TW202122369A - A preparing method of diethylamino hydroxybenzoyl hexylbenzoate - Google Patents

Abstract

A method for preparing diethylamino hydroxybenzoyl hexylbenzoate is practically related to a preparing method of the diethylamino hydroxybenzoyl hexylbenzoate that includes a simpler preparing process for commercially mass production and for producing particulate crystals of the diethylamino hydroxybenzoyl hexylbenzoate. By providing this preparing method, the particulate crystals of the diethylamino hydroxybenzoyl hexylbenzoate with an excellent anti-ultraviolet performance can be obtained in a more stable and efficienct manner.

Description

Method for preparing diethylamino hydroxybenzyl hexyl benzoate

The present invention relates to a preparation method of diethylamino hydroxybenzyl hexyl benzoate, and specifically relates to the preparation of diethylamino hydroxybenzyl hexyl benzoate, which is easy to prepare and can be mass-produced commercially Method, method for preparing crystal particles of diethylaminohydroxybenzyl hexyl benzoate and diethylaminohydroxybenzylhexyl benzoate prepared therefrom.

All ultraviolet rays including the ultraviolet rays contained in sunlight are carcinogens. IARC, the International Agency for Research on Cancer, classifies all types of ultraviolet rays as first-level carcinogens, that is, classified as substances that are confirmed to induce cancer.

In addition to carcinogenicity, ultraviolet rays also damage the skin, eyes, and immune system, and cause skin aging. Theoretically, not being exposed to ultraviolet rays will delay aging by 27 times. In particular, more UV-B (320nm ~ 280nm) contained in sunlight causes burns, and UV-C (280nm ~ 100nm) used for ultraviolet sterilization is more energy than UV-A (400nm ~ 320nm) or UV- B is more harmful. Moreover, it is reported that UV-A, which was known to be less harmful in the past, also has high energy, so that deoxyribonucleic acid (DNA) may be damaged by reactive oxygen species. The skin tans when exposed to the sun, which can be regarded as a phenomenon to protect the skin from harmful substances. In addition to health hazards such as skin aging and skin damage, ultraviolet rays are also harmful to beauty such as freckles or spots.

As mentioned above, ultraviolet rays are regarded as the main cause of various aging and wrinkles, and anti-ultraviolet agents are recommended for men and women of all ages. UV blocking agents are divided into physical blocking agents and chemical blocking agents. Physical blocking agents mainly use inorganic compounds that reflect ultraviolet rays (inorganic blocking agents), and chemical blocking agents use compositions that release ultraviolet energy into heat form (organic blocking agents). .

Inorganic barrier agents mainly use titanium dioxide and zinc oxide. Although the barrier effect is excellent, there is a problem of dryness when applied, and white turbidity of skin floating powder when applied in a large amount.

On the other hand, organic barrier agents are different from inorganic barrier agents. Their types are very diverse, but mainly use bis-ethylhexyloxyphenol methoxyphenyl triazine (BEMT) and butyl methoxy benzophenone. Butyl Methoxydibenzoylmethane (Butyl Methoxydibenzoylmethane), Diethylamino hydroxybenzoyl hexyl benzoate (DHHB), Disodium phenyl dibenzimidazole tetrasulfonate (DPDT), etc. Among them, DHHB represented by the following chemical formula, as a representative organic blocking agent for blocking UV-A, is the first product developed by BASF through the European Public Bulletin No. 1046391. It is currently the product name "Uvinul A plus" Products that are on sale in the market.

BASF Company introduced the method of preparing DHHB according to the following reaction formula through International Publication WO 03/097578.

However, this preparation method has the following problem: the use of sulfuric acid as a strong acid in the esterification step requires the reaction under high temperature (105-110°C) conditions, and red impurities are produced in the reaction result. In order to decolorize, Need to use a large amount of decolorizing agent, not only that, but also need to go through multiple purification processes.

On the other hand, BASF Corporation discloses a method for crystallization of DHHB in International Publication WO 2008/135360. However, the crystallization method disclosed in the above patent is a method in which DHHB is completely dissolved at the melting point (54°C) of DHHB and then cooled to below the melting point to obtain a solid form of DHHB, and pulverization is indispensable. It is difficult to apply to general mass production equipment, so there are restrictions on mass production. Therefore, there is a need to develop a method for preparing DHHB that is easy to prepare and can be mass-produced commercially.

The technical problem to be solved by the invention

The present invention provides a method for preparing diethylaminohydroxybenzylhexyl benzoate which can improve the existing preparation method that reacts in a strong acid to produce a large amount of red impurities and is difficult to decolorize, and a diethylaminohydroxybenzylhexyl benzoate prepared therefrom Hexyl benzoate.

In addition, the present invention provides a method for preparing diethylamino hydroxybenzyl hexyl benzoate, which can be produced with high yield and economic production, and diethylamino hydroxybenzyl hexyl ester prepared therefrom, which can reduce the number of purifications while using a small amount of decoloring agent. Benzoyl hexyl benzoate.

The technical scheme of the present invention is:

化學式II

化學式III

The present invention provides a diethyl group comprising a step of reacting N,N-diethylamino-hydroxybenzyl-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 Preparation method of aminohydroxybenzyl hexyl benzoate. Chemical formula I

Chemical formula II

Chemical formula III

L is chlorine, bromine, iodine, methanesulfonyl, toluenesulfonyl, benzenesulfonyl, trifluoromethanesulfonyl, hexyl sulfite, or hexylalkylsulfonyl.

In addition, the present invention provides a method for preparing crystal particles of diethylaminohydroxybenzylhexyl benzoate.

In addition, the present invention provides diethylamino hydroxybenzyl hexyl benzoate prepared according to the above preparation method.

Hereinafter, the embodiments of the present invention will be listed and described in detail, so that those of ordinary skill in the art to which the present invention pertains can be easily implemented. The embodiments of the present invention are provided to explain the present invention more completely to those of ordinary skill in the technical field to which the present invention belongs. Therefore, the embodiment of the present invention can be modified in a variety of different forms, and the scope of the present invention is not limited to the embodiment described below.

In the full text of the specification of the present invention, when a part "includes" another structural element, unless there is a special objection, it means that other structural elements may be included instead of excluding other structural elements.

In the full text of the specification of the present invention, when a step and another step are located "on" or "before", this not only includes the case where one step is in a direct time series relationship with another step, but also includes and is in the same way as each step. The mixed step after the step has the same right in the case of the indirect time series relationship in which the time series sequence can be changed in the order of the two steps.

When the manufacturing and material tolerances inherent in the mentioned meaning are proposed, the terms "about", "substantially" and the like used in the full text of the specification of the present invention are used as meanings from their value or close to their value. It is used to prevent conscientious infringers from improperly using the disclosure that mentions accurate or absolute values in order to facilitate the understanding of the present invention. The term "~ (of) step" or "~ step" used throughout the specification of the present invention does not mean "a step for ~".

化學式II

化學式II

The present invention provides diethyl including the step of reacting N,N-diethylamino-hydroxybenzyl-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 Preparation method of aminohydroxybenzyl hexyl benzoate. Chemical formula I

Chemical formula II

Chemical formula II

L is chlorine, bromine, iodine, methanesulfonyl, toluenesulfonyl, benzenesulfonyl, trifluoromethanesulfonyl, hexyl sulfite, or hexylalkylsulfonyl.

According to a specific example of the present invention, the above reaction can be carried out under alkaline environmental conditions provided by a basic compound.

Specifically, the above-mentioned basic compound may be an inorganic base selected from the group consisting of potassium carbonate, sodium carbonate, potassium bicarbonate, sodium bicarbonate, sodium hydroxide, and potassium hydroxide. However, it is not limited to this.

In addition, the basic compound may be an organic base selected from the group consisting of triethylamine, diisopropylethylamine, diethylamine, and pyridine. However, it is not limited to this.

Moreover, according to a specific example of the present invention, the compound represented by the above chemical formula II can be prepared by reacting 3-diethylaminophenol with phthalic anhydride. However, it is not limited to this.

Moreover, according to a specific example of the present invention, the compound represented by the above chemical formula III can be prepared using n-hexanol as a starting material.

According to the present invention, the present invention provides a method for preparing crystal particles of the compound of the following chemical formula I.

C1-C4 ethanol can be used as a crystallization solvent to perform the crystallization of the above-mentioned crystal particles. For example, the above-mentioned crystallization solvent may be methanol, ethanol, n-propanol, isopropanol, n-butanol, 2-butanol, isobutanol, or t-butanol.

Specifically, the above crystallization preparation method may include the following steps:

Step 1) Put the above crystallization solvent into the concentrated residue of diethylamino hydroxybenzyl hexyl benzoate represented by the above chemical formula I;

Step 2), increase the internal temperature to 30～50℃ for dissolution;

Step 3), after confirming complete dissolution, slowly cool at a rate of 2 to 4°C/hr to slowly precipitate crystals, and slowly cool to an internal temperature of 15 to 20°C;

Step 4), slowly cooling at a rate of 2 to 4°C/hr to cool to 0 to 5°C to prepare crystal particles.

According to the preparation method of the present invention as described above, the existing method for preparing diethylamino hydroxybenzyl hexyl benzoate, which is difficult to decolorize, can improve the red impurities produced in large quantities by reaction in strong acid. Specifically, the present invention not only uses a small amount of decoloring agent but also can reduce the number of purifications, can prepare diethylamino hydroxybenzyl hexyl benzoate with high yield, and can be produced in large quantities economically.

In addition, the present invention provides diethylamino hydroxybenzylhexyl benzoate crystal particles prepared according to the preparation method of the present invention.

The diethylaminohydroxybenzylhexyl benzoate crystal particles of the present invention are obtained according to the preparation method of the present invention and are obtained in a crystalline form, and therefore have the advantage of being directly used without being crushed.

The average particle size of the diethylamino hydroxybenzylhexyl benzoate crystal particles prepared according to the preparation method of the present invention may be 1 μm to 500 μm. Specifically, the average particle size is 10 μm to 100 μm.

In addition, the bulk density of the diethylaminohydroxybenzylhexyl benzoate crystal particles prepared according to the preparation method of the present invention is greater than 0.28 g/ml.

In addition, the purity of the diethylaminohydroxybenzylhexyl benzoate crystal particles prepared according to the preparation method of the present invention is 98% by weight or more.

Example

Hereinafter, the present invention will be described in detail based on preparation examples and examples. However, the following preparation examples or examples are only used to illustrate the present invention, and the content of the present invention is not limited to the following preparation examples or examples.

Preparation Example 1. Synthesis of 2-(4-N,N-diethylamino-2-hydroxybenzyl)benzoic acid

After putting 3-diethylaminophenol (1.0 kg, 7.87 mol) and phthalic anhydride (1.17 kg, 7.87 mol) into a three-neck flask, they were stirred with toluene (5.0 L). The internal temperature of the reactor was raised to 110-115°C, and after stirring for 2 hours, the solid precipitated after cooling to 0-10°C was filtered to obtain the target compound (1.7 kg, 89.9%).

The nuclear magnetic resonance spectrum data is ¹ H NMR (CDCl ₃ ): 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)

Preparation Example 2-1. Synthesis of 1-chlorohexane

While stirring 1-hexanol (1.2kg, 11.70mol) and dimethylformamide (DMF) (8.5g, 0.12mol) while maintaining the internal temperature below 30°C, SOCl ₂ (2.1kg, 17.6mol) was added dropwise . After completion of the dropping, the internal temperature was raised to 80 to 90°C and stirred for 5 hours. After confirming the completion of the reaction, it was cooled, 5 L of purified water was added, and layer separation was performed to obtain the target compound (1.3 kg, 94.2%).

¹ H NMR (CDCl ₃ ): 3.49 (t, 2H), 1.72 (m, 2H), 1.28 (m, 2H), 1.27 (m, 4H), 0.88 (m, 3H)

Preparation Example 2-2. Synthesis of 1-bromohexane

While stirring 1-hexanol (1.2 kg, 11.70 mol) and tetrahydrofuran (THF) (6.0 L), PBr ₃ (3.2 kg, 17.6 mol) was added dropwise while maintaining the internal temperature below 10°C. After the dropwise addition was completed, the internal temperature was maintained at 10°C or less and stirred for 3 hours. After confirming the completion of the reaction, 5 L of purified water was added, and layer separation was performed to obtain the target compound (1.8 kg, 91.4%).

The nuclear magnetic resonance spectrum data is ¹ H NMR (CDCl ₃ ): 3.40 (t, 2H), 1.85 (m, 2H), 1.43 (m, 2H), 1.31 (m, 4H), 0.90 (m, 3H)

Preparation Example 2-3. Synthesis of Hexyl Methanesulfonate

While stirring 1-hexanol (1.2kg, 11.70mol), triethylamine (2.4kg, 23.40mol), dichloromethane (12.0L) while maintaining the internal temperature below 10°C, MsCl (1.6kg, 14.0mol) was added dropwise ). After the dropwise addition was completed, the internal temperature was maintained at 10°C or less and stirred for 3 hours. After adding 5 L of purified water to perform layer separation, the separated organic layer was concentrated under reduced pressure to obtain the target compound (1.9 kg, 88.1%).

¹ H NMR (CDCl ₃ ): 4.23 (t, 2H), 3.00 (s, 3H), 1.75 (m, 2H), 1.40 (m, 3H), 1.32 (m, 3H), 0.90 (m, 3H)

Preparation example 2-4. Synthesis of 4-methylbenzenesulfonate hexyl ester

While stirring 1-hexanol (1.2kg, 11.70mol), TsCl (2.7kg, 14.0mol), dichloromethane (12.0L) while maintaining the internal temperature below 10°C, add triethylamine (2.4kg, 23.40mol) dropwise ). After the dropwise addition was completed, the internal temperature was maintained at 10°C or less and stirred for 6 hours. After adding 5 L of purified water to perform layer separation, the separated organic layer was concentrated under reduced pressure to obtain the target compound (2.8 kg, 93.2%).

The nuclear magnetic resonance spectrum data is ¹ H NMR (CDCl ₃ ): 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)

Preparation Example 2-5. Synthesis of Dihexyl Sulfite

While stirring 1-hexanol (1.2 kg, 11.70 mol) and DMF (8.5 g, 0.12 mol), SOCl ₂ (0.7 kg, 5.9 mol) was added dropwise while maintaining the internal temperature below 30°C. After completion of the dropping, the internal temperature was raised to 30 to 40°C and stirred for 8 hours. After confirming the completion of the reaction, it was cooled, 5 L of purified water was added, and layer separation was performed to obtain the target compound (1.3 kg, 90.0%).

¹ H NMR (CDCl ₃ ): 3.95 (m, 4H), 1.63 (m, 4H), 1.27 (m, 6H), 0.86 (m, 12H)

Preparation Example 2-6. Synthesis of Dihexyl Sulfate

While stirring 1-hexanol (1.2 kg, 11.70 mol) and DMF (8.5 g, 0.12 mol), SO ₂ Cl ₂ (0.8 kg, 5.9 mol) was added dropwise while maintaining the internal temperature below 30°C. After completion of the dropping, the internal temperature was raised to 30 to 40°C and stirred for 8 hours. After confirming the completion of the reaction, it was cooled, 5 L of purified water was added, and layer separation was performed to obtain the target compound (1.4 kg, 87.0%).

¹ H NMR (CDCl ₃ ): 4.00 (m, 4H), 1.69 (m, 4H), 1.30 (m, 6H), 0.90 (m, 12H)

Example 1: Synthesis of diethylamino hydroxybenzyl hexyl benzoate

Step 1: Preparation of hexyl diethylaminohydroxybenzyl benzoate

The 2-(4-N,N-diethylamino-2-hydroxybenzyl)benzoic acid (1.1kg, 3.51mol) synthesized in Preparation Example 1 and the 1-chlorohexyl synthesized in Preparation Example 2-1 Alkane (0.5 kg, 4.22 mol), K ₂ CO ₃ (0.9 kg, 7.02 mol) and 1.65 L of DMF were stirred. After raising the internal temperature to 100-110°C and stirring for 4 hours, it was cooled and extracted with 3.5 L of ethyl acetate and 3.5 L of purified water. At an internal temperature of 30 to 50°C, using 5% charcoal, the final organic layer separated was subjected to a decolorization treatment for 1 hour, and then concentrated under reduced pressure.

Step 2

In the concentrated residue obtained in step 1, 4v/w of methanol (that is, 4ml of methanol and 1g of methanol relative to 2-(4-N,N-diethylamino-2-hydroxybenzyl)benzoic acid) was added. After the 2-(4-N,N-diethylamino-2-hydroxybenzyl)benzoic acid is mixed), the internal temperature is increased to 30-50°C to make the solution clear. After confirming complete dissolution, it was slowly cooled at a rate of 3°C/hr to slowly precipitate crystals, and then slowly cooled to an internal temperature of 15-20°C. When the target temperature is reached, the temperature is maintained, and after stirring for 1 hour, it is slowly cooled again at a rate of 3°C/hr to cool to 0-5°C. When the target temperature is reached, the temperature is maintained, and after stirring for 1 hour, filtration is performed to obtain the target compound (1.2 kg, 86.0%) in the state of crystal particles.

The nuclear magnetic resonance spectrum data is ¹ H NMR (CDCl ₃ ): 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)

Average particle size: 80.3μm

Bulk density: 0.34g/ml

Purity: 99.4%

Example 2: Synthesis of Diethylamino hydroxybenzylhexyl benzoate

In the concentrated residue obtained in step 1 of Example 1, 4 v/w of ethanol (that is, 4 ml of ethanol) relative to 2-(4-N,N-diethylamino-2-hydroxybenzyl)benzoic acid was added. After ethanol is mixed with 1 g of 2-(4-N,N-diethylamino-2-hydroxybenzyl)benzoic acid), the internal temperature is raised to 30-50°C to dissolve and clarify. After confirming complete dissolution, it was slowly cooled at a rate of 3°C/hr to slowly precipitate crystals, and then slowly cooled to an internal temperature of 15-20°C. When the target temperature is reached, the temperature is maintained, and after stirring for 1 hour, it is slowly cooled again at a rate of 3°C/hr to cool to 0-5°C. When the target temperature is reached, the temperature is maintained, and after stirring for 1 hour, filtration is performed to obtain the target compound (1.1 kg, 80.0%) in the state of crystal particles.

The nuclear magnetic resonance spectrum data is ¹ H NMR (CDCl ₃ ): 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)

Average particle size: 73.7μm

Bulk density: 0.32g/ml

Purity: 99.6%

Example 3: Synthesis of Diethylamino hydroxybenzylhexyl benzoate

The concentrated residue obtained in step 1 of Example 1 was added with isopropanol (4v/w) relative to 2-(4-N,N-diethylamino-2-hydroxybenzyl)benzoic acid. After mixing 4ml of isopropanol with 1g of 2-(4-N,N-diethylamino-2-hydroxybenzyl)benzoic acid), the internal temperature is raised to 30-50°C to make it dissolve and clarify. After confirming complete dissolution, it was slowly cooled at a rate of 3°C/hr to slowly precipitate crystals, and then slowly cooled to an internal temperature of 15-20°C. When the target temperature is reached, the temperature is maintained, and after stirring for 1 hour, it is slowly cooled again at a rate of 3°C/hr to cool to 0-5°C. When the target temperature is reached, the temperature is maintained, and after stirring for 1 hour, filtration is performed to obtain the target compound (1.10 kg, 80.0%) in the state of crystal particles.

The nuclear magnetic resonance spectrum data is ¹ H NMR (CDCl ₃ ): 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)

Average particle size: 91.2μm

Bulk density: 0.38g/ml

Purity: 99.2%

Example 4: Synthesis of Diethylamino hydroxybenzylhexyl benzoate

After adding 4 v/w of 2-butanol to 2-(4-N,N-diethylamino-2-hydroxybenzyl)benzoic acid to the concentrated residue obtained in step 1 of Example 1, The internal temperature was raised to 30-50°C to dissolve and clarify. After confirming complete dissolution, it was slowly cooled at a rate of 3°C/hr to slowly precipitate crystals, and then slowly cooled to an internal temperature of 15-20°C. When the target temperature is reached, the temperature is maintained, and after stirring for 1 hour, it is slowly cooled again at a rate of 3°C/hr to cool to 0-5°C. When the target temperature is reached, the temperature is maintained, and after stirring for 1 hour, filtration is performed to obtain the target compound (1.00 kg, 75.0%) in the state of crystal particles.

The nuclear magnetic resonance spectrum data is ¹ H NMR (CDCl ₃ ): 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)

Average particle size: 12.0μm

Bulk density: 0.28g/ml

Purity: 99.5%

Example 5: Synthesis of Diethylaminohydroxybenzylhexyl benzoate

The 2-(4-N,N-diethylamino-2-hydroxybenzyl)benzoic acid (1.1kg, 3.51mol) synthesized in Preparation Example 1 and the 1-bromohexyl synthesized in Preparation Example 2-2 Alkane (0.7 kg, 4.22 mol), K ₂ CO ₃ (0.9 kg, 7.02 mol) and 1.65 L of DMF were stirred. After raising the internal temperature to 100-110°C and stirring for 4 hours, it was cooled and extracted with 3.5 L of ethyl acetate and 3.5 L of purified water. After decolorizing the separated final organic layer using 5% charcoal at an internal temperature of 30-50°C for 1 hour, it was concentrated under reduced pressure.

The concentrated residue was crystallized by the crystallization method of Example 3 to obtain the target compound (0.90 kg, 65.0%) in the state of crystal particles.

The nuclear magnetic resonance spectrum data is ¹ H NMR (CDCl ₃ ): 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)

Average particle size: 69.4μm

Bulk density: 0.32g/ml

Purity: 99.4%

Example 6: Synthesis of Diethylamino hydroxybenzylhexyl benzoate

The 2-(4-N,N-diethylamino-2-hydroxybenzyl)benzoic acid (1.1kg, 3.51mol) synthesized in Preparation Example 1 and the hexane methanesulfonate synthesized in Preparation Example 2-3 The ester (0.8 kg, 4.22 mol), K ₂ CO ₃ (0.9 kg, 7.02 mol) are stirred with 1.65 L of DMF. After raising the internal temperature to 100-110°C and stirring for 4 hours, it was cooled and extracted with 3.5 L of ethyl acetate and 3.5 L of purified water. After decolorizing the separated final organic layer using 5% charcoal at an internal temperature of 30-50°C for 1 hour, it was concentrated under reduced pressure.

The concentrated residue was crystallized by the crystallization method of Example 3 to obtain the target compound (0.73 kg, 52.4%) in the state of crystal particles.

The nuclear magnetic resonance spectrum data is ¹ H NMR (CDCl ₃ ): 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)

Average particle size: 25.8μm

Bulk density: 0.30g/ml

Purity: 99.8%

Example 7: Synthesis of Diethylamino hydroxybenzyl hexyl benzoate

The 2-(4-N,N-diethylamino-2-hydroxybenzyl)benzoic acid (1.1kg, 3.51mol) synthesized in Preparation Example 1 and the 4-methyl group synthesized in Preparation Example 2-4 Stirring hexyl benzenesulfonate (1.1 kg, 4.22 mol), K ₂ CO ₃ (0.9 kg, 7.02 mol) with 1.65 L of DMF. After raising the internal temperature to 100-110°C and stirring for 4 hours, it was cooled and extracted with 3.5 L of ethyl acetate and 3.5 L of purified water. After decolorizing the separated final organic layer using 5% charcoal at an internal temperature of 30-50°C for 1 hour, it was concentrated under reduced pressure.

The concentrated residue was crystallized by the crystallization method of Example 3 to obtain the target compound (0.66 kg, 47.6%) in the state of crystal particles.

The nuclear magnetic resonance spectrum data is ¹ H NMR (CDCl ₃ ): 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)

Average particle size: 81.3μm

Bulk density: 0.37g/ml

Purity: 99.5%

Example 8: Synthesis of Diethylamino hydroxybenzylhexyl benzoate

The 2-(4-N,N-diethylamino-2-hydroxybenzyl)benzoic acid (1.1kg, 3.51mol) synthesized in Preparation Example 1 and the dihexyl sulfite synthesized in Preparation Example 2-5 The ester (1.1 kg, 4.22 mol), K ₂ CO ₃ (0.9 kg, 7.02 mol) were stirred with 1.65 L of DMF. After raising the internal temperature to 100-110°C and stirring for 4 hours, it was cooled and extracted with 3.5 L of ethyl acetate and 3.5 L of purified water. After decolorizing the separated final organic layer using 5% charcoal at an internal temperature of 30-50°C for 1 hour, it was concentrated under reduced pressure.

The concentrated residue was crystallized by the crystallization method of Example 3 to obtain the target compound (1.12 kg, 80.0%) in the state of crystal particles.

¹ H NMR (CDCl ₃ ): 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)

Average particle size: 45.2μm

Bulk density: 0.32g/ml

Purity: 99.1%

Example 9: Synthesis of Diethylamino hydroxybenzylhexyl benzoate

The 2-(4-N,N-diethylamino-2-hydroxybenzyl)benzoic acid (1.1kg, 3.51mol) synthesized in Preparation Example 1 and the dihexyl sulfate synthesized in Preparation Example 2-6 (1.2kg, 4.22mol), K ₂ CO ₃ (0.9kg, 7.02mol) and 1.65L of DMF were stirred. After raising the internal temperature to 100-110°C and stirring for 4 hours, it was cooled and extracted with 3.5 L of ethyl acetate and 3.5 L of purified water. After decolorizing the separated final organic layer using 5% charcoal at an internal temperature of 30-50°C for 1 hour, it was concentrated under reduced pressure.

The concentrated residue was crystallized by the crystallization method of Example 3 to obtain the target compound (1.09 kg, 78.0%) in the state of crystal particles.

¹ H NMR (CDCl ₃ ): 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)

Average particle size: 82.0μm

Bulk density: 0.39g/ml

Purity: 99.4%

As confirmed in the examples, diethylamino hydroxybenzyl hexyl benzoate can be obtained in a high yield according to the preparation method of the present invention, which can simplify the decolorization and purification process, and thus can be economically mass-produced.

The above description of the present invention is for exemplification, and those of ordinary skill in the technical field of the present invention should understand that it can be easily deformed in other specific forms without changing the technical idea or essential features of the present invention. Therefore, it should be understood that the multiple embodiments described above are illustrative in all aspects and not restrictive. For example, each structural element described in a single type can be implemented in a dispersed manner, and similarly, a plurality of structural elements described as dispersed can also be implemented in a combined form.

The scope of the present invention is indicated by the appended claims rather than the above detailed description, and it should be construed that all changes or modifications derived from the meaning and scope of the claims and their equivalent concepts are included in the scope of the present invention.

The beneficial effects of the present invention are:

According to the preparation method of the present invention, the existing method for preparing diethylamino hydroxybenzyl hexyl benzoate, which is difficult to decolorize, can improve the red impurities produced by the reaction in strong acid. Specifically, the present invention not only uses a small amount of decoloring agent but also can reduce the number of purifications, can prepare diethylamino hydroxybenzyl hexyl benzoate with high yield, and can be produced in large quantities economically.

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Claims (8)

A method for preparing diethylaminohydroxybenzyl hexyl benzoate, which is characterized in that it comprises combining N,N-diethylamino-hydroxybenzyl-benzoic acid represented by the following chemical formula II with the following chemical formula III The step of reacting the compound to prepare the compound represented by the following chemical formula I: Chemical formula I

Chemical formula II

Chemical formula III

L is chlorine, bromine, iodine, methanesulfonyl, toluenesulfonyl, benzenesulfonyl, trifluoromethanesulfonyl, hexyl sulfite, or hexylalkylsulfonyl. The method for preparing diethylamino hydroxybenzyl hexyl benzoate according to patent application scope 1, is characterized in that the reaction is carried out under alkaline environmental conditions provided by a basic compound. The method for preparing diethylamino hydroxybenzyl hexyl benzoate according to the scope of patent application 2, characterized in that the basic compound is selected from potassium carbonate, sodium carbonate, potassium bicarbonate, sodium bicarbonate, hydrogen An inorganic base in the group consisting of sodium oxide and potassium hydroxide. The method for preparing diethylamino parabens hexyl benzoate according to the scope of patent application 2, characterized in that the alkaline reactant is selected from the group consisting of triethylamine, diisopropylethylamine, and diethylamine And pyridine in the group consisting of organic bases. A method for preparing crystal particles of diethylaminohydroxybenzylhexyl benzoate, characterized in that the diethylaminohydroxybenzylhexyl benzoate is represented by the following chemical formula I: Chemical formula I

The method for preparing crystal particles of diethylamino parabens hexyl benzoate according to the scope of the patent application 5 is characterized in that it is selected from methanol, ethanol, isopropanol, 1-propanol, 1-butanol Compounds in the group consisting of, 2-butanol, t-butanol, and mixtures thereof are used as crystallization solvents to perform crystallization of the crystal particles. The method for preparing crystal particles of diethylamino hydroxybenzyl hexyl benzoate according to the patent application scope 6 is characterized in that it comprises: Step 1) Put the crystallization solvent into the concentrated residue of diethylaminohydroxybenzyl hexyl benzoate represented by the chemical formula I; Step 2), increase the internal temperature to 30～50℃ for dissolution; Step 3), after confirming complete dissolution, slowly cool at a rate of 2 to 4°C/hr to slowly precipitate crystals, and slowly cool to an internal temperature of 15-20°C; Step 4), slowly cooling at a rate of 2 to 4°C/hr to cool to 0 to 5°C to prepare crystal particles. A diethylaminohydroxybenzylhexyl benzoate crystal particle, characterized in that the purity of the diethylaminohydroxybenzylhexyl benzoate is more than 98% by weight, the bulk density is greater than 0.28g/ml, and the average particle The size is from 10μm to 100μm.