Process for the preparation of dimethyl 2-methylglutarate

Abstract

The application discloses a preparation method of 2-methyl glutaric acid dimethyl ester, which comprises the following steps: taking methyl acrylate as a starting material, firstly adding to obtain an intermediate 2-methylene glutaric acid dimethyl ester, and then catalytically hydrogenating to obtain 2-methyl glutaric acid dimethyl ester; the catalyst used in the addition reaction is a composite catalyst of tributyl phosphine and 18-crown-6 ether-6; the amount of tributyl phosphine is 1-10% of the weight of methyl acrylate; the amount of 18-crown-6 ether-6 is 0.1-5% of the weight of methyl acrylate; and the molar ratio of tributyl phosphine to 18-crown-6 ether-6 is 1:0.1-1:0.3. The addition reaction of the application adopts a composite catalyst composed of a small amount of 18-crown-6 ether-6 and tributyl phosphine; the composite catalyst has high catalytic activity, can obtain high reaction conversion rate, and has low by-product content, so that the reaction yield is high; in particular, the price of the composite catalyst is obviously lower than that of a diamino phosphine catalyst, so that the production cost is obviously reduced.

Description

Technical Field

[0001] This invention belongs to the field of fine chemical technology, specifically relating to a method for preparing dimethyl 2-methylglutarate. Background Technology

[0002] Dimethyl 2-methylglutarate is an environmentally friendly organic solvent that is colorless, transparent, has a mild odor, and is completely biodegradable. It is an ideal alternative to existing toxic, hazardous, and pungent solvents (such as isophorone, cyclohexanone, and ethylene glycol ethyl ether acetate). Dimethyl 2-methylglutarate can be widely used in coatings, hardware, electronics, and other fields.

[0003] Dimethyl 2-methylglutarate is also the main raw material for the preparation of methyl 5-dimethylamino-2-methyl-5-oxovalerate, which is the main solvent for the formulation of plant hygiene surfactants and has broad market prospects.

[0004] Currently, there are two main synthetic routes for dimethyl 2-methylglutarate:

[0005] I. Using 2-methylglutaronitrile as the starting material, 2-methylglutaric acid is first hydrolyzed in the presence of concentrated sulfuric acid to obtain 2-methylglutaric acid, and then esterified with methanol to obtain dimethyl 2-methylglutarate (see Chinese patent documents CN101641318A, CN109824514A and CN113788755A).

[0006] This synthetic route requires the use of large amounts of concentrated sulfuric acid, which not only poses safety hazards but also has high equipment requirements and is very environmentally unfriendly, making it unsuitable for large-scale industrial production.

[0007] II. Starting with methyl acrylate, the intermediate 2-methylene glutarate dimethyl ester is first obtained by addition reaction in the presence of an organophosphorus catalyst, and then catalytic hydrogenation is carried out to obtain 2-methyl glutarate dimethyl ester.

[0008] This synthetic route does not require the use of concentrated sulfuric acid, making it safer, requiring less sophisticated equipment, and more environmentally friendly. However, existing preparation methods for the addition reaction in this synthetic route have the following shortcomings:

[0009] (1) The organophosphorus catalyst used is trialkylphosphorus, such as tributylphosphorus. The advantage of trialkylphosphorus catalyst is that it is inexpensive and widely available. The disadvantage is that it has low catalytic activity and the conversion rate of addition reaction is less than 50%, which is not suitable for large-scale industrial production (see US Patent Document US3227745A).

[0010] (2) The organophosphorus catalyst used is triaminophosphine, such as hexa(n-propyl)phosphine triamine. The advantage of triaminophosphine catalyst is that it has relatively high catalytic activity and high conversion rate of addition reaction. The disadvantage is that the content of by-product (2-methylene-4-methoxycarbonyl pimelic acid diester) is relatively high, and the price of triaminophosphine catalyst is relatively high, which is also not suitable for large-scale industrial production (see US Patent Document US3342853A).

[0011] (3) The organophosphorus catalyst used is diaminophosphorus, such as diisopropylaminopyrrolidinylphenylphosphorus; the advantage of diaminophosphorus catalyst is that it not only has high catalytic activity and high conversion rate of addition reaction, but also low content of by-products; the disadvantage is that the source is extremely limited, most of them need to be made in-house, and the price is extremely expensive, resulting in very high production costs, and it is still not suitable for large-scale industrial production (see international patent document WO2023066844A1). Summary of the Invention

[0012] The purpose of this invention is to overcome the shortcomings of the addition reaction in the above-mentioned methyl acrylate route and to provide a method for preparing dimethyl 2-methylglutarate that not only has relatively low production cost but also high reaction conversion rate and low by-product content.

[0013] The technical solution to achieve the purpose of this invention is: a method for preparing dimethyl 2-methylglutarate, which uses methyl acrylate as the starting material, firstly adds it to obtain the intermediate dimethyl 2-methyleneglutarate, and then catalytically hydrogenates it to obtain dimethyl 2-methylglutarate; characterized in that: the catalyst used in the addition reaction is a tributylphosphine and 18-crown ether-6 composite catalyst.

[0014] In the composite catalyst, the molar ratio of tributylphosphine to 18-crown ether-6 is 1:0.1 to 1:0.3.

[0015] The amount of tributylphosphine used is 1 to 10% of the weight of methyl acrylate, preferably 3 to 5%.

[0016] The amount of 18-crown ether-6 used is 0.1-5% of the weight of the methyl acrylate, preferably 0.5-1.5%.

[0017] The addition reaction temperature is 50–70°C.

[0018] The endpoint of the addition reaction is when the content of methyl acrylate in the raw material is <10%. This ensures both a high reaction yield and a low content of by-products, thereby achieving a high product content.

[0019] After the addition reaction is completed, a polymerization inhibitor is added; the amount of the polymerization inhibitor is 0.01 to 0.05% of the weight of the methyl acrylate.

[0020] The polymerization inhibitor is hydroquinone or p-hydroxyanisole.

[0021] The catalytic hydrogenation is a conventional method in the field.

[0022] The catalyst can be one of Raney nickel, palladium on carbon, or platinum on carbon, preferably Raney nickel.

[0023] The catalytic hydrogenation reaction temperature is -10℃ to 10℃, preferably 0℃.

[0024] The catalytic hydrogenation reaction pressure is 0.1–0.5 MPa, preferably 0.2 MPa.

[0025] The positive effects of this invention are:

[0026] (1) The addition reaction of the present invention uses a small amount of 18-crown ether-6 and tributylphosphine to form a composite catalyst. This composite catalyst not only has high catalytic activity and can obtain a high reaction conversion rate, but also has a low content of by-products, thus having a high reaction yield. In particular, it is significantly cheaper than diaminophosphine catalyst, thus significantly reducing production costs.

[0027] (2) After the addition reaction is completed, the present invention can ensure the stability of the reaction solution by adding an inhibitor, and avoid the further generation of by-products during the storage of the reaction solution. Detailed Implementation

[0028] (Example 1)

[0029] The preparation method of dimethyl 2-methylglutarate in this embodiment includes the following steps:

[0030] Under nitrogen protection, 198 g of methyl acrylate (2.3 mol) was added to a four-necked flask equipped with a thermometer and mechanical stirrer, followed by 1.98 g of 18-crown ether-6 (7.5 mmol). The temperature was raised to 53–57 °C, and 8.0 g of tributylphosphine (39.6 mmol) was added dropwise, maintaining the temperature at 53–57 °C during the addition. After the addition was complete, the temperature was raised to 63–67 °C and the reaction was maintained for 2 hours. Samples were taken for analysis, and the content of the intermediate 2-methylene glutarate dimethyl ester was 80%, the content of the byproduct 2-methylene-4-methoxycarbonyl pimecrolic acid diester was 4.5%, and the content of the raw material methyl acrylate was 8%. The reaction was terminated, and the temperature was lowered to 30–35 °C. 0.04 g of the polymerization inhibitor hydroquinone was added to the reaction solution for later use.

[0031] ② Add the reaction solution obtained in step ① to the hydrogenation reactor. Under nitrogen protection and stirring, add 400g of methanol. After the addition is complete, stop stirring. Then add 6g of Raney nickel. After the addition is complete, continue stirring and purge with nitrogen three times to lower the temperature inside the reactor to 0℃. Then purge with hydrogen once. Then introduce hydrogen and maintain the hydrogen pressure at 0.2MPa and the temperature at 0℃. After the hydrogen absorption is complete, continue the reaction at 0℃. Take samples for control. Terminate the reaction when the content of the reaction solution obtained in step ① is <0.1% and there are no other unknown impurity peaks.

[0032] After the reaction was completed, nitrogen protection was applied to release the pressure, and nitrogen replaced the hydrogen in the reactor. The reaction solution was then filtered through diatomaceous earth pressure filter. The filtrate was depressurized at a temperature of 60-70℃ and a vacuum of -0.08 to -0.09 MPa to recover methanol. The concentrated solution was cooled to about 50℃ and washed successively with 100g of brine, 100g of 5wt% sodium bisulfite aqueous solution, and 100g of water. After standing and separating the layers, 180g of organic layer (i.e., crude product) was obtained. Distillation yielded 140g of dimethyl 2-methylglutarate, with a yield of 69.9% and a GC content of 99.2%.

[0033] (Example 2)

[0034] The preparation method of dimethyl 2-methylglutarate in this embodiment includes the following steps:

[0035] Under nitrogen protection, 198 g of methyl acrylate (2.3 mol) was added to a four-necked flask equipped with a thermometer and mechanical stirrer, followed by 2.64 g of 18-crown ether-6 (10 mmol). The temperature was raised to 53–57 °C, and 12.0 g of tributylphosphine (59.4 mmol) was added dropwise, maintaining the temperature at 53–57 °C during the addition. After the addition was complete, the temperature was raised to 63–67 °C and the reaction was maintained for 2 hours. Samples were taken for analysis, and the content of the intermediate 2-methylene glutarate dimethyl ester was 79.2%, the content of the byproduct 2-methylene-4-methoxycarbonyl pimecrolic acid diester was 6.4%, and the content of the raw material methyl acrylate was 5.2%. The reaction was terminated, and the temperature was lowered to 30–35 °C. 0.04 g of the polymerization inhibitor hydroquinone was added to the reaction solution for later use.

[0036] ② Same as in Example 1, 183g of crude product was obtained, and 138.4g of dimethyl 2-methylglutarate was obtained by distillation, with a yield of 69.1% and a GC content of 98.8%.

[0037] (Example 3)

[0038] The preparation method of dimethyl 2-methylglutarate in this embodiment includes the following steps:

[0039] Under nitrogen protection, 198 g of methyl acrylate (2.3 mol) was added to a four-necked flask equipped with a thermometer and mechanical stirrer, followed by 1.32 g of 18-crown ether-6 (5 mmol). The temperature was raised to 53–57 °C, and 4.0 g of tributylphosphine (19.8 mmol) was added dropwise, maintaining the temperature at 53–57 °C during the addition. After the addition was complete, the temperature was raised to 63–67 °C, and the reaction was maintained at this temperature for 2 hours. Samples were taken for analysis, and the content of the intermediate dimethyl 2-methyleneglutarate was 68 g / mol. The content of the byproduct 2-methylene-4-methoxycarbonyl pimecrolic acid diester was 2.1%, and the content of the raw material methyl acrylate was 22%. The reaction was continued at a constant temperature for 5 hours. Samples were taken for testing. The content of the intermediate 2-methylene glutarate dimethyl ester was 73.5%, the content of the byproduct 2-methylene-4-methoxycarbonyl pimecrolic acid diester was 6.8%, and the content of the raw material methyl acrylate was 9.2%. The reaction was terminated, and the temperature was lowered to 30-35℃. 0.04g of the polymerization inhibitor hydroquinone was added to the reaction solution for later use.

[0040] ② Same as in Example 1, 175g of crude product was obtained, and 128.5g of dimethyl 2-methylglutarate was obtained by distillation, with a yield of 64.2% and a GC content of 99.0%.

[0041] (Comparative Example 1)

[0042] The preparation method of dimethyl 2-methylglutarate in this comparative example includes the following steps:

[0043] Under nitrogen protection, 198 g of methyl acrylate (2.3 mol) was added to a four-necked flask equipped with a thermometer and a mechanical stirrer. The temperature was raised to 53–57 °C, and 8.0 g of tributylphosphine (39.6 mmol) was added dropwise, maintaining the temperature at 53–57 °C during the addition. After the addition was complete, the temperature was raised to 63–67 °C and the reaction was maintained at this temperature for 2 hours. Samples were taken for testing, and the content of the intermediate 2-methylene glutarate dimethyl ester was 48%, the content of the byproduct 2-methylene-4-methoxycarbonyl pimecrolic acid diester was 2%, and the content of the raw material methyl acrylate was 42%. The reaction was maintained at this temperature for another 24 hours, and samples were taken for testing. The content of the intermediate 2-methylene glutarate dimethyl ester was 62%, the content of the byproduct 2-methylene-4-methoxycarbonyl pimecrolic acid diester was 20%, and the content of the raw material methyl acrylate was 8%. The reaction was terminated, and the temperature was lowered to 30–35 °C. 0.04 g of the polymerization inhibitor hydroquinone was added to the reaction solution for later use.

[0044] ② Same as in Example 1, 181g of crude product was obtained, and 108g of dimethyl 2-methylglutarate was obtained by distillation, with a yield of 53.9% and a GC content of 98.6%.

[0045] (Example 4)

[0046] The preparation method of dimethyl 2-methylglutarate in this embodiment includes the following steps:

[0047] Under nitrogen protection, 1980 kg of methyl acrylate (23 kmol) was added to a 3000 L reactor using a diaphragm pump, followed by 19.8 kg of 18-crown ether-6 (75 mol). The air was purged with nitrogen three times, and hot water was pumped through the reactor jacket to heat the reactor to 53–57 °C. Then, 80.0 kg of tributylphosphine (396 mol) was added to the reactor using a peristaltic pump. The entire feeding process was controlled within 11–13 hours. Maintain the temperature inside the reactor at 53-57℃. After adding the additives, heat the reactor to 63-67℃ and maintain the temperature for 3 hours. Take samples for testing. The content of the intermediate 2-methylene glutarate dimethyl ester is 78%, the content of the byproduct 2-methylene-4-methoxycarbonyl heptanoate diester is 5%, and the content of unreacted raw material methyl acrylate is 10%. Terminate the reaction, lower the temperature inside the reactor to 30-35℃, add 0.5 kg of the polymerization inhibitor hydroquinone, pack into a container, and set aside for later use.

[0048] ② Use a diaphragm pump to pump the reaction solution obtained in step ① into a hydrogenation reactor. Under nitrogen protection and stirring, add 1600 kg of methanol. After the addition is complete, stop stirring and add 80 kg of Raney nickel. Continue stirring after the addition is complete and purge with nitrogen twice to lower the temperature inside the reactor to 0℃. Then purge with hydrogen once and then introduce hydrogen gas to maintain the hydrogen pressure at 0.2 MPa and the temperature at 0℃. After hydrogen absorption stops, continue the reaction at 0℃, taking samples for monitoring. Terminate the reaction when the content of the reaction solution obtained in step ① is <0.1% and there are no other unknown impurity peaks.

[0049] After the reaction was completed, nitrogen protection was applied to release the pressure, and nitrogen was used to replace the hydrogen in the reactor. The reaction solution was then placed in a tonne drum and allowed to stand for 10 hours. The solution was then filtered using a filter press. The filtrate was depressurized at a temperature of 60–70°C and a vacuum of -0.08–-0.09 MPa to recover methanol. The concentrate was cooled to about 50°C, and 500 kg of brine was added and stirred for 30 minutes. Then, 6 kg of sodium bisulfite was added and stirred for another 30 minutes. The mixture was allowed to stand and separate into layers. The organic layer was then washed with 500 kg of water and allowed to stand and separate into layers again, yielding 1810 kg of crude organic product. Finally, the product was distilled to obtain 1382 kg of dimethyl 2-methylglutarate, with a yield of 69% and a GC content of 98.8%.

Claims

1. A method for preparing 2-methylglutaric acid dimethyl ester, which is prepared by using methyl acrylate as a starting material, first adding to obtain an intermediate 2-methylene glutaric acid dimethyl ester, and then catalytically hydrogenating to obtain 2-methylglutaric acid dimethyl ester; characterized in that: The catalyst used in the addition reaction is a composite catalyst of tributylphosphine and 18-crown-6 ether; ​ The amount of tributylphosphine is 3-5% of the weight of methyl acrylate; the amount of 18-crown-6 ether is 0.5-1.5% of the weight of methyl acrylate; In the composite catalyst, the molar ratio of tributylphosphine to 18-crown-6 ether is 1:0.1-1:0.

3.

2. The method of claim 1, wherein: The temperature of the addition reaction is 50-70℃.

3. The method of claim 1, wherein: After the addition reaction, a polymerization inhibitor is added; the amount of the polymerization inhibitor is 0.01-0.05% of the weight of methyl acrylate.

4. The process for the preparation of dimethyl 2-methylglutarate according to claim 3, characterized in that: The polymerization inhibitor is hydroquinone or p-hydroxyanisole.

5. The method of claim 1, wherein: The catalyst used in the catalytic hydrogenation is one of Raney nickel, palladium-carbon and platinum-carbon.

6. The method of claim 1, wherein: The temperature of the catalytic hydrogenation reaction is -10-10℃, and the pressure of the catalytic hydrogenation reaction is 0.1-0.5 MPa.