Compositions comprising 1, 3, 5-triazine, 2, 4, 6-tris [1, 1 '-biphenyl]-4-yl having lower impurity amount

Abstract

A composition comprising 1, 3, 5-triazine, 2, 4, 6-tri [1, 2, 4] triazine, 2, 4, 6-tri [1, 2, 4] triazine, 2, 4 1, 1 '-biphenyl]-4-yl (TBPT) and a first impurity consisting of one or more halogen-containing triazines and a second impurity consisting of biphenyl wherein the amount of the first impurity is equal to or less than 900 ppm by weight relative to the total weight of the composition and wherein the amount of the second impurity is equal to or less than 4000 ppm by weight relative to the total weight of the composition.

Description

Technical Field

[0001] The present invention relates to a composition comprising 1,3,5-triazine, 2,4,6-tris[1,1'-biphenyl]-4-yl with fewer impurities, in particular in the new crystalline form A, a process for its preparation and a cosmetic composition containing the composition comprising TBPT, as well as the use of the composition comprising TBPT as a UV filter. Background Art

[0002] To comply with cosmetic regulations, purity standards are set for the chemical ingredients in cosmetic products. These purity standards may be particularly relevant for cosmetic products containing chemical ingredients that may contain impurities, which may be detrimental to the health of the user. In particular, aromatic hydrocarbon impurities, when present in cosmetic products, may cause adverse effects on humans or animals. To reduce the undesirable side effects of impurities, the chemical ingredients in cosmetic products should be produced in a manner that focuses on reducing these impurities.

[0003] A widely used chemical ingredient in cosmetics is 1,3,5-triazine, 2,4,6-tris[1,1'-biphenyl]-4-yl (TBPT). TBPT is commonly used as a highly effective photostable filter against UVB and UVAII radiation in cosmetic products (such as anti-aging facial care products or sunscreens) designed to protect human or animal hair or skin from the damaging effects of UV radiation. TBPT is also known for use in electroluminescent devices (e.g., US 6,225,467 B1, WO 2020 / 226300, WO 2020 / 231197).

[0004] US 2004 / 0191191 A1 describes a synthetic procedure for obtaining TBPT from cyanuric chloride and 1,1′-biphenyl in 1,2-dichlorobenzene in an aluminum chloride-catalyzed reaction. Without adequate purification steps, there is a risk that residual starting materials may remain in the final product and, consequently, in the cosmetic product.

[0005] In order to avoid impurities that may appear during the synthesis of TBPT in, for example, cosmetic products, it is necessary to reduce impurities that are already present during the synthesis or purification steps.

[0006] Therefore, there is a continuing need for a rapid and efficient method for the production of TBPT. In this regard, the object of the present invention is to provide an optimized method for the synthesis, isolation and purification of TBPT. Summary of the Invention

[0007] It is an object of the present invention to provide a composition with an increased amount of TBPT in crystalline form, which composition allows for use as a UV filter. In particular, it is an object of the present invention to provide a composition with a high content of TBPT in crystalline form A.

[0008] Another object of the present invention is to provide a method for synthesizing, isolating and purifying a crystalline form of TBPT. In addition, another object of the present invention is to provide a method for providing TBPT having a large amount of crystalline Form A.

[0009] In a first aspect, the present invention provides a composition comprising 1,3,5-triazine, 2,4,6-tris[1,1′-biphenyl]-4-yl (TBPT) and a first impurity consisting of one or more halogen-containing triazines and a second impurity consisting of biphenyl, wherein the amount of the first impurity is equal to or less than 900 ppm by weight relative to the total weight of the composition, and wherein the amount of the second impurity is equal to or less than 4000 ppm by weight relative to the total weight of the composition.

[0010] In a second aspect, the present invention provides a crystalline form A of TBPT, which exhibits in its X-ray powder diffraction pattern using Cu-Kα radiation at room temperature (20°C) at least 3 of the following 5 reflections given as 2θ values: 11.6±0.2, 17.8±0.2, 21.1±0.2, 23.4±0.2 and 24.4±0.2°θ.

[0011] In a third aspect, the present invention provides a crystalline form B of TBPT, which exhibits in its X-ray powder diffraction pattern at room temperature using Cu-Kα radiation at least three of the following five reflections given as 2θ values: 8.6±0.2, 10.9±0.2, 17.5±0.2, 18.5±0.2, 19.5±0.2, 19.9±0.2 and 20.7±0.2°θ.

[0012] In a fourth aspect, the present invention provides a method for interconverting crystalline Form B of 2,4,6-tris(biphenyl-4-yl)-1,3,5-triazine (TBPT) into crystalline Form A of TBPT, the method comprising the steps of: a) providing a composition C comprising TBPT in crystalline Form B; B ; b) the composition C B mixing in a solvent (S1) to obtain a first mixture; c) stirring the first mixture at a temperature T1 for a time t1, and thereby obtaining TBPT in crystalline form A, and thereby providing a second mixture; d) isolating a composition C comprising TBPT in crystalline form A from the second mixture A .

[0013] In a fifth aspect, the present invention provides a cosmetic product comprising a composition according to the first aspect of the invention, preferably wherein more than 80 wt-%, preferably 100 wt-% of TBPT is present in crystalline form A in micronized form.

[0014] In a sixth aspect, the present invention provides the use of a composition according to the first aspect of the invention as a UV filter in a cosmetic product for protecting the hair and / or skin of a subject from the damaging effects of UV radiation, wherein preferably more than 80 wt-%, preferably 100 wt-% of the TBPT is present in crystalline form A.

[0015] The present invention will be described with respect to particular embodiments and with reference to certain examples but the invention is not limited thereto and only by the appended claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 The DSC graph of RE1 is shown. TBPT is indicated by an endothermic peak at 221°C-256°C, with ΔH=39-43 J / g.

[0017] Figure 2 PXRD pattern of RE1, Cu Kα radiation is shown.

[0018] Figure 3 PXRD pattern of IE1, Cu Kα radiation is shown.

[0019] Figure 4 PXRD pattern of CE3, Cu Kα radiation is shown.

[0020] Figure 5 PXRD pattern of CE2, Cu Kα radiation is shown.

[0021] Figure 6 Comparison of PXRD patterns of Forms A (top) and B (bottom), Cu Ka radiation, is shown.

[0022] Figure 7 A comparison of the UV absorption spectra of TBPT Forms A and B is shown.

[0023] definition

[0024] Before describing exemplary embodiments of the present invention in detail, definitions important to understanding the present invention are given.

[0025] Unless otherwise indicated, the terms set forth below should generally be understood in their common sense.

[0026] The term "comprising" does not exclude other elements. For the purposes of the present invention, the term "consisting of" is considered a preferred embodiment of the term "comprising". If a group is defined hereinafter as comprising at least a certain number of embodiments, this should also be understood as disclosing a group that preferably consists only of these embodiments.

[0027] Where an indefinite or definite article is used when referring to a singular noun, for example "a / an" or "the", this includes a plural of that noun unless something else is specifically stated.

[0028] The term "at least one" numerically means "one or more." In a preferred embodiment, the term numerically means "one."

[0029] The terms "include" and "comprising" mean that other components may be present in addition to those mentioned. These terms are intended to be inclusive and thus include "consisting of." "Consisting of" means explicitly and means that no additional ingredients may be present. In embodiments, the terms "comprise" and "comprising" mean "consisting of."

[0030] Terms like "obtainable" and "obtained" are used interchangeably. For example, this means that, unless the context clearly dictates otherwise, the term "obtained" is not intended to indicate that, for example, an embodiment must be obtained by, for example, the sequence of steps following the term "obtained," even though such a limited understanding is always encompassed by the term "obtained" as a preferred embodiment.

[0031] In addition, the terms "first", "second", "third" or "(a)", "(b)", "(c)", "(d)" and the like in this specification and claims are used to distinguish similar elements and are not necessarily used to describe a sequential order or a chronological order. It is to be understood that the terms so used are interchangeable where appropriate and that the embodiments of the invention described herein are capable of operation in other sequences than those described or illustrated herein. Where the terms "first", "second", "third" or "(a)", "(b)", "(c)", "(d)", "i", "ii" and the like refer to steps of a method or use or an assay, unless otherwise indicated in this application as described above or below, there is no temporal or temporal time interval coherence between such steps, i.e., the steps may be performed simultaneously or there may be a time interval of seconds, minutes, hours, days, weeks, months or even years between such steps.

[0032] It should be understood that the present invention is not limited to the specific methodology, protocols, reagents, etc. described herein, as these may vary. It should also be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention, which will be limited only by the appended claims.

[0033] The terms "about" or "approximately" allow deviations from the indicated numerical value of ±20%, preferably ±15%, more preferably ±10%, even more preferably ±5%, and in strongly preferred embodiments ±1%, and in the most preferred embodiments, "about" and "approximately" mean "exactly".

[0034] A range defined by numbers such as "80°C to 120°C" means that both numerical values ​​and each value within the range are disclosed individually.

[0035] As used herein, the term "room temperature" relates to 20° C. As used herein, the term "standard pressure" relates to 1013 mbar.

[0036] The organic moieties mentioned above in the definitions of the variables, like the term halogen, are collective terms for individual lists of individual group members. The prefix Cn-Cm indicates in each case the possible number of carbon atoms in the group.

[0037] The term "halogen" denotes in each case fluorine, bromine, chlorine or iodine, in particular fluorine, chlorine or bromine.

[0038] The term "crystalline form" with respect to TBPT according to the present disclosure specifically includes crystalline form A and crystalline form B. However, it is not excluded that additional crystalline forms may exist.

[0039] The term "polymorph" describes an interconversion relationship, meaning that each form has a temperature range within which it is stable relative to the other form and a transition point at which the forms are iso-stable and, in principle, interchangeable. Above this temperature, the thermodynamic tendency is to form only the form that is stable at the higher temperature. Below the transition temperature, the lower-temperature form is the only stable form relative to the other form, although the higher-temperature form is generally more likely to freeze and persist outside its stability range than the lower-temperature form. Forms outside their stability range are described herein as metastable.

[0040] The term "alkyl" as used herein denotes in each case a straight-chain or branched alkyl group generally having 1 to 5 carbon atoms, preferably 1 to 4 carbon atoms. Examples of alkyl groups are methyl, ethyl, n-propyl, isopropyl, n-butyl, 2-butyl, isobutyl, tert-butyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, 1,1-dimethylpropyl and 1,2-dimethylpropyl. Methyl, ethyl, n-propyl, isopropyl and isobutyl are particularly preferred.

[0041] The term "aryl" preferably includes 6-membered aromatic carbocyclic rings based on carbon atoms as ring members. A preferred example is phenyl. In aromatic ring systems, the Hückel (4n+2) rule is satisfied.

[0042] In this context, the term "purity" relates to the purity of a batch obtained by a "production process," wherein the product obtained from the production process typically contains impurities. The purity of a batch can be determined by quantifying the TBPT content in the batch via HPLC. Experimental details of the method used for quantification are further described in the examples given below. According to the present disclosure, TBPT can exhibit a purity of, for example, 95 wt-%, 98 wt-%, 98.5 wt-%, 99.0 wt-% or even 100 wt-%. Thus, a purity of 98.5 wt-% can represent a mixture of 98.5 wt-% pure TBPT and 1.5 wt-% impurities.

[0043] The term "impurity" as used herein relates to compounds that are not TBPT in the batch TBPT obtained by the production process. Therefore, the term "impurity" relates to inorganic and organic impurities. In the context of the present disclosure, particularly relevant impurities are impurities from residual starting materials, intermediates or solvents, which may be used or appear during the production process. Among these impurities, there may be impurities that are problematic due to toxicological problems, which are, for example, aromatic hydrocarbons such as biphenyl or xylene, or halogenated triazines such as 2,4-bis([1,1′-biphenyl]-4-yl)-6-chloro-1,3,5-triazine (BBCT). The list of "impurities" is not to be understood as a comprehensive or definitive list of impurities. In the context of the present disclosure, certain known "impurities" are quantified by GC or HPLC. The experimental details of the method for quantification are further described in the examples given below.

[0044] The term "xylene" as referred to herein encompasses all xylene isomers and mixtures thereof, including 1,2-dimethylbenzene, 1,3-dimethylbenzene and 1,4-dimethylbenzene, corresponding to ortho-xylene, meta-xylene, para-xylene, as well as o-xylene, m-xylene and p-xylene.

[0045] The term "production method" refers to a method that may include the steps of synthesis, isolation and purification. A production method may consist of only one or two of these steps and may optionally include additional steps. Therefore, if not otherwise stated, a production method should not be understood as being limited to these steps or even the order of the steps.

[0046] The term 'TBPT' as used herein must be understood as an abbreviation of the compound name 1,3,5-triazine, 2,4,6-tris[1,1′-biphenyl]-4-yl (CAS No.: 31274-51-8, i.e.: 2,4,6-tris([1,1′-biphenyl]-4-yl)-1,3,5-triazine), which is described according to formula (I).

[0047]

[0048] TBPT can occur in amorphous or crystalline forms and mixtures thereof. The compound of formula (I) can exist in at least two crystal modifications or in a mixture of two or more crystalline states. Polymorph Form A can be distinguished from Polymorph Form B by powder X-ray diffraction (XRD) and differential scanning calorimetry (DSC). Only Polymorph Form A is distinguished by its specific UV absorption properties (see Figure 7 ) and is suitable for sunscreen applications. In addition, polymorph Form B is metastable at room temperature. Methods and data for polymorph Forms A and B are provided.

[0049] The term "raw TBPT" or "TBPT raw material" according to the present disclosure refers to TBPT as a crude product. "Raw TBPT" or "TBPT raw material" can be obtained from a production process that produces a product with a higher level of impurities. The TBPT raw material can include TBPT in crystalline Form A. DETAILED DESCRIPTION

[0050] Thus, in a first aspect, the present invention relates to a composition comprising TBPT and a first impurity consisting of one or more halogen-containing triazines and a second impurity consisting of biphenyl, wherein the amount of the first impurity is equal to or less than 900 ppm by weight relative to the total weight of the composition, and wherein the amount of the second impurity is equal to or less than 4000 ppm by weight relative to the total weight of the composition.

[0051] Both the first and second impurities, but particularly the second impurity, biphenyl, are byproducts of a commonly used TBPT production process, such as that described in US 2004 / 0191191 A1. Both impurities contain aromatic entities, which are known to increase the risk of diseases such as cancer. Therefore, a first aspect of the present invention provides a composition comprising TBPT having lower levels of such impurities than achieved in the prior art.

[0052] Therefore, preferably, the halogen-containing triazine of the first impurity of the composition of the first aspect of the present invention is selected from the group consisting of chlorine-containing triazines, bromine-containing triazines and mixtures thereof. Halogen-containing triazines such as chlorine-containing triazines and bromine-containing triazines include 1,3,5-triazines, in particular phenyl-substituted 1,3,5-triazines such as 2,4,6-triphenyl or biphenyl-substituted 1,3,5-triazines such as 2,4-di([1,1'-biphenyl]-4-yl), wherein one or more hydrogen atoms are replaced by halogen atoms such as chlorine or bromine, for example, on the 1,3,5-triazine ring or the phenyl ring. In various embodiments, the first impurity is more preferably 1,3,5-triazine, 2,4,6-tris(4-bromophenyl) and / or 1,3,5-triazine, 2,4-bis([1,1′-biphenyl]-4-yl)-6-chloro (BBCT), and most preferably 1,3,5-triazine, 2,4-bis([1,1′-biphenyl]-4-yl)-6-chloro (BBCT).

[0053] Particularly preferably, the amount of the first impurity in the composition of the first aspect of the present invention is equal to or less than 800 ppm by weight, more preferably equal to or less than 600 ppm by weight, and most preferably equal to or less than 400 ppm by weight relative to the total weight of the composition. This further reduces the risk of disease if the composition is used in a cosmetic product.

[0054] In a preferred embodiment of the first aspect of the present invention, the amount of the first impurity in the composition of the present invention is equal to or greater than 0.01 ppm by weight relative to the total weight of the composition, preferably equal to or greater than 0.1 ppm by weight relative to the total weight of the composition, more preferably equal to or greater than 1 ppm by weight, still more preferably equal to or greater than 10 ppm by weight and most preferably equal to or greater than 100 ppm by weight.

[0055] It should be understood that the amount of the first impurity given above can refer to the first impurity, that is, the total amount of all compounds containing halogen triazines in the sense of the present invention, or to the more specifically defined first impurity described herein. In various embodiments, the amount can therefore also refer to one of the more specifically defined first impurities defined above, such as 1,3,5-triazine, 2,4,6-tris (4-bromophenyl) and / or 1,3,5-triazine, 2,4-bis ([1,1′-biphenyl]-4-yl)-6-chloro (BBCT). However, it may be preferred that the given maximum amount of the first impurity covers the total amount of all compounds that meet the halogen triazine. These amounts can also be combined so that the total amount of halogen triazines is equal to or less than 900 ppm by weight relative to the total weight of the composition, and the amount of specific impurities such as 1,3,5-triazine, 2,4-bis ([1,1′-biphenyl]-4-yl)-6-chloro (BBCT) is equal to or less than 400 ppm by weight.

[0056] For the same reasons as explained above for the first impurity, preferably, the amount of the second impurity in the composition of the first aspect of the invention is equal to or less than 3000 ppm by weight, more preferably equal to or less than 600 ppm by weight, and most preferably equal to or less than 300 ppm by weight relative to the total weight of the composition.

[0057] In a further preferred embodiment of the first aspect of the invention, the amount of the second impurity in the composition is equal to or greater than 0.01 ppm by weight, more preferably equal to or greater than 0.1 ppm by weight, still more preferably equal to or greater than 1 ppm by weight, and even more preferably equal to or greater than 10 ppm by weight, and most preferably equal to or greater than 100 ppm by weight, relative to the total weight of the composition.

[0058] In the production process for TBPT, as described in US 2004 / 0191191 A1, aromatic solvents are typically used. These aromatic solvents can be condensed aromatic systems. Examples of such solvents include benzene, toluene, xylene, ethylbenzene, naphthalene, fluorene, and mixtures thereof. However, these aromatic compounds can also be problematic in light of the health effects associated with the use of TBPT-containing compositions in cosmetic products. Therefore, the present invention further aims to reduce the amount of these solvents in TBPT-containing compositions.

[0059] Therefore, preferably, the composition according to the first aspect of the present invention further comprises a third impurity, the third impurity comprising, preferably consisting of, an aromatic hydrocarbon, wherein the third impurity does not comprise biphenyl. This means that the third impurity may comprise or consist of an aromatic hydrocarbon. Preferably, the one or more aromatic hydrocarbons are selected from the group consisting of monocyclic aromatic hydrocarbons, polycyclic aromatic hydrocarbons (PAHs) and mixtures thereof, preferably selected from the group consisting of alkyl-substituted benzene compounds (Cn-benzenes), condensed aromatic hydrocarbons and mixtures thereof, more preferably selected from the group consisting of benzene, toluene, xylene, ethylbenzene, naphthalene, fluorene, and mixtures thereof, and most preferably xylene.

[0060] In a preferred embodiment of the first aspect of the present invention, the amount of the third impurity in the composition is equal to or lower than 4000 ppm by weight, preferably equal to or lower than 800 ppm by weight, and more preferably equal to or lower than 400 ppm by weight, relative to the total weight of the composition. Preferably, the amount of the third impurity in the composition of the present invention is equal to or higher than 5 ppm by weight, preferably equal to or higher than 10 ppm by weight, and more preferably equal to or higher than 20 ppm by weight, relative to the total weight of the composition.

[0061] Similar to the definition of the amount of the first impurity given above, it should be understood that the amount of the third impurity can refer to the compound that meets the third impurity, that is, the total amount of all compounds that are aromatic hydrocarbons in the sense of the present invention, or to the more specifically defined third impurity described herein. In various embodiments, the amount can therefore also refer to one of the more specifically defined third impurities defined above, such as xylene. However, it may be preferred that the given maximum amount of the third impurity covers the total amount of all compounds that meet the aromatic hydrocarbons. These amounts can also be combined so that the total amount of aromatic hydrocarbons is equal to or less than 4000 ppm by weight relative to the total weight of the composition, and the amount of a specific impurity such as xylene is equal to or less than 400 ppm by weight.

[0062] Preferably, the composition according to the first aspect of the invention comprises TBPT in an amount ranging from 98.0 to 99.9 wt-%, more preferably from 98.5 to 99.9 wt-%, relative to the total weight of the composition.

[0063] As a result of the method of the third aspect of the invention described in further detail below, the composition of the first aspect of the invention may comprise an additional compound, wherein the additional compound may be a compound having a pressure p at 1 bar. B1 At a temperature T equal to or lower than 235°C, preferably lower than 230°C, more preferably equal to or lower than 200°C, equal to or lower than 180°C, equal to or lower than 160°C, most preferably equal to or lower than 140°C B1 Furthermore, preferably, the additional compound has a boiling point B1 at a pressure p of 1 bar. B2 At a temperature equal to or lower than 20°C B2 The melting point M2.

[0064] Preferably, the additional compound is a solvent (S1), preferably a polar solvent, more preferably a polar organic compound or water. Preferably, the polar organic compound is selected from the group consisting of esters, alcohols, ethers, aldehydes, ketones, and mixtures thereof. Particularly preferably, the polar organic compound is a methyl ketone or an alcohol, most preferably acetone, methyl ethyl ketone, or ethanol. Therefore, preferably, the additional compound is selected from the list consisting of acetone, methyl ethyl ketone, water, ethanol, or mixtures thereof.

[0065] Furthermore, it has been surprisingly found that TBPT occurs in the form of two crystalline polymorphs, referred to herein as polymorphs A and B or (crystalline) forms A and B. Crystalline form A can be distinguished from crystalline form B by X-ray powder diffraction spectroscopy. Thus, it was observed that the quantitative ratio of the two crystalline forms varies depending on the conditions used during the production of TBPT. Furthermore, it was observed that in particular crystalline form A exhibits thermal stability at temperatures of about 15°C to 45°C. Thus, crystalline form A of TBPT has improved storability compared to crystalline form B, although crystalline form B also exhibits a long storage time. Furthermore, due to the specific UV filter properties, i.e. the UV absorption spectrum of form A (see Figure 7 ), Form A of TBPT is suitable for sunscreen applications.

[0066] Thus, in the second aspect of the present invention, the composition preferably comprises at least a portion, preferably all, of the TBPT in crystalline form A, which exhibits in an X-ray powder diffraction pattern at room temperature using Cu-Ka radiation at least three of the following five reflections given as 2θ values: 11.6±0.2, 17.8±0.2, 21.1±0.2, 23.4±0.2, and 24.4±0.2°θ. More preferably, the crystalline form A exhibits in an X-ray powder diffraction pattern at room temperature using Cu-Ka radiation at least three of the following reflections: 11.6±0.2, 17.8±0.2, and 21.1±0.2°θ, and preferably at least five of the following reflections: 11.6±0.2, 17.8±0.2, 21.1±0.2, 23.4±0.2, and 24.4±0.2°θ.

[0067] It has been found that Form A provides an optimal UV absorption spectrum for sunscreen applications compared to Form B, also found as a metastable polymorph of TBPT (see Figure 7 ). Thus, it is beneficial to have a majority of the TBPT present in the composition in Form A. Thus, preferably, the amount of TBPT in the composition in crystalline Form A is greater than 50 wt-%, preferably greater than 60 wt-%, greater than 65 wt-%, greater than 70 wt-%, greater than 75 wt-%, greater than 80 wt-%, greater than 81 wt-%, greater than 82 wt-%, greater than 83 wt-%, greater than 84 wt-%, greater than 85 wt-%, greater than 86 wt-%, greater than 87 wt-%, greater than 88 wt-%, greater than 89 wt-%, greater than 90 wt-%, greater than 91 wt-%, greater than 92 wt-%, greater than 93 wt-%, greater than 94 wt-%, greater than 95 wt-%, greater than 96 wt-%, greater than 97 wt-%, greater than 98 wt-%, greater than 99 wt-%, and most preferably 100 wt-%, relative to the total weight of TBPT in the composition.

[0068] Preferably, the crystalline form A exhibits an endothermic peak from 221° C. to 256° C. in a DSC curve, wherein the DSC curve is measured by a differential scanning calorimeter at a scanning rate of 10° C. / min (see Figure 1 ). More preferably, the crystalline form A exhibits an endothermic peak from about 221° C. to about 256° C. in the DSC curve, further preferably wherein the enthalpy ΔH measured at the endothermic peak is in the range of about 35 J / g to about 50 J / g, more preferably wherein the enthalpy ΔH measured at the endothermic peak is in the range of about 38 J / g to about 45 J / g.

[0069] It has further been found that polymorphic forms A and B interconvert with each other. The transition temperature between these two forms is in the range of 230°C to 250°C. Heating TBPT to this high temperature induces a phase transition from the low-temperature stable form A to the high-temperature stable form B. These two forms are presumably an interconverting system of polymorphic forms, but the transition is not readily reversed upon cooling.

[0070] Furthermore, in the third aspect of the present invention, the composition preferably comprises at least a portion of the TBPT, preferably all of the TBPT, contained in the composition in crystalline form B, which crystalline form B exhibits in an X-ray powder diffraction pattern at room temperature using Cu-Kα radiation at least 3 of the following 5 reflections given as 2θ values: 8.6±0.2, 10.9±0.2, 17.5±0.2, 18.5±0.2, 19.5±0.2, 19.9±0.2 and 20.7±0.2 °θ.

[0071] Preferably, the crystalline form B exhibits an endothermic peak from 282° C. to 293° C. in a DSC curve, wherein the DSC curve is measured by a differential scanning calorimeter at a scanning rate of 10° C. / min. Preferably, in some embodiments, TBPT is contained in the composition in crystalline Form B in a weight ratio relative to the total weight of TBPT in the composition of greater than 50 wt-%, preferably greater than 60 wt-%, greater than 65 wt-%, greater than 70 wt-%, greater than 75 wt-%, greater than 80 wt-%, greater than 81 wt-%, greater than 82 wt-%, greater than 83 wt-%, greater than 84 wt-%, greater than 85 wt-%, greater than 86 wt-%, greater than 87 wt-%, greater than 88 wt-%, greater than 89 wt-%, greater than 90 wt-%, greater than 91 wt-%, greater than 92 wt-%, greater than 93 wt-%, greater than 94 wt-%, greater than 95 wt-%, greater than 96 wt-%, greater than 97 wt-%, greater than 98 wt-%, greater than 99 wt-%, and most preferably 100 wt-%.

[0072] Form A is suitable for sunscreen applications due to its specific UV absorption properties. However, biphenyl and xylene in the TBPT raw material are problematic aromatic hydrocarbons due to toxicological issues. It is not possible to significantly reduce impurities by multiple recrystallizations from xylene or from xylene / biphenyl mixtures because the low-temperature stable Form A is easily incorporated into small amounts of almost any solvent. However, at least for therapeutic applications or personal care applications (e.g., sunscreen applications), further purification of the TBPT raw material is necessary. Therefore, it is desirable to find a method that not only purifies the raw TBPT composition but also converts TBPT present in Form B in such compositions into Form A.

[0073] Thus, in a fourth aspect, the present disclosure provides a method for interconverting crystalline Form B of 2,4,6-tris(biphenyl-4-yl)-1,3,5-triazine (TBPT) into crystalline Form A of TBPT, the method comprising the steps of: a) providing (in a TBPT providing step) a composition C comprising TBPT in crystalline Form B; B ; b) the composition C B mixing (in a first mixing step) in a solvent (S1) to obtain a first mixture; c) stirring (in a stirring step) the first mixture at a temperature T1 for a time t1 and thereby obtaining TBPT in crystalline form A and thereby providing a second mixture; and d) separating (in a separating step) a composition C comprising TBPT in crystalline form A from the second mixture A .

[0074] Without being bound by theory, it is believed that the conversion of Form B to Form A of the present invention is accelerated by a process known as "solvent interaction transition."

[0075] In general, the method of the fourth aspect of the present invention can be used to purify and interconvert any starting TBPT. However, the method is preferably carried out using a composition comprising TBPT prepared using a method involving biphenyl and / or xylene. Therefore, in the method according to the fourth aspect of the present invention, the TBPT-providing step preferably further comprises the step of reacting 2,4,6-trihalogen-1,3,5-triazine with biphenyl. More preferably, the step of reacting 2,4,6-trihalogen-1,3,5-triazine with biphenyl comprises the following steps: a') reacting cyanuric chloride with biphenyl in heptane at a temperature in the range of about 90°C to about 120°C after adding hydrochloric acid and aluminum chloride; b') removing heptane from the reaction mixture under reduced pressure; and c') adding water, sodium hydroxide, and xylene to the reaction mixture.

[0076] Preferably, the step of reacting 2,4,6-trihalo-1,3,5-triazine with biphenyl further comprises one or more of the following optional steps:

[0077] d') optionally separating the organic phase from the aqueous phase and washing the organic phase with water, separating the organic phase from the aqueous phase and completely removing water from the organic phase by azeotropic distillation, heating the suspension at a temperature of about 130° C. to about 160° C.,

[0078] e') optionally filtering the suspension at a temperature of about 130°C to about 160°C, cooling the filtrate to a temperature of about 40°C to about 60°C and allowing TBPT to crystallize, isolating the product by filtration, washing the filtered product with a solvent (S2) and drying the product to obtain raw material TBPT.

[0079] Preferably, in the step of reacting 2,4,6-trihalogen-1,3,5-triazine with biphenyl, 2,4,6-trihalogen-1,3,5-triazine is cyanuric chloride. Further preferably, in the step of reacting 2,4,6-trihalogen-1,3,5-triazine with biphenyl, a solvent is used in the reaction mixture. In another preferred embodiment, the solvent is a non-polar solvent. In particular, a C1-C3 alkyl, alkyl-aryl ether, alkyl-alkyl ether containing C1-C3 alkyl radicals can be used. 20 A linear, branched, or cyclic aliphatic or aromatic hydrocarbon of carbon atoms, optionally substituted with an alkoxy, halide, or carbonyl moiety. In a preferred embodiment, a linear aliphatic hydrocarbon is used, most preferably hexane. The step of reacting 2,4,6-trihalo-1,3,5-triazine with biphenyl can be carried out in the absence of a solvent such as 1,2-dichlorobenzene.

[0080] In one embodiment, in the step of reacting 2,4,6-trihalogen-1,3,5-triazine with biphenyl, a catalyst is used. The catalyst can act as a Lewis acid. The catalyst can be selected from the group consisting of: acid halides, metal alkyls and alkoxides, protic acids, acidic oxides, cation exchange resins, and mixtures thereof, preferably selected from the group consisting of: AlCl 3 , AlBr 3 , BF 3 , BCl 3 , BBr 3 , BeCl 2 , CdCl 2 , ZnCl 2 , GaCl 3 , GaBr 3 , FeCl 3 , SbCl 3 , BiCl 3 , TiCl 4 , ZrCl 4 , SnCl 4 , UCl 4 , SbCl 5 , and mixtures thereof. In a preferred embodiment, the catalyst is used in a stoichiometric amount or in excess. As a co-catalyst, alcohol, water, HCl, HF, H 2 SO 4 , H 2 PO 4 , RCOOH (organic acid), sulfonic acid (such as p-toluenesulfonic acid) can be used. Most preferably, gaseous HCl is used as a co-catalyst. The co-catalyst can also be used in a stoichiometric amount or in excess. The step of reacting 2,4,6-trihalogen-1,3,5-triazine with biphenyl works particularly well when gaseous HCl is discharged into the reaction mixture. Preferably, in the step of reacting 2,4,6-trihalogen-1,3,5-triazine with biphenyl, the reaction temperature is from about -10°C to about 250°C, more preferably from about 5°C to about 150°C, and most preferably from about 70°C to about 130°C.

[0081] Furthermore, the step of reacting 2,4,6-trihalo-1,3,5-triazine with biphenyl can be carried out in an ionic fluid such as, for example, 1-butyl-pyridinium chloride-aluminum chloride (HI) and 1-butyl-3-methylimidazolium chloride-aluminum chloride (HI) (see, for example, 1-ethyl-3-methylimidazolium halogenoaluminate ionic liquids as solvents for Friedel-Crafts acylation reactions of ferrocene. Journal of the Chemical Society, Dalton Transactions: Inorganic Chemistry 1999 (1), 63).

[0082] Preferably, in the method according to the fourth aspect of the present invention, the TBPT providing step further comprises a step of treating the unpurified composition with a second solvent (S2) (see step e'). Furthermore, preferably, the separation step of the method according to the fourth aspect of the present invention further comprises a step of filtering and washing the crystals with at least one second solvent (S2).

[0083] In a preferred embodiment of the fourth aspect of the present invention, the second solvent (S2) is immiscible with water, preferably a hydrocarbon solvent, more preferably selected from the list consisting of toluene, mesitylene, xylene, and mixtures thereof. These additional steps further improve the purity of the product in view of the first and second impurities contained in the unpurified composition.

[0084] Furthermore, preferably, the method according to the fourth aspect of the present invention further comprises the steps of: e) providing (in a second providing step) an unpurified composition comprising TBPT and at least a first impurity consisting of one or more halogen-containing triazines, wherein the amount of the first impurity in the composition is equal to or higher than 950 ppm by weight relative to the total weight of the composition; and f) heating (in a heating step) the unpurified composition to a transition temperature T in the range of 235° C. to 280° C. T This step ensures that residual solvent and other molecules can be removed from the composition by evaporation. This further facilitates purification of the composition of the first aspect of the invention by the method according to the fourth aspect of the invention.

[0085] Preferably, during the stirring step, the temperature T1 is in the range of 10° C. to 180° C., more preferably 50° C. to 140° C. Likewise, preferably, during the stirring step, the pressure p1 is in the range of 900 mbar to 4000 mbar, preferably 950 mbar to 3000 mbar, and most preferably 970 mbar to 2700 mbar.

[0086] In a preferred embodiment of the fourth aspect of the invention, the first mixture of the first mixing step comprises a solvent (S1) in an amount in the range of 5 wt-% to 50 wt-%, preferably in the range of 5 to 40 wt-%, 5 to 35 wt-%, 6 to 34 wt-%, 7 to 33 wt-%, 8 to 32 wt-%, 9 to 31 wt-%, 10 to 30 wt-%, relative to the total weight of the first mixture. Preferably, in the stirring step, the time t1 is in the range of 1 h to 12 h, preferably 2 to 11 h, and most preferably 3 to 10 h. Preferably, the first mixing step is a mixing step involving intensive mixing, most preferably, the first mixing step comprises, preferably consists of, a kneading step. Therefore, most preferably, the first mixing step is carried out in a kneader reactor. Therefore, most preferably, the process of the fourth aspect of the invention is carried out in a kneader reactor.

[0087] In a preferred embodiment of the fourth aspect of the present invention, the separation step comprises heating the first mixture to a temperature T2 and / or reducing the pressure to a pressure p2 and thereby removing the solvent (S1) to obtain a composition C A Preferably, the temperature T2 is in the range of 100 to 150° C., more preferably 120 to 140° C. Likewise, the pressure p2 is preferably in the range of 10 to 300 mbar, more preferably 50 to 150 mbar.

[0088] Preferably, the solvent (S1) has a pressure p of 1 bar. B1 At a temperature T equal to or lower than 235°C, preferably lower than 230°C, more preferably equal to or lower than 200°C, equal to or lower than 180°C, equal to or lower than 160°C, most preferably equal to or lower than 140°C B1 Furthermore, preferably, the solvent (S1) has a boiling point B1 at a pressure p of 1 bar. B2 At a temperature equal to or lower than 20°C B2 This ensures that no further crystalline form B of TBPT is formed during the process.

[0089] Preferably, the solvent (S1) is a polar solvent, more preferably a polar organic compound or water. Preferably, the polar organic compound is selected from the group consisting of esters, alcohols, ethers, aldehydes, ketones, and mixtures thereof. Particularly preferably, the polar organic compound is a methyl ketone or an alcohol, most preferably acetone, methyl ethyl ketone, or ethanol. Therefore, preferably, the solvent (S1) is selected from the list consisting of acetone, methyl ethyl ketone, ethanol, water, or mixtures thereof. It has been surprisingly found that such solvents are suitable for the process of the present invention, even though TBPT has minimal solubility in these solvents.

[0090] Solvent residues of halogenated hydrocarbons (US2004 / 191191) can be removed by using the method of the fourth aspect of the present invention. When TBPT is synthesized in the absence of a solvent (US2004 / 191191), biphenyl residues can be removed by using the method of the fourth aspect of the present invention. Furthermore, when TBPT is synthesized in the absence of AlCl, biphenyl residues can be removed by using the method of the fourth aspect of the present invention.

[0091] In a fifth aspect, the present invention provides a cosmetic product comprising a composition according to the first aspect of the invention, preferably wherein TBPT is present in crystalline Form A in micronized form.

[0092] In a sixth aspect, the present invention provides the use of a composition according to the first aspect of the invention as a UV filter in a cosmetic product for protecting the hair and / or skin of a subject from the damaging effects of UV radiation.

[0093] Examples

[0094] The present invention is further illustrated by the following examples.

[0095] List of abbreviations

[0096] DSC Differential Scanning Calorimetry

[0097] PXRD powder X-ray diffraction spectrometry

[0098] GC gas chromatography

[0099] HPLC high-performance liquid chromatography

[0100] Flame Ionization Detector (FID)

[0101] DAD diode array detector

[0102] g grams

[0103] min

[0104] h hour

[0105] T temperature

[0106] K Kelvin

[0107] ℃ degrees Celsius

[0108] ΔH enthalpy change

[0109] J Joule

[0110] m meters

[0111] L liter

[0112] k thousand

[0113] m millimeter

[0114] μ micro

[0115] TBPT 1,3,5-Triazine, 2,4,6-tris[1,1'-biphenyl]-4-yl

[0116] BBCT 2,4-bis([1,1′-biphenyl]-4-yl)-6-chloro-1,3,5-triazine

[0117] approx.

[0118] PSD particle size distribution

[0119] method

[0120] a) Characterization of TBPT polymorphs

[0121] The DSC experiment was carried out in an open pan. In this case, volatile solvents and impurities evaporate irreversibly. Scan rate 10K / min, 20°C-300°C, N2 50ml / min. Instrument: DSC3+ module, Mettler-Toledo or similar instrument. PXRD patterns were recorded using a PANalytical X Pert Pro X-ray diffractometer using Cu Kα radiation in reflection geometry (Bragg-Brentano). The sample was placed in a silicon single crystal sample holder at a depth of 0.2 mm and gently and precisely flattened. The tube voltage was 45 kV and the current was 40 mA. PXRD data were collected at room temperature in a range of 2θ=3.0°-40.0° with an increment of 0.017° and a measurement time of 20 s / step. PXRD data were analyzed using HighScore Plus 4.9 (Malvern Panalytical BV). Peak picking was performed using the following parameters: minimum significance: 7.00, minimum cap width: 0.01° 2θ, maximum cap width: 1.00° 2θ, peak base width: 2.00° 2θ, and smoothing of peak tops.

[0122] b) Quantification of impurities

[0123] GC analysis was used for the quantification of 2-propanol, xylene (mixture of isomers), biphenyl, and isopropyl palmitate. Instrument: Agilent 6850-2GC. Column: Agilent HP-5, 30 m x 320 μm x 0.25 μm. Oven temperature: 70°C for 3 min, 50 K / min → 300°C; 300°C for 5 min. Sample preparation: The sample was completely dissolved in 1,4-dioxane at 80°C (the turbid solution was filtered after cooling to 20°C). Detector: FID. Calibration was performed using external standards of xylene (mixture of isomers) and biphenyl. HPLC analysis was used for the quantification of TBPT and BBCT. Instrument: Agilent 1200 HPLC. Column: Phenomenex C18 / 5 μm, length: 150 mm. Oven temperature: 40°C. Injection volume: 5 μL. Eluent: 900 parts acetonitrile + 50 parts tetrahydrofuran + 50 parts water (isocratic elution). Sample preparation: Completely dissolve the sample in tetrahydrofuran. Detector: DAD. Calibration is performed using external standards of TBPT and BBCT.

[0124] c) UV absorption

[0125] The UV spectra of micronized TBPT forms A and B were recorded as described in WO 2004 / 085412 A1 (Example 7: Preparation of micronized UV absorbers).

[0126] Thus, d(50) is the average particle size. In the case of UV absorbers for cosmetics, the spectral range between 290 nm and 400 nm is of most interest. The wavelength of the extinction maximum can be searched for, and the extinction value at this wavelength is taken to characterize the absorptive capacity of the substance. Using the Beer-Lambert law, the molar decimal extinction coefficient at any wavelength is obtained, where:

[0127]

[0128] The corresponding specific extinction E1,1(λ) can be obtained by

[0129] The equation is obtained:

[0130]

[0131] Where M = molecular weight of the UV absorber.

[0132] Reference Example RE1 - Preparation of 1,3,5-triazine, 2,4,6-tris[1,1'-biphenyl]-4-yl (TBPT)

[0133] Suitable materials for the reactor / container are, for example, Hastelloy C or enameled steel or glass. 207 kg of cyanuric chloride, 2080 kg of biphenyl (melted) and 340 kg of heptane are placed in a container (T = 105 ° C - 110 ° C). 21 kg of gaseous hydrochloric acid is added below the surface of the stirred mixture (T = 105 ° C - 110 ° C). At 110 ° C, 300 kg of aluminum chloride is added in batches according to the temperature development. After the last aluminum chloride is added for about 4 hours, the reaction mass is stirred at 110 ° C - 114 ° C for about one hour until the reaction is complete. Afterwards, the heptane is removed by distillation under vacuum (≥ 100 mbar). The reaction mixture is carefully added to a mixture of 2500 kg of water, 135 kg of sodium hydroxide and 1670 kg of xylene at 85 ° C for hydrolysis. The mixture is stirred at 85 ° C - 90 ° C for about 30 minutes until complete hydrolysis. The lower aqueous phase was separated from the organic product suspension at 90°C. The organic phase (suspension) was then washed with 1000 kg of water at 90°C. After separation of the aqueous phase, the organic phase (suspension) was dried by azeotropic distillation under vacuum. The water was completely removed from the suspension. By heating the yellow suspension to 143°C-150°C, the product dissolved and a turbid solution was obtained. Hot filtration was performed to remove traces of insoluble impurities. Within 4 hours, the orange to brown solution was cooled to 40°C to obtain crystalline TBPT. The product was isolated by filtration, washed with 2000 kg of xylene and dried under vacuum at 100°C-140°C.

[0134] Comparative Examples CE1-3: Conventional Purification of TBPT

[0135] The TBPT raw materials were purified in a Büchi glass oven (Kugelrohr, Büchi Laboratory Technology AG). was performed in a 1:1 ratio (1:1) 1:1 ratio of 1:1 to 1:1. The results were obtained from a 1:1 ratio of 1:1 ratio ...

[0136] CE1: 1-5 g of TBPT starting material, synthesized according to the synthetic procedure of RE1, was heated under reduced pressure (<100 mbar, 1-22 h) until it became liquid (melting point approximately 285° C.). Volatile impurities were removed, and the product solidified until cooled to room temperature. The longer the product was heated, the darker it became.

[0137] CE2: 1-5 g of TBPT starting material synthesized according to the synthetic procedure of RE1 was heated under reduced pressure (<100 mbar, 8-24 h) until 245-255° C. without melting. Volatile impurities were removed.

[0138] CE3: 1-5 g of TBPT starting material synthesized according to the synthetic procedure of Example 1 was heated under reduced pressure (<10 mbar, 22 h) until 240° C. without melting. Volatile impurities were removed.

[0139] Example of the present invention: Purification of TBPT

[0140] Experimental setup: 8-liter stainless steel (Hastelloy) kneader reactor with reverse hook, 70% fill volume (approximately 1.9 kg TBPT), rotation speed 20 / min. The kneader was heated with an oil thermostat. Exhaust gases were drawn off from the kneader, and the gas stream was condensed in a spiral cooler. The product was always cooled before opening the apparatus to prevent contact with hot oxygen, which could affect the color.

[0141] Inventive Example IE1 (Solvent Methyl Ethyl Ketone)

[0142] IE1_A: Conversion of polymorph A to polymorph B

[0143] The TBPT raw material was loaded into the kneader reactor. The kneader reactor was evacuated and purged with nitrogen for inertization. A constant nitrogen purge of 10 L / h was present during the process. The kneader was placed at p T The product temperature is heated to above 243°C with a heating medium for t T The temperature in the product was measured with several PT sensors along the kneader to observe the temperature distribution in the product and to control the temperature to be above 243° C. as the minimum temperature of the complete product. The vacuum was kept constant at 100-600 mbar.

[0144] Temperature (T T ) should not exceed 255°C. At higher temperatures, the product color darkens and the product approaches the melting point of 280°C, which must be avoided. If the temperature approaches the melting point, the product may become viscous. The machine is also additionally insulated, so cold spots are unlikely. Good mixing of the material is necessary for a consistent temperature distribution and the removal of impurities.

[0145] Table 1: Preparation conditions for the conversion of polymorph B of Example IE1_A

[0146]

[0147] The products from IE1_A_a, IE1_A_b, IE1_A_c and IE1_A_d were removed from the reactor, mixed and homogenized to produce IE1_A_x.

[0148] IE1_B: Conversion of polymorph B to polymorph A

[0149] A portion of the TBPT mixture IE1_A_x obtained from Example IE1_A was loaded into a kneader reactor. The kneader reactor was evacuated and purged with nitrogen for inertization. The pressure was adjusted to p1 and the temperature to T1. The solvent was metered into the kneader reactor at 10 to 30% by mass of the total inserted mass of TBPT. The solid product was moistened with the solvent inside the apparatus to form a slurry. The temperature was adjusted to p1. T The mixture was kept below the boiling point of the solvent. The solvent should remain in the product mixture. The duration of mixing (t1 at T1) and the type of solvent were process parameters that varied from experiment to experiment. The solvent was then dried at 140°C and 100 mbar vacuum (1-6 h). Before opening the instrument, the product was cooled to prevent contact with hot oxygen, which could affect the color. The purified TBPT was analyzed.

[0150] Table 2: Preparation conditions for the conversion of polymorph A of Example IE1_B

[0151]

[0152] Inventive Example IE2 (Solvent Acetone)

[0153] IE2_A: Conversion of polymorph A to polymorph B

[0154] The process steps were carried out as described in Example IE1_A. The kneader reactor was opened to obtain a product sample of TBPT for analysis. The product remained in the reactor.

[0155] Table 3: Preparation conditions for the conversion of polymorph B of Example IE2_A

[0156]

[0157] IE2_B: Conversion of polymorph B to polymorph A

[0158] The process steps were carried out as described in Example IE1_B, except that acetone was used as solvent.

[0159] Table 4: Preparation conditions for the conversion of polymorph A of Example IE2_B

[0160]

[0161] Inventive Example IE3 (Solvent Ethanol)

[0162] IE3_A: Conversion of polymorph A to polymorph B

[0163] The process steps were carried out as described in Example IE1_A. The kneader reactor was opened to obtain a product sample of TBPT for analysis. The product remained in the reactor.

[0164] Table 5: Preparation conditions for the conversion of polymorph B of Example IE3_A

[0165]

[0166] IE3_B: Conversion of polymorph B to polymorph A

[0167] The process steps were carried out as described in Example IE1_B, except that ethanol was used as solvent.

[0168] Table 6: Preparation conditions for the conversion of polymorph A of Example IE3_B

[0169]

[0170] Inventive Example IE4 (Solvent Water)

[0171] IE4_A: Conversion of polymorph A to polymorph B

[0172] The process steps were carried out as described in Example IE1_A. The kneader reactor was opened to obtain a product sample of TBPT for analysis. The product remained in the reactor.

[0173] Table 7: Preparation conditions for the conversion of polymorph B of Example IE4_A

[0174]

[0175] IE4_B: Conversion of polymorph B to polymorph A

[0176] The process steps were carried out as described in Example IE1_A, except that water was used as solvent.

[0177] Table 8: Preparation conditions for the conversion of polymorph A of Example IE4_B

[0178]

[0179] Quantification of impurities

[0180] Table 9: Overview of the purity in % and the impurity contents of 2,4-bis([1,1′-biphenyl]-4-yl)-6-chloro-1,3,5-triazine (BBCT), biphenyl and xylene in ppm for the corresponding examples.

[0181] TBPT (%) BBCT(ppm) Biphenyl (ppm) Xylene (ppm) RE1 98.4 1000 5000 5000 CE1 99.5 200 <50 400 CE2 CE3 99.5 300 <50 <100 IE1_A_a <200 <200 IE1_A_b <200 <200 IE1_A_c <200 <200 IE1_A_d <200 <200 IE1_A_x 98.5 500 100 <100 IE1_B_a* 98.6 500 200 <100 IE1_B_b* 97.8 600 300 <100 IE2_A 98.9 500 <100 <100 IE2_B** 98.5 500 100 <100 IE3_A 99.3 400 <100 <100 IE3_B*** 99.0 400 <100 <100 IE4_A 99.3 500 <100 <100 IE4_B 98.6 500 <100 <100

[0182] *Contains 0.6%-1% methyl ethyl ketone

[0183] **Contains 0.7%-1% acetone

[0184] ***Contains 0.3%-1% ethanol

[0185] After purification, the concentrations of impurities such as xylene, toluene, 1,1′-biphenyl, BBCT were reduced.

[0186] result

[0187] DSC measurements

[0188] Table 10: Comparative ΔH of DSC endothermic peaks at 221°C-256°C and 282°C-293°C.

[0189]

[0190] PXRD measurements

[0191] Table 11: Polymorph types determined based on DSC and PXRD data

[0192]

[0193]

[0194] *May contain residues of polymorph A. Complete conversion can be achieved by extended heat treatment as described in the conversion process step from Form A to Form B

[0195] **May contain residues of polymorph B. Complete conversion can be achieved by extended treatment as described in the conversion process step from Form B to Form A

[0196] In CE1-3, polymorph A transforms into polymorph B due to high temperature. Only polymorph A transforms into polymorph B due to its specific UV absorption characteristics (see Figure 7 ) and is suitable for sunscreen applications. In addition, polymorph B is metastable at room temperature.

[0197] XRD peak

[0198] Table 4: PXRD peaks of RE1

[0199]

[0200]

[0201] Table 5: PXRD peaks of CE3

[0202]

[0203] Table 6: PXRD peaks of CE2

[0204]

[0205]

[0206] Table 7: PXRD peaks of TBPT pure batch IE1

[0207]

[0208]

Claims

1. A composition comprising 1,3,5-Triazine, 2,4,6-tris[1,1'-biphenyl]-4-yl (TBPT), and a first impurity consisting of one or more halogen-containing triazines, and A second impurity consisting of biphenyl, wherein the amount of the first impurity is equal to or less than 900 ppm by weight relative to the total weight of the composition, and wherein the amount of the second impurity is equal to or less than 4000 ppm by weight relative to the total weight of the composition.

2. The composition according to claim 1, wherein (1) the amount of the first impurity in the composition is equal to or less than 800 ppm by weight, more preferably equal to or less than 600 ppm by weight, and most preferably equal to or less than 400 ppm by weight, relative to the total weight of the composition; and / or (2) The halogen-containing triazine is selected from chlorine-containing triazines, bromine-containing triazines, and mixtures thereof, preferably 1,3,5-triazine, 2,4,6-tris(4-bromophenyl) and / or 1,3,5-triazine, 2,4-bis([1,1′-biphenyl]-4-yl)-6-chloro(BBCT), and most preferably 1,3,5-triazine, 2,4-bis([1,1′-biphenyl]-4-yl)-6-chloro(BBCT).

3. The composition according to claim 1 or 2, wherein The amount of the second impurity in the composition is equal to or less than 3000 ppm by weight, more preferably equal to or less than 600 ppm by weight, and most preferably equal to or less than 300 ppm by weight relative to the total weight of the composition.

4. A composition according to any one of the preceding claims, wherein The composition further comprises a third impurity comprising, preferably consisting of, an aromatic hydrocarbon, wherein the third impurity does not comprise biphenyl, and wherein the amount of the third impurity in the composition is equal to or lower than 4000 ppm by weight, preferably equal to or lower than 800 ppm by weight, and more preferably equal to or lower than 400 ppm by weight, relative to the total weight of the composition.

5. The composition according to claim 4, wherein The aromatic hydrocarbon is selected from the group consisting of monocyclic aromatic hydrocarbons, polycyclic aromatic hydrocarbons (PAH), and mixtures thereof, preferably selected from the group consisting of alkyl-substituted benzene compounds (Cn-benzene), condensed aromatic hydrocarbons, and mixtures thereof, more preferably selected from the group consisting of benzene, toluene, xylene, ethylbenzene, naphthalene, and mixtures thereof, and most preferably xylene.

6. A composition according to any one of the preceding claims, wherein At least a portion of the TBPT, preferably more than 80 wt-%, preferably more than 90 wt-%, more preferably more than 95 wt-%, and most preferably 100 wt-% of the TBPT is contained in the composition in the form of crystalline form A, which crystalline form A exhibits in an X-ray powder diffraction pattern at room temperature using Cu-Kα radiation at least 3 of the following 5 reflections given as 2θ values: 11.6±0.2, 17.8±0.2, 21.1±0.2, 23.4±0.2 and 24.4±0.2 °θ.

7. A composition according to any one of the preceding claims, wherein At least a portion of the TBPT, preferably more than 80 wt-%, preferably more than 90 wt-%, more preferably more than 95 wt-%, and most preferably 100 wt-% of the TBPT is contained in the composition in the form of crystalline form B, which crystalline form B exhibits in an X-ray powder diffraction pattern at room temperature using Cu-Kα radiation at least 3 of the following 5 reflections given as 2θ values: 8.6±0.2, 10.9±0.2, 17.5±0.2, 18.5±0.2, 19.5±0.2, 19.9±0.2 and 20.7±0.2 °θ.

8. A composition according to any one of the preceding claims, wherein The composition further comprises an additional compound, wherein the additional compound is a solvent (S1) and has a pressure p at 1 bar. B1 At a temperature T of 235°C or lower, preferably 230°C or lower, more preferably 200°C or lower, 180°C or lower, 160°C or lower, and most preferably 140°C or lower. B1 The boiling point is B1.

9. The composition according to claim 8, wherein The additional compound has a pressure p at 1 bar B2 At a temperature equal to or lower than 20°C B2 The melting point M2.

10. The composition according to any one of claims 8 or 9, wherein The additional compound is selected from the list consisting of acetone, methyl ethyl ketone, ethanol, water, and mixtures thereof.

11. A process for interconverting crystalline Form B of 2,4,6-tris(biphenyl-4-yl)-1,3,5-triazine (TBPT) into crystalline Form A of TBPT, the process comprising the steps of: a) Providing a composition C comprising TBPT in crystalline form B B ; b) the composition C B mixing in a solvent (S1) to obtain a first mixture; c) stirring the first mixture at temperature T1 for time t1 and thereby obtaining TBPT in crystalline form A and thereby providing a second mixture; and d) isolating composition C comprising TBPT in crystalline form A from the second mixture A .

12. The method according to claim 11, wherein TBPT provides steps including a1) providing, in a second providing step, an unpurified composition comprising TBPT and at least a first impurity consisting of one or more halogen-containing triazines, wherein the amount of the first impurity in the composition is preferably equal to or higher than 950 ppm by weight relative to the total weight of the composition; a2) heating the unpurified composition to a transition temperature T of 235° C. to 280° C. in a heating step T scope.

13. The method according to claim 12, wherein: The heating step comprises maintaining the pressure p1 in the range of 5 mbar to standard pressure, preferably 900 mbar to standard pressure.

14. A cosmetic product comprising a composition according to any one of claims 1 to 6 and 8 to 10, preferably wherein more than 80 wt-%, preferably 100 wt-% of TBPT is present in micronized form A, which crystalline form A exhibits in an X-ray powder diffraction pattern at room temperature using Cu-Kα radiation at least 3 of the following 5 reflections given as 2θ values: 11.6±0.2, 17.8±0.2, 21.1±0.2, 23.4±0.2 and 24.4±0.2 °θ.

15. Use of a composition according to any one of claims 1 to 6 and 8 to 10 as a UV filter in a cosmetic product for protecting the hair and / or skin of a subject from the damaging effects of UV radiation, wherein Preferably, more than 80 wt-%, preferably 100 wt-% of the TBPT is present in crystalline form A, which exhibits in an X-ray powder diffraction pattern at room temperature using Cu-Kα radiation at least 3 of the following 5 reflections given as 2θ values: 11.6±0.2, 17.8±0.2, 21.1±0.2, 23.4±0.2 and 24.4±0.2 °θ.

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