Preparation method of bromoacetic anhydride
By employing a dehydration condensation process with the batch addition of DIC and nitrogen protection, the problems of low yield and purity in the synthesis of bromoacetic anhydride were solved, achieving the preparation of high-purity, high-yield bromoacetic anhydride, which is suitable for industrial production.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-12-26
- Publication Date
- 2026-03-27
AI Technical Summary
Existing methods for synthesizing bromoacetic anhydride suffer from low yield and low purity, and the product is prone to decomposition, especially in high humidity conditions, making it difficult to store for long periods.
N,N-diisopropylcarbodiimide (DIC) was added in batches as a dehydrating agent and carried out a dehydration condensation reaction with bromoacetic acid in an organic solvent. Combined with nitrogen protection and crystallization process, the reaction temperature and time were controlled to reduce the occurrence of side reactions.
It improves the yield and purity of bromoacetic anhydride, enhances product stability, facilitates storage and transportation, and is suitable for industrial production.
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Figure CN121735759A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of organic synthesis technology, and specifically relates to a method for preparing bromoacetic anhydride. Background Technology
[0002] Bromoacetic anhydride is an organic compound belonging to the acid anhydride class. It has a wide range of applications in organic chemistry. For example, bromoacetic anhydride can be used as an activating agent for carboxylic acids in esterification, acylation and other reactions to generate the corresponding carboxylic acid esters or acylation products. It is also a key reaction reagent in the synthesis of herbicides, insecticides and certain pharmaceutical intermediates. It can also be used to synthesize organic materials with specific functions, such as polymers and surfactants.
[0003] Currently, there are several methods for synthesizing bromoacetic anhydride: Method 1: Bromoacetic acid reacts with the condensing agent DCC to undergo dehydration condensation to produce dicyclohexylurea (DCU) and bromoacetic anhydride. The product is then obtained by filtration and concentration.
[0004] Method 2: Bromoacetyl bromide reacts with sodium bromoacetate in toluene solution, the filtrates are combined after filtration and concentrated to obtain the target product.
[0005] Method 3: Acetic acid is first reacted with a brominating agent to obtain bromoacetic acid, which is then transferred to a dehydration reactor and further condensed under acidic conditions to generate bromoacetic anhydride.
[0006] The above methods have significant drawbacks: Method 1 generates a large amount of highly soluble byproduct DCU, and during filtration, bromoacetic anhydride easily absorbs water and decomposes into the raw material bromoacetic acid, greatly reducing product purity; Method 2 suffers from numerous side reactions, solvent limitations, harsh reaction conditions, safety hazards, and difficulties in product separation; Method 3 involves cumbersome steps, generates a large amount of acidic gas during acidification that needs to be treated, and requires strict control of reaction time and temperature, resulting in high operational requirements and reduced product yield. Furthermore, there are no methods for separate production preparation; most methods use the product directly in the next step without purification after synthesis. This is mainly because the product is highly hygroscopic and hydrolyzed, making complete reaction difficult. The product is greatly affected by ambient temperature and humidity; when the air humidity is greater than 40%, post-processing is extremely difficult, and the product decomposes rapidly. Therefore, products prepared according to normal reaction procedures have yields below 40%, purity below 90%, and are rarely suitable for long-term room temperature storage, requiring nitrogen-filled, cryogenic storage.
[0007] In summary, the current process suffers from low yield and low purity. Therefore, how to improve the process to increase yield and purity has become a pressing technical challenge in this field. Summary of the Invention
[0008] The purpose of this invention is to provide a method for preparing bromoacetic anhydride. The preparation method provided by this invention can improve the yield and purity.
[0009] To achieve the above-mentioned objectives, the present invention provides the following technical solution: This invention provides a method for preparing bromoacetic anhydride, comprising: Bromoacetic acid and an organic solvent were mixed, and then N,N-diisopropylcarbodiimide was added in batches to carry out dehydration condensation to obtain bromoacetic anhydride.
[0010] Preferably, the organic solvent is at least one selected from ethyl acetate, dichloromethane, toluene, and ethanol.
[0011] Preferably, the mass ratio of bromoacetic acid to organic solvent is 1:(2~3).
[0012] Preferably, the mass ratio of bromoacetic acid to N,N-diisopropylcarbodiimide is (1~2):1.
[0013] Preferably, the dehydration condensation temperature is 10~20℃, and the dehydration condensation time is 1~2h.
[0014] Preferably, the dehydration condensation is carried out under nitrogen protection.
[0015] Preferably, the N,N-diisopropylcarbodiimide is added in two batches. The operation of adding the N,N-diisopropylcarbodiimide in two batches is as follows: first, one-third of the total mass of N,N-diisopropylcarbodiimide is added, then the temperature is maintained for 0.1 to 1 hour, and then the remaining N,N-diisopropylcarbodiimide is added.
[0016] Preferably, after the dehydration and condensation are completed, the process further includes a first filtration to obtain a mother liquor, and then the mother liquor is subjected to crystallization and a second filtration in sequence.
[0017] Preferably, the crystallization temperature is -30 to -10°C, and the crystallization time is 1 to 3 hours.
[0018] Preferably, petroleum ether is added during crystallization; the mass ratio of the organic solvent to petroleum ether is 1:(1~2).
[0019] This invention provides a method for preparing bromoacetic anhydride, comprising: mixing bromoacetic acid and an organic solvent, then adding N,N-diisopropylcarbodiimide in batches for dehydration condensation to obtain bromoacetic anhydride. This invention uses the batch addition of the dehydrating agent N,N-diisopropylcarbodiimide (DIC). The DIC added in the early stages reacts with bromoacetic acid to generate bromoacetic anhydride, which consumes water in the system. The bromoacetic anhydride generated from the reaction of subsequently added DIC with bromoacetic acid in the system is less prone to decomposition, ensuring complete reaction of the raw materials, reducing side reactions, and thus improving product purity and yield. The results of the examples show that the preparation method provided by this invention has a yield of 86-91% and a purity of 97.8-98.6%. Attached Figure Description
[0020] Figure 1 The NMR spectrum of bromoacetic anhydride prepared in Example 1; Figure 2 The data are gas phase spectral data of bromoacetic anhydride prepared in Example 1. Detailed Implementation
[0021] This invention provides a method for preparing bromoacetic anhydride, comprising: Bromoacetic acid and an organic solvent were mixed, and then N,N-diisopropylcarbodiimide was added in batches to carry out dehydration condensation to obtain bromoacetic anhydride.
[0022] The present invention does not have any special limitations on the source of the raw materials, and commercially available products known to those skilled in the art can be used.
[0023] In this invention, the organic solvent is preferably at least one selected from ethyl acetate, dichloromethane, toluene, and ethanol; the mass ratio of bromoacetic acid to the organic solvent is preferably 1:(2-3). As one embodiment, the mass ratio of bromoacetic acid to the organic solvent can be 1:2.5. In this invention, the organic solvent is used to dissolve the raw materials.
[0024] In this invention, the water content in the organic solvent is preferably <450ppm.
[0025] The present invention does not have any special limitations on the operation of mixing bromoacetic acid and organic solvent; any technical solution for preparing the mixture well known to those skilled in the art can be used.
[0026] In this invention, the preferred mass ratio of bromoacetic acid to N,N-diisopropylcarbodiimide is (1~2):1. As one embodiment, the mass ratio of bromoacetic acid to N,N-diisopropylcarbodiimide can be 1.5:1. In this invention, N,N-diisopropylcarbodiimide is a dehydrating agent, and limiting the mass ratio of bromoacetic acid to N,N-diisopropylcarbodiimide within the above range can further improve the purity and yield of the product.
[0027] In this invention, the N,N-diisopropylcarbodiimide is preferably added in two batches. The preferred method is to first add one-third of the total mass of N,N-diisopropylcarbodiimide, then maintain the temperature for 0.1-1 hour, and then add the remaining N,N-diisopropylcarbodiimide. As one embodiment, the maintaining time can be 0.5 hours. In this invention, the dehydrating agent DIC is added first at one-third of its total mass, maintained for 0.1-1 hour, and then the remaining DIC is added. This allows the bromoacetic anhydride generated in the early stage to consume the water in the system and be reduced to the raw material bromoacetic acid, which then reacts with the remaining DIC. This ensures a complete reaction of the raw material, reduces side reactions, and improves product purity.
[0028] In this invention, the preferred temperature for the dehydration condensation is 10-20°C; the preferred time for the dehydration condensation is 1-2 hours. As one embodiment, the temperature for the dehydration condensation can be 11°C, 12°C, 13°C, 14°C, 15°C, 16°C, 17°C, 18°C, or 19°C; the preferred time for the dehydration condensation is 1.5 hours. In this invention, the dehydration condensation time refers to the reaction time after the complete addition of N,N-diisopropylcarbodiimide.
[0029] In this invention, the dehydration condensation is preferably carried out under nitrogen protection.
[0030] In this invention, after the dehydration condensation is completed, it is preferable to further perform a first filtration to obtain a mother liquor, and then perform crystallization and a second filtration on the mother liquor in sequence.
[0031] The present invention does not have any special limitations on the operation of the first filtration. Any operation known to those skilled in the art can be used to obtain the filtrate.
[0032] In this invention, the crystallization temperature is preferably -30 to -10°C, more preferably -20°C; the crystallization time is preferably 1 to 3 hours, more preferably 2 hours. By limiting the crystallization process parameters within the above range, this invention can further improve the product yield.
[0033] In this invention, petroleum ether is preferably added during crystallization; the mass ratio of the organic solvent to petroleum ether is preferably 1:(1~2). As one embodiment, the mass ratio of the organic solvent to petroleum ether can be 1:1.5.
[0034] In this invention, the water content of the petroleum ether is preferably <450ppm.
[0035] The present invention does not impose any special limitations on the operation of the secondary filtration; any operation well known to those skilled in the art can be used to obtain a solid.
[0036] The preparation method of this invention has a moderate reaction temperature, eliminating the need for excessive heating or cooling, thus reducing energy consumption; the product can be obtained by filtration and crystallization after the reaction, which is simple and convenient; the addition of the dehydrating agent DIC in batches can effectively reduce the decomposition of bromoacetic anhydride, control the occurrence of side reactions, and improve the purity of the product; the raw material cost is low, the operation is easy, the product quality is high, and it is easy to industrialize.
[0037] Compared to existing preparation methods, this invention can be produced and prepared separately, and can be stored and transported stably.
[0038] Considering that the product is highly susceptible to absorbing water during the reaction, leading to incomplete reaction and low purity, it is necessary not only to dry the materials but also to carry out the reaction under nitrogen protection. We tried adding desiccants such as molecular sieves to remove the moisture generated during the reaction, but found that it had some effect but not much. Later, we found that directly adding the key material (dehydrating agent) in batches and slightly increasing the dosage could effectively absorb water and promote the reaction, thereby greatly improving the purity of the product.
[0039] The technical solutions of this invention will be clearly and completely described below with reference to the embodiments thereof. Obviously, the described embodiments are only a part of the embodiments of this invention, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.
[0040] In the examples and comparative examples, the moisture content of ethyl acetate was first controlled below 450 ppm to ensure that the reaction vessel was absolutely dry and free from excess moisture interference.
[0041] Example 1 A method for preparing bromoacetic anhydride is as follows: 200g of bromoacetic acid was dissolved in 400g of ethyl acetate. Under nitrogen protection, 43g of DIC was added and the temperature was controlled at 15℃. After holding at this temperature for 0.5h, 87g of DIC was added. After the dehydration condensation reaction was carried out for 2h, the byproduct urea was separated by filtration, and the mother liquor was obtained. Then, 600g of petroleum ether was added to the mother liquor and crystallized at -20℃ for 2h. After filtration, 172g of bromoacetic anhydride was obtained, with a yield of 86% and a purity of 98.6%.
[0042] The NMR spectrum of bromoacetic anhydride prepared in Example 1 is shown below. Figure 1 As shown; the gas phase spectrum data of bromoacetic anhydride prepared in Example 1 are as follows. Figure 2 As shown.
[0043] from Figure 1 and 2 It can be seen that the preparation method of the present invention can prepare bromoacetic anhydride.
[0044] Example 2 A method for preparing bromoacetic anhydride is as follows: 200g of bromoacetic acid was dissolved in 400g of ethyl acetate. Under nitrogen protection, 33g of DIC was added, and the temperature was controlled at 15℃. After holding at this temperature for 0.5h, 67g of DIC was added. After a dehydration condensation reaction for 2h, the byproduct urea was separated by filtration, and the mother liquor was obtained. Then, 600g of petroleum ether was added to the mother liquor, and crystallization was carried out at -20℃ for 2h. Subsequently, filtration yielded 180g of bromoacetic anhydride, with a yield of 90% and a purity of 98.3%. The product can be stored stably at room temperature. Example 3 A method for preparing bromoacetic anhydride is as follows: 300g of bromoacetic acid was dissolved in 600g of ethyl acetate. Under nitrogen protection, 100g of DIC was added and the temperature was controlled at 15℃. After holding at this temperature for 0.5h, 200g of DIC was added. After the dehydration condensation reaction was carried out for 2h, the byproduct urea was separated by filtration to obtain the mother liquor. Then, 900g of petroleum ether was added to the mother liquor and crystallized at -20℃ for 2h. After filtration, 273g of bromoacetic anhydride was obtained, with a yield of 91% and a purity of 97.9%. The product can be stored stably at room temperature.
[0045] Example 4 A method for preparing bromoacetic anhydride is as follows: 300g of bromoacetic acid was dissolved in 750g of ethyl acetate. Under nitrogen protection, 65g of DIC was added and the temperature was controlled at 15℃. After holding at this temperature for 0.5h, 130g of DIC was added. After the dehydration condensation reaction was carried out for 2h, the byproduct urea was separated by filtration to obtain the mother liquor. Then, 1125g of petroleum ether was added to the mother liquor and crystallized at -20℃ for 2h. After filtration, 270g of bromoacetic anhydride was obtained, with a yield of 90% and a purity of 97.8%. The product can be stored stably at room temperature.
[0046] Example 5 A method for preparing bromoacetic anhydride is as follows: 350g of bromoacetic acid was dissolved in 1050g of ethyl acetate. Under nitrogen protection, 76g of DIC was added, and the temperature was controlled at 15℃. After holding at this temperature for 0.5h, 151.5g of DIC was added. After the dehydration condensation reaction for 2h, the byproduct urea was separated by filtration, and the mother liquor was obtained. Then, 1550g of petroleum ether was added to the mother liquor, and crystallization was carried out at -20℃ for 2h. After filtration, 316.75g of bromoacetic anhydride was obtained, with a yield of 90.5% and a purity of 97.9%. The product can be stored stably at room temperature.
[0047] Example 6 A method for preparing bromoacetic anhydride is as follows: 300g of bromoacetic acid was dissolved in 600g of ethyl acetate. Under nitrogen protection, 65g of DIC was added and the temperature was controlled at 15℃. After holding at this temperature for 0.5h, 130g of DIC was added. After the dehydration condensation reaction was carried out for 2h, the byproduct urea was separated by filtration to obtain the mother liquor. Then, 1200g of petroleum ether was added to the mother liquor and crystallized at -20℃ for 2h. After filtration, 270g of bromoacetic anhydride was obtained, with a yield of 90% and a purity of 97.8%. The product can be stored stably at room temperature.
[0048] Comparative Example 1 A method for preparing bromoacetic anhydride is as follows: 300g of bromoacetic acid was dissolved in 600g of ethyl acetate. Under nitrogen protection, 195g of DIC was added and the temperature was controlled at 15℃. After the dehydration condensation reaction was carried out for 2 hours, the byproduct urea was separated by filtration to obtain the mother liquor. Then, 900g of petroleum ether was added to the mother liquor and crystallized at -20℃ for 2 hours. After filtration, 162g of bromoacetic anhydride was obtained, with a yield of 54% and a purity of 63.3%. The product changed color and clumped after being left at room temperature for one day.
[0049] Analysis of experimental results: In Comparative Example 1, the dehydrating agent DIC was added to the system all at once. The resulting bromoacetic anhydride would further hydrolyze with the water in the system, reducing it to bromoacetic acid, which seriously affected the final purity and yield of the product. In this invention, DIC is added in batches. The bromoacetic anhydride generated first can consume the water in the system. The bromoacetic anhydride product generated by the reaction of the DIC added later with the bromoacetic acid in the system is no longer easily decomposed, thereby improving the purity and yield of the final product. It can also be produced and prepared separately and stored and transported stably.
[0050] As can be seen from the above examples and comparative examples, the preparation method provided by the present invention can improve the yield and purity.
[0051] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.
Claims
1. A method for preparing bromoacetic anhydride, comprising: Bromoacetic acid and an organic solvent were mixed, and then N,N-diisopropylcarbodiimide was added in batches to carry out dehydration condensation to obtain bromoacetic anhydride.
2. The preparation method according to claim 1, characterized in that, The organic solvent is at least one of ethyl acetate, dichloromethane, toluene, and ethanol.
3. The preparation method according to claim 1, characterized in that, The mass ratio of bromoacetic acid to organic solvent is 1:(2~3).
4. The preparation method according to claim 1, characterized in that, The mass ratio of bromoacetic acid to N,N-diisopropylcarbodiimide is (1~2):
1.
5. The preparation method according to claim 1, characterized in that, The dehydration condensation temperature is 10~20℃, and the dehydration condensation time is 1~2h.
6. The preparation method according to claim 1, characterized in that, The dehydration condensation is carried out under nitrogen protection.
7. The preparation method according to claim 1, characterized in that, The N,N-diisopropylcarbodiimide is added in two batches. The operation of adding the N,N-diisopropylcarbodiimide in two batches is as follows: first, one-third of the total mass of N,N-diisopropylcarbodiimide is added, and then the temperature is maintained for 0.1~1h, and then the remaining N,N-diisopropylcarbodiimide is added.
8. The preparation method according to claim 1, characterized in that, After the dehydration and condensation are completed, the process also includes a first filtration to obtain the mother liquor, and then the mother liquor is subjected to crystallization and a second filtration in sequence.
9. The preparation method according to claim 1, characterized in that, The crystallization temperature is -30 to -10°C, and the crystallization time is 1 to 3 hours.
10. The preparation method according to claim 1, characterized in that, Petroleum ether is added during crystallization; the mass ratio of the organic solvent to petroleum ether is 1:(1~2).