Process for isolating 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine (DIOPAT)

Abstract

The present invention relates to an improved process for isolating 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine (DIOPAT) from a DIOPAT-containing aqueous mixture N, which comprises the steps of concentrating the aqueous mixture N to obtain a DIOPAT-containing aqueous suspension S1 having a specific solids content, evaporating the solvent from the aqueous suspension S1, and drying the DIOPAT to obtain a solids content of more than 90% by weight, based on the total weight of DIOPAT.

Description

[Technical field]

[0001] The present invention provides an improved process for isolating 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine (DIOPAT) from a DIOPAT-containing aqueous mixture N, which comprises the steps of concentrating the aqueous mixture N to obtain a DIOPAT-containing aqueous suspension S1 having a specific solids content, evaporating the solvent from the aqueous suspension S1, and drying the DIOPAT to obtain a solids content of more than 90 wt. %, based on the total weight of DIOPAT and the DIOPAT obtained by the improved process having a specific bulk density. [Background technology]

[0002] 2,4-Bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine (DIOPAT) is a starting material for the production of the UV absorber Tinosorb® S (also known as 2,2-[6-(4-methoxyphenyl)-1,3,5-triazine-2,4-diyl]bis{5-[(2-ethylhexyl)oxy]phenol}, anisotriazine, bis-ethylhexyloxyphenol methoxyphenyl triazine, or bemotridinol, CAS number 187393-00-6), which has the following chemical formula: [ka]

[0003] Tinosorb® S is a broadband UV absorber, absorbing both UVB and UVA rays, and is therefore an important ingredient for sunscreen compositions and cosmetic applications.

[0004] One possible synthetic route to DIOPAT is carried out via two steps starting from 4-bromoanisole and cyanuric chloride under Grignard conditions to form the intermediate DICAT. In the second synthetic step, DICA reacts with resorcinol in a Friedel-Crafts reaction to form DIOPAT. Below, a synthetic route to DIOPAT starting from 4-bromoanisole and cyanuric chloride is shown, where the parameters a) Mg, THF, b) cyanuric chloride, THF, and c) resorcinol, toluene / benzonitrile, AlCl3 are typically applied. [ka]

[0005] To complete the synthesis of Tinosorb® S, a third step is typically carried out: alkylation of DIOPAT with isooctyl chloride. Below, the reaction to Tinosorb® S is shown, where the parameters a) isooctyl chloride, base, DMF are typically applied. [ka]

[0006] Associated with the preparation of DIOPAT is the workup procedure, and isolating DIOPAT, which can be difficult.

[0007] Typically, the reaction mixture containing DIOPAT is quenched with a pre-charged sodium hydroxide solution. The product DIOPAT and aluminum salts (Al salts) from the Friedel-Crafts reaction are then dissolved in alkaline aqueous sodium hydroxide solution. The organic reaction solvent (e.g. a mixture of toluene and benzonitrile) is separated by phase separation. Residual organic solvents can be removed to ensure an organic solvent-free aqueous phase. DIOPAT is then precipitated from the alkaline DIOPAT / Al salt solution by acidifying the mixture. When a low pH is established (pH<1), the Al salts still dissolve in the aqueous phase, but DIOPAT precipitates as a solid.

[0008] However, standard filtration processes such as the use of filter presses to separate the precipitated DIOPAT from the Al salt solution have drawbacks. In particular, the filtration process is a manual, time-consuming and open process, which is economically unattractive and poses safety issues on a technical scale. Furthermore, DIOPAT is obtained together with an undesirable organic impurity, 2,4-dihydroxybenzophenone (2,4-DHBP), which is a by-product of the manufacture of DIOPAT. The undesirable by-product 2,4-DHBP impurity in DIOPAT, which is used in the final reaction step to Tinosorb® S, increases the consumption of isooctyl chloride, an expensive reactant, and leads to undesirable by-products, which in turn increase the production costs.

[0009] It is difficult to improve the separation of Al salts from DIOPAT. The low solubility of DIOPAT in organic solvents with a complete miscibility gap between the aqueous and organic phases makes separation of Al salts from DIOPAT by phase separation not feasible. On the other hand, due to the corrosive nature of acidic AlCl3 / DIOPAT suspensions, most filtration devices in which metallic materials are in contact with these suspensions are not suitable. However, like the organic by-products obtained in the Friedel-Crafts reaction with AlCl3, the Al salts are unfavorable for the subsequent reaction to the final Tinosorb® S and need to be separated from DIOPAT.

[0010] WO2020089323 and WO202016366 provide separation techniques based on ultrafiltration. The resulting suspension can be dried by spray drying, which is energy consuming. Summary of the Invention [Problem to be solved by the invention]

[0011] It is therefore an object of the present invention to provide an energy efficient process for isolating DIOPAT.

[0012] It is a further object of the present invention to provide an improved process for isolating DIOPAT from the DIOPAT / Al salt solution obtained after quenching the reaction mixture of the Friedel-Crafts reaction to produce DIOPAT and removing the organic solvent.

[0013] It is a further object of the present invention to provide a process for isolating DIOPAT which avoids the manual and time-consuming open filtration process.

[0014] Another object of the present invention is to provide an improved process for isolating DIOPAT, in which not only the aluminum salts but also the organic by-products are simultaneously separated from DIOPAT.

[0015] Another object of the present invention is to provide an improved process for isolating DIOPAT, which improves the bulk density of DIOPAT. [Means for solving the problem]

[0016] Surprisingly, at least one of these objectives is a) concentrating the aqueous mixture N to obtain a 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine-containing aqueous suspension S1 having a solid content of 3 to 30% by weight based on the total weight of the aqueous suspension S1; b) evaporating the solvent from the aqueous suspension S1 by means of an agitation contact dryer; c) drying the 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine to obtain a solids content of greater than 90 wt. %, based on the total weight of the 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine.

[0017] Preferred embodiments of the invention can be found in the claims, the description and the examples. It is to be understood that the above-mentioned features of the subject matter of the invention and those further illustrated below are preferred not only in each given combination but also in other combinations without departing from the scope of the invention.

[0018] Before describing exemplary embodiments of the invention in detail, definitions that are important for understanding the invention are presented. [Brief description of the drawings]

[0019] [Figure 1] FIG. 1 shows a schematic diagram of microfiltration. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0020] As used in this specification and the appended claims, the singular forms "a" and "an" also include the respective plural forms, unless the context clearly dictates otherwise. In the context of the present invention, the term "about" or "approximately" (approximately) indicates a range of precision that a person skilled in the art can understand to further ensure the technical effect of the feature in question. This term typically represents a deviation of ±20%, preferably ±15%, more preferably ±10%, even more preferably ±5%, in particular ±2% from the indicated numerical value. The term "comprising" should be understood to be non-limiting. For the purposes of the present invention, the term "consisting of" is considered to be a preferred embodiment of the term "comprising".

[0021] As used herein, the term "solids content" of a sample refers to the solids in said sample. The solids content SC in the retentate (mainly DIOPAT) was calculated as the difference between the evaporation residue in the retentate (also called "dry mass") minus the evaporation residue in the permeate. The evaporation residue was measured by an infrared drying balance (Mettler Toledo HX204, 110°C, constant mass for 140 seconds).

[0022] As used herein, the term "aqueous alkaline mixture M" refers to a mixture comprising components (i), (ii) and (iii) as defined herein, which is typically obtained after quenching the Friedel-Crafts reaction mixture to prepare DIOPAT, i.e., component (i), with aqueous sodium hydroxide solution and removing the organic phase. The pH of the aqueous alkaline mixture M is 10 or higher, preferably ranging from 10 to 15, more preferably from 12 to 14, in particular from 12 to 13.5. The amount of Al salt is typically in the range of 1 to 20% by weight, preferably from 1 to 10% by weight, based on the amount of the total weight of the aqueous alkaline mixture M, and the amount of 2,4-DHBPDIOPAT is typically in the range of 0.5 to 5% by weight, preferably from 0.5 to 2% by weight, based on the total weight of the aqueous alkaline mixture M. Meanwhile, the amount of DIOPAT is typically in the range of 6 to 20% by weight, preferably from 7 to 14% by weight, based on the total weight of the aqueous alkaline mixture M.

[0023] As used herein, "2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine" (DIOPAT) is the compound of interest in the process of the present invention, since, as explained above, it is a precursor for preparing Tinosorb® S and 2,4-dihydroxybenzophenone is a by-product of its preparation by one of the possible synthetic routes. As used herein, the term "aluminum salts" (Al salts) refers to aluminum salts including aluminum trichloride and / or aluminum hydroxide, as well as sodium aluminum oxide (NaAlO2) or mixtures thereof. These aluminum salts are obtained in the preparation of DIOPAT, since aluminum trichloride is required for the Friedel-Crafts reaction.

[0024] It should be understood that the aqueous alkaline mixture M may contain further components in addition to sodium hydroxide, such as sodium chloride, as a result of aluminum trichloride reacting with sodium hydroxide during the quench. Additionally, sodium aluminum oxide (NaAlO2) may be formed during the quench and thus may be present in the aqueous alkaline mixture M. Furthermore, residual amounts of the starting DICAT and resorcinol may be present if the conversion to DIOPAT is incomplete or if excess DICAT or resorcinol is used.

[0025] As used herein, the term "acidified mixture M" refers to a mixture containing components (i), (ii), and (iii) as defined herein, obtained from the aqueous alkaline mixture M after acidification. In addition, the acidified mixture M contains a certain amount of salt, preferably sodium chloride, obtained from the neutralization reaction. The preferred amount of salt obtained from the neutralization reaction ranges from 5% to 15% by weight, based on the total weight of the acidified mixture M. Furthermore, instead of a base such as sodium hydroxide, an acid, preferably hydrogen chloride, is present. The pH of the acidified mixture M is preferably less than 1.

[0026] As used herein, the term "acidification" refers to the addition of an acid. Preferred acids include strong inorganic acids such as sulfuric acid or hydrochloric acid. Preferably, the "acidification" in step ia) of the process is carried out with hydrochloric acid, in particular with aqueous hydrogen chloride. The preferred concentration of the hydrogen chloride solution is in the range of 20-37%, preferably in the range of 36-37%. As a result of the acidification step ia), sodium chloride may be formed by reaction of sodium hydroxide with hydrogen chloride.

[0027] As used herein, the term "pH<1" refers to a pH less than 1.

[0028] After separation step ii.a) of the process by nanofiltration, DIOPAT is obtained in the form of an aqueous alkaline solution S as retentate. In this context, the term "aqueous solution S" refers to the solution obtained in step ii.a) which contains DIOPAT. When obtained in step ii.a), the aqueous solution S typically has a pH value of 7 or more or 14 or less, preferably between 7 and 14, more preferably between 8 and 14, in particular between 9 and 13.5, and is therefore called "aqueous alkaline solution S". It should be understood that the aqueous alkaline solution S may contain not only DIOPAT, but also residual amounts of Al salts and 2,4-DHBP, as well as possibly other impurities as mentioned above. However, the residual amount of aluminum is typically less than 1 wt.-%, preferably less than 0.5 wt.-% or even less than 0.2 wt.-%, based on the total weight of the aqueous alkaline solution S, the residual amount of 2,4-DHBP is typically less than 2 wt.-%, preferably less than 0.8 wt.-% or even less than 0.7 wt.-%, based on the total weight of the aqueous alkaline solution S, while the amount of DIOPAT is typically at least 4 wt.-%, preferably at least 5 wt.-%, or at least 6 wt.-%, or at least 7 wt.-%, or at least 8 wt.-% of the aqueous alkaline solution S. In step ii.b) of the process, the pH of the aqueous solution S is then adjusted to a pH of 9.5 or less in order to precipitate DIOPAT. As used herein, "adjusting the pH to pH 9.5 or less" is performed with an acid. Preferred acids include strong inorganic acids such as sulfuric acid or hydrochloric acid. Preferably, "adjusting the pH to pH 9.5 or less" in step ii.b) of the process is performed with hydrochloric acid, in particular with aqueous hydrogen chloride. The preferred concentration of the hydrogen chloride solution is in the range of 20-37%, preferably in the range of 36-37%. Preferably, the pH is adjusted to a value below 8, preferably in the range of 6-8. As a result of the pH adjustment step ii.b), further sodium chloride may be formed by reaction of sodium hydroxide with hydrogen chloride. Therefore, after step ii.b), the aqueous solution S preferably contains a further amount of sodium chloride.

[0029] As used herein, the term "precipitate" refers to the solid formation of a compound.

[0030] As used herein, the term "diafiltration" (DF) is a subtype of cross-flow filtration and refers to a process in which a suspension containing precipitated compounds is separated from dissolved components that can permeate the membrane in terms of their size. The suspension that does not pass through the membrane is called the "retentate" and the solution containing dissolved components that pass through the membrane is called the "permeate". During diafiltration, the suspension is preferably continuously pumped from a feed vessel to the membrane and from behind the membrane to a feed vessel. Diafiltration can be performed as a continuous process, whereby further solvent is continuously added to the retentate and the permeate is continuously removed. This washes the precipitated compounds in the retentate. Preferably, the diafiltration step ic) comprises washing with water having a wash factor of 3 to 6, preferably 4 to 5, more preferably 4.5, where the term "wash factor" refers to the amount of water, also known as the "diafiltration factor" and also called the diafiltration solvent, relative to the suspension used in step ic). In this context, WO2020016366 discloses a suitable process.

[0031] As used herein, the expression "pH increases from less than 1 up to 3" in relation to step ic) of the process outlined below means that the pH may increase during the diafiltration step due to removal of HCl or other acids by the further solvent, in this case preferably water. The amount of further solvent is selected accordingly. For example, a washing factor of 4.5 results in a pH in the range of 2 to 3, preferably 2.3 to 2.8. An acidic pH value makes it possible to avoid dissolution of precipitated DIOPAT and thus a reduction in the amount of isolated DIOPAT. Of course, it should be understood that the pH does not necessarily increase to the above values. If a small amount of diafiltration solvent is used, the increase in pH may not be very large. Moreover, since the further solvent is added in a continuous process over time, the pH value increases only slowly even if the amount of diafiltration solvent increases.

[0032] As used herein, in connection with step ic) of the process of the present invention, the expression "the temperature remains in the range of 80°C to 95°C" means that the temperature of the mixture subjected to the diafiltration step, in particular the temperature of the retentate, is maintained at a temperature of 80°C to 95°C, for example by using a heating device or by adding preheated wash water. It is important to keep the temperature in this high range in order to keep the 2,4-dihydroxybenzophenone in solution and to enable this by-product to be further removed by the diafiltration step. It should be understood that when step ic) of the process is carried out, the temperature can vary within the range of 80°C to 95°C. Preferably, the temperature at the start of the diafiltration of step ic) is in the range of 85°C to 95°C, and then the temperature is reduced over time to the range of 80°C to 90°C, for example due to dilution with further solvent brought at a temperature in the range of 80°C to 90°C. Thus, if the diafiltration step is carried out under continuous addition of further solvent, the temperature can be in the range of 80°C to 90°C.

[0033] As used herein, the term "concentration factor" refers to the ratio of the starting volume of the suspension containing the precipitated compound and dissolved components to the final volume of the suspension containing the precipitated compound (retentate) after the dissolved components and portions of the solvent (permeate) have been removed during the diafiltration process. It should be understood that the concentration factor of additional solvent that may be continuously added to the retentate does not affect the concentration factor, since the same amount of additional solvent that is continuously added to the retentate is continuously removed from the system by removing the permeate.

[0034] As used herein, "nanofiltration" is carried out using a nanofiltration membrane with a pore size of 2 nm or less. Such nanofiltration membranes are also referred to in the art as having a standard NaCl retention of 70%. Since nanofiltration is carried out using the alkaline mixture M according to the present invention, the nanofiltration membrane is preferably a polymeric nanofiltration membrane, in particular a polyethersulfone membrane filter, for example available from Nitto Denko, which is stable in strong alkaline solutions even at high temperatures.

[0035] In the nanofiltration step ii.a), DIOPAT is obtained in the retentate of the nanofiltration, taking into account its higher molecular size and high anionic charge, since it is retained from the membrane. In the filtration step ii.c), DIOPAT is obtained in the retentate of the filtration, taking into account its precipitated state, since it is retained from the membrane. As used herein, the term "retentate" refers to a solution or suspension containing components that do not pass through the membrane, while the term "permeate" refers to a solution containing components that have passed through the membrane and are permeable to the membrane, i.e., that pass through the membrane. In this context, WO2020089323 discloses a suitable process.

[0036] As used herein, the term "suspension" refers to a heterogeneous mixture that includes a solvent and a precipitate. In the diafiltration process, the precipitate particles must be larger than the pore size of the membrane.

[0037] As used herein, the term "lysate" or "solution" refers to a homogeneous mixture that includes a solvent and dissolved components, e.g., ions of a salt. In a diafiltration process, the dissolved components must be small enough to pass through a membrane.

[0038] In step b) of the process of the invention, the solvent is evaporated from the aqueous suspension S1 by means of an agitated contact dryer. The term "solvent" in this context encompasses any type of solvent present in the aqueous suspension S1, in particular also water.

[0039] As used herein, the terms "microfiltration" and "ultrafiltration" both refer to a process in which a suspension containing precipitated compounds is separated from dissolved components that can permeate the membrane, taking into account their size. Typically, the pore size of the membrane used for microfiltration and / or ultrafiltration is in the range of about 10 nm to 50 μm, preferably 20 to 3000 nm, in particular 30 to 2000 nm. Further preferred pore sizes may be in the range of 100 nm to 50 μm, preferably 500 nm to 35 μm, in particular 1 to 30 μm. Further preferred pore sizes may be in the range of 10 to 200 nm, preferably 20 to 150 nm, in particular 30 to 80 nm.

[0040] Preferred embodiments of the process of the present invention are described below.

[0041] In a preferred embodiment of the present invention, steps a) to c) are carried out by different means, ie, by different devices.

[0042] As already indicated above, the present invention relates to a process for isolating 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine (DIOPAT) from a DIOPAT-containing aqueous mixture N. Preferably, the DIOPAT-containing aqueous mixture N has a pH of 6 to 14, preferably 7 to 13, more preferably 8 to 12, particularly preferably 9 to 11.

[0043] As mentioned above, DIOPAT can be formed via the Friedel-Crafts reaction of DICAT with resorcinol and subsequent quenching with pre-charged sodium hydroxide solution. Subsequent acidification as outlined above generally results in an aqueous Al-salt-containing phase, but DIOPAT precipitates as a solid, which can be filtered and neutralized to the desired pH. Thus, it may be an option to provide aqueous mixture N via the aforementioned route.

[0044] Alternatively, the DIOPAT-containing aqueous mixture N can be brought about via the aforementioned filtration, for example steps i) / ii), which are explained further below. In this connection ultrafiltration and nanofiltration can be specified.

[0045] In this context, the DIOPAT-containing aqueous mixture N is (i) 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine, (ii) 2,4-dihydroxybenzophenone, (iii) an aluminum salt; and a process for isolating 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine (DIOPAT) from the aqueous alkaline mixture M comprising the aluminum salt, In this case, the process is ia) precipitating 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine by acidifying mixture M to a pH < 1; ib) heating the acidified mixture M to a temperature in the range of 80° C. to 95° C.; ic) separating the precipitated 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine from the dissolved 2,4-dihydroxybenzophenone and dissolved aluminum salts using a ceramic membrane by diafiltration with water, whereby the pH is increased from less than 1 up to 3 and the temperature remains in the range of 80° C. to 95° C.; In this case, as disclosed in WO2020016366, the separation step ic) results in the precipitated 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine in the form of an aqueous suspension in the retentate and the dissolved 2,4-dihydroxybenzophenone and the dissolved aluminum salts in the form of an aqueous solution in the permeate, the process preferably comprising a neutralization step id) in which the aqueous suspension of the retentate obtained in step ic) is neutralized to obtain a pH of 5 to 11, preferably 6 to 10, more preferably 6 to 8, in particular about 7. The aqueous suspension of the retentate can also be adjusted to a pH of 6 to 14, preferably 7 to 13, more preferably 8 to 12, in particular 9 to 11.

[0046] Furthermore, the DIOPAT-containing aqueous mixture N has a pH of 10 or more, (i) 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine, (ii) 2,4-dihydroxybenzophenone, (iii) an aluminum salt; and a process for isolating 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine (DIOPAT) from the aqueous alkaline mixture M comprising the aluminum salt, In this case, the process is ii.a) separation of 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine from the aluminum salts and 2,4-dihydroxybenzophenone by nanofiltration of the alkaline mixture M, the latter being obtained in the form of an aqueous alkaline solution S as retentate; ii.b) precipitating 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine by adjusting the pH of the aqueous solution S to a value below 9.5; ii.c) separating the precipitated 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine from the aqueous solution S by filtration, whereby 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine is obtained in the form of an aqueous suspension SP as a retentate, In this case, the nanofiltration step ii.a) is carried out at a pressure of 10-40 bar and at a temperature in the range of 20-60° C., as disclosed in WO2020089323. Preferably, the process results in a DIOPAT-containing aqueous mixture N having a pH of 6-14, preferably 7-13, more preferably 8-12, in particular 9-11.

[0047] Preferably, the aqueous mixture N from step a) has a solids content of 0 to less than 10% by weight, preferably 1 to 8% by weight, in particular 1 to 6% by weight, based on the total weight of the aqueous mixture N. It is particularly preferred that said aqueous mixture N from step a) is obtained by a filtration step as described above, preferably by an ultrafiltration or nanofiltration step as described above. In a particular embodiment, said aqueous mixture N from step a) is obtained by a filtration step i) as described above. In another particular embodiment, said aqueous mixture N from step a) is obtained by a nanofiltration step ii) as described above.

[0048] In a preferred embodiment, the aqueous suspension S1 has a solids content of 4 to 28% by weight, preferably 5 to 26% by weight, more preferably 6 to 25% by weight, in particular >6 to 20% by weight or >6 to 17% by weight, based on the total weight of the aqueous suspension S1. In this context, the solids content of the aqueous suspension S1 preferably comprises 90 to 99.9% by weight, more preferably 95 to 99.7% by weight, in particular 97 to 99.5% by weight of DIOPAT, based on the total weight of the solids.

[0049] Preferably, when comparing the solids content (wt %) of the aqueous mixture N with the solids content (wt %) of the aqueous suspension S1, the concentration in step a) increases the solids content by 1.2 to 5 times, more preferably 1.5 to 4.5 times, even more preferably 1.8 to 4.0 times, and in particular 2.0 to 3.5 times.

[0050] In a preferred embodiment, the concentration in step a) is carried out by filtration, preferably by dynamic cross-flow filtration and / or microfiltration.

[0051] In another preferred embodiment, the concentration in step a) is performed by dynamic cross-flow filtration, preferably by microfiltration, in which case the aqueous suspension S1 is the retentate and preferably the output flow in step a) is controlled by the solids concentration, the density, the viscosity and / or the ratio of permeate to retentate.

[0052] In a preferred embodiment, the aqueous mixture N is concentrated in step a) by dynamic cross-flow filtration, preferably by microfiltration, in which case the membrane has a pore size of 0.01 to 50 μm, preferably 0.01 to 5.0 μm, more preferably 0.1 to 1.5 μm. It is particularly preferred that the membrane has a pore size of 0.01 to 4.0 μm, preferably 0.05 to 2.0 μm, more preferably 0.1 to 0.5 μm.

[0053] In a preferred embodiment, the aqueous mixture N is concentrated in step a) by dynamic cross-flow filtration, preferably by microfiltration, involving a membrane, in which case the membrane is preferably selected from the group consisting of polymeric membranes made from polyvinylidene fluoride (PVDF), polysulfone (PSU), polyethersulfone (PES), polyphenylenesulfone (PPSU), polytetrafluoroethylene (PTFE), regenerated cellulose (RC), polyethylene (PE), polypropylene (PP) and mixtures thereof, ceramic materials, preferably aluminum oxide, and metal sieves, preferably made from stainless steel, and it is preferred that the membrane material is a polymeric membrane made from polyvinylidene fluoride (PVDF), polyethersulfone (PES) or polytetrafluoroethylene (PTFE), in particular polyvinylidene fluoride (PVDF).

[0054] Preferably, the membrane has a thermal stability in the range of 40-300° C., more preferably 50-200° C., even more preferably 60-150° C., and especially 80-120° C. In this context, the thermal stability of the polymer membrane is preferably in the range of 40-150° C., more preferably 50-130° C., even more preferably 65-110° C., and especially 80-100° C.

[0055] Preferably, the transmembrane pressure (TMP, determined as the difference between the retentate pressure and the permeate pressure) in step a) is in the range of 0.2 to 5 bar, more preferably in the range of 0.3 to 3 bar, even more preferably in the range of 0.4 to 2 bar, in particular in the range of 0.5 bar to 1 bar.

[0056] The average surface speed is preferably in the range of from 1 to 20 m / s, more preferably from 2 to 16 m / s, especially from 3 to 10 m / s.

[0057] The concentration in step a) is preferably carried out by a single filtration step or by a series of successive filtration steps. In a preferred embodiment, the concentration in step a) is carried out in 1 to 50 steps, more preferably in 8 to 30 steps, even more preferably in 9 to 21 steps.

[0058] In another preferred embodiment, the concentration in step a) is carried out by means of an agitated contact dryer, preferably a thin-film evaporator. Any thin-film evaporator known in the art can be used. Preferably, the average wall temperature in step b) is between 70 and 250°C, preferably between 90 and 180°C, in particular between 100 and 160°C.

[0059] It should be understood that if the concentration in step a) is carried out via an agitated contact dryer, the aqueous suspension S1 obtained is transferred to a further agitated contact dryer to precede the evaporation in step b), in which case these contact dryers are preferably connected in series. The further contact dryers may be of the same or different type.

[0060] In a preferred embodiment, the evaporation in step b) gives a DIOPAT-containing aqueous suspension S2 having a solids content of 10 to 90% by weight, preferably 20 to 85% by weight, more preferably 30 to 85% by weight and in particular 40 to 80% by weight, based on the total weight of the aqueous suspension S2. Particularly preferred, the evaporation in step b) gives a DIOPAT-containing aqueous suspension S2 having a solids content of 20 to 90% by weight, preferably 40 to 85% by weight, more preferably 60 to 85% by weight and in particular 65 to 80% by weight, based on the total weight of the aqueous suspension S2.

[0061] When comparing the solid content (wt %) of the aqueous suspension S1 with the solid content (wt %) of the aqueous suspension S2, the evaporation in step b) preferably increases the solid content by 1.5 to 20.0 times, more preferably by 2.0 to 15.0 times, even more preferably by 2.5 to 10.0 times, and particularly preferably by 3.0 to 5.5 times.

[0062] Preferably, the average wall temperature in step b) is between 70 and 250°C, preferably between 90 and 180°C, in particular between 100 and 160°C.

[0063] In a preferred embodiment, the agitated contact dryer of step b) is a thin film evaporator. Any thin film evaporator known in the art can be used.

[0064] Preferably, the average heat transfer coefficient in step b) is between 100 and 1000 W / m 2 *K, more preferably 200 to 800 W / m 2 *K, especially 400~700W / m 2 *K range.

[0065] Preferably, step b) is carried out under atmospheric conditions.

[0066] If a thin film evaporator is used in step b), the rotation is preferably in the range of 200-1000 rpm, more preferably 300-900 rpm, even more preferably 400-800 rpm, in particular 500-700 rpm.

[0067] Preferably, the DIOPAT in the DIOPAT-containing suspension S2 in step b) has a particle size of 0.5 to 20 mm, more preferably 0.8 to 15 mm, in particular 1 to 10 mm.

[0068] In a preferred embodiment, the DIOPAT of step c) is dried by means of an agitated contact dryer, more preferably a slow rotating linear dryer.

[0069] Preferably, the DIOPAT in step c) is dried by means of a disc dryer, more preferably the jacket is heated but the disc is not heated.

[0070] Preferably, the temperature in step c) is from 120 to 200°C, more preferably from 130 to 180°C, especially from 140 to 170°C.

[0071] Preferably, the 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine is obtained with a solids content of more than 93% by weight, more preferably more than 95% by weight, especially more than 97% by weight, based on the total weight of the 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine.

[0072] In a preferred embodiment, the process is a continuous process, ie the equipment for steps a) to c) is connected in series.

[0073] In this regard, the exhaust gas line preferably includes a filter to avoid potential dust introduction.

[0074] In a preferred embodiment, the total heat transfer of steps b) and c) is in the range of 300 to 1600 kW, preferably 400 to 1300 kW, in particular 450 to 800 kW.

[0075] Preferably, the process of the invention results in a DIOPAT having a bulk density, preferably determined according to DIN ISO 697 / EN ISO 60, in particular DIN ISO 697, more particularly DIN ISO 697:1984, of more than 0.4 g / mL, more preferably more than 0.5 g / mL, even more preferably more than 0.6 g / mL, in particular more than 0.7 g / mL. The process of the invention results in a DIOPAT having a bulk density of 0.4 to 1.2 g / mL, more preferably 0.6 to 1.1 g / mL, even more preferably more than 0.7 to 1.0 g / mL, in particular more than 0.8 to 0.9 g / mL.

[0076] In a second aspect, the present invention relates to 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine (DIOPAT) having a bulk density of 0.40 to 1.20 g / mL as determined by DIN ISO 697, in particular DIN ISO 697: 1984. Preferably, the bulk density of 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine as determined by DIN ISO 697, in particular DIN ISO 697: 1984, is 0.50 to 1.10, more preferably 0.6 to 1.05 g / mL, even more preferably >0.7 to 1.0 g / mL, in particular >0.8 to 0.9 g / mL. The 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine (DIOPAT) of the second aspect of the invention is obtainable by the process according to the invention. EXAMPLES

[0077] Example 1: Microfiltration at 91°C A neutralized DIOPAT-containing aqueous mixture having a solids content of about 5.9 wt. % was prepared according to Example UF1 of WO 2020016366. The neutralized suspension was further treated as follows.

[0078] [Table 1]

[0079] Fresh feed was fed into the feed drum B1 and pumped by pump P1 level controlled in the feed vessel B2 (see Figure 1). The feed vessel B2 was pressurized with pressurized air to provide a constant transmembrane pressure (TMP) in the Dynotest filter F1. To ensure a clear discharge of the retentate (also called concentrate) even at low retentate fluxes, a peristaltic discharge system was used consisting of a pinch valve X1, a buffer of pressurized air B3 and clocked valves H1, H2 and H3. The vessels for the discharged concentrate B5, the generated permeate B4 and the feed B1 were weighed continuously. The content of B2 was recorded by the level in B2 and by a calibration curve.

[0080] The equipment was operated in continuous operation mode. The feedstock was neutralized Diopat Wet with 12 wt.% of the evaporation residue. The feedstock was generated from the press cake of a filter press by mixing with water, homogenizing and neutralizing with NaOH.

[0081] The material was diluted with deionized water in drum B1 to a residue of 3.1 wt.%. Dry mass (DM) is the total (soluble and insoluble) dry matter in the sample measured by infrared drying balance (Mettler Toledo HX204, 110° C., constant mass for 140 s).

[0082] First, the feed vessel B2 was filled with the diluted Diopat suspension, stirred and thermostated at 91° C. B2 was pressurized to 1 bar. The rotor of the Dynotest filter F1 was started with an output frequency of the VFD drive of 35 Hz. The average surface speed was 5.7 m / s.

[0083] As soon as the permeate produced was collected in drum B4, the peristaltic discharge system was switched on and the concentrate was sent to drum B5. Using a control loop, the pinch valve was periodically actuated after a given waiting time. By varying the waiting time, a constant concentrate mass flow rate could be established. To obtain a constant concentration factor, the waiting time was controlled by the permeate to retentate ratio, the permeate mass flow rate and the concentrate mass flow rate (P / R). The P / R ratio was set to 10. The device was operated for 2 hours. The retentate mass flow rate was 0.27 kg / h. The permeate mass flow rate was 2.58 kg / h. Retentate and permeate samples were taken and analyzed for evaporation residue as described above. The solids content SC (mainly DIOPAT) in the retentate was calculated as the difference between the dry mass in the retentate minus the dry mass in the permeate. The evaporation residue of the permeate was 0.5 wt. %. The evaporation residue of the retentate was 25.0 wt. %. The solids content of the retentate (mainly DIOPAT) was therefore 24.5 wt %.

[0084] Example 2: Microfiltration at 46°C The apparatus was operated as described in Example 1. The feed was diluted in drum B1 with deionized water to a evaporation residue of 1.1 wt. %.

[0085] The temperature in vessel B2 was 46° C. The P / R ratio was set to 14. The apparatus was run for 1 hour. The mass flow rate of the retentate was 0.31 kg / h. The mass flow rate of the permeate was 4.31 kg / h. The evaporation residue of the permeate was 0.2% by weight. The evaporation residue of the retentate was 12.1% by weight. The solids content of the retentate (mainly DIOPAT) was therefore 11.9% by weight.

[0086] Example 3: Drying A DIOPAT-containing suspension having a solids content of 11.2% by weight was mixed with 0.025 ml of water under the conditions shown in Table 1. 2The DIOPAT-containing suspension is obtained according to Example 1b of EP 0 775 698 B1 and is then hydrolyzed under alkaline conditions, phase separated and subsequently subjected to acid precipitation. The DIOPAT obtained can then be suspended in the respective amount of water.

[0087] [Table 2]

[0088] As can be seen from Table 1 above, when aiming for higher feed rates, it is unlikely to achieve a residual moisture content below 3 wt.%.

[0089] A DIOPAT-containing suspension with a solids content of 12.0% by weight, filtered according to Example UF1 of WO 202016366, was filtered through a 0.025 m 2 The suspension was subjected to a thin-film evaporator with a heat exchange area of ​​10 ...

[0090] [Table 3]

[0091] As can be seen from Table 2 above, when aiming for higher feed rates it is even less possible to obtain a residual water content below 3 wt.-% for DIOPAT-containing suspensions with reduced Al-salt content.

[0092] A second dryer was connected in series.

[0093] A DIOPAT-containing suspension with a solids content of 11.2% by weight, obtainable according to Example 1b of EP 0 775 698 B1 (the product obtained in Example 1b was suspended in the respective amount of water) was stirred at 0.025 ml under the conditions shown in Table 3. 2The mixture was subjected to a thin-film evaporator having a heat exchange area of ​​1000 mm.

[0094] [Table 4]

[0095] In the next example, a linear dryer was added. A combined run of 17 hours in total was established with the parameters shown in Table 4. Residual moisture was 0.1-0.6 wt% over the combined run.

[0096] [Table 5]

[0097] After the thin film evaporator, DIOPAT particles with a size of 1-8 mm were obtained. After the linear dryer, the particle size of DIOPAT was about 1 mm.

[0098] The bulk density was determined in accordance with DIN ISO 697.

[0099] The bulk density of DIOPAT by thin film drying and linear drying is significantly higher compared to the commercial (spray dried) sample (about 0.38 g / cm3). After the thin film dryer the bulk density of the wet DIOPAT is about 0.7 g / cm3, while the bulk density of the dried powder from the linear dryer reaches more than 0.8 g / m3. The broad particle size distribution and the relatively large particles in the new drying route allow for much better particle alignment compared to spray drying, resulting in more than double the bulk density. The spray dried DIOPAT powder is small enough (d90 at about 120 μm) that intraparticle cohesion forces come into play, typically preventing a perfect alignment of the bulk powder. More details can be taken from Table 5.

[0100] [Table 6]

[0101] Example 4: Mass and Energy Balance The effective heat exchange area of ​​the pilot-scale thin-film dryer is 1.5 m 2 At a wall temperature of 155° C., 70 kg / h of Diopat feed with a solids concentration of about 12 wt % could be processed (compare Example 3). Thin film dryers are scaled up depending on the heat exchange area. Thus, using adapted heat exchange areas, the process outlined above can be scaled up as required to provide an energy-saving Diopat separation.

Claims

1. 1. A process for isolating 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine (DIOPAT) from a 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine-containing aqueous mixture N, comprising: a) concentrating the aqueous mixture N to obtain the 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine-containing aqueous suspension S1 having a solid content of 3 to 30 wt % based on the total weight of the 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine-containing aqueous suspension S1; b) evaporating the solvent from the aqueous suspension S1 by means of an agitation contact dryer; c) drying the 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine to obtain a solids content of greater than 90 wt. % based on the total weight of the 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine; wherein said solvent includes any type of solvent present in said aqueous suspension S1, including water.

2. 2. The process according to claim 1, wherein the aqueous suspension S1 has a solids content of 4 to 28 wt.-%, preferably 5 to 26 wt.-%, more preferably 6 to 25 wt.-%, in particular more than 6 to 20 wt.-%, or more than 6 to 17 wt.-%, based on the total weight of the aqueous suspension S1.

3. The process according to claim 1, wherein the aqueous mixture N has a pH of 6 to 14, preferably 7 to 13, more preferably 8 to 12, in particular 9 to 11.

4. 2. The process of claim 1, wherein the concentration in step a) is carried out by filtration.

5. 2. The process according to claim 1, wherein the concentration in step a) is carried out by dynamic cross-flow filtration, said aqueous suspension S1 being the retentate, and wherein preferably the discharge flow in step a) is controlled by the solids concentration, density, viscosity and / or the ratio of permeate to retentate.

6. said aqueous mixture N is concentrated in step a) by dynamic cross-flow filtration involving a membrane, said membrane having a pore size of 0.01 to 50 μm, preferably 0.01 to 5.0 μm, more preferably 0.1 to 1.5 μm; and / or 2. The process according to claim 1, wherein the membrane material is preferably selected from the group consisting of polymeric membranes made from polyvinylidene fluoride (PVDF), polysulfone (PSU), polyethersulfone (PES), polyphenylenesulfone (PPSU), polytetrafluoroethylene (PTFE), regenerated cellulose (RC), polyethylene (PE), polypropylene (PP), and mixtures thereof, ceramic materials, preferably aluminum oxide, and metal sieves, preferably metal sieves made from stainless steel, and preferably the membrane material is a polymeric membrane made from polyvinylidene fluoride (PVDF).

7. 2. The process according to claim 1, wherein the concentration in step a) is carried out by means of an agitated contact dryer, preferably a thin film evaporator.

8. 10. The process of claim 1, wherein the agitated contact dryer in step b) is a thin film evaporator.

9. 2. The process according to claim 1, wherein the evaporation in step b) gives a 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine-containing aqueous suspension S2 having a solids content of 10 to 90% by weight, preferably 20 to 85% by weight, more preferably 30 to 85% by weight, and in particular 40 to 80% by weight, based on the total weight of the 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine-containing aqueous suspension S2.

10. 2. The process according to claim 1, wherein the average wall temperature in step b) is from 70 to 250°C, preferably from 90 to 180°C, in particular from 100 to 160°C.

11. 2. The process of claim 1, wherein the 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine in step c) is dried by an agitated contact dryer, more preferably a low speed rotary linear dryer.

12. 2. The process of claim 1, wherein the 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine in step c) is dried by a disk dryer, preferably with a heated jacket but not a heated disk.

13. 2. The process according to claim 1, wherein the temperature in step c) is from 120 to 200°C, preferably from 130 to 180°C, in particular from 140 to 170°C.

14. The process of claim 1 , wherein the process is a continuous process.

15. 2. The process according to claim 1, wherein the aqueous mixture N from step a) has a solids content of 0 to less than 10 wt.-%, preferably 1 to 8 wt.-%, in particular 1 to 6 wt.-%, based on the total weight of the aqueous mixture N, and / or is obtained by the filtration step, preferably the ultrafiltration step or the nanofiltration step.

16. 2,4-bis-(2,4-dihydroxyphenyl)-6-(4-methoxyphenyl)-1,3,5-triazine (DIOPAT) obtainable by the process of any one of claims 1 to 15, having a bulk density of 0.40 to 1.20 g / mL determined by DIN ISO 697:1984.

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