Synthetic method of alpha-bromo-gamma-butyrolactone

Abstract

The invention provides a method for synthesizing alpha-bromo-gamma-butyrolactone, which comprises the following step: by using 1-propyl phosphoric anhydride or 1-butyl phosphoric anhydride as a catalyst, reacting a substrate gamma-butyrolactone with a bromination reagent to obtain the alpha-bromo-gamma-butyrolactone. According to the method, the used raw material gamma-butyrolactone is cheap and easy to obtain, the route is short, the operation is convenient, the finally obtained by-products are few and easy to treat and purify, and the product with higher purity can be obtained without rectification.

Description

Technical Field

[0001] This application relates to the field of organic chemical synthesis technology, and in particular to a novel synthetic route for α-bromo-γ-butyrolactone. Background Technology

[0002] α-Bromo-γ-Butyrolactone is an oxygen-containing five-membered heterocyclic compound with wide applications in industrial raw materials, pharmaceutical intermediates, pesticide intermediates, and new energy materials.

[0003] Currently, the main synthetic routes for α-bromo-γ-butyrolactone include those using γ-butyrolactone and 2,4-dibromobutyryl bromide as raw materials, bromine, hydrobromic acid, or N-bromosuccinimide (NBS) as brominating agents, and phosphorus tribromooxy, phosphorus trichloride, ferric chloride, or sulfur as catalysts, as well as biological methods utilizing fermentation with specific strains. For example, Paul A. Grieco et al. provided a method for synthesizing α-bromo-γ-butyrolactone in the literature *Trimet Hylsilylacetic Acid Dianion: Application to Organic Synthesis* [J]. JCSCHEM.COMM, 1975. Trimethylsilylacetic acid readily forms trimethylsilyl-γ-butyrolactone. This literature demonstrates the efficient synthesis of α-bromo-γ-butyrolactone from (trimethylsilyl)acetic acid and ethylene oxide catalyzed by lithium diisopropylamide. Arch. Pharm et al., in the literature *Synthese dihydroxylierter Diphenylethylamine iiber*, further explored this approach. α-Amino-γ-lactone, 241-249 (1982), reported detailed steps for the synthesis of dihydroxylated diphenylethylamine via the synthesis of α-amino-γ-lactone; Chinese patent application CN109232644A disclosed a method for the synthesis of glyphosate, in which α-bromo-γ-butyrolactone is an intermediate in the glyphosate synthesis process. This method discloses a synthesis method of α-bromo-γ-butyrolactone using γ-butyrolactone as a raw material, red phosphorus as a catalyst, and liquid bromine as bromine; Yuki Yamamoto et al., in the literature A Two-Phase Bromination Process Using Tetraalky Lammonium Hydroxide for the Practical Synthesis of αBromolactones from Lactones. Beilstein J.Org.Chem.2021,17:2906-2914 discloses a process route for synthesizing α-bromo-γ-butyrolactone from 2,4-dibromobutyric acid under the catalysis of tetra-n-butylammonium hydroxide; Chinese patent application CN114276317A discloses a method for preparing a photoresist resin monomer containing a lactone structure, and Example 1 in the specification discloses the process of preparing α-bromo-γ-butyrolactone using 1,4-butyrolactone as raw material, liquid bromine as brominating agent, and sulfur powder as catalyst; Chinese patent application CN114181177A discloses a novel method for producing α-bromo-γ-butyrolactone, wherein the bromine source is bromine or HBr, the raw material is butyrolactone, and the catalyst is any one of PCl3, FeCl3, FeCl2, CuBr, or FeBr2.

[0004] The existing production methods for synthesizing α-bromo-γ-butyrolactone suffer from low yield, high cost, and low purity. The products on the market mostly have a purity of 98%, making it difficult to achieve mass production. They are usually only available for sale at the kilogram level, with very few available at the hundred-kilogram or ton level. Summary of the Invention

[0005] To address the aforementioned technical problems, this application provides a novel method for synthesizing α-bromo-γ-butyrolactone.

[0006] This application involves the following:

[0007] 1. A method for synthesizing α-bromo-γ-butyrolactone, comprising the following steps:

[0008] The substrate γ-butyrolactone is reacted with a brominated reagent using 1-propylphosphoric anhydride or 1-butylphosphoric anhydride as a catalyst.

[0009] 2. The method according to item 1, wherein,

[0010] The γ-butyrolactone reacts with the brominated reagent at a given temperature for a period of time.

[0011] Preferably, the reaction temperature is 65-95°C, more preferably 80-90°C;

[0012] Preferably, the reaction time is 5-10 hours, more preferably 7-8 hours.

[0013] 3. The method according to item 1 or 2 further includes:

[0014] The crude α-bromo-γ-butyrolactone obtained by reacting the γ-butyrolactone with a brominating reagent was purified.

[0015] 4. The method according to item 3, wherein the purification includes phase separation, extraction of the aqueous phase, merging of the organic phases, and washing with water.

[0016] 5. The method according to item 1 or 2, wherein the molar ratio of the catalyst 1-propylphosphoric anhydride or 1-butylphosphoric anhydride to γ-butyrolactone is (0.05-0.1):1.

[0017] 6. The method according to item 1 or 2, wherein the molar ratio of the brominated reagent to γ-butyrolactone is (1.2-1.5):1.

[0018] 7. The method according to claim 1 or 2, wherein the brominating agent is selected from bromine, hydrobromic acid or N-bromosuccinimide.

[0019] 8. Use of 1-propylphosphoric anhydride or 1-butylphosphoric anhydride as catalysts.

[0020] 9. According to the use described in item 8, the catalyst is a catalyst for reacting the substrate γ-butyrolactone with a brominated reagent to obtain α-bromo-γ-butyrolactone.

[0021] Invention effects:

[0022] The raw material γ-butyrolactone used in this application is readily available and inexpensive on the market;

[0023] The method described in this application has a short route, is easy to operate, and is conducive to industrial production;

[0024] The method described in this application yields few byproducts, is easy to process and purify, and can produce a high-purity product without distillation. Attached Figure Description

[0025] Figure 1 The image shows a gas chromatogram of α-bromo-γ-butyrolactone, the product prepared in Example 1.

[0026] Figure 2 The NMR spectrum of α-bromo-γ-butyrolactone, the product prepared in Example 1.

[0027] Figure 3 The image shows a gas chromatogram of α-bromo-γ-butyrolactone, the product prepared in Example 2.

[0028] Figure 4 The NMR spectrum of α-bromo-γ-butyrolactone, the product prepared in Example 2.

[0029] Figure 5 The image shows a gas chromatogram of α-bromo-γ-butyrolactone, the product prepared in Example 3.

[0030] Figure 6 The NMR spectrum of α-bromo-γ-butyrolactone, the product prepared in Example 3.

[0031] Figure 7 The gas chromatogram of α-bromo-γ-butyrolactone, the product prepared in Example 4.

[0032] Figure 8 The NMR spectrum of α-bromo-γ-butyrolactone, the product prepared in Example 4.

[0033] Figure 9 The gas chromatogram of α-bromo-γ-butyrolactone, the product prepared in Example 5.

[0034] Figure 10 The NMR spectrum of α-bromo-γ-butyrolactone, the product prepared in Example 5. Detailed Implementation

[0035] The following description provides exemplary embodiments of this application, including various details to aid understanding, and should be considered merely exemplary. Therefore, those skilled in the art will recognize that various changes and modifications can be made to the embodiments described herein without departing from the scope and spirit of this application. Similarly, for clarity and brevity, descriptions of well-known functions and structures are omitted in the following description.

[0036] In this application, T3P refers to 1-propylphosphoric anhydride; T4P refers to 1-butylphosphoric anhydride; and NBS refers to N-bromosuccinimide.

[0037] This application provides a method for synthesizing α-bromo-γ-butyrolactone, comprising the following steps: using 1-propylphosphoric anhydride (T3P) or 1-butylphosphoric anhydride (T4P) as a catalyst, reacting the substrate γ-butyrolactone with a brominating reagent to obtain α-bromo-γ-butyrolactone.

[0038] In this application, the γ-butyrolactone reacts with the brominated reagent at a given temperature for a period of time, wherein the temperature is 65-95°C and the time is 5-10 hours.

[0039] 65-95℃ means any temperature between 65℃ and 95℃. For example, the reaction temperature is 65℃, 66℃, 67℃, 68℃, 69℃, 70℃, 71℃, 72℃, 73℃, 74℃, 75℃, 76℃, 77℃, 78℃, 79℃, 80℃, 81℃, 82℃, 83℃, 84℃, 85℃, 86℃, 87℃, 88℃, 89℃, 90℃, 91℃, 92℃, 93℃, 94℃, or 95℃.

[0040] 5-10h means any time between 5h and 10h, for example, the reaction time is 5h, 6h, 7h, 8h, 9h, or 10h.

[0041] In some embodiments, the reaction temperature is 80-90°C.

[0042] In some implementations, the reaction time is 7-8 hours.

[0043] In this application, after the reaction of the γ-butyrolactone with the brominated reagent is completed at a given temperature, the crude α-bromo-γ-butyrolactone product is then purified.

[0044] In this application, the purification is a purification method known in the art, such as extraction, washing with water, column separation, etc.

[0045] In this application, the purification preferably includes phase separation, extraction of the aqueous phase, merging of the organic phases, and washing with water.

[0046] In this application, no limitations are made on the reagents and methods used in the purification process of crude α-bromo-γ-butyrolactone. The process can be carried out in accordance with techniques known to those skilled in the art. For example, the extractant can be dichloromethane, ethyl acetate, toluene, chloroform, etc.

[0047] In some embodiments, dichloromethane is used as the extractant to extract the aqueous phase, the organic phases are combined, washed with water, and then concentrated to remove the dichloromethane, yielding purified α-bromo-γ-butyrolactone.

[0048] In this application, the molar ratio of the catalyst 1-propylphosphoric anhydride (T3P) or 1-butylphosphoric anhydride (T4P) to γ-butyrolactone is (0.05-0.1):1.

[0049] For example, the molar ratio of 1-propylphosphoric anhydride (T3P) or 1-butylphosphoric anhydride (T4P) to γ-butyrolactone is 0.05:1, 0.06:1, 0.07:1, 0.08:1, 0.09:1 or 0.1:1.

[0050] In some embodiments, the molar ratio of the catalyst 1-propylphosphoric anhydride (T3P) to γ-butyrolactone is 0.05:1 or 0.1:1.

[0051] In some embodiments, the molar ratio of the catalyst 1-butylphosphoanhydride (T4P) to γ-butyrolactone is 0.05:1 or 0.1:1.

[0052] In this application, the molar ratio of the brominated reagent to γ-butyrolactone is (1.2-1.5):1.

[0053] For example, the molar ratio of the brominated reagent to γ-butyrolactone is 1.2:1, 1.3:1, 1.4:1, or 1.5:1.

[0054] In this application, the brominating agent is selected from one of bromine, hydrobromic acid, or N-bromosuccinimide (NBS).

[0055] In some embodiments, the molar ratio of bromine to γ-butyrolactone is 1.2:1 or 1.5:1.

[0056] This application provides the use of 1-propylphosphoric anhydride (T3P) or 1-butylphosphoric anhydride (T4P) as a catalyst.

[0057] In this application, the catalyst 1-propylphosphoric anhydride (T3P) or 1-butylphosphoric anhydride (T4P) is used to react the substrate γ-butyrolactone with a brominating agent to obtain α-bromo-γ-butyrolactone.

[0058] Example

[0059] This application provides a general and / or specific description of the materials and test methods used in the experiments. In the following examples, unless otherwise specified, % represents wt%, i.e., weight percentage. Reagents or instruments used, unless otherwise specified, are all commercially available conventional reagent products.

[0060] Example 1: 86.1g of γ-butyrolactone was added to the reaction system, followed by 15.9g of T3P (1-propylphosphonic anhydride). The system was heated to 85±5℃, and then 195g of bromine was slowly added dropwise (over 3-4 hours). After the addition was complete, the reaction was maintained at this temperature for 7-8 hours. The gas phase analysis showed that the raw materials were qualified, and then post-processing was performed.

[0061] Post-processing included: cooling the system to room temperature; to remove excess bromine, adding 430g of 5% sodium sulfite solution to the product and stirring for 1 hour for phase separation; extracting the aqueous phase with 100g of dichloromethane; combining the organic phases; washing twice with 150g of water; initial recovery and reuse under normal pressure (45-50℃); subsequent concentration under reduced pressure (vacuum degree not lower than -0.095MPa) and controlled temperature (35-45℃) to remove dichloromethane, finally yielding 140g of light brown liquid with a purity of 99.3% and a yield of 85.0%. Gas phase purity analysis is shown in [reference needed]. Figure 1 See the NMR spectrum. Figure 2 Product NMR data: 1 H NMR (400MHz, CDCl3-d): δ2.47-2.52 (m, 1H), δ2.80-2.82 (m, 1H), δ4.40-4.43 (m, 2H), δ4.44-4.53 (m, 1H).

[0062] Example 2: 86.1g of γ-butyrolactone was added to the reaction system, followed by 31.8g of T3P (1-propylphosphonic anhydride). The system was heated to 85±5℃, and then 195g of bromine was slowly added dropwise (over 3-4 hours). After the addition was complete, the reaction was maintained at this temperature for 7-8 hours. The gas phase analysis showed that the raw materials were qualified, and then post-processing was performed.

[0063] The post-processing method was the same as in Example 1, ultimately yielding 135.3 g of light brown liquid with a purity of 98.9% and a yield of 82.0%. The purity was determined by gas chromatography (GC). Figure 3 See the NMR spectrum. Figure 4 Product NMR data: 1 H NMR (400MHz, CDCl3-d): δ2.47-2.54 (m, 1H), δ2.77-2.86 (m, 1H), δ4.41-4.44 (m, 2H), δ4.45-4.55 (m, 1H).

[0064] Example 3: 86.1g of γ-butyrolactone was added to the reaction system, followed by 15.9g of T3P (1-propylphosphonic anhydride). The system was heated to 85±5℃, and then 235g of bromine was slowly added dropwise (over 3-4 hours). After the addition was complete, the reaction was maintained at this temperature for 7-8 hours. The gas phase analysis showed that the raw materials were qualified, and then post-processing was performed.

[0065] The post-processing method was the same as in Example 1, ultimately yielding 138.3g of light brown liquid with a purity of 98.3% and a yield of 83.8%. The purity was determined by gas chromatography (GC). Figure 5 See the NMR spectrum. Figure 6 Product NMR data: 1 H NMR (400MHz, CDCl3-d): δ2.45-2.52 (m, 1H), δ2.78-2.86 (m, 1H), δ4.39-4.44 (m, 2H), δ4.45-4.52 (m, 1H).

[0066] Example 4: 86.1g of γ-butyrolactone was added to the reaction system, followed by 18g of T4P (1-butylphosphine anhydride). The system was heated to 85±5℃, and then 195g of bromine was slowly added dropwise (over 3-4 hours). After the addition was complete, the reaction was maintained at this temperature for 7-8 hours. The gas phase analysis showed that the raw materials were qualified, and then post-processing was performed.

[0067] The post-processing method was the same as in Example 1. A final yield of 137g of light brown liquid was obtained, with a purity of 98.9% and a yield of 83.0%. The purity was determined by gas chromatography (GC). Figure 7 See the NMR spectrum. Figure 8 Product NMR data: 1 H NMR (400MHz, CDCl3-d): δ2.43-2.50 (m, 1H), δ2.75-2.85 (m, 1H), δ4.38-4.42 (m, 2H), δ4.43-4.50 (m, 1H).

[0068] Example 5: 86.1g of γ-butyrolactone was added to the reaction system, followed by 36g of T4P (1-butylphosphine anhydride). The system was heated to 85±5℃, and then 195g of bromine was slowly added dropwise (over 3-4 hours). After the addition was complete, the reaction was maintained at this temperature for 7-8 hours. The gas phase analysis showed that the raw materials were qualified, and then post-processing was performed.

[0069] The post-processing method was the same as in Example 1, ultimately yielding 136g of light brown liquid with a purity of 98.7% and a yield of 82.4%. The purity was determined by gas chromatography (GC). Figure 9 See the NMR spectrum. Figure 10 Product NMR data: 1H NMR (400MHz, CDCl3-d): δ2.47-2.53 (m, 1H), δ2.78-2.82 (m, 1H), δ4.41-4.43 (m, 2H), δ4.50-4.52 (m, 1H).

[0070] Comparative Example 1: 86.1g of γ-butyrolactone was added to the reaction system, followed by 25.9g of phosphorus tribromide. The system was heated to 85±5℃, and then 195g of bromine was slowly added dropwise (over 3-4 hours). After the addition was complete, the reaction was maintained at this temperature for 7-8 hours. The gas phase analysis showed that the raw materials were qualified, and then post-processing was performed.

[0071] The post-processing included: cooling the system to room temperature; adding 430g of 5% sodium sulfite solution to the product and stirring for 1 hour to remove excess bromine; separating the phases; extracting the aqueous phase with 100g of dichloromethane; combining the organic phases; washing twice with 150g of water; recovering and reusing the product under normal pressure (45-50℃) in the early stage; and then reducing the pressure (vacuum degree not lower than -0.095MPa) and controlling the temperature at 35-45℃ to concentrate and remove dichloromethane, finally yielding 132g of light brown liquid with a purity of 98.3% and a yield of 80.0%.

[0072] Comparative Example 2: 86.1g of γ-butyrolactone was added to the reaction system, followed by 13.2g of phosphorus trichloride. The system was heated to 85±5℃, and then 195g of bromine was slowly added dropwise (over 3-4 hours). After the addition was complete, the reaction was maintained at this temperature for 7-8 hours. The gas phase analysis showed that the raw materials were qualified, and then post-processing was performed.

[0073] The post-processing method was the same as that of Comparative Example 1, and 128g of light brown liquid with a purity of 98.5% and a yield of 78.0% was finally obtained.

[0074] In summary, as can be seen from Examples 1-5 and Comparative Examples 1-2, the method for synthesizing α-bromo-γ-butyrolactone provided in this application uses 1-propylphosphoric anhydride (T3P) or 1-butylphosphoric anhydride (T4P) as a catalyst to react the substrate γ-butyrolactone with a brominating reagent to obtain α-bromo-γ-butyrolactone. The final product has high purity and high yield, making it suitable for large-scale industrial production.

[0075] The description in this disclosure is provided for illustrative and descriptive purposes only and is not intended to be exhaustive or to limit the disclosure to its forms. Many modifications and variations will be apparent to those skilled in the art. The embodiments were chosen and described in order to better illustrate the principles and practical application of this disclosure and to enable those skilled in the art to understand this disclosure and to design various embodiments with various modifications suitable for a particular purpose.

Claims

1. A method for synthesizing α-bromo-γ-butyrolactone, wherein, Includes the following steps: The substrate γ-butyrolactone is reacted with a brominated reagent using 1-propylphosphoric anhydride or 1-butylphosphoric anhydride as a catalyst.

2. The method according to claim 1, wherein, The γ-butyrolactone reacts with the brominated reagent at a given temperature for a period of time. The reaction temperature is 65-95℃, preferably 80-90℃; The reaction time is 5-10 hours, preferably 7-8 hours.

3. The method according to claim 1 or 2, further comprising: The crude α-bromo-γ-butyrolactone obtained by reacting the γ-butyrolactone with a brominating reagent was purified.

4. The method according to claim 3, wherein, The purification process includes phase separation, extraction of the aqueous phase, merging of the organic phases, and washing with water.

5. The method according to claim 1 or 2, wherein, The molar ratio of the catalyst 1-propylphosphoric anhydride or 1-butylphosphoric anhydride to γ-butyrolactone is (0.05-0.1):

1.

6. The method according to claim 1 or 2, wherein, The molar ratio of the brominated reagent to γ-butyrolactone is (1.2-1.5):

1.

7. The method according to claim 1 or 2, wherein, The brominating reagent is selected from bromine, hydrobromic acid, or N-bromosuccinimide.

8. Use of 1-propylphosphoric anhydride or 1-butylphosphoric anhydride as catalysts.

9. The use according to claim 8, wherein the catalyst is a catalyst for reacting the substrate γ-butyrolactone with a brominated reagent to obtain α-bromo-γ-butyrolactone.

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