Method for producing hexyl diethylaminohydroxybenzoylbenzoate

Abstract

The present invention relates to a hexyl diethylaminohydroxybenzoylbenzoate, crystalline particles of the hexyl diethylaminohydroxybenzoylbenzoate, and methods for producing the hexyl diethylaminohydroxybenzoylbenzoate and crystalline particles of the hexyl diethylaminohydroxybenzoylbenzoate. Specifically, the present invention relates to: a method for producing hexyl diethylaminohydroxybenzoylbenzoate, which is easy in production engineering and enables commercial mass production; and crystalline particles of hexyl diethylaminohydroxybenzoylbenzoate produced by the production method. The purity of the diethylaminohydroxybenzoyl hexyl benzoate is 99.1 wt% or more, the volume density is more than 0.28 g / ml and less than 0.39 g / ml, and the average particle size is 10 [mu] m-100 [mu] m. According to the present invention, crystalline particles of diethylaminohydroxybenzoylhexyl benzoate having an excellent ultraviolet blocking effect can be stably obtained at a high yield.

Description

[0001] This application is a divisional application of the Chinese patent application with an application date of March 2, 2020, application number "202080042581.9", and invention name "Method for producing diethylaminohydroxybenzoyl hexyl benzoate". The original application is the Chinese national phase application of international application PCT / KR2020 / 002959. Technical Field

[0002] The present invention relates to a method for producing diethylaminohydroxybenzoyl hexyl benzoate, and more particularly to a method for producing diethylaminohydroxybenzoyl hexyl benzoate which is easy to produce and can be commercially mass-produced, a method for producing crystalline particles of diethylaminohydroxybenzoyl hexyl benzoate, and diethylaminohydroxybenzoyl hexyl benzoate produced by the production method. Background Art

[0003] All ultraviolet rays, including those contained in sunlight, are carcinogenic. The International Agency for Research on Cancer, or IARC, classifies all types of ultraviolet rays as Class 1 carcinogens, which are substances that have been confirmed to cause cancer.

[0004] In addition to being carcinogenic, UV rays can also damage the skin, eyes, and immune system and induce skin aging. Theoretically, when not exposed to UV rays, aging can be delayed by 27 times. In particular, UV-B (320nm to 280nm), which is contained in large quantities in sunlight, can cause burns, while UV-C (280nm to 100nm), which is used for UV sterilization, has higher energy and is more harmful than UV-A (400nm to 320nm) or UV-B. In addition, UV-A was previously thought to not cause excessive damage, but it has recently been found that it can cause DNA damage through active oxygen due to its high energy. Burning of the skin when exposed to sunlight can be considered a phenomenon that occurs to protect the skin from harmful substances. In addition to health damage such as skin aging and skin damage, UV rays can also cause beauty damage such as the formation of freckles or spots.

[0005] As mentioned above, ultraviolet rays are considered to be the main culprits for various aging and wrinkles, so it is recommended that all people, young and old, use ultraviolet blockers. Ultraviolet blockers are divided into physical blockers and chemical blockers. Physical blockers mainly use inorganic compounds that reflect ultraviolet rays (inorganic blockers), while chemical blockers mainly use compositions that convert ultraviolet energy into heat and release it (organic blockers).

[0006] Inorganic barrier agents mainly use titanium dioxide and zinc oxide. Although they have excellent barrier effects, they are easy to spread and may cause the skin to become white and cloudy when applied too much.

[0007] In addition, organic barrier agents are different from inorganic barrier agents and their types are very diverse, but mainly used are bis-ethylhexyloxyphenol methoxyphenyl triazine (BEMT), butyl methoxydibenzoylmethane (Butyl Methoxydibenzoylmethane), diethylamino hydroxybenzoyl hexyl benzoate (DHHB), and disodium phenyl dibenzimidazole tetrasulfonate (DPDT). Among them, DHHB represented by the following chemical formula is a representative organic barrier agent for blocking UV-A. It is a product originally developed by BASF through European Publication No. 1046391 and is currently sold under the trade name of Uvinul Aplus.

[0008]

[0009] BASF introduced a method for producing DHHB according to the following reaction formula in International Publication No. WO 03 / 097578.

[0010]

[0011] However, the manufacturing method requires the use of a strong acid, namely sulfuric acid, in the esterification step and the reaction is carried out at a high temperature (105-110° C.), and red impurities are generated in the reaction result. Therefore, a large amount of decolorizing agent is required for decolorization, and multiple purification processes are required.

[0012] In addition, BASF disclosed a method for crystallizing DHHB in WO 2008 / 135360. However, the crystallization method disclosed in the patent is a method for obtaining solid DHHB by completely dissolving it under conditions higher than the melting point (54°C) of DHHB and then cooling it down to a temperature lower than the melting point, which requires a crushing process. This method is difficult to apply to general mass production equipment, and therefore will be restricted in terms of mass production. Therefore, it is urgent to develop a DHHB manufacturing method that is easy to manufacture and can achieve mass production. Summary of the invention

[0013] Technical issues

[0014] The object of the present invention is to provide a method for producing diethylaminohydroxybenzoyl hexyl benzoate, which can improve the existing production method in which a large amount of red impurities are generated due to the reaction in a strong acid and thus it is difficult to decolorize, and diethylaminohydroxybenzoyl hexyl benzoate produced by the production method.

[0015] In addition, the present invention aims to provide a method for producing diethylaminohydroxybenzoyl hexyl benzoate which can use a small amount of decolorizing agent and reduce the number of purification times to achieve high yield and economical production, and diethylaminohydroxybenzoyl hexyl benzoate produced by the production method.

[0016] Solution to the problem

[0017] The present invention provides a method for preparing diethylaminohydroxybenzoyl hexyl benzoate, comprising: reacting N,N-diethylamino-hydroxybenzoyl-benzoic acid represented by the following chemical formula II with a compound represented by the following chemical formula III to prepare a compound represented by the following chemical formula I.

[0018] [Chemical Formula I]

[0019]

[0020] [Chemical Formula II]

[0021]

[0022] [Chemical Formula III]

[0023]

[0024] L is chloro, bromo, iodo, methanesulfonyl, toluenesulfonyl, benzenesulfonyl, trifluoromethanesulfonyl, hexylsulfite or hexylalkylsulfonyl.

[0025] Furthermore, the present invention provides a method for producing crystalline particles of diethylaminohydroxybenzoyl hexyl benzoate.

[0026] In addition, the present invention provides diethylaminohydroxybenzoyl hexyl benzoate produced by the production method.

[0027] Effects of the Invention

[0028] The production method of the present invention can improve the existing production method of diethylaminohydroxybenzoyl hexyl benzoate, which is difficult to decolorize because a large amount of red impurities are generated due to the reaction in a strong acid. Specifically, the present invention can use a small amount of decolorizing agent and reduce the number of purification times to produce diethylaminohydroxybenzoyl hexyl benzoate with a high yield, and can also achieve mass production economically. DETAILED DESCRIPTION

[0029] Next, in order to facilitate the personnel with general knowledge in the technical field to which the present invention belongs to easily implement the present invention, the embodiment of the present invention will be described in detail. The embodiment of the present invention is provided only to more completely describe the present invention to the personnel with average knowledge of the industry. Therefore, the embodiment of the present invention can be deformed into other various forms, and the scope of the present invention is not limited to the embodiment described in the following content.

[0030] Throughout the specification of the present invention, when a certain part is described as “comprising” a certain constituent element, unless otherwise clearly described to the contrary, it does not mean that other constituent elements are excluded but that other constituent elements may also be included.

[0031] Throughout the specification of the present invention, when a certain step is recorded as being "above" or "before" other steps, it not only includes the case where a certain step has a direct time series relationship with other steps, but also includes the same rights as the case where a certain step has an indirect time series relationship where the time series of the order of two steps is changed, such as a mixing step after each step.

[0032] The degree terms such as "approximately", "substantially", etc. used throughout the specification of the present invention are used in the meaning of the stated value or close to the stated value when the inherent manufacturing and material tolerances are proposed in the mentioned meaning, and are intended to prevent unscrupulous infringers from improperly using the disclosure content that mentions exact or absolute values ​​to help understand the present invention. The terms such as "(perform) the step of ~" or "the step of ~" used throughout the specification of the present invention do not mean "the step for ~".

[0033] The present invention provides a method for preparing diethylaminohydroxybenzoyl hexyl benzoate, comprising: reacting N,N-diethylamino-hydroxybenzoyl-benzoic acid represented by the following chemical formula II with a compound represented by the following chemical formula III to prepare a compound represented by the following chemical formula I:

[0034] [Chemical Formula I]

[0035]

[0036] [Chemical Formula II]

[0037]

[0038] [Chemical Formula III]

[0039]

[0040] L is chloro, bromo, iodo, methanesulfonyl, toluenesulfonyl, benzenesulfonyl, trifluoromethanesulfonyl, hexylsulfite or hexylalkylsulfonyl.

[0041] In one embodiment of the present invention, the reaction can be performed under alkaline conditions.

[0042] Specifically, the base may be an inorganic base selected from the group consisting of potassium carbonate, sodium carbonate, sodium bicarbonate, sodium hydroxide, and potassium hydroxide, but is not limited thereto.

[0043] In addition, the base may be an organic base selected from the group consisting of triethylamine, diisopropylethylamine, diethylamine, and pyridine, but is not limited thereto.

[0044] In addition, in one specific example of the present invention, the compound represented by the chemical formula II can be prepared by reacting 3-diethylaminophenol with phthalic anhydride, but is not limited thereto.

[0045] In addition, in one embodiment of the present invention, the compound represented by the chemical formula III can be prepared using n-hexanol as a starting material.

[0046] In the present invention, a method for producing crystalline particles of a compound of the following chemical formula I is provided.

[0047] The crystallization may be performed using a C1-C4 alcohol as a crystallization solvent. For example, the crystallization solvent may be methanol, ethanol, n-propanol, isopropanol, n-butanol, 2-butanol, isobutanol, or tert-butanol.

[0048] Specifically, the crystallization manufacturing method may include the following steps.

[0049] 1) A step of adding the crystallization solvent to the concentrated residue of diethylaminohydroxybenzoyl hexyl benzoate represented by the chemical formula I.

[0050] 2) raising the internal temperature to 30-50° C. for dissolving;

[0051] 3) After confirming complete dissolution, slowly cool the internal temperature to 15-20°C at a rate of 2-4°C / hr to allow crystals to slowly precipitate;

[0052] 4) A step of slowly cooling the temperature to 0 to 5°C at a rate of 2 to 4°C / hr to produce crystalline particles.

[0053] By the production method of the present invention as described above, the existing production method of diethylaminohydroxybenzoyl hexyl benzoate, which is difficult to decolorize due to the large amount of red impurities produced by the reaction in a strong acid, can be improved. Specifically, the present invention can use a small amount of decolorizing agent and reduce the number of purification times to produce diethylaminohydroxybenzoyl hexyl benzoate with a high yield, and can also achieve mass production economically.

[0054] The present invention also provides crystalline particles of diethylaminohydroxybenzoyl hexyl benzoate produced by the production method of the present invention.

[0055] The crystalline particles of diethylaminohydroxybenzoyl hexyl benzoate of the present invention are obtained in a crystalline form according to the production method of the present invention, and therefore can be used directly without being pulverized.

[0056] The average particle size of the crystalline particles of diethylaminohydroxybenzoyl hexyl benzoate produced by the production method of the present invention may be 1 μm to 500 μm. Specifically, the average particle size is 10 μm to 100 μm.

[0057] Furthermore, the bulk density of the crystalline particles of diethylaminohydroxybenzoyl hexyl benzoate produced by the production method of the present invention exceeds 0.28 g / ml.

[0058] Furthermore, the purity of the crystalline particles of diethylaminohydroxybenzoyl hexyl benzoate produced by the production method of the present invention is 98% by weight or more.

[0059] Modes for carrying out the invention

[0060] Example

[0061] Next, the present invention will be described in detail with reference to the preparation examples and examples. However, the following preparation examples and examples are merely illustrative of the present invention, and the content of the present invention is not limited by the following preparation examples and examples.

[0062] Preparation Example 1. Synthesis of 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoic acid

[0063] 3-Diethylaminophenol (1.0 kg, 7.87 mol) and phthalic anhydride (1.17 kg, 7.87 mol) were placed in a 3-neck flask and stirred with toluene (5.0 L). The internal temperature of the reactor was raised to 110-115° C. and stirred for 2 hours, then cooled to 0-10° C. and the precipitated solid was filtered to obtain the title compound (1.7 kg, 89.9%).

[0064] 1H NMR(CDCl3): 12.52(s,1H),7.91(dd,1H),7.62(m,2H),7.33(dd,1H),6.74(d,1H),6.13(dd,1H),6.20(d,1H),1.16(m,6H)

[0065] Preparation Example 2-1. Synthesis of 1-chlorohexane

[0066] 1-Hexanol (1.2 kg, 11.70 mol) and dimethylformamide (DMF, 8.5 g, 0.12 mol) were stirred and SOCl2 (2.1 kg, 17.6 mol) was added dropwise while maintaining an internal temperature below 30°C. After the addition was completed, the internal temperature was raised to 80-90°C and stirred for 5 hours. After confirming that the reaction was finished, it was cooled and separated by adding 5 L of pure water to obtain the title compound (1.3 kg, 94.2%).

[0067] 1 H NMR(CDCl3): 3.49(t,2H),1.72(m,2H),1.28(m,2H),1.27(m,4H),0.88(m,3H).

[0068] Preparation Example 2-2.1-Synthesis of Bromohexane

[0069] 1-Hexanol (1.2 kg, 11.70 mol) and tetrahydrofuran (THF, 6.0 L) were stirred, and PBr3 (3.2 kg, 17.6 mol) was added dropwise while maintaining an internal temperature below 10°C. After the addition was completed, the internal temperature was maintained below 10°C and stirred for 3 hours. After confirming the completion of the reaction, the layers were separated by adding 5 L of pure water to obtain the title compound (1.8 kg, 91.4%).

[0070] 1 H NMR(CDCI3): 3.40(t,2H),1.85(m,2H),1.43(m,2H),1.31(m,4H),0.90(m,3H).

[0071] Preparation Example 2-3. Synthesis of Hexyl Methanesulfonate

[0072] 1-Hexanol (1.2 kg, 11.70 mol), triethylamine (2.4 kg, 23.40 mol) and dichloromethane (12.0 L) were stirred, and MsCl (1.6 kg, 14.0 mol) was added dropwise while maintaining the internal temperature below 10°C. After the addition was completed, the internal temperature was maintained below 10°C and stirred for 3 hours. After layer separation by adding 5 L of pure water, the separated organic layer was concentrated under reduced pressure to obtain the title compound (1.9 kg, 88.1%).

[0073] 1 H NMR(CDCl3): 4.23(t,2H),3.00(s,3H),1.75(m,2H),1.40(m,3H),1.32(m,3H),0.90(m,3H).

[0074] Preparation Example 2-4. Synthesis of 4-methylbenzenesulfonic acid hexyl ester

[0075] 1-Hexanol (1.2 kg, 11.70 mol), TsCl (2.7 kg, 14.0 mol) and dichloromethane (12.0 L) were stirred, and triethylamine (2.4 kg, 23.40 mol) was added dropwise while maintaining the internal temperature below 10°C. After the addition was completed, the internal temperature was maintained below 10°C and stirred for 6 hours. After layer separation by adding 5 L of pure water, the separated organic layer was concentrated under reduced pressure to obtain the title compound (2.8 kg, 93.2%).

[0076] 1 H NMR(CDCl3): 7.78(m,2H),7.34(m,2H),4.02(m,2H),2.45(s,3H),1.65(m,2H),1.47-1.04(m,6H),0.85(m,3H).

[0077] Preparation Example 2-5. Synthesis of dihexyl sulfite

[0078] 1-Hexanol (1.2 kg, 11.70 mol) and dimethylformamide (DMF, 8.5 g, 0.12 mol) were stirred and SOCl2 (0.7 kg, 5.9 mol) was added dropwise while maintaining an internal temperature below 30°C. After the addition was completed, the internal temperature was raised to 30-40°C and stirred for 8 hours. After confirming that the reaction was finished, it was cooled and separated by adding 5 L of pure water to obtain the title compound (1.3 kg, 90.0%).

[0079] 1H NMR(CDCI3): 3.95(m,4H),1.63(m,4H),1.27(m,6H),0.86(m,12H).

[0080] Preparation Example 2-6. Synthesis of dihexyl sulfate

[0081] 1-Hexanol (1.2 kg, 11.70 mol) and dimethylformamide (DMF, 8.5 g, 0.12 mol) were stirred, and SO2Cl2 (0.8 kg, 5.9 mol) was added dropwise while maintaining an internal temperature below 30°C. After the addition was completed, the internal temperature was raised to 30-40°C and stirred for 8 hours. After confirming that the reaction was completed, the reaction was cooled and separated by adding 5 L of pure water, thereby obtaining the title compound (1.4 kg, 87.0%).

[0082] 1 H NMR(CDCl3): 4.00(m,4H),1.69(m,4H),1.30(m,6H),0.90(m,12H).

[0083] Example 1: Synthesis of diethylaminohydroxybenzoyl hexyl benzoate

[0084] Step 1: Preparation of diethylaminohydroxybenzoyl hexyl benzoate

[0085] 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoic acid (1.1 kg, 3.51 mol) synthesized in Preparation Example 1, 1-chlorohexane (0.5 kg, 4.22 mol) synthesized in Preparation Example 2-1, and K2CO3 (0.9 kg, 7.02 mol) were stirred with 1.65 L of dimethylformamide (DMF). After the internal temperature was raised to 100 to 110° C. and stirred for 4 hours, the mixture was cooled and then extracted with 3.5 L of ethyl acetate and 3.5 L of purified water. The separated final organic layer was decolorized with 5% charcoal at an internal temperature of 30 to 50° C. for 1 hour and then concentrated under reduced pressure.

[0086] Step 2

[0087] After adding 4 v / w of methanol compared to 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoic acid to the concentrated residue obtained in step 1, the internal temperature is raised to 30-50°C until the solution is clear. After confirming complete dissolution, the internal temperature is slowly cooled to 15-20°C at a rate of 3°C / hr to allow crystals to slowly precipitate. After reaching the target temperature, the corresponding temperature is maintained and stirred for 1 hour, and then slowly cooled to 0-5°C at a rate of 3°C / hr. After reaching the target temperature, the corresponding temperature is maintained and stirred for 1 hour, and then the title compound (1.2 kg, 86.0%) is obtained in the form of crystalline particles by filtering.

[0088] 1 H NMR(CDCl3): 12.59(s,1H),8.04(dd,1H),7.55(m,2H),7.34(dd,1H),6.87(d,1H),6.12( d,1H),6.02(dd,1H),4.10(t,2H),3.35(q,4H),1.45(m,2H),1.16(m,12H),0.82(t,3H);

[0089] Average particle size: 80.3 μm;

[0090] Bulk density: 0.34 g / ml;

[0091] Purity: 99.4%.

[0092] Example 2: Synthesis of diethylamino hydroxybenzoyl hexyl benzoate

[0093] After adding 4 v / w of ethanol compared to 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoic acid to the concentrated residue obtained by step 1 of Example 1, the internal temperature is raised to 30-50°C until the solution is clear. After confirming complete dissolution, the internal temperature is slowly cooled to 15-20°C at a rate of 3°C / hr to allow crystals to slowly precipitate. After reaching the target temperature, the corresponding temperature is maintained and stirred for 1 hour, and then slowly cooled to 0-5°C at a rate of 3°C / hr. After reaching the target temperature, the corresponding temperature is maintained and stirred for 1 hour, and then the title compound (1.1 kg, 80.0%) is obtained in the state of crystalline particles by filtering.

[0094] 1H NMR(CDCl3): 12.59(s,1H),8.04(dd,1H),7.55(m,2H),7.34(dd,1H),6.87(d,1H),6.12( d,1H),6.02(dd,1H),4.10(t,2H),3.35(q,4H),1.45(m,2H),1.16(m,12H),0.82(t,3H);

[0095] Average particle size: 73.7 μm;

[0096] Bulk density: 0.32g / ml;

[0097] Purity: 99.6%.

[0098] Example 3: Synthesis of diethylaminohydroxybenzoyl hexyl benzoate

[0099] After adding 4 v / w of isopropanol compared to 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoic acid to the concentrated residue obtained by step 1 of Example 1, the internal temperature is raised to 30-50°C until the solution is clear. After confirming complete dissolution, the internal temperature is slowly cooled to 15-20°C at a rate of 3°C / hr to allow crystals to slowly precipitate. After reaching the target temperature, the corresponding temperature is maintained and stirred for 1 hour, and then slowly cooled to 0-5°C at a rate of 3°C / hr. After reaching the target temperature, the corresponding temperature is maintained and stirred for 1 hour, and then the title compound (1.10 kg, 80.0%) is obtained in the state of crystalline particles by filtering.

[0100] 1 H NMR(CDCl3): 12.59(s,1H),8.04(dd,1H),7.55(m,2H),7.34(dd,1H),6.87(d,1H),6.12( d,1H),6.02(dd,1H),4.10(t,2H),3.35(q,4H),1.45(m,2H),1.16(m,12H),0.82(t,3H);

[0101] Average particle size: 91.2 μm;

[0102] Bulk density: 0.38 g / ml;

[0103] Purity: 99.2%.

[0104] Example 4: Synthesis of diethylaminohydroxybenzoyl hexyl benzoate

[0105] After adding 4 v / w of 2-butanol compared to 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoic acid to the concentrated residue obtained by step 1 of Example 1, the internal temperature is raised to 30-50°C until the solution is clear. After confirming complete dissolution, the internal temperature is slowly cooled to 15-20°C at a rate of 3°C / hr to allow crystals to slowly precipitate. After reaching the target temperature, the corresponding temperature is maintained and stirred for 1 hour, and then slowly cooled to 0-5°C at a rate of 3°C / hr. After reaching the target temperature, the corresponding temperature is maintained and stirred for 1 hour, and then the title compound (1.00 kg, 75.0%) is obtained in the state of crystalline particles by filtering.

[0106] 1 H NMR(CDCl3): 12.59(s,1H),8.04(dd,1H),7.55(m,2H),7.34(dd,1H),6.87(d,1H),6.12( d,1H),6.02(dd,1H),4.10(t,2H),3.35(q,4H),1.45(m,2H),1.16(m,12H),0.82(t,3H);

[0107] Average particle size: 12.0 μm;

[0108] Bulk density: 0.28g / ml;

[0109] Purity: 99.5%.

[0110] Example 5: Synthesis of diethylamino hydroxybenzoyl hexyl benzoate

[0111] 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoic acid (1.1 kg, 3.51 mol) synthesized in Preparation Example 1, 1-bromohexane (0.7 kg, 4.22 mol) synthesized in Preparation Example 2-2, and K2CO3 (0.9 kg, 7.02 mol) were stirred with 1.65 L of dimethylformamide (DMF). After the internal temperature was raised to 100 to 110° C. and stirred for 4 hours, the mixture was cooled and then extracted with 3.5 L of ethyl acetate and 3.5 L of purified water. The separated final organic layer was decolorized with 5% charcoal at an internal temperature of 30 to 50° C. for 1 hour and then concentrated under reduced pressure.

[0112] The concentrated residue was crystallized by the crystallization method of Example 3 to obtain the title compound (0.90 kg, 65.0%) in the form of crystalline particles.

[0113] 1H NMR(CDCl3): 12.59(s,1H),8.04(dd,1H),7.55(m,2H),7.34(dd,1H),6.87(d,1H),6.12( d,1H),6.02(dd,1H),4.10(t,2H),3.35(q,4H),1.45(m,2H),1.16(m,12H),0.82(t,3H);

[0114] Average particle size: 69.4 μm;

[0115] Bulk density: 0.32g / ml;

[0116] Purity: 99.4%.

[0117] Example 6: Synthesis of diethylaminohydroxybenzoyl hexyl benzoate

[0118] 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoic acid (1.1 kg, 3.51 mol) synthesized in Preparation Example 1, hexyl methanesulfonate (0.8 kg, 4.22 mol) synthesized in Preparation Example 2-3, and K2CO3 (0.9 kg, 7.02 mol) were stirred with 1.65 L of dimethylformamide (DMF). After the internal temperature was raised to 100-110° C. and stirred for 4 hours, the mixture was cooled and then extracted with 3.5 L of ethyl acetate and 3.5 L of purified water. The separated final organic layer was decolorized with 5% charcoal at an internal temperature of 30-50° C. for 1 hour and then concentrated under reduced pressure.

[0119] The concentrated residue was crystallized by the crystallization method of Example 3 to obtain the title compound (0.73 kg, 52.4%) in the form of crystalline particles.

[0120] 1 H NMR(CDCl3): 12.59(s,1H),8.04(dd,1H),7.55(m,2H),7.34(dd,1H),6.87(d,1H),6.12( d,1H),6.02(dd,1H),4.10(t,2H),3.35(q,4H),1.45(m,2H),1.16(m,12H),0.82(t,3H);

[0121] Average particle size: 25.8 μm;

[0122] Bulk density: 0.30g / ml;

[0123] Purity: 99.8%.

[0124] Example 7: Synthesis of diethylaminohydroxybenzoyl hexyl benzoate

[0125] 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoic acid (1.1 kg, 3.51 mol) synthesized in Preparation Example 1, 4-methylbenzenesulfonic acid hexyl ester (1.1 kg, 4.22 mol) synthesized in Preparation Example 2-4, and K2CO3 (0.9 kg, 7.02 mol) were stirred with 1.65 L of dimethylformamide (DMF). After the internal temperature was raised to 100-110° C. and stirred for 4 hours, the mixture was cooled and then extracted with 3.5 L of ethyl acetate and 3.5 L of purified water. The separated final organic layer was decolorized with 5% charcoal at an internal temperature of 30-50° C. for 1 hour and then concentrated under reduced pressure.

[0126] The concentrated residue was crystallized by the crystallization method of Example 3 to obtain the title compound (0.66 kg, 47.6%) in the form of crystalline particles.

[0127] 1 H NMR(CDCl3): 12.59(s,1H),8.04(dd,1H),7.55(m,2H),7.34(dd,1H),6.87(d,1H),6.12( d,1H),6.02(dd,1H),4.10(t,2H),3.35(q,4H),1.45(m,2H),1.16(m,12H),0.82(t,3H);

[0128] Average particle size: 81.3 μm;

[0129] Bulk density: 0.37 g / ml;

[0130] Purity: 99.5%.

[0131] Example 8: Synthesis of diethylaminohydroxybenzoyl hexyl benzoate

[0132] 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoic acid (1.1 kg, 3.51 mol) synthesized in Preparation Example 1, dihexyl sulfite (1.1 kg, 4.22 mol) synthesized in Preparation Example 2-5, and K2CO3 (0.9 kg, 7.02 mol) were stirred with 1.65 L of dimethylformamide (DMF). After the internal temperature was raised to 100 to 110° C. and stirred for 4 hours, the mixture was cooled and then extracted with 3.5 L of ethyl acetate and 3.5 L of purified water. The separated final organic layer was decolorized with 5% charcoal at an internal temperature of 30 to 50° C. for 1 hour and then concentrated under reduced pressure.

[0133] The concentrated residue was crystallized by the crystallization method of Example 3 to obtain the title compound (1.12 kg, 80.0%) in the form of crystalline particles.

[0134] 1 H NMR(CDCl3): 12.59(s,1H),8.04(dd,1H),7.55(m,2H),7.34(dd,1H),6.87(d,1H),6.12( d,1H),6.02(dd,1H),4.10(t,2H),3.35(q,4H),1.45(m,2H),1.16(m,12H),0.82(t,3H);

[0135] Average particle size: 45.2 μm;

[0136] Bulk density: 0.32g / ml;

[0137] Purity: 99.1%.

[0138] Example 9: Synthesis of diethylaminohydroxybenzoyl hexyl benzoate

[0139] 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoic acid (1.1 kg, 3.51 mol) synthesized in Preparation Example 1, dihexyl sulfate (1.2 kg, 4.22 mol) synthesized in Preparation Example 2-6, and K2CO3 (0.9 kg, 7.02 mol) were stirred with 1.65 L of dimethylformamide (DMF). After the internal temperature was raised to 100-110° C. and stirred for 4 hours, the mixture was cooled and then extracted with 3.5 L of ethyl acetate and 3.5 L of purified water. The separated final organic layer was decolorized with 5% charcoal at an internal temperature of 30-50° C. for 1 hour and then concentrated under reduced pressure.

[0140] The concentrated residue was crystallized by the crystallization method of Example 3 to obtain the title compound (1.09 kg, 78.0%) in the form of crystalline particles.

[0141] 1 H NMR(CDCl3): 12.59(s,1H),8.04(dd,1H),7.55(m,2H),7.34(dd,1H),6.87(d,1H),6.12( d,1H),6.02(dd,1H),4.10(t,2H),3.35(q,4H),1.45(m,2H),1.16(m,12H),0.82(t,3H);

[0142] Average particle size: 82.0 μm;

[0143] Bulk density: 0.39 g / ml;

[0144] Purity: 99.4%.

[0145] The examples show that the production method of the present invention can obtain diethylaminohydroxybenzoyl hexyl benzoate in high yield, and can also simplify the decolorization and purification processes, thereby achieving economical mass production.

[0146] The above description of the present invention is for exemplary purposes only. Personnel with general knowledge of the technical field to which the present invention belongs should understand that the present invention can be easily transformed into other specific forms without changing the technical ideas or essential features of the present invention. Therefore, the embodiments described in the above content should be understood as exemplary rather than limiting in all aspects. For example, each component described in a single form can also be implemented in a dispersed manner. Similarly, the components described in a dispersed form can also be implemented in a combined form.

[0147] The scope of the present invention should be defined by the appended claims rather than the above detailed description. The meaning and scope of the claims and all changes or deformations derived from their equivalent concepts should be interpreted as being included in the scope of the present invention.

[0148] The present invention relates to the following embodiments:

[0149] Embodiment 1: A method for producing diethylamino hydroxybenzoyl hexyl benzoate, comprising:

[0150] A step of preparing a compound represented by the following chemical formula I by reacting N,N-diethylamino-hydroxybenzoyl-benzoic acid represented by the following chemical formula II with a compound represented by the following chemical formula III:

[0151] [Chemical Formula I]

[0152]

[0153] [Chemical Formula II]

[0154]

[0155] [Chemical Formula III]

[0156]

[0157] L is chloro, bromo, iodo, methanesulfonyl, toluenesulfonyl, benzenesulfonyl, trifluoromethanesulfonyl, hexylsulfite or hexylalkylsulfonyl.

[0158] Embodiment 2: The manufacturing method according to embodiment 1:

[0159] The reaction is performed under alkaline conditions.

[0160] Embodiment 3: The manufacturing method according to Embodiment 2:

[0161] The base is an inorganic base selected from the group consisting of potassium carbonate, sodium carbonate, sodium bicarbonate, sodium hydroxide and potassium hydroxide.

[0162] Embodiment 4: The manufacturing method according to Embodiment 2:

[0163] The base is an organic base selected from the group consisting of triethylamine, diisopropylethylamine, diethylamine and pyridine.

[0164] Embodiment 5: A method for producing crystalline particles of diethylaminohydroxybenzoyl hexyl benzoate represented by the following chemical formula I:

[0165] [Chemical Formula I]

[0166]

[0167] Embodiment 6: A method for producing crystalline particles according to Embodiment 5:

[0168] The crystallization is performed using a substance selected from the group consisting of methanol, ethanol, isopropanol, 1-propanol, 1-butanol, 2-butanol, tert-butanol, and a mixture thereof as a crystallization solvent.

[0169] Embodiment 7: A method for producing crystalline particles according to Embodiment 6:

[0170] 1) adding the crystallization solvent to the concentrated residue of diethylaminohydroxybenzoyl hexyl benzoate represented by the chemical formula I;

[0171] 2) raising the internal temperature to 30-50° C. for dissolving;

[0172] 3) After confirming complete dissolution, slowly cool the internal temperature to 15-20°C at a rate of 2-4°C / hr to allow crystals to slowly precipitate;

[0173] 4) A step of slowly cooling the temperature to 0 to 5°C at a rate of 2 to 4°C / hr to produce crystalline particles.

[0174] Embodiment 8: A crystalline particle of diethylaminohydroxybenzoyl hexyl benzoate:

[0175] The purity of the diethylaminohydroxybenzoyl hexyl benzoate is above 98% by weight, the volume density exceeds 0.28 g / ml, and the average particle size is 10 μm to 100 μm.

Claims

1. A crystalline particle of diethylaminohydroxybenzoyl hexyl benzoate: The crystallization solvent is selected from the group consisting of methanol, ethanol, isopropanol, 1-propanol, 1-butanol, 2-butanol, tert-butanol and a mixture thereof, the purity of the diethylaminohydroxybenzoyl hexyl benzoate is greater than 99.1% by weight, the volume density exceeds 0.28 g / ml and is less than 0.39 g / ml, and the average particle size is 10 μm to 100 μm.

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