Synthesis method of 3-chloropropionyl chloride

Abstract

The invention discloses a synthesis method of 3-chloropropionyl chloride, and relates to the field of fine chemical engineering. Acrylic acid and bis (trichloromethyl) carbonate are used as raw materials and react under the action of a catalyst to generate acryloyl chloride, meanwhile, generated hydrogen chloride and double bonds in the acryloyl chloride are subjected to an addition reaction, and finally 3-chloropropionyl chloride is obtained. Acrylic acid and triphosgene are adopted as raw materials, the price is low, safety is high, and the method is suitable for industrial production; the reaction is a one-pot method, and the operation is simple. The hydrogen chloride gas generated in the synthesis method is directly recycled, so that the emission of waste gas is reduced, the method is economical and environment-friendly, the atom utilization rate is high, the unique by-product carbon dioxide of the reaction can be directly discharged after being simply treated, no by-products such as sulfur dioxide and phosphorous acid are generated, and the environment-friendly cost is low. After the synthetic product is simply distilled, the content of the product reaches 99% or above, the yield is close to 90%, and the purpose of simply synthesizing the high-purity 3-chloropropionyl chloride with high yield is achieved.

Description

Technical Field

[0001] The present invention relates to the field of fine chemicals, and specifically relates to a method for synthesizing 3-chloropropionyl chloride. Background Art

[0002] 3-chloropropionyl chloride is a widely used fine pharmaceutical and chemical intermediate, and is a key intermediate for synthesizing 2,3-dihydro-1-indanone, L-carnosine, duloxetine, indoxacarb, etc., and is mainly applied in the fields of pharmaceutical chemicals, etc. At present, there are mainly two relatively mature methods for synthesizing 3-chloropropionyl chloride:

[0003] (1) One-step method: The preparation method disclosed in Chinese Patent CN 103819329A is to mix acrylic acid and water, dropwise add thionyl chloride and heat under reflux, and then distill under reduced pressure to remove the unreacted thionyl chloride to obtain 3-chloropropionyl chloride. The yield of this reaction is not high, and thionyl chloride is used as the chlorinating reagent, generating a large amount of sulfur dioxide which will have a great impact on the environment and is difficult to recycle. The preparation method disclosed in Chinese Patent CN 111777505A is to react β-propiolactone and triphosgene under the action of a catalyst to generate 3-chloropropionyl chloride. This reaction uses β-propiolactone as the raw material, and the cost is relatively high.

[0004] (2) Two-step method: First, 3-chloropropionic acid is synthesized from acrylic acid, and then chlorinated with phosphorus trichloride or thionyl chloride. Similar reports mainly include: The preparation method disclosed in Chinese Patent CN 1349969A is to use acrylic acid as the raw material, react with hydrogen chloride to prepare 3-chloropropionic acid, and then obtain 3-chloropropionyl chloride through phosphorus oxychlorination. The preparation cost of hydrogen chloride in this invention is high, and it is difficult for 3-chloropropionic acid to be completely converted into acyl chloride. The crude product often contains 3-chloropropionic acid and phosphorous acid by-products, and the product content is not high, resulting in great environmental protection pressure. The preparation method disclosed in Chinese Patent CN 118405974A is to use hydrogen chloride gas generated by the reaction of phosphorus trichloride and concentrated hydrochloric acid as the chlorinating reagent for acrylic acid, generate 3-chloropropionic acid and then react with phosphorus trichloride to obtain 3-chloropropionyl chloride. In this invention, the consumption of phosphorus trichloride is extremely large, the reaction uses concentrated hydrochloric acid, which has strong corrosiveness and high requirements for equipment, has many by-products, and the subsequent rectification process is complex, resulting in high production costs.

[0005] Therefore, for the currently known synthetic technical routes of 3-chloropropionyl chloride, the raw materials used have high costs, and the operations are cumbersome with great environmental protection pressure. Summary of the Invention

[0006] The purpose of the present invention is to propose a method for synthesizing 3-chloropropionyl chloride to solve the above-mentioned technical problems existing in the current 3-chloropropionyl chloride synthesis process.

[0007] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0008] A method for synthesizing 3-chloropropionyl chloride, and the synthesis reaction is shown as follows:

[0009]

[0010] Specifically, acrylic acid and bis(trichloromethyl) carbonate (triphosgene) are used as raw materials, and under the action of a catalyst, acryloyl chloride is generated. At the same time, the generated hydrogen chloride undergoes an addition reaction with the double bond in acryloyl chloride, and finally 3-chloropropionyl chloride is obtained.

[0011] As a preferred technical solution of the present invention, the catalyst used in the synthesis method is preferably diethylamine, triethylamine, tri-n-propylamine, N,N-dimethylformamide, N,N-dimethylacetamide, pyridine, 4-dimethylaminopyridine, imidazole, 2-methylimidazole, 1,2-dimethylimidazole or aluminum trichloride, and more preferably N,N-dimethylformamide or imidazole.

[0012] As a preferred technical solution of the present invention, the addition amount of the catalyst in the synthesis method is preferably 0.5% - 15% of the mass of acrylic acid, more preferably 1% - 10% of the mass of acrylic acid, further preferably 2% - 6% of the mass of acrylic acid, and most preferably 4% of the mass of acrylic acid.

[0013] As a preferred technical solution of the present invention, the addition amount of the bis(trichloromethyl) carbonate (triphosgene) in the synthesis method is preferably 0.3 - 0.6 times the molar amount of acrylic acid, more preferably 0.4 - 0.5 times the molar amount of acrylic acid, and most preferably 0.4 times the molar amount of acrylic acid.

[0014] As a preferred technical solution of the present invention, a solvent is added to the synthesis reaction, preferably dichloromethane, dioxane, toluene, ether or carbon tetrachloride, and more preferably dioxane.

[0015] As a preferred technical solution of the present invention, the synthesis reaction temperature is preferably 20 - 80 °C, and more preferably 50 - 70 °C.

[0016] As a preferred technical solution of the present invention, the synthesis reaction time is preferably 2 - 24 h, and more preferably 5 - 10 h.

[0017] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0018] (1) The present invention uses acrylic acid and triphosgene as raw materials, which are inexpensive and have high safety, and are suitable for industrial production; the reaction is a "one-pot method" and the operation is simple.

[0019] (2) In the synthesis method of the present invention, the hydrogen chloride gas generated is directly reused, which not only reduces the emission of waste gas, but also is economical, environmentally friendly, has a high atom utilization rate. The only by-product carbon dioxide of the reaction can be directly discharged after simple treatment, without the generation of by-products such as sulfur dioxide and phosphorous acid, and the environmental protection cost is low.

[0020] (3) After simple distillation of the synthesis product, the product content reaches more than 99%, and the yield is close to 90%, realizing the purpose of high yield and simple synthesis of high-purity 3-chloropropionyl chloride. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 1H NMR spectrum of the product 3-chloropropionyl chloride prepared in Example 1.

[0022] Figure 2 13C NMR spectrum of the product 3-chloropropionyl chloride prepared in Example 1.

[0023] Figure 3 GC detection spectrum of the reaction end in Example 1 using methanol derivatization method. DETAILED DESCRIPTION OF THE INVENTION

[0024] The present invention will be further described in detail below in conjunction with examples and drawings.

[0025] Examples 1 to 4

[0026] A synthesis method of 3-chloropropionyl chloride, comprising the following steps:

[0027] In a 500 mL reaction flask, acrylic acid (10 g, 0.14 mol, 1.0 eq), catalyst dosage (0.4 g, 4%), triphosgene (1.65 g, 0.055 mol, 0.4 eq), and dioxane (40 mL) were added in sequence, sealed, heated to 60 °C, and maintained at this temperature for reaction for 5 h. Gas chromatography was used to analyze and determine whether the reaction was complete. After the reaction was complete, the crude product was subjected to vacuum distillation to obtain high-purity 3-chloropropionyl chloride.

[0028] The above gas chromatography analysis method specifically comprises the following steps:

[0029] 1) Take a sample of 3-chloropropionyl chloride in a container, add methanol for esterification and shake well, and inject the sample after derivatization.

[0030] 2) Separate and detect the injected sample through a gas chromatograph to obtain a gas chromatogram.

[0031] 3) Calculate the percentage content of 3-chloropropionyl chloride by the area normalization method.

[0032] The gas chromatograph used was an Asicotech M3 gas chromatograph, with an FID detector and a split / splitless injector. The separation and detection working conditions of the gas chromatograph are as follows:

[0033] Chromatographic column: 30m×0.32mm×0.33um HT-FFAP capillary column.

[0034] The carrier gas was nitrogen, with a carrier gas pressure of 70 kPa; a hydrogen pressure of 35 kPa; and an air pressure of 350 kPa.

[0035] Detector temperature: 280°C; vaporization chamber temperature: 280°C; column temperature: 60 - 200°C; split ratio: 50:1; injection volume: 1 uL.

[0036] In addition, by changing the type of catalyst, the yield results are shown in Table 1:

[0037] Table 1

[0038]

[0039] The 3-chloropropionyl chloride prepared in Example 1 had its 1H NMR and 13C NMR spectra as shown in Figure 1 , 2 respectively, and the spectral analysis was as follows:

[0040] 1 1H NMR (CDCl3, 400 MHz), δ ppm: 3.75 - 3.79 (m, 2H), 3.35 - 3.38 (m, 2H), 13 13C NMR (CDCl3, 400 MHz), δ ppm: 171.2, 49.2, 37.8

[0041] Figure 3 This is the gas chromatogram after sample derivatization. The content of 3-chloropropionyl chloride finally measured by the area normalization method was 99.08%.

[0042] Examples 5 - 8

[0043] The reaction conditions were the same as in Example 1. The catalyst was N,N-dimethylformamide, and the amount of the catalyst was changed. The results are shown in Table 2:

[0044] Table 2

[0045]

[0046] Examples 9 - 11

[0047] The reaction conditions were the same as in Example 1. The catalyst was N,N-dimethylformamide, and the amount of triphosgene was changed. The results are shown in Table 3:

[0048] Table 3

[0049]

[0050] Examples 12 - 15

[0051] The reaction conditions were the same as in Example 1, with N,N - dimethylformamide as the catalyst. By changing the reaction temperature, the results are shown in Table 4 as follows:

[0052] Table 4

[0053]

[0054] Examples 16 - 18

[0055] The reaction conditions were the same as in Example 1, with N,N - dimethylformamide as the catalyst. By changing the reaction time, the results are shown in Table 5 as follows:

[0056] Table 5

[0057]

[0058] It can be seen from the above examples that under the conditions of acrylic acid (1.0 eq), N,N - dimethylformamide (dosage 4%), triphosgene (0.4 eq) and dioxane, maintaining the reaction at 60 °C for 5 h is the optimal synthesis process parameters, and the yield is close to 90%.

[0059] The above content is only an example and explanation of the concept of the present invention. Those skilled in the art of this technology can make various modifications, supplements or use similar methods to replace the specific embodiments described. As long as they do not deviate from the concept of the invention or exceed the scope defined by this claim book, they should belong to the protection scope of the present invention.

Claims

1. A method for synthesizing 3-chloropropionyl chloride, characterized in that, The synthesis reaction is shown by the following formula: Specifically, acrylic acid and bis(trichloromethyl) carbonate (triphosgene) are used as raw materials, and acryloyl chloride is generated through reaction under the action of a catalyst. Meanwhile, the generated hydrogen chloride undergoes an addition reaction with the double bond in acryloyl chloride, and finally 3-chloropropionyl chloride is obtained.

2. The synthesis method according to claim 1, wherein The catalyst used is preferably diethylamine, triethylamine, tri-n-propylamine, N,N-dimethylformamide, N,N-dimethylacetamide, pyridine, 4-dimethylaminopyridine, imidazole, 2-methylimidazole, 1,2-dimethylimidazole or aluminum trichloride, more preferably N,N-dimethylformamide or imidazole.

3. The synthesis method according to claim 1 or 2, characterized in that, The addition amount of the catalyst is preferably 0.5% to 15% of the mass of acrylic acid, more preferably 1% to 10% of the mass of acrylic acid, further preferably 2% to 6% of the mass of acrylic acid, and most preferably 4% of the mass of acrylic acid.

4. The synthesis method according to claim 1, wherein The addition amount of the bis(trichloromethyl) carbonate (triphosgene) is preferably 0.3 to 0.6 times the molar amount of acrylic acid, more preferably 0.4 to 0.5 times the molar amount of acrylic acid, and most preferably 0.4 times the molar amount of acrylic acid.

5. The synthesis method according to claim 1, characterized in that, A solvent is added in the synthesis reaction, preferably dichloromethane, dioxane, toluene, diethyl ether or carbon tetrachloride, more preferably dioxane.

6. The synthesis method according to claim 1, characterized in that, The synthesis reaction temperature is preferably 20 to 80 °C, more preferably 50 to 70 °C.

7. The synthesis method according to claim 1, wherein The synthesis reaction time is preferably 2 to 24 h, more preferably 5 to 10 h.

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