Preparation method of crystal copper pyrrolidone carboxylate

Abstract

The invention belongs to the technical field of organic chemistry, and discloses a preparation method of crystal copper pyrrolidonecarboxylate, which comprises the following steps: dissolving L-pyroglutamic acid serving as a raw material under an alkaline condition, carrying out complex reaction with copper ions to obtain a copper pyrrolidonecarboxylate reaction solution, carrying out hot filtration and impurity removal on the reaction solution, and concentrating the filtrate to obtain the crystal copper pyrrolidonecarboxylate. Cooling to separate out crystals, filtering, washing and drying to obtain blue-green crystals, namely the copper pyrrolidone carboxylate. The process has the characteristics of high yield, simple post-treatment and the like. The invention provides a novel industrial preparation method which is low in production cost, efficient and environment-friendly.

Description

Technical Field

[0001] This invention belongs to the field of chemical synthesis technology, specifically relating to a method for preparing crystalline pyrrolidone copper carboxylate, and more specifically to a simple industrial-grade preparation, separation, and purification cosmetic-grade technical solution for crystalline pyrrolidone copper carboxylate. Background Technology

[0002] Copper pyrrolidone carboxylate, also known as copper PCA, is the copper salt of L-pyrrolidone carboxylic acid (L-PCA). L-PCA is obtained by cyclizing the plant-derived amino acid L-glutamic acid. Copper has antibacterial properties and is one of the essential trace elements for the human body. Copper PCA is a combination of copper and L-PCA, regulating sebaceous gland activity by reducing skin sebum levels. It is an active ingredient in oily skin lotions and also gives them their distinctive lagoon blue color.

[0003] Copper offers numerous benefits in skin applications. Collagen, as well as connective tissue in the skin, uses copper as a catalyst in many metabolic and synthetic reactions, resulting in renewed and healthy skin. It also accelerates wound healing. PCA copper can also be used as a colorant in cosmetics. It helps cleanse the skin of dead skin cells, loosening them from the epithelial tissue, aiding in skin cleansing and restoring a refreshed appearance. Copper generally has antibacterial properties, with a mechanism similar to that of the skin. It binds to a key component of microorganisms, causing dysfunction in their metabolic processes. Therefore, it can address problems caused by microorganisms at their root, such as acne or redness. It reduces sebum secretion, preventing overactivity in acne cases. Such effects can help positively condition acne-affected skin. Oily skin appears to benefit even more. It is used in body care, skin care, baby care, facial care, and facial cleansing. Its benefits include: 1. Helping to repair damaged skin's protective barrier; 2. Providing immediate hydration; 3. Improving skin elasticity and firmness; 4. Enhancing skin's radiance and luminosity; 5. Reducing sunburn / redness, etc. Recommended dosage: 1-10%

[0004] The synthesis method of copper pyrrolidone carboxylate involves using L-pyroglutamic acid as a raw material, which undergoes a complexation reaction with a copper-containing compound under alkaline conditions. The reaction solution is then concentrated and precipitated, resulting in a one-step process to obtain crystalline copper pyrrolidone carboxylate. According to reports, invention patent 201710687779.2 relates to the application of an amino acid compound and its bactericidal composition in agriculture. This patent uses L-pyroglutamic acid as a raw material, water or methanol as a solvent, adjusts the pH to 7-8, and adds dropwise a methanol or aqueous solution containing copper chloride. After the addition is complete, the reaction is carried out for 1 hour, and the solution is concentrated to obtain solid copper pyrrolidone carboxylate. However, the patent claims do not clearly specify the specific reaction control and condition selection, including the influence of process parameters such as temperature, pH, and solvent selection on the yield—a key industrial preparation indicator—as well as the specific methods and experimental data for achieving this indicator. Furthermore, the target product prepared by the synthesis method is not qualitatively analyzed, failing to meet the relevant requirements for application in the cosmetic field and the industrial preparation method of this product. Summary of the Invention

[0005] This invention provides a synthetic method for preparing crystalline copper pyrrolidone carboxylate for skin care applications, suitable for industrial production. It utilizes L-pyroglutamic acid as the main raw material, which undergoes a complexation reaction with a copper-containing compound under alkaline conditions to obtain a copper pyrrolidone carboxylate reaction solution in one step. The reaction solution is then subjected to post-treatment processes such as filtration to remove impurities, crystallization, and solid drying to obtain blue-green crystalline copper pyrrolidone carboxylate. The preparation process features high yield, simple post-processing, and the acquisition of high-purity crystalline powder.

[0006] This invention provides a novel, low-cost, efficient, and environmentally friendly industrial preparation method. The entire preparation process includes two stages: a reaction stage (S1) and a post-treatment stage (S2). The characteristics are as follows: S1: Under alkaline conditions, L-pyroglutamic acid is dissolved in the reaction solution system by stirring. After heating to the target temperature required by the process, an appropriate pH value is controlled, and a solution containing a certain equivalent amount of copper ions is added. A complexation reaction is carried out at a set temperature. After the reaction is completed and an appropriate pH value is reached, a reaction solution is obtained. S2: The reaction solution is hot-filtered at a set temperature to remove insoluble impurities, then concentrated under reduced pressure or precipitated by cooling. Blue crystals precipitate at a set temperature, and after filtration, washing, and drying, the blue-green crystalline target product, copper pyrrolidone carboxylate, is obtained.

[0007] The reaction equation using sodium hydroxide as an inorganic base and copper chloride dihydrate as a copper ion-containing compound is as follows:

[0008]

[0009] (1) The main raw material mentioned in the reaction stage (S1) of this preparation process is L-pyroglutamic acid. The copper ion-containing compound includes one of the following: copper sulfate, copper chloride, copper nitrate, basic copper carbonate, cuprous chloride, copper gluconate and their hydrates, preferably copper chloride dihydrate; the alkaline conditions used are inorganic bases, including one or more of sodium hydroxide, potassium hydroxide, lithium hydroxide, and sodium bicarbonate, preferably sodium hydroxide; the reaction solvent includes one of water, isopropanol, methanol, ethanol, and n-butanol. Or several, preferably an aqueous solution; the molar ratio of L-pyroglutamic acid: copper ion compound: inorganic base used is 2:1~1.5:1~2.5, preferably 2:1:1.95; the pH value is controlled at 6-14 under the alkaline reaction conditions, preferably pH=7±0.5; the temperature for adding alkali is controlled at 0~30℃, preferably 20±2℃; the reaction temperature is controlled at 20-80℃, preferably 60±2℃; the pH value is controlled at 3-5 after the reaction is completed, preferably pH=4.5±0.5.

[0010] (2) In the post-processing stage (S2) mentioned above, the heat filtration temperature is controlled at 60-80℃, preferably 70±2℃; the filtration temperature for crystallization at the set temperature is 0-60℃, preferably 10±2℃.

[0011] Beneficial effects

[0012] This process features high yield and simple post-processing. This invention provides a novel, low-cost, efficient, and environmentally friendly industrial preparation method. Attached Figure Description

[0013] Figure 1 This is the infrared spectrum of the copper pyrrolidone carboxylate prepared in Example 1.

[0014] Figure 2 This is the mass spectrum of the copper pyrrolidone carboxylate prepared in Example 1. Detailed Implementation

[0015] A method for preparing crystalline copper pyrrolidone carboxylate involves using L-pyroglutamic acid as a raw material, dissolving it under alkaline conditions, and then reacting it with copper ions to obtain a copper pyrrolidone carboxylate reaction solution. The reaction solution is then subjected to hot filtration to remove impurities, the filtrate is concentrated, cooled to precipitate crystals, filtered, washed, and dried to obtain blue-green crystalline copper pyrrolidone carboxylate.

[0016] Specifically, the following steps are included:

[0017] S1: L-pyroglutamic acid is dissolved in the reaction solvent system by stirring, an alkaline solution is added dropwise, the temperature is raised to the target temperature required by the process, and a solution containing a certain amount of copper ions is added to carry out a complexation reaction. After the reaction is completed, the reaction solution is obtained.

[0018] S2: The reaction solution is filtered at a set temperature to remove insoluble impurities, cooled to precipitate crystals, and then filtered, washed, and dried to obtain the target product, blue-green crystals of pyrrolidone carboxylic acid copper.

[0019] In S1: the alkaline solution is prepared by adding an inorganic base to the reaction solution, wherein the molar ratio of L-pyroglutamic acid:copper ions:inorganic base is 2:1~1.5:1~2.5, preferably 2:1:1.95.

[0020] In S1, the copper ions are derived from copper-containing compounds, which include one or more of copper sulfate, copper chloride, copper nitrate, basic copper carbonate, cuprous chloride, copper gluconate and their hydrates, preferably copper chloride dihydrate.

[0021] The inorganic bases used include one or more of sodium hydroxide, potassium hydroxide, lithium hydroxide, and sodium bicarbonate, with sodium hydroxide being preferred;

[0022] The reaction solvents used include one or more of water, isopropanol, methanol, ethanol, and n-butanol, preferably an aqueous solution.

[0023] In S1,

[0024] The alkaline solution is added dropwise to control the pH value between 6.5 and 14, preferably with a pH value of 7 ± 0.5;

[0025] The temperature is controlled at 0~30℃ when adding the alkaline solution, preferably at 20±2℃.

[0026] The complexation reaction is controlled at a temperature of 20~80℃, preferably 60±2℃;

[0027] The reaction is terminated with the pH value controlled at 3-5, preferably 4.5 ± 0.5.

[0028] In S2,

[0029] The temperature of the heat filter is controlled at 20-80℃ under the set temperature; preferably, the temperature is controlled at 70±2℃.

[0030] The filtration temperature for crystallization is 0-60℃, preferably 10±2℃.

[0031] Example 1

[0032] In a 100ml round-bottom flask, 6.5g (0.05mol) of L-pyroglutamic acid was weighed and added to 65ml of methanol. After dissolving by stirring at 25±2℃, a 20% aqueous solution of 2.1g (0.053mmol) of sodium hydroxide was added dropwise, and the pH was measured to be 8±0.5. Then, 20mL of a methanol solution containing 4.3g (0.025mol) of copper chloride dihydrate was slowly added dropwise over 1 hour, during which the solution color changed from colorless to blue-green. After the addition was complete, the reaction was continued at 25±2℃ for another hour, during which a solid precipitated. The reaction was then checked for completeness, and the pH was 4±0.5. The solid was filtered and washed with a small amount of methanol. The filtrate was concentrated to precipitate a blue solid, which was dried at 120℃ for 4 hours to obtain 4.8g of blue-green crystalline powder, with a yield of 60%. The infrared spectrum is shown below. Figure 1 As shown, the data are as follows: IR (KBr, cm -1 ): 3282.8, 1674.2, 1674.2, 1415.8, 1302.0, 680.9. Mass spectrometry data as follows: Figure 2 As shown, TOF MS ES+: 319.

[0033] Example 2

[0034] In a 100ml round-bottom flask, 6.5g (0.05mol) of L-pyroglutamic acid was weighed and added to 65ml of methanol. After dissolving by stirring at 25±2℃, a 20% aqueous solution of 3g (0.053mol) of sodium hydroxide was added dropwise, and the pH was measured to be 8±0.5. 20mL of a methanol solution containing 4.3g (0.025mol) of copper chloride dihydrate was slowly added dropwise, controlling the dropping rate for 1 hour. The solution color changed from colorless to blue-green. After the addition was complete, the reaction was continued at (25±2)℃ for 1 hour, resulting in the precipitation of a solid. The reaction was confirmed to be complete, with a pH of 4±0.5. The solid was filtered and washed with a small amount of methanol. The filtrate was concentrated to precipitate a blue solid, which was dried at 120℃ for 4 hours to obtain 4.5g of blue-green crystalline powder, with a yield of 56%.

[0035] Example 3

[0036] In a 100ml round-bottom flask, weigh 6.5 g (0.05mol) of L-pyroglutamic acid and 3.01 g (0.013mol) of basic copper carbonate monohydrate. Add 60ml of anhydrous ethanol, stir, and heat to 80±2℃ for 24 hours. The solution changes from colorless to green, and the pH of the solution is 3±0.5, indicating that the reaction of the starting materials is complete. After removing insoluble impurities by hot filtration at 70±2℃, cool the filtrate to room temperature, filter again, wash the solid with a small amount of anhydrous ethanol, and dry the solid at 120℃ for 4 hours to obtain 6.15g of blue-green crystalline powder. The yield is 76%.

[0037] Example 4

[0038] In a 100ml round-bottom flask, weigh 6.5 g (0.05mol) of L-pyroglutamic acid and 3.01 g (0.013mol) of basic copper carbonate monohydrate. Add 60ml of deionized water, start stirring, and heat to 80±2℃ for 8 hours. The solution changes from colorless to blue, and a small amount of solid precipitates. The pH of the solution is 4±0.5, indicating that the reaction of the starting materials is complete. After removing insoluble impurities by hot filtration at 70±2℃, the solid is washed with a small amount of deionized water. The filtrates are combined and recovered to dryness under reduced pressure at 55-60℃. The resulting blue solid is washed with a small amount of anhydrous ethanol, filtered, and dried at 120℃ for 4 hours to obtain 6.384g of blue-green crystalline powder, with a yield of 79.8%.

[0039] Example 5

[0040] In a 2000ml round-bottom flask, 258 g (2.0 mol) of L-pyroglutamic acid was weighed and added to 258 ml of deionized water. The mixture was stirred and dissolved, and the temperature was lowered to 0℃. 84 g (2.1 mol) of a 33% aqueous solution of sodium hydroxide was added dropwise. After the addition was complete, the temperature was raised to 60±2℃, and 170.5 g (1.0 mol) of a 33% aqueous solution of copper chloride dihydrate was added dropwise. The reaction was controlled at the dropping rate for 1-2 hours, and the color changed from colorless to blue-green. The temperature was maintained and the reaction was continued for 2 hours. The pH of the solution was 4±0.5. The reaction was then detected as complete. The solution was hot-filtered at 60±2℃ to remove a small amount of mechanical impurities. The filtrate was slowly cooled to 10℃, and a large amount of blue crystalline solid precipitated. The temperature was then rapidly lowered to 0±2℃, and the solution was filtered. After the filtrate was dried, the solid was washed once with a small amount of anhydrous ethanol. The solid was then dried at 120℃ for 4 hours to obtain 252 g of blue-green crystalline powder, with a yield of 87.5%.

[0041] Example 6

[0042] In a 200-liter glass reactor, add 25.8 L of deionized water, weigh 25.8 kg (200 mol) of L-pyroglutamic acid and stir until dissolved. Cool to 0±2℃, and add 7.8 kg (195 mol) of a 33% aqueous solution of sodium hydroxide dropwise, controlling the dropping rate for 1-2 hours, with the temperature not exceeding 20±2℃. After the addition is complete and the solid is completely dissolved, check the pH = 7±0.5. Raise the temperature to 60±2℃, and add 17.05 kg (1 mol) of a 30% aqueous solution of copper chloride dihydrate dropwise, controlling the dropping rate for 1-2 hours. The color changes from colorless to blue-green. After the addition is complete, keep the temperature and continue the reaction for 1 hour. The solution pH = 4.5±0.5, and the reaction is complete. The solution was heated to 70±2℃ and hot filtered to remove a small amount of mechanical impurities. The filtrate was then gradually cooled to 20±2℃ and stirred for 1 hour. The solution was then rapidly cooled to 10±2℃, resulting in the precipitation of a large amount of blue large-particle crystals. The solution was filtered by centrifugation, and the solid was washed with a small amount of cold ethanol. The solid was then dried at 120℃ for 4 hours to obtain 28.5 kg of blue-green crystalline powder, copper pyrrolidone carboxylate, with a yield of 90%.

Claims

1. A method for preparing crystalline pyrrolidone copper carboxylate, characterized in that, L-pyroglutamic acid was dissolved under alkaline conditions and then reacted with copper ions to obtain a copper pyrrolidone carboxylate reaction solution. The reaction solution was then filtered to remove impurities, cooled to precipitate crystals, filtered, washed, and dried to obtain blue-green copper pyrrolidone carboxylate crystals.

2. The method for preparing crystalline pyrrolidone carboxylic acid copper according to claim 1, characterized in that, Specifically, the following steps are included: S1: L-pyroglutamic acid is dissolved in the reaction solvent system by stirring, an alkaline solution is added dropwise, the temperature is raised to the target temperature required by the process, and a solution containing a certain amount of copper ions is added to carry out a complexation reaction. After the reaction is completed, the reaction solution is obtained. S2: The reaction solution is filtered at a set temperature to remove insoluble impurities, cooled to precipitate crystals, and then filtered, washed, and dried to obtain the target product, blue-green crystals of pyrrolidone carboxylic acid copper.

3. The method for preparing crystalline pyrrolidone carboxylic acid copper according to claim 2, characterized in that, In S1: the alkaline solution is prepared by adding an inorganic base to the reaction solution, wherein the molar ratio of L-pyroglutamic acid:copper ions:inorganic base is 2:1~1.5:1~2.5, preferably 2:1:1.

95.

4. The method for preparing crystalline pyrrolidone carboxylic acid copper according to claim 3, characterized in that, In S1, the copper ions are derived from copper-containing compounds, which include one or more of copper sulfate, copper chloride, copper nitrate, basic copper carbonate, cuprous chloride, copper gluconate and their hydrates, preferably copper chloride dihydrate. The inorganic bases used include one or more of sodium hydroxide, potassium hydroxide, lithium hydroxide, and sodium bicarbonate, with sodium hydroxide being preferred; The reaction solvents used include one or more of water, isopropanol, methanol, ethanol, and n-butanol, preferably an aqueous solution.

5. The method for preparing crystalline pyrrolidone carboxylic acid copper according to claim 2, characterized in that: In S1, The alkaline solution is added dropwise to control the pH value between 6.5 and 14; The temperature is controlled at 0~30℃ when adding the alkaline solution. The complexation reaction is controlled at a temperature of 20~80℃; The pH value is controlled at 3-5 when the reaction is completed.

6. The method for preparing crystalline pyrrolidone carboxylic acid copper according to claim 5, characterized in that: In S1, The alkaline solution is added dropwise to control the pH value at 7 ± 0.5; The temperature is controlled at 20±2℃ when adding the alkaline solution. The complexation reaction is controlled at a temperature of 60±2℃; The reaction was terminated at a controlled pH of 4.5 ± 0.

5.

7. The method for preparing crystalline pyrrolidone carboxylic acid copper according to claim 2, characterized in that: In S2, The temperature of the heat filter is controlled between 20-80℃ at the set temperature. The filtration temperature for the precipitation crystals is 0-60℃.

8. The method for preparing crystalline pyrrolidone carboxylic acid copper according to claim 2, characterized in that: In S2, The temperature of the heat filter is controlled at 70±2℃ under the specified temperature. The filtration temperature for the precipitation crystals is 10±2℃.

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