A method for preparing chloroacetyl chloride

Abstract

This invention discloses a method for preparing chloroacetyl chloride. Acetyl chloride is dispersed in a solvent, an initiator is added, and then N-chlorosuccinimide is added dropwise. After incubation, the solid succinimide is separated by filtration, and the filtrate is externally evaporated to collect the distillate, yielding the chloroacetyl chloride product. This invention uses N-chlorosuccinimide as the chlorination reagent, and by controlling the reaction temperature and the dropping rate of N-chlorosuccinimide, the formation of polychlorinated acetyl chloride is reduced, thus improving reaction selectivity. The reaction conditions of this invention are mild, the operation is simple, and it is suitable for industrial production.

Description

Technical Field

[0001] This invention belongs to the field of organic chemical synthesis technology, and specifically relates to a method for preparing chloroacetyl chloride. Background Technology

[0002] Chloroacetyl chloride is an important organic acyl chloride compound widely used in fine chemical industries such as pharmaceuticals, pesticides, dyes, and polymer materials. For example, in the synthesis of antibiotics (such as cefotaxime and cefazolin) and herbicides (such as propargite and metolachlor), chloroacetyl chloride often serves as a key acylation and chlorination intermediate. Due to its high reactivity and multifunctionality, industrial applications place high demands on the purity, yield, and production efficiency of chloroacetyl chloride.

[0003] Currently, there are four main industrial methods for preparing chloroacetyl chloride: direct acetic acid chlorination, chloroacetic acid chlorination, acetyl chloride chlorination, and ketene chlorination. Direct acetic acid chlorination uses inexpensive and readily available raw materials and has a mature process, but it suffers from poor reaction selectivity, numerous byproducts, and difficulties in separation and purification, as well as significant equipment corrosion and waste treatment issues. Chloroacetic acid chlorination offers better reaction directionality, fewer byproducts, and can achieve co-production, but its raw material costs are high, and it faces corrosion and tail gas treatment problems. Ketene chlorination offers good atom economy, allows for continuous production, and produces high-quality products; however, ketene intermediates are highly toxic and unstable, resulting in high technological barriers and high investment and safety management costs. Acetyl chloride chlorination offers high reaction selectivity, mild conditions, and excellent product purity, but it suffers from a long reaction cycle.

[0004] In conclusion, developing a method for preparing chloroacetyl chloride that can reduce equipment corrosion, achieve high selectivity, and shorten the reaction cycle is of great significance. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention provides a method for preparing chloroacetyl chloride, in which N-chlorosuccinimide is used as a chlorinating agent under the action of free radicals of an initiator to obtain chloroacetyl chloride with high selectivity at low temperature.

[0006] This invention is achieved through the following technical solution: A method for preparing chloroacetyl chloride specifically includes the following steps: (1) Under a nitrogen atmosphere, the solvent is added to the reaction vessel, acetyl chloride is slowly added, the stirring is turned on and the mixture is stirred evenly, the initiator is added, and after the initiator is completely dissolved, the temperature is raised, N-chlorosuccinimide is added, and the reaction is kept at the temperature for 1 to 5 hours. (2) Cool to room temperature, filter, rinse the filter cake with solvent, combine the filtrate and the rinsing liquid, remove the solvent and unreacted acetyl chloride by external evaporation under normal pressure, and collect the fraction at 80-82℃ by vacuum distillation under 20-22 kPa to obtain chloroacetyl chloride product.

[0007] According to the preparation method described above, the molar ratio of acetyl chloride and N-chlorosuccinimide in step (1) is 1:1.05~1.2.

[0008] According to the preparation method described above, the solvent in step (1) is one of dichloromethane, chloroform, carbon tetrachloride, dichloroethane, diethyl ether, petroleum ether, and ethyl acetate, and the amount of solvent used is 2 to 6 times the mass of acetyl chloride.

[0009] According to the preparation method described above, the initiator in step (1) is one of azobisisobutyronitrile, azobis(ethylheptanitrile), di-tert-butyl peroxide, and benzoyl peroxide, and the amount of initiator used is 1.5 to 3.5% of the mass of acetyl chloride.

[0010] According to the preparation method described above, the heating temperature in step (1) is 25-65℃.

[0011] According to the preparation method described above, in step (1), N-chlorosuccinimide is added by dropping, with a dropping rate of 5.7 to 9.4 g / min; N-chlorosuccinimide is dissolved in a solvent with a mass fraction of 25 to 75%.

[0012] According to the preparation method described above, the solvent used for rinsing the filter cake in step (2) is 5-20% of the mass of acetyl chloride.

[0013] According to the preparation method described above, the ambient pressure external evaporation temperature in step (2) varies depending on the solvent used, and the externally evaporated solvent and unreacted acetyl chloride are recycled.

[0014] The reaction mechanism of this invention involves the initiator undergoing thermal decomposition to generate free radicals. These free radicals preferentially abstract the α-H atom from acetyl chloride to form an α-acyl free radical. The α-acyl free radical then undergoes a chlorine atom transfer reaction with N-chlorosuccinimide to generate chloroacetyl chloride, and the free radicals are regenerated to maintain the chain reaction. Finally, the entire reaction is completed through a free radical termination step. Notably, the N-Cl bond in N-chlorosuccinimide has a low bond energy but is not a hydrogen donor; therefore, the free radicals do not preferentially attack N-chlorosuccinimide but instead preferentially seek sites where hydrogen can be abstracted. The α-H atom of acetyl chloride is affected by the strong electron-withdrawing effect of the carbonyl group, resulting in a low bond energy and easy homolytic cleavage. The generated acyl free radical is highly stable by the carbonyl group conjugation, thereby inhibiting the formation of dichloroacetyl chloride.

[0015] The beneficial effects of this invention are as follows: This invention uses N-chlorosuccinimide as a chlorination reagent, and reduces the formation of polychlorinated acetyl chloride by controlling the reaction temperature and the dropping rate of N-chlorosuccinimide, thereby improving the reaction selectivity; the conditions of this invention are mild, the operation is simple, and it is suitable for industrial production. Detailed Implementation

[0016] The following is a detailed description of the contents of this invention: The preparation method of chloroacetyl chloride of the present invention includes the following steps: (1) Under a nitrogen atmosphere, add solvent to the reaction vessel, slowly add acetyl chloride, start stirring to mix evenly, add initiator, and after the initiator is completely dissolved, raise the temperature to 25-65℃, add N-chlorosuccinimide dropwise, the molar ratio of acetyl chloride to N-chlorosuccinimide is 1:1.05-1.2, and keep the reaction at this temperature for 1-5 hours; the solvent is one of dichloromethane, chloroform, carbon tetrachloride, dichloroethane, diethyl ether, petroleum ether, ethyl acetate, and the amount of solvent used is 2-6 times the mass of acetyl chloride. The initiator is one of azobisisobutyronitrile, azobis(ethylheptanitrile), di-tert-butyl peroxide, benzoyl peroxide, and the amount of initiator used is 1.5-3.5% of the mass of acetyl chloride. When adding N-chlorosuccinimide, first dissolve it in the solvent to form a solution with a mass fraction of 25-75%.

[0017] (2) Cool to room temperature, filter, wash the filter cake with solvent, combine the filtrate and the washing liquid, remove the solvent and unreacted acetyl chloride by external evaporation at normal pressure, and collect the fraction at 80-82℃ by vacuum distillation under 20-22 kPa to obtain the chloroacetyl chloride product. The solvent used to wash the filter cake is 5-20% of the mass of acetyl chloride. The externally distilled solvent and unreacted acetyl chloride are recovered and recycled.

[0018] The following describes the content of this invention in further detail using specific parameters: Example 1:

[0019] Under a nitrogen atmosphere, 628g of ethyl acetate was added to a reaction vessel, and 314g of acetyl chloride was slowly added. The mixture was stirred until homogeneous, and 5.3g of azobisisobutyronitrile (AIB) initiator was added. After the initiator was completely dissolved, the temperature was raised to 35-40℃. 560.8g of N-chlorosuccinimide was dissolved in ethyl acetate to prepare a 75% solution and added dropwise at a rate of 7.8g / min. After the addition was completed, the reaction was maintained at this temperature for 2 hours. The mixture was cooled to room temperature, filtered, and 26.7g of ethyl acetate was used to wash the filter cake. The filtrate and the washing liquid were combined, and ethyl acetate and unreacted acetyl chloride were removed by external evaporation under normal pressure. The fraction collected at 80-82℃ / 20kPa was distilled under reduced pressure to obtain chloroacetyl chloride.

[0020] Based on acetyl chloride, the conversion rate was 99.63%, the selectivity was 99.87%, the yield was 99.48%, and the purity was 99.83% as determined by gas chromatography.

[0021] Example 2:

[0022] Under a nitrogen atmosphere, 1884 g of dichloromethane was added to a reaction vessel, and 314 g of acetyl chloride was slowly added. The mixture was stirred until homogeneous, and 8.2 g of benzoyl peroxide initiator was added. After the initiator was completely dissolved, the temperature was raised to 30–35 °C. 640.9 g of N-chlorosuccinimide was dissolved in dichloromethane to prepare a 25% solution, which was then added dropwise at a rate of 5.7 g / min. After the addition was completed, the reaction was maintained at this temperature for 5 h. The mixture was cooled to room temperature, filtered, and 51.8 g of dichloromethane was used to wash the filter cake. The filtrate and the washing liquid were combined, and dichloromethane and unreacted acetyl chloride were removed by external evaporation under normal pressure. The fraction collected at 80–82 °C / 20 kPa was obtained by vacuum distillation to obtain chloroacetyl chloride.

[0023] Based on acetyl chloride, the conversion rate was 98.73%, the selectivity was 97.46%, the yield was 96.21%, and the purity was 96.71% as determined by gas chromatography.

[0024] Example 3:

[0025] Under a nitrogen atmosphere, 1413g of carbon tetrachloride was added to a reaction vessel, followed by the slow addition of 314g of acetyl chloride. The mixture was stirred until homogeneous, and then 10.3g of di-tert-butyl peroxide initiator was added. After the initiator was completely dissolved, the temperature was raised to 60–65°C. 587.5g of N-chlorosuccinimide was dissolved in carbon tetrachloride to prepare a 50% solution, which was then added dropwise at a rate of 6.3g / min. The reaction was maintained at this temperature for 4 hours after the addition was completed. The mixture was then cooled to room temperature, filtered, and 40g of carbon tetrachloride was used to wash the filter cake. The filtrate and washing liquid were combined, and carbon tetrachloride and unreacted acetyl chloride were removed by external evaporation under normal pressure. The fraction distilled under reduced pressure at 80–82°C / 20kPa was collected to obtain chloroacetyl chloride.

[0026] Based on acetyl chloride, the conversion rate was 97.51%, the selectivity was 96.62%, the yield was 94.19%, and the purity was 95.63% as determined by gas chromatography.

[0027] Example 4:

[0028] Under a nitrogen atmosphere, 942g of chloroform was added to a reaction vessel, followed by the slow addition of 314g of acetyl chloride. The mixture was stirred until homogeneous, and then 5.3g of azobisisobutyronitrile (AIB) initiator was added. After the initiator was completely dissolved, the temperature was raised to 35–40°C. 560.8g of N-chlorosuccinimide was dissolved in chloroform to prepare a 75% solution, which was then added dropwise at a rate of 7.8g / min. The reaction was maintained at this temperature for 2 hours after the addition was completed. The mixture was cooled to room temperature, filtered, and 49.2g of chloroform was used to wash the filter cake. The filtrate and the washing liquid were combined, and chloroform and unreacted acetyl chloride were removed by external evaporation under normal pressure. The fraction collected at 80–82°C / 20kPa was distilled under reduced pressure to obtain chloroacetyl chloride.

[0029] Based on acetyl chloride, the conversion rate was 99.15%, the selectivity was 99.67%, the yield was 98.80%, and the purity was 99.57% as determined by gas chromatography.

[0030] Example 5:

[0031] Under a nitrogen atmosphere, 628g of ethyl acetate was added to a reaction vessel, and 314g of acetyl chloride was slowly added. The mixture was stirred until homogeneous, and 5.3g of azobisisobutyronitrile (AIB) initiator was added. After the initiator was completely dissolved, the temperature was raised to 35–40°C. 560.8g of N-chlorosuccinimide was added to the reaction solution in four equal batches with an interval of 20 min between additions. The reaction was maintained at this temperature for 2 h. After cooling to room temperature, the mixture was filtered, and 26.7g of ethyl acetate was used to wash the filter cake. The filtrate and the washing liquid were combined, and ethyl acetate and unreacted acetyl chloride were removed by external evaporation under normal pressure. The fraction collected at 80–82°C / 20 kPa was obtained by vacuum distillation to obtain chloroacetyl chloride.

[0032] Based on acetyl chloride, the conversion rate was 99.36%, the selectivity was 97.47%, the yield was 96.83%, and the purity was 96.73% as determined by gas chromatography.

[0033] Comparative Example 1: Under a nitrogen atmosphere, 628g of ethyl acetate was added to the reactor, followed by the slow addition of 314g of acetyl chloride. The mixture was stirred until homogeneous, and then 6.3g of sulfuric acid was added. The temperature was raised to 35-40℃. N-chlorosuccinimide was dissolved in ethyl acetate to prepare a 75% solution, which was then added dropwise at a rate of 7.8g / min. The reaction was maintained at this temperature for 2 hours.

[0034] Comparative Example 2: Under a nitrogen atmosphere, 628 g of ethyl acetate was added to a reaction vessel, followed by the slow addition of 314 g of acetyl chloride. The mixture was stirred until homogeneous, and then 6.3 g of elemental iodine was added. The temperature was raised to 60–65 °C. N-chlorosuccinimide was dissolved in ethyl acetate to prepare a 75% solution, which was then added dropwise at a rate of 7.8 g / min. After the addition was completed, the reaction was maintained at this temperature for 2 hours. The mixture was cooled to room temperature, filtered, and 42.4 g of ethyl acetate was used to wash the filter cake. The filtrate and the washing liquid were combined, and ethyl acetate and unreacted acetyl chloride were removed by external evaporation under normal pressure. The fraction collected at 80–82 °C / 20 kPa was distilled under reduced pressure to obtain chloroacetyl chloride.

[0035] Based on acetyl chloride, the conversion rate was 62.82%, the selectivity was 88.38%, the yield was 55.52%, and the purity was 85.25% as determined by gas chromatography.

[0036] The data from the examples and comparative examples are summarized below: Example 1 Azobisisobutyronitrile 99.63% 99.87% 99.48% 99.83% Example 2 Benzoyl peroxide 98.73% 97.46% 96.21% 96.71% Example 3 di-tert-butyl peroxide 97.51% 96.62% 94.19% 95.63% Example 4 Azobisisobutyronitrile 99.15% 99.67% 98.80% 99.57% Example 5 Azobisisobutyronitrile 99.36% 97.47% 96.83% 96.73% Comparative Example 1 sulfuric acid / / 0.00% / Comparative Example 2 Elemental iodine 62.82% 88.38% 55.52% 85.25% Comparing Examples 1-4, it can be seen that azo initiators have a better promoting effect on the reaction than organic peroxide initiators. Comparing Examples 1 and 5, it can be seen that the dropwise addition method is better than the batch addition method. This is because the batch addition method leads to an excessively high concentration of N-chlorosuccinimide in some areas, resulting in excessive chlorination of α-acyl radicals and the generation of polychlorinated acetyl chloride byproducts. No chloroacetyl chloride was generated in Comparative Example 1 because the strong acidity of sulfuric acid caused the N-chlorosuccinimide to decompose and deteriorate, thus failing to provide a chlorine source. In Comparative Example 2, elemental iodine was used as a free radical initiator to drive the reaction, which had low compatibility with the conditions described in this invention, and the product yield was only 55.52%.

[0037] 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 inventive concept, various simple modifications can be made to the technical solutions of the present invention, including combinations of various technical features in any other suitable manner. These simple modifications and combinations should also be considered as the content disclosed in the present invention and are all within the protection scope of the present invention.

Claims

1. A method for preparing chloroacetyl chloride, characterized in that, Includes the following steps: (1) Under a nitrogen atmosphere, add solvent to the reaction vessel, slowly add acetyl chloride, start stirring to mix evenly, add initiator, and after the initiator is completely dissolved, raise the temperature, add N-chlorosuccinimide solution, and keep the reaction at the temperature for 1 to 5 hours. (2) Cool to room temperature, filter, wash the filter cake with solvent, combine the filtrate and the washing liquid, remove the solvent and unreacted acetyl chloride by external evaporation under normal pressure, and collect the fraction at 80-82℃ by vacuum distillation under 20-22 kPa to obtain chloroacetyl chloride product.

2. The method for preparing chloroacetyl chloride according to claim 1, characterized in that, In step (1), the molar ratio of acetyl chloride and N-chlorosuccinimide is 1:1.05 to 1.

2.

3. The method for preparing chloroacetyl chloride according to claim 1, characterized in that, In step (1), the solvent is one of dichloromethane, chloroform, carbon tetrachloride, dichloroethane, diethyl ether, petroleum ether, or ethyl acetate, and the amount of solvent used is 2 to 6 times the mass of acetyl chloride.

4. The method for preparing chloroacetyl chloride according to claim 1, characterized in that, In step (1), the initiator is one of azobisisobutyronitrile, azobis(ethylheptanitrile), di-tert-butyl peroxide, or benzoyl peroxide, and the amount of initiator used is 1.5 to 3.5% of the mass of acetyl chloride.

5. The method for preparing chloroacetyl chloride according to claim 1, characterized in that, In step (1), the heating temperature is 25-65℃.

6. The method for preparing chloroacetyl chloride according to claim 1, characterized in that, In step (1), N-chlorosuccinimide is dissolved in a solvent to form a solution with a mass fraction of 25-75%.

7. The method for preparing chloroacetyl chloride according to claim 6, characterized in that, The N-chlorosuccinimide solution is added dropwise.

8. The method for preparing chloroacetyl chloride according to claim 1, characterized in that, The solvent used to wash the filter cake in step (2) is 5-20% of the mass of acetyl chloride.

9. The method for preparing chloroacetyl chloride according to claim 1, characterized in that, In step (2), the externally evaporated solvent and unreacted acetyl chloride are recovered and recycled.