JP2002241367A - Method for producing quinolinecarboxaldehyde derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an industrially advantageous method for producing a quinolinecarboxaldehyde derivative with which the quinolinecarboxaldehyde derivative can be produced by a simple method with a high yield. SOLUTION: This method for producing the quinolinecarboxaldehyde derivative is characterized by comprising (A) a cyclization reaction process of reacting β-ketonitrile with o-acylaniline in the presence of an acid to obtain a quinolinecarbonitrile derivative and (B) a reduction reaction process or then reducing the quinolinecarbonitrile derivative to obtain the quinolinecarboxaldehyde derivative.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a quinolinecarboxaldehyde derivative by reacting β-ketonitrile with o-acylaniline to form a quinolinecarbonitrile derivative, and then reducing the quinolinecarbonitrile derivative. A quinoline carboxaldehyde derivative is a compound useful as a synthetic intermediate such as a medicine.

[0002]

2. Description of the Related Art Conventionally, as a method of reacting β-ketonitrile with o-acylaniline to obtain a quinolinecarbonitrile derivative, benzoylacetonitrile is reacted with o-aminobenzophenone to prepare 2,4-diphenyl-3-quinolinecarbonate. A method for producing nitrile is disclosed (J. He
terocycl.Chem., 1967 , 565). However, in this method, acetic acid, which requires complicated post-treatment, is used as a solvent, and the reaction is performed under severe conditions that promote the polymerization of the raw material β-ketonitrile. The rates were also low.

[0003]

SUMMARY OF THE INVENTION The object of the present invention is to solve the above problems and to produce quinoline carboxaldehyde derivatives in a high yield by a simple method. The present invention provides a method for producing a carboxaldehyde derivative.

[0004]

The object of the present invention is to provide (A)
Formula (1) in the presence of an acid

[0005]

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(R ¹ represents a group which does not participate in the reaction.)
Β-ketonitrile represented by the general formula (2)

[0007]

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(R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ have the same meanings as described above), and are reacted with an o-acylaniline represented by the following general formula (3):

[0009]

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(R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ have the same meanings as described above), a cyclization reaction step for preparing a quinolinecarbonitrile derivative, (B) a quinoline The carbonitrile derivative is reduced to obtain a compound of the general formula (4)

[0011]

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Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ have the same meanings as defined above, and a reduction reaction step for producing a quinolinecarboxaldehyde derivative. And a quinoline carboxaldehyde derivative.

The present invention also relates to a compound represented by the general formula (1):

[0014]

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(R ¹ represents a group that does not participate in the reaction.)
Β-ketonitrile represented by the general formula (2)

[0016]

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(R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ have the same meanings as described above), and are reacted with an o-acylaniline represented by the following general formula (3):

[0018]

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(R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ have the same meanings as defined above), characterized in that they are quinolinecarbonitrile derivatives represented by the following formula: It is solved by the manufacturing method.

[0020]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention relates to a method of reacting a β-ketonitrile of the general formula (1) with an o-acylaniline of the general formula (2) in the presence of an acid (A). A cyclization reaction step of forming a quinolinecarbonitrile derivative represented by (3); (B) a quinolinecarbonitrile derivative represented by the general formula (3) is reduced to give a quinolinecarboxaldehyde represented by the general formula (4) A quinolinecarboxaldehyde derivative is obtained as a reaction product by two steps including a reduction reaction step of forming a derivative.

Subsequently, the above two steps will be sequentially described. (A) Cyclization Reaction Step In the cyclization reaction step of the present invention, a β-ketonitrile represented by the general formula (1) is added to a β-ketonitrile represented by the general formula (2) in the presence of an acid.
-Reacting an acylaniline into a quinolinecarbonitrile derivative represented by the general formula (3).

Β used in the cyclization reaction step of the present invention
-Ketonitrile is represented by the above general formula (1). In the general formula (1), R ¹ is a group which does not participate in the reaction, and specifically, is an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group which may have a substituent.

The alkyl group is preferably a compound having 1 to 1 carbon atoms.
Preferred are 10 alkyl groups, for example, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, and decyl. In addition, these groups also include various isomers.

The cycloalkyl group is preferably a cycloalkyl group having 3 to 7 carbon atoms, and examples thereof include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group and a cycloheptyl group. In addition, these groups also include various isomers.

The aralkyl group preferably has 7 carbon atoms.
Preferred is an alkyl group of 10 to 10, for example, a benzyl group,
Examples include a phenethyl group, a phenylpropyl group, and a phenylbutyl group. In addition, these groups also include various isomers.

The aryl group is particularly preferably a compound having 6 to 6 carbon atoms.
Preferred are 14 aryl groups, for example, phenyl, tolyl, naphthyl, anthranyl and the like.
In addition, these groups also include various isomers.

The alkyl group, cycloalkyl group, aralkyl group or aryl group may have a substituent.
Examples of the substituent include at least one of a halogen atom, a substituent formed through a carbon atom, a substituent formed through an oxygen atom, and a substituent formed through a nitrogen atom.

Examples of the halogen atom include fluorine, chlorine, bromine and iodine.

Examples of the substituent formed through the carbon atom include alkyl groups such as methyl group, ethyl group, propyl group and butyl group; aralkyl groups such as benzyl group; alkenyl groups such as ethenyl group; alkynyl groups such as ethynyl group. An aryl group such as a phenyl group; a carboxyl group; an alkoxycarbonyl group such as a methoxycarbonyl group and an ethoxycarbonyl group; and an aryloxycarbonyl group such as a phenoxycarbonyl group.

Examples of the substituent formed through the oxygen atom include an alkoxy group such as a methoxy group, an ethoxy group, a propoxy group, a butoxy group and a benzyloxy group; an aryloxy group such as a phenoxy group; an acetyloxy group and a benzoyloxy group. And the like.

Examples of the substituent formed through the nitrogen atom include a dialkylamino group such as a dimethylamino group; and a nitro group.

The amount of the β-ketonitrile used is preferably 0.8 to 2.0 times mol, more preferably 1.0 to 1.5 times mol of o-acylaniline.

O- used in the cyclization reaction step of the present invention
Acylaniline is represented by the above general formula (2). In the general formula (2), R ² is a group which does not participate in the reaction, has the same meaning as R ¹ , and R ³ , R ⁴ , R ⁵ and R
⁶ is specifically a hydrogen atom, a halogen atom, an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group.

Examples of the halogen atom include fluorine, chlorine, bromine and iodine.

The alkyl group is preferably a compound having 1 to 1 carbon atoms.
Preferred are 10 alkyl groups, for example, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, and decyl. In addition, these groups also include various isomers.

As the cycloalkyl group, a cycloalkyl group having 3 to 7 carbon atoms is particularly preferable, and examples thereof include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, and a cycloheptyl group. In addition, these groups also include various isomers.

The aralkyl group preferably has 7 carbon atoms.
Preferred is an alkyl group of 10 to 10, for example, a benzyl group,
Examples include a phenethyl group, a phenylpropyl group, and a phenylbutyl group. In addition, these groups also include various isomers.

The aryl group is preferably a compound having 6 to 6 carbon atoms.
Preferred are 14 aryl groups, for example, phenyl, tolyl, naphthyl, anthranyl and the like.
In addition, these groups also include various isomers.

Examples of the acid used in the cyclization reaction step of the present invention include organic sulfonic acids such as methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-bromobenzenesulfonic acid and p-toluenesulfonic acid; Inorganic acids such as acid, pyrophosphoric acid, polyphosphoric acid, sulfuric acid, and hydrochloric acid; and halogenated organic carboxylic acids such as monochloroacetic acid, dichloroacetic acid, and trifluoroacetic acid, and preferably, organic sulfonic acid is used.

The amount of the acid used is preferably 0.1 to 5.0 moles, more preferably 0.5 mole, relative to the o-acylaniline.
It is about 3.0 times mol.

The cyclization step of the present invention is carried out in the presence or absence of a solvent. The solvent used is not particularly limited as long as it does not inhibit the reaction, for example, pentane, hexane, heptane, 2-methylbutane,
Aliphatic hydrocarbons such as 2-methylpentane, 2-methylhexane, cyclopentane, cyclohexane and cycloheptane; halogenated aliphatic hydrocarbons such as methylene chloride, chloroform and dichloroethane; benzene, toluene,
Aromatic hydrocarbons such as xylene and mesitylene; halogenated aromatic hydrocarbons such as chlorobenzene and dichlorobenzene; diisopropyl ether, tetrahydrofuran,
Ethers such as dioxane; methanol, ethanol,
Alcohols such as isopropyl alcohol, 2-butyl alcohol and t-butyl alcohol; and organic carboxylic acids such as acetic acid and propionic acid.

The amount of the solvent to be used is preferably 2 to 50 times by mass, more preferably 3 to 10 times by mass relative to o-acylaniline.
It is mass times. These solvents may be used alone or in combination of two or more.

In the cyclization reaction step of the present invention, β
-It is preferable to contact o-acyl aniline in the liquid phase with ketonitrile, for example, in an inert gas atmosphere, acid,
β-Ketonitrile, o-acylaniline and a solvent are mixed, and the mixture is heated and stirred, for example, under normal pressure, increased pressure or reduced pressure. The reaction temperature at that time is preferably
It is 50-160 ° C, more preferably 70-140 ° C. In addition, the reaction of the present invention may be carried out while removing water generated during the reaction, if necessary. The o-acyl aniline may be used in the form of a salt with the above-mentioned acid (for example, an o-acyl aniline organic sulfonate).

The quinolinecarbonitrile derivative obtained as the main product in the cyclization reaction step is
It may be used in the next reduction reaction step as it is without post-treatment, or after separation and purification by a general method such as distillation, recrystallization, column chromatography or the like.

(B) Reduction Reaction Step The reduction reaction step of the present invention is a step of reducing a quinolinecarbonitrile derivative represented by the general formula (3) into a quinolinecarboxaldehyde derivative represented by the general formula (4). is there.

The reduction step of the present invention is not particularly limited as long as it is a general reduction method for converting a cyano group into a formyl group. For example, reduction with an aluminum hydride compound (for example, diisobutylaluminum hydride), Hydrogen in the presence of Raney nickel, reduction with formic acid or ammonium formate, reduction with stannous chloride, reduction with hydrogen in the presence of palladium, and the like, preferably reduction with diisobutylaluminum hydride (hereinafter, reduction reaction (a) ), Reduction with formic acid in the presence of Raney nickel (hereinafter referred to as reduction reaction (b)), reduction with hydrogen in the presence of Raney nickel (hereinafter referred to as reduction reaction (c)), more preferably diisobutylaluminum hydride Reduction (reduction reaction
(a)).

Reduction reaction (a); Reduction with diisobutylaluminum hydride The amount of diisobutylaluminum hydride used in the reduction reaction (a) of the present invention is preferably 0.5 to 5.0 times the molar amount of the quinolinecarbonitrile derivative. And more preferably 0.9 to 1.5 moles. The diisobutylaluminum hydride used is hexane, cyclohexane,
It may be diluted with an inert solvent such as toluene, dichloromethane, or tetrahydrofuran.

The reduction reaction (a) of the present invention is carried out in the presence or absence of a solvent. The solvent used is not particularly limited as long as it does not inhibit the reaction, and examples thereof include aromatic hydrocarbons such as benzene, toluene, and xylene; and ethers such as diisopropyl ether, tetrahydrofuran, and dioxane. Is an aromatic hydrocarbon, more preferably toluene.

The amount of the solvent to be used is preferably 2 to 50 times by mass, more preferably 3 to 20 times by mass, based on the quinoline carbonitrile derivative. These solvents may be used alone or in combination of two or more.

In the reduction reaction (a) of the present invention, diisobutylaluminum hydride is preferably brought into contact with a quinolinecarbonitrile derivative in a liquid phase. For example, diisobutylaluminum hydride and quinolinecarbonitrile The reaction is carried out under normal pressure or under pressure, for example, by mixing and reacting the solvent under cooling. The reaction temperature at that time is preferably -50
~ 60 ° C, more preferably -20 ~ 40 ° C.

Reduction reaction (b); Reduction with formic acid in the presence of Raney nickel Raney nickel used in the reduction reaction (b) of the present invention is an alloy containing nickel and aluminum as main components, and having a nickel content of Preferably 10 to 90% by mass, more preferably 40 to 80% by mass is used. Normal,
Although expanded Raney nickel is used, pretreated Raney nickel or stabilized Raney nickel can be used by various methods. Furthermore, in Raney nickel, cobalt, iron, lead, chromium, titanium, molybdenum,
Those containing metals such as vanadium, manganese, tin, and tungsten can also be used.

The amount of the Raney nickel used is, in terms of nickel atom, based on the quinolinecarbonitrile derivative.
Preferably it is 0.30 to 2 times by mass, more preferably 0.30 to 1.2 times by mass.

As the formic acid used in the reduction reaction (b) of the present invention, formic acid itself may be used.
It is performed in the presence of 0.25 to 1 volume of water with respect to formic acid.

The amount of formic acid used is preferably 0.25 to 50 times, more preferably 1 to 40 times the mass of the quinolinecarbonitrile derivative.

The reduction reaction (b) of the present invention is carried out in the presence or absence of a solvent other than formic acid or water. The solvent used is not particularly limited as long as it does not inhibit the reaction, and examples thereof include amides such as N, N-dimethylformamide; alcohols such as methanol, ethanol, isopropyl alcohol and t-butyl alcohol; pentane;
Aliphatic hydrocarbons such as cyclohexane; aromatic hydrocarbons such as toluene and xylene; and organic carboxylic acids such as acetic acid and propionic acid.

The amount of the solvent to be used is preferably 0 to 60 times by mass, more preferably 0 to 10 times by mass, based on the quinoline carbonitrile derivative. These solvents may be used alone or in combination of two or more.

In the reduction reaction (b) of the present invention, formic acid and water are preferably brought into contact with the quinolinecarbonitrile derivative in the liquid phase in the presence of Raney nickel. For example, the Raney nickel and quinolinecarbonitrile derivatives are contacted in an inert gas atmosphere. , Formic acid and water, and stirring under heating or the like, at normal pressure or under pressure. The reaction temperature at that time is preferably 20 to 110 ° C., more preferably 30 to 80 ° C.
It is.

If necessary, the reactivity may be adjusted by adding an inorganic base, an organic base, a platinum salt, a lead salt, a cadmium salt or the like to the system (Tetsuo Kubo, Shinichiro Komatsu, Raney catalyst (published by Kawaken Fine Chemical Co., Ltd.), pages 123-147 and described in HU 45958).

The quinolinecarboxaldehyde derivative, which is the final product, is separated and purified by a general method such as distillation, recrystallization, column chromatography or the like after completion of the reaction.

Reduction reaction (c); Reduction with hydrogen in the presence of Raney nickel Raney nickel used in the reduction reaction (c) of the present invention is an alloy containing nickel and aluminum as main components, and having a nickel content of Preferably 10 to 90% by mass, more preferably 40 to 80% by mass is used. Normal,
Although expanded Raney nickel is used, pretreated Raney nickel or stabilized Raney nickel can be used by various methods. Furthermore, in Raney nickel, cobalt, iron, lead, chromium, titanium, molybdenum,
Those containing metals such as vanadium, manganese, tin, and tungsten can also be used.

The amount of the Raney nickel used is calculated based on the quinoline carbonitrile derivative in terms of nickel atoms.
Preferably 0.001 to 2 times by mass, more preferably 0.01 to 1.2 times.
It is mass times.

The reduction reaction (c) of the present invention is preferably carried out in the presence of an acid, for example, sulfuric acid, methanesulfonic acid,
Acetic acid, trifluoroacetic acid and the like are used, and the amount thereof is preferably 1 to 1
The molar amount is 0 times, more preferably 1.5 to 5 times.

[0063] The reduction reaction (c) of the present invention is carried out in the presence of a solvent. The solvent used is not particularly limited as long as it does not inhibit the reaction, and examples thereof include water; alcohols such as methanol, ethanol, isopropyl alcohol and t-butyl alcohol; amides such as N, N-dimethylformamide; Aliphatic hydrocarbons such as pentane and cyclohexane; aromatic hydrocarbons such as toluene and xylene; carboxylic acids such as formic acid, acetic acid and propionic acid; and ethers such as diisopropyl ether, tetrahydrofuran and dioxane.

The amount of the solvent to be used is preferably 1 to 50 times by mass, more preferably 2 to 20 times by mass, based on the quinoline carbonitrile derivative. These solvents may be used alone or in combination of two or more.

In the reduction reaction (c) of the present invention, it is preferable that hydrogen is brought into contact with the quinolinecarbonitrile derivative in the liquid phase in the presence of Raney nickel, for example, in a hydrogen atmosphere (which may be diluted with an inert gas). Then, Raney nickel, a quinolinecarbonitrile derivative and a solvent are mixed, and the mixture is heated and agitated, for example, under a pressure of 0.1 to 5 MPa, in a sealed manner or with flowing hydrogen. The reaction temperature at that time is preferably 10 to 100 ° C, more preferably 20 to 70 ° C.

If necessary, the reactivity may be adjusted by adding an inorganic base, an organic base, a platinum salt, a lead salt, a cadmium salt or the like to the system (Tetsuo Kubo, Shinichiro Komatsu, Raney catalyst (published by Kawaken Fine Chemical Co., Ltd.), pages 123-147 and described in HU 45958).

The quinolinecarboxaldehyde derivative, which is the final product, is separated and purified by a general method such as distillation, recrystallization, column chromatography and the like after completion of the reaction.

[0068]

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

Example 1 A 50 ml glass flask equipped with a stirrer, a thermometer, a reflux condenser and a Dean-Stark device was placed under a nitrogen atmosphere.
Toluene (10 ml) and cyclohexane (10 ml) were added, and while stirring, methanesulfonic acid (1.56 g (16.3 mmol), 3-phenyl-3-phenyl) was added.
2.19 g (14.8 mmol) of oxopropanenitrile and 2.00 g (14.8 mmol) of 2-aminoacetophenone were added. Then 105
The temperature was raised to ° C., and the mixture was reacted for 3 hours while removing generated water. After the reaction is completed, cool to room temperature and stir 1m
25 ml (25 mmol) of an ol / l aqueous sodium hydroxide solution were added. After extracting the obtained reaction solution three times with 100 ml of ethyl acetate,
The organic layer was separated and dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure to obtain 3.66 g of 2-phenyl-4-methylquinoline-3-carbonitrile as a pale yellow solid having a purity of 94% (area percentage by high performance liquid chromatography).
(Isolation yield 95%). Further, recrystallized with acetone, purity 99.5
2.27 g of white crystals (% by area (percentage by high performance liquid chromatography)) were obtained. 2-phenyl-4-methylquinoline-3
-The physical properties of carbonitrile were as follows.

Melting point: 164-165 ° C. Elemental analysis: 83.72% of carbon, 4.97% of hydrogen, 11.41% of nitrogen (theoretical value (C ₁₇ H ₁₂ N ₂ ); 83.58% of carbon, 4.95% of hydrogen, 1% of nitrogen)
1.47%) CI-MS (m / e); 244 (M) ¹ H-NMR (CDCl ₃ , δ (ppm)); 3.04 (s, 3H), 7.50 to 7.60 (m, 3
H), 7.62-7.70 (m, 1H), 7.80-8.00 (m, 3H), 8.05-8.15
(m, 1H), 8.17 to 8.22 (m, 1H)

Example 2 The same operation as in Example 1 was performed, except that β-ketonitrile was changed to 1.65 g (14.8 mmol) of 3-cyclopropyl-3-oxopropanenitrile. As a result, 3.01 g of 2-cyclopropyl-4-methylquinoline-3-carbonitrile having a purity of 96% (area percentage by high performance liquid chromatography) was obtained as a pale yellow solid (94% isolated yield). Furthermore, recrystallized with ethyl acetate / chloroform,
0.60 g of white crystals having a purity of 99.8% (area percentage by high performance liquid chromatography) was obtained. Physical properties of 2-cyclopropyl-4-methylquinoline-3-carbonitrile were as follows.

Melting point: 139 ° C. Elemental analysis: carbon 80.81%, hydrogen 5.90%, nitrogen 13.35% (theoretical value (C ₁₄ H ₁₂ N ₂ ); carbon 80.74%, hydrogen 5.81%, nitrogen 1
3.45%) CI-MS (m / e); 209 (M + 1) ¹ H-NMR (CDCl ₃ , δ (ppm)); 1.13 to 1.19 (m, 2H), 1.31 to 1.
36 (m, 2H), 2.58-2.67 (m, 1H), 2.93 (s, 3H), 7.51-7.56
(m, 1H), 7.72 ~ 7.77 (m, 1H), 7.92 ~ 7.99 (m, 2H)

Example 3 In Example 1, the amount of methanesulfonic acid was changed to 1.07 g (11.2 g).
mmol) and β-ketonitrile in 3-oxobutanenitrile 0.
The same operation as in Example 1 was performed, except that 84 g (10.1 mmol) and 2-aminoacetophenone were changed to 2.00 g (10.1 mmol) of 2-aminobenzophenone. As a result, 2.08 g of 2-methyl-4-phenylquinoline-3-carbonitrile having a purity of 96% (area percentage by high performance liquid chromatography) was obtained as a pale yellow solid (isolation yield: 81%). The crystals were recrystallized from ethyl acetate / chloroform, and 0.80 g of white crystals having a purity of 99.6% (area percentage by high performance liquid chromatography).
I got Physical properties of 2-methyl-4-phenylquinoline-3-carbonitrile were as follows.

Melting point: 199-200 ° C. Elemental analysis: 83.88% carbon, 4.96% hydrogen, 11.50% nitrogen (theoretical value (C ₁₇ H ₁₂ N ₂ ); 83.58% carbon, 4.95% hydrogen, 1 nitrogen
1.47%) CI-MS (m / e); 245 (M + 1) ¹ H-NMR (CDCl ₃ , δ (ppm)); 2.99 (s, 3H), 7.45 to 7.62 (m, 6
H), 7.67 (dd, J = 1.2,8.1Hz, 1H), 7.81 (dt, J = 1.5,6.6Hz, 1
H), 8.11 (d, J = 8.1Hz, 1H)

Example 4 2-Cyclopropyl-4-methylquinoline-3-carbonitrile synthesized in Example 2 was placed in a 50 ml glass flask equipped with a stirrer, a thermometer and a dropping funnel under an argon atmosphere. Add 0.50 g (2.4 mmol) and 50 ml of toluene, and in an ice bath
Cooled to -10 ° C. Subsequently, 1.63 ml (2.5 mmol) of a 1.5 mol / l diisobutylaluminum hydride toluene solution was slowly added dropwise while maintaining the liquid temperature at -10 to 0 ° C. After completion of the dropwise addition, the temperature was raised to room temperature, and the mixture was stirred for 1 hour. After completion of the reaction, 5 ml of methanol was added to the obtained reaction solution, the mixture was stirred for 10 minutes, and neutralized by adding 2.5 ml of 1 mmol / l hydrochloric acid. Thereafter, the mixture was concentrated under reduced pressure, added with 15 ml of water, and extracted twice with 100 ml of ethyl acetate. Next, the organic layer was separated and dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure to obtain 0.47 g of 2-cyclopropyl-4-methylquinoline-3-carboxaldehyde having a purity of 92% (area percentage by high performance liquid chromatography) as a light brown solid (isolation yield). 85%). Furthermore, silica gel column chromatography (filler: Wakogel C-200 (manufactured by Wako Pure Chemical Industries, Ltd.), developing solvent: toluene)
After further purification with chloroform / hexane,
0.20 g of yellow crystals having a purity of 99.9% (area percentage by high performance liquid chromatography) was obtained. Physical property values of 2-cyclopropyl-4-methylquinoline-3-carboxaldehyde were as follows.

Melting point: 89-90 ° C. Elemental analysis: 79.59% of carbon, 6.19% of hydrogen, 6.63% of nitrogen (theoretical value (C ₁₄ H ₁₃ NO); 79.59% of carbon, 6.20% of hydrogen, nitrogen
6.63%) CI-MS (m / e); 212 (M + 1) ¹ H-NMR (CDCl ₃ , δ (ppm)); 1.05 to 1.11 (m, 2H), 1.32 to 1.
37 (m, 2H), 2.57-2.66 (m, 1H), 2.88 (s, 3H), 7.49 (dt, J =
1.5,8.4Hz, 1H), 7.71 (dt, J = 1.5,8.1Hz, 1H), 7.93 (d, J =
8.1Hz, 1H), 8.06 (dd, J = 1.0,8.1Hz, 1H), 10.96 (s, 1H)

[0077]

Industrial Applicability According to the present invention, there is provided an industrially advantageous method for producing a quinoline carboxaldehyde derivative, which can produce a quinoline carboxaldehyde derivative in a high yield by a simple method.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Takashi Harada 5, 1978 Kogushi, Obe City, Ube City, Yamaguchi Prefecture

Claims (3)

[Claims] (A) In the presence of an acid (A), a compound represented by the general formula (1): (R ¹ represents a group that does not participate in the reaction.)
Ketonitrile has the general formula (2) (Wherein R ² , R ³ , R ⁴ , R ⁵ and R ⁶ represent groups that do not participate in the reaction), and are reacted with an o-acylaniline represented by the following general formula (3). (R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ have the same meanings as described above), a cyclization reaction step for preparing a quinolinecarbonitrile derivative, (B) a quinolinecarbonitrile derivative To reduce to the general formula (4) (Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ have the same meanings as described above).
A method for producing a quinoline carboxaldehyde derivative. 2. A compound of the formula (1) in the presence of an acid (R ¹ represents a group that does not participate in the reaction.)
Ketonitrile has the general formula (2) (R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ each represent a group which does not participate in the reaction) to react with an o-acylaniline represented by the following general formula (3): (Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ have the same meanings as described above), which is a quinolinecarbonitrile derivative represented by the formula: 3. The method according to claim 1, wherein the acid is an organic sulfonic acid.
2. The method for producing a quinoline carboxaldehyde derivative according to item 1.