Method for preparing 4-alkylresorcinol

Abstract

The present invention relates to a method for preparing alkylresorcinol, particularly, 4-alkylresorcinol, and to a preparation method capable of preparing high purity 4-alkylresorcinol in a high yield in an eco-friendly manner.

Description

Method for producing 4-alkylresorcinol

[0001] The present invention relates to a method for producing alkylresorcinol, specifically, 4-alkylresorcinol, and to a method for producing 4-alkylresorcinol in a high yield and high purity while being environmentally friendly.

[0002] Skin pigmentation is commonly known to occur when melanin pigment is produced when the skin is exposed to ultraviolet rays. In skin exposed to ultraviolet rays, melanocyte-stimulating hormone (α-MSH) is secreted from keratinocytes in the epidermis, stimulating melanocytes. Melanocytes stimulated by α-MSH promote tyrosinase gene expression, and the tyrosinase enzyme oxidizes the amino acid tyrosine, initiating the melanin biosynthesis process. The high-molecular-weight melanin produced in melanocytes moves to keratinocytes, and over time, newly formed keratinocytes push melanin-containing keratinocytes up into the stratum corneum. Ultimately, the black color of the melanin pigment contained in the keratinocytes causes the skin to appear dark.

[0003] Whitening cosmetics are products that inhibit this process and whiten the skin. Whitening cosmetics typically achieve their whitening effects by blocking external stimuli from reaching melanocytes, inhibiting the synthesis or activity of tyrosinase, an enzyme essential for melanin production, reducing the produced melanin, or promoting melanin excretion through rapid exfoliation.

[0004] Among these, blocking the early stages of melanin production by inhibiting tyrosinase activity is known to be the most potent whitening mechanism. Whitening agents used to block this early stage of melanin production include hydroquinone, kojic acid, and arbutin. However, existing whitening agents have safety issues such as toxicity, skin irritation, and side effects, and their whitening effects are also minimal, necessitating the development of alternatives.

[0005] 4-alkylresorcinol, especially 4-n-butylresorcinol, discovered as a next-generation whitening material, exhibits unparalleled whitening efficacy by simultaneously inhibiting tyrosinase and tyrosinase-activating protein. It also has the advantage of being safe to use without side effects and easy to be combined with other raw materials due to its high formulation compatibility.

[0006] However, conventional 4-alkylresorcinol manufacturing methods have long reaction times, resulting in low productivity. Furthermore, product purity and yield are also low, making them uncompetitive in price compared to conventional whitening agents. Furthermore, the manufacturing process uses hazardous solvents, such as toluene or methanol, making it unfriendly to the environment. Therefore, the development of a manufacturing method for 4-alkylresorcinol that can improve productivity and environmental friendliness is urgently needed.

[0007] The present invention has been devised to solve the above-described technical problems, and the problem to be solved by the present invention is to provide a method for producing 4-alkylresorcinol with high purity and high yield by performing a chemical reaction through microwave irradiation, thereby significantly shortening the reaction time.

[0008] Another problem to be solved by the present invention is to provide an environmentally friendly method for producing 4-alkylresorcinol.

[0009] The purposes of the present invention are not limited to those mentioned above, and other unmentioned purposes and advantages of the present invention can be understood through the following description and will be more clearly understood through the embodiments of the present invention. Furthermore, it will be readily apparent that the purposes and advantages of the present invention can be realized by the means and combinations thereof set forth in the claims.

[0010] In order to achieve the above-described technical task, the present invention provides a method for producing 4-alkylresorcinol, comprising the steps of (S10) generating an intermediate by acylating resorcinol and an acyl halide having C3 to C8 carbon atoms; and (S20) reducing a carbonyl group of the intermediate, wherein at least one of the steps (S10) and (S20) is performed while irradiating a microwave.

[0011] In one embodiment of the present invention, the microwave may be irradiated at an intensity of 0.1 W / ml to 15 W / ml, preferably at an intensity of 0.5 W / ml to 6 W / ml.

[0012] In one embodiment of the present invention, at least one of steps (S10) and (S20) can be performed solvent-free.

[0013] In one embodiment of the present invention, at least one of steps (S10) and (S20) may be performed under a zinc catalyst.

[0014] In one embodiment of the present invention, the step (S10) may further include a step of purifying the intermediate, and the step of purifying the intermediate may include a step (S11) of extracting the intermediate using a first organic solvent and an aqueous sodium chloride solution; and a step (S12) of precipitating a by-product from the extract extracted in the step (S11) using a second organic solvent.

[0015] According to the manufacturing method of the present invention, the manufacturing time of 4-alkylresorcinol can be significantly shortened, and the yield and purity of 4-alkylresorcinol can be improved.

[0016] According to the manufacturing method of the present invention, an environmentally friendly method for manufacturing 4-alkylresorcinol can be provided by excluding the use of solvents such as mercury-based catalysts and toluene during the manufacturing process.

[0017] In addition to the effects described above, specific effects of the present invention are described below while explaining specific details for carrying out the invention.

[0018] Figure 1 is a reaction formula showing the chemical reactions of each step of a method for producing 4-alkylresorcinol according to one embodiment of the present invention.

[0019] Figure 2a is the chemical structural formula of 1-(2,4-dihydroxyphenyl)butan-1-one.

[0020] Figure 2b is a diagram of a product of the first step benzene ring acylation reaction in a method for producing 4-alkylresorcinol according to an embodiment of the present invention. 1 The H-NMR spectrum is shown.

[0021] FIG. 2c illustrates the LC-MS spectrum of the first-step benzene ring acylation reaction product in the 4-alkylresorcinol production method according to one embodiment of the present invention.

[0022] Figure 3a is the chemical structural formula of 4-butylresorcinol.

[0023] Figure 3b is a diagram showing the product of the two-step carbonyl group reduction reaction in the 4-alkylresorcinol production method according to one embodiment of the present invention. 1 The H-NMR spectrum is shown.

[0024] Figure 3c illustrates the LC-MS spectrum of a two-step carbonyl group reduction reaction product in a method for producing 4-alkylresorcinol according to one embodiment of the present invention.

[0025] The principles of preferred embodiments of the present invention will be described in detail with reference to the attached drawings and descriptions below. However, the drawings and descriptions below are intended to illustrate preferred implementation methods among various methods for effectively explaining the features of the present invention, and the present invention is not limited to the drawings and descriptions below.

[0026] While terms such as "first" or "second" may be used to describe various components, these terms should be interpreted solely to distinguish one component from another. For example, a first component may be referred to as a second component, and similarly, a second component may also be referred to as a first component.

[0027] Singular expressions include plural expressions unless the context clearly dictates otherwise. In this specification, the terms "comprises" or "has" should be understood to indicate the presence of a described feature, number, step, operation, component, part, or combination thereof, but not to exclude the possibility of the presence or addition of one or more other features, numbers, steps, operations, components, parts, or combinations thereof.

[0028] In this specification, excess means more than one equivalent.

[0029] Unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art. Terms defined in commonly used dictionaries should be interpreted to have a meaning consistent with their meaning in the context of the relevant technology, and will not be interpreted in an idealized or overly formal sense unless explicitly defined herein.

[0030] As described above, the conventional manufacturing method for 4-alkylresorcinol, which is attracting attention as a next-generation whitening agent, has the problems of long reaction times and the use of large amounts of catalysts and solvents that are harmful to the human body during the manufacturing process. As a result of the present inventors' diligent efforts to solve the above problems, they discovered that the manufacturing time of 4-alkylresorcinol can be shortened using microwaves, significantly improving productivity, and significantly reducing manufacturing costs by improving yield and purity.

[0031] The present invention provides a method for producing 4-alkylresorcinol, comprising the steps of (S10) producing an intermediate by acylating resorcinol and an acyl halide having C3 to C8 carbon atoms; and (S20) reducing a carbonyl group of the intermediate, wherein at least one of the steps (S10) and (S20) is performed while irradiating with microwaves.

[0032] Figure 1 is a chemical reaction formula showing each step of a 4-alkylresorcinol manufacturing reaction according to one embodiment of the present invention.

[0033] Conventional methods for producing 4-alkylresorcinol compounds involved reacting a resorcinol compound with an alkyl halide. This reaction had the problem of generating unwanted by-products such as 2-alkylresorcinol and 4,6-dialkylresorcinol due to its low regioselectivity with respect to the benzene ring. The present invention obtains an aromatic ketone having a structure represented by the following chemical formula 1 as a product (intermediate) of the (S10) step reaction, and by reducing it, it has high regioselectivity with respect to the benzene ring, thereby significantly improving the yield.

[0034] [Chemical Formula 1]

[0035]

[0036] In the above chemical formula 1, R is a C2~C7 alkyl group.

[0037] In addition, even if the reaction of first introducing an acyl group to the benzene ring of resorcinol using an acyl halide is followed, the conventional manufacturing method has the problem of using substances that are harmful to the human body and cause environmental pollution, such as a Lewis acid catalyst such as zinc chloride (ZnCl2) and an organic solvent such as toluene, and the reaction time is also long.

[0038] According to the manufacturing method according to the present invention, the use of catalysts and solvents that cause environmental pollution can be eliminated by performing an acylation reaction while irradiating microwaves.

[0039] Below, each step is explained in detail.

[0040] In the present invention, the step (S10) is a step of generating an intermediate having a structure of the following chemical formula 1 by reacting resorcinol and acyl halide while irradiating them with microwaves to cause an acylation reaction.

[0041] [Chemical Formula 1]

[0042]

[0043] In the above chemical formula 1, R is a C2~C7 alkyl group.

[0044] According to the present invention, by improving the position selectivity of the acylation reaction of resorcinol through step (S10), the production of byproducts having acyl groups bonded at other positions, such as 2-acylesorcinol and 4,6-diacylesorcinol, can be minimized, thereby increasing the yield and reducing the manufacturing cost. Specifically, the acylation reaction may follow the mechanism of the Friedel-Crafts acylation reaction.

[0045] In a preferred embodiment of the present invention, the acylation reaction of step (S10) may be performed under a zinc (Zn) catalyst. Preferably, the zinc catalyst may be added in powder form in an amount of 0.8 to 1.2 equivalents relative to the resorcinol. Preferably, the amount may be 0.5 to 1.5 equivalents, and most preferably, 0.8 to 1.2 equivalents.

[0046] In a preferred embodiment of the present invention, the step (S10) can be performed as a non-solvent reaction without using a solvent. That is, the step (S10) of the present invention is performed as a solvent-free reaction while irradiating microwaves, so that it is environmentally friendly and an intermediate can be obtained in a high yield.

[0047] In the present invention, a non-solvent reaction that does not use a solvent means that a solvent capable of dissolving the reactants is not used.

[0048] In a preferred embodiment of the present invention, the acyl halide may be butyryl chloride, pentanoyl chloride, or 3-methylpropionyl chloride. Most preferably, butyryl chloride may be used.

[0049] The present invention can cause an acylation reaction without using a strong Lewis acid catalyst such as zinc chloride (ZnCl2) or aluminum chloride (AlCl3) by performing the acylation reaction while irradiating microwaves, and can significantly shorten the reaction time.

[0050] Microwaves are a type of electromagnetic wave with a wavelength longer than infrared rays, typically having a wavelength (λ) of 1 mm or longer. Specifically, microwaves with a wavelength of approximately 1 mm to 10 cm can be irradiated.

[0051] In a preferred embodiment of the present invention, the microwave has a correlation with the volume of the reactant being irradiated, and the volume of the reactant is hereinafter referred to as unit volume.

[0052] In one embodiment of the present invention, the intensity of microwaves per unit volume may be irradiated at an intensity of 0.1 W / ml to 15 W / ml, more preferably at an intensity of 0.5 W / ml to 6 W / ml. In addition, the reaction temperature may preferably be 45°C to 140°C, more preferably at 55°C to 130°C.

[0053] In the method for producing 4-alkylresorcinol of the present invention, a higher synthesis efficiency can be obtained when microwave irradiated, and the purpose of the present invention can be achieved without using an excessive amount or without using at all an organic solvent or Lewis acid that causes environmental pollution.

[0054] If the microwave intensity per unit volume is less than 0.1 W / ml or the reaction temperature is less than 45°C, the reaction rate may be low, so the effect of improving productivity may not be significant, and the temperature inside the reactant may be uneven, which may lower the yield.

[0055] If the microwave intensity per unit volume exceeds 15 W / ml or the reaction temperature exceeds 75°C, side reactions may be accelerated and the reaction yield may decrease.

[0056] Meanwhile, the above step (S10) can be performed for 3 to 30 minutes. This is a significant reduction in time compared to the conventional 4-acylesorcinol production method, which took a total of 4 to 10 hours.

[0057] According to the manufacturing method of the present invention, the step (S10) performs the reaction by irradiating microwaves and without using a solvent, thereby obtaining an intermediate in an environmentally friendly manner and with a high yield.

[0058] In the present invention, the step (S10) may further include a step of purifying the generated intermediate.

[0059] In one embodiment of the present invention, the purification step may include (S11) a step of extracting the intermediate using a first organic solvent and an aqueous sodium chloride solution; and (S12) a step of precipitating impurities from the extract extracted in step (S11) using a second organic solvent.

[0060] The first organic solvent may be a non-polar solvent such as ether, chloroform, benzene, hexane or dichloromethane, or a mixed solvent thereof, preferably dichloromethane, and an additional solvent, a mixed solvent of saturated chloride, may be used as an extraction solvent for extraction, preferably an aqueous sodium chloride solution.

[0061] At this time, the sodium chloride aqueous solution may be a saturated sodium chloride aqueous solution (Brine).

[0062] In one embodiment of the present invention, the mixing weight ratio of the first organic solvent and the sodium chloride aqueous solution in the extraction solvent may be 1:0.1 to 1:10, preferably 1:0.5 to 1:3, and most preferably 1:0.8 to 1:1.2.

[0063] In addition, the purity of the intermediate extracted in the step (S11) can be improved by precipitating impurities using a second organic solvent in the step (S12). The second organic solvent may preferably be a non-polar solvent such as ether, chloroform, benzene, hexane, or dichloromethane, or a mixed solvent thereof, but preferably, the second organic solvent may use hexane.

[0064] The above step (S20) is a step of performing a reaction to obtain a 4-alkylresorcinol compound by reducing the carbonyl group in the 4-acyl resorcinol compound, which is an intermediate produced in the above step (S10).

[0065] In one embodiment of the present invention, the reaction for reducing the carbonyl group of the intermediate is also performed by irradiating microwaves, so that the reaction can be performed in high yield without using a harmful mercury-based catalyst.

[0066] The reduction reaction of the above step (S20) may preferably follow the mechanism of the Wolf-Kishner reduction reaction or the Clemmensen reduction reaction. Preferably, it may be performed following the Clemmensen reduction mechanism.

[0067] In a preferred embodiment of the present invention, the step (S20) can also be performed as a non-solvent reaction without using a solvent.

[0068] In a preferred embodiment of the present invention, the step (S20) may use a non-mercury catalyst, and the non-mercury catalyst may be zinc (Zn). Specifically, the zinc may be provided as a powder and may be provided in an excess amount relative to the intermediate. Preferably, the non-mercury catalyst may be provided to the reaction in an amount of 12 to 15 equivalents relative to the intermediate. Unlike the Clemenson reduction reaction that typically uses an amalgam catalyst, the present invention can increase the environmental friendliness of the process by using a simple zinc catalyst.

[0069] In addition, in a preferred embodiment of the present invention, in the step (S20), the reduction reaction can be performed by irradiating microwaves per unit volume at an intensity of 0.1 W / ml to 15 W / ml, more preferably 0.5 W / ml to 6 W / ml, and most preferably 1 W / ml to 3 W / ml.

[0070] If the intensity of microwaves per unit volume is less than 0.1 W / ml, the reduction reaction may not be performed with only the zinc catalyst, and if it exceeds 15 W / ml, the temperature inside the reactant may rise too rapidly, causing carbonization.

[0071] In addition, the reduction reaction of the above step (S20) may preferably be performed at a temperature of 70°C to 110°C. If the reaction temperature is lower than 70°C, the reaction rate may decrease, thereby lowering the yield of the 4-alkylresorcinol production reaction.

[0072] In addition, in a preferred embodiment of the present invention, the reduction reaction of step (S20) may use one or more solvents selected from the group consisting of C2 to C5 aliphatic alcohols and water, or a mixed solvent of two or more solvents. Preferably, ethanol may be used as the solvent. In a preferred embodiment of the present invention, the reduction reaction of step (S20) may minimize human hazards and environmental pollution by using a solvent composed of alcohol and water instead of an organic solvent that is harmful to the environment and without using a mercury-based catalyst.

[0073] The compound produced by the reaction is 4-alkylresorcinol represented by the following chemical formula 2.

[0074] [Chemical Formula 2]

[0075]

[0076] In the above chemical formula 2, R' is a C3~C8 alkyl group.

[0077] In the conventional 4-alkylresorcinol manufacturing method, when the Clemenson reduction reaction is used, there was a problem that the reduction reaction was carried out at room temperature for more than 10 hours, resulting in very low productivity due to the long reaction time.

[0078] According to the present invention, when the reduction reaction is performed while irradiating microwaves in the above (S20) Clemenson reduction reaction, the reaction time can be significantly shortened, and 4-alkylresorcinol can be obtained in a high yield.

[0079] The above step (S20) includes a step of purifying 4-alkylresorcinol produced by a reduction reaction. Specifically, the purification step

[0080] (S21) A step of extracting 4-alkylresorcinol using a first organic solvent and an aqueous sodium chloride solution; and

[0081] (S22) It may be performed through a step of precipitating impurities from 4-alkylresorcinol extracted using a second organic solvent.

[0082] Preferably, the first organic solvent may be a non-polar solvent such as ether, chloroform, benzene, hexane, or dichloromethane, or a mixed solvent thereof. However, the type of the first organic solvent is not limited thereto.

[0083] In one embodiment of the present invention, it is most preferable that the step (S21) be performed by using a mixed solvent of dichloromethane and an aqueous sodium chloride solution as an extraction solvent.

[0084] In one embodiment of the present invention, the mixing weight ratio of the first organic solvent and the sodium chloride aqueous solution in the extraction solvent may be 1:0.1 to 1:5, preferably 1:0.5 to 1:3, and most preferably 1:0.8 to 1:1.2.

[0085] In addition, the 4-butylresorcinol extracted in the step (S21) can be used to precipitate impurities using a second organic solvent in the step (S22), and the purity can be improved in this process. The second organic solvent may preferably be a non-polar solvent such as ether, chloroform, benzene, hexane, or dichloromethane, or a mixed solvent thereof, but preferably, the second organic solvent may use hexane.

[0086] In this way, the 4-alkylresorcinol produced in the step (S20) can be purified by removing the precipitated impurities through the step (S22).

[0087] Preferably, the first organic solvent may be a non-polar solvent such as ether, chloroform, benzene, hexane or dichloromethane, or a mixed solvent thereof.

[0088] In one embodiment of the present invention, it is most preferable that the purification step be performed by extracting using a mixed solvent of dichloromethane and an aqueous sodium chloride solution as an extraction solvent.

[0089] In one embodiment of the present invention, the mixing weight ratio of the first organic solvent and the sodium chloride aqueous solution in the extraction solvent may be 1:0.1 to 1:5, preferably 1:0.5 to 1:3, and most preferably 1:0.8 to 1:1.2.

[0090] In the conventional 4-alkylresorcinol manufacturing method, column chromatography purification was used to purify 4-alkylresorcinol, but the purification method using column chromatography was very difficult, had very low productivity due to the long purification time, and had problems with residual chemicals, so there were also problems in terms of product purity.

[0091] According to the present invention, by performing the step of extracting 4-alkylresorcinol using the first organic solvent and the sodium chloride aqueous solution (S21); and the step of precipitating impurities from the 4-alkylresorcinol using the second organic solvent and recrystallizing to obtain 4-butylresorcinol from which impurities have been removed, the process is relatively simpler than the conventional column chromatography purification method, the purification time is drastically reduced, and high-purity 4-butylresorcinol can be obtained.

[0092] Hereinafter, the present invention will be described in more detail through examples and experimental examples. These examples and experimental examples are intended only to specifically illustrate the present invention, and the scope of the present invention is not limited by these examples and experimental examples.

[0093] Synthesis Example 1

[0094] [Example 1]

[0095] 1.1613 g of Zn powder, 1 g of resorcinol, and 1.13 ml of butyryl chloride were added to a microwave reaction vessel. Then, the reaction was performed by irradiating the mixture with microwaves at an intensity of 6 W / ml for approximately 5 minutes while stirring at a temperature of 65°C.

[0096] Next, the reaction by-products were removed using a mixed solvent of sodium chloride aqueous solution and dichloromethane in a 1:1 weight ratio, and then the intermediate 1-(2,4-dihydroxyphenyl)butan-1-one of the following chemical formula 3 was obtained.

[0097] [Chemical Formula 3]

[0098]

[0099] Below is the NMR data for 1-(2,4-dihydroxyphenyl)butan-1-one [chemical formula 3], and the NMR and mass spectroscopy data are shown in Figures 2b to 2c.

[0100] 1H-NMR (400 MHz, DMSO-d6)

[0101] δ 8.25-8.23 (d, 1H), 8.08 (t, 1H), 4.19-4.14 (m, 1H), 4.01-4.03 (m, 2H), 3.08-3.07 (m, 2H), 2.64-2.61 (t, 2H), 2.37-2.33 (t, 2H), 2.13-2.09 (t, 1H), 2.08 (s, 3H)1.74-1.67 (m, 1H), 1.65-1.55 (m, 1H), 1.53-1.47 (m, 4H), 1.28-1.22 (m, 16H), 1.18-1.14 (t, 3H), 0.86-0.82 (t, 3H).

[0102] [Comparative Example 1]

[0103] 1-(2,4-dihydroxyphenyl)butan-1-one was prepared in the same manner as in Example 1, but the sample was placed in a glass reaction vessel and the reaction was carried out for 5 minutes under temperature conditions of 65°C without microwave irradiation.

[0104] [Comparative Example 2]

[0105] 1-(2,4-dihydroxyphenyl)butan-1-one was prepared in the same manner as in Example 1, but instead of using a mixed solvent during the intermediate purification, an aqueous sodium chloride solution was used to remove impurities, and then the intermediate 1-(2,4-dihydroxyphenyl)butan-1-one was obtained.

[0106] [Comparative Example 3]

[0107] 1-(2,4-dihydroxyphenyl)butan-1-one was prepared in the same manner as in Example 1, but instead of using a mixed solvent during the intermediate purification, impurities were removed using dichloromethane, and then the intermediate 1-(2,4-dihydroxyphenyl)butan-1-one was obtained.

[0108] Synthesis Example 2

[0109] [Example 2]

[0110] 4.97 g of Zn powder was added to a microwave reaction vessel, and 1 g of 1-(2,4-dihydroxyphenyl)butan-1-one, the intermediate prepared in Example 1, and 2 mL of ethanol were added. Then, concentrated hydrochloric acid was added at a rate of 0.25 mL / min for 40 minutes using an additional funnel.

[0111] Next, the reaction was carried out by irradiating the microwave at 6 W / ml for about 20 minutes at a temperature of 80℃. After the reaction, 4-butylresorcinol was extracted using a first mixed solvent containing dichloromethane and sodium chloride aqueous solution in a weight ratio of 1:1, and impurities were precipitated from the extracted 4-butylresorcinol using a second mixed solvent containing dichloromethane and hexane in a weight ratio of 1:50 and then removed. Finally, the separated 4-butylresorcinol was precipitated in ice water for 2 hours, and after recrystallization, high-purity 4-butylresorcinol having a structure as shown in the following chemical formula 4 was obtained.

[0112] [Chemical Formula 4]

[0113]

[0114] Below is the chemical formula for 4-butylresorcinol (4-Butylresorcinol). 1 H-NMR data, and NMR and mass spectroscopy data are shown in Figure 3.

[0115] 1 H-NMR (400 MHz, DMSO-d6)

[0116] δ 8.25-8.23 (d, 1H), 8.08 (t, 1H), 4.19-4.14 (m, 1H), 4.01-4.03 (m, 2H), 3.08-3.07 (m, 2H), 2.64-2.61 (t, 2H), 2.37-2.33 (t, 2H), 2.13-2.09 (t, 1H), 2.08 (s, 3H)1.74-1.67 (m, 1H), 1.65-1.55 (m, 1H), 1.53-1.47 (m, 4H), 1.28-1.22 (m, 16H), 1.18-1.14 (t, 3H), 0.86-0.82 (t, 3H).

[0117] [Comparative Example 4]

[0118] 4-Butylresorcinol was prepared in the same manner as in Example 2, but without microwave irradiation, the reduction reaction was carried out at a temperature of 80°C for 20 minutes.

[0119] [Comparative Example 5]

[0120] 4-Butylresorcinol was prepared in the same manner as in Example 2, but the step of extracting 4-butylresorcinol with the first mixed solvent was omitted.

[0121] [Comparative Example 6]

[0122] 4-Butylresorcinol was prepared in the same manner as in Example 2, but the step of precipitating impurities from 4-butylresorcinol extracted with the first mixed solvent using a second mixed solvent of dichloromethane and hexane was omitted.

[0123] Experimental Example 1: Measurement of the yield and purity of the intermediate 1-(2,4-dihydroxyphenyl)butan-1-one of [Chemical Formula 1]

[0124] The yield and purity of the intermediate 1-(2,4-dihydroxyphenyl)butan-1-one prepared in Example 1 and Comparative Examples 1 to 3 were measured and shown in Table 1 below.

[0125] Experimental conditions Yield (%) Purity (%) Microwave purification Solvent Example 1 ○ DCM: Sodium chloride aqueous solution 72.7 9 5.87 Comparative example 1 - DCM: Sodium chloride aqueous solution 28.9 8 5.64 Comparative example 2 ○ Sodium chloride aqueous solution 64.8 5 5.42 Comparative example 3 ○ DCM 5 9.7 7 1.48

[0126] *DCM is dichloromethane

[0127] As can be confirmed in Table 1 above, when the Friedel-Crafts acylation reaction was performed while irradiating with microwaves (Example 1), it was confirmed that an intermediate was obtained in a higher yield than when the acylation reaction was performed without irradiating with microwaves (Comparative Example 1).

[0128] In addition, it was confirmed that when purifying with a mixed solvent of dichloromethane and sodium chloride aqueous solution (Example 1), the intermediate 1-(2,4-dihydroxyphenyl)butan-1-one was obtained with higher purity than when purifying with a single solvent of sodium chloride aqueous solution (Comparative Example 2) or a single solvent of dichloromethane (Comparative Example 3).

[0129] Experimental Example 2: Measurement of the yield and purity of 4-butylresorcinol of [chemical formula 2].

[0130] The yield and purity of 4-butylresorcinol prepared in Example 2 and Comparative Examples 4 to 6 were measured and shown in Table 2 below.

[0131] Experimental conditions Yield (%) Purity (%) Microwave purification Solvent Example 2 ○ DCM: Sodium chloride aqueous solution DCM: Hx8 5.3 9 8.99 Comparative example 4 - DCM: Sodium chloride aqueous solution DCM: Hx4 2.8 9 7.22 Comparative example 5 ○ DCM: Sodium chloride aqueous solution -6 8.9 7 0.55 Comparative example 6 ○ - DCM: Hx7 0.2 7 5.48

[0132] As can be seen in Table 2 above, when the reduction reaction was performed while irradiating microwaves (Example 2), it was confirmed that 4-butylresorcinol was obtained in a higher yield and purity than when the reduction reaction was performed without irradiating microwaves (Comparative Example 4). In addition, when 4-butylresorcinol was purified in two steps using a first mixed solvent containing a mixture of dichloromethane and an aqueous sodium chloride solution and a second mixed solvent containing a mixture of dichloromethane and hexane (Example 2), it was confirmed that 4-butylresorcinol was obtained in a higher purity than when only the extraction step with the first mixed solvent containing a mixture of dichloromethane and an aqueous sodium chloride solution was performed and the impurity precipitation step was omitted (Comparative Example 5) or when the extraction step with the first mixed solvent was omitted and only the impurity precipitation step with the second mixed solvent containing a mixture of dichloromethane and hexane was performed (Comparative Example 6).

[0133] It should be understood that the above-described embodiments are illustrative in all respects and not restrictive, and the scope of the present invention is indicated by the patent registration claims described below rather than the detailed description, and all changes or modified forms derived from the meaning and scope of the patent registration claims and their equivalent concepts should be interpreted as being included in the scope of the present invention.

Claims

1. (S10) A step of generating an intermediate by acylation reaction of resorcinol and an acyl halide having C3 to C8 carbon atoms; and (S20) A method for producing 4-alkylresorcinol, comprising a step of reducing a carbonyl group of the intermediate; At least one of the above steps (S10) and (S20) is performed while irradiating a microwave. Method for producing 4-alkylresorcinol.

2. In paragraph 1, A method for producing 4-alkylresorcinol, wherein the microwave is irradiated at an intensity of 0.1 W / mL to 15 W / mL per unit volume.

3. In paragraph 1, A method for producing 4-alkylresorcinol, wherein at least one of the above steps (S10) and (S20) is performed solvent free.

4. In paragraph 1, A method for producing 4-alkylresorcinol, wherein at least one of the above steps (S10) and (S20) is performed under a non-mercury catalyst.

5. In paragraph 1, The above step (S10) further includes a step of purifying the intermediate, The step of purifying the intermediate is (S11) a step of extracting the intermediate using a first organic solvent and a sodium chloride aqueous solution; and (S12) a step of precipitating a by-product from the extract extracted in step (S11) using a second organic solvent; Method for producing 4-alkylresorcinol.

6. In paragraph 4, The above non-mercury catalyst is zinc powder. Method for producing 4-alkylresorcinol.

7. In paragraph 6, A method for producing 4-alkylresorcinol, wherein the zinc powder used in the step (S20) is added to the reaction in an amount of 12 to 15 equivalents of the intermediate.

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