Preparation method and application of cetyl-PG hydroxyethyl palmitamide
Through simplified synthesis methods, including the synthesis of glycerol ether and secondary amine derivatives, the existing cetyl-PG hydroxyethyl palmitamide synthesis methods are solved, and high purity and low cost industrial production is achieved.
Patent Information
- Application Number
- CN202411808698.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-10
- Publication Date
- 2025-03-18
- Estimated Expiration
- Not applicable · inactive patent
AI Technical Summary
The existing synthesis method of cetyl-PG hydroxyethyl palmitamide is relatively complex, has low purity, has many impurities and high costs, making it difficult to achieve industrial production.
A simplified synthesis method is adopted, including the synthesis of glycerol ether intermediate 1, the synthesis of secondary amine derivative intermediate 2, and the synthesis of cetyl-PG hydroxyethyl palmitamide 3, by reacting in an organic solvent containing a catalyst and a base, the side reaction is reduced and the purity is improved.
The process is simplified, the side reaction is reduced, the purity of cetyl-PG hydroxyethyl palmitamide is improved, the production cost is reduced, and it is suitable for industrial production.
Smart Images
Figure CN119638591A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of cosmetics, and particularly relates to a preparation method and application of cetyl-PG hydroxyethyl palmitamide. Background Art
[0002] The skin is the first layer of the body's defense against external factors, and the barrier function of the skin is maintained and supported by a healthy stratum corneum. The stratum corneum of the skin is composed of keratinocytes and intercellular lipids, and is usually described as a "brick wall structure". The "bricks" are keratinocytes, the "rebars" are the desmosomes connecting the keratinocytes, and the "cement" is the intercellular lipids. Among them, intercellular lipids are composed of 50% ceramides, 25% cholesterol, 15% free fatty acids, and very small amounts of phospholipids and other lipids. The lipid composition of intercellular lipids will change significantly during the differentiation process from the basal layer to the stratum corneum, thereby preventing the abnormal loss of water and electrolytes in the body, while preventing the invasion of harmful substances and maintaining the body's homeostasis.
[0003] As the main component of intercellular lipids in the stratum corneum of the skin, ceramide can not only help the skin lock in moisture, but also promote the self-repair of the skin barrier and regulate skin cells. It has been found that there are 16 natural ceramides of different subtypes of ceramide in the stratum corneum of the skin. Cetyl-PG hydroxyethyl palmitamide, also known as ceramide E, is a synthetic ceramide-like substance. Studies have shown that ceramide E can not only repair the skin barrier function, but also inhibit the production of inflammatory factors, effectively reduce the amount of transepidermal water loss, enhance the hydration of the skin, and reduce the severity of skin damage. It is a strong and effective cosmetic ingredient and is suitable for all kinds of skin care products. At present, with the gradual increase in the market demand for cetyl-PG hydroxyethyl palmitamide, the synthesis requirements of cetyl-PG hydroxyethyl palmitamide are constantly increasing. The current synthesis methods of cetyl-PG hydroxyethyl palmitamide are relatively scarce, and there are many impurities, low purity and high cost, which makes it difficult to achieve industrial production. Summary of the invention
[0004] In view of the problems in the prior art, the present invention provides a method for preparing cetyl-PG hydroxyethyl palmitamide, which solves the problems of complex process and low purity of the existing ceramide E. The synthesis process is simple, does not require high temperature and pressure, effectively reduces side reactions, and improves the purity of ceramide E.
[0005] In order to achieve the above technical objectives, the technical solution of the present invention is:
[0006] A method for preparing cetyl-PG hydroxyethyl palmitamide comprises the following steps:
[0007] Step 1, synthesis of glycerol ether intermediate 1: adding hexadecanol and epichlorohydrin to an organic solvent containing a catalyst and a base, and reacting to obtain hexadecyl glycidyl ether intermediate 1, the reaction formula of which is as follows:
[0008]
[0009] Step 2, synthesis of secondary amine derivative intermediate 2: the hexadecyl glycidyl ether intermediate 1 is subjected to a ring-opening reaction with ethanolamine in an organic solvent, and the secondary amine derivative intermediate 2 is obtained by recrystallization. The reaction formula is as follows:
[0010]
[0011] Step 3, synthesis of cetyl-PG hydroxyethyl palmitamide 3: condense the amine derivative intermediate 2 with methyl palmitate under the action of a base to obtain cetyl-PG hydroxyethyl palmitamide 3, the reaction formula of which is as follows:
[0012]
[0013] Furthermore, the catalyst in step 1 is one or both of tetrabutylammonium bromide and tetrabutylammonium iodide.
[0014] Furthermore, the base in step 1 is a strong base, and the base is one of NaOH, KOH, NaH, and t-BuOK.
[0015] Furthermore, the organic solvent in step 1 is anhydrous tetrahydrofuran or N,N-dimethylformamide, and the molar volume ratio of the hexadecanol to the organic solvent is 0.5-1.5 mol / L.
[0016] Furthermore, the molar ratio of the catalyst to hexadecanol in step 1 is 0.01-005:1, the molar ratio of the alkali to hexadecanol is 1-1.2:1, and the molar ratio of epichlorohydrin to hexadecanol is 1.5-1.8:1.
[0017] Furthermore, the reaction temperature is 30-50°C, and the reaction time is 12-18h; preferably, the reaction time is 12h.
[0018] Furthermore, the synthesis of the glycerol ether intermediate 1 includes: a1, ultrasonically blending hexadecanol and an organic solvent to obtain a mixed solution, the ultrasonic blending temperature is 20-30°C, and the ultrasonic frequency is 60-90kHz; a2, adding a catalyst and a base to the mixed solution and stirring for 10-20 minutes to obtain a reaction solution, the stirring speed is 200-400r / min, a3, slowly dropping epichlorohydrin into the reaction solution and reacting at a constant temperature, filtering and washing after the reaction is completed, and evaporating the filtrate under reduced pressure to obtain a light yellow oily crude product, the slow dropping speed is 1-3mL / min, and the pressure of the reduced pressure evaporation is 80-90% of the atmospheric pressure.
[0019] Furthermore, the organic solvent in step 2 is one of methanol, ethanol, dichloromethane, dichloroethane, and petroleum ether.
[0020] Furthermore, the molar ratio of the hexadecyl glycidyl ether intermediate 1 to ethanolamine in step 2 is 1-2:2.5.
[0021] Furthermore, the temperature of the ring-opening reaction in step 2 is 30-50° C., and the reaction time is 18-22 h. Preferably, the reaction time is 20 h.
[0022] Furthermore, the synthesis of the secondary amine derivative intermediate 2 in step 2 includes the following steps: b1, placing the hexadecyl glycidyl ether intermediate 1 and ethanolamine in an organic solvent, stirring at room temperature and performing a ring-opening reaction for 20-22 hours; b2, distilling the solution after the reaction under reduced pressure to obtain a white solid and a filtrate after distilling off part of the solvent; the pressure of the reduced pressure distillation is 90-95% of the atmospheric pressure; b3, rotary evaporating the filtrate, and recrystallizing with cyclohexane and vacuum drying to obtain a crude secondary amine derivative intermediate 2.
[0023] Furthermore, the base in step 3 is NaOH, Na 2 CO 3 , one of KOH, NaOMe, NaOEt, t-BuONa, and LDA.
[0024] Furthermore, in step 3, the molar ratio of the secondary amine derivative intermediate 2 to the base is 1:0.1-0.2; the molar ratio of the secondary amine derivative intermediate to methyl palmitate is 1:1.2-1.5.
[0025] Furthermore, the reaction temperature in step 3 is 70-90° C., and the reaction time is 6-8 h.
[0026] Furthermore, the synthesis of the cetyl-PG hydroxyethyl palmitamide 3 includes the following steps: c1, adding the secondary amine derivative intermediate 2 and the base to ethanol in sequence, heating and stirring to dissolve, to obtain a dissolving solution, the temperature of the heating and stirring is 60-70°C; the stirring speed is 100-400r / min, c2, slowly adding methyl palmitate to the dissolving solution and reacting at a constant temperature, after the reaction is completed, post-treatment is performed to obtain ceramide E, the pressure of the slow addition is 90% of the atmospheric pressure, and the temperature of the constant temperature reaction is 70-75°C; the methyl palmitate is added within 0.5-3h, and preferably, the methyl palmitate is added within 1-2h, the post-treatment includes: cooling, recrystallization and vacuum drying, the cooling temperature is 10-20°C, and the recrystallization includes: first recrystallizing once with cyclohexane, and then crystallizing twice with ethanol.
[0027] The cetyl-PG hydroxyethyl palmitamide is used in the preparation of cosmetics, which have anti-inflammatory, moisturizing, soothing, repairing and other effects and are suitable for sensitive skin.
[0028] It can be seen from the above description that the present invention has the following advantages:
[0029] 1. The present invention solves the problems of complex process and low purity of existing ceramide E. The synthesis process is simple, high temperature and pressure are not required, side reactions are effectively reduced, and the purity of ceramide E is improved.
[0030] 2. The synthesis route provided by the present invention is simple, the raw material sources are abundant, the catalysts and solvents used are conventional reagents, the safety is high, the production cycle is short, and the economic benefits are high.
[0031] 3. The present invention uses cetyl-PG hydroxyethyl palmitamide as an active ingredient and applies it to a repair cream, which has obvious in vitro soothing and repairing effects. BRIEF DESCRIPTION OF THE DRAWINGS
[0032] Figure 1 This is the overall preparation route of cetyl-PG hydroxyethyl palmitamide in the embodiments of the present invention.
[0033] Figure 2 This is an observation diagram of the tissue morphology of the skin model after H&E staining.
[0034] Figure 3 This is a bar graph of the relative integrated optical density (IOD) values of FLG, LOR and Claudin-1
[0035] Figure 4 It is a bar graph showing the test results of inflammatory factors IL-1α and TNF-α. DETAILED DESCRIPTION
[0036] Combination Figures 1 to 4 , describes in detail a specific embodiment of the present invention, but does not limit the claims of the present invention.
[0037] Example 1
[0038] like Figure 1 As shown, a method for preparing cetyl-PG hydroxyethyl palmitamide comprises the following steps:
[0039] Step 1, synthesis of glycerol ether intermediate 1: add 100mmol (24.244g) of hexadecanol and 200mL of tetrahydrofuran to a round-bottom flask, and dissolve them completely by ultrasound; then add 1mmol (0.324g) of TBAI and 100mmol (2.400g) of NaH; after stirring for 10min, add 150mmol (13.875g) of epichlorohydrin dropwise. After the addition is completed, continue the reaction at 30°C for 12h, and after the reaction is completed. Filter, wash the filter cake with a small amount of tetrahydrofuran, combine the filtrate, and concentrate under reduced pressure to obtain a pale yellow oily crude product. The hexadecyl glycidyl ether 1 does not need to be purified and is directly used for the next step. The temperature of the ultrasound is 20°C, the frequency is 60kHz, the stirring speed is 200r / min, the dropping speed is 1mL / min, and the pressure of the reduced pressure concentration is 90% of the atmospheric pressure;
[0040] Step 2, synthesis of secondary amine derivative intermediate 2: Take all the above hexadecyl glycidyl ether intermediate 1, add 300mL of ethanol and 250mmol (22.90g) of ethanolamine, stir at room temperature, and react for about 20 hours. Distill under reduced pressure to obtain a white solid, filter, concentrate the filtrate, and recrystallize from cyclohexane to obtain a crude secondary amine derivative intermediate 2, which can be directly carried out to the next step without further purification; the reaction is a ring-opening reaction at 30°C, and the pressure of the reduced pressure distillation is 95% of the atmospheric pressure;
[0041] Step 3, synthesis of cetyl-PG hydroxyethyl palmitamide 3: take all the crude secondary amine derivative intermediates 2 mentioned above, add 10 mmol (0.961 g) of sodium tert-butoxide into a round-bottom flask, then add 200 mL of ethanol, heat to 60°C, and stir to dissolve at a speed of 100 r / min; slowly add 120 mmol (32.400 g) of methyl palmitate dropwise at a pressure of 90% of atmospheric pressure; the addition is completed in about 0.5 hour; the reaction is continued at 70°C for 6 hours, and the reaction is stopped; recrystallization is performed twice from cyclohexane / ethanol to obtain cetyl-PG hydroxyethyl palmitamide 3 with a total yield of 45% and a purity of 96.7%.
[0042] Example 2
[0043] A method for preparing cetyl-PG hydroxyethyl palmitamide comprises the following steps:
[0044] Step 1, synthesis of glycerol ether intermediate 1: add 100mmol (24.244g) of hexadecanol and 70mL of N,N-dimethylformamide to a round-bottom flask, and dissolve them completely by ultrasound; then add 5mmol (1.409g) of tetrabutylammonium bromide and 120mmol (4.795g) of NaOH; after stirring for 10min, add 180mmol (16.657g) of epichlorohydrin dropwise. After the addition, continue the reaction at 50°C for 18h, and after the reaction is completed. Filter, wash the filter cake with a small amount of tetrahydrofuran, combine the filtrate, and concentrate under reduced pressure to obtain a pale yellow oily crude product. The hexadecyl glycidyl ether 1 does not need to be purified and is directly used for the next step. The temperature of the ultrasound is 30°C, the frequency is 90kHz, the stirring speed is 200r / min, the dropping speed is 3mL / min, and the pressure of the reduced pressure concentration is 80% of the atmospheric pressure;
[0045] Step 2, synthesis of secondary amine derivative intermediate 2: Take all the above hexadecyl glycidyl ether intermediate 1, add 400mL of dichloroethane and 125mmol (11.45g) of ethanolamine, stir at room temperature, and react for about 22 hours. Distill under reduced pressure to obtain a white solid, filter, concentrate the filtrate, and recrystallize from cyclohexane to obtain a crude secondary amine derivative intermediate 2, which can be directly carried out to the next step without further purification; wherein, the reaction is a ring-opening reaction at 50°C, and the pressure of the reduced pressure distillation is 90% of the atmospheric pressure;
[0046] Step 3, synthesis of cetyl-PG hydroxyethyl palmitamide 3: take all the crude secondary amine derivative intermediates 2 mentioned above, add 20 mmol (0.805 g) of sodium hydroxide into a round-bottom flask, then add 300 mL of ethanol, heat to 70°C, and stir to dissolve at 400 r / min; slowly add 150 mmol (40.509 g) of methyl palmitate dropwise at 90% of atmospheric pressure; the addition is completed in about 3 hours; continue to keep warm at 75°C for 5 hours, and stop the reaction; recrystallize twice from cyclohexane / ethanol to obtain cetyl-PG hydroxyethyl palmitamide 3 with a total yield of 46.8% and a purity of 97.3%.
[0047] Example 3
[0048] A method for preparing cetyl-PG hydroxyethyl palmitamide comprises the following steps:
[0049] Step 1, synthesis of glycerol ether intermediate 1: add 100mmol (24.244g) of hexadecanol and 150mL of tetrahydrofuran to a round-bottom flask, and dissolve them completely by ultrasound; then add 5mmol (1.612g) of TBAI and 110mmol (2.640g) of NaH; after stirring for 10min, add 160mmol (14.804g) of epichlorohydrin dropwise. After the addition, continue the reaction at 40°C for 14h, and after the reaction is completed. Filter, wash the filter cake with a small amount of tetrahydrofuran, combine the filtrate, and concentrate under reduced pressure to obtain a pale yellow oily crude product. The hexadecyl glycidyl ether 1 does not need to be purified and is directly used for the next step. The temperature of the ultrasound is 25°C, the frequency is 80kHz, the stirring speed is 300r / min, the speed of the addition is 2mL / min, and the pressure of the reduced pressure concentration is 85% of the atmospheric pressure.
[0050] Step 2, synthesis of secondary amine derivative intermediate 2: Take all the above hexadecyl glycidyl ether intermediate 1, add 300mL petroleum ether, 200mmol (18.32g) of ethanolamine, stir at room temperature, and react completely in about 21 hours. Distill under reduced pressure to obtain a white solid, filter, concentrate the filtrate, and recrystallize from cyclohexane to obtain a crude secondary amine derivative intermediate 2, which can be directly carried out to the next step without further purification; the reaction is a ring-opening reaction at 40°C, and the pressure of the reduced pressure distillation is 90% of the atmospheric pressure;
[0051] Step 3, synthesis of cetyl-PG hydroxyethyl palmitamide 3: Take all the crude secondary amine derivative intermediates 2 above, add 15 mmol (2.399 g) of sodium carbonate into a round-bottom flask, add 300 mL of ethanol, heat to 65°C and stir to dissolve; slowly add 140 mmol (37.800 g) of methyl palmitate under reduced pressure; add the mixture for about 1 hour; continue to heat at 72°C for 6 hours, and stop the reaction. Recrystallize twice from cyclohexane / ethanol to obtain cetyl-PG hydroxyethyl palmitamide 3, with a total yield of 46.2% and a purity of 97.3%.
[0052] The product of Example 3 was used as a raw material to prepare a repair cream, and the repair cream was used as a test sample to perform performance testing.
[0053] The preparation process of the high moisturizing repair cream containing 1% ceramide E is as follows:
[0054] (1) Material preparation: Prepare in advance various ingredients such as cetyl-PG hydroxyethyl palmitamide, ectoine, sucrose stearate, cetearyl alcohol, propyl heptyl caprylate, squalane, water, glycerin, p-hydroxyacetophenone, xanthan gum, disodium EDTA, and arginine; the specific mass ratio is: sucrose stearate 1%, propyl heptyl caprylate 4%, squalane 2%, cetyl-PG hydroxyethyl palmitamide 1%, glycerin 5%, ectoine 1%, p-hydroxyacetophenone 0.3%, xanthan gum 0.4%, disodium EDTA 0.1%, arginine 0.5%, and the balance is water;
[0055] (2) Preparation of repair cream: Weigh sucrose stearate, propyl heptyl caprylate, squalane and other emulsifiers, stabilizers, oils and cetyl-PG hydroxyethyl palmitamide to prepare phase A; weigh water, glycerin, ectoine, p-hydroxyacetophenone, xanthocollagen, disodium EDTA and other ingredients to prepare phase B; weigh water and arginine to prepare phase C. Heat phases A and B to 85°C until completely dissolved, homogenize phase B until uniform and free of particles; pour phase A into phase B, homogenize until uniform and free of particles, add phase C, stir and cool to below 45°C, and the preparation is complete.
[0056] Test 1: Repair efficacy test of 1% ceramide E high moisturizing repair cream
[0057] The 3D epidermal skin model has been used as an animal test and model substitute in fields such as toxicology and skin biology. It has a multi-layered structure, physiological and metabolic functions that are highly similar to natural skin. It is of great significance in simulating the process of cosmetics penetrating into the body and causing toxicity to the deep layers of the skin.
[0058] A healthy skin barrier is formed by tight junctions of keratinocytes. Flaglin (FLG), loricrin (LOR), and claudin-1 play an important role in the formation of a healthy skin barrier. Loricrin is equivalent to the armor of keratinocytes, making them stronger, while Flaglin supports the internal structure of keratinocytes. Claudin-1 is a skeleton protein component of cell connections and participates in the regulation of cell material flow.
[0059] The test used sodium lauryl sulfate (SLS) to stimulate the 3D epidermal skin model The repair efficacy of the sample to be tested was evaluated by detecting the changes in tissue morphology and the content of FLG, LOR, and Claudin-1.
[0060] Observation of skin model tissue morphology results:
[0061] Dosage group 1
[0062]
[0063] (1) Prepare 0.1% SLS and positive control (WY14643) working solutions; (2) Transfer the model to a 6-well plate (add 0.9 mL EpiGrowth culture solution in advance), mark the test group number, add 25 μL 0.1% SLS solution to the surface of the NC group, PC group and sample group, and incubate for 30 min; (3) After the incubation, add 0.9 mL of model culture solution containing WY14643 to each well of the PC1 group, and take 12.5 μL of the working solution of the sample to be tested and add it to the surface of the model in the sample group. Apply it evenly and place it in a CO2 incubator. 2 Incubator (37°C, 5% CO 2 ) and incubate for 24 h; (4) After the incubation, wash the remaining test substance with sterile PBS solution and wipe off the remaining liquid with a sterile cotton swab.
[0064] After cleaning, the model was fixed with 4% paraformaldehyde, embedded in tissue, sliced, and stained with H&E. The slices were collected and photographed using a microscope. Plus image processing software was used for analysis. The test results are shown in Figure 2 shown.
[0065] (1) Compared with the BC group, the living cell layer of the epidermal model in the NC group was damaged and vacuoles appeared, indicating that the stimulation conditions of this test were effective; (2) Compared with the NC group, the living cell layer of the PC1 group was compactly arranged, the vacuoles were reduced, and the damage to the living cells was significantly improved, indicating that the positive control of this test was effective; (3) Compared with the NC group, the living cell layer of the sample 1% Ceramide E High Moisturizing Repair Cream was compactly arranged, the vacuoles were reduced, and the damage to the living cells was significantly improved.
[0066] D Epidermal skin model FLG, LOR, Claudin-1 content test:
[0067] Table 2 Dosage group 2
[0068]
[0069] The specific operation of the experiment is consistent with the 3D epidermal skin model tissue morphology observation operation.
[0070] The model used for testing was removed by ring cutting and fixed with 4% paraformaldehyde for 24 hours, and then immunofluorescence detection was performed. The images were taken and analyzed under a microscope, and the protein increase rate was calculated. The test results are as follows: Figure 3 shown.
[0071]
[0072] GraphPad Prism was used for drawing, and the results were expressed as Mean±SD. The t-test statistical analysis was used for comparison between the groups. Compared with the BC group, the significance was indicated by #, P-value < 0.05 was indicated by #, and P-value < 0.01 was indicated by ##; compared with the NC group, the significance was indicated by *, P-value < 0.05 was indicated by *, and P-value < 0.01 was indicated by **.
[0073] (1) Compared with the BC group, the FLG, LOR, and Claudin-1 contents of the NC group were significantly decreased, indicating that the stimulation conditions of this test were effective; (2) Compared with the NC group, the FLG, LOR, and Claudin-1 contents of the PC1 group were significantly increased, indicating that the positive control of this test was effective; (3) Compared with the NC group, the FLG, LOR, and Claudin-1 contents of the sample 1% Ceramide E High Moisturizing Repair Cream were significantly increased, with increase rates of 348.39%, 196.77%, and 188.46%, respectively.
[0074] (II) Soothing effect test of 1% ceramide E high moisturizing repair cream:
[0075] After foreign irritants and allergens enter the skin, they trigger allergic reactions and inflammatory reactions. Inflammatory factors stimulate the production of mediators such as histamine, prostaglandin D2, and leukotrienes, and the activation of proteases, causing the human body to produce heat, itching, pain, etc. Therefore, the soothing effect of cosmetics can be evaluated by reducing the release of cytokines such as inflammatory factors.
[0076] Dosage Group 3
[0077]
[0078]
[0079] The specific operation of the experiment was consistent with the 3D epidermal skin model tissue morphology observation operation, but the positive control group was replaced by dexamethasone from WY14643.
[0080] After the incubation, the model culture fluid was collected in a centrifuge tube. After collection, the samples for ELISA detection were placed in a -80°C refrigerator for freezing and storage. The detection and analysis were performed according to the operating instructions of the ELISA kit. The test results are shown in Figure 4 .
[0081]
[0082] The graphing method and statistical analysis were consistent with the previous ones.
[0083] (1) Compared with the BC group, the IL-1α and TNF-α contents in the NC group increased significantly, indicating that the stimulation conditions of this test were effective; (2) Compared with the NC group, the IL-1α and TNF-α contents in the PC2 group decreased significantly, indicating that the positive control of this test was effective; (3) Compared with the NC group, the IL-1α and TNF-α contents in the sample 1% Ceramide E High Moisturizing Repair Cream decreased significantly, with inhibition rates of 33.27% and 25.01%, respectively.
[0084] These research results show that after using 1% ceramide E highly moisturizing repair cream, the cells in the living cell layer of the tissue can be arranged compactly, vacuoles can be reduced, the damage to living cells can be significantly improved, the levels of filaggrin (FLG), loricrin (LOR), and tight junction protein 1 (Claudin-1) can be significantly increased, and the levels of inflammatory factors IL-1α and TNF-α can be reduced, indicating that the sample has good repair and soothing effects.
[0085] In summary, the preparation method and application of cetyl-PG hydroxyethyl palmitamide in the embodiment of the present invention have beneficial effects. Cetyl-PG hydroxyethyl palmitamide can be used as an active ingredient in cosmetics and applied to skin care products. It can form a tight network structure in the stratum corneum to maintain skin moisture, prevent water loss, and improve the skin's water retention capacity. In addition, ceramide E can help repair the skin barrier, make the skin soft and shiny, and restore its original health, which is suitable for people with dry, sensitive skin and rough skin.
[0086] It is understood that the above specific description of the present invention is only used to illustrate the present invention and is not limited to the technical solutions described in the embodiments of the present invention. Those skilled in the art should understand that the present invention can still be modified or replaced by equivalents to achieve the same technical effects; as long as the use requirements are met, they are within the protection scope of the present invention.
Claims
1. A method for preparing cetyl-PG hydroxyethyl palmitamide, characterized in that: The steps include: Step 1, synthesis of glycerol ether intermediate 1: adding hexadecanol and epichlorohydrin to an organic solvent containing a catalyst and a base, and reacting to obtain hexadecyl glycidyl ether intermediate 1, the reaction formula of which is as follows: Step 2, synthesis of secondary amine derivative intermediate 2: subjecting hexadecyl glycidyl ether intermediate 1 to a ring-opening reaction with ethanolamine in an organic solvent, and obtaining secondary amine derivative intermediate 2 by recrystallization, wherein the reaction formula is as follows: Step 3, synthesis of cetyl-PG hydroxyethyl palmitamide 3: condense the amine derivative intermediate 2 with methyl palmitate under the action of a base to obtain cetyl-PG hydroxyethyl palmitamide 3, the reaction formula of which is as follows:
2. The method for preparing cetyl-PG hydroxyethyl palmitamide according to claim 1, characterized in that: The catalyst in step 1 is one or both of tetrabutylammonium bromide and tetrabutylammonium iodide.
3. The method for preparing cetyl-PG hydroxyethyl palmitamide according to claim 1, wherein the base in step 1 is a strong base, and the base is one of NaOH, KOH, NaH, and t-BuOK.
4. The method for preparing cetyl-PG hydroxyethyl palmitamide according to claim 1, wherein the organic solvent in step 1 is anhydrous tetrahydrofuran or N,N-dimethylformamide, and the molar volume ratio of the hexadecanol to the organic solvent is 0.5-1.5 mol / L.
5. The method for preparing cetyl-PG hydroxyethyl palmitamide according to claim 1, wherein the molar ratio of the catalyst to hexadecanol in step 1 is 0.01-005:1, the molar ratio of the alkali to hexadecanol is 1-1.2:1, and the molar ratio of epichlorohydrin to hexadecanol is 1.5-1.8:
1.
6. The method for preparing cetyl-PG hydroxyethyl palmitamide according to claim 1, wherein the organic solvent in step 2 is one of methanol, ethanol, dichloromethane, dichloroethane and petroleum ether.
7. The method for preparing cetyl-PG hydroxyethyl palmitamide according to claim 1, wherein the molar ratio of the hexadecyl glycidyl ether intermediate 1 to ethanolamine in step 2 is 1-2:2.
5.
8. The method for preparing cetyl-PG hydroxyethyl palmitamide according to claim 1, wherein the temperature of the ring-opening reaction in step 2 is 30-50°C, and the reaction time is 18-22h.
9. The method for preparing cetyl-PG hydroxyethyl palmitamide according to claim 1, wherein the base in step 3 is one of NaOH, Na2CO3, KOH, NaOMe, NaOEt, t-BuONa, and LDA; the molar ratio of the secondary amine derivative intermediate 2 to the base is 1:0.1-0.2; the molar ratio of the secondary amine derivative intermediate to methyl palmitate is 1:1.2-1.5; the reaction temperature is 70-90°C, and the reaction time is 6-8h.
10. The method for preparing cetyl-PG hydroxyethyl palmitamide according to claim 1, wherein the cetyl-PG hydroxyethyl palmitamide is used for preparing cosmetics, and the cosmetics have anti-inflammatory, moisturizing, soothing, repairing and other effects, and are suitable for sensitive skin.