JPH04305558A - Benzoylethaneamide derivative, ultraviolet absorbing agent and cosmetic containing the same derivative - Google Patents

Abstract

PURPOSE:To obtain a new compound useful as an ultraviolet absorbing agent and cosmetic having excellent ultraviolet ray absorbing action over wide wavelength region and having excellent sun-burn preventing effect. CONSTITUTION:A compound expressed by formula I [R<1> to R<4> are H, 1-6C alkyl (R<1> and R<2> or R<3> and R<4> may form alkylene together) or 6-10C aryl), e.g. 1-dimethylamino-3-(4-dimethylaminophenyl)-1,3-propanedione. The compound expressed by formula I can be obtained by condensing benzoate expressed by formula II (R is methyl, ethyl, n-propyl or n-butyl) and acetamide expressed by formula III in the presence of a catalyst (e.g. sodium hydride) in a solvent such as THF at 20-150 deg.C. The compound expressed by formula I is blended at an mount of 0.1-20wt.% based on total composition to provide the objective ultraviolet absorbing agent or cosmetic.

Description

Detailed Description of the Invention [0001] [Industrial Application Field] The present invention provides a novel benzoylethanamide derivative that exhibits an excellent ultraviolet absorption effect over a wide wavelength range, and a novel benzoylethanamide derivative that contains the same and has an excellent sun protection effect. This invention relates to ultraviolet absorbers and cosmetics. BACKGROUND OF THE INVENTION It is known that ultraviolet rays cause various changes in the skin. Dermatologically, the action wavelength is divided into long wavelength ultraviolet rays from 400 to 320 nm, medium wavelength ultraviolet rays from 320 to 290 nm, and short wavelength ultraviolet rays below 290 nm.
They are called A, UV-B, and UV-C. Ultraviolet rays in sunlight are UV-A and UV-B, and UV-C is absorbed in the ozone layer and hardly reaches the ground. [0003] When UV-B is irradiated onto the skin in an amount exceeding a certain level, it causes changes in the skin, such as forming erythema and blisters, promoting melanin formation, and causing pigmentation. The destruction of the ozone layer in the sky due to air pollution in recent years has become a serious problem because it causes an increase in UV-B. On the other hand, UV-A causes a blackening effect on the skin (immediate blackening) immediately after irradiation, and since its energy reaches the dermis, it causes changes in blood vessel walls and elastic fibers in connective tissues. Such UV-A and UV
- Both effects of B accelerate skin aging, causing age spots, wrinkles, and
It is thought to cause freckles, etc., and in the long term, to cause skin cancer. [0004] As the effects of ultraviolet rays on human skin become clearer, compounds that absorb UV-A and UV-B have been developed. Such ultraviolet absorbers include (1) UV-B or UV-
(2) be stable to light and heat; (3) have no toxic, irritating, or other toxic effects on the skin; and (4) be effective. It is said that it is desirable that all conditions such as (5) excellent compatibility with the cosmetic base be satisfied. Conventionally, as UV-A absorbers, for example,
Dibenzoylmethane derivatives are used as UV-B absorbers, and derivatives such as cinnamic acid ester, benzophenone, p-aminobenzoic acid, and salicylic acid are used. However, these conventional ultraviolet absorbers only absorb in a specific UV-A or UV-B wavelength range, and do not necessarily fully satisfy the above conditions. [0007]Therefore, there has been a desire for compounds with excellent UV-A and UV-B absorption effects, as well as ultraviolet absorbers and cosmetics with excellent sun protection effects. [Means for Solving the Problems] Under these circumstances, the present inventors conducted extensive research and found that benzoylethanamide derivatives represented by general formulas (1) and (2) below are
The present invention was completed based on the discovery that it exhibits excellent ultraviolet absorption over a wide wavelength range. That is, the present invention provides the following general formula (1) or (2) [In the formula, R1, R2, R3 and R4 are the same or different, hydrogen atom, carbon number 1-6] represents a lower alkyl group (R1 and R2 or R3 and R4 may be combined to form an alkylene group) or an aryl group having 6 to 10 carbon atoms]
[In the formula, R5, R6, R7 and R8 are the same or different, and are a hydrogen atom or a lower alkyl group having 1 to 6 carbon atoms (R5 and R6 or R7 and R8 combine to form an alkylene group) ) or an aryl group having 6 to 10 carbon atoms, and R
9 represents an alkylene group having 1 to 6 carbon atoms], and ultraviolet absorbers and cosmetics containing the benzoylethanamide derivative. In the present invention, general formulas (1) and (2)
Examples of lower alkyl groups having 1 to 6 carbon atoms represented by R1, R2, R3, R4, R5, R6, R7 and R8 include methyl group, ethyl group, n-propyl group, iso
-propyl group, n-butyl group, iso-butyl group, t-
Examples include butyl group, n-pentyl group, 2-methylbutyl group, etc. R1 and R2, R3 and R4, R5 and R6 or R7
and R8 may be combined to form an alkylene group. Further, examples of the aryl group having 6 to 10 carbon atoms include phenyl group, o-tolyl group, m-tolyl group, p-tolyl group,
2,3-xylyl group, 2,4-xylyl group, o-cumenyl group, m-cumenyl group, p-cumenyl group, mesityl group,
Examples include benzyl group, 1-naphthyl group, and 2-naphthyl group. Furthermore, the alkylene group having 1 to 6 carbon atoms represented by R9 includes, for example, a methylene group, an ethylene group, a trimethylene group, a tetramethylene group, a pentamethylene group, a hexamethylene group, and the like. Further, among these compounds of the present invention, a compound represented by the general formula (2) in which R7 and R8 are bonded to form an ethylene group is particularly preferred. Benzoylethanamide derivatives of the present invention (
1) and (2) can be carried out, for example, by known methods [J. Am. Ch
em. Soc. , 80, 4891 (1958); J
．． Chromatogr. , 312, 109 (19
84) ;J. Polym. Sci. Poly. Che
m. Ed. , 20, 3079 (1982)], it can be produced by the following method (a) or (b). Method (a) [In the formula, R represents a methyl group, ethyl group, n-propyl group or n-butyl group, and R1, R2, R3 and R4 have the same meanings as above] That is, the benzoylethanamide derivative (1) of the present invention can be produced by condensing benzoate (3) and acetamide (4). The reaction involves anhydrous tetrahydrofuran, toluene,
The reaction is carried out in a solvent such as xylene, preferably using a base as a catalyst, at 20 to 150°C for several tens of minutes to 10 hours. Examples of the base used here include metal hydrides such as sodium hydride; metal alkylated compounds such as butyllithium; amines such as triethylamine; metal amides such as sodium amide; metal alkoxide compounds such as sodium methoxide, etc. Can be mentioned. Method (b) [In the formula, R, R5, R6, R7, R8 and R9 have the same meanings as above] That is, condensing benzoate (5) and diacetamide (6) Accordingly, the benzoylethanamide derivative (2) of the present invention can be produced. The reaction is carried out under the same conditions as in method (a) above. The ultraviolet absorber of the present invention is a benzoylethanamide derivative (1) or (2) obtained as described above.
) may be used as is, but preferably in the form of a mixture added to a carrier. As a carrier, the above benzoylethanamide derivative (1
) or (2), it is not particularly limited as long as it is inert, and it may be solid, liquid, emulsion, foam, gel, etc. Typical examples include water, alcohol, fats and oils (e.g. hydrocarbon oils, fatty acid esters, long chain alcohols, silicone oils, etc.), fine powders (e.g. starch, talc, etc.), and low-carbon compounds used as aerosol propellants. Examples include boiling point hydrocarbons and halogenated hydrocarbons. Furthermore, the ultraviolet absorber of the present invention may contain other ingredients, such as preservatives, fragrances, colorants, surfactants, etc., to the extent that the ultraviolet absorbing effect of the benzoylethanamide derivative (1) or (2) is not impaired. They can be blended as appropriate. The cosmetic composition of the present invention contains a benzoylethanamide derivative (1) or (2), which has an affinity for the cosmetic base. ) can be manufactured by blending one or more of them into a known cosmetic base by a conventional method, and can be made into a dosage form such as a cream, solution, oil, spray, stick, emulsion, foundation, ointment, etc. can. That is, by selectively using benzoylethanamide derivatives (1) or (2) according to the cosmetic base, oil-based cosmetic oils, oil-based creams and oil-based emulsions containing a large amount of oil, and large amounts of water can be used. From basic cosmetics such as weakly oily creams, weakly oily emulsions, and water-based lotions, to make-up cosmetics such as oil-based foundations and lipsticks, all forms of UV-absorbing products are used. Cosmetics can be manufactured. Suitable bases and solvents include hydrocarbons such as solid or liquid paraffin, crystal oil, ceresin, ozokerite, montan wax; vegetable oils or animal oils such as olive oil, earth wax, carnauba wax, lanolin, spermaceti. Fats and oils; stearic acid, palmitic acid,
Oleic acid, glycerin monostearate, glycerin distearate, glycerin monooleate, isopropyl myristate,
Examples include fatty acids and their esters such as isopropyl stearate and butyl stearate; alcohols such as ethyl alcohol, isopropyl alcohol, cetyl alcohol, stearyl alcohol, palmityl alcohol, and hexyldodecyl alcohol. Further, polyhydric alcohols having a moisturizing effect such as glycol, glycerin, and sorbitol can also be used. In the ultraviolet absorber and cosmetics of the present invention, the amount of the benzoylethanamide derivative varies depending on the form of use, so it is not particularly limited as long as it is present in an effective amount, but generally 0% is present in the entire composition. .1 to 20% by weight,
Preferably, it is blended in an amount of 0.5 to 10% by weight. The ultraviolet absorber and cosmetics of the present invention can be used in combination with other UV-B absorbers or UV-A absorbers in addition to the benzoylethanamide derivative (1) or (2), and can be used in ordinary sunscreen cosmetics. It is more preferable to use it as a supplement. Such UV-B absorbers include, for example, p-
Methylbenzylidene-D(L)-camphor or its sulfonic acid sodium salt, 2-phenylbenzimidazole-5-sulfonic acid sodium salt, 3,4-dimethylphenylglyoxylic acid sodium salt, 4-phenylbenzophenone, 4-phenylbenzophenone- 2'-carboxylic acid isooctyl ester, p-methoxycinnamic acid ester, 2-phenyl-5-methylbenzoxazole,
Examples include p-dimethylaminobenzoic acid esters,
As the UV-A absorber, for example, 4-methoxy-2'-
Carboxydibenzoylmethane, 4-methoxy-4'-
Examples include t-butyldibenzoylmethane, 4-isopropyldibenzoylmethane, 2-hydroxy-4-methoxybenzophenone, and dibenzylidene camphor. In addition to the above-mentioned components, the cosmetic of the present invention contains various additives, such as commonly used W/O type and O/W type.
Type emulsifiers; thickeners such as methylcellulose, ethylcellulose, carboxymethylcellulose, polyacrylic acid, tragacanth, agar, gelatin; other fragrances, preservatives, humectants, emulsion stabilizers, medicinal ingredients, physiologically acceptable colorants etc. may be appropriately blended within a range that does not impair the effects of the present invention. [Examples] Next, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited to these Examples. Example 1 1-dimethylamino-3-(4-dimethylaminophenyl)-1,3-propanedione (Compound 1 of the present invention;
Synthesis of R1=R2=R3=R4=CH3 in general formula (1): 2.48 g of 60% sodium hydride was placed in a 300 ml three-necked flask equipped with a stirrer, a dropping funnel, a reflux condenser, and a nitrogen inlet tube. (62 mmol) and 10.0 g (51.7 mmol) of ethyl 4-dimethylbenzoate were added, dispersed and mixed in 100 ml of tetrahydrofuran, and heated under reflux. To this, 5.41 g of dimethylacetamide
A solution of (62 mmol) dissolved in 50 ml of tetrahydrofuran was carefully added dropwise, and the mixture was heated and stirred overnight. After cooling, the reaction mixture was poured into 100 ml of 1N hydrochloric acid.
Organics were extracted twice with chloroform. The extract was thoroughly washed with water and then dried over anhydrous magnesium sulfate. After evaporating the solvent, it was dissolved in a 4:6 mixed solvent of hexane and ethyl acetate and left overnight to obtain a yellow solid. This solid was recrystallized from acetone to obtain 5.16 g (yield: 42%) of the desired title compound as yellow needles. Melting point: 135.5°C IR (ν KBr, cm-1): 2930, 166
0, 1590, 1550, 1490, 1440
, 1420, 1380, 1330, 1240,
1190, 1170, 1130, 1070,
1020, 990, 970, 950, 840,
820, 740, 650, 610, 580,
5701H-NMR (CDCl3, δ): 2.98 (s
, 6H, N-CH3), 3.06(s, 6H, N-C
H3), 4.02 (s, 2H, -CH2-), 6.
65 (d, 2H, J=9.0Hz, Aromatic)
, 7.95 (d, 2H, J=9.0Hz, Aroma
tic) Example 2 N,N'-bis((4-dimethylaminophenyl)-1
,3-propanedionyl)piperazine (Compound 2 of the present invention; in general formula (2), R5=R6=CH3, R7-R
Synthesis of 8=CH2-CH2, R9=CH2CH2): In a 500 ml three-necked flask equipped with a stirring device, dropping funnel, reflux condenser, and nitrogen inlet tube, 2.40 g (60 mmol) of 60% sodium hydride and 4-dimethyl Add 16.9 g (87.5 mmol) of ethyl benzoate and
The mixture was dispersed and mixed in ml of tetrahydrofuran, and the mixture was heated to reflux. To this, N,N'-bisacetylpiperazine 8.
A solution of 0 g (42 mmol) dissolved in 300 ml of tetrahydrofuran and 10 ml of dimethylformamide was carefully added dropwise, and the mixture was heated and stirred overnight. After cooling, the reaction mixture was poured into 100 ml of 1N hydrochloric acid, and the organic matter was extracted three times with chloroform. After washing the extract thoroughly with water,
It was dried with anhydrous magnesium sulfate. After distilling off the solvent,
A yellow solid was obtained by dissolving in a 4:6 mixed solvent of hexane and ethyl acetate and standing overnight. This solid was recrystallized from acetone to obtain 11.1 g (yield 57%) of the desired title compound as yellow needles. Melting point: 255.6°C (decomposition) IR (ν KBr, cm-1): 3500, 292
0, 1660, 1640, 1600, 1550
, 1440, 1380, 1320, 1310,
1250, 1160, 1050, 1020,
810, 5801H-NMR (CDCl3, δ): 3
．． 08(s,12H,N-CH3), 3.41 ~3
．． 78 (m, 8H, piperazine ring), 4.01 ~ 4
．． 05 (d-like, 4H, CH2), 6.65 (
d, 4H, J=9.0Hz, Aromatic), 7
．． 92 (d, 2H, J=9.0Hz, Aromatic
) Test Example 1 Compounds 1 and 2 of the present invention obtained in Examples 1 and 2, as well as comparative compounds 2-hydroxy-4-methoxybenzophenone (UV-A absorber; comparative compound 1) and 2-
Using ethylhexyl-p-methoxycinnamic acid (UV-B absorber; comparative compound 2), the ultraviolet absorption effect (absorbance) was investigated. The results are shown in Table 1. (Measurement method) Dissolve the test compound in ethanol (99.5% reagent grade) and add 2.5
A solution with a concentration of ×10 −5 mol/l was prepared and placed in a quartz cell (1 cm × 1 cm), and then the absorbance was measured using a self-recording spectrophotometer (model U-3410 manufactured by Hitachi). [Table 1] [0023] As is clear from Table 1, the compound of the present invention has a stronger absorption effect for UV-A ultraviolet rays and UV-B ultraviolet rays than the comparative compound, and is found to have a high sunscreen effect. . Example 3 O/W type cream:
An O/W type cream having the following composition was produced by a conventional method. (composition)

(wt%) 1-dimethylamino-3-(4-dimethylaminophenyl)-1,3-propanedione

2.0 Stearic acid

1.0 Lipophilic monostearic acid glyceride
2.0 Polyoxyethylene (23) Sorbitan Monostearate 1.0 Cetyl Alcohol
1.0
stearyl alcohol
1.
0 squalane

10.0 Liquid paraffin

20.0 Vaseline

5.0 Butylparaben
0.
1 Methylparaben

0.1 Triethanolamine

1.0 Glycerin

10.0 Fragrance

Appropriate amount
water

balance

Example 4 O/W type emulsion: An O/W type emulsion having the following composition was produced by a conventional method. (composition)

(wt%) 1-dimethylamino-3-(4-dimethylaminophenyl)-1,3-propanedione

3.0 Stearic acid

2.0 Sorbitan monostearate

1.5 Polyoxyethylene (23) Sorbitan Monostearate 1.0
cetyl alcohol
0
．． 4 Stearyl alcohol

0.3 Isopropyl myristate

7.0 Squalane

5.0 Liquid paraffin

5.0 Solid paraffin
2.0 Ethylparaben
0.
1 Methylparaben

0.1 Carboxyvinyl polymer (Carbopol, manufactured by Goodrich)
0.2 Potassium hydroxide
0.4
fragrance

Appropriate amount of water

balance

100
．． Example 5 Lotion: A lotion having the following composition was produced by a conventional method. (composition)

(wt%) 1-dimethylamino-3-(4-dimethylaminophenyl)-1,3-propanedione

2.0 Polyoxyethylene (23) lauryl ether 4.0
ethanol

10.0 Glycerin

3.0 Dipropylene glycol
7.0 Lactic acid

0.05
sodium lactate

0.12 Methylparaben

0.1 Fragrance

Appropriate amount of pigment


trace amount water

balance

100.0 [
Example 6 W/O type cream:
A W/O type cream having the following composition was produced by a conventional method. (composition)

(wt%) 1-dimethylamino-3-(4-dimethylaminophenyl)-1,3-propanedione

2.0 Sorbitan Sesquioleate
4
．． 0 aluminum stearate
0
．． 5 Cetyl alcohol

4.0 Liquid paraffin

16.0 Squalane

10.0 Isopropyl myristate
5.0 Sodium Benzoate
0.3 Glycerin
1
0.0 fragrance

Appropriate amount of water

balance


100.0 [0028] The benzoylethanamide derivatives (1) and (2) of the present invention exhibit excellent ultraviolet absorbing action over a wide wavelength range, and the ultraviolet rays of the present invention containing the same The absorbent and cosmetic have excellent sun protection effects.

Claims (3)

[Claims] Claim 1: General formula (1) or (2) [Formula 1, R1, R2, R3 and R4 are the same or different, hydrogen atom, lower alkyl group having 1 to 6 carbon atoms (R1 and R2 or R3 and R4 may be combined to form an alkylene group) or an aryl group having 6 to 10 carbon atoms]
[In the formula, R5, R6, R7 and R8 are the same or different, and are a hydrogen atom or a lower alkyl group having 1 to 6 carbon atoms (R5 and R6 or R7 and R8 combine to form an alkylene group) ) or an aryl group having 6 to 10 carbon atoms, and R
9 represents an alkylene group having 1 to 6 carbon atoms]. 2. An ultraviolet absorber containing the benzoylethanamide derivative according to claim 1. 3. A cosmetic comprising the benzoylethanamide derivative according to claim 1.