Improved process for preparing s-triazine derivatives

Abstract

The present invention relates to a process for preparing s-triazine derivatives, which comprises reacting a cyanuric halide with a p-aminobenzoic acid ester in a non-polar solvent, and purifying the reaction product by gas / steam stripping. The present invention also relates to s-triazine derivatives with high purity and / or optimal particle properties, their use as photoprotective agents, and cosmetic compositions containing the same.

Description

[Technical Field]

[0001] The present invention relates to a process for preparing s-triazine derivatives, which comprises reacting a cyanuric halide with a p-aminobenzoic acid ester in a non-polar solvent, and purifying the reaction product by gas / steam stripping. The present invention also relates to s-triazine derivatives with high purity and / or optimal particle properties, their use as photoprotective agents, and cosmetic compositions containing the same. [Background technology]

[0002] s-Triazine derivatives, i.e., 1,3,5-triazine derivatives, are known to exhibit absorption efficiency across a wide UV range, absorbing both UVB and UVA rays while also exhibiting high photostability. Therefore, s-triazine derivatives are used as photoprotective agents, particularly in cosmetics and sunscreen compositions. Considering that these applications involve contact with human skin, s-triazine derivatives must be highly pure. Typically, s-triazine derivatives are prepared by reacting cyanuric halide (also known as "cyanuric acid halide") with p-aminobenzoic acid esters in a nonpolar solvent. To achieve the desired product quality, by-products and residual solvents must be removed, which is not only time-consuming but also energy- and cost-intensive for large-scale industrial applications. Desolventization is particularly difficult because rapid drying at excessively high temperatures can produce products that are poorly soluble in the oils used in cosmetics.

[0003] EP 3674293 A1 describes a process for reacting a cyanuric halide with a p-aminobenzoic acid ester, followed by precipitation of the product on carbon and Hyflow TM A process for synthesizing s-triazine derivatives has been disclosed, which includes a step of purifying the derivatives using a bed. However, this procedure involves an additional adsorption step and uses a large amount of solvent, which increases the complexity and cost. Especially considering large-scale applications, this procedure is economically disadvantageous.

[0004] EP 2688875 discloses a technically simple and economical synthesis process for s-triazine derivatives, which involves the reaction of cyanuric halide with p-aminobenzoic acid ester, with significantly reduced solvent usage. However, the purity of the product achieved in the laboratory examples is only 90.5 area % and the content of minor components is 0.5 wt %. Summary of the Invention [Problem to be solved by the invention]

[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 and with cost-effective purification of the product.

[0006] In this context, it was desirable to provide a process that not only ensures the production of a highly pure product, but also provides a product that exhibits high solubility and stability in cosmetics. A further objective was to provide a process that is suitable for large-scale applications. Furthermore, it was desirable for this process to be economically and environmentally advantageous, for example, requiring less solvent and fewer process steps. [Means for solving the problem]

[0007] Surprisingly, it has been found that the above mentioned objects can be achieved by the process described herein below and in the claims.

[0008] In one embodiment, the present invention provides a compound of formula (I): [ka] 1. A process for preparing an s-triazine derivative of formula (I), which comprises reacting in a non-polar solvent: (i) cyanuric halide; (ii) p-aminobenzoic acid esters: [ka] (In the formula, R 1 , R 2 and R 3 are the same or different and are hydrogen, alkali metal, ammonium, substituted ammonium, C1 to C 12 -alkyl or polyoxyethylene) reacting with; The process involves the reaction product being purified by gas / steam stripping.

[0009] Surprisingly, the present inventors have found that the process of the present invention allows the production of highly pure s-triazine derivatives without complex product purification. In particular, the s-triazine derivatives can be obtained in high purity and high yield by purifying the product by gas / steam stripping. In contrast to the purification methods described in the prior art, such as those using adsorption techniques, the gas / steam stripping method of the present invention can be easily applied to large industrial scales. Furthermore, when purification by gas / steam stripping is performed before further purification steps such as recrystallization, washing, and drying, the impurities introduced into the solvents used in these purification steps are reduced, making the subsequent purification and regeneration of the solvents economically and environmentally advantageous. In particular, since not only the solvent used in the reaction but also any by-products are removed, the solvents used in subsequent purification steps are not contaminated. Furthermore, it has been found that the process of the present invention allows for a significant increase in product yield. Furthermore, the resulting s-triazine derivatives have optimal physical properties in terms of particle size, flowability, and solubility and stability in oils used in cosmetic formulations.

[0010] The process of the present invention is therefore particularly advantageous in that it combines providing products in optimum purity and yield with an efficient and economical process for large scale applications. [Brief explanation of the drawings]

[0011] [Figure 1]Illustrates a preferred method of carrying out gas / steam stripping. [Figure 2] Characterization by IR spectroscopy is shown. DETAILED DESCRIPTION OF THE INVENTION

[0012] 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.

[0013] In one embodiment of the present invention, the s-triazine derivative has the following chemical formula (Ia): [ka] The compound is 2,4,6-trianilino-p-(carbo-2'-ethylhexyl-1'-oxy)-1,3,5-triazine having the formula:

[0014] In one embodiment of the present invention, gas / steam stripping is carried out by feeding the reaction product to a vessel or reactor and stripping off the non-polar solvent and optionally the by-products by adding water or a polar solvent or water vapor or a polar solvent vapor or gas or a mixture thereof to the vessel or reactor.

[0015] In one embodiment of the present invention, gas / steam stripping is carried out by adding water vapor, ethanol vapor or nitrogen gas, preferably water vapor or nitrogen gas, preferably from the bottom of the vessel / reactor.

[0016] In one embodiment of the present invention, the temperature during steam / gas stripping is below 200°C, preferably below 180°C; and / or the steam / gas pressure during steam / gas stripping is at most 100 bar, preferably at most 20 bar.

[0017] In one embodiment of the present invention, the s-triazine derivative after stripping is dissolved in a polar solvent, preferably a C1-C8 alcohol or water or a mixture thereof.

[0018] In one embodiment of the present invention, the s-triazine derivative after stripping 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.

[0019] In one embodiment of the present invention, the reaction is carried out in an aromatic solvent, preferably toluene, xylene, a xylene isomer mixture, trimethylbenzene, a trimethylbenzene isomer mixture or a mixture thereof, which solvent is particularly preferably azeotropically dehydrated before the start of the reaction.

[0020] In one embodiment of the present invention, the reaction is carried out at a temperature between 75° C. and the boiling point of the solvent used for up to 48 hours.

[0021] In one embodiment of the present invention, the cyanuric halide is selected from cyanuric chloride, cyanuric bromide and mixtures thereof, preferably the cyanuric halide is cyanuric chloride.

[0022] In one embodiment of the present invention, the process 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.

[0023] In one embodiment of the present invention, the process further comprises preparing p-nitrobenzoic acid-2-ethylhexyl ester comprising reacting p-nitrobenzoic acid with 2-ethylhexanol.

[0024] In one embodiment, the present invention relates to an s-triazine derivative of formula (I), particularly 2,4,6-trianilino-p-(carbo-2'ethylhexyl-1'-oxy)-1,3,5-triazine, having a purity of at least 98% by weight, preferably at least 99% by weight, and more preferably at least 99.5% by weight. In 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 the tautomer I of 2,4,6-trianilino-p-(carbo-2'ethylhexyl-1'-oxy)-1,3,5-triazine (disclosed in WO 03 / 074499 A1).

[0025] In one embodiment, the present invention relates to s-triazine derivatives in pourable or flowable particulate form, preferably crystalline form, particularly preferably having an average particle size of 5 μm up to 500 μm and / or a bulk density of more than 0.2 g / mL.

[0026] In one embodiment, the present invention relates to an s-triazine derivative obtainable by the process of the present invention. In one embodiment, the s-triazine derivative of formula (I) is tautomer I of 2,4,6-trianilino-p-(carbo-2'ethylhexyl-1'-oxy)-1,3,5-triazine.

[0027] In one embodiment, the present invention relates to the use of s-triazine derivatives of formula (I) as photoprotective agents.

[0028] In one embodiment, the present invention relates to a cosmetic preparation comprising an s-triazine derivative of formula (I).

[0029] Preferred embodiments of the present invention are set forth in the claims, the description and the examples. It is to be understood that the features of the subject matter of the present invention mentioned above and hereinafter exemplified are not only preferred in each given combination, but also in other combinations without departing from the scope of the present invention.

[0030] The following definitions are relevant to the above-described embodiments of the present invention.

[0031] In the context of the present invention, the s-triazine derivatives of formula (I) are obtained by reacting a cyanuric halide with the same or different p-aminobenzoic acid ester in a non-polar solvent.

[0032] As used herein, the term "s-triazine derivative of formula (I)" or "s-triazine derivative according to the present invention" or "s-triazine derivative" refers to a compound of formula (I) as defined herein, i.e., a 2,4,6-trisubstituted 1,3,5-triazine, in which the substituents at the 2-, 4-, and 6-positions are derived from the same or different p-aminobenzoic acid esters, such that these p-aminobenzoic acid esters are attached via the p-amino group. As shown above, the substituents attached to the 2-, 4-, and 6-positions are derived from the same or different p-aminobenzoic acid esters. Thus, R 1 , R 2 and R 3 may be the same or different according to the present invention. However, preferably R 1 =R 2 =R 3 That is, the substituents attached to the 2-, 4-, and 6-positions are derived from the same p-aminobenzoic acid ester.

[0033] Nonpolar solvents generally include alkanes, aromatic solvents, and ethers, or mixtures thereof. Preferred nonpolar solvents according to the present invention are aromatic solvents, particularly toluene, xylene, a xylene isomer mixture, trimethylbenzene, a trimethylbenzene isomer mixture, or mixtures thereof. Furthermore, it is preferable to azeotropically dehydrate the solvent before starting the reaction. Because cyanuric halide tends to hydrolyze to form mono-, di-, and / or trihydroxytriazine, residual moisture reduces the yield and increases the amount of by-products. Furthermore, high process temperatures during the formation of s-triazine derivatives can cause partial or complete hydrolysis of the p-aminobenzoic acid ester, intermediates, and / or product s-triazine derivatives.

[0034] As used herein, the term "cyanuric halide" or "cyanuric acid halide" refers to a 1,3,5-triazine substituted with the same halide at the 2-, 4-, and 6-positions. The cyanuric halide is preferably cyanuric bromide, cyanuric chloride, or a mixture thereof, more preferably cyanuric chloride (CAS No.: 108-77-0). Cyanuric halide is a highly reactive chemical species. The substitution of three halides at the 2-, 4-, and 6-positions to obtain 2,4,6-trisubstituted 1,3,5-triazines can be easily achieved using nucleophiles. Since three halides are substituted in such a reaction, the cyanuric halide is typically reacted with at least three equivalents of a nucleophile. When different types of nucleophiles are used, the molar ratio of cyanuric acid to nucleophile is also typically at least 1:3, preferably 1:3 to 1:5. However, the nucleophile in this case may represent multiple different types of nucleophiles. In that case, the reaction can be carried out stepwise such that different types of nucleophiles react sequentially with the cyanuric halide.

[0035] As used herein, the term "p-aminobenzoic acid ester" or "4-aminobenzoic acid ester" refers to a compound having the following general formula: [ka] (In the formula, R 1 , R 2 and R 3 are the same or different and are hydrogen, alkali metal, ammonium, substituted ammonium, C1 to C 12 -alkyl or polyoxyethylene).

[0036] As shown above, the s-triazine derivatives of formula (I) can be obtained by reacting a cyanuric halide with the same or different p-aminobenzoic acid esters. When the molar ratio of cyanuric halide to p-aminobenzoic acid ester is specified as 1:3 to 1:5 in accordance with the present invention, this molar ratio represents the molar ratio of cyanuric halide to p-aminobenzoic acid ester, regardless of whether the p-aminobenzoic acid esters used in the reaction are the same or different. In other words, when 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 should be understood to mean that the cyanuric halide reacts with 3 to 5 equivalents of one specific p-aminobenzoic acid ester. On the other hand, the cyanuric halide reacted with the p-aminobenzoic acid ester may be 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 the 3 to 5 equivalents of p-aminobenzoic acid ester to cyanuric halide represents the total amount of different types of p-aminobenzoic acid esters.

[0037] Preferably, the p-aminobenzoic acid ester is purified by distillation before use.

[0038] As used herein, "alkali metal" includes sodium, potassium, or lithium, with sodium or potassium being preferred.

[0039] As used herein, the term "substituted ammonium" refers to ammonium in which one to four hydrogen atoms are independently replaced with C1-C6-alkyl, preferably C1-C2-alkyl.

[0040] As used herein, "C1-C 12 The term "alkyl" refers to a straight or branched alkyl group having 1 to 12 carbon atoms. Preferred alkyl groups are C6-C 10 -alkyl, with 2-ethylhexyl being particularly preferred.

[0041] As used herein, "polyoxyethylene" refers to a compound having the structure H-(O-CH-CH) n It refers to a substituent having —OH, and in the formula, n is 1 to 1000, preferably 1 to 100.

[0042] The process for preparing an s-triazine derivative of the present invention further includes purifying the product by gas / steam stripping. Generally, stripping is a physical separation process that uses a steam stream to remove components from a liquid sample. As used herein, gas / steam stripping is carried out by supplying the reaction product to a vessel or reactor and adding water, a polar solvent, water vapor, a polar solvent vapor, a gas, or a mixture thereof to the vessel or reactor to strip off the nonpolar solvent and, optionally, by-products. Therefore, gas / steam stripping according to the present invention also includes flashing, which refers to a process in which liquid-phase water or a polar solvent is added from the top of the vessel / reactor. Preferably, gas / steam stripping is carried out by adding water vapor, a polar solvent vapor, a gas, or a mixture thereof from the top or bottom of the vessel / reactor. More preferably, gas / steam stripping is carried out by adding water vapor, a polar solvent vapor, a gas, or a mixture thereof from the bottom of the vessel / reactor. The overhead stream containing the desorbed solvent and optional reaction by-products can be condensed and separated. The term "steam" as used herein in connection with gas / steam stripping refers to water vapor or polar solvent vapor, particularly alcohol vapor, preferably ethanol vapor. The term "gas" as used herein in connection with gas / steam stripping refers to a non-chemically reactive inert gas, particularly nitrogen gas. As noted above, the term gas / steam stripping according to the present invention also includes flashing or flushing water or polar solvent, preferably ethanol, in the liquid phase.

[0043] As used herein, pressure in "bar" units refers to relative or gauge pressure, with zero reference to ambient atmospheric pressure, and is therefore equal to absolute pressure minus atmospheric pressure. Gauge pressure is sometimes expressed in "barg" units. Only when the "bar(abs)" unit is used does pressure refer to absolute pressure.

[0044] FIG. 1 illustrates a preferred method of carrying out gas / steam stripping according to the present invention, i.e., feeding the reaction product to a vessel or reactor and stripping 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 through the bottom of the vessel / reactor.

[0045] Preferred embodiments of the process of the present invention are described below: The following general considerations apply to the process:

[0046] Generally, the reaction steps are carried out in a reaction vessel conventionally used for such reactions, such as a conventional stirred tank reactor. The reaction can be carried out continuously, semi-batch, or batchwise. Particularly preferably, the process of the present invention is carried out in a semi-batch mode, where at least one reactant is fed to the reaction vessel and at least one other reactant is added over a specific charging time. Generally, the process steps are preferably carried out under atmospheric pressure. Details regarding reaction temperatures are provided below. Reaction completion can be monitored by methods known to those skilled in the art, such as thin layer chromatography, GC, HPLC, or NMR.

[0047] Unless otherwise indicated, the reactants can in principle be contacted with one another in any desired order.

[0048] Furthermore, it is emphasized that the reaction process can be carried out on a technical scale.

[0049] Preferred embodiments of the present invention are set forth below. It should be understood that the preferred embodiments of the present invention are preferred both alone and in combination with each other.

[0050] As indicated above, the present invention provides a process for preparing s-triazine derivatives of formula (I) shown above, which comprises reacting a cyanuric halide with a p-aminobenzoic acid ester: [ka] (In the formula, R 1 , R2 and R 3 are the same or different and are hydrogen, alkali metal, ammonium, substituted ammonium, C1 to C 12 and p-aminobenzoic acid ester (independently selected from the group consisting of s-alkyl, hydroxypropyl ...

[0051] In one embodiment of the process 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. 1 , R 2 and R 3 where each represents a 2-ethylhexyl group, the product is 2,4,6-trianilino-p-(carbo-2'-ethylhexyl-1'-oxy)-1,3,5-triazine, which represents the well-known and highly effective UV absorber ethylhexyltriazone (Uvinul T 150, CAS number: 88122-99-0).

[0052] Thus, in one embodiment of the process of the present invention, the s-triazine derivative has the following chemical formula (Ia): [ka] The compound is 2,4,6-trianilino-p-(carbo-2'-ethylhexyl-1'-oxy)-1,3,5-triazine having the formula:

[0053] As indicated above, gas / steam stripping is carried out to purify the product s-triazine derivative of formula (I).

[0054] In one embodiment of the process of the present invention, gas / steam stripping is carried out by feeding the reaction product to a vessel or reactor and stripping the nonpolar solvent by adding water, a polar solvent, water vapor, a polar solvent vapor, or a gaseous mixture thereof to the vessel or reactor from the top or bottom of the vessel / reactor. Preferably, water vapor, a polar solvent vapor, or a gaseous mixture thereof is added from the bottom of the vessel / reactor. When stripping is carried out using a polar solvent vapor, ethanol vapor is preferably used. When stripping is carried out using a gas, nitrogen gas is preferably used. Thus, in one embodiment, gas / steam stripping is carried out by adding water vapor, ethanol vapor, or nitrogen gas, preferably water vapor or nitrogen gas, preferably from the bottom of the vessel / reactor. The overhead stream containing the desorbed solvent and optional reaction by-products can be condensed and separated. Therefore, gas / steam stripping is advantageous for effectively removing residual solvent and by-products from the desired s-triazine derivative. As a result, s-triazine derivatives are obtained in high yield and purity. Furthermore, gas / steam stripping has the advantage that it is applicable to large-scale industrial scale. Furthermore, it has been found that this process offers the advantage of obtaining reaction products with optimal physical properties in terms of solubility and stability in oils used in cosmetic formulations. As mentioned above, if the temperature used to remove the solvent is too high, the solubility in the oil decreases.

[0055] In one embodiment of the process of the present invention, the temperature during gas / steam stripping is less than 200°C, preferably less than 180°C. In another embodiment, the temperature during gas / steam stripping is between 100°C and 200°C, preferably between 100°C and 180°C. In another embodiment, the temperature during gas / steam stripping is between 120°C and 170°C. In another embodiment, the temperature during gas / steam stripping is between 140°C and 160°C.

[0056] In one embodiment, the gas / steam stripping is carried out for up to 48 hours. In another embodiment, the gas / steam stripping is carried out for 1 to 24 hours. In another embodiment, the gas / steam stripping is carried out for 2 to 12 hours. In another embodiment, the gas / steam stripping is carried out for 4 to 7 hours.

[0057] In one embodiment of the present invention, the gas / steam pressure during gas / steam stripping is up to 100 bar, preferably up to 20 bar. In another embodiment, the gas / steam pressure during gas / steam stripping is 0.1 bar to 20 bar. In another embodiment, the gas / steam pressure during gas / steam stripping is 0.5 bar to 10 bar. In another embodiment, the gas / steam pressure during gas / steam stripping is 1 bar to 6 bar. In one embodiment, the temperature during steam / gas stripping is less than 200°C, preferably less than 180°C; the steam / gas pressure during steam / gas stripping is up to 100 bar, preferably up to 20 bar. In one embodiment, the temperature during gas / steam stripping is 120°C to 170°C, and the gas / steam pressure during gas / steam stripping is 0.1 bar to 20 bar. In one embodiment, the temperature during gas / steam stripping is 120°C to 170°C, and the gas / steam pressure 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 gas / steam pressure 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 gas / steam pressure 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 gas / steam pressure 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 steam / gas pressure during gas / steam stripping is 1 bar to 6 bar. In one particular embodiment, gas / steam stripping is carried out 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 particular embodiment, gas / steam stripping is carried out at a temperature of 120° C. to 170° C. and a pressure of 0.5 bar to 10 bar for a period of 3 to 7 hours.

[0058] In one embodiment of the process of the present 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.

[0059] In one embodiment of the process of the present invention, the non-polar solvent and water are azeotropically distilled prior to gas / steam stripping. In one embodiment, the temperature during azeotropic distillation is less than 200°C, preferably less than 180°C. In another embodiment, the temperature during azeotropic distillation is between 140°C and 180°C. In one embodiment, the temperature during azeotropic distillation is between 140°C and 180°C and the pressure is between 1 mbar (abs) and 2 bar (abs). In another embodiment, the temperature during azeotropic distillation is between 140°C and 180°C and the pressure is between 10 mbar (abs) and 1 bar (abs). In another embodiment, the temperature during azeotropic distillation is between 140°C and 180°C and the pressure is between 20 mbar (abs) and 100 mbar (abs).

[0060] In one embodiment, the s-triazine derivative is dissolved in a polar solvent after gas / steam stripping followed by crystallization of the product.

[0061] In one embodiment of the process of the present invention, the s-triazine derivative is dissolved in a polar solvent, preferably a C1-C8 alcohol or water, or a mixture thereof. C1-C8 alcohols include linear, branched, or cyclic alcohols having 1 to 8 carbon atoms or mixtures thereof, preferably ethanol, n-propanol, isopropanol, n-butanol, tert-butanol, n-pentanol, n-hexanol, n-octanol, 2-ethylhexanol, and cyclohexanol, with ethanol being particularly preferred. Therefore, in another embodiment of the process of the present invention, the s-triazine derivative is optionally dissolved in an 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 a mixture of at least one C2-C4 alcohol and up to 10% by weight of water. In other embodiments, the s-triazine derivative is dissolved in a mixture of ethanol and at least one C3- or C4-alcohol with up to 10% by weight of water. In other embodiments, the s-triazine derivative is dissolved in ethanol containing up to 10% by weight of water. The water content may be lower, for example, up to 5% by weight, up to 3% by weight, or even less. In some embodiments, the water content may be less than 1% by weight. In various embodiments, the s-triazine derivative is washed with pure ethanol.

[0062] When the solvent or mixture contains ethanol, a common denaturant, such as butan-2-one, 3-methylbutan-2-one, 5-methylheptan-3-one, isopropanol, tert-butanol, petroleum ether, toluene, cyclohexane, or 2-methylpropan-2-ol, can be additionally used. Therefore, in one embodiment, the phrase "at least one C1-C4 alcohol," "at least one C2-C4 alcohol," or "at least one C3- or C4-alcohol" refers only to the denaturant used to denature the ethanol. The addition of the polar solvent reduces the temperature of the tank / reactor, thereby preventing hydrolysis of the ester of the s-triazine derivative or transesterification of the s-triazine derivative. Therefore, in one embodiment, the temperature of the tank / reactor is reduced before crystallization. In a specific embodiment, the temperature is already reduced to some extent by flushing with water before adding the polar solvent. As a side effect of flushing, residual solvent and, optionally, impurities are also removed. In one embodiment, the s-triazine derivative is dissolved in a polar solvent, the solution is filtered, the s-triazine derivative is crystallized, washed with a polar solvent, and dried. The polar solvent is preferably an alcohol as described above. In various embodiments, the process includes crystallizing in the presence of one or more alcohol solvents as described above to produce tautomer I of the compound of Formula (Ia).

[0063] As noted above, the reaction between the cyanuric halide and the p-aminobenzoic acid ester is carried out in a nonpolar solvent. In one embodiment of the process of the present invention, the reaction is carried out in an aromatic solvent, preferably toluene, xylene, a mixture of xylene isomers, trimethylbenzene, a mixture of trimethylbenzene isomers, or a mixture thereof. In a preferred embodiment, the solvent is azeotropically dehydrated before the reaction begins. Because cyanuric halide has a tendency to hydrolyze to form mono-, di-, and / or trihydroxytriazines, removing residual water is advantageous in terms of increasing yield and reducing the number of by-products. Additionally, high process temperatures during the formation of the s-triazine derivative can result in partial or complete hydrolysis and / or re-esterification of the p-aminobenzoic acid ester, intermediates, and / or the desired s-triazine derivative. In a particular embodiment, the water content is less than 300 mg / kg.

[0064] In another embodiment of the process of the present invention, the cyanuric halide is introduced as an initial charge as a suspension in a dehydrated non-polar solvent. In certain embodiments, the vessel / reactor is precharged with solvent, preferably at an elevated temperature, more preferably between 50° C. and 90° C. This is advantageous to prevent (partial) hydrolysis of the cyanuric halide at excessively high temperatures.

[0065] In another embodiment of the process of the present invention, the p-aminobenzoic acid ester is added to a dehydrated nonpolar solvent in a separate vessel / reactor. Preferably, the p-aminobenzoic acid ester is previously purified by vacuum distillation. In one embodiment, a cyanuric halide suspension is then added to the p-aminobenzoic acid ester in the dehydrated nonpolar solvent to initiate the reaction. In certain embodiments, the dehydrated nonpolar solvent is added.

[0066] In one embodiment of the process of the present invention, the reaction is carried out at a temperature between 75°C and the boiling point of the solvent used for up to 48 hours. In another embodiment, the reaction is carried out at a temperature between 75°C and the boiling point of the solvent used for 0.5 hours to 24 hours. In another embodiment, the reaction is carried out at a temperature between 75°C and the boiling point of the solvent used for 0.5 hours to 12 hours. In another embodiment, the reaction is carried out at a temperature between 75°C and the boiling point of the solvent used for 1 hour to 3 hours. In another embodiment, the reaction is carried out at a temperature between 100°C and 150°C for 0.5 hours to 12 hours. In another embodiment, the reaction is carried out at a temperature between 100°C and 150°C for 1 hour to 3 hours. In another embodiment, the reaction is carried out at a temperature between 110°C and 130°C for 0.5 hours to 12 hours. In another embodiment, the reaction is carried out at a temperature between 110°C and 130°C for 1 hour to 3 hours. Longer reaction times do not adversely affect the yield and purity of the product, but they decrease the space-time yield of the process, thereby increasing waste and costs.

[0067] In another embodiment, a base is added after the reaction to neutralize the reaction mixture. Preferably, the base is selected from ammonia, an alkali metal hydroxide, an alkali metal carbonate, or an alkali metal bicarbonate. In one embodiment, the base is selected from an alkali metal carbonate, preferably potassium carbonate or sodium carbonate. In another embodiment, the base is sodium carbonate.

[0068] In one embodiment of the process of the present invention, the cyanuric halide is selected from cyanuric chloride, cyanuric bromide and mixtures thereof. Preferably, the cyanuric halide is cyanuric chloride.

[0069] As described above, the s-triazine derivatives of formula (I) are prepared by reacting a cyanuric halide with the same or different p-aminobenzoic acid esters. In one embodiment of the process of the present invention, the process further comprises preparing a p-aminobenzoic acid ester by reacting a p-nitrobenzoic acid ester with hydrogen in the presence of a catalyst; preferably, preparing a p-aminobenzoic acid 2-ethylhexyl ester by reacting a p-nitrobenzoic acid 2-ethylhexyl ester with hydrogen in the presence of a catalyst. In another embodiment, the process further comprises preparing a p-nitrobenzoic acid ester by reacting p-nitrobenzoic acid with an alcohol or polyoxyethylene; preferably, preparing a p-nitrobenzoic acid 2-ethylhexyl ester by reacting p-nitrobenzoic acid with 2-ethylhexanol.

[0070] As mentioned above, the process of the present invention allows for the production of highly pure s-triazine derivatives by purifying the product with gas / steam stripping. Accordingly, one embodiment of the present invention relates to an s-triazine derivative of formula (I) having a purity of at least 98% by weight. In another embodiment, the present invention relates to an s-triazine derivative of formula (I) having a purity of at least 99% by weight. In another embodiment, the present invention relates to an s-triazine derivative of formula (I) having a purity of at least 99.5% by weight.

[0071] In addition, the s-triazine derivatives obtained by this process have optimal physical properties, such as particle size. Thus, in one embodiment, the present invention relates to s-triazine derivatives in a pourable or flowable particulate form, preferably a crystalline form, particularly preferably having an average particle size of 5 μm to a maximum of 500 μm and / or a bulk density of more than 0.2 g / mL. In another embodiment, the present invention relates to s-triazine derivatives having an average particle size of 5 μm to a maximum of 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 s-triazine derivatives having an average particle size of 5 μm to a maximum of 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 s-triazine derivatives having an average particle size of 20 μm to a maximum of 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 an s-triazine derivative having an average particle size of 30 μm to a maximum of 100 μm and / or a bulk density of 0.4 g / mL to 0.8 g / mL. These properties are advantageous in that they have high solubility and stability in, for example, oils used in cosmetic formulations. Furthermore, the flowability and particle size of these s-triazine derivatives make them easy to handle and dispense.

[0072] Therefore, in one embodiment, the present invention relates to an s-triazine derivative having the above-mentioned properties, which can be obtained by the process of the present invention. As mentioned above, s-triazine derivatives are known for their UV absorption efficiency in both the UVB and UVA regions and their high photostability. In one embodiment, the present invention relates to the use of the s-triazine derivative of formula (I) as a photoprotective agent. Considering the high purity and physical properties of the s-triazine derivative obtained by the process of the present invention, it is advantageous to use it as a photoprotective agent, for example, in cosmetics.

[0073] Thus, 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 pourable or flowable particulate form, preferably in crystalline form, and preferably having the above-mentioned average particle size and bulk density.

[0074] In further aspects and embodiments, the present invention relates to a process for preparing an s-triazine derivative, the s-triazine derivative having the following chemical formula (Ia): [ka] 2,4,6-trianilino-p-(carbo-2'-ethylhexyl-1'-oxy)-1,3,5-triazine having the formula In a non-polar solvent, cyanuric halide is converted to p-aminobenzoic acid-2-ethylhexyl ester: [ka] (In the formula, R 1 , R 2 and R 3 and each represent a 2-ethylhexyl group), and 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. To achieve complete conversion of the cyanuric halide, i.e., to replace all three halides with the same or different p-aminobenzoic acid ester, it is advantageous to use an excess of p-aminobenzoic acid ester relative to the cyanuric halide. The p-aminobenzoic acid ester remaining after the reaction can be removed by crystallizing the resulting s-triazine derivative in a polar solvent.

[0075] As indicated above, gas / steam stripping is carried out to purify the product s-triazine derivative of formula (Ia).

[0076] In one embodiment of the process of the present invention, gas / steam stripping is carried out by feeding the reaction product to a vessel or reactor and stripping the nonpolar solvent by adding water, a polar solvent, water vapor, a polar solvent vapor, or a gaseous mixture thereof to the vessel or reactor from the top or bottom of the vessel / reactor. Preferably, water vapor, a polar solvent vapor, or a gaseous mixture thereof is added from the bottom of the vessel / reactor. When stripping is carried out using a polar solvent vapor, ethanol vapor is preferably used. When stripping is carried out using a gas, nitrogen gas is preferably used. Thus, in one embodiment, gas / steam stripping is carried out by adding water vapor, ethanol vapor, or nitrogen gas, preferably water vapor or nitrogen gas, preferably from the bottom of the vessel / reactor. The overhead stream containing the desorbed solvent and optional reaction by-products can be condensed and separated. Therefore, gas / steam stripping is advantageous for effectively removing residual solvent and by-products from the desired s-triazine derivative. As a result, s-triazine derivatives are obtained in high yield and purity. Furthermore, gas / steam stripping has the advantage that it is applicable to large-scale industrial scale. Furthermore, it has been found that this process offers the advantage of obtaining reaction products with optimal physical properties in terms of solubility and stability in oils used in cosmetic formulations. As mentioned above, if the temperature used to remove the solvent is too high, the solubility in the oil decreases.

[0077] In one embodiment of the process of the present invention, the temperature during gas / steam stripping is less than 200°C, preferably less than 180°C. In another embodiment, the temperature during gas / steam stripping is between 100°C and 200°C, preferably between 100°C and 180°C. In another embodiment, the temperature during gas / steam stripping is between 120°C and 170°C. In another embodiment, the temperature during gas / steam stripping is between 140°C and 160°C.

[0078] In one embodiment, the gas / steam stripping is carried out for up to 48 hours. In another embodiment, the gas / steam stripping is carried out for 1 to 24 hours. In another embodiment, the gas / steam stripping is carried out for 2 to 12 hours. In another embodiment, the gas / steam stripping is carried out for 4 to 7 hours.

[0079] In one embodiment of the present invention, the gas / steam pressure during gas / steam stripping is up to 100 bar, preferably up to 20 bar. In another embodiment, the gas / steam pressure during gas / steam stripping is 0.1 bar to 20 bar. In another embodiment, the gas / steam pressure during gas / steam stripping is 0.5 bar to 10 bar. In another embodiment, the gas / steam pressure during gas / steam stripping is 1 bar to 6 bar. In one embodiment, the temperature during steam / gas stripping is less than 200°C, preferably less than 180°C; the steam / gas pressure during steam / gas stripping is up to 100 bar, preferably up to 20 bar. In one embodiment, the temperature during gas / steam stripping is 120°C to 170°C, and the gas / steam pressure during gas / steam stripping is 0.1 bar to 20 bar. In one embodiment, the temperature during gas / steam stripping is 120°C to 170°C, and the gas / steam pressure 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 gas / steam pressure 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 gas / steam pressure 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 gas / steam pressure 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 steam / gas pressure during gas / steam stripping is 1 bar to 6 bar. In one particular embodiment, gas / steam stripping is carried out 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 particular embodiment, gas / steam stripping is carried out at a temperature of 120° C. to 170° C. and a pressure of 0.5 bar to 10 bar for a period of 3 to 7 hours.

[0080] In one embodiment of the process of the present 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.

[0081] In one embodiment of the process of the present invention, the non-polar solvent and water are azeotropically distilled prior to gas / steam stripping. In one embodiment, the temperature during azeotropic distillation is less than 200°C, preferably less than 180°C. In another embodiment, the temperature during azeotropic distillation is between 140°C and 180°C. In one embodiment, the temperature during azeotropic distillation is between 140°C and 180°C and the pressure is between 1 mbar (abs) and 2 bar (abs). In another embodiment, the temperature during azeotropic distillation is between 140°C and 180°C and the pressure is between 10 mbar (abs) and 1 bar (abs). In another embodiment, the temperature during azeotropic distillation is between 140°C and 180°C and the pressure is between 20 mbar (abs) and 100 mbar (abs).

[0082] In one embodiment, the s-triazine derivative is dissolved in a polar solvent after gas / steam stripping for subsequent crystallization of the product, which may be an alcohol, as described herein above.

[0083] In one embodiment of the process of the present invention, the s-triazine derivative is dissolved in a polar solvent, preferably a C1-C8 alcohol or water, or a mixture thereof. C1-C8 alcohols include linear, branched, or cyclic alcohols having 1 to 8 carbon atoms, or mixtures thereof, preferably ethanol, n-propanol, isopropanol, n-butanol, tert-butanol, n-pentanol, n-hexanol, n-octanol, 2-ethylhexanol, and cyclohexanol, with ethanol being particularly preferred. Accordingly, in another embodiment of the process 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 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 ethanol containing up to 10% by weight of water. When the solvent or mixture contains ethanol, common denaturants, such as butan-2-one, 3-methylbutan-2-one, 5-methylheptan-3-one, isopropyl alcohol, petroleum ether, toluene, cyclohexane, and 2-methylpropan-2-ol, can be additionally used. Therefore, in one embodiment, the phrase "at least one C1-C4 alcohol," "at least one C2-C4 alcohol," or "at least one C3- or C4-alcohol" refers only to the denaturant used to denature the ethanol. The addition of the polar solvent reduces the temperature of the vessel / reactor, thereby avoiding hydrolysis of the ester of the s-triazine derivative or transesterification of the s-triazine derivative. Therefore, in one embodiment, the vessel / reactor temperature is reduced before crystallization. In a specific embodiment, the temperature is already reduced to some extent by flushing water before adding the polar solvent. As a side effect of flushing, residual solvent and, optionally, impurities are also removed.In one embodiment, the s-triazine derivative is dissolved in a polar solvent, and then the solution is filtered and the s-triazine derivative is crystallized, washed with a polar solvent, and dried.

[0084] As noted above, the reaction between the cyanuric halide and the p-aminobenzoic acid ester is carried out in a nonpolar solvent. In one embodiment of the process of the present invention, the reaction is carried out in an aromatic solvent, preferably toluene, xylene, a mixture of xylene isomers, trimethylbenzene, a mixture of trimethylbenzene isomers, or a mixture thereof. In a preferred embodiment, the solvent is azeotropically dehydrated before the reaction begins. Because cyanuric halide has a tendency to hydrolyze to form mono-, di-, and / or trihydroxytriazines, removing residual water is advantageous in terms of increasing yield and reducing the number of by-products. Additionally, high process temperatures during the formation of the s-triazine derivative can result in partial or complete hydrolysis and / or re-esterification of the p-aminobenzoic acid ester, intermediates, and / or the desired s-triazine derivative. In a particular embodiment, the water content is less than 300 mg / kg.

[0085] In another embodiment of the process of the present invention, the cyanuric halide is introduced as an initial charge as a suspension in a dehydrated non-polar solvent. In certain embodiments, the vessel / reactor is precharged with solvent, preferably at an elevated temperature, more preferably between 50° C. and 90° C. This is advantageous to prevent (partial) hydrolysis of the cyanuric halide at excessively high temperatures.

[0086] In another embodiment of the process of the present invention, p-aminobenzoic acid 2-ethylhexyl ester is added to a dehydrated non-polar solvent in a separate vessel / reactor. Preferably, the p-aminobenzoic acid 2-ethylhexyl ester is previously purified by vacuum distillation. In one embodiment, a cyanuric halide suspension is then added to the p-aminobenzoic acid 2-ethylhexyl ester in the dehydrated non-polar solvent to initiate the reaction. In certain embodiments, the dehydrated non-polar solvent is added.

[0087] In one embodiment of the process of the present invention, the reaction is carried out at a temperature between 75°C and the boiling point of the solvent used for up to 48 hours. In another embodiment, the reaction is carried out at a temperature between 75°C and the boiling point of the solvent used for 0.5 hours to 24 hours. In another embodiment, the reaction is carried out at a temperature between 75°C and the boiling point of the solvent used for 0.5 hours to 12 hours. In another embodiment, the reaction is carried out at a temperature between 75°C and the boiling point of the solvent used for 1 hour to 3 hours. In another embodiment, the reaction is carried out at a temperature between 100°C and 150°C for 0.5 hours to 12 hours. In another embodiment, the reaction is carried out at a temperature between 100°C and 150°C for 1 hour to 3 hours. In another embodiment, the reaction is carried out at a temperature between 110°C and 130°C for 0.5 hours to 12 hours. In another embodiment, the reaction is carried out at a temperature between 110°C and 130°C for 1 hour to 3 hours. Longer reaction times do not adversely affect the yield and purity of the product, but they decrease the space-time yield of the process, thereby increasing waste and costs.

[0088] In another embodiment, a base is added after the reaction to neutralize the reaction mixture. Preferably, the base is selected from ammonia, an alkali metal hydroxide, an alkali metal carbonate, or an alkali metal bicarbonate. In one embodiment, the base is selected from an alkali metal carbonate, preferably potassium carbonate or sodium carbonate. In another embodiment, the base is sodium carbonate.

[0089] In one embodiment of the process of the present invention, the cyanuric halide is selected from cyanuric chloride, cyanuric bromide and mixtures thereof. Preferably, the cyanuric halide is cyanuric chloride.

[0090] As mentioned above, the s-triazine derivative of formula (Ia) is prepared by reacting a cyanuric halide with p-aminobenzoic acid-2-ethylhexyl ester. In one embodiment of the process of the present invention, the process further comprises preparing p-aminobenzoic acid-2-ethylhexyl ester by reacting p-nitrobenzoic acid-2-ethylhexyl ester with hydrogen in the presence of a catalyst. In another embodiment, the process further comprises preparing p-nitrobenzoic acid-2-ethylhexyl ester by reacting p-nitrobenzoic acid with 2-ethylhexanol.

[0091] As mentioned above, the process of the present invention allows for the production of highly pure s-triazine derivatives by purifying the product with gas / steam stripping. Accordingly, one embodiment of the present invention relates to an s-triazine derivative of Formula (Ia) having a purity of at least 98% by weight. In another embodiment, the present invention relates to an s-triazine derivative of Formula (Ia) having a purity of at least 99% by weight. In another embodiment, the present invention relates to an s-triazine derivative of Formula (Ia) having a purity of at least 99.5% by weight. In more preferred embodiments, the purity may be at least 99.6, 99.7, 99.8, or 99.9% by weight. It may be preferable that the content of any one of specific impurities in the final product, such as p-aminobenzoic acid (AB), monohydroxide of ethylhexyltriazone (MHT), monocarboxylic acid of ethylhexyltriazone (MCS), and monoethyl ester of ethylhexyltriazone (MEE), be less than 0.2% by weight, preferably 0.1% by weight or less, and 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 ​​represent concentrations measured by HPLC. Optionally, in addition to low concentrations of other impurities, the residual content of solvents such as xylene, as measured by GC, can also be 100 ppm or less, preferably 10 ppm or less.

[0092] In various embodiments, the s-triazine derivative is tautomer I of 2,4,6-trianilino-p-(carbo-2'ethylhexyl-1'-oxy)-1,3,5-triazine, which can be obtained by synthesis as described in WO 03 / 074499 A1 or as described below in Example 1, followed by further purification steps as described herein. Thus, the present invention also relates to tautomer I of 2,4,6-trianilino-p-(carbo-2'ethylhexyl-1'-oxy)-1,3,5-triazine, which can be obtained by the process of the present invention.

[0093] In various embodiments, the tautomeric purity of the product, 2,4,6-trianilino-p-(carbo-2'ethylhexyl-1'-oxy)-1,3,5-triazine, as determined by IR spectroscopy, is 1694 and 1717 cm -1 The two absorption bands of the carbonyl group are not present at 1697 cm -1 There is only one absorption band at about 1697 cm -1 It may also be advantageous to have a single band at 2,4,6-trianilino-p-(carbo-2'ethylhexyl-1'-oxy)-1,3,5-triazine without a shoulder, which would suggest the presence of some amount of the undesired tautomer of 2,4,6-trianilino-p-(carbo-2'ethylhexyl-1'-oxy)-1,3,5-triazine. The tautomeric purity of the product from the synthesis described in Example 1 below and also in WO 03 / 074499 A1 was found to be unchanged by subsequent additional steam / gas stripping purification steps.

[0094] In addition, the s-triazine derivatives obtained by this process have optimal physical properties, such as particle size. Thus, in one embodiment, the present invention relates to s-triazine derivatives in a pourable or flowable particulate form, preferably a crystalline form, particularly preferably having an average particle size of 5 μm to a maximum of 500 μm and / or a bulk density of more than 0.2 g / mL. In another embodiment, the present invention relates to s-triazine derivatives having an average particle size of 5 μm to a maximum of 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 s-triazine derivatives having an average particle size of 5 μm to a maximum of 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 s-triazine derivatives having an average particle size of 20 μm to a maximum of 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 an s-triazine derivative having an average particle size of 30 μm to a maximum of 100 μm and / or a bulk density of 0.4 g / mL to 0.8 g / mL. These properties are advantageous in that they have high solubility and stability in, for example, oils used in cosmetic formulations. Furthermore, the flowability and particle size of these s-triazine derivatives make them easy to handle and dispense.

[0095] Therefore, in one embodiment, the present invention relates to an s-triazine derivative having the above-mentioned properties, which can be obtained by the process of the present invention. As mentioned above, s-triazine derivatives are known for their UV absorption efficiency in both the UVB and UVA regions and their high photostability. In one embodiment, the present invention relates to the use of the s-triazine derivative of formula (Ia) as a photoprotective agent. Considering the high purity and physical properties of the s-triazine derivative obtained by the process of the present invention, it is advantageous to use it as a photoprotective agent, for example, in cosmetics.

[0096] Thus, 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 pourable or flowable particulate form, preferably in crystalline form, and preferably having the above-mentioned average particle size and bulk density.

[0097] The following examples further illustrate the present invention. [Example]

[0098] 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.

[0099] In this example, GC analysis is performed on an Agilent Technologies 7890B using the following conditions and parameters: Detector: FID Solvent: dichloromethane Column: Agilent Technologies HP-5 (30 m, inner diameter 0.32 mm, film thickness 0.25 μm) Carrier gas: Nitrogen 1 mL / min (split ratio 100:1) Injector temperature: 270℃ Detector temperature: 300℃ Temperature program: 80°C for 3 minutes, followed by 50°C / minute to 130°C and hold at 130°C for 4 minutes.

[0100] In this example, HPLC analysis is performed on an Agilent Technologies 1260 using the following conditions and parameters: Detector: UV 295nm Column: PerfectBond C8-HD (5 μm, 125 × 4 mm) manufactured by MZ Analysentechnik Flow rate: 0.7mL / min Solvents: THF (solvent A) and 0.1% H2SO4 aqueous solution (pH 1.5) (solvent B) Gradient Program:

[0101] [Table 1]

[0102] Example 1: Preparation of ethylhexyl triazone (Uvinul T 150) In reactor 1, 378 kg of xylene was refluxed until the water content was less than 250 mg / kg. 180 kg of purified xylene was discharged into another reactor 2. This transfer was preferably carried out at a temperature of 60 to 80 °C. Next, 100 kg of cyanuric chloride was added to reactor 2 and stirred at a high temperature below 100 °C to obtain a suspension of cyanuric chloride in xylene. Next, 430 kg of purified 2-ethylhexyl p-aminobenzoate, which had previously been purified by distillation, was added to the purified xylene remaining in reactor 1. The reaction was then initiated by adding the suspension from reactor 2 and an additional 110 L of pure xylene to reactor 1. During this reaction, reactor 1 was heated to 122 °C. After 2 hours, 175 kg of 20 wt % Na2CO3 in water was added to reactor 1 in four portions to reach a pH value of 6.5 to 8.0. The contents of reactor 1 were then transferred to reactor 3. Azeotropic distillation of xylene and water was then carried out at 155°C and a pressure of 30 mbar (abs) for 6 hours. The temperature was then set to 160°C. The xylene content at this stage was 5500 ppm (measured by GC). The remaining evanescent residue (mainly water and xylene) was then stripped by blowing in steam at a pressure of 5.5 bar (abs) and a temperature of 155°C at a flow rate of 50 kg / h for 5 hours. The temperature of Reactor 3 was then reduced by flushing in 11 L of water. An ethanolic solution of ethylhexyltriazone was obtained by adding 790 kg of purified denatured ethanol (e.g., denatured by adding 78 g of tert-butanol and 5 kg of isopropanol to 100 L of ethanol) and further reducing the temperature. This ethylhexyltriazone solution was then filtered, crystallized, washed with additional ethanol, and dried to obtain a pure ethylhexyltriazone powder in a yield of 420 kg. The HPLC characterization of the final product is shown in Table 1, and the IR spectroscopic characterization is shown in Figure 2. From the IR spectroscopic analysis, the obtained product had a peak at 1700-1720 cm -1 No peak or shoulder is seen in the range of 1690cm -1A single peak is observed only at 1000 kJ / cm2, indicating high tautomeric purity (tautomer I). The xylene content measured by GC is <10 ppm.

[0103] [Table 2]

[0104] Examples 2 to 6: Purification by steam stripping Following a reaction procedure similar to that described in Example 1, 1254 g of the reaction product from reactor 1 was then transferred to reactor 3 for azeotropic distillation. The remaining residue to be dissipated was then stripped by blowing in steam at a temperature of 155°C and pressure p at a flow rate f for a time t. The sample was then filtered, washed with ethanol and dried. Characterization by HPLC (AB, MHT, MCS, MEE) and GC (xylene) is shown in Table 2.

[0105] [Table 3]

[0106] Example 7: Purification by gas stripping Following a reaction procedure similar to that described in Example 1, 1254 g of the reaction product from reactor 1 was then transferred to reactor 3 for azeotropic distillation. The remaining residue to be dissipated was then stripped with nitrogen gas. Nitrogen gas was bubbled in at a pressure of 0.6 barg and a flow rate of 0.33 liters / min for 360 minutes. The sample was then filtered and washed with ethanol. Characterization by HPLC (AB, MHT, MCS, MEE) and GC (xylene) is shown in Table 3.

[0107] [Table 4]

[0108] Example 8: Purification by steam stripping Following a reaction procedure similar to that described in Example 1, 1254 g of the reaction product from reactor 1 was then transferred to reactor 3 for azeotropic distillation. The remaining residue to be dissipated was then stripped by ethanol steam stripping. Ethanol steam was introduced at a pressure of 2.0 barg and a flow rate of 1.85 g / min for 300 minutes. The sample was then filtered and washed with ethanol. Characterization by HPLC (AB, MHT, MCS, MEE) and GC (xylene) is shown in Table 4.

[0109] [Table 5]

[0110] A side effect of ethanol stripping is an increase in the amount of monoethyl ester of ethylhexyltriazone (MEE), the by-product most likely formed as a result of transesterification.

[0111] Example 9: Purification without stripping After azeotropic distillation, the reaction product was filtered, washed with ethanol and dried. Characterization by HPLC (AB, MHT, MCS, MEE) and GC (xylene) is shown in Table 5.

[0112] [Table 6]

[0113] Comparing the results of Example 9 with those of Examples 1-8, it can be seen that the absence of gas / steam stripping significantly increases the xylene content in the product. Surprisingly, the absence of gas / steam stripping also results in higher amounts of impurities / by-products (AB, MHT, MCS, MEE) present in the product.

Claims

1. Equation (I): 【Chemistry 1】 A method for preparing an s-triazine derivative, wherein in a nonpolar solvent selected from alkanes, aromatic solvents, and mixtures thereof, (i) Cyanuryl halogens; (ii) p-aminobenzoic acid ester: 【Chemistry 2】 (In the formula, R １ , R ２ and R ３ These are either identical or different, and include hydrogen, alkali metals, ammonium, substituted ammonium, and C. １ ~C １２ - Independently selected from the group consisting of alkyl or polyoxyethylene) This includes causing a reaction; A method in which the reaction product is purified by gas / steam stripping.

2. R ２ = R １ And; Preferably R ３ = R ２ = R １ and; Particularly preferred R １ , R ２ and R ３ The method according to claim 1, wherein each represents a 2-ethylhexyl group.

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

4. The method according to claim 1, wherein gas / steam stripping is performed by supplying the reaction product to a tank or reactor and adding water or a polar solvent or water vapor or vapor or gas of a polar solvent or a mixture thereof to the tank or reactor to remove the nonpolar solvent and optionally the by-products.

5. The method according to claim 1, wherein gas / steam stripping is performed by adding water vapor, ethanol vapor, or nitrogen gas, preferably water vapor or nitrogen gas, preferably from the bottom of the tank / reactor.

6. The method according to claim 1, wherein the temperature during steam / gas stripping is less than 200°C, preferably less than 180°C; and / or the steam / gas pressure during steam / gas stripping is a maximum of 100 bar, preferably a maximum of 20 bar.

7. After stripping, the s-triazine derivative is dissolved in a polar solvent, preferably C １ ~C ８ - The method according to claim 1, wherein the alcohol is dissolved in water or a mixture thereof.

8. After stripping, the s-triazine derivative is subjected to at least one C １ ~C ４ - A mixture of alcohol and up to 10% by weight of water, preferably at least one C ２ ~C ４ - The method according to claim 1, wherein the alcohol is dissolved in a mixture of up to 10% by weight of water.

9. The method according to claim 1, wherein the reaction is preferably carried out in an aromatic solvent which is toluene, xylene, a mixture of xylene isomers, trimethylbenzene, a mixture of trimethylbenzene isomers, or a mixture thereof, and the solvent is particularly preferably azeotropically dehydrated before the reaction is initiated.

10. The method according to claim 1, wherein the reaction is carried out at a temperature of 75°C to the boiling point of the solvent used for a maximum of 48 hours.

11. The method according to claim 1, wherein the halogenated cyanuryl is selected from cyanuryl chloride, cyanuryl bromide, and mixtures thereof, and preferably the halogenated cyanuryl is cyanuryl chloride.

12. The method according to claim 3, further comprising preparing p-aminobenzoic acid-2-ethylhexyl ester by reacting p-nitrobenzoic acid-2-ethylhexyl ester with hydrogen in the presence of a catalyst.

13. The method according to claim 12, further comprising the preparation of p-nitrobenzoic acid-2-ethylhexyl ester by reacting p-nitrobenzoic acid with 2-ethylhexanol.

14. An 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, and even more preferably at least 99.8% by weight, and the residual amount of solvent, as determined by GC, being 100 ppm or less, preferably 10 ppm or less.

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

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

17. The s-triazine derivative according to claim 14, which is in a pourable or flowable particle form, preferably in a crystalline form, and particularly preferably has an average particle diameter of 5 μm to a maximum of 500 μm, and / or a bulk density of more than 0.2 g / mL.

18. The s-triazine derivative according to claim 14, which can be obtained by the method described in any one of claims 1 to 12.

19. Use of the s-triazine derivative of formula (I) described in claim 14 as a photoprotective agent.

20. A cosmetic composition comprising the s-triazine derivative of formula (I) described in claim 14.

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