JP2857774B2 - 5-Nitro-2-substituted aminopyridine derivatives and their production - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a novel 5-nitro-2-substituted aminopyridine derivative and a method for producing the same.

[Conventional technology and its problems]

2. Description of the Related Art For dyeing keratinous fibers such as hair, a so-called oxidation dye, which uses a combination of a color developing substance and a coupling substance, has been widely used. This oxidative dye is generated by oxidative coupling of a developing substance and a coupling substance,
This is based on the fact that so-called oxidation dyes dye hair and the like strongly. As a color developing substance, a p-phenylenediamine derivative, a diaminopyridine, a 4-aminopyrazolone derivative, a heterocyclic hydrazone, or the like is generally used.

However, conventional oxidative dyes have not yet been satisfactory in terms of chroma, dyeing power and fastness.

Under such circumstances, the present inventors have studied the general formula (IV) (Wherein R ¹ represents an alkyl group having 1 to 5 carbon atoms, and R ² represents a hydroxyalkyl group or a polyhydroxyalkyl group having 1 to 5 carbon atoms). Alternatively, they have found that a keratinous fiber dyeing composition capable of dyeing with high chroma and excellent fastness can be obtained by using a salt thereof as a color developing substance of an oxidation dye.

An object of the present invention is to provide an intermediate capable of industrially advantageously producing the novel 2,5-diaminopyridine derivative and a salt thereof, and a method for producing the intermediate.

[Means for solving the problem]

The present inventor has reported that the following novel 5-nitro-2-substituted aminopyridine derivative (I) is useful in developing the keratinous fiber dyeing composition, as the 2,5-diaminopyridine derivative (I).
V) was found to be an intermediate that can be easily obtained in high yield.

That is, the present invention relates to the general (I) (Wherein R ¹ and R ² have the same meanings as described above), a 5-nitro-2-substituted aminopyridine derivative, a salt thereof, and a method for producing the same.

In the present invention, in formula (I), the number of carbon atoms represented by R ¹ is 1
Examples of the alkyl group having 5 to 5 include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group and a pentyl group, and examples of the hydroxyalkyl group having 1 to 5 carbon atoms represented by R ² include a hydroxymethyl group, A hydroxyethyl group, a hydroxypropyl group, a hydroxybutyl group and the like, and a polyhydroxyalkyl group include a 2,3-dihydroxypropyl group and a 1,2,3-trihydroxypropyl group. Specific examples of the 5-nitro-2-substituted aminopyridine derivative (I) include 5-nitro-
2- (3-hydroxypropylamino) -4-methylpyridine, 5-nitro-2- (2,3-dihydroxypropylamino) -4-methylpyridine, 5-nitro-2-
(2-hydroxyethylamino) -4-methylpyridine and the like. Examples of the salt include salts of inorganic acids or organic acids such as hydrochloric acid, sulfuric acid, phosphoric acid, acetic acid, propionic acid, lactic acid, and citric acid.

The 5-nitro-2-substituted aminopyridine derivative (I) of the present invention is produced, for example, by reacting a 2-halo-5-nitropyridine derivative (II) with an amine (III) according to the following reaction formula. Is done.

(In the formula, R ¹ , R ² and X have the same meanings as described above.) In the method of the present invention, examples of the halogen atom represented by X in the raw material compound (II) include a chlorine atom, a bromine atom and an iodine atom. Can be The amounts of the 2-halo-5-nitropyridine derivative (II) and the amines (III) used are preferably in a molar ratio of (III) / (II) = 1 to 10. If the molar ratio is below the range, unreacted 2-halo-
The 5-nitropyridine derivative (II) remains,
Separation from the nitro-2-substituted aminopyridine derivative (I) becomes difficult, and when the molar ratio exceeds the range, the amines (II)
I) has the effect as a solvent,
This will reduce container efficiency.

A reaction solvent can be used in the method of the present invention. Reaction solvents generally include alcohols such as methanol and ethanol; hydrocarbons such as hexane, benzene, toluene, and xylene; polar solvents such as DMF and DMSO; and organic compounds inert to the reaction such as halogen compounds such as chloroform and carbon tetrachloride. Solvents are preferred.

The reaction temperature of the method of the present invention is not particularly limited as long as the reaction proceeds, but is preferably in the range of 30 to 150 ° C.
If the reaction temperature is lower than 30 ° C., the reaction rate is remarkably reduced, so that a long time is required or the yield tends to decrease. On the other hand, when the reaction temperature is higher than 150 ° C., a rapid reaction proceeds, and by-products are easily generated, which is industrially disadvantageous. The reaction time varies depending on the combination of the 5-nitro-2-substituted aminopyridine (II) and the amines (III), but usually in the range of 3 to 10 hours is sufficient.

The thus obtained 5-nitro-2-substituted aminopyridine derivative (I) of the present invention can be easily converted to a 2,5-diaminopyridine derivative (IV) by hydrogenation in the presence of a hydrogenation catalyst. be able to.

〔Example〕

Next, the present invention will be described specifically with reference to examples, but the present invention is not limited to these examples.

Example 1 Synthesis of 5-nitro-2- (2-hydroxyethylamino) -4-methylpyridine: In a 500 ml four-necked flask equipped with a thermometer, a dropping funnel, a reflux condenser and a stirrer, 2-chloro was added. -5-nitro-4-methylpyridine 200 g (1.16 mol) and ethanol 20
0g was charged. Next, while maintaining the internal temperature at 70 ° C., 85 g (1.392 mol) of ethanolamine was added dropwise over 2 hours.
After completion of the dropwise addition, the mixture was stirred at the same temperature for 4 hours. The reaction solution was concentrated to obtain 283 g of residual crystals.

To the crystals was added 464 g of a 10% aqueous sodium hydroxide solution,
Stir for about 1 hour. The reaction solution was extracted three times with 500 g of benzene. The extracted oil was washed with water, concentrated, then cooled, crystallized and separated by filtration to give 5-nitro-2- (2-hydroxyethylamino) in an 80% yield from 2-chloro-5-nitro-4-methylpyridine. 183 g of -4-methylpyridine were obtained.

mp 117.6 ° C Mass analysis: (EI) m / e = 197,178,166 Elemental analysis (assuming C ₈ H ₁₁ N ₃ O ₃ = 197): Reference Example A Synthesis of 5-nitro-2- (3-hydroxypropylamino) pyridine: In a flask similar to that in Example 1, 158 g (1 mol) of 2-chloro-5-nitropyridine and 500 g of ethanol were charged.
At an internal temperature of 80 ° C, 3-amino-1-propanol (113 g, 1.5 mol) was added dropwise over 2 hours. After completion of the dropwise addition, the mixture was stirred at the same temperature for 3 hours, and then concentrated to remove ethanol. The obtained residue was transferred to a separating funnel, and 500 g of benzene and 400 g of a 10% aqueous sodium hydroxide solution were added thereto, followed by shaking. After standing for 30 minutes, the mixture was separated, and the obtained oil layer was washed with water, and then concentrated to remove benzene and unreacted raw materials, and to give 5-nitro-2- (3-hydroxypropyl) as a viscous oil. 187 g of amino) pyridine (95% yield from 2-chloro-5-nidopyridine) were obtained.

Mass analysis: (EI) m / e = 197,166,152 Elemental analysis (assuming C ₈ H ₁₁ N ₃ O ₃ = 197): Example 2 Synthesis of 5-nitro-2- (3-hydroxypropylamino) -4-methylpyridine: 2-chloro-5-nitro-4-methylpyridine was used instead of 2-chloro-5-nitropyridine. Other than the above, a viscous oily 5-nitro-2-
(3-Hydroxypropylamino) -4-methylpyridine (92% yield from 2-chloro-5-nitro-4-methylpyridine) was obtained.

Mass analysis: (EI) m / e = 211, 180, 166 Elemental analysis (assuming C ₉ H ₁₃ N ₃ O ₃ = 211): Example 3 Synthesis of 5-nitro-2- (2,3-dihydroxypropylamino) -4-methylpyridine: 2-Chloro-5-nitropyridine and 3-amino-
2-chloro-5-nitro-4 in place of 1-propanol
-Methylpyridine and 3-amino-2-hydroxy-
A viscous oily 5-nitro-2- (2,3-dihydroxypropylamino) -4-methylpyridine (2-chloro-5-nitro) was prepared in the same manner as in Reference Example A except that 1-propanol was used. 89 yield from 4-methylpyridine
%).

mp 128.2-128.6 ° C Mass analysis: (EI) m / e = 196,166 (CI) m / e = 228 Elemental analysis (as C ₉ H ₁₃ N ₃ O ₄ = 227): Reference Example 1 Synthesis of 5-amino-2- (3-hydroxypropylamino) -4-methylpyridine dihydrochloride:
100 g of-(3-hydroxypropylamino) -4-methylpyridine, 400 g of ethanol and 30 g of Raney nickel were charged, and the inside of the vessel was replaced with hydrogen, and the hydrogen pressure was adjusted to 10 kg / cm ² . Next, when hydrogen was continuously supplied at 50 ° C. under 20 kg / cm ² , the absorption of hydrogen stopped in 2 hours, and the reaction was completed.

After completion of the reaction, the reaction solution was cooled and filtered. The filtrate was sparged with 30 g of hydrogen chloride, then concentrated and cooled, and crystals crystallized out. The result was filtered and dried to give 5-nitro-2-
5-amino-2- (3-hydroxypropylamino) -4-methylpyridine dihydrochloride in a yield of 92.6% from (3-hydroxypropylamino) -4-methylpyridine
95 g were obtained.

mp 207.0 ° C Mass analysis: (EI) m / e = 181,165,150,136 Reference Example 2 Synthesis of 5-amino-2- (2-hydroxyethylamino) -4-methylpyridine dihydrochloride: Nitro-2-
(2-hydroxyethylamino) -4-methylpyridine
After charging 60 g, 400 g of ethanol and 18 g of Raney nickel, the inside of the vessel was replaced with hydrogen, and the hydrogen pressure was adjusted to 5 kg / cm ² . Next, when hydrogen was continuously supplied at 90 ° C. under 5 to 6 kg / cm ² , the absorption of hydrogen stopped in 2 hours, and the reaction was completed.

After completion of the reaction, the reaction solution was cooled and filtered. The filtrate was sparged with 25 g of hydrogen chloride, then concentrated and cooled, and crystals crystallized out. The result was filtered and dried to give 5-nitro-2-
68.8% of 5-amino-2- (2-hydroxyethylamino) -4-methylpyridine dihydrochloride was obtained in a yield of 94.2% from (2-hydroxyethylamino) -4-methylpyridine.
g was obtained.

mp 222.0 ° C Mass analysis: (EI) m / e = 167,148,136 Reference Example 3 Synthesis of 5-amino-2- (3-hydroxypropylamino) pyridine dihydrochloride: 5-nitro-2- (3-hydroxy The reaction was carried out in the same manner as in Reference Example 2 except that 75 g of propylamino) pyridine, 400 g of methanol and 25 g of Raney nickel were used, to give 72.6 g of 5-amino-2- (3-hydroxypropylamino) pyridine dihydrochloride. (Yield = 94
%).

mp 202.9 ° C Mass analysis: (EI) m / e = 167,151,136,122 Reference Example 4 Synthesis of 5-amino-2- (2,3-dihydroxypropylamino) pyridine dihydrochloride: 5-nitro-2- (2 The reaction was carried out in the same manner as in Reference Example 2 except that 100 g of 3,3-dihydroxypropylamino) pyridine, 50 g of methanol and 30 g of Raney cobalt were used. As a result, 5-amino-2- (2,3-dihydroxypropylamino) 99.5 g (yield = 97.2%) of pyridine dihydrochloride was obtained as a viscous oil.

Mass analysis: (EI) m / e = 183,122 (CI) m / e = 184 Reference Example 5 Synthesis of 5-amino-2- (2,3-dihydroxypropylamino) -4-methylpyridine dihydrochloride: Raw material 5-nitro-2- (2,3-dihydroxypropylamino) -4-methylpyridine 100 g, methanol 500 g
The reaction was carried out in the same manner as in Reference Example 2 except that 30 g of Raney nickel was used.
113 g (yield = 95%) of (2,3-dihydroxypropylamino) -4-methylpyridine dihydrochloride was obtained as a viscous oil.

Mass analysis: (EI) m / e = 197,166,136 [Effect of the Invention] As described above, according to the present invention, a novel 5-nitro-2 is used.
-Substituted aminopyridine derivatives (I) and their preparation are provided. This 5-nitro-2-substituted aminopyridine derivative (I) is useful as an intermediate capable of producing a 2,5-diaminopyridine derivative, which is an excellent color developing substance of a keratinous fiber dyeing composition, in a high yield. It is.

──────────────────────────────────────────────────続 き Continued on the front page (58) Field surveyed (Int.Cl. ⁶ , DB name) C07D 213/74 REGISTRY (STN) CA (STN)

Claims (2)

(57) [Claims] 1. The compound of the general formula (I) (Wherein, R ¹ represents an alkyl group having 1 to 5 carbon atoms, and R ² represents a hydroxyalkyl group or a polyhydroxyalkyl group having 1 to 5 carbon atoms). Derivatives or salts thereof. 2. A compound of the general formula (II) (Wherein, R ¹ represents an alkyl group having 1 to 5 carbon atoms, and X represents a halogen atom), and a 2-halo-5-nitropyridine derivative represented by the following formula:
Reacting with an amine represented by the general formula (III) R ² NH ₂ (III) (wherein R ² represents a hydroxyalkyl group having 1 to 5 carbon atoms or a polyhydroxyalkyl group) A method for producing a 5-nitro-2-substituted aminopyridine derivative according to claim 1.