Preparation method of chlorphenesin_Kain Industrial Additives

Background and Overview^[1]

Chlorphenesin, Chinese aliases: chlorophenesin, chlorophenol ether, 3-p-chlorophenoxy-1,2-propanediol. English name Chlorphenesin, English aliases: Chlorophenesin; Gecophen; Adermykon; Chlorphenesinum, 3- (4-chlorophenoxy)propane-1,2-dio. Molecular formula C9H11ClO3, molecular weight 202.635, melting point 77-79°C. It is a white crystalline powder, odorless, bitter in taste, slightly soluble in water, and soluble in most organic solvents such as ethanol, methylene chloride, and ethyl acetate.

In medicine, chlorphenesin-related preparations are antigen-related immunosuppressants that inhibit IgE-mediated histamine release. Chlorphenesin also acts as a muscle relaxant. Chlorophene is also used as an antifungal drug. It is suitable for antifungal, bacterial, vaginal mold, and trichomoniasis diseases. There are many pharmaceutical dosage forms.

In cosmetics, chlorphenesin is used as a cosmetic bactericide in the “International Dictionary and Manual of Cosmetic Raw Materials”. Chlorphenesin can effectively resist Gram-positive and negative bacteria, especially Aspergillus niger IMI 149007 and Penicillium pinophilum IMI 87160 has strong bactericidal activity and has good inhibitory effect on Candida albicans NCPF 3179 and Saccharomyces cerevisiae NCPF 3275.

In the past ten years, chlorophenesin has been used in foreign countries to manufacture skin care products, medicated toothpastes, soaps, soaps, shampoo products, nail polish and other cosmetics and toiletries. According to FDA data provided by the industry, analysis of cosmetics using chlorophenesin shows that the maximum concentration of chlorphenesin in rinse-off products is 0.32%, and in leave-on products, the maximum concentration is 0.3%. Cosmetics containing chlorophenyl ether can be applied to the skin and hair, and can also be applied to cosmetics that come into contact with the eyes and mucous membranes. Products containing these ingredients are used very frequently, and some cosmetics containing chlorophene oleyl ether are often in contact with skin or hair. Chlorphenesin is also commonly used in hair, feet and sunscreen sprays and may also be inhaled. Based on further toxicological safety assessment, this inhalation may not pose a significant risk. According to the EU cosmetics labeling, chlorphenylsin is listed Out is a preservative whose maximum allowable concentration is 0.3%. The catalog on page 70 of China’s “Hygienic Standards for Cosmetics (2007 Edition)” states that chlorophenesin can be used as a restricted preservative in cosmetics, and its maximum allowable concentration in cosmetics is 0.3%.

Preparation^[1]

A green, efficient and selective method for synthesizing chlorphenesin. The specific operations are as follows:

In a 500ml three-necked flask, add 55.25g (0.60mol) of glycerin, 25.3g (0.28mol) of dimethyl carbonate, 25.8g (0.20mol) of p-chlorophenol, and 0.8g (0.02mol) of sodium hydroxide. Among them, the molar ratio of glycerol: diethyl carbonate: p-chlorophenol in the system is 3:1.4:1, and the molar ratio of p-chlorophenol and sodium hydroxide is 1:0.1. When feeding, maintain low-speed stirring at 30 rpm, heat to 110°C, and react for 11 hours. After the reaction is completed, cool down to 22°C, add 552.5g of the supernatant of saturated sodium chloride solution to the above reaction solution for washing, then add 552.5g of methylene chloride, mix evenly, let stand, separate layers, and take the organic phase. Concentrate to obtain a yellow-white solid, which is recrystallized with dichloromethane and suction-filtered to obtain a pure white powdery product. The solid powder is vacuum dried at 45°C to obtain 33.23g of chlorophenanglyceryl ether, with a calculated yield of 82%. HPLC detection Purity is 95.4%.

Detection method^[2]

Chlorphenesin is a white to off-white crystalline powder. It is a broad-spectrum bacteriostatic agent and preservative. It has good bactericidal and bactericidal effects on Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, mold and other microorganisms. Effect. Currently, chlorphenesin is allowed to be used as a preservative in cosmetics, but studies have shown that chlorphenesin may cause shortness of breath in infants. Therefore, it is recommended that infants not use products containing chlorphenesin. Europe’s “Toy Safety” Part 7: Finger Paints – Requirements and Test Methods” and the domestic GB 6675.14-2014 “Toy Safety Part 14: Finger Paints Requirements and Test Methods” allow the use of chlorphenesin as a restricted preservative, stipulating the maximum allowable use The concentration is 0.15%.

A liquid chromatography method for detecting chlorphenesin in toy materials, including the following steps:

(1) Prepare standard solution and fit standard curve equation

Weigh 0.05g (accurate to 0.0001g) chlorphenesin, add methanol-water (50:50, v/v), dissolve with ultrasonic, transfer to a 50mL volumetric flask, and dilute to volume with methanol-water solution Scale, shake well, and prepare a standard stock solution with a mass concentration of 1000mg/L;

Transfer 5.0 mL of 1000 mg/L standard stock solution into a 100 mL volumetric flask, dilute to volume with methanol-water (50:50, v/v) solution, shake well, and prepare a mass concentration of 50 mg/L. Intermediate working standard solution;

Transfer 0.20, 1.00, 2.00, 10.0mL of chlorphenesin intermediate working standard solution and 1.00, 2.50, 5.00mL of standard stock solution into 10mL volumetric flasks, and use methanol-water (50:50, v/ v) Dilute to the mark and shake well to obtain a series of concentration standard solutions with mass concentrations of 1.00, 5.00, 10.0, 50.0, 100, 250 and 500;

Carry out linear regression with the peak area as the ordinate (Y) and the mass concentration in the standard solution as the abscissa (X). The regression equation of chlorphenesin is obtained as Y=4.11(e+003)X-1.46(e +004).

(2)Sample processing

Weigh 1.0g of the sample (accurate to 0.0001g) into a 10mL colorimetric tube with a stopper, add the extraction solution (methanol-water (50:50, v/v)) to the mark and seal it with a sealing film, vortex Shake for 1.0min, perform ultrasonic extraction for 20-35min, and then filter through a 0.22μm filter membrane. The filtrate will be used as the sample liquid to be tested;

(3) Chromatographic detection

Use methanol-water as the mobile phase for gradient elution according to Table 1, use a C-18 column as the chromatographic column (100mm×2.1mm, 1.7μm), and use a photodiode array (PDA) detector with a detection wavelength of 280nm ( The detection wavelength of chlorphenesin), the flow rate is 0.2mL/min, the column temperature is 30°C, and the injection volume is 1μL. Substitute the measured peak area into the regression equation of step (1) to obtain the mass of chlorphenesin in the sample. concentration.

Table 1 Mobile phase gradient elution table

In the range of (1.000~500)mg/L, the peak area and mass concentration show a good linear relationship, and the correlation coefficient is 0.9995. The recovery rate of high and low levels of standard addition is 98.3% to 104%, and the relative standard deviation (ie, precision) is 0.51% to 2.13%.

Apply^[3]

An instant skin repair nutrient solution, characterized by being composed of water, butylene glycol, glycerin, diethoxyethyl succinate, snail extract, panthenol, nicotinamide, sodium hyaluronate, dipeptide dipeptide Aminobutyryl benzyl amide diacetate, phenoxyethanol, octanediol and chlorphenesin are mixed. The ratio of other ingredients is: water 75-100g, butylene glycol 5-10g, glycerin 2-5g, succinic acid Diethoxyethyl ester 1-3g, snail extract 0.2-2g, panthenol 0.1-1g, nicotinamide 0.2-2g, sodium hyaluronate 0.1-1g, dipeptide diaminobutyryl benzylamide diacetate 0.08-0.1g, phenoxyethanol 0.1-0.3g, octanediol 0.05-0.15g, chlorphenesin 0.1-0.2g. Advantages of the invention: snail is a health food with no toxic or side effects. The snail meat has high protein content and low fat content of only 2%. The snail meat contains more than 20 different types of essential amino acids for the human body. It also contains calcium, phosphorus, alkaloids, selenium, boron, zinc and other trace elements. Therefore, snails have high nutritional value.

References

[1][Invented in China] CN201810439851.4 A green, efficient and selective method for synthesizing chlorphenesin

[2] [Chinese invention] CN201910262416.3 A liquid chromatographic detection method for chlorphenesin in toy materials

[3]CN201510152573.0 An instant skin repair nutrient solution