Method for synthesizing dimethyl malonate through homogeneous-phase continuous carbonylation

Abstract

The invention discloses a method for synthesizing dimethyl malonate through homogeneous-phase continuous carbonylation, which comprises the following steps of: carrying out carbonylation reaction on chloracetate serving as a raw material at a certain temperature and pressure in the presence of a liquid acid-binding agent and a catalyst to synthesize the dimethyl malonate. The problems that in a batch process of a traditional dimethyl malonate carbonylation synthesis method, carbon monoxide in a reactor is high in pressure and large in consumption, and once leakage or other faults occur, great risks are brought to safety production are solved; the invention solves the technical problems in the prior art that an acid-binding agent is in a solid state before and after acid-binding, the solid content is high, if continuous production transformation is needed, the requirement for feeding and discharging conveying of equipment is high, large-scale production is not facilitated, and the product and a catalyst are difficult to separate and recover after the reaction is finished, so that the production cost is increased.

Description

Technical Field

[0001] This invention relates to the field of fine chemicals, and specifically to a method for homogeneous continuous carbonylation synthesis of dimethyl malonate. Background Technology

[0002] In the field of organic chemistry, carbonylation is an important reaction type, widely used in the synthesis of various organic compounds. Dimethyl malonate is an important chemical raw material, widely used in pharmaceuticals, dyes, plastics, and other industries. The traditional method for synthesizing dimethyl malonate by carbonylation mainly involves using chloroacetic acid ester as a raw material, cobalt or palladium compounds, and corresponding phosphine ligands as catalysts, reacting with carbon monoxide in an acid-binding agent such as sodium carbonate and an alcohol as a solvent.

[0003] A typical example of this technology is the 2001 Degussa patent (DE 10008899A1), which demonstrates high reproducibility. This route uses Co2(CO)8 as a catalyst and Na2CO3 as an acid-binding agent, achieving good reaction results under conditions of 25 bar CO pressure and 91°C. However, this method requires high carbon monoxide pressure and large quantities in the reactor during batch processes, posing significant risks to safe production should leaks or other malfunctions occur. Furthermore, since the acid-binding agent remains solid before and after acid binding and has a high solids content, continuous production requires sophisticated equipment feeding and discharging systems, hindering large-scale production.

[0004] Inspired by the explorations of predecessors, the technicians boldly explored and attempted to completely solve the problem from the perspective of engineering difficulty, thus obtaining the homogeneous continuous carbonylation technology described in this article. Summary of the Invention

[0005] In summary, the traditional batch process for the carbonylation synthesis of dimethyl malonate involves high carbon monoxide pressure and large quantities in the reactor, posing a significant risk to safe production should leaks or other malfunctions occur. Furthermore, the acid-binding agent remains solid before and after binding the acid, with a high solid content. Continuous production requires sophisticated equipment feeding and discharging systems, which is not conducive to large-scale production. Moreover, the separation and recovery of products and catalysts after the reaction are difficult, increasing production costs.

[0006] To address the aforementioned issues, this invention develops a homogeneous and continuous carbonylation method for the synthesis of dimethyl malonate. This method improves reaction efficiency in terms of conversion and selectivity, directly separates the product dimethyl malonate with high gas-phase purity, simplifies the separation and recovery process of the product and catalyst, reduces production costs, allows for catalyst regeneration and reuse, further lowering production costs and reducing waste generation. The homogeneous and continuous reaction process avoids the problems of high carbon monoxide pressure and large consumption in the reactor during batch processes, improving production safety, reducing the requirements for continuous equipment and maintenance costs, and enhancing the operational stability of continuous production. Thus, this invention is complete.

[0007] Specifically, one of the objectives of this invention is to provide a homogeneous and continuous carbonylation method for synthesizing dimethyl malonate, using chloroacetic acid ester as a raw material, and carrying out a carbonylation reaction in the presence of a liquid acid binder and a catalyst at a certain temperature and pressure to synthesize dimethyl malonate.

[0008] The synthesis method of the present invention includes the following steps:

[0009] Step 1: Carbonylation reaction

[0010] Chloroacetate undergoes a carbonylation reaction in the presence of a liquid acid-binding agent and a catalyst to synthesize dimethyl malonate;

[0011] Step 2: Post-reaction treatment

[0012] After the carbonylation reaction in step 1 is completed, the target product is obtained by separation.

[0013] In this invention, the chloroacetic acid ester raw material is a chloroacetic acid ester, including methyl chloroacetate, ethyl chloroacetate, and other chloroacetic acid ester compounds. The catalyst is one or more of octacarbonyldicobalt and dodecyltetracobalt. The liquid acid-binding agent can be an organic base, such as a nitrogen-containing heterocyclic compound or a trialkylamine, preferably a trialkylamine, such as an organic amine having the following general formula:

[0014] (C n H 2n+1 )3N, where n is a natural number from 2 to 18.

[0015] According to the present invention, the carbonylation reaction is carried out in a solvent, such as an alcohol solvent or an ester solvent, wherein the alcohol solvent is preferably methanol or ethanol, more preferably methanol, and the ester solvent may be a monocarboxylic acid ester, such as methyl formate or ethyl acetate, or a polycarboxylic acid ester, such as dimethyl oxalate, diethyl oxalate, dimethyl malonate or diethyl malonate.

[0016] The carbonylation reaction described in this invention uses carbon monoxide as the carbonylation reagent, the reaction temperature is 50-150℃, preferably 70-130℃, and the carbon monoxide pressure is 0.2-10 MPa, preferably 0.5-5 MPa.

[0017] In step 2 of this invention, after the carbonylation reaction is completed, the hydrogen chloride generated during the reaction reacts with an acid-binding agent such as an organic base to form a hydrochloride salt. This hydrochloride salt is mixed with the product and separated by filtration and / or layering to obtain the product dimethyl malonate. The acid-binding agent and catalyst components are separated by acid-base neutralization, and the catalyst and / or acid-binding agent are recovered, preferably reused in the reaction of step 1.

[0018] Another objective of this invention is to provide dimethyl malonate, which is obtained according to the above-described synthesis method.

[0019] The method provided by this invention achieves the following beneficial effects:

[0020] 1) The reaction selectivity can reach 90-96.5% and the conversion rate is over 99% by means of the method of the present invention, which greatly improves the reaction efficiency.

[0021] 2) After the reaction, the trioctylamine and other acid-binding agents in hydrochloride are in a liquid state, and the product mixture system is also in a liquid state. Dimethyl malonate can be directly separated from the product with a gas phase purity of up to 99.3%. This method not only simplifies the separation and recovery process of the product and catalyst and reduces production costs, but also improves the purity of the product.

[0022] 3) The acid-binding agent and catalyst components can be separated through simple acid-base neutralization, allowing for subsequent catalyst regeneration and reuse. This method not only achieves catalyst recycling and reduces production costs but also reduces waste generation, meeting environmental protection requirements.

[0023] 4) The entire reaction process is homogeneous and continuous, avoiding the problems of high carbon monoxide pressure and large consumption in the reactor of batch processes, thus improving production safety. At the same time, it also reduces the requirements for continuous equipment and the cost of wear and maintenance, and improves the operational stability of continuous production. Attached Figure Description

[0024] Figure 1 The gas chromatogram of dimethyl malonate obtained by reaction separation in Example 2 is shown.

[0025] Figure 2 A schematic diagram of the tubular reactor used in Example 3 is shown, which has a built-in static mixer;

[0026] Figure 3 The gas phase detection spectrum of dimethyl malonate obtained by reaction separation in Example 4 is shown. Detailed Implementation

[0027] The present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Through these descriptions, the features and advantages of the present invention will become clearer and more apparent.

[0028] The term “exemplary” as used herein means “serving as an example, embodiment, or illustration.” Any embodiment illustrated herein as “exemplary” is not necessarily to be construed as superior to or better than other embodiments. Although various aspects of embodiments are shown in the accompanying drawings, the drawings are not necessarily drawn to scale unless specifically indicated otherwise.

[0029] In one aspect, this invention provides a homogeneous and continuous carbonylation method for synthesizing dimethyl malonate, using chloroacetic acid ester as a raw material, and carrying out a carbonylation reaction in the presence of a liquid acid binder and a catalyst at a certain temperature and pressure to synthesize dimethyl malonate.

[0030] The present invention will now be described in detail.

[0031] The method of the present invention includes the following steps:

[0032] Step 1: Carbonylation reaction

[0033] Chloroacetic acid esters undergo carbonylation in the presence of a liquid acid-binding agent and a catalyst to synthesize dimethyl malonate.

[0034] The raw materials used in this invention are chloroacetic esters, including methyl chloroacetate, ethyl chloroacetate, and other chloroacetic ester compounds.

[0035] In this invention, the catalyst is one or more of octacarbonyldicobalt and dodecacarbonyltetracobalt.

[0036] According to the present invention, the liquid acid-binding agent may be an organic base, such as a nitrogen-containing heterocyclic compound or a trialkylamine, preferably a trialkylamine, such as an organic amine having the following general formula:

[0037] (C n H 2n+1 )3N,

[0038] Wherein, n is a natural number from 2 to 18, preferably 4 to 12, and more preferably 6 to 10.

[0039] According to a preferred embodiment of the present invention, the carbonylation reaction is carried out in a solvent, such as an alcohol solvent or an ester solvent, preferably methanol or ethanol, more preferably methanol. The intraester solvent can be a monocarboxylic acid ester, such as methyl formate or ethyl acetate, or a polycarboxylic acid ester, such as dimethyl oxalate, diethyl oxalate, dimethyl malonate or diethyl malonate, preferably dimethyl malonate.

[0040] When dimethyl malonate is used as the reaction solvent, only the organic acid-binding agent needs to be separated after the reaction to obtain relatively pure dimethyl malonate, eliminating the need to separate methanol when methanol is used as the solvent, thus saving energy.

[0041] In this invention, carbon monoxide is used as the carbonylating agent in the carbonylation reaction, the reaction temperature is 50-150℃, preferably 70-130℃, and the carbon monoxide pressure is 0.2-10 MPa, preferably 0.5-5 MPa.

[0042] The method described in this invention can be carried out in a conventional reactor, such as a pressure vessel, or in a tubular continuous reactor with a static mixer (e.g., Figure 1 The synthesis can be carried out in either a tubular or a series-connected continuous reactor. Continuous synthesis can be achieved in tubular or series-connected reactors.

[0043] Because of the use of homogeneous acid-binding agents in this invention, the conventional three-phase reaction of gas, liquid, and solid is transformed into a two-phase reaction of gas and liquid, which reduces the requirements for conveying equipment and allows for continuous production through a simpler continuous reactor.

[0044] Step 2: Post-reaction treatment

[0045] After the carbonylation reaction in step 1 of this invention is completed, the target product is obtained by separation.

[0046] According to the present invention, after the carbonylation reaction is completed, the hydrogen chloride generated during the reaction reacts with an acid-binding agent such as an organic base to form a hydrochloride, which is in a liquid state. The product mixture system is in a liquid state and can be treated with an alkali to dissociate the organic base. After filtration and separation, the product dimethyl malonate is obtained, and its gas phase purity can reach more than 99%.

[0047] The method of this invention not only simplifies the separation and recovery process of products and catalysts and reduces production costs, but also improves the purity of the products.

[0048] After separating the products, the acid-binding agent and catalyst components can be separated by simple acid-base neutralization, and the catalyst and / or acid-binding agent can be recovered and preferably used in the reaction of step 1.

[0049] The method of this invention not only enables the recycling of catalysts and reduces production costs, but also reduces waste generation, thus meeting environmental protection requirements.

[0050] According to a second aspect of the present invention, a dimethyl malonate is provided, which is prepared by the above method.

[0051] Example

[0052] The present invention is further described below through specific examples; however, these examples are merely exemplary and do not constitute any limitation on the scope of protection of the present invention.

[0053] In this invention, the conversion rate, product selectivity, and yield of the reaction are determined by liquid chromatography with external standard detection. Specifically, solutions of methanol + dimethyl malonate + methyl chloroacetate at different concentrations are prepared, and concentration-peak area curves are obtained by liquid chromatography detection. Then, based on the liquid chromatography detection results of the samples, the conversion rate of the raw materials and the product selectivity of the corresponding reactions are calculated, and the yield is calculated.

[0054] Example 1:

[0055] Using a 500ml stainless steel pressure vessel and an 8L carbon monoxide cylinder as the gas source, under nitrogen protection, 27.4g of methyl chloroacetate, 120ml of methanol, 70g of trihexylamine, and 1.05g of cobalt octacarbonyl were added in one batch.

[0056] After feeding is completed, nitrogen and carbon monoxide are replaced in the pressure vessel to remove air from the system. The replacement effect is monitored using a pump-suction gas detector.

[0057] After the displacement reaction was completed, the pressure was increased and the temperature was raised to 4 MPa and 110 °C for further reaction. After holding at this temperature for 30 minutes, the reaction was completed, yielding a blue product mother liquor. Liquid chromatography with external standard analysis showed a raw material conversion rate of 99.5% and a selectivity of 93.5% for the product dimethyl malonate.

[0058] 10g of sodium hydroxide was added to the obtained liquid mixture under ice bath conditions. After stirring for 30 minutes, the mixture was filtered and separated to obtain a mixture of dimethyl malonate and methanol. The final product yield was 92.4% and the gas phase purity was 98.7% as determined by external standard analysis in liquid chromatography.

[0059] Example 2:

[0060] Using a 500ml stainless steel pressure vessel, add 54.81g of methyl chloroacetate, 50g of dimethyl malonate, 22ml of methanol, 180g of trioctylamine, and 2.2g of dicobalt octacarbonyl. React at 3MPa and 120℃. After 1 hour, a blue mixture is obtained.

[0061] Liquid chromatography with external standard analysis showed a reaction conversion rate of 99.9% and a product selectivity of 96.7%.

[0062] 21g of solid sodium hydroxide was added to the mixture in an ice-water bath, stirred for 30 min, and then allowed to stand for 30 min. After separation, the upper layer was 113.4g of dimethyl malonate, and the lower layer was filtered and washed with water to recover 173.2g of trioctylamine. The filter residue was washed with water to remove sodium chloride, yielding 1.18g of recovered cobalt hydroxide. The yield of dimethyl malonate was 95.7%, and its gas chromatography chromatogram is shown below. Figure 1 As shown, the purity is 99.3%.

[0063] Example 3:

[0064] The reactor is a tubular reactor with a built-in static mixer, such as... Figure 1 As shown, the reactor is placed in an oil bath. Octacarbonyl dicobalt, methanol, and trihexylamine in the same proportions as in Example 1 are used as flow path A, and methyl chloroacetate and methanol are used as flow path B. The concentration of methyl chloroacetate in flow path B is 30 wt.%. The mixture is pumped into the premixer via plunger pumps A and B for mixing, and then enters the tubular reactor. Carbon monoxide is introduced into the mixture before the heating section of the reaction. The reaction is carried out at 150°C and 1.5 MPa, and the residence time is controlled at 17-21 min.

[0065] After passing through a back pressure valve, the material is cooled to below 20°C in a circulating water bath at the discharge end. Liquid chromatography with external standard analysis showed a reaction conversion rate of 99.9% and a product selectivity of 89.5%.

[0066] The blue liquid was cooled to below 5°C in the reactor, and 1.05 times the molar amount of trihexylamine sodium hydroxide solid was added. The mixture was kept at this temperature for 1 hour, filtered, and separated to obtain a methanol mixture of dimethyl malonate. The final yield was 88.3%, and the gas phase purity was 98.5%.

[0067] Example 4:

[0068] Unlike Example 3, the reaction selectivity was improved by enhancing the gas dispersion effect. A three-stage series reactor was used for the reaction, with a total liquid holding volume of 15L. A self-suction impeller was selected as the agitator.

[0069] After nitrogen and carbon monoxide were replaced, the same proportions of materials as in Example 2 were mixed thoroughly in a premix tank under nitrogen protection and then pumped into the reactor via a high-pressure diaphragm pump. The temperature of the first-stage reactor was 110°C, the temperature of the second-stage reactor was 100°C, and the temperature of the third-stage reactor was 30°C. The material was continuously discharged through the discharge valve at the bottom of the third-stage reactor.

[0070] After discharge, liquid chromatography with external standard analysis showed that the raw material conversion rate of the reaction mother liquor was 99.8% and the product selectivity was 93.7%.

[0071] The reaction solution was cooled to below 8°C, and 1.1 times the molar amount of trioctylamine in sodium hydroxide solid was added. The mixture was kept at this temperature for 1.5 hours and then allowed to stand to separate into layers. The upper layer, dimethyl malonate, was separated, yielding a product yield of 92.1%. Its gas chromatography chromatogram is shown below. Figure 3 As shown, the gas phase purity is 99.1%.

[0072] The present invention has been described in detail above with reference to preferred embodiments and exemplary examples. However, it should be noted that these specific embodiments are merely illustrative explanations of the invention and do not constitute any limitation on the scope of protection of the invention. Various improvements, equivalent substitutions, or modifications can be made to the technical content and embodiments of the present invention without departing from the spirit and scope of protection of the invention, and all such modifications fall within the scope of protection of the present invention. The scope of protection of the present invention is defined by the appended claims.

Claims

1. A method for homogeneous continuous carbonylation synthesis of dimethyl malonate, characterized in that, Dimethyl malonate was synthesized by carbonylation reaction using chloroacetic acid ester as a raw material in the presence of a liquid acid binder and catalyst at a certain temperature and pressure.

2. The synthesis method according to claim 1, characterized in that, Includes the following steps: Step 1: Carbonylation reaction, Chloroacetate undergoes a carbonylation reaction in the presence of a liquid acid-binding agent and a catalyst to synthesize dimethyl malonate; Step 2: Post-reaction treatment After the carbonylation reaction in step 1 is completed, the target product is obtained by separation.

3. The synthesis method according to claim 1 or 2, characterized in that, The chloroacetic acid ester raw material is chloroacetic acid ester, including chloroacetic acid ester compounds such as methyl chloroacetate and ethyl chloroacetate.

4. The synthesis method according to any one of claims 1 to 3, characterized in that, The catalyst is one or more of octacarbonyldicobalt and dodecacarbonyltetracobalt.

5. The synthesis method according to any one of claims 1 to 4, characterized in that, The liquid acid-binding agent can be an organic base, such as a nitrogen-containing heterocyclic compound or a trialkylamine, preferably a trialkylamine, such as an organic amine having the following general formula: (C n H 2n+1 )3N, Wherein, n is a natural number from 2 to 18, preferably 4 to 12, and more preferably 6 to 10.

6. The synthesis method according to any one of claims 1 to 5, characterized in that, The carbonylation reaction is carried out in a solvent, such as an alcohol solvent or an ester solvent, preferably methanol or ethanol, more preferably methanol. The ester solvent can be a monocarboxylic acid ester, such as methyl formate or ethyl acetate, or a polycarboxylic acid ester, such as dimethyl oxalate, diethyl oxalate, dimethyl malonate or diethyl malonate.

7. The synthesis method according to any one of claims 1 to 6, characterized in that, The carbonylation reaction uses carbon monoxide as the carbonylating agent, the reaction temperature is 50-150℃, preferably 70-130℃, and the carbon monoxide pressure is 0.2-10 MPa, preferably 0.5-5 MPa.

8. The synthesis method according to any one of claims 2 to 7, characterized in that, In step 2, after the carbonylation reaction is completed, the hydrogen chloride generated during the reaction reacts with organic bases and other acid-binding agents to form hydrochloride, which is mixed with the product and separated by filtration and / or layering to obtain the product dimethyl malonate.

9. The synthesis method according to any one of claims 2 to 8, characterized in that, In step 2, the acid-binding agent and catalyst components are separated by acid-base neutralization, and the catalyst and / or acid-binding agent are recovered and preferably used in the reaction of step 1.

10. Dimethyl malonate, obtained by the synthetic method according to any one of claims 1 to 9.

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