Purification method of 2-(4'-diethylamino-2'-hydroxybenzoyl) benzoic acid hexyl ester

Abstract

The present invention relates to a method for purifying 2-(4'-diethylamino-2'-hydroxybenzoyl) hexyl benzoate to provide high purity and low dialkyl phthalate content.

Description

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

[0002] UV radiation causes harmful effects on human skin. In addition to the acute effects of sunburn, UV radiation is also known to increase the risk of skin cancer. In addition, prolonged exposure to UV-A and UV-B light can cause phototoxic and photoallergic reactions in the skin and accelerate skin aging.

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

[0004] Since 2006, the European Commission has recommended that all sunscreens or cosmetic compositions should have a UV-A protection factor of at least one third of the labelled Sun Protection Factor (SPF), where the SPF refers primarily to UV-B protection.

[0005] 2-(4'-Diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester is an effective UV-A filter used to protect the skin from the effects of UV radiation (e.g. sunscreen). 2-(4'-Diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester is shown below and is also referred to below as the compound of formula (I).

[0006]

[0007] Processes for the preparation of hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate are known, for example, from DE 10011317, EP 2155660 and WO 2003097578. In this regard, some challenges are observed.

[0008] During the synthesis, dihexyl phthalate (also called PSDHE, 1,2-dihexyl phthalate) is formed as a byproduct. The final product may still contain up to 50-150 ppm of PSDHE. According to recent findings, the PSDHE content should be as low as possible, because according to the harmonised classification and labelling (ATP05), this substance can impair fertility and possibly harm the unborn child.

[0009] In addition, during the synthesis of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester, rhodamine B dyes (e.g. [9-(2-carboxyphenyl)-6-diethylamino-3-xanthenyl]-diethylammonium salt) and corresponding esters are formed as impurities, which can lead to undesirable discoloration of the final product. In order to purify the final product (less than 10 ppm rhodamine B dye), additional purification steps are required. So far, the purification steps have included dissolving the contaminated 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester in a non-polar solvent (e.g. cyclohexane or toluene), adsorbing on an activated carbon or silicic acid bed, and evaporating the solvent after the solvent has passed through the bed.

[0010] After separation of toluene and / or 1-hexanol by distillation and subsequent separation of 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester, the clean end product is bottled as a melt. However, the resulting product still contains dialkyl phthalates in contents of 15 ppm and higher.

[0011] Therefore, there is a continuous need to purify 2-(4'-diethylamino-2'-hydroxybenzoyl) hexyl benzoate quickly and effectively. In this regard, the object of the present invention is to provide an optimized method for separating 2-(4'-diethylamino-2'-hydroxybenzoyl) hexyl benzoate. In particular, the object is to provide a method for purifying 2-(4'-diethylamino-2'-hydroxybenzoyl) hexyl benzoate, wherein the amount of dihexyl phthalate is reduced. Finally, the object of the present invention is to provide a method for rapidly purifying 2-(4'-diethylamino-2'-hydroxybenzoyl) hexyl benzoate, which further provides a safe and convenient final product treatment.

[0012] Surprisingly it has been found that at least one of the above objects can be achieved by the process of the present invention.The process of the present invention provides hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate having a low PSDHE content (less than 20 ppm).

[0013] In particular, the inventors of the present invention have found a method for effectively purifying the compound of formula (I).

[0014] Therefore, the present invention relates to a method for purifying 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester, which comprises the steps of:

[0015] a) distilling crude 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester at a temperature of 100-250° C. and a pressure of less than 10 mbar;

[0016] b) Hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate is separated as a high boiler.

[0017] Preferred embodiments of the method are described in further detail below. It should be understood that each preferred embodiment is relevant both by itself and in combination with other preferred embodiments.

[0018] In a preferred embodiment A1, the crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate in step a) contains from 15 to 1000 ppm of dihexyl phthalate.

[0019] In a preferred embodiment A2, dihexyl phthalate is removed as light boiler from crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate in step a).

[0020] In a preferred embodiment A3, the distillation in step a) is carried out at a temperature of 160-220°C, preferably 190-210°C.

[0021] In a preferred embodiment A4, the distillation in step a) is carried out at a pressure of 0.01 to 10 mbar, preferably 0.05 to 5 mbar.

[0022] In a preferred embodiment A5, the distillation in step a) is carried out at a temperature of 120-180°C, preferably 130-170°C.

[0023] In a preferred embodiment A6, the distillation in step a) is carried out at a pressure of 0.0001 to 0.03 mbar, preferably 0.001 to 0.007 mbar.

[0024] In preferred embodiment A7, the method further comprises the steps of:

[0025] c) collecting light boiling fractions;

[0026] d) distilling the light boiling fraction collected from step c) at a temperature of 100-250° C. and a pressure of less than 10 mbar; and

[0027] e) Hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate is separated as a further fraction of high boilers.

[0028] In a preferred embodiment A8, in step d), the light-boiling fraction collected from step c) contains 50 to 1000 ppm of dihexyl phthalate.

[0029] In a preferred embodiment A9, the hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate separated in step b) contains less than 20 ppm, preferably less than 15 ppm, more preferably less than 13 ppm of dihexyl phthalate.

[0030] In a preferred embodiment A10, the 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester isolated in step b) has a Gardner value of 9.5 or less.

[0031] In preferred embodiment A11, the 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester 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%.

[0032] In a preferred embodiment A12, the process is carried out as a continuous process, wherein crude 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester is fed continuously and high boilers and light boilers are removed continuously.

[0033] In a preferred embodiment A13, the distillation in step a) is carried out at a temperature of 180-220° C. and a pressure of 0.01-10 mbar, or

[0034] The distillation in step a) is carried out at a temperature of 120-180° C. and a pressure of 0.0001-0.03 mbar.

[0035] Attached photos

[0036] Figure 1 A thin film evaporator-based process is schematically depicted, comprising (1) waste gas, (2) scrubber, (3) cooling trap, and (4) staged feed.

[0037] Figure 2 A short path evaporator is schematically depicted, including (1) exhaust, (2) 2L feed, (3) trough, (4) header, (5) cooling trap, (6) vent, (7) rotary vane pump, and (8) oil diffusion pump.

[0038] Detailed Description

[0039] Before describing exemplary embodiments of the present invention in detail, definitions important for understanding the present invention are given.

[0040] The singular forms "one" and "a" used in this specification and the appended claims also include the respective plural forms, unless the context clearly dictates otherwise. In the context of the present invention, the terms "about" and "approximately" represent the precision intervals understood by those skilled in the art that still ensure the technical effects of the features. The term generally indicates a deviation of ±20%, preferably ±15%, more preferably ±10%, and even more preferably ±5% from the numerical values ​​shown. It should be understood that the term "comprising" is not restrictive. For the purposes of the present invention, the term "consisting of..." is considered as a preferred embodiment of the term "comprising". If a group is defined below as comprising at least a certain number of embodiments, this means that a group preferably consisting only of these embodiments is also included. In addition, the terms "first", "second", "third" or "(a)", "(b)", "(c)", "(d)" and the like in the specification and claims are used to distinguish similar elements, and are not necessarily used to describe order or time sequence. It should be understood that the terms used in this way are interchangeable where appropriate, and the embodiments of the present invention described herein can be operated in other orders than the order described or illustrated herein. If the terms "first", "second", "third" or "(a)", "(b)", "(c)", "(d)", "i", "ii", etc. refer to steps of a method or use or an analytical method, there is no temporal or temporal coherence between the steps, i.e., the steps may be performed simultaneously or there may be a time interval of seconds, minutes, hours, days, weeks, months or even years between such steps, unless otherwise indicated in the present application described above or below. It should be understood that the present invention is not limited to the specific methods, protocols, reagents, etc. described herein, as these may vary. It should also be understood that the terminology used herein is only used to describe specific embodiments and is not intended to limit the scope of the invention, which is limited only by the appended claims. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art.

[0041] The term "compound of the present invention" or "compound of formula (I)" refers to 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester.

[0042] The term "alkyl" as used herein denotes in each case a straight-chain or branched alkyl radical having generally 1 to 20 carbon atoms, preferably 2 to 18 carbon atoms, more preferably 4 to 12 carbon atoms. Examples of alkyl radicals are 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. Preference is given to isobutyl and n-hexyl, in particular n-hexyl.

[0043] As used herein, the term “ n -C m "alkyl)" in each case denotes a linker moiety, wherein the linker moiety is attached to the terminal carbon.

[0044] The term "body care product" refers to any product which is applied to the human body, for example sunscreen compositions, bath and shower products, preparations containing perfumes and odoriferous substances, hair care products, toothpastes, decorative preparations and cosmetic formulations containing active ingredients. Sunscreen compositions are preferred.

[0045] The term "sunscreen composition" or "sunscreen" or "skin care product" refers to any topical product that is capable of reflecting and / or absorbing a certain portion of UV radiation. Therefore, the term "sunscreen composition" is to be understood as including not only sunscreen compositions, but also any cosmetic composition that provides UV protection. The term "topical product" refers to a product that is applied to the skin and may refer to, for example, a spray, a lotion, a cream, an oil, a foam, a powder or a gel. According to the present invention, a sunscreen composition may comprise one or more active agents, such as organic UV filters, and other ingredients or additives, such as emulsifiers, emollients, viscosity regulators, stabilizers, preservatives or fragrances.

[0046] The term "daily care composition" refers to any product that is capable of reflecting or absorbing a certain portion of UV radiation and is used as a daily care product for the human body, such as a topical product for the face, body or hair. Daily care compositions may contain one or more active agents, such as organic or inorganic UV filters, and other ingredients or additives, such as emulsifiers, emollients, viscosity regulators, stabilizers, preservatives or fragrances.

[0047] Suitable bath and shower additives are, for example, shower gels, bath salts, bubble baths and soaps.

[0048] Suitable preparations containing fragrance and odor substances are, in particular, perfumes, toilet waters and shaving lotions (aftershave preparations).

[0049] Suitable hair care products are, for example, human and animal shampoos, in particular dog shampoos, hair conditioners, hair styling and treatment products, hair permanent wave preparations, hair sprays and lacquers, hair gels, hair fixatives and hair dyes or bleaches.

[0050] Suitable dentifrices are, for example, tooth creams, toothpastes, mouthwashes, mouth rinses, antiplaque preparations and denture cleansers.

[0051] Suitable decorative preparations are, for example, lipsticks, nail varnishes, eye shadows, mascaras, dry and wet make-up, rouge, powders, depilatories and suntan lotions.

[0052] Suitable cosmetic formulations containing active ingredients are, for example, hormone preparations, vitamin preparations, plant extract preparations and antibacterial preparations.

[0053] The body care products may be in the form of creams, ointments, pastes, foams, gels, lotions, powders, cosmetics, sprays, sticks or aerosols. They preferably contain the compound of formula (I) in the aqueous phase. Therefore, the compound of formula (I) can act as a light stabilizer.

[0054] The term "photostability" refers to the ability of a UV filter or any other molecule exposed to sunlight to remain stable upon irradiation. In particular, this means that the compound does not undergo degradation processes under UV radiation.

[0055] The term "critical wavelength" is defined as the wavelength at which the area under the UV protection curve (% protection vs. wavelength) accounts for 90% of the total area in the UV region of the curve (280-400 nm). For example, a critical wavelength of 370 nm indicates that the protection of the sunscreen composition is not limited to wavelengths of UV-B, i.e. wavelengths of 280-320 nm, but extends to 370 nm in such a way that 90% of the total area of ​​the protection curve in the UV region is reached at 370 nm.

[0056] As used herein, the term "ultraviolet filter" or "UV filter" refers to an organic or inorganic compound that absorbs and / or reflects UV radiation caused by sunlight. Based on their UV protection curve, UV filters can be divided into UV-A, UV-B or broadband filters. In the context of this application, broadband filters can be listed as UV-A filters, because they also provide UV-A protection. In other words, preferred UV-A filters also include broadband filters.

[0057] The definition of "broadband" protection (also called broad spectrum or wide protection) is based on the "critical wavelength". For broadband coverage, both UV-B and UV-A protection must be provided. According to the US requirements, a critical wavelength of at least 370nm is required to achieve broad spectrum protection. In addition, the European Commission recommends that all sunscreens or cosmetic compositions should have a UVA protection factor of at least one third of the label sun protection factor (SPF), e.g. if the sunscreen composition has an SPF of 30, the UVA protection factor must be at least 10.

[0058] Preferred embodiments of the method of the present invention are described below. It should be understood that the preferred embodiments of the present invention are preferred individually or in combination with each other.

[0059] As described above, the present invention relates in one embodiment to a method for purifying 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester, comprising the steps of:

[0060] a) distilling crude 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester at a temperature of 100-250° C. and a pressure of less than 10 mbar;

[0061] b) Isolation of hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate as high boiler.

[0062] Preferred embodiments of the method are defined below.

[0063] In one embodiment of the present invention, the crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate in step a) contains dialkyl phthalates, in particular dihexyl phthalate, as an impurity.

[0064] Preferably, the crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate in step a) contains 15-1000 ppm, preferably 30-500 ppm, more preferably 40-450 ppm, even more preferably 50-400 ppm of dialkyl phthalate.

[0065] In this regard, it is to be understood that, according to the present invention, dialkyl phthalates are defined as having formula (A):

[0066]

[0067] Where R 1 and R 2 C4-C 12 Alkyl, preferably, wherein R 1 With R 2 All are n-hexyl.

[0068] Preferably, in step a), dialkyl phthalates are removed as light boilers from crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate.

[0069] In this regard, it should be noted that removing dialkyl phthalate refers to separating the impurity dialkyl phthalate from crude 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester. The separated dialkyl phthalate can be collected or discarded.

[0070] The method of the present invention provides a light boiling fraction. The light boiling fraction contains light boiling substances (i.e. dialkyl phthalate, especially dihexyl phthalate). The light boiling fraction may further contain other impurities, such as colored impurities or solvents.

[0071] In a preferred embodiment of the present invention, the crude 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester 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, especially preferably 40 to 400 ppm, in particular 40 to 300 ppm of dihexyl phthalate.

[0072] In this context, preference is given to removing dihexyl phthalate as light boiler from crude hexyl 2-(4′-diethylamino-2′-hydroxybenzoyl)benzoate in step a).

[0073] In one embodiment of the present invention, the distillation in step a) is carried out at a temperature of 160-220°C, preferably 180-215°C, more preferably 190-210°C, even more preferably 200-210°C.

[0074] In one embodiment of the present invention, the distillation in step a) is carried out at a pressure of 0.01-10 mbar, preferably 0.02-8 mbar, more preferably 0.03-5 mbar, even more preferably 0.04-3 mbar, in particular 0.05-2 mbar.

[0075] In another embodiment of the present invention, the distillation in step a) is carried out at a pressure of greater than 0.01 mbar to less than 10 mbar, preferably greater than 0.02 mbar to less than 8 mbar, more preferably greater than 0.03 mbar to less than 5 mbar, even more preferably greater than 0.05 mbar to less than 3 mbar, in particular greater than 0.05 mbar to less than 2 mbar.

[0076] In another embodiment of the present invention, the distillation in step a) is carried out at a temperature of 120-180°C, preferably 130-170°C, more preferably 135-150°C, in particular 140-150°C.

[0077] In this context, the distillation in step a) is preferably carried out at a pressure of 0.0001 to 0.03 mbar, preferably 0.001 to 0.01 mbar, more preferably 0.001 to 0.007 mbar.

[0078] In a preferred embodiment of the present invention, the distillation in step a) is carried out at a temperature of 180-220°C, preferably 185-215°C, more preferably 190-210°C, even more preferably 200-210°C, at a pressure of 0.01-10 mbar, preferably 0.02-8 mbar, more preferably 0.03-5 mbar, even more preferably 0.04-3 mbar, in particular 0.05-2 mbar; or the distillation in step a) is carried out at a temperature of 120-180°C, preferably 130-170°C, more preferably 135-150°C, in particular 140-150°C, at a pressure of 0.0001-0.03 mbar, preferably 0.001-0.01 mbar, more preferably 0.001-0.007 mbar.

[0079] In one embodiment of the present invention, the method further comprises the steps of:

[0080] c) collecting light boiling fractions;

[0081] d) distilling the light boiling fraction collected from step c) at a temperature of 100-250° C. and a pressure of less than 10 mbar; and

[0082] e) Hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate is separated as a further fraction of high boilers.

[0083] If hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate is partially distilled off and contained in the light-boiling fraction, steps c) to e) offer the possibility of recovering hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate from the light-boiling fraction collected.

[0084] In one embodiment, the method further comprises the steps of:

[0085] c) collecting light boiling fractions;

[0086] d) distilling the light boiling fraction collected from step c) at a temperature of 160-220° C., preferably 190-210° C., at a pressure of less than 10 mbar, preferably less than 5 mbar, in particular less than 0.1 mbar; and

[0087] e) Hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate is separated as a further fraction of high boilers.

[0088] In one embodiment of the present invention, the light boiling fraction collected from step c) in step d) contains 50 to 1000 ppm of dialkyl phthalate, in particular dihexyl phthalate.

[0089] According to the present invention, any suitable evaporator may be used.

[0090] In one embodiment of the invention, a thin film evaporator is used. Mention may be made of a thin film evaporator (also called wiped film evaporator) or a short path evaporator.

[0091] Short path evaporators offer a continuous distillation process, very low operating pressures, short residence times, high evaporation rates, low fouling on the evaporator walls and / or a compact design.

[0092] In one embodiment of the present invention, the hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate separated 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, in particular less than 5 ppm of dialkyl phthalate. Preferably, the hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate separated 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, in particular less than 5 ppm of dihexyl phthalate.

[0093] In a particular embodiment of the present invention, the hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate isolated in step b) contains no dialkyl phthalates, in particular no dihexyl phthalate.

[0094] In one embodiment of the present invention, the crude 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester in step a) has a Gardner value of 8.2 or more.

[0095] In one embodiment of the present invention, the 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester 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, especially preferably 8.0, in particular 7.5 or less.

[0096] In one embodiment of the present invention, the 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester separated 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, in particular 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, in particular 7.5 or less.

[0097] In a preferred embodiment of the present invention, the 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester separated 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, in particular 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, in particular 7.5 or less.

[0098] In one embodiment of the present invention, the 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester 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%.

[0099] In one embodiment of the present invention, the 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester separated in step b) is obtained in a yield of at least 90%, preferably at least 95%, more preferably at least 99%, which contains less than 20 ppm, preferably less than 15 ppm, more preferably less than 13 ppm, even more preferably less than 10 ppm, in particular less than 5 ppm of dihexyl phthalate and has a Gardner value of 9.5 or less, preferably 9 or less.

[0100] In one embodiment of the present invention, the 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester separated in step b) is obtained in a yield of at least 60%, preferably at least 65%, more preferably at least 70%, which contains less than 20 ppm, preferably less than 15 ppm, more preferably less than 13 ppm, even more preferably less than 10 ppm, in particular 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, in particular 7.5 or less.

[0101] In one embodiment of the invention, the process is carried out as a continuous process, wherein at least 50 g, preferably at least 80 g, of crude 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester is continuously fed per hour and high boilers and light boilers are continuously removed.

[0102] In one embodiment, the present invention relates to a body care product or daily care composition comprising 2-(4'-diethylamino-2'-hydroxybenzoyl) benzoic acid hexyl ester obtained according to the method. In particular, the present invention relates to a sunscreen composition comprising 2-(4'-diethylamino-2'-hydroxybenzoyl) benzoic acid hexyl ester obtained according to the method.

[0103] In one embodiment, the present invention relates to the use of hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate obtained according to the process as UV filter in body care products or daily care compositions, in particular in sunscreen compositions.

[0104] The following examples further illustrate the present invention. Example

[0105] method

[0106] The HPLC method for the determination of hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate, phthalic acid esters and rhodamine-type colored compounds was carried out according to standard methods of the prior art.

[0107] The PSDHE content of Examples 11, 14A and 14B was determined by HPLC analysis using a UPLC Agilent 1290 Infinity.

[0108] The PSDHE content of Examples 1-10, 12, 13 and 15 was determined by GC analysis using an Agilent 6890.

[0109] The Gardner value is determined according to the standard method of the prior art using a spectrocolorimeter LICO500 from Hach Lange, with the sample heated to 75° C. and cooled at room temperature for 5-7 minutes.

[0110] Calibration with analytical standards was performed according to standard methods in the art.

[0111] The crude 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester of Examples 1-14B was obtained according to EP 1 506159, Example 3, except that the product was not taken off as a melt but was further processed as described below.

[0112] In Examples 1 to 3 of the present invention and Comparative Example 8, crude 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester having a PSDHE content of 78 ppm and a Gardner of 7.5 was fed.

[0113] In Examples 4-7 of the present invention, crude 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester having a PSDHE content of 68 ppm and a Gardner of 7.5 was fed.

[0114] In Examples 9-14B of the present invention, crude 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester having a PSDHE content of 82 ppm and a Gardner of 7.5 was fed.

[0115] Examples 1-7 of the present invention were prepared in a wiped film evaporator (Sambay type, evaporation area 920 cm 2 ) is carried out in

[0116] Crude 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester (crude UVA+) was fed to a thin film evaporator and purified under the conditions of Table 1. The analytical results are summarized in Table 2.

[0117] Comparative Example 8 used steam stripping.

[0118] Table 1: Sambay thin film evaporator and steam stripping conditions and residual PSDHE content in the high boiling fraction

[0119] Example T[℃] p[millibar] Feed [g / h] 1 220 0.1-0.03 100 2 160-180 0.1-0.05 100 3 220 0.1-0.03 100-150 4 180 0.25 150-200 5 190 0.013 100 6 200 0.07 100 7 210 0.05 100 8 60 2

[0120] Table 2: Summary of analyses from Sambay thin film evaporator and steam stripping. nd means “not detected”.

[0121] Gardner refers to the value of the product after the thin film evaporator.

[0122]

[0123]

[0124] Inventive Examples 9 to 15 were carried out in a short path evaporator (wiped film evaporator, KDL-5 from UIC Corporation).

[0125] The crude 2-(4′-diethylamino-2′-hydroxybenzoyl)benzoic acid hexyl ester was fed to a short path evaporator and purified under the conditions of Table 3. The analytical results are summarized in Table 4.

[0126] The light boiling fractions of Inventive Examples 14A and 14B were collected and combined. The combined light boiling fractions were again subjected to the purification method (Inventive Example 15).

[0127] Separately, in Example 15 of the present invention, crude 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester having a PSDHE content of 482 ppm and a Gardner of 6.9 was fed.

[0128] Table 3: Short path evaporator conditions and residual PSDHE content in the high boiling fraction

[0129] Example T[℃] p[millibar] Feed [g / h] rpm 9 145 0.001 150 170 10 145 0.001 80 200 11 145 0.001 150 200 12 130 0.001 115 200 13 145 0.006 120 200 14A 145 0.001 120 200 14B 145 0.001 120 200 15 145 0.001 120 200

[0130] Table 4: Summary of the analyses of the short path evaporator. nd means "not detected". Gardner refers to the value of the product after the thin film evaporator.

[0131]

[0132] As can be seen from Tables 1-4, all of the examples of the present invention provide a reduced PSDHE content in the final 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester. In addition, compared to Comparative Example 8, all of the examples of the present invention provide an improved reduced PSDHE content in the final 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester.

Claims

1. A method for purifying 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester, comprising the steps of: a) distilling crude 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester at a temperature of 100-250° C. and a pressure of 0.0001 mbar to less than 2 mbar; b) separating hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate as high boilers, wherein the crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate in step a) comprises from 15 to 1000 ppm of dihexyl phthalate.

2. The process according to claim 1, wherein in step a) dihexyl phthalate is removed as a light boiler from crude hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate.

3. The process according to claim 1, wherein the distillation in step a) is carried out at a temperature of 160-220°C.

4. The process according to claim 2, wherein the distillation in step a) is carried out at a temperature of 160-220°C.

5. The process according to claim 3, wherein the distillation in step a) is carried out at a temperature of 190-210°C.

6. The process according to claim 4, wherein the distillation in step a) is carried out at a temperature of 190-210°C.

7. The process according to claim 1, wherein the distillation in step a) is carried out at a pressure of 0.01 mbar to less than 2 mbar.

8. The process according to claim 2, wherein the distillation in step a) is carried out at a pressure of 0.01 mbar to less than 2 mbar.

9. The process according to claim 3, wherein the distillation in step a) is carried out at a pressure of 0.01 mbar to less than 2 mbar.

10. The process according to claim 4, wherein the distillation in step a) is carried out at a pressure of 0.01 mbar to less than 2 mbar.

11. The process according to any one of claims 7 to 10, wherein the distillation in step a) is carried out at a pressure of 0.05 mbar to less than 2 mbar.

12. The process according to claim 1 or 2, wherein the distillation in step a) is carried out at a temperature of 120-180°C.

13. The process according to claim 12, wherein the distillation in step a) is carried out at a temperature of 130-170°C.

14. The process according to claim 1 or 2, wherein the distillation in step a) is carried out at a pressure of 0.0001-0.03 mbar.

15. The process according to claim 12, wherein the distillation in step a) is carried out at a pressure of 0.0001-0.03 mbar.

16. The process according to claim 14, wherein the distillation in step a) is carried out at a pressure of 0.001-0.007 mbar.

17. The process according to claim 1 or 2, wherein the distillation in step a) is carried out at a temperature of 180-220°C and a pressure of 0.01 mbar to less than 2 mbar, or The distillation in step a) is carried out at a temperature of 120-180° C. and a pressure of 0.0001-0.03 mbar.

18. The method according to claim 1 or 2, further comprising the steps of: c) collecting light boiling fractions; d) distilling the light boiling fraction collected from step c) at a temperature of 100-250° C. at a pressure of 0.0001 mbar to less than 0.1 mbar; and e) Hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate is separated as a further fraction of high boilers.

19. The method according to claim 17, further comprising the steps of: c) collecting light boiling fractions; d) distilling the light boiling fraction collected from step c) at a temperature of 100-250° C. at a pressure of 0.0001 mbar to less than 0.1 mbar; and e) Hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate is separated as a further fraction of high boilers.

20. The method according to claim 18, wherein in step d), the light boiling fraction collected from step c) contains 50-1000 ppm of dihexyl phthalate.

21. The method according to claim 19, wherein in step d), the light boiling fraction collected from step c) contains 50-1000 ppm of dihexyl phthalate.

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

23. The process of claim 21, wherein the 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester separated in step b) contains less than 20 ppm of dihexyl phthalate.

24. The process of claim 22, wherein the 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester separated in step b) contains less than 15 ppm of dihexyl phthalate.

25. The process of claim 22, wherein the 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester separated in step b) contains less than 13 ppm of dihexyl phthalate.

26. The method according to any one of claims 1 to 10, wherein the 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester separated in step b) has a Gardner value of 9.5 or less.

27. The method of claim 23, wherein the 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester separated in step b) has a Gardner value of 9.5 or less.

28. The process according to any one of claims 1 to 10, wherein the hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate isolated in step b) is obtained in a yield of at least 60%.

29. The process according to claim 27, wherein the hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate isolated in step b) is obtained in a yield of at least 60%.

30. The process of claim 28, wherein the hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate isolated in step b) is obtained in a yield of at least 80%.

31. The process of claim 28, wherein the hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate isolated in step b) is obtained in a yield of at least 90%.

32. The process of claim 28, wherein the hexyl 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoate isolated in step b) is obtained in a yield of at least 99%.

33. The process according to any one of claims 1 to 10, wherein the process is carried out as a continuous process, wherein crude 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester is fed continuously and high boilers and light boilers are removed continuously.

34. The process according to claim 29, wherein the process is carried out as a continuous process, wherein crude 2-(4'-diethylamino-2'-hydroxybenzoyl)benzoic acid hexyl ester is continuously fed in and high boilers and light boilers are continuously removed.

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