Method for purifying hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate

Abstract

The present invention relates to a method for purifying 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester, which provides high purity and a low content of dialkyl phthalate esters.

Description

Technical Field

[0001] The present invention relates to a method for purifying hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate, which provides high purity and low content of dialkyl phthalate esters.

Background Art

[0002] UV radiation causes harmful effects on human skin. UV radiation is known not only to cause acute effects such as sunburn of the skin but also to increase the risk of skin cancer. Furthermore, long-term exposure to UV-A and UV-B light can cause phototoxic and photoallergic reactions in the skin and can accelerate skin aging.

[0003] To protect human skin from UV radiation, there are various ultraviolet protection filters (also referred to as UV absorbers), including UV-A filters, UV-B filters, and broadband filters. These filters are added to sunscreen or cosmetic compositions. UV filters are organic or inorganic particulate or non-particulate compounds, all of which have a high absorption effect in the UV light range. Generally, UV light can be divided into UV-A radiation (320 - 400 nm) and UV-B radiation (280 - 320 nm). Depending on the position of maximum absorption, UV filters are divided into UV-A filters and UV-B filters. When a UV filter absorbs both UV-A light and UV-B light, it is called a broadband absorber.

[0004] Since 2006, the European Commission has recommended that all sunscreen or cosmetic compositions must have a UV-A protection index of at least one-third of the indicated sun protection factor (SPF), where the sun protection factor in this case mainly refers to UV-B protection.

[0005] Hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate is an effective UV-A filter and is used to protect the skin from UV radiation (e.g., in sunscreens). Hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate is shown below and will hereinafter also be referred to as the compound of formula (I).

[0006] [Chemical formula]

[0007] Processes for preparing hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate are known, for example, from DE 10011317, EP2155660, and WO 2003097578. In this context, several problems have been found.

[0008] During the synthesis, the by-product dihexyl phthalate (PSDHE, also known as dihexyl phthalate) is formed. Even in the final product, it may contain 50 to 150 ppm or less of PSDHE. Recent findings suggest that the PSDHE content should be minimized as much as possible because, according to harmonized classification and labeling (ATP05), this substance may impair fertility and may also damage the fetus.

[0009] Furthermore, during the synthesis of hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate, rhodamine B-type dyes (e.g., [9-(2-carboxyphenyl)-6-diethylamino-3-xanthenylidene]-diethylammonium salt) and the corresponding esters are formed as impurities, which cause undesirable discoloration of the final product. In order to purify the final product (with less than 10 ppm of rhodamine B-type dyes), further purification steps are required. Conventional purification steps include dissolution of the contaminated hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate in a nonpolar solvent such as cyclohexane or toluene, adsorption on activated carbon or a silica bed, and evaporation of the solvent after passing through the bed.

[0010] Subsequently, after separating and removing toluene and / or 1-hexanol by distillation to isolate hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate, the clear final product is bottled as a melt. However, the resulting product still contains a phthalic acid dialkyl ester content in an amount of 15 ppm or more.

Prior Art Documents

Patent Documents

[0011]

Patent Document 1

Patent Document 2

Patent Document 3

Summary of the Invention

Problems to be Solved by the Invention

[0012] Therefore, there is currently a need for a rapid and efficient purification method for hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate. In this regard, the present invention aims to provide an optimized method for isolating hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate. In particular, it aims to provide a method for purifying hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate with a reduced amount of dihexyl phthalate. Finally, the present invention aims to provide a rapid method for purifying hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate, which further provides a final product that is safe and convenient to handle.

[0013] Surprisingly, it has been found that at least one of the above objects can be achieved by the method according to the present invention. By the method of the present invention, hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate with a low PSDHE content (less than 20 ppm) can be obtained.

[0014] In particular, the inventors of the present invention have found a method for effectively purifying the compound of formula (I).

Means for Solving the Problems

[0015] Therefore, the present invention provides a) a step of subjecting crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate to distillation at a temperature in the range of 100 to 250 °C and a pressure of less than 10 mbar, b) a step of isolating hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate as a high boiler and relates to a method for purifying hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate.

[0016] Hereinafter, the preferred embodiments of the method will be described in more detail. It will be understood that each preferred embodiment is applicable not only as it is, but also in combination with other preferred embodiments.

[0017] In preferred embodiment A1, the crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate in step a) contains 15 to 1000 ppm of dihexyl phthalate.

[0018] In preferred embodiment A2, during step a), dihexyl phthalate is removed from the crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate as a low-boiling substance.

[0019] In preferred embodiment A3, during step a), distillation is carried out at a temperature in the range of 160 to 220 °C, preferably in the range of 190 to 210 °C.

[0020] In preferred embodiment A4, during step a), distillation is carried out at a pressure of 0.01 to 10 mbar, preferably 0.05 to 5 mbar.

[0021] In preferred embodiment A5, during step a), distillation is carried out at a temperature in the range of 120 to 180 °C, preferably in the range of 130 to 170 °C.

[0022] In preferred embodiment A6, during step a), distillation is carried out at a pressure of 0.0001 to 0.03 mbar, preferably 0.001 to 0.007 mbar.

[0023] In preferred embodiment A7, the method comprises c) a step of collecting a low-boiling substance fraction, d) a step of subjecting the low-boiling substance fraction collected from step c) to distillation at a temperature in the range of 100 to 250 °C and a pressure of less than 10 mbar, e) a step of isolating hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate as a further fraction of high-boiling substances further comprises.

[0024] In a preferred embodiment A8, the light-boiling substance fraction collected from step c) contains dihexyl phthalate in an amount of 50 to 1000 ppm in step d).

[0025] In a preferred embodiment A9, the hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate isolated in step b) contains less than 20 ppm, preferably less than 15 ppm, more preferably less than 13 ppm of dihexyl phthalate.

[0026] In a preferred embodiment A10, the hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate isolated in step b) has a Gardner value of 9.5 or less.

[0027] In a preferred embodiment A11, the hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate isolated in step b) is obtained in a yield of at least 60%, preferably at least 80%, more preferably at least 90%, even more preferably at least 99%.

[0028] In a preferred embodiment A12, the method is carried out as a continuous process involving a continuous supply of crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate and a continuous removal of high-boiling and light-boiling substances.

[0029] In a preferred embodiment A13, during step a), the distillation is carried out at a temperature in the range of above 180 to 220 °C and a pressure of 0.01 to 10 mbar, or during step a), the distillation is carried out at a temperature in the range of 120 to 180 °C and a pressure of 0.0001 to 0.03 mbar. BRIEF DESCRIPTION OF THE DRAWINGS

[0030]

Figure 1

Figure 2

Embodiments for Carrying Out the Invention

[0031] Before describing exemplary embodiments of the present invention in detail, important definitions are given to understand the present invention.

[0032] As used in this specification and the appended claims, the singular forms "a" and "an" include the respective plural forms as well, unless the context clearly dictates otherwise. In the context of the present invention, the terms "about" and "approximately" represent the interval of accuracy that a person skilled in the art understands to ensure the technical effects of the relevant features. This term typically represents a deviation of ±20%, preferably ±15%, more preferably ±10%, and even more preferably ±5% from the indicated numerical value. It should be understood that the term "comprising" is not limiting. For the purposes of the present invention, the term "consisting of" is considered a preferred embodiment of the term "comprising". When a group is defined below as including at least a certain number of embodiments, this means that it preferably also includes a group consisting of only those embodiments. Further, in this specification and the claims, the terms "first", "second", "third", or "(a)", "(b)", "(c)", "(d)", etc. are used to distinguish between similar elements and do not necessarily describe an order in terms of arrangement or time. It should be understood that these terms, as used in this way, are interchangeable under appropriate circumstances and that the embodiments of the present invention described herein can operate in an order different from that described or illustrated herein. When terms such as "first", "second", "third", or "(a)", "(b)", "(c)", "(d)", "i", "ii", etc. relate to steps of a method or use or assay, there is no consistency in time or time interval between the steps, that is, unless otherwise indicated in the applicable examples described above or below in this specification, each step may be performed simultaneously, and there may be a time interval of seconds, minutes, hours, days, weeks, months, or years between such steps. It should be understood that the present invention is not limited to the specific methodologies, protocols, reagents, etc. that may be modified in this specification. The terminology used in this specification is for the purpose of describing only specific embodiments and is not intended to limit the scope of the present invention, and it should also be understood that the scope of the present invention is limited only by the appended claims. Unless otherwise defined, all scientific and technical terms used in this specification have the same meaning as commonly understood by a person skilled in the art.

[0033] The term "compound according to the present invention" or "compound of formula (I)" refers to hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate.

[0034] The term "alkyl", as used herein, in each case, usually represents a straight-chain or branched alkyl group having 1 to 20 carbon atoms, preferably 2 to 18 carbon atoms, more preferably 4 to 12 carbon atoms. Examples of alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, 2-butyl, isobutyl, tert-butyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, and n-dodecyl. Isobutyl and n-hexyl, particularly n-hexyl, are preferred.

[0035] The term "(Cn-Cm-alkyl)", as used herein, in each case represents a linker moiety, and the moiety attached thereto is attached to the terminal carbon.

[0036] The term "body care product" refers to any product suitable for application to the human body, such as sunscreen compositions, bath and shower products, preparations containing fragrances and aromatic substances, hair care products, toothpastes, decorative preparations, and cosmetic formulations containing active ingredients. Sunscreen compositions are preferred.

[0037] The term "sunblock composition" or "sunblock" or "skin care product" refers to any topically administered product that reflects and / or absorbs certain portions of UV radiation. Thus, the term "sunblock composition" will be understood to include not only sunblock compositions but also any cosmetic composition that provides UV protection. The term "topically administered product" refers to a product that is applied to the skin and can refer to, for example, a spray, lotion, cream, oil, foam, powder, or gel. According to the present invention, a sunblock composition may contain one or more active agents, such as organic UV filters, in addition to other raw materials or additives, such as emulsifiers, emollients, viscosity modifiers, stabilizers, preservatives, or fragrances.

[0038] The term "daily care composition" refers to any topically administered product that reflects or absorbs certain portions of UV radiation and is used as a product for daily care of the human body, such as the face, body, or hair. A daily care composition may contain one or more active agents, such as organic or inorganic UV filters, in addition to other raw materials or additives, such as emulsifiers, emollients, viscosity modifiers, stabilizers, preservatives, or fragrances.

[0039] Suitable additives for bathing and showering are, for example, shower gels, bath salts, bath foaming agents, and soaps.

[0040] Suitable preparations containing fragrances and aromatic substances are, in particular, perfumed substances, perfumes, lotions, and shaving lotions (aftershave preparations).

[0041] Suitable hair care products are, for example, shampoos, hair conditioners, products for styling and treating hair for humans and animals, especially dogs, perming agents, hair sprays and lacquers, hair gels, hair fixatives, and hair coloring or bleaching agents.

[0042] Suitable dentifrices are, for example, toothpaste, toothpaste, mouthwash, mouth rinse, anti-tartar preparations, and denture cleaners.

[0043] Suitable decorative preparations are, for example, lipsticks, manicures, eyeshadows, mascaras, dry and moist make-ups, rouges, powders, depilatory agents, and sun-tanning lotions.

[0044] Suitable cosmetic formulations containing the active ingredient are, for example, hormonal preparations, vitamin preparations, vegetable extract preparations, and antibacterial preparations.

[0045] The body care products mentioned can be in the form of creams, ointments, pastes, foams, gels, lotions, powders, make-ups, sprays, sticks, or aerosols. These preferably contain the compound of formula (I) in the aqueous phase. Thereby, the compound of formula (I) can act as a light stabilizer.

[0046] The term "light stability" refers to the ability to remain stable against irradiation by a UV filter or any other arbitrary molecule exposed to sunlight. In particular, this term means that the compound does not follow a decomposition process when irradiated with UV.

[0047] The term "critical wavelength" is defined as the wavelength at which the area under the UV protection curve (% protection against wavelength) represents 90% of the total area under the curve in the UV region (280 - 400 nm). For example, a critical wavelength of 370 nm means that the protection by the sunblock composition is not limited to the wavelengths of UV-B, i.e., wavelengths of 280 - 320 nm, but extends up to 370 nm in such a way that 90% of the total area under the protection curve in the UV region reaches 370 nm.

[0048] The term "ultraviolet filter" or "UV filter", as used herein, refers to an organic or inorganic compound that can absorb and / or reflect UV radiation caused by sunlight. UV filters can be classified into UV-A filters, UV-B filters, or broadband filters based on their UV protection curves. In the context of this application, broadband filters also provide UV-A protection and may be listed as UV-A filters. In other words, preferred UV-A filters include broadband filters.

[0049] The definition of "broadband" protection (also referred to as broad-spectrum or wide-band protection) is based on the "critical wavelength". To cover the broadband, both UV-B and UV-A protection must be obtained. According to the requirements in the United States, a critical wavelength of at least 370 nm is required to achieve broad-spectrum protection. Furthermore, the European Commission recommends that all sunscreen or cosmetic compositions must have a UVA protection index of at least one-third of the indicated sun protection factor (SPF). For example, if a sunscreen composition has an SPF of 30, the UVA protection index must be at least 10.

[0050] Preferred embodiments of the method according to the present invention will be described below. It will be understood that the preferred embodiments of the present invention are preferred either alone or in combination with each other.

[0051] As indicated above, in one embodiment, the present invention a) a step of subjecting crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate to distillation at a temperature in the range of 100 to 250 °C and a pressure of less than 10 mbar; b) a step of isolating hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate as a high-boiling substance and relates to a method for purifying hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate.

[0052] Preferred embodiments of the present method are defined below.

[0053] In one embodiment of the present invention, the crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate in step a) contains dialkyl phthalate, particularly dihexyl phthalate, as an impurity.

[0054] Preferably, the crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate in step a) contains 15 to 1000 ppm, preferably 30 to 500 ppm, more preferably 40 to 450 ppm, and even more preferably 50 to 400 ppm of dialkyl phthalate.

[0055] In this connection, according to the present invention, the dialkyl phthalate has the formula (A) [Chemical formula] [wherein, R 1 and R 2 are C4-C 12 -alkyl, preferably, both R 1 and R 2 are n-hexyl.] It will be understood that it is defined by having

[0056] The dialkyl phthalate is preferably removed from the crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate as a low-boiling substance during step a).

[0057] In this connection, it should be noted that the removal of the dialkyl phthalate refers to separating the dialkyl phthalate, which is an impurity, from the crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate. The separated dialkyl phthalate may be collected or discarded.

[0058] The method according to the present invention provides a light-boiling substance fraction. This light-boiling substance fraction contains light-boiling substances (i.e., dialkyl phthalate esters, especially dihexyl phthalate). The light-boiling substance fraction may further contain additional impurities, such as colored impurities or solvents.

[0059] In a preferred embodiment of the present invention, the crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate in step a) contains 15 to 1000 ppm, preferably 20 to 800 ppm, more preferably 30 to 600 ppm, even more preferably 35 to 500 ppm, particularly preferably 40 to 400 ppm, especially 40 to 300 ppm of dihexyl phthalate.

[0060] In this connection, preferably, dihexyl phthalate is removed from the crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate as a light-boiling substance during step a).

[0061] In one embodiment of the present invention, during step a), the distillation is carried out at a temperature in the range of 160 to 220 °C, preferably in the range of 180 to 215 °C, more preferably in the range of 190 to 210 °C, even more preferably in the range of 200 to 210 °C.

[0062] In one embodiment of the present invention, during step a), the distillation is carried out at a pressure of 0.01 to 10 mbar, preferably 0.02 to 8 mbar, more preferably 0.03 to 5 mbar, even more preferably 0.04 to 3 mbar, especially 0.05 to 2 mbar.

[0063] In another embodiment of the present invention, during step a), the distillation is carried out at a pressure of greater than 0.01 and less than 10 mbar, preferably greater than 0.02 and less than 8 mbar, more preferably greater than 0.03 and less than 5 mbar, even more preferably greater than 0.04 and less than 3 mbar, especially greater than 0.05 and less than 2 mbar.

[0064] In another embodiment of the present invention, during step a), the distillation is carried out at a temperature in the range of 120 to 180 °C, preferably in the range of 130 to 170 °C, more preferably in the range of 135 to 150 °C, particularly in the range of 140 to 150 °C.

[0065] In connection with this, during step a), it is preferred that the distillation is carried out at a pressure of 0.0001 to 0.03 mbar, preferably 0.001 to 0.01, more preferably 0.001 to 0.007 mbar.

[0066] In a preferred embodiment of the present invention, during step a), the distillation is carried out at a temperature in the range of above 180 to 220 °C, preferably in the range of 185 to 215 °C, more preferably in the range of 190 to 210 °C, even more preferably in the range of 200 to 210 °C, and at a pressure of 0.01 to 10 mbar, preferably 0.02 to 8 mbar, more preferably 0.03 to 5 mbar, even more preferably 0.04 to 3 mbar, particularly 0.05 to 2 mbar, or during step a), the distillation is carried out at a temperature in the range of 120 to 180 °C, preferably in the range of 130 to 170 °C, more preferably in the range of 135 to 150 °C, particularly in the range of 140 to 150 °C, and at a pressure of 0.0001 to 0.03 mbar, preferably 0.001 to 0.01, more preferably 0.001 to 0.007 mbar.

[0067] In one embodiment of the present invention, the method comprises c) a step of collecting a light-boiling fraction, d) a step of subjecting the light-boiling fraction collected from step c) to distillation at a temperature in the range of 100 to 250 °C and at a pressure of less than 10 mbar, and e) a step of isolating 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester as a further fraction of high-boiling substances and further comprises.

[0068] When hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate is partially distilled off and contained in the light-boiling fraction, steps c) to e) make it possible to recover hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate from the collected light-boiling fraction.

[0069] In one embodiment, the method comprises c) collecting a light-boiling substance fraction, d) subjecting the light-boiling substance fraction collected in step c) to distillation at a temperature in the range of 160 to 220 °C, preferably in the range of 190 to 210 °C, and at a pressure of less than 10 mbar, preferably less than 5 mbar, particularly less than 0.1 mbar, and e) isolating hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate as a further fraction of high-boiling substances and further comprises.

[0070] In one embodiment of the invention, the light-boiling substance fraction collected in step c) contains 50 to 1000 ppm of a dialkyl phthalate, in particular dihexyl phthalate, in step d).

[0071] According to the invention, any suitable evaporator may be used.

[0072] In one embodiment of the invention, a thin-film evaporator is used. It is also sometimes called a wiped-film evaporator or a short-path evaporator.

[0073] A short-path evaporator provides a continuous distillation process, a very low operating pressure, a short residence time, a high evaporation rate, low adhesion to the evaporator wall, and / or a compact design.

[0074] In one embodiment of the present invention, the hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate isolated in step b) contains less than 20 ppm, preferably less than 15 ppm, more preferably less than 13 ppm, even more preferably less than 10 ppm, and particularly less than 5 ppm of dialkyl phthalate. Preferably, the hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate isolated in step b) contains less than 20 ppm, preferably less than 15 ppm, more preferably less than 13 ppm, even more preferably less than 10 ppm, and particularly less than 5 ppm of dihexyl phthalate.

[0075] In a specific embodiment of the present invention, the hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate isolated in step b) is free of dialkyl phthalate, and particularly free of dihexyl phthalate.

[0076] In one embodiment of the present invention, the crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate in step a) has a Gardner value of 8.2 or more.

[0077] In one embodiment of the present invention, the hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate isolated in step b) has a Gardner value of 9.5 or less, preferably 9 or less, more preferably 8.5 or less, even more preferably 8.2 or less, particularly preferably 8.0, and especially 7.5 or less.

[0078] In one embodiment of the present invention, the hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate isolated in step b) contains less than 20 ppm, preferably less than 15 ppm, more preferably less than 13 ppm, even more preferably less than 10 ppm, and particularly less than 5 ppm of dialkyl phthalate, and has a Gardner value of 9.5 or less, preferably 9 or less, more preferably 8.5 or less, even more preferably 8.2 or less, particularly preferably 8.0, and especially 7.5 or less.

[0079] In a preferred embodiment of the present invention, the hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate isolated in step b) contains less than 20 ppm, preferably less than 15 ppm, more preferably less than 13 ppm, even more preferably less than 10 ppm, and particularly less than 5 ppm of dihexyl phthalate, and has a Gardner value of 9.5 or less, preferably 9 or less, more preferably 8.5 or less, even more preferably 8.2 or less, particularly preferably 8.0, and especially 7.5 or less.

[0080] In one embodiment of the present invention, the hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate isolated in step b) is obtained in a yield of at least 60%, preferably at least 80%, more preferably at least 90%, and even more preferably at least 99%.

[0081] In one embodiment of the present invention, the hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate isolated in step b) is obtained in a yield of at least 90%, preferably at least 95%, more preferably at least 99%, contains less than 20 ppm, preferably less than 15 ppm, more preferably less than 13 ppm, even more preferably less than 10 ppm, and particularly less than 5 ppm of dihexyl phthalate, and has a Gardner value of 9.5 or less, preferably 9 or less.

[0082] In one embodiment of the present invention, the hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate isolated in step b) is obtained in a yield of at least 60%, preferably at least 65%, more preferably at least 70%, contains less than 20 ppm, preferably less than 15 ppm, more preferably less than 13 ppm, even more preferably less than 10 ppm, and particularly less than 5 ppm of dihexyl phthalate, and has a Gardner value of 9 or less, preferably 8.2 or less, more preferably 8.0 or less, and especially 7.5 or less.

[0083] In one embodiment of the present invention, the method is carried out as a continuous process involving a continuous supply of at least 50 g, preferably at least 80 g, per hour of crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate, and a continuous removal of high-boiling and low-boiling substances.

[0084] In one embodiment, the present invention relates to a body care product or a daily care composition comprising hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate obtained according to the claimed method. In particular, the present invention relates to a sunscreen composition comprising hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate obtained according to the claimed method.

[0085] In one embodiment, the present invention relates to the use of hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate obtained according to the claimed method as a UV filter in a body care product or a daily care composition, particularly in a sunscreen composition.

[0086] The present invention will be further illustrated by the following examples.

Examples

[0087] Method The HPLC method for the determination of hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate, phthalic acid esters, and rhodamine-type coloring compounds was carried out by standard state-of-the-art methods.

[0088] The PSDHE content of Examples 11, 14A, and 14B was measured by HPLC analysis using UPLC Agilent 1290 Infinity.

[0089] The PSDHE content of Examples 1 to 10, 12, 13, and 15 was measured by GC analysis using Agilent 6890.

[0090] The Gardner value was determined by the standard state-of-the-art method using a spectrophotometer LICO 500 from Hach Lange, heating the sample to 75 °C and cooling it at room temperature for 5 - 7 minutes.

[0091] Analytical reference materials for calibration have already been prepared by the standard state-of-the-art method.

[0092] For Examples 1 - 14B, crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate was obtained according to Example 3 of EP 1 506 159, except that the product was not taken out as a melt and was further processed as outlined below.

[0093] In Examples 1 - 3 and Comparative Example 8 of the present invention, crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate having a PSDHE content of 78 ppm and a Gardner value of 7.5 was supplied.

[0094] In Examples 4 - 7 of the present invention, crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate having a PSDHE content of 68 ppm and a Gardner value of 7.5 was supplied.

[0095] In Examples 9 - 14B of the present invention, crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate having a PSDHE content of 82 ppm and a Gardner value of 7.5 was supplied.

[0096] Examples 1 - 7 of the present invention were carried out in a wiped film evaporator (Sambay type, evaporation surface area 920 cm 2 )

[0097] Crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate (crude UVA+) was fed to a thin film evaporator and purified under the conditions based on Table 1. The analysis results are summarized in Table 2.

[0098] For Comparative Example 8, steam stripping was used.

[0099]

Table 1

[0100]

Table 2

[0101] Examples 9 to 15 of the present invention were carried out using a short-path evaporator (wiped film evaporator, KDL-5 from UIC).

[0102] Crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate was fed to a short-path evaporator and purified under the conditions based on Table 3. The analysis results are summarized in Table 4.

[0103] The light-boiling fractions of Examples 14A and 14B of the present invention were collected and combined. The combined light-boiling fraction was subjected to the purification method again (Example 15 of the present invention).

[0104] In Example 15 of the present invention, crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate having a PSDHE content of 482 ppm and a Gardner of 6.9 was supplied, respectively.

[0105]

Table 3

[0106]

Table 4

[0107] As can be seen from Tables 1 to 4, all examples of the present invention provided a reduction in the PSDHE content in the final hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate. Furthermore, all examples of the present invention provided an improved reduction in the PSDHE content in the final hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate when compared to Comparative Example 8.

Claims

1. a) a step of subjecting crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate to distillation at a temperature in the range of 100 to 250 °C and a pressure of less than 10 mbar; b) a step of isolating hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate as a high-boiling substance A method for purifying hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate, comprising the steps.

2. The method according to claim 1, wherein the crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate in step a) contains 15 to 1000 ppm of dihexyl phthalate.

3. The method according to claim 1 or 2, wherein in step a), dihexyl phthalate is removed from the crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate as a low-boiling substance.

4. The method according to any one of claims 1 to 3, wherein in step a), the distillation is carried out at a temperature in the range of 160 to 220 °C.

5. The method according to any one of claims 1 to 4, wherein in step a), the distillation is carried out at a pressure of 0.01 to 10 mbar.

6. The method according to any one of claims 1 to 3, wherein in step a), the distillation is carried out at a temperature in the range of 120 to 180 °C.

7. The method according to any one of claims 1 to 3 or 6, wherein in step a), the distillation is carried out at a pressure of 0.0001 to 0.03 mbar.

8. In step a), the distillation is carried out at a temperature in the range of above 180 to 220 °C and a pressure of 0.01 to 10 mbar, or In step a), the distillation is carried out at a temperature in the range of 120 to 180 °C and a pressure of 0.0001 to 0.03 mbar. The method according to any one of claims 1 to 3.

9. c) a step of collecting a low-boiling substance fraction containing hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate partially distilled off in step a); d) a step of subjecting the low-boiling substance fraction collected in step c) to distillation at a temperature in the range of 100 to 250 °C and a pressure of less than 10 mbar; and e) a step of isolating hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate as a further fraction of a high-boiling substance The method according to any one of claims 1 to 3 or 6 to 8, further comprising the steps.

10. The method according to any one of claims 1 to 3 or 6 to 9, wherein the low-boiling substance fraction collected from step c) contains 50 to 1000 ppm of dihexyl phthalate in step d).

11. The method according to any one of claims 1 to 10, wherein the hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate isolated in step b) contains less than 20 ppm of dihexyl phthalate.

12. The method according to any one of claims 1 to 11, wherein the hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate isolated in step b) has a Gardner value of 9.5 or less.

13. The method according to any one of claims 1 to 12, wherein the hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate isolated in step b) is obtained in a yield of at least 60%.

14. The method according to any one of claims 1 to 13, which is carried out as a continuous process involving the continuous supply of crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate and the continuous removal of high-boiling and low-boiling substances.

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