JPH04178368A - Heteroaromatic ketone derivative and uv absorber containing the same derivative and cosmetic containing the same absorber - Google Patents

Abstract

NEW MATERIAL:A heteroaromatic ketone derivative expressed by formula I [m is 0-3; n is 2 or 3, provided that m+n are <=5; R is OH, 1-8C hydrocarbon, 1-8C alkoxy, 1-8C alkenyloxy, 1-8C (polyoxyalkylene)oxy or two R together form alpha-methylenedioxy]. EXAMPLE:2,6-Bis(4,4-dimethylpentane-1,3-dionyl)pyridine. USE:A UV absorber. Cosmetic having excellent sun burn preventing effect. The derivative expressed by formula I has remarkable stability. PREPARATION:For example, a heteroaromatic carboxylic acid derivative expressed by formula II (R<1> is methyl, ethyl, n-propyl or n-butyl) is condensed with pinacolin expressed by III to provide the compound expressed by formula I.

Description

Detailed Description of the Invention [Industrial Application Field] The present invention provides a novel heteroaromatic ketone derivative that has ultraviolet absorbing action and excellent photostability, and a novel heteroaromatic ketone derivative containing the same that prevents sunburn. This invention relates to highly effective ultraviolet absorbers and cosmetics.

[Conventional technology]

Ultraviolet rays are known to cause various changes in the skin. Dermatologically, the working wavelength is 400 to 320n.
It is divided into long wavelength ultraviolet rays of m, medium wavelength ultraviolet rays of 320 to 290 nm, and short wavelength ultraviolet rays of 290 nm or less.
They are called VA, 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.

When UV-B is irradiated to the skin with a certain amount of light, it causes changes in the skin, such as the formation of erythema and chickenpox, as well as accelerated melanin formation and pigmentation. On the other hand, UV
-A causes a blackening effect on the skin (immediate blackening) immediately after irradiation, and since the energy reaches the dermis, it causes changes in the elastic fibers in blood vessel walls and connective tissues. It is believed that the effects of both UV-A and UV-B accelerate skin aging and are a factor in the appearance of age spots, wrinkles, and freckles.

As the effects of ultraviolet rays on human skin become clearer, compounds that absorb UV-A and UV-B have been developed.

It is said that it is desirable that such ultraviolet absorbers satisfy all of the following conditions.

■ Absorb UV-B or UV-A light as completely as possible.

■ Stable against light and heat.

■ No toxicity, irritation or other adverse effects on the skin.

■　Effects should last.

■ Excellent compatibility with cosmetic bases.

Conventionally, as UV-A absorbers, for example, dibenzoylmethane derivatives have been used, and as UV-B absorbers, derivatives such as cinnamic acid ester, benzophenone, paraminobenzoic acid, and salicylic acid have been used.

[Problem to be solved by the invention]

However, these conventional ultraviolet absorbers do not necessarily fully satisfy the above-mentioned conditions, and in particular, their stability against light is insufficient, and it is known that they decompose or react with ultraviolet light [Int, J.

Cosmetic 5science, 10.53(1
98g)] o Such decomposition of ultraviolet absorbers not only leads to a reduction in the duration of their effects, but also the effects on the skin of the decomposed products themselves or products generated by reaction with the formulation cannot be ignored [Fragrance Journal, 84 .34
(1987)].

Therefore, there has been a desire for an ultraviolet absorber that satisfies the above conditions, particularly an ultraviolet absorber that has excellent stability against light.

[Means to solve the problem]

Under such circumstances, the present inventors have made extensive studies to solve the above problems, and have found that the heteroaromatic ketone derivative represented by the general formula (I) below has excellent UV-A and UV-B properties.
The present invention was completed based on the discovery that it has an absorbing effect and is extremely stable against light, and that by blending it, a cosmetic with excellent sunburn prevention effects can be obtained.

That is, the present invention provides the following general formula (I) (R)-Ar (:C[]CH2C[1C(CH
3) In the formula (I)C, p represents an integer of O to 3, and q represents an integer of 1 to 3. However, p+q is 5
It is as follows. Ar represents a heteroaromatic ring containing one or more heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom, and a sulfur atom; p R's may be the same or different; a hydroxyl group; 8 straight chain or branched hydrocarbon group, alkoxy group having 1 to 8 carbon atoms, 1 carbon number
~8 alkenyloxy group or (polyoxyalkylene)oxy group, and two R's may be taken together to form an α-methylenedioxy group] Contains a heteroaromatic ketone derivative represented by It provides ultraviolet absorbers and cosmetics.

Furthermore, among the compounds of general formula (I), the following general formula (I)
The heteroaromatic ketone derivative represented by ' is a new compound.

Therefore, the present invention is directed to the following general formula (I)' [wherein m represents a number from 0 to 3, and n represents an integer of 2 or 3]. However, m+n is 5 or less. The m R's may be the same or different, and include a hydroxyl group, a linear or branched hydrocarbon group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, and an alkenyloxy group having 1 to 8 carbon atoms. or (polyoxyalkylene)oxy group, and two R's may be taken together to form an α-methylenedioxy group].

In the above general formulas (I) and (1)', the straight or branched hydrocarbon group having 1 to 8 carbon atoms represented by R is, for example, a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group. , isobutyl group, 5ec-butyl group, tart-
Butyl group, pentyl group, isopentyl group, neopentyl group, tert-pentyl group, 1-methylbutyl group, 2-
Methylbutyl group, 1,2-dimethylpropyl group, hexyl group, isohexyl group, 1-methylpentyl group, 2-methylpentyl group, 3-methylpentyl group, 1.1-dimethylbutyl group, 1,2-dimethylbutyl group , 2.2-
Dimethylbutyl group, 1,3-dimethylbutyl group, 2.
3-dimethylbutyl group, 3,3-dimethylbutyl group, l
, 1. Alkyl groups such as 2-trimethylpropyl group, heptyl group, octyl group; vinyl group, 1-propenyl group,
Allyl group, isopropenyl group, 1-butenyl group, 2-butenyl group, 2-pentenyl group, l-hexenyl group, 1-
Alkenyl groups such as octenyl; alkynyl groups such as ethynyl, propynyl, and butynyl; cycloalkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohebutyl, and cyclooctyl; phenyl, etc. aryl groups; aralkyl groups such as benzyl groups; and the like.

Further, in the above general formulas (1) and (I)', examples of the alkoxy group having 1 to 8 carbon atoms represented by R include methoxy group, ethoxy group, n-propyloxy group, n-butoxy group, tert- Butoxy group etc.; carbon number 1-8
Examples of the alkenyloxy group include allyloxy group, butenyloxy group, pentenyloxy group, hexenyloxy group, etc.; Examples of the (polyoxyalkylene)oxy group include methoxymethoxy group, methoxyethoxymethoxy group, etc.

Furthermore, two Rs can also form an α-methylenedioxy group.

Among these R, an alkoxy group or an alkenyloxy group having 1 to 3 carbon atoms is particularly preferable, and specific examples thereof include a methoxy group, an ethoxy group, an n-propyloxy group, and an aryoloxy group.

Further, in the above general formula (I), the heteroaromatic ring represented by Ar includes a furan ring, a thiophene ring, a pyrrole ring,
Oxazole ring, thiazole ring, pyrazole ring, imidazole ring, 1: 2.3-) IJRyozole ring, 1,
2. Heteroaromatic five-membered rings such as 4-triazole ring and tetrazole ring; Heteroaromatic six-membered rings such as pyridine ring, pyridazine ring, pyrimidine ring, pyrazine ring: indole ring,
Examples include heteroaromatic rings in which multiple rings are condensed, such as purine ring, quinoline ring, isoquinoline ring, cinnoline ring, quinazoline ring, quinoxaline ring, phthalazine ring, pterin ring, chromone ring, acridine ring, phenazine ring, and bovine santhone ring. It will be done.

Moreover, in general formula (I), q is an integer of 1 to 3, but 2 or 3 is particularly preferable.

The heteroaromatic ketone derivative (I) in the present invention can be produced by a known method, for example, J, Am
, Chem, Sac, 73.5514 (1951
), J. Am.

Chem, Soc, 80.4891 (1958)
, J,' prakt, Chem.

315, 3H1973) according to the reaction formula (a) or (ra) shown below.

(a) (R)p-Ar-(COOR'), + q
C83COC(CH3)3(n)
(I) (R) p-Ar −[COCH2C0C(CH5)=)
.

(I) [In the formula, Rl represents a methyl group, ethyl group, n-propyl group, or n-butyl group, and R, Ar, p and q have the same meanings as above] That is, a heteroaromatic carboxylic acid derivative ( II) Heteroaromatic ketone derivative (I) is produced by condensing with Tojinacolon (I).

This reaction is carried out in a solvent such as anhydrous tetrahydrofuran, toluene, or xylene at 20 to 150°C using a base as a catalyst.
It is preferable to carry out the heating for several tens of minutes to 10 hours. In addition, the bases used here include metal hydrides such as IJium; metal alkylates such as butyl lithium; amines such as triethylamine; metal amides such as sodium amide; metal alkoxides such as sodium methoxide. Examples include compounds.

(b) (R)p-Ar-(C[]CH3), +q
(CH3) 3CCOOR' (TV)
(V) (R)P Ar [C[1CLC(IC(C
L) 3 pieces.

(I) [In the formula, R', R, Ar, p and q have the same meanings as above] That is, by condensing the acetyl heteroaromatic derivative (1'V) and the ester compound (V) , a heteroaromatic ketone derivative (1) is produced.

The ester (V) used in this reaction includes methyl pivalate, ethyl pivalate, propyl pivalate,
Examples include butyl pivalate.

Moreover, this reaction is carried out under the same conditions as in the previous method (a).

The ultraviolet absorber of the present invention containing the heteroaromatic ketone derivative (I) thus obtained may use one or more of these heteroaromatic ketone derivatives (I) as is, Preferably, it is added to a carrier and mixed therewith. This carrier may be in any form as long as it is inert to the heteroaromatic ketone derivative (I), and may be in any form such as solid, liquid, emulsion, foam, or gel. Typical examples include water, alcohol,
Examples include oils and fats (for example, hydrocarbon oils, fatty acid esters, long-chain alcohols, silicone oils), fine powders such as starch or talc, and low-boiling hydrocarbons or halogenated hydrocarbons used as aerosol propellants. The ultraviolet absorber of the present invention further includes a heteroaromatic ketone derivative (I) of the present invention.
) Other ingredients such as preservatives, fragrances, colorants, surfactants, etc. may be added as long as they do not impair the ultraviolet absorbing effect of the ingredients.

In addition, the cosmetic composition of the present invention containing the heteroaromatic ketone derivative (I) can be prepared by appropriately selecting one or more heteroaromatic ketone derivatives (I) that have an affinity for the cosmetic base. It is prepared by blending this into a known cosmetic base by a conventional method and making it into a dosage form such as a cream, solution, oil, spray, stick, milky lotion, foundation, or ointment.

That is, by selectively using the heteroaromatic ketone derivative (1) according to the cosmetic base, oil-based cosmetic oils, oil-based creams and emulsions that contain a large amount of oil, and weak oil-based cosmetics that contain a large amount of water can be used. We manufacture all types of cosmetics with UV absorption properties, from basic cosmetics such as oil-based creams, weak oil-based emulsions, and water-based lotions to makeup products such as oil-based foundations and lipsticks. can do. Suitable bases and solvents for the cosmetics of the present invention include hydrocarbons such as solid or liquid halafine, crystal oil, ceresin, osikelite or montan wax; vegetable oils such as olive, earth wax, carnauba wax, lanolin or spermaceti. Or animal fat or wax; also stearic acid, valmitic acid,
Oleic acid, glycerin thenostearate, glycerin distearate, glycerin thenoleate, isopropyl myristate,
Fatty acids and their esters such as isopropyl stearate or butyl stearate; alcohols such as ethyl alcohol, isopropyl alcohol, cetyl alcohol, stearyl alcohol, palmityl alcohol or hexyldodecyl alcohol; and the like.

Further, polyhydric alcohols having a moisturizing effect such as glycol, glycerin or sorbitol can also be used.

The amount of the heteroaromatic ketone derivative (I) in the ultraviolet absorber and cosmetics of the present invention is not particularly limited as it may vary depending on the form of use, and it is sufficient that it is present in an effective amount, but generally in the entire composition. It is preferable that the amount is 0.1 to 20% by weight, particularly 0.5 to 10% by weight.

The UV absorbers and cosmetics of the present invention may contain only the heteroaromatic ketone derivative (1), but may also contain other UV absorbers and cosmetics.
It is more preferable to use it as an ordinary sunscreen cosmetic in combination with a B absorber or a UV-A absorber.

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-methoxycinnamate ester, 2
Examples include -phenyl-5-methylbenzoxazole and p-dimethylaminobenzoic acid esters. In addition, as a UV-A absorber, for example, 4-methoxy-2
・-carboxybenzoylmethane, 4-methoxy-4'
Examples include -t-butyldibenzoylmethane, 4-isopropyldibenzoylmethane, 2-hydroxy-4-methoxybenzophenone, and dibenzylidene camphor.

Furthermore, in addition to the above-mentioned components, various additives can be added to the cosmetic composition of the present invention. Suitable additives include, for example, W2O type and O/W type emulsifiers. As this emulsifier, a commercially available emulsifier can be used. Thickeners such as methylcellulose, ethylcellulose or carboxymethylcellulose, polyacrylic acid, tragacanth, agar or gelatin can also be added as additives.

Furthermore, fragrances, preservatives, humectants, emulsion stabilizers, medicinal ingredients, and/or physiologically acceptable colorants may be added as necessary.

〔Example〕

EXAMPLES The present invention will be described in more detail below with reference to Examples and Test Examples.

Example 1 2.6-bis(4,4-dimethylpencune-1,3-dionyl)pyridine (Ia) (m in general formula (I)'
=0. Synthesis of n=2): 18.14 g (0,45 moj2) of 60% sodium hydride, 2,6-pyridine in a 500 ml three-lough flask equipped with a stirrer, dropping funnel, reflux condenser and nitrogen inlet tube. Methyl dicarboxylate 19.53g (0.10m
oj2), dispersed and mixed in 200 companies' xylene,
It was heated to 120°C. Here, 22.0g of Vinacologne
(0.22 moA) was carefully added dropwise, and heating and stirring was continued for 1 hour. After cooling, the reaction mixture was diluted with 1N hydrochloric acid 100-
The organic matter was extracted twice with chloroform. The extract was thoroughly washed with water and then dried over anhydrous magnesium sulfate.

After distilling off the solvent, silica gel column chromatography was performed using hexane and 5% ethyl acetate as a developing solvent to obtain 9.10 g (yield 27%) of the title compound as a colorless solid.

Melting point: 124.9-125.4°C IR (v K-, cm-'): 3100, 29
72.1612.1572.1464.1366, 13
0B.

1268, 1222. 1130. 1098. 1
076, 996. 940°930, 884.806
．． 740.684.642.560.476'H-NM
R(CCβ4.δ): 1,30 (18H,s, t-Bu)7,05 (2
H, s) 7, 78-8.35 (3H, m, Aromatic)
15,83 (2H, bs) Example 2 2.5-bis(4,4-dimethylpentane-1,3-dionyl)pyridine (Ib) (general formula (m=
0. Synthesis of n = 2): 60% sodium hydride 1 in a 500-meter flask equipped with a stirrer, dropping funnel, reflux condenser and nitrogen inlet tube.
8.06 g (0.45 mojl), 19.52 g (0.10 mojl) of methyl 2.5-pyridinedicarboxylate
A), disperse and mix in 200-g xylene,
Heated to 0°C. Here, 33.0g of Vinacologne (0
, 33 moA) was carefully added dropwise, and heating and stirring were continued for 3 hours. After cooling, the reaction mixture was poured into 1N hydrochloric acid (100%), and the organic matter was extracted twice with chloroform. The extract was thoroughly washed with water and then dried over anhydrous magnesium sulfate. After distilling off the solvent, silica gel column chromatography was performed using hexane and 5% ethyl acetate as a developing solvent to obtain 24.80 g (yield: 75%) of the title compound as a colorless solid.

Melting point: 93.3-93.8°C IR (XBr, Cm-'): 296B, 1594.1458.1:364.128
2.1220.1124°1092, 1016.970
．． 846.824.798.742.474' H-N
MR (CCffl 4+δ): 1, 23 (18H,s
, t-Bu)6,27 (11-1,s) 6,93 (LH,s) 7,97~8.40 (2H,m, Aromatic
)9,03 (LH,d, J=2.0Hz, Aro
matic) 15,90 (IH, bs) 16.35 (LH, bs) Test Example 1 Ultraviolet absorption effect of the compound of the present invention: 2,6- obtained in Examples 1 and 2 as the compound of the present invention
Bis(4,4-dimethylpentane-1,3-dionyl)
Pyridine (I a) and 2,5-bis(4,4-dimethylpentane-1,3-dionyl)pyridine (I b)
and 2-hydroxy-4-methoxybenzophenone (UV-, 'I collector: comparative compound 1) as a comparative compound.
and 2-ethylhexyl-p-methoxycinnamate (UV-Btu absorbent: comparative compound 2), and the ultraviolet absorption effect (absorbance) was measured by the following measuring method. The results are shown in Table 1.

(Measurement method) 2.5 x 10-'m of the present invention compound and comparative compound
After preparing an ethanol (99.5% reagent special grade) solution with o R/l concentration and placing it in a quartz cell (1 cm x 1 cm),
It was measured using a self-recording spectrophotometer, model U-3410 manufactured by Hitachi.

Table 1 Ultraviolet absorption effect
For V-B ultraviolet light, the comparative compound 2-hydroxy-4
-methoxybenzophenone or 2-ethylhexyl-p
-It has a stronger absorption effect than methoxycinnamate, indicating that it has a high sun protection effect.

Test Example 2 Stability of the compound of the present invention against ultraviolet light: (Experimental method) The compound of the present invention and the comparative compound were dissolved in a solvent of 99.5% ethanol/distilled water (3/2) to a concentration of 2 mmol/A, and exposed to sunlight. Ultraviolet rays were irradiated for 14 hours using a xenon light resistance tester having a wavelength and intensity very similar to that of light. After distilling off the solvent, quantitative analysis was performed and stability was evaluated from the residual rate. The results are shown in Table 2.

Below is a blank table 2 Ia: 2.6-bis(4,4-dimethylpenkune-1,
3-dionyl)pyridine Ib: 2,5-bis(4,4-dimethylpencune-1,
3-dionyl)pyridine Ic: 2-(4,4-dimethylpentane-1,3
-dionyl)pyridine (p = 0. q = 1° in general formula (I) of pyridine as a heteroaromatic ring) I d : 3-(4,4-dimethylpencune-1,3
-dionyl)pyridine (Pyridine as p=0.q=1° heteroaromatic 88 in general formula (I)) Ie: 2-(4,4-dimethylpentane-1,3
-dionyl)furan (p=0.q=1° in general formula (I) of furan as a heteroaromatic ring) If: 2-(4,4-dimethylpencune-1,3
-dionyl)thiophene (in general formula (I) p=o, q=1° of thiophene as a heteroaromatic ring) 1:2-hydroxy-4
-methoxybenzophenone 2:2-ethylhexyl-p
-Methoxycinnamate From the results in Table 2, 4-methoxy-4'-t-butyldibenzoylmethane, which is commonly used as a UV-A absorber, or 2-ethylhexyl-, which is commonly used as a UV-Btu absorbent, It is clear that, compared to p-methoxycinnamate, the compounds of the present invention have significantly better stability against ultraviolet light.

Example 3 0/W type cream: The following composition was blended according to a conventional method to prepare a 0/W type cream.

[Composition] (% by weight)2.
5-bis (4,4-dimethylpentane 2.0-
1,3-dionyl)pyridine (I b) stearic acid
1.0 Lipophilic monostearic acid glyceride 2,0 Cetyl alcohol
1.0 stearyl alcohol
1.0 Squalane 1
0.0 Liquid paraffin 20.
0 Vaseline 5,0
Butylparaben 0.1 Methylparaben 0.1 Triethanolamine 1.0 Glycerin
10.0 fragrance
Appropriate amount 100.0 Example 4 0/W type cream: The following composition was blended according to a conventional method to prepare a W/○ type cream.

[Composition] (% by weight) Sorbitan sesquioleate 4.0 Aluminum stearate 0.5 Hetyl alcohol 4.0 Liquid paraffin
16.0 squalane
10.0 Isopropyl myristate
5.0 Sodium benzoate
0.3 Glycerin 10.
0 Fragrance Appropriate amount 100.0 Example 5 0/W type emulsion: The following composition was blended according to a conventional method to prepare an 0/W type emulsion.

[Composition] (% by weight)2.
5-bis(4,4-dimethylpentane 3.0-1
,3-dionyl)pyridine(Ib) stearic acid
2.0 Sorbitan monostearate 1.5 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 carb ball
0.2 caustic potash
0.4 fragrance
appropriate amount of water
Balance 100.0 Example 6 Lotion: The following composition was blended according to a conventional method to prepare a lotion.

〔Effect of the invention〕

Since the heteroaromatic ketone derivative (I) of the present invention has an excellent ultraviolet absorbing effect and excellent stability, an ultraviolet absorber or cosmetic containing the same has an excellent sunburn prevention effect. .

that's all

Claims (1)

[Claims] 1. The following general formula (I)' ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I)' [In the formula, m represents a number from 0 to 3, and n represents a number of 2 or 3. Indicates an integer. However, m+n is 5 or less. The m R's may be the same or different, and include a hydroxyl group, a linear or branched hydrocarbon group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, and an alkenyloxy group having 1 to 8 carbon atoms. or (polyoxyalkylene)oxy group, and two R's may be taken together to form an α-methylenedioxy group]. 2. The following general formula (I) (R)_p-Ar-[COCH_2COC(CH_3)
＿3〕＿q(I)〔In the formula, p represents an integer from 0 to 3,
q represents an integer of 1 to 3. However, p+q is 5 or less. Ar represents a heteroaromatic ring containing one or more heteroatoms selected from the group consisting of nitrogen atoms, oxygen atoms, and sulfur atoms, and p R's may be the same or different,
Indicates a hydroxyl group, a linear or branched hydrocarbon group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkenyloxy group having 1 to 8 carbon atoms, or a (polyoxyalkylene)oxy group, and two R may be taken together to form an α-methylenedioxy group.] An ultraviolet absorber containing a heteroaromatic ketone derivative represented by the following. 3. A cosmetic containing the heteroaromatic ketone derivative according to claim 2.