Method for obtaining crystalline hexyl diethylaminohydroxybenzoyl benzoate

Abstract

The present invention relates to a method for obtaining crystalline diethylamino hydroxybenzoyl benzoic acid hexyl (I), comprising steps (a) to (d): (a) providing a feedstock containing diethylamino hydroxybenzoyl benzoic acid hexyl (I) and at least a first crystallization solvent, and heating this feedstock to obtain a solution, wherein the diethylamino hydroxybenzoyl benzoic acid hexyl (I) has a dihexyl phthalate ester (PSDHE) (II) content of at most 100,000 ppm based on the weight of the diethylamino hydroxybenzoyl benzoic acid hexyl (I), and the amount of diethylamino hydroxybenzoyl benzoic acid hexyl (I) in the feedstock is in the range of 15.0 to 65.0% by weight based on the total weight of the feedstock; (b) cooling the solution obtained in step (a) to obtain a supersaturated solution of diethylamino hydroxybenzoyl benzoic acid hexyl (I); (c) adding seed crystals of diethylamino hydroxybenzoyl benzoic acid hexyl (I) to the supersaturated solution obtained in step (b), wherein the amount of the seed crystals is 0.01 to 15 based on the weight of the diethylamino hydroxybenzoyl benzoic acid hexyl (I) in the solution.A step in the range of 0% by weight, and (d) cooling the solution obtained in step (c) to a temperature in the range of -20 to 17 °C to obtain a suspension containing crystalline diethylamino hydroxybenzoyl hexyl benzoate (I), then separating the crystalline diethylamino hydroxybenzoyl hexyl benzoate (I), and washing the separated crystalline diethylamino hydroxybenzoyl hexyl benzoate (I) at least once and twice using a washing solvent; (e) Optionally, a step of recrystallizing the diethylamino hydroxybenzoyl hexyl benzoate (I) obtained in step (d), comprising mixing the diethylamino hydroxybenzoyl hexyl benzoate (I) obtained in step (d) with at least a second crystallization solvent to obtain a feedstock, heating the feedstock to obtain a solution, and using method steps (b) to (d), wherein the amount of the washing solvent is at least 63% by weight based on the weight of diethylamino hydroxybenzoyl hexyl benzoate (I) in the corresponding solution in step (b) in each of the at least first and second washings in at least one of the crystallization step (d) or the recrystallization step (d) of the recrystallization (e). The present invention discloses a method. In addition, the present invention discloses crystalline diethylamino hydroxybenzoyl hexyl benzoate obtained by the method of the present invention, purified diethylamino hydroxybenzoyl hexyl benzoate obtained by the method of the present invention, and a cosmetic composition containing the purified diethylamino hydroxybenzoyl hexyl benzoate according to the present invention.

Description

Technical Field

[0001] The present invention claimed in this specification relates to a method for obtaining crystalline hexyl diethylaminohydroxybenzoyl benzoate. Further, the present invention claimed in this specification relates to crystalline hexyl diethylaminohydroxybenzoyl benzoate obtained by the method of the present invention, purified hexyl diethylaminohydroxybenzoyl benzoate obtained by the method of the present invention, and a cosmetic composition containing the purified hexyl diethylaminohydroxybenzoyl benzoate according to the present invention.

Background Art

[0002] UV radiation causes harmful effects on human skin such as sunburn, phototoxic reactions and photoallergic reactions, promotion of skin aging, and an increased risk of skin cancer. To protect human skin from UV radiation, sunscreen compositions or cosmetic compositions containing UV filters (also called UV absorbers) are used.

[0003] Generally, UV light can be divided into UV-A radiation (320 - 400 nm) and UV-B radiation (280 - 320 nm). The sun protection factor (SPF) mainly indicates protection against UV-B, but since 2006, the European Commission has recommended that all sunscreen or cosmetic compositions should have a UV-A protection factor of at least one-third of the indicated sun protection factor.

[0004] 2-(4’-Diethylamino-2’-hydroxybenzoyl) hexyl benzoate (DHHB) is an effective UV-A filter. It is represented by the formula (I):

Chem.

[0005] The preparation of hexyl 2-(4’-diethylamino-2’-hydroxybenzoyl)benzoate (I) is known, for example, from German Patent Application Publication No. 10011317, European Patent No. 2155660, and International Publication No. 2003097578 pamphlet.

[0006] However, the products obtained from the known processes are accompanied by several drawbacks.

[0007] Generally, hexyl 2-(4’-diethylamino-2’-hydroxybenzoyl)benzoate (I) is obtained as a melt after the synthesis process and stored in the same form as such. Crystal growth occurs in the melt after about 6 weeks at room temperature. In order to be able to take out the product from the storage container during use, the user has to heat the whole container to a temperature above the melting point of (I).

[0008] This product contains dihexyl phthalate (II) (also known as PSDHE or dihexyl phthalate or di-n-hexyl phthalate) as an impurity. This substance is toxic, may impair reproductive ability, and can have harmful effects on the fetus, so the content of PSDHE should be as low as possible. According to the harmonized classification and labeling (ATP05), the tolerance of PSDHE (II) in the final product is at most 150 ppm.

Chemical formula

[0009] Furthermore, the products obtained by the known processes contain rhodamine-type dyes (for example, [9-(2-carboxyphenyl)-6-diethylamino-3-xanthenylidene]-diethylammonium salt) (III) and the corresponding esters (IV) as impurities, which cause undesirable discoloration of the final product.

Chemical formula

[0010] Furthermore, the product obtained by a known process may contain 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid (V), which is a possible intermediate.

Chemical formula

[0011] Due to these problems, there is a continuing need for a rapid and efficient method for obtaining crystalline 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester (I), in which (II) is in small amounts and (III), (IV) and (V) are in small amounts.

Summary of the Invention

Problems to be Solved by the Invention

[0012] Accordingly, an object of the present invention is to provide a method for obtaining crystalline 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester (I). Further, it is an object to provide a method for obtaining crystalline 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester (I) in which the contained dihexyl phthalate (II) is in small amounts. Further, it is desirable that the crystalline 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester provided by this method contains small amounts of the contained rhodamine-based impurities (III) and (IV) and 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid (V).

Means for Solving the Problems

[0013] Surprisingly, it has been found that at least one of the above objects is achieved by the present invention claimed herein.

[0014] In a first aspect, the present invention is a method for obtaining crystalline diethylaminohydroxybenzoylbenzoic acid hexyl (I), comprising steps (a) to (d) (a) Providing a feedstock comprising hexyl diethylaminohydroxybenzoate (I) and at least a first crystallization solvent, and heating the feedstock to obtain a solution, wherein hexyl diethylaminohydroxybenzoate (I) has i) a content of dihexyl phthalate ester (PSDHE) (II) of up to 100,000 ppm based on the weight of hexyl diethylaminohydroxybenzoate (I), and the amount of hexyl diethylaminohydroxybenzoate (I) in the feedstock is in the range of 15.0 to 65.0% by weight based on the total weight of the feedstock, the step; (b) Cooling the solution obtained in step (a) to obtain a supersaturated solution of hexyl diethylaminohydroxybenzoate (I); (c) Adding seed crystals of hexyl diethylaminohydroxybenzoate (I) to the supersaturated solution obtained in step (b), wherein the amount of the seed crystals is in the range of 0.01 to 15.0% by weight based on the weight of hexyl diethylaminohydroxybenzoate (I) in the solution, the step; (d) Cooling the solution obtained in step (c) to a temperature in the range of -20 to 17 °C to obtain a suspension containing crystalline hexyl diethylaminohydroxybenzoate (I), then separating the crystalline hexyl diethylaminohydroxybenzoate (I), and washing the separated crystalline hexyl diethylaminohydroxybenzoate (I) at least once and twice with a washing solvent; (e) Optionally, a step of recrystallizing the hexyl diethylaminohydroxybenzoate (I) obtained in step (d), which involves mixing the hexyl diethylaminohydroxybenzoate (I) obtained in step (d) with at least a second crystallization solvent to obtain a feedstock, heating the feedstock to obtain a solution, and using method steps (b) to (d); comprising, wherein the amount of the washing solvent is at least 63% by weight based on the weight of hexyl diethylaminohydroxybenzoyl benzoate (I) in the corresponding solution in step (b) in each of at least the first and second washings in at least one of the crystallization step (d) or the recrystallization (e) step (d), and the first crystallization solvent comprises at least one C4-C8 alcohol, relates to a method.

[0015] In a second aspect, the present invention is a method for obtaining crystalline hexyl diethylaminohydroxybenzoyl benzoate (I), comprising steps (a) to (d) (a) providing a feedstock comprising hexyl diethylaminohydroxybenzoyl benzoate (I) and at least a first crystallization solvent, and heating the feedstock to obtain a solution, wherein the hexyl diethylaminohydroxybenzoyl benzoate (I) i) has a maximum content of 100,000 ppm of dihexyl phthalate (PSDHE) (II) based on the weight of hexyl diethylaminohydroxybenzoyl benzoate (I), and the amount of hexyl diethylaminohydroxybenzoyl benzoate (I) in the feedstock is in the range of 15.0 to 65.0% by weight based on the total weight of the feedstock, the step; and (b) cooling the solution obtained in step (a) to obtain a supersaturated solution of hexyl diethylaminohydroxybenzoyl benzoate (I); (c) adding seed crystals of hexyl diethylaminohydroxybenzoyl benzoate (I) to the supersaturated solution obtained in step (b), wherein the amount of the seed crystals is in the range of 0.01 to 15.0% by weight based on the weight of hexyl diethylaminohydroxybenzoyl benzoate (I) in the solution, the step; (d) The solution obtained in step (c) is cooled to a temperature in the range of -20 to 17 °C to obtain a suspension containing crystalline diethylamino hydroxybenzoyl benzoic acid hexyl (I), and then the crystalline diethylamino hydroxybenzoyl benzoic acid hexyl (I) is separated, and the separated crystalline diethylamino hydroxybenzoyl benzoic acid hexyl (I) is washed with a washing solvent; (e) Optionally, a step of recrystallizing the diethylamino hydroxybenzoyl benzoic acid hexyl (I) obtained in step (d), which involves mixing the diethylamino hydroxybenzoyl benzoic acid hexyl (I) obtained in step (d) with at least a second crystallization solvent to obtain a feedstock, heating the feedstock to obtain a solution, and using method steps (b) to (d); The method includes that the amount of the washing solvent is at least 130% by weight based on the weight of diethylamino hydroxybenzoyl benzoic acid hexyl (I) in the corresponding solution in step (b) in at least one of step (d) of crystallization or step (d) of recrystallization (e), and the first crystallization solvent contains at least one C4 - C8 alcohol.

[0016] In a third aspect, the present invention relates to crystalline diethylamino hydroxybenzoyl benzoic acid hexyl (I) obtained by one of the methods according to the present invention, and based on the weight of the crystalline diethylamino hydroxybenzoyl benzoic acid hexyl (I) respectively, i) a content of less than 250 ppm of dihexyl phthalate ester (PSDHE) (II), ii) a content of less than 150 ppm of rhodamine (III), and a content of less than 150 ppm of rhodamine hexyl ester (IV) relates to crystalline diethylamino hydroxybenzoyl benzoic acid hexyl (I) having the above.

[0017] In a fourth aspect, the present invention is a purified hexyl diethylaminohydroxybenzoyl benzoate (I) obtained by one of the methods according to the present invention, based on the weight of the purified hexyl diethylaminohydroxybenzoyl benzoate (I) respectively, i) having a dihexyl phthalate ester (PSDHE) (II) content of less than 250 ppm, ii) having a rhodamine (III) content of less than 10 ppm, and a rhodamine hexyl ester (IV) content of less than 10 ppm relates to a purified hexyl diethylaminohydroxybenzoyl benzoate (I).

[0018] In a fifth aspect, the present invention relates to a cosmetic composition comprising the purified hexyl diethylaminohydroxybenzoyl benzoate (I) of the present invention.

Mode for Carrying Out the Invention

[0019] Before describing the compositions and formulations of the present invention claimed herein, it should be understood that such compositions and formulations can, of course, vary, and thus the present invention is not limited to the specific compositions and formulations described. Since the scope of the present invention claimed herein is limited only by the appended claims, it should also be understood that the terms used herein are not intended to be limiting.

[0020] Hereinafter, when a group is defined to include at least a certain number of embodiments, this means that it also includes a preferred group consisting of only these embodiments. Further, terms such as "first", "second", "third" or "a", "b", "c", etc. and the like in this specification and the claims are used to distinguish similar elements and do not necessarily represent a consecutive order or chronological order. The terms used in this way are interchangeable under appropriate circumstances, and it should be understood that the embodiments of the invention described and claimed in this specification can be implemented in an order other than the order described or illustrated in this specification. When terms such as "first", "second", "third", or "(A)", "(B)", and "(C)", or "(a)", "(b)", "(c)", "(d)", "i", "ii", etc. relate to steps of a method or use or assay, unless otherwise specified in this application, as described above or below in this specification, no time is placed between these steps or there is no consistency in the time intervals, that is, these steps can be implemented simultaneously, or there can be time intervals of seconds, minutes, hours, days, weeks, months or even years between such steps.

[0021] Furthermore, the ranges defined throughout this specification include the boundary values, that is, the range of 1 to 10 means that both 1 and 10 are included in the range. To avoid doubt, the applicant hereby claims rights to all equivalents in accordance with the applicable law.

[0022] In the following sections, various aspects of the invention claimed in this specification are defined in more detail. Each aspect so defined can be combined with any one or more other aspects unless clearly indicated otherwise. In particular, any feature shown to be preferred or advantageous can be combined with any one or more other features shown to be preferred or advantageous.

[0023] References to "one embodiment" or "an embodiment" throughout this specification mean that a particular feature, structure, or characteristic described in connection with that embodiment is included in at least one embodiment of the invention claimed herein. Thus, appearances of the phrases "in one embodiment" or "in an embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment, although they may.

[0024] Furthermore, as will be apparent to those skilled in the art from this disclosure, this particular feature, structure, or characteristic may be combined in any suitable manner in one or more embodiments. Additionally, as understood by those skilled in the art, the fact that one embodiment described herein includes some features but not others of other embodiments means that combinations of features of different embodiments are within the scope of the invention claimed herein and form separate embodiments. For example, in the appended claims, any combination of the claimed embodiments may be used.

[0025] As used herein, the terms "ultraviolet filter" or "UV filter" refer to organic or inorganic compounds capable of absorbing and / or reflecting UV radiation generated by sunlight. UV filters can be classified as UV-A, UV-B, or broad-spectrum filters based on their UV protection curves. The broad-spectrum filters relevant to this application can be described as UV-A filters since they also protect against UV-A. In other words, preferred UV-A filters include broad-spectrum filters.

[0026] The definition of "broad-spectrum" protection (also referred to as broad-spectrum or broad protection) is based on the "critical wavelength". In order to cover a wide wavelength range, it is necessary to protect against UV-B and UV-A. According to the requirements in the United States, in order to achieve broad-spectrum protection, the critical wavelength must be at least 370 nm. Furthermore, the European Commission recommends that all sunscreen or cosmetic compositions should have a UVA protection index of at least one-third of the indicated ultraviolet protection factor (SPF). For example, if the SPF of a sunscreen composition is 30, the UVA protection index must be at least 10.

[0027] The term "sunscreen composition", or "sunscreen", or "skin care product" refers to any topical product that reflects and / or absorbs specific parts of UV radiation. It should be understood that the term "sunscreen composition" includes not only sunscreen compositions but also any cosmetic composition that protects against UV. The term "topical product" refers to a product applied to the skin and can refer to, for example, sprays, lotions, creams, oils, foams, powders or gels. According to the present invention, the sunscreen composition may contain one or more active agents, such as organic UV filters, and other components or additives, such as emulsifiers, emollients, viscosity modifiers, stabilizers, preservatives or fragrances.

[0028] The terms "hexyl diethylaminohydroxybenzoyl benzoate", and "DHHB", and "compound (I)" or "(I)" are used synonymously in the present invention. They all refer to the compound of formula (I) shown above.

[0029] The term "crystallization solvent" refers to a solvent used for the crystallization of a material. The crystallization solvent gives a specific threshold to the solubility of the material to be crystallized at a specific temperature or concentration. Therefore, this material can be dissolved in the crystallization solvent at a specific temperature and / or concentration, but crystallization may start when the temperature decreases or the concentration of the material in the crystallization solvent increases.

[0030] The term "washing solvent" refers to a solvent used for washing solid materials. Generally, the washing solvent should not dissolve the solid material during washing such that only impurities and by-products are removed from the solid material.

[0031] The term "solvent" is to be understood as a substance that dissolves a solute and as a result forms a solution.

[0032] The terms "n-hexanol" and "1-hexanol" are used synonymously in the present invention.

[0033] The terms "C1-C8 alcohol" or "C4-C8 alcohol" and similar terms refer to a compound containing at least one hydroxyl group "-OH" and a carbon chain with the amount of carbon atoms indicated by the subscript, i.e., 3 carbon atoms if C3. This alcohol can be a primary (RCH2OH), secondary (R2CHOH) or tertiary (R3COH) alcohol. Further, the carbon chain of this alcohol can be straight-chain like n-propanol or n-hexanol, branched like isobutanol, cyclic like cyclohexanol, and can be saturated or unsaturated.

[0034] This alcohol can contain one (monohydric alcohol) or a plurality (polyhydric alcohol) of hydroxyl groups. Further, this alcohol can have other functional groups at other positions of the molecule. Those skilled in the art understand other functional groups that can be present in C1-C8 or C4-C8 alcohols.

[0035] Surprisingly, it has been found that the method according to the invention claimed herein provides crystalline 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester (I) with a low content of PSDHE (II) and also low contents of rhodamine-based impurities (III) and (IV). The method of the invention claimed herein is rapid and efficient.

[0036] The process of the present invention claimed herein improves the quality and purity of crystalline (I) and reduces the time required for crystallization by selecting appropriate crystallization process parameters such as crystallization solvent, degree of supersaturation, amount of (I) seeds, seeding temperature, process temperature, amount of washing solvent and time of each process step.

[0037] According to a first aspect of the present invention, there is provided a method for obtaining crystalline diethylaminohydroxybenzoyl hexyl benzoate (I), comprising the steps of (a) to (d): (a) providing a feedstock comprising diethylamino hydroxybenzoyl hexyl benzoate (I) and at least a first crystallization solvent, and heating the feedstock to obtain a solution, wherein the diethylamino hydroxybenzoyl hexyl benzoate (I) is i) A maximum content of 100,000 ppm of dihexyl phthalate (PSDHE) (II) based on the weight of diethylamino hydroxybenzoyl hexyl benzoate (I) wherein the amount of diethylamino hydroxybenzoyl hexyl benzoate (I) in the feedstock is in the range of 15.0 to 65.0 wt. %, based on the total weight of the feedstock; (b) cooling the solution obtained in step (a) to obtain a supersaturated solution of diethylaminohydroxybenzoylhexyl benzoate (I); (c) adding seed crystals of diethylamino hydroxybenzoyl hexyl benzoate (I) to the supersaturated solution obtained in step (b), the amount of seed crystals being in the range of 0.01-15.0 wt % based on the weight of diethylamino hydroxybenzoyl hexyl benzoate (I) in the solution; (d) cooling the solution obtained in step (c) to a temperature in the range of −20 to 17° C. to obtain a suspension containing crystalline diethylamino hydroxybenzoyl hexyl benzoate (I), then isolating the crystalline diethylamino hydroxybenzoyl hexyl benzoate (I), and washing the separated crystalline diethylamino hydroxybenzoyl hexyl benzoate (I) with a washing solvent at least once and twice; (e) Optionally, a step of recrystallizing hexyl diethylaminohydroxybenzoyl benzoate (I) obtained in step (d), which involves mixing hexyl diethylaminohydroxybenzoyl benzoate (I) obtained in step (d) with at least a second crystallization solvent to obtain a feedstock, heating this feedstock to obtain a solution, and using method steps (b) to (d). The method includes that the amount of the washing solvent is at least 63% by weight based on the weight of hexyl diethylaminohydroxybenzoyl benzoate (I) in the corresponding solution in step (b) in each of the at least first and second washings in at least one of the crystallization step (d) or the recrystallization step (d) of step (e), and the first crystallization solvent contains at least one C4 - C8 alcohol.

[0038] Therefore, according to one aspect of the present invention, the washing of the separated crystalline DHHB is carried out as at least the first and second washings with a washing solvent. The amount of the washing solvent is at least 63% by weight based on the weight of hexyl diethylaminohydroxybenzoyl benzoate (I) in the corresponding solution in step (b) in each of the at least first and second washings in at least one of the crystallization step (d) or the recrystallization step (d) of step (e). By performing the third, fourth, fifth, sixth, etc. washings of the separated crystalline DHHB in this method, it is also possible to add further washing steps.

[0039] According to a preferred embodiment of the first aspect of the present invention, the amount of the washing solvent is at least 65% by weight, preferably at least 68% by weight, more preferably at least 70% by weight, and most preferably at least 74% by weight based on the weight of hexyl diethylaminohydroxybenzoyl benzoate (I) in the corresponding solution in step (b) in each of the at least first and second washings in at least one of the crystallization step (d) or the recrystallization step (d) of step (e).

[0040] According to a second aspect of the present invention, the present invention is a method for obtaining crystalline diethylaminohydroxybenzoyl benzoic acid hexyl (I), comprising steps (a) to (d) (a) providing a feedstock comprising diethylaminohydroxybenzoyl benzoic acid hexyl (I) and at least a first crystallization solvent, and heating the feedstock to obtain a solution, wherein the diethylaminohydroxybenzoyl benzoic acid hexyl (I) has i) a content of dihexyl phthalate ester (PSDHE) (II) of at most 100,000 ppm based on the weight of diethylaminohydroxybenzoyl benzoic acid hexyl (I) and the amount of diethylaminohydroxybenzoyl benzoic acid hexyl (I) in the feedstock is in the range of 15.0 to 65.0% by weight based on the total weight of the feedstock, the step; (b) cooling the solution obtained in step (a) to obtain a supersaturated solution of diethylaminohydroxybenzoyl benzoic acid hexyl (I); (c) adding seed crystals of diethylaminohydroxybenzoyl benzoic acid hexyl (I) to the supersaturated solution obtained in step (b), wherein the amount of the seed crystals is in the range of 0.01 to 15.0% by weight based on the weight of diethylaminohydroxybenzoyl benzoic acid hexyl (I) in the solution, the step; (d) cooling the solution obtained in step (c) to a temperature in the range of -20 to 17 °C to obtain a suspension containing crystalline diethylaminohydroxybenzoyl benzoic acid hexyl (I), then separating the crystalline diethylaminohydroxybenzoyl benzoic acid hexyl (I), and washing the separated crystalline diethylaminohydroxybenzoyl benzoic acid hexyl (I) with a washing solvent; (e) Optionally, a step of recrystallizing hexyl diethylaminohydroxybenzoyl benzoate (I) obtained in step (d), which involves mixing hexyl diethylaminohydroxybenzoyl benzoate (I) obtained in step (d) with at least a second crystallization solvent to obtain a feedstock, heating this feedstock to obtain a solution, and using method steps (b) to (d). It includes , and the amount of the washing solvent is at least 130% by weight based on the weight of hexyl diethylaminohydroxybenzoyl benzoate (I) in the corresponding solution in step (b) in at least one of step (d) of crystallization or step (d) of recrystallization (e). The first crystallization solvent contains at least one C4 - C8 alcohol. The present invention relates to a method.

[0041] In a second aspect of the present invention, the separated crystalline DHHB is washed with a washing solvent, and the amount of the washing solvent is at least 130% by weight based on the weight of hexyl diethylaminohydroxybenzoyl benzoate (I) in the corresponding solution in step (b) in at least one of step (d) of crystallization or step (d) of recrystallization (e). In this aspect of the present invention, the essential total amount of the washing solvent used in the washing step is defined. It is possible to perform the washing by washing the crystalline DHHB once using the total amount of this washing solvent. On the other hand, it is also possible to divide the total amount of the washing solvent used into several washing portions, for example, washing the separated crystalline DHHB at least once and twice, or washing the separated crystalline DHHB at least once, twice, and three times, or washing the separated crystalline DHHB at least once, twice, three times, and four times. Generally, there is no limit to the number of washing times of the separated crystalline DHHB. It has been found that when the number of washing times of the separated crystalline DHHB is 2 - 6 times, especially 2 - 3 times, the balance between process efficiency and product purity is optimized.

[0042] The following embodiments relate to the methods of the first and second aspects of the present invention.

[0043] When the washing of the separated crystalline DHHB is carried out by at least the first and second washings of the crystalline DHHB, the amount of the washing solvent can be equal in both the first and second washings. On the other hand, it is also possible to use different amounts of the washing solvent for the first and second washings. For example, the amount of the washing solvent used for the first washing may be more than the amount of the washing solvent used for the second washing. Instead, the amount of the washing solvent used for the second washing may be more than the amount of the washing solvent used for the first washing.

[0044] When the crystalline DHHB is subjected to the third, fourth, fifth, sixth, etc. washings, the amount of each of these DHHB washings can be selected independently of the amount of the washing solvent used for the first and second washings.

[0045] According to a preferred embodiment of the present invention, the total amount of the washing solvent used for the washing of the separated crystalline DHHB is at least 132% by weight, more preferably at least 135% by weight, still more preferably at least 140% by weight or at least 145% by weight, particularly preferably at least 150% by weight, most preferably at least 160% by weight based on the weight of hexyl diethylaminohydroxybenzoylbenzoate (I) in the corresponding solution of step (b).

[0046] According to a preferred embodiment of the present invention, the hexyl diethylaminohydroxybenzoylbenzoate (I) in step (a) is, respectively, based on the weight of hexyl diethylaminohydroxybenzoylbenzoate (I), i) having a rhodamine (III) content of less than 15000 ppm, and / or ii) having a rhodamine hexyl ester (IV) content of less than 15000 ppm DHHB having such an impurity profile with respect to rhodamine (III) and rhodamine hexyl ester (IV) can be completely and effectively purified by the crystallization method of the present invention.

[0047] According to another preferred embodiment of the present invention, the hexyl diethylaminohydroxybenzoylbenzoate (I) in step (a) has a content of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid (V) of less than 5000 ppm based on the weight of the hexyl diethylaminohydroxybenzoylbenzoate (I).

[0048] According to a preferred embodiment of the present invention, the solution in step (b) is at a temperature such that the ratio of the concentration c of the dissolved hexyl diethylaminohydroxybenzoylbenzoate (I) to the equilibrium solubility c of the hexyl diethylaminohydroxybenzoylbenzoate (I) at that temperature * is in the range of 1.1:1.0 to 9.0:1.0. More preferably, the ratio of c:c * is in the range of 1.5:1.0 to 7.0:1.0, even more preferably in the range of 2.0:1.0 to 6.0:1.0. The temperatures at which the ratio of c:c * is 3.8:1.0, 4.0:1.0 and 4.1:1.0 are most preferred. In this crystallization process, it has been found that an optimal balance between the crystallization rate and the purity of the resulting product is found at the temperature at which such a specific c:c * ratio is obtained. *

[0049] According to another preferred embodiment, the hexyl diethylaminohydroxybenzoylbenzoate (I) (DHHB) in step (a) has a content of 10 to 70000 ppm, particularly 500 to 50000 ppm or 5000 to 40000 or 7000 to 30000 ppm of dihexyl phthalate ester (PSDHE) (II) based on the weight of the hexyl diethylaminohydroxybenzoylbenzoate (I). It has been found that DHHB having such a PSDHE content can be particularly rapidly and effectively purified by the method of the present invention.

[0050] ​The method of the present invention uses a first crystallization solvent in step (a). According to a preferred embodiment, the first crystallization solvent comprises or consists of at least one selected from the group consisting of C1-C8 alcohols. It has been found that C1-C8 alcohols are very good crystallization solvents for DHHB in this method. At low temperatures, DHHB shows only low solubility in these, but at higher temperatures it shows good solubility, so when the supersaturated solution of DHHB in step (b) is cooled, it is possible to effectively crystallize DHHB.

[0051] As the first crystallization solvent, it has been found that C4-C8 alcohols are particularly preferred. Thus, according to a particularly preferred embodiment, the first crystallization solvent comprises or consists of C4-C8 alcohols.

[0052] When the recrystallization step (e) is carried out, a second crystallization solvent is used. In that case, preferably, the second crystallization solvent comprises or consists of at least one selected from the group consisting of C1-C8 alcohols. It has been found that C1-C8 alcohols are very good crystallization solvents for DHHB in this method. At low temperatures, DHHB shows only low solubility in these, but at higher temperatures it shows good solubility, so when the supersaturated solution of DHHB in step (b) is cooled, it is possible to effectively crystallize DHHB. As the second crystallization solvent, it has been found that C4-C8 alcohols are particularly preferred. Thus, according to a particularly preferred embodiment, the second crystallization solvent comprises or consists of C4-C8 alcohols.

[0053] When the recrystallization step (e) is carried out, preferably, both the first and second crystallization solvents are C1-C8 alcohols. According to a preferred embodiment, the first and second crystallization solvents can be the same. For example, both the first and second crystallization solvents can be 1-hexanol. Such a method enables an effective and resource-saving approach. On the other hand, according to the present invention, it is also possible to use different first and second crystallization solvents. For example, the first crystallization solvent is 1-hexanol and the second crystallization solvent is isopropanol. This approach enables optimal fine-tuning of the crystallization step and the recrystallization step, and in particular, enables the obtaining of a highly pure crystalline DHHB product.

[0054] When the recrystallization step (e) is carried out, it has been found preferable that the first crystallization solvent is selected from the group consisting of C4-C8 alcohols and the second crystallization solvent is selected from the group consisting of C1-C8 alcohols. Particularly preferably, the first crystallization solvent contains or consists of 1-hexanol, and the second crystallization solvent contains or consists of an alcohol selected from methanol, ethanol, n-propanol and isopropanol. Using such a combination of the first and second crystallization solvents in the method of the present invention makes it possible to particularly effectively remove any corresponding by-products and impurities.

[0055] According to a particularly preferred embodiment, the first crystallization solvent contains or consists of 1-hexanol.

[0056] When the final step of the synthesis of hexyl diethylaminohydroxybenzoylbenzoate (I) is the esterification of diethylaminohydroxybenzoylbenzoic acid with 1-hexanol, the product obtained from this esterification step contains a mixture of hexyl diethylaminohydroxybenzoylbenzoate (I) and 1-hexanol. In this case, in a preferred embodiment, the feedstock taken out from the esterification reaction is directly used in the crystallization method of the present invention.

[0057] In a preferred embodiment, the product containing hexyl diethylaminohydroxybenzoyl benzoate (I) obtained from the esterification and 1 - hexanol is used as it is as a feedstock for crystallization.

[0058] According to another preferred embodiment of the present invention, the second crystallization solvent contains or consists of 1 - hexanol.

[0059] In step (d) of the method of the present invention, the separated crystalline DHHB is washed with a washing solvent. According to a preferred embodiment of the present invention, the washing solvent contains or consists of an alcohol, particularly a C1 - C8 alcohol. In the present invention, the washing solvent preferably contains an alcohol selected from methanol, ethanol, isopropanol, n - propanol, isobutanol, tert - butanol, n - butanol, n - pentanol, sec - pentanol, cyclopentanol, n - hexanol, sec - hexanol, cyclohexanol, n - heptanol, sec - heptanol, n - octanol, sec - octanol. Alcohols, particularly the alcohols listed here, have been found to be well - suited as washing solvents in the method of the present invention. They effectively remove impurities from the crystalline DHHB. Particularly preferably, the washing solvent is 1 - hexanol.

[0060] When the recrystallization step (e) is carried out, the washing solvent used for recrystallization can be the same as that used for crystallization. On the other hand, it is also possible to use a washing solvent different from the washing solvent used for crystallization in the recrystallization step (e). For example, it is possible that the washing solvent used for crystallization contains or consists of 1 - hexanol and the washing solvent used for recrystallization contains or consists of isopropanol. Therefore, the first crystallization solvent, the second crystallization solvent, the washing solvent in crystallization, and the washing solvent in recrystallization can all be independently selected from the preferred solvents specified herein.

[0061] The washing of the separated crystalline diethylamino hydroxybenzoyl benzoic acid hexyl (I) is preferably carried out using a washing solvent having a temperature within ±5 °C of the temperature at which the solution is cooled in step (d). In this way, only the impurities are surely removed without dissolving DHHB in the washing solvent.

[0062] In another preferred embodiment, the first washing solvent and / or the second washing solvent is cooled within the range of -5 to 5 °C of a predetermined temperature. In this way, only the impurities are surely removed without dissolving DHHB in the washing solvent.

[0063] The crystalline DHHB in step d is separated by any technically reasonable method. Those skilled in the art recognize various techniques for filtering crystalline substances in chemical processes, such as Nutsche filters or stirred Nutsche filters or centrifugation, such as pusher type, decanter type, sieve decanter type or peeler type centrifugation or cylindrical filters, such as rotary or vacuum cylindrical filters or belt filters and the like. For example, the filtration can be carried out by suction or pressure.

[0064] Generally, the washing of the separated crystalline DHHB with a washing solvent can be carried out by any technically reasonable method. Those skilled in the art recognize various techniques for washing crystalline substances in chemical processes. However, particularly preferably, the washing is carried out by displacement washing or reslurry washing / suspension washing.

[0065] In displacement washing, the washing solvent is passed through the filtered crystalline DHHB and the first or second crystallization solvent. The displacement washing can be carried out by suction, pressure or gravity.

[0066] On the one hand, in the reslurry washing / suspension washing, first, a suspension of the separated crystalline DHHB in a washing solvent is prepared, and stirring is preferably carried out for, for example, 2 to 50 minutes, more preferably 10 to 30 minutes. Then, the suspension is filtered to obtain crystalline DHHB. The filter can be passed through again by suction, pressure or gravity. A stirred Nutsche filter is particularly preferred for reslurry washing / suspension washing.

[0067] According to a particularly preferred embodiment of the present invention, the first and / or second crystallization solvent and / or the washing solvent are recycled after use. In the present invention, it has been found that the first and / or second crystallization solvent and the washing solvent can be effectively reused by recycling. This results in an environmentally friendly and resource-saving process.

[0068] When recycling the first and / or second crystallization solvent and / or the washing solvent after use, according to one embodiment, it is preferable to purify the first and / or second crystallization solvent and / or the washing solvent for recycling after use. This is preferable when the impurity content of the starting material DHHB is high. On the other hand, according to other embodiments, it is also preferable to recycle the first and / or second crystallization solvent and / or the washing solvent without purification after use. Thereby, the recycling of the solvent is carried out more efficiently and the complexity is reduced. In addition, more resources are saved and the cost is reduced.

[0069] In a preferred embodiment, in step (a), the feedstock is heated to a temperature in the range of 25 to 80 °C. In a more preferred embodiment, in step (a), the feedstock is heated to a range of 35 to 80 °C, most preferably in the range of 40 to 60 °C, particularly preferably in the range of 43 to 52 °C. These have been found to be ideal temperatures for completely dissolving DHHB in the crystallization solvent without wasting energy.

[0070] In a preferred embodiment, in step (b), the solution is cooled to a temperature in the range of 18 to 35 °C, more preferably in the range of 18 to 32 °C, and most preferably in the range of 23 to 30 °C. Through extensive experiments, it has been found that this is the ideal temperature range for obtaining a supersaturated solution of DHHB that serves as the basis for crystallizing DHHB.

[0071] (I)'s liquid has high metastability, so crystallization of (I) is very slow as it is. Adding seed crystals to the supersaturated solution is an important step in the crystallization of the present invention claimed herein. By adding seed crystals, crystallization starts earlier compared to the case without adding seed crystals. Therefore, through the overall process of the present invention claimed herein, crystalline (I) can be obtained more rapidly compared to a process without the seed crystal addition step.

[0072] In addition to other process parameters, after adding seed crystals using an appropriate amount of crystals of (I), performing stirring at the temperature at which the seed crystals are added is important for the success of the present invention claimed herein.

[0073] The quality of the crystalline (I) obtained by crystallization depends on the temperature at which the seed crystal addition is performed and the amount of the seed crystals.

[0074] In a preferred embodiment, the seed crystal addition in step (c) is carried out at a temperature in the range of 18 to 35 °C, more preferably in the range of 18 to 32 °C, and most preferably in the range of 23 to 30 °C.

[0075] In a preferred embodiment, the seed crystals of hexyl diethylaminohydroxybenzoyl benzoate (I) in step (c) are used in at least one form selected from a solid crystal mass and a suspension in a solvent.

[0076] In a preferred embodiment, the seed crystals of hexyl diethylaminohydroxybenzoyl benzoate (I) in step (c) are used in the form of a suspension in the crystallization solvent of step (a).

[0077] In a more preferred embodiment, the seed crystals of hexyl diethylaminohydroxybenzoylbenzoate (I) in step (c) are used in the form of a suspension in 1-hexanol.

[0078] In a preferred embodiment, the amount of the seed crystals ranges from 0.01 to 15.0% by weight, more preferably from 0.5 to 10.0% by weight, still more preferably from 1.0 to 5.0% by weight, and most preferably from 1.5 to 4.5% by weight based on the weight of hexyl diethylaminohydroxybenzoylbenzoate (I). It has been found that this amount of the seed crystals is particularly effective in promoting rapid crystallization.

[0079] More preferably, after adding the seed crystals of hexyl diethylaminohydroxybenzoylbenzoate (I) to the supersaturated solution obtained in step (b), the supersaturated solution containing the seed crystals is stirred for up to 8 hours, particularly for 20 minutes to 7 hours, before performing the cooling in step (d). By stirring the supersaturated solution of DHHB after introducing the seed crystals of DHHB, it has been found that the particle size distribution of the crystals becomes good and the crystals are surely formed rapidly. The stirring speed is selected to be suitable for crystal formation. For example, the stirring speed is high enough to give a good distribution and to flow the dissolved particles well, while being selected so as not to have an adverse effect on crystal formation.

[0080] In a preferred embodiment, step (d) involves cooling the solution obtained in step (c) to -10 to 15°C, more preferably to -5 to 10°C, and most preferably to 0 to 5°C. In this way, the crystallization of DHHB present in the supersaturated solution of step (b) is achieved with a high yield and high energy efficiency.

[0081] In a preferred embodiment, step (d) involves cooling the solution obtained in step (c) at a cooling rate of 1 to 15 K / h, more preferably 3 to 10 K / h, and most preferably 4.5 to 8 K / h. These cooling rates have been found to be particularly beneficial for the crystallization process of DHHB.

[0082] It is also possible to use different cooling methods for the cooling in step (d). Those skilled in the art are aware of many different cooling methods. Preferably, the cooling of the solution is by one of the following modes: linear, segmented linear cooling profile, parabolic cooling profile with increasing cooling rate, dynamic cooling profile to maintain a relatively constant supersaturation within the crystallization apparatus, or vacuum cooling method.

[0083] According to a preferred embodiment of the present invention, the suspension obtained in step (d) is stirred for up to 12 hours, preferably up to 2 hours, and most preferably up to 1 hour at the cooling temperature of step (d) before separating the crystalline DHHB.

[0084] In a preferred embodiment, in step (d), the separation of the crystals is carried out by filtration while maintaining the temperature of the solution within ±5 °C of the temperature at which the solution is cooled in step (d). This ensures that DHHB does not dissolve during this step.

[0085] The filter cake, which is the solid residue remaining on the filter after filtering the suspension, is preferably dried after filtration. This is preferably done by suction or by passing a drying gas, such as air or nitrogen, especially nitrogen. In the manufacturing process, it is preferred to dry the filter cake by passing nitrogen gas through the filter cake. The filter cake is preferably dried for up to 5 hours, more preferably up to 1 hour, and most preferably for 5 - 30 minutes.

[0086] In a preferred embodiment, the method of the present invention claimed herein is i. a step of dissolving the crystalline diethylamino hydroxybenzoyl hexyl benzoate (I) obtained in step (d) or step (e) in a purification solvent; ii. a step of contacting the solution obtained in step (i) with an adsorbent; iii. A step of removing the adsorbent and the purification solvent from the solution obtained in step (ii) to obtain purified diethylamino hydroxybenzoyl hexyl benzoate (I); It further includes.

[0087] In a preferred embodiment, the purification solvent is selected from toluene, cyclohexane, and combinations thereof.

[0088] In a preferred embodiment, the adsorbent is selected from silica, carbon, and combinations thereof.

[0089] In a preferred embodiment, the purified diethylamino hydroxybenzoyl hexyl benzoate is then solidified, particularly granulated. Methods for solidifying the purified diethylamino hydroxybenzoyl hexyl benzoate are known to those skilled in the art. Performing melt crystallization at a specific shear rate with or without the addition of seed crystals is a preferred method for solidifying DHHB. According to a particularly preferred embodiment, the purified diethylamino hydroxybenzoyl hexyl benzoate is solidified according to at least one of the solidification methods described in WO 2008 / 135360 A1 pamphlet, PCT application PCT / EP2022 / 055088 specification, and PCT application PCT / EP2022 / 055089 specification. The solidified DHHB is preferably further processed into injectable / flowable particles, tablets, or flakes. Methods for producing such particles, tablets, or flakes from the solidified material are known to those skilled in the art.

[0090] The crystallization and stirring of the material according to the present invention can be carried out with any suitable crystallization and stirring apparatus. Those skilled in the art are familiar with general process apparatuses for crystallizing and stirring materials. In a preferred embodiment, the crystallization is carried out with a crystallization apparatus selected from a stirred tank with baffles, a forced circulation type crystallization apparatus, a draft tube type crystallization apparatus, a draft tube baffle type crystallization apparatus, and an Oslo type crystallization apparatus. Any type of stirrer can be used. Preferred stirrers are, for example, single-stage or multi-stage inclined or non-inclined cross blade type stirrers, impeller stirrers, or propeller stirrers. Anchor type stirrers or inclined anchor type stirrers are particularly preferred.

[0091] By the method of the present invention claimed herein, crystalline diethylamino hydroxybenzoyl hexyl benzoate (I) is obtained in a yield of 75.0 to 99.5%, more preferably 90.0 to 99.0%, based on the total of (I) in the feedstock.

[0092] Another aspect of the present invention is crystalline diethylamino hydroxybenzoyl hexyl benzoate (I) obtained by the method of the present invention. Crystalline diethylamino hydroxybenzoyl hexyl benzoate (I) according to the present invention has, based on the weight of diethylamino hydroxybenzoyl hexyl benzoate (I) respectively, i) a content of less than 250 ppm of dihexyl phthalate ester (PSDHE) (II), ii) a content of less than 150 ppm of rhodamine (III), and iii) a content of less than 150 ppm of rhodamine hexyl ester (IV) having.

[0093] In a preferred method of the present invention, crystalline diethylamino hydroxybenzoyl hexyl benzoate (I) has a PSDHE (II) content of less than 120 ppm, preferably less than 60 ppm, more preferably less than 20 ppm, still more preferably less than 5 ppm, and most preferably less than 1 ppm, based on the weight of crystalline diethylamino hydroxybenzoyl hexyl benzoate (I).

[0094] In a preferred embodiment of the present invention, crystalline hexyl diethylaminohydroxybenzoyl benzoate (I) has a rhodamine (III) content of less than 80 ppm, preferably less than 40 ppm, more preferably less than 20 ppm, still more preferably less than 10 ppm, and most preferably less than 5 ppm, based on the weight of crystalline hexyl diethylaminohydroxybenzoyl benzoate (I).

[0095] In a preferred embodiment of the present invention, crystalline hexyl diethylaminohydroxybenzoyl benzoate (I) has a rhodamine hexyl ester (IV) content of less than 120 ppm, preferably less than 100 ppm, more preferably less than 50 ppm, still more preferably less than 10 ppm, and most preferably less than 5 ppm, based on the weight of crystalline hexyl diethylaminohydroxybenzoyl benzoate (I).

[0096] According to one embodiment of the present invention, crystalline hexyl diethylaminohydroxybenzoyl benzoate (I) has a 2-(4'-diethylamino-2'-hydroxybenzoyl) benzoic acid (V) content of less than 250 ppm, based on the weight of crystalline hexyl diethylaminohydroxybenzoyl benzoate (I).

[0097] In a preferred embodiment of the present invention, crystalline hexyl diethylaminohydroxybenzoyl benzoate (I) has a 2-(4'-diethylamino-2'-hydroxybenzoyl) benzoic acid (V) content of less than 100 ppm, preferably less than 60 ppm, more preferably less than 15 ppm, still more preferably less than 5 ppm, and most preferably less than 1 ppm, based on the weight of crystalline hexyl diethylaminohydroxybenzoyl benzoate (I).

[0098] Particularly preferably, the crystalline hexyl diethylaminohydroxybenzoyl benzoate (I) obtained by the method of the present invention contains by-products in a specific combination. Specifically, the crystalline hexyl diethylaminohydroxybenzoyl benzoate (I) of the present invention preferably has a PSDHE (II) content of less than 120 ppm, a rhodamine (III) content of less than 150 ppm, and a rhodamine hexyl ester (IV) content of less than 150 ppm, more preferably a PSDHE (II) content of less than 90 ppm, a rhodamine (III) content of less than 80 ppm, and a rhodamine hexyl ester (IV) content of less than 120 ppm, still more preferably a PSDHE (II) content of less than 5 ppm, a rhodamine (III) content of less than 10 ppm, and a rhodamine hexyl ester (IV) content of less than 10 ppm, and most preferably a PSDHE (II) content of less than 1 ppm, a rhodamine (III) content of less than 5 ppm, and a rhodamine hexyl ester (IV) content of less than 5 ppm, based on the weight of the crystalline hexyl diethylaminohydroxybenzoyl benzoate (I).

[0099] The crystalline diethylamino hydroxybenzoyl benzoic acid hexyl (I) obtained by the method of the present invention particularly preferably also contains by-products in other specific combinations. Specifically, the crystalline diethylamino hydroxybenzoyl benzoic acid hexyl (I) of the present invention preferably has a PSDHE (II) content of less than 120 ppm, a rhodamine (III) content of less than 150 ppm, a rhodamine hexyl ester (IV) content of less than 150 ppm, and a 2-(4'-diethylamino-2'-hydroxybenzoyl) benzoic acid (V) content of less than 100 ppm, more preferably a PSDHE (II) content of less than 90 ppm, a rhodamine (III) content of less than 80 ppm, a rhodamine hexyl ester (IV) content of less than 120 ppm, and a 2-(4'-diethylamino-2'-hydroxybenzoyl) benzoic acid (V) content of less than 60 ppm, still more preferably a PSDHE (II) content of less than 5 ppm, a rhodamine (III) content of less than 10 ppm, a rhodamine hexyl ester (IV) content of less than 10 ppm, and a 2-(4'-diethylamino-2'-hydroxybenzoyl) benzoic acid (V) content of less than 10 ppm, and most preferably a PSDHE (II) content of less than 1 ppm, a rhodamine (III) content of less than 5 ppm, a rhodamine hexyl ester (IV) content of less than 5 ppm, and a 2-(4'-diethylamino-2'-hydroxybenzoyl) benzoic acid (V) content of less than 1 ppm, based on the weight of the crystalline diethylamino hydroxybenzoyl benzoic acid hexyl (I).

[0100] Such highly pure crystalline DHHB with a small amount of problematic by-products could not be obtained by conventional crystallization methods.

[0101] Another aspect of the present invention is purified diethylamino hydroxybenzoyl benzoic acid hexyl (I), which, based on the weight of the purified diethylamino hydroxybenzoyl benzoic acid hexyl (I), respectively, i) has a dihexyl phthalate (PSDHE) (II) content of less than 250 ppm, ii) has a rhodamine (III) content of less than 10 ppm, and iii) a rhodamine hexyl ester (IV) content of less than 10 ppm relates to a purified hexyl diethylaminohydroxybenzoylbenzoate (I) having. The purified DHHB is obtained by dissolving crystalline DHHB in a purification solvent and contacting it with an adsorbent that is removed in a later stage by the method of the present invention.

[0102] According to a preferred embodiment of the present invention, the purified DHHB of the present invention is a solid. Particularly preferably, the purified DHHB is in the form of injectable / flowable particles, tablets or flakes.

[0103] In a preferred embodiment of the present invention, the purified hexyl diethylaminohydroxybenzoylbenzoate (I) has a PSDHE (II) content of less than 120 ppm, preferably less than 60 ppm, more preferably less than 20 ppm, still more preferably less than 5 ppm, and most preferably less than 1 ppm, based on the weight of the purified hexyl diethylaminohydroxybenzoylbenzoate (I).

[0104] In a preferred embodiment of the present invention, the purified hexyl diethylaminohydroxybenzoylbenzoate (I) has a rhodamine (III) content of less than 8 ppm, preferably less than 5 ppm, and most preferably less than 1 ppm, based on the weight of the purified hexyl diethylaminohydroxybenzoylbenzoate (I).

[0105] In a preferred embodiment of the present invention, the purified hexyl diethylaminohydroxybenzoylbenzoate (I) has a rhodamine hexyl ester (IV) content of less than 8 ppm, preferably less than 5 ppm, and most preferably less than 1 ppm, based on the weight of the purified hexyl diethylaminohydroxybenzoylbenzoate (I).

[0106] According to one embodiment of the present invention, the purified hexyl diethylaminohydroxybenzoyl benzoate (I) has a content of 2-(4'-diethylamino-2'-hydroxybenzoyl) benzoic acid (V) of less than 250 ppm based on the weight of the purified hexyl diethylaminohydroxybenzoyl benzoate (I).

[0107] In a preferred embodiment of the present invention, the purified hexyl diethylaminohydroxybenzoyl benzoate (I) has a content of 2-(4'-diethylamino-2'-hydroxybenzoyl) benzoic acid (V) of less than 100 ppm, preferably less than 60 ppm, more preferably less than 15 ppm, still more preferably less than 5 ppm, and most preferably less than 1 ppm based on the weight of the crystalline hexyl diethylaminohydroxybenzoyl benzoate (I).

[0108] Particularly preferably, the purified crystalline hexyl diethylaminohydroxybenzoyl benzoate (I) obtained by the method of the present invention contains by-products in a specific combination. Specifically, the purified crystalline hexyl diethylaminohydroxybenzoyl benzoate (I) of the present invention preferably has a content of PSDHE (II) of less than 120 ppm, a content of rhodamine (III) of less than 10 ppm, and a content of rhodamine hexyl ester (IV) of less than 10 ppm, more preferably a content of PSDHE (II) of less than 5 ppm, a content of rhodamine (III) of less than 5 ppm, and a content of rhodamine hexyl ester (IV) of less than 5 ppm, still more preferably a content of PSDHE (II) of less than 5 ppm, a content of rhodamine (III) of less than 1 ppm, and a content of rhodamine hexyl ester (IV) of less than 1 ppm, and most preferably a content of PSDHE (II) of less than 1 ppm, a content of rhodamine (III) of less than 1 ppm, and a content of rhodamine hexyl ester (IV) of less than 1 ppm, each based on the weight of the purified crystalline hexyl diethylaminohydroxybenzoyl benzoate (I).

[0109] It is particularly preferred that the purified crystalline diethylamino hydroxybenzoyl hexyl benzoate (I) obtained by the method of the present invention also contains by-products in other specific combinations. Specifically, the purified crystalline diethylamino hydroxybenzoyl hexyl benzoate (I) of the present invention preferably has a PSDHE (II) content of less than 120 ppm, a rhodamine (III) content of less than 10 ppm, a rhodamine hexyl ester (IV) content of less than 10 ppm, and a 2-(4'-diethylamino-2'-hydroxybenzoyl) benzoic acid (V) content of less than 100 ppm, more preferably a PSDHE (II) content of less than 5 ppm, a rhodamine (III) content of less than 5 ppm, a rhodamine hexyl ester (IV) content of less than 5 ppm, and a 2-(4'-diethylamino-2'-hydroxybenzoyl) benzoic acid (V) content of less than 60 ppm, still more preferably a PSDHE (II) content of less than 5 ppm, a rhodamine (III) content of less than 1 ppm, a rhodamine hexyl ester (IV) content of less than 1 ppm, and a 2-(4'-diethylamino-2'-hydroxybenzoyl) benzoic acid (V) content of less than 10 ppm, and most preferably a PSDHE (II) content of less than 1 ppm, a rhodamine (III) content of less than 1 ppm, a rhodamine hexyl ester (IV) content of less than 1 ppm, and a 2-(4'-diethylamino-2'-hydroxybenzoyl) benzoic acid (V) content of less than 1 ppm, based on the weight of the crystalline diethylamino hydroxybenzoyl hexyl benzoate (I).

[0110] Another preferred embodiment of the purified diethylamino hydroxybenzoyl hexyl benzoate (I) obtained by the method of the present invention has a PSDHE (II) content of less than 120 ppm, a rhodamine (III) content of less than 1 ppm, a rhodamine hexyl ester (IV) content of less than 1 ppm, and a 2-(4'-diethylamino-2'-hydroxybenzoyl) benzoic acid (V) content of less than 15 ppm, based on the weight of the crystalline diethylamino hydroxybenzoyl hexyl benzoate (I).

[0111] Another aspect of the present invention relates to a cosmetic composition comprising the purified hexyl diethylaminohydroxybenzoyl benzoate (I) of the present invention. Particularly preferably, the purified DHHB in the cosmetic composition is in the form of injectable / flowable particles, tablets or flakes.

[0112] In a preferred embodiment, the cosmetic composition further comprises additives and adjuvants.

[0113] In a preferred embodiment, the cosmetic composition can be in the form of a cream, gel, lotion, alcoholic and aqueous / alcoholic solutions, emulsion, wax / fat composition, stick formulation, powder and ointment.

[0114] In a preferred embodiment, the cosmetic composition further comprises adjuvants and additives selected from low-irritation surfactants, superfatting agents, nacreous waxes, consistency modifiers, thickeners, polymers, silicone compounds, fats, waxes, stabilizers, bio-derived active ingredients, anti-odor active ingredients, dandruff inhibitors, film formers, swelling agents, antioxidants, hydrotropes, preservatives, insect repellents, self-tanning agents, solubilizers, oil perfumes, colorants, antibacterial agents and the like.

[0115] In a preferred embodiment, the cosmetic composition according to the present invention claimed herein may further comprise, as adjuvants, defoamers, structuring agents, solubilizers, opacifiers, complexing agents, propellants, couplers and developer components as oxidation dye precursors, reducing agents and oxidizing agents.

[0116] In a preferred embodiment, the present cosmetic composition is contained in various cosmetic formulations, particularly the following formulations: - Skin care formulations, such as skin cleansers and cleansing agents in the form of tablet-type or liquid soaps, synthetic detergents or cleansing pastes, - Bath agents, such as liquid bath agents (bubble bath agents, emulsion bath agents, shower bath agents) or solid bath agents, such as bath tablets and bath salts, - Skin care formulations, such as skin lotions, multi-emulsions or skin oils, - Cosmetic personal care formulations, such as day creams or cream foundations, foundations (loose or pressed), blushes or cream makeup cosmetics, eye care formulations, such as eyeshadow cosmetics, mascaras, eyeliners, eye creams or eye area repair creams, lip care formulations, such as lipstick in stick form, lip gloss, face makeup cosmetics in the form of lip contour pencils, nail care cosmetics, such as nail enamels, nail enamel removers, nail strengtheners or cuticle removers, - Foot care formulations, such as foot bath agents, foot powders, foot creams or foot balms, special deodorants and antiperspirants or callus removers, - Light protection formulations, such as sunscreens in emulsion, lotion, cream or oil form, sunblocks or tropicals (, pre-sun formulations or after-sun formulations, - Skin tanning formulations, such as self-tanning creams, - Pigmentation inhibition formulations, such as formulations for skin decolorization or skin whitening formulations, - Insect repellents, such as insect repellent oils, lotions, sprays or sticks, - Antiperspirants, such as antiperspirant sprays, pump sprays, antiperspirant gels, sticks or roll-ons, - Antiperspirants, such as antiperspirant sticks, creams or roll-ons, - Formulations for cleaning and caring for pimply skin, such as synthetic detergents (solid or liquid), keratolytic or scrub formulations or keratolytic packs, - Hair removal formulations in pharmaceutical form (depilation), such as powder hair removal agents, liquid hair removal formulations, hair removal formulations in cream or paste form, hair removal formulations in gel form or aerosol foam, - Beard shaving formulations, such as beard shaving soaps, foaming beard shaving creams, non-foaming beard shaving creams, foams and gels, pre-shave cosmetics for dry shaving, after-shave agents or after-shave lotions, - Cosmetics, such as fragrances (eau de cologne, eau de toilette, eau de parfum, parfum de toilette, parfum), oil perfumes or solid perfumes, - Cosmetic preparations for hair treatment, such as hair cleansing preparations in the form of shampoos and conditioners, hair care preparations, such as pretreatment preparations, hair tonics, hair styling creams, hair styling gels, pomades, hair rinses, treatment packs, intensive hair treatments, hair shaping agents, such as hair wave forming agents for permanent waves (hot perms, medium perms, cold perms), straightening agents, liquid hair setting preparations, hair foams, hair sprays, bleaching preparations, such as hydrogen peroxide solutions, brightening shampoos, bleaching creams, bleaching powders, bleaching pastes or oils, temporary, semi-permanent or permanent hair coloring agents, preparations containing self-oxidizing dyes or natural hair coloring agents such as henna or chamomile.

[0117] All descriptions of the purified DHHB of the present invention herein apply also to the purified DHHB contained in the cosmetic compositions of the present invention.

[0118] The present invention as claimed herein provides one or more of the following advantages: 1) The method of the present invention as claimed herein provides crystalline DHHB with high purity and low amounts of impurities (II), (III), (IV) and (V). The method of the present invention as claimed herein provides crystalline DHHB with less than 10 ppm of (II). The low amount of (II) is appropriate from the perspective of regulatory requirements. 2) The method of the present invention as claimed herein is rapid. 3) The method of the present invention as claimed herein is efficient because DHHB can be obtained in a high yield in the range of 85 - 99% based on the total DHHB in the feedstock. 4) The crystalline DHHB obtained by the process of the present invention as claimed herein has a low amount of fine particles.

Examples

[0119] Overview According to Example 2 of U.S. Patent Application Publication No. 20050165099, hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate (I) was prepared in hexanol.

[0120] The product obtained by this process was subjected to crystallization as described in the experiment.

[0121] Method To measure 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid in addition to hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate (I), phthalic acid ester (II), and rhodamine-type compounds (III) and (IV), the HPLC method was carried out by the standard method of the prior art.

[0122] To measure phthalic acid esters and residual solvents, the GC method was carried out by the standard method of the prior art.

[0123] Analytical reference substances for calibration were carried out by the standard method of the prior art.

[0124] Comparative Example according to WO 03 / 097578 Pamphlet Comparative Example C1: Crystallization according to WO 03 / 097578 Pamphlet 664.3 g of a feedstock containing 49.0% by weight of hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate, 0.74% by weight of di-n-hexyl phthalate, 0.14% by weight of rhodamine, and 0.32% by weight of rhodamine-hexyl ester (calculated based on hexyl 2-(4'-diethylamino-2'-hydroxy-benzoyl)benzoate (above), corresponding to 14847 ppm of di-n-hexyl phthalate, 2786 ppm of rhodamine, and 6397 ppm of rhodamine-hexyl ester) was charged into a 1.6 L reactor.

[0125] A solution was obtained by heating this feedstock to 40°C. This solution was cooled to 20°C within 1.3 hours, c:c* A supersaturated solution with a ratio of 5.4 was obtained.

[0126] After 4 hours at 20 °C, crystallization began. This suspension was stirred at 20 °C overnight (12 hours), then cooled to 0 °C within 4 hours and stirred at 0 °C. The product was filtered off, washed with 183 g of 1 - hexanol pre - cooled to (0 °C), and then washed with another 200 g of 1 - hexanol pre - cooled to (0 °C). Thus, 371.5 g of 2 - (4’ - diethylamino - 2’ - hydroxybenzoyl) benzoic acid hexyl ester moist with hexanol and having a content of 2 - (4’ - diethylamino - 2’ - hydroxybenzoyl) benzoic acid hexyl ester of 80.6% by weight was obtained.

[0127] Content of by - products calculated based on (I): Rhodamine (III) 110 ppm, Rhodamine - hexyl ester (IV) 131 ppm, and Di - n - hexyl phthalate (II) 271 ppm.

[0128] Comparative Example C2: Crystallization according to WO 03 / 097578 pamphlet 605.6 g of a feedstock containing 45.0% by weight of 2 - (4’ - diethylamino - 2’ - hydroxybenzoyl) benzoic acid hexyl ester, 0.71% by weight of di - n - hexyl phthalate, 0.06% by weight of rhodamine, and 0.33% by weight of rhodamine - hexyl ester (corresponding to 15546 ppm of di - n - hexyl phthalate, 1298 ppm of rhodamine, and 7292 ppm of rhodamine - hexyl ester when calculated based on 2 - (4’ - diethylamino - 2’ - hydroxy - benzoyl) benzoic acid hexyl ester) was charged into a 1.6 L reactor, and a solution was obtained by heating the feedstock to 40 °C.

[0129] This solution was cooled to 20 °C within 1 hour, and a supersaturated solution with a ratio of 5.0 was obtained. * A supersaturated solution with a ratio of 5.0 was obtained.

[0130] Crystallization started after 3.5 hours at 20 °C. The mixture was stirred at 20 °C for an additional 1 hour, then cooled to 0 °C within 4 hours and stirred at 0 °C. The product was filtered off and washed with 169 g of 1-hexanol, cooled in advance (0 °C), and then washed with 183 g of 1-hexanol, cooled in advance (0 °C), to obtain 310.9 g of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester, moist with hexanol, with a content of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester of 79.1% by weight.

[0131] Content of by-products calculated based on (I): rhodamine (III) 73 ppm, rhodamine-hexyl ester (IV) 187 ppm, and di-n-hexyl phthalate (II) 344 ppm.

[0132] Example 1: Crystallization 659 g of feedstock containing 45.9% by weight of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester, 2.28% by weight of di-n-hexyl phthalate, 0.07% by weight of rhodamine, 0.26% by weight of rhodamine-hexyl ester, and 0.01% by weight of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid (calculated relative to 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester, corresponding to 47385 ppm of di-n-hexyl phthalate, 1555 ppm of rhodamine, 5724 ppm of rhodamine-hexyl ester, and 218 ppm of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid) was charged into a 1.6 L reactor, and a solution was obtained by heating the feedstock to 60 °C.

[0133] This solution was cooled to 25 °C within 1.0 hour to obtain a supersaturated solution with a c:c * ratio of 3.2.

[0134] To this supersaturated solution, 5.2 g (1.5% by weight calculated based on I) of seed crystals of hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate (87.2% by weight) were added, and the mixture was stirred at 25 °C for 3.5 hours. This suspension was further cooled to 0 °C within 5 hours and stirred at 0 °C. The product was filtered off and washed with 187.4 g of 1-hexanol for the first portion pre-cooled to (0 °C), and then washed with 202.5 g (total 389.9 g) of 1-hexanol for the second portion pre-cooled to (0 °C), whereby 309.8 g of hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate (I) moist with hexanol and having a content of hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate (I) of 85.3% by weight was obtained.

[0135] Content of by-products calculated based on (I): 246 ppm of di-n-hexyl phthalate (II), 35 ppm of rhodamine (III), 68 ppm of rhodamine-hexyl ester (IV), and 5 ppm of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid (V).

[0136] Example 2: Recrystallization of the crystalline (I) obtained in Example 1 278.4 g of a filter cake moist with hexanol containing hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate (85.3% by weight) obtained in Example 1 and 235 g of hexanol were charged into a 1.6 L reactor, and a solution was obtained by heating the feedstock to 60 °C.

[0137] This solution was cooled to 25 °C within 1.0 hour to obtain a supersaturated solution with a c:c * ratio of 2.9.

[0138] To this supersaturated solution, 4.1 g (1.5% by weight calculated based on I) of seed crystals of hexyl 2-(4’-diethylamino-2’-hydroxybenzoyl)benzoate (87.2% by weight) was added, and then the mixture was stirred at 25 °C for 3.5 hours. This suspension was further cooled to 0 °C within 5 hours and stirred at 0 °C. The suspension was filtered, and the product was washed three times (at 0 °C, a total of 555.6 g) with 185.2 g of 1-hexanol that had been pre-cooled, thereby obtaining 232.3 g of hexyl 2-(4’-diethylamino-2’-hydroxybenzoyl)benzoate moist with hexanol and having a content of hexyl 2-(4’-diethylamino-2’-hydroxybenzoyl)benzoate of 82.9% by weight.

[0139] (I)-based content of by-products: di-n-hexyl phthalate (II) 0.4 ppm, rhodamine (III) 3 ppm, rhodamine-hexyl ester (IV) 2 ppm, and 2-(4’-diethylamino-2’-hydroxybenzoyl)benzoic acid (V) 1 ppm.

[0140] Example 3: Crystallization 687 g of a feedstock containing 44.0% by weight of hexyl 2-(4’-diethylamino-2’-hydroxybenzoyl)benzoate, 0.63% by weight of di-n-hexyl phthalate, 0.10% by weight of rhodamine, 0.29% by weight of rhodamine-hexyl ester, and <0.01% by weight of 2-(4’-diethylamino-2’-hydroxybenzoyl)benzoic acid (equivalent to 14187 ppm of di-n-hexyl phthalate, 2294 ppm of rhodamine, 6501 ppm of rhodamine-hexyl ester, and 12 ppm of 2-(4’-diethylamino-2’-hydroxybenzoyl)benzoic acid when calculated based on hexyl 2-(4’-diethylamino-2’-hydroxybenzoyl)benzoate) was charged into a 1.6 L reactor, and the feedstock was heated to 60 °C to obtain a solution.

[0141] This solution was cooled to 25 °C within 1.0 hour to obtain a supersaturated solution with a c:c * ratio of 3.0.

[0142] To this supersaturated solution, 5.2 g (1.5% by weight calculated based on I) of seed crystals of hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate (87.2% by weight) were added, and then the mixture was stirred at 25 °C for 3.5 hours. This suspension was cooled to 0 °C within 5 hours and stirred at 0 °C. The product was filtered off and washed 4 times (at 0 °C, a total of 967.2 g of 1-hexanol) with 241.8 g of pre-cooled 1-hexanol, whereby 266.4 g of hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate (I) moistened with hexanol and having a content of hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate (I) of 84.9% by weight was obtained.

[0143] Content of by-products calculated based on (I): di-n-hexyl phthalate (II) 36 ppm, rhodamine (III) 34 ppm, rhodamine-hexyl ester (IV) 61 ppm, and 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid (V) 3 ppm.

[0144] Example 4: Recrystallization of the crystalline (I) obtained in Example 3 237.4 g of a filter cake moistened with hexanol containing hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate (84.9% by weight) obtained in Example 3 and 200 g of hexanol were charged into a 1.6 L reactor, and a solution was obtained by heating the feedstock to 60 °C.

[0145] This solution was cooled to 25 °C within 1.0 hour to obtain a supersaturated solution with a c:c * ratio of 2.9.

[0146] To this supersaturated solution, 3.4 g (1.5% by weight calculated based on I) of seed crystals of hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate (87.2% by weight) was added, and then it was stirred at 25 °C for 3.5 hours. This suspension was further cooled to 0 °C within 5 hours and stirred at 0 °C. The suspension was filtered, and the product was washed with 125.0 g of 1-hexanol for the first portion pre-cooled to (0 °C) and 135.1 g of 1-hexanol for the second portion pre-cooled to (0 °C) (total 260.1 g at 0 °C), to obtain 209.5 g of hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate moist with hexanol and having a content of hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate of 84.3% by weight.

[0147] (I)-based content of by-products: Di-n-hexyl phthalate (II) < 1 ppm, Rhodamine (III) 3 ppm, Rhodamine-hexyl ester (IV) 2 ppm, and 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid (V) 1 ppm.

[0148] Conclusion As shown in the examples, by the method of the present invention, it becomes possible to prepare highly pure crystalline DHHB (I) with a very small amount of by-products as compared with the conventional method for crystallizing DHHB.

Claims

1. A method for obtaining crystalline diethylaminohydroxybenzoyl hexyl benzoate (I), comprising steps (a) to (d) (a) Providing a feedstock comprising diethylaminohydroxybenzoyl hexyl benzoate (I) and at least a first crystallization solvent, and heating the feedstock to obtain a solution, wherein the diethylaminohydroxybenzoyl hexyl benzoate (I) is i) Maximum content of dihexyl phthalate (PSDHE)(II) of 100,000 ppm based on the weight of diethylaminohydroxybenzoyl hexyl benzoate(I). The step is to have the following, wherein the amount of diethylaminohydroxybenzoyl hexyl benzoate (I) in the supply raw material is in the range of 15.0 to 65.0% by weight based on the total weight of the supply raw material, (b) The step of cooling the solution obtained in step (a) to obtain a supersaturated solution of diethylaminohydroxybenzoyl hexyl(I) benzoate, (c) A step of adding seed crystals of diethylaminohydroxybenzoylhexyl(I) benzoate to the supersaturated solution obtained in step (b), wherein the amount of seed crystals is in the range of 0.01 to 15.0% by weight based on the weight of diethylaminohydroxybenzoylhexyl(I) benzoate in the solution, (d) The solution obtained in step (c) is cooled to a temperature in the range of -20 to 17°C to obtain a suspension containing crystalline diethylaminohydroxybenzoyl hexyl benzoate (I), then the crystalline diethylaminohydroxybenzoyl hexyl benzoate (I) is separated, and the separated crystalline diethylaminohydroxybenzoyl hexyl benzoate (I) is washed at least once and twice with a washing solvent, (e) an optional step of recrystallizing the diethylaminohydroxybenzoyl hexyl benzoate (I) obtained in step (d), comprising: mixing the diethylaminohydroxybenzoyl hexyl benzoate (I) obtained in step (d) with at least a second crystallization solvent to obtain a feed material; heating the feed material to obtain a solution; and using the method steps (b) to (d). The amount of the washing solvent is at least 63% by weight, based on the weight of the diethylaminohydroxybenzoyl hexyl(I) in the corresponding solution in step (b), in each of the at least first and second washings in at least one of the crystallization step (d) or step (d) of the recrystallization (e), and the first crystallization solvent is at least one C ４ ~C ８ A method involving alcohol.

2. A method for obtaining crystalline diethylaminohydroxybenzoyl hexyl benzoate (I), comprising steps (a) to (d) (a) Providing a feedstock comprising diethylaminohydroxybenzoyl hexyl benzoate (I) and at least a first crystallization solvent, and heating the feedstock to obtain a solution, wherein the diethylaminohydroxybenzoyl hexyl benzoate (I) is i) Maximum content of dihexyl phthalate (PSDHE)(II) of 100,000 ppm based on the weight of diethylaminohydroxybenzoyl hexyl benzoate(I). The step is to have the following, wherein the amount of diethylaminohydroxybenzoyl hexyl benzoate (I) in the supply raw material is in the range of 15.0 to 65.0% by weight based on the total weight of the supply raw material, (b) The step of cooling the solution obtained in step (a) to obtain a supersaturated solution of diethylaminohydroxybenzoyl hexyl(I) benzoate, (c) A step of adding seed crystals of diethylaminohydroxybenzoylhexyl(I) benzoate to the supersaturated solution obtained in step (b), wherein the amount of seed crystals is in the range of 0.01 to 15.0% by weight based on the weight of diethylaminohydroxybenzoylhexyl(I) benzoate in the solution, (d) The solution obtained in step (c) is cooled to a temperature in the range of -20 to 17°C to obtain a suspension containing crystalline diethylaminohydroxybenzoyl hexyl benzoate (I), then the crystalline diethylaminohydroxybenzoyl hexyl benzoate (I) is separated, and the separated crystalline diethylaminohydroxybenzoyl hexyl benzoate (I) is washed with a washing solvent, (e) an optional step of recrystallizing the diethylaminohydroxybenzoyl hexyl benzoate (I) obtained in step (d), comprising: mixing the diethylaminohydroxybenzoyl hexyl benzoate (I) obtained in step (d) with at least a second crystallization solvent to obtain a feed material; heating the feed material to obtain a solution; and using the method steps (b) to (d). The amount of the washing solvent is at least 130% by weight based on the weight of the diethylaminohydroxybenzoyl hexyl(I) in the corresponding solution in step (b) in at least one of the crystallization step (d) or step (d) of the recrystallization step (e), and the first crystallization solvent is at least one C ４ ~C ８ A method involving alcohol.

3. The solution in step (b) is the temperature, where c is the concentration of the dissolved diethylaminohydroxybenzoyl hexyl benzoate (I) versus the equilibrium solubility c of diethylaminohydroxybenzoyl hexyl benzoate (I) at the temperature. ＊ c:c ＊ The method according to claim 1 or 2, characterized in that the solution is cooled to a temperature such that the ratio of the two components is in the range of 1.1:1.0 to 9.0:1.0, and / or the diethylaminohydroxybenzoyl hexyl benzoate (I) in step (a) has a content of dihexyl phthalate (PSDHE) (II) of 10 to 70,000 ppm, particularly 500 to 50,000 ppm or 5,000 to 40,000 or 7,000 to 30,000 ppm, based on the weight of the diethylaminohydroxybenzoyl hexyl benzoate (I), and / or the supersaturated solution obtained in step (b) is mixed with a seed crystal of diethylaminohydroxybenzoyl hexyl benzoate (I), and the supersaturated solution containing the seed crystal is stirred for a maximum of 8 hours, particularly 20 minutes to 7 hours, before being cooled in step (d).

4. The first and / or second crystallization solvent is C ４ ~C ８ The method according to claim 1 or 2, characterized in that it comprises or consists of at least one selected from the group consisting of alcohols, and / or the first and / or second crystallization solvent comprises or consists of 1-hexanol.

5. The cleaning solvent is particularly C １ -C ８ The method according to claim 1 or 2, characterized in that it contains an alcohol selected from the group consisting of alcohols, particularly methanol, ethanol, isopropanol, n-propanol, isobutanol, tert-butanol, n-butanol, n-pentanol, sec-pentanol, cyclopentanol, n-hexanol, sec-hexanol, cyclohexanol, n-heptanol, sec-heptanol, n-octanol, sec-octanol.

6. The method according to claim 1 or 2, characterized in that the washing solvent is different from the first crystallization solvent and / or the second crystallization solvent, or the washing solvent and the first crystallization solvent and / or the second crystallization solvent are the same.

7. The method according to claim 1 or 2, characterized in that the washing is carried out by displacement washing and / or reslurry washing / suspension washing, and / or in step (a), the feed material is heated to a temperature in the range of 25 to 80°C, particularly in the range of 35 to 60°C, and / or in step (b), the solution is cooled to a temperature in the range of 20 to 35°C, and / or in step (c), the seed crystal addition is carried out at a temperature in the range of 20 to 35°C, and / or in step (d), the solution is cooled at a cooling rate of 1 to 15 K / h.

8. The method according to claim 1 or 2, characterized in that in step (d), the solution is cooled linearly, or in step (d), the solution is cooled with a piecewise linear cooling profile, or in step (d), the solution is cooled with a parabolic cooling profile in which the cooling rate increases, or in step (d), the solution is cooled with a dynamic cooling profile in which a relatively constant degree of supersaturation is maintained in the crystallizer, or in step (d), the solution is cooled by a vacuum cooling method.

9. The method according to claim 1 or 2, characterized in that, in step (d), the separation of the crystals is carried out by filtration while maintaining the temperature of the solution within ±5°C of the temperature at which the solution is cooled in step (d), and / or the washing of the separated crystalline diethylaminohydroxybenzoyl hexyl benzoate (I) is carried out using a washing solvent having a temperature within ±5°C of the temperature at which the solution is cooled in step (d), and / or the crystallization is carried out in a crystallizer selected from a baffled stirring tank, a forced-circulation crystallizer, a fume tubing crystallizer, a fume tubing baffle crystallizer, and an Oslo crystallizer.

10. i. A step of dissolving the crystalline diethylaminohydroxybenzoyl hexyl(I) obtained in step (d) or step (e) in a purification solvent, ii. A step of bringing the solution obtained in step (i) into contact with the adsorbent, iii. The step of removing the solvent from the solution obtained in step (ii) to obtain purified diethylaminohydroxybenzoyl hexyl(I) benzoate. The method according to claim 1 or 2, further comprising:

11. The method according to claim 10, characterized in that the purification solvent is selected from toluene, cyclohexane, and combinations thereof, and / or the adsorbent is selected from silica, carbon, and combinations thereof.

12. Crystalline diethylaminohydroxybenzoyl hexyl benzoate (I) obtained by the method described in claim 1 or 2, wherein the weight of the crystalline diethylaminohydroxybenzoyl hexyl benzoate (I) is used as a reference. i) Dihexyl phthalate (PSDHE)(II) content of less than 250 ppm, ii) Rhodamine (III) content of less than 150 ppm, and iii) Rhodamine hexyl ester (IV) content less than 150 ppm Crystalline diethylaminohydroxybenzoyl hexyl(I) benzoate having [a specific characteristic].

13. The crystalline diethylamino hydroxybenzoyl hexyl benzoate (I) according to claim 12, characterized in that, based on the weight of the crystalline diethylamino hydroxybenzoyl hexyl benzoate (I), the content of dihexyl phthalate (PSDHE) (II) is less than 1 ppm, and / or the content of rhodamine (III) is less than 10 ppm, and / or the content of rhodamine hexyl ester (IV) is less than 10 ppm.

14. Purified diethylaminohydroxybenzoyl hexyl(I) benzoate obtained by the method of claim 10, wherein each is based on the weight of the purified diethylaminohydroxybenzoyl hexyl(I) benzoate, i) Dihexyl phthalate (PSDHE)(II) content of less than 250 ppm, ii) Rhodamine (III) content of less than 10 ppm, iii) Rhodamine hexyl ester (IV) content of less than 10 ppm Purified diethylaminohydroxybenzoyl hexyl(I) benzoate having [a specific characteristic].

15. A cosmetic composition comprising the purified diethylaminohydroxybenzoyl hexyl(I) benzoate according to claim 14.