KR20230046796A - Method for preparing p-Hydroxyacetophenone and cosmetic composition containing p-Hydroxyacetophenone - Google Patents

Abstract

A disclosed method for preparing para-hydroxyacetophenone is characterized by not going through any additional chemical reaction steps other than a chemical reaction step of adding an acid catalyst to phenol and acetyl and reacting at 0℃ to 30℃ for a set time, and accordingly, has the advantage of synthesizing para-hydroxyacetophenone simply and efficiently by using a one-step synthesis reaction to prepare para-hydroxyacetophenone through a single c-acylation reaction.

Description

Method for preparing p-Hydroxyacetophenone and cosmetic composition containing p-Hydroxyacetophenone

The present invention (Disclosure) is a method for producing parahydroxyacetophenone in high yield by simplifying the existing two-step synthesis process of parahydroxyacetophenone into one step while increasing the synthesis yield, and parahydroxyacetophenone It relates to a cosmetic composition comprising

Here, background art related to the present invention is provided, and they do not necessarily mean prior art (This section provides background information related to the present disclosure which is not necessarily prior art).

In cosmetics, preservatives are essential substances due to the nature of cosmetics that are easily perishable, but consumer perception of preservatives has been negative since the humidifier disinfectant crisis.

As a way to solve this problem, I want to use only natural extracts, but the efficacy is low and the price is high, so it is difficult to use alone. Preservative boosters such as Ethylhexylglycerin, 1,2-Octanediol, Methylpropand - Mixed with iol and 1,2-Hexanediol, etc., we are using the concept of “use of natural extracts and no preservatives”.

Diol types such as 1,2-Octanediol, 1,2-pentanediol, Methyl-propandiol, and 1,2-Hexanediol are widely used as representative raw materials for preservative boosters. fall and are relatively expensive. In particular, 1,2-Hexanediol, which is most commonly used due to its good usability and efficacy, has recently been registered as a preservative and cannot be used in preservative-free concept products, so an alternative raw material is needed.

p-hydroxyacetophenone is listed as an antioxidant in the Cosmetic Ingredient Standards Guide and is emerging as a preservative booster as it is safe for the human body and can control a wide spectrum of microorganisms without being a preservative.

However, despite the useful properties of para-hydroxyacetophenone, it is difficult to synthesize and expensive raw materials, making it less widely used than the diol type.

In patent CN104591990A, parahydroxyacetophenone is synthesized by using p-ethylphenol as a catalyst with metallop-orphyrin-metal salt in methanol solvent, and the yield is extremely low at 11%.

In patent EP0167286A1, 30 molar equivalents of HF to phenol and acetic anhydride are reacted by adding a very large amount of catalyst, but the synthesis yield is 80%, and HF is a very difficult material to handle, so mass production is difficult and production It has a high unit price disadvantage.

In WO2008099418A2, a solid heteropoly acid such as phosphotungstic acid is used as a catalyst, but the synthesis yield is only 50%.

Patent No. 10-2195387 is inefficient because it consists of a two-step reaction in which phenylacetate obtained through an o-acylation reaction with an acetyl compound such as acetyl chloride is prepared and Fries arrangement reaction is performed therein under an acid catalyst.

The present inventors have developed a simple and efficient method for synthesizing para-hydroxyacetophenone through a single c-acylation reaction of phenol.

1. Chinese Patent Publication No. 104591990 2. European Patent Publication No. 0167286

The present invention (Disclosure) aims to provide a method for producing para-hydroxyacetophenone in high yield while simplifying the existing two-step synthesis process into one step and increasing the synthesis yield, and a cosmetic composition containing the same.

The present invention (Disclosure) provides a manufacturing method that minimizes the production of isomers of phenylacetate or parahydroxyacetophenone by applying an acid catalyst at a relatively low temperature in the production of parahydroxyacetophenone, which is a preservative for cosmetics and pharmaceuticals. The purpose.

This section provides a general summary of the disclosure and is not a comprehensive disclosure of its full scope or all of its features).

In order to solve the above problems, a method for producing parahydroxyacetophenone according to any one of the various aspects described in the present invention is to add an acid catalyst to phenol and acetyl and set at 0 ° C to 30 ° C It is characterized in that it does not undergo an additional chemical reaction step other than the chemical reaction step of reacting for a period of time.

In the method for producing parahydroxyacetophenone according to any one of the various aspects described in the present invention, after the chemical reaction step, the acid catalyst is removed using water, and the solvent, A step of obtaining crude para-hydroxyacetophenone by removing side reactants and unreacted materials may be included.

In the method for producing parahydroxyacetophenone according to any one of the various aspects of the present invention, the chemical reaction step is performed by adding the acid catalyst to the phenol and the acetyl group at 5 ° C to 25 ° C It can be characterized by reacting for a set time in

In the method for producing parahydroxyacetophenone according to any one of the various aspects of the present invention, the set time may be 1 to 48 hours.

In the method for producing para-hydroxyacetophenone according to any one of the various aspects described in the present invention, the acetyls include at least one of acetyl chloride, acetic anhydride and acetic acid. can

In the method for producing parahydroxyacetophenone according to any one of the various aspects of the present invention, the acid catalyst is aluminum chloride, methanesulfonic acid, polyphosphoric acid, trifluoromethanesulfonic acid, hydrochloric acid, hydrofluoric acid, It may be characterized in that it includes at least one of sulfuric acid and paratoluene acid.

In the method for producing parahydroxyacetophenone according to any one of the various aspects described in the present invention, the acid catalyst is 0.5 to 4.0 equivalents, preferably 1.0 to 2.0 equivalents, relative to the phenol. can be characterized.

In the method for preparing parahydroxyacetophenone according to any one of the various aspects described in the present invention, the chemical reaction step is performed in a solvent selected from organic chlorine compounds, haloalkyl ethers or alkyl acetates. can be characterized as being

In the method for producing parahydroxyacetophenone according to any one of the various aspects described in the present invention, the solvent is methylene chloride, ethylene chloride, ethyl acetate, methyl acetate, isopropyle acetate, cyclohexane acetate, Bis (2-chloroethyl) ether, 1-chloro-3-methoxypropane, 2-chloroethyl ethyl ether, 1,2-Bis (2-chloroethoxy) ethane, at least one selected from 2-chloroethyl chloromethyl ether and 2-chloroethyl propyl ether Characterized in that, the solvent may be characterized in that it is provided in a weight ratio of greater than 0 and less than 10, preferably greater than 0 and less than 2, relative to the weight of the phenol.

In the method for producing parahydroxyacetophenone according to any one of the various aspects described in the present invention, high purity parahydroxyacetophenone is obtained from the crude parahydroxyacetophenone through recrystallization. It may include steps to obtain.

Here, solutions such as organic solvents, water, and acids may be used for recrystallization.

In the cosmetic composition containing para-hydroxyacetophenone according to any one of the various aspects described in the present invention, the para-hydroxyacetophenone is contained in an amount of 0.1 to 5% by weight based on the total weight of the cosmetic composition. However, it is preferably included in 0.1 to 2% by weight, and the formulation is softening lotion, astringent lotion, nutrient lotion, nutrient cream, massage cream, essence, eye essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack and powder It may be characterized in that it is any one selected from among.

Para-hydroxyacetophenone according to the present invention can also be applied as an antioxidant and preservative in pharmaceuticals.

According to the present invention, it has the advantage of being able to synthesize para-hydroxyacetophenone simply and efficiently by using a one-step synthesis reaction for producing para-hydroxyacetophenone through a single c-acylation reaction of phenol.

According to the present invention, it has the advantage of obtaining a cosmetic and pharmaceutical composition having an antibacterial effect using para-hydroxyacetophenone.

Hereinafter, an embodiment implementing a method for preparing para-hydroxyacetophenone and a cosmetic composition containing para-hydroxyacetophenone according to the present invention will be described in detail.

However, the essential (intrinsic) technical idea of the present invention cannot be said to be limited by the embodiments described below, and based on the essential (intrinsic) technical idea of the present invention, a person skilled in the art below It is revealed that the embodiments described in include the range that can be easily proposed as a method of substitution or change.

In addition, since the terms used below are selected for convenience of description, in grasping the essential (intrinsic) technical idea of the present invention, they are not limited to the dictionary meaning and are appropriately interpreted in a meaning consistent with the technical idea of the present invention. It should be.

The method for producing parahydroxyacetophenone according to the present invention minimizes the production of isomers of phenylacetate or parahydroxyacetophenone in the production of parahydroxyacetophenone, which is a preservative for cosmetics. It is characterized by the fact that it was solved by an acetylation reaction in

When phenol is subjected to an acetylation reaction, O-acylation results in the formation of phenylacetate, or C-acylation results in the formation of ortho, meta, para-hydroxyacetophenones, as shown in the following reaction formula.

In the acylation reaction of phenol, the O-acylation reaction in which phenylacetate is formed occurs thermodynamically quickly. there is.

The method for producing parahydroxyacetophenone according to the present invention is characterized in that it does not undergo an additional chemical reaction step other than the chemical reaction step of adding an acid catalyst to phenol and acetyls and reacting for a set time at 0 ° C to 30 ° C.

Here, after the chemical reaction step, it may include removing the acid catalyst using water, and obtaining crude parahydroxyacetophenone by removing the solvent, by-reactants and unreacted materials through distillation under reduced pressure.

In addition, in the chemical reaction step, it is preferable to add the acid catalyst to the phenol and the acetyls and react for a set time at 5 ° C to 25 ° C.

At a temperature of 25 ° C or higher, O-acylation of phenol described above is rapidly induced to form phenyl acetate, and the yield of parahydroxyacetophenone is very low.

In addition, it is preferable that the set time is 1 to 48 hours.

Meanwhile, in the method for producing para-hydroxyacetophenone according to the present invention, the acetyl group includes at least one of acetyl chloride, acetic anhydride, and acetic acid.

The acid catalyst includes at least one of aluminum chloride, methanesulfonic acid, polyphosphoric acid, trifluoromethanesulfonic acid, hydrochloric acid, hydrofluoric acid, sulfuric acid, and paratoluene acid.

In addition, the acid catalyst is 0.5 to 4.0 equivalents, preferably 1.0 to 2.0 equivalents compared to the phenol.

After completion of the reaction, since the acid catalyst exists in the form of a complex compound with the reactant until work-up is performed through water, a desirable equivalent should be maintained because the synthesis conversion rate is lowered below the equivalent of the reactant.

In addition, in the method for preparing para-hydroxyacetophenone according to the present invention, the chemical reaction step may be performed in a solvent selected from organic chlorine compounds, haloalkyl ethers, and alkyl acetates.

The solvent is methylene chloride, ethylene chloride, ethyl acetate, methyl acetate, isopropyle acetate, cyclohexane acetate, Bis(2-chloroethyl) ether, 1-chloro-3-methoxypropane, 2-chloroethyl ethyl ether, 1,2-Bis(2 -chloroethoxy) ethane, characterized in that at least one selected from 2-chloroethyl chloromethyl Ether and 2-chloroethyl propyl ether, the solvent is provided in a weight ratio of greater than 0 and less than 10, preferably greater than 0 2 It may be provided in the following weight ratio.

In solvents other than the above solvents, c-acylation is hardly induced, so parahydroxyacetophenone is not synthesized. However, in the case of using a liquid acid catalyst such as methanesulfonic acid, since the acid catalyst acts as a solvent, the c-acylation reaction can be maintained without using an additional solvent.

Meanwhile, in the method for preparing para-hydroxyacetophenone according to the present invention, a step of obtaining high-purity para-hydroxyacetophenone from the crude para-hydroxyacetophenone through recrystallization may be included.

Here, solutions such as organic solvents, water, and acids may be used for recrystallization.

On the other hand, in the cosmetic composition containing para-hydroxyacetophenone according to the present invention, the para-hydroxyacetophenone is included in an amount of 0.1 to 5% by weight, preferably 0.1 to 2% by weight, based on the total weight of the cosmetic composition. It can be characterized in that the formulation is any one selected from softening lotion, astringent lotion, nutrient lotion, nutrient cream, massage cream, essence, eye essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, and powder. And it can also be applied to pharmaceuticals.

Hereinafter, it is shown that para-hydroxyacetophenone is produced in high yield by various examples according to the method for producing para-hydroxyacetophenone according to the present invention, and unlike the present invention, those that do not follow the method for producing para-hydroxyacetophenone In this case, it will be described as a comparative example that para-hydroxyacetophenone is not prepared with only one chemical reaction step.

Example 1

23.0 g of aluminum chloride was added to 60 ml of methylene chloride at room temperature, and 12.3 g of acetyl chloride was slowly added while maintaining the reaction solution at 20 ° C and stirring for 30 minutes.

Here, 14.9 g of phenol was slowly added, and the reaction solution was maintained not to exceed 20 ° C. After adding all liquids, stirring was performed at 15 - 20 ° C. for 6 hours, and then 100 g of purified water was added, and the lower layer in which water and aluminum chloride were mixed was removed.

From the upper layer, solvent, by-products and unreacted phenol were removed under reduced pressure to obtain 13.4 g of crude parahydroxyacetophenone. The resulting crude para-hydroxyacetophenone was recrystallized from ethyl acetate and cyclohexane to obtain 13.1 g of the target compound.

Example 2

23.0 g of aluminum chloride was added to 60 ml of methylene chloride at room temperature, and 12.3 g of acetyl chloride was slowly added while maintaining the reaction solution at 20 ° C and stirring for 30 minutes.

Here, 17.1 g of phenol was slowly added, and the reaction solution was maintained not to exceed 20 ° C. After adding all liquids, stirring was performed at 15 - 20 ° C. for 6 hours, and then 100 g of purified water was added, and the lower layer in which water and aluminum chloride were mixed was removed.

From the upper layer, solvent, by-products and unreacted phenol were removed under reduced pressure to obtain 15.6 g of crude parahydroxyacetophenone. The resulting crude para-hydroxyacetophenone was recrystallized from ethyl acetate and cyclohexane to obtain 13.8 g of the target compound.

Example 3

23.0 g of aluminum chloride was added to 60 ml of methylene chloride at room temperature, and 14.2 g of acetyl chloride was slowly added while maintaining the reaction solution at 20 ° C and stirring for 30 minutes.

Here, 14.9 g of phenol was slowly added, and the reaction solution was maintained not to exceed 20 ° C. After adding all liquids, stirring was performed at 15 - 20 ° C. for 6 hours, and then 100 g of purified water was added, and the lower layer in which water and aluminum chloride were mixed was removed.

From the upper layer, solvent, by-products and unreacted phenol were removed under reduced pressure to obtain 11.7 g of crude parahydroxyacetophenone. The resulting crude para-hydroxyacetophenone was recrystallized from ethyl acetate and cyclohexane to obtain 9.5 g of the target compound.

Example 4

23.0 g of aluminum chloride was added to 60 ml of ethylene chloride at room temperature, and 14.9 g of acetyl chloride was slowly added while maintaining the reaction solution at 20 ° C and stirring for 30 minutes.

Here, 12.3 g of phenol was slowly added, and the reaction solution was maintained not to exceed 20 ° C. After adding all liquids, stirring was performed at 15 - 20 ° C. for 6 hours, and then 100 g of purified water was added, and the lower layer in which water and aluminum chloride were mixed was removed.

From the upper layer, solvent, by-products and unreacted phenol were removed under reduced pressure to obtain 12.5 g of crude parahydroxyacetophenone. The resulting crude para-hydroxyacetophenone was recrystallized from ethyl acetate and cyclohexane to obtain 11.2 g of the target compound.

Example 5

16.5 g of methanesulfonic acid was added to 60 ml of methylene chloride at room temperature, and 12.3 g of acetyl chloride was slowly added while maintaining the reaction solution at 20 ° C and stirring for 30 minutes.

Here, 14.9 g of phenol was slowly added, and the reaction solution was maintained not to exceed 20 ° C. After adding all liquids, stirring was performed at 15 - 20 ° C. for 6 hours, and then 100 g of purified water was added, and the lower layer in which water and aluminum chloride were mixed was removed.

From the upper layer, solvent, by-products and unreacted phenol were removed under reduced pressure to obtain 12.5 g of crude parahydroxyacetophenone. The resulting crude para-hydroxyacetophenone was recrystallized from ethyl acetate and cyclohexane to obtain 11.8 g of the target compound.

Example 6

16.5 g of methanesulfonic acid was added at room temperature, and 12.3 g of acetyl chloride was slowly added while maintaining the reaction solution at 20° C. and stirring for 30 minutes.

Here, 14.9 g of phenol was slowly added, and the reaction solution was maintained not to exceed 20 ° C. After adding all liquids, stirring was performed at 15 - 20 ° C. for 6 hours, and then 100 g of purified water was added, and the lower layer in which water and aluminum chloride were mixed was removed.

From the upper layer, solvent, by-products and unreacted phenol were removed under reduced pressure to obtain 14.1 g of crude parahydroxyacetophenone. The resulting crude para-hydroxyacetophenone was recrystallized from ethyl acetate and cyclohexane to obtain 13.2 g of the target compound.

Example 7

16.5 g of methanesulfonic acid was added at room temperature, and 14.9 g of phenol was slowly added while maintaining the reaction solution at 20° C. and stirring for 30 minutes.

Here, 12.3 g of acetyl chloride was slowly added, and the reaction solution was maintained not to exceed 20 ° C. After adding all liquids, stirring was performed at 15 - 20 ° C. for 6 hours, and then 100 g of purified water was added, and the lower layer in which water and aluminum chloride were mixed was removed.

From the upper layer, solvent, by-products and unreacted phenol were removed under reduced pressure to obtain 15.4 g of crude parahydroxyacetophenone. The resulting crude para-hydroxyacetophenone was recrystallized from ethyl acetate and cyclohexane to obtain 14.1 g of the target compound.

Comparative Example 1 (when the reaction temperature is high)

23.0 g of aluminum chloride was added to 60 ml of methylene chloride at room temperature, and 12.3 g of acetyl chloride was slowly added and stirred for 30 minutes.

After slowly adding 14.9 g of phenol to this mixture, the mixture was stirred at 45° C. for 6 hours, and then 100 g of purified water was added, and the lower layer in which water and aluminum chloride were mixed was removed.

As a result of removing the solvent, by-products, and unreacted phenol from the upper layer under reduced pressure, it was confirmed that more than 95% was converted to phenyl acetate, and as a result, parahydroxyacetophenone could not be obtained.

Comparative Example 2 (In case of high reaction temperature when using Methanesulfonic acid catalyst without solvent)

16.5 g of methanesulfonic acid was added at room temperature, and 14.9 g of phenol was slowly added while maintaining the reaction solution at 20° C. and stirring for 30 minutes.

Here, 12.3 g of acetyl chloride was slowly added, and the reaction solution was maintained not to exceed 20 ° C.

After adding all the liquids, the mixture was stirred at 70° C. for 6 hours, and then 100 g of purified water was added, and the lower layer in which water and aluminum chloride were mixed was removed.

As a result of removing the solvent, by-products, and unreacted phenol from the upper layer under reduced pressure, it was confirmed that more than 98% was converted to phenyl acetate, and as a result, parahydroxyacetophenone could not be obtained.

Comparative Example 3 (when the solvent is different)

23.0 g of aluminum chloride was added to 60 ml of dioxane at room temperature, and 12.3 g of acetyl chloride was slowly added while maintaining the reaction solution at 20 ° C and stirring for 30 minutes.

Here, 14.9 g of phenol was slowly added, and the reaction solution was maintained not to exceed 20 ° C.

After adding all liquids, stirring was performed at 15 - 20 ° C. for 6 hours, and then 100 g of purified water was added, and the lower layer in which water and aluminum chloride were mixed was removed.

As a result of removing the solvent, by-products, and unreacted phenol from the upper layer under reduced pressure, it was confirmed that more than 98% was converted to phenyl acetate, and as a result, parahydroxyacetophenone could not be obtained.

Test Example 1: Measurement of antibacterial activity (MIC) of parahydroxyacetophenone

A minimum inhibitory concentration (MIC) test was conducted to examine the antibacterial activity of para-hydroxyacetophenone prepared in Example 1.

As test strains, Staphylococcus aureus ATCC 6538, Escherichia coli ATCC 8739, Pseudomonas aeruginosa ATCC 9027, Candida albicans ATCC 10231, Aspergillus niger ATCC 16404 were used. was diluted in sterile physiological saline solution added at a rate of 0.05% to prepare a bacterial solution of 10 ⁶ CFU/mL.

After preparing a test solution with a maximum concentration of 1% using a sample of 30% concentration, a 1% to 0.1% 10-step diluted solution is sequentially prepared using Mueller Hinton broth, a medium for bacteria, and Glucose Phosphate broth, a medium for fungi. manufactured.

The prepared dilution series is inoculated with bacterial and spore fluids, and the final concentration of bacteria is 1.0 × 10 ⁴ ~ 1.0 × 10 ⁵ CFU / mL, and the final concentration of fungi is 1.0 × 10 ³ ~ 1.0 × 10 ⁴ CFU / mL After culturing bacteria at 35 ° C. for 20 hours and fungi for 48-50 hours, the MIC was determined by visually observing the growth of inoculated bacteria and fungi (see Table 1).

Antibacterial activity (MIC) measurement result Fungus type E. coli P. aeruginosa S. aureus C. albicans A. brasiliensis MIC concentration (%) 0.2 0.3 0.3 0.2 0.3

Test Example 2: Stimulus test

A primary skin irritation test was conducted to determine whether or not the skin was irritated. The patch was attached to the upper back of the subject, and 25 μl of 1% compound of Example 1 was applied using an IQ Ultra chamber. The patch was attached and after 24 hours elapsed, the patch was removed.

The first reading was performed 30 minutes after the patch was removed, the second reading after 24 hours, and the third reading after 48 hours had elapsed by two experts by the International Contact Demartitis Research Group (ICDRG). ), the degree of stimulation was observed according to the criterion of

The primary skin irritation index (P.C.I) was obtained according to the following calculation formula, the skin irritation of the sample was determined according to the criteria of Tables 2 and 3, and the skin irritation index was calculated as shown in Figure 2, and the result was It is shown in Table 4 below.

Skin irritation evaluation criteria degree of stimulation Score Types of skin symptoms or signs - 0 Negative ± 0.5 Doubletful skin sign such as weak erythema + One Slight erythema, either spotty or diffuse ++ 2 Moderate uniform erythema +++ 3 Intense erythema with edema ++++ 4 Intense erythema with edema & vesicles IR (irritant reaction) - Other forms of stimulation response (including adhesive stimulation) NT (not tested) - interruption of test due to occurrence of irritant response or other reason)

Criteria for skin irritation rating Average Skin Irritation Index judgment grade 0.00 to 0.75 non-irritating 0.76 to 1.50 hypoallergenic 1.51 to 2.50 light stimulation 2.51 to 4.00 moderate stimulation 4.01 ~ strong stimulation

The test subjects who participated in this human application test were 30 healthy adults with an average age of 40.2 ± 7.9 years, and 30 participating test subjects completed the final test without dropping out.

Skin irritation index judgment result Sum of skin irritation response intensity skin irritation index skin irritation
Judgment grade Primary Secondary tertiary Example 1 0.00 0.00 0.00 0.00 non-irritating D (negative contrast) 0.00 0.00 0.00 0.00 non-irritating 1% SLS
(positive control) 4.00 3.00 2.50 3.52 moderate stimulation

As shown in Table 4, it was confirmed that parahydroxyacetophenone according to the present invention can be safely applied to the skin.

Cosmetic Composition Formulation Example 1 and Comparative Example 1: Lotion Preparation

The cosmetic composition containing para-hydroxyacetophenone prepared in Example 1 was prepared in Formulation Example 1 to confirm compatibility and stability with the cosmetic formulation.

For comparison, Comparative Example 1 was prepared in which 1,2-hexanediol was added instead of parahydroxyacetophenone of Formulation Example 1. Detailed compositions of Formulation Example 1 and Comparative Example 1 are shown in Table 5.

Composition of Formulation Example 1 and Comparative Example 1 division ingredient Prescription amount (%) Formulation example 1 Comparative Example 1 Paid Caprylic/capric triglycerides 7.5 15 Polyglyceryl 10 distearate 2 2 GMS One One Cetearyl alcohol 2 2 parahydroxyacetophenone 0.7 - 1,2 hexanediol - 2 Awards Water balance balance Glycerin 10 10 L-Arginine (10%) 3 3 thickener Carbomer (2%) 15 15 total 100% 100%

Specifically, the emulsifier, oil, and para-hydroxyacetophenone are heated and dissolved at 75 to 85 ° C in the oil phase dissolution unit, put into the aqueous phase production unit where the emulsifier, oil, and parahydroxyacetophenone are heated and dissolved at 75 to 85 ° C, emulsified using a homomixer, and then 50 to 60 It was cooled to °C, a thickener was added, mixing, stirring, and cooling were completed.

Test Example 3. Evaluation of stability for cosmetics

The stability of the lotion formulation containing parahydroxyacetophenone prepared in Formulation Example 1 was measured for a certain period of time at each temperature (5 ° C, 25 ° C, 40 ° C), and as a result, the formulation was stable in terms of pH, appearance, and odor. was able to secure Table 6 below shows the results of observing the properties of each item.

Safety evaluation results for cosmetics temperature Property item Formulation Example 1 Comparative Example 1 0 days 15th 30 days 60 days 60 days 5℃ pH 6.5 6.5 6.5 6.5 6.5 appearance G G G G G dreadlocks Good Good Good Good Good 25℃ pH 6.5 6.6 6.6 6.5 6.5 appearance G G G G G dreadlocks Good Good Good Good Good 40℃ pH 6.5 6.5 6.6 6.5 6.5 appearance G G G G G dreadlocks Good Good Good Good Good

pH: 5% aqueous solution

Appearance: Good - G, slightly discolored - SC, discolored - C

Test Example 4: Preservation effect test

In Formulation Example 1, the test for the preservation effect in the lotion formulation was conducted according to the method of ISO 11930.

The test bacteria were inoculated on Tryptic soy agar (TSA), and the yeast was inoculated on Sabouraud dextrose agar (SDA), incubated at 32.5 ° C for 24 hours, and then inoculated bacterial solution was prepared using sterile physiological saline.

The fungus was inoculated on Potato dextrose agar (PDA) and cultured at 25 ° C for one week to prepare a spore solution. Each sample was inoculated with the test bacterial solution and cultured at 25 ° C. Immediately after incubation, 14 days and 28 days after neutralization in a neutralization medium, a 10-fold dilution series was prepared.

The prepared dilution was inoculated into TSA for bacteria, SDA for yeast, and PDA for fungi, and cultured at 32.5℃ for bacteria and yeast for 48-72 hours and 25℃ for mold for 3-5 days, counting the number of viable cells formed on the medium. was converted.

Preservation effect test result test bacteria initial bacterial count
(CFU/mL) Log Reduction Day 14 Day 28 S. aureus 3.8×10 ⁶ >5.6 >5.6 E. coli 4.3×10 ⁶ >5.6 >5.6 P. aeruginosa 4.3×10 ⁶ >5.6 >5.6 C. albicans 4.5×10 ⁵ >4.7 >4.7 A. brasiliensis 1.9×10 ⁵ 1.1 4.1

* Limit of detection: <10 ¹ CFU/mL

Through the above results, it was confirmed that the parahydroxyacetophenone of the present invention is useful as an external skin preparation such as a cosmetic composition because it has excellent antibacterial activity and does not cause skin irritation, irritation, or allergy due to the use of the antibacterial agent, The compatibility and stability of the cosmetic containing para-hydroxyacetophenone were confirmed.

Formulation Example 2: Preparation of skin formulation

The cosmetic composition containing para-hydroxyacetophenone prepared in Example 1 was prepared in Formulation Example 2 to confirm compatibility and stability with the cosmetic formulation.

division composition Prescription amount (%) Paid glycerin 3 Disodium EDT 0.02 Polyglyceryl-3-methylglucose distearate 1.5 Cetearyl Alcohol 0.5 Awards Polyacrylamide & C13-14 Isoparaffin & Laureth-7 7 polyacrylamide 0.6 parahydroxyacetophenone 0.7 Purified water balance total 100

Test Example 5. Stability evaluation for Formulation Example 2

The stability of the skin formulation containing parahydroxyacetophenone prepared in Formulation Example 2 was measured for a certain period of time at each temperature (5 ° C, 25 ° C, 40 ° C), and as a result, the formulation was stable in terms of pH, appearance, and fragrance. was able to secure Table 6 below shows the results of observing the properties of each item.

Safety evaluation results for cosmetics temperature Property item Formulation Example 2 0 days 15th 30 days 60 days 5℃ pH 6.4 6.4 6.5 6.4 appearance G G G G dreadlocks Good Good Good Good 25℃ pH 6.4 6.3 6.4 6.3 appearance G G G G dreadlocks Good Good Good Good 40℃ pH 6.4 6.3 6.5 6.2 appearance G G G G dreadlocks Good Good Good Good

pH: 5% aqueous solution

Appearance: Good - G, slightly discolored - SC, discolored - C

Claims (10)

A method for producing parahydroxyacetophenone, characterized in that it does not undergo an additional chemical reaction step other than the chemical reaction step of adding an acid catalyst to phenol and acetyl and reacting for a set time at 0 ° C to 30 ° C. The method of claim 1,
After the chemical reaction step,
Method for producing parahydroxyacetophenone comprising the step of removing the acid catalyst using water and obtaining crude parahydroxyacetophenone by removing the solvent, side reactants and unreacted materials through distillation under reduced pressure. The method of claim 1,
The chemical reaction step is a method for producing parahydroxyacetophenone, characterized in that the acid catalyst is added to the phenol and the acetyls and reacted for a set time at 5 ° C to 25 ° C. The method of claim 3,
The acetyl group is a method for producing parahydroxyacetophenone, characterized in that it comprises at least one of acetyl chloride, acetic anhydride and acetic acid. The method of claim 3,
The acid catalyst is para-hydroxyacetophenone, characterized in that it comprises at least one of aluminum chloride, methanesulfonic acid, polyphosphoric acid, trifluoromethanesulfonic acid, hydrochloric acid, hydrofluoric acid, sulfuric acid and paratoluene acid Manufacturing method. The method of claim 5,
The acid catalyst is a method for producing parahydroxyacetophenone, characterized in that 0.5 to 4.0 equivalents compared to the phenol. The method of claim 3,
The chemical reaction step is a method for producing parahydroxyacetophenone, characterized in that carried out in a solvent selected from organic chlorine compounds, haloalkyl ethers or alkyl acetates. The method of claim 7,
The solvent is methylene chloride, ethylene chloride, ethyl acetate, methyl acetate, isopropyle acetate, cyclohexane acetate, Bis(2-chloroethyl) ether, 1-chloro-3-methoxypropane, 2-chloroethyl ethyl ether, 1,2-Bis(2 -chloroethoxy) ethane, characterized in that at least one selected from 2-chloroethyl chloromethyl Ether and 2-chloroethyl propyl ether,
The solvent is a method for producing parahydroxyacetophenone, characterized in that provided in a weight ratio of more than 0 and less than 10 relative to the weight of the phenol. The method of claim 2,
A method for producing parahydroxyacetophenone comprising the step of obtaining high purity parahydroxyacetophenone from the crude parahydroxyacetophenone through recrystallization. A cosmetic composition containing para-hydroxyacetophenone prepared by the method of claim 1,
The para-hydroxyacetophenone is included in an amount of 0.1 to 5% by weight based on the total weight of the cosmetic composition,
Parahydroxy, characterized in that the formulation is any one selected from softening lotion, astringent lotion, nutrient lotion, nutrient cream, massage cream, essence, eye essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack and powder A cosmetic composition comprising acetophenone.