A process for the preparation of 1-bromoethyl acetate
By reacting sodium bromide with vinyl acetate in the presence of an oxidant and a catalyst, combined with extraction and drying steps, the environmental pollution and cost problems in the preparation of 1-bromoethyl acetate in existing technologies have been solved, achieving industrial production with high selectivity and high yield.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- GUANGDONG LIGUO PHARMACY
- Filing Date
- 2026-02-27
- Publication Date
- 2026-05-29
AI Technical Summary
Existing methods for preparing 1-bromoethyl acetate suffer from problems such as significant environmental pollution, poor atom economy, low reaction selectivity, poor product purity, and high production costs, making it difficult to achieve industrial-scale production.
Sodium bromide, a catalyst, and an oxidant are used to react with vinyl acetate in a solvent. In-situ activation of bromide ions is achieved through a mild oxidant and a phase transfer catalyst, avoiding the use of corrosive catalysts and high concentrations of bromide. Post-processing involves extraction and drying steps to obtain a high-purity product.
The preparation of 1-bromoethyl acetate with high selectivity, high yield, and low cost has been achieved, which meets the requirements of green chemistry, is suitable for industrial production, and reduces pollution from waste gas, wastewater, and solid waste and production costs.
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Figure CN122102903A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of organic synthesis technology, and in particular to a method for preparing 1-bromoethyl acetate. Background Technology
[0002] 1-Bromoethyl acetate is an important organic synthesis intermediate. Both the bromine atom and the ester group in its molecule possess high reactivity, making it widely used in the synthesis of pharmaceuticals, pesticides, and other fine chemicals. For example, it is a key side chain in the synthesis of certain antibiotic drugs.
[0003] Currently, common methods for preparing 1-bromoethyl acetate mainly include:
[0004] (1) Addition of vinyl acetate with hydrogen bromide:
[0005] This is the most classic route. However, this method usually requires the use of Lewis acids (such as ferric chloride, aluminum chloride, etc.) as catalysts, which has problems such as difficulty in catalyst recovery, equipment corrosion, and the generation of large amounts of saline wastewater. It is not environmentally friendly, and the purity of the product is not easy to control, often accompanied by byproducts such as dibromodimethylamine.
[0006] (2) Esterification of 1-bromoethanol:
[0007] Esterification is carried out using 1-bromoethanol and acetic anhydride (or acetyl chloride) as raw materials. This route is relatively complicated. 1-bromoethanol itself is unstable and easily decomposes. Furthermore, the esterification process may trigger elimination or substitution side reactions of bromine, resulting in low yields.
[0008] (3) Other methods:
[0009] For example, brominating reagents such as N-bromosuccinimide (NBS) can be used, but these reagents are expensive and can only be used for small-scale preparation in the laboratory, making it difficult to achieve industrial production.
[0010] Existing technologies generally suffer from problems such as significant environmental pollution, poor atom economy, low reaction selectivity, poor product purity, or high production costs. Therefore, developing a new method with mild reaction conditions, simple operation, environmental friendliness, high yield, and suitability for industrial production has important practical significance and economic value. Summary of the Invention
[0011] In view of this, the object of the present invention is to provide a method for preparing 1-bromoethyl acetate that is simple to operate, has mild reaction conditions, good selectivity, high yield, low waste, and low cost. To achieve the above object, the present invention provides the following technical solution:
[0012] A method for preparing 1-bromoethyl acetate includes the following steps:
[0013] (1) Add sodium bromide and catalyst to solvent, then add a mixture of vinyl acetate and oxidant solution dropwise, stir the reaction until vinyl acetate reacts completely, and obtain a solution containing 1-bromoethyl acetate;
[0014] (2) After the reaction is completed, the aqueous phase is separated and extracted with ethyl acetate to obtain the organic phase. The organic phase is washed successively with sodium thiosulfate aqueous solution, water, and saturated brine, and then dried with anhydrous sodium sulfate to remove water. The solvent is removed by filtration and vacuum distillation to obtain a colorless and transparent crude liquid.
[0015] (3) The crude product was distilled under reduced pressure to obtain a colorless and transparent liquid product, 1-bromoethyl acetate.
[0016] Preferably, the catalyst in step (1) is one or more of tetrabutylammonium bromide (TBAB), tetrabutylammonium bisulfate (TBAHS) or benzyltriethylammonium chloride (BTEAC).
[0017] Preferably, the oxidant in step (1) is one or more of hydrogen peroxide (H2O2), peracetic acid, or sodium hypochlorite (NaClO).
[0018] Preferably, the molar ratio of vinyl acetate, sodium bromide, oxidant and catalyst in step (1) is 1:1.0-1.5:1.0-1.5:0.05-0.2.
[0019] Preferably, the solvent in step (1) is one or more of water, ethyl acetate, dichloromethane, chloroform, 1,2-dichloroethane, or acetonitrile.
[0020] More preferably, the solvent in step (1) is a mixture of ethyl acetate and water, wherein the volume ratio of ethyl acetate to water is 1:1 to 5:1.
[0021] Preferably, the volume-to-mass ratio of the solvent to sodium bromide in step (1) is 50-100 mL: 12-15 g.
[0022] Preferably, the addition in step (1) is carried out at a rate of 8-9 g / h of vinyl acetate.
[0023] Preferably, the stirring reaction time in step (1) is 3-5 hours.
[0024] Preferably, the temperature of the stirring reaction in step (1) is 0°C to 50°C; more preferably, the temperature of the stirring reaction is 20°C to 30°C.
[0025] Compared with the prior art, the present invention has the following beneficial effects:
[0026] (1) High economic efficiency and environmental protection: This invention uses sodium bromide as the bromine source, which is widely available and inexpensive, replacing the highly toxic and volatile hydrogen bromide gas, as well as the more expensive N-bromosuccinimide (NBS). At the same time, it avoids the use of corrosive Lewis acid catalysts, reducing pollution from the source and conforming to the development direction of green chemistry.
[0027] (2) The reaction conditions are mild and the operation is safe and simple: The reaction of the present invention can be carried out smoothly at room temperature and pressure without the need for special pressurization or high temperature equipment. The equipment requirements are low and the operation is safe. It is very suitable for industrial scale-up production.
[0028] (3) High reaction selectivity, high yield and purity: By using a mild oxidant and a phase transfer catalyst, in-situ and controllable activation of bromide ions is achieved, avoiding the safety risks and side reactions caused by directly using high concentrations of Br2 or corrosive HBr. The system continuously provides low concentrations of active bromine species under mild conditions, which is conducive to achieving highly selective monobromination addition to vinyl acetate, effectively suppressing competing side reactions such as dibromination and elimination, resulting in strong reaction specificity, high yield of the target product (up to 85%), and good purity (up to 98%).
[0029] (4) Low cost: The main raw materials, such as sodium bromide and hydrogen peroxide, are bulk industrial products with low prices. The catalyst is used in small quantities and can be recycled, which significantly reduces production costs. Attached Figure Description
[0030] Figure 1 This is a flowchart of the preparation method of 1-bromoethyl acetate described in Example 1. Detailed Implementation
[0031] This invention provides a method for preparing 1-bromoethyl acetate (flowchart shown below). Figure 1 The steps are as follows:
[0032] (1) Add sodium bromide and catalyst to solvent, then add a mixture of vinyl acetate and oxidant solution dropwise, stir the reaction until vinyl acetate reacts completely, and obtain a solution containing 1-bromoethyl acetate;
[0033] (2) After the reaction is completed, the aqueous phase is separated and extracted with ethyl acetate to obtain the organic phase. The organic phase is washed successively with sodium thiosulfate aqueous solution, water, and saturated brine, and then dried with anhydrous sodium sulfate to remove water. The solvent is removed by filtration and vacuum distillation to obtain a colorless and transparent crude liquid.
[0034] (3) The crude product was distilled under reduced pressure to obtain a colorless and transparent liquid product, 1-bromoethyl acetate.
[0035] Preferably, the catalyst in step (1) is one or more of tetrabutylammonium bromide (TBAB), tetrabutylammonium bisulfate (TBAHS), or benzyltriethylammonium chloride (BTEAC). More preferably, the catalyst is tetrabutylammonium bromide (TBAB).
[0036] Preferably, the oxidant in step (1) is one or more of hydrogen peroxide (H2O2), peracetic acid, sodium hypochlorite (NaClO), or m-chloroperoxybenzoic acid (m-CPBA). In a specific embodiment of the present invention, the oxidant solution is a 30% (w / w) aqueous solution of hydrogen peroxide or an aqueous solution of sodium hypochlorite with an effective chlorine content of 10%.
[0037] More preferably, the oxidant is hydrogen peroxide.
[0038] Preferably, the molar ratio of vinyl acetate, sodium bromide, oxidant, and catalyst in step (1) is 1:1.0-1.5:1.0-1.5:0.05-0.2. More preferably, the molar ratio of vinyl acetate, sodium bromide, oxidant, and catalyst is 1:1.2:1.2:0.1.
[0039] Preferably, the solvent in step (1) is one or more of water, ethyl acetate, dichloromethane, chloroform, 1,2-dichloroethane, or acetonitrile.
[0040] More preferably, the solvent in step (1) is a mixture of ethyl acetate and water, wherein the volume ratio of ethyl acetate to water is 1:1 to 5:1.
[0041] Preferably, the volume-to-mass ratio of the solvent to sodium bromide in step (1) is 50-100 mL: 12-15 g.
[0042] Preferably, the addition in step (1) is carried out at a rate of 8-9 g / h of vinyl acetate.
[0043] Preferably, the stirring reaction time in step (1) is 3-5 hours.
[0044] Preferably, the temperature of the stirring reaction in step (1) is 0°C to 50°C; more preferably, the temperature of the stirring reaction is 20°C to 30°C.
[0045] In a specific embodiment of the present invention, gas chromatography (GC) is used to monitor whether vinyl acetate has reacted completely.
[0046] The present invention will be further described below with reference to the embodiments.
[0047] Example 1
[0048] A method for preparing 1-bromoethyl acetate, comprising the following steps:
[0049] (1) In a 250 mL three-necked flask equipped with a stirrer, thermometer and constant pressure dropping funnel, sodium bromide (12.36 g, 120 mmol) and the catalyst tetrabutylammonium bromide (3.22 g, 10 mmol) were added to a solvent (50 mL ethyl acetate and 25 mL purified water) and stirred until dissolved to obtain mixed solution A. Then, vinyl acetate (8.61 g, 100 mmol) and oxidant solution (30% hydrogen peroxide aqueous solution, 13.6 g, 120 mmol) were mixed to obtain mixed solution B. Mixed solution B was added dropwise to mixed solution A. The addition was completed in 1 hour. The reaction was stirred at 25 °C for 4 hours. Gas chromatography (GC) monitoring showed that the raw material vinyl acetate reacted completely to obtain a solution containing 1-bromoethyl acetate.
[0050] (2) Pour the solution containing 1-bromoethyl acetate into a separatory funnel, let it stand and separate the phases. Extract the aqueous phase twice with ethyl acetate (20 mL × 2). Combine the organic phases and wash them successively with 10% sodium thiosulfate aqueous solution (20 mL), water (20 mL), and saturated saline (20 mL). After washing, dry the organic phase with anhydrous sodium sulfate (7.1 g, 50 mmol) to remove water. Filter the solution and remove the solvents such as ethyl acetate by vacuum distillation at 55 °C and a vacuum degree of -0.098 MPa to obtain a colorless and transparent crude liquid.
[0051] (3) The crude product was subjected to vacuum distillation (the distillation vacuum was controlled at -0.098 MPa, the external temperature was 90 °C, and the fraction with a boiling range of 65-68 °C was collected) to obtain 15.2 g (91 mmol) of colorless and transparent liquid product 1-bromoethyl acetate. The purity was 99.1% and the molar yield based on vinyl acetate was 91.0% by gas chromatography (GC).
[0052] Example 2
[0053] A method for preparing 1-bromoethyl acetate, following the same steps as in Example 1, except that in Example 2, the catalyst tetrabutylammonium bromide (TBAB, 3.22 g, 10 mmol) was replaced with tetrabutylammonium hydrogen sulfate (TBAHS, 3.40 g, 10 mmol). 14.7 g (88 mmol) of 1-bromoethyl acetate was obtained, with a purity of 98.7% and a molar yield of 88.0% based on vinyl acetate, as determined by gas chromatography (GC).
[0054] Example 3
[0055] A method for preparing 1-bromoethyl acetate, following the same steps as in Example 1, except that in Example 3, the oxidant 30% hydrogen peroxide (13.6 g, 120 mmol) was replaced with an aqueous solution of sodium hypochlorite (43 ml, based on providing 120 mmol of available chlorine) with an available chlorine content of 10%. 13.8 g (83 mmol) of 1-bromoethyl acetate was obtained, and its purity was 98.2% by gas chromatography (GC), with a molar yield of 83.0% based on vinyl acetate.
[0056] Comparative Example 1
[0057] A method for preparing 1-bromoethyl acetate, the steps are the same as in Example 1, except that no phase transfer catalyst is added in Comparative Example 1.
[0058] After 8 hours of reaction, gas chromatography (GC) monitoring showed that a large amount of raw material remained unreacted. Post-processing yielded 6.5 g (39 mmol) of 1-bromoethyl acetate product with a GC purity of 95.0% and a molar yield of only 39.0%.
[0059] Comparative Example 2 (Traditional HBr Addition Method)
[0060] A method for preparing 1-bromoethyl acetate, comprising the following steps:
[0061] Under ice-water bath cooling, dry hydrogen bromide gas (120 mmol) was bubbled into a 50 mL solution of vinyl acetate (8.61 g, 100 mmol) in ethyl acetate. After bubbling, the ice bath was removed, and the mixture was stirred at room temperature for 2 hours. Post-treatment was performed as in steps (2) and (3) of Example 1. 13.1 g of a pale yellow liquid product was obtained. GC analysis showed that it contained approximately 3% dibromo byproducts, the purity of 1-bromoethyl acetate was 96.5%, and the molar yield was 76.1%.
[0062] Comparative Example 3
[0063] A method for preparing 1-bromoethyl acetate, the steps of which are the same as in Example 1, except that no oxidant is added in Comparative Example 3. 4.1 g (24.6 mmol) of the product 1-bromoethyl acetate was obtained, and the purity was 93.5% by gas chromatography (GC), with a molar yield of 24.6% based on vinyl acetate.
[0064] 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 1-bromoethyl acetate, characterized in that, Includes the following steps: (1) Add sodium bromide and catalyst to solvent, then add a mixture of vinyl acetate and oxidant solution dropwise, stir the reaction until vinyl acetate reacts completely, and obtain a solution containing 1-bromoethyl acetate; (2) After the reaction is completed, the aqueous phase is separated and extracted with ethyl acetate to obtain the organic phase. The organic phase is washed successively with sodium thiosulfate aqueous solution, water, and saturated brine, and then dried with anhydrous sodium sulfate to remove water. The solvent is removed by filtration and vacuum distillation to obtain a colorless and transparent crude liquid. (3) The crude product was distilled under reduced pressure to obtain a colorless and transparent liquid product, 1-bromoethyl acetate.
2. The method for preparing 1-bromoethyl acetate according to claim 1, characterized in that, The catalyst in step (1) is one or more of tetrabutylammonium bromide, tetrabutylammonium hydrogen sulfate or benzyltriethylammonium chloride.
3. The method for preparing 1-bromoethyl acetate according to claim 1, characterized in that, The oxidant in step (1) is one or more of hydrogen peroxide, peracetic acid, or sodium hypochlorite.
4. The method for preparing 1-bromoethyl acetate according to claim 1, characterized in that, The molar ratio of vinyl acetate, sodium bromide, oxidant and catalyst in step (1) is 1:1.0-1.5:1.0-1.5:0.05-0.
2.
5. The method for preparing 1-bromoethyl acetate according to claim 1, characterized in that, The solvent in step (1) is one or more of water, ethyl acetate, dichloromethane, chloroform, 1,2-dichloroethane, or acetonitrile.
6. The method for preparing 1-bromoethyl acetate according to claim 5, characterized in that, The solvent in step (1) is a mixture of ethyl acetate and water, wherein the volume ratio of ethyl acetate to water is 1:1-5:
1.
7. The method for preparing 1-bromoethyl acetate according to claim 1, characterized in that, The volume-to-mass ratio of the solvent to sodium bromide in step (1) is 50-100 mL: 12-15 g.
8. The method for preparing 1-bromoethyl acetate according to claim 1, characterized in that, The addition in step (1) is carried out at a rate of 8-9 g / h of vinyl acetate.
9. The method for preparing 1-bromoethyl acetate according to claim 1, characterized in that, The stirring reaction time in step (1) is 3-5 hours.
10. The method for preparing 1-bromoethyl acetate according to claim 1, characterized in that, The temperature of the stirring reaction in step (1) is from 0°C to 50°C.