JPS6253953A - 4'-lower alkoxy-2-(n,n-dilower alkylcarbamoyl) dibenzoylmethane - Google Patents

Abstract

NEW MATERIAL:A compound expressed by formula i (R1-R3 are lower alkyl). EXAMPLE:4'-Methoxy-2-(N,N-diethylcarbamoyl)dibenzoylmethane. USE:An ultraviolet light absorber for cosmetics, capable of effectively absorbing ultraviolet rays in the UV-A region, stable to light and heat with time, scarcely hydrolyzed in cosmetics and capable of exhibiting improved solubility in solvents normally used in cosmetics. PREPARATION:A compound expressed by formula II is reacted with a halogenating reagent in an inert solvent to give an intermediate 3-(4'-lower alkoxyphenacylidene)phthalide expressed by formula III, which is reacted with a secondary amine expressed by formula IV in an inert solvent to afford the compound expressed by formula I.

Description

[Detailed description of the invention] [Industrial application field] The present invention provides novel 4'-lower alkoxy-2-(N.

N-di-lower alkylcarbamoyl) dibenzoylmethane, more particularly 4'-lower alkoxy-2-(N-dibenzoylmethane), which is useful, for example, as a UV absorber for cosmetics.

The present invention relates to N-dilower alkylcarbamoyl)dibenzoylmethane derivatives.・ [Conventional technology] Ultraviolet rays are known to cause various changes in the skin. Dermatologically, the working wavelength is 400 to 320n.
Ultraviolet rays are divided into long wavelength ultraviolet rays of m, medium wavelength ultraviolet rays of 320 to 2901 m, and short wavelength ultraviolet rays of 29 Qnm or less, and are called UV-A% UV-B and UV-C, respectively.

Normally, most of the sources of ultraviolet radiation to which humans are exposed are sunlight, but the ultraviolet rays that reach the ground are UV-A and UV-B, and UV-C is absorbed in the ozone layer and almost never reaches the ground. Among the ultraviolet rays that reach the ground, UV-B
When the skin is exposed to more than a certain amount of light, erythema and chickenpox are formed, and melanin formation is advanced, causing changes in the skin such as pigmentation. On the other hand, conventionally,
It was thought that UV-A did not cause significant changes in the skin. However, it has recently been revealed through electron microscopy and histochemical techniques that the skin undergoes changes even after UV-A irradiation. In particular, UV-A
is different from U''/-B, and its energy reaches the dermis, causing microchronic changes in the elastic fibers in blood vessel walls and connective tissue, and these changes are thought to lead to accelerated skin aging. It is also known that UV-A has the effect of darkening the skin immediately after irradiation (immediate blackening) and that it enhances the degenerative effect of TFF-H on the skin.
UV-A is thought to be a factor in the occurrence and aggravation of age spots and freckles.

These things are obvious, not only UV-B (U
Protecting the skin from V-A is important in terms of preventing accelerated aging of the skin and preventing the occurrence and aggravation of age spots and freckles.

[Problem that the invention seeks to solve]

However, research on the effects of UV-A on the skin has a short history, and when applied to the skin, UV-A
In reality, there are no known substances that absorb A, and currently only dibenzoylmethane derivatives and cinnamon powder are known (West German Patent Publication No. 272).
Publication No. 8241, Publication No. 2728243, JP-A-5
No. 1-61641, No. 52-46056, No. 57-197209, and Japanese Unexamined Patent Publication No. 57-59840). Moreover, these substances lack versatility;
When attempting to add and blend this into cosmetics as a UV-A absorber, there was a drawback that restrictions were placed on the properties of the base of the cosmetics.

Therefore, it has been desired to develop a more versatile UV-A absorber. Such UV-A absorbers must meet the following conditions:

■It has a maximum absorption wavelength around 350 nm.

(2) The molar extinction coefficient (ε) is sufficiently large at the above wavelength.

■ Since coloring is not desirable in cosmetic compositions, absorption in the visible region must be small, that is, g
To be O.

■ Stable against heat and light.

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

■ Excellent compatibility with cosmetic bases.

■ When applied to the skin, it is difficult to be absorbed through the skin and difficult to remove through sweating, etc. Therefore, the effect lasts effectively.

■ It must be inexpensive.

[Means for solving problems]

The inventors of the present invention conducted extensive research in view of the current situation, and found that
A new compound, 4'-lower alkoxy-2-(N
, N-dilower alkylcarbamoyl)dibenzoylmethane absorbs light in the UV-A region, and completed the present invention.

That is, the present invention provides a 4'-lower alkoxy-2-(N,N-cy lower alkyl carbamoyl) dibenzoylmethane.

The compound (1) of the present invention is, for example, 4'-lower alkoxy-
It is produced using 2-carboxydibenzoylmethane (old) as a raw material according to the following reaction formula.

That is, the compound of the present invention (Il is a compound of the intermediate 3-(4'-lower alkoxyphenacylidene) phthalide (1), and then reacting this compound (1) with a secondary amine in a solvent inert to the reaction.

To obtain 4'-lower alkoxy-2-carboxydibenzoylmethane (formerly intermediate 3-(4'-lower alkoxyphenacylidene) phthalide (1)), halogenating reagents such as thionyl chloride are effective. .

This reaction is carried out by adding a halogenating reagent such as 4'-lower alkoxy-2-carboxydibenzoylmethane (formerly and a small amount of thionyl chloride) to a reaction-inert solvent such as chloroform or dichloromethane, and starting at -10°C. The reaction is carried out at a temperature of 200°C, preferably 30 to 100°C. After the reaction is complete, the solvent and excess halogenating reagent are distilled off under reduced pressure to obtain the desired 3-(4'-lower alkoxy7enacylidene)7.
Thalide ([) is obtained quantitatively. This thing is two bodies and E
Although they are often obtained as a mixture of substances, either can be used in the next reaction.

Next, 3-(4'-lower alkoxy7enacylidene)7
To react with talide ([)t secondary amine to obtain the desired 4'-lower alkoxy-2-(N,N-dilower alkylcarbamoyl)dibenzoylmethane (I), add 3- to a solvent inert to the reaction. Add (4'-lower alkoxy 7-enacylidene) 7-thallide (1) and an excess amount of secondary amine to
The reaction is completed at a temperature of 0°C to 200°C, preferably 10 to 100°C. After completion of the reaction, post-treatments such as extraction and washing are performed, and the solvent is distilled off under reduced pressure to obtain pale yellow crystals or oil. Further purification is performed by recrystallization or silica gel column chromatography to obtain the desired 4'-lower alkoxy-2-(N.

N-dilower alkylcarbamoyl)dibenzoylmethane (1) is obtained.

[, action and effect of the invention]

The 4'-lower alkoxy-2-(N,N-di(l) of the present invention
t-alkyl, lucarpamoyl) dibenzoylmethane (I)
is an odorless, pale yellow crystal or oily substance that effectively absorbs ultraviolet rays in the UV-A region that cause harmful effects as described above, and protects the skin from the harmful effects of these. It is stable against light and heat over time, hardly undergoes hydrolysis in cosmetics, and exhibits excellent solubility in solvents commonly used for cosmetics. etc., are extremely useful as UV absorbers for cosmetics.

〔Example〕

Next, reference examples, working examples, and test examples will be given and explained.

Reference Example 3 - Synthesis of (4'-methoxy7enacylidene)7thalide: 4'-methoxy-2-carboxydibenzoylmethane (
10054,0.34 mol) in methylene chloride (40
In addition to this suspension, thionyl chloride (60,9
4S', 0.51 mol) was added at once, and 30
The mixture was stirred at ℃ for 1 hour and then at reflux temperature for 3 hours to complete the reaction.

When the solvent and excess thionyl chloride are distilled off from the reaction mixture solution under reduced pressure, the desired 3-(4'-methoxy7enacylidene) phthalide (mixture of 2 and E forms) is almost quantitatively obtained. The ratio of the 2-isomer and the E-isomer was determined from the integral ratio of olefin hydrogen in NMR, and it was found to be 30 near 0, with the E-isomer being produced in a larger amount.

By washing this mixture with hot acetone, almost pure E form can be isolated as yellow needle-shaped crystals (yield: about 65%).

mp163-164℃ NMR (CD (JS) δppm: 3.91 (3H, s, -OCH,) 7.00 (2
H, d, J-8,5Hz, benzene nuclear hydrogen Hb17
．． 19 (IH, s, olefin hydrogen Hc17.67-7
．． 88 (2H, m, benzene nuclear hydrogen He, Hf 1
7.95-8.02 (I H, m, benzene nuclear hydrogen H
d) 8.04 (2H, d, J-8, 5Hz, benzene nuclear hydrogen Ha) 9.00 (IH, d, J-8, lH
z, be/zea nuclear hydrogen Hg) E body RVmaz (KBrl (M-' ?1795,1
660,1605.1510,1470,1420゜1
395.1310, 1255, 1180, 1065.9
75 Also, the compound dissolved in heated acetone was purified by silica gel column chromatography to obtain two pure compounds as yellow needles.

mp172-173℃ NMR (CDCI3s) δppm: 3.89
(3H,s, -OCH,)6.72 (IH,S, olefin hydrogen Ha)6.93~7.03 (2H,m
, benzene nuclear hydrogen Hb) 7.66-7.91 (3H,
m, benzene nuclear hydrogen He, Hf, Hg 17.94
~8.05 (3H, m, benzene nuclear hydrogen Ha, Hd
) Engineering Rvmax (KBr) cm-': 1795
．． 1670, 1615, 1590, 1510, 1470
゜1365.1330,1300,1260,1220
, 1165°1080.1005.965 Example 4'-methoxy-2-(N,N-diethylcarbamoyl)dibenzoylmethane; 10fi4.35
．． 7mmal l and diethylamide 7 (10,3t
, 140.8 mmol l was added, and stirring was continued for 6 hours under heating and reflux.

The reaction mixture solution was cooled to room temperature, diluted with ether, and diluted twice with 12-hydrochloric acid aqueous solution, followed by hydrogen carbonate).
Wash once with a saturated aqueous solution of Jum and once with a saturated saline solution.

After drying using sodium sulfate, the solvent was distilled off under reduced pressure to obtain a brown oil.

This product was purified by silica gel column chromatography (eluent: hexane/ethyl acetate = 200/1 to 3/1) to obtain the desired 4'-methoxy-2-(N,N -diethylcarbamoyl)dibenzoylmethane (9,69)) was obtained (yield near 7 cm).

mp77-78.8℃ NMR (CD(J, ) δppm: 0.97 (
3H,t, J-7Hz, -CH,11,14(3H
,t, J-7Hz, -CH81186~3.73 (
4H,m, -CH:lCH3X2 )3.80 (3
H, s, -α■3) 6.67 (IH, a, olefin hydrogen) 6.76-7
．． 10 (2H, m, Hairsen nuclear hydrogen) 7.14-8
．． 10 (6H, m, benzene nuclear hydrogen) 16.58
(IH, bs, enol hydrogen) engineering RA/max (KB
r) cm-': 2970, 2950.2890.1
730.1600.1510゜1465, 1290.1
260.1230.1175.1115°1090, 1
060.1035 UVλmaz (EtOH) nm: 353nml-
gogελmax=4.38 Test Example A ΦW-type cream having the following composition containing 4 units of the compound of the present invention (hereinafter referred to as the product of the present invention) was used.
The effect of protecting the skin from -A irradiation was investigated using the following method. The results are shown in Table 1.

Composition Nistearic acid 1.0 Monostearic acid glyceride zO Cetyl alcohol 1.0 Stearyl alcohol 1.0 Squalane
10.0 Liquid paraffin
20.0 Vaseline 5.0 Phylparaben 0.
1 Methylparaben 0.1
Triethanolamine 1.0
Glycerin 10.0 fragrance
Adequate amount of water
balance io
o.

Test method: Method such as Gschnait [Archives op Dermadological Research (Arc
hives of dermatological R
e5arch ) 263-+181~188 (1
9781). That is, the skin of a guinea pig was exposed by brushing the hair on its back, and its sensitivity to UV-A was previously increased by intraperitoneal administration of 8-methoxypsoralen. Next, the product of the present invention having the composition shown above was applied to the skin of the back brush area in an amount of 2 .mu./d, and 15 minutes later, UV-A irradiation was performed. After 24 hours of irradiation, the appearance of erythema on the skin was observed, and the minimum UV-A irradiation time that caused erythema on the skin was determined. This time was compared with the minimum UV-A irradiation time that causes erythema on the skin of the vermilion-applied area, and the sun protective factor (hereinafter abbreviated as SPF) was calculated from the following formula to examine the skin protective effect of each compound. . In addition, as a comparative product, a cream-based product was used.

Table 1 From Table 1, it can be seen that the cream containing 4'-methoxy-2-(N,N-diethylcarbamoyl)dipenzoylmethane effectively protects the skin from σV-A radiation.

Written amendment to the above procedure (voluntary) 1. Indication of the case 1985 Patent Application No. 194674 2. Title of the invention 4'-Lower alkoxy-2-(N,N-di-lower alkylcarbamoyl) dipenzoylmethane 3. Amendment. Applicant Address 1-14-10 Kayabacho, Nihonbashi, Chuo-ku, Tokyo Name (091) Kao Soap Co., Ltd. Representative Maru 1) Yoshi Department 4, Agent 6, Specification subject to amendment Column 76 of "Detailed Description of the Invention" Contents of the Amendment (1) In the specification, the phrase "cinnamic acid" in the first line of page 4 is corrected to read "cinnamic acid derivative."

Claims (1)

[Claims] 1. Represented by the following formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, R_1, R_2, and R_3 are each the same or different and represent a lower alkyl group) 4'-lower alkoxy-2-(N,N-dilower alkylcarbamoyl)dibenzoylmethane.