Method for synthesizing ethyl chloroacetate

Abstract

The invention discloses a method for synthesizing ethyl chloroacetate, which comprises the following steps of: adding ethanol and chloroacetic acid in a certain proportion into a rectification reaction kettle, filling a solid catalyst into a fixed bed reactor, extracting the ethanol and the chloroacetic acid from the bottom of the reaction kettle through a circulating pump, passing through the fixed bed reactor, returning to the reaction kettle, and heating to react; after the material steam passes through the rectifying tower, an azeotrope of ethanol and water is condensed to a membrane separation dehydration device through a condenser, the dehydrated ethanol returns to the reaction kettle, and the reaction is stopped until the chloroacetic acid is completely reacted; through vacuum distillation, ethanol and a small amount of water are collected to a membrane separation dehydration device and can be recycled after dehydration, ethyl chloroacetate is collected to a product collection tank, and normal-pressure synthesis of ethyl chloroacetate and vacuum distillation purification operation are realized in the same reaction kettle. According to the method, the production steps are simplified, and the condition of product deterioration caused by catalyst or metal ion residues is avoided.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of organic synthesis, in particular to a method for continuously synthesizing ethyl chloroacetate. BACKGROUND

[0002] Ethyl chloroacetate is a colorless transparent liquid with a pungent irritating odor, which is widely used in the fields of medicine, pesticide, perfume, etc. It is an important intermediate for synthesizing antitumor drugs such as 5-fluorouracil, and can also be used for preparing insecticide imidacloprid and herbicide benalaxyl-ethyl, and for synthesizing perfumes and as a solvent or various organic synthesis raw materials.

[0003] The traditional production method of ethyl chloroacetate is to directly esterify chloroacetic acid and anhydrous ethanol as raw materials under the catalysis of concentrated sulfuric acid in a homogeneous phase. This method has the disadvantages of low reaction selectivity, complex post-treatment process, unrecyclable catalyst, and large amount of waste liquid discharge. Subsequent researchers found that strong acid type cation exchange resin, solid superacid, heteropoly acid, molecular sieve and inorganic salt can be used for esterification reaction. These catalysts show certain advantages in the synthesis of ethyl chloroacetate. However, there are still many problems in the post-treatment steps, such as 1. The solid catalyst has a small particle size, which is complex to recover, and is easily stirred and crushed during stirring reaction, which is easy to remain in the product, causing the product to become acid or deteriorate after long-term storage; 2. The acid solid catalyst has free H + ions, which will adhere to the C=O bond of ethyl chloroacetate after the reaction is completed, causing the product to be unqualified, and the use of alkaline liquid neutralization will cause the product to decompose and reduce the yield; 3. Ethanol and byproduct water are easy to form azeotrope, and it is difficult to obtain ethanol with low water content when using rectification recovery, and the energy consumption is high; 4. The existing production device needs more post-treatment steps, and the device investment is large, and the production process is time-consuming.

[0004] In view of the above problems, a new process with higher catalytic efficiency, more efficient post-treatment, lower equipment investment and operating cost should be researched.

[0005] Membrane separation dehydration equipment is an industrial equipment that uses membrane separation technology to separate solvent and water, mainly applied in the fields of pharmaceuticals, petroleum chemical industry, biological medicine, etc. Its operating principle is that the solvent vapor mixture is pushed by the component vapor pressure difference, and the material separation process is realized by using the different adsorption and diffusion speeds of components through the membrane. In the permeation process, it undergoes a transformation from liquid phase to gas phase, and the separation mechanism can be divided into three steps: (1) the separated substances are selectively adsorbed on the membrane surface; (2) the components permeate in the membrane in the form of diffusion; (3) desorption from the downstream side surface into gas phase and separated from the membrane. Compared with the traditional rectification purification dehydration, the membrane separation technology has the advantages of low investment and operating cost, small equipment occupation area, high dehydration efficiency, stable operation, etc.

[0006] Esterification catalyst resin is a solid particulate material composed of polymeric compounds encapsulating sulfonic acid groups. Primarily used in water treatment, it has since been discovered to be suitable for esterification reactions. Compared to concentrated sulfuric acid, a traditional esterification catalyst, it exhibits advantages such as easier separation from the product, reusability, and a milder reaction process. However, it also presents challenges, including small particle size leading to breakage during stirring, easy residue in the product, and complex recovery processes. Therefore, a device that facilitates recycling without compromising the catalyst's catalytic activity is needed.

[0007] A fixed-bed reactor is a reactor filled with granular solid catalysts or solid reactants, forming a bed of a certain height. Gas or liquid materials flow through the static fixed bed through the gaps between the particles, simultaneously achieving a heterogeneous reaction process. It offers advantages such as: 1. minimal backmixing, allowing effective contact between the fluid and the catalyst, resulting in high selectivity when the reaction is accompanied by cascaded side reactions; 2. low catalyst mechanical loss; and 3. simple structure. The mechanism of action of strongly acidic cation exchange resins in esterification reactions allows for excellent multi-batch recycling in fixed-bed reactors. Summary of the Invention

[0008] This invention presents a novel method for synthesizing ethyl chloroacetate, using ethanol and chloroacetic acid as raw materials and an esterification reaction catalytic resin as a catalyst. The process involves a reaction vessel, a fixed-bed reactor, a circulating pump, a distillation column, a condenser, and a membrane separation unit to produce ethyl chloroacetate. Compared to traditional esterification processes, this method offers advantages such as lower equipment investment, smaller footprint, lower operating costs, and superior product quality.

[0009] The technical solution of the present invention is as follows:

[0010] The reaction equation is shown above. The reaction mechanism is as follows: the esterification reaction catalyzes the donation of hydrogen from the sulfonic acid groups in the resin. + The proton preferentially binds to the carbonyl oxygen of the carboxylic acid to form an oxonium ion intermediate. This process significantly enhances the positive charge of the carbonyl carbon, making it more susceptible to nucleophilic attack. The hydroxyl oxygen of the alcohol acts as a nucleophile, attacking the activated carbonyl carbon to generate a positively charged tetrahedral oxonium intermediate. This intermediate contains two hydroxyl (-OH) groups, with the hydroxyl group attached to the carbonyl carbon undergoing structural rearrangement via intramolecular proton transfer. The rearranged intermediate undergoes dehydration, with the hydroxyl group protonated and reacting as H₃O. + The esterification process involves the removal of water molecules, followed by the loss of H⁺ to restore catalytic activity, ultimately producing ester products. Throughout the process, the esterification catalytic resin participates in the cyclical process, and its sulfonic acid groups are not consumed, allowing for multiple recycling.

[0011] The reaction steps are as follows: Ethanol and chloroacetic acid are added to a reaction vessel, and the esterification reaction catalyst resin is placed in a fixed-bed reactor. The circulating pump is turned on and the reaction vessel temperature is controlled, and the reaction is carried out at atmospheric pressure. By controlling the temperature and reflux ratio of the distillation column, the azeotrope of ethanol and water is distilled out of the reaction system, while ethyl chloroacetate and chloroacetic acid remain in the reaction vessel. The aqueous ethanol is then dehydrated by a membrane separator and returned to the reaction vessel, completing the recovery and reuse of ethanol. In this reaction, ethanol acts as both a reactant and a dehydrating agent, carrying the byproduct water out of the reaction system, allowing the esterification reaction (a reversible reaction) to proceed in the forward direction. After the reaction is completed, excess ethanol and a small amount of water are distilled out by negative pressure distillation and then dehydrated by a membrane separator for recovery and reuse. The ethyl chloroacetate product is then distilled out.

[0012] The molar ratio of ethanol to chloroacetic acid is 2-5:1.

[0013] The esterification reaction catalyst resins are Seplite® catalyst resin (LCX-105), solid acid catalyst resin (T-63MP), polymeric acid catalyst (T-77), and catalyst resin Tulsimer® (T-8052 MP). The addition amount in the fixed-bed reactor is 10 kg.

[0014] The circulating pumps mentioned are diaphragm metering pumps and magnetic pumps, with pulse-type and steady-state inlet flow rates of 4-6 m³ / h. 3 / h.

[0015] Preferably, the reaction temperature is 70-80℃, and the distillation column temperature is controlled at 70-75℃ during atmospheric pressure reaction, at which point ethanol and water will be distilled out of the reaction system. After the chloroacetic acid reaction is complete, it is purified by vacuum distillation. The ethanol-water azeotrope is collected at a temperature of 70-80℃ and a pressure of 50-80 kPa; the ethyl chloroacetate is collected at a temperature of 89-85℃ and a pressure of 5-15 kPa.

[0016] The beneficial effects of this invention are as follows: This invention selects an esterification reaction catalytic resin as the catalyst, which is placed in a fixed-bed reactor. Compared with the traditional esterification catalyst concentrated sulfuric acid, it has the advantages of being recyclable, easier to separate the product from the catalyst, and having a mild reaction and high yield. Simultaneously, using a circulating pump instead of stirring prevents the catalyst from being broken up, avoiding catalyst residue and product deterioration. After the reaction, direct distillation is carried out in the reactor, eliminating the neutralization step, which greatly reduces post-processing costs and prevents product decomposition during alkali neutralization, avoiding metal ion residue. A membrane separation device is used for ethanol dehydration and recovery, which has lower equipment investment and operating costs compared to traditional distillation recovery. The product yield obtained using the technical solution of this invention can reach over 99% (purity ≥99.5%), and the ethyl chloroacetate product will not show back-acidification or deterioration after long-term exposure to air. The NaA membrane separation and dehydration device of Jiangsu Jiutian High-Tech Co., Ltd. achieves an ethanol recovery rate of over 98% (purity >99%). Detailed Implementation

[0017] To better understand the features and advantages of this invention, further explanation is provided below with reference to the embodiments, which illustrate various scenarios in reaction design. However, the content of this invention is not limited to the embodiments below.

[0018] Example 1 Ethanol (146.25 kg) and chloroacetic acid (100 kg) were added to the reactor, and Seplite® catalyst resin (LCX-105) (10 kg) was packed into the fixed-bed reactor. The magnetic pump was then started (flow rate 6 m / s). 3 The ethanol and chloroacetic acid in the reactor are transferred to a fixed-bed reactor (stable flow to the fixed-bed reactor) and then returned to the reactor. The reactor temperature is controlled at 75℃ and the distillation column temperature at 70℃, and the reaction is maintained at this temperature. The azeotrope of ethanol and water distilled from the distillation column is dehydrated by a membrane separator and returned to the reactor. A sample is taken at the outlet branch of the magnetic pump for liquid phase testing. The reaction is stopped when the amounts of chloroacetic acid and ethyl chloroacetate no longer change. After 20 hours of holding the reaction at this temperature, the contents of chloroacetic acid and ethyl chloroacetate no longer change. At this point, the vacuum unit is turned on for reduced pressure distillation. The temperature of the reactor and distillation column is raised to 80℃ and the pressure is 50 kPa. Unreacted ethanol and a small amount of water are collected in a membrane separator for dehydration and reuse. When no fractions are distilled off, the temperature of the column bottom is raised to 85°C and the pressure is reduced to 10 kPa. Ethyl chloroacetate is collected in the product tank. After the distillation is completed, it is weighed. The yield of ethyl chloroacetate is 99.3% (based on chloroacetic acid), the purity is 99.5%, and the pH is 6.2.

[0019] Example 2 Ethanol (146.25 kg) and chloroacetic acid (100 kg) were added to the reactor, and solid acid catalyst resin (T-63MP) (10 kg) was packed into the fixed-bed reactor. Then, the magnetic pump (flow rate 6 m / s) was started. 3 The ethanol and chloroacetic acid in the reactor are transferred to a fixed-bed reactor (stable flow to the fixed-bed reactor) and then returned to the reactor. The reactor temperature is controlled at 75℃ and the distillation column temperature at 70℃, and the reaction is maintained at this temperature. The azeotrope of ethanol and water distilled from the distillation column is dehydrated by a membrane separator and returned to the reactor. A sample is taken at the outlet branch of the magnetic pump for liquid phase testing. The reaction is stopped when the amounts of chloroacetic acid and ethyl chloroacetate no longer change. After maintaining the temperature for 15 hours, the contents of chloroacetic acid and ethyl chloroacetate no longer change. At this time, the vacuum unit is turned on for reduced pressure distillation. The temperature of the reactor and distillation column is raised to 80℃ and the pressure is 50 kPa. Unreacted ethanol and a small amount of water are collected in a membrane separator for dehydration and reuse. When no fractions are distilled off, the temperature of the column bottom is raised to 85°C and the pressure is reduced to 10 kPa. Ethyl chloroacetate is collected in the product tank. After the distillation is completed, it is weighed. The yield of ethyl chloroacetate is 99.5% (based on chloroacetic acid), the purity is 99.7%, and the pH is 6.4.

[0020] Example 3 Ethanol (146.25 kg) and chloroacetic acid (100 kg) were added to the reactor, and the polymeric acid catalyst (T-77) (10 kg) was packed into the fixed-bed reactor. The magnetic pump was then started (flow rate 6 m / s). 3 The ethanol and chloroacetic acid in the reactor are transferred to a fixed-bed reactor (stable flow to the fixed-bed reactor) and then returned to the reactor. The reactor temperature is controlled at 75℃ and the distillation column temperature at 70℃, and the reaction is maintained at this temperature. The azeotrope of ethanol and water distilled from the distillation column is dehydrated by a membrane separator and returned to the reactor. A sample is taken at the outlet branch of the circulating pump for liquid phase testing. The reaction is stopped when the amounts of chloroacetic acid and ethyl chloroacetate no longer change. After 8 hours of holding the reaction at this temperature, the contents of chloroacetic acid and ethyl chloroacetate no longer change. At this point, the vacuum unit is turned on for reduced pressure distillation. The temperature of the reactor and distillation column is raised to 80℃ and the pressure is 50 kPa. Unreacted ethanol and a small amount of water are collected in the membrane separator for dehydration and reuse. When no fraction is distilled off, the temperature of the column bottom is raised to 85℃ and the pressure is reduced to 10 kPa. Ethyl chloroacetate is collected in a product tank. After distillation, it is weighed. The yield of ethyl chloroacetate is 99.4% (based on chloroacetic acid), the purity is 99.6%, and the pH is 6.5.

[0021] Example 4 Ethanol (146.25 kg) and chloroacetic acid (100 kg) were added to the reactor, and the catalyst resin Tulsimer® (T-8052 MP) (10 kg) was packed into the fixed-bed reactor. The magnetic pump was then started (flow rate 6 m / s).3 The ethanol and chloroacetic acid in the reactor are transferred to a fixed-bed reactor (stable flow to the fixed-bed reactor) and then returned to the reactor. The reactor temperature is controlled at 75℃ and the distillation column temperature at 70℃, and the reaction is maintained at this temperature. The azeotrope of ethanol and water distilled from the distillation column is dehydrated by a membrane separator and returned to the reactor. A sample is taken at the outlet branch of the magnetic pump for liquid phase testing. The reaction is stopped when the amounts of chloroacetic acid and ethyl chloroacetate no longer change. After 6 hours of holding the reaction at this temperature, the contents of chloroacetic acid and ethyl chloroacetate no longer change. At this point, the vacuum unit is turned on for reduced pressure distillation. The temperature of the reactor and distillation column is raised to 80℃ and the pressure is 50 kPa. Unreacted ethanol and a small amount of water are collected in the membrane separator for dehydration and reuse. When no fraction is distilled off, the temperature of the column bottom is raised to 85℃ and the pressure is reduced to 10 kPa. Ethyl chloroacetate is collected in a product tank. After distillation, it is weighed. The yield of ethyl chloroacetate is 99.6% (based on chloroacetic acid), the purity is 99.8%, and the pH is 6.3.

[0022] Example 5 Ethanol (146.25 kg) and chloroacetic acid (100 kg) were added to the reactor, and the catalyst resin Tulsimer® (T-8052 MP) (10 kg) was packed into the fixed-bed reactor. The diaphragm pump was then started (flow rate 6 m / s). 3 The ethanol and chloroacetic acid in the reactor are transferred to a fixed-bed reactor (pulsed flow to the fixed-bed reactor) and then returned to the reactor. The reactor temperature is controlled at 75℃ and the distillation column temperature at 70℃, and the reaction is maintained at this temperature. The azeotrope of ethanol and water distilled from the distillation column is dehydrated by a membrane separator and returned to the reactor. A sample is taken at the outlet branch of the diaphragm pump for liquid phase testing. The reaction is stopped when the amounts of chloroacetic acid and ethyl chloroacetate no longer change. After 4 hours of holding the reaction at this temperature, the contents of chloroacetic acid and ethyl chloroacetate no longer change. At this point, the vacuum unit is turned on for reduced pressure distillation. The temperature of the reactor and distillation column is raised to 80℃ and the pressure is 50 kPa. Unreacted ethanol and a small amount of water are collected in the membrane separator for dehydration and reuse. When no fraction is distilled off, the temperature of the column bottom is raised to 85℃ and the pressure is reduced to 10 kPa. Ethyl chloroacetate is collected in a product tank. After distillation, it is weighed. The yield of ethyl chloroacetate is 99.9% (based on chloroacetic acid), the purity is 99.9%, and the pH is 6.1.

[0023] Comparing Examples 4 and 5, the catalyst activity and yield were improved by changing the way the liquid entered the fixed-bed reactor (a magnetic pump was used for steady-flow introduction, model IMCF40-25-160, flow rate 6 m³ / h, pump outlet pressure 0.3 MPa; a diaphragm pump was used for pulsed introduction, model SC-D100, pump outlet pressure 0.6 MPa, pulse frequency 50 Hz, pulsed introduction). This is likely because when the liquid is pulsedly introduced into the reactor, the contact between the reactants and the catalyst is better, resulting in more effective collisions, which enhances the catalytic activity, thereby shortening the reaction time and increasing the reaction yield.

[0024] Example 6 Ethanol (146.25 kg), chloroacetic acid (100 kg), and concentrated sulfuric acid (10 kg) were added to a reactor and stirred. The reactor temperature was controlled at 82°C and the distillation column temperature at 71°C, and the reaction was maintained at these temperatures. The azeotrope of ethanol and water distilled from the distillation column was dehydrated using a membrane separator and returned to the reactor. After 24 hours of holding the reaction at these temperatures, the reaction was stopped, and liquid alkali (20%) was added to neutralize the solution. The upper organic phase was then purified by distillation. The temperature of the reactor and distillation column was raised to 80°C and the pressure to 52 kPa. Unreacted ethanol and a small amount of water were collected in a membrane separator for dehydration and reuse. When no fraction was distilled off, the temperature of the distillation column was raised to 85°C and the pressure was reduced to 10 kPa. Ethyl chloroacetate was collected in a product tank. After distillation, the product was weighed. The yield of ethyl chloroacetate was 69% (based on chloroacetic acid), the purity was 98%, and the pH was 6.2.

[0025] The ethyl chloroacetate products from the above examples were left exposed to air at 25°C for one month, and the pH of the ethyl chloroacetate products was tested using a pH meter. The results showed that the pH of the products in Examples 1-5 was 6.4, 6.0, 6.2, 6.1, and 6.0 respectively, meaning that there was essentially no change, and no solid precipitation occurred.

[0026] In Example 6, the product obtained after stirring and neutralization was left exposed to air at 25°C for one month. A pH meter showed a decrease in pH to 5.2, and a white solid precipitated. Analysis revealed this white solid to be sodium chloroacetate. This deterioration was likely due to residual catalyst and liquid alkali from the neutralization process, leading to prolonged storage and decomposition. Comparison of these results shows that the processes and catalysts used in Examples 1-5 are superior.

[0027] In summary, a continuous synthesis method for ethyl chloroacetate uses ethanol and chloroacetic acid as reactants, Tulsimer® (T-8052 MP) as a catalyst, and employs equipment such as a reaction vessel, distillation column, diaphragm pump, fixed-bed reactor, and membrane separation dehydration unit for reaction and post-processing. This method yields ethyl chloroacetate with a yield of 99.9% and a purity of 99.9%. This invention offers advantages such as low equipment investment, low operating costs, mild and controllable reaction conditions, high product purity, and no deterioration even after prolonged exposure to air.

[0028] The above embodiments are merely preferred embodiments of the present invention, and the scope of protection of the present invention is not limited to the above embodiments. All implementation methods derived from the concept of the present invention fall within the scope of protection of the present invention. It should be noted that for researchers in this field, improvements and modifications made based on the reaction principles and concepts described in the present invention should also be considered within the scope of protection of the present invention.

Claims

1. A method for synthesizing ethyl chloroacetate, characterized in that, Includes the following steps: (1) Add a certain proportion of ethanol and chloroacetic acid to the distillation reactor, pack the solid catalyst into the fixed bed reactor, and use a circulating pump to draw ethanol and chloroacetic acid from the bottom of the reactor through the fixed bed reactor and then return them to the reactor for heating and reaction. (2) During the reaction, after the material vapor passes through the distillation column, the azeotrope of ethanol and water is condensed by the condenser to the membrane separation dehydration device. The dehydrated ethanol is then returned to the reactor until the chloroacetic acid reaction is complete and the reaction is stopped. (3) Ethanol and a small amount of water are collected in a membrane separation dehydration device by vacuum distillation. After dehydration, they can be recycled. Ethyl chloroacetate is collected in a product collection tank. The reaction formula is as follows: 。 2. The method according to claim 1, characterized in that, The molar ratio of ethanol to chloroacetic acid is 2-5:

1.

3. The method according to claim 1, characterized in that, The solid acid catalyst is a strong acid ion exchange resin containing sulfonic acid groups, and the strong acid ion exchange resin is selected from at least one of styrene-divinylbenzene copolymer sulfonated resin and fluorocarbon polymer sulfonated resin; the esterification reaction temperature is 60~90℃.

4. The method according to claim 3, characterized in that, The solid catalyst is Seplite® catalyst resin (LCX-105), solid acid catalyst resin (T-63MP), polymeric acid catalyst (T-77), or catalyst resin Tulsimer® (T-8052 MP).

5. The method according to claim 1, characterized in that, In step (2), the temperature of the distillate is controlled to be 65~75℃ by controlling the temperature of the separation unit, so as to achieve selective removal of ethanol-water azeotrope.

6. The method according to claim 1, characterized in that, The product separation is achieved by vacuum distillation. First, the residual ethanol and water are distilled off under a pressure of 50-80 kPa, and then the ethyl chloroacetate product with a distillation range of 84-90°C is collected under a pressure of 5-15 kPa.

7. The method according to claim 1, characterized in that, In step (2), the flow rate of the reaction mixture through the circulating catalytic unit is such that the catalyst bed produces a pulsed flow or a steady flow.

8. The method according to claim 1, characterized in that, In step (2), the distillation column is a packed column, the column body is carbon steel with PTFE coating inside, and the packing is Hastelloy C276 packing.

9. The method according to claim 1, characterized in that, In step (3), the separation process uses membrane separation to achieve an ethanol recovery rate of >98% and a purity of >99%.

10. An ethyl chloroacetate, characterized in that, The ethyl chloroacetate prepared by any of the methods described in claims 1-9, after being stored at 25°C under normal pressure in a sealed and light-protected environment for 30 days, exhibits an acid value change rate of less than 5% and produces no visible turbidity or precipitate.

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