A method for synthesizing malonate compounds

Abstract

The application belongs to the technical field of fine chemical industry, and discloses a synthesis method of malonic acid ester compounds, which comprises the following steps: under the action of a heterogeneous catalyst, cyanoacetic acid and alcohol are subjected to hydrolysis-esterification reaction, and after the reaction is completed, post-treatment is performed to obtain the malonic acid ester compounds; the heterogeneous catalyst comprises a carrier and an active component; the active component comprises an ionic liquid and an active metal; the carrier is an ordered mesoporous material; and the active metal is an alkaline earth metal. The method can obtain malonic acid ester products, solves the problems of low yield, serious equipment corrosion and large amount of "three wastes", realizes efficient synthesis of malonic acid ester compounds, improves production efficiency, and greatly reduces environmental pollution.

Description

Technical Field

[0001] This invention belongs to the field of fine chemical technology, and in particular relates to a method for synthesizing malonic acid esters. Background Technology

[0002] Dimethyl malonate (DMM), commonly known as dimethyl carotene, is a colorless, transparent liquid with an aromatic odor. It is slightly soluble in water and soluble in many organic solvents, including ether, alcohol, benzene, and chloroform. The industrial grade is a pale yellow, transparent liquid. The DMM molecule contains an active methylene group, allowing it to undergo various substitution reactions such as alkylation, acylation, hydroxyalkylation, and amidation. It is an important raw material for the synthesis of pharmaceuticals, pesticides, fragrances, dyes, antioxidants, and many other fine chemicals. For example, DMM is a crucial raw material for the synthesis of the precious fragrance methyl dihydrojasmonate, and it can also be used as a hydrogenation feedstock to synthesize 1,3-propanediol. It is also a key raw material for the production of pharmaceuticals such as pipemidic acid and coumarin dimethyl malonate.

[0003] Currently, the domestic industrial production of dimethyl malonate is via the cyanidation esterification method. Using chloroacetic acid as raw material, the process involves neutralization with sodium carbonate, cyanidation with sodium cyanide, acidification, and then esterification with methanol to obtain dimethyl malonate. This method is relatively mature and can achieve stable production. However, it suffers from a long process flow, low yield, and the generation of large amounts of waste salt and wastewater, making post-treatment complex and prone to causing serious environmental pollution, resulting in high production costs for dimethyl malonate.

[0004]

[0005] Patent CN106496031A discloses a method for synthesizing malonic acid esters, using cyanoacetic acid and alcohol as raw materials, and carrying out an esterification reaction under the catalysis of hydrogen chloride gas. This method uses hydrogen chloride gas instead of concentrated sulfuric acid as a catalyst, and the resulting crude product still requires washing, neutralization, and other post-treatment operations. This not only causes equipment corrosion but also generates large amounts of waste salt and wastewater, failing to fundamentally solve the problems existing in the synthesis of malonic acid esters via cyanide esterification.

[0006] Patent CN103319338A discloses a method for synthesizing dimethyl malonate from chloroacetic acid through neutralization, cyanation, acidification, and esterification processes. It also discloses the esterification reaction method and catalyst. Specifically, concentrated sulfuric acid, 4-6 times the weight of methanol (based on chloroacetic acid weight), and a catalyst are added to a solution of cyanoacetic acid for the reaction. The catalyst consists of 8-10 wt% lead chloride, 65-72 wt% triphenylphosphine, 10-15 wt% dimethyl sulfoxide, and 8-12 wt% hydrazine hydrate. This method still uses concentrated sulfuric acid as one of the catalytic components, and the catalyst cannot be recycled, making it impossible to avoid environmental pollution and equipment corrosion.

[0007] Patent CN103304411A uses cyanoacetic acid as a raw material to synthesize malonate by simultaneously carrying out hydrolysis and esterification reactions in the presence of ionic liquid and water. The reaction products naturally separate into layers with the acidic water. However, it suffers from problems such as expensive catalysts, low product yield, and difficulty in recycling and using the ionic liquid phase.

[0008] Patent CN103936588A uses cyanoacetic acid with a water content ≤5%, alcohol, and hydrogen chloride gas or hydrogen chloride alcohol solution as raw materials, and obtains malonic acid ester through five steps: esterification, dealcoholization and desalting, neutralization and distillation. However, obtaining cyanoacetic acid with a water content ≤5% is difficult in industrial production. Currently, the water content of industrial 70% cyanoacetic acid is about 20%. During evaporation, as the water content concentrates to 1-5%, prolonged dehydration and concentration cause dissolved salts to precipitate, increasing the viscosity of the material and easily leading to the thermal decomposition of large amounts of cyanoacetic acid, especially during large-scale production. Using organic acid esters or hydrocarbon solvents to extract the cyanoacetic acid solution to obtain low-water or anhydrous cyanoacetic acid raw materials results in a complex raw material acquisition process and reduced socio-economic benefits. Furthermore, during alcoholysis, the nucleation rate of ammonium chloride, a byproduct, is much greater than its crystal growth rate, resulting in small, unevenly distributed ammonium chloride particles that contain a large amount of ester products, making washing difficult and leading to a high organic content in the ammonium chloride product.

[0009] CN107540543A discloses a method for synthesizing malonic esters. Using 80wt% cyanoacetic acid as a raw material, malonic esters are synthesized via hydrogen chloride alcoholysis. Excess hydrogen chloride is neutralized with ammonia water, and then hydrogen chloride gas is absorbed by alcohol to obtain a hydrogen chloride-alcohol solution. This method uses sulfuric acid or hydrogen chloride gas as a catalyst, which not only causes severe equipment corrosion but also allows excess hydrogen chloride gas to escape into the air, leading to environmental pollution.

[0010] Jing Chaohe et al. [“Improvement of Dimethyl Malonate Synthesis Process”, Henan Chemical Industry, 1999, 15, (1), 90-92] studied the synthesis process of dimethyl malonate. The core technology of the cyanoesterification method consists of two aspects: first, hydrolysis of cyanoacetic acid to generate malonic acid; second, esterification of malonic acid with methanol to generate dimethyl malonate. Both steps are usually carried out under the action of strong inorganic acids (such as concentrated sulfuric acid), causing serious equipment corrosion and environmental pollution problems. Among them, esterification is the rate-controlling step, and the rate of esterification determines the rate of the entire reaction. In addition, the esterification reaction is an exothermic reaction. During the esterification process, as the reaction temperature increases, the decomposition of cyanoacetic acid intensifies, resulting in a low overall yield. Under strong acidic conditions, the esterification reaction is a reversible process, and the large equilibrium conversion rate limits its esterification rate. Therefore, increasing the esterification reaction rate, reducing the decomposition of cyanoacetic acid, improving the reaction yield and esterification rate, reducing waste salt and wastewater, and simplifying the post-treatment process are the key points and challenges in the synthesis of dimethyl malonate via cyanide esterification. Developing a more economical and environmentally friendly process for the synthesis of dimethyl malonate has significant economic and environmental implications. Summary of the Invention

[0011] To address the shortcomings of existing technologies, this invention provides a method for synthesizing malonic acid esters and its catalyst. This method can yield malonic acid ester products, solving the problems of low yield, severe equipment corrosion, and large amounts of waste. It achieves efficient synthesis of malonic acid esters, while improving production efficiency and greatly reducing environmental pollution.

[0012] To achieve the above objectives, a first aspect of the present invention provides a method for synthesizing malonic ester compounds, comprising:

[0013] 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.

[0014] The reaction formula is as follows:

[0015]

[0016] Among them, R 1 Selected from C1~C6 alkyl groups;

[0017] The heterogeneous catalyst includes a support and an active component;

[0018] The active components include ionic liquids and active metals;

[0019] The carrier is an ordered mesoporous material;

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

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

[0022]

[0023] Wherein, R is selected from C4~C 12 alkyl.

[0024] This invention simplifies the production process by using a "one-pot" method to produce malonic acid esters through the selection of appropriate catalysts. It also achieves the coupling of reaction heat, reduces production energy consumption, and lowers the production cost of malonic acid esters, which is conducive to their large-scale industrial production.

[0025] The specific process is as follows: After mixing the aqueous solution of cyanoacetic acid, alcohol, and heterogeneous catalyst, the mixture is heated and kept at a constant temperature for reaction. After the reaction is completed, the alcohol and catalyst are recovered, and the resulting reaction solution containing malonic acid esters is separated and purified to obtain malonic acid ester products.

[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 to 3, preferably 1:1.1 to 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-alkylimidazolium chloride ([C n Mim]Cl), wherein R is preferably C4~C 10 Alkyl groups, more preferably one or more selected from n-butyl, n-hexyl, n-octyl, and n-decyl; specifically, 1-methyl-3-n-butylimidazolium chloride ([C4Mim]Cl), 1-methyl-3-n-hexylimidazolium chloride ([C6Mim]Cl), 1-methyl-3-n-octylimidazolium chloride ([C8Mim]Cl), 1-methyl-3-n-decylimidazolium chloride ([C4Mim]Cl), etc. 10 One or more of the following: Mim]Cl.

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

[0032] The catalyst support 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 method for preparing the heterogeneous catalyst of this invention includes the following steps:

[0034] (1) Add ionic liquid and alkaline earth metal salt to deionized water, heat and stir to complex, and obtain a mixed solution;

[0035] (2) Add the carrier to the above mixture, heat and stir to adsorb, then remove the excess solvent and dry to obtain the heterogeneous catalyst.

[0036] 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.

[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 beneficial effects of the present invention are as follows:

[0042] (1) This invention provides a method for synthesizing malonate. The catalyst of this invention simultaneously catalyzes the hydrolysis and esterification reactions, which reduces equipment investment, simplifies the production process, and achieves the coupling of reaction heat, thereby reducing production energy consumption. It also reduces the amount of alcohol used and the energy consumption for separation after the reaction is completed, ensuring that the production process is green and efficient, which is conducive to the large-scale industrial production of malonate.

[0043] (2) The malonic ester synthesis method of the present invention can effectively reduce the reaction temperature, reduce the side reactions of cyanoacetic acid decomposition at high temperature and the hydrolysis of generated esters, and improve the overall yield of the reaction. The heterogeneous catalyst provided by the present invention is easy to separate and recover, solves the problem that traditional acid catalysts cannot be reused, and avoids equipment corrosion caused by traditional strong acid catalysts; at the same time, it reduces the generation of wastewater and waste salt during the reaction process, making it green and environmentally friendly. Attached Figure Description

[0044] Figure 1 The mass spectrum of the product obtained from Example 1 is shown. Detailed Implementation

[0045] Unless otherwise defined, the technical terms used in the following embodiments have the same meanings as commonly understood by those skilled in the art. Unless otherwise specified, the experimental reagents used in the following embodiments are conventional biochemical reagents; and the experimental methods described are conventional methods.

[0046] The mass concentration of the purchased cyanoacetic acid solution is 70%~80%, and the cyanoacetic acid aqueous solution with a mass fraction of 70% used in this invention is the most commonly used industrial cyanoacetic acid aqueous solution.

[0047] Catalyst Preparation Example 1

[0048] 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 MSU-V, stir for 4 hours, cool to room temperature, filter, and dry the resulting filter cake to constant weight to obtain catalyst 1.

[0049] Catalyst Preparation Examples 2-4

[0050] Examples 2-4 of this catalyst preparation method provide a method for preparing a heterogeneous catalyst. The only difference from Example 1 is that the MgSO4•7H2O metal salt in Example 1 is replaced sequentially with CaCl2 (1.938g, 0.0175mol), Ba(NO3)2 (1.517g, 0.0051mol), and MgCl2 (2.742g, 0.0288mol), while keeping the type and amount of support unchanged, thus obtaining catalysts 2-4. See Table 1 for details.

[0051] Table 1

[0052]

[0053] Catalyst Preparation Examples 5-7

[0054] Examples 5-7 provide methods for preparing heterogeneous catalysts, differing from Example 4 only in that the [C6Mim]Cl ionic liquid in Example 1 is replaced with [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), while keeping the type and amount of alkaline earth metal salt and support constant, catalysts 5-7 were obtained.

[0055] Catalyst Preparation Examples 8-11

[0056] Examples 8-11 provide a method for preparing a heterogeneous catalyst. The only difference from Example 4 is that the support MSU-V in Example 4 is replaced with MSU-X, MSU-G, MSU-S, and MSU-H, while keeping the type and amount of alkaline earth metal salt and ionic liquid unchanged, thus obtaining catalysts 8-11.

[0057] Catalyst Preparation Examples 12-14

[0058] Examples 12-14 provide a method for preparing a heterogeneous catalyst. The difference from Example 4 is that the loading of alkaline earth metal elements is 0.03:1, 0.05:1, and 0.09:1, respectively. At the same time, the amount of ionic liquid added 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 provide a method for preparing heterogeneous catalysts. The difference from 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, and 1:10 respectively. By adjusting the [C6Mim]Cl ionic liquid, while keeping the type and amount of alkaline earth metal salt and support unchanged, catalysts 15-17 are obtained, as shown in Table 3.

[0063] Table 3

[0064]

[0065] Catalyst Preparation Examples 18-23

[0066] Examples 18-23 provide a method for preparing a heterogeneous catalyst. The difference from Example 4 is only in adjusting the temperature and time for complexation of the metal salt and ligand, and adjusting the temperature and time for adsorption and stirring of the support, so as 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 active metal is an alkaline earth metal; The alkaline earth metal is one or two of magnesium, calcium, and barium. The structural formula of the ionic liquid is as follows: ； Wherein, R is selected from C4~C 12 alkyl; The carrier is selected from one or more of MSU-X, MSU-V, MSU-G, MSU-S, and MSU-H.

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 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.

6. The method for synthesizing the malonate ester compound according to any one of claims 1 to 5, 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.

7. The method for synthesizing malonic ester compounds according to claim 6, 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.

8. The method for synthesizing malonic ester compounds according to claim 6, 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.

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