A high purity N ε Process for the synthesis of lauroyl lysine

Abstract

The application discloses high-purity N ε The application discloses a synthesis method of lauroyl lysine, and belongs to the technical field of fine synthesis. The method comprises the following steps: uniformly stirring raw materials including lysine and / or lysine salt, an alkaline compound, water, a low-carbon alcohol and a non-water-soluble solvent to form a two-phase microemulsion; adding lauric acid and / or lauroyl halide dropwise in the two-phase microemulsion and stirring to react; after the reaction is completed, N ε Lauroyl lysine is obtained through acid neutralization and precipitation. The method ingeniously solves the reaction selectivity problem of an alpha-amino group and an epsilon-amino group, high-purity N ε Lauroyl lysine is obtained with a good yield, the reaction condition is mild, the product is simple to separate and purify, and the method is suitable for industrial production.

Description

Technical Field

[0001] This invention relates to an N ε A method for synthesizing lauroyl lysine, particularly a two-phase method for highly selective synthesis of high-purity N-lysine. ε The method for synthesizing 1-lauroyl lysine belongs to the field of chemical synthesis technology. Background Technology

[0002] N ε -Lauroyl lysine is an amino acid derivative with poor solubility, insoluble in water and most organic solvents. It is a functional hydrophobic powder that is insensitive to solvents. It possesses advantages such as high lubricity, good skin affinity, antistatic properties, antioxidant properties, antibacterial properties, and good biodegradability. It is often used as a surface modifier for powders in hair and skin conditioning, makeup and cosmetic powder processing, and as an additive in cosmetics such as foundation, eyeshadow, blush, and high-end cleansers. Although regarding N... ε There are many reports on the synthesis of α-lauroyl lysine, but most methods are not suitable for industrial production. Therefore, domestic demand currently relies mainly on imports.

[0003] For N ε The most common chemical synthesis method for preparing -lauroyl lysine involves the condensation of lysine (lysine hydrochloride) with lauric acid or lauroyl chloride. However, due to the presence of both α- and ε-amino groups in the lysine structure, the condensation reaction (acylation) exhibits poor selectivity and readily generates a large amount of the byproduct N. α -Lauroyl lysine and N,N-dilauroyl lysine lead to the target product N ε The isolation and purification of -lauroyl lysine is difficult and yields are low. Therefore, the key to this type of synthesis method is how to solve the problem of poor reaction selectivity, so as to achieve efficient and highly selective preparation of N. ε -Lauroyl lysine. To improve the reaction selectivity of α- and ε-amino groups, two common strategies are used: one is to use group protection, which can achieve precise synthesis, but involves many steps and has high production costs; the other is to use metal ion chelation, which easily leads to metal residues in the product and generates a large amount of wastewater containing metal ions during post-processing. For example, patent publication number CN 102617390 B discloses an N ε The preparation method of -lauroyl lysine involves using lysine or its salt and lauroyl chloride as raw materials. A divalent metal salt (CaCl2, ZnCl2, MgCl2, ZnSO4, FeSO4, and CuSO4, etc.) is used for chelation protection. First, lysine or its salt forms a chelate with the divalent metal ion, protecting the α-amino and carboxyl groups. Subsequently, its ε-amino group undergoes a condensation reaction with lauroyl chloride. Finally, acid hydrolysis destroys the chelate structure to obtain N... ε -Lauroyl lysine. Summary of the Invention

[0004] Regarding N in existing technologies ε The synthesis of lauroyl lysine suffers from poor reaction selectivity, and the purpose of this invention is to provide a high-purity N... ε A method for synthesizing α-lauroyl lysine is based on a two-phase synthesis approach. This method utilizes a two-phase reaction system to control the aggregation of the α-amino and carboxyl groups of lysine in the aqueous phase, while the ε-amino group aggregates in the oil phase to react with lauric acid or lauroyl halide. This significantly reduces side reactions, thereby achieving high selectivity for N-lysine. ε -Lauroyl lysine.

[0005] To achieve the above technical objectives, the present invention provides a high-purity N ε A method for synthesizing lauroyl lysine, comprising the following steps:

[0006] 1) The raw materials, including lysine and / or lysine salts, basic compounds, water, low-carbon alcohols and non-water-soluble solvents, are stirred evenly to form a two-phase microemulsion;

[0007] 2) Lauric acid and / or lauric acid derivatives are added dropwise to a two-phase microemulsion and the mixture is stirred to react. After the reaction is complete, N is obtained by acid neutralization and precipitation. ε -Lauroyl lysine.

[0008] This invention uses lysine salt directly as a raw material, or neutralizes lysine into a salt using a basic compound, thereby enhancing the hydrophilicity of the carboxylate end and relatively strengthening the hydrophobicity of the ε-amino end, resulting in an amphiphilic-hydrophobic reaction system. Based on this, a two-phase microemulsion reaction system is constructed. The α-amino group near the carboxylate end is forcibly dissolved in the aqueous phase and protected, thus not participating in the reaction. The ε-amino group, however, remains free at the interface between the oil and aqueous phases or is dissolved in the oil phase. The added lauric acid or its derivatives are primarily in the oil phase, enabling them to react with the amino group at the oil-water interface or in the oil phase, thereby achieving highly selective synthesis of N... ε -Lauroyl lysine.

[0009] As a preferred embodiment, the volume ratio of the total volume of water and the lower alcohol to the volume of the insoluble solvent is 1:1 to 1:5. The lower alcohol is an important component in constructing the two-phase microemulsion. While lower alcohols are miscible with water, they have relatively low solubility in insoluble solvents such as petroleum ether, n-hexane, cyclohexane, toluene, and dichloromethane. Therefore, mixing these insoluble solvents with water and the lower alcohol within the preferred ratio range is beneficial for constructing a stable two-phase microemulsion, primarily forming a water-in-oil microemulsion. If the proportion of the insoluble solvent is too high, it will lead to low subsequent reaction efficiency and increased costs. If the proportion is too low, it will be difficult to form a stable two-phase microemulsion, resulting in reduced reaction selectivity and difficult product handling. The volume ratio of the total volume of water and the lower alcohol to the volume of the insoluble solvent is further preferably 0.8:1 to 1:2.

[0010] As a preferred embodiment, the volume ratio of water to the lower alcohol is (5-20):40. The introduction of an appropriate amount of lower alcohol not only facilitates the formation of a stable two-phase microemulsion, but also, due to its compatibility with non-water-soluble solvents, allows it to act as a phase transfer agent, facilitating the transfer of the lipophilic end of the sodium lysine salt into the oil phase and improving reaction efficiency. Without the addition of alcohol, water and non-water-soluble solvents cannot form a two-phase microemulsion, leading to side reactions. For example, lauroyl chloride largely forms sodium laurylate, a hydrolysis product of acyl chloride.

[0011] As a preferred embodiment, the lower alcohol is a C1-C4 alcohol, specifically including at least one of methanol, ethanol, isopropanol, and n-butanol. More preferably, methanol or ethanol is used.

[0012] As a preferred embodiment, the non-aqueous solvent includes at least one selected from petroleum ether, n-hexane, cyclohexane, toluene, and dichloromethane. Preferred non-aqueous solvents can dissolve lauric acid derivatives well but are not miscible with water, and these solvents are less effective at dissolving ethanol than water.

[0013] As a preferred embodiment, the alkaline compound includes at least one of sodium hydroxide, potassium hydroxide, and triethylamine.

[0014] As a preferred embodiment, the molar ratio of the basic compound to the lysine and / or lysine salt is (1.0–2.0):1. The basic compound can convert lysine or lysine salt into sodium or potassium salts, making them readily soluble in water; at the same time, the basic compound also acts as an acid-binding agent, which is beneficial for promoting the reaction.

[0015] As a preferred embodiment, the raw material includes an emulsifier. As a more preferred embodiment, the emulsifier includes at least one selected from sodium lauryl sulfate, sodium oleate, polyoxyethylene hexadecyl alcohol, and polyoxyethylene monooleate. As a more preferred embodiment, the amount of emulsifier used is less than 20% of the mass of lysine and / or lysine salt. Emulsifiers help improve the stability of the emulsion, and their addition and dosage can be selected according to actual needs.

[0016] As a preferred embodiment, the lauroyl halide has the following structural expression:

[0017] X can be a halogen, specifically fluorine, chlorine, bromine, etc. Lauroyl halogen is most preferably lauroyl chloride.

[0018] As a preferred embodiment, the molar ratio of lysine and / or lysine salt to lauric acid and / or lauric acid derivative is 2:1 to 1:2.

[0019] As a preferred embodiment, the reaction process is as follows: At a temperature of -5 to 50°C, an alkaline compound is added to the two-phase microemulsion to control its pH within the range of 9 to 14. Simultaneously, lauric acid and / or lauroyl halide are added dropwise to the two-phase microemulsion over a period of 1 to 2 hours. After the addition is complete, the reaction is continued with stirring for 0.5 to 12 hours. An alkaline compound is added during the reaction to control the pH of the system. The alkaline compound is at least one of sodium hydroxide, potassium hydroxide, and triethylamine. The reaction temperature is further preferably -5 to 10°C. Higher temperatures result in poorer stability of the two-phase microemulsion and also increase side reactions; for example, the hydrolysis products of lauroyl halide increase with increasing reaction temperature.

[0020] As a preferred embodiment, the lysine salt includes lysine hydrochloride, lysine sulfate, sodium lysine, potassium lysine, etc.

[0021] As a preferred embodiment, the neutralization reaction uses hydrochloric acid, sulfuric acid, acetic acid, etc., as the neutralizing agent, with hydrochloric acid being the preferred choice. The pH of the solution is controlled between 3 and 8 during the neutralization reaction.

[0022] Compared with existing technologies, the beneficial technical effects of the present invention are as follows:

[0023] The technical solution of this invention utilizes a "two-phase method" to obtain N with high selectivity. ε -Lauroyl lysine significantly reduces N α This method eliminates the generation of side reactions such as lauroyl lysine, and does not require group protection or metal ion chelation protection. It is a one-step reaction synthesis with high reaction selectivity, simple operation, mild reaction conditions, simple product separation and purification, and high yield, making it suitable for industrial production. Attached Figure Description

[0024] Figure 1 In the table, 'a' represents the blank control and 'b' represents N. α HPLC analysis of -lauroyl lysine, c is N prepared in Comparative Example 2. α / N ε Liquid chromatography analysis of a mixture of lauroyl lysine and d, where N is the concentration of lauroyl lysine. ε -Lauroyl lysine (a foreign competitor), e is N prepared in Example 1 ε HPLC analysis of -lauroyl lysine; from Figure 1 As can be seen from the above, Example 1 prepared high-purity N. ε - Lauroyl lysine products. Detailed Implementation

[0025] The present invention will be further described in detail below with reference to specific embodiments, but this is not intended to limit the scope of protection of the claims.

[0026] Example 1

[0027] In a 500 mL four-necked round-bottom flask equipped with a stirrer, 11.0 g of lysine hydrochloride, 4.0 g of sodium hydroxide, and 12.0 g of water were added and stirred at room temperature to dissolve. Then, 40 mL of ethanol, 80 mL of n-hexane, and 0.2 g of sodium lauryl sulfate (emulsifier) ​​were added and stirred until homogeneous. After about 30 minutes, a transparent microemulsion was formed. The reaction solution was cooled to 10 °C, and 12.5 g of lauroyl chloride (0.95 equivalents) was slowly added dropwise while simultaneously adding 30% sodium hydroxide aqueous solution to maintain the pH at 11. The addition process took about 1.5 hours. After the addition was completed, the mixture was stirred for another hour. After the reaction was completed, the mixture was allowed to return to room temperature, and 6 M hydrochloric acid was slowly added dropwise to adjust the pH to around 6. The mixture was transferred to a separatory funnel, allowed to stand and separate into layers, and the lower aqueous phase was removed. The product was filtered to obtain a white solid product, washed with a small amount of ethanol / water solution (2:1 volume ratio), and dried in an oven to obtain the target product N. ε -Lauroyl lysine, white powder, 14.2 g, yield 76%, HPLC purity greater than 97%.

[0028] Example 2

[0029] In a 500 mL four-necked round-bottom flask equipped with a stirrer, 11.0 g of lysine hydrochloride, 4.0 g of sodium hydroxide, and 12.0 g of water were added and stirred at room temperature to dissolve. Then, 40 mL of ethanol, 80 mL of n-hexane, and 0.2 g of sodium lauryl sulfate (emulsifier) ​​were added and stirred until homogeneous. After about 30 minutes, a transparent microemulsion was formed. The reaction solution was cooled to 10 °C, and 13.8 g of lauroyl chloride (1.05 equivalents) was slowly added dropwise while simultaneously adding 30% sodium hydroxide aqueous solution to maintain the pH at 11. The addition process took about 1.5 hours. After the addition was completed, the mixture was stirred for another hour. After the reaction was completed, the mixture was allowed to return to room temperature, and 6 M hydrochloric acid was slowly added dropwise to adjust the pH to around 6. The mixture was transferred to a separatory funnel, allowed to stand and separate into layers, and the lower aqueous phase was removed. The product was filtered to obtain a white solid product, washed with a small amount of ethanol / water solution (2:1 volume ratio), and dried in an oven to obtain the target product N. ε -Lauroyl lysine, white powder, 13.4 g, yield 68%, HPLC purity 94%.

[0030] Example 3

[0031] In a 500 mL four-necked round-bottom flask equipped with a stirrer, 11.0 g of lysine hydrochloride, 4.0 g of sodium hydroxide, and 12.0 g of water were added and stirred at room temperature to dissolve. Then, 40 mL of ethanol, 80 mL of n-hexane, and 0.2 g of sodium lauryl sulfate (emulsifier) ​​were added and stirred until homogeneous. After about 30 minutes, a transparent microemulsion was formed. The reaction solution was cooled to 10 °C, and 15.8 g of lauroyl chloride (1.2 equivalents) was slowly added dropwise while simultaneously adding 30% sodium hydroxide aqueous solution to maintain the pH at 11. The addition process took about 1.5 hours. After the addition was completed, the mixture was stirred for another hour. After the reaction was completed, the mixture was allowed to return to room temperature, and 6 M hydrochloric acid was slowly added dropwise to adjust the pH to around 6. The mixture was transferred to a separatory funnel, allowed to stand and separate into layers, and the lower aqueous phase was removed. The product was filtered to obtain a white solid product, washed with a small amount of ethanol / water solution (2:1 volume ratio), and dried in an oven to obtain the target product N. ε -Lauroyl lysine, white powder, 13.8 g, yield 70%, HPLC purity 92%.

[0032] Example 4

[0033] In a 500 mL four-necked round-bottom flask equipped with a stirrer, 11.0 g of lysine hydrochloride, 4.0 g of sodium hydroxide, and 12.0 g of water were added and stirred at room temperature to dissolve. Then, 50 mL of ethanol, 80 mL of n-hexane, and 0.2 g of polyoxyethylene hexadecyl alcohol (emulsifier) ​​were added and stirred until homogeneous. After about 30 minutes, a transparent microemulsion was formed. The reaction solution was cooled to 10 °C, and 12.5 g of lauroyl chloride (0.95 equivalents) was slowly added dropwise while simultaneously adding 30% sodium hydroxide aqueous solution to maintain the pH at 11. The dropwise addition process took about 1.5 hours. After the addition was completed, the mixture was stirred for another hour. After the reaction was completed, the mixture was allowed to return to room temperature, and 6 M hydrochloric acid was slowly added dropwise to adjust the pH to around 6. The mixture was transferred to a separatory funnel, allowed to stand and separate into layers, and the lower aqueous phase was removed. The product was filtered to obtain a white solid product, washed with a small amount of ethanol / water solution (2:1 volume ratio), and dried in an oven to obtain the target product N. ε -Lauroyl lysine, white powder, 13.1 g, yield 70%, HPLC purity greater than 97%.

[0034] Example 5

[0035] In a 500 mL four-necked round-bottom flask equipped with a stirrer, 11.0 g of lysine hydrochloride, 4.0 g of sodium hydroxide, and 12.0 g of water were added and stirred at room temperature to dissolve. Then, 30 mL of ethanol and 80 mL of n-hexane (without emulsifier) ​​were added, and the mixture was stirred until homogeneous. After about 30 minutes, a transparent microemulsion was formed. The reaction solution was cooled to 10 °C, and 12.5 g of lauroyl chloride (0.95 equivalents) was slowly added dropwise while simultaneously adding 30% sodium hydroxide aqueous solution to maintain the pH at 11. The addition process took about 1.5 hours. After the addition was completed, the mixture was stirred for another hour. After the reaction was completed, the mixture was allowed to return to room temperature, and 6 M hydrochloric acid was slowly added dropwise to adjust the pH to around 6. The mixture was transferred to a separatory funnel, allowed to stand and separate into layers, and the lower aqueous phase was removed. The product was filtered to obtain a white solid product, washed with a small amount of ethanol / water solution (2:1 volume ratio), and dried in an oven to obtain the target product N. ε -Lauroyl lysine, white powder, 11.6 g, yield 62%, HPLC purity greater than 97%.

[0036] Example 6

[0037] In a 500 mL four-necked round-bottom flask equipped with a stirrer, 11.0 g of lysine hydrochloride, 4.0 g of potassium hydroxide, and 12.0 g of water were added and stirred at room temperature to dissolve. Then, 40 mL of ethanol, 80 mL of n-hexane, and 0.2 g of sodium lauryl sulfate (emulsifier) ​​were added and stirred until homogeneous. After about 30 minutes, a transparent microemulsion was formed. At room temperature, 12.5 g of lauroyl chloride (0.95 equivalents) was slowly added dropwise while simultaneously adding 30% sodium hydroxide aqueous solution to maintain the pH at 12. The addition process took about 1.5 hours. After the addition was completed, the mixture was stirred for another hour. After the reaction was completed, the mixture was allowed to return to room temperature, and 6 M hydrochloric acid was slowly added dropwise to adjust the pH to around 6. The mixture was transferred to a separatory funnel, allowed to stand to separate the layers, and the lower aqueous phase was removed. The product was filtered to obtain a white solid product, washed with a small amount of ethanol / water solution (2:1 volume ratio), and dried in an oven to obtain the target product N. ε -Lauroyl lysine, white powder, 13.3 g, yield 71%, HPLC purity 92%.

[0038] Example 7

[0039] In a 500 mL four-necked round-bottom flask equipped with a stirrer, 11.0 g of lysine hydrochloride, 4.0 g of sodium hydroxide, and 12.0 g of water were added and stirred at room temperature to dissolve. Then, 40 mL of methanol, 80 mL of n-hexane, and 0.2 g of sodium lauryl sulfate (emulsifier) ​​were added and stirred until homogeneous. After about 30 minutes, a transparent microemulsion was formed. At room temperature, 12.5 g of lauroyl chloride (0.95 equivalents) was slowly added dropwise while simultaneously adding 30% sodium hydroxide aqueous solution to maintain the pH at 11. The dropwise addition process took about 1.5 hours. After the addition was completed, the mixture was stirred for another hour. After the reaction was complete, 6 M hydrochloric acid was slowly added dropwise at room temperature to adjust the pH to about 6. The mixture was transferred to a separatory funnel, allowed to stand and separate into layers, the lower aqueous phase was removed, and the product was filtered to obtain a white solid product. The product was washed with a small amount of ethanol / water solution (2:1 volume ratio), dried in an oven, and the target product N was obtained. ε -Lauroyl lysine, white powder, 10.3 g, yield 55%, HPLC purity greater than 97%.

[0040] Example 8

[0041] In a 500 mL four-necked round-bottom flask equipped with a stirrer, 11.0 g of lysine hydrochloride, 4.0 g of sodium hydroxide, and 12.0 g of water were added and stirred at room temperature to dissolve. Then, 40 mL of isopropanol, 80 mL of n-hexane, and 0.2 g of sodium lauryl sulfate (emulsifier) ​​were added and stirred until homogeneous. After about 30 minutes, a transparent microemulsion was formed. At room temperature, 12.5 g of lauroyl chloride (0.95 equivalents) was slowly added dropwise while simultaneously adding 30% sodium hydroxide aqueous solution to maintain the pH at 11. The addition process took about 1.5 hours. After the addition was completed, the mixture was stirred for another hour. After the reaction was complete, 6 M hydrochloric acid was slowly added dropwise at room temperature to adjust the pH to about 6. The mixture was transferred to a separatory funnel, allowed to stand and separate into layers, and the lower aqueous phase was removed. The product was filtered to obtain a white solid product, washed with a small amount of ethanol / water solution (2:1 volume ratio), and dried in an oven to obtain the target product N. ε -Lauroyl lysine, white powder, 7.8 g, yield 42%, HPLC purity greater than 97%.

[0042] Example 9

[0043] In a 500 mL four-necked round-bottom flask equipped with a stirrer, 11.0 g of lysine hydrochloride, 4.0 g of sodium hydroxide, and 12.0 g of water were added and stirred at room temperature to dissolve. Then, 40 mL of ethanol, 80 mL of petroleum ether, and 0.2 g of sodium lauryl sulfate (emulsifier) ​​were added and stirred until homogeneous. After about 30 minutes, a transparent microemulsion was formed. The reaction solution was cooled to 10 °C, and 12.5 g of lauroyl chloride (0.95 equivalents) was slowly added dropwise while simultaneously adding 30% sodium hydroxide aqueous solution to maintain the pH at 11. The addition process took about 1.5 hours. After the addition was completed, the mixture was stirred for another hour. After the reaction was completed, the mixture was allowed to return to room temperature, and 6 M hydrochloric acid was slowly added dropwise to adjust the pH to around 6. The mixture was transferred to a separatory funnel, allowed to stand and separate into layers, and the lower aqueous phase was removed. The product was filtered to obtain a white solid product, washed with a small amount of ethanol / water solution (2:1 volume ratio), and dried in an oven to obtain the target product N. ε -Lauroyl lysine, white powder, 13.8 g, yield 74%, HPLC purity greater than 97%.

[0044] Example 10

[0045] In a 500 mL four-necked round-bottom flask equipped with a stirrer, 11.0 g of lysine hydrochloride, 4.0 g of sodium hydroxide, and 12.0 g of water were added and stirred at room temperature to dissolve. Then, 40 mL of ethanol, 60 mL of n-hexane, and 0.2 g of sodium lauryl sulfate (emulsifier) ​​were added and stirred until homogeneous. After about 30 minutes, a transparent microemulsion was formed. The reaction solution was cooled to 10 °C, and 12.5 g of lauroyl chloride (0.95 equivalents) was slowly added dropwise while simultaneously adding 30% sodium hydroxide aqueous solution to maintain the pH at 10. The dropwise addition process took about 1.5 hours. After the addition was completed, the mixture was stirred for another hour. After the reaction was completed, the mixture was allowed to return to room temperature, and 6 M hydrochloric acid was slowly added dropwise to adjust the pH to around 6. The mixture was transferred to a separatory funnel, allowed to stand to separate the layers, and the lower aqueous phase was removed. The product was filtered to obtain a white solid product, washed with a small amount of ethanol / water solution (2:1 volume ratio), and dried in an oven to obtain the target product N. ε -Lauroyl lysine, white powder, 12.42 g, yield 66%, HPLC purity greater than 97%.

[0046] Example 11

[0047] In a 500 mL four-necked round-bottom flask equipped with a stirrer, 11.0 g of lysine hydrochloride, 4.0 g of sodium hydroxide, and 12.0 g of water were added and stirred at room temperature to dissolve. Then, 40 mL of ethanol, 40 mL of n-hexane, and 0.2 g of sodium lauryl sulfate (emulsifier) ​​were added and stirred until homogeneous. After about 30 minutes, a transparent microemulsion was formed. The reaction solution was cooled to 10 °C, and 12.5 g of lauroyl chloride (0.95 equivalents) was slowly added dropwise while simultaneously adding 30% sodium hydroxide aqueous solution to maintain the pH at 11. The addition process took about 1.5 hours. After the addition was completed, the mixture was stirred for another 1 hour. After the reaction was completed, the mixture was allowed to return to room temperature, and 6 M hydrochloric acid was slowly added dropwise to adjust the pH to around 6. The mixture was transferred to a separatory funnel, allowed to stand and separate into layers, and the lower aqueous phase was removed. The product was filtered to obtain a white solid product, washed with a small amount of ethanol / water solution (2:1 volume ratio), and dried in an oven to obtain the target product N. ε -Lauroyl lysine, white powder, 10.1 g, yield 54%, HPLC purity greater than 97%.

[0048] Example 12

[0049] In a 500 mL four-necked round-bottom flask equipped with a stirrer, 11.0 g of lysine hydrochloride, 4.0 g of sodium hydroxide, and 12.0 g of water were added and stirred at room temperature to dissolve. Then, 20 mL of ethanol, 80 mL of n-hexane, and 0.2 g of sodium lauryl sulfate (emulsifier) ​​were added and stirred until homogeneous. After about 30 minutes, a transparent microemulsion was formed. The reaction solution was cooled to 10 °C, and 12.5 g of lauroyl chloride (0.95 equivalents) was slowly added dropwise while simultaneously adding 30% sodium hydroxide aqueous solution to maintain the pH at 11. The addition process took about 1.5 hours. After the addition was completed, the mixture was stirred for another hour. After the reaction was completed, the mixture was allowed to return to room temperature, and 6 M hydrochloric acid was slowly added dropwise to adjust the pH to around 6. The mixture was transferred to a separatory funnel, allowed to stand and separate into layers, and the lower aqueous phase was removed. The product was filtered to obtain a white solid product, washed with a small amount of ethanol / water solution (2:1 volume ratio), and dried in an oven to obtain the target product N. ε -Lauroyl lysine, white powder, 11.6 g, yield 62%, HPLC purity greater than 97%.

[0050] Comparative Example 1

[0051] In a 500 mL four-necked round-bottom flask equipped with a stirrer, add 11.0 g of lysine hydrochloride, 4.0 g of sodium hydroxide, and 12.0 g of water. Dissolve by stirring at room temperature. Add 80 mL of n-hexane and 0.2 g of sodium lauryl sulfate (emulsifier) ​​and stir until homogeneous. Cool the reaction solution to 10 °C and slowly add 12.5 g of lauroyl chloride (0.95 equivalents) dropwise while simultaneously adding 30% sodium hydroxide aqueous solution to maintain the pH at approximately 11. The dropwise addition process takes about 1.5 h. After the addition is complete, stir for another 1 h. After the reaction is complete, return to room temperature and slowly add 6 M hydrochloric acid to adjust the pH to approximately 6. Transfer the solution to a separatory funnel, allow it to stand and separate into layers. Separate and remove the lower aqueous phase. Filter to obtain a white solid product. The product is very viscous and difficult to dry. Perform simple recrystallization with ethanol / water (2:1 volume ratio), filter again, wash with a small amount of ethanol / water aqueous solution (2:1 volume ratio), and dry in an oven to obtain the target product N. ε -Lauroyl lysine, white powder, 3.0 g, yield 16%, HPLC purity greater than 97%.

[0052] Comparative Example 2

[0053] In a 500 mL four-necked round-bottom flask equipped with a stirrer, 11.0 g of lysine hydrochloride, 4.0 g of sodium hydroxide, and 12.0 g of water were added and stirred at room temperature to dissolve. Then, 40 mL of ethanol was added and stirred until homogeneous. The reaction solution was cooled to 10 °C, and 12.5 g of lauroyl chloride (0.95 equivalents) was slowly added dropwise while simultaneously adding 30% sodium hydroxide aqueous solution to maintain the pH at approximately 11. The dropwise addition process took about 1.5 h. After the addition was complete, the mixture was stirred for another 1 h. After the reaction was completed, the mixture was allowed to return to room temperature, and 6 M hydrochloric acid was slowly added dropwise to adjust the pH to approximately 6. The product was filtered to obtain a white solid product. The product was very viscous and difficult to dry. Simple recrystallization was performed with ethanol / water (2:1 volume ratio), followed by filtration. The product was washed with a small amount of ethanol / water aqueous solution (2:1 volume ratio), dried in an oven, and the target product was obtained as a white powder, 6.1 g, yield 33%. ε The HPLC purity of 1,4-lauroyl lysine was 36.44%.

[0054] In summary, the above description is merely a preferred experimental method of the present invention, and the scope of protection of the present invention is not limited thereto. Any simple changes or equivalent substitutions of the technical solutions that can be obviously obtained by those skilled in the art within the scope of the technology disclosed in the present invention shall be included within the scope of protection of the present invention.

Claims

1. A kind of N ε A method for synthesizing -lauroyl lysine, characterized in that: Includes the following steps: 1) The raw materials, including lysine and / or lysine salts, basic compounds, water, low-carbon alcohols and non-water-soluble solvents, are stirred evenly to form a two-phase microemulsion; The ratio of the total volume of the water and the low-carbon alcohol to the volume of the non-water-soluble solvent is 1:1 to 1:

5. The volume ratio of water to the lower alcohol is (5~20):40; the lower alcohol is a C1~C4 alcohol. 2) Lauroyl halide was added dropwise to the two-phase microemulsion and stirred until the reaction was complete. The precipitate was then obtained by acid neutralization. ε -Lauroyl lysine.

2. The N according to claim 1 ε A method for synthesizing -lauroyl lysine, characterized in that: The non-water-soluble solvent includes at least one of petroleum ether, n-hexane, cyclohexane, toluene, and dichloromethane.

3. An N according to claim 1 ε A method for synthesizing -lauroyl lysine, characterized in that: The alkaline compound includes at least one of sodium hydroxide, potassium hydroxide, and triethylamine; The molar ratio of the basic compound to the lysine and / or lysine salt is (1.0~2.0):

1.

4. An N according to claim 1 ε A method for synthesizing -lauroyl lysine, characterized in that: The raw material contains an emulsifier; The emulsifier includes at least one of sodium lauryl sulfate, sodium oleate, polyoxyethylene hexadecyl alcohol, and polyoxyethylene monooleate.

5. An N according to claim 4 ε A method for synthesizing -lauroyl lysine, characterized in that: The amount of emulsifier used is less than 20% of the mass of lysine and / or lysine salt.

6. An N according to claim 1 ε A method for synthesizing -lauroyl lysine, characterized in that: The molar ratio of lysine and / or lysine salt to lauroyl halide is 2:1 to 1:

2.

7. An N according to claim 1 ε A method for synthesizing -lauroyl lysine, characterized in that: The reaction process is as follows: at a temperature of -5 to 50°C, an alkaline compound is added to the two-phase microemulsion to control its pH in the range of 9 to 14. At the same time, lauroyl halide is added dropwise to the two-phase microemulsion for reaction, and the dropwise addition time is controlled within 1 to 2 hours. After the dropwise addition is completed, the reaction is stirred for 0.5 to 12 hours.

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