Preparation method of dimethyl 1,2-dimethylcyclopropane-1,2-dicarboxylate

Abstract

The present invention relates to the field of pesticide preparation, and discloses a method for preparing dimethyl 1,2-dimethylcyclopropane-1,2-dicarboxylate. The method comprises: 1) reacting methyl 2-chloropropionate, methyl 2-methylacrylate and sodium methoxide in the presence of a solvent and a catalyst; 2) performing a first solid-liquid separation on the reaction product obtained in step 1) to obtain a first solid phase and a first liquid phase, wherein the catalyst is calcium chloride. This method can avoid using sodium hydride, can greatly improve the safety in the production process, will not generate a large amount of salty wastewater, and can greatly improve the yield.

Description

Technical Field

[0001] The present invention relates to the field of pesticide preparation, and particularly relates to a method for preparing dimethyl 1,2 - dimethylcyclopropane - 1,2 - dicarboxylate. Background Art

[0002] Procymidone (N-(3,5 - dichlorophenyl)-1,2 - dimethylcyclopropane - 1,2 - dicarbonimide) is a low - toxicity fungicide. After its use, it has good protective effect and long residual period, and can prevent the development and spread of disease spots. Therefore, it is widely used at present.

[0003] In the prior art, the synthesis of procymidone generally uses dimethyl 1,2 - dimethylcyclopropane - 1,2 - dicarboxylate as the raw material, which has the following structure:

[0004]

[0005] Currently, the classical synthesis reaction of dimethyl 1,2 - dimethylcyclopropane - 1,2 - dicarboxylate is as follows:

[0006]

[0007] In the above - mentioned synthesis reaction process, generally, toluene, sodium hydride and alkylbenzenesulfonate are added into the reaction kettle and stirred, and then a mixture of methyl 2 - methylacrylate and methyl 2 - chloropropionate is gradually added. A large amount of hydrogen gas will be released immediately after the addition. The reaction system needs to be heated to boiling, and after the above reaction is completed, the cooled reactants need to be added into an acidic aqueous solution, the pH is adjusted to 7, followed by water washing, and then the organic phase is separated to finally obtain dimethyl 1,2 - dimethylcyclopropane - 1,2 - dicarboxylate.

[0008] The above - mentioned synthesis process needs to use sodium hydride, which has high reaction activity and is very unstable in nature. It can spontaneously combust in humid air, and the danger is very high.

[0009] Secondly, a large amount of wastewater containing sodium chloride and alkylbenzenesulfonate and filter residues containing methyl methacrylate polymers will be generated during the post - treatment process of the above reaction, and the subsequent treatment cost is very high. In addition, the yield of the above - mentioned synthesis method is only about 80%.

[0010] Therefore, it is urgent to develop a method for preparing dimethyl 1,2 - dimethylcyclopropane - 1,2 - dicarboxylate that is safe, environmentally friendly, low - cost and has a high yield. Summary of the Invention

[0011] The object of the present invention is to overcome the problems in the production process of dimethyl 1,2 - dimethylcyclopropane - 1,2 - dicarboxylate, such as being unsafe, having high costs, and low yields in the prior art, and to provide a preparation method of dimethyl 1,2 - dimethylcyclopropane - 1,2 - dicarboxylate. This method can avoid using sodium hydride, can greatly enhance the safety in the production process, will not produce a large amount of salty wastewater, and can significantly increase the yield.

[0012] The inventor of the present invention found that sodium methoxide can be used as a catalyst for preparing dimethyl 1,2 - dimethylcyclopropane - 1,2 - dicarboxylate, thus completing the present invention.

[0013] Therefore, the present invention provides a preparation method of dimethyl 1,2 - dimethylcyclopropane - 1,2 - dicarboxylate, and the method comprises the following steps:

[0014] 1) React methyl 2 - chloropropionate, methyl 2 - methylacrylate and sodium methoxide in the presence of a solvent and a catalyst;

[0015] 2) Perform a first solid - liquid separation on the reaction product obtained in step 1) to obtain a first solid phase and a first liquid phase,

[0016] wherein, the catalyst is calcium chloride.

[0017] Preferably, in step 1), the molar ratio of methyl 2 - methylacrylate to methyl 2 - chloropropionate is 1:0.8 - 1.5; more preferably, the molar ratio of methyl 2 - methylacrylate to methyl 2 - chloropropionate is 1:1 - 1.2.

[0018] Preferably, in step 1), the molar ratio of methyl 2 - methylacrylate to sodium methoxide is 1:0.8 - 3; more preferably, the molar ratio of methyl 2 - methylacrylate to sodium methoxide is 1:1 - 2.5.

[0019] Preferably, the molar ratio of methyl 2 - methylacrylate to the catalyst is 1:0.1 - 1.5; more preferably, the molar ratio of methyl 2 - methylacrylate to the catalyst is 1:0.1 - 1.

[0020] Preferably, in step 1), the solvent is one or more of toluene, tert - butanol and n - butanol; more preferably, the solvent is toluene.

[0021] Preferably, relative to 1 mol of methyl 2 - methylacrylate, the amount of the solvent used is 180 - 300 g; more preferably, relative to 1 mol of methyl 2 - methylacrylate, the amount of the solvent used is 200 - 250 g.

[0022] Preferably, in step 1), the reaction conditions include: the reaction temperature is 5 - 45 °C, and the reaction time is 5 - 16 h; more preferably, the reaction conditions include: the reaction temperature is 20 - 40 °C, and the reaction time is 4 - 8 h.

[0023] Preferably, the method further comprises: 3) mixing the first solid phase obtained in step 2) with methanol for slurrying and then performing a second solid-liquid separation to obtain a second solid phase and a second liquid phase.

[0024] Preferably, the method further comprises: 4) subjecting the second liquid phase obtained in step 3) to a desolvation treatment to obtain methanol and calcium chloride.

[0025] Preferably, the methanol obtained in step 4) is recycled to step 3).

[0026] Preferably, the calcium chloride obtained in step 4) is recycled to step 1).

[0027] Through the above technical solution, it is possible to avoid using sodium hydride with poor safety and stability as a catalyst, but instead use very stable calcium chloride for catalysis, and the reaction is very mild. Thus, the safety during raw material storage and the production process can be significantly improved.

[0028] Secondly, the method of the present invention does not produce a large amount of salty wastewater, and there is no need to use acidic solutions during the post-treatment process, which is more environmentally friendly.

[0029] In addition, the methanol and calcium chloride separated during the post-treatment process of the present invention can be recycled to the reaction and post-treatment processes, enabling recycling. Thus, not only can the discharge of waste liquid and waste residue be significantly reduced, but also the production cost can be significantly reduced.

[0030] When using the method of the present invention to prepare dimethyl 1,2-dimethylcyclopropane-1,2-dicarboxylate, the product yield can also be increased to over 98%. Detailed Embodiments

[0031] In the ranges disclosed herein, the endpoints and any value are not limited to the exact range or value, and these ranges or values should be understood to include values close to these ranges or values. For numerical ranges, between the endpoint values of each range, between the endpoint values of each range and individual point values, and between individual point values, they can be combined with each other to obtain one or more new numerical ranges, and these numerical ranges should be regarded as specifically disclosed herein.

[0032] The present invention provides a method for preparing dimethyl 1,2-dimethylcyclopropane-1,2-dicarboxylate, wherein the method comprises the following steps:

[0033] 1) Reacting methyl 2-chloropropionate, methyl 2-methylacrylate and sodium methoxide in the presence of a solvent and a catalyst;

[0034] 2) Perform a first solid-liquid separation on the reaction product obtained in step 1) to obtain a first solid phase and a first liquid phase.

[0035] Wherein, the catalyst is calcium chloride.

[0036] According to the present invention, calcium chloride is used as the catalyst. Calcium chloride not only has high stability and is easy to store, but also the reaction is mild when catalyzing the above reaction. At the same time, a yield as high as 98% can be obtained, which is very suitable for the preparation and production of dimethyl 1,2-dimethylcyclopropane-1,2-dicarboxylate.

[0037] In the present invention, first, in the presence of a solvent and a catalyst, methyl 2-chloropropionate, methyl 2-methylacrylate and sodium methoxide are made to react.

[0038] According to the present invention, the solvent can be various conventional solvents in the art for preparing dimethyl 1,2-dimethylcyclopropane-1,2-dicarboxylate, and there is no particular limitation. The solvent can be, for example, one or more of toluene, tert-butanol and n-butanol. Preferably, the solvent is toluene.

[0039] According to the present invention, the amount of the solvent can be determined according to the amount of the reactants. For example, the amount of the solvent can be determined according to the amount of the methyl 2-methylacrylate. Relative to the methyl 2-methylacrylate, the solvent can be used in an excessive amount. For example, relative to 1 mol of methyl 2-methylacrylate, the amount of the solvent used can be 180 - 300 g; in order to ensure that the reaction proceeds more smoothly and reduce the waste of the solvent, preferably, relative to 1 mol of methyl 2-methylacrylate, the amount of the solvent used is 200 - 250 g.

[0040] According to the present invention, the amounts of the reactants methyl 2-methylacrylate and methyl 2-chloropropionate can vary within a relatively wide range as long as the reaction can proceed smoothly. For example, the molar ratio of the methyl 2-methylacrylate to the methyl 2-chloropropionate can be 1:0.8 - 1.5; in order to further promote the reaction and improve the yield, preferably, the molar ratio of the methyl 2-methylacrylate to the methyl 2-chloropropionate is 1:1 - 1.2.

[0041] According to the present invention, the amount of the sodium methoxide can also be determined according to the amount of the methyl 2-methylacrylate. For example, the molar ratio of the methyl 2-methylacrylate to the sodium methoxide can be 1:0.8 - 3; preferably, the molar ratio of the methyl 2-methylacrylate to the sodium methoxide is 1:1 - 2.5. By controlling the molar ratio of the two within the above range, the reaction rate can be further increased and the yield of the dimethyl 1,2-dimethylcyclopropane-1,2-dicarboxylate can be improved.

[0042] According to the present invention, the dosage of the catalyst can also be determined according to the dosage of the methyl methacrylate. For example, the molar ratio of the methyl methacrylate to the catalyst can be 1:0.1 - 1.5; in order to further promote the reaction rate and increase the yield, preferably, the molar ratio of the methyl methacrylate to the catalyst is 1:0.1 - 1.

[0043] In the present invention, the conditions of the reaction are not particularly limited, and the reaction can be achieved at a relatively low temperature. The conditions of the reaction can include, for example: the reaction temperature is 5 - 45 °C, and the reaction time is 5 - 16 h. Preferably, the conditions of the reaction include: the reaction temperature is 20 - 40 °C, and the reaction time is 5 - 8 h. Thus, the reaction can be carried out under relatively mild conditions.

[0044] After the above reaction is completed, the reaction product obtained in step 1) is subjected to a first solid-liquid separation to obtain a first solid phase and a first liquid phase.

[0045] According to the present invention, the method for the first solid-liquid separation is not particularly limited, and various conventional methods for solid-liquid separation in the art can be used. For example, solid-liquid separation can be carried out by filtration, centrifugation, etc.

[0046] In the present invention, the first solid phase obtained by the first solid-liquid separation can be washed with the solvent (such as toluene) used in the reaction in step 1) to collect the product attached to the first solid phase. After that, the mixture of the product and the solvent obtained by washing can be combined with the first liquid phase, thereby further increasing the yield.

[0047] According to the present invention, the first solid phase contains CaCl2·4CH3OH and sodium chloride. In order to further separate the CaCl2·4CH3OH and sodium chloride, in the present invention, preferably, the method can further include: 3) a step of mixing and slurrying the first solid phase obtained in step 2) with methanol and then performing a second solid-liquid separation to obtain a second solid phase and a second liquid phase.

[0048] Through the above step 3), the separation of CaCl2·4CH3OH and sodium chloride can be achieved, that is, through the second solid-liquid separation, the sodium chloride is separated into the second solid phase, and the CaCl2·4CH3OH is separated into the second liquid phase. Thus, not only the zero discharge of the salty wastewater is realized, greatly reducing the environmental protection pressure, but also the recovery of CaCl2·4CH3OH is realized. Combining with the subsequent treatment steps, the recovery and utilization of CaCl2 and methanol can be realized, thereby significantly reducing the cost.

[0049] In the present invention, the second liquid phase contains CaCl2·4CH3OH and methanol. In order to separate and recover CaCl2 and methanol from CaCl2·4CH3OH, preferably, the method of the present invention further comprises: 4) subjecting the second liquid phase obtained in step 3) to stripping treatment to obtain methanol and calcium chloride.

[0050] According to the present invention, there is no particular limitation on the stripping treatment, as long as the separation of methanol and calcium chloride can be achieved. For example, the conditions for the stripping may include: a temperature of 30-200°C and a time of 0.1-1.5 h; preferably, the conditions for the stripping include: a temperature of 30-160°C and a time of 0.1-0.5 h; more preferably, the conditions for the stripping include: a temperature of 100-120°C and a time of 0.3-0.5 h.

[0051] By performing stripping under the above conditions, CaCl2·4CH3OH can be decomposed and methanol can be distilled out from the mixture of CaCl2·4CH3OH and methanol, thereby separating CaCl2 and methanol.

[0052] According to the method of the present invention, the calcium chloride separated in step 4) can be reused in the reaction described in step 1), that is, reused as a catalyst to catalyze the next reaction. Thus, the recycling of calcium chloride can be achieved, reducing emissions while significantly reducing production costs.

[0053] According to the present invention, the methanol separated in step 4) can be reused in step 3), that is, mixed and slurried with the first solid phase. Thus, the recycling of methanol can be achieved, reducing emissions while significantly reducing production costs.

[0054] The present invention will be described in detail below through examples. It should be understood that the specific embodiments described herein are only used to illustrate and explain the present invention and are not used to limit the present invention.

[0055] In the following examples, unless otherwise specified, the raw materials are all commercially available products.

[0056] Example 1

[0057] 1) In a 500 mL four-necked flask, 58 g of toluene, sodium methoxide (0.25 mol), and calcium chloride (0.25 mol) were added. After stirring for 15 min, a mixture of methyl 2-chloropropionate and methyl 2-methylacrylate (wherein 0.25 mol of methyl 2-chloropropionate and 0.25 mol of methyl 2-methylacrylate) was added dropwise. After the addition was complete, the temperature was raised to 30°C and the reaction was carried out for 4 h;

[0058] 2) Filter the reaction product obtained in step 1), wash the obtained first solid phase with 100 g of toluene twice, and mix the washed liquid with the first liquid phase;

[0059] 3) Mix the washed first solid phase obtained in step 2) with 300 g of methanol at 60 °C and grind for 2 h, then filter the grinding product to separate a second solid phase (sodium chloride) and a second liquid phase;

[0060] 4) Decant the second liquid phase obtained in step 3) at 110 °C for 0.4 h to obtain methanol and calcium chloride. The obtained methanol and calcium chloride can be recycled to step 3) and step 1) of the next batch reaction respectively.

[0061] The yield of the obtained dimethyl 1,2 - dimethylcyclopropane - 1,2 - dicarboxylate (the structure is determined by NMR and MS to be dimethyl 1,2 - dimethylcyclopropane - 1,2 - dicarboxylate, the same below) is 98.7 wt%.

[0062] Example 2

[0063] 1) In a 500 mL four - necked flask, add 58 g of toluene, sodium methoxide (0.38 mol), calcium chloride (0.13 mol), stir for 15 min, and then dropwise add a mixture of methyl 2 - chloropropionate and methyl 2 - methylacrylate (where methyl 2 - chloropropionate is 0.26 mol and methyl 2 - methylacrylate is 0.25 mol). After the addition is complete, raise the temperature to 40 °C and react for 5 h;

[0064] 2) Filter the reaction product obtained in step 1), wash the obtained first solid phase with 100 g of toluene twice, and mix the washed liquid with the first liquid phase;

[0065] 3) Mix the washed first solid phase obtained in step 2) with 280 g of methanol at 60 °C and grind for 1.5 h, then filter the grinding product to separate a second solid phase (sodium chloride) and a second liquid phase;

[0066] 4) Decant the second liquid phase obtained in step 3) at 100 °C for 0.5 h to obtain methanol and calcium chloride. The obtained methanol and calcium chloride can be recycled to step 3) and step 1) of the next batch reaction respectively.

[0067] The yield of the obtained dimethyl 1,2 - dimethylcyclopropane - 1,2 - dicarboxylate is 98.6 wt%.

[0068] Example 3

[0069] 1) In a 500 mL four-necked flask, add 58 g of toluene, sodium methoxide (0.45 mol), and calcium chloride (0.2 mol). After stirring for 15 min, dropwise add a mixture of methyl 2-chloropropionate and methyl 2-methylacrylate (wherein 0.3 mol of methyl 2-chloropropionate and 0.25 mol of methyl 2-methylacrylate). After the addition is complete, raise the temperature to 20 °C and react for 8 h;

[0070] 2) Filter the reaction product obtained in step 1). Wash the obtained first solid phase twice with 100 g of toluene, and mix the washed liquid with the first liquid phase;

[0071] 3) Mix the washed first solid phase obtained in step 2) with 300 g of methanol at 60 °C and grind for 1 h. Then filter the grinding product to separate the second solid phase (sodium chloride) and the second liquid phase;

[0072] 4) Evaporate the second liquid phase obtained in step 3) at 110 °C for 0.3 h to obtain methanol and calcium chloride. The obtained methanol and calcium chloride can be recycled to step 3) and step 1) of the next batch reaction respectively.

[0073] The yield of dimethyl 1,2-dimethylcyclopropane-1,2-dicarboxylate is 98.1 wt%.

[0074] Example 4

[0075] Carry out according to the method of Example 1, except that

[0076] In step 1), the amount of calcium chloride used is 0.025 mol.

[0077] The yield of dimethyl 1,2-dimethylcyclopropane-1,2-dicarboxylate is 98 wt%.

[0078] Comparative Example 1

[0079] 1) Weigh 0.2 tons of toluene, 0.2 tons of sodium hydride, and 0.1 ton of alkylbenzenesulfonate and add them to the reaction kettle for stirring. Then gradually add a mixture of 0.6 tons of methyl 2-methylacrylate and 0.45 tons of methyl 2-chloropropionate to the reaction kettle. Immediately, a large amount of hydrogen gas is released. After heating to boiling, keep the temperature for reaction for 9 h until the hydrogen gas reduces to 0.3% and the reaction is completed;

[0080] 2) Cool the product obtained in step 1) to 40 °C, discharge it into dilute hydrochloric acid aqueous solution for washing twice, separate the organic phase, dry and filter it. Distill the filtrate to obtain the intermediate dimethyl 1,2-dimethylcyclopropane-1,2-dicarboxylate.

[0081] The yield of dimethyl 1,2-dimethylcyclopropane-1,2-dicarboxylate is 84 wt%.

[0082] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited thereto. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solutions of the present invention, including any other suitable combination of each technical feature. These simple modifications and combinations should also be regarded as the disclosed content of the present invention and fall within the protection scope of the present invention.

Claims

1. A method for preparing dimethyl 1,2 - dimethylcyclopropane - 1,2 - dicarboxylate, characterized in that, The method comprises the following steps: 1) React methyl 2-chloropropionate, methyl methacrylate and sodium methoxide in the presence of a solvent and a catalyst; 2) Perform a first solid-liquid separation on the reaction product obtained in step 1) to obtain a first solid phase and a first liquid phase, wherein, the catalyst is calcium chloride and the solvent is toluene.

2. The method according to claim 1, wherein In step 1), the molar ratio of methyl methacrylate to methyl 2-chloropropionate is 1:0.8 - 1.

5.

3. The method according to claim 2, wherein In step 1), the molar ratio of methyl methacrylate to methyl 2-chloropropionate is 1:1 - 1.

2.

4. The method according to claim 1, wherein In step 1), the molar ratio of methyl methacrylate to sodium methoxide is 1:0.8 - 3.

5. The method according to claim 4, wherein, In step 1), the molar ratio of methyl methacrylate to sodium methoxide is 1:1 - 2.

5.

6. The method according to claim 1, wherein The molar ratio of methyl methacrylate to the catalyst is 1:0.1 - 1.

5.

7. According to the method of claim 6, wherein The molar ratio of methyl methacrylate to the catalyst is 1:0.1 - 1.

8. The method according to any one of claims 1-7, wherein Relative to 1 mol of methyl methacrylate, the amount of the solvent used is 180 - 300 g.

9. The method according to claim 8, wherein, Relative to 1 mol of methyl methacrylate, the amount of the solvent used is 200 - 250 g.

10. The method according to any one of claims 1-7, wherein, In step 1), the reaction conditions include: the reaction temperature is 5 - 45 °C and the reaction time is 5 - 16 h.

11. The method according to any one of claims 1-7, wherein, The reaction conditions include: the reaction temperature is 20 - 40 °C and the reaction time is 4 - 8 h.

12. The method according to any one of claims 1-7, wherein The method further comprises: 3) Mix the first solid phase obtained in step 2) with methanol for pulping and then perform a second solid-liquid separation to obtain a second solid phase and a second liquid phase.

13. The method according to claim 12, wherein, The method further comprises: 4) Perform a desolvation treatment on the second liquid phase obtained in step 3) to obtain methanol and calcium chloride.

14. The method according to claim 13, wherein, The methanol obtained in step 4) is recycled to step 3).

15. The method according to claim 13, wherein, The calcium chloride obtained in step 4) is recycled to step 1).

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