Process for preparing 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine

Abstract

The present invention relates to a process for preparing 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine comprising: a) reacting benzil with terephthalamidrazone in a solvent consisting of 2-methyltetrahydrofuran to form a suspension of 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine in a reaction medium, then b) separating the 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine from the reaction medium obtained in step a), then c) washing the 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine obtained in step b) at least once, characterized in that the implementation of washing step c) does not involve diethyl ether.

Description

[0001] DESCRIPTION TITLE: Process for preparing 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine TECHNICAL FIELD OF THE INVENTION The present invention relates to a process for preparing 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine using 2-methyltetrahydrofuran (MeTHF) as a solvent. PRIORITY OF THE TECHNOLOGY 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine (CAS No.: 55514-22-2, trade name: TriasorbTM), also called bis-diphenyltriazine, has the following formula: This is an organic sunscreen filter with the unique ability to absorb and reflect the harmful portion of the solar spectrum, which includes UVB, short-wave UVA, long-wave UVA, and high-energy blue light (Bacqueville et al. 20212). Its properties make it a particularly interesting sunscreen filter for photoprotection and the prevention of photoaging. The term "sunscreen filter" refers to a substance capable of filtering solar radiation to protect a surface, typically the skin or hair, from the harmful effects of this radiation. 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine is an insoluble filter, meaning it is insoluble in the aqueous or oily phases used to prepare sunscreen formulations. It is therefore present in particulate form in sunscreen formulations, particularly cosmetic sunscreens.The request WO2005 / 121128. 1Example 4 describes a process for the synthesis of 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine by reacting benzyl with laterephthalamidrazone. The conditions described in this prior art process are those of a laboratory synthesis. This synthesis is carried out in ethanol as the solvent and requires washing the precipitate successively with ethanol and then diethyl ether, with a diethyl ether wash being necessary to remove certain impurities. Ethanol is not a suitable solvent for industrial-scale synthesis, as the reaction time in ethanol is very long. Furthermore, the use of diethyl ether as a solvent is not recommended on an industrial scale, in addition to the fact that the implementation and management of two different solvents complicates the process and represents a significant obstacle to its industrial development.Diethyl ether has several major drawbacks, including its high flammability, which increases the risk of fire and explosion; its toxicity, which can affect health through inhalation, ingestion, or skin contact; and its volatility, which leads to solvent losses and occupational exposure. Furthermore, it is prone to the formation of explosive peroxides when stored, necessitating special precautions. Moreover, with environmental concerns becoming increasingly important, the use of a green solvent with minimal environmental impact is desirable. Therefore, there is a need to develop a new industrial-scale synthetic process for 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine that minimizes environmental impact.SUMMARY OF THE INVENTION The present invention thus relates to a process for preparing 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine comprising: a) the reaction of benzile with terephthalamidrazone in a solvent consisting of 2-methyltetrahydrofuran to form a suspension of 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine in a reaction medium, then b) the separation of 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine from the reaction medium obtained in step a).Preferably, the present invention relates to a process for preparing 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine comprising: a) reacting benzyl with terephthalamidrazone in a solvent consisting of 2-methyltetrahydrofuran to form a suspension of 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine in a reaction medium, then b) separating the 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine from the reaction medium obtained in step a), then c) one or more washings of the 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine obtained step b), characterized in that the implementation of the washing step c) does not involve diethyl ether.Indeed, among the various solvents tested for this same synthetic route, only 2-methyltetrahydrofuran enabled the synthesis of 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine, and furthermore, allowed the development of an improved process for obtaining 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine, in that this complete process, including the reaction and separation steps, is efficient and rapid on an industrial scale. Regarding the separation step of 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine, for example by filtration with or without washing, this step is particularly facilitated with the process according to the invention using 2-methyltetrahydrofuran. This efficiency translates into a short filtration time. In addition, 2-methyltetrahydrofuran is a green solvent from renewable sources that can be recycled, which limits the environmental impact of the process.This is all the more true since it is possible to wash the 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine obtained by the process according to the invention with this same solvent. Thus, the same solvent, 2-methyltetrahydrofuran, can be advantageously used for the reaction and washing steps. The process for obtaining 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine according to the invention is simpler and more suitable for industrial implementation with optimized costs and conditions. This improved process according to the invention is all the more efficient as it does not require the use of solvents subject to stringent regulations, such as those recognized as CMR (carcinogenic, mutagenic, or toxic to reproduction) or those of class less than or equal to class 2 according to the ICH Q3C (International Conference on Harmonisation) Guidelines.These ICH guidelines describe recommendations regarding toxicologically acceptable concentrations of residual solvents in pharmaceutical products for patient safety. Furthermore, 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine, as prepared by the process according to the invention, exhibits all the required properties of purity and solar radiation filtering efficiency. It can also be easily ground using any conventional liquid-phase grinding process, preferably aqueous, in the presence of a dispersant such as PPG-1-PEG-9 Lauryl Glycol Ether (Eumulgin® L, marketed by BASF) to obtain a D50 particle size between 150 and 200 nm.DETAILED DESCRIPTION OF THE INVENTION The process according to the invention thus comprises the following two steps: step a): reaction of benzile with terephthalamidrazone in a solvent consisting of 2-methyltetrahydrofuran to form a suspension of 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine in a reaction medium, and step b): separation of 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine from the reaction medium obtained in step a).Preferably, the process according to the invention comprises the following steps: step a): reaction of benzile with terephthalamidrazone in a solvent consisting of 2-methyltetrahydrofuran to form a suspension of 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine in a reaction medium; then step b): separation of the 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine from the reaction medium obtained in step a); then step c): one or more washings of the 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine obtained in step b), characterized in that the implementation of the washing step c) does not involve ether. diethyl. Step a): 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine is synthesized from two reactants: benzile and terephthalamidrazone. Benzile, also called 1,2-diphenylethane-1,2-dione, is a diketone with the formula ci-. dessous : Terephthalamidrazone, also called Dihydrazone a, has CAS number 19173-40-1 and the formula: The reaction between these two reagents to synthesize 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine is carried out in 2-methyltetrahydrofuran as a solvent. This is a green solvent derived from renewable sources. 2-Methyltetrahydrofuran is also chemically and thermally stable. Its boiling point of 80°C does not require very high reaction pressures. It can also be recovered and recycled after use, which is economically advantageous and reduces the environmental impact of its use. Furthermore, it is a solvent with low toxicity: it is a Class 3 solvent according to ICH guidelines, meaning it has a low potential for human toxicity.In a particular embodiment, the molar ratio between benzile and laterephthalamidrazone is greater than or equal to 2, preferably greater than 2, and preferably less than or equal to 5; and even more preferably less than or equal to 3. For example, in one embodiment, the quantity of terephthalamidrazone is between 10 kg and 300 kg, preferably between 20 and 200 kg, in step a). During step a), the volume (in liters) of solvent used is 5 to 20 times greater, advantageously 5 to 15 times greater than the weight (in kilograms) of terephthalamidrazone used in step a). The reaction temperature typically ranges from 80°C to 130°C, preferably from 90°C to 120°C. Step a) can be carried out at a pressure of 1 to 5 bar including atmospheric pressure, and preferably from 1 to 3 bar.In a particular embodiment, the reaction time of step a) ranges from 2 to 10 hours, preferably from 3 to 8 hours, and even more preferably from 3 to 5 hours. Since 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine is not soluble in 2-methyltetrahydrofuran (MeTHF), it precipitates in the reaction medium during its formation. Thus, it is obtained as a suspension in the reaction medium. The reaction medium will include, in addition to 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine and the solvent (MeTHF), possibly one or more of the reagents (benzile and / or benzene-1,4-dicarbohydrazonamide) that did not react and impurities that may form during the synthesis reaction. Step b): The 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine is then separated from the reaction medium obtained at the end of step a).Since 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine is present as a solid suspension in the reaction medium, it can be separated from the reaction medium by any solid / liquid separation method, such as filtration, preferably with a washer-dryer; or centrifugation, preferably with filtration, for example, using a washer-dryer. The use of a washer-dryer is appropriate when the optional steps c) and d) (described below) are also performed, as this allows steps b), c), and d) to be carried out in the same apparatus.In one particular embodiment, step b) of the process according to the invention is carried out for a duration of 1 to 20 hours, preferably from 1 to 10 hours, and even more preferably from 1 to 5 hours; and typically from 1 to 3 hours. Optional step c): Step b) may be followed by a step c) of one or more washes, preferably 1 to 5 washes, typically 1 or 2 washes, of 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine. This or each of these washes may be carried out with the same solvent as that of step a) (reaction solvent) or a different solvent from the reaction solvent, such as a C1 to C4 alcohol like, for example, ethanol or isopropanol. Thus, this or each of these washes can be carried out with an identical or different solvent, advantageously chosen from 2-methyltetrahydrofuran, C1 to C4 alcohols (e.g. ethanol or isopropanol), and mixtures thereof.Preferably, this or each of these washes is carried out with a solvent comprising, preferably, 2-methyltetrahydrofuran. For the purposes of this invention, "C1-C4 alcohol" means an alcohol R2OH whose R2 chain is a saturated hydrocarbon chain, linear or branched, comprising 1 to 4 carbon atoms. This may, in particular, be ethanol or isopropanol. In a particular embodiment, at least one wash is carried out with 2-methyltetrahydrofuran as the solvent. Preferably, one to five washes, typically one or two, are carried out with a solvent comprising, preferably, 2-methyltetrahydrofuran. In a particular embodiment, this or these washes are carried out with one and the same solvent, and advantageously this or these washes are carried out with 2-methyltetrahydrofuran as the solvent, which allows the use of one and the same solvent for the synthesis reaction and the washes.Unlike ethanol, which was insufficient on its own to remove impurities in the prior art process, the solvent 2-methyltetrahydrofuran used in the process according to the invention does so. Thus, in a preferred embodiment of the invention, the process for preparing 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine does not involve any solvent other than 2-methyltetrahydrofuran for carrying out steps a) and / or b) and / or c), in particular any one of steps a) and b) and c). Furthermore, the process for preparing 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine does not involve diethyl ether for the implementation of steps a) and / or b) and / or c), in particular any one of steps a) and b) and c); and more particularly for all of steps a) and b) and c).Thus, the process for preparing 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine does not include diethyl ether for carrying out steps a) and / or b) and / or c), in particular any one of steps a) and b) and c); and more particularly for all of steps a) and b) and c). By "does not include diethyl ether for carrying out" a step, it is understood in the context of the present invention to mean an amount of diethyl ether less than or equal to 1% by weight of the mixture considered, preferably less than or equal to 0.5% by weight of the mixture considered, preferably in an amount less than the detection threshold of ether by the usual analytical techniques (NMR, IR, Raman, MS, HPLC possibly coupled with MS, GC possibly coupled with MS, etc.).Preferably, the process for preparing 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine is free of diethyl ether for the implementation of steps a) and / or b) and / or c), in particular any one of steps a) and b) and c); and more particularly for all of steps a) and b) and c). The absence of ethyl ether can further be verified by checking for the absence of ethyl ether in the production chain of the various reagents used in the process according to the present invention. In particular, the process for preparing 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine does not involve any solvent recognized as CMR or any solvent of class less than or equal to class 2 according to the ICH Q3C Guidelines for the implementation of steps a) and / or b) and / or c), in particular any of steps a) and b) and c).In a preferred embodiment of the invention, during step c), the volume (in liters) of solvent used is 5 to 20 times greater, advantageously 5 to 15 times greater than the weight (in kilograms) of terephthalamidrazone used in step a). In another preferred embodiment of the invention, the total volume (in liters) of solvent used in the entire process (steps a) to c)) is 10 to 40 times greater, advantageously 10 to 30 times greater, even more advantageously 15 to 20 times greater than the weight (in kilograms) of terephthalamidrazone used in step a). Optional step d): Step b) and / or step c), as appropriate, may be followed by at least one optional drying step d). The relatively low boiling point of 2-methyltetrahydrofuran (below 100°C) compared to many of the solvents tested allows the drying step to be implemented in an optimized way in terms of both drying time and energy required.This drying step is conventionally carried out at a temperature of 40°C to 80°C, preferably 50°C to 70°C, advantageously for a duration of 1 to 10 hours, preferably 1 to 5 hours. Finally, the recommended or regulatory requirement for the concentration of residual solvent(s) in the product obtained (for example, according to ICH Guidelines the residual solvent concentration must be less than 5000 ppm for a class 3 solvent) requires optimized drying efficiency, which is further facilitated here by the use of 2-methyltetrahydrofuran as the sole reaction and washing solvent in the process according to the invention. The present invention therefore also relates to 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine which can be obtained by the process according to the invention, comprising in particular steps a), b), optionally c), and optionally d).The present invention also relates to a cosmetic composition comprising 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine obtainable by the process according to the invention, comprising in particular steps a), b), optionally c), and optionally d), and at least one cosmetically acceptable excipient. Recycling: The 2-methyltetrahydrofuran used in step a) and / or in step c), when present, can be recycled, i.e., it can be recovered and reused in a new step a). This recycling is possible due to the thermal stability of the solvent during the reaction. This benefit is all the more important since the process according to the invention can be carried out with this single solvent for the synthesis reaction and the washing step(s). Here too, its boiling point allows for its separation and recycling in an optimized manner.These different aspects make 2-methyltetrahydrofuran an economically advantageous solvent for industrial development, particularly when using closed-loop recycling. Optional step e): Step b) or step c) or d) when present may be followed by an optional step d) of grinding. In a preferred embodiment, the 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine obtained by the process according to the invention will be subjected to a further grinding step and will typically be in the form of a dispersion in a liquid, aqueous or oily phase, preferably aqueous, advantageously comprising from 20% to 50%, in particular from 40% to 50%, by weight of active material (organic filter = 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine) relative to the total weight of the dispersion.The grinding is advantageously carried out in the presence of a grinding aid, and more particularly in a liquid phase, aqueous or oily, preferably aqueous. Advantageously, the process for preparing such a dispersion consists of grinding the organic filter (5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine) into particles, using a grinding apparatus and in the presence of a grinding aid. Conventionally, wet grinding processes such as wet grinding or wet mixing, well known to those skilled in the art, are used for this purpose. The grinding apparatus can be, for example, a micro-bead mill, a vibrating mill, or a ball mill. Depending on the grinding process, the grinding aid is chosen from the group consisting of anionic, non-ionic or amphoteric surfactants, emulsifiers, dispersants, and their combinations.As a grinding aid, one example is the dispersant PPG-1-PEG-9 Lauryl Glycol Ether (Eumulgin® L, marketed by BASF). This aqueous dispersion advantageously comprises: - 45% to 55% by weight of water, - 40% to 50% of 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine, - 4% to 5%, in particular approximately 4.5%, of a grinding aid such as PPG-1-PEG-9 Lauryl Glycol Ether, the percentages being expressed by weight relative to the total weight of the aqueous dispersion. In particular embodiments of the invention, the size D50 of the 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine particles contained in aqueous dispersion is from 100 nm to 1000 nm, more particularly from 100 nm to 500 nm, even more particularly from 120 nm to 400 nm, especially from 120 nm to 250 nm, especially from 120 nm to 200 nm, typically from 150 nm to 200 nm.By "size D50" or "median size", we mean the size for which the cumulative function F(D) of particle size distribution is equal to 50%. F(D) is defined according to the following relation: in which: f(D) is the particle size distribution by number, and D iis a size class. The D50 size value can be determined using a Mastersizer 3000 liquid-based laser diffraction particle size analyzer. The present invention therefore also relates to a dispersion in a liquid, aqueous or oily phase, preferably aqueous, of 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine, which can be obtained by the process according to the invention, comprising in particular steps a), b), optionally c), optionally d), and e). The present invention also relates to a cosmetic composition comprising a dispersion in a liquid, aqueous or oily phase, preferably aqueous, of 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine, which can be obtained by the process according to the invention, comprising in particular steps a), b), optionally c), optionally d), and e), and at least one cosmetically acceptable excipient.The dispersion is more particularly as defined above. Thus, the dispersion is a dispersion of 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine in a liquid phase, aqueous or oily, preferably aqueous, advantageously comprising from 20% to 50%, in particular from 40% to 50%, by weight, of 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine relative to the total weight of the dispersion. Advantageously, the dispersion also contains a grinding aid advantageously selected from the group consisting of anionic, nonionic, or amphoteric surfactants, emulsifiers, dispersants, and combinations thereof. The grinding aid is more specifically the dispersant PPG-1-PEG-9 Lauryl Glycol Ether (Eumulgin® L, marketed by BASF). The aqueous dispersion advantageously comprises: - 45% to 55% by weight of water, - 40% to 50% of 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine, - 4% to 5%, in particular about 4.5% of a grinding aid such as PPG-1-PEG-9 Lauryl Glycol Ether, the % being expressed by weight relative to the total weight of the aqueous dispersion. 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine is found particularly in the form of particles. The D50 particle size of 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine contained in the aqueous dispersion is preferably from 100 nm to 1000 nm, more particularly from 100 nm to 500 nm, even more particularly from 120 nm to 400 nm, notably from 120 nm to 250 nm, especially from 120 nm to 200 nm, typically from 150 nm to 200 nm. EXAMPLES The present invention is illustrated by the following non-limiting examples. Example 1: Different solvents were tested with a view to replacing the ethanol used in application WO2005 / 121128 (see example 4) to synthesize the 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine.5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine is obtained by the condensation of two benzile moieties with terephthalamidrazone in one of the solvents shown below. Benzile is a commercially available substance, while terephthalamidrazone must be prepared in two steps from terephthalonitrile: first, the imidate is prepared by the addition of ethanol in the presence of HCl, and then the addition of hydrazine monohydrate leads to the laterephthalamidrazone (see scheme below). This synthesis is described in particular in Examples 2-3 of WO2005 / 121128. The quantities of reagents and solvents used are as follows: - 10-20 g of terephthalamidrazone, - Benzyl / terephthalamidrazone molar ratio of 2 to 5, - Solvent: 10-15 volumes. The synthesis of 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine is carried out at a temperature between 90°C and 120°C, at atmospheric pressure and for a reaction time of 1h to 5h depending on the solvents.The results obtained are presented in Table 1 below: [Table 1] Solvent Result Dihydrolevoglucosenone No reactivity 4-Methyltetrahydropyran Partial reaction Butan-2-ol Pasty reaction medium difficult to transport Pentan-1-ol Pasty reaction medium difficult to transport Isobutyl acetate Pasty reaction medium difficult to transport γ-Valerolactone Incomplete reaction Dioxolane Pasty reaction medium difficult to transport Isosorbide dimethyl ether Incomplete reaction Tert-amyl methyl ether No reactivity (TAME) 2-Methyltetrahydrofuran Complete reaction and transportable medium Thus, among the different solvents tested, only 2-methyltetrahydrofuran proved effective in synthesizing 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine as a replacement for ethanol.Example 2: Process for preparing an industrial batch of 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine according to the invention. The synthesis of 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine was carried out using 2-methyltetrahydrofuran as a solvent. This process comprises the following successive steps:^ step a: reaction between benzile and terephthalamidrazone to give 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine;^ step b: separation by filtration of 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine from the reaction medium;^ step c: washing of 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine;^ step d: drying of 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine.The operating conditions and the results obtained are presented in the following table 2: [Table 2] Operations Conditions Step a: Reaction Reagents: 20 to 200 kg of terephthalamidrazone Molar ratio benzile / terephthalamidrazone of 2 to 3. Solvant : 10 to 15 volumes of 2-methyltetrahydrofuran (L per kg of deterephthalamidrazone used) Temperature: 80°C to 120°C Pressure: 1 to 3 bars Duration: 3 to 5 h Step b: Separation Filtration on a Hastelloy® stirred filter Duration: 1h30 Step c: Washing 2 successive washes with 2-methyltetrahydrofuran Step d: Drying Duration: 6 to 13 h Conclusion Total process time: 24 h Total solvent volume: 15 to 20 volumes (L per kg of deterephthalamidrazone used) Quantity of 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine obtained: 50 to 500 kg Yield > 92% Purity > 95% References: 1. WO2005 / 121128 ;2. Bacqueville et al., Photochemical & Photobiological Sciences (2021) 20: 1475–1486.

Claims

CLAIMS 1. A process for preparing 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine comprising: a) reacting benzile with terephthalamidrazone in a solvent consisting of 2-methyltetrahydrofuran to form a suspension of 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine in a reaction medium, then b) separating the 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine from the reaction medium obtained in step a), then c) one or more washings of the 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine obtained in step b), ; characterized in that the implementation of the washing step c) does not involve diethyl ether.

2. Process according to claim 1, wherein the molar ratio between benzile and laterephthalamidrazone is greater than or equal to 2, and preferably less than or equal to 5.3.A process according to claim 1 or 2, wherein the volume of solvent used in step a) is 5 to 20 times greater, advantageously 5 to 15 times greater, than the weight of terephthalamidrazone used in step a), the volume being expressed in liters and the weight being expressed in kilograms.

4. A process according to any one of claims 1 to 3, wherein the reaction in step a) is carried out at a temperature from 80°C to 130°C, preferably from 90°C to 120°C, and at a pressure of 1 to 5 bar, preferably from 1 to 3 bar.

5. A process according to any one of claims 1 to 4, wherein the separation in step b) is carried out by filtration.

6. A method according to any one of claims 1 to 5, wherein each of the washes in step c) is carried out with an identical or different solvent, advantageously chosen from 2-methyltetrahydrofuran, C1 to C4 alcohols and mixtures thereof.7.A process according to claim 6, wherein each of these washes is carried out with 2-methyltetrahydrofuran.

8. A process according to any one of claims 1 to 7, further comprising a step d) comprising drying the 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine obtained in step b) or in step c) when present.

9. A process according to any one of claims 1 to 8, wherein the 2-methyltetrahydrofuran used in step a) and / or in step c) is recycled.

10. A process according to any one of claims 1 to 9, further comprising a step (e) comprising grinding the 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine obtained in step b) or in step c) or d) when present, in the presence of a grinding aid.

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