MXPA99004545A - Symmetrical triazine derivatives - Google Patents

Abstract

A description is given of symmetrical triazine derivatives of formula (1), wherein R 1 and R 2 are each independently of the other hydrogen;C 1-C 12alkyl, C 1-C 12alkoxy;and R 3 is C 1-C 12alkyl;or C 1-C 12alkoxy. The easily accessible triazine derivatives are suitable for protecting ultraviolet-sensitive materials, in particular skin and hair of humans and animals, from the harmful effects of UV radiation.

Description

RAL TRIACINE SYMMETRICAL DERIVATIVES The present invention relates to symmetrical derivatives of triazine, with the preparation of those compounds as well as their use to protect organic materials from the dangerous effects of UV radiation. O-hydroxyphenyltriazines (HPT) alkylated at the O atom containing at least one o-hydroxyl group or at least two alkoxyphenyl substituents are known from EP-A-0 743, 309, as UV cosmetic absorbers having good spectproperties and good properties of technical application. However, the preparation of such triazine derivatives, which are derivatives of the Asymmetric basic structure, requires multi-step synthesis processes. In the above formula, Ra and Rb are a reactive radical, in particular a phenyl radical which is mono- or polysubstituted by hydroxyl groups. The symmetrical triazine compounds that can be prepared from the symmetric basic structure they are easily accessible in simple batch processes. Such basic triazine structures can be prepared, for example, by trimerising the corresponding benzonitrile compounds or, starting from cyanuric chloride, by Grignard reaction or Friedel-Crafts alkylation.The subsequent etherification of the free OH groups makes it possible to prepare the derivatives of Desired Triazine in a Two Step Reaction Accordingly, this invention relates to the symmetrical triazine derivatives of the formula wherein Ri and R2 are each independently hydrogen; C? -C? 2 alkyl; or C? -C? 2 alkoxy; and R3 is C? -C? 2 alkyl; or C? -C? 2 alkoxy.

C 1 -C 12 alkoxy or C 1 -C 12 alkoxy are straight or branched chain alkyl radicals, typically methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, amyl, isoamyl or tert -amyl, heptyl, octyl, isooctyl, nonyl, decyl, undecyl or dodecyl, or methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy, decyloxy, undecyloxy or dodecyloxy. Particularly preferred compounds are those of formula (1), in which R3 is C1-C12 alkoxy, in particular C5- '12 alkoxy, and Ri and R2 have the meaning given in the formula (1) - Very particularly preferred compounds are those that conform to the formula in which R4 and R5 are each independently hydrogen; C1-C12 alkyl; s C1-C12 alkoxy; And R6 is 1-C12 alkyl; or C1-C12 alkoxy. Important compounds are, in particular, those of formula (2), in which R 4 is hydrogen; and R5 and R6 are C5-C2 alkoxy; or those compounds of formula (2), wherein R 4 and R 5 are C 1 -C 12 alkyl; and R6 is hydrogen. Very particularly preferred compounds are those of formula wherein R7 is C5-C12 alkoxy; and R8 is hydrogen; or C1-C12 alkyl- The triazine derivatives of this invention can be used as single compounds or as mixtures of different unique compounds. The novel symmetrical triazine derivatives of formula (1) can, in particular, also be used as mixtures with triazine compounds of formula In formula (4), Rio is hydrogen; C6-C2alkyl; or alkenyl of C2-C6; and Rn is C? -C? 2 alkoxy. C2-C6 alkenyl is, for example, allyl, methallyl, isopropenyl, 2-butenyl, 3-butenyl, isobutenyl, n-penta-2,4-dienyl or 3-methyl-but-2-enyl. The mixtures of triazine compounds of formula (1) and formula (4) are another subject matter of this invention. The novel triazine derivatives of formula (1) can be prepared in different ways. In a Grignard reaction, for example, one mole of chloride is reacted cyanuric with 3 mol of the corresponding phenylmagnesium bromide compound which, depending on the meaning of Rx, R2 and R3 of formula (1), may contain an alkyl radical and / or one or more free hydroxyl groups. The processes for the preparation of this intermediate are known and described inter alia in EP-A-0, 557, 559. This intermediate can also be obtained by alkylation of Friedel-Crafts of cyanuric chloride with the corresponding phenyl compounds which, depending on the meaning of Ri, R2 and R3 in the formula (1), can contain an alkyl radical and / or one or more free hydroxyl groups, in the presence of a Lewis acid, preferably aluminum chloride. According to A. Ninagawa, M. Kawazoe, H. Matsuada, Ma rsmol. Chem. 180, (1979), 2123, this intermediate can also be obtained by cyclotrimerization of a benzonitrile compound containing an alkyl radical and / or one or more of a hydroxy group, depending on the meaning of Ri, R2 and R3 in the formula (1) . The final products corresponding to formula (1) can be obtained in a second reaction step by etherifying the hydroxyl group of the intermediates obtained in the first reaction step by alkylation according to customary methods.

A further subject matter of this invention relates to processes for the preparation of novel triazine derivatives. The symmetrical triazine derivatives of the invention of formula (1) or mixtures of those compounds with triazine compounds of formula (4) as well as the compounds of formula in which Ár is a radical of formula Ri is hydrogen, hydroxy; C? -C? 2 alkyl; or C1-C12 alkoxy R2 is hydroxy; C1-C12 alkoxy; or benzyloxy; R3 is hydroxy; C1-C12 alkyl; or C1-C12 alkoxy; and R4 is hydrogen; or C? -C? 2 alkoxy; or Ri and R2 / together with the phenyl radical, are a five-membered heterocyclic ring which is condensed with benzene, preferably a radical of formula (5a) , are particularly suitable as UV filters, that is, to protect organic materials sensitive to ultraviolet light, in particular the skin of humans and animals, against the dangerous effects of UV radiation. Illustrative examples of the compounds of formula (5) are Accordingly, these compounds are suitable as photostabilizers in cosmetic, pharmaceutical and veterinary preparations. They can be obtained in dissolved form or, if they are only poorly soluble or insoluble, they can be incorporated into the preparations in micronized form having an average particle size in the range of 0. 02 to 2, preferably from 0.05 to 1.5 and, more preferably, from 0.01 to 1.0 μm. Accordingly, another object of this invention is to provide a cosmetic preparation for the skin or hair, which comprises at least one compound of formula (1) or (5) as well as carriers or auxiliaries which are cosmetically compatible with the skin and the hair, or with a cosmetic formulation for the skin or hair, which comprises a mixture of a) at least one or more of a compound of formula (1) or (5), and b) a compound of formula (4) together with carriers or auxiliaries which are cosmetically compatible with the skin and hair. In addition to the novel UV absorbers, the cosmetic formulations may also contain one or more of an additional UV protector of the following classes of substances: 1. p-aminobenzoic acid derivatives, typically 2-ethylhexyl 4-dimethylaminobenzoate; 2. salicylic acid derivatives, typically 2-ethylhexyl salicylate; 3. benzophenone derivatives, typically, 2-hydroxy-4-methoxybenzophenone and its 5-sulfonic acid derivative; 4. dibenzoylmethane derivatives, typically, 1- (4-tert-butylphenyl) -3- (4-methoxyphenyl) propan-1,3-dione; 5. diphenylacrylates, typically 2-ethylhexyl-2-cyano-3, 3-diphenylacrylate and 3- (benzo-furanyl) -2-cyanoacrylate; 6. 3-imidazol-4-yl-acrylic acid and 3-imidazol-4-yl-acrylate; 7. benzofuran derivatives, preferably derivatives of 2- (p-aminophenyl) benzofuran, described in EP-A-582,189, US-A-5, 338, 539, US-A-5, 518, 713 and in EP-A-613,893; 8. polymeric UV absorbers, such as the benzylidenemalonate derivatives described, inter alia, in EPA-709,080; 9. Cinnamic acid derivatives, typically 2-ethylhexyl 4-methoxycinnamate or cinnamic acid derivatives described, inter alia, in US-A-5, 601, 811 and WO 97100851; 10. Camfor derivatives, typically, 3- (4'-ethyl) benzylidenbornan-2-one, 3-benzylidene-2-one-nane, N- [2 (and 4) -2-oxiboorn-3-ylidenmethyl polymer ) benzyl] acrylamide, methyl sulfate of 3- (4'-trimethylammonium) benzylidenbornan-2-one, 3,3'- (1,4-phenylenedimetin) -bis (7,7-dimethyl-2-oxo acid) -bicyclo- [2.2.1] heptan-1-methanesulfonic acid) and the salts thereof, 3- (4'-sulfo) benzylidenbornan-2-one and the salts thereof; 11. trianilino-s-triazine derivatives, typically 2, 4, 6-trianilin- (p-carbo-2'-ethyl-1'-oxy) -1, 3, 5-triazines as well as the UV absorbers described in US Pat. -A-5,332,568, EP-A-517, 104, EP-A-507, 691, WO 93/1 7002 and EP-A-570,838; 12. 2-hydroxyphenylbenzotriazole derivatives; 13. 2-phenylbenzimidazole-5-sulfonic acid and the salts thereof; 14. Menthyl-o-aminobenzoate; 15. Ti02 (coated differently), ZnO and mica. The UV absorbers described in * Sunscreen ", > Eds. N.J. Lowe, N.A. Shaat, Marcel Dek-ker, Inc., New York and Basel or Cosmetics & Toiletries (107), 50 et seq. (1992), can also be used as additional UV protectants in the formulations of the invention. The cosmetic formulations may also be used in conjunction with known antioxidants, such as vitamin E, carotenoids or HALS compounds. The novel cosmetic formulations usually comprise from 0.1 to 25, preferably from 0.5 to 10,% by weight, based on the total weight of the formulation, of a UV absorber of formula (1) or (5) or of a mixture of UV absorber of formula (1) and formula (4) and a cosmetically compatible auxiliary.

The cosmetic formulations can be prepared by physically mixing the UV absorbers with the auxiliaries by conventional methods, such as simply stirring the individual components together. The cosmetic formulations of this invention can be formulated as water-in-oil or oil-in-water emulsions, as an oil-in-alcohol lotion, as a vesicular dispersion of an ionic or non-ionic amphiphilic liquid, such as gel, solid stick or aerosol formulation. As a water-in-oil or oil-in-water emulsion, the cosmetically compatible auxiliary preferably comprises 5 to 50% of an oil phase, 5 to 20% of an emulsifier and 30 to 90% of water. The oil phase may contain any oil suitable for cosmetic formulations, for example one or more hydrocarbon oils, wax, natural oil, silicone oil, fatty acid ester or fatty alcohol. Preferred mono or polyols are ethanol, isopropanol, propylene glycol, hexylene glycol, glycerol and sorbitol. The cosmetic hair formulations may be present - in the form of a shampoo, lotion, gel or emulsion for rinsing before or after shampooing, before or after drying or removal of dye, before or after a permanent or casting process, in the form of a lotion, foam or gel for fixing or treating the hair, - in the form of a lotion or gel for brushing or curling the hair, - in the form of a hair spray, in the form of a composition for permanent or straightening the hair, to dye or remove dye. It is possible to use, for example, the following hair cosmetic formulations: a) spontaneously emulsify standard formulations, consisting of the UV absorbent, PEG-6, Cio oxoalcohol and sorbitan schiolate, which are charged with water and any quaternary ammonium compound, such as minkamidopropyl dimethyl-2-hydroxyethyl ammonium chloride 4% or Quatemium 80; a2) spontaneously emulsifying a standard formulation, consisting of the UV absorber, tributyl citrate and sorbitan monooleate PEG-20, which are charged with water and any quaternary ammonium compound, such as minkamidopropyl dimethyl-2-hydroxyethyl ammonium chloride at 4% or Quatemium 80; b) quaternary mixed solutions of the UV absorber in butyl triglycol and tributyl citrate; c) dispersions of microfluidized UV absorbers obtained by known methods (precipitation of solutions or mixture of solutions, grinding) having an average diameter of 0.05-1.0 μm in APG (for example Plantaren), and a compound quaternary (for example minkamidopropyl dimethyl-2-hydroxyethyl ammonium chloride) in an aqueous formulation; d) mixtures or solutions of the UV absorber with n-alkylpyrrolidone. Cosmetic formulations for the skin or hair may also have other components, such as emollients, emulsion stabilizers, skin moisturizers, tan promoters, thickeners, such as xanthan, moisture retention agents, such as glycerol, preservatives, fragrances and dyes. Novel cosmetic formulations for skin or hair are distinguished by excellent protection of human skin and hair against the dangerous effects of sunlight. The following non-limiting Examples illustrate the invention in more detail. The percentages are by weight.

Example 1; Preparation of 2,4,6-tris (4-2-ethyl-hexyloxyphenyl) - (1,3,5) -triazine The basic structure of formula (101a) is prepared by cyclotrimerizing p-hydroxy-benzonitrile according to Ninagawa, M. Kawazoe, H. Matxoda, Makromol, chem. 180 (1979), 2123. Sp dissolved 5.36 g of the compound of formula (101a) in 50 ml of dimethylformamide (DMF) and charged with 6.53 g of finely powdered potassium carbonate at 100-105 ° C. This mixture is stirred for 30 minutes and then 8.23 g of 3- (chloromethyl) -ethane, dissolved in 10 ml of DMF, are added dropwise, for another 30 minutes at 100-105 ° C. The temperature rises slowly to 135 ° C for 6 hours. After cooling to 100 ° C, 50 ml of toluene are added and the precipitated salts are removed by filtration. The filtrate is concentrated to dryness by evaporation and the residue is extracted with 50 ml of toluene and 100 ml of water, acidified and extracted by stirring. The dried organic phase is concentrated by evaporation. The crude product (c.7g) is purified by column chromatography (silica gel, cyclohexane / toluene 7: 3). Yield: 4.8 g of colorless oil (46% of theory).

Example 2: Preparation of 2,4,6-tris [3,5-dimethyl-4- (2-ethylhexyloxyphenyl) - (1,3,5) -triazine The basic structure of formula (102a) is obtained for example, doing reacting 2,6-dimethylphenol with cyanuric chloride under Friedel-Crafts conditions (see DE-A-2,219, 012). 6.62 g of the compound of formula (102a) are dissolved in 70 ml of dimethylformamide and charged with 6.53 g of finely powdered potassium carbonate at 100-105 ° C. This mixture is stirred for 30 minutes and then 11.65 g of 3- (chloromethyl) heptane, dissolved in 10 ml of DMF, are added dropwise for a further 30 minutes a. 100-105 ° C. The temperature is maintained at 100-105 ° C for 3 hours. After cooling to 100 ° C, 50 ml of toluene are added and the precipitated salts are removed by filtration. The filtrate is concentrated to dryness by evaporation and the residue is charged with 100 ml of toluene and 100 ml of water, acidified and extracted by stirring. The organic phase is washed with water until neutralized, separated, dried and concentrated by evaporation. The crude product (0.10 g) is purified by column chromatography (silica gel, cyclohexane / toluene 65:35). Yield: 4.7 g of colorless crystals, m.p. 83-84 ° C, (40% of theoretical).

Example 3: The compounds of formula they can be prepared by general analogy with the procedure of Example 1.

Application of Examples Example 3: The compositions of a cosmetic formulation with the benzotriazole compound of formula (101) of Example 1 (the individual components are named according to CTFA or INCI): (ai) ceteareth 6 (and) stearyl alcohol 2.0% (a2) ceteareth 25 2.0% (a3) cetearyl alcohol 5.0% (a4) caprilic / capric triglyceride 5.0% (a5) cetearyl octanate 10.0% (a6) Vaseline 5.0% (a7) compound of formula (101) 4.0% (bi) propylene glycol 3.0% (b2) carbopol 934 0.2% (b3) H20 63.53% (c) triethanol amine 0.27% The components (a?) - (a7) (= phase A) and (b?) - (b3) (= phase B) are heated to 75-80 ° C. Then phase B is added to phase A and homogenized. Next, component (c) (= phase C) is added and again homogenized. This Oil / Water emulsion has a sun protection factor of 4. The UVA / UVB ratio is 1.23, which is a very good value for a sunscreen formulation. The sun protection factors are determined according to the method of Diffey and Robson, J. Soc. Cosmet. Chem. 40, 127-133 (1989) using an SPF analyzer (solar test factor) (Optometrix, SPF 290).

Examples of Use Example 4: Preparation of an emulsion Oil / Water Formulation (names according to CTFA or INCI): (ai) ceteareth 6 (y) stearyl alcohol 2.0% (a2) ceteareth 25 2.0% (a3) cetearyl alcohol 5.0% (a4) caprilic / capric triglyceride 5.0% (a5) cetearyl octanate 10.0% (a6) Vaseline 5.0% ( a7) compound of formula (101) 4.0% (bi) propylene glycol 3.0% (b2) carbopol 934 0.2% (b3) H20 63.53% (c) triethanolamine 0.27% The components (a?) - (a7) (= phase A) and (bx) - (b3) (= phase B) are heated to 75-80 ° C. Then phase B is added to phase A and homogenized. Next, component (c) (= phase C) is added and again homogenized. The sun protection factors are determined by the method of Diffey and Robson, J. Soc.

Cosmet. Chem. £ 0, 127-133 (1989) using an SPF analyzer (sun protection factor) (Optometrix, SPF 290). This Oil / Water emulsion has a sun protection factor of 7.8.

Example 5: Preparation of a tanning cream: Formulation (the individual components were named from the CTFA or INCI): Phase A: (ai) dimethicone 2.0% (a2) isopropyl myristate 9.0% (a3) cetearyl alcohol 10.0% (a4) ) 4.0% (a5) stearic acid compound of formula (102) 4.0% (a6) 2,4-bis (phenyl) -6- (2-hydroxy-4-methoxyphenyl) - (1, 3, 5) -triazine micronized (0 0.25 μm) 3.2% (bi) triethanol amine 1.2% (b2) carbomer 934 (1%) 5.0% (b3) H20 61.6% The components (a?) - (a6) (= phase A) are homogenized separately very carefully and then, like the components (bi) - (b3) (= phase B), they are heated separately at 75-80 ° C. Then phase B is added to phase A with vigorous stirring. With stirring, the mixture is allowed to cool. The tanning cream has a sun protection factor of 11.

Claims (17)

1. CLAIMS A compound of formula characterized in that fli and R2 are each independently hydrogen; C? -C? 2 alkyl; C? -C? 2 alkoxy; and 3 is C1-C12 alkyl; or C? -C? 2 alkoxy.
2. 2. The compound according to claim 1, characterized in that, in the formula (1), R3 is C? -C? 2 alkoxy.
3. 3. The compound according to any of claims 1 or 2, characterized in that R3 is C5-C2 alkoxy.
4. 4. The compound according to claim 1 of formula characterized in that R4 and Rs. are each independently hydrogen; C] -C? alkyl; or C? -C? 2 alkoxy; and R6 is C? -C? 2 alkyl; or Ca-C 2 alkoxy.
5. 5. The compound according to claim 4, characterized in that R is hydrogen; and R5 and R6 are C5-C2 alkoxy;
6. 6. The compound according to claim 4, characterized in that R4 and R5 are C5-C2 alkoxy; and R6 is hydrogen.
7. 7. The compound according to any of claim 1 or claim 3 of formula characterized in that R7 is C5-C12 alkoxy; and Rβ is hydrogen; or C? -C5 alkyl.
8. 8. A mixture of the compounds of formula (1) and of formula (4), characterized in that Rio is hydrogen; C6-C2alkyl; or c2-c6 alkenyl; Y Rn is C? -C? 2 alkoxy.
9. 9. The process for the preparation of the compounds of formula (1) according to claim 1, characterized in that it comprises reacting in a first reaction step one mole of cyanuric chloride with 3 mole of the corresponding phenylmagnesium bromide compound which , depending on the meaning of Ri, R2, and R3 in the formula (1), may contain an alkyl radical and / or one or more of a free hydroxyl group, and etherify in a second reaction step the free hydroxyl groups in a reaction of alkylation.
10. 10. The process for the preparation of the compounds of formula (1) according to claim 1, characterized in that it comprises reacting in a first reaction step 1 mol of cyanuric chloride with 3 mol of the corresponding phenyl compound which, depending on of the meaning of Ri, R2 and R3 of the compound of formula (1), may contain an alkyl radical and / or one or more of a free hydroxyl group, by alkylation of Friedel-Crafts in the presence of a Lewis acid and, in a second reaction step, etherify the free hydroxyl groups in an alkylation reaction.
11. 11. The process for the preparation of the compounds of formula (1) according to claim 1, characterized in that it comprises cyclotrimerizing in a first reaction step a benzonitrile compound which, depending on the meaning of Rx, R2 and R3 in the formula (1), may contain an alkyl radical and / or one or more than one hydroxyl group and, in one second reaction step, etherify the free hydroxyl groups in an alkylation reaction.
12. 12. The use of the compounds of formula (1) or where Ar is a radical of formula Ri is hydrogen; hydroxy; C? ~ C? 2 alkyl; or C? -C? 2 alkoxy; R2 is hydroxy; C? -C? 2 alkoxy; or benzyloxy; R3 is hydroxy; C? ~ C? 2 alkyl; or C? -C? 2 alkoxy; R-i is hydrogen; or C? -C? 2 alkoxy; or Ri and 2 together with the phenyl radical, are a five-membered heterocyclic ring which is condensed with benzene, to protect hair and human and animal skin from the dangerous effects of UV radiation.
13. 13. A cosmetic preparation for the skin or hair, characterized in that it comprises at least one or more of a compound of formula (1) or (5) together with carriers or auxiliaries that are cosmetically compatible with the hair and the skin.
14. 14. A cosmetic preparation for the skin or hair, characterized in that it comprises a mixture of a) at least one compound of formula (1) or (5), and b) a compound of formula (4) together with carriers or auxiliaries which They are cosmetically compatible with hair and skin.
15. 15. The cosmetic preparation for the skin or hair according to any of claim 13 or claim 14, characterized in that it comprises at least 0.1 to 25% by weight, based on the total weight of the formulation, of a UV absorber of formula (1) or (5) or of a mixture of absorbers of formula (1) and of formula (4) as well as at least one auxiliary which is compatible with the skin and hair.
16. 16. The use of the hair cosmetic preparation according to any of claims 13 to 15 to protect the hair from UV radiation, which is obtained in the form of a shampoo, lotion, gel or emulsion for the hair. rinse, before or after shampooing, before or after dyeing or removing the dye, before or after a permanent combing or straightening process, in the form of a lotion, foam or gel to fix or treat, in the form of a lotion, foam or gel for brushing or curling, in the form of a hairspray, in the form of a permanent styling formulation, dyeing or removing dye.
17. 17. A process for treating human hair to protect human hair from the dangerous effects of UV radiation, characterized in that it comprises treating the hair with a shampoo, lotion, gel or emulsion for rinsing, before or after shampooing, before or after the dyeing or removing the dye, before or after a permanent or straightened combing process, in the form of a lotion, foam or gel to fix or treat, in the form of a lotion, foam or gel to brush or wave, in the form of a hair lacquer, in the form of a formulation for permanent combing, dyeing or removing dye, comprising at least one UV absorber of formula (1) or (5) or a mixture of a UV absorber of formula (1) and of formula (4).