maleate as an organic synthesis intermediate by continuous catalysis of a solid salt according to claim 3, characterized in that: The water-carrying agent A is one of toluene, benzene, xylene, n-hexane, petroleum ether, dichloromethane, chloroform and carbon tetrachloride.

5. The method for producing diethyl maleate as an organic synthesis intermediate by continuous catalysis of solid salt according to claim 1, characterized in that: The amount of the water-carrying agent A is 100-300% of the amount of maleic anhydride.

6. The method for producing diethyl maleate as an organic synthesis intermediate by continuous catalysis of solid salt according to claim 1, characterized in that: The molar ratio of maleic anhydride to ethanol is 1:2 to 1:

5.

7. The method for producing diethyl maleate as an organic synthesis intermediate by continuous catalysis of solid salt according to claim 1, characterized in that: The temperature C is 60-90°C.

8. The method for producing diethyl maleate as an organic synthesis intermediate by continuous catalysis of solid salt according to claim 1, characterized in that: The alkali D is one or any combination of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, ammonia water, and ammonia gas.

9. The method for producing diethyl maleate as an organic synthesis intermediate by continuous catalysis of solid salt according to claim 8, characterized in that: The amount of the base D used is 1.25-25% of the amount of maleic anhydride used.

10. The method for producing diethyl maleate as an organic synthesis intermediate by continuous catalysis of solid salt according to claim 1, characterized in that: It also includes S3, the application stage: testing the quality and content of the recovered ethanol, water-carrying agent, and catalyst, adding fresh ethanol, water-carrying agent, and catalyst to within the qualified range for application in the next esterification reaction.

Images