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) 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).

Description

Title of the invention: Method for preparing the 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine TECHNICAL FIELD OF THE INVENTION

[0001] The present invention relates to a process for preparing 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine using 2-methyltetrahydrofuran (MeTHF) as a solvent. STATE OF THE ART

[0002] 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine (CAS No.: 55514-22-2, trade name: Triasorb™), also known as bis-diphenyltriazine, corresponds to the following formula:

[0003] This is an organic solar filter with the particularity of absorbing and reflecting the harmful part of the solar spectrum, which includes UVB, short UVA, long UVA, and also high-energy blue light (Bacqueville et al. 20212). Its properties thus make it a particularly interesting solar filter for the field of photoprotection and the prevention of photoaging.

[0004] The term “sunscreen” refers to a substance capable of filtering solar radiation to protect a surface, typically the skin or hair, against the harmful effects of this radiation.

[0005] 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine is an insoluble filter, meaning that it is insoluble in the aqueous or oily phases used to prepare sunscreen compositions. It is therefore present in particulate form in sunscreen compositions, particularly in cosmetic sunscreen compositions.

[0006] Application WO2005 / 1211281 describes, in Example 4, a process for the synthesis of 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine by reacting benzile with terephthalamidrazone. 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 successive washing of the precipitate with ethanol, then diethyl ether, a diethyl ether wash being necessary to remove certain impurities.

[0007] 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.

[0008] 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.

[0009] In addition, with environmental issues becoming increasingly important, the use of a green solvent with the least impact on our environment is desired.

[0010] There is therefore a need to develop a new process for the synthesis of 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine which can be used on an industrial scale and which has the least impact on our environment. Summary of the invention

[0011] 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 benzil with terephthalamidrazone in a solvent consisting of 2-methyltetrahydrofuran to form a suspension of 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine in a reaction medium, then b) the separation of 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine from the reaction medium obtained in step a).

[0012] Indeed, among the different solvents tested for this same synthetic route, only 2-methyltetrahydrofuran enabled the synthesis of 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine, and also enabled the development of an improved process for obtaining 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine, in the sense that this complete process including the reaction and separation steps is efficient and rapid on an industrial scale.

[0013] 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 results in a short filtration time.

[0014] Furthermore, 2-methyltetrahydrofuran is a green solvent derived from renewable sources that can be recycled, thus limiting 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'-(l,4-phenylene)-bis[l,2,4]triazine obtained by the process according to the invention with this same solvent. Thus, the same 2-methyltetrahydrofuran solvent can advantageously be used for both the reaction and washing steps.

[0015] The process for obtaining 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine according to the invention is simpler, and more suitable for industrial implementation at optimized costs and conditions.

[0016] This improved process according to the invention is all the more efficient because 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 2 or lower 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.

[0017] Furthermore, 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine as prepared by the process according to the invention exhibits all the required properties of purity and filtering efficiency with respect to solar radiation. It can also be ground without any difficulty by any conventional liquid-phase grinding process, preferably in aqueous phase, and in the presence of a dispersant such as PPG-1-PEG-9 Lauryl Glycol Ether (Eumulgin® L, marketed by BASF) to give a D50 particle size between 150 and 200 nm. DETAILED DESCRIPTION OF THE INVENTION

[0018] 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'-(l,4-phenylene)-bis[l,2,4]triazine in a reaction medium, and step b): separation of 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine from the reaction medium obtained in step a).

[0019] Step a):

[0020] 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine is synthesized from two reagents: benzile and terephthalamidrazone.

[0021] Benzil, also called 1,2-diphenylethane-1,2-dione, is a diketone with the following formula:

[0022] Terephthalamidrazone, also called Dihydrazone a, has CAS number 19173-40-1 and the formula:

[0023]

[0024]

[0025]

[0026]

[0027]

[0028]

[0029]

[0030]

[0031] The reaction between these two reagents, which synthesizes 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylenc)-bis|L2,4]triazinc, is carried out in 2-methyltetrahydrofuran as the 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. Furthermore, it can be recovered and recycled after use, which is economically advantageous and reduces the environmental impact of its application. It is also a solvent with reduced toxicity: it is a class 3 solvent according to ICH guidelines, meaning a solvent with low potential toxicity to humans. In a particular embodiment, the molar ratio between benzile and terephthalamidrazone 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 In step a), the volume (in litres) of solvent used is 5 to 20 times greater, advantageously 5 to 15 times greater than the weight (in kilograms) of terephthalamidrazo 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 implemented at a pressure of 1 to 5 bars including atmospheric pressure, and preferably from 1 to 3 bars. In a particular embodiment, the reaction time of step a) ranges from 2h to 10h, preferably from 3h to 8h, even more preferably from 3h to 5h. Since 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine is not soluble in 2-methyltetrahydrofuran (MeTHF), it precipitates in the reaction medium. during its formation. Thus, it is obtained in the form of a suspension in the reaction medium.

[0032] The reaction medium will comprise, in addition to 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine and solvent (MeTHF), possibly one or more of the reagents (benzile and / or benzene-1,4-dicarbohydrazonamide) that would not have reacted and impurities that may form during the synthesis reaction.

[0033] Step b):

[0034] The 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine is then separated from the reaction medium obtained at the end of step a).

[0035] Since 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine is in the form of a solid suspension in the reaction medium, it can be separated from the reaction medium by any solid / liquid separation method such as, for example, filtration, preferably with a washer-dryer; or centrifugation; preferably by filtration, for example with a washer-dryer. The use of a washer-dryer is appropriate when the optional steps c) and d) (described below) are also carried out, as this allows steps b), c), and d) to be performed in the same apparatus.

[0036] In a particular embodiment, step b) of the process according to the invention is carried out for a period of 1h to 20h, preferably from 1h to 10h, even more preferably from 1h to 5h; and typically from 1h to 3h

[0037] Optional step c):

[0038] Step b) may be followed by an optional 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'-(l,4-phenylene)-bis[l,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 with a different solvent than the reaction solvent, such as a C4-Cl alcohol like, for example, ethanol or isopropanol. Thus, this or each of these washes may be carried out with the same or a different solvent, advantageously chosen from 2-methyltetrahydrofuran, C4-Cl alcohols (e.g., ethanol or isopropanol), and mixtures thereof. Preferably, this or each of these washes is carried out with a solvent comprising, preferably consisting of 2-methyltetrahydrofuran.

[0039] For the purposes of this invention, "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.

[0040] In a particular embodiment, at least one wash is performed with 2-methyltetrahydrofuran as the solvent. Preferably, one to five washes, typically one or Two washes are carried out with a solvent comprising, preferably, 2-methyltetrahydrofuran.

[0041] 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 solvent, which makes it possible to use one and the same solvent for the synthesis reaction and the washes.

[0042] Unlike ethanol, which was not sufficient on its own to purge impurities in the prior art process, the 2-methyltetrahydrofuran solvent used in the process according to the invention allows this.

[0043] Thus, in a preferred embodiment of the invention, the process for preparing 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,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).

[0044] Furthermore, the process for preparing 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine does not involve diethyl ether for carrying out steps a) and / or b) and / or c), in particular any one of steps a) and b) and c).

[0045] More particularly, the process for preparing 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,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 carrying out steps a) and / or b) and / or c), in particular any one of steps a) and b) and c).

[0046] In a preferred embodiment of the invention, during step c), the volume (in litres) 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).

[0047] In another preferred embodiment of the invention, the total volume (in litres) of solvent used in the whole 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).

[0048] Optional step d:

[0049] Step b) or step c) when present may be followed by an optional drying step d).

[0050] 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.

[0051] This drying step is classically carried out at a temperature of 40°C to 80°C, preferably from 50°C to 70°C, advantageously for a period of 1 hour to 10 hours, preferably from 1 hour to 5 hours.

[0052] Finally, the recommended or legally mandated value of residual solvent(s) concentration in the product obtained (for example, according to the ICH Guidelines the residual solvent concentration must be less than 5000ppm 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.

[0053] The present invention therefore also relates to the 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine that can be obtained by the process according to the invention, comprising in particular steps a), b), optionally c), and optionally d).

[0054] The present invention also relates to a cosmetic composition comprising 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine capable of being obtained 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.

[0055] Recycling:

[0056] 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).

[0057] This recycling is possible due to the thermal stability of the solvent during the reaction.

[0058] This benefit is all the more important since the process according to the invention can be implemented with this single solvent for both the synthesis reaction and the washing step(s).

[0059] Here too, its boiling point allows for its separation and recycling in an optimized way.

[0060] These different aspects make 2-methyltetrahydrofuran an economically advantageous solvent for industrial development, in particular using closed-loop recycling.

[0061] Optional step e:

[0062] Step b) or step c) or d) when present may be followed by an optional step d) of grinding.

[0063] In a preferred embodiment, the 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine obtained by the process according to the invention will be subjected to a subsequent 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'-(l,4-phenylene)-bis[l,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'-(l,4-phenylene)-bis[l,2,4]triazine) into particles using a grinding apparatus and in the presence of a grinding aid. Conventionally, wet grinding processes such as wet milling or wet mixing, well known to those skilled in the art, are used for this purpose. The grinding apparatus may 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, nonionic, or amphoteric surfactants, emulsifiers, dispersants, and combinations thereof. Examples of grinding aids include the dispersant PPG-1-PEG-9 Lauryl Glycol Ether (Eumulgin® L, marketed by BASF),

[0064] This aqueous dispersion advantageously comprises: - 45% to 55% water by weight, - 40% to 50% of 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine, - from 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.

[0065] In particular embodiments of the invention, the D50 size of the 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine particles contained in the 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, in particular from 120 nm to 250 nm, in particular from 120 nm to 200 nm, typically from 150 nm to 200 nm.

[0066] By "size D50" or "median size" is meant the size for which the cumulative particle size distribution function F(D) is equal to 50%. F(D) is defined according to the following relation:

[0067] D< F(D t ) = § f (D)dD 0

[0068] in which:

[0069] f(D) is the number size distribution of the particles, and

[0070] Di is a size class.

[0071] The value of the D50 size can be determined using a Mastersizer 3000 liquid-mode laser diffraction particle size analyzer.

[0072] 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'-(l,4-phenylene)-bis[l,2,4]triazine which can be obtained by the process according to the invention, including in particular steps a), b), optionally c), optionally d), and e).

[0073] 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'-(l,4-phenylene)-bis[l,2,4]triazine capable of being 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.

[0074] The dispersion is more particularly as defined above. Thus, the dispersion is a dispersion of 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine in a liquid, aqueous or oily phase, preferably aqueous, advantageously comprising from 20% to 50%, in particular from 40% to 50%, by weight, of 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,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'-(l,4-phenylene)-bis[l,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.

[0075] 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine is most particularly found in particulate form. The D50 size of the 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine particles 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, especially from 120 nm to 250 nm, particularly from 120 nm to 200 nm, typically from 150 nm to 200 nm. EXAMPLES

[0076] The present invention is illustrated by the following non-limiting examples. Example 1:

[0077] Various solvents have been tested with a view to replacing the ethanol used in application WO2005 / 121128 (see example 4) to synthesize 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazine.

[0078] 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine is obtained by condensation of two benzile moieties with terephthalamidrazone in one of the solvents shown below. Benzile is a commercially available substance, while terephthalamidrazone is 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 terephthalamidrazone (see diagram below). This synthesis is described in particular in Examples 2-3 of WO2005 / 121128. Hydrazin® monohydrate Etap® / TéFépbWtjrdhfe Benzene- 1,4-dicafbohydrazonamide

[0079] 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.

[0080] The synthesis of 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,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.

[0081] The results obtained are presented in the following table 1:

[0082] [Tables 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 (TA ME) No reactivity 2-Methyltetrahydrofuran Complete reaction and transportable medium

[0083]

[0084]

[0085]

[0086]

[0087]

[0088] Thus, among the different solvents tested, only 2-methyltetrahydrofuran proved effective in synthesizing 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine as a replacement for ethanol. Example 2: Method for preparing an industrial batch of 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine according to the invention The synthesis of 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine was carried out using 2-methyltetrahydrofuran as the solvent. This process comprises the following successive steps: • step a: reaction between benzile and terephthalamidrazone to give 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine; • step b: separation by filtration of 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine from the reaction medium; • step c: washing of 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine; • step d: drying of 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine. The operating conditions and the results obtained are presented in Table 2 below: [Tables 2] Operation s Conditions Step a: Reaction Reagents: 20 to 200 kg of terephthalamidrazone Benzyl / terephthalamidrazone molar ratio of 2 to 3 Solvent: 10 to 15 volumes of 2-methyltetrahydrofuran (L per kg of terephthalamidrazone used) Temperature: 80°C to 120°C Pressure: 1 to 3 bar Duration: 3 to 5 h Step b: Separation Filtration on a Hastelloy® stirred filter Duration: 1.5 h Step c: Washing 2 successive washes with 2-methyltetrahydrofuran Step d: Drying Duration: 6 to 13 hours Conclusion Total process time: 24 hours Total solvent volume: 15 to 20 volumes (L per kg of terephtha lamidrazone 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%

[0089] Bibliographic references: 1. WO2005 / 121128; 2. Bacqueville et al., Photochemical & Photobiological Sciences (2021) 20: 1475-1486.

Claims

Demands

1. A process for preparing 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,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'-(l,4-phenylene)-bis[l,2,4]triazine in a reaction medium, and then b) separating 5,6,5',6'-tetraphenyl-3,3'-(l,4-phenylene)-bis[l,2,4]triazine from the reaction medium obtained in step a).

2. A method according to claim 1, wherein the molar ratio between benzile and terephthalamidrazone 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 method 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 bars, preferably from 1 to 3 bars.

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

6. A process according to any one of claims 1 to 5, further comprising a step c) comprising one or more washes of the 5,6,5',6'-tetraphenyl-3,3'-(1,4-phenylene)-bis[1,2,4]triazin obtained in step b), each of these washes being carried out with an identical or different solvent, advantageously selected from 2-methyltetrahydrofuran, Cl- to C4 alcohols and mixtures thereof.

7. A method 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'-(l,4-phenylene)-bis[l,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) when present 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'-(l,4-phenylene)-bis[l,2,4]triazine obtained in step b) or in step c) or d) when present, in the presence of a grinding aid.