JPH0761990A - New phosphoric acid diester having uv absoptivity, its production and cosmetic containing thereof - Google Patents

Abstract

PURPOSE:To obtain a new phosphoric acid diester useful as an effective component for sun protection cosmetics, being highly safe for skin and having UV preventing effect with high remaining ability and excellent persistency on skin. CONSTITUTION:A phosphoric acid diester of the formula I[R1 is at least an acyl having 1 benzene ring (preferably p-methoxycinnamoyl, etc.); R2 is a 2-12C alkylene; L is a 2-40C alkyl or a R1-O-R2 group; M is H or an alkali metal ion, etc.; n is valence of M]. E.g. a compound of the formula II, etc. The compound of the formula I is obtained, e.g. by reacting a carboxylic acid having at least 1 benzene ring with a diol having 2-12C alkylene to obtain a monoester derivative, which is reacted with phosphorus oxychloride and then salt-exchanged or neutralized.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a phosphoric acid diester compound having an ultraviolet (UV) absorbing group, which is useful as an active ingredient of sunscreen cosmetics, a process for producing the same, and cosmetics containing the same.

[0002]

2. Description of the Related Art In recent years, it has become clear that ultraviolet rays are deeply involved in skin diseases such as sunburn, aging, and skin cancer, and in addition to the topic of increasing the amount of ultraviolet rays due to the destruction of the ozone layer in recent years, The harmfulness of UV rays to the skin is a problem.

Under these circumstances, it has been recently emphasized that the skin is protected from ultraviolet rays, and various cosmetics such as sunscreen preparations, skin care products, foundations and the like containing ultraviolet protection substances have been put on the market.

Ultraviolet rays are long wavelength ultraviolet rays (UV-A; 32).
0-400 nm), medium wavelength ultraviolet (UV-B; 290-3)
20 nm) and short wavelength ultraviolet rays (UV-C; ~ 290 nm), and the harmfulness of UV-A and UV-B reaching the surface of the earth to the skin is revealed. UV protection substances are being developed.

For example, as UV-A protective substances, inorganic compounds such as titanium oxide, iron oxide and zinc oxide, and oil-soluble organic compounds such as 4-t-butyl-4'-methoxydibenzoylmethane are known. In addition, para-aminobenzoic acid, salicylic acid, methoxycinnamic acid, benzophenone derivatives and the like are known as UV-B protective substances. The former is
The latter can be used as a derivative such as a metal salt to enhance the UV protection effect or can be used as a cosmetic material depending on the purpose, by methods such as microparticulation, ultrafine particle formation, hydrophobic surface treatment, and complexing with other substances. The material is devised. When devising to enhance the effect of such an ultraviolet absorber, safety to the skin and persistence on the skin are particularly important.

Regarding the safety of applying an ultraviolet absorber to the skin, not only the skin irritation of the ultraviolet absorber itself but also the skin irritation caused when the ultraviolet absorber absorbs light must be considered. In order to deal with this problem, measures have been taken to prevent direct contact with the skin without lowering the ultraviolet protection effect of the ultraviolet absorber. For example, JP-A-6
2-181213 and JP-A-60-81124 disclose a method of intercalating an ultraviolet absorber with a clay mineral such as montmorillonite. According to this method, the UV absorber can be inserted between the layers of the clay mineral to enhance the safety to the skin. However, mixing such UV absorbers with oils,
When blended in an emulsion system, there is a problem in that the ultraviolet absorber inserted between layers is exchanged for an oil agent or a surfactant molecule, and the ultraviolet absorber oozes out to come into direct contact with the skin.

Regarding the persistence on the skin, there is a problem that the ultraviolet absorbing effect does not last long because the organic ultraviolet absorbing agent is easily washed off by sweat or oil. In order to solve this problem, a technique of forming an insoluble metal salt as an ultraviolet absorber and coating it on a powder is disclosed in JP-A-60-
It is disclosed in Japanese Patent No. 130655. However, in this case, the ultraviolet absorber effect of the ultraviolet absorber-coated powder is not sufficient, and in order to obtain a high effect, it is necessary to increase the amount of the powder compounded, and the squeaky or powdery feeling is bad. There is a problem that becomes.

On the other hand, a technique for microencapsulating an ultraviolet absorber with an appropriate microcapsule forming agent is disclosed in Japanese Patent Application Laid-Open No. 2-202.
It is disclosed in Japanese Patent No. 251240. In this case, it is technically difficult to use a substance having high safety in cosmetics as a microcapsule-forming agent, and to control the film thickness and shape of the capsule so as not to reduce the UV protection effect. There was a problem.

[0009]

SUMMARY OF THE INVENTION Therefore, an object of the present invention is to provide a UV absorber having a high level of safety on the skin, a high persistence on the skin and a good durability.

[0010]

[Means for Solving the Problems] In view of such circumstances, the present inventors have conducted earnest research to obtain a safe and long-lasting UV absorber. Succeeded in introducing an absorbing group,
This product forms a good thixotropic gel with various oils and other organic oil-based UV absorbers, and as a result, not only is it safe, but it also has excellent persistence on the skin and retention of oil-based UV absorbers. The inventors have found that they are extremely useful as a UV absorber for cosmetics, and completed the present invention.

That is, the present invention provides the following general formula (1):

[0012]

[Chemical 5]

(In the formula, R ¹ represents an acyl group having at least one benzene ring, and R ² is a linear or branched chain in which an oxygen atom may be inserted between carbon atoms having 2 to 12 carbon atoms. Represents an alkylene group, L represents a linear or branched alkyl group in which an oxygen atom may be inserted between carbon atoms having 2 to 40, or R ¹ —O—R ² —, and M represents hydrogen. An atom, an alkali metal ion, a divalent or higher polyvalent metal ion, an ammonium group, an alkanolammonium group having 2 to 14 carbon atoms, an alkylammonium group having 1 to 14 carbon atoms, and n represents a valence of M). Provided are a phosphoric acid diester represented, a cosmetic containing the same, and a method for producing the phosphoric acid diester.

The phosphodiesters of the present invention are represented by the above-mentioned general formula (1), wherein R ¹ represents an acyl group having at least one benzene ring, and the presence of this benzene nucleus causes ultraviolet rays. , For example wavelengths 290-320
Although it has an ultraviolet absorbing ability at nm, a cinnamoyl or benzoyl group which may have a substituent is particularly preferable. Examples of this substituent include an alkoxy group, a hydroxy group, an amino group, an alkylamino group and a dialkylamino group. These may have 1 to 3 substituents on the benzene nucleus of the cinnamoyl or benzoyl group. Here, the alkoxy group is preferably one having 1 to 22 carbon atoms, particularly 1 to 10 carbon atoms, and examples thereof include a methoxy group, an ethoxy group, a propyloxy group, an isopropyloxy group, and n.
-Butyloxy group, tert-butyloxy group, sec
-Butyloxy group, isoamyloxy group, n-hexyloxy group, n-octyloxy group, 2-ethylhexyloxy group, dodecyloxy group, hexadecyloxy group and the like. The alkyl group of the alkylamino group and the dialkylamino group is preferably one having 1 to 22 carbon atoms, more preferably one having 1 to 10 carbon atoms, and as such an alkyl group, a methyl group, an ethyl group, a propyl group, an isopropyl group. Group, n-butyl group, tert-butyl group, sec-butyl group, isoamyl group, n-hexyl group, n-octyl group, 2-ethylhexyl group, dodecyl group, hexadecyl group and the like. More preferable specific examples of R ¹ include p-methoxycinnamoyl group and o-
Methoxycinnamoyl group, p-ethoxycinnamoyl group, o-ethoxycinnamoyl group, o, p-dimethoxycinnamoyl group, 3-hydroxy-4-methoxycinnamoyl group, benzoyl group, p- (N, N-dimethyl) Amino) benzoyl group, p- (N, N-diethylamino) benzoyl group, p-hydroxybenzoyl group, o-hydroxybenzoyl group, p-aminobenzoyl group, o-aminobenzoyl group and the like. Among these, the most preferable are p-methoxycinnamoyl group and benzoyl group.

In the alkylene group represented by R ² in the formula (1), the number of oxygen atoms to be inserted is preferably 1 to 3. Specific examples of R ² include ethylene, propylene, butylene, pentamethylene, hexamethylene, heptamethylene, octamethylene, nonamethylene, decamethylene,
Undecamethylene, dodecamethylene, 3-methylpentamethylene, monooxapentamethylene, trioxaundecamethylene, methylethylene, methylpropylene, methylbutylene, methylpentamethylene groups and the like can be mentioned.

In the formula (1), the alkyl group in which an oxygen atom represented by L may be inserted may be linear or branched, and the carbon number thereof is preferably 8 to 20 and is inserted. The number of oxygen atoms is preferably 1 to 3. Specific examples of L include ethyl group, propyl group, butyl group, pentyl group, hexyl group, heptyl group, octyl group, nonyl group, decyl group, undecyl group, dodecyl group, tridecyl group, tetradecyl group, pentadecyl group, hexadecyl group. , Heptadecyl group, octadecyl group, nonadecyl group,
Eicosyl group, hexaeicosyl group, 2-ethylhexyl group, isostearyl group, 3,7-dimethyloctyl group, methoxyhexyl group, ethoxyhexyl group, 6-
(2-ethylhexyloxy) hexyl group and the like can be mentioned.

Examples of those represented by M include a hydrogen atom, a sodium atom, a potassium atom, a barium atom, a calcium atom, a magnesium atom, an aluminum atom, an iron atom, ethanolammonium, ammonium and ethylammonium, and especially calcium. Atoms and aluminum atoms are particularly preferred.

In the general formula (1), R ¹ is a cinnamoyl group which may have a substituent or a benzoyl group which may have a substituent, and R ² is an alkylene group having 2 to 12 carbon atoms. And L is a linear or branched alkyl group having 8 to 20 carbon atoms, or R ¹ —O—R ² — (wherein R ¹ is a cinnamoyl group which may have a substituent or a substituent. A benzoyl group which may have, R ¹ is an alkylene group having 2 to 12 carbon atoms, and a compound in which M is a calcium atom or an aluminum atom is more preferable; among these, L is a straight chain having 8 to 20 carbon atoms. Alternatively, a compound having a branched chain alkyl group is particularly preferable.

Particularly preferred compounds (1) of the present invention include those represented by the following formulas (1a) to (1w).

[0020]

[Chemical 6]

[0021]

[Chemical 7]

[0022]

[Chemical 8]

[0023]

[Chemical 9]

The compound (1) of the present invention can be produced, for example, by the following reaction formula A or B.

[0025]

[Chemical 10]

(In the formula, R ¹ , R ² , n and M have the same meanings as described above, R ³ represents a residue obtained by removing a carbonyl group from the acyl group represented by R ¹ , and X represents a halogen atom. Show)
That is, as shown in reaction formula A, a carboxylic acid (2) or its acid halide (2 ') is reacted with a diol (3) to obtain a monoester body (4), which is reacted with phosphorus oxychloride. Compounds (1a) to (1i) of the present invention can be obtained by salt exchange or neutralization with phosphoric acid diester (5).

The reaction between the carboxylic acid (2) and the diol (3) is carried out in an inert solvent such as benzene, toluene or hexane,
In the presence of an acid catalyst such as p-toluenesulfonic acid, the diol (3) is used in an amount of 1 to 10 mol times, preferably 3 to 5 mol times, of the carboxylic acid, and the reaction may be performed at 70 to 130 ° C. for 3 to 50 hours. The reaction between the acid halide (2 ′) of the carboxylic acid (2) and the diol (3) is preferably carried out at 0 to 100 ° C. in the presence of a basic catalyst such as pyridine, trialkylamine and alkali metal hydroxide. The reaction of the obtained monoester (4) with phosphorus oxychloride is carried out in an inert solvent such as tetrahydrofuran (THF) in the presence of a base such as triethylamine to give 1.5 to phosphorus oxychloride.
It is advisable to use a 2.5 mol times amount, preferably 2.0 to 2.2 mol times amount of the monoester body (4) at −10 to 10 ° C. The phosphoric acid diester thus obtained can be easily neutralized or salt-exchanged by using sodium hydroxide, potassium hydroxide, calcium chloride, calcium acetate, aluminum acetate or the like in a polar solvent such as methanol, ethanol or water. The compounds (1a) to (1i) of the present invention can be obtained.

[0028]

[Chemical 11]

(In the formula, R ¹ , R ² , R ³ , L, n, M and X are the same as above.) According to reaction formula B, the carboxylic acid (2)
Alternatively, the halide (2 ') thereof is reacted with a diol (3) to obtain a monoester body (4), which is then reacted with phosphorus oxychloride at a low temperature to give an intermediate (6), and an alcohol ( 7) is reacted to form a phosphoric acid diester (8), and then the present compounds (1h) to (1w) are subjected to salt exchange.
Is obtained. The reaction to obtain the intermediate (6) from the monoester (4) and phosphorus oxychloride is carried out by reacting the monoester (4) with phosphorus oxychloride in an inert solvent such as THF in the presence of a base such as triethylamine. 0.5-1.5mol
Double amount, preferably 1.0-1.1 mol double amount -80
It may be performed at -10 ° C, but is preferably performed at -50 to 5 ° C. The reaction between the intermediate (6) and the alcohol (7) is carried out by adding 1.0 to 1.5 mol of the alcohol (7) to the intermediate (6).
THF in 1-fold amount, preferably 1.0-1.1 mol amount
It can be carried out at -10 to 10 ° C in an inert solvent such as. The diphosphate ester (8) thus obtained is subjected to neutralization or salt exchange with sodium hydroxide, potassium hydroxide, calcium chloride, calcium acetate, aluminum acetate or the like in a polar solvent such as methanol, ethanol or water. Thus, the compounds (1h) to (1w) of the present invention can be easily obtained.

The compound (1) of the present invention thus obtained has an excellent ultraviolet absorbing action, particularly a UV-B absorbing action, and exhibits an excellent gelling ability against various oil agents and organic oily ultraviolet absorbers. It is possible to obtain a cosmetic having a high persistence on the skin and a retention of the organic oil-based ultraviolet absorber, that is, a high durability.

Examples of various oil agents used here are hydrocarbon oils, ester oils, silicone oils used for the purpose of suppressing evaporation of water from the skin and improving the feeling of use.
Examples thereof include animal and vegetable oils, and aromatic hydrocarbon oils, aliphatic hydrocarbon oils, saturated or unsaturated fats and oils or synthetic ester oils which are particularly likely to form a thixotropic gel with the phosphodiester salt of the present invention are preferable. Specifically, for example, liquid paraffin, squalane, hexadecane, isohexadecane, neopentyl glycol dicaprate, diisopropyl adipate, myristyl isooctanoate,
1-isostearoyl-3-myristoyl glycerin,
Hexyl laurate, jojoba oil, octyldodecyl oleate, oleyl oleate, glyceryl trioctanoate and the like can be mentioned.

Further, as the organic oily ultraviolet absorber,
Examples thereof include a benzophenone derivative, a paraaminobenzoic acid derivative, a paramethoxycinnamic acid derivative, and a salicylic acid derivative. Specifically, for example, 2-methoxyhexyl paramethoxycinnamate, para-N, N-dimethylaminobenzoic acid 2-
Examples thereof include ethylhexyl, 2-aminohexyl para-aminobenzoate, 2-ethylhexyl para-methoxysalicylate and the like.

The compounding amount of the compound (1) of the present invention in the cosmetic of the present invention is not particularly limited, but if it is too small, the ultraviolet absorbing effect is small, and if it is too large, the skin feel is deteriorated.
0.01 to 80% by weight, particularly 0.1 to 30% by weight is preferable. Further, the above various oil agents are 0.1 to 99.9% by weight,
It is particularly preferable to add 1.0 to 80% by weight.

In addition to the above essential ingredients, the cosmetic composition of the present invention comprises
Depending on the purpose, as long as the effect of the present invention is not impaired, solid or semi-solid fats and oils, moisturizers, intercellular lipids (ceramide, etc.), other UV absorbers, chelating agents, pH adjusters, preservatives, thickeners Agents, dyes, fragrances, medicinal components, anionic surfactants, emulsifiers such as nonionic surfactants (including polyether-modified silicone), detergents, inorganic pigments, organic powders and the like can be appropriately added.

The cosmetic of the present invention can be produced by mixing and stirring the above components in a conventional manner. Since the compound (1) of the present invention can gelate various oil agents and organic oily ultraviolet absorbers as described above, it can be made into an oily cosmetic, an O / W or a W / O emulsion cosmetic, and specifically, It can be used as an emulsion, cream, foundation, etc.

[0036]

The cosmetics using the compound (1) of the present invention are difficult to penetrate into the skin and diffuse on the skin, and thus exhibit a long-term UV protection effect, and It is highly safe to the skin.

[0037]

EXAMPLES The present invention will be described in detail below with reference to examples, but the present invention is not limited thereto. In addition, the compounds (1a) to (1
w) is the same as above.

Example 1 Synthesis of Compound (1a): 1) 20 g (0.112 mol) of paramethoxycinnamic acid,
90 g (0.517 mol) of 1,10-decanediol,
p-toluenesulfonic acid 0.5 g, toluene 300 ml,
150 ml of hexane was placed in a 1 L four-necked flask, and the mixture was refluxed under nitrogen with a Dean Stark trap until no water was distilled off. After completion of the reaction, the mixture was washed with saturated aqueous sodium hydrogen carbonate and dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off, and the residue was purified by silica gel column chromatography,
38 g of monoester was obtained as white crystals. GLC
98% purity by analysis, 200 MHz ¹ H-NMR
(Solvent CDCl ₃ , TMS standard), δ = 1.7 for hydroxyl group, δ = 3.8 for methoxy group, δ = 1.5-1.9 and 3.7, 4.2 for methylene, δ = 6. Proton signals of olefins were confirmed at 3 and 7.7, and proton signals of aromatic rings were confirmed at δ = 6.9 and 7.5, respectively.

2) 0.93 g (6.07 g) of phosphorus oxychloride
(8 mmol) was dissolved in THF and placed in a 100 ml four-necked flask, and cooled with ice under nitrogen introduction. 4.43 g (13.3 mmol) of the monoester compound synthesized in 1) and 1.22 g of triethylamine were dissolved in 30 ml of THF and added dropwise. At this time, the reaction temperature was kept at -5 to 5 ° C. After continuously stirring for 24 hours, 0.25 g of water and 0.62 of triethylamine were added.
After adding g, the mixture was stirred again at 0 ° C. for 24 hours, the precipitated solid was removed by filtration, the solvent was distilled off, and the obtained residue was dissolved in ethyl acetate and washed with water. The residue obtained by distilling off the solvent was further dispersed in 50 ml of 1N hydrochloric acid and stirred at 50 ° C. for 7 hours. After cooling to room temperature, extraction with ethyl acetate gave 2.5 g of phosphoric acid diester (1a) as white crystals. 200 MHz ¹ H-NMR (solvent CD
Cl ₃ , TMS standard), a methoxy group at δ = 3.8,
δ = 1.3-1.7 and 3.95-4.15 and 4.2.
To methylene, δ = 6.3, 7.7 to olefin, δ =
Proton signals of the aromatic rings were confirmed at 6.9 and 7.5, respectively. ^The purity was 99% from ³¹ P-NMR.

Example 2 Synthesis of compound (1b): 1.4 g of phosphoric acid diester (1a) obtained in Example 1 was dissolved in ethanol, 1.0 g of calcium acetate, water and ethanol were added, and the mixture was heated at 60 ° C. for 5 hours. After stirring, add double the amount of water,
Cooled to room temperature. The precipitated solid was collected by filtration, washed with water and acetone, and then dried to obtain 1.3 g of a phosphoric acid diester calcium salt (1b) as a white solid. 200 MHz ¹ H-NMR (solvent CDCl ₃ , TM
S standard), a methoxy group at δ = 3.8, δ = 1.2-
Methylene at 1.6 and 3.75-3.95 and 4.2,
Olefin at δ = 6.3, 7.7, δ = 6.9, 7.5
A proton signal of each aromatic ring was confirmed. ³¹ P
-The purity was 99% from NMR.

Example 3 Synthesis of compound (1j): 1) 70 g (0.393 mol) of paramethoxycinnamic acid,
266 g (2.25 mol) of 1,6-hexanediol,
p-toluenesulfonic acid 2.0 g, toluene 600 ml,
300 ml of hexane was placed in a 2 L four-necked flask, and the mixture was refluxed under nitrogen with a Dean Stark trap until no water was distilled off. After completion of the reaction, the mixture was washed with saturated aqueous sodium hydrogen carbonate and dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off to obtain 92.6 g of a monoester body as white crystals. 95% purity by GLC analysis, 200
From MHz ¹ H-NMR (solvent CDCl ₃ , TMS standard), δ = 1.7 hydroxyl group, δ = 3.8 methoxy group, δ =
Methylene at 1.5-1.9 and 3.7, 4.2, δ =
Proton signals of the olefin were confirmed at 6.3 and 7.7, and proton signals of the aromatic ring were confirmed at δ = 6.9 and 7.5, respectively.

2) 15.8 g (0.10) of phosphorus oxychloride
3 mol) in THF and put in a 300 ml four-necked flask, cooled to -60 ° C under nitrogen introduction, and stirred 1).
30 g (0.108 mol) of the monoester compound synthesized in 1 and 11 g of triethylamine were dissolved in 100 ml of THF and added dropwise. At this time, the reaction temperature was kept at -30 ° C or lower. After continuing stirring for 3 hours, the temperature was raised to 0 ° C., 26.1 g (0.108 mol) of hexadecanol and 11 g of triethylamine were dissolved in THF and added dropwise. At this time, the reaction temperature was kept below 5 ° C. The mixture was stirred at 0 ° C. for 24 hours, 2 g of water was added, and the mixture was further stirred for 6 hours. Then, the precipitated solid was removed by filtration, the solvent was distilled off, and the obtained residue was dissolved in ethyl acetate and washed with dilute hydrochloric acid.
Washed with water. The solvent was distilled off and the obtained solid was washed with ether to obtain 30 g of phosphoric acid diester (1j) as white crystals. 200 MHz ¹ H-NMR (solvent CD
Cl ₃ , TMS standard), a methoxy group at δ = 3.8,
Methyl group at δ = 0.8-0.9, methylene at δ = 1.2-1.6 and 3.95-4.15 and 4.2, δ = 6.
Proton signals of olefins were confirmed at 3 and 7.7, and proton signals of aromatic rings were confirmed at δ = 6.9 and 7.5, respectively. ³¹ P-NMR
The purity was 99%.

Example 4 Synthesis of compound (1k): 14 g of phosphoric acid diester (1j) obtained in Examples 3 and 2)
Was dissolved in ethanol, 10 g of calcium acetate, water and ethanol were added, and the mixture was stirred at 60 ° C. for 5 hours, then double the amount of water was added and cooled to room temperature. The precipitated solid was collected by filtration, washed with water and acetone, and then dried to obtain 14 g of a phosphoric acid diester calcium salt (1k) as a white solid. 200 MHz ¹ H-NMR (solvent CDCl ₃ , T
According to MS standard), methoxy group at δ = 3.8, δ = 0.8
Methyl group at -0.9, delta = 1.2-1.6 and 3.75
Methylene at -3.95 and 4.2, δ = 6.3, 7.7
The proton signals of the olefin and the aromatic rings of δ = 6.9 and 7.5 were confirmed. ^The purity was 99% from ³¹ P-NMR.

Example 5 Synthesis of compound (1l): 10 g of phosphodiester (1j) obtained in Examples 3 and 2)
Dissolved in ethanol, aluminum acetate 10g, water,
After adding ethanol and stirring at 50 ° C. for 1 hour, a double amount of water was added and the mixture was cooled to room temperature. The precipitated solid was collected by filtration, washed with water and acetone, and dried to give 10 g of a white solid of phosphoric acid diester aluminum salt (1
l) was obtained. 200 MHz ¹ H-NMR (solvent CDC
l ₃ , TMS standard), δ = 3.8 with methoxy group, δ
= 0.8-0.9 to a methyl group, δ = 1.2-1.6 and 3.9-4.1 and 4.2 to methylene, δ = 6.3.
Proton signals of the olefin were confirmed at 7.7 and the aromatic rings at δ = 6.9 and 7.5, respectively. ^The purity was 99% from ³¹ P-NMR.

Example 6 Synthesis of compound (1c): 1) 25 g (0.152 mol) of parahydroxycinnamic acid was dissolved in 100 ml of methanol, 1 g of concentrated sulfuric acid was added, and the mixture was refluxed for 8 hours. After cooling to room temperature, twice the amount of water was added and the precipitated solid was collected by filtration, washed with water and dried to give 25 g.
Was obtained as a yellowish white solid. This is recrystallized with toluene,
Obtained 21 g of parahydroxycinnamic acid methyl ester as a pale yellow solid.

2) 10 g (0.056 mol) of parahydroxycinnamic acid methyl ester obtained in 1) was dissolved in 50 ml of acetone, and 7.8 g of potassium carbonate (0.057 mol).
l) was added. 12 g of 1-octyl bromide (0.0
(62 mol) was added and the mixture was heated under reflux for 50 hours. After cooling to room temperature, the precipitated solid was removed by filtration, the solvent was distilled off from the filtered mother liquor, the resulting residue was dissolved in 100 ml of ethyl acetate, washed with water and the solvent was further distilled off to give 15 g of yellowish white crystals. Obtained. This was recrystallized from hexane to obtain 14 g of para-octyloxycinnamic acid methyl ester as a white solid.

3) 8.0 g (0.028 mol) of paraoctyloxycinnamic acid methyl ester obtained in 2), 1,6
40 g (0.198 mol) of hexanediol and 0.35 g of p-toluenesulfonic acid were added to 100 ml of toluene and heated under reflux for 20 hours using a Dean Stark trap. After cooling to room temperature, it was diluted with 300 ml of toluene, washed with water, saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated, the obtained residue was purified by silica gel column chromatography, and
2 g of hexanediol monoparaoctyloxycinnamic acid ester was obtained as a yellow oil. 98% purity by GLC analysis, 200 MHz ¹ H-NMR (solvent CDC
( ₃ , TMS standard), a methyl group at δ = 0.9, δ =
1.4-1.9 and 3.7, 4.0, 4.2 methylene, δ = 1.6 hydroxyl group, δ = 6.3, 7.7 olefin, δ = 6.9, 7. The proton signals of each aromatic ring were confirmed in No. 5.

4) 0.956 g of phosphorus oxychloride (0.0
(06 mmol) was dissolved in THF, placed in a 100 ml four-necked flask, and cooled with ice under nitrogen. 5.0 g (0.013 mol) of the monoester obtained in 3) and 1.31 g of triethylamine were dissolved in 50 ml of THF and added dropwise. At this time, the reaction temperature was kept at -5 to 5 ° C. After continuously stirring for 24 hours, 1 g of water was added, and the mixture was stirred again at 0 ° C. for 24 hours, the precipitated solid was removed by filtration, the solvent was distilled off, and the obtained residue was dispersed in 100 ml of 2N hydrochloric acid. 40 ° C
It was stirred for 4 hours. After allowing to cool to room temperature, extraction with ethyl acetate, washing with water, evaporation of the solvent, dissolution of the residue obtained in ethanol, addition of 5.0 g of calcium acetate and water and stirring at 40 ° C. for 1 hour, then doubling A quantity of water was added and cooled to room temperature. The precipitated solid was collected by filtration, washed with water and acetone, and then dried to obtain 3.6 g of a phosphoric acid diester calcium salt (1c) as a white solid. 200 MHz
^{From 1} H-NMR (solvent CDCl ₃ , TMS standard) δ =
A methyl group at 0.9, δ = 1.3-1.75 and 3.7,
Proton signals of methylene at 3.9 and 4.2, olefin at δ = 6.3 and 7.7, and aromatic ring at δ = 6.9 and 7.5 were confirmed. 98% purity from ³¹ P-NMR
Met.

Example 7 Synthesis of compound (1p): 1) 100 g (0.562 mol) of paramethoxycinnamic acid,
250 g (2.78 mol) of 1,4-butanediol, p
-Toluenesulfonic acid 4.0 g, toluene 300 ml 2
The mixture was placed in an L four-necked flask, and the mixture was refluxed under nitrogen introduction using a Dean Stark trap until water did not distill.
After completion of the reaction, the mixture was diluted with a double amount of toluene, washed with water, saturated aqueous sodium hydrogen carbonate, water and saturated saline, and dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off to obtain 134.5 g of a monoester body as white crystals. 95% purity by GLC analysis, 200 MHz ¹ H-NMR (solvent CDCl ₃ , TMS standard) gave δ = 1.7 hydroxyl group,
A methoxy group at δ = 3.8, δ = 1.55, 1.6-1.
9 and 3.7, 4.25 methylene, δ = 6.3, 7.
Proton signals of the olefin were confirmed at 7 and proton signals of the aromatic ring at δ = 6.9 and 7.5, respectively. 2) 17 g (0.11 mol) of phosphorus oxychloride was dissolved in THF and placed in a 500 ml four-necked flask, and under nitrogen introduction,-
After cooling to 60 ° C., 31 g (0.118 mol) of the monoester compound synthesized in 1) and 11.5 g of triethylamine were dissolved in 100 ml of THF and added dropwise with stirring. At this time, the reaction temperature was kept at -30 ° C or lower. After stirring for 3 hours, the temperature was raised to 0 ° C and 30 g of hexadecanol was added.
(0.124 mol), and triethylamine 11.5 g
Was dissolved in THF and added dropwise. At this time, the reaction temperature was kept below 5 ° C. After stirring at 0 ° C. for 24 hours, water 2
g was added and the mixture was further stirred for 6 hours. After that, the precipitated solid was removed by filtration, the solvent was distilled off, and the obtained residue was dissolved in ethyl acetate, washed with dilute hydrochloric acid, and then washed with water. The solvent was distilled off and the obtained solid was recrystallized from hexane to give 50 g.
The phosphoric acid diester of was obtained as white crystals. 200
From MHz ¹ H-NMR (solvent CDCl ₃ , TMS standard), methoxy group at δ = 3.8, methyl group at δ = 0.8-0.9, δ = 1.2-1.5, 1.7. , 1.85 and 3.85, 4.1, 4.25 methylene, δ = 6.3.
Proton signals of the olefin were confirmed at 7.7 and the aromatic rings at δ = 6.9 and 7.5, respectively. ^The purity was 99% from ³¹ P-NMR. 15 g of the phosphoric acid diester obtained in 2) was dissolved in ethanol to give 10 parts of aluminum acetate.
After adding g, water and ethanol and stirring at 60 ° C. for 5 hours,
Double amount of water was added and cooled to room temperature. The precipitated solid was collected by filtration, washed with water and acetone, and then dried,
15 g of phosphoric acid diester aluminum salt (1p) was obtained as a white solid. From 200 MHz ¹ H-NMR (solvent CDCl ₃ , TMS standard), methoxy group at δ = 3.8, methyl group at δ = 0.8-0.9, δ = 1.2-1.
5,1.6,1.75 and 3.85,3.95,4.2
5, methylene, δ = 6.3, 7.7 olefin, δ =
Proton signals of the aromatic rings were confirmed at 6.9 and 7.5, respectively. ^The purity was 99% from ³¹ P-NMR.

Example 8 Synthesis of compound (1w): 15 g of diphosphate ester (1p) obtained in Example 7, 2)
Was dissolved in ethanol, 10 g of calcium acetate, water and ethanol were added, and the mixture was stirred at 60 ° C. for 5 hours, then double the amount of water was added and cooled to room temperature. The precipitated solid was collected by filtration, washed with water and acetone, and then dried to obtain 15 g of a phosphoric acid diester calcium salt (1w) as a white solid. 200 MHz ¹ H-NMR (solvent CDCl ₃ , T
According to MS standard), methoxy group at δ = 3.8, δ = 0.8
A methyl group at −0.9, δ = 1.2-1.6, 1.75 and 3.85, 3.95 and 4.2 methylene, δ = 6.
Proton signals of olefins were confirmed at 3 and 7.7, and proton signals of aromatic rings were confirmed at δ = 6.9 and 7.5, respectively. ³¹ P-NMR
The purity was 99%.

Example 9 Synthesis of compound (1t): 1) 41 g (0.23 mol) of paramethoxycinnamic acid, 3-
266 g (2.25 mol) of methylpentanediol, p
-Toluenesulfonic acid 1.0 g, toluene 600 ml 2
The mixture was placed in an L four-necked flask and refluxed under nitrogen using a Dean Stark trap until no water was distilled off. After completion of the reaction, the mixture was washed with saturated aqueous sodium hydrogen carbonate and dried over anhydrous magnesium sulfate. After filtration, the solvent is distilled off, giving 53 g.
Was obtained as a colorless viscous liquid. GL
95% purity by C analysis, 200 MHz ¹ H-NM
From R (solvent CDCl ₃ , TMS standard), δ = 1.7 hydroxyl group, δ = 3.8 methoxy group, δ = 1.0 methyl group, δ = 1.5-1.9 and 3.7, 4.2 methylene, δ = 6.3, 7.7 olefin, δ = 6.9,
Proton signals of the aromatic rings were confirmed at 7.5.

2) 15.3 g of phosphorus oxychloride (0.10
0 mol) was dissolved in THF and put in a 300 ml four-necked flask, cooled to −60 ° C. under nitrogen introduction, and stirred to obtain 30 g (0.108 mol) of the monoester compound synthesized in 1).
l) and 11 g of triethylamine were dissolved in 100 ml of THF and added dropwise. At this time, the reaction temperature was kept at -30 ° C or lower. After continuing stirring for 3 hours, the temperature was raised to 0 ° C., 26.1 g (0.108 mol) of hexadecanol and 11 g of triethylamine were dissolved in THF and added dropwise. At this time, the reaction temperature was kept below 5 ° C. The mixture was stirred at 0 ° C. for 24 hours, 2 g of water was added, and the mixture was further stirred for 6 hours. Thereafter, the precipitated solid was removed by filtration, the solvent was distilled off, and the obtained residue was dissolved in ethyl acetate, washed with dilute hydrochloric acid, and then washed with water. The solvent was evaporated and the obtained solid was washed with ether to obtain 30 g of phosphoric acid diester as white crystals. 200 MHz ¹ H-NMR (solvent CDC
l ₃ , TMS standard), δ = 3.8 with methoxy group, δ
= 0.8-0.9 and 1.0 with a methyl group, δ = 1.2-
Methylene at 1.6 and 3.95-4.15 and 4.2,
Olefin at δ = 6.3, 7.7, δ = 6.9, 7.5
A proton signal of each aromatic ring was confirmed. ³¹ P
-The purity was 99% from NMR.

3) Phosphoric acid diester 14 obtained in 2)
g dissolved in ethanol, calcium acetate 10 g, water,
After adding ethanol and stirring at 60 ° C. for 5 hours, a double amount of water was added and the mixture was cooled to room temperature. The precipitated solid was collected by filtration, washed with water and acetone, and dried to give 14 g of a white phosphoric acid diester calcium salt (1t).
Got 200 MHz ¹ H-NMR (solvent CDCl ₃ ,
TMS standard), a methoxy group at δ = 3.8, δ = 0.
Methyl group at 8-0.9 and 1.0, δ = 1.2-1.6
And methylene at 3.8-4.0, 4.2, δ = 6.3,
Proton signals of the olefin were confirmed at 7.7 and the aromatic rings at δ = 6.9 and 7.5, respectively. ^The purity was 99% from ³¹ P-NMR.

Example 10 Synthesis of compound (1v): 1) 64 g (0.525 mol) of benzoic acid, 500 g (5.68 mol) of 1,4-butanediol, 0.5 g of p-toluenesulfonic acid, and 2 L of 500 ml of toluene. The mixture was placed in a four-necked flask and refluxed using a Dean Stark trap until water did not distill. After completion of the reaction, the reaction mixture was diluted with a double amount of toluene, washed several times, further washed with saturated aqueous sodium hydrogen carbonate, water and saturated brine, and dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off to obtain 80 g of a monoester body as a colorless oil, and 200 MHz ¹ H-NMR (solvent CDC
l ₃ , TMS standard), δ = 1.55-2.0,
Proton signals of a methylene group at 3.68 and 4.35, an aromatic ring at δ = 8.05 and 7.4-7.6, and a hydroxyl group at δ = 2.65 were confirmed.

2) 25 g of phosphorus oxychloride (0.163 mo
l) is dissolved in 50 ml of THF, put in a 500 ml four-necked flask, and dried with dry ice / acetone under nitrogen.
It was cooled to 50 ° C or lower. Next, monobenzoate (4-
Benzoyloxy-1-butanol) 32.3 g (0.
167 mol), 16.5 g of triethylamine (0.16)
3 mol) was dissolved in about 50 ml of THF and added dropwise. At this time, the reaction temperature was kept at -30 ° C or lower. After stirring for 3 hours, the temperature was raised to 0 ° C and 1-hexadecanol 4 was added.
1.5 g (0.171 mol), triethylamine 16.
5 g (0.163 mol) was dissolved in about 100 ml of THF and added dropwise. At this time, the reaction temperature was kept at 5 ° C or lower. After continuing stirring under ice-cooling overnight, 10 g of water was added and the mixture was stirred for a while, the precipitated white solid (hydrochloride) was removed by filtration, and then the solvent was distilled off. 2N HC was added to the obtained residue.
About 200 ml was added and the mixture was stirred at 40 to 50 ° C for 2 hours. After allowing to cool, the mixture was diluted with a double amount of water, the precipitated solid was collected by filtration, washed with water, and recrystallized with ethanol to obtain phosphodiester as white crystals of 50 g, 200 MHz
^{By 1} H-NMR (solvent CDCl ₃ , TMS standard), δ
= 0.8-0.9 for a methyl group, δ = 1.2-1.6 and 3.9-4.1, 4.35 for a methylene group, δ = 8.05.
And 7.4-7.6 confirmed the respective proton signals of the aromatic ring. ^The purity was 99% from ³¹ P-NMR.

3) Phosphoric acid diester 20 obtained in 2)
g was dissolved in 100 ml of ethanol and calcium acetate 19
g was dissolved in water and added, and the mixture was stirred at 50 ° C. for 2 hours. It was then diluted with twice the amount of water and cooled to 0 ° C. The precipitated solid was collected by filtration, washed with water, washed with acetone, dried and then 2
Phosphoric acid diester calcium salt (1v) was obtained as 0 g of a white solid, and 200 MHz ¹ H-NMR (solvent CD
Cl ₃ , TMS standard), methyl groups at δ = 0.8-0.9, δ = 1.2-1.6 and 3.7-3.9, 4.
The proton signals of the methylene group at 35 and the aromatic ring at δ = 8.05 and 7.4-7.6 were confirmed. ³¹ P-
The purity was 99% by NMR.

Test Example 1 (Gel Forming Ability for Various Oil Agents) The oil gelling ability of various phosphodiester metal salts was evaluated.
As an evaluation method, 1 g of each compound was weighed in a sample tube, 19 g of an oil agent was added thereto, and the mixture was mixed with an ultrasonic mixer for about 3 minutes to be uniformly dispersed or dissolved. This was left to stand for a whole day and night, and then the state was visually observed and evaluated according to the following criteria. The results are shown in Table 2. The oil gelling ability was evaluated according to the following criteria.

[Table 1] ⊚: Transparent viscous gel ◯: Gel with low viscosity Δ: Gel is formed, but oil bleeding is observed x: Insoluble

[0058]

[Table 2]

From Table 2 above, it can be seen that the compound of the present invention is effective in gelling a hydrophilic oil agent having an aromatic ring, an ester bond or the like.

Test Example 2 (UV Absorption Ability) An oil gel was formed from the compound (1l) of the present invention in an oil agent (diisopropyl adipate). When 10 mg of this was sandwiched between quartz plates (optical path length 8 μm) and the UV spectrum was measured, it showed a sufficient UV-B absorption ability as shown in FIG.

Example 11 A sunscreen O / W cream having the following composition was prepared by a conventional method.

[0062]

Table 3 (Composition) (wt%) Compound (1b) of Example 2 3.0 Monocetylphosphate 0.5 Squalane 2.0 Isopropyl palmitate 2.0 Olive oil 2.0 Dimethylpolysiloxane 2.0 Butylparaben 0 .1 Glycerin 5.0 L-arginine 0.5 Ethanol 5.0 Methylparaben 0.3 Carbopol 941 (BF Goodrich) 0.25 Purified water Residue

This product has a long-lasting UV protection effect and is excellent in skin safety.

Example 12 A sunscreen W / O type foundation having the following composition was prepared by a conventional method.

[0065]

Table 4 (Composition) (wt%) Compound (1) of Example 5 10.0 Squalane 10.0 Dimethylpolysiloxane 5.0 Perfluoropolyether 15.0 Dimethylpolysiloxane / polyoxyalkylene copolymer 2 0.0 Glycerin 2.0 Purified water Residual pigment Sericite 6.0 Titanium oxide 8.0 Iron oxide (red, yellow, black) 1.2 Nylon powder 5.0 Perfume 0.06

This product had a long-lasting UV protection effect and was excellent in safety to the skin.

Example 13 A two-layer sunscreen emulsion having the following composition was prepared by a conventional method.

[0068]

Table 5 (Composition) (wt%) Compound of Example 4 (1k) 5.0 Liquid paraffin 10.0 Squalane 5.0 Octamethylcyclotetrasiloxane 5.0 Perfluoropolyether 10.0 Dimethylpolysiloxane Polyoxyalkylene copolymer 1.0 Glycerin 2.0 Ethanol 5.0 Purified water Residual zinc oxide 7.5 Octyl methoxycinnamate 2.0 Perfume 0.01

This product exhibited an ultraviolet protection effect for a long time and was excellent in safety to the skin.

Example 14 An O / W sunscreen cream having the following composition was prepared by a conventional method.

[0071]

Table 6 (Composition) (wt%) Compound (1t) of Example 9 0.5 Neopentyl glycol dicaprate 5.0 Jojoba oil 1.0 Methylphenylpolysiloxane 3.0 Cetanol 2.0 Stearyl alcohol 1. 0 Self-emulsifying glyceride monostearate 2.0 Sorbitan monostearate 1.0 2-Ethylhexyl p-methoxycinnamate 5.0 Butylparaben 0.2 Glycerin 5.0 Ethanol 1.0 Purified water Residual methylparaben 0.5

This product had a long-lasting UV protection effect and excellent safety to the skin.

Example 15 A W / O sunscreen cream having the following composition was prepared by a conventional method.

Table 7 (Composition) (wt%) Compound of Example 7 (1p) 1.0 Squalane 2.0 Octyldodecyl myristate 3.0 α-Isostearyl glyceryl ether 2.0 Dimethylpolysiloxane 3.0 Fine particle oxidation Titanium 3.0 Butylparaben 0.2 Glycerin 10.0 Magnesium sulfate 1.0 Purified water Residual methylparaben 0.3

This product had a long-lasting ultraviolet protection effect and was excellent in safety to the skin.

Example 16 A two-layer sunscreen emulsion having the following composition was prepared by a conventional method.

[0076]

Table 8 (Composition) (wt%) Compound (1v) of Example 10 5.0 Liquid paraffin 10.0 Squalane 5.0 Octamethylcyclotetrasiloxane 5.0 Perfluoropolyether 10.0 Dimethylpolysiloxane Polyoxyalkylene copolymer 1.0 Glycerin 2.0 Ethanol 5.0 Purified water Residual zinc oxide 7.5 Octyl methoxycinnamate 2.0 Perfume 0.01

This product exhibited an ultraviolet protection effect for a long time and was excellent in safety to the skin.

[Brief description of drawings]

FIG. 1 shows the UV-of the compound (1) of the present invention in Test Example 2.
It is a figure which shows B absorbency.

Claims (11)

[Claims] 1. The following general formula (1): (In the formula, R ¹ represents an acyl group having at least one benzene ring, and R ² represents a linear or branched alkylene group in which an oxygen atom may be inserted between carbon atoms having 2 to 12 carbon atoms. L represents a linear or branched alkyl group in which an oxygen atom may be inserted between carbon atoms having 2 to 40, or R ¹ —O—R ² —, and M represents a hydrogen atom or an alkali. A metal ion, a divalent or higher polyvalent metal ion, an ammonium group, an alkanol ammonium group having 2 to 14 carbon atoms,
Phosphoric acid diesters represented by an alkylammonium group having 1 to 14 carbon atoms, where n represents a valence of M). 2. The phosphoric acid diesters according to claim 1, wherein in the general formula (1), R ¹ is a cinnamoyl group which may have a substituent or a benzoyl group which may have a substituent. 3. The phosphoric acid diester according to claim 2, wherein R ¹ is a p-methoxycinnamoyl group. 4. The phosphoric acid diester according to claim 2, wherein R ¹ is a benzoyl group. 5. The phosphoric acid diester according to claim 1, 2, 3 or 4, wherein M is a calcium atom or an aluminum atom in the general formula (1). 6. The phosphoric acid diester according to claim 1, wherein L is a linear or branched alkyl group having 8 to 20 carbon atoms in the general formula (1). 7. A cosmetic containing the phosphoric acid diester according to any one of claims 1 to 6. 8. A cosmetic containing 0.01 to 80% by weight of the phosphoric acid diester according to any one of claims 1 to 6. 9. A cosmetic containing the phosphoric acid diester according to claim 1 and an oil agent and / or an organic oily ultraviolet absorber. 10. A carboxylic acid having at least one benzene ring or an acid halide thereof has 2 to 12 carbon atoms.
Reacting a diol having a linear or branched alkylene group in which an oxygen atom may be inserted between the carbon atoms of
The obtained monoester is reacted with phosphorus oxychloride,
Then, salt exchange or neutralization is carried out, which is characterized by the general formula (1 ′): (In the formula, R ¹ represents an acyl group having at least one benzene ring, and R ² represents a linear or branched alkylene group in which an oxygen atom may be inserted between carbon atoms having 2 to 12 carbon atoms. Shows, M is a hydrogen atom, an alkali metal ion, 2
Valent or higher polyvalent metal ion, ammonium group, carbon number 2
14 alkanol ammonium group represents an alkyl ammonium group having 1 to 14 carbon atoms, and n represents a valence of M)
A method for producing a phosphoric acid diester represented by: 11. A carboxylic acid having at least one benzene ring or an acid halide thereof has 2 to 12 carbon atoms.
Reacting a diol having a linear or branched alkylene group in which an oxygen atom may be inserted between the carbon atoms of
The obtained monoester is reacted with phosphorus oxychloride to give a compound of the general formula (6): (In the formula, R ¹ represents an acyl group having at least one benzene ring, and R ² represents a linear or branched alkylene group in which an oxygen atom may be inserted between carbon atoms having 2 to 12 carbon atoms. The compound (6) is represented by the general formula L-OH (where L is a linear or branched chain in which an oxygen atom may be inserted between carbon atoms having 2 to 40 carbon atoms). An alkyl group or an alcohol represented by R ¹ —O—R ² —) is reacted, and then salt exchange or neutralization is carried out. (In the formula, M represents a hydrogen atom, an alkali metal ion, a divalent or higher polyvalent metal ion, an ammonium group, an alkanol ammonium group having 2 to 14 carbon atoms, an alkylammonium group having 1 to 14 carbon atoms, and n is M Indicates the valence of
R ¹ , R ² and L are the same as defined above, and a process for producing a phosphodiester salt.