Process for producing dichloro phenyltriazine

Abstract

The present invention generally relates to a process for producing process for producing a dichloro phenyltriazine derivative according to the general formula IV, as well as to a processs for producing bis-ethylhexyloxyphenol methoxyphenyl triazine of formula I' (BMT). The invention further relates to UV filter compositions and cosmetic compositions comprising the same.

Description

[0001] Eisenfiihr Speiser

[0002] Munich, 24 March 2026

[0003] Our Ref.: SM 6965-02WO SOE / TWS

[0004] Applicant: Symrise AG

[0005] Serial Number: Subsequent Application based on PCT / EP2025 / 057937

[0006] Symrise AG

[0007] MiihlenfeldstraBe 1, 37603 Holzminden,

[0008] Germany

[0009] Process for producing dichloro phenyltriazine

[0010] The present invention relates to the field of organic synthesis of substituted triazine compounds. In particular, the invention relates to an improved process for producing dichloro phenyltriazine derivatives, especially 2,4-dichloro-6-(4-methoxyphenyl)-1 ,3,5-triazine (DICAT), and to a process for producing bis-ethylhexyloxyphenol methoxyphenyl triazine (BMT) from DICAT. The invention further relates to high-purity BMT compositions with an advantageous impurity profile, to UV filter compositions comprising such BMT compositions, and to cosmetic compositions for topical application on skin or hair.

[0011] 2,4,6-substituted triazines are known in the art. A well-known example is 2,4-Bis-{[4-(2-ethyl-hexyloxy)-2-hydroxy]-phenyl}-6-(4-methoxy-phenyl)-1 ,3,5-triazine, which is also referred to as bemotrizinol (BMT or BEMT), or Bis-ethylhexyloxyphenol methoxyphenyl triazine (INCI name). It is an oil-soluble I hydrophobic organic compound that is used in sunscreens and cosmetic applications to efficiently absorb UV rays.

[0012] BMT is a broad-spectrum UV absorber, absorbing both UVB and UVA rays. It has two absorption peaks and is highly photostable. It helps prevent the photodegradation of sunscreen actives like avobenzone. BMT is approved for use in sunscreens in the European Union and other parts of the world.

[0013] Industrial production of BMT typically involves (i) preparation of a substituted phenyl Grignard reagent; (ii) reaction with cyanuric chloride (IUPAC name: 2, 4, 6-trichloro-1 ,3,5-triazine) to form DICAT, a monosubstituted product; (iii) reaction with resorcinol (IUPACname: benzene-1 ,3-diol) in a Friedel-Crafts acylation to obtain a trisubstituted product: 4,4'-[6-(4-methoxyphenyl)-1 ,3,5-triazine-2,4-diyl]bis(benzene-1 ,3-diol), also known as DIOPAT; and (iv) alkylation with 3-bromo-2-methylheptane to form BMT.

[0014] Products obtained according to conventional manufacturing routes may exhibit a comparatively complex impurity distribution, characterized by the presence of multiple structurally related process-derived impurities, such as incompletely substituted triazine derivatives, hydrolysis products of the triazine core, residual phenolic starting materials, regioisomeric substitution products, and oxidative degradation products, potentially leading to color drift and cosmetic unacceptability. Many industrial-scale manufacturing processes exhibit batch-to-batch variability in the impurity profile. Certain impurities may possess physicochemical properties similar to those of the target compound, such as comparable solubility, similar salt-formation behavior, comparable volatility, or similar selectivity. As a result, separation of such impurities from the target compound can be challenging and may require substantial time and effort. Furthermore, the manufacturing processes themselves may exert corrosive effects on stainless-steel apparatuses, which can influence the formation of additional impurities. These observations suggest that key process parameters affecting impurity formation are not tightly controlled in industrial-scale manufacture.

[0015] Accordingly, there remains a need for a robust production process that allows to obtain BMT ultimately in cosmetic quality, can be carried out on an industrial manufacturing scale and shows low product variability, in particular with respect to the product’s impurity profile.

[0016] OBJECT OF THE INVENTION

[0017] An overall aim is an improved process for the chemical synthesis of BMT or related 2, 4, 6-trisubstituted triazines, which addresses the disadvantages of many conventional industrial processes. Specifically, an industrially robust synthesis process is sought after which resulting synthesis product shows a reproducible impurity profile under industrially relevant conditions with little batch-to-batch variability.

[0018] An emphasis lies on the prevention that multiple impurity species and / or large impurity levels are formed during the chemical synthetic route with a focus on the Grignard reaction step. Avoiding impurities including side products during upstream processing so as to form an intermediate with less complex impurity profile, will likely have a positive impact on the level of the product (increased purity, increased yield) and the level of the process, especially downstream process, such as simplification of the downstream part, reduction of downstream steps, shortening of process times. Reduction of the required chemicalsand equipment, replacement of dangerous chemicals, and increase in sustainability are optional targets.

[0019] Desirable impurity-related properties of the resulting product targeted by the present invention in particular include: low total impurity content, few impurity species, low level of specific critical impurities, and absence of certain toxic impurities.

[0020] The object is achieved by the present invention.

[0021] SUMMARY OF THE INVENTION

[0022] The invention provides a process for producing a dichloro phenyltriazine derivative of formula IV, or a composition comprising the same,

[0023] from a phenylmagnesium halogenide of formula V,

[0024] R1I— 4 - Mg Hall

[0025]

[0026] V / /

[0027] (V).

[0028] In formulae IV and V, the substituents are defined as disclosed herein.

[0029] The production of the dichloro phenyltriazine derivative is based on the reaction of cyanuric chloride with a phenylmagnesium halogenide (formula V) in a 2-methyltetrahydrofuran (2- MeTHF) solvent under iron-free conditions. The invention is based on the finding that this combination - the use of 2-MeTHF in combination with strict control of iron including defined magnesium source - enables the production of the dichloro phenyltriazine derivative, preferably DICAT, with a robust impurity profile. The impurity profile is further characterized by a low total impurity content, few impurity species, low level of critical impurities (iron), and absence of certain dangerous reactants (THF).In fact, the use of 2-MeTHF as a process solvent provides several advantages over the conventionally used solvent THF. In particular, 2-MeTHF exhibits limited miscibility with water, which facilitates phase separation and enables more efficient recovery of the solvent. This allows easier process-design usable for industrial-scale manufacture. As a consequence, the overall process can be carried out with fewer separation steps and with reduced operational effort.

[0030] Furthermore, the use of 2-MeTHF can lead to a reduction in the number of process steps and the overall processing time. In addition, 2-MeTHF exhibits lower toxicity than THF, which may improve the safety profile of the process. Furthermore 2-Me-THF could be produced from renewable sources.

[0031] The process for the production of BMT starts with the production of DICAT, and subjects the reaction mass to a multi-step conversion to form BMT. Advantageously, the favorable impurity profile obtained on the DICAT stage translates into a corresponding favorable impurity profile on the final BMT stage.

[0032] Accordingly, the invention further provides a composition comprising BMT and specified impurities, obtainable by the above process. Such composition is particularly suitable as UV filter in a skin or hair care or sunscreen product. The invention thus further relates to a UV filter composition and to a skin or hair or sun protection case composition comprising the same.

[0033] DETAILED DESCRIPTION OF THE INVENTION

[0034] Dichloro phenyltriazine production

[0035] The process for producing a dichloro phenyltriazine derivative comprises a) providing a phenylmagnesium halogenide of formula V,

[0036]

[0037] The process further comprises b) reacting cyanuric chloride with the phenylmagnesium halogenide. Cyanuric chloride is a compound of formula III,

[0038]

[0039] The reaction mechanism is a Grignard-mediated nucleophilic aromatic substitution.

[0040] The process further comprises c) obtaining a reaction mass comprising a dichloro phenyltriazine derivative of formula IV,

[0041] R1

[0042]

[0043] In formulae IV and V, R1 is selected from the group of:

[0044] ■ linear alkyl with a chain length of C1 to C10, preferably C2 to C10;

[0045] ■ linear alkyl with a chain length of C2 to C10 with branches in alpha-(a) I beta-(p) I gamma-(y)-position to the phenyl group selected from the group of methyl, ethyl, propyl and butyl;

[0046] ■ linear alkoxyl with a chain length of C1 to C10, preferably C2 to C10;

[0047] ■ linear alkoxyl with a chain length of C2 to C10 with branches in alpha-(a) I beta-(p) I gamma-(y)-position to the oxygen selected from the group of methyl, ethyl, propyl and butyl;

[0048] ■ linear alkenyl with a chain length of C2 to C10;

[0049] ■ linear alkenyl with a chain length of C2 to C10 with branches in alpha-(a) I beta-(p) I gamma-(y)-position to the phenyl selected from the group of methyl, ethyl, propyl and butyl;

[0050] ■ linear alkenoxyl with a chain length from C2 to C10;

[0051] ■ linear alkenoxyl with a chain length of C2 to C10 with branches in alpha-(a) I beta-(p) I gamma-(y)-position to the oxygen selected from the group of methyl, ethyl, propyl and butyl;

[0052] ■ phenyl; and

[0053] ■ phenoxy.In formula V, Hal is chlorine or bromine. Bromine is preferred.

[0054] The dichloro phenyltriazine derivative formed in the process of the invention is obtained in a reaction mass in admixture with other components. The term “reaction mass” as used herein refers to the mixture resulting from a chemical reaction, comprising the substance or substances formed in the reaction together with any other components present in the mixture. Typically, the reaction mass comprises one or more reaction products and optionally further components selected from starting materials, intermediates, by-products, solvents, catalysts, additives, and / or any other substances present or formed during the reaction.

[0055] Reaction solvent and conditions

[0056] The reaction with cyanuric chloride in b) proceeds in an oxolane solvent. An “oxolane solvent” as understood herein is a solvent comprising one or more liquids that are oxolanes, i.e. five-membered saturated cyclic ethers (tetrahydrofurans) having an oxygen atom in the ring. Oxolane solvents include THF and substituted THFs such as 2-MeTHF, as well as mixtures thereof. In the present invention, the oxolane solvent comprises 2-MeTHF as a main component.

[0057] An advantage of 2-MeTHF as compared to THF is its lower miscibility with water, which enables the design of synthesis processes based on phase separation and phase transfer principles, resulting in easier workup, improved phase separation, and more efficient solvent regeneration. THF belongs to the carcinogenic compounds of category 2, while 2-MeTHF is not carcinogenic. Moreover, 2-Me-THF has the advantage that it may be produced from renewable sources.

[0058] Importantly, the reaction is conducted in an iron-free environment. An iron-free environment means one that is free of exposed iron surfaces such as iron reactor inner walls, iron impellers or sensors with outer iron surfaces, or one that is substantially free of exposed iron surfaces. For example, step (ii) can be carried out in an emaille (enamel) reactor, glass line reactor or tantalum reactor. If present at all, exposed iron surface area is preferably so low such that the overall aim of the reaction step is not compromised and side reactions occur at most to a technically negligible extent, e.g. the total amount of all side products I byproducts is less than 10% (m / m), less than 8%, less than 6%, less than 4%, less than 2%, less than 1%, or even less than 0.5%.

[0059] The expression “iron-free environment” thus in particular excludes the case where the reaction mixture comes in contact with iron (e.g., exposed iron surfaces such as ironreaction vessel, iron impellers, etc.), e.g. where the reaction mixture is encased by an iron reaction vessel. By carrying out step (ii) in an iron-free environment, undesired byproduct formation is avoided. Less formation of byproducts leads to an increase of the yield, a simplification of the recovery and / or reduction of purification effort for the intermediates and the final product.

[0060] The preferred reaction temperature is between 0-40 °C. Furthermore, a nitrogen atmosphere or an oxygen-free atmosphere is favorable for this step b).

[0061] In preferred embodiments, the oxolane solvent may comprise at least 85% by volume of 2-MeTHF. The oxolane solvent may comprise at least 90% by volume of 2-MeTHF. The oxolane solvent may comprise at least 95% by volume of 2-MeTHF. The solvent may consist essentially of 2-MeTHF.

[0062] The oxolane solvent may alternatively comprise a mixture of 2-MeTHF and THF, provided 2-MeTHF remains the main component. The volumetric ratio of 2-MeTHF to THF may be 99:1. The volumetric ratio of 2-MeTHF to THF may be 95:5. The volumetric ratio of 2-MeTHF to THF may be 90:10. The volumetric ratio of 2-MeTHF to THF may be 85:15. The volumetric ratio of 2-MeTHF to THF may be 80:20. The volumetric ratio of 2-MeTHF to THF may be 75:25. The volumetric ratio of 2-MeTHF to THF may be 70:30.

[0063] The 2-MeTHF can be any one of racemic 2-MeTHF (rac 2 - MeTHF) with ( S ) - ( + ) / ( R ) - ( - ) ratio of 1:1 , ( S ) - ( + ) - stereoisomer of 2 - MeTHF and ( / ? ) - ( - ) - stereoisomer of 2 - MeTHF and mixtures of (S)-(+)-stereoisomers and (R)-(-)-stereoisomers of 2-MeTHF. The process of the present invention is not limited to a particular ratio of (S)-(+) to (R)-(-); exemplary mixtures have a ratio of ( S ) - ( + ) / ( / ? ) - ( - ) of 99.9:0.1 , 99:1 , 98:2, 95:5, 90:10, 85:15, 80:20, 70:30, 65:35, 60:40, 55:45, 52:48, 51 :49, 49:51 , 48:52, 45:55, 40:60, 35:65, 30:70, 20:80, 15:85, 10:90, 5:95, 2:98, 1 :99 und 0.1 :99.9.

[0064] Control of impurities

[0065] The resulting reaction mass comprises the dichloro phenyltriazine derivative suspended or dissolved in the 2-MeTHF solvent in admixture with impurities. The process is characterized in that the reaction mass comprises a low level of defined impurities, in particular sideproducts. The reduced formation of these side-products is attributed to the use of 2-MeTHF as oxolane solvent in combination with an iron-free environment including a defined magnesium quality.The reaction mass comprising the dichloro phenyltriazine derivative may comprise a compound of formula (VI),

[0066]

[0067] (VI).

[0068] In some embodiments, the amount of compound (VI) may be less than 1%. In other embodiments, the amount of compound (VI) may be less than 0.5%, preferably less than 0.3 %.

[0069] The reaction mass comprising the dichloro phenyltriazine derivative may comprise a compound of formula (VII),

[0070]

[0071] (VII).

[0072] In some embodiments, the amount of compound (VII) may be less than 5%. In other embodiments, the amount of compound (VII) may be less than 3%. In yet other embodiments, the amount of compound (VII) may be less than 1.5%, preferably less than 1 %, more preferably less than 0.5 %.

[0073] The reaction mass comprising the dichloro phenyltriazine derivative may further comprise residual (non-reacted) cyanuric chloride. The content of unreacted cyanuric chloride is preferably less than 1 %, preferably less than 0.5 %, more preferably less than 0.3%.

[0074] Unless otherwise indicated, purity or impurity content (in %) is expressed as HPLC area percent, preferably determined according to LC-MS analysis with additional UV detection technology described in the example section.

[0075] A preferred dichloro phenyltriazine derivative is DICAT. DICAT is a compound of formula IV, in which R is OMe, and is accessible by reacting 4-methoxyphenyl magnesium halogenide with cyanuric chloride. In addition to DICAT, the reaction mass may furthercomprise, as impurities, a compound of formula VI in which R is OMe, i.e. dimethoxyphenyl triazine of formula Via,

[0076] N

[0077]

[0078] (Via),

[0079] and / or a compound of formula VII in which R is OMe, i.e. dimethoxy biphenyl of formula Vila,

[0080]

[0081] (Vila).

[0082] A specific embodiment concerns the reaction of 4-Methoxyphenyl magnesium bromide with cyanuric chloride in 2-MeTHF, preferred under nitrogen atmosphere or oxygen-free atmosphere, further preferred in iron-free environment, to obtain a reaction mass including DICAT, unreacted cyanuric chloride and side products, preferably dimethoxyphenyl triazine of formula Via and dimethoxy biphenyl of formula Vila.

[0083] In some embodiments, the content of unreacted cyanuric chloride is less than 1 %. In other embodiments, the content of unreacted cyanuric chloride is less than 0.5 %. In yet other embodiments, the content of unreacted cyanuric chloride is less than 0.3%.

[0084] In some embodiments, the content of dimethoxyphenyl triazine (formula Via) is less than 1 %. In other embodiments, the content of dimethoxyphenyl triazine is less than 0.5%. In yet other embodiments, the content of dimethoxyphenyl triazine is less than 0.3 %.

[0085] In some embodiments, the content of dimethoxy biphenyl (formula Vila) is less than 5 %. In other embodiments, the content of dimethoxy biphenyl is less than 3%. In yet other embodiments, the content of dimethoxy biphenyl is less than 1.5%. In yet other embodiments, the content of dimethoxy biphenyl is less than 1 %. In yet other embodiments, the content of dimethoxy biphenyl is less than 0.5 %..In further embodiments, the composition satisfies at least one of the above-defined limitations relating to the content of

[0086] (a) unreacted cyanuric chloride,

[0087] (b) dimethoxyphenyl triazine and

[0088] (c) dimethoxy biphenyl.

[0089] In some embodiments, the composition satisfies at least two of the above-defined limitations relating to the content of unreacted cyanuric chloride, the content of dimethoxyphenyl triazine and the content of dimethoxy biphenyl. For example, the composition satisfies the limitations relating to any two of: (a) and (b), (a) and (c), (b) and (c).

[0090] In some embodiments, the composition satisfies all of the above-defined limitations relating to the content of unreacted cyanuric chloride, the content of dimethoxyphenyl triazine and the content of dimethoxy biphenyl.

[0091] The preferred molar ratio of 4-methoxyphenyl magnesium bromide and cyanuric chloride is between 1.4: 1 and 1 :1 , more preferably 1 .3 : 1 , 1.15 : 1 or 1.05 : 1 (n / n).

[0092] The reaction between the phenylmagnesium halogenide, preferably 4-methoxyphenyl magnesium bromide, and the cyanuric chloride in b) is preferably carried out at a temperature in a range of 0 to 40°C. Alternatively or additionally, the reaction between the phenylmagnesium halogenide, preferably 4-methoxyphenyl magnesium bromide, and the cyanuric chloride in b) is preferably carried out under nitrogen or an oxygen-free atmosphere. As mentioned above, the reaction is carried out in an iron-free environment. The reaction may be conducted in an emaille reactor, glass line reactor or tantalum reactor. These conditions may contribute to controlling side reactions and facilitating a reproducible impurity profile.

[0093] Phenylmagnesium halogenide preparation

[0094] The phenylmagnesium halogenide may be prepared in situ. In a preferred embodiment, the phenylmagnesium halogenide is produced by the following steps:

[0095] a1) providing a magnesium (Mg) source,

[0096] a2) providing a compound of formula II,

[0097]

[0098] Ha'

[0099] (II), anda3) reacting the Mg source with the compound of formula II in the oxolane solvent 2- MeTHF.

[0100] The Mg source provided in a1) is or includes Mg swarfs and / or Mg turnings that may be characterized in terms of reactivity and / or impurity as follows.

[0101] ■ The Mg source may include reactive or “fresh” Mg swarfs and / or turnings. Reactive Mg may be Mg having a non-oxidised or low-oxidised surface. To this end, the Mg may be freshly produced directly before use. The Mg may be unpackaged from an oxygen-free container immediately prior to use. The Mg may be unpackaged from a water-free container immediately prior to use.

[0102] ■ The Mg source may have a total impurity content of less than 0.1 wt%. The total impurity content may be from 0.03 to 0.1 wt%.

[0103] ■ The Mg source may contain iron in an amount less than 0.005 wt%. The iron content may range from 0.0001 to 0.005 wt%.

[0104] The Mg source may fulfil at least one of the above characteristics. The Mg source preferably fulfils at least two of the above characteristics. The Mg source more preferably fulfils all three characteristics.

[0105] Iron content may be determined by inductively coupled plasma mass spectrometry (ICP-MS). The ICP-MS method may be performed according to ISO 17294-2 or an equivalent validated method. Iron values are expressed in % (weight per weight).

[0106] The Mg source may comprise one or more further impurities selected from Si, Cu, Al, Mn and Ni. The Mg source may comprise Si in an amount of 0.01 to 0.05 wt%. The Mg source may comprise Cu in an amount of 0.0002 to 0.001 wt%. The Mg source may comprise Al in an amount of 0.007 to 0.03 wt%. The Mg source may comprise Mn in an amount of 0.015 to 0.05 wt%. The Mg source may comprise Ni in an amount of 0.00015 to 0.0006 wt%.

[0107] The Mg source may contain Mg in an amount of 99.90 to 99.99%.

[0108] A specific Mg source has the following composition (in percentages by weight): Mg: 99.90 to 99.99%, Si: 0.01 to 0.05%, Fe: 0.002 to 0.008%, Cu: 0.0002 to 0.001%, Al: 0.007 to 0.03%, Mn: 0.015 to 0.05%, and Ni: 0.00015 to 0.0006%, with the proviso that the percentages sum up to 100%.

[0109] The reaction between magnesium and the compound of formula II in a3) is preferably performed in the oxolane solvent 2-MeTHF.The compound of formula II is a substituted haloarene. A preferred compound of formula II is 4-bromoanisole.

[0110] As regards preferred reaction conditions in a3), the reaction temperature may be in the range of 60 to 80°C. The reaction may be performed under an inert or oxygen-free atmosphere. The inert atmosphere may be nitrogen, argon, or carbon dioxide. The reaction may be performed in the presence of iodine. A weight ratio of the compound of formula II to the Mg in the Mg source may be within the range of 7:1 to 5:1.

[0111] The above conditions provide the phenylmagnesium halogenide and contribute to a high degree of conversion and specifically facilitate that the residual amount of the compound of formula II becomes less than 0.5% by weight. Accordingly, the residual amount of compound II after Grignard formation may be less than 0.5 wt%. The residual amount is based on the total weight of compounds of formulae II and (V) present.

[0112] A preferred phenylmagnesium halogenide is a 4-methoxyphenyl magnesium halogenide, in particular in which the halogenide is bromide.

[0113] BMT production

[0114] The invention further provides a process for producing BMT of formula I’,

[0115]

[0116] (I’), The process comprises the following stages:DICAT stage (I)

[0117] The process for producing BMT comprises (i) producing DICAT by the process disclosed herein.

[0118] A solvent replacement step may be performed between the DICAT stage and the resorcinol reaction stage. The solvent replacement step may replace the oxolane solvent with the benzene solvent. This can be achieved by conducting the following steps:

[0119] ■ adjusting a pH of the second composition to a value below 4, preferably with the aid of an aqueous acidic solution, forming a water phase and an organic phase: through the pH shift, a biphasic system is formed comprising the water phase and the organic phase. The intermediate is preferentially dissolved (enriched) in the organic phase. The adjustment of the pH of the second composition to a pH value below 4 may be done by adding an acidic solution in water;

[0120] ■ extracting the water phase using an oxolane solvent as organic phase: The intermediate that is partitioned into the water phase is extracted into the organic phase using an oxolane solvent, preferably 2-Me-THF;

[0121] ■ removing the oxolane solvent from the organic phase by distillation, leaving a suspension or solid as residue behind: distillation of the oxolane solvent from the organic phase yields the second intermediate. This step aims at removing the intermediate from the oxolane solvent. The prior extraction step allows the removal of the oxolane solvent together with the organic phase by distillation in a simple and energy-efficient manner;

[0122] and optionally the further steps:

[0123] ■ adding the benzene solvent to the residue, optionally after washing the residue with an alcohol: one or more washing cycles allows the removal of residual oxolane solvent, resulting in a residue as suspension or solid with an increased overall process yield and purity and / or easier work-up.

[0124] ■ adding the benzene solvent to the residue.

[0125] The above procedure yields a solid residue or a solution / suspension in benzene solvent.

[0126] Resorcinol reaction stage (ii)

[0127] The process for producing BMT further comprises (ii) reacting DICAT with resorcinol. The reaction with resorcinol is performed in the presence of a Lewis acid. The Lewis acid maybe selected among AICI3, FeCI3, benzene sulfonic acid (BSA), para-toluene sulfonic acid (pTSA), trifluoromethane sulfonic acid (TF-MSA) and methanesulfonic acid (MSA).

[0128] The reaction temperature during the resorcinol reaction may be 35 °C to 75 °C, preferably 39 °C to 70 °C. The resorcinol reaction may yield a bis-resorcinyl triazine intermediate. The purity of this intermediate may be about 89% as determined by HPLC.

[0129] The reaction may be performed under an inert gas or oxygen-free atmosphere. The inert gas may be nitrogen. The inert gas may be argon. The inert gas may be carbon dioxide. The water content during the reaction with resorcinol may be maintained below 2% (w / v). This aims at providing a defined, almost water-free condition, thereby contributing to the suppression of hydrolysis side reactions.

[0130] The term “benzene solvent” as understood herein denotes an aromatic solvent comprising at least one benzene derivative consisting of a unsubstituted or substituted, preferably monosubstituted, benzene ring. The substituent(s) are independently selected from halogen, C1-C4 alkyl, and nitrile groups. The halogen substituent is preferably chloro. The alkyl substituent is preferably methyl. The nitrile substituent is preferably cyano.

[0131] The reaction with resorcinol is performed in a benzene solvent selected from group of chlorobenzene, methylbenzene, cyanobenzene and mixtures thereof. The benzene solvent may be a mixture of chlorobenzene and cyanobenzene. For example, the weight ratio of chlorobenzene to cyanobenzene may be from 90:10 to 60:40. The preferred benzene solvent is methylbenzene (toluol) or chlorobenzene. Methylbenzene is more preferred because an azeotrope can be formed at a lower temperature than with chlorobenzene. Azeotropic distillation is preferably carried out until no water or only traces of water will be separated, preferably until internal temperature reaches the boiling point of the benzene solvent. Pressure can be optionally increased above normal. Residual organic solvents are preferably removed by vacuum distillation.

[0132] This treatment results in formation of a solution in which the intermediate (resorcinol reaction stage product) is dissolved in the benzene solvent. The solution may further contain residual (non-reacted) compound(s) and / or solvent(s) from previous steps.

[0133] Using the process of the invention, a high purity of the intermediate can be obtained. Specifically, the obtained purity as determined by HPLC is around 89%.A specific aspect of this stage is a reaction of DICAT with resorcinol and an organic sulfonic acid as lewis acid, wherein the organic sulfonic acid is selected from the group of methanesulfonic acid (MSA), benzene sulfonic acid (BSA), para-toluene sulfonic acid (pTSA) and trifluoromethane sulfonic acid (TF-MSA), in the benzene solvent, preferably chlorobenzene or mixture of chlorobenzene:cyanobenzene with a weight ratio ranging from 90:10 to 60:40, and in an inert gas such as nitrogen, argon or carbon dioxide (i.e. in an inert gas atmosphere).

[0134] A further specific aspect of the stage is a reaction with resorcinol and AlCh or MSA or BSA as the lewis acid in inert gas such as nitrogen, argon or carbon dioxide and in a benzene solvent chlorobenzene or mixture of chlorobenzene and cyanobenzene. The benzene solvent mixture preferably has a weight ratio of chlorobenzene:cyanobenzene ranging from 90:10 to 60:40. A particular preferred ratio of chlorobenzene:cyanobenzene in a specific mixture ranges from 2:1 to 10:1 , preferably 4:1 to 6:1 , most preferably 5:1 (chlorobenzene:cyanobenzene) (v / v).

[0135] A further specific aspect of the stage is a reaction of a solution of AlCh as lewis acid and resorcinol in a benzene solvent mixture of chlorobenzene and cyanobenzene with solid DICAT, wherein the solid DICAT is stepwise added to the solution at reaction temperature of 35 °C to 55°C, preferably 39°C to 51 °C.

[0136] The benzene solvent mixture preferably has a weight ratio of chloro-benzene:cyanobenzene ranging from 90:10 to 60:40. A particular preferred ratio of chlorobenzene:cyanobenzene in a specific mixture ranges from 2:1 to 10:1 , preferably 4:1 to 6:1 , most preferably 5:1 (chlorobenzene:cyanobenzene) (v / v).

[0137] When aluminum chloride is used as Lewis acid, a weight ratio of resorcinol to aluminum chloride may be within a range of 1 :2 to 1 :1. The weight ratio may be within a range of 1 :1.7 to 1 :1.18.

[0138] Ethylhexylation stage (Hi)

[0139] The process may further comprise (iii) reacting the resorcinyl intermediate with an ethylhexyl halogenide. The ethylhexyl halogenide may be a compound of formula VIII, Ha: - X

[0140] (VIII),in which X is 2-ethylhexyl and Hal is selected from the group of chlorine (Cl), bromine (Br) and iodine (I). The ethylhexyl halogenide may be 2-ethylhexyl chloride or 2-ethylhexyl bromine, preferably 2-ethylhexyl chloride.

[0141] The reaction may be performed in the presence of a salt selected from the group of Na2CO3, NaHCCh, K2CO3, KHCO3, NasPC and mixtures thereof. The preferred salt is KHCO3. KHCO3 has the advantage that it facilitates release of carbon dioxide under basic conditions which resulted in an increase of the pressure and an acceleration of the reaction. Water can be added optionally.

[0142] The reaction temperature may be in a range of 135 to 155°C. The preferred reaction temperature ranges from 140 to 145°C. In a preferred embodiment, the temperature is maintained until conversion is completed. The pressure may be increased above ambient pressure. The pressure can have positive effects. The pressure may be up to 0.5 MPa, preferably up to 0.4 MPa. For example, the pressure may range from 0.2 to 0.4 MPa, prefereably 0.25 MPa to 0.35 MPa. Nitrogen may be used to provide pressure.

[0143] A specific aspect of this stage is a reaction in presence of KHCO3 in DMAc at a reaction temperature ranging from 135 to 155°C to obtain BMT.

[0144] The reaction may be carried out in an amide solvent. The term “amide solvent” denotes an organic solvent comprising an amide compound having the functional group -C(=O)-NR1R2, wherein R1and R2are independently selected from C1-C2 alkyl, and wherein the carbonyl carbon is bound to hydrogen or to a C1-C2 alkyl group. Accordingly, the term amide solvent encompasses N,N-dimethylacetamide (DMAc), N,N-dimethylformamide (DMF), N,N-dimethylpropionamide (DMPr), N,N-diethylformamide (DEF), N,N-diethylacetamide (DEAc), and N,N-diethylpropionamide (DEPr), as well as mixtures consisting of two or more thereof in any proportion.

[0145] A preferred amide solvent for use in (iii) is selected among dimethylacetamide (DMAc), dimethylformamide (DMF), dimethylpropionamide (DMPr), diethylformamide (DEF), diethylacetamide (DEAc), diethylpropionamide (DEPr) and mixtures thereof. A more preferred amide solvent for use in (iii) is selected among dimethylacetamide (DMAc), dimethylpropionamide (DMPr), diethylformamide (DEF), diethylacetamide (DEAc), diethylpropionamide (DEPr) and mixtures thereof. Particular preferred is DMAc. DMAc has a higher boiling temperature than DMF and thus allows the process to be performed at a higher temperature (e.g., 140 to 150°C at normal pressure), thereby accelerating processing.When aluminum chloride is used as Lewis acid, the reaction step (iii) is done under pressure of range from 0.2 to 0.4 MPa in presence of KHCO3 and an amide solvent selected from the group essentially consisting of dimethylacetamide (DMAc), dimethylpropionamide (DMPr), diethylformamide (DEF), diethylacetamide (DEAc), diethylpropionamide (DEPr) and mixtures thereof.

[0146] Preferably, a pH value in a range of 7.0 to 7.5 is set as initial reaction pH value in b). Specifically, an aqueous solution of the amide solvent is formed by mixing with diluted base, e.g. a strong base in diluted form, until the desired pH value has been reached. For example, an aqueous solution of 40 to 50% by weight strong base (e.g., NaOH or KOH; preferably NaOH) are useful.

[0147] It is yet further preferred that the reaction is carried out in a stirred reactor, and the ethylhexyl halogenide is added below or in the vicinity of the stirrer, preferred at the bottom of the reactor. In case the reactor has more than one stirrer, the compound of formula III is preferably added below or in the vicinity of the lowest stirrer. Thereby, a favorable mass transfer effect is achieved.

[0148] The process may further comprise replacing the benzene solvent with an amide solvent.

[0149] A specific approach in this regard comprises:

[0150] • adding a protic solvent selected from the group of water, MeOH and diluted HCI, thereby creating a multiphase system comprising a solid phase and a liquid phase, the liquid phase consisting of a single organic or aqueous phase, or the liquid phase consisting of a binary phase system of aqueous and organic phases;

[0151] • separating the solid phase from the liquid phase, the separating optionally comprising removing the organic phase by distillation and / or removing the aqueous phase by filtration, leaving the solid phase as a residue behind; and

[0152] • dissolving the separated solid phase in the amide solvent and adding diluted base to adjust the pH.

[0153] A preferred protic solvent is a diluted hydrochloric acid solution. The protic solvent leads to precipitation of the bis-resorcinyl-phenyl triazine derivative of formula IX. Optionally, salts can be washed from the precipitate (residue) using water, preferably hot water (e.g., 85 to 90°C).

[0154] In addition to the aforementioned steps, it is preferred that one or both of the following steps are included:• adding benzene solvent and removing residual water by azeotropic distillation until the solution has a water content below 1%, and / or adding amide solvent and removing residual organic solvent and water from the solution by distillation, leaving a distillation residue behind; and

[0155] • adding further amide solvent to the distillation residue.

[0156] Preferred amide solvents added to the distillation residue include dimethylacetamide (DMAc), dimethylpropionamide (DMPr), diethylformamide (DEF), diethylacetamide (DEAc), diethylpropionamide (DEPr) and mixtures thereof. More preferred amide solvents used in step (v) include DMAc, DMPr, DEF, DEAc, DEPr and mixtures thereof. Particular preferred in step (v) is DMAc.

[0157] Recovery stage (iv)

[0158] The process may further comprise (iv) recovering BMT. The recovery stage may generally include any work-up, isolation, purification, or separation technique adapted to obtain or retain BMT. It may involve isolation, purification, distillation, crystallization, separation, washing, removal or any combination thereof. This stage may also include refinement techniques such as drying, milling or sieving.

[0159] In the context of the present invention, water may be removed by azeotropic distillation. A benzene solvent may be used for azeotropic distillation. The benzene solvent may be methylbenzene or chlorobenzene. Salt may be removed by filtration. The amide solvent may be removed by distillation. Crystallization may be performed from acetone or 2-butanol, or a mixture of acetone and 2-butanol. A weight ratio of acetone to 2-butanol may be from 9:1 to 20:1. Seeding may be performed during crystallization. Seeding may be performed at 4 to 8°C. Seeding may be performed at about 5°C. Washing may be performed with cold acetone (0 to 5°C). Pressure up to 6 bar may be applied during filtration or washing. Nitrogen may be used to apply pressure. Drying may be performed in a vacuum paddle dryer.

[0160] The term “recovering” as used herein in relation to a certain compound broadly denotes the act of enriching this compound relative to one or more other compounds. Thus, a recovery results in an increase of a mass ratio of the compound to one or more other compounds, preferably to one or more side products and / or impurities. Useful recovery approaches for the BMT include in particular: steps of washing, filtration, distillation, separation, crystallization, drying, milling and sieving. It is preferred that 1 , 2, 3, 4, 5, 6, 7, or all of the aforementioned different steps are combined.A preferred recovery strategy includes one or more of the following steps:

[0161] • adding diluted protic acid;

[0162] • removing the amide solvent and water from the composition (reaction mass) comprising the compound of formula I’ until the water content is below 1% (w / w);

[0163] • crystallizing the compound of formula I’ from acetone and / or 2-butanol;

[0164] • isolating the compound of formula I’ by filtration;

[0165] • washing the compound of I’;

[0166] • drying the compound of formula I’; and

[0167] • milling the compound of formula I’.

[0168] Particular preferred is a recovery in which all aforementioned steps are included, and, preferably, carried out in the indicated sequence.

[0169] Azeotropic distillation primarily aims at removing the water or solvent. It is preferably carried out until no water or only traces of water will be separated, preferably until internal temperature reaches the boiling point of the solvent. Pressure can be optionally increased above normal. Residual organic solvents are preferably removed by vacuum distillation. This step aims at providing a defined, almost water-free condition, thereby contributing to the suppression of hydrolysis side reactions.

[0170] BMT compositions

[0171] The invention further provides a composition, preferably obtainable by the process disclosed herein, comprising specified amounts of BMT; iron; and specific impurities in the form of side-products.

[0172] The invention further provides various BMT-containing UV filter compositions, skin care compositions and haircare compositions. Such compositions may be in the form ofcreams, lotions, gels, sprays, emulsions, sticks or other cosmetically acceptable formulations and provide effective UV protection while benefiting from the economic advantages of a strict impurity control already at an early stage of the overall process.

[0173] The compositions of the invention reflect the impurity profile that is characteristic for the BMT production process of the invention.

[0174] The composition, preferably obtainable by the process disclosed herein, comprises at least 98% BMT. The composition may comprise at least 99% BMT. The percentages are weight percentages.The composition may be essentially iron-free or iron-limited. The composition may contain iron as unavoidable impurity species, provided the iron content is less than 2 mg / kg, i.e. less than 2 mg iron per kg composition (dry mass). The composition may contain less than 1.5 mg / kg iron. The composition may contain less than 1.35 mg / kg iron. Iron can have negative influence on product quality which comprises this BMT, especially the stability of cosmetic formulation by increasing oxidation process, formation of off-notes or discoloration issues.

[0175] Comparison of commercially available BMT samples and BMT samples produced according to this inventive process:

[0176] BMT Iron (FeJ

[0177] [mg / kg] [mg / kg]

[0178] Composition A 98.8 0.9

[0179] Composition B 98.7 1.0

[0180] Market sample 1 98.2 4.3

[0181] Market sample 2 9S.3 3.7

[0182] Market sample 3 98.4 2.6

[0183] Market sample 4 98.3 3.3

[0184]

[0185] The composition further comprises dimethoxyphenyltriazine of formula Via,

[0186]

[0187] (Via),

[0188] in an amount of less than 1%. In other embodiments, the amount of compound (Via) may be less than 0.5%, preferably less than 0.3 %.

[0189] The composition comprises dimethoxybiphenyl of formula Vila,

[0190]

[0191] (Vila),

[0192] in an amount of less than 5%. Preferably, the composition may contain dimethoxybiphenyl in an amount of less than 3%. In yet other embodiments, the amount of dimethoxybiphenyl may be less than 1.5%, preferably less than 1 %, more preferably less than 0.5 %.A preferred composition, preferably obtainable by the process disclosed herein, comprises the following:

[0193] ■ at least 98% BMT percentages are weight percentages;

[0194] ■ less than 2 mg iron per kg composition (dry mass);

[0195] ■ dimethoxyphenyltriazine of formula Via in an amount of less than 1%; dimethoxybiphenyl of formula Vila in an amount of less than 5%.

[0196] In various embodiments, the composition comprises:

[0197] (i) at least 98 wt.% BMT or at least 99 wt.% BMT;

[0198] and is characterized by at least one of the following:

[0199] (ii) an iron content of less than 2 mg / kg, less than 1.5 mg / kg, or less than 1.35 mg / kg; (iii) dimethoxyphenyltriazine in an amount of less than 1 wt.%, less than 0.5 wt.%, or less than 0.3 wt.%; and

[0200] (iv) dimethoxybiphenyl in an amount of less than 5 wt.%, less than 3 wt.%, less than 1.5 wt.%, less than 1 wt.%, or less than 0.5 wt.%,

[0201] wherein each alternative of (i) is combinable with each alternative of (ii), (iii), and (iv), and wherein (ii)-(iv) are independently selected.

[0202] In some embodiments, the composition comprises:

[0203] (i) at least 98 wt.% BMT or at least 99 wt.% BMT;

[0204] and satisfies at least two of the limitations defined in (ii) to (iv).

[0205] In some embodiments, the composition comprises:

[0206] (i) at least 98 wt.% BMT or at least 99 wt.% BMT;

[0207] and satisfies at least three of the limitations defined in (ii) to (iv).

[0208] In some embodiments, the composition comprises:

[0209] (i) at least 98 wt.% BMT or at least 99 wt.% BMT;

[0210] and satisfies all of the limitations defined in (ii) to (iv).

[0211] In some embodiments, the composition comprises at least 98 wt.% BMT or at least 99 wt.% BMT and has an iron content of less than 2 mg / kg.

[0212] In some embodiments, the composition comprises at least 98 wt.% BMT or at least 99 wt.% BMT and has an iron content of less than 1.5 mg / kg.

[0213] In some embodiments, the composition comprises at least 98 wt.% BMT or at least 99 wt.% BMT and has an iron content of less than 1.35 mg / kg.

[0214] In some embodiments, the composition comprises at least 98 wt.% BMT or at least 99 wt.% BMT and comprises dimethoxyphenyltriazine in an amount of less than 1 wt.%.In some embodiments, the composition comprises at least 98 wt.% BMT or at least 99 wt.% BMT and comprises dimethoxyphenyltriazine in an amount of less than 0.5 wt.%.

[0215] In some embodiments, the composition comprises at least 98 wt.% BMT or at least 99 wt.% BMT and comprises dimethoxyphenyltriazine in an amount of less than 0.3 wt.%.

[0216] In some embodiments, the composition comprises at least 98 wt.% BMT or at least 99 wt.% BMT and comprises dimethoxybiphenyl in an amount of less than 5 wt.%.

[0217] In some embodiments, the composition comprises at least 98 wt.% BMT or at least 99 wt.% BMT and comprises dimethoxybiphenyl in an amount of less than 3 wt.%.

[0218] In some embodiments, the composition comprises at least 98 wt.% BMT or at least 99 wt.% BMT and comprises dimethoxybiphenyl in an amount of less than 1.5 wt.%.

[0219] In some embodiments, the composition comprises at least 98 wt.% BMT or at least 99 wt.% BMT and comprises dimethoxybiphenyl in an amount of less than 1 wt.%.

[0220] In some embodiments, the composition comprises at least 98 wt.% BMT or at least 99 wt.% BMT and comprises dimethoxybiphenyl in an amount of less than 0.5 wt.%.

[0221] In some embodiments, the composition comprises at least 98 wt.% BMT or at least 99 wt.% BMT, has an iron content of less than 2 mg / kg, and comprises dimethoxyphenyltriazine in an amount of less than 1 wt.%.

[0222] In some embodiments, the composition comprises at least 98 wt.% BMT or at least 99 wt.% BMT, has an iron content of less than 1 .5 mg / kg, and comprises dimethoxyphenyltriazine in an amount of less than 0.5 wt.%.

[0223] In some embodiments, the composition comprises at least 98 wt.% BMT or at least 99 wt.% BMT, has an iron content of less than 1 .35 mg / kg, and comprises dimethoxyphenyltriazine in an amount of less than 0.3 wt.%.

[0224] In some embodiments, the composition comprises at least 98 wt.% BMT or at least 99 wt.% BMT, has an iron content of less than 2 mg / kg, and comprises dimethoxybiphenyl in an amount of less than 5 wt.%.

[0225] In some embodiments, the composition comprises at least 98 wt.% BMT or at least 99 wt.% BMT, has an iron content of less than 1.5 mg / kg, and comprises dimethoxybiphenyl in an amount of less than 1 wt.%.In some embodiments, the composition comprises at least 98 wt.% BMT or at least 99 wt.% BMT, has an iron content of less than 1.35 mg / kg, and comprises dimethoxybiphenyl in an amount of less than 0.5 wt.%.

[0226] In some embodiments, the composition comprises at least 98 wt.% BMT or at least 99 wt.% BMT, comprises dimethoxyphenyltriazine in an amount of less than 0.5 wt.%, and comprises dimethoxybiphenyl in an amount of less than 1 wt.%.

[0227] In some embodiments, the composition comprises at least 98 wt.% BMT or at least 99 wt.% BMT, comprises dimethoxyphenyltriazine in an amount of less than 0.3 wt.%, and comprises dimethoxybiphenyl in an amount of less than 0.5 wt.%.

[0228] In some embodiments, the composition comprises at least 98 wt.% BMT or at least 99 wt.% BMT, has an iron content of less than 2 mg / kg, comprises dimethoxyphenyltriazine in an amount of less than 1 wt.%, and comprises dimethoxybiphenyl in an amount of less than 5 wt.%.

[0229] In some embodiments, the composition comprises at least 98 wt.% BMT or at least 99 wt.% BMT, has an iron content of less than 1 .5 mg / kg, comprises dimethoxyphenyltriazine in an amount of less than 0.5 wt.%, and comprises dimethoxybiphenyl in an amount of less than 1 wt.%.

[0230] In some embodiments, the composition comprises at least 98 wt.% BMT or at least 99 wt.% BMT, has an iron content of less than 1.35 mg / kg, comprises dimethoxyphenyltriazine in an amount of less than 0.3 wt.%, and comprises dimethoxybiphenyl in an amount of less than 0.5 wt.%.

[0231] In some embodiments, the composition comprises at least 99 wt.% BMT, has an iron content of less than 1.35 mg / kg, comprises dimethoxyphenyltriazine in an amount of less than 0.3 wt.%, and comprises dimethoxybiphenyl in an amount of less than 0.5 wt.%. In some embodiments, the composition comprises at least 99 wt.% BMT, has an iron content of less than 1.5 mg / kg, comprises dimethoxyphenyltriazine in an amount of less than 0.5 wt.%, and comprises dimethoxybiphenyl in an amount of less than 1 wt.%. In some embodiments, the composition comprises at least 98 wt.% BMT, has an iron content of less than 2 mg / kg, comprises dimethoxyphenyltriazine in an amount of less than 1 wt.%, and comprises dimethoxybiphenyl in an amount of less than 5 wt.%. Optionally, the composition comprising BMT may further comprise one or more of the following:

[0232] ■ 2-butanol in an amount from 1 to 15 mg / kg;■ < 0.1 %, preferably < 0.05 %, Bemotrizinol resorcinol analog with peak identity MM 515 and C30H33N3O5 and retention time (RT) 12.9 min according to the method description of LCMS analysis with additional UV detection of Bemotrizinol resorcinol analog; ■ < 0.03 %, preferably < 0.015 %, Bemotrizinol triethylhexylether analog with peak identity MM 739 and C46H65N3O5 and retention time of 22.2 min according to the method description of LCMS analysis with additional UV detection of Bemotrizinol triethylhexylether analog.

[0233] In various embodiments, the composition comprises:

[0234] (i) at least 98 wt.% BMT or at least 99 wt.% BMT;

[0235] and is characterized by at least one of the following:

[0236] (ii) an iron content of less than 2 mg / kg, less than 1.5 mg / kg, or less than 1.35 mg / kg; (iii) dimethoxyphenyltriazine in an amount of less than 1 wt.%, less than 0.5 wt.%, or less than 0.3 wt.%;

[0237] (iv) dimethoxybiphenyl in an amount of less than 5 wt.%, less than 3 wt.%, less than 1.5 wt.%, less than 1 wt.%, or less than 0.5 wt.%;

[0238] and optionally further comprises one or more of:

[0239] (v) 2-butanol in an amount from 1 to 15 mg / kg;

[0240] (vi) a Bemotrizinol resorcinol analog having a peak identity MM 515, molecular formula C30H33N3O5, and a retention time of 12.9 min according to LCMS analysis with additional UV detection, in an amount of < 0.1 %, preferably < 0.05%; and

[0241] (vii) a Bemotrizinol triethylhexylether analog having a peak identity MM 739, molecular formula C46H65N3O5, and a retention time of 22.2 min according to LCMS analysis with additional UV detection, in an amount of < 0.03 %, preferably < 0.015%, wherein each alternative of (i) is combinable with each alternative of (ii) to (vii), and wherein (ii) to (vii) are independently selected.

[0242] In some embodiments, the composition comprises one or more of components (v), (vi), and (vii).

[0243] In some embodiments, the composition comprises two or more of components (v), (vi), and (vii).

[0244] In some embodiments, the composition comprises all of components (v), (vi), and (vii). In some embodiments, the composition comprises:

[0245] (i) at least 98 wt.% BMT or at least 99 wt.% BMT;

[0246] (ii) an iron content of less than 2 mg / kg, less than 1.5 mg / kg, or less than 1.35 mg / kg; and further comprises 2-butanol in an amount from 1 to 15 mg / kg.In some embodiments, the composition comprises:

[0247] (i) at least 98 wt.% BMT or at least 99 wt.% BMT;

[0248] (ii) an iron content of less than 1.5 mg / kg or less than 1.35 mg / kg;

[0249] and further comprises a Bemotrizinol resorcinol analog according to (vi) in an amount of < 0.1 %, preferably < 0.05%.

[0250] In some embodiments, the composition comprises:

[0251] (i) at least 98 wt.% BMT or at least 99 wt.% BMT;

[0252] (ii) an iron content of less than 1.5 mg / kg or less than 1.35 mg / kg;

[0253] and further comprises a Bemotrizinol triethylhexylether analog according to (vii) in an amount of < 0.03 %, preferably < 0.015%.

[0254] In some embodiments, the composition comprises at least 99 wt.% BMT, has an iron content of less than 1.35 mg / kg, and further comprises 2-butanol in an amount from 1 to 15 mg / kg.

[0255] In some embodiments, the composition comprises at least 99 wt.% BMT, has an iron content of less than 1.35 mg / kg, and further comprises the Bemotrizinol resorcinol analog according to (vi) in an amount of < 0.1 %, preferably < 0.05%.

[0256] In some embodiments, the composition comprises at least 99 wt.% BMT, has an iron content of less than 1.35 mg / kg, and further comprises the Bemotrizinol triethylhexylether analog according to (vii) in an amount of < 0.03 %, preferably < 0.015%.

[0257] In some embodiments, the composition comprises at least 99 wt.% BMT, has an iron content of less than 1.35 mg / kg, comprises dimethoxyphenyltriazine in an amount of less than 0.3 wt.%, and further comprises 2-butanol in an amount from 1 to 15 mg / kg.

[0258] In some embodiments, the composition comprises at least 99 wt.% BMT, has an iron content of less than 1.35 mg / kg, comprises dimethoxybiphenyl in an amount of less than 0.5 wt.%, and further comprises 2-butanol in an amount from 1 to 15 mg / kg.

[0259] In some embodiments, the composition comprises:

[0260] (i) at least 99 wt.% BMT;

[0261] (ii) an iron content of less than 1.35 mg / kg;

[0262] (iii) dimethoxyphenyltriazine in an amount of less than 0.3 wt.%;

[0263] (iv) dimethoxybiphenyl in an amount of less than 0.5 wt.%; and

[0264] (v) 2-butanol in an amount from 1 to 15 mg / kg.

[0265] In some embodiments, the composition comprises:

[0266] (i) at least 99 wt.% BMT;(ii) an iron content of less than 1.35 mg / kg;

[0267] (iii) dimethoxyphenyltriazine in an amount of less than 0.3 wt.%;

[0268] (iv) dimethoxybiphenyl in an amount of less than 0.5 wt.%;

[0269] (vi) a Bemotrizinol resorcinol analog according to (vi) in an amount of < 0.1 %, preferably < 0.05%; and

[0270] (vii) a Bemotrizinol triethylhexylether analog according to (vii) in an amount of < 0.03 %, preferably < 0.015%.

[0271] In some embodiments, the composition comprises

[0272] (i) at least 99 wt.% BMT,

[0273] (ii) an iron content of less than 1.35 mg / kg,

[0274] (iii) dimethoxyphenyltriazine in an amount of less than 0.3 wt.%,

[0275] (iv) dimethoxybiphenyl in an amount of less than 0.5 wt.%,

[0276] (v) 2-butanol in an amount from 1 to 15 mg / kg,:

[0277] (vi) a Bemotrizinol resorcinol analog according to (vi) in an amount of < 0.1 %, preferably < 0.05%; and

[0278] (vii) a Bemotrizinol triethylhexylether analog according to (vii) in an amount of < 0.03 %, preferably < 0.015%.

[0279] A preferred composition, preferably obtainable by the process disclosed herein, comprises the following:

[0280] ■ at least 98 wt.% BMT;

[0281] ■ less than 2 mg / kg iron (per kg composition on a dry mass basis);

[0282] ■ dimethoxyphenyltriazine of formula Via in an amount of less than 1%;

[0283] ■ dimethoxybiphenyl of formula Vila in an amount of less than 5%;

[0284] ■ < 0.1 %, preferably < 0.05 % Bemotrizinol resorcinol analog (determined as described herein);

[0285] ■ < 0.03 %, preferably < 0.015 % Bemotrizinol triethylhexylether (determined as described herein).

[0286] Another preferred composition, preferably obtainable by the process disclosed herein, comprises the following:

[0287] ■ at least 98 wt.% BMT;

[0288] ■ less than 2 mg / kg iron;

[0289] ■ dimethoxyphenyltriazine of formula Via in an amount of less than 1%;

[0290] ■ dimethoxybiphenyl of formula Vila in an amount of less than 5%;

[0291] ■ < 0.1 %, preferably < 0.05 % Bemotrizinol resorcinol analog;

[0292] ■ < 0.03 %, preferably < 0.015 % Bemotrizinol triethylhexylether analog;

[0293] ■ 2-butanol in an amount from 1 to 15 mg / kg.The following table shows amounts / values experimentally determined in two exemplary compositions, composition A and composition B. Accordingly, the compositions defined in the table define specific embodiments of the composition of the invention.

[0294] composition composition

[0295] A B BMT [g / 100g] 98.8 98.75

[0296] 2-BuOH [mg / kg] 11.5 6.6

[0297] Bemotrizinol resorcinol analog [%] 0.006 0.026

[0298]

[0299] Bemotrizinol triethylhexylether analog [%] 0.009 0.010

[0300] In preferred embodiments of the invention, the amount of Bemotrizinol resorcinol analog and / or the amount of Bemotrizinol triethylhexylether analog indicated herein is the percentage as determined by LC-MS analysis. It is further preferred that the amount of Bemotrizinol resorcinol analog and / or the amount of Bemotrizinol triethylhexylether analog indicated herein refers to the percentage as determined by LC-MS analysis with additional UV detection described in the example section:

[0301] A UV filter composition of the present invention comprises the BMT composition described herein. The UV filter composition may comprise BMT in an amount of 0.1 to 15 wt%. The UV filter composition may comprise BMT in an amount of 1 to 10 wt%.

[0302] The UV filter composition may further comprise at least one additional UV filter active selected from the group of Phenylbenzimidazole Sulfonic Acid, Butyl Methoxydibenzoylmethane, Ethylhexyl Triazone, Ethylhexyl Salicylate, Disodium Phenyl Dibenzimidazole Tetrasulfonate, Diethylhexyl Butamido Triazone, Menthyl Anthranilate, Zinc Oxide, Zinc oxide (nano), Diethylamino Hydroxybenzoyl Hexyl Benzoate, Benzophenone-3, Homosalate, Octocrylene, Ethylhexyl Methoxycinnamate, Isoamyl p-Methoxycinnamate, 4-Methylbenzylidene Camphor, Titanium Dioxide, Titanium Dioxide (nano), Terephthalylidene Dicamphor Sulfonic Acid, Butyl Methoxydibenzoylmethane, Methylene Bis-Benzotriazolyl Tetramethylbutylphenol, Tris-Biphenyl Triazine, Phenylene Bis-Diphenyltriazine, Methoxypropylamino Cyclohexenylidene Ethoxyethylcyanoacetate, Bis-(Diethylaminohydroxybenzoyl Benzoyl) Piperazine, Drometrizole Trisiloxane, Benzylidene Camphor Sulfonic Acid, , Polysilicone-15, Ethylhexyl Dimethyl PABA.

[0303] A preferred additional UV filter active is selected from the group of Phenylbenzimidazole Sulfonic Acid, Butyl Methoxydibenzoylmethane, Ethylhexyl Triazone, Ethylhexyl Salicylate, Disodium Phenyl Dibenzimidazole Tetrasulfonate, Diethylhexyl Butamido Triazone, Zinc Oxide, Zinc Oxide (nano), Diethylamino Hydroxy benzoyl Hexyl Benzoate, Tris-BiphenylTriazine, Phenylene Bis-Diphenyltriazine, Methylene Bis-Benzotriazolyl Tetramethylbutylphenol, Methoxypropylamino Cyclohexenylidene Ethoxyethylcyanoacetate, Bis-(Diethylaminohydroxybenzoyl Benzoyl) Piperazine, Terephthalylidene Dicamphor Sulfonic Acid, Octocrylene, Titanium Dioxide, Titanium Dioxide (nano).

[0304] The invention also relates to a cosmetic composition for topical application on skin or hair or sun protection comprising an UV filter composition as disclosed herein.

[0305] The cosmetic composition of the present invention comprises the UV filter composition of the invention. The cosmetic composition may comprise BMT in an amount of 0.1 to 15 wt%. The cosmetic composition preferably comprises BMT in an amount of 1.0 to 10 wt%.

[0306] Further optional variants of the disclosure

[0307] In the following are provided further examples and corresponding or related to the present invention or particular aspects thereof. Among others, these further examples describe specific features or functionalities optionally embodied in the invention in more detail. The disclosure shall thus be understood as providing further optional variants of the present invention.

[0308] A first aspect pertains to a process for producing a compound (2,4,6-substituted triazine) of formula I or a composition comprising the compound of formula I:

[0309] R

[0310]

[0311] wherein X is selected from the group of:

[0312] ■ linear alkyl with a chain length of C1 to C10, preferably C2 to C10;

[0313] ■ linear alkyl with a chain length of C2 to C10 with branches in alpha-(a) I beta-(p) I gamma-(y)-position to the oxygen selected from the group of methyl, ethyl, propyl and butyl;■ benzyl;

[0314] ■ linear alkenyl with a chain length of C3 to C10; and

[0315] ■ linear alkenyl with a chain length of C3 to C10 with branches in alpha-(a) I beta-(p) I gamma-(y)-position to the oxygen selected from the group of methyl, ethyl, propyl and butyl; and

[0316] R is selected from the group of:

[0317] ■ linear alkyl with a chain length of C1 to C10, preferably C2 to C10;

[0318] ■ linear alkyl with a chain length of C2 to C10 with branches in alpha-(a) I beta-(p) I gamma-(y)-position to the phenyl selected from the group of methyl, ethyl, propyl and butyl;

[0319] ■ linear alkoxyl with a chain length of C1 to C10, preferably C2 to C10;

[0320] ■ linear alkoxyl with a chain length of C2 to C10 with branches in alpha-(a) I beta-(p) I gamma-(y)-position to the oxygen selected from the group of methyl, ethyl, propyl and butyl;

[0321] ■ linear alkenyl with a chain length of C2 to C10;

[0322] ■ linear alkenyl with a chain length of C2 to C10 with branches in alpha-(a) I beta-(p) I gamma-(y)-position to the phenyl selected from the group of methyl, ethyl, propyl and butyl;

[0323] ■ linear alkenoxyl with a chain length from C2 to C10;

[0324] ■ linear alkenoxyl with a chain length of C2 to C10 with branches in alpha-(a) I beta- (p) I gamma-(y)-position to the oxygen selected from the group of methyl, ethyl, propyl and butyl;

[0325] ■ phenyl;

[0326] ■ phenoxy.

[0327] The process comprises the following steps (i) to (vii), whereby step (vii) is optional. The individual steps are described in the following:

[0328] Step (i) involves a compound of formula II,

[0329]

[0330] wherein R is as in the compound of formula I and Hal is selected from the group of chlorine (Cl), bromine (Br) and iodine (I).

[0331] The compound of formula II and a magnesium (Mg) source comprising Mg swarfs and I or turnings are reacted in an oxolane solvent to obtain a first composition. The firstcomposition comprises the reaction product of the compound of formula II and the Mg source (hereinafter, first intermediate), and the oxolane solvent. The first composition may further include residual (non-reacted) compound(s) and / or side produces).

[0332] In step (ii) the first composition is reacted with cyanuric chloride (formula III). More precisely, the first composition and cyanuric chloride are contacted under conditions that facilitate reaction between the first intermediate and the cyanuric chloride. To this end, cyanuric chloride and the first composition can be brought into contact and mixed with each other. The structure of cyanuric chloride is shown in formula III:

[0333]

[0334] The reaction proceeds in the solvent of the first composition, i.e. in the oxolane solvent. Importantly, the reaction is conducted in an iron-free environment. An iron-free environment means one that is free of exposed iron surfaces such as iron reactor inner walls, iron impellers or sensors with outer iron surfaces, or one that is substantially free of exposed iron surfaces. For example, step (ii) can be carried out in an emaille (enamel) reactor, glass line reactor or tantalum reactor. If present at all, exposed iron surface area is preferably so low such that the overall aim of the reaction step is not compromised and side reactions occur at most to a technically negligible extent, e.g. the total amount of all side products I byproducts is less than 10% (m / m), less than 8%, less than 6%, less than 4%, less than 2%, less than 1%, or even less than 0.5%. The expression “iron-free environment” thus in particular excludes the case where the reaction mixture comes in contact with iron (e.g., exposed iron surfaces such as iron reaction vessel, iron impellers, etc.), e.g. where the reaction mixture is encased by an iron reaction vessel. By carrying out step (ii) in an iron-free environment, undesired byproduct formation is avoided. Less formation of byproducts leads to an increase of the yield, a simplification of the recovery and / or reduction of purification effort for the intermediates and the final product. The preferred reaction temperature is between 0-40 °C. Furthermore, a nitrogen atmosphere or an oxygen-free atmosphere is favorable for this step (ii).

[0335] Step (ii) yields a second composition. The second composition comprises the reaction product of the first intermediate and the cyanuric chloride (hereinafter, second intermediate) and the oxolane solvent. The second composition may further contain residual (non-reacted) compound(s) from step (ii) and / or step (i).A specific aspect of step (ii) is the reaction of a composition comprising 4-Methoxyphenyl magnesium bromide with cyanuric chloride of formula III in 2-MeTHF, preferred under nitrogen atmosphere or oxygen-free atmosphere, further preferred in iron-free environment, to obtain a composition comprising Dichloromethyloxyphenyltriazine (DICAT), unreacted cyanuric chloride of formula III and side products, preferably selected from the group of dimethoxyphenyltriazine of formula Via and dimethoxybiphenyl of formula Vila. The content of unreacted cyanuric chloride of formula III is preferably less than 1 %. The content of dimethoxyphenyltriazine of formula Via is preferably less than 1 %. The content of dimethoxybiphenyl of formula Vila is preferably less than 5 %, more preferably less than 1.5 %. The preferred molar ratios of 4-methoxyphenyl magnesium bromide and cyanuric chloride of formula III are between 1.4: 1 and 1 :1 , more preferably 1.3 : 1 , 1.15 : 1 and 1.05 : 1 (n / n). The preferred reaction temperature of step (ii) is between 0 and 40 °C.

[0336] In step (iii), the oxolane solvent of the second composition is replaced by a benzene solvent. This is achieved by conducting steps (iii-1) to (iii-4):

[0337] (iii-1) adjusting a pH of the second composition to a value below 4, preferably with the aid of an aqueous acidic solution, forming a water phase and an organic phase: through the pH shift, a biphasic system is formed comprising the water phase and the organic phase. The second intermediate is preferentially dissolved (enriched) in the organic phase.

[0338] (iii-2) extracting the water phase using an oxolane solvent as organic phase: Second intermediate that is partitioned into the water phase is extracted into the organic phase using an oxolane solvent, preferably 2-Me-THF.

[0339] (iii-3) removing the oxolane solvent from the organic phase by distillation, leaving a suspension or solid as residue behind: distillation of the oxolane solvent from the organic phase yields the second intermediate. Step (iii-3) aims at removing the second intermediate from the oxolane solvent. The prior extraction step (iii-2) allows the removal of the oxolane solvent together with the organic phase by distillation in a simple and energy-efficient manner.

[0340] and optionally the further steps:

[0341] (iii-4) mixing the benzene solvent and the residue, optionally after washing the residue with an alcohol: one or more washing cycles allows the removal of residual oxolane solvent, resulting in a residue as suspension or solid with an increased overall process yield and purity and / or easier work-up.(iii-5) adding benzene solvent to the residue.

[0342] A specific aspect of step (iii-1) is that the adjusting the pH of the second composition to a pH value below 4 is done by adding of an acidic solution in water.

[0343] Step (iii) gives a third composition as solid residue or in the form of a solution / suspension in the benzene solvent. That is, the components contained in the third composition are dissolved. The third composition comprises the second intermediate and the benzene solvent. The third composition may further contain residual (non-reacted) compound(s) and / or solvent(s) from any of steps (i), (ii) and (iii).

[0344] Step (iv) is reacting the third composition with resorcinol and a lewis acid selected from the group of AICH, FeCH, benzene sulfonic acid (BSA), para-toluene sulfonic acid (pTSA), trifluoromethane sulfonic acid (TF-MSA) and methanesulfonic acid (MSA). Thereby, the second intermediate reacting with resorcinol is converted into the third intermediate. The reaction is carried out in inert gas such as nitrogen, argon or carbon dioxide. The water content is maintained below 2% (w / v). A fourth composition is obtained. The fourth composition comprises the third intermediate dissolved in the benzene solvent. Using the process of the disclosure, a high purity of the third intermediate can be obtained. Specifically, the obtained purity as determined by HPLC is around 89%. The fourth composition may further contain residual (non-reacted) compound(s) and / or solvents) from any of steps (i) to (iv).

[0345] A specific aspect of step (iv) is a reaction of the third composition with resorcinol and an organic sulfonic acid as lewis acid, wherein the organic sulfonic acid is selected from the group of methanesulfonic acid (MSA), benzene sulfonic acid (BSA), para-toluene sulfonic acid (pTSA) and trifluoromethane sulfonic acid (TF-MSA), in the benzene solvent, preferably chlorobenzene, and in an inert gas such as nitrogen, argon or carbon dioxide (i.e. in an inert gas atmosphere), to obtain the fourth composition.

[0346] A further specific aspect of step (iv) is a reaction of the third composition with resorcinol and AICH or MSA or BSA as the lewis acid in inert gas such as nitrogen, argon or carbon dioxide under pressure in a range of 0.2 to 0.4 MPa and in a benzene solvent mixture of chlorobenzene and cyanobenzene to obtain the fourth composition. The benzene solvent mixture preferably has a weight ratio of chlorobenzene:cyanobenzene ranging from 90:10 to 60:40. A particular preferred ratio of chlorobenzene:cyanobenzene in a specific mixture ranges from 2:1 to 10:1 , preferably 4:1 to 6:1 , most preferably 5:1 (chlorobenzene:cyanobenzene) (v / v).In step (v), the benzene solvent of the fourth composition is replaced by an amide solvent, and a solution having a pH ranging from 7.0 to 7.5 is formed. This provides a fifth composition. The fifth composition comprises the third intermediate dissolved in the amide solvent. The fifth composition may further contain residual (non-reacted) compound(s) and / or solvent(s) from any of steps (i) to (v).

[0347] In step (vi), the fifth composition is reacted with a liquid compound of formula VIII,

[0348] Hal - X

[0349]

[0350] wherein X and Hal are as in formulae I and II, respectively.

[0351] Thereby, the third intermediate and the compound of formula VIII are converted to yield the compound of formula (I). The reaction is carried out in the presence of a salt selected from the group of Na2COs, NaHCCh, K2CO3, KHCO3, NasPC and mixtures thereof. The preferred salt is KHCO3. Water can be added optionally. The reaction temperature ranges from 135 to 155°C. The preferred reaction temperature ranges from 140 to 145°C. The pressure may be increased above ambient pressure and can have positive effects. The pressure may be up to 0.4 MPa, such as in a range of 0.2 MPa to 0.4 MPa, preferably 0.25 MPa to 0.35 MPa. Besides the compound of formula I, the composition comprising the compound of formula I may include residual (non-reacted) compound(s) and / or solvent(s) from any of steps (i) to (vi).

[0352] A specific aspect of step (vi) is a reaction of the fifth composition with the compound of formula VIII in presence of KHCO3 in DMAc at a reaction temperature ranging from 135 to 155°C to obtain a composition comprising the compound of formula I. The composition comprising the compound of formula I may include residual (non-reacted) compound(s) and / or solvent(s) from any of steps (i) to (vi).

[0353] Step (vii) is optional and includes one or more steps for recovering, isolating and / or purifying the compound of formula I. The term “recovering” as used herein in relation to a certain compound broadly denotes the act of enriching this compound relative to one or more other compounds. Thus, a recovery results in an increase of a mass ratio of the compound to one or more other compounds, preferably to one or more side products. Further aspects relate to the production of intermediates. Accordingly, an aspect of the present disclosure pertains to a process of producing a first composition as described herein, the method comprising step (i) as described herein. Another aspect of the present disclosure pertains to a process of producing a second composition as described herein, the method comprising step (ii) as described herein, or steps (i) and (ii) as described herein.Another aspect of the present disclosure pertains to a process of producing a third composition as described herein, the method comprising step (iii) as described herein, or steps (ii) and (iii) as described herein, or steps (i), (ii) and (iii) as described herein. Another aspect of the present disclosure pertains to a process of producing a fourth composition as described herein, the method comprising step (iv) as described herein, or steps (iii) and (iv) as described herein, or steps (ii), (iii) and (iv) as described herein, or steps (i), (ii), (iii) and (iv) as described herein. A first composition as described herein, a second composition as described herein, a third composition as described herein as well as a fourth composition as described herein (i.e. the intermediates as such) form further independent aspects of the present disclosure.

[0354] With respect to the compounds of formulae I, II, IV, V, VI, VII, VIII, IX, XI, XII, XIII, XIV and / or XV it is preferred that one or more of the following applies: X is 2-ethylhexyl; R is methoxy (OMe); and Hal is bromine (Br) or chlorine (Cl), preferably chlorine (Cl). Preferably, X is 2-ethylhexyl and R is methoxy (OMe), or Hal is bromine (Br) or chlorine (Cl) and R is methoxy. More preferably, X is 2-ethylhexyl, R is methoxy (OMe) and Hal is bromine or chlorine. When X is 2-ethylhexyl and R is methoxy (OMe), the compound of formula I is Bemotrizinol (BMT).

[0355] The compounds referred to herein can be produced in any stereoisoform and as mixtures of different isoforms. Stereoisoforms of BMT include meso-BMT (shown in Formula la), R.R-BMT (shown in Formula lb) and S,S-BMT (shown in Formula Ic).

[0356]

[0357]

[0358] In the following, preferred embodiments or variants of the process of the disclosure are described for each step separately. However, each embodiment or variant should be understood to be generally combinable with each other embodiment or variant, unless the context dictates otherwise or the combination is technically not reasonable.

[0359] Referring again to step (i), the first intermediate contained in the first composition is a compound of formula V:

[0360]

[0361] in which R and Hal are defined as in the compounds of formulae I and II. A preferred compound of formula V is 4-methoxyphenyl magnesium bromide.

[0362] A preferred variant uses reactive or “fresh” Mg swarfs and / or turnings. These refer to Mg swarfs or turnings that have a surface that is a non- or low-oxidated. For example, the Mg swarfs and / or turnings are produced directly before use, or unpackaged from an oxygen-free and / or water-free container directly before use.

[0363] In a further preferred variant of step (i), the Mg source contains impurities ranging from 0.030 to 0.1% by weight based on the total weight of the Mg. The impurities contained in the magnesium source are preferably selected from the group of elements consisting of Mg, Si, Fe, Cu, Al, Mn, Ni, and mixtures of one, two, three, four, five, six or seven of the aforementioned elements.

[0364] A specific Mg source has the following composition (in percentages by weight): Mg: 99.90 to 99.99%, Si: 0.01 to 0.05%, Fe: 0.002 to 0.008%, Cu: 0.0002 to 0.001%, Al: 0.007 to 0.03%, Mn: 0.015 to 0.05%, and Ni: 0.00015 to 0.0006%, with the proviso that the percentages sum up to 100%.It is further preferred that step (i) is carried out in inert atmosphere. The inert atmosphere may in particular be selected from the group consisting of oxygen (O2)-free atmospheres, nitrogen atmospheres, CO2 atmospheres, argon atmospheres, etc.

[0365] It is further preferred that iodine can additionally be used in step (i).

[0366] Moreover, a weight ratio of the compound of formula II to the Mg source preferably ranges from 7:1 to 5:1 by weight. A reaction temperature in step (i) preferably ranges from 60 to 80°C.

[0367] The above conditions contribute to a high degree of conversion and specifically facilitate that the residual amount of the compound of formula II in the first composition is less than 0.5% by weight. Accordingly, in the first composition the compound of formula II is preferably 0.5% by weight or less, relative to the total weight of compounds of formulae II and V contained in the first composition.

[0368] The second composition may further comprise, as a side product, a compound of formula VI,

[0369]

[0370] wherein R is the same as in the compound of formula II and V. A preferred compound of formula VI is chloro-bis-methoxyphenyltriazine (R = OMe). The compound of formula VI may be contained in the second composition in residual amounts.

[0371] Another possible side product is a compound of formula VII,

[0372]

[0373] wherein R is the same as in the compound of formula IV. The compound of formula VII may be contained in the second composition in residual amounts. A preferred compound of formula VII is dimethoxy biphenyl (R = OMe).In addition, residual amounts of cyanuric chloride can be contained in the second composition.

[0374] In a further preferred embodiment, one or more of the following applies with respect to step (ii):

[0375] • the content of compound of formula VI is 1 % by weight or less;

[0376] • the content of compound of formula VII is 5% by weight or less, preferably 1.5% or less;

[0377] • the content of cyanuric chloride of formula III is 1% by weight or less;

[0378] • the reaction is conducted under nitrogen atmosphere; and

[0379] • the reaction temperature ranges between 0 and 40°C.

[0380] Preferably, all of the above applies.

[0381] As regards step (ii), the second intermediate obtained, and hence included in the second composition, is a compound of formula IV,

[0382]

[0383] wherein R is defined as in the compound of formulae II and V. A preferred compound of formula IV in which residue R is OMe, which is known as dichloromethyloxyphenyltriazine (DI CAT).

[0384] A preferred variant employs an oxolane solvent selected from the group consisting of 2-methyltetrahydrofuran (2-MeTHF), tetrahydrofuran (THF) and mixtures thereof. Exemplary mixtures include 2-MeTHF and THF in a ratio of 2-MeTHF:THF of 99:1 (V I V), 95:5 (V I V), 90:10 (V / V), 85:15 (V / V), 80:20 (V / V), 75:25 (V / V) or 70:30 (V / V). A preferred oxolane solvent is Methyltetrahydrofuran (2 - MeTHF). The 2-MeTHF can be any one of racemic 2-MeTHF (rac 2 - MeTHF) with ( S ) - ( + ) / ( R) - ( - ) ratio of 1 :1 , ( S ) - ( + ) - stereoisomer of 2 - MeTHF and ( R ) - ( - ) - stereoisomer of 2 - MeTHF and mixtures of (S)-(+)-stereoisomers and (R)-(-)-stereoisomers of 2-MeTHF. The process of the present disclosure is not limited to a particular ratio of (S)-(+) to (R)-(-); exemplary mixtures have a ratio of ( S) - ( + ) / ( R) - ( - ) of 99.9:0.1 , 99:1 , 98:2, 95:5, 90:10, 85:15, 80:20, 70:30, 65:35, 60:40, 55:45, 52:48, 51 :49, 49:51 , 48:52, 45:55, 40:60, 35:65, 30:70, 20:80, 15:85, 10:90, 5:95, 2:98, 1 :99 und 0.1 :99.9.It is further preferred that a molar ratio of the 4-Methoxyphenyl magnesium bromide to the cyanuric chloride ranges from 1.4: 1 and 1 :1 , more preferably 1.3:1 and 1 :1 , such as 1.3:1 , 1.2:1 , 1.15:1 or 1.05:1 (n / n).

[0385] As mentioned above, the reaction is carried out in an iron-free environment. Preferably, the reaction is conducted in an emaille reactor, glass line reactor or tantalum reactor. Thereby, side reactions can be efficiently suppressed.

[0386] Referring to step (iii), steps (iii-1) to (iii-4) are preferably carried out in this order. However, step (iii-3), and optionally step (iii-4), can also be carried out before or simultaneously with step (iii-2). Moreover, it is possible and envisaged by the present disclosure that one or more additional steps are carried out in between the steps (iii-1) to (iii-4).

[0387] In a preferred embodiment, in step (iii-1) the pH of the second composition is adjusted to a value below 3.8, preferably below 3.5, or to a value ranging from 3.0 to 3.8, preferably 3.0 to 3.5. To this end, an aqueous hydrochloric acid solution can be added to the second composition. The content of hydrochloric acid is preferably 5% by weight relative to the total weight of the aqueous hydrochloric acid solution. This concentration can advantageously be used in other steps, i.e. the same solution can be used in multiple steps throughout the process. Thereby, the number of containers can be reduced, and the process simplified.

[0388] Moreover, in step (iii-1) the temperature is preferably adjusted between 60 and 65°C. As mentioned above, step (iii-1) results in a biphasic system in which the second intermediate is enriched in the organic phase. After separating the water phase and the organic phase from each other, steps (iii-2) and (iii-3) are carried out. The extraction in step (iii-2) can be carried out in batch mode (one or more cycles) or continuously. Continuous extraction is preferred from the viewpoint of a large-scale process in order to keep equipment small, facilitate automation and reduce time. Extraction helps to remove the second intermediate from the water phase. As mentioned above, step (iii-3) aims at removing the second intermediate from the oxolane solvent. Preferably, the organic phase subjected to distillation in step (iii-3) encompasses all organic fractions obtained in step (iii-2). This means, when multiple cycles of batch extractions are conducted, all fractions of isolated organic phases are pooled and subsequently used in step (iii-3). Thereby, the yield can be increased.

[0389] In step (iii-4) the benzene solvent and the residue are mixed. According to a preferred embodiment, the benzene solvent is selected among chlorobenzene, methylbenzene, cyanobenzene and mixtures thereof. Generally, the mixtures can include any of thebenzene solvents in any amount. Preferred mixtures include two different benzene solvents. Preferred mixtures include chlorobenzene and cyanobenzene, preferably in a weight ratio ranging from 90:10 to 60:40. A particular preferred ratio of chlorobenzene and cyanobenzene in a specific mixture ranges from 2:1 to 10:1 , preferably 4:1 to 6:1 , most preferably 5:1 (chlorobenzene:cyanobenzene) (v / v). An advantage of a chlorobenzene I cyanobenzene-mixture as compared to a toluol I cyanobenzene mixture is that phase separation, phase inversion and solvent regeneration is improved. Moreover, chlorobenzene has low reactivity, thereby suppressing side reactions.

[0390] Step (iii) results in the third composition comprising the second intermediate and the benzene solvent.

[0391] Referring to step (iv), it is important to maintain the water content below 2% (w / v) to avoid side reactions (hydrolysis). When reference is made herein to the water content, the stated value is preferably meant to characterize the water content determined according to Karl-Fischer.

[0392] When using AlCh (acidic chloride) as Lewis acid, it is preferred that the weight ratio of resorcinol to the acidic chloride ranges from 1 :2 to 1 :1 (w / w). AlCh has the highest reactivity and yield compared to FeCh, and is therefore most preferred. Due to the high reactivity, its amount can be reduced, resulting in an easier workup. Preferably, a weight ratio of resorcinol to AlCh of 1 :1.7 to 1.18 (w / w) is used. The reaction is carried out in the benzene solvent added in the previous step (iii-4). The preferred reaction temperature in step (iv) ranges from 35°C to 75°C, preferably 39°C to 70°C. In some embodiments, the reaction temperature may range from 39 to 55°C. The reaction results in a compound of formula IX as the third intermediate,

[0393] R

[0394]

[0395] wherein R is the same as in the compound of formula I. The compound of formula IX is a bis-resorcinyl-triazine derivative. A preferred third intermediate is 2,4-Bis(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1 ,3,5-triazine (DIOPAT) of formula IX with OMe as R.The fourth composition may further include one or more of the following compounds (side products):

[0396] Resorcinyl-triazine derivatives such as tris-resorcinyl-triazine of formula XVI or bis- methoxyphenyl-resorcinyl-triazine (DMPRT) of formula XVII with OMe as R,

[0397] OH

[0398]

[0399] (XVI) (XVII), whereby the content is preferably 1 % by weight or less for each of said side products,

[0400] Mono-Resorcinyl-triazine derivatives of formula XVIII,

[0401] OH

[0402] (XVIII),

[0403]

[0404] such as Methoxyphenyl-resorcinyl-hydroxy-triazine of formula XIX,

[0405] OH

[0406]

[0407] (XIX),

[0408] whereby the content is preferably 7% by weight or less;

[0409] Bis-resorcinyl-triazine derivative^) such as bis-resorcinyl-hydroxyphenyl-triazine derivative of formula IXb with OH as R,

[0410]

[0411] OH (IXb),

[0412] whereby the content of the further bis-resorcinyl-triazine derivative is preferably 1 % by weight or less;

[0413] • Resorcinol derivative(s) such as benzoresorcinol (= 4-benzoylresorcinol I 2,4- dihydroxybenzophenone), whereby the content of the Resorcinol derivative such as benzoresorcinol is 6% or less;

[0414] • a compound of formula VII such as dimethoxybiphenyl of formula Vila with OMe as R,

[0415]

[0416] (VII),

[0417] whereby the content of the compound of formula VII is preferably 1% by weight or less; and

[0418] • resorcinol in residual amount, whereby the content of resorcinol is preferably 10 ppm or less.

[0419] The contents referred to above are given in relation to the total weight of the fourth composition.

[0420] Step (v) aims at replacing the benzene solvent by an amide solvent. A preferred approach comprises the following steps (v-1) to (v-3):

[0421] (v-1) adding a protic solvent selected from the group of water, MeOH and diluted HCI, thereby creating a multiphase system comprising a solid phase and a liquid phase, the liquid phase consisting of a single organic or aqueous phase, or the liquid phase consisting of a binary phase system of aqueous and organic phases;

[0422] (v-2) separating the solid phase from the liquid phase, the separating optionally comprising removing the organic phase by distillation and / or removing the aqueous phase by filtration, leaving the solid phase as a residue behind; and

[0423] (v-3) dissolving the separated solid phase in the amide solvent and adding diluted base to adjust the pH.Preferably, step (v) further comprises steps (v-4) and (v-5):

[0424] (v-4) adding benzene or amide solvent and removing residual water by distillation until the solution has a water content below 1%, and / or adding amide solvent and removing residual organic solvent and water from the solution by distillation, leaving a distillation residue behind; and

[0425] (v-5) adding further amide solvent to the distillation residue.

[0426] A preferred protic solvent used in step (v-1) is a diluted hydrochloric acid solution. Advantageously, the same diluted hydrochloric acid solution can be used as in step (iii-1) to reduce the number of chemicals and containers required by the process. The protic solvent leads to precipitation of the third intermediate. Optionally, salts can be washed from the precipitate (residue) using water, preferably hot water (e.g., 85 to 90°C).

[0427] In step (v-3), the pH is preferably adjusted to 7 to 7.5 as initial reaction pH value. Specifically, an aqueous solution of the amide solvent is formed by mixing with a diluted base until the desired pH value has been reached. For example, an aqueous solution of 40 to 50% by weight base is useful. A strong base, preferably NaOH or KOH, more preferably NaOH, is preferred, which is added as an aqueous solution. The preferred solution is a solution of 40 to 50% by weight NaOH in water.

[0428] Moreover, in step (v-3) the temperature can be brought to between 40 and 50°C.

[0429] The preferred benzene solvent of step (v-4) is methylbenzene (toluol) or chlorobenzene. Methylbenzene is preferred because an azeotrope can be formed at a lower temperature than with chlorobenzene. Azeotropic distillation is preferably carried out until no water or only traces of water will be separated, preferably until internal temperature reaches the boiling point of the benzene solvent. Pressure can be optionally increased above normal. Residual organic solvents are preferably removed by vacuum distillation. Step (v-4) aims at providing a defined, almost water-free condition, thereby contributing to the suppression of hydrolysis side reactions.

[0430] Preferred amide solvents used in step (v) include dimethylacetamide (DMAc), dimethylformamide (DMF), dimethylpropionamide (DMPr), diethylformamide (DEF), diethylacetamide (DEAc), diethylpropionamide (DEPr) and mixtures thereof. More preferred amide solvents used in step (v) include DMAc, DMPr, DEF, DEAc, DEPr and mixtures thereof. Particular preferred is DMAc.

[0431] Referring to step (vi), the preferred salt is KHCO3. It facilitates release of carbon dioxide under basic conditions and acceleration of the reaction. Water can be added optionally.The preferred reaction temperature ranges from 140 to 145°C. As regards the compound of formula VIII, 2-ethylhexylchloride (CAS 123-04-6) is preferably used.

[0432] In a preferred embodiment, the temperature in step (vi) is maintained until conversion is completed. The pressure can be optionally increased above ambient pressure, for example using nitrogen or released carbon dioxide. The pressure may be increased up to 0.50 MPa, preferably up to 0.40 MPa. For instance, the pressure may be in a range of 0.20 MP to 0.40 MPa, preferably 0.25 MP to 0.35 MPa.

[0433] In a preferred embodiment, a process for producing a compound of formula I or a composition comprising the compound of formula I,

[0434] R

[0435]

[0436] comprises the following steps:

[0437] (i) reacting a compound of formula II and a magnesium (Mg) source comprising Mg swarfs and / or turnings in an oxolane solvent,

[0438]

[0439] to obtain a first composition;

[0440] (ii) reacting the first composition and cyanuric chloride in the oxolane solvent in an iron- free environment to obtain a second composition; the iron-free environment denoting an environment free of exposed iron surfaces;

[0441] (iii) replacing the oxolane solvent of the second composition by a benzene solvent through the steps of:

[0442] adjusting a pH of the second composition to a value below 4 with an aqueous acidic solution, forming a water phase and an organic phase, extracting the water phase using an oxolane solvent as organic phase, removing the oxolane solvent from the organic phase by distillation, leaving a solid residue behind, and

[0443] optionally after washing the residue with an alcohol,to provide a third composition, the third composition being a solid residue;

[0444] (iv) reacting the third composition with a solution of resorcinol and a Lewis acid selected from the group of AlCh in benzene solvent mixture of chlorobenzene and cyanobenzene, the reaction being carried out in inert gas, at reaction temperature of preferably 40-50°C, and at a water content below 2% (w / v), to obtain a fourth composition, the fourth composition being a solution comprising the benzene solvent mixture of chlorobenzene and cyanobenzene;

[0445] (v) replacing the benzene solvent of the fourth composition by an amide solvent and forming a solution having a pH ranging from 7.0 to 7.5 by adding a solution of strong base in water, to provide a fifth composition;

[0446] (vi) reacting the fifth composition with a liquid compound of formula III,

[0447] Hal - X

[0448]

[0449] in the presence of KHCO3 in amide solvent DMAc, at a temperature ranging from 135 to 155°C and under pressure in range between 0.2 MPa and 0.4 MPa to obtain the compound of formula (I) or the composition comprising the compound of formula (I); and

[0450] (vii) optionally, further purification steps for recovering the compound of formula (I); wherein the oxolane solvent is selected from the group consisting of 2-MeTHF; wherein in the compounds of formulae (I), (II) and (III):

[0451] X is 2-ethylhexyl;

[0452] R is methoxy;

[0453] Hal is bromine or chlorine;

[0454] preferably, wherein X is 2-ethylhexyl and R is methoxy, or Hal is bromine or chlorine and R is methoxy;

[0455] more preferably, wherein X is 2-ethylhexyl, R is methoxy and Hal is bromine or chlorine.

[0456] It is yet further preferred that the reaction in step (vi) is carried out in a stirred reactor, and the compound of formula VIII is added below or in the vicinity of the stirrer. In case the reactor has more than one stirrer, the compound of formula III is preferably added below or in the vicinity of the lowest stirrer. Thereby, a favorable mass transfer effect is achieved. Step (vi) yields the compound of formula I, which can be referred to as a triazine derivative. The preferred triazine derivative is BMT with OMe as R and with 2-ethylhexyl as X. The triazine derivative may be obtained in admixture, i.e. in a common composition, with one or more of the following (side) compounds:

[0457] one or more compounds selected from the triazine-side-compound group of formulae XI, XII, XIII, XIV and XV,

[0458]

[0459] in which R and X are the same as in compound of formula I, specifically monoresorcinyl-2,4-dihydroxy-phenyl-triazine derivatives of formula XI, e.g. compound with CAS 633308-76-6 with OMe as R and with 2-ethylhexyl as X, bis-resorcinyl-hydroxyphenyl-triazine derivatives of formula XII, e.g. tris-isooctyl-bis-resorcinyl-hydroxyphenyl-triazine with 2-ethylhexyl as X, monoresorcinyl-bis-phenyl-triazine derivatives of formula XIII, e.g. compound with CAS 562813-88-1 with OMe as R and 2-ethylhexylas X, bis-resorcinyl-phenyl-triazine derivatives of formula XIV and tris-resorcinyl-triazine derivatives of formula XV, e.g. compound with CAS 345658-37-9 with OMe as R and with 2-ethylhexyl as X, whereby the content of compound of formula XI is 1.5% by weight or less, preferably 1 % by weight or less, more preferably 0.5 % by weight or less;• one or more benzophenone derivatives, preferably 2-Hydroxy-4- isooctyloxybenzophenone (CAS 2549-90-8).

[0460] According to a preferred embodiment of step (vii), one or more technologies typically used for isolation or purification such as water removal I drying, filtration, distillation, crystallization, milling, and / or sieving are used.

[0461] A specific approach comprises one or more of the following steps (vii-1) to (vii-6):

[0462] (vii-1) adding diluted protic acid;

[0463] (vii-2) removing the water and organic solvent(s), in particular the amide solvent, from the compound of formula I orthe composition comprising the compound of formula I until the water content is below 1% (w / w);

[0464] (vii-3) crystallizing the compound of formula I from acetone and / or 2-butanol;

[0465] (vii-4) isolating the compound of formula I by filtration;

[0466] (vii-5) washing the compound of formula I;

[0467] (vii-6) drying the compound of formula I; and

[0468] (vii-7) milling the compound of formula I.

[0469] More specifically, water may be removed by azeotropic distillation using a benzene solvent (as described herein), preferably methylbenzene (toluol) or chlorobenzene, more preferably methylbenzene.

[0470] Salt can be removed by filtration.

[0471] Distillation can be carried out to remove the amide solvent (as described herein).

[0472] Crystallization can be conducted to solid ify / isolate the compound of formula I. Any of isothermal, adiabatic and suspension crystallizations can be used. A preferred isothermal crystallization involves seeding at low temperature (e.g. 4 to 8°C, such as 5°C) and maintaining low temperature by cooling. A preferred adiabatic crystallization involves seeding at low temperature and allowing a temperature rise due to heat of crystallization. A preferred suspension crystallization involves using crystallization sample from a previous batch, adding the compound of formula I in dissolved form and maintaining low temperature.

[0473] After filtration, the filtrate may be washed in cold (e.g. 0 to 5°C) acetone, optionally applying a pressure above ambient pressure up to 6 bar, e.g. using nitrogen.

[0474] Drying may be carried out with a vacuum paddle dryer.- M -

[0475] Milling and sieving may be conducted to obtain a sold product comprising or consisting of, preferably essentially consisting of the compound of formula I.

[0476] The crystallization may be done in acetone, 2-butanol, or a mixture thereof (e.g., a weight ratio of acetone : 2-butanol ranges from 9:1 to 20:1), preferably 2-butanol, preferably racemic 2-butanol. Carbon may be added optionally. 2-Butanol showed better selectivity during crystallization as other solvents.

[0477] Another aspect of the disclosure pertains to a compound of formula I, or a composition comprising the compound of formula I, as described herein, produced or producible by the process of the disclosure. A preferred compound of formula I includes 2-ethylhexyl as X and / or methoxy as R. Moreover, the variations (embodiments) described above in relation to the process of the disclosure shall be understood to define corresponding variations of the compound of formula I, and corresponding variations of the composition comprising the compound of formula I.

[0478] In a preferred embodiment, the composition comprising the compound of formula I described herein, produced or producible by the process of the disclosure, includes the following components:

[0479] - a compound of formula I with methoxy as R and 2-ethylhexyl as X (= BMT) in an amount of > 98 g / 100g (i.e. > 98 g compound of formula I per 100g composition),

[0480] and

[0481] - 2-BuOH in an amount of 1 < x < 15 mg / kg.

[0482] Optionally, the composition may further include:

[0483] - < 0.05 % Bemotrizinol resorcinol analog with peak identity MM 515 and C30H33N3O5 and retention time (RT) 12.9 min according to the method description of LCMS analysis with additional UV detection of Bemotrizinol resorcinol analog;

[0484] and I or

[0485] - < 0.015 % Bemotrizinol triethylhexylether analog with peak identity MM 739 and C46H65N3O5 and retention time of 22.2 min according to the method description of LCMS analysis with additional UV detection of Bemotrizinol triethylhexylether analog.

[0486] A further variant of the disclosure relates to the side products that may be formed in the process, specifically in the production of bemotrizinol. The following table summarizes the side products that may occur along the reaction route according to the present disclosure. Thus, one or more of the side products may be included in the composition of the disclosure comprising compound of formula I.Analyte Mass Formula Monoethylhexyl bemotrizinol 515 C30H33N3O5 Bemotrizinol benzophenone analog 326 C21H26O3 Bemotrizinol resorcinol analog 515 C30H33N3O5 Bemotrizinol dianisole analog 513 C31H35N3O4 Bemotrizinol tolyl analog 497 C31H35N3O3 Bemotrizinol methyl analog 641 C39H51N3O5 Bemotrizinol triethylhexyl analog 739 C46H65N3O5 Bemotrizinol triethylhexylether analog 739 C46H65N3O5 Bemotrizinol triethylhexyl isomer 741 C45H63N3O6 Deoxybemotrizinol triethylhexyl isomer 725 C45H63N3O5

[0487]

[0488] The compound of formula I is accessible not only via precursors of petrochemical origin, but advantageously also in a sustainable and / or cost-efficient way from biobased starting materials comprising only non-fossil fuel-based carbon. Assessment of the biobased carbon in a material can be performed through standard test methods. Using radiocarbon and isotope ratio mass spectrometry analysis, the biobased content of materials can be determined. ASTM International, formally known as the American Society for Testing and Materials, has established a standard test method for assessing the biobased content of materials. The ASTM method is designated ASTM D6866. According to a preferred embodiment of the present disclosure, more than 50% of the carbon atoms contained in a compound of formula (I) are biobased (non-petrochemical), based on the total number of carbon atoms contained in said compound of formula I. More preferably, more than 60%, 70%, 75%, 80%, 85%, or 90% of the carbon atoms contained in a compound of formula (I) are biobased, based on the total number of carbon atoms contained in said compound of formula I.

[0489] According to a final aspect of the disclosure, a cosmetic product comprises a compound of formula I, or a composition comprising the compound of formula I, as described herein. Preferred cosmetic products include creams and lotions with light protection factor as well as (dedicated) sunscreens.

[0490] The present invention is further described with reference to the following examples, which are merely illustrative for, but do not limit, the present invention.EXAMPLES

[0491] Examples of the invention

[0492] Experimental example 1

[0493] Experiments were performed according to the following protocol: Take 2 It round bottom flask provided with a stirrer, dropping funnel, condenser and thermometer socket which are free of exposed iron surfaces, and nitrogen inlet and outlet. Charge 64.4 g of magnesium turnings with Fe content of 0.0038 g / 100g and total impurity content of 0.079 g / 100g under nitrogen atmosphere. Heat the contents to 45°C under nitrogen atmosphere. Charge 1.2 g of iodine and 300 ml of 2-MeTHF (rac 2 - MeTHF). Raise the temperature of reaction mass to 60-65°C. Add slowly 40 g of 4-bromoanisole of formula V with OMe as R and Br as Hal at 60-70°C in 10-15 min. Add 355.5 g of 4 bromoanisole of formula V with OMe as R and Br as Hal, dissolved in 750 ml of 2 MeTHF, at 65-70°C in 2h. Maintain the reaction mass at 65-70°C for 90 minutes. Cool the composition comprising 4 methoxy phenyl magnesium bromide (formula II with OMe as R) solution to 40-45°C under nitrogen atmosphere. Take 5 It round bottom flask provided with mechanical stirrer, thermometer socket and condenser which are free of exposed iron surfaces. Charge 600 ml of 2-MeTHF and 300 g (0.542 mol) cyanuric chloride under nitrogen atmosphere and cool the contents to 5-15°C. Add slowly the composition comprising 4-methoxy phenyl magnesium bromide (formula II with OMe as R) in 2h duration at 5-15°C under nitrogen atmosphere and form a composition comprising DICAT of formula (I) with OMe as R. Maintain this composition for 30-40 min at 5-15°C. After full conversion of cyanuric chloride, add 750 ml of water and 290 ml of 5 % HCI solution at 15-20°C to pH < 4. A water phase and an organic phase is formed. Heat the contents to 60-65°C, separate the layers. Extract the aqueous layer with 300 ml of 2-MeTHF. The combined organic layers are distilled atmospherically at below 90°C. After completion of distillation, apply vacuum distillation to remove 2-MeTHF traces cool the mass to 40-45°C.

[0494] Experimental example 2

[0495] Take 5 It round bottom flask installed with a stirrer, dropping funnel, condenser, thermometer socket as well as a nitrogen inlet and outlet. The installation was free of exposed iron surfaces. Charge 107.5 g of magnesium turnings with Fe content of 0.0038 g / 100g and total impurity content of 0.079 g / 100g under nitrogen atmosphere. Heat the contents to 45°C under nitrogen atmosphere. Charge 2 g of iodine and 500 ml of 2-MeTHF (rac 2 - MeTHF). Raise the temperature of reaction mass to 60-65°C. Add slowly 66 g of 4-bromoanisole of formula V with OMe as R and Br as Hal at 60-70°C in 10-15 min. Add 594 g of 4-bromoanisole of formula Vwith OMe as R and Br as Hal, dissolved in 1250 ml of 2-MeTHF, at 65-70°C in 1 1.5h to form a composition comprising 4 methoxy phenyl magnesium bromide (formula II with OMe as R). Maintain this composition at 65-70°C for 90 minutes. Cool the composition comprising 4 methoxy phenyl magnesium bromide (formula II with OMe as R) to 40-45°C under nitrogen atmosphere. Take 10 It round bottom flask provided with mechanical stirrer, thermometer socket and condenser. Charge 1000 ml of 2-MeTHF and 500 g cyanuric chloride under nitrogen atmosphere and cool the contents to 5-15°C. Add slowly the composition comprising 4-methoxy phenyl magnesium bromide (formula II with OMe as R) to form a composition comprising DICAT of formula (I) with OMe as R in 2-2.5h duration at 5-15°C under nitrogen atmosphere. Maintain this composition for 30-40 min at 5-15°C. After complete conversion of cyanuric chloride, add 1250 ml of water and 450 ml of 5% HCI solution at 15-20°C. Separate the layers, extract the aqueous layer with 500 ml of 2-MeTHF. The combined organic layers are distilled completely under vacuum at below 65°C

[0496] Experimental example 3

[0497] Take 1 It round bottom flask provided with a stirrer, dropping funnel, condenser and thermometer socket which are free of exposed iron surfaces and nitrogen inlet and outlet. Charge 16.61 g of magnesium turnings with Fe content of 0.0038 g / 100g and total impurity content of 0.079 g / 100g under nitrogen atmosphere. Heat the contents to 45°C under nitrogen atmosphere. Charge 4 g of iodine and 100 ml of 2 MeTHF (rac 2 - MeTHF). Raise the temperature of reaction mass to 60-65°C. Add slowly 12.78 g of 4 bromoanisole of formula V with OMe as R and Br as Hal at 60-70°C in 10-15 min. Add 127.8 g of 4 bromoanisole of formula Vwith OMe as R and Br as Hal, dissolved in 200 ml of 2 MeTHF, at 65-70° C in 1-1 ,5h to form a composition comprising 4 methoxy phenyl magnesium bromide (formula II with OMe as R). Maintain the reaction mass at 65-70°C for 90 minutes. Cool the composition comprising 4 methoxy phenyl magnesium bromide to 40-45°C under nitrogen atmosphere. Take four neckround bottom flask provided with mechanical stirrer, thermometer socket and condenser. Charge 150 ml of 2 MeTHF and 100 g of cyanuric chloride under nitrogen atmosphere and cool the contents to 5-15°C. Add slowly the composition comprising 4 methoxy phenyl magnesium bromide (formula II with OMe as R) in 2-2.5h duration at 5-15°C under nitrogen atmosphere. Maintain the reaction mass for 30-40 min at 5-15°C. After complete conversion of cyanuric chloride, add 300 ml of water and 100 ml of 5 % HCI solution at 15-20°C. Separate the layers, extract the aqueous layer with 150 ml of 2 MeTHF. The combined organic layer is distilled completely under vacuum at below 65°C to remove 2-MeTHF.Method description

[0498] a) Water content (%, w / w) determination by Karl-Fischer Titrator procedure:

[0499] Take about 30-40 ml of methanol (ensure that electrode is dipped in the medium) for water determination in a dried titration flask, fill the burette by Karl-Fischer reagent and titrate the water content with Karl-Fischer reagent to make the content of the flask anhydrous. Quickly add 1 g of test sample accurately weighed, into the titration vessel, dissolve the contents by stirring and titrate with Karl-Fischer reagent to the electrometric end point under vigorous stirring. Repeat the titration in two replicates and report the average result. The % difference between the results of consecutive measurements is ± 20 %.

[0500] Calculate the percentage of water content by using the following formula.

[0501] , Titer value (ml) x Karl — Fischer — Reagent factor (^r) X 100 Water content (% — I = - , - — - - — — — — — - — -

[0502]

[0503] V w' Weight of the sample (g) x 1000

[0504] The % difference between the results of consecutive measurements shall be calculated as follows:

[0505] > (A - B) or (B - A) x 100

[0506] Average of two results

[0507] in which A is the result of the first replicate, and B is the result of the second replicate.

[0508] b) LCMS analysis with additional UV detection

[0509] 1. Sample preparation

[0510] Approximately 3 mg of a solid sample were transferred into a 2 mL glass vial with screw caps (Agilent, catalogue number 5182-0714). Afterwards, 200 pL Methyl tert-butyl ether (Honeywell, CHROMASOLV > 99.8 % purity, catalogue number 34875) were added. The sample was then agitated until the solid material was completely dissolved and further diluted by addition of 800 pL Acetonitrile (Biosolve, LCMS quality, catalogue number 012078). After homogenisation via shaking, the vial was then transferred into the Autosampler.

[0511] 2. Measuring parameters

[0512] LC-instrument: Waters Acquity UPLC

[0513] MS-instrument: Bruker micrOTOF II2.1 LC parameters

[0514] LC column: Kinetex RP-C18, 1 ,7pm ( 100 x 2.1 mm )

[0515] (Phenomenex, catalogue number 00D-4475-AN)

[0516] Mobile phase: A: H2O (Honeywell, CHROMASOLV LC-MS, catalogue number 39253) + 0,05% formic acid (Biosolve, 99% purity ULC / MS - CC / SFC, catalogue number 069141)

[0517] B: Acetonitril (Biosolve, LCMS quality, catalogue number 012078) + 0,05% formic acid

[0518] 0.0 min A: 80 % B: 0 %

[0519] 15.0 min A: 0 % B: 100 %

[0520] 30.0 min A: 0 % B: 100 %

[0521] PreRun time 3 min

[0522] Flow rate: 0.55 ml / min

[0523] Mode: Gradient

[0524] Temperature: 50°C

[0525] Injection volume: 2 pl

[0526] UV: SCAN 200-799 nm; Integration at 332 nm

[0527] 2.2 MS parameters

[0528] Scan range: 50-1600 Da

[0529] Internal calibration: sodium formate solution, injected between 28 min and 30 min of every measurement (505 mL water + 500 mL 2-Propanol (Merck Supelco, LCMS LiChrosolve, catalogue number 102781) + 2 mL formic acid + 0.2 g sodium hydroxide (Sigma Aldrich, purity > 98%, catalogue number 30620)

[0530] Lock mass: Hexakis(2,2-difluoroethoxy)phosphazene (Apolloscientific, purity 95%, catalogue number PC1165), continuously added via a foam sponge in the ESI source.

[0531] Source parameters

[0532] source: ESI + with in source fragmentation

[0533] End Plate Offset: 500 V

[0534] Capillary voltage: 4500 V

[0535] Nebulizer gas pressure (nitrogen): 4.0 bar

[0536] Drying gas (nitrogen): 8.0 l / min, 250 °C

[0537] Transfer voltages

[0538] Kapillary exit: 90V

[0539] Skimmer 1 : 30V

[0540] Hexapol 1 : 23V

[0541] Hexapol RF voltage: 75 Vpp

[0542] Skimmer 2: 24V

[0543] T ransfer time Lense 1 : 65 ps

[0544] Linse 1 pre pulse storage: 1 psMS / MS experiments (in-Source CID)

[0545] Kapillary exit: 90V

[0546] Skimmer 1 : 30V

[0547] 3. Evaluation, Identification and calcuation

[0548] Evaluation was performed using the DataAnalysis software (Bruker Daltonics, Compass DataAnalysis Version 5.3, Build 556.6383). First, the UV chromatogram at wavelength 332 nm was extracted. From this extracted UV chromatogram at 332 nm, the area of each peak was determined by integration of each single peak which is the single peak area. The total sum of all integrated single peak area was calculated and formed the total peak area.

[0549] The identity of each visual peak was investigated by extracting the mass spectra of each peak and generating sum formulae using the “SmartFormula Manually” tool of the DataAnalysis software. Generated sum formulae were assessed based on their mass error, isotope matching and general reasonableness and the best fitting one was selected. The percentage of the single peak area in relation to the total peak area of the UV chromatogram at 332 nm is calculated and multiplied with its relative response factor (RRF) which is shown in the following table.

[0550] relative response factor (RRF) * single peak area at 332 nm * 100 Percentage [%] = - — - — - - - — - - total sum or all peak areas at 332 nm

[0551] c) Element content by ICP-MS

[0552] Element content of Fe, Si, Cu, Al, Mn and Ni may be determined by inductively coupled plasma mass spectrometry (ICP-MS). The ICP-MS method may be performed according to ISO 17294-2 or an equivalent validated method. Iron values are expressed in % (weight per weight).

[0553] Further examples of the disclosure

[0554] Example 1

[0555] Composition A and composition B comprising compound of formula I with methoxy as R and 2-Ethylhexyll as X, produced or producible by the process disclosed herein, were analyzed in comparison with commercially available market samples 1 to 4 of BMT, applying the above LCMS analysis with additional UV detection procedure.The following table shows the determined areas at 332 nm.

[0556] peak area at 332nm (mAu*s)

[0557] total sum of all peak Bemotrizinol Bemotrizinol areas at 332nm resorcinol triethylhexylether (mAu*s)

[0558] analog analog

[0559] Composition A 1.4369 3.287 27531.2203 Composition B 7.897 4.0309 32809.705

[0560] Market sample 1 48.990 19.1843 34299.5158

[0561] Market sample 2 42.5623 19.645 31489.479

[0562] Market sample 3 38.8529 7.9429 35450.1778

[0563] Market sample 4 42.7456 8.2293 39096.0217

[0564]

[0565] The following table shows the identity of the peaks:

[0566] Peak identity

[0567] Bemotrizinol Bemotrizinol

[0568] resorcinol triethylhexylether

[0569] analog analog

[0570] molar mass 515 739

[0571] formula C30H33N3O5 C46H65N3O5

[0572] relative response factor

[0573] 1.1 0.77

[0574] (RRF) UV 332 nm

[0575] retention time RT (min) 12.9 22.2

[0576]

[0577] The percentage of the single peak area in relation to the total peak area of the UV chromatogram at 332 nm multiplied with its relative response factor (RRF) is shown in the following table.

[0578] percentage [%]

[0579] - according method description of LCMS

[0580] analysis with additional UV detection

[0581] Bemotrizinol Bemotrizinol

[0582] resorcinol triethylhexylether

[0583] analog analog

[0584] Composition A 0.006 0.009

[0585] Composition B 0.026 0.010

[0586] Market sample 1 0.157 0.043

[0587] Market sample 2 0.149 0.048

[0588] Market sample 3 0.121 0.017

[0589] Market sample 4 0.120 0.016

[0590]

[0591] Example 2

[0592] Experiments were performed according to the following protocol: Take 2 It round bottom flask provided with a stirrer, dropping funnel, condenser and thermometer socket which are free of exposed iron surfaces, and nitrogen inlet and outlet. Charge 64.4 g of magnesium turnings under nitrogen atmosphere. Heat the contents to 45°C under nitrogen atmosphere. Charge 1.2 g of iodine and 300 ml of 2-MeTHF. Raise the temperature of reaction mass to 60-65°C. Add slowly 40 g of 4-bromoanisole of formula II with OMe as R and Br as Hal at 60-70°C in 10-15 min. Add 355.5 g of 4-bromoanisole of formula II with OMe as R and Br as Hal, dissolved in 750 ml of 2-MeTHF, at 65-70°C in 2h. Maintain the reaction mass at 65-70°C for 90 minutes. Cool the composition comprising 4-methoxy phenyl magnesium bromide solution to 40-45°C under nitrogen atmosphere. Take 5 It round bottom flask provided with mechanical stirrer, thermometer socket and condenser which are free of exposed iron surfaces. Charge 600 ml of 2-MeTHF and 300 g (0.542 mol) cyanuric chloride (formula III) under nitrogen atmosphere and cool the contents to 5-15°C. Add slowly the composition comprising 4-methoxy phenyl magnesium bromide in 2h duration at 5-15°C under nitrogen atmosphere and form a composition comprising DICAT of formula (IVa). Maintain this composition for 30-40 min at 5-15°C. After full conversion of cyanuric chloride, add 750 ml of water and 290 ml of 5 % HCI solution at 15-20°C to pH < 4. A water phase and an organic phase is formed. Heat the contents to 60-65°C, separate the layers. Extract the aqueous layer with 300 ml of 2-MeTHF. The combined organic layers are distilled atmospherically at below 90°C. After completion of distillation, apply vacuum distillation to remove 2-MeTHF traces cool the mass to 40-45°C. Charge 600 ml of methanol and stir for 1 h at 10-15°C. Filter the solid and wash the solid with 150 ml of methanol and dry the solid atmospherically at 70°C to obtain >350 g of composition comprising DICAT with >90 % purity. Take four neck round bottom flask provided with a stirrer, dropping funnel, condenser and thermometer socket. Charge 300 ml of chlorobenzene, 60 ml of cyanobenzene, 120.2 g of resorcinol and 130 g of the composition comprising DICAT under nitrogen atmosphere at a water content below 2%. Heat the contents to 40-45°C under nitrogen atmosphere. Add slowly 67.7 g of aluminum chloride lot wise in 3h duration at 40-45°C to form a composition comprising DIOPAT (formula IXa). Heat this composition to 60-65°C and stir for 3-4h at 60-65°C. After full conversion of DICAT, cool the composition to 25-30°C. Charge 850 ml of water and 150 ml of cone. HCI. Heat the content to reflux temperature and distill the solvent azeotropically. After completion of distillation of the benzene solvent, charge 1700 ml of water, filter the solid at 80-85°C and wash the solid with 150 ml of water and suck dry. Take the wet solid in round bottom flask and charge 1700 ml of water. Heat the contents to 80-85°C and stir for 60 min. Filter the solid and wash the solid with 150 ml of water and suck dry to obtain >500 g of composition comprisingDIOPAT (formula IXa, wet) with HPLC purity of at least >80 %. Take 2 It four neck round bottom flask provided with a stirrer, dropping funnel, condenser, thermometer socket and azeotropic distillation unit. Charge 700 ml of dimethyl acetamide, 200 ml of methylbenzene and 545 g of composition comprising DIOPAT (formula IXa, wet). Adjust the pH of the mass to 7.0-7.5 with 50 % NaOH solution. Remove water by azeotropic distillation at 120-130°C. Distill the benzene solvent completely under vacuum to replace the benzene solvent. Charge 800 ml of dimethyl acetamide and 119.4 g of potassium bicarbonate and heat to 140°C under nitrogen atmosphere. Add slowly 230 g of 2-ethylhexyl chloride offormula VIII with 2-Ethylhexyl as X and Br as Hal in 6h and stir of 8-1 Oh at 135-140°C to form a composition comprising BMT of formula I with OMe as R and 2-Ethylhexyl as X. Cool this composition to 80-90°C, filter the inorganic salts and wash the salts with 200 ml of methylbenzene. Take the clean filtrate in round bottom flask, adjust the pH to 7.0 -7.5 with 5 % HCI solution. Remove water from the reaction mass by azeotropic distillation. Filter the salts and wash the salts with 50 ml of methylbenzene. Take the clean filtrate in round bottom flask and distil the solvent completely under vacuum. Cool the mass to 45°C. Add 1100 g of acetone and 55 g of 2-butanol. Heat the contents to 40-45°C to get clear solution. Charge 3 g of carbon, stirfor30 min and filterthe carbon. Take clean filtrate in round bottom flask, cool the mass to 0-5°C. Add seed (BMT pharma) and stir for 6-8h at 0-5°C for complete precipitation. Filter the solid and wash the solid with 150 ml of chilled acetone and suck dry. Take the wet solid in 2 It round bottom flask. Charge 500 ml of acetone at 40-45°C to get clear solution. Cool the mass to 5-10°C and stir for 4-5h at 5-10°C. Filter the solid and wash the solid with 150 ml of chilled acetone. Dry the solid under vacuum below 60°C for 3-4h to obtain 201 g of composition comprising BMT of formula I with OMe as R and 2-Ethylhexyl as X with HPLC purity of at least 98 %.

[0593] Example 3

[0594] Take 5 It round bottom flask installed with a stirrer, dropping funnel, condenser, thermometer socket as well as a nitrogen inlet and outlet. The installation was free of exposed iron surfaces. Charge 107.5 g of magnesium turnings under nitrogen atmosphere. Heat the contents to 45°C under nitrogen atmosphere. Charge 2 g of iodine and 500 ml of 2-MeTHF. Raise the temperature of reaction mass to 60-65°C. Add slowly 66 g of 4-bromoanisole of formula II with OMe as R and Br as Hal at 60-70°C in 10-15 min. Add 594 g of 4-bromoanisole of formula II with OMe as R and Br as Hal, dissolved in 1250 ml of 2-MeTHF, at 65-70°C in 1-1 ,5h to form a composition comprising 4-methoxy phenyl magnesium bromide. Maintain this composition at 65-70°C for 90 minutes. Cool the composition comprising 4-methoxy phenyl magnesium bromide to 40-45°C under nitrogen atmosphere. Take 10 It round bottom flask provided with mechanical stirrer, thermometer socket and condenser. Charge 1000 ml of 2-MeTHF and 500 g cyanuric chloride undernitrogen atmosphere and cool the contents to 5-15°C. Add slowly the composition comprising 4-methoxy phenyl magnesium bromide to form a composition comprising DICAT in 2-2.5h duration at 5-15°C under nitrogen atmosphere. Maintain this composition for 30-40 min at 5-15°C. After complete conversion of cyanuric chloride, add 1250 ml of water and 450 ml of 5% HCI solution at 15-20°C. Separate the layers, extract the aqueous layer with 500 ml of 2-MeTHF. The combined organic layers are distilled completely under vacuum at below 65°C Cool the mass to 25-30°C. Charge 1000 ml of methanol and maintain for 1h at 10-15°C. Filter the solid and dry the solid at 70°C atmospherically to obtain >575 g of composition comprising DICAT with >90 % purity.

[0595] Option a) Take 3 It four neck round bottom flask provided with a stirrer, dropping funnel, condenser and thermometer socket (free of exposed iron surfaces). Charge 500 ml of chlorobenzene, 120.17 g of resorcinol and 109.75 g of methane sulfonic acid under nitrogen atmosphere. Add slowly 130 g of composition comprising DICAT lot wise in 2h duration at ambient temperature. Stir the contents for 3-4h. After complete conversion of DICAT, charge 1500 ml of methanol. Heat the contents to 40-45°C and stirfor60 min. Filter the solid and wash the solid with 300 ml of methanol and dry the wet solid at 70°C atmospherically to obtain <200 g of composition comprising DIOPAT (formula IXa) with HPLC purity of at least > 85 %. Take 2 It four neck round bottom flask provided with a stirrer, dropping funnel, condenser, and thermometer socket. Charge 800 ml of dimethyl acetamide and 225 g of composition comprising DIOPAT (formula IXa). Charge 158 g of potassium bicarbonate at 30-40°C. Raise the temperature of the composition to 145°C under nitrogen atmosphere. Add slowly 220 g of 2-ethylhexyl chloride in 6h to form a composition comprising BMT of formula I with OMe as R and 2-Ethylhexyl as X. After completion of the addition, stir the composition for 8-10h. After complete conversation of DIOPAT (formula IXa), cool the composition to 80-90°C. Filter the inorganic salts and wash the salts with 200 ml of methylbenzene. Take the clean filtrate in round bottom flask. Adjust the pH to 7.0 with 5 % HCI solution and remove water from the reaction mass by azeotropic distillation. Filter the salts and wash the salts with 50 ml of methylbenzene. Take the clean filtrate in round bottom flask and distil the solvent completely under vacuum, cool the mass to 45°C. Add 1100 g of acetone and 55 g of 2butanol. Heat the contents to 40-45°C to get clear solution. Charge 3 g of carbon, stir for 30 min and filter the carbon. Take clean filtrate in round bottom flask, cool the mass to 0- 5 C. Add seed (BMT pharma) and stir for 6-8h at 0-5°C for complete precipitation. Filter the solid and wash the solid with 150 ml of chilled acetone and suck dry. Take the wet solid in 2 It round bottom flask. Charge 500 ml of acetone. Heat the content to 40-45°C get clear solution. Cool the mass to 5-10°C and stir for 4-5h. Filter the solid and wash the solid with 150 ml of chilled acetone. Dry the solidunder vacuum below 60°C for 3-4h to obtain >160 g of composition comprising BMT of formula I with OMe as R and 2-Ethylhexyl as X with HPLC purity of at least > 98 %.

[0596] Option b) Take 3 It four neck round bottom flask provided with a stirrer, dropping funnel, condenser and thermometer socket (free of exposed iron surfaces). Charge 500 ml of chlorobenzene, 120.92 g of resorcinol and 93.8 g of methane sulfonic acid under nitrogen atmosphere. Add slowly 125 g of composition comprising DICAT lot wise in 2h duration at 10-15°C. Stir the contents for 4-6h at ambient temperature. After complete conversion of DICAT add 1000 ml of ice-cold water and distil the organic solvent azeotropically. Filter the solid and wash with 500 ml of water and suck dry to obtain >500 g composition comprising DIOPAT (formula IXa) (wet) with HPLC purity of at least > 80 %. Take 2 It four neck round bottom flask provided with a stirrer, dropping funnel, condenser, thermometer socket and azeotropic distillation unit. Charge 600 ml of dimethyl acetamide, 200 ml of methylbenzene and 540g of composition comprising DIOPAT (formula IXa). Adjust the pH of the mass to 7.0-7.5 with 50 % NaOH solution. Remove water by azeotropic distillation at 120-130°C. Distill the solvent completely under vacuum. Charge 800 ml of dimethyl acetamide and 118.2 g of potassium bicarbonate and heat to 140°C under nitrogen atmosphere. Add slowly 220 g of 2ethylhexyl chloride in 6h and stir of 8-1 Oh at 135-140° C to form a composition comprising BMT of formula I with OMe as R and 2-Ethylhexyl as X. Cool the mass to 80-90°C, filter the inorganic salts at 80-90°C and wash the salts with 200 ml of methylbenzene. Take the clean filtrate in round bottom flask, adjust the pH to 7.0 -7.5 with 5 % HCI solution. Remove water from the reaction mass by azeotropic distillation. Filter the salts and wash the salts with 30 ml of methylbenzene. Take the clean filtrate in round bottom flask and distil the solvent completely under vacuum, cool the mass to 45°C. Add 1100 g of acetone and 55 g of 2butanol. Heat the contents to 40-45°C to get clear solution. Charge 3 g of carbon, stirfor30 min and filterthe carbon. Take clean filtrate in round bottom flask, cool the mass to 0-5°C. Add seed (BMT pharma) and stir for 6-8h at 0-5°C for complete precipitation. Filter the solid and wash the solid with 150 ml of chilled acetone and suck dry. Take the wet solid in 2 It round bottom flask. Charge 500 ml of acetone at 40-45°C to get clear solution. Cool the mass to 5-10°C and stir for 4-5h at 5-10°C. Filter the solid and wash the solid with 150 ml of chilled acetone. Dry the solid under vacuum below 60°C for 3-4h to obtain 175 g of a composition comprising BMT of formula I with OMe as R and 2-Ethylhexyl as X with HPLC purity of at least 98 %.

[0597] Example 4

[0598] Take 1 It round bottom flask provided with a stirrer, dropping funnel, condenser and thermometer socket which are free of exposed iron surfaces and nitrogen inlet and outlet. Charge 16.61 g of magnesium turnings under nitrogen atmosphere. Heat the contents to45°C under nitrogen atmosphere. Charge 4 g of iodine and 100 ml of 2-MeTHF. Raise the temperature of reaction mass to 60-65°C. Add slowly 12.78 g of 4-bromoanisole of formula II with OMe as R and Br as Hal at 60-70°C in 10-15 min. Add 127.8 g of 4-bromoanisole of formula II with OMe as R and Br as Hal, dissolved in 200 ml of 2-MeTHF, at 65-70° C in 1-1 ,5h to form a composition comprising 4-methoxy phenyl magnesium bromide. Maintain the reaction mass at 65-70°C for 90 minutes. Cool the composition comprising 4-methoxy phenyl magnesium bromide to 40-45°C under nitrogen atmosphere. Take four neckround bottom flask provided with mechanical stirrer, thermometer socket and condenser. Charge 150 ml of 2-MeTHF and 100 g of cyanuric chloride under nitrogen atmosphere and cool the contents to 5-15°C. Add slowly the composition comprising 4-methoxy phenyl magnesium bromide in 2-2.5h duration at 5-15°C under nitrogen atmosphere. Maintain the reaction mass for 30-40 min at 5-15°C. After complete conversion of cyanuric chloride, add 300 ml of water and 100 ml of 5 % HCI solution at 15-20°C. Separate the layers, extract the aqueous layer with 150 ml of 2-MeTHF. The combined organic layer is distilled completely under vacuum at below 65°C to remove 2-MeTHF. Cool the mass to 25-30°C. Charge 200 ml of methanol and maintain for 1h at 10-15°C. Filter the solid, wash the solid with 50 ml of methanol and dry the solid at 70°C atmospherically to obtain >110 g composition comprising DICAT with at least > 90 % purity. Take four neck round bottom flask provided with a stirrer, dropping funnel, condenser and thermometer socket. Charge 500 ml of chlorobenzene, 115.5 g of resorcinol and 173.68 g of benzene sulfonic acid (BSA) under nitrogen atmosphere. Add slowly 125 g of composition comprising DICAT lot wise in 2h duration at ambient temperature. Stir the contents for 3-4h. After complete conversion of DICAT, add 1000 ml of ice cold water and distil the organic solvent azeotropically. Filter the solid and wash with 300 ml of water. Take the wet solid in round bottom flask charge 1000 ml of DM water. Heat the contents to 80-90°C. Stir the contents for 1h and filter the solid and wash the solid with 300 ml of water. Suck dry to obtain >350 g of composition comprising DIOPAT (formula IXa) (wet) with HPLC purity of at least >80 %. Take four neck round bottom flask provided with a stirrer, dropping funnel, condenser, thermometer socket and azeotropic distillation unit. Charge 600 ml of dimethyl acetamide, 200 ml of methylbenzene and 390 g of composition comprising DIOPAT (formula IXa) (wet). Adjust the pH of the mass to 7.0-7.5 with 50 % NaOH solution. Remove water by azeotropic distillation at 120-130°C. Distill the solvent completely under vacuum. Charge 800 ml of dimethyl acetamide and 109.9 g of potassium bicarbonate and heat to 140°C under nitrogen atmosphere. Add slowly 225 g of 2-ethylhexyl chloride in 6h and stir of 8-1 Oh at 135-140°C to form a composition comprising BMT of formula I with OMe as R and 2-Ethylhexyl as X. Cool the mass to 80-90°C, filter the inorganic salts at 80-90°C and wash the salts with 200°ml of methylbenzene. Take the clean filtrate in round bottom flask, adjust the pH to 7.0 -7.5 with 5 % HCI solution. Remove water from the reaction mass byazeotropic distillation. Filterthe salts and wash the salts with 50 ml of methylbenzene. Take the clean filtrate in round bottom flask and distil the solvent completely under vacuum, cool the mass to 45°C. Add 1100 g of acetone and 50 g of 2-butanol. Heat the contents to 40-45°C to get clear solution. Charge 3 g of carbon, stir for 30 min and filter the carbon. Take clean filtrate in round bottom flask, cool the mass to 0-5°C. Add seed (BMT pharma) and stir for 6-8h at 0-5°C for complete precipitation. Filter the solid and wash the solid with 150 ml of chilled acetone and suck dry. Take the wet solid in 2 It round bottom flask. Charge 500 ml of acetone at 40-45°C to get clear solution. Cool the mass to 5-10°C and stir for 4-5h at 5-10°C. Filterthe solid and wash the solid with 150 ml of chilled acetone. Dry the solid under vacuum below 60°C for 3-4h to obtain >150 g of composition comprising BMT (formula I with OMe as R and 2-ethylhexyl as X) with HPLC purity of at least 98 %.

[0599] Example 5

[0600] Water content removal from composition comprising DIOPAT (formula IXa) wet procedure: Take 4 neck round bottom flask provided with a stirrer, dropping funnel, condenser, thermometer socket and azeotropic distillation unit. Charge 300 ml of dimethyl acetamide, 150 ml of methylbenzene and 216 g composition comprising of DIOPAT (formula IXa). Adjust the pH of the mass to 7.0-7.5 with 50 % NaOH solution. Remove water by azeotropic distillation at 120-130°C. After completion of azeotropic distillation, send the sample to quality control for the analysis of water content by Karl-Fischer (KF) Titrator. The analysis showed water content of mass sample as 8.20 %. After one hour maintenance reaction mass under stirring at 130°C, send the sample to quality control for the analysis of water content by KF Titrator. A water content up to ca. 15 % was found. It indicates that the water content of reaction mass is not completely removed by azeotropic distillation. To get water free, the temperature of reaction mass is increased to 140°C and the solvents (DMAc and methylbenzene) distilled completely. After completion of distillation of solvents, the water content of mass is analyzed by KF Titrator. The analysis showed the water content of the mass sample as < 1 %. So after ensuring the water content of reaction mass below 1 % by Karl-Fischer Titrator, alkylation of composition comprising DIOPAT (formula IXa) with ethyl hexyl chloride in the presence of potassium bicarbonate base is proceeded.

[0601] Example 6

[0602] 2-(4-hexyl phenyl)-4,6-dichlorotriazine preparation is the condensation of 4-hexyl phenyl magnesium chloride with cyanuric chloride in 2-MeTHF at 0-5°C and in work up mass is quenched with 1N HCI solution and water. Organic layer is separated and distilled to get compound of 2-(4-hexyl phenyl)-4,6-dichlorotriazine. 4-hexyl phenyl magnesium chloride is prepared by the reaction of 4-hexyl-1 -chlorobenzene with magnesium metal in thepresence of iodine in 2-MeTHF medium at 60-70°C under nitrogen atmosphere. After complete formation of 4-hexyl phenyl magnesium chloride at 60-70°C, the mass is cooled to 40-50°C under nitrogen atmosphere and used directly for coupling with cyanuric chloride 2,4-bis(2,4-dihydroxyphenyl)-6-(4-hexyl phenyl)-1 ,3,5-triazine) is prepared by the acylation of resorcinol with 2-(4-hexyl phenyl)-4,6-dichlorotriazine in the presence of aluminum chloride in chlorobenzene medium at 60-65°C. After completion of the reaction in work up the reaction mass is diluted with water and solvent is removed by azeotropic distillation. The solid product is isolated from water by filtration at hot condition. The wet solid of 2,4-bis(2,4-dihydroxyphenyl)-6-(4-hexyl phenyl)-1 ,3,5-triazine is used directly in Bisoctyloxyphenol hexyl phenyl triazine. Bis-octyloxyphenol hexyl phenyl triazine is prepared by the alkylation of 2,4-bis(2,4-dihydroxyphenyl)-6-(4-hexyl phenyl)-1 ,3,5-triazine with n-octyl chloride in the presence of sodium carbonate base in dimethyl acetamide medium at 140°C for 10h and in work up the inorganic salts are removed by filtration and the solvent is distilled completely under vacuum. To the residue a mixture of acetone and 2-butanol added and isolated the solid. Later the solid is slurred in acetone to form pure Bis-octyloxyphenol hexyl phenyl triazine.

[0603] Example 7

[0604] 2-(4-pentyl oxy phenyl) -4,6-dichloro triazine preparation process is the condensation of 4-pentyl oxy phenyl magnesium bromide with cyanuric chloride in THF at 0-5°C and in work up THF is completely distilled, residue is quenched with dilute HCI and extracted with methyl benzene. Organic layer is completely distilled. Methanol is added and filtered the solid and dried the solid to obtain 2-(4-pentyl oxy phenyl)-4,6-dichloro triazine. 4- pentyl oxo phenyl magnesium bromide is prepared by the reaction of 1 -bromo 4-pentyl oxy benzene with magnesium metal in the presence of iodine in THF medium at 60-70°C under nitrogen atmosphere. After completion of the formation of Grignard reagent (4-pentyl oxo phenyl magnesium bromide), mass is cooled to 40-45°C under nitrogen atmosphere and is used directly for coupling with cyanuric chloride. 2,4-bis(2,4-dihydroxyphenyl)-6-(4-pentyl oxy phenyl)-1 ,3,5-triazine is prepared by the condensation of 2-(4-pentyl oxy phenyl) -4,6-dichloro triazine with 2.2 eq of resorcinol in the presence of catalytic quantity of ferric chloride in methyl benzene at 60-65°C. After completion of the reaction mass is diluted with water and distilled the organic solvent and DIOPAT wet is isolated from hot water. The wet solid is purified with water slurry. The wet 2,4-bis(2,4-dihydroxyphenyl)-6-(4-pentyl oxy phenyl)-1 ,3,5-triazine is used directly in the preparation of Bis-benzyl oxyphenol pentyl oxy phenyl triazine. Bis-benzyl oxyphenol pentyl oxy phenyl triazine preparation process is the alkylation of 2,4-bis(2,4-dihydroxyphenyl)-6-(4-pentyl oxy phenyl)-1 ,3,5-triazine with benzyl bromide in the presence of sodium carbonate in Dimethyl formamide medium at 140°C in 8h time. After completion of the reaction inorganic salts were removed by filtration. Theclean filtrate is distilled completely. To the residue a mixture of acetone and 2-butanol is added, and product is isolated at 0-5°C, the wet solid is purified with acetone slurry and dried under vacuum to obtain Bis-benzyl oxyphenol pentyl oxy phenyl triazine, Example 8

[0605] 2-(4-decenyl phenyl) -4,6-dichlorotriazine preparation process is the condensation of 4-decenyl phenyl magnesium iodide with cyanuric chloride in 50% THF and 50% 2-Me.THF at 0-5°C. After completion of the reaction, mass is quenched with water and HCI at 10-15°C. Organic layer is separated and distilled, to the residue methanol is added and filtered and dried the solid to obtain 2-(4- dec-2-enyl phenyl)-4,6-dichlorotriazine. 4-dec-2-enyl phenyl magnesium iodide is prepared by the reaction of 4-iodo dec-2-enyl benzene with magnesium metal in the presence of iodine in 50% THF and 50% 2-MeTHF medium at 60-70°C under nitrogen atmosphere. After completion of the Grignard reagent (4- dec-2-enyl phenyl magnesium iodide), the mass is cooled to 40-45°C under nitrogen atmosphere and is used for coupling with cyanuric chloride. 2,4-bis(2,4-dihydroxyphenyl)-6-(4-dec-2-enyl phenyl)-1 ,3,5-triazine preparation process is the condensation of 2-(4- dec-2-enyl phenyl) -4,6-dichlorotriazine with resorcinol in the presence of methane sulfonic acid (MSA) in cyano benzene at 60-65°C. in work up reaction mass is diluted with water and filtered the solid. The wet solid of 2,4-bis(2,4-dihydroxyphenyl)-6-(4-dec-2-enyl phenyl)-1 ,3,5-triazine is used for alkylation, Bis-hexenyl oxyphenol dec-2-enyl phenyl triazine preparation process is the alkylation of bis(2,4-dihydroxyphenyl)-6-(4-dec-2-enyl phenyl)-1 ,3,5-triazine with iodohexene in the presence of potassium carbonate in dimethyl propionamide medium at 140°C for 8 to 10h and in work up, inorganic salts were removed by filtration. The clean filtrate is distilled and to the residue, a mixture of acetone and 2-butanol and filtered the solid at 0-5°C. The wet solid is purified with acetone to obtain Bis-hexenyl oxyphenol dec-2-enyl phenyl triazine.

[0606] Example 9

[0607] 2-(4-allyloxy phenyl)-4,6-dichlorotriazine preparation process is the condensation of 4-allyloxy phenyl magnesium chloride with cyanuric chloride in 2-Me-THF at 0-5°C in work up water and dilute HCI is added, and organic layer is separated. Organic layer is distilled, to the residue methanol is added and filtered the solid and dry the solid to get 2-(4-allyloxy phenyl)-4,6-dichlorotriazine. 4-allyloxy phenyl magnesium chloride is prepared by the reaction of 4-chloro allyloxy benzene with magnesium metal in the presence of iodine in 2-Me-THF medium at 60-70°C. After completion of 4-allyloxy phenyl magnesium chloride formation, the mass is cooled to 40-45°C and is used as it is for coupling with cyanuric chloride. 2,4-bis(2,4-dihydroxyphenyl)-6-(4-allyloxy phenyl)-1 ,3,5-triazine preparationprocess is the condensation of with resorcinol in the presence of aluminum chloride in 50% chlorobenzene and 50% cyanobenzene at 60-65°C in work up mass is diluted with water and chlorobenzene is distilled azeotropically. After distillation of solvent, product is isolated by filtration. The wet 2,4-bis(2,4-dihydroxyphenyl)-6-(4-allyloxy phenyl)-1 ,3,5-triazine is used for alkylation. Bis-octenyl oxyphenol allyloxy phenyl triazine preparation process is the alkylation of 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-allyloxy phenyl)-1 ,3,5-triazine with 2-Octenyl chloride in the presence of potassium bi carbonate in diethyl formamide medium at 140°C for 10h. In work up, the inorganic salts were removed by filtration. The filtrate is distilled. To the residue, acetone and 2-butanol is added and filtered the solid. Later it is purified with acetone to get pure Bis-octenyl oxyphenol allyloxy phenyl triazine.

[0608] Example 10

[0609] 2-(4-biphenyl)-4,6-dichlorotriazine preparation process is the condensation of 4-biphenyl magnesium bromide with cyanuric chloride in THF at 0-5°C in work up solvent is distilled completely and water and dilute HCI is added to residue and is extracted with methyl benzene. Distillation of organic solvent and isolated of solid with methanol obtain pure 2-(4-biphenyl)-4,6-dichlorotriazine. 4-biphenyl magnesium bromide is prepared by the reaction of 4-bromo biphenyl with magnesium metal in the presence of iodine in THF medium at 60-70°C. After complete formation of 4-biphenyl magnesium bromide, the mass is cooled to 40-45°C under nitrogen atmosphere and is used for coupling with cyanuric chloride. 2, 4-bis(2,4-dihydroxyphenyl)-6-(4-biphenyl)-1 ,3,5-triazine preparation process is the condensation of 2-(4-biphenyl)-4,6-dichlorotriazine with resorcinol in the presence of ferric chloride in methyl benzene at 60-65°C in work up water is added and distilled the solvent by azeotropic distillation, and the solid product is filtered. The wet solid of 2,4-bis-(2, 4-dihydroxyphenyl)-6-(4-biphenyl)-1 ,3,5-triazine is used for alkylation. Bis-hept-2-enyl oxyphenol biphenyl triazine preparation process is the alkylation of 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-biphenyl)-1 ,3,5-triazine with 2-heptenyl bromide in the presence of sodium phosphate in diethyl acetamide medium at 140°C for 10 h and in work up the inorganic salts were removed by filtration and the clean filtrate is distilled under vacuum from the residue the solid isolation with a mixture of acetone and 2-butanol and the wet solid is purified with acetone to obtain Bis-hept-2-enyl oxyphenol biphenyl triazine.

[0610] Example 11

[0611] 2-(4-phenyl oxy phenyl)-4,6-dichlorotriazine preparation process is the condensation of 4-phenyl oxy phenyl magnesium iodide with cyanuric chloride in 50% THF and 50% 2-Me-THF at 0-5°C. In work up dilute HCI and water is added. Organic layer is separated and distilled the residue, trituration with methanol to get pure 2-(4-phenyl oxy phenyl)-4,6-dichlorotriazine. 4-phenyl oxy phenyl magnesium iodide is prepared by the reaction of 4-iodo phenyl oxy benzene with magnesium metal in the presence of iodine in 50% THF and 50% 2-Me-THF medium at 60-70°C. After completion of the Grignard reagent (4-phenyl oxy phenyl magnesium iodide) formation, the mass is cooled to 40-45°C under nitrogen atmosphere and used for coupling with cyanuric chloride. 2,4-bis(2,4-dihydroxyphenyl)-6-(4-phenyl oxy phenyl)-1 ,3,5-triazine process is the condensation of 2-(4-phenyl oxy phenyl)-4,6-dichlorotriazine with resorcinol in the presence of methane sulfonic acid (MSA) in cyanobenzene at 60-65°C in work up water is added and filtered the product at 60-70°C. The wet solid of (2,4-bis(2,4-dihydroxyphenyl)-6-(4-phenyl oxy phenyl)-1 ,3,5-triazine) is used for alkylation. Bis-propyl oxyphenol phenyl oxy phenyl triazine preparation process is the alkylation of (2,4-bis(2,4-dihydroxyphenyl)-6-(4-phenyl oxy phenyl)-1 ,3,5-triazine) with propyl iodide in the presence of sodium carbonate in diethyl propionamide medium at 140°C and work up the inorganic salts are removed by filtration. The clean filtrate is distilled and from the residue product is isolated with a mixture of acetone and 2-butanol and is purified with acetone to get Bis-propyl oxyphenol phenyl oxyphenyl triazine.

Claims

CLAIMS1. A process for producing a dichloro phenyltriazine derivative of formula IV,comprising the following steps:a) providing a phenylmagnesium halogenide of formula (V),- Mg Hal(V),b) reacting cyanuric chloride with the phenylmagnesium halogenide of formula (V) in an oxolane solvent in an iron-free environment, the oxolane solvent being 2- Methyltetrahydrofuran (2-MeTHF); andc) obtaining a reaction mass comprising the dichloro phenyltriazene derivative;wherein R1 is selected from the group of■ linear alkyl with a chain length of C1 to C10, preferably C2 to C10;■ linear alkyl with a chain length of C2 to C10 with branches in alpha-(a) I beta- (p) I gamma-(y)-position to the phenyl group selected from the group of methyl, ethyl, propyl and butyl;■ linear alkoxyl with a chain length of C1 to C10, preferably C2 to C10;■ linear alkoxyl with a chain length of C2 to C10 with branches in alpha-(a) I beta-(p) I gamma-(y)-position to the oxygen selected from the group of methyl, ethyl, propyl and butyl;■ linear alkenyl with a chain length of C2 to C10;■ linear alkenyl with a chain length of C2 to C10 with branches in alpha-(a) I beta-(p) I gamma-(y)-position to the phenyl selected from the group of methyl, ethyl, propyl and butyl;■ linear alkenoxyl with a chain length from C2 to C10;■ linear alkenoxyl with a chain length of C2 to C10 with branches in alpha-(a) I beta-(p) I gamma-(y)-position to the oxygen selected from the group of methyl, ethyl, propyl and butyl;■ phenyl; and■ phenoxy; andwherein Hal is selected from the group of chlorine (Cl) and bromine (Br), preferably Br.

2. The process of claim 1 , wherein the reaction mass comprises a compound of formula VI in an amount of less than 1 %,(VI),wherein reside R1 is as defined in claim 1.

3. The process of claim 1 or 2, wherein the reaction mass comprises a compound of formula VII in an amount of less than 5%,(VII),wherein reside R1 is as defined in claim 1.

4. The process of any of claims 1 to 3, wherein the phenylmagnesium halogenide of formula V is produced by the following steps:a1) providing an Mg source, the Mg source being Mg swarfs or turnings characterized by one or more of the following:produced directly before use, or unpackaged from an oxygen-free and / or water-free container directly before use;total impurity content less than 0.1%, preferably in a range of 0.03 toiron impurity content less than 0.005 %, preferably in a range of 0.0001 and 0.005%;a2) providing a compound of formula II,(II), anda3) reacting the Mg source with the compound of formula II in the oxolane solvent.

5. The process of claim 4, wherein one or more of the following applies:a ratio of the compound of formula II and the Mg source is in a range of 7:1 to 5:1 by weight;the reaction of step a3) is carried out in the presence of iodine;the reaction of step a3) is carried out under nitrogen or oxygen-free atmosphere, the reaction of step a3) is carried out at a temperature in a range of 60 to 80°C, 6. The process of any of claims 1 to 5, wherein one or both of the following applies:the reaction of step b) is carried out at a temperature in a range of 0-40°C; the reaction of step b) is conducted in nitrogen or an oxygen-free atmosphere.

7. The process of any of claims 1 to 6, wherein the compound of formula II is 4- Bromoanisol.

8. A process for producing bis-ethylhexyloxyphenol methoxyphenyl triazine (BMT) of formula I’,(I’), comprising the following steps:(i) producing a reaction mass comprising the dichloro phenyltriazene derivative of formula IV by the process of any of claims 1 to 7, the dichloro phenyltriazene derivative being Dichloromethyloxyphenyltriazine (DICAT);(ii) reacting the dichloro phenyltriazene derivative from step (i) with resorcinol and a lewis acid in a benzene solvent,the lewis acid being selected from the group of AICI3, FeCI3, benzene sulfonic acid (BSA), para-toluene sulfonic acid (pTSA), trifluoromethane sulfonic acid (TF-MSA) and methanesulfonic acid (MSA),the benzene solvent being selected from group of chlorobenzene, methylbenzene, cyanobenzene and mixtures thereof;(iii) reacting the product obtained in step (ii) with an ethylhexyl halogenide in the presence of a salt in an amide solvent,the salt being selected from the group of Na2CO3, NaHCO3, K2CO3, KHCO3, Na3PO;(iv) recovering the compound of formula (I) or the composition comprising the same.

9. The process of claim 8, wherein step (iv) comprises one or more of isolation, purification, crystallisation, drying, milling and sieving.

10. Composition, preferably producible by the process of claim 8 or 9, comprisinga) at least 98% BMT of formula (I’);b) iron in an amount less than 2 mg / kg, preferably less than 1.5 mg / kg, more preferably less than 1.35 mg / kg; andside products, the side products beingc) dimethoxyphenyl triazine of formula Via in an amount less than 1%,"NI I(Via);d) dimethoxy biphenyl of formula (Vila) in an amount less than 5%, preferably less than 1.5 %,(Vila).

11. UV filter composition comprising the composition of claim 10 and further comprising side products being:■ < 0.05 % Bemotrizinol resorcinol analog with peak identity MM 515 and C30H33N3O5 and retention time (RT) 12.9 min according to the method description of LCMS analysis with additional UV detection of Bemotrizinol resorcinol analog;■ < 0.015 % Bemotrizinol triethylhexylether analog with peak identity MM 739 and C46H65N3O5 and retention time of 22.2 min according to the method description of LCMS analysis with additional UV detection of Bemotrizinol triethylhexylether analog.

12. The composition of claim 10 or the UV filter composition of claim 11, further comprising:one, two, three, four, five or more UV filter actives selected from the group of Phenylbenzimidazole Sulfonic Acid, Butyl Methoxydibenzoylmethane, Ethylhexyl Triazone, Ethylhexyl Salicylate, Disodium Phenyl Dibenzimidazole Tetrasulfonate, Diethylhexyl Butamido Triazone, Menthyl Anthranilate, Zinc Oxide, Zinc Oxide (nano), Diethylamino Hydroxy benzoyl Hexyl Benzoate, Benzophenone-3,Homosalate, Octocrylene, Ethylhexyl Methoxycinnamate, Isoamyl p-Methoxy- cinnamate, 4-Methylbenzylidene Camphor, Titanium Dioxide, Titanium Dioxide (nano), Terephthalylidene Dicamphor Sulfonic Acid, Methylene Bis-Benzotriazolyl Tetramethylbutylphenol, Tris-Biphenyl Triazine, Phenylene Bis-Diphenyltriazine, Methoxypropylamino Cyclohexenylidene Ethoxyethylcyanoacetate, Bis-(Diethyl- aminohydroxybenzoyl Benzoyl) Piperazine; Drometrizole Trisiloxane, Benzylidene Camphor Sulfonic Acid, Polysilicone-15, Ethylhexyl Dimethyl PABA; preferably UV filter actives selected from the group of Phenylbenzimidazole Sulfonic Acid, Butyl Methoxydibenzoylmethane, Ethylhexyl Triazone, Ethylhexyl Salicylate, Disodium Phenyl Dibenzimidazole Tetrasulfonate, Diethylhexyl Butamido Triazone, Zinc Oxide, Zinc Oxide (nano), Diethylamino Hydroxybenzoyl Hexyl Benzoate, Tris- Biphenyl Triazine, Phenylene Bis-Diphenyltriazine, Methylene Bis-Benzotriazolyl Tetramethylbutylphenol, Methoxypropylamino Cyclohexenylidene Ethoxyethylcyanoacetate, Bis-(Diethylaminohydroxybenzoyl Benzoyl) Piperazine, Terephthalylidene Dicamphor Sulfonic Acid, Octocrylene, Titanium Dioxide, Titanium Dioxide (nano).

13. Skin or hair care or sun protection composition, the composition being formulated for topical application on skin or hair, and comprising the composition of claim 10, or the UV filter composition of claim 11 or 12.

14. The process according of any of claims 1 to 9, wherein the oxolane solvent comprises 2-MeTHF in an amount of at least 85%, preferably at least 90%, more preferably at least 95%.

15. The process according of any of claims 1 to 9 and 14, wherein the oxolane solvent comprises 2-MeTHF in one of the following isomeric configurations:racemic with (S)-(+) I (R)-(-) ratio of 1 :1 ;(S)-(+)-stereoisomer;(R)-(-)-stereoisomer;a mixture of (S)-(+)-stereoisomer and (R)-(-)-stereoisomer with ratio of (S)-(+) to (R)- (-) selected from the group consisting of 98:2, 2:98, 95:5, 5:95, 90:10, 10:90, 85:15, 15:85 (v / v).

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