| N?-Lauroyl-L-arginine ethyl ester monohydrochloride(LAE)is a cationic surfactant.The molecular formula of LAE is C20H41ClN4O3.In recent years LAE has been widely researched and applied as a new food preservative.LAE has a significant inhibitory effect on gram-positive bacteria,gram-negative bacteria,yeast and mold,which is a broad-spectrum antibacterial agent.LAE can be degraded by human body with high biological safety.LAE has been approved by United States Food and Drug Administration(FDA),United States Department of agriculture(USDA),European Food Safety Authority(EFSA),Codex Alimentarius Commission for food preservation with wide application prospect and huge market demand.LAE is obtained by amide condensation of arginine ethyl ester hydrochloride(C8H18NaO2·2HCl)and lauryl chloride(C12H23ClO).The preparation of LAE is divided into three steps:acid-base neutralization,amide condensation,separation and purification.This work selected water as reaction solvent,and optimized the synthesis stage to enhance conversion ratio.This work optimized the extraction stage to enhance productivity and purity.The optimum synthesis conditions and the optimum extraction conditions were used for the kilogram scale preparation test to obtain large batch LAE product with high yield and high purity.The main results are as follows:(1)Through research of reaction pH,temperature,substrate concentration,substrate molar ratio,concentration of sodium hydroxide solution,adding method of sodium hydroxide and dropping rate of lauroyl chloride to obtain the best reaction conditions in synthesis stage.The optimum synthesis conditions were:reaction pH?7.3 ± 0.2,temperature 15.0 ±1.0 ?,substrate concentration 0.3 mol/L,substrate molar ratio 1:1,concentration of sodium hydroxide solution 20%,dropping rate of lauroyl chloride<0.20 mL/min.On this condition,conversion ratio was above 90%.(2)Through optimization of extraction solvent,extraction time,amount of extraction solvent,extraction temperature,washing and drying conditions to obtain the best process conditions in extraction stage.The optimum extraction conditions were:extraction solvent was ethyl acetate.Extraction time was longer than 15 min.Amount of ethyl acetate was 1/2(v/v)of reaction solution.Extraction temperature was maintained at 20-30 ?.Ethyl acetate was washed by saturated sodium chloride solution.Ethyl acetate was rotary evaporated to obtain the product.On this condition,preparation yield was above 90%,and product purity was above 90%.(3)The optimum synthesis conditions and the optimum extraction conditions were used for the kilogram scale preparation.In synthesis stage,reaction pH,temperature,substrate concentration,substrate molar ratio and sodium hydroxide solution concentration were consistent with experimental scale conditions.Dropping rate of lauroyl chloride was adjusted to 6.00 mL/min.Stirring rate was above 250 rpm.On this condition,conversion rate was above 90%,and reaction time was shortened.In extraction stage,extraction solvent,extraction time,amount of ethyl acetate,extraction temperature,saturated sodium chloride solution washing and rotary evaporation conditions were consistent with experimental scale conditions.The vacuum degree of rotary evaporation was-0.1 MPa,and loss caused by transfer was reduced.On this condition,preparation yield was above 90%,and product purity was above 90%.In the study,90%of product was LAE,and 10%was lauric acid.Results reported in the literature indicated that LAE was rapidly degraded into arginine arginine(LAS)in human body,and then decomposed into arginine.Finally LAE was hydrolyzed into endogenous compounds.LAE had no acute toxicity(LD50 was greater than 2000 mg/kg body weight),no subchronic toxicity,no chronic toxicity,no mutagenicity and teratogenicity,no reproductive and developmental toxicity.Lauric acid is widely existed in nature such as human milk,and had no acute toxicity(LD50 was 12000 mg/kg body weight).Therefore the product prepared in this study is extremely safe. |
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