JP2759325B2 - 1,2-bis (dimethylaminocinnamoyloxy) propane derivative and ultraviolet absorber containing the propane derivative - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a novel compound, a 1,2-bis (dimethylaminocinnamoyloxy) propane derivative, and an ultraviolet absorbent containing the propane derivative.

(Prior Art) Conventionally, ultraviolet absorbers have been used in various technical fields. For example, in the field of cosmetics, various ultraviolet absorbers have been developed for the purpose of protecting the skin.

By the way, ultraviolet rays generally have UV-
A (320-400 nm), UV-B (280-320 nm), and UV-
C (at 280 nm or less). Regarding the effect on the skin, it is known that ultraviolet rays in the above-mentioned UV-B region form erythema and blisters, or cause skin disorders such as skin cancer. Therefore, most of the conventional ultraviolet absorbers in the cosmetics field absorb ultraviolet rays in the UV-B region.

However, ultraviolet rays in the UV-A region, which was conventionally recognized as having little effect on the skin,
Subsequent studies showed that pigmentation of spots, freckles, etc.
It was found that UV-B exhibited an effect of enhancing skin degeneration. Accordingly, ultraviolet absorbers for absorbing UV-A ultraviolet rays have been developed in recent years, and for example, dibenzoylmethane derivatives (JP-A-55-66535 and JP-A-62-56454) and benzophenone derivatives are known. ing.

(Problems to be Solved by the Invention) However, such conventional UV-A UV absorbers are not satisfactory in all respects such as safety, compatibility, absorption effect and the like, and are not always practical. Was difficult to serve.

The present invention has been made to solve such a problem, and an object of the present invention is to provide an ultraviolet absorber excellent in all aspects such as safety, compatibility, and absorption effect.

(Means for Solving the Problems) The present inventors have conducted intensive studies in order to solve such problems, and found that a novel substance, 1,2-bis (dimethylaminocinnamoyloxy) propane derivative, is a UV-A Not only effectively absorbs the light of the area, but also has no toxicity and irritation to the skin, and shows good compatibility with various bases and organic solvents for cosmetics, and long wavelength ultraviolet rays for cosmetics. The present inventors have found that they are extremely useful as absorbents, and have completed the present invention.

That is, the present invention has been made as a novel substance and an ultraviolet absorber in order to solve the above-mentioned problems. (R ₁ is an alkyl group having 1 to 18 carbon atoms or an acyl group having 2 to 18 carbon atoms, and R ₂ is an ortho- or para-position dimethylamino group [−
N (CH ₃ ) ₂ ]).

The gist of the constitution as the ultraviolet absorber is that it contains a 1,2-bis (dimethylaminocinnamoyloxy) propane derivative represented by the above general formula.

The above-mentioned compound of the present invention can be produced by various methods. Next, an example of the case where R ₁ is an alkyl group and an acyl group will be described.

First, when R ₁ is an alkyl group, 1,2 of glycerin
A glycerin monoether [b] synthesized by a conventional method using the following compound [a] in which a hydroxy site is protected with an acetal or the like in advance, and dimethylaminocinnamic acid directly without a catalyst or a general esterification catalyst Or by a transesterification reaction of dimethylaminocinnamic acid with a lower alcohol ester such as methyl ester, ethyl ester, propyl ester and the like.

On the other hand, when R ₁ is an acyl group, LAWRENCE C.MITCHEL
According to the method of L [J. Am. Oil. Chem. Soc. 49,281 (1972)], 1,2-dihydroxy-3-chloropropane is esterified with dimethylaminocinnamic acid chloride, and then sodium carboxylate (R- COONa) and react with the desired
A 1,2-bis (dimethylaminocinnamoyloxy) propane derivative can be synthesized.

Furthermore, dimethylaminocinnamic acid, the required carboxylic acid and glycerin can be directly synthesized without a catalyst, or can be easily prepared by transesterification of dimethylaminocinnamic acid, the lower alcohol ester of the required carboxylic acid with glycerin. Can be synthesized. However, in this case, the above 1,2-bis (dimethylaminocinnamoyloxy) propane derivative and the 1,3-bis (dimethylaminocinnamoyloxy) propane derivative [c] having the following structure
Can only be obtained in a mixture with

Moreover, it is not preferable to use a large amount of the 1,3-bis (dimethylaminocinnamoyloxy) propane derivative from the viewpoint of photostability.

(Example) Hereinafter, an example of the present invention will be described.

Example 1 This example is an example of the compound [I] represented by the following formula [A].

A mixture of 0.51 g of 1,2-dihydroxy-3- (2-ethylhexyloxy) propane, 1.42 g of ethyl para-dimethylaminocinnamate and 0.1 g of potassium carbonate was added under a nitrogen atmosphere to a mixture of 16 g.
The mixture was heated to 0 to 170 ° C. to remove ethyl alcohol generated by the reaction.

After reacting for 2 hours, the reaction solution was cooled, and the reaction solution to which 60 ml of chloroform was added was sufficiently washed with a 5% aqueous solution of potassium hydroxide and then with water, and then dried over magnesium sulfate to remove the solvent.

The residue thus obtained was purified by silica gel column chromatography using a mixture of ethyl acetate and dichloromethane (3:97) as an eluent, and 0.6 g of a pale yellow viscous oily substance represented by the following formula: Compound [I] of [A] was obtained.

The NMR of the compound [I] was measured and found to be as follows.

In the NMR measurement, ¹ H was used as a nuclide, CDCl ₃ was used as a solvent, and tetramethylsilane (TMS) was used as a standard for calculating a chemical shift δ ppm. Further, the resonance frequency was measured at 60 MHz.

0.6-1.1 (m, 6H), 1.1-1.6 (m, 9H), 3.03 (s, 12H),
3.40 (d, 2H, J = 5Hz), 3.68 (d, 2H, J = 5Hz), 4.45 (d, 2
H, J = 5Hz), 5.2−5.6 (1H), 6.25 (d, 2H, J = 16Hz), 6.6
5 (d, 4H, J = 9 Hz), 7.44 (d, 4H, J = 9 Hz), 7.67 (d, 2H, J
= 16 Hz Example 2 This is an example of the compound [II] represented by the following formula [B].

As a starting material, 0.37 g of 1,2-dihydroxy-3- (1,1-dimethylethyloxy) propane was used instead of 1,2-dihydroxy-3- (2-ethylhexyloxy) propane of Example 1 above. Using the same procedure as in Example 1, 0.5 g of compound [II] as pale yellow crystals was obtained.
The melting point of this compound [II] was 184 to 188 ° C.
Also, when NMR was measured for this compound [II],
It was as follows.

 The measurement conditions are the same as in Example 1 above.

1.20 (s, 9H), 3.02 (s, 12H), 3.62 (d, 2H, J = 5Hz),
4.47 (d, 2H, J = 5Hz), 5.1-5.5 (1H), 6.25 (d, 2H, J = 1
6Hz), 6.66 (d, 4H, J = 9Hz), 7.43 (d, 4H, J = 9Hz), 7.66
(D, 2H, J = 16 Hz) Example 3 This example is an example of a mixture [III] of a compound of the following formula [C] and a compound of the following formula [D].

Glycerin 0.56 g, ethyl paradimethylaminocinnamate
1.46 g, ethyl 2-ethylhexanoate 1.14 g, potassium carbonate
Using 0.1 g, the same procedure as in Example 1 was carried out to obtain 90 mg of a pale yellow viscous oily mixture [III].

However, dichloromethane was used as an eluate for chromatography during purification.

The NMR of the above mixture [III] was as follows.

 The measurement conditions are the same as in Example 1.

0.7-1.1 (m, 6H), 1.1-1.6 (m, 9H), 2.2-2.5 (2
H), 3.03 (s, 12H), 4.42 (d, 4H, J = 5Hz), 5.3-5.6 (1
H), 6.23 (d, 2H, J = 16 Hz), 6.65 (d, 4H, J = 9 Hz), 7.42
(D, 4H, J = 9 Hz), 7.66 (d, 2H, J = 16 Hz) (1) Protective effect against UV-A (a) Spectral characteristic value The ultraviolet absorption spectrum of each compound or mixture was measured. The spectral characteristic values are as shown in Table 1 below.

In addition, ethanol was used as a solvent at the time of measurement of each sample. In Table 1, λ _max indicates the maximum absorption wavelength (maximum absorption value), ε indicates the molecular extinction coefficient at the maximum absorption wavelength, and E indicates the absorbance at 360 nm of a 10 mg / l solution.

Further, in Table 1 above, Comparative Examples [I] and [II] are the following compounds, respectively.

Comparative Example [I]: 2-Hydroxy-4-methoxybenzophenone Comparative Example [II]: 2,2 ′, 4,4′-tetrahydroxybenzophenone From the spectral characteristic values in Table 1 above, the following for each of the above compounds and mixtures was obtained. Such excellence was recognized.

(A) The maximum absorption wavelength is around 366 nm. This is UV-A
This is a good position near the center in the area.

(B) Comparative Example [I] with a molecular extinction coefficient of 63000-67000
It is considerably higher than the benzophenone-based absorbent of [II].

(C) The value of the absorbance at 360 nm indicating the UV-A absorption capacity per unit weight is higher than that of the benzophenone-based absorbent.

As for the above mixture [III], the mixture [II
Compound [C] which is an example of the compound of the present invention from among [I]
Since it was difficult to isolate only the compound [C], the measurement could not be performed on the compound [C], and the measurement was performed in the state of the mixture [III].

However, the compound [C] in the mixture [III] is considered to contain at least 60% by weight or more, and the compound [C] in the mixture [III]
And [D] both have a dimethylaminocinnamoyl group, and the dimethylaminocinnamoyl group itself is
Considering that the compound has the property of having a maximum absorption wavelength near the center of UV-A, even if only the compound [C] is measured for an ultraviolet absorption spectrum, it is estimated that the compound also has a maximum absorption wavelength near 366 nm. it can.

(B) Protective effect test using animals Compound [I] and mixture [III] in the above Examples
Of a castor oil solution containing 2 or 5% by weight of UV-
The effect of protecting the skin from A-irradiation was measured by the following test method.

A healthy Hartley white guinea pig weighing 400 to 500 g (5 animals per group) shaves the back, exposes the skin, and
Thirty minutes before A irradiation, a 0.3% methanol solution of 8-methoxypsoralen was previously applied in an amount of 4 μl / cm ² to increase the sensitivity to UV-A.

The sample was applied evenly at ² mg / cm2 15 minutes before UV-A irradiation, and a glass filter was attached to 10 Toshiba FL20S-BLB lamps, and a UV-A light source that blocked UV-B by a distance of 15 cm was used. From 3.
Irradiation was performed at an intensity of 5 mW / cm ² .

At 24 hours after the irradiation, the appearance of erythema on the skin was observed, and the minimum UV-A irradiation time for producing erythema on the skin was determined. The time and uncoated portion compares the minimum UV-A irradiation time cause erythema in the skin, UV-A-preventing effect (protection factor _A, PF A) the following formula measuring the skin protective effect of each sample seeking did.

Incidentally, wherein t ₁ is the minimum UV-A irradiation time causing erythema on the skin using a sample, and, t ₂ is the minimum UV-A irradiation time causes erythema uncoated portion Skin .

The results of the above measurements are shown in the bar graph in the attached drawing.

And the following things became clear from such a measurement result.

(A) In Comparative Example [II] where only castor oil base was applied, UV
-A cannot be defended.

(B) in comparison with the comparative examples of the benzophenone-based absorbers 5% mixed product [I], the compound [I] and mixtures [III] and PF _A 6.5-7.0 same amount of about 2 times higher effect showed that.

(C) Further, the compound [I], the amount of the mixture (III) showed a higher value as the PF _A from 4.3 to 4.6 even when reduced to 2%.

(2) Compatibility Solubility at room temperature in castor oil, a typical vegetable oil, and cetyl 2-ethylhexanoate, a general-purpose ester as a cosmetic raw material, was measured, and as shown in Table 2, a commercially available benzophenone-based absorption was measured. Excellent results were obtained compared to the preparation.

In Table 2, Comparative Examples [I] and [II] are the following compounds, respectively.

Comparative Example [I]: 2-hydroxy-4-methoxybenzophenone Comparative Example [II]: 2,2 ′, 4,4′-tetrahydroxybenzophenone (3) Safety As shown in (a) to (c), the above compounds [I],
With respect to [II] and the mixture [III], no abnormalities were observed in any of the cumulative skin irritation, phototoxicity and contact sensitization, and the safety on the skin was confirmed.

(B) Cumulative skin irritation Using five healthy Japanese white rabbits weighing 2.8 to 3.2 kg, the back was shaved and shaved, and then the compound [I],
0.2 g of a castor oil solution of 2 or 5% by weight of [II] and the mixture [III] was applied once a day for 5 days in a range of 2.5 cm × 2.5 cm, and the presence or absence of irritation was visually determined every day. No abnormalities were observed.

 Table 3 shows the test results of the cumulative skin irritation.

(B) Phototoxicity The phototoxicity of the compound [I], the compound [II], and the mixture [III] was determined using a castor oil solution of 2 or 5% by weight as a sample. The test method was carried out according to the phototoxicity test method described on page 277 of "New skin physiology and safety, toxicity evaluation of contact chemicals" edited by Yoshio Takase.

However, in this test, five healthy Hartley white guinea pigs weighing 400 to 500 g were used, and the total energy amount was 2.0.
Light irradiation was performed at × 10 ⁸ erg / cm ² .

As shown in Table 4 below, the results of the phototoxicity test were as follows: Compound [I], Compound [II], Mixture [II
I] In both cases, no phototoxic reaction was observed.

(C) Contact sensitizing properties The test for contact sensitizing properties was conducted using the Modified method described on page 262 of Takase Yoshio, edited by Yoshio Takase, “New Skin Physiology and Safety, Toxicity Evaluation of Contact Chemicals” (Seishinshoin Publishing). (Adijuvant a
nd Patch Test method).

However, in this test, 10 healthy Hartley white guinea pigs weighing 400 to 500 g were used. To induce sensitization, a 5% by weight castor oil solution was used for the compound [I] and the mixture [III]. For II), a 2% by weight castor oil solution was used, and for the provocation test, for the compound [I] and the mixture [III], a 5,1,0.1% by weight castor oil solution was used. For each, a castor oil solution of 2,1,0.1% by weight was used.

As shown in the following Table 5, no sensitization was observed for the compounds [I] and [II] and the mixture [III] in the test results of the contact sensitization.

Next, formulation examples when the compound [I] and the mixture [III] are blended in a cosmetic will be described.

Formulation Example 1 (% by weight) Liquid phase Stearic acid 10.0 Stearyl alcohol 4.0 Butyl stearate 6.0 Glycerin monostearate 2.0 2-Ethylhexyl paramethoxycinnamate 2.0 Compound [I] 2.0 Water phase Propylene glycol 10.0 Glycerin 4.0 Potassium hydroxide 0.4 Fragrance And preservatives Micro- purified water Total remaining amount 100.0 Formulation Example 2 (% by weight) Liquid phase stearic acid 5.0 beeswax 1.0 lanolin 0.5 glyceryl monostearate 0.5 cetyl 2-ethylhexanoate 7.0 octyldodecyl myristate 3.0 sorbitan sesquioleate 1.0 paradimethyl aminobenzoic acid-2-ethylhexyl 4.0 mixture (III) 3.0 aqueous phase propylene glycol 2.0 triethanolamine 0.6 carboxyvinyl polymer 0.2 perfume and preservative trace purified water Balance total 100.0 in the above both formulation example, UV-A Not only the compound [I] or the mixture [III] which is a UV absorber in the UV region, but also 2-ethylhexyl paramethoxycinnamate or 2-ethylhexyl paradimethylaminobenzoate which is a UV absorber in the UV-B region. Since each of them is contained, there is an advantage that it is possible to provide a cosmetic that can appropriately absorb ultraviolet rays in both regions.

(Effects of the Invention) (a) As described above, the present invention can provide a completely novel compound of a 1,2-bis (dimethylaminocinnamoyloxy) propane derivative.

In particular, the compound of the present invention has an absorption maximum near 366 nm, which is a substantially central portion thereof, in a UV-A (320 to 400 nm) region, and furthermore, has a high molecular extinction coefficient at the absorption maximum, so -A has the real benefit that it can be reliably provided as an ultraviolet absorber exclusively for A.

(B) Further, since the ultraviolet absorbent of the present invention contains the above compound having a good spectral characteristic value such as an absorption maximum value as described above, it has an excellent effect of absorbing ultraviolet rays in the UV-A region, and Good compatibility, no irritation to skin, no phototoxicity, no sensitization, etc., and very good safety.

Therefore, it is possible to provide a UV absorber exclusively for the UV-A region, which is superior in all aspects, such as safety, compatibility, absorption effect, etc., as compared with the conventional one, and the versatility of the UV absorber for UV-A Can be enhanced.

[Brief description of the drawings]

Drawings is a graph showing the value of PF _A as protective effect test against ultraviolet rays UV-A region.

Claims (2)

(57) [Claims] (1) General formula (R ₁ is an alkyl group having 1 to 18 carbon atoms or an acyl group having 2 to 18 carbon atoms, and R ₂ is an ortho- or para-position dimethylamino group [−
N (CH ₃ ) ₂ ]), which is a 1,2-bis (dimethylaminocinnamoyloxy) propane derivative represented by the formula: 2. The general formula (R ₁ is an alkyl group having 1 to 18 carbon atoms or an acyl group having 2 to 18 carbon atoms, and R ₂ is an ortho- or para-position dimethylamino group [−
N (CH ₃ ) ₂ ]), which comprises a 1,2-bis (dimethylaminocinnamoyloxy) propane derivative represented by the following formula: