Synthesis method of malonate compound

Abstract

The invention belongs to the technical field of fine chemical engineering, and discloses a synthesis method of a malonate compound, which comprises the following steps: under the action of a heterogeneous catalyst, carrying out hydrolysis-esterification reaction on cyanoacetic acid and alcohol, and after the reaction is finished, carrying out post-treatment to obtain the malonate compound, the heterogeneous catalyst comprises a carrier and an active component; the active component comprises ionic liquid and active metal; the carrier is an ordered mesoporous material; the active metal is alkaline earth metal. According to the method, malonate products can be obtained, the problems of low yield, serious equipment corrosion and large amount of three wastes are solved, efficient synthesis of malonate compounds is realized, meanwhile, the production efficiency is improved, and the environmental pollution is greatly reduced.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of fine chemical industry, and particularly relates to a synthesis method of malonic acid ester. BACKGROUND

[0002] Dimethyl malonate (DMM for short), commonly known as dimethyl carotene, is a colorless transparent liquid with aromatic odor, slightly soluble in water, and soluble in ether, alcohol, benzene, chloroform and other organic solvents. Industrial product is a light yellow transparent liquid. Dimethyl malonate contains active methylene in the molecule, which can undergo various substitution reactions such as alkylation, acylation, hydroxyalkylation and amidation, and is an important raw material for synthesizing various fine chemicals such as medicines, pesticides, spices, dyes and antioxidants. For example, dimethyl malonate is an important raw material for synthesizing the precious spice dihydrojasmone acid methyl ester, and can also be used as a hydrogenation raw material to synthesize 1,3-propanediol, and is a key raw material for producing the medicine pyrithyldicarboxylic acid and the coumarin dimethyl malonate.

[0003] At present, the industrial production of dimethyl malonate in China is cyanation esterification method, which uses chloroacetic acid as raw material, neutralizes with sodium carbonate, cyanates with sodium cyanide, acidifies, and then esterifies with methanol to obtain dimethyl malonate. This method is relatively mature in technology and can realize stable production. However, there are long process flow, low yield, large amount of waste salt and waste water, which makes the post-treatment more complex, and easily causes serious environmental pollution, resulting in high production cost of dimethyl malonate.

[0004]

[0005] Patent CN106496031A discloses a synthesis method of malonic acid ester, which uses cyanacetic acid and alcohol as raw materials to carry out esterification reaction under the catalysis of hydrogen chloride gas. This method uses hydrogen chloride gas instead of concentrated sulfuric acid as catalyst, and the obtained crude product still needs to be treated by washing, neutralization and other post-treatment operations, which not only causes equipment corrosion, but also produces a large amount of waste salt and waste water, and does not fundamentally solve the problems existing in the process of synthesizing malonic acid ester by cyanation esterification method.

[0006] Patent CN103319338A discloses a method for synthesizing dimethyl malonate by using chloroacetic acid as raw material, through neutralization, cyanation, acidification and esterification process, and discloses the method and catalyst of esterification reaction. Specifically, concentrated sulfuric acid, 4-6 times of chloroacetic acid weight of methanol and catalyst are added into the solution of cyanacetic acid to carry out reaction, wherein the catalyst is composed of 8-10wt% of lead chloride, 65-72wt% of triphenylphosphine, 10-15wt% of dimethyl sulfoxide and 8-12wt% of hydrazine hydrate. This method still uses concentrated sulfuric acid as one of the catalytic components, and the catalyst cannot be recycled and used, which cannot avoid the problems such as environmental pollution and equipment corrosion.

[0007] Patent CN103304411A uses cyanoacetic acid as raw material, hydrolysis and esterification are carried out simultaneously in the presence of ionic liquid and water to synthesize malonic acid ester, the reaction product is naturally separated with acid water, but there are problems of expensive catalyst, low product yield, and difficulty in recycling and using ionic liquid phase.

[0008] Patent CN103936588A uses cyanoacetic acid with water content ≤5%, alcohol and hydrogen chloride gas or hydrogen chloride alcohol solution as raw material, and obtains malonic acid ester through esterification, de-alcoholization and desalting, neutralization and rectification five-step process. In the process, cyanoacetic acid with water content ≤5% is difficult to obtain effectively in industrial production. At present, the water content in 70% cyanoacetic acid industrial product is about 20%, and the water content is concentrated to 1-5% in the evaporation process. Long-term dehydration and concentration, the dissolved salt gradually precipitates, the viscosity of the material gradually increases, which easily leads to thermal decomposition of a large amount of cyanoacetic acid, especially in the process of large-scale production. The method of extracting cyanoacetic acid solution with organic acid ester and hydrocarbon solvent to obtain low-water or anhydrous cyanoacetic acid raw material will lead to the problem of complex raw material acquisition process and reduced social and economic benefits. At the same time, the crystallization nucleation rate of ammonium chloride by-produced in alcoholysis is much greater than the crystal growth rate, resulting in fine and unevenly distributed ammonium chloride particles, which are more likely to be encapsulated with ester products, and the alcohol washing operation is difficult to wash, which easily leads to high organic matter content in ammonium chloride product.

[0009] CN107540543A discloses a synthesis method of malonic acid ester, which uses 80wt% concentration of cyanoacetic acid as raw material to synthesize malonic acid ester by hydrogen chloride alcoholysis method, and then uses ammonia to neutralize excess hydrogen chloride, and then absorbs hydrogen chloride gas with alcohol to obtain hydrogen chloride-alcohol solution. This method uses sulfuric acid or hydrogen chloride gas catalyst, which not only causes serious equipment corrosion, but also causes environmental pollution due to the escape of excess hydrogen chloride gas into the air.

[0010] Jingchahe et al. [“Improvement of dimethyl malonate synthesis process”, Henan Chemical Industry, 1999, 15, (1), 90-92] studied the synthesis process of dimethyl malonate, and the core technology of cyanide esterification method is two aspects: one is: cyanacetic acid hydrolysis to generate malonic acid, two is: malonic acid and methanol esterification to generate dimethyl malonate, the two reactions are usually carried out under the action of strong inorganic acid (such as concentrated sulfuric acid), which causes serious equipment corrosion and environmental pollution problems. Among them, esterification is the rate-determining step, and the rate of esterification step determines the rate of the whole reaction. In addition, the esterification reaction is an exothermic reaction, and with the increase of reaction temperature in the esterification process, the decomposition of cyanacetic acid is intensified, which leads to low total yield. Under strong acid conditions, the esterification reaction is a reversible process, and the large equilibrium conversion rate limits the esterification rate. Therefore, improving the esterification reaction rate, reducing the decomposition of cyanacetic acid, improving the reaction yield and esterification rate, reducing waste salt and waste water, and simplifying the post-processing process are the key and difficult points of the cyanide esterification method for synthesizing dimethyl malonate. It is of great economic and environmental significance to develop a more economical and green dimethyl malonate synthesis process. SUMMARY

[0011] In view of the deficiencies of the prior art, the present application provides a synthesis method of malonic acid ester compounds and a catalyst thereof. The malonic acid ester product can be obtained by applying the method, the problems of low yield, serious equipment corrosion and large amount of “three wastes” are solved, the efficient synthesis of malonic acid ester compounds is realized, the production efficiency is improved, and the environmental pollution is greatly reduced.

[0012] In order to achieve the above-mentioned purpose, the first aspect of the present application provides a synthesis method of malonic acid ester compounds, comprising:

[0013] Under the action of the heterogeneous catalyst, cyanacetic acid and alcohol are subjected to hydrolysis-esterification reaction in the presence of water, and after the reaction is completed, the malonic acid ester compound is obtained through post-processing;

[0014] The reaction formula is as follows:

[0015]

[0016] Among them, R 1 is selected from C1-C6 alkyl;

[0017] The heterogeneous catalyst comprises a carrier and an active component;

[0018] The active component comprises an ionic liquid and an active metal;

[0019] The carrier is an ordered mesoporous material;

[0020] The active metal is an alkaline earth metal;

[0021] The structure formula of the ionic liquid is as follows:

[0022]

[0023] wherein R is selected from C4-C 12 alkyl.

[0024] The application greatly simplifies the production process, realizes coupling of reaction heat, reduces production energy consumption and production cost of malonic acid ester products, and is beneficial to industrialized mass production by selecting appropriate catalyst and using one-pot production of malonic acid ester compounds.

[0025] The specific process is as follows: after mixing the aqueous solution of cyanoacetic acid, alcohol and heterogeneous catalyst, heating and holding, the alcohol and catalyst are recovered after the reaction is completed, and the obtained reaction liquid containing malonic acid ester is separated and purified to obtain the malonic acid ester product.

[0026] The alcohol is at least one of methanol, ethanol, n-propanol, isopropanol or n-butanol.

[0027] The mass ratio of the cyanoacetic acid to the alcohol is 1:1-3, preferably 1:1.1-1.5.

[0028] The mass ratio of the heterogeneous catalyst to the cyanoacetic acid is 0.01-0.09:1, preferably 0.03-0.07:1.

[0029] The reaction temperature is 60-100℃, and the reaction time is 1-4 hours.

[0030] In the heterogeneous catalyst, the ionic liquid is 1-methyl-3-alkyl imidazole chloride ([C n Mim]Cl), and R is preferably C4-C 10 alkyl, further preferably one or more of n-butyl, n-hexyl, n-octyl and n-decyl; specifically one or more of 1-methyl-3-n-butyl imidazole chloride ([C4Mim]Cl), 1-methyl-3-n-hexyl imidazole chloride ([C6Mim]Cl), 1-methyl-3-n-octyl imidazole chloride ([C8Mim]Cl) and 1-methyl-3-n-decyl imidazole chloride ([C 10 Mim]Cl).

[0031] The active metal is an alkaline earth metal, selected from one or two of magnesium, calcium and barium.

[0032] The carrier of the catalyst is an ordered mesoporous material, selected from one or more of MSU-X (neutral), MSU-V, MSU-G, MSU-S and MSU-H (acidic).

[0033] The preparation method of the heterogeneous catalyst in the application comprises the following steps:

[0034] (1) adding an ionic liquid, an alkaline earth metal salt into deionized water, heating and stirring to carry out complexation, to obtain a mixed solution;

[0035] (2) adding a carrier into the mixed solution, heating and stirring to carry out adsorption, and then removing excess solvent and drying to obtain the heterogeneous catalyst.

[0036] The alkaline earth metal salt is selected from one or more of chlorides, sulfates, nitrates and carbonates containing magnesium, calcium and barium which are soluble in water.

[0037] The molar ratio of the alkaline earth metal salt to the ionic liquid is 1:4-10; preferably 1:6-10.

[0038] The mass ratio of the alkaline earth metal to the carrier is 0.03-0.09:1, preferably 0.05-0.09:1.

[0039] In step (1), the complexation temperature is 80-120℃, and the complexation time is 1-4 hours.

[0040] In step (2), the adsorption temperature is 40-60℃, and the adsorption time is 4-6 hours.

[0041] Compared with the prior art, the present application has the following advantages:

[0042] (1) The present application provides a method for synthesizing malonic acid ester, which uses the catalyst of the present application to simultaneously catalyze the hydrolysis and esterification reactions, thereby reducing the equipment investment, simplifying the production process, realizing the coupling of reaction heat, reducing the alcohol consumption, reducing the energy consumption for separation after the reaction, ensuring the green and efficient production process, and being conducive to the industrialized mass production of malonic acid ester.

[0043] (2) The malonic acid ester synthesis method of the present application can effectively reduce the reaction temperature, reduce the side reactions of decomposition of cyanoacetic acid and hydrolysis of esters generated at high temperature, and improve the overall yield of the reaction. The heterogeneous catalyst provided by the present application is easy to separate and recover, solves the problem that the traditional acid catalyst cannot be repeatedly used, avoids the equipment corrosion caused by the traditional strong acid catalyst, and reduces the generation of waste water and waste salt in the reaction process, which is green and environmentally friendly. BRIEF DESCRIPTION OF DRAWINGS

[0044] Figure 1 The mass spectrum of the product obtained in application example 1. DETAILED DESCRIPTION

[0045] Unless otherwise defined, the technical terms used in the following examples have the same meanings as commonly understood by those skilled in the art to which this application belongs. The test reagents used in the following examples are all conventional biochemical reagents unless otherwise specified; and the experimental methods used are all conventional methods unless otherwise specified.

[0046] The mass concentration of the cyanacetic acid solution purchased is 70% to 80%, and the cyanacetic acid aqueous solution with a mass fraction of 70% commonly used in industry is used in the present application.

[0047] Catalyst preparation example 1

[0048] In 60 ml of deionized water, MgSO4·7H2O (7.097 g, 0.0288 mol) was added, [C6Mim]Cl ionic liquid (46.763 g, 0.2304 mol) was added, the temperature was raised to 100°C, and after heating and stirring for 2 hours, the temperature was lowered to 40°C, the carrier MSU-V (10 g) was added, and after incubation and stirring for 4 hours, the temperature was lowered to room temperature, and the filter cake was dried to constant weight to obtain catalyst 1.

[0049] Catalyst preparation examples 2 to 4

[0050] The catalyst preparation examples 2 to 4 each provide a preparation method of a heterogeneous catalyst, and the only difference compared with example 1 is that the MgSO4·7H2O metal salt in example 1 is replaced by CaCl2 (1.938 g, 0.0175 mol), Ba(NO3)2 (1.517 g, 0.0051 mol), and MgCl2 (2.742 g, 0.0288 mol), respectively, and the type and amount of the carrier remain unchanged, to obtain catalysts 2 to 4. See Table 1 for details.

[0051] Table 1

[0052]

[0053] Catalyst preparation examples 5 to 7

[0054] The catalyst preparation examples 5 to 7 each provide a preparation method of a heterogeneous catalyst, and the only difference compared with example 4 is that the [C6Mim]Cl ionic liquid in example 1 is replaced by [C4Mim]Cl (40.082 g, 0.2304 mol), [C8Mim]Cl (52.982 g, 0.2304 mol), and [C 10 Mim]Cl (59.4322 g, 0.2304 mol), and the type and amount of the alkaline earth metal salt and the carrier remain unchanged, to obtain catalysts 5 to 7.

[0055] Catalyst preparation examples 8 to 11

[0056] Examples 8-11 respectively provide a preparation method of a heterogeneous catalyst, the difference compared with Example 4 is only that the carrier MSU-V in Example 4 is replaced by MSU-X, MSU-G, MSU-S, MSU-H, and the types and amounts of the alkaline earth metal salt and the ionic liquid remain unchanged, to obtain catalysts 8-11.

[0057] Catalyst preparation examples 12-14

[0058] Examples 12-14 respectively provide a preparation method of a heterogeneous catalyst, the difference compared with Example 4 is that the loading amount of alkaline earth metal element is 0.03:1, 0.05:1, 0.09:1 respectively, and the amount of ionic liquid is adjusted, to obtain catalysts 12-14, as shown in Table 2.

[0059] Table 2

[0060]

[0061] Catalyst preparation examples 15-17

[0062] Examples 15-17 respectively provide a preparation method of a heterogeneous catalyst, the difference compared with Example 4 is that the molar ratio of metal element and [C6Mim]Cl ionic liquid in Example 4 is adjusted to 1:4, 1:6, 1:10 respectively, by adjusting the [C6Mim]Cl ionic liquid, keeping the types and amounts of the alkaline earth metal salt and the carrier unchanged, to obtain catalysts 15-17, as shown in Table 3.

[0063] Table 3

[0064]

[0065] Catalyst preparation examples 18-23

[0066] Examples 18-23 respectively provide a preparation method of a heterogeneous catalyst, the difference compared with Example 4 is only that the temperature and time of complexing the metal salt with the ligand are adjusted, and the temperature and time of adsorbing and stirring the carrier are adjusted, to obtain catalysts 18-23, as shown in Table 4.

[0067] Table 4

[0068]

[0069] Comparative Example 1

[0070] Add MgSO4•7H2O (7.097 g, 0.0288 mol) to 60 ml of deionized water, heat to 100 °C, stir for 2 hours, cool to 40 °C, add support MSU-V (10 g), stir for 4 hours, cool to room temperature, filter, and dry the resulting filter cake to constant weight to obtain the catalyst of Comparative Example 1.

[0071] Comparative Example 2

[0072] Add [C6Mim]Cl ionic liquid (46.763 g, 0.2304 mol) to 60 ml of deionized water, heat to 100 °C, stir for 2 hours, cool to 40 °C, add support MSU-V (10 g), keep warm and stir for 4 hours, cool to room temperature, filter, and dry the resulting filter cake to constant weight to obtain the catalyst of Comparative Example 2.

[0073] Comparative Example 3

[0074] Add 7.097 g of MgSO4•7H2O (0.0288 mol) to 60 ml of deionized water, add 46.763 g of [C6Mim]Cl ionic liquid (0.2304 mol), heat to 100 °C, stir for 2 hours, cool to 40 °C, add 10 g of support ZSM-5, stir for 4 hours, cool to room temperature, filter, and dry the resulting filter cake to constant weight to obtain the catalyst of Comparative Example 3.

[0075] Application examples

[0076] Application Example 1

[0077] In a 500 ml three-necked flask, 110 g of methanol, 5.0 g of catalyst 4, and 142.86 g of cyanoacetic acid (70% aqueous cyanoacetic acid solution, with a purified molar mass of 1.176 mol) were added sequentially. The mixture was stirred and heated in a water bath to 80 °C for 2 hours. After the reaction was complete, the catalyst was filtered off and washed with deionized water for later use. Unreacted methanol was recovered from the reaction solution under normal pressure, and 153.03 g of dimethyl malonate was obtained by distillation. The mass spectrum is shown below. Figure 1 The calculated yield was 98.53%.

[0078] Application Examples 2-5

[0079] The only difference between Application Examples 2-5 and Application Example 1 is that the concentration of the catalyst is changed to 1.0%, 3.0%, 7.0%, and 9.0% respectively, and the corresponding catalyst dosages are 1.0g, 3.0g, 7.0g, and 9.0g respectively. Everything else is the same as in Application Example 1. The results are shown in Table 5.

[0080] Application Examples 6-9

[0081] The only difference between Application Examples 6-9 and Application Example 1 is the change in reaction temperature and reaction time; otherwise, they are the same as Application Example 1. The temperatures for Application Examples 6 and 7 are 100℃ and 120℃, respectively, and otherwise, they are the same as Application Example 1. The reaction times for Application Examples 8 and 9 are 1 hour and 4 hours, respectively, and otherwise, they are the same as Application Example 1. The results are shown in Table 5.

[0082] Application Examples 10-12

[0083] The only difference between Application Examples 10-12 and Application Example 1 is that the amount of methanol used is changed to 100g, 200g, and 300g respectively; otherwise, they are the same as Application Example 1. The results are shown in Table 5.

[0084] Application Examples 13-16

[0085] The difference between Application Examples 13-16 and Application Example 1 is only that the types of alcohols are changed in the order of ethanol, n-propanol, isopropanol, and n-butanol. The catalyst is recovered by filtration, the solvent is recovered at atmospheric pressure, and distillation is performed to obtain dimethyl malonate product. Everything else is the same as in Application Example 1. The results are shown in Table 5.

[0086] Application Examples 17-38

[0087] In Application Examples 17-38, the heterogeneous catalysts were modified, and the catalysts used were the heterogeneous catalysts provided in Examples 1-3 and 5-23, respectively, for the synthesis of dimethyl malonate. Other aspects were the same as in Application Example 1. The results are shown in Table 5.

[0088] Application Comparative Examples 1-3

[0089] Comparative Examples 1-3 provide applications of heterogeneous catalysts, differing from Application Example 1 only in that the heterogeneous catalysts used are the heterogeneous catalysts provided in Comparative Examples 1-3, respectively; otherwise, they are the same as in Application Example 1. The results are shown in Table 5.

[0090] Table 5

[0091]

[0092] Catalyst application examples

[0093] The catalyst recovered in Application Example 1 was washed with deionized water 2-3 times to obtain the recovered catalyst. The catalyst was then reused. The first use of the recovered catalyst was considered as one reuse, the second use of the recovered catalyst was considered as two reuses, and so on. The specific results are shown in Table 6.

[0094] Table 6

[0095]

[0096] The applicant declares that the above description is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention fall within the protection and disclosure scope of the present invention.

Claims

1. A method for synthesizing a malonate ester compound, characterized in that, include: Under the action of a heterogeneous catalyst, cyanoacetic acid and alcohol undergo hydrolysis-esterification reaction in the presence of water. After the reaction is completed, the malonate compound is obtained by post-treatment. The reaction formula is as follows: ； Among them, R 1 Selected from C1~C6 alkyl groups; The heterogeneous catalyst includes a support and an active component; The active components include ionic liquids and active metals; The carrier is an ordered mesoporous material; The active metal is an alkaline earth metal; The structural formula of the ionic liquid is as follows: ； Wherein, R is selected from C4~C 12 alkyl.

2. The method for synthesizing malonic ester compounds according to claim 1, characterized in that, The alcohol is at least one of methanol, ethanol, n-propanol, isopropanol, or n-butanol.

3. The method for synthesizing malonic ester compounds according to claim 1, characterized in that, The mass ratio of the cyanoacetic acid to the alcohol is 1:1~3; The mass ratio of the heterogeneous catalyst to the cyanoacetic acid is 0.01~0.09:1; The cyanoacetic acid is added in the form of an aqueous solution of cyanoacetic acid, with a concentration of 70-80 wt%.

4. The method for synthesizing malonic ester compounds according to claim 1, characterized in that, The hydrolysis-esterification reaction is carried out at a temperature of 60~100℃ for 1~4 hours.

5. The method for synthesizing malonic ester compounds according to claim 1, characterized in that, The carrier is selected from one or more of MSU-X, MSU-V, MSU-G, MSU-S, and MSU-H.

6. The method for synthesizing malonic ester compounds according to claim 1, characterized in that, The active metal is one or two of magnesium, calcium, and barium.

7. The method for synthesizing malonic ester compounds according to claim 1, characterized in that, The ionic liquid is one or more of 1-methyl-3-n-butylimidazolium chloride, 1-methyl-3-n-hexylimidazolium chloride, 1-methyl-3-n-octylimidazolium chloride, and 1-methyl-3-n-decylimidazolium chloride.

8. The method for synthesizing the malonate ester compound according to any one of claims 1 to 7, characterized in that, The method for preparing the heterogeneous catalyst includes the following steps: (1) Add ionic liquid and alkaline earth metal salt to deionized water, heat and stir to complex, and obtain a mixed solution; (2) Add the carrier to the above mixture, heat and stir to adsorb, then filter and dry to obtain the heterogeneous catalyst.

9. The method for synthesizing malonic ester compounds according to claim 8, characterized in that, The alkaline earth metal salt is selected from one or more of the following: magnesium, calcium, and barium chlorides, sulfates, nitrates, and carbonates that are soluble in water. The molar ratio of the alkaline earth metal salt to the ionic liquid is 1:4~10; The mass ratio of the alkaline earth metal salt to the carrier is 0.03 to 0.09:1, calculated based on alkaline earth metals.

10. The method for synthesizing malonic ester compounds according to claim 8, characterized in that, In step (1), the temperature of the complexation is 80~120℃, and the complexation time is 1~4 hours; In step (2), the adsorption temperature is 40~60℃ and the adsorption time is 4~6 hours.

Images