JP3224577B2 - 1,2,3,4-tetrahydroquinoline and method for producing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to 1,2,3,4-tetrahydroquinoline, a method for producing the same, and anilinopropanoic acid.

[0002]

2. Description of the Related Art Japanese Patent Laid-Open Publication No.
It is described that 7-dichloro-4- (2-fluorophenoquin) quinoline exhibits excellent plant fungicidal activity as an agricultural and horticultural fungicide. The reaction product of aniline and Meldrum's acid is heated to give 4-oxo-5,7-dichloro-1,4
-Dihydroquinoline is formed and then reacted with phosphorus oxychloride to give 4,5,7-trichloroquinoline and further 2-
A method for producing the same by reacting with fluorophenol is described.

[0003]

However, since it is difficult to obtain Meldrum's acid used in the conventional method in large quantities at low cost, there is a need for a production method suitable for industrial implementation.

[0004]

Means for Solving the Problems The present inventors have studied conventional methods, and in particular, have studied the aforementioned 4-oxo-5,7-dichloro-1,
While studying an industrially advantageous method for producing 4-dihydroquinoline, the reaction product of 3,5-dichloroaniline and acrylic acid or a derivative thereof was cyclized, and the product was oxidized to produce the desired product. I found to do. Since this acrylic acid or its derivative can be obtained in a large amount at a lower cost than Meldrum's acid, it has been found that the 4-oxo-5,7-dichloro-1,4-dihydroquinoline can be produced industrially advantageously. .

The present invention relates to a reaction product of 3,5-dichloroaniline with acrylic acid or a derivative thereof, a cyclization reaction product thereof, and a method for producing a cyclization reaction product. -5,7-dichloro-1,2,3,4-
The second invention is tetrahydroquinoline or a salt thereof, and 3- (3,5-dichloroanilino) propanoic acid, a salt or ester thereof is reacted with a cyclizing agent to give 4-oxo-5.
A method for producing 1,2,3,4-tetrahydroquinoline for producing 7-dichloro-1,2,3,4-tetrahydroquinoline or a salt thereof, and the third invention is directed to 3- (3,5-
Dichloroanilino) propanoic acid, its salts or esters.

[0006] 3,5-Dichloroaniline and acrylic acid or a derivative thereof are generally reacted in the presence of a solvent to produce 3- (3,5-dichloroanilino) propanoic acid, a salt or ester thereof in a satisfactory manner. can do. Examples of the derivative of acrylic acid include salts or esters. Examples of the salt of acrylic acid or anilinopropanoic acid include salts of alkali metals or alkaline earth metals such as sodium, potassium, calcium, and magnesium; Examples of the ester of linopropanoic acid include C ₁ -C ₆ alkyl esters such as methyl, ethyl and phenyl, and phenyl esters. Examples of the solvent include water; organic carboxylic acids or organic sulfonic acids such as formic acid, acetic acid, propionic acid, benzoic acid, and benzenesulfonic acid; linear or cyclic hydrocarbons such as n-hexane, benzene, toluene, and xylene; methylene chloride, dichloroethane Halogenated hydrocarbons such as; ethers such as diethyl ether, tetrahydrofuran, and dioxane; organic sulfur such as dimethyl sulfoxide and sulfolane; ketones such as acetone and methyl ethyl ketone; ethyl acetate;
Esters such as ethyl benzoate; amides such as dimethylacetamide, dimethylformamide and N-methylpyrrolidone; and pyridines such as pyridine.

In this reaction, acrylic acid or a derivative thereof is generally used in an amount of 1 mol per 3,5-dichloroaniline.
10 to 10 mol, preferably 1 to 3 mol, and the solvent is 3,
It is used in an amount of 100 parts by weight or less, preferably 0.05 to 10 parts by weight, per 1 part by weight of 5-dichloroaniline. The reaction is performed under reaction conditions suitable for the raw materials used, the reaction apparatus, etc.
Although the reaction conditions cannot be specified unequivocally, the reaction temperature is 0-1.
50 ° C, desirably 10 to 100 ° C for 0.1 to 5 days. Purification and separation of 3- (3,5-dichloroanilino) propanoic acid, a salt or ester thereof from the reaction mixture can be easily performed by a conventional method such as washing with water, extraction, and distillation.

The above-mentioned anilinopropanoic acid, its salt or ester is reacted with a cyclizing agent to form 4-oxo-5,7-dichloro-1,2,3,4-tetrahydroquinoline or its salt. be able to. Examples of the salt include salts of alkali metals or alkaline earth metals such as sodium, potassium, calcium, and magnesium. Examples of the cyclizing agent include polyphosphoric acid and phosphorus oxychloride. Polyphosphoric acid is desirable, and its concentration is usually 10 to 90%, preferably 70 to 90%.
It is. In this cyclization reaction, generally, 3- (3,5-
Dichloroanilino) propanoic acid, its salt or ester 1
The cyclizing agent is used in an amount of 0.5 to 30 moles, preferably 5 to 1 mole per mole.
The reaction is carried out at a reaction temperature of 30 to 100 ° C, preferably 50 to 100 ° C for 0.2 to 5 hours. 4-Oxo-5,7-dichloro-1,2,2 from reaction mixture
Purification and separation of 3,4-tetrahydroquinoline or a salt thereof are performed by a conventional method such as washing with water and filtration.

Further, the quinoline or a salt thereof is reacted with an oxidizing agent to form 4-oxo-5,7-dichloro-.
1,4-dihydroquinoline can be produced favorably. Manganese dioxide, palladium /
Carbon, palladium / black, platinum / carbon, platinum / black, sulfur, hydrogen peroxide, nitrobenzene, chloranil, 2,3-dichloro-5,6-dicyano-1,
Examples thereof include 4-benzoquinone, and manganese dioxide, chloranil, and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone are preferable. This reaction is generally carried out in the presence of a solvent, and as the solvent, those similar to the solvents used in the reaction of the aforementioned 3,5-dichloroaniline with acrylic acid, a salt or ester thereof can be used. .

In this reaction, generally, 4-oxo-
The oxidizing agent is used in an amount of 0.01 to 100 per part by weight of 5,7-dichloro-1,2,3,4-tetrahydroquinoline or a salt thereof.
The solvent is used in an amount of preferably 0.1 to 10 parts by weight, and the solvent is used in an amount of 100 parts by weight or less, preferably 0.2 to 30 parts by weight. This reaction is carried out at a reaction temperature of 0 to 200 ° C., preferably 30 to 180 ° C. for 0.5 to 100 hours, if necessary, in a non-oxidizing atmosphere such as a nitrogen gas stream. The reaction mixture is washed with water, distilled, The desired 4-oxo-5,7-dichloro- can be obtained by ordinary purification and separation operations such as filtration.
1,4-dihydroquinoline can be easily obtained.
Next, experimental examples according to the present invention will be described.

[0011]

EXAMPLES Example 1.3 Synthesis of 3- (3,5-dichloroanilino) propanoic acid 81 g (0.5 mol) of 3,5-dichloroaniline, 64.8 g (0.9 mol) of acrylic acid and water 80 ml was charged into a four-necked flask and reacted under stirring in a nitrogen stream at room temperature for 2 days. After completion of the reaction, the precipitated crystals were separated by filtration, washed with water, and dried by heating to obtain 116 g of crude 3- (3,5-dichloroanilino) propanoic acid. A part thereof was recrystallized with a mixed solvent (n-hexane: isopropyl ether = 1: 1) to obtain one having a melting point of 104.4 to 106.0 ° C.

Example 2.3 Synthesis of methyl 3- (3,5-dichloroanilino) propanoate 162 g (1.0 mol) of 3,5-dichloroaniline, 103.2 g (1.2 mol) of methyl acrylate ) And acetic acid (10 ml) were charged into a four-necked flask, and the mixture was stirred and reacted for 29 hours while refluxing under a nitrogen stream. After cooling the reaction mixture, it was poured into 300 ml of water and 300 ml of methylene chloride, the reaction product was extracted, the methylene chloride layer was dried over sodium sulfate, and methylene chloride was distilled off. Further, the residue was evaporated under reduced pressure to remove the liquid substance, thereby obtaining 4.0 g of creamy 3- (3,5-dichloroanilino) propanoic acid methyl ester crystals. (Melting point: 154-158 ° C).

EXAMPLE Synthesis of ethyl 3,3- (3,5-dichloroanilino) propanoate 81 g (0.5 mol) of 3,5-dichloroaniline, 50 g (0.5 mol) of ethyl acrylate and 6.4 ml of acetic acid was charged into a four-necked flask and placed under a nitrogen stream.
The mixture was reacted by stirring at 0 ° C. for 64 hours. After cooling, the reaction mixture was poured into 150 ml of water and 150 ml of methylene chloride,
The reaction product was extracted and the methylene chloride layer was dried over sodium sulfate, and then methylene chloride was distilled off. Further, the residue is 185 ° C / 8mm
The liquid was distilled off with Hg to obtain 45.0 g of light red 3- (3,5-dichloroanilino) propanoic acid ethyl ester. (Melting point: 76-81 ° C).

Example 4.4 Synthesis of 4-oxo-5,7-dichloro-1,2,3,4-tetrahydroquinoline 50 g of 3- (3,5-dichloroanilino) propanoic acid
(0.21 mol) and 500 g of 88% polyphosphoric acid were charged into a four-necked flask, heated to 90 ° C., and reacted by stirring for 2 hours. Thereafter, the reaction mixture was poured into warm water of No. 11 and cooled. The precipitated crystals were collected by filtration, washed with water, and dried by heating to obtain crude 4-oxo-5,7-dichloro-1,2,3.
44.4 g of 4-tetrahydroquinoline were obtained. A part thereof was recrystallized from toluene to give a melting point of 177.2 to 183.6 ° C.
Got something.

Reference Example 1.4 Synthesis of 4-oxo-5,7-dichloro-1,4-dihydroquinoline 10 g of 4-oxo-5,7-dichloro-1,2,3,4-tetrahydroquinoline (0.046 Mol), 41.2 g (0.47 mol) of manganese dioxide and 80 sulfolane
The mixture was charged into a four-necked flask, heated to 180 ° C. under a nitrogen stream, and stirred for 2 hours to react. Thereafter, the reaction mixture was filtered, and the solvent was distilled off from the filtrate under reduced pressure. Water was added to the residue, and the precipitated crystals were collected by filtration and dried to give crude 4-oxo-.
4.5 g of 5,7-dichloro-1,4-dihydroquinoline
I got

Reference Example 2.4 Synthesis of 4-oxo-5,7-dichloro-1,4-dihydroquinoline 5 g of 4-oxo-5,7-dichloro-1,2,3,4-tetrahydroquinoline (0.023) Mol), 14.2 g (0.058 mol) of chloranil and 40 ml of acetic acid were charged into a four-necked flask, and the mixture was refluxed under a stream of nitrogen for 3.5.
The mixture was stirred for an hour to react. Thereafter, 100 ml of water was added, and the precipitated crystals were collected by filtration. The crystals are further heated in toluene 80m
After stirring for 10 minutes, the mixture was filtered. The crystals were washed with isopropyl ether and dried to obtain 4.1 g of 4-oxo-5,7-dichloro-1,4-dihydroquinoline.

────────────────────────────────────────────────── ─── Continuation of the front page (56) References JP-A-1-246263 (JP, A) JP-A-59-7170 (JP, A) JP-A-57-171970 (JP, A) Indian Journal of Chemistry, (1976), Vol. 14B, p. 323-325 (58) Fields investigated (Int. Cl. ⁷ , DB name) C07D 215/22 CA (STN) REGISTRY (STN)

Claims (1)

(57) [Claims] 1. A method for producing 3- (3,5-dichloroanilino) propanoic acid, a salt or ester thereof , and polyphosphoric acid or oxy
Reaction with a cyclizing agent consisting of phosphorus chloride to give 4-oxo-
A method for producing 5,7-dichloro-1,2,3,4-tetrahydroquinoline or a salt thereof,
A method for producing 3,4-tetrahydroquinoline.