Silicone type cinnamic acid derivative, preparation method thereof, uv-ray absorber, and external skin treatment agent.

Abstract: A silicone type cinnamic acid derivative which is a siloxane having at least one unit represented by the formula (I): and having the other units which may exist in the siloxane being represented by the formula: O (4-m)/2 SiR³ m wherein R¹ represents an alkyl group having 1 to 4 carbon atoms, a phenyl group, or a trimethylsiloxy group, R² is a divalent hydrocarbon group having at least two carbon atoms, which may include a heteroatom O, X is an alkoxy group, n is an integer of 0 to 3, a is an integer of 2 or 3, R³ is an alkyl group having 1 to 4 carbon atoms, a phenyl group, or a trimethylsiloxy group, and m is an integer of 0 to 3.

Description: BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel silicone type cinnamic acid derivative and a method of preparing same, and to a novel UV-ray absorber and an external skin treatment agent. More specifically, the present invention relates to a novel silicone type cinnamic acid derivative which can be dissolved in silicone oil, has an excellent water resistance and oil resistance, and has an UV-ray absorbing characteristic at wavelengths in the UV-B region, and to a novel external treatment agent having an excellent sunburn-prevention effect, useability, and prolonged cosmetic effects. 2. Description of the Related Art As is well known, UV-rays cause various changes to the skin, and dermatologically, the acting wavelengths thereof are classified into long wavelength UV-rays of 400 to 320 nm, medium wavelength UV-rays of 320 to 290 nm, and short wavelength UV-rays shorter than 290 nm; called UV-A, UV-B, and UV-C, respectively. Generally, most of the UV-rays to which humans are exposed are sunlight rays, and consist of UV-rays reaching the earth, i.e., UV-A and UV-B, and UV-rays absorbed in the ozone layer and not reaching the earth, i.e., UV-C. Of the UV-rays reaching the earth, UV-B rays cause erythema or blistering when irradiated on the skin at a certain dose or higher, and further, promote the forming of melanine in the skin, i.e., cause a darkening or dyeing of the skin. Accordingly, protection of the skin from UV-B rays is very important from the viewpoint of preventing an accelerated aging of the skin and a generation or increase of splotching or freckling of the skin, and thus various UV-B absorbers to be used for this purpose have been developed. Among existing UV-B absorbers, there are known PABA derivatives, cinnamic acid derivatives, salicylic acid derivatives, camphor derivatives, urocannic acid derivatives, benzophenone derivatives, and heterocyclic derivatives, and these UV-B absorbers are utilized exclusively by formulation in external treatment agents such as cosmetics and quasi-drugs. As the external agent bases, silicone type bases with low molecular weights, such as dimethylsiloxane, are widely used, as is well known in the art, due to the excellent useability characteristics of such silicone type bases, e.g., a good extendability, plain feeling, and no stickiness, and an excellent function thereof in that they are not easily removed by sweat or water. On the other hand, since sun-protection cosmetics in which UV-ray absorbers are formulated are used during hot summer, they are liable to be removed by excessive sweating or skin fat extrusions, and when these products are used at the beach or at a swimming pool, a problem arises in that they are removed when the skin is immersed in water. Therefore, there is obviously a need to enhance the cosmetic durability of these cosmetics, and accordingly, a silicone type base with a low molecular weight such as dimethylsiloxane, etc., is now widely used as the external treatment agent base, due in the most part to the properties possessed by silicone type bases; for example, a useability such as good spreadability, a plain feeling, no stickiness, and further, functional characteristics such as an excellent water resistance, oil resistance, and resistance to easy removal by sweat or water. Nevertheless, existing UV-B absorbers have a remarkably low compatibility with or low solubility in silicone type bases, and accordingly, to formulate such UV-B absorbers in an external treatment agent having a silicone type base, an oily base must be added, and therefore, a drawback arises in that the useful properties of the silicon type base as described above are lost, and further, these compositions have an inferior water resistance and oil resistance. Japanese Examined Patent Publication (Kokoku) No. 29866/1969, Japanese Unexamined Patent Publications (Kokai) Nos. 58991/1985 and 108431/1985 disclose compositions having a UV-ray absorbability, but the chemical structures thereof include unsubstituted cinnamic acid as the basic skeleton, which has an absorption maximum wavelength on the UV-C side, in silicone oil, and thus the UV-B absorbability thereof is not satisfactory. Figure 3 shows the UV absorption spectrum of 3-bis(trimethysiloxy)-methylsilyl-2-methylpropyl-cinnamate, from which it can be understood that this composition does not have an adequate wavelength region for a UV-B absorber. In US-A-4562278 a cinnamic acid derivative is described in Example 2 but its performance in the presence of a solvent is inferior to that of the cinnamic acid derivative of the present invention. In accordance with the present invention, there is provided a silicone type cinnamic acid derivative which is a siloxane having at least one unit represented by the formula (I): and having the other units which can exist in said siloxane being represented by the formula O (4-m)/2 SiR³ m wherein R¹ represents an alkyl group having 1 to 4 carbon atoms, a phenyl group, or a trimethylsiloxy group, R²is a divalent hydrocarbon group having at least two carbon atoms, which may include a heteroatom O, X is an alkoxy group, n is an integer of 0 to 2, a is an integer of 2 or 3, R³ is an alkyl group having 1 to 4 carbon atoms, a phenyl group, or trimethylsiloxy group, and m is an integer of 0 to 3. In accordance with the present invention, there is further provided a silane type cinnamic acid derivative represented by the formula (I'): wherein R¹ represents an alkyl group having 1 to 4 carbon atoms, a phenyl group, or a trimethylsiloxy group, R² is a divalent hydrocarbon group having at least two carbon atoms, which may include a heteroatom O, X is an alkoxy group, and a is an integer of 2 or 3. In accordance with the present invention, there is also provided a method of preparing the above-mentioned silane and siloxane type cinnamic acid derivatives, which comprises reacting a cinnamic acid ester represented by the formula: wherein Y represents a monovalent hydrocarbon group having at least two carbon atoms, which may include a heteroatom O, and an olefinic unsaturated bond, X is an alkoxy group, and a is 2 or 3, with a siloxane having an unit and optionally a R³ m SiO (4-m)/2 unit, wherein R¹ and R³ represent an alkyl group having 1 to 4 carbon atoms, a phenyl group, or a trimethylsiloxy group, and n and m are integers of 0 to 3, in an organic solvent in the presence of a catalyst. In accordance with the present invention, there is further provided a method of preparing a silane or siloxane type cinnamic acid derivative of claim 1 or 3, comprising the step of reacting a cinnamic acid salt having the formula: wherein X represents an alkoxy group, Z represents an alkali metal, and a is 2 or 3, with a halogeno alkylene silicone derivative having the formula: wherein W represents a halogen, R¹ represents an alkyl group having 1 to 4 carbon atoms, a phenyl group, or a trimethylsiloxy group, R² is a divalent hydrocarbon group having at least two carbon atoms, which may include a heteroatom O, and n is an integer of 0 to 3 in an organic solvent. In accordance with the present invention, there is further provided a UV-ray absorber comprising the above -mentioned derivative (I') or derivative (I). In accordance with the present invention, there is still further provided an external treatment agent comprising the above-mentioned derivative (I') or derivative (I). BRIEF DESCRIPTION OF THE DRAWINGS The present invention will be better understood from the description set forth below with reference to the accompanying drawings, in which: Figure 1 shows a UV-spectrum of the silicone type cinnamic derivative obtained in Synthesis Example 2 at a concentration of 10 ppm (solvent, ethanol); Fig. 2 shows a UV-spectrum of the silicone type cinnamic derivative obtained in Synthesis Example 6 at a concentration of 10 ppm (solvent, ethanol); and, Fig. 3 shows a UV-spectrum of an unsubstituted silicone, which is a known compound, at a concentration of 10 ppm (solvent, ethanol). DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention is now described in detail. The silicone type cinnamic acid derivative is constituted by the unit represent by the formula (I) and the formula Examples of R¹ as defined in the formula include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, phenyl groups, and a trimethylsiloxy group, but preferably a methyl group, a partially phenyl group, or a trimethylsiloxy group is used as the starting materials since they are readily available. Here, n represents the substitution number of R¹. Examples of R² include -CH₂CH₂-, -CH₂CH₂CH₂-, -CH₂CH₂CH₂CH₂-, -CH₂CH₂OCH₂CH₂- hexylene, cyclohexylene, and decylene groups, preferably an alkylene group having 2 to 4 carbon atoms, but to ensure a relatively smaller side reaction from a hydrosilylation reaction, is particularly preferred. Examples of X include an methoxy group, ethoxy group, isopropoxy group and the like. Although these are not remarkably different with regard to a solubility thereof in silicone type bases and in UV-B absorption wavelength, from the aspect of availability or reagents, the methoxy group is particularly preferred. Here, a represents the substitution number of X. In the siloxane unit represented by the formula O (4-m)/2 SiR³m, R³ may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, phenyl groups, and trimethylsiloxy group but preferably a methyl group, partially phenyl group, or trimethylsiloxy group is used, from the aspect of a ready availability thereof as starting materials. Here m is the substitution number of R³. The silicone type cinnamic acid derivative of the present invention can be synthesized according to the preparation method of the present invention. The ester of the formula (II) is obtained by converting the corresponding substituted cinnamic acid in a conventional manner into acid chloride and then reacting it with a monohydric alcohol having an olefinic unsaturated bond in the presence of an amine. As the reaction solvent, conventional organic solvents can be used, but aromatic organic solvents such as toluene, benzene, and xylene are preferred, and preferably the reaction is carried out at a high temperature, more preferably a reflux temperature. Depending on the alcohol to be used for the reaction, Y in the formula (II) is different but is a monovalent hydrocarbon group having at least two carbon atoms and an olefinic unsaturated bond, which may include a heteroatom O, and includes for example, straight hydrocarbon groups such as CH₂ = CH-, CH₂ = CHCH₂-, CH₂ = CHCH₂CH₂-, CH₂ = CH-CH₂CH₂CH₂-, and CH₂ = CH-CH₂-O-CH₂CH₂-; branched hydrocarbon groups such as CH₂ = CH-CH(Me)-, CH₂ = CH-C(Me)₂-, CH₂ = CH-CH(Et)-, CH₂ = CHC(Et)₂-, CH₂ = CHCH₂CH(Me)-, CH₂ = CHCH(Me)-CH₂ , and CH₂ = C(Me)CH₂- and having a double bond at the terminal end, and those having an internal double bond such as MeCH = CH-, MeCH = CHCH₂-, (Me)₂C = CH-, (Me)₂C = CHCH₂-, MeCH = CHCH₂-, and MeCH₂CH = CH- and those having two double bonds such as CH₂ = CH-CH = CH₂-, CH₂ = C(Me)CH = CH₂-, and MeCH = CH-CH =CH₂-, but an ester having one double bond at the terminal end is desirable from the viewpoint of the superior esterification reaction, hydrosilylation reaction, and stability of the silicone type cinnamic acid derivative derived from these esters (including light stability). The silicone type cinnamic acid derivative of the present invention is obtained by allowing the ester of the formula (II) thus obtained to undergo a hydrosilylation reaction with siloxane. The siloxane to be used is an organic silicon compound having at least one Si-H, which is represented as the siloxane having an unit and R 3 / mSiO (4-m)/2 unit, for example, (EtO)₃SiH, (Me₃SiO)₂MeSiH, (Me₃SiO)₃SiH, (Me₃SiO)MePhSiH, (Me₃OSi)EtMeSiH, (Me₃OSi)EtPhSiH, and H(Me)₂SiOSi(Me)₂OSi(Me)₂H but from the aspect of a superior hydrosilylation reaction, ready availability of the silane and siloxane, and solubility in silicone type bases, 1,1,1,3,5,5,5-heptamethyltrisiloxane is preferred. Note, this is not limitative of the present invention, and similar compositions may be used provided that the silicone type cinnamic derivative of the present invention can be prepared without hidrance. As the reaction solvent, conventional solvents can be used, preferably aromatic organic solvents such as toluene, benzene, and xylene, and preferably the reaction can be carried out at a high temperature, more preferably at a reflux temperature. As the catalyst for hydrosilylation, a rhodium complex (Wilkinson complex), ruthenium complex, platinum complex, and chloroplatinate generally well known in the art can be used, but in view of the ready availability of the catalyst and of the simplicity of the operation of the synthetic reaction, a chloroplatinate catalyst is preferred. The silicone type cinnamic acid derivative of the present invention can be provided with from low to high molecular weights by selecting the ester of the formula (II) and the above siloxane depending on the purpose, including the properties of changing a liquid to a resinous solid at room temperature. The silicone type cinnamic acid derivative of the present invention can also be synthesized according to the preparation method of the present invention. The cinnamic acid salt of the formula (IV) is obtained by reacting the corresponding substituted cinnamic acid with an alkali metal hydroxide in an aqueous or alcoholic solution. The preferable alkali metal is sodium or potassium. Then, the salt (IV) is dried and is reacted with the halogeno alkylene silicone derivative of the formula (V) is an organic solvent (e.g., dimethyl-formamide, dimethylsulfoxide) at an elevated temperature,preferably at 120°C. The preferable halogen is chlorine. The fields of application of the UV-ray absorber according to the present invention, regardless of the its development history described above, are not particularly limited and it can be utilized for various articles in which UV-ray absorbers are incorporated, depending on the characteristics and the purpose of the silicone type cinnamic acid derivative according to the present invention. The amount when formulated for external agents such as cosmetics and quasi-drugs may depend on the dosage, but preferably is 0.1 to 20% by weight, more preferably 0.5 to 10% by weight. Any base can be used in the present invention, provided that silicone type cinnamic acid derivatives can be dissolved therein, but particularly when a silicone type base is used, effects such as a good spreadability, plain feeling, no stickiness, etc., and functions such as an excellent water resistance, oil resistance and a resistance to removal by sweat or water, can be obtained. The silicone type base to be used in the present invention is not particularly limited, and includes, for example, chain polysiloxanes such as dimethylpolysiloxane, methylpolysiloxane, and methylhydrogenpolysiloxane; cyclic polysiloxanes such as decamethylpolysiloxane, dodecamethyl-polysiloxane, and tetramethyltetrahydrogenpolysiloxane; and polyether, fatty acid-modified polysiloxanes, higher alcohol modified polysiloxanes, and amino-modified polysiloxanes. The dermatological external treatment agent of the present invention can also formulate other components conventionally used in cosmetics and quasi-drugs, such as oil components, lubricants, UV-ray absorbers other than those of the present invention, antioxidants, surfactants, preservatives, perfumes, water, alcohols, and thickeners, if desired. The fields of application of the dermatological external treatment agent of the present invention are not limited, and it can be utilized for cosmetics and quasi-drugs, depending on the characteristics and the purpose of the silicone type cinnamic acid derivative to be used in the present invention. Here, any dosage form of the dermatological external treatment agent of the present invention may be used, for example, a powder, cream, paste, stick, liquid, spray, foundation may be utilized, and it may be also emulsified by an emulsifier to produce a W/O or O/W emulsion. The amount thereof to be formulated may differ depending on the dosage form, as mentioned above, but is generally 0.1 to 20% by weight, preferably 0.5 to 10% by weight. Examples The present invention will now be further illustrated by, but is by no means limited to, the following Examples, wherein all parts and percentages are expressed on a weight basis unless otherwise noted. Synthesis Examples The present invention is described in more detail with reference to synthesis examples of the novel silicone type cinnamic derivative of the present invention and the physicochemical properties thereof. Synthesis Example 1 An amount of 11.94 g of 3,4,5-trimethoxycinnamic acid and 11 ml of thionyl chloride were stirred in 80 ml of benzene at reflux temperature for 3 hours, to be converted to acid chloride, and after removal of the solvent, 80 ml of toluene containing 7.20 g of 1-butene-3-ol was added, followed by cooling the reaction system in an ice bath. Then 40 ml of toluene containing 5.25 g of triethylamine was slowly added and the mixture was stirred for one hour, followed by stirring the mixture at room temperature for one day. After filtration, the toluene layer was washed with water, and after removal of the water, subjected to silica gel column chromatography, using toluene as the solvent, to obtain 10.93 g (74.6%) of 3,4,5-trimethoxycinnamic acid ester. GC-MS M⁺292 NMR(CDCl₃)7.60(1H, d(J=15.77 Hz)), 6.36(1H, d(J=16.14 Hz)), 6.74(2H, s), 5.92(1H, m), 5.49(1H, m), 5.29(1H, d(J=17.60 Hz)), 5.15(1H, d(J=10.64HZ)), 3.85(9H, s), 1.38(3H, d(J=6.60 Hz)). Synthesis Example 2 The ester obtained in Synthesis Example 1 (2.9319 g) and 2.2270 g of siloxane (1,1,1,3,5,5,5-Heptamethylsiloxane, hereinafter abbreviated as MHM) were poured into 50 ml of toluene, and 2 or 3 drops of 0.1 M chloroplatinate isopropyl alcoholic solution were added, followed by stirring at reflux temperature for 5 hours to carry out the hydrosilylation reaction. The product was isolated by silica gel column chromatography, using toluene as the solvent, to obtain 3.0880 g (59.8%) of an oily silicone type cinnamic acid derivative of the present invention. This product was identified by the following analytical values. Name of substance: [3-bis(trimethylsiloxy)methylsilyl-1-methylpropyl]-3,4,5-trimethoxycinnamate GC-MS M⁺ 514 NMR(CDCl₃) 7.59(1H, d (J=16.13 Hz)), 6.35(1H, d (J=15.77 Hz)), 6.75(2H, s), 4.95(1H, q), 3.86(9H, s), 1.65 (2H, m), 1.29(3H, d(J=6.23 Hz)), 0.54(2H, m), 0.11(18H, s), 0.09(3H, s). Figure 1 shows the UV-spectrum at a concentration of 10 ppm (solvent, ethanol), and it was confirmed that the silicone type cinnamic acid derivative, which is the novel compound of the present invention, has a satisfactory absorption in the UV-B wavelength region. Synthesis Example 3 A hydrosilylation reaction was carried out in the same manner as in Synthesis Example 2 except that benzene was used as the solvent. Then purification was conducted in the same manner to obtain 3.1570 g (61.1%) of the product. Synthesis Example 4 A hydrosilylation reaction was carried out in the same manner as in Synthesis Example 2, except that xylene was used as the solvent. Then purification was conducted in the same manner to obtain 3.5240 g (68.2%) of the product. Synthesis Example 5 An amount of 10.48 g of 3,4-dimethoxycinnamic acid and 11 ml of thionyl chloride were stirred in 200 ml of benzene at reflux temperature for 2 hours to be converted to acid chloride, and after the solvent was removed, 80 ml of toluene containing 3.63 g of 1-butene-3-ol was added, followed by cooling the reaction system in an ice bath. Then 40 ml of toluene containing 5.10 g of triethylamine was slowly added and the mixture was stirred for one hour, followed by stirring the mixture at room temperature for one day. After filtration, the toluene layer was washed with water, and after removal of the water, subjected to silica gel column chromatography, using toluene as the solvent, to obtain 6.886 g (52.2%) of 3,4-dimethoxycinnamic acid ester. GC-MS M⁺ 262 NMR (CDCl₃) 7.63 (1H, d (J=15.62 Hz)), 6.32 (1H, d (J=15.62Hz), 6.85 (1H, d(J=8.30 Hz), 7.05 (1H, s), 7.10 (1H, d(J=8.30 Hz)), 5.92 (1H, m), 5.50 (1H, m), 5.30 (1H, d (J=17.09 Hz)), 5.16 (1H, d (J=10.75 Hz)), 3.90 (6H, s), 1.29 (3H, d(J=6.83 Hz)). Synthesis Example 6 The ester obtained in Synthesis Example 5 (2.6231 g) and 2.2291 g of siloxane (MHM) were poured into 50 ml of toluene, then 2 or 3 drops of 0.1 M chloroplatinate isopropyl alcoholic solution were added, followed by stirring at reflux temperature for 5 hours to carry out the hydrosilylation reaction. The product was isolated by silica gel columm chromatography, using toluene as the solvent, to obtain 2.9157 g (60.1%) of an oily silicone type cinnamic acid derivative of the present invention. This product was identified by the following analytical values. Name of substance: [3-bis(trimethylsiloxy)methylsilyl-1-methylpropyl]-3,4-dimethoxycinnamate GC-MS M⁺ 484 NMR (CDCl₃) 7.63 (1H, d (J=15.62 Hz)), 6.32 (1H, d (15.62 Hz)), 6.85 (1H, d (J=8.30 Hz)), 7.05 (1H, s), 7.10 (1H, d (J=8.30 Hz)), 4.95 (1H, q), 3.90 (6H, s), 1.65 (2H, m), 1.29 (3H, d (J=6.83 Hz)), 0.54 (2H, m), 0.11 (18H, s), 0.09 (3H, s). Figure 2 shows the UV-spectrum at the concentration of 10 ppm (solvent, ethanol), and it was confirmed that the silicone type cinnamic acid derivative, which is the novel compound of the present invention, has a satisfactory absorption in the UV-B wavelength region. Synthesis Example 7 An amount of 24.1550 g of 3,4,5-trimethoxycinnamic acid and 22 ml of thionyl chloride were stirred in 160 ml of benzene at reflux temperature for 4 hours, to be converted to acid chloride, and after removal of the solvent, 160 ml of toluene containing 5.8550 g of allyl alcohol was added, followed by cooling the reaction system in an ice bath. Then 80 ml of toluene containing 10.111 g of triethylamine was slowly added and the mixture was stirred for 12 hour. After filtration, the toluene layer was washed with water, and after removal of the water, subjected to silica gel columm chromatography, using toluene as the solvent, to obtain 20.3039 g (72.0%) of 3,4,5-trimethoxycinnamic acid ester. The product was in the form of a white crystal and the melting point was 67.0 - 68.2°C. GC-MS M⁺278 Synthesis Example 8 The ester obtained in Synthesis Example 7 (5.6054 g) and 4.4713 g of siloxane (MHM) were poured into 100 ml of benzene, and several drops of H₂PtCl₆ isopropyl alcoholic solution were added, followed by stirring at reflux temperature for 4 hours to carry out the hydrosilylation reaction. The product was isolated by silica gel column chromatography, using toluene as the solvent, to obtain 2.7846 g (27.6%) of an oily silicone derivative of the present invention. This product was identified by the following analytical values: [3-bis(trimethylsiloxy)methylsilylpropyl]-3,4,5-trimethoxycinnamate GC-MS: M⁺ 500 ¹H-NMR(CDCl₃) 7.55(1H, d (J=16.12 Hz)), 6.31(1H, d (J=15.63 Hz)), 6.70(2H, s), 4.11(2H, t), 3.82(9H, s), 1.69 (2H, m), 0.51(2H, t), 0.06(18H, s). The UV-spectrum at a concentration of 10 ppm (solvent, ethanol) of the product was not substantially changed from that (Fig. 1) of the compound of Synthetic Example 2. Synthesis Example 9 The ester obtained in Synthesis Example 7 (5.000 g) and 5.500 g of siloxane HSi (OSiMe₃)₃ were poured into 100 ml of benzene, and several drops of H₂PtCl₆ isopropyl alcoholic solution were added, followed by stirring at reflux temperature for 4 hours to carry out the hydrosilylation reaction. The product was isolated by silica gel column chromatography, using toluene as the solvent, to obtain 2.077 g (20.1%) of an oily silicone derivative of the present invention. This product was identified by the following analytical values. [3-tris(trimethylsiloxy)silylpropyl]-3,4,5-trimethoxycinnamate GC-MS: M⁺ 574 ¹H-NMR(CDCl₃) 7.61(1H, d (J=15.87 Hz)), 6.36(1H, d (J=15.87 Hz)), 6.77(2H, s), 4.17(2H, t), 3.90(9H, s), 1.74 (2H, m), 0.53(2H, t), 0.13(18H, s). The chemical shift was determined by using hydrogen (7.27 ppm) of CHCl₃. The UV-spectrum at a concentration of 10 ppm (solvent, ethanol) of the product was not substantially changed from that of the compound of Synthetic Example 2. Synthesis Example 10 An amount of 11.960 g of 3,4,5-trimethoxycinnamic acid and 11 ml of thionyl chloride were stirred in 80 ml of benzene at reflux temperature for 3 hours, to be converted to acid chloride, and after removal of the solvent, 80 ml of toluene containing 3.640 g of 1-butene-4-ol was added, followed by cooling the reaction system in an ice bath. Then 40 ml of toluene containing 5.340 g of triethylamine was slowly added and the mixture was stirred for 24 hour, followed by stirring the mixture at room temperature for 24 hours. After filtration, the toluene layer was washed with water, and after removal of the water, subjected to silica gel column chromatography, using toluene as the solvent, to obtain 10.0342 g (68.4%) of 3,4,5-tri-methoxycinnamic acid ester. The product was in the form of white crystal having a melting point of 61.8 - 63.8°C. GC-MS: M⁺ 292 Synthesis Example 11 The ester obtained in Synthesis Example 10 (2.9303 g) and 2.2289 g of siloxane (MHM) were poured into 100 ml of benzene, and several drops of H₂PtCl₆ isopropyl alcoholic solution were added, followed by stirring at reflux temperature for 2 hours to carry out the hydrosilylation reaction. The product was isolated by silica gel columr chromatography, using toluene as the solvent, to obtain 3.1488 g (61.0%) of an oily silicone derivative of the present invention. This product was identified by the following analytical values. [3-bis(trimethylsiloxy)methylsilylbutyl]-3,4,5-trimethoxycinnamate GC-MS: M⁺ 514 ¹H-NMR(CDCl₃) 7.59(1H, d (J=15.62 Hz)), 6.35(1H, d (J=16.11 Hz)), 6.74(2H, s), 4.21(1H, t), 3.87(9H, s), 1.75 (2H, m), 1.47(2H, m), 0.51(2H, m), 0.10(18H, s), 0.01(3H, s). The UV-spectrum at a concentration of 10 ppm (solvent, ethanol), of the product was not substantially changed from that of the compound obtained in Synthesis Example 2 (Fig. 1). Synthesis Example 12 A hydrosilylation reaction was carried out in the same manner as in Synthesis Example 11, except that siloxane HSi(OSiMe₃)₃ was used. By silica gel column chromatography, an oily silicone derivative of the present invention was obtained. This product was identified by the following analytical data. [3-bis(trimethylsiloxy)silylbutyl]-3,4,5-trimethoxycinnamate GC-MS: M⁺ 588 ¹H-NMR(CDCl₃) 7.59(1H, d (J=15.62 Hz)), 6.35(1H, d (J=16.11 Hz)), 6.74(2H, s), 4.21(2H, t), 3.87(9H, s), 1.75 (2H, m), 1.47(2H, m), 0.51(2H, m), 0.10(27H, s). The UV-spectrum at a concentration of 10 ppm (solvent, ethanol), of the product was not substantially changed from that of the compound obtained in Synthesis Example 2 (Fig. 1). Synthesis Example 13 A hydrosilylation reaction was carried out in the same manner as in Synthesis Example 6, except that siloxane HSi(OSiMe₃)₃ was used. By silica gel column chromatography, an oily silicone derivative of the present invention was obtained. This product was identified by the following analytical data. [3-tris(trimethylsiloxy)silyl-1-methylpropyl]-3,4,-dimethoxycinnamate GC-MS: M⁺ 558 ¹H-NMR(CDCl₃) 7.63(1H, d (J=15.62 Hz)), 6.32(1H, d (J=15.62 Hz)), 6.85(1H, d(J=8.30 Hz), 7.05(1H, s), 7.10(1H, d(J=8.30 Hz), 4.95(1H, q), 3.90(6H, s), 1.65 (2H, m), 1.29 (3H, d(J=6.83 Hz), 0.54 (2H, m), 0.10 (27H, s) The UV-spectrum at a concentration of 10 ppm (solvent, ethanol), of the product was not substantially changed from that of the compound obtained in Synthesis Example 6 (Fig. 2). Synthesis Example 14 An amount of 23.912 g of 3,4,5-trimethoxycinnamic acid and 22 ml of thionyl chloride were stirred in 700 ml of benzene at reflux temperature for 2 hours, to be converted to acid chloride, and after removal of the solvent, 160 ml of toluene containing 10.332 g of ethylene glycol monoallyl ether (CH₂ = CHCH₂OCH₂CH₂OH), was added, followed by cooling the reaction system in an ice bath. Then 80 ml of toluene containing 10.233 g of triethylamine was slowly added and the mixture was stirred for 24 hours. After filtration, the toluene layer was washed with water, and after removal of the water, subjected to silica gel column chromatography, using toluene as the solvent, to obtain 23.189 g (71.7%) of 3,4,5-trimethoxycinnamic acid ester. GC-MS: M⁺ 322 ¹H-NMR(CDCl₃)7.62(1H, d(J=15.63 Hz)), 6.39(1H, d(J=16.32 Hz)), 6.76(2H, s), 5.92(1H, m), 5.31(1H, d(17.09 Hz)), 5.21(1H, d(J=10.74 Hz)), 4.37(2H, t), 4.06 (2H, d(J=5.37 Hz)), 3.88 (9H, s), 3.72(2H, t). Synthesis Example 15 The ester obtained in Synthesis Example 14 (3.2329 g) and 2.2896 g of siloxane (MHM) were refluxed in 50 ml of toluene for 2 hours to carry out the hydrosilylation reaction. The product was isolated by silica gel column chromatography to obtain 3.9251 g (71.8%) of an oily silicone derivative of the present invention. This product was identified by the following analytical values. GC-MS: M⁺ 544 The UV-spectrum at a concentration of 10 ppm (solvent, ethanol) of the product was not substantially changed from that of the compound obtained in Synthesis Example 2 (Fig. 1). Synthesis Example 16 A 2.613 g amount of sodium 3,4,5-trimethoxycinnamate was added to toluene and the mixture was stirred under reflux for a while, followed by removing the solvent from the mixture. Thereafter, 100 ml of dimethylformamide was added and 3.015 g of 3-(3-chloropropyl)heptamethyl trisiloxane was gradually added thereto, followed by stirring at 120°C for 4 hours. After the reaction was completed, the solvent was removed and the product was isolated by silica gel column chromatography, using toluene as the solvent, to obtain 3.261 g (65.1 %) of an oily silicone derivative of the present invention. The spectrum was identical with that of the derivative obtained by the hydrosilylation. Synthesis Example 17 A 2.625 g amount of sodium 3,4,5-trimethoxycinnamate was added to toluene and the mixture was stirred under reflux for a while, followed by removing the solvent from the mixture. Thereafter, 100 ml of dimethylformamide was added and 3.732 g of 3-chloropropyltris (trimethylsiloxy)silane was gradually added thereto, followed by stirring at 120°C for 4 hours. After the reaction was completed, the solvent was removed and the product was isolated by silica gel column chromatography, using toluene as the solvent, to obtain 3.432 g (59.7 %) of an oily silicone derivative of the present invention. The spectrum was identical with that of the derivative obtained by the hydrosilylation. To determine the solubilities of the silicone type cinnamic acid derivatives (dimethoxy, trimethoxy substituted derivatives) obtained in Synthesis Examples 2-4, 6, 8, 9, 11-13, and 15, the solubility tests in dimethylpolysiloxane and methylphenylpolysiloxane were conducted at 25°C. In all of the tests, these derivatives were dissolved at 10% by weight or more, thus exhibiting an excellent solubility. Note, the esters obtained as precursors exhibited substantially no solubility. To test the water resistance and oil resistance thereof, the silicone type cinnamic acid derivatives (dimethoxy, trimethoxy substituted derivatives) of the present invention were mixed, while stirring with water, a 50% ethanolic solution, and oils such as fluid paraffin, and were left to stand at 50°C for 60 days. No hydrolysis occurred, and thus it was confirmed that these derivatives had an excellent water resistance and oil resistance. Examples of the use thereof as UV-ray absorbers are shown, and from the UV-spectra shown in Figs. 1 and 2, it is obvious that these derivatives had particularly excellent UV-B absorption effect. The conventional UV-ray absorbers sometimes have properties such that the electron spectra thereof are shifted by, for example, 10 to 20 nm in a base or solvent into which UV-ray absorbers are incorporated. For example, the electron spectrum of N,N-dimethyl 2-ethylhexylcinnamate is shifted by about 10 nm in ethanol and dimethyl polysiloxane. It is required in the art that the solvent dependency of UV-ray absorbers be small. The silicone cinnamic acid derivatives of the present invention advantageously meet the above-mentioned requirements. Furthermore, UV-ray absorbers are required to possess the safety as a UV-ray absorber and the stabilities against heat and light. The silicone type cinnamic acid derivatives according to the present invention have no problems in the safety of, for example, the contact sensitization, photo-contact sensitization, mutagenicity, and photo-toxicity and also have good heat stability including hydrolysis. Regarding the light stability, the present cinnamic acid derivatives are quite stable under normal sunlight irradiation conditions. The photo-isomerization (i.e., trans → cis) occurs only when an ultra-high-pressure mercury lamp is irradiated, but the absorption is still observed in the UV-B region. Thus, the present cinnamic acid derivative is still useful as an excellent UV-ray absorber even after the photo-isomerization. The UV-ray absorption effect when dissolved in a silicone base is shown below. Example 1: UV-ray absorber (oily type) : These components were mixed until dissolved, and then filtered to obtain a product. Comparative Example 1 A product was obtained in the same way as above, except that (5) was omitted from the recipe of Example 1. Measurements of the UV-ray prevention effect of Example 1 and Comparative Example 1 obtained as described above were conducted. The UV-ray prevention effect was measured by using the UV-ray sensitive composition described in Japanese Unexamined Patent Publication (Kokai) No. 62-112020. The method of preparing the inventive composition is now described. A solution of 1.0 g of Leuco Crystal Violet, 0.1 g of tetrabromodimethylsulfone, 10 g of an ethylene-vinyl acetate copolymer, and 100 ml of toluene was prepared to provide a Solution I. Separately, a solution of 7 g of N,N-dimethyl-p-aminobenzoic acid-2-ethylhexyl ester, 10 g of an ethylene-vinyl acetate copolymer, and 100 ml of toluene was prepared to provide a Solution II. The solution I was coated on an original for photography, and dried to an amount of 1 g/m² as a solid, and then Solution II was coated thereon to an amount of 5 g/m² as a solid, to obtain a UV-ray sensitive composition. This UV-ray sensitive composition was a paper which changed color from white to pale purple to purple to deep purple in accordance with the increase in the dosage of UV-rays irradiated thereon. An amount of 40 mg of the sample to be measured was mixed with 12 g of castor oil and subjected to the roller treatment to be uniformly dispersed therein. A transparent PET film was placed on the above UV-ray sensitive composition shaped as a circle 5 cm in diameter, and 1.5 g of the composition was coated to a uniform thickness thereon and irradiated by a UV-ray lamp for 8 minutes. Then, the PET film was removed, together with the sample, and the color of the UV-ray sensitive composition was measured by a model 607 Spectrophotometer (Hitachi), and the color difference was calculated according to the LAB system with the color of the UV-ray sensitive composition, with the dosage of UV-rays at zero as the standard. The results are shown below. Synthesis Color difference Example. 2 21 3 21 4 21 6 21 8 20 9 21 11 20 12 20 13 22 15 20 Comparative Example 1 58 It can be seen that the color differences of the above-mentioned Examples are smaller than that of Comparative Example 1, and thus exhibits a greater UV-ray prevention effect. Namely, it can be seen that an excellent UV-ray prevention effect can be obtained by formulating the silicone type cinnamic acid derivative of the present invention. Example 2 Suntan proof cosmetic (oily type) (Preparation method) The components (1) to (5) were mixed and thoroughly dissolved, and then filtered to provide a product. Comparative Example 2 A product was obtained by using the same procedure as in Example 2, except that the component (5) in the recipe of Example 2 was omitted. Example 3: Suntan proof cosmetic (W/O cream) (Preparation method) The components (1) to (6), (11) were mixed, dissolved by heating and maintained at 70°C to form an oil phase portion, and separately, the components (7) to (10) were dissolved by heating and maintained at 70°C to form an aqueous phase portion. The aqueous phase portion was added to the oil phase portion, followed by emulsification by an emulsifying machine. After emulsification, the emulsion was cooled while stirring, and when the temperature became 35°C or lower, the emulsion was cast into a vessel and left to cool and solidify. Comparative Example 3 A product was obtained by using the same procedure as in Example 3, except that the component (5) in the recipe of Example 3 was omitted. Example 4 Suntan proof cosmetic (O/W cream) (Preparation method) The components (1) to (10) were heated at 70°C while stirring to form an oil phase portion, and the components (11) to (15) were completely dissolved by heating at 70°C to form an aqueous phase portion. The oil phase portion was added to the aqueous phase portion and the mixture was emulsified by an emulsifying machine. The emulsified product was cooled through a heat exchanger to 30°C and then filled to obtain a product. Comparative Example 4 A product was obtained by using the same procedure as in Example 4, except that the component (8) in the recipe of Example 4 was omitted. Example 5: Suntan proof lotion (Preparation method) The components (1) to (6) were heated at 70°C while stirring to form an oil phase portion, and the components (7) to (10) were dissolved by heating at 70°C to form an aqueous phase portion. The oil phase portion was added to the aqueous phase portion, and the mixture was emulsified by an emulsifying machine. The emulsified product was cooled through a heat exchanger to 30°C and then filled to obtain a suntan proof lotion. Comparative Example 5 A product was obtained by using the same procedure as in Example 5, except that the component (4) in the recipe of Example 5 was omitted. The UV-ray prevention effects of Examples 2 to 5 and Comparative Examples 2 to 5 were then measured by using the UV-ray sensitive composition shown below. The UV-ray prevention effect was measured by using of the UV-ray sensitive composition described in Japanese Unexamined Patent Publication (Kokai) No. 62-112020. The method of preparing the UV-ray sensitive composition is further described. A liquid comprising 1.0 g of leuco crystal violet, 0.1 g of tetrabromodimethylsulfone, 10 g of an ethylene-vinyl acetate copolymer, and 100 ml of toluene was prepared to provide a Liquid I, and separately, a liquid comprising 7 g of N,N-dimethyl-p-aminobenzoic acid-2-ethylhexyl ester, 10 g of an ethylene-vinyl acetate copolymer and 100 ml of toluene was prepared to provide a Liquid II. First, on an original paper for photography, the Liquid I was coated to 1 g/m² as the solid, and after drying, the Liquid II was coated thereon to 5 g/m² as the solid, to obtain a UV-ray sensitive composition. The UV-ray sensitive composition is a paper which indicates color changes due to an irradiation of UV-ray, such as white to pale violet to violet to deep violet, as the UV-ray irradiation dosage is increased. An amount of 40 mg of the sample to be measured was mixed in 12 g of castor oil and subjected to the roller treatment to be uniformly dispersed therein. On the above UV-ray sensitive composition shaped as a circle 5 cm in diameter, a transparent PET film was placed and 1.5 g of the dispersion was coated thereon to a uniform thickness, followed by irradiation of a UV-ray lamp for 8 minutes. The PET film was removed together with the sample and the UV-ray sensitive composition, which indicated the color, was measured by a model 607 spectrophotometer (Hitachi) and the color difference was calculated according to the LAB system, by comparing the color of the UV-ray sensitive composition when the UV-ray irradiated dosage is zero as the standard. The results are shown in Table 1. Color difference Example 2 21 Comparative Example 2 58 Example 3 32 Comparative Example 3 45 Example 4 38 Comparative Example 4 57 Example 5 28 Comparative Example 5 52 As can be seen from Table 1, the color differences in the Examples are smaller than those in the corresponding Comparative Examples, and thus have a greater UV-ray prevention effect. Therefore, it is clear that a superior UV-ray prevention effect can be obtained by formulating the silicone type cinnamic acid derivative of the present invention. Example 6: Suntan proof amphibious foundation (Preparation method) The components (1) to (5) were mixed by a Henschel mixer and a mixture of the components (6) to (13) were mixed and dissolved by heating and then added thereto and pulverized, followed by molding into a dish to obtain a suntan proof amphibious foundation. Example 6 was found to have light spreadability, provide a natural finish with a good cosmetic durability, and to have a prolonged UV-ray prevention effect. Example 7: Suntan proof stick cosmetic (Preparation method) The components (1) to (6) were mixed by a Henschel mixer, and the mixture was added to the components (7) to (9), (13), (15) and (16), which were dissolved by heating while stirring, and mixed therewith. Next, the melted components of (1) to (12) and (14) were added to the above mixture, and after thoroughly mixing, molded into a stick to obtain a suntan proof stick cosmetic. Example 7 was found to have a high UV-ray prevention effect and an excellent cosmetic durability. Example 8: Suntan proof cosmetic base (Preparation method) The components (1) to (5), (9), (11) and (12) were dissolved while stirring, the components (6) to (8) and (10) previously heated to 70°C were added thereto, and the mixture was emulsified and then cooled to obtain the desired suntan proof cosmetic base. Example 8 was found to have a high UV-ray prevention effect and an excellent cosmetic durability. Example 9: Suntan proof stick cosmetic (Preparation method) The components (1) to (6) were mixed by a Henschel mixer, and the mixture was added to the components (7) to (9), (13), (15) and (16) which were dissolved by heating under stirring to be mixed therewith. Next, the melted components of (10) to (12) and (14) were added to the above mixture, and after thorough mixing, molded into a stick to obtain a suntan proof stick cosmetic. Example 9 was found to have high UV-ray prevention effect and also excellent cosmetic durability, similarly as in Example 7. Example 10: Suntan proof cosmetic base (Preparation method) The components (1) to (5), (9), (11) and (12) were dissolved under stirring, and the components (6) to (8) and (10) previously heated to 70°C were added thereto and the mixture was emulsified and then cooled to obtain the desired suntan proof cosmetic base. Example 10 was found to have high UV-ray prevention effect and also excellent cosmetic durability, similarly as in Example 8. The silicone type cinnamic acid derivative according to the present invention is an extremely useful substance which absorbs the UV-B wavelength region, exhibits an excellent solubility in silicone oils, and has an excellent water resistance and oil resistance. The method according to the present invention is extremely efficiently when preparing the compound, and the UV-ray absorber according to the present invention is an excellent UV-ray absorber particularly suitable for external agents such as cosmetics and quasi-drugs. Namely, since this agent can withstand wavelengths in the UV-B region and at the same time, has an excellent solubility in silicone oils, it can be formulated in any desired amount without impairing the characteristics of the silicone type bases, and is a UV-ray absorber having an excellent water resistance and oil resistance. The dermatological external treatment agent of the present invention can provide a desired protection against the wavelengths in the UV-B region. Also, the UV-B absorber to be used in the present invention has an excellent water resistance and oil resistance, and therefore, can provide a dermatological external treatment agent in which the base and the components to be formulated can be freely selected, and at the same time, has the advantage of an excellent stability even when left to stand under severe conditions, such as in direct sun light. The dermatological external treatment agent of the present invention, which employs a silicone type base, provides a superior useability such as a good spreadability, plain feeling and no stickiness, and a strong resistance to removal by sweat or water (good cosmetic durability), in addition to the above effect. Further, a UV-B absorber can be formulated in any desired amount, and thus another effect is provided in that a dermatological external treatment agent having a widely based UV-ray prevention effect can be obtained.

Claims: A silane type cinnamic acid derivative represented by the formula (I'): wherein R¹ represents an alkyl group having 1 to 4 carbon atoms, a phenyl group, or a trimethylsiloxy group, R² is a divalent hydrocarbon group having at least two carbon atoms, which may include a heteroatom O, X is an alkoxy group, and a is an integer of 2 or 3. A silane type cinnamic acid derivative as claimed in claim 1, wherein R¹ is a methyl or a trimethylsiloxy group, R² is a linear or branched alkylene group having 3 or 4 carbon atoms, X is methoxy, and a is 2 or 3. A silicone type cinnamic acid derivative which is a siloxane having at least one unit represented by the formula (I): and having other units which can exist in said siloxane being represented by the formula: O (4-m)/2 SiR 3 / m wherein R¹ represents an alkyl group having 1 to 4 carbon atoms, a phenyl group, or a trimethylsiloxy group, R² is a divalent hydrocarbon group having at least two carbon atoms, which may include a heteroatom O, X is an alkoxy group, n is an integer of 0 to 2, a is an integer of 2 or 3, R³ is an alkyl group having 1 to 4 carbon atoms, a phenyl group, or a trimethylsiloxy group, and m is an integer of 0 to 3. A method of preparing a silane type cinnamic acid derivative of claim 1 or a silicone type cinnamic acid derivative of claim 3, comprising the step of reacting a cinnamic acid ester having the formula: wherein Y represents a monovalent hydrocarbon group having at least two carbon atoms and an olefinic unsaturated bond, which may include a heteroatom O, X is an alkoxy group, and a is 2 or 3 with a siloxane having an unit and optionally a R 3 / mSiO (4-m)/2 unit wherein R¹ and R³ independently represent an alkyl group having 1 to 4 carbon atoms, a phenyl group, or a trimethylsiloxy group, and n and m are integers of 0 to 3, in an organic solvent in the presence of a catalyst. A method of preparing a silane type cinnamic acid derivative of claim 1 or a silicone type cinnamic acid derivative of claim 3, comprising the step of reacting a cinnamic acid salt having the formula: wherein X represents an alkoxy group, Z represents an alkali metal, and a is 2 or 3, with a halogeno alkylene silicone derivative having the formula: wherein W represents a halogen, R¹ represents an alkyl group having 1 to 4 carbon atoms, a phenyl group, or a trimethylsiloxy group, R² is a divalent hydrocarbon group having at least two carbon atoms, which may include a heteroatom O, and n is an integer of 0 to 3 in an organic solvent. A UV-ray absorber comprising a silane type cinnamic acid derivative of claim 1 or claim 2 or a silicone type cinnamic acid derivative of claim 3. An external skin treatment agent comprising a silane type cinnamic acid derivative of claim 1 or claim 2 or a silicone type cinnamic acid derivative of claim 3. An external skin treatment agent as claimed in claim 7, wherein a silicone base is used as a base for the external treatment agent.

Inventors: NANBA TOMIYUKI C O SHISEIDO LA, UEHARA KEIICHI C O SHISEIDO LA, YOSHIDA MASASHI C O SHISEIDO L, NANBA, TOMIYUKI C/O SHISEIDO LABORATORIES, UEHARA, KEIICHI C/O SHISEIDO LABORATORIES, YOSHIDA, MASASHI C/O SHISEIDO LABORATORIES
Applicants: SHISEIDO CO LTD, SHISEIDO COMPANY LIMITED
Application year: 1989
Main classification: C07F7
IPC codes: A61K8, C07F7, A61Q17