JPS6116258B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to light shielding agents. It is known that sunlight accelerates the aging of the skin and that this undesirable effect is initially caused by the direct tanning of the skin by ultraviolet A-rays having a wavelength in the range of about 320 nm to 40 nm. According to the invention, 4-(1,1-dimethylethyl)-
4'-Methoxydibenzoylmethane, i.e. the formula Compounds with are excellent ultraviolet A filters,
It was found to significantly prevent skin aging and to have excellent skin tolerance and stability (light, heat and moisture). According to the invention, the maximum absorption of a compound of formula is approximately
330nm to 360nm, but not 290nm to 320nm, but in this range of about 290nm to 320nm, the compound of formula was also found to improve. The present invention is based on the above findings and one aspect relates to a light-screening agent comprising a compound of the above formula, preferably in combination with an ultraviolet B filter. Another feature of the invention relates to the use of the compounds of the formula in light screening agents, preferably in conjunction with ultraviolet B filters. If the light shielding agent contains a compound of the formula along with an ultraviolet B filter, it will completely absorb ultraviolet rays in the range of 280 nm to 380 nm (so-called "A+B complete shielding").
and protect the skin from premature aging and often photodermatitis. The production of the light-screening agents according to the invention, in particular the skin protection preparations for everyday cosmetics, is carried out by mixing the compounds of the formula, preferably in combination with an ultraviolet B-ray filter, into customary cosmetic bases for light-screening agents. UV B-ray filters within the scope of the invention, i.e. about
As substances having maximum absorption between 290 nm and 320 nm, organic compounds belonging to the following various substance classes can be cited as general ultraviolet B-ray filters. (1) p-aminobenzoic acid derivatives, such as ethyl p-aminobenzoate, and other esters (p-
propyl aminobenzoate, butyl p-aminobenzoate, isobutyl p-aminobenzoate, etc.) ethyl p-dimethylaminobenzoate, p-
Glyceryl aminobenzoate and amyl p-dimethylaminobenzoate. (2) Cinnamic acid derivatives, such as 2-ethoxyethyl p
- Methoxycinnamic acid ester, 2-ethylhexyl p-methoxycinnamic acid ester, p-methoxycinnamic acid ester mixture and cinnamic acid ester mixture. (3) Dibenzaladin. (4) Heterocyclic nitrogen-containing compounds, such as 2-phenylbenzimidazole derivatives (eg 2-phenylbenzimidazole-5-sulfonic acid). (5) Salicylic acid derivatives, such as salicylic acid menthyl ester, salicylic acid homomenthyl ester, and salicylic acid phenyl ester. (6) Benzophenone derivatives, such as 4-phenylbenzophenone, 4-phenylbenzophenone-2-carboxylic acid isooctyl ester and 2-carboxylic acid isooctyl ester.
-Hydroxy-4-methoxybenzophenone-
5-Sulfonic acid. (7) Coumarin derivatives, such as 7-hydroxycoumarin, β-umbelliferone acetic acid, 6,7-dihydroxycoumarin. (8) Gallic acid derivatives such as digalloyl-triolate. (9) Arylidenecycloalkanones such as benzylidene camphor, p-tert-butylbenzylidene camphor (preferred) and methylbenzylidene camphor. (10) Derivatives of anthranilic acid, such as anthranilic acid methyl ester. (11) Hydroxyphenylbenztriazole. The compound (2) is preferred, and 2-ethylhexyl p-methoxycinnamate is particularly preferred. The cosmetic base commonly used for the light-screening agent according to the invention can be any cosmetic formulation, provided it meets the cosmetic requirements. For example, creams, lotions, emulsions, ointments, gels, solutions, sprays, stickers, etc. (GA. Nowak, “Die Kosme
-tischen Praparate”, 1st edition 1969, 2nd edition,
(See August 1975). The light-shielding effect usually also depends on the base material used. Furthermore, the strength of the light-shielding effect when using the same base depends on the concentration of active substance. A suitable concentration of a compound of formula in the light screening agent is 1
It ranges from 2% to 5% by weight, preferably from 2% to 5% by weight. The ratio of compound of formula to ultraviolet B filter is not critical. For economic reasons, for example, for compound 1 of the formula, 1 ultraviolet B filter
~2% amount. Being lipophilic, the compounds of the formula can be easily mixed into oil- and fat-containing cosmetics, such as dianisoylmethane A, which is disclosed in German Patent Application No. 2540798. This is an advantage that structurally similar compounds do not have. The compound of the formula is also registered in German patent application 2544180
For example, 4-isopropyl-[or 4-(1,1-dimethylethyl)]-dibenzoylmethane (B, C)
superior to structurally similar compounds such as The fat solubility of B and C is very good, but the absorption of ultraviolet A rays is low (at 355 nm, ε = 348 nm compared to 33866).
at ε=26344 or ε=27396 at 347 nm). The compounds of the formula have optimal properties with respect to adequate fat solubility and absorption of UV A radiation. The compounds of formula are new and form part of the present invention.
It can be prepared by a known method, Claisen condensation of an aromatic ester and a substituted acetophenone (R. Hauser et al., "Organic Reactions" 8.
Volume, p59, John Wiley and Sons Inc., New
(see York 1954). That is, the expression A compound with the formula (In the formula, X is a methoxycarbonyl group and Y is an acetyl group, or X is an acetyl group and Y is a methoxycarbonyl group.) The reaction between a compound of formula and a compound of
Alkali metal amides (e.g. sodium amide)
Alternatively, it may be carried out in the presence of a strong base such as an alkali metal alcoholate (for example, sodium methylate or sodium ethylate). The reaction is preferably carried out in the presence of an inert solvent such as an ether (eg, tetrahydrofuran) or a hydrocarbon (eg, toluene). The reaction temperature is preferably about 20°C to 70°C, particularly about 50°C. The separation of the compound of formula is carried out by adding ice and an acid (e.g. a mineral acid or an alkane carboxylic acid such as acetic acid) to the metal salt of the compound of formula which is separated as a solid precipitate, and the compound of formula thus liberated is , it is desirable to obtain by concentrating the organic phase. If necessary, compounds of formula can be further purified by recrystallization from lower alcohols such as methanol or ethanol. The following examples are illustrative of light screening agents provided by the present invention. Example 1

[Table] Mix ingredients A, heat on a water bath to 85℃, and add B at this time. Heat mixture C to 75°C and
and B to the mixture. After cooling to 25℃~35℃,
Replenish any moisture lost and add D.

【table】

[Table] Heat mixture A to 80°C in a water bath. Disperse the Alugel in paraffin oil at room temperature and stir the mixture to completely eliminate large particles. Next, add B to A and stir to make a homogeneous solution. Heat C to 75°C to 80°C. Add C to the mixture of A and B while stirring vigorously. After cooling to 25°C to 30°C, compensate for evaporated water and add D. Homogenize the resulting mixture.

Table: Mixture A is heated on a water bath to 80° C. to 85° C. and at this temperature B is dissolved therein. Mixture C is preheated to 75°C and added to the mixture of A and B. After cooling to 25°C to 30°C, replace the lost moisture and add D. Stir the mixture further and reduce the temperature to 25
Bring the temperature to between ℃ and 30℃.

Table: Mixture A is heated to 85° C. in a steam bath and B is added at this temperature. Mix ingredients of C, heat to 75°C and add to mixture of A and B. After cooling to 25°C to 30°C, replace the lost water and then add D. The mixture is further stirred and the temperature is lowered to 25°C to 30°C. The following example is an illustration of the preparation of a compound of formula. Example 2 (a) 356 g (2 mol) of p-tert-butylbenzoic acid, 243 g (7.6 mol) of methyl alcohol and sulfuric acid (96 mol)
%) into a four-necked round-bottomed flask equipped with a stirrer and condenser. The mixture is refluxed for 8 hours with gentle stirring. Replace the condenser with a distillation column and remove excess methyl alcohol by distilling it off. The pressure will be slightly reduced at the end, but the temperature should not exceed 100℃. Cool the mixture and pour over ice. The phases are separated and the organic phase is washed with ice water, saturated sodium carbonate solution with ice and finally with ice until neutral. The organic phase was dried with sodium sulfate, thus leaving 393 g of precipitate.
can get. When distilled using a Widmer rectifier (120 mm), an ester with a boiling point of 76°C/0.02 mmHg is produced.
345 g (90% yield) are obtained. (b) 85 g of sodium amide (50% suspension in toluene) in a completely dry, nitrogen-flushed round bottom flask.
(1.1 mol) and 180 g of isopropyl ether are added thereto, and a solution of 150.2 g (1 mol) of acetyl anisole dissolved in 180 g of isopropyl ether is added dropwise at a temperature of 50°C to 60°C. The reaction begins immediately and a white paste-like mass forms. Once the addition is complete, add another 30 g of the mixture.
Stir for a minute and then quickly add 192.3 g of p-tert-butylbenzoic acid methyl ester at 25°C to 30°C. Heat the mixture at room temperature for 30 minutes, then at 60°C to 70°C
Stir for 3 hours and leave for 12 hours. 200
g of ice was added and the mixture was dissolved in 128 g (1.1 g) of industrial hydrochloric acid.
mol) and acidify with 200 ml of ice water. The mixture is stirred until the sodium salt of the product is dissolved. The phases separate and the organic phase is washed with ice water until neutral. The organic phase is concentrated on a rotary evaporator and 290 g of isopropyl ether are recovered. The crude product weighs 347 g and contains solvent. Recrystallization from methanol gives 199.8 g (64.5%) of 4-(1,1-dimethylethyl)-4'-methoxydibenzoylmethane, melting point 83.5°C. (c) 36 g (1.2 moles) of 80% sodium amide and 300 g of dry toluene are placed in a round bottom flask flushed with nitrogen. Heat the mixture to 50°C,
150.2g (1 mol) of acetylanisole in 309
g dissolved in toluene is added within 1.5 hours. After the addition was complete, the mixture was kept at 50°C for 15 minutes and then at this temperature 192.3 g (1 mol) of p.
-Tertiary butylbenzoic acid methyl ester for 1 hour
Add within 50 minutes. The mixture is further stirred at 50° C. for 1 hour, and after the product has separated out as a solid precipitate, it is heated at 100° C. for 1 hour. Let the mixture stand for 12 hours, then add there 300 ml of ice water, then 100 ml of ice water
Add a mixture of ml pure hydrochloric acid and 250 ml ice water. The phases separate and the organic phase is washed twice with water. Dry the organic phase with sodium sulfate and simultaneously
Treat with 20g activated carbon. After filtration, the liquid is concentrated until crystallization begins. Add 50 ml of hexane, cool the mixture and filter through a Buchner funnel. When recrystallized from 600ml of methanol, 4
-(1,1-dimethylethyl)-4'-methoxydibenzoylmethane total yield 220.91g (71.2%)
obtained, with a melting point of 83.5°C.

Claims (1)

[Claims] 1 4-(1,1-dimethylethyl)-4'-methoxydibenzoylmethane. 2. A UV-absorbing light-shielding agent containing 4-(1,1-dimethylethyl)-4'-methoxydibenzoylmethane. 3. The light shielding agent according to claim 2, wherein an ultraviolet B filter is used when 4-(1,1-dimethylethyl)-4'-methoxydibenzoylmethane is used. 4 formula Compounds and formulas with 4-(1,1- A method for producing (dimethylethyl)-4'-methoxydibenzoylmethane.