JP3378451B2 - Cosmetics - Google Patents

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a cosmetic composition containing a pigment, which moisturizes the skin and prevents skin roughness and inflammation.
The present invention relates to a cosmetic that can be improved and has excellent feeling in use and long-lasting makeup.

[0002]

2. Description of the Related Art To moisturize and soften the skin,
It is known that the water content of the stratum corneum is important. And the retention of the water content, the water-soluble components contained in the stratum corneum,
That is, it is attributed to free amino acids, organic acids, urea or inorganic ions. From these viewpoints, improvement or prevention of rough skin is attempted by blending these substances alone or in combination with a medicated external skin preparation or a cosmetic. In addition to these substances, many moisturizing substances with high affinity with water have been developed to improve rough skin and
It is used for the purpose of imparting a moist feeling.

However, even when these moisturizing substances are applied to the skin, the effect is temporary, and fundamentally improves the hydration ability of the whole stratum corneum and essentially prevents and improves rough skin. I couldn't. Further, in the case of cosmetics having a relatively high oil content, a moisturizing effect due to the clogging of the oil layer can be expected, but when the powder content is high, a moisturizing effect can be imparted to prevent or improve rough skin. It was very difficult.

Further, it is known that a compound having an amide bond, for example, sphingolipid in intercellular lipid is also effective as a compound having an effect of fundamentally improving the water-retaining ability of the stratum corneum. It has a relatively high melting point, and it is difficult to mix it in a cosmetic composition in a stable manner, and there is a problem in that the usability and stability are impaired.

[0005]

SUMMARY OF THE INVENTION Therefore, the object of the present invention is to moisturize the skin and prevent and improve rough skin, even if it contains a pigment, and is excellent in the feeling of use and the durability of makeup. To provide cosmetics.

[0006]

Under the circumstances, as a result of intensive studies by the present inventor, as a result, a cosmetic containing a specific amide compound and a pigment does not affect the skin even though it contains the pigment. The present invention has been completed based on the finding that it is excellent in the effect of moisturizing, preventing and improving rough skin, and that the feeling of use and makeup lasting are good.

That is, the present invention provides the following components (A) and (B): (A) one or more amide compounds represented by the following general formula (1), (2) or (3), (B) To provide a cosmetic containing a pigment.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION The amide compound of component (A) used in the present invention has a melting point of 0 to 50 ° C., preferably 10 to 50 ° C.
40 ° C. If the amount is out of this range, it is difficult to stably compound the composition. In the present invention, the melting point is JIS-K7121-1987-9-
It is shown by the extrapolated melting point onset temperature measured according to 9.1 (2).

Examples of such amide compounds include the following general formula (1), (2) or (3)

[0010]

[Chemical 4]

(In the formula, R ¹ and R ² are the same or different and each represents an optionally hydroxylated hydrocarbon group having 1 to 40 carbon atoms, and R ³ is a linear or branched chain having 1 to 6 carbon atoms. Represents an alkylene group or a single bond, R ⁴ is a hydrogen atom,
A linear or branched alkoxy group having 1 to 12 carbon atoms or a 2,3-dihydroxypropyloxy group is shown. However, when R ³ is a single bond, R ⁴ is a hydrogen atom. )

[0012]

[Chemical 5]

(In the formula, R ¹ and R ² have the same meanings as described above, R ^3a represents a linear or branched alkylene group having 3 to 6 carbon atoms, and R ^4a represents a straight chain having 1 to 12 carbon atoms. Indicates a chain or branched chain alkoxy group.)

[0014]

[Chemical 6]

(In the formula, R ¹ , R ² and R ³ have the same meanings as described above, and R ^4b is a hydrogen atom, a linear or branched alkoxy group having 1 to 12 carbon atoms or 2,3-epoxypropyl. An oxy group, provided that when R ³ is a single bond, R ^4b
Is a hydrogen atom. ) And the like.

Of these, in the amide derivative (1), R ¹ and R ² are the same or different and are linear or branched, saturated or unsaturated, optionally hydroxylated hydrocarbons having 1 to 40 carbon atoms. Indicates a group. R ¹ and R ² are methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, heneicosyl, docosyl, Nonacosyl, triacontyl, isostearyl, isoheptadecyl, 2
-Ethylhexyl, 1-ethylheptyl, 8-heptadecyl, 8-heptadecenyl, 8,11-heptadecadienyl, 2-heptylundecyl, 9-octadecenyl,
1-hydroxynonyl, 1-hydroxypentadecyl,
2-hydroxypentadecyl, 15-hydroxypentadecyl, 11-hydroxyheptadecyl, 11-hydroxy-8-heptadecenyl and the like can be mentioned.

R ¹ is preferably a linear or branched alkyl or alkenyl group having 8 to 26 carbon atoms, for example, octyl, decyl, dodecyl, tetradecyl, hexadecyl, octadecyl, docosyl, triacontyl, isostearyl, 2-ethylhexyl, 2-heptyl undecyl, 9-octadecenyl and the like can be mentioned. A particularly preferable hydrocarbon group as R ¹ is a linear or branched alkyl group having 12 to 22 carbon atoms, and examples thereof include dodecyl, tetradecyl, hexadecyl, octadecyl, docosyl and methyl-branched isostearyl groups.

R ² is preferably a linear or branched alkyl or alkenyl group having 9 to 25 carbon atoms, for example, nonyl, undecyl, tridecyl, pentadecyl, heptadecyl, heneicosyl, nonacosyl, isoheptadecyl, 1-ethylheptyl, 8- Heptadecyl, 8-heptadecenyl, 8,11-heptadecadienyl, 1-hydroxynonyl, 1-hydroxypentadecyl, 2-hydroxypentadecyl, 15-hydroxypentadecyl,
11-hydroxyheptadecyl and 11-hydroxy-
8-heptadecenyl and the like can be mentioned. A particularly preferred hydrocarbon group for R ² is a linear or branched alkyl group having 11 to 21 carbon atoms, such as undecyl, tridecyl,
Pentadecyl, heptadecyl, heneicosyl, methyl-branched isoheptadecyl group and the like can be mentioned.

R³Is a straight or branched chain having 1 to 6 carbon atoms
Represents an alkylene group or a single bond, and as an alkylene group
Is, for example, methylene, ethylene, trimethylene, tetrame
Tylene, pentamethylene, hexamethylene, 1-methyl
Ethylene, 1-methyltrimethylene, 2-methyltrimethyl
Ethylene, 1,1-dimethylethylene, 1-ethylethylene
1-methyltetramethylene, 2-ethyltrimethylene
And the like. R ³As a straight chain having 1 to 6 carbon atoms
Alkylene groups are preferred, of which methylene and ethylene
And trimethylene are particularly preferred.

R ⁴ represents a hydrogen atom, a linear or branched alkoxy group having 1 to 12 carbon atoms or a 2,3-dihydroxypropyloxy group, and examples of the alkoxy group include methoxy, ethoxy, propoxy, butoxy and hexyloxy. , Octyloxy, decyloxy, 1-methylethoxy, 2-ethylhexyloxy and the like.
R ⁴ is preferably a hydrogen atom, an alkoxy group having 1 to 8 carbon atoms or a 2,3-dihydroxypropyloxy group,
Of these, hydrogen atom, methoxy, ethoxy, propoxy,
Butoxy, 1-methylethoxy, 2-ethylhexyloxy and 2,3-dihydroxypropyloxy groups are particularly preferred.

As the amide derivative (1), a compound in which R ¹ , R ² , R ³ and R ⁴ in the general formula are each a group in the above particularly preferable range is particularly preferable.

In the amide derivative (2), R ¹
And R ² have the same meanings as described above, and the same groups are preferable. Examples of R ^3a include groups obtained by removing methylene and ethylene from the alkylene group exemplified in R ³ of the amide derivative (1). As R ^3a , a linear alkylene group having 3 to 6 carbon atoms is preferable, and of these, trimethylene is particularly preferable. The alkoxy group of R ^4a, include the same groups as R ⁴ in the amide derivative (1), the same groups are preferred.

In the amide derivative (3),
R ¹ , R ² and R ³ have the same meanings as described above, and R ^4b represents a hydrogen atom, a linear or branched alkoxy group having 1 to 12 carbon atoms or a 2,3-epoxypropyloxy group. Specific examples of R ¹ , R ² and R ³ include the same groups as the amide derivative (1), and the same groups are preferable.
Examples of the linear or branched alkoxy group having 1 to 12 carbon atoms of R ^4b include the same groups as R ⁴ of the amide derivative (1), and a hydrogen atom, an alkoxy group similar to R ⁴ and 2,3 -Epoxypropyloxy groups are preferred.

Among these amide derivatives (1) to (3), those represented by the general formula (1) are particularly preferable.

The amide derivative (1) can be obtained, for example, by the following production method 1 or production method 2.

[0026]

[Chemical 7]

[0027]

[Chemical 8]

(In the formula, R ¹ , R ² and R ³ have the same meanings as described above, and R ^4f represents a hydrogen atom or a linear or branched alkoxy group having 1 to 12 carbon atoms. ³
When is a single bond, R ^4f is a hydrogen atom. R ⁶ , R ⁸ ,
R ¹⁰ and R ¹¹ represent a linear or branched saturated or unsaturated hydrocarbon group having 1 to 8 carbon atoms, preferably a linear or branched alkyl group having 1 to 5 carbon atoms, and particularly preferably Is a methyl group. R ⁹ represents a hydrogen atom, an alkali metal atom or a COR ⁸ group, and R ⁷ and R ¹² represent a leaving group such as a halogen atom, a mesylate group and a tosylate group. R ⁷ is preferably a chlorine atom or a bromine atom, particularly a chlorine atom, from the viewpoint of easy availability, and R ¹² is preferably a mesylate group or a tosylate group from the viewpoint of easy availability. )

[0029]

[Chemical 9]

[0030]

[Chemical 10]

(In the formula, R ¹ , R ² , and R ^{6 to} R ¹² have the same meanings as described above, and R ^3g represents a linear or branched alkylene group having 1 to 6 carbon atoms.)

The reaction conditions in each step of production method 1 and production method 2 are as follows.

Step 1) Glycidyl ether (7) and amine (8F) or (8G), without solvent, or with water or a lower alcohol such as methanol, ethanol or isopropanol, or an ether system such as tetrahydrofuran, dioxane or ethylene glycol dimethyl ether. Amino alcohol derivative (4F) or (4G) is produced by reacting at room temperature to 150 ° C. in a solvent, a hydrocarbon solvent such as hexane, benzene, toluene, xylene, or an arbitrary mixed solvent thereof. You can

Step 2) Amino alcohol derivative (4F)
Alternatively, in (4G), fatty acid ester (9), preferably fatty acid lower alkyl ester such as fatty acid methyl ester and fatty acid ethyl ester, alkali metal hydroxide such as potassium hydroxide and sodium hydroxide, alkaline earth such as calcium hydroxide and the like. Of basic catalysts such as alkali metal carbonates such as group metal hydroxides, potassium carbonate and other alkali metal carbonates, calcium carbonate and other alkaline earth metal carbonates, sodium methoxide, sodium ethoxide, potassium tert-butoxide and the like. The amide derivative (2F) or (2G) can be produced by reacting in the presence of atmospheric pressure to 0.01 mmHg under reduced pressure at room temperature to 150 ° C. At this time, the amount of the basic catalyst used is preferably 0.01 to 0.2 equivalents with respect to the amino alcohol derivative (4F) or (4G), and when the alcohol generated by the reaction is removed outside the system, the reaction Is preferable because it progresses rapidly.

Step 3) Amide derivative (2F) or (2
G) is also an amino alcohol derivative (4F) or (4
G) is fatty acid chloride (10) without solvent or a halogenated hydrocarbon solvent such as chloroform, methylene chloride, 1,2-dichloroethane, tetrahydrofuran,
In the presence of a base such as pyridine or a tertiary amine such as triethylamine in an ether solvent such as dioxane or ethylene glycol dimethyl ether, a hydrocarbon solvent such as hexane, benzene, toluene, or xylene, or an arbitrary mixed solvent thereof. Or, in the absence, room temperature to 10
After reacting at 0 ° C. to convert to an amide-ester derivative (11F) or (11G),

Step 4) The ester group is converted to an alkali metal hydroxide such as potassium hydroxide or sodium hydroxide, an alkaline earth metal hydroxide such as calcium hydroxide, an alkali metal carbonate such as potassium carbonate or calcium carbonate. Alkaline earth metal carbonates such as, sodium methoxide, sodium ethoxide, potassium-tert-butoxide and the like, under alkaline conditions such as alkali metal alcoholates, etc., can also be produced by selective hydrolysis. .

Step 5) Amide derivative (2F) or (2
1 to 20 equivalents of epoxide (12), preferably epichlorohydrin, in G) without solvent or with water or an ether solvent such as tetrahydrofuran, dioxane, ethylene glycol dimethyl ether, hexane, benzene,
1 to 10 equivalents of an alkali metal hydroxide such as potassium hydroxide or sodium hydroxide or an alkaline earth metal water such as calcium hydroxide in a hydrocarbon solvent such as toluene or xylene, or an arbitrary mixed solvent thereof. Oxide,
Room temperature to 150 ° C in the presence of an alkali metal carbonate such as potassium carbonate or an alkaline earth metal carbonate such as calcium carbonate
The amide derivative (3F) or (3
G) can be produced. At this time, tetrabutylammonium bromide, tetrabutylammonium chloride, hexadecyltrimethylammonium chloride, hexadecyltrimethylammonium bromide,
Stearyl trimethyl ammonium chloride, bis-tetraoxyethylene stearyl methyl ammonium chloride and the like quaternary ammonium salts and lauryl dimethylcarboxyammonium betaine It is preferable to perform the reaction in the presence of a phase transfer catalyst such as betaine in terms of yield and the like. .

Step 6) Amide derivative (3F) or (3
G) is an alkali metal hydroxide such as potassium hydroxide or sodium hydroxide, an alkaline earth metal hydroxide such as calcium hydroxide, an alkali metal carbonate such as potassium carbonate, an alkaline earth metal carbonate such as calcium carbonate Basic conditions such as salts or mineral acids such as sulfuric acid and hydrochloric acid, Lewis acids such as boron trifluoride and tin tetrachloride, carboxylic acids such as acetic acid, tetradecanoic acid and hexadecanoic acid, and sulfonic acids such as p-toluenesulfonic acid. The amide derivative (1F) or (1G) can be produced by hydrating at room temperature to 300 ° C. under acidic conditions such as the above or under mixed conditions of base and acid.

Step 7) Amide derivative (1F) or (1
G) also includes a carboxylic acid derivative (13), preferably a lower fatty acid such as acetic acid, a lower fatty acid alkali metal salt such as sodium acetate, or a lower fatty acid anhydride such as acetic anhydride, in addition to the amide derivative (3F) or (3G). Alternatively, in combination, after reacting in the presence or absence of a basic catalyst such as a tertiary amine such as triethylamine to convert the ester-amide derivative (14F) or (14G),

Step 8) The ester group is converted to an alkali metal hydroxide such as potassium hydroxide or sodium hydroxide, an alkaline earth metal hydroxide such as calcium hydroxide, an alkali metal carbonate such as potassium carbonate or calcium carbonate. Alkaline earth metal carbonates such as, sodium methoxide, sodium ethoxide, potassium-tert-butoxide and the like, under alkaline conditions such as alkali metal alcoholates, etc., can also be produced by selective hydrolysis. .

Step 9) Amide derivative (1F) or (1
G) is also a carbonyl derivative (3F) or (3G) with a carbonyl compound (15), preferably a lower aliphatic ketone such as acetone or methyl ethyl ketone, a mineral acid such as sulfuric acid, hydrochloric acid or phosphoric acid, or a carboxylic acid such as acetic acid. After conversion into a 1,3-dioxolane-amide derivative (16F) or (16G) by reacting in the presence of an acid catalyst such as Lewis acid such as boron trifluoride or tin tetrachloride,

Step 10) Mineral acids such as sulfuric acid, hydrochloric acid and phosphoric acid,
It can also be produced by deketalization under acidic conditions such as carboxylic acid such as acetic acid and sulfonic acid such as p-toluenesulfonic acid.

Step 11) The 1,3-dioxolane-amide derivative (16F) or (16G) is also converted into the amide derivative (2F) or (2G) by the glycerol derivative (17).
An alkali metal hydroxide such as potassium hydroxide or sodium hydroxide, an alkaline earth metal hydroxide such as calcium hydroxide, an alkali metal carbonate such as potassium carbonate, an alkaline earth metal carbonate such as calcium carbonate, In the presence of a base such as an alkali metal hydride such as sodium hydride, or without a solvent, or an aprotic polar solvent such as N, N-dimethylformamide or dimethylsulfoxide, an ether solvent such as tetrahydrofuran, dioxane, or ethylene glycol dimethyl ether. It can also be produced by reacting in a hydrocarbon solvent such as hexane, benzene, toluene, xylene, or a mixed solvent thereof.

The amide derivative (1) thus obtained can be purified by a known method. In the present invention, the purified product obtained by purifying the amide derivative (1) to a purity of 100%, or the mixture having a purity of 70 to 100% containing an intermediate or a reaction by-product without any purification is effective and effective. It is excellent and can be used without any problems in safety. The amide derivative (1) also includes solvates represented by hydrates.

Examples of the amide derivative (1) obtained by the production method 1 include the following.

[0046]

[Chemical 11]

[0047]

[Chemical 12]

Examples of the amide derivative (1) obtained by the production method 2 include the following.

[0049]

[Chemical 13]

As the amide compound as the component (A), an N-substituted amide compound having a total carbon number of 30 or more is particularly preferable.
In addition, the amide compound contains 1% by weight or more of bound water, especially 5
It is more preferable that the content can be held at not less than wt%. Here, the content of bound water is defined as the amount of bound water by first adding water to the sample at room temperature and measuring the maximum addition amount that can maintain a homogeneous phase, and then the total weight of bound water to the total weight of the sample as a percentage. The value can be calculated according to the following equation.

[0051]

[Equation 1]

The amide compound as the component (A) may be one kind or two kinds.
A combination of two or more species can be used, and 0.0
It is preferable to add 01 to 50% by weight, particularly 0.1 to 50% by weight.
It is preferable to add 20% by weight, and further 0.1 to 10% by weight, because a sufficient effect can be obtained and a feeling is good.

The component (B) pigment used in the present invention is not particularly limited as long as it is used in ordinary cosmetics, and examples thereof include silica, alumina, silicic acid, silicic anhydride, magnesium silicate, and the like. Aluminum silicate, talc, sericite, kaolin, mica, red iron oxide, clay,
Bentonite, zirconium oxide, magnesium oxide,
Zinc oxide, titanium oxide, aluminum oxide, calcium sulfate, barium sulfate, magnesium sulfate, titanium mica,
Inorganic powder such as bismuth oxychloride, calcium carbonate, magnesium carbonate, iron oxide, ultramarine blue, dark blue, chromium oxide, aluminum hydroxide, chromium hydroxide, calamine and carbon black and their composites; polyamide resin, polyester resin, polyethylene Resin, polypropylene resin, polystyrene resin, polyurethane resin, vinyl resin, urea resin, phenol resin, fluororesin, silicon resin, (meth) acrylic resin, melamine resin, epoxy resin, polycarbonate resin, divinylbenzene-styrene copolymer, silk Powder, cellulose Organic powders such as composites thereof; organic tar dyes, lakes and other organic coloring pigments.

These pigments may be surface-treated with various agents for the purpose of improving the feel, or may be coated or encapsulated with a coloring pigment, dye, dye, metal ion, etc. It is preferable to use the hydrophobized pigment that has been subjected to the chemical treatment, because the makeup retention is further improved.

The method of hydrophobizing treatment is not particularly limited. For example, oil or fat is adsorbed on the surface of the pigment, or esterification or etherification is caused by using a functional group such as a hydroxyl group to make the pigment lipophilic. Examples include oil and fat treatment method, metal soap treatment method using zinc salt or magnesium salt of fatty acid, silicone treatment method using dimethylpolysiloxane or methylhydrogenpolysiloxane, and treatment method with fluorine compound having perfluoroalkyl group. . Here, as the fluorine compound having a perfluoroalkyl group, for example, [C _m F _{2m + 1} C _n H _2n O] _y PO (OH) _3-y (in the formula, m is an integer of 3 to 18 and n is An integer from 1 to 12, y
Indicates a number from 1 to 3. ), A polyfluoroalkylphosphoric acid (US Pat. No. 3,632,744), a fluoroalkyldi (oxyethyl) amine phosphoric acid ester (JP-A-62-250074), and a resin having a perfluoroalkyl group (JP-A-55-55). 167209), tetrafluoroethylene resin, perfluoroalcohol,
Perfluoroepoxy compound, sulfoamide type fluorophosphoric acid, perfluorosulfate, perfluorocarboxylate, perfluoroalkylsilane (JP-A-2-2186)
No. 03) and the like.

Among these pigments, when the cosmetics of the present invention are makeup cosmetics and the like, in addition to organic color pigments such as organic tar dyes and lakes, color pigments such as iron oxide and ultramarine, talc, Sericite, kaolin, zinc oxide,
It is preferable to use an inorganic pigment such as titanium oxide.

The pigment of the component (B) can be used alone or in combination of two or more kinds, and the compounding amount thereof is not particularly limited and depends on the kind of the cosmetics, but it is 0.
It is preferable to add 01 to 98% by weight, particularly 0.1 to 98% by weight.
90% by weight, more preferably 0.5 to 85% by weight, is preferable because the makeup retention and the feeling of use are more excellent.

In addition to the above essential ingredients, the cosmetic of the present invention also comprises
Ingredients that are usually added to cosmetics, for example, vaseline, lanolin, ceresin, microcrystalline wax, carnauba wax, candelilla wax, higher fatty acids, higher alcohols, solid / semisolid oils; olive oil, jojoba oil, castor oil, squalane, Liquid oil such as liquid paraffin, ester oil, diglyceride, triglyceride, silicone oil, and fluorine-based oil agent; water-soluble, oil-soluble and fluorine-based polymer; nonionic surfactant, anionic surfactant, cationic interface Surfactants such as activators and polyether-modified silicones; gelling agents such as dextrin fatty acid esters and alkyl-modified silicones; coloring agents such as organic dyes;
Antiseptic, antioxidant, pigment, thickener, pH adjuster, fragrance,
UV absorber, moisturizer, blood circulation promoter, cooling sensation, antiperspirant,
A bactericidal agent, a skin activating agent and the like can be appropriately added within a qualitative and quantitative range that does not impair the purpose and effects of the present invention.

The cosmetics of the present invention can be produced according to a conventional method, for example, skin care creams, UV protection creams, foundations, blushers, white powders, eye shadows, eyebrows, eyeliners, mascaras, lipsticks and lip balms. It can be made into a dosage form for makeup cosmetics such as nail enamel. In particular, it is suitable as an emulsion (w / o, o / w) cosmetic.

[0060]

EFFECT OF THE INVENTION The cosmetic composition of the present invention provides sufficient moisturization to the skin, enhances the water retention ability, and is effective in preventing and improving rough skin and inflammation, and also has a good feeling in use and long-lasting makeup. Is.

[0061]

EXAMPLES Next, the present invention will be described with reference to examples, but the present invention is not limited to these examples. In addition, in Production Examples 1 to 10, the amide derivative (1) was produced according to the above Production Method 1.

The melting points shown in the examples were measured by using a differential scanning calorimeter (DSC) manufactured by Seiko Denshi Kogyo Co., Ltd.
Approximately 1 mg of the sample was placed in a DSC cell (5 μl) and measured at a scanning temperature of -10 to 200 ° C and a heating rate of 2 ° C / min.
The extrapolation melting point onset temperature of -K7121-1987-9-9.1 (2) is shown as the melting point.

Production Example 1 743.2 g (8.34 mol) of 3-methoxypropylamine and 15 parts of ethanol were placed in a 2-liter 5-neck flask equipped with a stirrer, a dropping funnel, a nitrogen introducing tube and a distillation device.
16 ml of hexadecyl glycidyl ether was added thereto while stirring and heating to 80 ° C. under a nitrogen atmosphere.
g (0.56 mol) was added dropwise over 3 hours. After completion of dropping, the mixture was further stirred at 80 ° C. for 12 hours, ethanol and excess 3-methoxypropylamine were distilled off by heating under reduced pressure, and the residue was purified by silica gel column chromatography to give the amino alcohol derivative (4a). 19
6.5 g (yield 91% based on hexadecyl glycidyl ether) was obtained (step 1).

[0064]

[Chemical 14]

Obtained amino alcohol derivative (4a)
The physical properties of are as follows.

White solid melting point; 53 ° C. IR (ν _neat , cm ^-1 ); 3340, 2930, 285
5,1470,1310,1120,1065,95
5,900,720. ¹ H-NMR (CDCl ₃ , δ); 0.88 (t, J =
6.3 Hz, 3 H), 1.25 to 1.45 (m, 26
H), 1.45 to 1.85 (m, 6H), 2.57 to
2.76 (m, 4H), 3.32 (s, 3H), 3.3
8 to 3.48 (m, 6H), 3.77 to 3.89 (m,
1H).

61.3 g (15) of the melted compound (4a) obtained in the above (Step 1) was placed in a 1 liter 5-neck flask equipped with a stirrer, a dropping funnel, a nitrogen introducing tube and a distillation apparatus.
(8.1 mmol) and 1.53 g (7.91 mmol) of a sodium methoxide 28% methanol solution were charged, and the mixture was stirred at 60 ° C. for 30 minutes under a nitrogen atmosphere. Then, under the same conditions, 38.3 g (158.1 mmol) of methyl tetradecanoate was added thereto.
Was added dropwise over 1 hour. After the dropping is completed, the pressure is further reduced (8
The reaction was completed by stirring at 60 ° C for 5 hours. After cooling the reaction mixture, the amide derivative (2a) was purified by silica gel column chromatography.
88.7 g (94% yield) was obtained (step 2).

[0068]

[Chemical 15]

The followings are physical properties of the amide derivative (2a) so obtained.

White solid melting point; 48 ° C. IR (ν _neat , cm ^-1 ); 3440, 2930, 286
0, 1650, 1625, 1470, 1225, 121
0, 1110, 950, 720. ¹ H-NMR (CDCl ₃ , δ); 0.88 (br t,
J = 6.3 Hz, 6H), 1.15 to 1.95 (m, 5
3H), 2.36 (t, J = 7.5Hz, 2H), 3.
29 to 3.55 (m, 10H), 3.33 (s, 3
H), 3.85-3.95 (m, 1H).

94.5 g (158.0 mmol) of compound (2a) obtained in the above (Step 2) and 1.53 g of tetrabutylammonium bromide were placed in a 1 liter 5-necked flask equipped with a stirrer, a nitrogen introducing tube and a distillation apparatus. (4.74 mmo
l), epichlorohydrin 32.2 g (347.6 mmo)
l), 12.6 g (315.0 mmol) of sodium hydroxide
And 66 ml of toluene were charged, and 1 at 45 ° C under a nitrogen atmosphere.
Stir for 0 hours. The obtained reaction mixture was washed 3 times with water at 70 ° C., toluene and excess epichlorohydrin were distilled off by heating under reduced pressure, and the residue was purified by silica gel column chromatography to give an amide derivative (3
a) 94.9 g (yield 92%) was obtained (step 5).

[0072]

[Chemical 16]

The followings are physical properties of the amide derivative (3a) so obtained.

White solid melting point; 38 to 39 ° C. IR (ν _neat , cm ^-1 ); 2930, 2855, 165
0, 1470, 1425, 1380, 1210, 112
0,905,840,720. ¹ H-NMR (CDCl ₃ , δ); 0.88 (br t,
J = 6.0 Hz, 6H), 1.10 to 1.45 (m, 4
6H), 1.45 to 1.90 (m, 6H), 2.25 to
2.48 (m, 2H), 2.50 to 2.68 (m, 1
H), 2.70 to 2.85 (m, 1H), 3.02
3.20 (m, 1H), 3.20 to 4.00 (m, 13
H), 3.32 (s, 3H).

Compound (3a) 7 obtained in the above (Step 5) was placed in a 100 ml autoclave equipped with a stirrer.
1.3 g (109.0 mmol), 11.78 g of water (65
4.1 mmol), 0.087 g of sodium hydroxide (2.1
8 mmol) and tetradecanoic acid 0.87 g (4.36 mmo)
l) was charged and the mixture was stirred at 160 ° C. for 6 hours in a closed system.
The reaction mixture was cooled, washed twice with 2% saline at 80 ° C., and purified by silica gel column chromatography to give the desired amide derivative (1a) 68.
3 g (yield 93%) was obtained (step 6).

[0076]

[Chemical 17]

The followings are physical properties of the amide derivative (1a) so obtained.

Colorless transparent liquid IR (ν _neat , cm ^-1 ); 3445, 2930, 286
0, 1630, 1470, 1420, 1380, 130
5,1210,1120,720. ¹ H-NMR (CDCl ₃ , δ); 0.88 (br t,
J = 6.7 Hz, 6H), 1.15 to 1.44 (m, 4
6H), 1.44 to 1.95 (m, 8H), 2.25 to
2.45 (m, 2H), 3.20 to 3.90 (m, 16
H), 3.33 (s, 3H).

In a 500 ml four-necked flask equipped with a stirrer, a nitrogen inlet tube and a distillation device, the above (step 5)
31.0 g (47.4 mmol) of the compound (3a) obtained in 1., 11.9 g (663.7 mmol) of water, sodium acetate 13.
6 g (165.9 mmol) and 104.9 g acetic acid (174
(6.8 mmol) was charged and the mixture was stirred at 70 ° C. for 19 hours under a nitrogen atmosphere. Excess acetic acid was distilled off by heating under reduced pressure, and ester-
Amide derivatives (14a-1), (14a-2) and (1
A mixture containing 4a-3) was obtained (step 7).

[0080]

[Chemical 18]

The mixture containing these ester-amide derivatives was then added to this without removal from the flask.
59.3 g of 8% aqueous sodium hydroxide solution (711.2 mm
ol), 18 g of water and 200 ml of butanol are added, and the temperature is 80 ° C.
And stirred for 3 hours. Butanol was distilled off by heating under reduced pressure,
The residue was diluted with 250 ml of toluene and washed twice with water at 70 ° C. Toluene was distilled off by heating under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 22.3 g (yield 70%) of the desired amide derivative (1a) (step 8).

Production Example 2 4680 g (52.5 mol) of 3-methoxypropylamine and 90 parts of ethanol were placed in a 10-liter five-necked flask equipped with a stirrer, a dropping funnel, a nitrogen introducing tube and a distillation apparatus.
0 g was charged, and while heating and stirring at 80 ° C. under a nitrogen atmosphere, 1045 g of hexadecyl glycidyl ether was added to this.
(3.50 mol) was added dropwise over 3 hours. After completion of the dropping, the mixture was further stirred at 80 ° C. for 1 hour, ethanol and excess 3-methoxypropylamine were distilled off by heating under reduced pressure to obtain a product containing the amino alcohol derivative (4a) as a main component (step 1).

The product containing the compound (2a) as the main component in the 10-liter, 5-neck flask obtained in the above (Step 1) was added to
9.82 g (0.175 mol) of potassium hydroxide was added,
The mixture was stirred for 3 hours under a reduced pressure (60 to 10 Torr) at 80 ° C. while distilling off water produced under nitrogen blowing. Next, while stirring under the same conditions, add methyl tetradecanoate 8
82.3 g (3.64 mol) was added dropwise over 3 hours.
At this time, the produced methanol was distilled off. After completion of dropping, under nitrogen blowing and under reduced pressure (60 to 10 Torr) 6
While distilling off the methanol produced at 0 to 45 ° C, 1
The reaction was completed by stirring for 0 hours, and the amide derivative (2a) was obtained.
A product containing as a main component was obtained (step 2).

The product containing the compound (2a) in the 10-liter, 5-necked flask obtained in the above (Step 2) as the main component was added to
Tetrabutylammonium bromide 33.9 g (0.
105 mol), 712.5 g of epichlorohydrin (7.
70 mol) and 2100 g of toluene are added, and 1750.0 g (2%) of a 48% sodium hydroxide aqueous solution is added under stirring at 45 ° C. under reduced pressure (150 to 50 Torr) under nitrogen blowing.
1.0 mol) was added dropwise over 2 hours. After completion of dropping, the reaction was further completed by stirring for 10 hours under the same conditions. The reaction mixture was washed with water at 70 ° C. four times, and toluene and excess epichlorohydrin were distilled off by heating under reduced pressure to obtain a product containing the amide derivative (3a) as a main component (step 5).

The product containing the compound (3a) as the main component in the 10-liter, 5-neck flask obtained in the above (Step 5) was added to
378.2 g (21.0 mol) of water, 5.83 g (0.070 mol) of 48% aqueous sodium hydroxide solution and 32.0 g (0.14 mol) of tetradecanoic acid were added, and the mixture was stirred at 100 ° C. for 2.5 days under a nitrogen atmosphere. . The reaction mixture is 80
After being washed 3 times with a 2% saline solution at ℃, the product 2 containing the desired compound (1a) as the main component was dehydrated by heating under reduced pressure.
261.5 g was obtained (step 6). This product contained 70% of the compound (1a), and additionally contained an intermediate shown by the following formula and a reaction by-product.

[0086]

[Chemical 19]

[0087]

[Chemical 20]

Production Example 3 Production Example 1 except that methyl hexadecanoate was used in place of methyl tetradecanoate in Step 2 of Production Example 1.
The reaction is performed in the same manner as in Steps 1 and 2 of the
b) was obtained (steps 1 and 2).

[0089]

[Chemical 21]

The followings are physical properties of the amide derivative (2b) so obtained.

White solid Melting point; 55 ° C. IR (ν _neat , cm ^-1 ); 3430, 2930, 285
5,1620,1470,1205,1110,95
0,720. ¹ H-NMR (CDCl ₃ , δ); 0.88 (br t,
J = 6.4 Hz, 6 H), 1.26 to 1.89 (m, 5
7H), 2.36 (t, J = 7.6Hz, 2H), 3.
29 to 3.52 (m, 10H), 3.33 (s, 3
H), 3.88-3.95 (m, 1H).

In the step 5 of Production Example 1, the compound (2
A reaction was carried out in the same manner as in Step 5 of Production Example 1 except that the compound (2b) obtained in (Step 2) above was used instead of a),
The amide derivative (3b) was obtained (step 5).

[0093]

[Chemical formula 22]

The followings are physical properties of the amide derivative (3b) so obtained.

White solid Melting point: 44-45 ° C. IR (ν _neat , cm ⁻¹ ); 2930, 2860, 165
0, 1470, 1425, 1380, 1210, 112
0,910,845,755,720. ¹ H-NMR (CDCl ₃ , δ); 0.88 (br t,
J = 6.7 Hz, 6H), 1.15 to 1.45 (m, 5
0H), 1.45 to 1.73 (m, 4H), 1.73 to
1.90 (m, 2H), 2.25 to 2.48 (m, 2
H), 2.50 to 2.68 (m, 1H), 2.70 to
2.85 (m, 1H), 3.00 to 3.18 (m, 1
H), 3.18 to 4.00 (m, 13H), 3.32
(S, 3H).

In Step 6 of Production Example 1, compound (3
Compound (3b) obtained in the above (Step 5) instead of a)
Was reacted in the same manner as in Step 6 of Production Example 1 except that hexadecanoic acid was used instead of tetradecanoic acid to obtain the desired amide derivative (1b) (Step 6).

[0097]

[Chemical formula 23]

The followings are physical properties of the amide derivative (1b) so obtained.

White solid Melting point; 33 ° C. IR (ν _neat , cm ⁻¹ ); 3445, 2930, 286
0, 1650, 1630, 1470, 1420, 138
0, 1305, 1210, 1120, 1080. ¹ H-NMR (CDCl ₃ , δ); 0.88 (br t,
J = 6.4 Hz, 6H), 1.15 to 1.45 (m, 5
0H), 1.45 to 1.95 (m, 7H), 2.25 to
2.55 (m, 3H), 3.20 to 3.92 (m, 16
H), 3.33 (s, 3H).

In a 500 ml four-necked flask equipped with a stirrer and a nitrogen inlet tube, 34.1 g (50.0 mmol) of compound (3b) obtained in the above (Step 5) and acetic anhydride 2
5.5 g (250.0 mmol) and triethylamine 2
Charge 5.3g (250.0mmol), under nitrogen atmosphere 1
The mixture was stirred at 00 ° C for 10 hours. The reaction mixture was concentrated under reduced pressure with heating, and the obtained residue was purified by silica gel column chromatography to obtain 34.9 g (yield 89%) of the ester-amide derivative (14b) (step 7).

[0101]

[Chemical formula 24]

The ester-amide derivative (14
The physical properties of b) are as follows.

Brown transparent liquid ¹ H-NMR (CDCl ₃ , δ); 0.88 (br t,
J = 6.4 Hz, 6 H), 1.26 to 1.83 (m, 5
6H), 2.03 to 2.20 (m, 6H), 2.33.
(T, J = 7.1 Hz, 2H), 3.12 to 4.35.
(M, 15H), 3.32 (s, 3H), 5.04 ~
5.43 (m, 1H).

In a 200 ml four-necked flask equipped with a stirrer and a nitrogen introducing tube, 33.9 g (43.2 mmol) of the compound (14b) obtained in the above (Step 7), sodium methoxide 28% methanol solution 0.42 g. (2.16
mmol) and 200 ml of methanol were charged, and the mixture was stirred at room temperature for 3.5 hours under a nitrogen atmosphere. Heating the reaction mixture,
After concentration under reduced pressure, the obtained residue was purified by silica gel column chromatography to obtain 16.0 g (yield 53%) of the desired amide derivative (1b) (step 8).

In a 3 liter 4-necked flask equipped with a stirrer and a nitrogen inlet tube, the compound (2
b) 45.2 g (72.0 mmol), 2.86 g (119.2 mmol) of sodium hydride and 800 ml of toluene were charged, and the mixture was stirred at 55 ° C. for 30 minutes under a nitrogen atmosphere. Next, 34.8 g (121.5 mmol) of 1,2-isopropylidenedioxy-3-tosyloxypropane was added thereto, and the mixture was stirred at 100 ° C. for 18 hours. The reaction mixture was added with 20 ml of 2-propanol under ice cooling to inactivate unreacted sodium hydride, and then concentrated under reduced pressure with heating. The obtained residue was purified by silica gel column chromatography to obtain 51.0 g (yield 96%) of 1,3-dioxolane-amide derivative (16b) (step 1
1).

[0106]

[Chemical 25]

The physical properties of the obtained 1,3-dioxolane-amide derivative (16b) are as follows.

Colorless transparent liquid ¹ H-NMR (CDCl ₃ , δ); 0.88 (br t,
J = 6.4 Hz, 6 H), 1.20 to 1.90 (m, 6
2H), 2.36 (t, J = 7.0Hz, 2H), 3.
30-4.25 (m, 19H).

A 2 liter 4-necked flask equipped with a stirrer and a nitrogen introducing tube was placed in the compound (1) obtained in the above (Step 11).
6b) 51.0 g (68.9 mmol), tosyl acid monohydrate 0.50 g (2.63 mmol) and 500 ml methanol.
Was charged, and the mixture was stirred under a nitrogen atmosphere at room temperature for 12 hours. The reaction mixture was concentrated under reduced pressure with heating, and the obtained residue was purified by silica gel column chromatography to give 41.0 g of the desired amide derivative (1b) (yield: 85
%) Was obtained (step 10).

Production Example 4 Reactions were performed in the same manner as in Steps 1 and 2 of Production Example 1 except that methyl dodecanoate was used in place of methyl tetradecanoate in Step 2 of Production Example 1, and the amide derivative (2
c) was obtained (steps 1 and 2).

[0111]

[Chemical formula 26]

The followings are physical properties of the amide derivative (2c) so obtained.

Colorless transparent liquid IR (ν _neat , cm ^-1 ); 3435, 2930, 285
5,1620,1470,1220,1110,72
0. ¹ H-NMR (CDCl ₃ , δ); 0.88 (br t,
J = 6.4 Hz, 6 H), 1.20 to 1.90 (m, 4
9H), 2.36 (t, J = 7.6Hz, 2H), 3.
25-3.52 (m, 10H), 3.33 (s, 3
H), 3.88-3.95 (m, 1H).

In Step 5 of Production Example 1, compound (2
Instead of a), the compound (2c) obtained in the above (Step 2)
Reaction was performed in the same manner as in Step 5 of Production Example 1 except that was used to obtain the amide derivative (3c) (Step 5).

[0115]

[Chemical 27]

The followings are physical properties of the amide derivative (3c) so obtained.

Pale yellow liquid IR (ν _neat , cm ^-1 ); 2940, 2875, 175
0, 1650, 1470, 1380, 1210, 112
0,910,845. ¹ H-NMR (CDCl ₃ , δ); 0.88 (br t,
J = 6.4 Hz, 6H), 1.15 to 1.45 (m, 4
2H), 1.45 to 1.75 (m, 4H), 1.75 to
1.90 (m, 2H), 2.25 to 2.50 (m, 2H)
H), 2.50 to 2.68 (m, 1H), 2.70 to
2.85 (m, 1H), 3.00 to 3.18 (m, 1
H), 3.18 to 4.00 (m, 13H), 3.32
(S, 3H).

In Step 7 of Production Example 1, compound (3
The reaction was performed in the same manner as in Steps 7 and 8 of Production Example 1 except that the compound (3c) obtained in (Step 5) above was used instead of a) to obtain the desired amide derivative (1c) ( Process 7
And 8).

[0119]

[Chemical 28]

The followings are physical properties of the amide derivative (1c) so obtained.

Colorless transparent liquid IR (ν _neat , cm ^-1 ); 3430, 2930, 286
0, 1650, 1630, 1470, 1380, 126
0,1210,1115,1080,795,720. ¹ H-NMR (CDCl ₃ , δ); 0.88 (br t,
J = 6.7 Hz, 6H), 1.15 to 1.45 (m, 4
2H), 1.45 to 1.97 (m, 8H), 2.25 to
2.45 (m, 2H), 3.15 to 3.92 (m, 16)
H), 3.33 (s, 3H).

Production Example 5 In the process 2 of Production Example 1, Lunac P-70 (tetradecanoic acid, hexadecanoic acid, octadecanoic acid in a weight ratio of 3: 7) manufactured by Kao Corporation was used in place of methyl tetradecanoate.
(0:27 mixture) under heating to reflux and reacted with methanol in the presence of a sulfuric acid catalyst to produce Lunack P.
The reaction was performed in the same manner as in Step 1 and Step 2 of Production Example 1 except that the -70 methyl ester was used, and the amide derivative (2
d) was obtained (steps 1 and 2).

[0123]

[Chemical 29]

The followings are physical properties of the amide derivative (2d) so obtained.

White solid Melting point; 50 ° C. IR (ν _neat , cm ⁻¹ ); 3430, 2930, 286
0,1620,1470,1205,1110,95
0,720.

In Step 11 of Production Example 3, compound (2
The compound (2d) obtained in the above (Step 2) was used instead of b) for the reaction, and the obtained 1,3-dioxolane-amide derivative (16d) was purified in the following Step 10
The reaction was performed in the same manner as in Steps 11 and 10 of Production Example 3 except that the above reaction was performed to obtain the desired amide derivative (1d) (Steps 11 and 10).

[0127]

[Chemical 30]

The followings are physical properties of the amide derivative (1d) so obtained.

White solid Melting point; 32 ° C. IR (ν _neat , cm ^-1 ); 3445, 2930, 286
0, 1650, 1630, 1470, 1380, 121
0, 1120, 1080, 720.

Production Example 6 Amino alcohol derivative (4e) was obtained by carrying out the reaction in the same manner as in Step 1 of Production Example 1 except that octadecyl glycidyl ether was used in place of hexadecyl glycidyl ether in Step 1 of Production Example 1. Obtained (step 1).

[0131]

[Chemical 31]

Obtained amino alcohol derivative (4e)
The physical properties of are as follows.

White solid Melting point; 57 to 58 ° C. IR (ν _neat , cm ⁻¹ ); 3340, 2930, 285
5,1470,1120,960,900,840,7
20. ¹ H-NMR (CDCl ₃ , δ); 0.88 (t, J =
6.3 Hz, 3 H), 1.25 to 1.45 (m, 30
H), 1.45 to 1.85 (m, 6H), 2.55
2.75 (m, 4H), 3.32 (s, 3H), 3.3
5 to 3.50 (m, 6H), 3.77 to 3.89 (m,
1H).

In Step 2 of Production Example 1, compound (4
A reaction was performed in the same manner as in Step 2 of Production Example 1 except that the compound (4e) obtained in (Step 1) above was used instead of a),
The amide derivative (2e) was obtained (step 2).

[0135]

[Chemical 32]

The followings are physical properties of the amide derivative (2e) so obtained.

White solid Melting point; 49 ° C. IR (ν _neat , cm ⁻¹ ); 3440, 2930, 286
0, 1650, 1625, 1470, 1225, 121
0, 1110, 950, 720. ¹ H-NMR (CDCl ₃ , δ); 0.88 (br t,
J = 6.3 Hz, 6H), 1.15 to 1.95 (m, 5
7H), 2.36 (t, J = 7.5Hz, 2H), 3.
30 to 3.55 (m, 10H), 3.33 (s, 3
H), 3.85-3.95 (m, 1H).

In Step 5 of Production Example 1, compound (2
A reaction was performed in the same manner as in Production Example 1, Step 5, except that the compound (2e) obtained in (Step 2) above was used instead of a).
The amide derivative (3e) was obtained (step 5).

[0139]

[Chemical 33]

The followings are physical properties of the amide derivative (3e) so obtained.

Colorless transparent liquid IR (ν _neat , cm ^-1 ); 2930, 2860, 165
0, 1425, 1380, 1260, 1210, 112
0,910,720. ¹ H-NMR (CDCl ₃ , δ); 0.88 (br t,
J = 6.0 Hz, 6H), 1.10 to 1.45 (m, 5
0H), 1.45 to 1.90 (m, 6H), 2.25 to
2.50 (m, 2H), 2.50 to 2.68 (m, 1
H), 2.70 to 2.85 (m, 1H), 3.01
3.20 (m, 1H), 3.20 to 4.00 (m, 13
H), 3.32 (s, 3H).

In Step 7 of Production Example 1, compound (3
The reaction was performed in the same manner as in Steps 7 and 8 of Production Example 1 except that the compound (3e) obtained in (Step 5) above was used instead of a) to obtain the target amide derivative (1e) ( Process 7
And 8).

[0143]

[Chemical 34]

The followings are physical properties of the amide derivative (1e) so obtained.

White solid Melting point; 23 ° C. IR (ν _neat , cm ^-1 ); 3425, 2930, 286
0, 1650, 1630, 1470, 1380, 122
0,1210,1120,720. ¹ H-NMR (CDCl ₃ , δ); 0.88 (br t,
J = 6.7 Hz, 6H), 1.17 to 1.45 (m, 4
9H), 1.45 to 1.92 (m, 8H), 2.22 to
2.45 (m, 2H), 3.20 to 3.90 (m, 17
H), 3.33 (s, 3H).

Production Example 7 In the same manner as in Production Example 1, except that the compound (4a) obtained in Step 1 of Production Example 6 was used in place of the compound (4a), and methyl tetradecanoate was replaced with methyl hexadecanoate. Reacted in the same manner as in Step 2 of Production Example 1 to obtain an amide derivative (2f) (Steps 1 and 2).

[0147]

[Chemical 35]

The followings are physical properties of the amide derivative (2f) so obtained.

White solid Melting point; 54 to 55 ° C. IR (ν _neat , cm ⁻¹ ); 3430, 2930, 285
5,1620,1470,1220,1205,111
0,950,885,720. ¹ H-NMR (CDCl ₃ , δ); 0.88 (br t,
J = 6.4 Hz, 6H), 1.25 to 1.95 (m, 6
1H), 2.36 (t, J = 7.6Hz, 2H), 3.
29 to 3.52 (m, 10H), 3.33 (s, 3
H), 3.88-3.95 (m, 1H).

In Step 5 of Production Example 1, compound (2
The reaction was carried out in the same manner as in Step 5 of Production Example 1 except that the compound (2f) was used in place of a) to obtain the amide derivative (3f).
Was obtained (step 5).

[0151]

[Chemical 36]

The followings are physical properties of the amide derivative (3f) so obtained.

White solid Melting point; 45 to 47 ° C. IR (ν _neat , cm ⁻¹ ); 2930, 2860, 165
0, 1470, 1425, 1380, 1210, 112
0,910,845,755,720. ¹ H-NMR (CDCl ₃ , δ); 0.88 (br t,
J = 6.7 Hz, 6H), 1.15 to 1.45 (m, 5
4H), 1.45 to 1.73 (m, 4H), 1.73 to
1.90 (m, 2H), 2.25 to 2.48 (m, 2
H), 2.50 to 2.68 (m, 1H), 2.70 to
2.85 (m, 1H), 3.00 to 3.18 (m, 1
H), 3.18 to 4.00 (m, 13H), 3.32
(S, 3H).

In Step 7 of Production Example 1, compound (3
The reaction was performed in the same manner as in Steps 7 and 8 of Production Example 1 except that the compound (3f) obtained in (Step 5) above was used instead of a) to obtain the desired amide derivative (1f) ( Process 7
And 8).

[0155]

[Chemical 37]

The followings are physical properties of the amide derivative (1f) so obtained.

White solid Melting point; 35 ° C. IR (ν _neat , cm ⁻¹ ); 3445, 2930, 286
0, 1650, 1630, 1470, 1420, 138
0, 1305, 1210, 1120, 1080. ¹ H-NMR (CDCl ₃ , δ); 0.88 (br t,
J = 6.4 Hz, 6H), 1.15 to 1.45 (m, 5
4H), 1.45 to 1.95 (m, 7H), 2.25 to
2.55 (m, 3H), 3.20 to 3.95 (m, 16
H), 3.33 (s, 3H).

Production Example 8 Amino alcohol derivative (4 g) was prepared in the same manner as in Step 1 of Production Example 1 except that tetradecyl glycidyl ether was used in place of hexadecyl glycidyl ether in Step 1 of Production Example 1. Was obtained (step 1).

[0159]

[Chemical 38]

The amino alcohol derivative obtained (4 g)
The physical properties of are as follows.

White solid Melting point; 47 ° C. IR (ν _neat , cm ^-1 ); 3340, 2930, 285
5,1470,1310,1120,1065,99
5,900,720. ¹ H-NMR (CDCl ₃ , δ); 0.88 (t, J =
6.3 Hz, 3 H), 1.25 to 1.45 (m, 26
H), 1.45 to 1.85 (m, 6H), 2.57 to
2.75 (m, 4H), 3.32 (s, 3H), 3.3
8 to 3.48 (m, 6H), 3.75 to 3.88 (m,
1H).

In Step 2 of Production Example 1, compound (4
Compound (4 g) obtained in the above (Step 1) instead of a)
Was reacted in the same manner as in Step 2 of Production Example 1 except that methyl hexadecanoate was used instead of methyl tetradecanoate to obtain an amide derivative (2 g) (Step 2).

[0163]

[Chemical Formula 39]

The followings are physical properties of the amide derivative (2g) so obtained.

White solid Melting point; 47 ° C. IR (ν _neat , cm ^-1 ); 3440, 2930, 285
5,1620,1470,1205,1110,95
0,720. ¹ H-NMR (CDCl ₃ , δ); 0.88 (br t,
J = 6.4 Hz, 6 H), 1.26 to 1.89 (m, 5
2H), 2.36 (t, J = 7.6Hz, 2H), 3.
29 to 3.52 (m, 11H), 3.33 (s, 3
H), 3.88-3.95 (m, 1H).

In Step 5 of Production Example 1, compound (2
Instead of a), the compound (2g) obtained in the above (Step 2)
Reaction was performed in the same manner as in Step 5 of Production Example 1 except that was used to obtain an amide derivative (3 g) (Step 5).

[0167]

[Chemical 40]

The followings are physical properties of the amide derivative (3g) so obtained.

Colorless transparent liquid IR (ν _neat , cm ^-1 ); 2930, 2860, 165
0, 1470, 1425, 1380, 1210, 112
0,910,845,755,720. ¹ H-NMR (CDCl ₃ , δ); 0.88 (br t,
J = 6.7 Hz, 6H), 1.15 to 1.45 (m, 4
6H), 1.45 to 1.73 (m, 4H), 1.73 to
1.90 (m, 2H), 2.25 to 2.50 (m, 2H)
H), 2.50 to 2.68 (m, 1H), 2.70 to
2.85 (m, 1H), 3.00 to 3.18 (m, 1
H), 3.18 to 4.00 (m, 13H), 3.32
(S, 3H).

In Step 7 of Production Example 1, compound (3
Instead of a), the compound (3 g) obtained in the above (Step 5)
The reaction was performed in the same manner as in Steps 7 and 8 of Production Example 1 except that the above was used to obtain the desired amide derivative (1 g) (Steps 7 and 8).

[0171]

[Chemical 41]

The followings are physical properties of the amide derivative (1g) so obtained.

White solid Melting point; 27 ° C. IR (ν _neat , cm ^-1 ); 3445, 2930, 286
0, 1650, 1630, 1470, 1420, 138
0,1305,1210,1120,1080,72
0. ¹ H-NMR (CDCl ₃ , δ); 0.88 (br t,
J = 6.4 Hz, 6H), 1.15 to 1.45 (m, 4
5H), 1.45 to 1.93 (m, 7H), 2.20 to
2.60 (m, 3H), 3.20 to 3.90 (m, 17
H), 3.33 (s, 3H).

Production Example 9 The reaction was performed in the same manner as in Step 1 of Production Example 1 except that 2-methoxyethylamine was used in place of 3-methoxypropylamine in Step 1 of Production Example 1, and the amino alcohol derivative (4h ) Was obtained (step 1).

[0175]

[Chemical 42]

Obtained amino alcohol derivative (4h)
The physical properties of are as follows.

White solid Melting point; 54 to 55 ° C. IR (ν _neat , cm ⁻¹ ); 3430, 2920, 285
5,1470,1120,1065,900,720. ¹ H-NMR (CDCl ₃ , δ); 0.88 (t, J =
6.3 Hz, 3 H), 1.25 to 1.70 (m, 30
H), 2.57 to 2.76 (m, 4H), 3.32.
(S, 3H), 3.38 to 3.48 (m, 6H), 3.
77-3.89 (m, 1H).

In Step 2 of Production Example 1, compound (4
Compound (4h) obtained in the above (Step 1) instead of a)
Was further reacted in the same manner as in Step 2 of Production Example 1 except that methyl hexadecanoate was used in place of methyl tetradecanoate to obtain an amide derivative (2h) (Step 2).

[0179]

[Chemical 43]

The followings are physical properties of the amide derivative (2h) so obtained.

White solid Melting point: 51 to 52 ° C. IR (ν _neat , cm ⁻¹ ); 3420, 2920, 285
5,1620,1470,1110,720. ¹ H-NMR (CDCl ₃ , δ); 0.87 (t, J =
6.4 Hz, 6 H), 1.15 to 1.70 (m, 55
H), 2.25 to 2.50 (m, 2H), 3.20 to
4.00 (m, 11H), 3.34 (s, 3H).

In Step 5 of Production Example 1, compound (2
A reaction was performed in the same manner as in Step 5 of Production Example 1 except that the compound (2h) obtained in (Step 2) above was used instead of a),
The amide derivative (3h) was obtained (step 5).

[0183]

[Chemical 44]

The followings are physical properties of the amide derivative (3h) so obtained.

Colorless transparent liquid IR (ν _neat , cm ^-1 ); 2930, 2855, 165
0,1470,1420,1380,1310,125
0, 1190, 1120, 910, 850, 720. ¹ H-NMR (CDCl ₃ , δ); 0.88 (br t,
J = 6.4 Hz, 6 H), 1.13 to 1.45 (m, 5
0H), 1.45 to 1.70 (m, 4H), 2.30 to
2.50 (m, 2H), 2.50 to 2.70 (m, 1
H), 2.70 to 2.85 (m, 1H), 3.00
3.20 (m, 1H), 3.20 to 4.00 (m, 13
H), 3.32 (s, 3H).

In Step 6 of Production Example 1, compound (3
A reaction was performed in the same manner as in Step 6 of Production Example 1 except that the compound (3h) obtained in (Step 5) above was used instead of a),
The desired amide derivative (1h) was obtained (step 6).

[0187]

[Chemical formula 45]

The followings are physical properties of the amide derivative (1h) so obtained.

White solid Melting point: 31 to 32 ° C. IR (ν _neat , cm ⁻¹ ); 3450, 2930, 286
0, 1630, 1470, 1380, 1300, 119
0,1160,720. ¹ H-NMR (CDCl ₃ , δ); 0.88 (t, J =
6.4 Hz, 6 H), 1.15 to 1.75 (m, 54
H), 2.20 to 2.45 (m, 3H), 3.20 to
3.90 (m, 17H), 3.33 (s, 3H).

In Step 11 of Production Example 3, compound (2
The reaction was performed in the same manner as in Step 11 of Production Example 3 except that the compound (2h) obtained in (Step 2) above was used instead of b) to obtain a 1,3-dioxolane-amide derivative (16h). (Step 11).

[0191]

[Chemical formula 46]

The followings are physical properties of the 1,3-dioxolane-amide derivative (16h) so obtained.

Colorless transparent liquid ¹ H-NMR (CDCl ₃ , δ); 0.88 (t, J =
6.4 Hz, 6 H), 1.15 to 1.70 (m, 54
H), 1.34 (s, 3H), 1.40 (s, 3H),
2.36 (t, J = 7.0Hz, 2H), 3.25 ~
4.30 (m, 19H).

In Step 10 of Production Example 3, compound (1
Instead of 6b), the compound (16) obtained in the above (Step 11)
A reaction was performed in the same manner as in Step 11 of Production Example 3 except that h) was used to obtain the desired amide derivative (1h) (Step 10).

Production Example 10 Amino alcohol derivative (4i) was obtained by carrying out the reaction in the same manner as in Step 1 of Production Example 1 except that ethylamine was used in place of 3-methoxypropylamine in Step 1 of Production Example 1. (Step 1).

[0196]

[Chemical 47]

Obtained amino alcohol derivative (4i)
The physical properties of are as follows.

White solid Melting point: 60 to 61 ° C. IR (ν _neat , cm ⁻¹ ); 3400, 2930, 285
5,1470,1310,1110,955,720. ¹ H-NMR (CDCl ₃ , δ); 0.88 (t, J =
6.4 Hz, 3 H), 1.11 (t, J = 7.2 Hz,
3H), 1.15 to 1.70 (m, 30H), 2.55
~ 2.80 (m, 4H), 3.35-3.53 (m, 4
H), 3.79-3.93 (m, 1H).

In the step 2 of Production Example 1, the compound (4
Compound (4i) obtained in the above (Step 1) instead of a)
Was reacted in the same manner as in Step 2 of Production Example 1 except that methyl hexadecanoate was used instead of methyl tetradecanoate to obtain an amide derivative (2i) (Step 2).

[0200]

[Chemical 48]

The followings are physical properties of the amide derivative (2i) so obtained.

White solid Melting point; 56 ° C. IR (ν _neat , cm ^-1 ); 3410, 2930, 286
0,1625,1470,1380,1305,124
5,1210,1110,950,855,720. ¹ H-NMR (CDCl ₃ , δ); 0.88 (t, J =
6.4 Hz, 6 H), 1.15 to 1.75 (m, 57
H), 2.34 (t, J = 7.6 Hz, 2H), 3.3.
0 to 3.55 (m, 9H), 3.85 to 4.00 (m,
1H).

In Step 5 of Production Example 1, compound (2
A reaction was performed in the same manner as in Step 5 of Production Example 1 except that the compound (2i) obtained in (Step 2) above was used instead of a),
The amide derivative (3i) was obtained (step 5).

[0204]

[Chemical 49]

The followings are physical properties of the amide derivative (3i) so obtained.

Colorless transparent liquid IR (ν _neat , cm ^-1 ); 2930, 2855, 165
0, 1470, 1425, 1380, 1210, 112
0,905,840,720. ¹ H-NMR (CDCl ₃ , δ); 0.88 (br t,
J = 6.4 Hz, 6H), 1.10 to 1.75 (m, 5
7H), 2.25 to 2.50 (m, 2H), 2.50
2.70 (m, 1H), 2.70 to 2.85 (m, 1
H), 3.00 to 4.00 (m, 12H).

In Step 6 of Production Example 1, compound (3
A reaction was performed in the same manner as in Step 6 of Production Example 1 except that the compound (3i) obtained in (Step 5) above was used instead of a),
The target amide derivative (1i) was obtained (step 6).

[0208]

[Chemical 50]

The followings are physical properties of the amide derivative (1i) so obtained.

White solid Melting point: 35 to 36 ° C. IR (ν _neat , cm ⁻¹ ); 3445, 2930, 286
0, 1630, 1470, 1420, 1380, 130
5,1210,1120,720. ¹ H-NMR (CDCl ₃ , δ); 0.88 (br t,
J = 6.4 Hz, 6 H), 1.13 to 1.75 (m, 5
7H), 2.31 (t, J = 7.5Hz, 2H), 3.
20-3.90 (m, 16H).

Production Example 11 150 g of pigment was placed in a round bottom flask (or kneader),
To this, 7.5 g of (C ₈ F ₁₇ CH ₂ CH ₂ O) ₂ P (O) OH and 1500 g of isopropyl alcohol dissolved by heating (50 ° C.) was added, and mixed at 60 ° C. for 4 hours. Then 40 ~
Isopropyl alcohol was distilled off under reduced pressure at 50 ° C. and dried to obtain 155 g of the target hydrophobically treated pigment.

Example 1 (Oil solid foundation) An oil solid foundation having the composition shown in Table 1 was produced,
The makeup retention, feeling of use and moisturizing effect were evaluated. The results are shown in Table 2.

[0213]

[Table 1]

(Production Method) The components (1) to (9) are heated to 90 ° C. and mixed and dissolved. Furthermore, the components (10) to (21) are added, and the mixture is sufficiently stirred and mixed while maintaining the temperature at 90 ° C. until uniform. An oily solid foundation was obtained by filling this mixture in a gold plate and cooling it.

(Evaluation method) (1) Make-up lasting and feeling of use: Make-up lasting when a foundation was applied by 10 professional panelists,
Sensory evaluations were made for the spread, moist feeling and bulkiness, and the evaluation was made according to the following criteria. ○: 8 or more are “good”. Δ: “Good” is 4 to 7 people. ×: “Good” is less than 4 people.

(2) Moisturizing effect: Ten women with rough skin on the cheeks were used as subjects, and the foundation was applied for one week. Measure skin conductance before and after application,
The values before and after coating were compared. Skin conductance is 37
After washing the face with warm water of ° C and resting in a room at a temperature of 20 ° C and a humidity of 40% for 20 minutes, the water content of the stratum corneum was measured with a skin conductance meter (manufactured by IBS). The results are shown based on the following criteria. ○: “Conductance value increased after application” was 8 or more. Δ: “Conductance value increased after application” was 4 to 7 people. ×: “Conductance value increased after application” was less than 4 people.

[0217]

[Table 2]

As is clear from the results shown in Table 2, the oily solid foundation of the present invention was excellent in makeup retention, feeling in use and moisturizing effect.

Example 2 (two-layer liquid foundation) A two-layer liquid foundation having the following composition was produced by the following production method.

[Table 3] (Component) (% by weight) (1) Octamethylcyclotetrasiloxane 20.0 (2) Dimethyl polysiloxane / polyoxyalkylene copolymer 0.5 (3) Amide derivative (1e; melting point 23 ° C.) 7.0 (4) Octyl methoxycinnamate 2.0 (5) Glycerin 2.0 (6) Ethanol 15.0 (7) Water balance (8) Hydrophobized titanium oxide (Production Example 11) 6.0 (9) Hydrophobized sericite (Production Example 11) 8.0 (10) Hydrophobized red iron oxide (Production Example 11) 0.5 (11) Hydrophobized yellow iron oxide (Production Example 11) 1.5 (12) Hydrophobized black iron oxide (Production Example 11) 0.1

(Production method) After dissolving the components (1) to (4) at room temperature, the components (8) to (12) are dispersed with a disper. Ingredients (5) to (7) were added to this with stirring to emulsify to obtain the intended two-layer liquid foundation.

Example 3 (blusher) A blusher having the following composition was produced according to the following production method.

[Table 4] (Components) (% by weight) (1) Liquid isoparaffin balance (2) Amide derivative (1f; melting point 35 ° C) 5.0 (3) Paraffin wax 20.0 (4) Preservative 0.3 (5) ) Silicone treated sericite ^{* 1} 30.0 (6) Silicone treated titanium oxide ^{* 1} 15.0 (7) Silicone treated red iron oxide ^{* 1} 2.0 (8) Silicone treated yellow iron oxide ^{* 1} 1.0 (9) Fragrance 0.01 * 1: Methyl hydrogen polysiloxane 2% treatment

(Production Method) Components (1) to (4) are heated to 90 ° C. and mixed and dissolved. Further, the components (5) to (9) are added, mixed for about 5 minutes, and then further pulverized. It pressed to the gold plate with the press machine and obtained the blusher.

Example 4 (Powder Foundation) A powder foundation having the following composition was produced by the following production method.

[Table 5] (Component) (% by weight) (1) Hydrophobized titanium oxide (Production Example 11) 10.0 (2) Hydrophobized sericite (Production Example 11) 30.0 (3) Hydrophobized mica (Production Example 11) Balance (4) Hydrophobized Kaolin (Production Example 11) 5.0 (5) Hydrophobized red iron oxide (Production Example 11) 0.8 (6) Hydrophobized yellow iron oxide (Production Example 11) 2.5 (7) Hydrophobized black iron oxide (Production Example 11) 0.1 (8) Amide derivative (1 g; melting point 27 ° C.) 8.0 (9) Beeswax 2.0 (10) Preservative 0.2 (11) Perfume 0.01

(Production method) The pigments of the components (1) to (7) are mixed and passed through a pulverizer for pulverization. This is transferred to a high-speed blender, components (8) to (11) are heated and mixed, and the homogenized product is added to the pigment and further mixed to homogenize. This was treated with a crusher, passed through a sieve to adjust the particle size, left for several days, and then compression-molded in a container such as a gold plate to obtain a powder foundation.

Example 5 (Powder eyeshadow) A powder eyeshadow having the following composition was produced by the following production method.

[Table 6] (Components) (% by weight) (1) Silicone treated mica titanium ^{* 1} 5.0 (2) Silicone treated sericite ^{* 1} balance (3) Silicone treated mica ^{* 1} 25.0 (4) Silicone treated oxidation Iron (red, yellow, black) ^{* 1} 2.0 (5) Ultramarine 9.0 (6) Dark blue 12.0 (7) Amide derivative (1h; melting point 31 ° C) 8.0 (8) Squalane 2.0 ( 9) Vaseline 1.5 (10) Sorbitan trioleate 1.0 (11) Preservative 0.1 (12) Perfume 0.01 * 1: Methyl hydrogen polysiloxane 2% treatment

(Manufacturing Method) The pigments of the components (2) to (6) are first mixed and pulverized, and then the mica titanium of the component (1) is mixed. Others were carried out similarly to Example 3, and obtained the target powder eye shadow.

Example 6 (Sunscreen Emulsion) A sunscreen emulsion having the following composition was produced according to the following composition.

Table 7 (Components) (wt%) (1) Dimethylpolysiloxane / polyoxyalkylene copolymer 2.0 (2) Amide derivative (1i; melting point 35 ° C) 8.0 (3) Aluminum stearate 2 (4) 1-Isostearoyl-3-myristoyl glycerol 2.0 (5) Silicone-treated zinc oxide ^{* 1} 9.0 (6) Decamethylcyclopentasiloxane 15.0 (7) Butyl paraoxybenzoate 0.1 ( 8) Magnesium sulfate 0.5 (9) Glycerin 5.0 (10) Water balance (11) Perfume 0.01 * 1: Methyl hydrogen polysiloxane 2% treatment

(Production method) Components (1) to (4) were mixed, and
Heat to 5 ° C. (5) is dispersed in this with a disper. The mixture of (7) to (10) is heated to 75 ° C. and gradually added with stirring to emulsify. Then, it cooled at 30 degreeC, (6) and (11) were added, and also it cooled to room temperature, and the target sunscreen emulsion was obtained.

The various cosmetics obtained in Examples 2 to 6 all had a good feeling in use, and were excellent in moisturizing feeling, difficulty in feeling dry, and long-lasting makeup.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁷ identification code FI A61K 7/035 A61K 7/035 (58) Fields investigated (Int.Cl. ⁷ , DB name) A61K ^7/ 00-7/50

Claims (3)

(57) [Claims] 1. The following components (A) and (B): (A) One or more amide compounds represented by the following general formula (1), (2) or (3): (In the formula, R ¹ and R ² are the same or different and have 1 to 40 carbon atoms.
Represents an optionally hydroxylated hydrocarbon group of
R ³ represents a linear or branched alkylene group having 1 to 6 carbon atoms or a single bond, R ⁴ represents a hydrogen atom, 1 to 12 carbon atoms
Is a linear or branched alkoxy group or a 2,3-dihydroxypropyloxy group. However, when R ³ is a single bond, R ⁴ is a hydrogen atom. ) [Chemical 2] (In the formula, R ¹ and R ² have the same meanings as described above, R ^3a represents a linear or branched alkylene group having 3 to 6 carbon atoms, and R ^4a represents a linear or branched chain having 1 to 12 carbon atoms. A chain alkoxy group is shown.) (In the formula, R ¹ , R ² and R ³ have the same meanings as described above, and
^4b represents a hydrogen atom, a linear or branched alkoxy group having 1 to 12 carbon atoms, or a 2,3-epoxypropyloxy group. However, when R ³ is a single bond, R ^4b is a hydrogen atom. ) (B) A cosmetic containing a pigment. 2. The cosmetic according to claim 1, wherein the component (B) is a hydrophobized pigment. 3. The cosmetic according to claim 1, which is an emulsion type cosmetic.