MXPA98003820A - Resorcinil-triazi - Google Patents

Abstract

Resorcinyltriazines of formula (See Formula) are disclosed. The compounds according to the present invention are especially suitable as sun screens in cosmetic, pharmaceutical and veterinary compositions.

Description

The present invention relates to novel resorcinyl triazines, to processes for the preparation of these compounds and to the use of selected resorcinyl triazines for cosmetic compositions. The new resorcinyl-triazines correspond to the formula: where Ri and R2 are each independently of the other a radical of the formula (1a) or I pI - < CH2) -C ^ \ R,! R3 is hydroxy; alkyl C? _5 which is unsubstituted or substituted by one or more OH groups; C1-5 alkoxy; Not me; mono- or dialkylamino C1-5; M; a radical of formula OR" where R ', R "and R'" are each independently of the other alkyl C? -? j r. * which is unsubstituted or substituted by one or more OH groups; R4 is hydrogen; M; C1.5 alkyl; or a radical of the formula - (CH2) m2 -O-TÍ; is a radical of the formula R5 is hydrogen; C1.10 alkyl; - (CH2CHR6-O) -n? R4, or a radical of the formula 15 -CH ^ CHI-OHJ-CHz-O-T !; RT is hydrogen or methyl; Ti is hydrogen or C 1 -β alkyl; Q1 is C? .18 alkyl; M is a metal cation; my is 1 to 3; and 20 m2 is from 1 to 4; m3 from 2 to 14; Y Alkyl C? -5, C? -8 alkyl, CMO alkyl, and C8 alkyl are straight, branched or straight chain alkyl radicals, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, ter- butyl, amyl, isoamyl, or ter-amyl, heptyl, octyl, isooctyl, nonyl, decyl, undecyl, dodecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl or octadecyl. Alkoxy C? -5 are rectilinear or branched chain radicals, for example, methoxy, ethoxy, n-propoxy, isopropoxy n-butoxy, sec-butoxy, tert-butoxy, amyloxy, isoamyloxy or ter-amyloxy. Examples of mono- or dialkylamino C1.5 are methylamino, propylamino, n-butylamino, sec-butylamino, tert-butylamino, pentylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, or methyl-ethylamine.

Examples of metal cations are lithium, potassium, sodium, calcium, magnesium, copper or zinc ion. Preference has been given to the resorcinyl compounds of the formula (1) wherein Ai is a radical of formula where Ri and R5 are as defined for formulas (1 h) and (1k). The important resorcinyl compounds according to the invention correspond to the formula or p, where Ri and R2 are each independently of the other a radical of the formula or -CH z-C \ O - R. R3 is hydrogen; or C1-5 alkyl and R5 is C alquilo _? 0 alkyl. The most important compounds of resorcinyl-triazine compounds correspond to the formula where R1, R2 and R5 are each independently of the others a radical of the formula -OH2- ^ O - R, and R3 is hydrogen or C1.5 alkyl. Particular preference is given to the compounds of the formula (3) wherein R1 (R2 and R5 have the same meaning) Examples of triazine derivatives according to the invention are given in Table 1.

The novel resorcinyltriazines can be prepared in various ways. For example, the compounds of the formula (1) wherein Ai, is a radical of the formula (1h) and Ri and R2 have the same meaning can be prepared in a three step reaction, starting from the cyanuric chloride. In that reaction, the phenylmagnesic bromide compound reacts in a Grignard reaction with cyanuric chloride to form a dichlorotriazine compound of formula (11) The processes for the preparation of that intermediary are known and described, for example, in European Patent No. A-0 577 559. The two groups of resorcinol are then introduced into Friedel-Crafts acylation in the presence of an acid. of Lewis, especially aluminum chloride. In the third step, the etherification of the free hydroxy groups of position p- is effected, depending on the meaning of the radicals Ri and R2 by alkylation or acid catalyzed addition of glycidyl ethers. Detailed information can be found in the Preparation Examples. The dichlorotriazine intermediate of the formula (11) can, in addition, be obtained without the use of the Grignard reagents, by ring-closing reaction. For that end, the suitably substituted benzonitrile reacts with dicyanodiamide to form 6-aryl, I.S.d.-triazine ^^ -dione, which is converted with thionyl chloride to the chloro derivative of the formula (11). Alternatively, the compound of the formula (11) can also be obtained by reaction of the N, N-dimethyl carboxylic acid amides suitably substituted with phosphorus oxychloride and N-cyano-chloro-formamidine. These reactions are already known and are described, for example, in Dyes and Pigments 7, 419-443 (1986). The compounds of formula (1), wherein IK \ is a radical of formula (1 h) can also be obtained by reaction of substituted phenyl benzoaxin-4-ones of the formula (1 m) with benzamidine compounds of formula where R (R2 and R5, are as defined by formula (1).) The preparation of said benzoxazinone intermediates and the reaction with amidines are described j • 'in Helv. Chim. Acta 55, 1566-1595 (1972). , in formula (1), A1 f is a radical of formula (1g) and Ri and R2 have the same meaning, resorcinyl triazines, according to the invention can be prepared, for example, in a three-step reaction, starting at from cyanuric chloride In this reaction the appropriate aminobenzoic acid ester reacts with cyanuric chloride to form a dichlorotriazine compound of the formula The two groups of resorcinol are then introduced in a known manner by Friedel-Crafts acylation of resorcinol in the presence of a Lewis acid, especially aluminum chloride. These reactions are described, for example, in European Patent No. A-165,608. Finally, the etherification of the free hydroxy groups, of position p-, is carried out depending on the meaning of the radicals R < and R2, by alkylation or acid catalyzed addition of glycidyl ethers. Detailed information can be found in the Synthesis Examples. The compounds of the formula (1) according to the invention can be further prepared by dehydrogenation of a dihydrotriazine compound of the formula where Ri, R2 and Ai are as defined in formula (1). The dehydrogenation agent used is generally chloranil. The dehydrogenation of the dihydrothriazine compounds to form 1, 3,5-triazines with the aid of chloranil is known, for example, from Khim. Geteritsikl. Soedin (2 P. 350-353 (1969). Compounds of formula (1) can be prepared, where A-i is a radical of formula (11) and Ri and R2 have the same meaning, for example, in a three step reaction, starting from cyanuric chloride. In the reaction the suitable N-alkylpyrrole reacts with cyanuric chloride in a Friedel-Crafts reaction selectively to form the dichlorotriazine compound of the formula 0q) where Qi is as defined in formula (1). The two resorcinol groups are then introduced, generally in a known manner by Friedel acylation. Crafts of resorcinol in the presence of a Lewis acid, especially aluminum chloride. These reactions are described, for example, in European Patent No. A-165 608. Finally, the etherification of the free hydroxy groups, of the p-position, is effected by alkylation or acid catalyzed addition of glycidyl ethers. Detailed information can be found in the Synthesis Examples. The compounds of the formula (1) according to the invention are especially suitable as ultraviolet filters, ie to protect organic materials sensitive to ultraviolet rays, especially for the protection of the skin and hair of humans and animals against the harmful effect of ultraviolet radiation. These compounds are therefore suitable as light stabilizers in cosmetic, pharmaceutical and veterinary compositions. The compounds can be used in dissolved form as well as in the micronized state. The invention, therefore, relates to a cosmetic composition comprising at least one compound of formula (1), as well as pharmaceutically acceptable carriers or auxiliaries. For cosmetic use, the light stabilizers according to the present invention generally have an average particle size ranging from 0.02 to 2 μ, preferably from 0.05 to 1.5 μ, and especially from 0.1 to 1.0. μ. The insoluble ultraviolet absorbents, according to the present invention, can be brought to the desired particle size by routine methods, for example, ground, using a jet grinder, ball mill, vibrating mill or hammer mill. The grinding is preferably carried out in the presence of between 0.1% to 30% by weight, especially of 0, 5 to 15% by weight, based on the ultraviolet absorber of a grinding aid, for example an alkylated polymer of pyrrolidone vinyl, a copolymer of vinyl pyrrolidone-vinyl acetate, an acyl glutamate or especially a phospholipid. In addition to the ultraviolet absorbent, according to the invention, the cosmetic composition may further comprise one or more UV classification agents of the following classes of substance: 1. p-aminobenzoic acid derivatives, DOG example, 2-ethylhexyl ester of acid -dimethylaminobenzoic acid; 2. Salicylic acid derivatives, for example, 2-ethylhexyI acid ester salicylic; 3. benzophenone derivatives, for example 2-hydroxy-4-methoxybenzophenone and the 5-sulfonic acid derivative thereof; 4. dibenzoylmethane derivatives, for example, 1- (4-tert-butylphenyl) -3- (4-methoxyphenyl) propane-1,3-dione; 5. diphenylacrylates, for example, 2-ethylhexyl-2-cyano-3,3-diphenylacrylate and 3- (benzofuranyl) -2-cyanoacrylate; 6. 3-imidazol-4-yl-acrylic acid and esters; 7. benzofuran derivatives, especially derivatives of 2- (p-aminophenyl) benzofuran, described in European Patent No. A-582189, US Patent No. -A- 5,338,539, US Patent No. -A- 5,518,713 and European Patent No. -A- 613,893; 8. UV polymeric absorbers, for example, benzylidene malonate derivatives described in European Patent No. -A-709080; 9. cinnamic acid derivatives, for example, 4-methoxycinnamic acid 2-ethylhexyl ester and isoamyl ester or cinnamic acid derivatives described in US Pat. No. -A-5,601,811 and International Patent WO 97/00851; . camphor derivatives, for example, 3- (4'-methyl) benzylidene-boman-2-one, 3- benzylidene-boron-2-one, N- [2 (and 4) -2-oxiborn-3-) polymer ylidene-methyl) -benzyl-acrylamide, 3- (4'-trimethylammonium) -benzylidene-boron-2-one sulphate. . Methyl, 3,3 '- (1,4-phenylene-dimetin) -bis- (7,7-dimethyl-2-oxo-bicyclo [2.2.1] heptane-1-methanesulfonic acid) and salts, 3- ( 4'-sulfo) benzylidene-bornan-2-one and salts; 1 1. trianilino-s-triazine derivatives, for example 2,4,6-trianilin- (p-carbo-2'-ethyl-1'-oxy) -1, 3,5-triazine and the UV absorbers disclosed in U.S. Patent No.-A-5,332,568 and European Patent No. A-517,104, Patent . £ r; European Patent No. A-507,691, International Patent WO 93/17002 and European Patent 10 No. A-570,838; 12. 2-hydroxyphenyl-benzotriazole derivatives; 13. 2-phenylbenzimidazole-5-sulfonic acid and salts thereof; 14. Methyl-o-aminobenzoate; 15. TiO2 (coated in various forms), ZnO and mica. The UV absorbers described in "Sunscreens" (Sunscreen), eds., N.J. Lowe, N.A. Shaath, Marcel Dekker, Inc., New York and Basel or in ÉF. "Cosmetics &Toiletries" (Cosmetics and Dressing Table) (107), 50 ff (1992) can also be used as additional UV classification agents in the formulation, according to the present invention. In addition, the cosmetic composition according to the invention can also be used together with known antioxidants, for example vitamin E, carotenoids or HALS (sterically hindered amino light stabilizer) compounds. The cosmetic composition according to the invention contains 0.1. to 15% by weight, preferably from 0.5 to 10% by weight, based on the total weight of the composition, of a UV absorber or a mixture of UV absorbers, and a cosmetically acceptable auxiliary.

The preparation of the cosmetic composition can be effected by physical mixing of the UV absorbent (s) with the auxiliary (s) by routine methods, for example, by simple agitation of the individual components as a whole. The cosmetic composition according to the invention can be formulated as a water-in-oil or oil-in-water emulsion, an oil-in-alcohol lotion, a vesicular dispersion of an ionic or non-ionic amphiphilic lipid, a gel, an aerosol formulation or solid in bar. As a water-in-oil or oil-in-water emulsion, the auxiliary The cosmetically acceptable compound preferably contains an oily phase of 5 to 50%, emulsifier of 5 to 20% and water of 30 to 90%. The oily phase may contain any oil suitable for the cosmetic formulations, for example, one or more hydrocarbon oils, a wax, a natural oil, a silicone oil, a fatty acid ester or a fatty alcohol. The preferred mono- or polyols are ethanol, isopropanol, propylene glycol, hexylene glycol, glycerol and sorbitol. t2. 1 ffc Any emulsifier conventionally usable can be used for the cosmetic composition, according to the invention, for example, one or more ethoxylated esters of natural derivatives, for example, polyethoxylated esters of hydrogenated castor oil or a silicone oil emulsifier, for example, a silicone polyol; an optionally ethoxylated fatty acid soap; an ethoxylated fatty alcohol; an optionally ethoxylated sorbitan ester; an ethoxylated fatty acid; or an ethoxylated glyceride. The cosmetic composition may further comprise other components, for example, emollients, emulsion stabilizers, skin moisturizers, skin tanning accelerators, thickeners, such as xanthan, moisture retention agents, such as glycerol, preservatives. , # perfumes and colorants. The cosmetic composition according to the invention is distinguished by the excellent protection of human skin against the harmful effect of sunlight. In the examples that follow, percentages refer to weight. In the case of the resorcinyltriazine compounds used, the amounts refer to the pure substance.

Preparation examples of the novel compounds Example 1 10 .05 g are placed. of 2,4-bis (2,4-dihydroxyphenyl) -6- (4-methoxyphenyl) -1, 3,5-triazine, 40 g. of dimethyl formamide (DMF) and 5.1 g. of sodium methanolate solution (30%), in a reactor and heated to 95 ° C in vacuo. 20 g approximately 10 g are distilled. of DMF / methanol mixture; the vacuum is released with nitrogen and then a solution of 3.96 g is added. of tert-butyl chloroacetate in 10 g. of DMF with complete agitation. The reaction mixture is stirred at 90 ° C for 12 hours. The reaction mass is then concentrated in a rotary evaporator and the semi-solid residue is extracted with acetone. A solution jjt of the crude product is concentrated in acetone in vacuo and the residue is recrystallized 2x using a mixture of toluene / cyclohexane (17.5: 12.5). Yield: 2.6 g. of yellow crystals 5 p.f .: 88 to 94 ° C Example 2 According to Example 1, 6.95 g are used. of 4-chloroacetamido-n-butyl benzoate, instead of tert-butyl chloroacetate. The process is carried out by extraction of the crude product with dioxane / water and methoxyethanol. The compound of the formula (102) is obtained Yield: 5.5 g. of yellow crystals, p.f .: 280 ° C Elemental analysis C N 20 Calculated 66.28% 8.0% Found 66.2% 8.0% UV spectrum (measured in DMF) Max: 286 nm; e = 57800? max2: 338 nm; e = 49600 Example 3a 22.3 g are reacted. of trisresorcinyl triazine with 16.8 g. of methyl chloroacetate, using sodium methanolate (30%) as the base in DMF, according to Example 1. The crude product is recrystallized from dioxane / methoxyethanol (1: 1 mixture). Yield: 9 g. of trisresorcinyl methyl ester of monoglycolic acid.

Example 3b Hydrolysis to tricarboxylic acid. They are stirred under reflux for 6 hours, 9 g. of the resulting methyl ester in a mixture formed by 150 ml. of 1 N NaOH and 50 ml. of dioxane. After cooling occurs, the reaction mass is adjusted with HCl to the pH value of 3.0. The tricarboxylic acid of formula it is slowly separated from the solution in the form of trihydrate.

Performance: 3g. of gray powder.

Elementary analysis C N Calculated 51, 2% 6.6% Found 50.5% 6.3% UV spectrum (measured in DMF)? Max1: 300 nm; e = 27700? max2: 348 nm; e = 44300 Example 4a 40.0 g are dissolved. of 2,4-bis (2,4-dihydroxyphenyl) -6- (4-methoxyphenyl) -1,5,5-triazine in. 750 ml. of DMF; 21, 8 g are added. of NaHCO 3 and the mixture is heated to 121 ° C with stirring, under reduced pressure (420 mbar). Over a period of about 3 hours, approximately 100 ml. of DMF / water are distilled from the reaction mass. After cooling to 20 ° C, the vacuum is released and 33 g are dissolved with stirring. of ethyl chloroacetate in 150 ml. of DMF that are added slowly by drip. The stirring is continued at room temperature for 12 hours to complete the reaction and the reaction mass is then heated to 80 ° C. The suspension is filtered and after the addition of 3 g. of formic acid, concentrated under a high vacuum. The evaporation residue is extracted with methyl ethyl ketone, with a yield of 34 g. of the compound of the formula - Example 4b Hydrolysis of the compound of formula (104a) 22.5g are stirred. of the compound of the formula (104a) in 50 ml. of water and 50 ml. of 2N NaOH for 10 hours at 95 ° C. The reddish orange solution is cooled to 20 ° C and then 100 ml are added thereto. of 1 N HCl. The free acid precipitates. The filter residue is dried in vacuo, with a yield of 20 g. of the formula compound OH Example 4c The compound of formula (104b) is dissolved in methoxyethanol, and 2 equivalents of triethanolamine are added thereto. The concentration of the solution by evaporation yields the compound of formula.

The spectrum data of the compound of formula (104c): The UV spectrum in water:? Maxi: 340 nm; e = 34268 Example 4d 11.5 g are suspended. of the compound of formula (104c) in 50 ml. of N, N-dimethylamino-propylamine; Sodium methanolate is added and the mixture is stirred at 130 ° C under a stream of N2 for 16 hours. The concentration of the reaction mass by evaporation produces the compound of the formula Example 4e 6 g are stirred. of the compound of formula (104d) in 50 ml. of dioxane with chloroacetamide at 75 ° C for 12 hours. Concentration of the reaction mass by evaporation and extraction of the crude product with acetone gives a yield of 7.1 g. of the compound of the formula * - Spectrum data:? Max: 339 nm; e = 36803? max2: 320 nm; e = 32104 Example 4f 20 6 g are reacted. of the compound of formula (104e) in 50 ml. dioxane with 2.64 g. of dimethyl sulfate at 75 ° C. Concentration of the reaction mass by evaporation and extraction of the crude product with acetone yields a yield of 7.2 g. of the formula compound Spectrum data:? Max1: 328 nm; e = 31763? max2: 306 nm; e = 30836 Example 5 According to Example 4a, 40.4 g are reacted. of 2,4-bis (2,4-dihydroxyphenyl) -6- (4-methoxyphenyl) -1, 3,5-triazine with 137 g. of D, L-α-tocopherol chloroacetate (prepared as tocopherol and acetyl chloride in pyridine / acetone). The process of the reaction mass by crystallization from methyl ethyl ketone yields 84 g. of the compound of the formula.

) # Spectrum data:? Max: 336 nm; e = 45999? ma a: 306 nm; e = 43748 Example of the application Example 6 Preparation of a sunscreen lotion (W / O) * 10 fifteen twenty The components of part A are heated to 75-80 ° C and part B, # previously mixed at 80 ° C, is added with agitation. The components of part C are heated to approximately 80-90 ° C and with vigorous stirring, partially homogenized A + B. With slow stirring, the mixture is cooled to room temperature and part D is stirred homogeneously. Solar exhibits cosmetically effective light stabilization.

Example 7 Preparation of a sunscreen lotion (O / W) 10 fifteen twenty The components of parts A and B are heated to approximately 80 ° C and shaken carefully. Then, the components of part C are added and homogenized. Then, from cooling, part D is added with stirring. The sunscreen lotion exhibits cosmetically effective light stabilization.

Example 8 Preparation of a hair conditioner that has UV protection (foam) The components of parts A and B are mixed together at approximately 50 ° C and after cooling, part C and perfumed oil are added as necessary. The mixture is introduced into an aerosol container and a propellant is added.

Claims (10)

CLAIMS Having thus, especially, described and determined the nature of the present invention and the way it is to be put into practice, it is claimed to claim as property and exclusive right:

1. A resorcinyl-triazine of formula where Ri and R2 are each independently of the other a radical of the formula (1 a) O II (CH2), - c R3 R3 is hydroxy; alkyl C? -5 which is unsubstituted or substituted by one or more OH groups; C5-alkoxy; Not me; mono- or dialkylamino C-5; M; a radical of formula l " where R ', R "and R'" are each independently of the other alkyl d.u which is unsubstituted or substituted by one or more OH groups; R 4 is hydrogen; M; C ^ .5 alkyl; or a radical of the formula - (CH2) m2 -O-T1; is a radical of the formula fifteen R5 is hydrogen; alkyl C? .10; - (CH2CHR6-O) -n? R4, or a radical of the formula -CH2-CH (-OH) -CH2-O-T ?; Re is hydrogen or methyl; 20 is hydrogen or C? 8 alkyl; Qi is alkyl C? -? 8; M is a metal cation; my is 1 to 3; and m2 is from 1 to 4;

2. A resorcinyltriazine, according to Claim 1, wherein Ai is a radical of formula Wherein Ri and R5 are as defined in Claim 1.

3. A resorcinyltriazine according to Claim 1 or 2 of formula where R1 and R2 are each independently of the other a radical of the 20 formula or -CH2-C O-R, R3 is hydrogen; C1-C alkyl) and Rs is C1-C10 alkyl.

4. A resorcinyltriazine, according to claim 1 or 2 of formula * 10 where Ri, R2 and R5 are each independently of the others a radical of the formula or - CH, O - R R is hydrogen or C1-5 alkyl.

5. A resorcinyltriazine according to Claim 4, wherein R1, R2 and R5 have the same meaning.

6. A process for the preparation of a resorcinyl-triazine (1) wherein Ai is a radical of formula (1 a) and R1 and R2 have the same meaning, by reaction of the appropriate phenyl magnesium bromide compound in a reaction of Grignard with cyanuric chloride to form a dichlorotriazine compound of formula introduction of the resorcinol groups by Friedel-Crafts acylation of resorcinol in the presence of a Lewis acid, especially aluminum chloride, and etherification of the free, p-position hydroxy groups, which depend on the meaning of the radicals Ri and R2 by alkylation or acid catalyzed addition of glycidyl ethers.

7. Use of a resorcinyl triazine of formula (1) for the protection of hair and skin of both humans and animals from the harmful effect of UV radiation.

8. A cosmetic composition, comprising at least one or more compound of formula (1), according to claim 1, with cosmetically acceptable carriers or auxiliaries.

9. A composition according to Claim 8, further comprising UV classification agents.

10. A composition according to claim 8 or 9, further comprising UV classification agents, triazines, oxanilides, triazoles, amides containing vinyl groups or cinnamic acid amides.