Improved process for preparation of s-triazine derivatives

Abstract

The present invention relates to a process for the preparation of s-triazine derivatives comprising reacting cyanuric halide with para aminobenzoate in a non-polar solvent wherein the reaction product is purified by gas / steam stripping. Furthermore, the invention relates to s-triazine derivatives having high purity and / or optimal particle properties, to the use thereof as photoprotectants, and to cosmetic preparations thereof.

Description

[0001] The invention relates to a process for preparing s-triazine derivatives, which comprises reacting a cyanuric halide with a p-aminobenzoic acid ester in a nonpolar solvent, wherein the reaction product is purified by gas / steam stripping. The invention also relates to s-triazine derivatives having high purity and / or optimal particle properties, their use as light protection agents, and cosmetic preparations thereof.

[0002] It is known that s-triazine derivatives (i.e., 1,3,5-triazine derivatives) have a wide range of UV absorption efficiency, absorption in both the UVB and UVA segments, and high photostability. Therefore, s-triazine derivatives are used as photoprotective agents, particularly in cosmetic applications and sunscreen compositions. In view of contact with human skin in these applications, high-purity s-triazine derivatives are required. Typically, s-triazine derivatives are prepared by reacting cyanuric halides (also known as "cyanuric acid halides") with p-aminobenzoic acid esters in non-polar solvents. In order to achieve the desired product quality, by-products and solvent residues must be removed, which is time-consuming and energy- and cost-intensive in large-scale industrial applications. Desolvation is particularly challenging because too fast drying at too high a temperature produces a product with low solubility in the oils used in cosmetics.

[0003] EP 3 674 293 A1 discloses a process for the synthesis of s-triazine derivatives, which comprises reacting a cyanuric halide with a p-aminobenzoic acid ester and subsequently reacting the cyanuric halide with a carbon and a hyflow TM The process of purifying the product by a bed is a process of purifying the product by a bed. However, this process involves an additional adsorption step and uses a large amount of solvent, which increases complexity and cost. Especially considering large-scale applications, this process is economically disadvantageous.

[0004] EP 2 688 875 discloses a technically simple and economical process for the synthesis of s-triazine derivatives, which comprises a step of reacting a cyanuric halide with a p-aminobenzoic acid ester in a significantly reduced amount of solvent. However, the product purity achieved in the laboratory examples shown was only 90.5% by area, with secondary components of 0.5% by weight.

[0005] It was therefore an object of the present invention to provide an improved process for preparing high-purity s-triazine derivatives in high yield with cost-effective product purification.

[0006] In this regard, it is desirable to provide a process which ensures not only a high purity of the product but also a high solubility and stability in cosmetic preparations. Furthermore, it is an object to provide a process which is suitable for large-scale applications. Furthermore, it is desirable that the process is economically and environmentally advantageous, e.g., the amount of solvent is low and the process steps are few.

[0007] It has surprisingly been found that the above objects can be achieved by the method described below and in the claims.

[0008] In one embodiment, the present invention relates to a method for preparing a triazine derivative having formula (I):

[0009]

[0010] The method comprises reacting the following in a non-polar solvent:

[0011] (i) cyanuric halides; and

[0012] (ii) p-Aminobenzoic acid esters

[0013]

[0014] in

[0015] R 1 , R 2 and R 3 are the same or different and are independently selected from hydrogen, alkali metals, ammonium, substituted ammonium, C1-C 12 - a group consisting of an alkyl group or a polyoxyethylene group; and

[0016] in

[0017] The reaction product is purified by gas / steam stripping.

[0018] The inventors of the present invention have surprisingly found that the inventive method provides high-purity s-triazine derivatives without the need for complex product purification. In particular, these s-triazine derivatives can be obtained with high purity and high yield by purifying the product with gas / steam stripping. Compared with the purification methods described in the prior art (e.g., using adsorption techniques), the gas / steam stripping according to the present invention can be easily applied on a large industrial scale. In addition, the purification by gas / steam stripping before further purification steps (e.g., recrystallization, washing and drying) reduces the impurities introduced into the solvent for these purification steps, which is economically and ecologically advantageous for the subsequent purification and recycling of the solvent. In particular, the solvent used for the reaction and optionally the by-products are removed and therefore do not contaminate the solvent used for purification afterwards. In addition, it has been found that the inventive method can significantly increase the product yield. In addition, the obtained s-triazine derivatives have optimal physical properties in terms of, for example, particle size, fluidity, and solubility and stability in the oil used in cosmetic formulations.

[0019] Thus, this process of the present invention is particularly advantageous in providing a combination of optimal product purity and yield with an efficient and economical process for large-scale application.

[0020] In one embodiment of the present invention, R 2 =R 1 ; and preferably R 3 =R 2 =R 1 ; and particularly preferably R 1 , R 2 , and R 3 Each represents a 2-ethylhexyl group.

[0021] In one embodiment of the present invention, the s-triazine derivative is 2,4,6-trianilino-p-(carbonyl-2'-ethylhexyl-1'-oxy)-1,3,5-triazine having the following chemical formula (Ia):

[0022]

[0023] In one embodiment of the invention, gas / steam stripping is performed by feeding the reaction product into a vessel or reactor and stripping off the non-polar solvent and optionally by-products by adding water or polar solvent or water vapor or polar solvent vapor or gas or mixtures thereof into the vessel or reactor.

[0024] In one embodiment of the present invention, gas / steam stripping is performed by adding water vapor, ethanol vapor or nitrogen, preferably water vapor or nitrogen, preferably from the bottom portion of the vessel / reactor.

[0025] In one embodiment of the invention, the temperature during steam / gas stripping is below 200°C, preferably below 180°C; and / or the pressure of the steam / gas during steam / gas stripping is up to 100 bar, preferably up to 20 bar.

[0026] In one embodiment of the present invention, after stripping, the s-triazine derivative is dissolved in a polar solvent, preferably a C1-C8-alcohol or water or a mixture thereof.

[0027] In one embodiment of the invention, after stripping, the s-triazine derivative is dissolved in a mixture of at least one C1-C4-alcohol and up to 10% by weight of water, preferably in a mixture of at least one C2-C4-alcohol and up to 10% by weight of water.

[0028] In one embodiment of the present invention, the reaction is carried out in an aromatic solvent, which is preferably toluene, xylene, a xylene isomer mixture, trimethylbenzene, a trimethylbenzene isomer mixture, or a mixture thereof, wherein the solvent is particularly preferably azeotropically dehydrated before the reaction begins.

[0029] In one embodiment of the present invention, the reaction is carried out at a temperature of 75°C up to the boiling point of the solvent used for a period of up to 48 h.

[0030] In one embodiment of the present invention, the cyanuric halide is selected from cyanuric chloride, cyanuric bromide and a mixture thereof, and the cyanuric halide is preferably cyanuric chloride.

[0031] In one embodiment of the present invention, the method further comprises preparing 2-ethylhexyl p-aminobenzoate, comprising reacting 2-ethylhexyl p-nitrobenzoate with hydrogen in the presence of a catalyst.

[0032] In one embodiment of the present invention, the method further comprises preparing 2-ethylhexyl p-nitrobenzoate, comprising reacting p-nitrobenzoic acid with 2-ethylhexanol.

[0033] In one embodiment, the present invention relates to a s-triazine derivative of formula (I), in particular 2,4,6-triphenylamino-p-(carbonyl-2'ethylhexyl-1'-oxy)-1,3,5-triazine, having a purity of at least 98% by weight, preferably at least 99% by weight, more preferably at least 99.5% by weight. In even more preferred embodiments, the purity may be at least 99.6%, 99.7%, 99.8% or 99.9% by weight. The s-triazine derivative of formula (I) may be tautomeric form I of 2,4,6-triphenylamino-p-(carbonyl-2'ethylhexyl-1'-oxy)-1,3,5-triazine (as disclosed in WO 03 / 074499A1).

[0034] In one embodiment, the present invention relates to s-triazine derivatives in the form of pourable or flowable particles, preferably in crystalline form, particularly preferably with an average particle size of 5 μm up to 500 μm and / or a bulk density of more than 0.2 g / mL.

[0035] In one embodiment, the present invention relates to s-triazine derivatives obtainable by the process of the present invention. In one embodiment, the s-triazine derivative having formula (I) is the tautomeric form I of 2,4,6-trianilino-p-(carbonyl-2'ethylhexyl-1'-oxy)-1,3,5-triazine.

[0036] In one embodiment, the present invention relates to the use of s-triazine derivatives having formula (I) as photoprotective agents.

[0037] In one embodiment, the present invention relates to a cosmetic formulation comprising an s-triazine derivative having formula (I).

[0038] Preferred embodiments of the present invention can be found in the claims, the specification and the examples. It should be understood that the above-mentioned features of the subject matter of the present invention and those features to be described below are preferred not only in the respective given combinations, but also in other combinations without departing from the scope of the present invention.

[0039] In conjunction with the above embodiments of the present invention, the following definitions are provided.

[0040] In the context of the present invention, the s-triazine derivatives of formula (I) are obtained by reacting cyanuric halides with identical or different p-aminobenzoic acid esters in a nonpolar solvent.

[0041] As used herein, the term "one or more s-triazine derivatives of formula (I)" or "one or more s-triazine derivatives according to the present invention" or "one or more s-triazine derivatives" refers to compounds of formula (I) as defined herein, i.e. 2,4,6-trisubstituted 1,3,5-triazines, wherein the substituents at the 2-, 4- and 6-positions are derived from the same or different p-aminobenzoates, such that these p-aminobenzoates are attached via their p-amino groups. As indicated above, the attached substituents at the 2-, 4- and 6-positions are derived from the same or different p-aminobenzoates. Thus, according to the present invention, R 1 , R 2 and R 3 can be the same or different. However, it is preferred that R 1 =R 2 =R 3 , i.e., the attached substituents at the 2-, 4-, and 6-positions are derived from the same p-aminobenzoate.

[0042] Non-polar solvent generally comprises alkane, aromatic solvent and ether or its mixture.Preferred non-polar solvent according to the present invention is aromatic solvent and particularly preferably toluene, xylene, xylene isomer mixture, trimethylbenzene, trimethylbenzene isomer mixture or its mixture.In addition, this solvent is preferably by azeotropic dehydration before this reaction starts.Remaining water can reduce productive rate and increase the amount of by product, because cyanuric halide has the tendency of hydrolysis to produce single-, two-and / or trihydroxy-triazine.In addition, under the process temperature of rising during the formation of s-triazine derivative, p-aminobenzoic acid ester, intermediate and / or product s-triazine derivative can be partially or completely hydrolyzed.

[0043] The term "cyanuric halide" or "cyanuric acid halide" as used herein refers to 1,3,5-triazine substituted by the same halide ion at the 2-, 4- and 6-positions. Cyanuric halide is preferably cyanuric bromide, cyanuric chloride, or a mixture thereof, and more preferably cyanuric chloride (CAS No.: 108-77-0). Cyanuric halide is a highly reactive substance. The three halide ions at the 2-, 4- and 6-positions can be easily replaced by nucleophilic substances to obtain 2,4,6-trisubstituted 1,3,5-triazines. Since three halide ions are replaced in such a reaction, cyanuric halide is typically reacted with at least three equivalents of nucleophilic reagents. If different types of nucleophilic reagents are used, the molar ratio of cyanuric acid to nucleophilic reagent is typically also at least 1:3, preferably 1:3 to 1:5. However, the nucleophilic reagent can be represented by different types of nucleophilic reagents. The reaction can then be carried out in a stepwise manner so that different types of nucleophilic reagents react with cyanuric halide in sequence.

[0044] As used herein, the term "para-aminobenzoate" or "4-aminobenzoate" refers to a compound having the following general formula:

[0045]

[0046] Where R 1 , R 2 and R 3 are the same or different and are independently selected from hydrogen, alkali metals, ammonium, substituted ammonium, C1-C 12 - a group consisting of an alkyl group or a polyoxyethylene group.

[0047] As indicated above, the s-triazine derivatives of formula (I) are obtained by reacting cyanuric halide with the same or different p-aminobenzoic acid esters. If, according to the present invention, the molar ratio of cyanuric halide to p-aminobenzoic acid ester is defined as 1:3 to 1:5, then this molar ratio refers to the molar ratio of cyanuric halide to p-aminobenzoic acid ester, regardless of whether the same p-aminobenzoic acid ester or different p-aminobenzoic acid esters are used in the reaction. In other words, it should be understood that if the p-aminobenzoic acid esters reacted with the cyanuric halide are the same (i.e., R 1 =R 2 =R 3 ), the molar ratio of cyanuric acid to p-aminobenzoic acid ester is 1:3 to 1:5, which means that three to five equivalents of a specific p-aminobenzoic acid ester react with the cyanuric halide. On the other hand, if the p-aminobenzoic acid ester reacted with the cyanuric halide is different (e.g., R 1 ≠R 2 ≠R 3 ), the molar ratio of cyanuric acid to p-aminobenzoic acid ester is also 1:3 to 1:5, but three to five equivalents of p-aminobenzoic acid ester relative to cyanuric halide are represented by the total amount of all different types of p-aminobenzoic acid esters.

[0048] Preferably, the p-aminobenzoic acid ester is purified by distillation before use.

[0049] As used herein, "alkali metal" includes sodium, potassium or lithium, preferably sodium or potassium.

[0050] As used herein, "substituted ammonium" refers to ammonium in which one to four hydrogen atoms are independently substituted by C1-C6-alkyl (preferably C1-C2-alkyl).

[0051] As used herein, the term "C1-C 12 "Alkyl" means a straight or branched chain alkyl group having 1 to 12 carbon atoms. Preferred alkyl groups are C6-C 10 -alkyl, and particularly preferably 2-ethylhexyl.

[0052] As used herein, "polyoxyethylene" refers to a polyoxyethylene having the structure H-(O-CH2-CH2) n A substituent of -OH, wherein n is 1 to 1000, preferably 1 to 100.

[0053] In the present invention, the method for preparing s-triazine derivatives further relates to purifying the product by gas / steam stripping. Generally, stripping is a physical separation method that uses a vapor stream to remove components from a liquid sample. As used herein, gas / steam stripping is by feeding the reaction product into a container or reactor and stripping off non-polar solvents and optionally by-products via adding water or polar solvents or water vapor or polar solvent vapor or gas or a mixture thereof to a container or reactor. Therefore, gas / steam stripping according to the present invention also includes flashing (flashing) or sudden distillation (flash), which describes a method in which water or polar solvents are added in a liquid phase from the top portion of a container / reactor. Preferably, gas / steam stripping is carried out by adding water vapor, polar solvent vapor, gas or a mixture thereof from the top or bottom portion of a container / reactor. More preferably, gas / steam stripping is carried out by adding water vapor, polar solvent vapor, gas or a mixture thereof from the bottom portion of a container / reactor. The overhead stream comprising the solvent desorbed and optionally reaction by-products can be condensed and separated. As used herein, the term "steam" in connection with gas / steam stripping refers to water vapor or polar solvent vapor, in particular alcohol vapor, preferably ethanol vapor. As used herein, the term "gas" in connection with gas / steam stripping refers to an inert gas that does not undergo chemical reactions, in particular nitrogen. As mentioned above, the term gas / steam stripping according to the present invention also includes flashing or sudden distillation with water or a polar solvent, preferably ethanol, in the liquid phase.

[0054] As used herein, pressure indicated by the pressure unit "bar" refers to relative pressure or gauge pressure, which is zero-referenced to ambient air pressure and is therefore equal to absolute pressure minus atmospheric pressure. Gauge pressure may also be indicated by the pressure unit "bar gauge". Pressure refers to absolute pressure only when the pressure unit "bar (absolute)" is used.

[0055] Figure 1 It is explained how gas / steam stripping is preferably carried out according to the invention, i.e. how it is carried out by feeding the reaction product into a vessel or reactor and stripping off the non-polar solvent and optionally by-products by adding water vapor, polar solvent vapor, gas or a mixture thereof to the vessel or reactor, preferably from the bottom part of the vessel / reactor.

[0056] The following describes a preferred embodiment of the method of the present invention. The following general considerations apply to the method.

[0057] Typically, the reaction step is carried out in a reaction vessel, such as a conventional stirred tank reactor, which is commonly used for such reactions. The reaction can be carried out continuously or in a semi-batch or batch manner. Particularly preferably, the inventive method is carried out in a semi-batch manner, wherein at least one reactant is provided in a reaction vessel, and at least one other reactant is added within a certain dosing time. Typically, these method steps are preferably carried out under atmospheric pressure. Details about the reaction temperature are provided below. The termination of the reaction can be monitored by methods known to those skilled in the art, such as, thin layer chromatography, GC, HPLC or NMR.

[0058] If not indicated otherwise, the reactants can in principle be brought into contact with one another in any desired order.

[0059] Furthermore, it is emphasized that these reaction steps can be performed on a technical scale.

[0060] In the following, preferred embodiments of the present invention are provided. It should be understood that the preferred embodiments of the present invention are preferred individually or in combination with each other.

[0061] As indicated above, the present invention relates to a process for preparing the s-triazine derivative having formula (I) as provided above, which comprises reacting a cyanuric halide with the following p-aminobenzoic acid ester in a non-polar solvent:

[0062]

[0063] Where R 1 , R 2 and R 3 are the same or different and are independently selected from hydrogen, alkali metals, ammonium, substituted ammonium, C1-C 12-alkyl or polyoxyethylene; and wherein the reaction product is purified by gas / steam stripping. In one embodiment, the molar ratio of cyanuric halide to p-aminobenzoic acid ester is 1:2.9 to 1:5, preferably 1:3 to 1:5. It is advantageous that p-aminobenzoic acid ester is in excess relative to cyanuric halide in order to achieve complete conversion of cyanuric halide, i.e., all three halide ions are replaced by the same or different p-aminobenzoic acid esters. The p-aminobenzoic acid ester remaining after the reaction can be removed by crystallizing the obtained s-triazine derivative in a polar solvent.

[0064] In one embodiment of the method of the present invention, R 2 =R 1 And preferably R 3 =R 2 =R 1 And particularly preferably R 1 , R 2 and R 3 Each represents 2-ethylhexyl. 1 , R 2 and R 3 Each represents 2-ethylhexyl) to produce as a product 2,4,6-trianilino-p-(carbonyl-2'-ethylhexyl-1'-oxy)-1,3,5-triazine, which represents the known highly efficient UV absorber ethylhexyl triazone (Uvinul T 150, CAS No.: 88122-99-0).

[0065] Therefore, in one embodiment of the method of the present invention, the s-triazine derivative is 2,4,6-trianilino-p-(carbonyl-2'-ethylhexyl-1'-oxy)-1,3,5-triazine having the following chemical formula (Ia):

[0066]

[0067] As indicated above, gas / steam stripping is performed to purify the product s-triazine derivative having formula (I).

[0068] In one embodiment of the method of the present invention, gas / steam stripping is carried out by feeding the reaction product into a container or reactor and stripping off the non-polar solvent by adding water or polar solvent or water vapor or polar solvent steam or gas or a mixture thereof to the container or reactor from the top or bottom portion of the container / reactor. Preferably, water vapor or polar solvent steam or gas or a mixture thereof is added from the bottom portion of the container / reactor. If stripping is carried out with polar solvent steam, ethanol steam is preferably used. If stripping is carried out with gas, nitrogen is preferably used. Therefore, in one embodiment, gas / steam stripping is carried out by preferably adding water vapor, ethanol steam or nitrogen, preferably water vapor or nitrogen, from the bottom portion of the container / reactor. The overhead stream containing the solvent desorbed and optionally the reaction by-products can be condensed and separated. Therefore, gas / steam stripping is conducive to effectively removing solvent residues and by-products from the desired s-triazine derivatives. The obtained s-triazine derivatives are obtained with high yield and high purity. In addition, gas / steam stripping has the advantage of being suitable for large industrial scale. Furthermore, it has been found that this process offers the advantage that the reaction product has optimal physical properties in terms of solubility and stability in oils for use in cosmetic formulations. As mentioned above, if too high a temperature is used to remove the solvent, the solubility in the oil is reduced.

[0069] In one embodiment of the process of the present invention, the temperature during the gas / steam stripping is below 200° C., preferably below 180° C. In another embodiment, the temperature during the gas / steam stripping is from 100° C. to 200° C., preferably from 100° C. to 180° C. In another embodiment, the temperature during the gas / steam stripping is from 120° C. to 170° C. In another embodiment, the temperature during the gas / steam stripping is from 140° C. to 160° C.

[0070] In one embodiment, gas / steam stripping is performed for a period of up to 48 hours. In another embodiment, gas / steam stripping is performed for a period of 1 to 24 hours. In another embodiment, gas / steam stripping is performed for a period of 2 to 12 hours. In another embodiment, gas / steam stripping is performed for a period of 4 to 7 hours.

[0071] In one embodiment of the invention, the pressure of the gas / steam during the gas / steam stripping is up to 100 bar, preferably up to 20 bar. In another embodiment, the pressure of the gas / steam during the gas / steam stripping is 0.1 bar to 20 bar. In another embodiment, the pressure of the gas / steam during the gas / steam stripping is 0.5 bar to 10 bar. In another embodiment, the pressure of the gas / steam during the gas / steam stripping is 1 bar to 6 bar. In one embodiment, the temperature during the steam / gas stripping is below 200°C, preferably below 180°C; and the pressure of the steam / gas during the steam / gas stripping is up to 100 bar, preferably up to 20 bar. In one embodiment, the temperature during the gas / steam stripping is 120°C to 170°C, and the pressure of the gas / steam during the gas / steam stripping is 0.1 bar to 20 bar. In one embodiment, the temperature during the gas / steam stripping is 120°C to 170°C, and the pressure of the gas / steam during the gas / steam stripping is 0.5 bar to 10 bar. In another embodiment, the temperature during gas / steam stripping is 140°C to 160°C, and the pressure of the gas / steam during gas / steam stripping is 1 bar to 6 bar. In one embodiment, the temperature during gas / steam stripping is 140°C to 160°C, and the pressure of the gas / steam during gas / steam stripping is 0.1 bar to 20 bar. In another embodiment, the temperature during gas / steam stripping is 140°C to 160°C, and the pressure of the gas / steam during gas / steam stripping is 0.5 bar to 10 bar. In another embodiment, the temperature during gas / steam stripping is 140°C to 160°C, and the pressure of the gas / steam during gas / steam stripping is 1 bar to 6 bar. In a specific embodiment, gas / steam stripping is performed at a temperature of 120°C to 170°C and a pressure of 0.5 bar to 10 bar for a period of 1 to 12 hours. In another specific embodiment, the gas / steam stripping is carried out at a temperature of 120 to 170°C and a pressure of 0.5 to 10 bar for a period of 3 to 7 hours.

[0072] In one embodiment of the process of the invention, the amount of gas / steam used for gas / steam stripping is at least 25% by weight relative to the crude product. In another embodiment, the amount of gas / steam used for gas / steam stripping is at least 50% by weight relative to the crude product.

[0073] In one embodiment of the inventive method, the non-polar solvent and water are azeotropically distilled before gas / steam stripping. In one embodiment, the temperature during the azeotropic distillation is less than 200°C, preferably less than 180°C. In another embodiment, the temperature during the azeotropic distillation is 140°C to 180°C. In one embodiment, the temperature during the azeotropic distillation is 140°C to 180°C and the pressure is 1 mbar (absolute) to 2 bar (absolute). In another embodiment, the temperature during the azeotropic distillation is 140°C to 180°C and the pressure is 10 mbar (absolute) to 1 bar (absolute). In another embodiment, the temperature during the azeotropic distillation is 140°C to 180°C and the pressure is 20 mbar (absolute) to 100 mbar (absolute).

[0074] In one embodiment, after gas / steam stripping, the s-triazine derivative is dissolved in a polar solvent for subsequent crystallization of the product.

[0075] In one embodiment of the method of the present invention, the s-triazine derivative is dissolved in a polar solvent, preferably C1-C8-alcohol or water or a mixture thereof. The C1-C8-alcohol includes a linear alcohol, a branched alcohol or a cyclic alcohol or a mixture thereof having 1 to 8 carbon atoms, preferably ethanol, n-propanol, isopropanol, n-butanol, tert-butanol, n-pentanol, n-hexanol, n-octanol, 2-ethylhexanol and cyclohexanol, and ethanol is particularly preferred. Therefore, in another embodiment of the method of the present invention, the s-triazine derivative is dissolved in an optionally aliphatic C2-C8-alcohol or water or a mixture thereof. In another embodiment, the s-triazine derivative is dissolved in a mixture of at least one C1-C4-alcohol and up to 10% by weight of water, preferably in a mixture of at least one C2-C4-alcohol and up to 10% by weight of water. In another embodiment, the s-triazine derivative is dissolved in a mixture of ethanol and at least one C3- or C4-alcohol and up to 10% by weight of water. In another embodiment, the s-triazine derivative is dissolved in ethanol with up to 10 wt % of water. The water content can be lower, for example up to 5 wt %, up to 3 wt % or even lower. In certain embodiments, the water content can be less than 1 wt %. In various embodiments, the s-triazine derivative is washed with pure ethanol.

[0076] If the solvent or mixture contains ethanol, common denaturants such as butan-2-one, 3-methylbutan-2-one, 5-methylheptan-3-one, isopropanol, tert-butyl alcohol, petroleum ether, toluene, cyclohexane, 2-methylpropan-2-ol can be used in addition. Therefore, in one embodiment, the at least one C1-C4 alcohol, at least one C2-C4-alcohol, at least one C3- or C4-alcohol only refers to the denaturant added to denature ethanol. Adding a polar solvent reduces the temperature of the container / reactor, thereby avoiding the hydrolysis of the ester of the s-triazine derivative or the transesterification of the s-triazine derivative. Therefore, in one embodiment, the temperature of the container / reactor is reduced before crystallization. In a specific embodiment, before adding a polar solvent, the temperature has been reduced to a certain extent by flashing with water. As a side effect, flashing further removes solvent residues and optionally impurities. In one embodiment, after dissolving the s-triazine derivative in a polar solvent, the filtration of the solution, the crystallization of the s-triazine derivative, washing with a polar solvent and drying are carried out. The polar solvent is preferably an alcohol as described above. In various embodiments, the method comprises performing crystallization in the presence of one or more alcohol solvents as described above to produce tautomeric Form I of the compound having formula (Ia).

[0077] As mentioned above, the reaction of cyanuric halide and para-aminobenzoic acid ester is carried out in a non-polar solvent. In one embodiment of the inventive method, the reaction is carried out in an aromatic solvent, and the aromatic solvent is preferably toluene, dimethylbenzene, dimethylbenzene isomer mixture, trimethylbenzene, trimethylbenzene isomer mixture or its mixture. In a preferred embodiment, the solvent is azeotropically dehydrated before the reaction begins. Removing residual water is advantageous with regard to high yield and a small amount of by-products, because cyanuric halide has the tendency of hydrolysis to produce mono-, di- and / or trihydroxy-triazine. In addition, under the process temperature of the rise during the formation of s-triazine derivatives, p-aminobenzoic acid ester, intermediate and / or desired s-triazine derivatives can be partially or completely hydrolyzed and / or re-esterified. In a specific embodiment, water content is less than 300mg / kg.

[0078] In another embodiment of the process of the invention, the cyanuric halide is introduced as an initial charge in the form of a suspension together with a dehydrated non-polar solvent. In a specific embodiment, the vessel / reactor is pre-charged with the solvent, preferably at elevated temperature and more preferably at a temperature of 50° C. to 90° C. This is advantageous in order to prevent (partial) hydrolysis of the cyanuric halide at too high a temperature.

[0079] In another embodiment of the inventive method, the p-aminobenzoic acid ester is added to a dehydrated non-polar solvent in a separate container / reactor. Preferably, the p-aminobenzoic acid ester is purified by vacuum distillation in advance. In one embodiment, the cyanuric halide suspension is then quantitatively fed to the p-aminobenzoic acid ester in the dehydrated non-polar solvent to start the reaction. In a specific embodiment, an additional dehydrated non-polar solvent is added.

[0080] In one embodiment of the method of the present invention, the reaction is carried out at a temperature of 75°C to the boiling point of the solvent used for a period of up to 48 hours. In another embodiment, the reaction is carried out at a temperature of 75°C to the boiling point of the solvent used for a period of 0.5h to 24h. In another embodiment, the reaction is carried out at a temperature of 75°C to the boiling point of the solvent used for a period of 0.5h to 12h. In another embodiment, the reaction is carried out at a temperature of 75°C to the boiling point of the solvent used for a period of 1h to 3h. In another embodiment, the reaction is carried out at a temperature of 100°C to 150°C for a period of 0.5h to 12h. In another embodiment, the reaction is carried out at a temperature of 100°C to 150°C for a period of 1h to 3h. In another embodiment, the reaction is carried out at a temperature of 110°C to 130°C for a period of 0.5h to 12h. In another embodiment, the reaction is carried out at a temperature of 110°C to 130°C for a period of 1h to 3h. Running the reaction for longer reaction times does not negatively affect product yield and purity, but reduces the space-time yield of the process and thus increases waste and cost.

[0081] In another embodiment, a base is added after the reaction to neutralize the reaction mixture. Preferably, the base is selected from ammonia, alkali metal hydroxides, alkali metal carbonates, or alkali metal bicarbonates. In one embodiment, the base is selected from alkali metal carbonates, preferably potassium carbonate or sodium carbonate. In another embodiment, the base is sodium carbonate.

[0082] In one embodiment of the method of the present invention, the cyanuric halide is selected from cyanuric chloride, cyanuric bromide and mixtures thereof. Preferably, the cyanuric halide is cyanuric chloride.

[0083] As described above, the s-triazine derivatives of formula (I) are prepared by reacting cyanuric halides with the same or different p-aminobenzoic acid esters. In one embodiment of the method of the present invention, the method further comprises preparing p-aminobenzoic acid esters, comprising reacting p-nitrobenzoic acid esters with hydrogen in the presence of a catalyst; preferably preparing p-aminobenzoic acid-2-ethylhexyl ester, comprising reacting p-nitrobenzoic acid-2-ethylhexyl ester with hydrogen in the presence of a catalyst. In another embodiment, the method further comprises preparing p-nitrobenzoic acid esters, comprising reacting p-nitrobenzoic acid with alcohol or polyethylene oxide; preferably preparing p-nitrobenzoic acid-2-ethylhexyl ester, comprising reacting p-nitrobenzoic acid with 2-ethylhexanol.

[0084] As mentioned above, high-purity s-triazine derivatives can be obtained by the process of the present invention by stripping the purified product with gas / steam. Therefore, in one embodiment, the present invention relates to a s-triazine derivative of formula (I) having a purity of at least 98% by weight. In another embodiment, the present invention relates to a s-triazine derivative of formula (I) having a purity of at least 99% by weight. In another embodiment, the present invention relates to a s-triazine derivative of formula (I) having a purity of at least 99.5% by weight.

[0085] In addition, the s-triazine derivatives obtained by this method have optimal physical properties, for example in terms of particle size. Therefore, in one embodiment, the present invention relates to a s-triazine derivative in the form of pourable or flowable particles, preferably in crystalline form, particularly preferably with an average particle size of 5 μm to up to 500 μm and / or a bulk density of greater than 0.2 g / mL. In another embodiment, the present invention relates to a s-triazine derivative with an average particle size of 5 μm to up to 500 μm and / or a bulk density of 0.3 g / mL to 1.5 g / mL. In another embodiment, the present invention relates to a s-triazine derivative with an average particle size of 5 μm to up to 500 μm and / or a bulk density of 0.4 g / mL to 0.8 g / mL. In another embodiment, the present invention relates to a s-triazine derivative with an average particle size of 20 μm to up to 200 μm and / or a bulk density of 0.4 g / mL to 0.8 g / mL. In another embodiment, the present invention relates to a s-triazine derivative having an average particle size of 30 μm to up to 100 μm and / or a bulk density of 0.4 g / mL to 0.8 g / mL. S-triazine derivatives having these properties are advantageous, for example, in terms of high solubility and stability in oils used in cosmetic formulations. In addition, the flowability and particle size provide advantages for easy handling and dosing.

[0086] Therefore, in one embodiment, the present invention relates to a s-triazine derivative having the above characteristics, which is obtainable by the method of the present invention. As mentioned above, it is known that s-triazine derivatives have UV absorption efficiency and high light stability in the UVB and UVA regions. In one embodiment, the present invention relates to the use of s-triazine derivatives of formula (I) as photoprotective agents. Considering the high purity and physical properties of the s-triazine derivatives obtained by the method of the present invention, it is advantageous to use them as photoprotective agents for, for example, cosmetic preparations.

[0087] Therefore, in one embodiment, the present invention relates to a cosmetic preparation comprising an s-triazine derivative of formula (I). In particular, in one embodiment, the present invention relates to a cosmetic preparation comprising an s-triazine derivative of formula (I) in the form of pourable or flowable particles, preferably in crystalline form, and particularly preferably having an average particle size and bulk density as described above.

[0088] In another aspect and embodiment, the present invention relates to a method for preparing an s-triazine derivative, wherein the s-triazine derivative is 2,4,6-trianilino-p-(carbonyl-2'-ethylhexyl-1'-oxy)-1,3,5-triazine having the following chemical formula (Ia):

[0089]

[0090] The method comprises reacting a cyanuric halide with the following p-aminobenzoic acid-2-ethylhexyl ester in a non-polar solvent:

[0091]

[0092] Where R 1 , R 2 , and R 3 Each represents 2-ethylhexyl; and wherein the reaction product is purified by gas / steam stripping. In one embodiment, the molar ratio of cyanuric halide to p-aminobenzoic acid ester is 1:2.9 to 1:5, preferably 1:3 to 1:5. It is advantageous for p-aminobenzoic acid ester to be in excess relative to cyanuric halide in order to achieve complete conversion of cyanuric halide, i.e., all three halide ions are replaced by the same or different p-aminobenzoic acid esters. The p-aminobenzoic acid ester remaining after the reaction can be removed by crystallizing the obtained s-triazine derivative in a polar solvent.

[0093] As indicated above, gas / steam stripping is performed to purify the product s-triazine derivative having formula (Ia).

[0094] In one embodiment of the method of the present invention, gas / steam stripping is carried out by feeding the reaction product into a container or reactor and stripping off the non-polar solvent by adding water or polar solvent or water vapor or polar solvent steam or gas or a mixture thereof to the container or reactor from the top or bottom portion of the container / reactor. Preferably, water vapor or polar solvent steam or gas or a mixture thereof is added from the bottom portion of the container / reactor. If stripping is carried out with polar solvent steam, ethanol steam is preferably used. If stripping is carried out with gas, nitrogen is preferably used. Therefore, in one embodiment, gas / steam stripping is carried out by preferably adding water vapor, ethanol steam or nitrogen, preferably water vapor or nitrogen, from the bottom portion of the container / reactor. The overhead stream containing the solvent desorbed and optionally the reaction by-products can be condensed and separated. Therefore, gas / steam stripping is conducive to effectively removing solvent residues and by-products from the desired s-triazine derivatives. The obtained s-triazine derivatives are obtained with high yield and high purity. In addition, gas / steam stripping has the advantage of being suitable for large industrial scale. Furthermore, it has been found that this process offers the advantage that the reaction product has optimal physical properties in terms of solubility and stability in oils for use in cosmetic formulations. As mentioned above, if too high a temperature is used to remove the solvent, the solubility in the oil is reduced.

[0095] In one embodiment of the process of the present invention, the temperature during the gas / steam stripping is below 200° C., preferably below 180° C. In another embodiment, the temperature during the gas / steam stripping is from 100° C. to 200° C., preferably from 100° C. to 180° C. In another embodiment, the temperature during the gas / steam stripping is from 120° C. to 170° C. In another embodiment, the temperature during the gas / steam stripping is from 140° C. to 160° C.

[0096] In one embodiment, gas / steam stripping is performed for a period of up to 48 hours. In another embodiment, gas / steam stripping is performed for a period of 1 to 24 hours. In another embodiment, gas / steam stripping is performed for a period of 2 to 12 hours. In another embodiment, gas / steam stripping is performed for a period of 4 to 7 hours.

[0097] In one embodiment of the invention, the pressure of the gas / steam during the gas / steam stripping is up to 100 bar, preferably up to 20 bar. In another embodiment, the pressure of the gas / steam during the gas / steam stripping is 0.1 bar to 20 bar. In another embodiment, the pressure of the gas / steam during the gas / steam stripping is 0.5 bar to 10 bar. In another embodiment, the pressure of the gas / steam during the gas / steam stripping is 1 bar to 6 bar. In one embodiment, the temperature during the steam / gas stripping is below 200°C, preferably below 180°C; and the pressure of the steam / gas during the steam / gas stripping is up to 100 bar, preferably up to 20 bar. In one embodiment, the temperature during the gas / steam stripping is 120°C to 170°C, and the pressure of the gas / steam during the gas / steam stripping is 0.1 bar to 20 bar. In one embodiment, the temperature during the gas / steam stripping is 120°C to 170°C, and the pressure of the gas / steam during the gas / steam stripping is 0.5 bar to 10 bar. In another embodiment, the temperature during gas / steam stripping is 140°C to 160°C, and the pressure of the gas / steam during gas / steam stripping is 1 bar to 6 bar. In one embodiment, the temperature during gas / steam stripping is 140°C to 160°C, and the pressure of the gas / steam during gas / steam stripping is 0.1 bar to 20 bar. In another embodiment, the temperature during gas / steam stripping is 140°C to 160°C, and the pressure of the gas / steam during gas / steam stripping is 0.5 bar to 10 bar. In another embodiment, the temperature during gas / steam stripping is 140°C to 160°C, and the pressure of the gas / steam during gas / steam stripping is 1 bar to 6 bar. In a specific embodiment, gas / steam stripping is performed at a temperature of 120°C to 170°C and a pressure of 0.5 bar to 10 bar for a period of 1 to 12 hours. In another specific embodiment, the gas / steam stripping is carried out at a temperature of 120 to 170°C and a pressure of 0.5 to 10 bar for a period of 3 to 7 hours.

[0098] In one embodiment of the process of the invention, the amount of gas / steam used for gas / steam stripping is at least 25% by weight relative to the crude product. In another embodiment, the amount of gas / steam used for gas / steam stripping is at least 50% by weight relative to the crude product.

[0099] In one embodiment of the inventive method, the non-polar solvent and water are azeotropically distilled before gas / steam stripping. In one embodiment, the temperature during the azeotropic distillation is less than 200°C, preferably less than 180°C. In another embodiment, the temperature during the azeotropic distillation is 140°C to 180°C. In one embodiment, the temperature during the azeotropic distillation is 140°C to 180°C and the pressure is 1 mbar (absolute) to 2 bar (absolute). In another embodiment, the temperature during the azeotropic distillation is 140°C to 180°C and the pressure is 10 mbar (absolute) to 1 bar (absolute). In another embodiment, the temperature during the azeotropic distillation is 140°C to 180°C and the pressure is 20 mbar (absolute) to 100 mbar (absolute).

[0100] In one embodiment, after gas / steam stripping, the s-triazine derivative is dissolved in a polar solvent for subsequent crystallization of the product. The solvent may be an alcohol as described above.

[0101] In one embodiment of the method of the present invention, the s-triazine derivative is dissolved in a polar solvent, preferably C1-C8-alcohol or water or a mixture thereof. The C1-C8-alcohol includes a linear alcohol, a branched alcohol or a cyclic alcohol or a mixture thereof having 1 to 8 carbon atoms, preferably ethanol, n-propanol, isopropanol, n-butanol, tert-butanol, n-pentanol, n-hexanol, n-octanol, 2-ethylhexanol and cyclohexanol, and ethanol is particularly preferred. Therefore, in another embodiment of the method of the present invention, the s-triazine derivative is dissolved in a C2-C8-alcohol or water or a mixture thereof. In another embodiment, the s-triazine derivative is dissolved in a mixture of at least one C1-C4-alcohol and up to 10% by weight of water, preferably in a mixture of at least one C2-C4-alcohol and up to 10% by weight of water. In another embodiment, the s-triazine derivative is dissolved in a mixture of ethanol and at least one C3- or C4-alcohol and up to 10% by weight of water. Therefore, in another embodiment, the s-triazine derivative is dissolved in the ethanol with up to 10% by weight of water. If the solvent or mixture contains ethanol, common denaturants can be used in addition, such as butan-2-one, 3-methylbutan-2-one, 5-methylheptan-3-one, isopropyl alcohol, petroleum ether, toluene, cyclohexane, 2-methylpropan-2-ol. Therefore, in one embodiment, the at least one C1-C4 alcohol, at least one C2-C4-alcohol, at least one C3- or C4-alcohol only refers to the denaturant added to denature ethanol. Adding a polar solvent reduces the temperature of the container / reactor, thereby avoiding the hydrolysis of the ester of the s-triazine derivative or the transesterification of the s-triazine derivative. Therefore, in one embodiment, the temperature of the container / reactor is reduced before crystallization. In a specific embodiment, before adding a polar solvent, the temperature has been reduced to a certain extent by flash distillation with water. As a side effect, flash distillation further removes solvent residues and optionally impurities. In one embodiment, dissolving the s-triazine derivative in the polar solvent is followed by filtering the solution, crystallizing the s-triazine derivative, washing with a polar solvent and drying.

[0102] As mentioned above, the reaction of cyanuric halide and para-aminobenzoic acid ester is carried out in a non-polar solvent. In one embodiment of the inventive method, the reaction is carried out in an aromatic solvent, and the aromatic solvent is preferably toluene, dimethylbenzene, dimethylbenzene isomer mixture, trimethylbenzene, trimethylbenzene isomer mixture or its mixture. In a preferred embodiment, the solvent is azeotropically dehydrated before the reaction begins. Removing residual water is advantageous with regard to high yield and a small amount of by-products, because cyanuric halide has the tendency of hydrolysis to produce mono-, di- and / or trihydroxy-triazine. In addition, under the process temperature of the rise during the formation of s-triazine derivatives, p-aminobenzoic acid ester, intermediate and / or desired s-triazine derivatives can be partially or completely hydrolyzed and / or re-esterified. In a specific embodiment, water content is less than 300mg / kg.

[0103] In another embodiment of the process according to the invention, the cyanuric halide is introduced as an initial charge in the form of a suspension together with a dehydrated non-polar solvent. In a specific embodiment, the container / reactor is pre-charged with the solvent, preferably at elevated temperature and more preferably at a temperature of 50° C. to 90° C. This is advantageous in order to prevent (partial) hydrolysis of the cyanuric halide at too high a temperature.

[0104] In another embodiment of the inventive method, p-aminobenzoic acid-2-ethylhexyl is added to the non-polar solvent of the dehydration in a separate container / reactor. Preferably, p-aminobenzoic acid-2-ethylhexyl is purified by vacuum distillation in advance. In one embodiment, then the cyanuric halide suspension is quantitatively fed to the p-aminobenzoic acid-2-ethylhexyl in the non-polar solvent of the dehydration to start the reaction. In a specific embodiment, an additional non-polar solvent of the dehydration is added.

[0105] In one embodiment of the method of the present invention, the reaction is carried out at a temperature of 75°C to the boiling point of the solvent used for a period of up to 48 hours. In another embodiment, the reaction is carried out at a temperature of 75°C to the boiling point of the solvent used for a period of 0.5h to 24h. In another embodiment, the reaction is carried out at a temperature of 75°C to the boiling point of the solvent used for a period of 0.5h to 12h. In another embodiment, the reaction is carried out at a temperature of 75°C to the boiling point of the solvent used for a period of 1h to 3h. In another embodiment, the reaction is carried out at a temperature of 100°C to 150°C for a period of 0.5h to 12h. In another embodiment, the reaction is carried out at a temperature of 100°C to 150°C for a period of 1h to 3h. In another embodiment, the reaction is carried out at a temperature of 110°C to 130°C for a period of 0.5h to 12h. In another embodiment, the reaction is carried out at a temperature of 110°C to 130°C for a period of 1h to 3h. Running the reaction for longer reaction times does not negatively affect product yield and purity, but reduces the space-time yield of the process and thus increases waste and cost.

[0106] In another embodiment, a base is added after the reaction to neutralize the reaction mixture. Preferably, the base is selected from ammonia, alkali metal hydroxides, alkali metal carbonates, or alkali metal bicarbonates. In one embodiment, the base is selected from alkali metal carbonates, preferably potassium carbonate or sodium carbonate. In another embodiment, the base is sodium carbonate.

[0107] In one embodiment of the method of the present invention, the cyanuric halide is selected from cyanuric chloride, cyanuric bromide and mixtures thereof. Preferably, the cyanuric halide is cyanuric chloride.

[0108] As mentioned above, the s-triazine derivative with formula (Ia) is prepared by reacting cyanuric halide with p-aminobenzoic acid-2-ethylhexyl ester. In one embodiment of the inventive method, the method further comprises preparing p-aminobenzoic acid-2-ethylhexyl ester, comprising reacting p-nitrobenzoic acid-2-ethylhexyl ester with hydrogen in the presence of a catalyst. In another embodiment, the method further comprises preparing p-nitrobenzoic acid-2-ethylhexyl ester, comprising reacting p-nitrobenzoic acid with 2-ethylhexanol.

[0109] As described above, high-purity s-triazine derivatives can be obtained by the process of the present invention by stripping the purified product with gas / steam. Therefore, in one embodiment, the present invention relates to a s-triazine derivative with a purity of at least 98% by weight of formula (Ia). In another embodiment, the present invention relates to a s-triazine derivative with a purity of at least 99% by weight of formula (Ia). In another embodiment, the present invention relates to a s-triazine derivative with a purity of at least 99% by weight of formula (Ia). In another embodiment, the present invention relates to a s-triazine derivative with a purity of at least 99.5% by weight of formula (Ia). In an even more preferred embodiment, the purity may be at least 99.6%, 99.7%, 99.8% or 99.9% by weight. It may be preferred that the content of a given impurity (such as any one of p-aminobenzoic acid (AB), monohydroxide (MHT) of ethylhexyl triazone, monocarboxylic acid (MCS) of ethylhexyl triazone and monoethyl ester (MEE) of ethylhexyl triazone) in the final product is less than 0.2% by weight, preferably 0.1% by weight or less, more preferably 0.05% by weight or less. In a preferred embodiment, the concentration of AB and / or MCS and / or MHT is 0.2 wt% or less, preferably 0.1 wt% or less, more preferably 0.05 wt% or less. In a preferred embodiment, the concentration of AB is 0.2 wt% or less, preferably 0.1 wt% or less, more preferably 0.05 wt% or less. These values ​​refer to the concentration as measured by HPLC. In addition, optionally, the residual content of solvents (such as xylene) can be 100 ppm or less, preferably 10 ppm or less, as determined by GC, in addition to low concentrations of other impurities.

[0110] In various embodiments, the s-triazine derivative is the tautomeric form I of 2,4,6-triphenylamino-p-(carbonyl-2'ethylhexyl-1'-oxy)-1,3,5-triazine. The tautomeric form can be obtained by synthesis as described in WO 03 / 074499A1 or as described in Example 1 below, and then subjected to further purification steps as described herein. Therefore, the present invention also relates to the tautomeric form I of 2,4,6-triphenylamino-p-(carbonyl-2'ethylhexyl-1'-oxy)-1,3,5-triazine, which is obtainable by the process of the present invention.

[0111] In various embodiments, the tautomeric purity of the product (i.e., 2,4,6-trianilino-p-(carbonyl-2'ethylhexyl-1'-oxy)-1,3,5-triazine) as determined by IR spectroscopy is such that there are no -1 The carbonyl double band at 1697 cm -1 It may also be preferred that the single band at about 1697 cm -1 The absence of a shoulder on the single band at 2,4,6-triphenylamino-p-(carbonyl-2'ethylhexyl-1'-oxy)-1,3,5-triazine indicates the presence of a certain amount of one or more undesired tautomeric forms. It has been found that the tautomeric purity of the product of the synthesis described in Example 1 below and also in WO 03 / 074499A1 is not altered by the subsequent additional steam / gas stripping purification step.

[0112] In addition, the s-triazine derivatives obtained by this method have optimal physical properties, for example in terms of particle size. Therefore, in one embodiment, the present invention relates to a s-triazine derivative in the form of pourable or flowable particles, preferably in crystalline form, particularly preferably with an average particle size of 5 μm to up to 500 μm and / or a bulk density of greater than 0.2 g / mL. In another embodiment, the present invention relates to a s-triazine derivative with an average particle size of 5 μm to up to 500 μm and / or a bulk density of 0.3 g / mL to 1.5 g / mL. In another embodiment, the present invention relates to a s-triazine derivative with an average particle size of 5 μm to up to 500 μm and / or a bulk density of 0.4 g / mL to 0.8 g / mL. In another embodiment, the present invention relates to a s-triazine derivative with an average particle size of 20 μm to up to 200 μm and / or a bulk density of 0.4 g / mL to 0.8 g / mL. In another embodiment, the present invention relates to a s-triazine derivative having an average particle size of 30 μm to up to 100 μm and / or a bulk density of 0.4 g / mL to 0.8 g / mL. S-triazine derivatives having these properties are advantageous, for example, in terms of high solubility and stability in oils used in cosmetic formulations. In addition, the flowability and particle size provide advantages for easy handling and dosing.

[0113] Therefore, in one embodiment, the present invention relates to a s-triazine derivative having the above characteristics, which is obtainable by the method of the present invention. As mentioned above, it is known that s-triazine derivatives have UV absorption efficiency and high light stability in the UVB and UVA regions. In one embodiment, the present invention relates to the use of s-triazine derivatives of formula (Ia) as photoprotective agents. Considering the high purity and physical properties of the s-triazine derivatives obtained by the method of the present invention, it is advantageous to use them as photoprotective agents for example for cosmetic preparations.

[0114] Therefore, in one embodiment, the present invention relates to a cosmetic preparation comprising an s-triazine derivative of formula (Ia). In particular, in one embodiment, the present invention relates to a cosmetic preparation comprising an s-triazine derivative of formula (Ia) in the form of pourable or flowable particles, preferably in crystalline form, and particularly preferably having an average particle size and bulk density as described above.

[0115] The present invention is further illustrated by the following examples.

[0116] Examples

[0117] The following abbreviations are used: AB: p-aminobenzoic acid, ABE: 2-ethylhexyl p-aminobenzoate, MHT: monohydroxide of ethylhexyl triazone, MCS: monocarboxylic acid of ethylhexyl triazone, MEE: monoethyl ester of ethylhexyl triazone, MCT: monochloride of ethylhexyl triazone, EHT: ethylhexyl triazone.

[0118] In the examples, GC analysis was performed on an Agilent Technologies 7890B using the following conditions and parameters:

[0119] Detector: FID

[0120] Solvent: dichloromethane

[0121] Column: HP-5 from Agilent Technologies (30 m, 0.32 mm ID, 0.25 μm film thickness)

[0122] Carrier gas: Nitrogen 1mL / min (split 100:1)

[0123] Injector temperature: 270°C

[0124] Detector temperature: 300°C

[0125] Temperature program: 80°C for 3 min, then 50°C / min up to 130°C and hold at 130°C for 4 min.

[0126] In the examples, HPLC analysis was performed on an Agilent Technologies 1260 using the following conditions and parameters:

[0127] Detector: UV at 295nm

[0128] Column: PerfectBond C8-HD (5 μm, 125×4 mm) from MZ Analysentechnik

[0129] Flow rate: 0.7mL / min

[0130] Solvent: THF (solvent A) and 0.1% H2SO4 aqueous solution (pH 1.5) (solvent B)

[0131] Gradient Program:

[0132] Time [min] Solvent A [vol%] Solvent B [vol%] 0.00 40.0 60.0 15.00 70.0 30.0 25.00 70.0 30.0 30.00 40.0 60.0 35.00 40.0 60.0

[0133] Example 1: Preparation of ethylhexyl triazone (Uvinul T 150)

[0134] 378 kg of xylenes are refluxed in reactor 1 until the water content is less than 250 mg / kg. 180 kg of xylenes as purified are purged into a separate reactor 2. The transfer is preferably carried out at a temperature of 60°C-80°C. Thereafter, 100 kg of cyanuric chloride is added to reactor 2 and stirred to receive a suspension of cyanuric chloride in xylene at an elevated temperature of less than 100°C. Thereafter, 430 kg of purified 2-ethylhexyl p-aminobenzoate, which has been previously purified by distillation, is quantitatively fed to the remaining purified xylenes in reactor 1. Thereafter, the suspension in reactor 2 and an additional 110 l of pure xylene are quantitatively fed to reactor 1 to start the reaction. During the reaction, reactor 1 is heated to a maximum of 122°C. After 2 hours, 175 kg of 20 wt % Na2CO3 in water is added to reactor 1 in 4 steps to reach a pH value of 6.5 to 8.0. Afterwards, the contents of reactor 1 are transferred to reactor 3. Afterwards, xylene and water are azeotropically distilled at 155°C and a pressure of 30 mbar (absolute) for 6 hours. Afterwards, the temperature is set to 160°C. In this step, the xylene content is 5500ppm (determined by GC). Afterwards, the remaining evanescent residue (mainly water and xylene) is stripped by adding water vapor at a pressure of 5.5 bar (absolute) and a temperature of 155°C and a flow rate of 50kg / h for 5 hours. Afterwards, the temperature of reactor 3 is reduced by flashing with 11l of water. Further temperature reduction is achieved by adding 790kg of purified denatured ethanol (e.g., 100 liters of ethanol are denatured by adding 78g of tert-butyl alcohol and 5kg of isopropanol) to obtain an ethanol solution of ethylhexyl triazone. Afterwards, the ethylhexyl triazone solution is filtered, crystallized and washed with additional ethanol, and then dried to obtain a pure ethylhexyl triazone powder with a yield of 420kg. The characterization of the final product by HPLC is provided in Table 1 and the characterization of the final product by IR spectroscopy is provided in Figure 2 The IR spectrum showed that the obtained product had high tautomeric purity (tautomer I) because there was no -1 There is no peak or shoulder in the range, but only the peak at 1690cm -1 The xylene content measured by GC was <10 ppm.

[0135] Table 1.

[0136]

[0137] Examples 2 to 6: Purification by steam stripping

[0138] Following a reaction procedure similar to that described in Example 1, 1254 g of the reaction product of Reactor 1 was transferred to Reactor 3 and azeotropically distilled. Afterwards, the remaining evanescent residue was stripped by adding water vapor at a temperature of 155° C., pressure p and flow rate f for a period of time t. Afterwards, the sample was filtered, washed with ethanol and dried. The characterizations performed by HPLC (AB, MHT, MCS, MEE) and GC (xylene) are provided in Table 2.

[0139] Table 2.

[0140]

[0141] Example 7: Purification by gas stripping

[0142] Following a reaction procedure similar to that described in Example 1, 1254 g of the reaction product of Reactor 1 was transferred to Reactor 3 and azeotropically distilled. Afterwards, the remaining evanescent residue was stripped with nitrogen stripping. Nitrogen was added at a pressure of 0.6 barg and a flow rate of 0.33 liters / minute for a period of 360 minutes. Afterwards, the sample was filtered, washed with ethanol and dried. The characterizations performed by HPLC (AB, MHT, MCS, MEE) and GC (xylene) are provided in Table 3.

[0143] Table 3.

[0144]

[0145] Example 8: Purification by steam stripping

[0146] Following a reaction procedure similar to that described in Example 1, 1254 g of the reaction product of Reactor 1 was transferred to Reactor 3 and azeotropically distilled. Afterwards, the remaining evanescent residue was stripped with ethanol vapor stripping. Ethanol vapor was added at a pressure of 2.0 barg and a flow rate of 1.85 g / min for a period of 300 minutes. Afterwards, the sample was filtered, washed with ethanol and dried. Characterization by HPLC (AB, MHT, MCS, MEE) and GC (xylene) is provided in Table 4.

[0147] Table 4.

[0148]

[0149] A side effect of ethanol stripping is higher amounts of the monoethyl ester of ethylhexyl triazone (MEE) as a byproduct, most likely resulting from transesterification.

[0150] Example 9: Purification without any stripping

[0151] The reaction product after azeotropic distillation was filtered, washed with ethanol and dried. Table 5 provides the characterizations performed by HPLC (AB, MHT, MCS, MEE) and GC (xylene).

[0152] Table 5.

[0153]

[0154] If no gas / steam stripping is performed, the xylene content in the product increases significantly, as can be seen by comparing the results of Example 9 with the results of Examples 1 to 8. Surprisingly, the amount of impurities / by-products (AB, MHT, MCS, MEE) present in the product is also higher if no gas / steam stripping is performed.

Claims

1. A method for preparing a triazine derivative having formula (I) The method comprises reacting the following in a non-polar solvent: (i) cyanuric halides; and (ii) p-Aminobenzoic acid esters in R 1 , R 2 and R 3 are the same or different and are independently selected from hydrogen, alkali metals, ammonium, substituted ammonium, C1-C 12 - a group consisting of an alkyl group or a polyoxyethylene group; and in The reaction product is purified by gas / steam stripping.

2. The method according to claim 1, wherein: R 2 =R 1 ; And preferably R 3 =R 2 =R 1 ; And particularly preferably R 1 , R 2 , and R 3 Each represents a 2-ethylhexyl group.

3. The method according to claim 1 or 2, wherein: The s-triazine derivative is 2,4,6-trianilino-p-(carbonyl-2'-ethylhexyl-1'-oxy)-1,3,5-triazine having the following chemical formula (Ia):

4. The method according to any one of claims 1 to 3, wherein: Gas / steam stripping is performed by feeding the reaction product into a vessel or reactor and stripping off the non-polar solvent and optionally by-products by adding water or polar solvent or water vapor or polar solvent vapor or gas or mixtures thereof into the vessel or reactor.

5. The method according to any one of claims 1 to 4, wherein: Gas / steam stripping is performed by adding water vapor, ethanol vapor or nitrogen, preferably water vapor or nitrogen, preferably from the bottom part of the vessel / reactor.

6. The method according to any one of claims 1 to 5, wherein: The temperature during steam / gas stripping is below 200°C, preferably below 180°C; and / or wherein the pressure of the steam / gas during steam / gas stripping is up to 100 bar, preferably up to 20 bar.

7. The method according to any one of claims 1 to 6, wherein: After stripping, the s-triazine derivative is dissolved in a polar solvent, preferably a C1 -C8 alcohol or water or a mixture thereof.

8. The method according to any one of claims 1 to 7, wherein: After stripping, the s-triazine derivative is dissolved in a mixture of at least one C1-C4-alcohol and up to 10% by weight of water, preferably in a mixture of at least one C2-C4-alcohol and up to 10% by weight of water.

9. The method according to any one of claims 1 to 8, wherein: The reaction is carried out in an aromatic solvent, which is preferably toluene, xylene, a xylene isomer mixture, trimethylbenzene, a trimethylbenzene isomer mixture, or a mixture thereof, wherein the solvent is particularly preferably azeotropically dehydrated before the reaction is started.

10. The method according to any one of claims 1 to 9, wherein: The reaction is carried out at a temperature of 75° C. to the boiling point of the solvent used for a period of up to 48 h.

11. The method according to any one of claims 1 to 10, wherein: The cyanuric halide is selected from cyanuric chloride, cyanuric bromide and mixtures thereof, and wherein the cyanuric halide is preferably cyanuric chloride.

12. The method according to any one of claims 3 to 11, wherein: The method further includes preparing 2-ethylhexyl p-aminobenzoate, comprising reacting 2-ethylhexyl p-nitrobenzoate with hydrogen in the presence of a catalyst.

13. The method according to claim 12, wherein: The method further includes preparing 2-ethylhexyl p-nitrobenzoate, comprising reacting p-nitrobenzoic acid with 2-ethylhexanol.

14. A s-triazine derivative of formula (I) having a purity of at least 98% by weight, preferably at least 99% by weight, more preferably at least 99.5% by weight, even more preferably at least 99.8% by weight.

15. The s-triazine derivative according to claim 14, wherein The concentration of each of p-aminobenzoic acid (AB), monohydroxide of ethylhexyl triazone (MHT), monocarboxylic acid of ethylhexyl triazone (MCS) and monoethyl ester of ethylhexyl triazone (MEE) in the final product is less than 0.2 wt %, preferably 0.1 wt % or less, more preferably 0.05 wt % or less, as measured by HPLC.

16. The s-triazine derivative according to claim 14 or 15, wherein The residual content of solvent, preferably xylene, is 100 ppm or less, preferably 10 ppm or less, as determined by GC.

17. The s-triazine derivative according to any one of claims 14 to 16, in the form of pourable or flowable granules, preferably in crystalline form, particularly preferably with an average particle size of 5 μm up to 500 μm and / or a bulk density of more than 0.2 g / mL.

18. The s-triazine derivative according to any one of claims 14 to 17, obtainable by a process according to any one of claims 1 to 12.

19. Use of the s-triazine derivative of formula (I) according to any one of claims 14 to 18 as a photoprotective agent.

20. A cosmetic preparation comprising the s-triazine derivative of formula (I) according to any one of claims 14 to 18.

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