Synthetic method of dimethyl 3, 3 '-thiodipropionate

Abstract

The invention relates to a preparation method of 3, 4-difluorobenzene. The invention relates to a synthetic method of 3, 3 '-dimethyl thiodipropionate, which comprises the following steps: by taking methyl 3-bromopropionate and methyl 3-mercaptopropionate as raw materials, methanol as a solvent and sodium hydroxide as a neutralizer, carrying out one-step reaction to obtain a reaction solution containing the 3, 3'-dimethyl thiodipropionate, extracting, washing, filtering, spin-drying and the like to obtain the 3, 3 '-dimethyl thiodipropionate. The synthesis method has the advantages that the molecular utilization rate of the raw materials is high, the synthesis cost is low, the yield and the purity of the final 3, 3 '-dimethyl thiodipropionate product are high, the highest yield can reach 96.560%, the highest purity can reach 99.997%, the whole synthesis process is environment-friendly, and the current green and environment-friendly chemical concept is met.

Description

Technical Field

[0001] The present application relates to the technical field of organic synthesis, and more specifically, to a method for synthesizing dimethyl 3,3'-thiodipropionate. Background Art

[0002] 3,3'-Dimethyl thiodipropionate is a widely used intermediate, especially as an intermediate for thioester antioxidants and medicines. There are few reports on the synthesis of this intermediate. Chinese patent CN 102503870A mentions a method for synthesizing dialkyl thiodipropionate, which is prepared by directly introducing hydrogen sulfide gas into alkyl acrylate. It is difficult to control the quantitative problem of gas during the ventilation process. If insufficient hydrogen sulfide gas is introduced, the raw material alkyl acrylate will remain, affecting the product yield; if excessive hydrogen sulfide gas is introduced, impurities methyl mercaptopropionate and dimethyl dithiodipropionate will be generated, which also affects the product yield, and a large amount of three wastes will be generated. In addition, two or more kettles are connected in series during the reaction process, which increases the investment cost of the equipment. In CN104177279A, methyl acrylate and sodium hydrosulfide are used as raw materials to react and synthesize dimethyl 3,3'-thiodipropionate, a proton solvent is used, and sodium hydrosulfide is used instead of hydrogen sulfide during the reaction process. The reaction mechanism is as follows: , That is, there are still technical problems such as relatively complicated reaction process. Summary of the invention

[0003] In order to solve the above-mentioned technical problems such as the complex synthesis reaction process of dimethyl 3,3'-thiodipropionate, the present application provides a method for synthesizing dimethyl 3,3'-thiodipropionate. The synthesis method has the advantages of simple synthesis process, and the reactant can be obtained in only one step of reaction, and the utilization rate of the raw material molecules is higher. At the same time, the purification process is also simple, and the final product has a high yield and high purity, which is in line with the current concept of green and environmentally friendly chemistry.

[0004] The technical solution of this application A method for synthesizing dimethyl 3,3'-thiodipropionate, wherein the reaction equation of the synthesis process is as follows: The above-mentioned synthesis method uses methyl 3-bromopropionate and methyl 3-mercaptopropionate as raw materials, methanol (MeOH) as solvent, and sodium hydroxide as neutralizer to synthesize dimethyl 3,3'-thiodipropionate through only one-step reaction.

[0005] By adopting the above technical scheme, methyl 3-bromopropionate and methyl 3-mercaptopropionate are directly reacted in a methanol solvent in one step to obtain dimethyl 3,3'-thiodipropionate. The hydrobromic acid produced during the reaction is neutralized with sodium hydroxide and then removed. Therefore, the molecular utilization rate of the raw materials is high and the final purification process of the product is simple.

[0006] Preferably, in the above-mentioned method for synthesizing dimethyl 3,3'-thiodipropionate, the synthesis reaction process is controlled at a temperature of 20-30°C and a rotation speed of 250-300 r / min.

[0007] By adopting the above technical scheme and controlling the appropriate reaction temperature and stirring rate, methyl 3-bromopropionate and methyl 3-mercaptopropionate can react more effectively and completely.

[0008] Preferably, in the above-mentioned method for synthesizing dimethyl 3,3'-thiodipropionate, the amounts of methyl 3-mercaptopropionate, methyl 3-bromopropionate and sodium hydroxide used in the synthesis process are calculated according to the molar ratio of methyl 3-mercaptopropionate:methyl 3-bromopropionate:sodium hydroxide of 1:1-2:1-3.

[0009] By adopting the above technical scheme, the formation reaction of dimethyl 3,3'-thiodipropionate can be made more inclined to a forward reaction, the substrate reaction can be made more complete, and the reaction yield can be high.

[0010] Preferably, the amount of methanol solvent used in the synthesis process is 1 mol: 1.0-2.0 L of methyl 3-mercaptopropionate: methanol.

[0011] By adopting the above technical solution and controlling the methanol content in an appropriate proportion, the methyl 3-mercaptopropionate and methyl 3-bromopropionate used in the reaction can be better dissolved therein and reacted, and the waste of raw materials can be avoided.

[0012] Preferably, the above-mentioned method for synthesizing dimethyl 3,3'-thiodipropionate is characterized in that the amounts of methyl 3-mercaptopropionate, methyl 3-bromopropionate and sodium hydroxide used in the above-mentioned synthesis process are calculated according to the molar ratio of methyl 3-mercaptopropionate:methyl 3-bromopropionate:sodium hydroxide of 1:1-2:2-3.

[0013] By adopting the above technical solution and controlling the appropriate amount of sodium hydroxide, the yield of dimethyl 3,3'-thiodipropionate can be improved. The reason for this may be that alkaline conditions are more conducive to the positive reaction.

[0014] Preferably, in the above-mentioned method for synthesizing dimethyl 3,3'-thiodipropionate, the amounts of methyl 3-mercaptopropionate, methyl 3-bromopropionate and sodium hydroxide used in the synthesis process are calculated according to a molar ratio of methyl 3-mercaptopropionate:methyl 3-bromopropionate:sodium hydroxide of 1:1.5:2.

[0015] By adopting the above technical scheme, the yield of dimethyl 3,3'-thiodipropionate can be maximized, and the maximum yield can reach 96.560%.

[0016] Furthermore, in order to achieve a better purification effect, in the above-mentioned method for synthesizing dimethyl 3,3'-thiodipropionate, the reaction liquid obtained in the synthesis process is filtered and dried for the first time, and then extracted with ethyl acetate and water, and the obtained organic phase is washed with saturated brine or dried over anhydrous sodium sulfate and then filtered and dried.

[0017] By adopting the above technical scheme, part of the methanol solution, excess methyl 3-bromopropionate and sodium hydroxide are removed by the first filtration and spin drying, and then the product is extracted with ethyl acetate and water in sequence, washed with saturated brine or dried with anhydrous sodium sulfate, and filtered and spin dried for the second time, so as to obtain high-purity dimethyl 3,3'-thiodipropionate.

[0018] Preferably, the above-mentioned method for synthesizing dimethyl 3,3'-thiodipropionate is characterized in that the speed of the first filtration and spin-drying process is controlled at 20-40r / min and the temperature is 40-48°C, and the speed of the second filtration and spin-drying process is controlled at 20-40r / min and the temperature is 40-48°C.

[0019] By adopting the above technical solution, the first and second filtration and spin drying processes are controlled at appropriate rotation speeds and temperatures to obtain higher purity dimethyl 3,3'-thiodipropionate, the highest purity of which can reach 99.997%.

[0020] Beneficial technical effects of this application The present invention discloses a method for synthesizing dimethyl 3,3'-thiodipropionate, which is obtained by directly reacting methyl 3-bromopropionate and methyl 3-mercaptopropionate to obtain dimethyl 3,3'-thiodipropionate by dehydrobromic acid, and therefore has a high molecular utilization rate of the raw materials.

[0021] Furthermore, the above-mentioned method for synthesizing dimethyl 3,3'-thiodipropionate has low synthesis cost because the raw materials used are methyl 3-bromopropionate and methyl 3-mercaptopropionate, which are easily available.

[0022] Furthermore, in the above-mentioned method for synthesizing dimethyl 3,3'-thiodipropionate, since methyl 3-bromopropionate and methyl 3-mercaptopropionate are used in a methanol solvent and NaOH is used as a neutralizer to neutralize the hydrobromic acid produced by the reaction, the purification process of the synthesis method is simple, that is, the reaction liquid is extracted, washed, filtered and spin-dried to obtain a 3,3'-thiodipropionate product with high yield and high purity. The final yield of the dimethyl 3,3'-thiodipropionate product can reach up to 96.56%, and the purity can reach 99.997%.

[0023] Furthermore, the entire preparation process of the above-mentioned method for synthesizing dimethyl 3,3'-thiodipropionate is environmentally friendly and conforms to the current concept of green and environmentally friendly chemistry. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 , the H-NMR spectrum of the colorless liquid product obtained in Example 1; Figure 2 , chromatogram of the colorless liquid product obtained in Example 1. DETAILED DESCRIPTION

[0025] The technical solution of the present application is described in detail below through specific embodiments and in combination with the accompanying drawings, but the present application is not limited thereto.

[0026] The raw materials used in each embodiment of the present application are commercially available: Methyl 3-mercaptopropionate, purity 99%, produced by Qingdao Reinars Polymer Materials Co., Ltd.; Methyl 3-bromopropionate, purity 97%, product number L14127, Chemical Book platform; Sodium hydroxide; In each embodiment of the present application: Nuclear magnetic resonance (NMR) spectrometer, model AVANCE NEO 400, produced by Bruker (Beijing) Technology Co., Ltd. Chromatography-mass spectrometry: The instrument used for the determination is a gas chromatograph-mass spectrometer, model GC8890-5977B, produced by Agilent Technologies Co., Ltd. In each embodiment of the present application: The content of dimethyl 3,3'-thiodipropionate in the obtained colorless liquid product was detected by gas chromatography-mass spectrometry (model GC8890-5977B, produced by Agilent Technologies Co., Ltd.), compared with the standard product, and calculated by the area normalization method; the yield of dimethyl 3,3'-thiodipropionate = (the amount of the colorless liquid product obtained in the embodiment / the amount of dimethyl 3,3'-thiodipropionate that should be obtained theoretically based on the amount of methyl 3-mercaptopropionate used in the embodiment) × 100%.

[0027] Example 1 A method for synthesizing dimethyl 3,3'-thiodipropionate, the specific steps are as follows: (1) Synthesis reaction In a 3000 mL round-bottom flask, methyl 3-bromopropionate (100 g, 598.80 mmol), methyl 3-mercaptopropionate (107.94 g, 898.2 mmol), NaOH (47.91 g, 1197.6 mmol) and MeOH solvent (1000 mL) were added in sequence, and then the temperature was controlled to be 25° C. and the rotation speed was stirred at 280 r / min. The reaction process was based on methyl 3-mercaptopropionate and monitored by GCMS until the reaction of methyl 3-mercaptopropionate was completed, that is, when the reaction reached 18 h, the reaction of methyl 3-mercaptopropionate was completed to obtain a reaction solution; The amounts of methyl 3-mercaptopropionate, methyl 3-bromopropionate and sodium hydroxide used in the above synthesis process are calculated according to the molar ratio of methyl 3-mercaptopropionate:methyl 3-bromopropionate:sodium hydroxide of 1:1.5:2; The amount of methanol used is calculated based on methyl 3-mercaptopropionate, with a ratio of methyl 3-mercaptopropionate:methanol of 1 mol:1.67 L; (2) Purification of reaction solution The reaction solution obtained above was filtered and dried for 30 minutes at a speed of 30 r / min and a temperature of 45°C to obtain a crude product. Add ethyl acetate and water to the crude product obtained above, control the speed to 260r / min, stir and mix, let stand to separate, and remove the water phase; The amount of ethyl acetate and water added to the above crude product is 1g:10mL:10mL of crude product:ethyl acetate:water; The organic phase obtained after removing the aqueous phase was washed with saturated brine until the effluent contained only saturated brine, and then filtered and dried for the second time at a speed of 30 r / min and a temperature of 45°C; Alternatively, the organic phase obtained after removing the aqueous phase is dried with anhydrous sodium sulfate, and then filtered and dried for the second time at a speed of 30 r / min and a temperature of 45° C. to obtain a colorless liquid product.

[0028] The colorless liquid product obtained above was subjected to nuclear magnetic hydrogen spectrum measurement, and the obtained nuclear magnetic hydrogen spectrum was as follows: Figure 1 As shown; The corresponding H NMR spectrum data are as follows: 1H NMR (400 MHz, CDC3) δ 3.69 (s, 6H), 2.82-2.78 (m, 4H), 2.63-2.59 (m, 4H).

[0029] The obtained chromatogram mass spectrum and corresponding data are as follows Figure 2 As shown; from Figure 1 The H NMR spectrum and Figure 2 Through comprehensive analysis of the chromatographic mass spectrum and the corresponding data, it can be concluded that the colorless liquid product obtained above is the structural formula The product is dimethyl 3,3'-thiodipropionate.

[0030] The colorless liquid product obtained above, namely dimethyl 3,3'-thiodipropionate, has a yield (after purification) of 96.56% and a purity of 99.997%.

[0031] Embodiment 2-5 A method for synthesizing dimethyl 3,3'-thiodipropionate, except that the amounts of methyl 3-mercaptopropionate, methyl 3-bromopropionate and sodium hydroxide used in the synthesis process are different, and the other uniform embodiments are the same as in Example 1. The amounts of methyl 3-mercaptopropionate, methyl 3-bromopropionate and sodium hydroxide used are specifically as shown in the following table: Example Molar ratio of methyl 3-mercaptopropionate:methyl 3-bromopropionate:sodium hydroxide Example 1 1:1.5:2.0 Example 2 1:1:2.5 Example 3 1:1.8:2.8 Example 4 1:1:1.6 Example 5 1:2:3.0 The colorless liquid products obtained in Examples 2-5 were measured by nuclear magnetic resonance hydrogen spectra and chromatographic mass spectra. The results showed that the structural formulas of the colorless liquid products obtained were of dimethyl 3,3'-thiodipropionate.

[0032] The yield and purity of dimethyl 3,3'-thiodipropionate obtained in the above Examples 2-5 are listed in the following table (the yield and purity of dimethyl 3,3'-thiodipropionate obtained in Example 1 are also listed): Example Yield (%) purity(%) Example 1 96.560 99.997 Example 2 96.475 98.608 Example 3 96.523 98.596 Example 4 94.270 98.550 Example 5 96.402 98.603 As can be seen from the above table, a preparation method of 3,3'-dimethyl thiodipropionate of the present application can obtain a 3,3'-dimethyl thiodipropionate product with a yield of 94.27-96.56% and a purity of more than 98.550% by only one-step reaction and purification. In particular, when the molar ratio of methyl 3-mercaptopropionate:methyl 3-bromopropionate:sodium hydroxide is 1:1-2:2-3, the yield of the purified 3,3'-dimethyl thiodipropionate product is 96.402-96.560% and the purity is more than 98.596%, and when the molar ratio of methyl 3-mercaptopropionate:methyl 3-bromopropionate:sodium hydroxide is 1:1.5:2, the yield of the purified 3,3'-dimethyl thiodipropionate product is 96.560% and the purity is 99.997%.

[0033] The specific embodiments of the present application are merely explanations of the present application and are not limitations of the present application. After reading this specification, those skilled in the art may make modifications to the embodiments without any creative contribution as needed. However, as long as they are within the scope of the claims of the present application, they are protected by the patent law.

Claims

1. A method for synthesizing dimethyl 3,3'-thiodipropionate, characterized in that: The reaction equation of its synthesis process is as follows: The above-mentioned synthesis method uses methyl 3-bromopropionate and methyl 3-mercaptopropionate as raw materials, methanol as solvent, and sodium hydroxide as neutralizer to carry out synthesis reaction to obtain dimethyl 3,3'-thiodipropionate.

2. A method for synthesizing dimethyl 3,3'-thiodipropionate as claimed in claim 1, characterized in that: The synthesis reaction process is carried out at a controlled temperature of 25-37°C and a rotation speed of 250-300 r / min.

3. The method for synthesizing dimethyl 3,3'-thiodipropionate according to claim 2, the method for synthesizing dimethyl 3,3'-thiodipropionate according to claim 1, characterized in that: The amounts of methyl 3-mercaptopropionate, methyl 3-bromopropionate and sodium hydroxide used in the synthesis process are calculated according to the molar ratio of methyl 3-mercaptopropionate:methyl 3-bromopropionate:sodium hydroxide of 1:1-2:1-3.

4. A method for synthesizing dimethyl 3,3'-thiodipropionate as claimed in claim 3, characterized in that: The amount of methanol solvent used in the synthesis process is 1 mol:1.0-2.0 L of methyl 3-mercaptopropionate:methanol.

5. A method for synthesizing dimethyl 3,3'-thiodipropionate as claimed in claim 3, characterized in that: The amounts of methyl 3-mercaptopropionate, methyl 3-bromopropionate and sodium hydroxide used in the synthesis process are calculated according to the molar ratio of methyl 3-mercaptopropionate:methyl 3-bromopropionate:sodium hydroxide of 1:1-2:2-3.

6. A method for synthesizing dimethyl 3,3'-thiodipropionate as claimed in claim 3, characterized in that: The amounts of methyl 3-mercaptopropionate, methyl 3-bromopropionate and sodium hydroxide used in the synthesis process are calculated based on a molar ratio of methyl 3-mercaptopropionate:methyl 3-bromopropionate:sodium hydroxide of 1:1.5:

2.

7. A method for synthesizing dimethyl 3,3'-thiodipropionate according to any one of claims 1 to 6, characterized in that: The reaction liquid obtained in the synthesis process is filtered and dried for the first time, and then extracted with ethyl acetate and water. The obtained organic phase is washed with saturated brine or dried over anhydrous sodium sulfate, and then filtered and dried for the second time.

8. A method for synthesizing dimethyl 3,3'-thiodipropionate as claimed in claim 7, characterized in that: The first filtering and drying process is controlled at a rotation speed of 20-40 r / min and a temperature of 40-48° C., and the second filtering and drying process is controlled at a rotation speed of 20-40 r / min and a temperature of 40-48° C.

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