Synthesis method of N-phenyl-N-benzyl-alanine acetone ester
By employing inorganic base catalysis and phase transfer catalysts, the problems of expensive raw materials and complex reactions in the production of N-phenyl-N-benzyl-alanine acetone ester have been solved, achieving a highly efficient and environmentally friendly synthesis process with significantly improved product yield and purity.
Patent Information
- Application Number
- CN202511751178.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-11-26
- Publication Date
- 2026-01-13
AI Technical Summary
The existing production process for N-phenyl-N-benzyl-alanine acetone ester is characterized by high raw material prices, harsh reaction conditions, and numerous side reactions, resulting in high production costs and severe environmental pollution.
N-phenyl-N-benzyl-alanine acetone ester was synthesized in a one-pot process using an inorganic base-catalyzed substitution reaction and a phase transfer catalyst. Benzyl chloride and chloroacetone were used as raw materials, avoiding the use of expensive bromoacetone and potassium iodide, thus simplifying the reaction process.
It improves product yield and purity, reduces raw material costs, simplifies reaction steps, reduces environmental pollution, increases product yield by more than 15%, and achieves purity of more than 99%.
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Abstract
Description
Technical Field
[0001] This invention relates to the field of chemical synthesis technology, and in particular to a method for synthesizing N-phenyl-N-benzyl-alanine acetone ester. Background Technology
[0002] Electroluminescence (EL) refers to the phenomenon where a luminescent material emits light when excited by an electric field and subjected to current and voltage. It is a process that directly converts electrical energy into light energy. Organic electroluminescent devices utilizing organic electroluminescence typically have a structure with a positive electrode, a negative electrode, and an organic layer between them. Organic electroluminescent devices (OLEDs) based on organic electroluminescence have wide applications in various fields due to their characteristics such as ultra-thinness, all-solidification, self-emissiveness, fast response speed, good temperature characteristics, and the ability to achieve flexible displays.
[0003] The luminescent properties of luminescent materials are closely related to the carrier injection and transport materials, luminescent materials, electrode materials, and device structure used in the device. Luminescent materials are considered the core components of OLED devices. N-phenyl-N-benzyl-alanine acetone ester is a novel intermediate for luminescent materials, with applications in liquid crystal materials, novel inks, and environmentally friendly dyes, showing broad market prospects.
[0004] The existing process for producing N-phenyl-N-benzyl-alanine acetone ester involves the condensation reaction of N-phenylalanine with benzyl chloride to obtain N-phenyl-N-benzylalanine, which is then reacted with bromoacetone under potassium iodide catalysis to yield the target product, N-phenyl-N-benzyl-alanine acetone ester. However, this method has significant drawbacks: bromoacetone and potassium iodide are expensive, leading to high production costs; the reaction conditions are demanding, resulting in numerous side reactions and low yields, further impacting production costs; and the byproducts cause environmental pollution. Therefore, a better method for synthesizing N-phenyl-N-benzyl-alanine acetone ester is needed. Summary of the Invention
[0005] To address the shortcomings of existing technologies, this invention provides a method for synthesizing N-phenyl-N-benzyl-alanine acetone ester, which solves the problems of high raw material prices, harsh reaction conditions, numerous side reactions leading to high production costs and environmental pollution in existing technologies.
[0006] According to an embodiment of the present invention, a method for synthesizing N-phenyl-N-benzyl-alanine acetone ester includes the following steps: Using N-phenylalanine and benzyl chloride as raw materials, a substitution reaction was carried out under the catalysis of an inorganic base to obtain the intermediate product N-phenyl-N-benzylalanine sodium salt. Then, the intermediate product was reacted with chloroacetone under the action of a phase transfer catalyst to obtain N-phenyl-N-benzylalanine acetone ester product. The reaction formula is as follows: (1) In formula (1), the compounds from left to right are the raw material N-phenylalanine, benzyl chloride and the intermediate product sodium N-phenyl-N-benzylalanine; (2) In formula (2), the compounds from left to right are the intermediate product sodium N-phenyl-N-benzylalanine, the raw material chloroacetone, and the sodium N-phenyl-N-benzylalanine product.
[0007] Preferably, the inorganic base includes a mixture of sodium carbonate and sodium hydroxide or a mixture of sodium bicarbonate and sodium hydroxide.
[0008] Preferably, the phase transfer catalyst comprises one of tetrabutylammonium bromide, tetramethylammonium chloride, or trimethylbenzylammonium bromide.
[0009] Furthermore, the synthesis method specifically includes the following steps: S1. Add the raw material N-phenylalanine and benzyl chloride to the reaction vessel, add solvent to completely dissolve the raw material, and then add an inorganic base, which is a mixture of sodium carbonate and sodium hydroxide or a mixture of sodium bicarbonate and sodium hydroxide. React at room temperature for 4 to 6 hours, and then heat to 90 to 110°C to dehydrate and obtain the intermediate product N-phenyl-N-benzylalanine sodium salt. S2. Cool the material in the reaction vessel to 60~75℃, add a phase transfer catalyst to the reaction system, and then add chloroacetone dropwise while stirring. Control the dropping rate so that the dropping time lasts for 2~4 hours. After the dropping is complete, keep the reaction at the temperature for 2~4 hours and then stop the reaction. Filter out the solid and evaporate the solvent to obtain N-phenyl-N-benzyl-alanine acetone ester product.
[0010] Furthermore, in step S1, after the reaction is completed at room temperature, 80%-88% of the amount of raw material sodium carbonate or sodium bicarbonate is added first, and then the temperature is raised for dehydration.
[0011] Preferably, the solvent includes one of toluene, xylene, and cyclohexane.
[0012] Preferably, in step S1, the molar ratio of the added N-phenylalanine, benzyl chloride raw material, and sodium carbonate or sodium bicarbonate in the inorganic base is 1:1~1.02:1.25~1.75.
[0013] Preferably, the molar ratio of sodium carbonate or sodium bicarbonate to sodium hydroxide in the inorganic alkali is 1~1.4:0.05-0.08.
[0014] Preferably, in step S2, the mass / molar ratio of the added phase transfer catalyst to the raw material N-phenylalanine is 1 g / mol.
[0015] Preferably, in step S2, the molar ratio of the added chloroacetone to the raw material N-phenylalanine is 1.
[0016] The technical principle of this invention is as follows: This invention incorporates an inorganic base and a base into the condensation reaction, creating an alkaline reaction environment. This results in a higher concentration of chloride ions, facilitating the formation and release of HCl, thus increasing the rate and extent of the condensation reaction and consequently increasing the content of N-phenyl-N-benzylalanine sodium salt. Subsequently, this invention prepares N-phenyl-N-benzyl-alanine acetone ester by reacting N-phenyl-N-benzylalanine sodium salt with chloroacetone. Because the sodium in N-phenyl-N-benzylalanine sodium salt is more easily separated as an ion, exposing the highly polar carbonyl group as the reaction terminus, it eliminates the need for bromoacetone, which has higher chemiselectivity, as a raw material. Furthermore, considering the stronger electron-withdrawing properties of the chloride group, potassium iodide is not required as a catalyst, thereby reducing the required reaction conditions and avoiding potential side reactions that may occur during the substitution process of bromoacetone.
[0017] Compared with the prior art, the present invention has the following beneficial effects: 1. In this invention, all reactions are carried out in the same reaction vessel, which is called "one-pot" synthesis. This eliminates the steps of separating intermediate products and transferring reaction vessels in traditional processes, thereby simplifying the reaction process, improving reaction efficiency, reducing product waste, and increasing product yield and content. The total molar yield is increased by more than 15% compared with the traditional method, and the content is increased from 92% to more than 99%. 2. In this invention, inexpensive chloroacetone is used as a raw material to replace the original expensive bromoacetone, thereby significantly reducing raw material costs and improving economic efficiency. Detailed Implementation
[0018] The technical solutions of the present invention will be further described below with reference to the embodiments.
[0019] Example 1: In this embodiment, N-phenyl-N-benzyl-alanine acetone ester was prepared using the following steps: S1: 0.2 mol of N-phenylalanine and 0.2 mol of benzyl chloride were added to a reaction vessel, and toluene was added as solvent to completely dissolve the raw materials. An inorganic base, including 0.25 mol of sodium carbonate and 0.5 g of sodium hydroxide, was added at room temperature (25°C). The reaction was carried out for 4 hours. HPLC analysis showed that N-phenylalanine was <0.5%. Then, 0.22 mol of sodium carbonate was added, and the temperature was raised to 90°C to dehydrate and obtain the intermediate product, sodium N-phenyl-N-benzylalanine.
[0020] S2: Cool the material in the reactor to 60℃, add 0.2g of phase transfer catalyst tetrabutylammonium bromide to the reaction system, and add 0.2mol of chloroacetone dropwise over 2 hours. After the addition is complete, maintain the reaction temperature for 2 hours. After HPLC detection shows that the intermediate product N-phenyl-N-benzylalanine sodium salt is <0.5%, stop the reaction, filter out the solid, and evaporate the solvent to obtain the product N-phenyl-N-benzylalanine acetone ester. The total molar yield of N-phenyl-N-benzylalanine acetone ester was 96.5%, and the HPLC purity was 99.2%.
[0021] Example 2: In this embodiment, N-phenyl-N-benzyl-alanine acetone ester was prepared using the following steps: S1: 0.2 mol of N-phenylalanine and 0.204 mol of benzyl chloride were added to a reaction vessel, and xylene was added as solvent to completely dissolve the raw materials. An inorganic base, including 0.35 mol of sodium bicarbonate and 0.8 g of sodium hydroxide, was added at room temperature (35°C). The reaction was carried out for 6 hours. HPLC analysis showed that N-phenylalanine was <0.5%. Then, 0.28 mol of sodium bicarbonate was added, and the temperature was raised to 110°C to dehydrate and obtain the intermediate product, sodium N-phenyl-N-benzylalanine.
[0022] S2: Cool the material in the reactor to 75℃, add 0.2g of the phase transfer catalyst tetramethylammonium chloride to the reaction system, and add 0.2mol of chloroacetone dropwise over 4 hours. After the addition is complete, maintain the reaction temperature for 4 hours. After HPLC detection shows that the intermediate product N-phenyl-N-benzylalanine sodium salt is <0.5%, stop the reaction, filter out the solid, and evaporate the solvent to obtain the product N-phenyl-N-benzylalanine acetone ester. The total molar yield of N-phenyl-N-benzylalanine acetone ester was 96.7%, and the HPLC purity was 99.4%.
[0023] Example 3: In this embodiment, N-phenyl-N-benzyl-alanine acetone ester was prepared using the following steps: S1: 0.2 mol of N-phenylalanine and 0.202 mol of benzyl chloride were added to a reaction vessel, and cyclohexane was added to completely dissolve the raw materials. An inorganic base, including 0.3 mol of sodium carbonate and 0.65 g of sodium hydroxide, was added at room temperature (30°C). The reaction was carried out for 5 hours. HPLC analysis showed that N-phenylalanine was <0.5%. Then, 0.25 mol of sodium carbonate was added, and the temperature was raised to 100°C to dehydrate and obtain the intermediate product, sodium N-phenyl-N-benzylalanine.
[0024] S2: Cool the material in the reactor to 68℃, add 0.2g of the phase transfer catalyst trimethylbenzylammonium bromide to the reaction system, and add 0.2mol of chloroacetone dropwise over 3 hours. After the addition is complete, maintain the reaction temperature for 3 hours. After HPLC detection shows that the intermediate product N-phenyl-N-benzylalanine sodium salt is <0.5%, stop the reaction, filter out the solid, and evaporate the solvent to obtain the product N-phenyl-N-benzyl-alanine acetone ester. The total molar yield of N-phenyl-N-benzyl-alanine acetone ester was 96.4%, and the HPLC purity was 99.2%.
[0025] Example 4: In this embodiment, N-phenyl-N-benzyl-alanine acetone ester was prepared using the following steps: S1: 0.2 mol of N-phenylalanine and 0.201 mol of benzyl chloride were added to a reaction vessel, and cyclohexane was added to completely dissolve the raw materials. An inorganic base, including 0.28 mol of sodium bicarbonate and 0.6 g of sodium hydroxide, was added at room temperature (27°C). The reaction was carried out for 4.5 hours. HPLC analysis showed that N-phenylalanine was <0.5%. Then, 0.24 mol of sodium bicarbonate was added, and the temperature was raised to 96°C to dehydrate and obtain the intermediate product, sodium N-phenyl-N-benzylalanine.
[0026] S2: Cool the material in the reactor to 65℃, add 0.2g of the phase transfer catalyst trimethylbenzylammonium bromide to the reaction system, and add 0.2mol of chloroacetone dropwise over 2.5 hours. After the addition is complete, maintain the reaction temperature for 2.5 hours. After HPLC detection shows that the intermediate product N-phenyl-N-benzylalanine sodium salt is <0.5%, stop the reaction, filter out the solid, and evaporate the solvent to obtain the product N-phenyl-N-benzyl-alanine acetone ester. The total molar yield of N-phenyl-N-benzyl-alanine acetone ester was 96.8%, and the HPLC purity was 99.4%.
[0027] Example 5: In this embodiment, N-phenyl-N-benzyl-alanine acetone ester was prepared using the following steps: S1: 0.2 mol of N-phenylalanine and 0.203 mol of benzyl chloride were added to a reaction vessel, and xylene was added to completely dissolve the raw materials. An inorganic base, including 0.33 mol of sodium carbonate and 0.7 g of sodium hydroxide, was added at room temperature (32°C). The reaction was carried out for 5.5 hours. HPLC analysis showed that N-phenylalanine was <0.5%. Then, 0.27 mol of sodium carbonate was added, and the temperature was raised to 108°C to dehydrate and obtain the intermediate product, sodium N-phenyl-N-benzylalanine.
[0028] S2: Cool the material in the reactor to 72℃, add 0.2g of the phase transfer catalyst tetrabutylammonium bromide to the reaction system, and add 0.2mol of chloroacetone dropwise over 3.5 hours. After the addition is complete, maintain the reaction temperature for 3.5 hours. After HPLC detection shows that the intermediate product N-phenyl-N-benzylalanine sodium salt is <0.5%, stop the reaction, filter out the solid, and evaporate the solvent to obtain the product N-phenyl-N-benzylalanine acetone ester. The total molar yield of N-phenyl-N-benzylalanine acetone ester was 96.3%, and the HPLC purity was 99.2%.
[0029] Comparative Example 1: The rest of the components in this embodiment are the same as in Example 1, except that the inorganic base includes 0.25 mol sodium carbonate and 1.5 g sodium hydroxide.
[0030] Comparative Example 2: The rest of the components in this embodiment are the same as in Example 1, except that the inorganic base includes 0.28 mol sodium bicarbonate and 1.75 g sodium hydroxide.
[0031] Comparative Example 3: The rest of the parts in this embodiment are the same as in embodiment 1, except that the temperature inside the reactor in step S2 is 82°C.
[0032] Comparative Example 4: The rest of the parts in this embodiment are the same as in embodiment 1, except that the temperature inside the reactor in step S2 is 95°C.
[0033] The N-phenyl-N-benzyl-alanine acetone ester products produced in Comparative Examples 1-4 were collected and analyzed, and compared with those in Examples 1-5. The results are shown in Table 1.
[0034]
[0035] Table 1 As shown in Table 1, when sodium hydroxide is in excess in the inorganic base, the product yield and HPLC column content (i.e., mass) decrease significantly; furthermore, when the reaction temperature in step S2 exceeds 75°C, the product yield and HPLC column content (i.e., mass) decrease even more drastically. This fully demonstrates that the present invention requires extensive and inventive experimentation under specific reaction conditions to achieve the desired technical effects.
[0036] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all such modifications or substitutions should be covered within the scope of the claims of the present invention.
Claims
1. A process for the synthesis of N-phenyl-N-benzyl-alanine propio- nitrile, characterized in that, The method comprises the following steps: The intermediate product N-phenyl-N-benzyl alanine sodium salt is obtained by substitution reaction of N-phenylalanine and benzyl chloride under the catalysis of inorganic base, and then the intermediate product is reacted with chloroacetone under the action of phase transfer catalyst to obtain N-phenyl-N-benzyl alanine acetone ester product; The reaction formula is as follows: （1） In formula (1), the compounds from left to right are raw material N-phenylalanine, benzyl chloride and intermediate product N-phenyl-N-benzyl alanine sodium salt; （2） In formula (2), the compounds from left to right are intermediate product N-phenyl-N-benzyl alanine sodium salt, raw material chloroacetone and N-phenyl-N-benzyl alanine sodium salt product.
2. A process for the synthesis of N-phenyl-N-benzyl-alanine propio- nitrile as claimed in claim 1, wherein: The inorganic base comprises a mixture of sodium carbonate and sodium hydroxide or a mixture of sodium bicarbonate and sodium hydroxide.
3. A process for the synthesis of N-phenyl-N-benzyl-alanine propenoyl ester as claimed in claim 1, wherein: The phase transfer catalyst comprises one of tetrabutylammonium bromide, tetramethylammonium chloride or trimethylbenzylammonium bromide.
4. The process for the synthesis of N-phenyl-N-benzyl-alanine propio- nitrile according to claim 1, characterized in that, The method comprises the following steps: S1, the raw material N-phenylalanine and benzyl chloride are added to a reaction container, a solvent is added to dissolve the raw material completely, then an inorganic base is added, the inorganic base is a mixture of sodium carbonate and sodium hydroxide or a mixture of sodium bicarbonate and sodium hydroxide, the reaction is carried out at room temperature for 4-6 hours, then the temperature is increased to 90-110 DEG C for dehydration to obtain the intermediate product N-phenyl-N-benzyl alanine sodium salt; S2, the material in the reaction container is cooled to 60-75 DEG C, a phase transfer catalyst is added to the reaction system, then chloroacetone is added dropwise while stirring, the dropwise adding speed is controlled to make the dropwise adding time last for 2-4 hours, after the dropwise adding is completed, the reaction is carried out for 2-4 hours, then the reaction is stopped, the solid is filtered out, and the solvent is evaporated to obtain N-phenyl-N-benzyl alanine acetone ester product.
5. A process for the synthesis of N-phenyl-N-benzyl-alanine propenoyl ester as claimed in claim 4, wherein: In step S1, after the reaction at room temperature is completed, 80%-88% of the amount of sodium carbonate or sodium bicarbonate of the raw material is added, and then the temperature is increased for dehydration.
6. A process for the synthesis of N-phenyl-N-benzyl-alanine propenoyl ester as claimed in claim 4, wherein: The solvent comprises one of toluene, xylene and cyclohexane.
7. A process for the synthesis of N-phenyl-N-benzyl-alanine propio- nitrile as claimed in claim 4, wherein: In step S1, the mass amount ratio of the added N-phenylalanine, benzyl chloride raw material and inorganic base sodium carbonate or sodium bicarbonate is 1:1-1.02:1.25-1.
75.
8. A process for the synthesis of N-phenyl-N-benzyl-alanine propio- nitrile as claimed in claim 4, wherein: The mass amount ratio of sodium carbonate or sodium bicarbonate to sodium hydroxide in the inorganic base is 1-1.4:0.05-0.
08.
9. A process for the synthesis of N-phenyl-N-benzyl-alanine propenoyl ester as claimed in claim 4, wherein: In step S2, the mass / mass amount ratio of the added phase transfer catalyst to the raw material N-phenylalanine is 1 g / mol.
10. A process for the synthesis of N-phenyl-N-benzyl-alanine propio- nitrile as claimed in claim 4, wherein: In step S2, the mass amount ratio of the added chloroacetone to the raw material N-phenylalanine is 1.