JP2007051098A - Aminopyrimidine derivative and hair-dyeing agent composition containing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new 5-amino-6-hydroxy-2-phenyl-4(1H)-pyrimidine derivative or its salts and a hair-dyeing agent composition containing them. <P>SOLUTION: As the 5-amino-6-hydroxy-2-phenyl-4(1H)-pyrimidine derivative expressed by general formula (1), 5-amino-6-hydroxy-2-phenyl-4-pyrimidine, 5-amino-6-hydroxy-2-(3-amino-4-hydroxyphenyl)-4-pyrimidine and 5-amino-6-hydroxy-2-(4-aminophenyl)-4-pyrimidine are synthesized and the hair-dyeing agent compositions containing them are also produced. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a novel 5-amino-6-hydroxy-2-phenyl-4 (1H) -pyrimidine derivative or a salt thereof, and a hair dye composition containing them.

Conventionally, as a hair dye composition, a hair dye first agent mainly composed of an oxidative dye such as paraphenylenediamine and paratoluylenediamine, and a hair dye mainly composed of an oxidant such as hydrogen peroxide. A two-component oxidative hair dye comprising an agent second agent is known. When the hair dyeing treatment is performed using this oxidative hair dye, the first agent and the second agent are mixed at the time of use and applied to the hair. Then, the oxidative dye contained in the hair dye first agent penetrates into the hair and is polymerized by the action of the oxidant contained in the hair dye second agent to form a pigment. The pigment is fixed on the hair so that the hair can be dyed (for example, see Non-Patent Document 1).
Edited by Takeo Mitsui, “New Cosmetics”, Nanzan-do Co., Ltd., January 12, 1993, p. 443-452

  The present invention relates to a novel 5-amino-6-hydroxy-2-phenyl-4 (1H) -pyrimidine derivative or a salt thereof that can be used as, for example, an oxidative dye of a hair dye composition, and a hair dye containing them. An object is to provide an agent composition.

  The present invention relates to a general formula (1):

(Wherein R ^{1 to} R ⁵ are each a hydrogen atom, a hydroxyl group, or an amino group) 5-amino-6-hydroxy-2-phenyl-4 (1H) -pyrimidine derivative Or the salt is made into a summary.

The derivative of the present invention or a salt thereof can be used as, for example, an oxidation dye contained in a hair dye composition.
In the derivative of the present invention, for example, all of R ^{1 to} R ⁵ can be hydrogen atoms. In this case, the derivative of the present invention is 5-amino-6-hydroxy-2-phenyl-4-pyrimidinone, and its structure is shown in chemical formula (2).

In the present invention, for example, R ¹ , R ⁴ , and R ⁵ can be hydrogen atoms, and at least one of R ² and R ³ can be a hydroxyl group or an amino group.
At this time, R ² can be an amino group and R ³ can be a hydroxyl group. The 5-amino-6-hydroxy-2-phenyl-4 (1H) -pyrimidine derivative in this case is 5-amino-6-hydroxy-2- (3-amino-4-hydroxyphenyl) -4-pyrimidinone. The structure is as shown in chemical formula (3).

In the present invention, R ¹ , R ⁴ , and R ⁵ can be hydrogen atoms, R ² can be a hydrogen atom, and R ³ can be an amino group. The 5-amino-6-hydroxy-2-phenyl-4 (1H) -pyrimidine derivative in this case is 5-amino-6-hydroxy-2- (4-aminophenyl) -4-pyrimidinone, and its structure is It will be shown in chemical formula (4).

The derivative represented by the chemical formula (3) can be produced, for example, by the following method.
(First step in producing derivative of chemical formula (3))
6-hydroxy-2- (4-hydroxyphenyl) -4-pyrimidinone hydrochloride and fuming nitric acid were mixed to give 5-nitro-6-hydroxy-2- (3-nitro-4-O-nitrophenyl) -4 -Pyrimidinone is produced.
(Second step in producing derivative of chemical formula (3))
5-Nitro-6-hydroxy-2- (3-nitro-4-O-nitrophenyl) -4-pyrimidinone, water and ethanol were mixed to give 5-amino-6-hydroxy-2- (3-amino- 4-hydroxyphenyl) -4-pyrimidinone is prepared.

Moreover, the derivative shown to the said Chemical formula (4) can be manufactured with the following method, for example.
(First step in manufacturing derivative of chemical formula (4))
Ethanol, sodium, 4-aminobenzamidine dihydrochloride and diethyl α-nitromalonate were mixed, and then acid was added to give 5-nitro-6-hydroxy-2- (4-aminophenyl) -4-pyrimidinone. To manufacture.
(Second step in producing derivative of chemical formula (4))
5-Nitro-6-hydroxy-2- (4-aminophenyl) -4-pyrimidinone, water and ethanol were mixed to give 5-amino-6-hydroxy-2- (4-aminophenyl) -4-pyrimidinone. To manufacture.

The gist of the present invention is a hair dye composition containing a 5-amino-6-hydroxy-2-phenyl-4 (1H) -pyrimidine derivative or a salt thereof.
The hair dye composition of the present invention contains a 5-amino-6-hydroxy-2-phenyl-4 (1H) -pyrimidine derivative or a salt thereof, so that the hair can have various colors (for example, reddish purple, orange, Can be dyed dark brown, brown, pink brown).

  The blending amount of the 5-amino-6-hydroxy-2-phenyl-4 (1H) -pyrimidine derivative or a salt thereof is preferably in the range of 0.01 to 5% by weight with respect to the total amount of the hair dye composition, among which A range of 0.5 to 3% by weight is particularly preferred.

The hair dye composition of the present invention can also contain other oxidation dyes. Examples of other oxidation dyes include main intermediates and couplers.
Specific examples of main intermediates include phenylenediamines, aminophenols, toluylenediamines, aminonitrophenols, diphenylamines, diaminophenylamines, N-phenylphenylenediamines, diaminopyridines, and salts thereof. And at least one selected from. Examples of the salt include hydrochloride, sulfate, acetate and the like.

  Among these, paraphenylenediamine, paratoluylenediamine, N, N-bis (2-hydroxyethyl) -paraphenylenediamine, N-phenyl-paraphenylenediamine, 4,4′-diaminodiphenylamine, 2-chloroparaphenylenediamine N, N-dimethylparaphenylenediamine, paraaminophenol, 2,6-dichloroparaphenylenediamine, paraaminophenylsulfamic acid and salts thereof are preferred from the viewpoint of hair dyeing power.

  The blending amount of the main intermediate is preferably 0.01 to 15% by weight with respect to the hair dye composition, and if it is less than 0.01% by weight, sufficient hair dyeing effect cannot be obtained and exceeds 15% by weight. However, the effect remains the same and is not economical. Furthermore, 0.1 to 10 weight% is especially preferable, and the more excellent hair dyeing effect is acquired by mix | blending 0.1 weight% or more. On the other hand, when it exceeds 10% by weight, the increase in the hair dyeing effect is reduced.

  Specific examples of couplers include resorcin, pyrogallol, catechol, metaaminophenol, metaphenylenediamine, orthoaminophenol, 2,4-diaminophenol, 1,2,4-benzenetriol, toluene-3,4-diamine, toluene -2,4-diamine, hydroquinone, α-naphthol, 2,6-diaminopyridine, 1,5-dihydroxynaphthalene, 5-aminoorthocresol, diphenylamine, paramethylaminophenol, phloroglucin, 2,4-diaminophenoxyethanol, gallic At least one selected from acids, tannic acid, ethyl gallate, methyl gallate, propyl gallate, pentaploid, 5- (2-hydroxyethylamino) -2-methylphenol, and salts thereof is used. In addition, those listed in "Quasi-drug raw material standards" (issued in June 1991, Yakuji Nippo) may be appropriately blended.

  The blending amount of the coupler is preferably 0.01 to 10% by weight, and if it is less than 0.01% by weight, sufficient dyeability cannot be obtained, and if it exceeds 10% by weight, the effect is not changed and it is not economical. . Furthermore, 0.1 to 5 weight% is especially preferable, and the more excellent dyeability is obtained by mix | blending 0.1 weight% or more. On the other hand, when it exceeds 5% by weight, the increase in dyeability is reduced.

  In the hair dye composition of the present invention, as other additive components, dyes other than oxidation dyes, alkaline agents, lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, cetostearyl alcohol, behenyl alcohol and other higher alcohols, jojoba oil , Oils and fats such as glyceride of olive oil, waxes such as beeswax and lanolin, hydrocarbons such as liquid paraffin, solid paraffin, isoparaffin and squalane, esters such as isopropyl myristate and octyldodecyl myristate, dimethylpolysiloxane, methyl Silicones such as phenylpolysiloxane, polyether-modified silicone, highly polymerized silicone, amino-modified silicone, fatty acids such as lauric acid, myristic acid and linolenic acid, and sugars such as sorbitol and maltose Alkyl glyceryl ethers such as polyhydric alcohols, batyl alcohols and chimyl alcohols, gum arabic, sodium alginate, xanthan gum, cellulose derivatives, natural or synthetic polymers such as cross-linked polyacrylic acid, preservatives such as parabens, EDTA-Na, etc. Chelating agents, phenacetin, 8-hydroxyquinoline, acetanilide, sodium pyrophosphate, barbituric acid, uric acid, tannic acid and other stabilizers, phosphoric acid, citric acid, sulfuric acid, acetic acid, lactic acid, tartaric acid and other pH adjusters, plants Contains at least one selected from extracts, herbal extracts, vitamins, fragrances, UV absorbers, and other substances listed in the “Quasi-drug Raw Material Standard” (issued June 1991, Yakuji Nippo) May be. The compounding amount of the other additive components is determined according to a conventional method of the hair dye composition.

  Specific examples of dyes other than oxidation dyes include direct dyes and basic dyes. As direct dyes, 4-nitro-o-phenylenediamine, 2-nitro-p-phenylenediamine, picramic acid, 1-amino-4-methylanthraquinone, 1,4-diaminoanthraquinone, 2-amino-4-nitrophenol , 2-amino-5-nitrophenol, picric acid and their salts, and acid dyes stipulated by "Ministerial Ordinance for Tar Tars that can be Used in Pharmaceuticals" (1960 Notification, Ministry of Health and Welfare) , Red No. 2, Red No. 3, Red No. 102, Red No. 104 (1), Red No. 105 (1), Red No. 106, Red No. 201, Red No. 227, Red No. 230 (1), Red 230 (2), Red 231, Red 232, Red 401, Red 502, Red 503, Red 504, Red 506, Yellow 4, Yellow No., yellow 202 (1), yellow 202 (2), yellow 203, yellow 402, yellow 403 (1), yellow 406, yellow 407, orange 205, orange 207 No., Daido No. 402, Green No. 3, Green No. 204, Green No. 205, Green No. 401, Green No. 402, Purple No. 401, Blue No. 1, Blue No. 2, Blue No. 202, Blue No. 203, Blue No. 205 At least one selected from brown 201, black 401 and the like is used. Further, by blending this direct dye, a more excellent effect can be obtained in dyeing and dyeability.

  The blending amount of the direct dye is preferably 0.001 to 10% by weight, and if it is less than 0.001% by weight, sufficient dyeing and dyeing properties cannot be obtained. Not right. Furthermore, 0.01 to 5% by weight is particularly preferable, and by blending 0.01% by weight or more, more excellent dyeing and dyeability can be obtained. On the other hand, when it exceeds 5% by weight, dyeing and dyeing are less likely to increase.

  The alkaline agent is added to swell the hair so that the dye and the oxidizing agent can easily penetrate into the hair. Specific examples of the alkali agent include ammonia, alkanolamines (triethanolamine, diethanolamine, monoethanolamine, isopropanolamine, diisopropanolamine, 2-amino-2-methyl-1-propanol, etc.), organic amines (2 -Amino-2-methyl-1,3-propanediol, guanidine, etc.), inorganic alkalis (sodium hydroxide, potassium hydroxide, etc.), basic amino acids (arginine, lysine, etc.) and salts thereof. These alkaline agents may be blended singly or in combination of two or more. Moreover, you may give a buffering effect to a hair dye composition by mix | blending suitably combining 2 or more types of alkaline agents.

  The blending amount of the alkaline agent is an amount such that the pH of the hair dye composition is preferably 8-12. If the pH of the hair dye composition is less than 8, the action of the oxidizing agent may not be sufficiently promoted. On the other hand, if it exceeds 12, problems such as damage may occur in the hair when hair is dyed.

The dosage form of the hair dye composition of the present invention can be, for example, liquid, emulsion, or cream.
Moreover, the hair dye composition of this invention may contain a polyhydric alcohol, surfactant, or both. The polyhydric alcohol has an effect of moisturizing the hair, and the surfactant has an action as an emulsifier or a solubilizer.

  Examples of the polyhydric alcohol include ethylene glycol, diethylene glycol, polyethylene glycol, glycerin, diglycerin, polyglycerin, propylene glycol, dipropylene glycol, and 1,3-butylene glycol.

  The blending amount of the polyhydric alcohol is 0.1 to 30% by weight, preferably 0.5 to 25% by weight, and more preferably 1.0 to 20% by weight. When it mixes less than 0.1 weight% and more than 30 weight%, the effect of reducing the sensitization property of a hair dye composition may become low.

  Examples of the surfactant include a cationic surfactant, an anionic surfactant, a nonionic surfactant, and an amphoteric surfactant. The cationic surfactant has the effect of improving the feel of hair in addition to the above-described action.

  Specific examples of the cationic surfactant include alkyltrimethylammonium chloride, lauryltrimethylammonium chloride, cetyltrimethylammonium chloride, stearyltrimethylammonium chloride, stearyltrimethylammonium bromide, lauryltrimethylammonium bromide, dialkyldimethylammonium chloride and the like. A quaternary ammonium salt etc. are mentioned.

  Specific examples of the anionic surfactant include coconut oil fatty acid potassium, coconut oil fatty acid sodium, coconut oil fatty acid triethanolamine, sodium laurate, potassium myristate, isopropanolamine myristate, sodium palmitate, sodium stearate, stearin. Fatty acid salts such as triethanolamine acid, potassium oleate, sodium oleate, metal soap such as magnesium stearate, calcium stearate, magnesium myristate, coconut oil fatty acid acyl potassium glutamate, coconut oil fatty acid acyl glutamate triethanolamine, lauroyl glutamic acid N-acyl glutamic acid and salts thereof such as triethanolamine, potassium myristoyl glutamate, sodium stearoyl glutamate Lauroylmethyl taurine potassium, coconut oil fatty acid methyl taurine sodium, palmitoyl methyl taurine sodium, stearoyl methyl taurine sodium and other N-acyl methyl taurine salts, sodium lauryl sulfate, alkyl sulfates such as lauryl sulfate triethanolamine, POE lauryl ether sulfate Sodium, alkyl ether sulfates such as POE lauryl ether sulfate triethanolamine, POE lauryl ether phosphate and salts thereof, monoalkyl phosphates such as lauryl phosphate, sodium lauryl phosphate, potassium cetyl phosphate and salts thereof, dodecylbenzene Examples include triethanolamine sulfonate, sodium tetradecenesulfonate, dioctyl sodium sulfosuccinate, and the like.

  Specific examples of the nonionic surfactant include polyoxyethylene (hereinafter referred to as POE) cetyl ether, POE stearyl ether, POE behenyl ether, POE oleyl ether, POE lauryl ether, POE octyldodecyl ether, POE hexyl decyl ether, Ether-type nonionic surfactants such as POE isostearyl ether, POE nonyl phenyl ether, POE octyl phenyl ether, monooleic acid POE sorbitan, monostearic acid POE sorbitan, monopalmitic acid POE sorbitan, monolauric acid POE sorbitan, trioleic acid POE sorbitan, POE glycerol monostearate, POE glycerol monomyristic acid, POE sorbitol tetraoleate, hexastearic acid P E sorbit, POE sorbite monolaurate, POE sorbite beeswax, polyethylene glycol monooleate, polyethylene glycol monostearate, polyethylene glycol monolaurate, oleophilic glycerin monooleate, oleophilic glycerin monostearate, self-emulsifying monostearate Glyceric acid, sorbitan monooleate, sorbitan sesquioleate, sorbitan trioleate, sorbitan monostearate, sorbitan monopalmitate, sorbitan monolaurate, sucrose fatty acid ester, decaglyceryl monolaurate, decaglyceryl monostearate, monoolein And ester-type nonionic surfactants such as decaglyceryl acid and decaglyceryl monomyristate.

  Specific examples of zwitterionic surfactants include 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, lauryldimethylaminoacetic acid betaine, undecylcarboxymethoxyethylcarboxymethylimidazolinium betaine sodium, Decylhydroxyethylimidazolinium betaine sodium, undecyl-N-hydroxyethyl-N-carboxymethylimidazolinium betaine, alkyldiaminoethylglycine hydrochloride, stearyldihydroxyethylbetaine, stearyldimethylaminoacetic acid betaine, stearyldimethylbetaine sodium solution, bis (Stearyl-N-hydroxyethylimidazoline) chloroacetic acid complex, coconut oil alkyl-N-carboxyethyl-N-hydroxyethyli Sodium dazolinium betaine, coconut oil alkyl-N-carboxyethoxyethyl-N-carboxyethyl imidazolinium disodium hydroxide, coconut oil alkyl-N-carboxymethoxyethyl-N-carboxyethyl imidazolinium disodium hydroxide, Coconut oil alkyl-N-carboxymethoxyethyl-N-carboxyethylimidazolinium disodium lauryl sulfate, palm oil alkyl betaine, palm oil fatty acid amidopropyl betaine, coconut oil fatty acid-N-carboxymethoxyethyl-N-carboxyethyl imidazole Sodium betaine, laurylaminopropionate triethanolamine, β-laurylaminopropionate sodium, lauryl N-carboxymethoxyethyl-N-carboxymethyl ester Examples include midazolinium disodium dodecanoyl sarcosine, sodium lauryldiaminoethylglycine, amidopropyl betaine laurate solution, lauryl sulfobetaine, and lauryl hydroxysulfobetaine.

  The compounding amount of the surfactant is 0.01 to 30% by weight, preferably 0.05 to 20% by weight, and more preferably 0.1 to 15% by weight. When less than 0.01% by weight and more than 30% by weight are blended, the effect of reducing the sensitization of the hair dye composition is lowered.

  The hair dye composition of this invention can be made into the 2 agent type comprised from the hair dye 1st agent containing an oxidation hair dye and the hair dye 2nd agent containing an oxidizing agent, for example. At the time of use, this hair dye composition mixes the hair dye first agent and the hair dye second agent and applies them to the hair. At this time, the oxidative dye contained in the hair dye first agent penetrates into the hair and is polymerized by the action of the oxidant contained in the hair dye second agent to produce a dye. I do. Moreover, the melanin contained in hair is decolored with an oxidizing agent.

  Examples of the oxidizing agent include hydrogen peroxide. The amount of the oxidizing agent is preferably such that the concentration of the oxidizing agent is 0.1 to 5% by weight in the mixed liquid in which the hair dye first agent and the hair dye second agent are mixed. % Is more preferable. If it is less than 0.1% by weight, there is a tendency that melanin cannot be sufficiently decolorized. On the other hand, if it exceeds 5% by weight, problems such as damage to the hair may occur.

  Hereinafter, specific examples will be described.

In the following manner, 5-amino-6-hydroxy-2-phenyl-4-pyrimidinone, which is one of 5-amino-6-hydroxy-2-phenyl-4 (1H) -pyrimidine derivatives, was synthesized. 1 and 2 show an outline of the synthesis procedure.
(i) Synthesis of 6-hydroxy-2-phenyl-4-pyrimidinone hydrochloride Into a 1 L three-necked flask previously dried in vacuo and purged with argon, 200 mL of ethanol and sodium (11.46 g, 498.4 mmol) were added. The mixture was stirred while being cooled to 2-3 ° C. in an ice bath, and completely dissolved.

  Benzamidine hydrochloride (23.60 g, 146.1 mmol) and ethanol (50 mL) were added to another 300 mL three-necked flask that had been vacuum-dried and purged with argon, and dissolved completely. A separately prepared solution of ethanol (80 mL) and sodium (4.484 g, 195.0 mmol) was transferred through a Teflon (registered trademark) tube using argon pressure.

  The contents were vacuum-dried and transferred to a filter part of a 300 mL three-necked flask equipped with a filter with a glass filter substituted with argon using a Teflon tube using argon pressure, and the resulting sodium chloride precipitate was filtered. Removed.

The obtained filtrate was transferred to the previous 1 L three-necked flask using a Teflon tube using argon pressure.
On the other hand, diethyl malonate (25.0 mL, 165.4 mmol) and ethanol 30 mL were added to another 100 mL two-necked flask that had been vacuum dried and purged with argon, and completely dissolved. This solution was transferred to the previous 1 L three-necked flask using argon pressure using a stainless steel tube and stirred at 130 ° C. for 15.5 hours. After completion of the reaction, the mixture was concentrated under reduced pressure.

  The pale yellow solid obtained by concentration was dissolved in 75 mL of distilled water, and the pH was adjusted to 3 to 4 with 1 M hydrochloric acid aqueous solution. The resulting white precipitate was filtered to obtain 6-hydroxy-2-phenyl-4-pyrimidinone hydrochloride (13.61 g, 49.5%).

As a result of NMR measurement of the obtained hydrochloride of 6-hydroxy-2-phenyl-4-pyrimidinone, it was as follows.
¹ H NMR (500 MHz, DMSO-d ₆ ) δ-0.084 (Br, s, 1, Pym (3) NH), 5.35 (s, 1, Hz, Pym C (5) H), 7.52 (t, 2, J = 7.3 Hz, Ph C (3) H, C (5) H), 7.58 (t 1, J = 7.4 Hz, Ph C (4) H ), 8.08 (d, 2, J = 7.8 Hz, Ph C (2) H, C (6) H), 11.96 (br, s 1, OH of PymC (6)). ¹³ C NMR (126 MHz, DMSO-d ₆ ) δ 88.37, 127.76, 128.59, 131.73, 132.32, 157.67.
(ii) Synthesis of 5-nitro-2-phenyl-6-hydroxy-4-pyrimidinone The 6-hydroxy-2-phenyl obtained in (i) above was placed in a 200 mL three-necked flask that had been previously vacuum-dried and purged with argon. -4-Pyrimidinone hydrochloride (5.111 g, 27.2 mmol) was added and cooled to 3 ° C in an ice bath.

  Fuming nitric acid (d1.50) (25.0 mL, 595.1 mmol) was placed in another 50 mL two-necked flask that had been vacuum dried and purged with argon, and cooled to 3 ° C. in an ice bath. This was transferred to the previous 200 mL three-necked flask using a Teflon tube using argon pressure. After stirring at 2 ° C for 25 minutes, the mixture was further stirred at 28 ° C for 40 minutes.

  After completion of the reaction, this was poured into 100 mL of distilled water cooled in an ice bath. The resulting red purple precipitate was filtered to obtain 5-nitro-2-phenyl-6-hydroxy-4-pyrimidinone (4.042 g, 63.8%).

As a result of NMR measurement of the obtained 5-nitro-2-phenyl-6-hydroxy-4-pyrimidinone, it was as follows.
¹ H NMR (500 MHz, DMSO-d ₆ ) δ-0.072 (NH of br, s, 1, Pym (3)), 7.59 (t, 2, J = 7.8 Hz, Ph C (3 ) H, C (5) H), 7.71 (t, 1, J = 6.9 Hz, Ph C (4) H), 7.91 (d, 1, J = 8.3 Ph C (2 ) H, C (6) H). ¹³ C NMR (126 MHz, DMSO-d ₆ ) δ 118.57, 127.16, 128.64, 129.16, 133.74, 156.96, 158.54.
(iii) Synthesis of 5-amino-6-hydroxy-2-phenyl-4-pyrimidinone 5-nitro-2-phenyl-6-hydroxy-4 obtained in (ii) above was placed in a glass inner tube of a high-pressure autoclave. -Pyrimidinone (2.014 g, 8.640 mmol), distilled water 10.0 mL, and ethanol 4.0 mL were added, and palladium-carbon (0.118 g) was further added as a catalyst.

  This was stirred at 30 ° C. for 23 hours under a hydrogen atmosphere of 50 atm in a suspended state. After completion of the reaction, methanol was added to dissolve the precipitate. Palladium-carbon was filtered off, and the filtrate was concentrated under reduced pressure. Concentration gave a yellow solid consisting of 5-amino-6-hydroxy-2-phenyl-4-pyrimidinone (1.720 g, 98.0%).

As a result of NMR measurement of the obtained 5-amino-6-hydroxy-2-phenyl-4-pyrimidinone, it was as follows.
^{1 H NMR (500MHz, DMSO-} d 6) δ-0.058 (br, s, 1, NH of Pym (3)), 3.42 ( br, s, 2, NH 2 of Pym (5)), 7.4-7.5 (3, Ph C (3) H, C (4) H, C (5) H), 8.00 (dd, 2, J = 12.1, 9.6 Hz, Ph C (2) H, C (6) H). ¹³ C NMR (126 MHz, DMSO-d ₆ ) δ 113.05, 126.61, 128.51, 129.99, 132.60, 144.58, 155.25.

5-amino-6-hydroxy-2- (3-amino-4-hydroxyphenyl), one of the 5-amino-6-hydroxy-2-phenyl-4 (1H) -pyrimidine derivatives, as follows: ) -4-pyrimidinone was synthesized. FIG. 3 shows an outline of the synthesis procedure.
(i) Synthesis of sodium 4-hydroxybenzamidine 4-cyanophenol (10.07 g, 80.31 mmol) and ammonium thiocyanate (24.77 g, 325.4 mmol) in a 100 mL two-necked flask previously dried in vacuo and purged with argon And stirred at 180 ° C. for 3 hours in the absence of solvent. After completion of the reaction, the reaction mixture was cooled to room temperature to obtain a yellow solid.

  Distilled water (20 mL) was added thereto, and the resulting white precipitate was filtered to recover unreacted 4-cyanophenol (2.028 g, 21.2%). The pH of the filtrate was adjusted to 8 with a 2M aqueous sodium hydroxide solution, and the resulting pale yellow precipitate was filtered to obtain sodium 4-hydroxybenzamidine (9.085 g, 87.5%).

As a result of NMR measurement of the obtained 4-hydroxybenzamidine sodium, it was as follows.
¹ H NMR (500 MHz, CD ₃ OD) δ 6.61 (d, 2, J = 7.4 Hz, Ph C (3) H, C (5) H), 7.53 (d, 2, J = 8 .7 Hz, Ph C (2) H, C (6) H). ¹³ C NMR (126 MHz, CD ₃ OD) δ 110.55, 120.76, 130.94, 167.08, 176.96.
(ii) Synthesis of 6-hydroxy-2- (4-hydroxyphenyl) -4-pyrimidinone hydrochloride 100 mL of ethanol and sodium (5.056 g, 220.0 mmol) in a 500 mL three-necked flask previously dried in vacuo and purged with argon ) And stirred while cooling to 2 to 5 ° C. in an ice bath to completely dissolve. 4-hydroxybenzamidine sodium obtained in the above (i) was added thereto and dissolved completely.

  To another 50 mL two-necked flask that was vacuum dried and purged with argon, diethyl malonate (24.0 mL, 159.0 mmol) and 15 mL of ethanol were added and completely dissolved. This solution was transferred to the previous 500 mL three-necked flask using a stainless steel tube using argon pressure, and stirred at 130 ° C. for 16.5 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, and the resulting pale yellow solid was dissolved in 40 mL of distilled water. The pH of the solution was adjusted to 2 with 2M aqueous hydrochloric acid, and the resulting pale yellow precipitate was filtered to obtain hydrochloride of 6-hydroxy-2- (4-hydroxyphenyl) -4-pyrimidinone.

The obtained 6-hydroxy-2- (4-hydroxyphenyl) -4-pyrimidinone hydrochloride was subjected to NMR measurement, and the results were as follows.
¹ H NMR (500 MHz, DMSO-d ₆ ) δ 5.22 (s, 1, Hz, Pym C (5) H), 6.84 (d, 2, J = 8.7 Hz, Ph C (3) H, C (5) H), 7.97 (d, 2, J = 8.7 Hz, Ph C (2) H, C (6) H), 10.26 (br, s, 1, PhC ( 4) OH), 11.71 (br, s, 1, OH of PymC (6)) ¹³ C NMR (126 MHz, DMSO-d ₆ ) δ 87.38, 115.33, 122.44, 129.70 157.10, 160.90, 167.50.
(iii) Synthesis of 5-nitro-6-hydroxy-2- (3-nitro-4-hydroxyphenyl) -4-pyrimidinone A 50 mL two-necked flask previously dried in vacuo and purged with argon was obtained in (ii) above. 6-Hydroxy-2- (4-hydroxyphenyl) -4-pyrimidinone hydrochloride (0.984 g, 4.089 mmol) was added and cooled to -74 ° C. with dry ice / methanol.

  Fuming nitric acid (d1.50) (10.0 mL, 238.1 mmol) was placed in another 50 mL two-necked flask that had been vacuum-dried and purged with argon, and cooled to −74 ° C. with dry ice / methanol. This fuming nitric acid was transferred to the previous 50 mL two-necked flask using a Teflon tube using argon pressure. Then, after stirring for 30 minutes at -74 degreeC, it stirred for 20 minutes at -10 degreeC.

  After completion of the reaction, the reaction mixture was cooled in an ice bath and 30 mL of distilled water was added. The resulting yellow precipitate was filtered to give 5-nitro-6-hydroxy-2- (3-nitro-4-hydroxyphenyl) -4-pyrimidinone (0.888 g, 57.8%).

The obtained 5-nitro-6-hydroxy-2- (3-nitro-4-hydroxyphenyl) -4-pyrimidinone was subjected to NMR measurement, and the results were as follows.
¹ H NMR (500 MHz, DMSO-d ₆ ) δ 7.27 (d, 1, J = 8.7 Hz, Ph C (6) H), 8.11 (dd, 1, J = 9.0, 2. 3 Hz, Ph C (5) H), 8.60 (d, 1, J = 2.3 Hz, Ph C (4) H), 12.30 (br, s, 1, PymC (6) OH ) ¹³ C NMR (126 MHz, DMSO-d ₆ ) δ 118.55, 119.21, 127.20, 135.04, 136.71, 156.01, 156.29, 157.70.
(iv) Synthesis of 5-amino-6-hydroxy-2- (3-amino-4-hydroxyphenyl) -4-pyrimidinone The 5-nitro compound obtained in (iii) above was placed in a glass inner tube of an autoclave for high pressure. -6-hydroxy-2- (3-nitro-4-O-nitrophenyl) -4-pyrimidinone (0.386 g, 1.14 mmol), 4.0 mL distilled water, and 2.0 mL ethanol were added. Furthermore, palladium-carbon (0.0188 g) was added as a catalyst, and the mixture was stirred in a suspended state at 30 ° C. for 17 hours in a hydrogen atmosphere of 50 atm.

  After completion of the reaction, methanol was added and the precipitate was filtered, and 5-amino-6-hydroxy-2- (3-amino-4-hydroxyphenyl) -4-pyrimidinone (0.222 g, 83.2%) as a green solid. Got.

The obtained 5-amino-6-hydroxy-2- (3-amino-4-hydroxyphenyl) -4-pyrimidinone was subjected to NMR measurement, and the results were as follows.
^{1 H NMR (500MHz, DMSO-} d 6) δ3.35 (br, s, 2, NH 2 of Ph (3)), (NH 2 of br, s, 2, Pym ( 5)) 4.73, 6 .66 (d, 1, J = 7.8, Ph C (6) H), 7.09 (dd, 1, J = 8.3, 2.3, Ph C (5) H), 7 .23 (d, 1, J = 2.3 Hz, Ph C (2) H), 9.37 (br, s, 1, PhC (4) OH) ¹³ C NMR (126 MHz, DMSO-d ₆ ) 111.49, 112.71, 113.73, 115.59, 123.82, 136.52, 144.94, 146.32.

One of 5-amino-6-hydroxy-2-phenyl-4 (1H) -pyrimidine derivatives, 5-amino-6-hydroxy-2- (4-aminophenyl) -4- Pyrimidinone was synthesized. 4 and 5 show an outline of the synthesis procedure.
(i) Synthesis of 4-nitrobenzamidine hydrochloride 4-Nitrobenzonitrile (1.0054 g, 6.788 mmol) and methanol were placed in a 50 mL two-necked flask previously dried in vacuo and purged with argon. To this, sodium (0.2029 g, 8.826 mmol) dissolved in 1.5 mL of methanol was added dropwise using a Teflon tube. The solution was cooled to 1 ° C., acetic acid (0.52 mL, 9.084 mmol) and ammonium chloride (0.4402 g, 8.230 mmol) were added, and the mixture was stirred at 23 ° C. for 1.5 hours and further at 95 ° C. for 2 hours. did. Then, it cooled to room temperature, 4-nitrobenzamidine hydrochloride (1.2048 g, 88.0%) was obtained by adding 9.96 wt% sodium hydroxide aqueous solution and leaving it to stand at room temperature.

As a result of NMR measurement of the obtained 4-nitrobenzamidine hydrochloride, it was as follows.
¹ H NMR (500 MHz, DMSO-d ₆ ) δ 6.75 (br, s, 4, NH ₂ (NH ₂ )), 8.04 (d, 2, J = 7.0 Hz, Ph C (2) H , C (6) H), 8.24 (d, 2, J = 7.0 Hz, Ph C (3) H, C (5) H) ¹³ C NMR (126 MHz, DMSO-d ₆ ) δ 123. 10, 128.00, 142.35, 148.14, 160.
(ii) Synthesis of 4-aminobenzamidine dihydrochloride 4-nitrobenzamidine hydrochloride (1.1832 g, 7.166 mmol) obtained in (i) above was placed in a 50 ml two-necked flask previously vacuum-dried and purged with argon. And 5.0 mL of ethanol were added, 2.5 mL of concentrated hydrochloric acid was further added, and the mixture was stirred at 27 ° C. for 2 hours.

  In another 50 mL two-necked flask, tin chloride (4.1651 g, 21.97 mmol) and 5.0 mL of ethanol were added and dissolved. This was added to the previous 50 mL two-necked flask using a Teflon tube. The solution after addition was allowed to stir at 27 ° C. for 2 hours, and then 5.0 mL of ethanol and 2.5 mL of concentrated hydrochloric acid were added to form a precipitate of 4-aminobenzamidine dihydrochloride (0.9406 g, 63.1% )was gotten.

As a result of NMR measurement of the obtained 4-aminobenzamidine dihydrochloride, it was as follows.
¹ H NMR (500 MHz, DMSO-d ₆ ) δ 6.65 (br, s, 3, NH ₃ ⁺ ), 6.81 (d, 2, J = 7.0 Hz, Ph C (3) H, C ( 5) H), 7.69 (d, 2, J = 7.0 Hz, Ph C (2) H, C (6) H), 8.89, 9.03 (s, 2, NH ₂ (NH ₂ )). ¹³ C NMR (126 MHz, DMSO-d ₆ ) δ 114.44, 129.77, 151.8, 164.53.
(iii) Synthesis of 5-nitro-6-hydroxy-2- (4-aminophenyl) -4-pyrimidinone 40 mL of ethanol and sodium (0.6057 g, 26. 33 mmol) and stirred while cooling to 2-3 ° C. in an ice bath to completely dissolve. To this was added 4-aminobenzamidine dihydrochloride (0.8081 g, 3.844 mmol) obtained in (ii) above and diethyl α-nitromalonate (1.2 mL, 7.233 mmol) at 90 ° C. Stir for 1 hour. After completion of the reaction, this was concentrated under reduced pressure.

  The concentrated product was dissolved in 8.0 mL of distilled water, and the pH was adjusted to around 1 with a 2M aqueous hydrochloric acid solution. The resulting precipitate was filtered to obtain 5-nitro-6-hydroxy-2- (4-aminophenyl) -4-pyrimidinone (0.6538 g, 60.2%).

The obtained 5-nitro-6-hydroxy-2- (4-aminophenyl) -4-pyrimidinone was subjected to NMR measurement, and the results were as follows.
¹ H NMR (500 MHz, DMSO-d ₆ ) δ-0.05 (Br, s, 1, NH of Pym (3)), 6.62 (d, 2, J = 7.3 Hz, Ph C (3 ) H, C (5) H), 7.73 (d, 2, J = 7.4 Hz, Ph C (2) H, C (6) H), 12-13 (br, s, 1, PymC (6) OH) · ¹³ C NMR (126 MHz, DMSO-d ₆ ) δ 109.9, 112.83, 116.92, 131.37, 155.17, 156.30, 156.58.
(iv) Synthesis of 5-amino-6-hydroxy-2- (4-aminophenyl) -4-pyrimidinone The 5-nitro-6-hydroxy-2 obtained in (iii) above was placed in a glass inner tube of a high pressure autoclave. -(4-Aminophenyl) -4-pyrimidinone (0.4009 g, 1.574 mmol), distilled water 8.0 mL, and ethanol 4.0 mL were added, and palladium-carbon (0.0476 g) was further added as a catalyst. . This was stirred at room temperature for 24 hours in a hydrogen atmosphere of 50 atm in a suspended state. After completion of the reaction, the solvent was distilled off to obtain 5-amino-6-hydroxy-2- (4-aminophenyl) -4-pyrimidinone (0.3613 g, 78.9%).

The obtained 5-amino-6-hydroxy-2- (4-aminophenyl) -4-pyrimidinone was subjected to NMR measurement, and the results were as follows.
¹ H NMR (500 MHz, DMSO-d ₆ ) δ-0.05 (NH of br, s, 1, Pym (3)), 5.4-6.0 (br, s, 4, Pym (5) NH ₂ , Ph (4) NH ₂ ), 6.56 (2, d, J = 7.0 Hz, Ph C (3) H, C (5) H), 7.72 (2, d, J = 7.0 Hz, Ph C (2) H, C (6) H) ¹³ C NMR (126 MHz, DMSO-d ₆ ) δ110.83, 113.09, 117.07, 127.92, 144.85 150.90.

  Two-component hair dyes of Examples 4 to 12 were produced as follows. First, the hair dye 1st agent of Examples 4-12 was manufactured by mix | blending each component shown in Table 1 and Table 2 only by the corresponding amount, respectively.

  In Tables 1 and 2, the novel dye 1 is 5-amino-6-hydroxy-2-phenyl-4-pyrimidinone prepared in Example 1 above. Further, the novel dye 2 is 5-amino-6-hydroxy-2- (3-amino-4-hydroxyphenyl) -4-pyrimidinone prepared in Example 2 above. Further, the novel dye 3 is 5-amino-6-hydroxy-2- (4-aminophenyl) -4-pyrimidinone produced in Example 3 above.

In Tables 1 and 2, the unit of the numerical value indicating the blending amount is parts by weight.
Next, the hair dye 2nd agent was manufactured by mix | blending only the quantity corresponding to each of the following each component. This hair dye 2nd agent is common in Examples 4-12.
(Hair dye 2nd agent)
35% hydrogen peroxide: 17 parts by weight Stearyl alcohol: 5 parts by weight POE (20) monostearate: 1 part by weight Phenacetin: 0.1 part by weight Phosphoric acid: Amount of pH 3 Purified water: 100 parts by weight in total Amount Next, about each of Examples 4-12, hair dye 1st agent and hair dye 2nd agent were mixed by equal amounts, and it applied to human hair according to the conventional method, and dyed hair. . Table 1 and Table 2 show the color of the hair after dyeing. From these results, it was found that the two-component hair dyes of Examples 4 to 12 can dye hair in various colors (red purple, orange, dark brown, brown, pink brown).

  Needless to say, the present invention is not limited to the above-described embodiments, and can be implemented in various modes without departing from the scope of the present invention.

It is explanatory drawing showing the synthetic | combination procedure of a 5-amino-6-hydroxy-2-phenyl-4 (1H) -pyrimidine derivative. It is explanatory drawing showing the synthetic | combination procedure of a 5-amino-6-hydroxy-2-phenyl-4 (1H) -pyrimidine derivative. It is explanatory drawing showing the synthetic | combination procedure of a 5-amino-6-hydroxy-2-phenyl-4 (1H) -pyrimidine derivative. It is explanatory drawing showing the synthetic | combination procedure of a 5-amino-6-hydroxy-2-phenyl-4 (1H) -pyrimidine derivative. It is explanatory drawing showing the synthetic | combination procedure of a 5-amino-6-hydroxy-2-phenyl-4 (1H) -pyrimidine derivative.

Claims (7)

General formula (1):

(Wherein R ^{1 to} R ⁵ are each a hydrogen atom, a hydroxyl group, or an amino group) 5-amino-6-hydroxy-2-phenyl-4 (1H) -pyrimidine derivative Or its salt. R ¹ , R ⁴ , and R ⁵ are hydrogen atoms,
The 5-amino-6-hydroxy-2-phenyl-4 (1H) -pyrimidine derivative according to claim 1, wherein at least one of R ² and R ³ is a hydroxyl group or an amino group. salt. The 5-amino-6-hydroxy-2-phenyl-4 (1H) -pyrimidine derivative or a salt thereof according to claim ^2, wherein R ² is an amino group, and R ³ is a hydroxyl group. The 5-amino-6-hydroxy-2-phenyl-4 (1H) -pyrimidine derivative or a salt thereof according to claim ^2, wherein R ² is a hydrogen atom, and R ³ is an amino group. . 6-hydroxy-2- (4-hydroxyphenyl) -4-pyrimidinone hydrochloride and fuming nitric acid were mixed to give 5-nitro-6-hydroxy-2- (3-nitro-4-O-nitrophenyl) -4 -A first step of producing pyrimidinone;
5-Nitro-6-hydroxy-2- (3-nitro-4-O-nitrophenyl) -4-pyrimidinone, water and ethanol were mixed to give 5-amino-6-hydroxy-2- (3-amino- A second step of producing 4-hydroxyphenyl) -4-pyrimidinone, or a 5-amino-6-hydroxy-2-phenyl-4 (1H) -pyrimidine derivative according to claim 3 or a method thereof. Method for producing salt. Ethanol, sodium, 4-aminobenzamidine dihydrochloride and diethyl α-nitromalonate were mixed, and then acid was added to give 5-nitro-6-hydroxy-2- (4-aminophenyl) -4-pyrimidinone. A first step of manufacturing;
5-Nitro-6-hydroxy-2- (4-aminophenyl) -4-pyrimidinone, water and ethanol are mixed to produce 5-amino-6-hydroxy-2- (4-aminophenyl) -4-pyrimidinone And a second step of producing a 5-amino-6-hydroxy-2-phenyl-4 (1H) -pyrimidine derivative or a salt thereof according to claim 4.   A hair dye composition comprising the 5-amino-6-hydroxy-2-phenyl-4 (1H) -pyrimidine derivative or a salt thereof according to any one of claims 1 to 4.

Images