JPH1112254A - 3-(3-pyridylmethylamino)-3,4-dihydro-2(1h)-quinazolinone derivative and production of its intermediate - Google Patents

Abstract

PROBLEM TO BE SOLVED: To industrially advantageously produce the subject compound useful as a new insecticide in an agricultural field by reacting quinazolinone derivative with a specific compound. SOLUTION: A quinazolinone derivative of formula I is reacted with a compound of the formula, R-CO-Z-R1 [R is H, a 1-8C alkyl or a 1-8C alkoxy; Z is oxygen or sulfur; R1 is a 1-8C alkyl, a (substituted) phenyl or CO-R2 (R2 is H, a 1-8C alkyl, a 1-8C alkoxy or a group of formula II)] in an inert solvent (e.g. an alcohol, a halogenated hydrocarbon, an aromatic hydrocarbon, a nitrile, an ether and an amide) in the presence of a base (e.g. an inorganic base such as sodium hydroxide, or an organic base such as n-butyllithium) at a temperature of (-80) to 200 deg.C, preferably 0 to 100 deg.C for several min to 48 hr to provide the objective compound of formula III, 3-(3-pyridylmethylamino)-3,4-dihydro-2(1H)- quinazolinone derivative.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to 3- (3-pyridylmethylamino)-useful as a novel insecticide in the field of agrochemicals.
The present invention relates to a method for producing a 3,4-dihydro-2 (1H) -quinazolinone derivative and an intermediate thereof.

[0002]

2. Description of the Related Art JP-A-8-325239 discloses 3- (3-pyridylmethylamino) -3,4-dihydro-2 (1H) represented by the general formula (I) produced by the present invention.
-Quinazolinone derivatives, their usefulness as insecticides and their preparation are described.

[0003]

The 3- (3-pyridylmethylamino) -3,4-dihydro-2 (1H) -quinazolinone derivative represented by the general formula (I) is disclosed in
The production method disclosed in Japanese Patent No. 3252394 is industrially low in practical use in terms of reaction, yield, and isolation method, and a new production method is desired from the viewpoint of economy and practicality.

[0004]

DISCLOSURE OF THE INVENTION The present inventors have studied 3- (3-pyridylmethylamino) -3,4- useful as an insecticide.
As a result of intensive studies to develop a novel method for producing a dihydro-2 (1H) -quinazolinone derivative, the present inventors have found the present invention and completed the present invention. 3- (3-pyridylmethylamino) represented by the general formula (I) of the present invention
In the definition of the following reaction formula showing the -3,4-dihydro-2 (1H) -quinazolinone derivative and the present invention, "(C ₁ -C ₈ ) alkyl group" or "(C ₁ -C ₈ ) alkoxy group" Is a linear or branched alkyl group having 1 to 8 carbon atoms, for example, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, n- Alkyl groups such as pentyl, neo-pentyl, n-hexyl, n-heptyl, n-octyl, methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, i-butoxy, s-butoxy, t-butoxy, n-pentyloxy, neo-pentyloxy, n-hexyloxy, n-heptyloxy, represents an alkoxy group such as n-octyloxy, as a substituent of the `` phenyl group which may have a substituent '', for example, Halogen atom, nitro group, cyano group, (C ₁ -C ₆ ) alkyl group, halo (C ₁ -C ₆ ) alkyl group, (C ₁ -C ₆ ) alkoxy group, halo (C ₁ -C ₆ ) alkoxy group, (C ₁ -C ₆ ) alkylthio group, halo (C ₁ -C ₆ ) alkylthio group, (C ₁ -C ₆ ) alkylsulfinyl group, halo (C _1-
1 to 5 identical or different substituents selected from substituents such as C ₆ ) alkylsulfinyl group, (C ₁ -C ₆ ) alkylsulfonyl group, halo (C ₁ -C ₆ ) alkylsulfonyl group Is shown. The production method of the present invention can be schematically shown as follows, for example.

[0005]

Embedded image

(Wherein, R represents a hydrogen atom, a (C ₁ -C ₈ ) alkyl group or a (C ₁ -C ₈ ) alkoxy group, and X represents a halogen atom or —ZR ₁ (where Z is a R ₁ represents a (C ₁ -C ₈ ) alkyl group, a phenyl group which may have a substituent or —CO—R ₂ (wherein R ₂ represents a hydrogen atom,
(C ₁ -C ₈ ) alkyl group, (C ₁ -C ₈ ) alkoxy group or

Embedded image Is shown. ). And R ₂ and R ₃ may be the same or different, and represent a (C ₁ -C ₈ ) alkyl group or a (C ₁ -C ₈ ) alkoxy group, and R ₂ and R ₃ together T
(CH ₂₎ n- (wherein, n shows. An integer of 2 to 5) may also indicate. )

[0007] 1. Structural formula (III) → General formula (I) By reacting the compound represented by Structural formula (III) with the compound represented by General formula (V) in the presence of an inert solvent and a base, )) Can be produced to produce a 3- (3-pyridylmethylamino) -3,4-dihydro-2 (1H) -quinazolinone derivative. The inert solvent used in the present reaction may be any inert solvent that does not significantly inhibit the progress of the present reaction, such as linear or branched alcohols such as methanol, ethanol, propanol, and butanol, dichloromethane, chloroform, Halogenated hydrocarbons such as carbon chloride, aromatic hydrocarbons such as benzene, toluene, xylene, nitriles such as acetonitrile and benzonitrile, cellosolves such as methyl cellosolve and ethyl cellosolve, dimethyl ether, diglyme, dioxane, tetrahydrofuran ( Linear or cyclic ethers such as THF), dimethylformamide (DMF),
Dimethylacetamide (DMA), dimethoxyethane (DME), 1,3-dimethylimidazolidinone, 1-
Amides such as methyl-2-pyrrolidinone, phosphoric amides such as hexamethylphosphoric triamide (HMPA), dimethyl sulfoxide (DMSO), sulfolane,
Inert solvents such as water can be exemplified, and these inert solvents can be used alone or in combination of two or more.

[0008] As the base used in this reaction, an organic base or an inorganic base can be used.
For example, sodium hydroxide, potassium hydroxide, hydroxides of alkali metal atoms or alkaline earth metal atoms such as magnesium hydroxide, sodium carbonate, sodium hydrogen carbonate,
As an organic base, for example, an alkali metal atom or an alkaline earth metal atom carbonate such as potassium carbonate or the like, an organic base such as triethylamine or pyridine, sodium methoxide, sodium ethoxide, sodium-t-butoxide, potassium methoxide And the like, alcohol metals such as n-butyllithium, alkali metal hydrides such as sodium hydride, etc., but the present invention is not limited to these bases. The amount of the base used may be appropriately selected and used from the range of equivalent to 5 equivalents to the compound represented by the structural formula (III).

Since this reaction is an equimolar reaction, the structural formula (I
The compound represented by the formula (II) and the compound represented by the general formula (V) may be used in equimolar amounts, but any of the reactants (compounds) may be used in excess. The reaction temperature of this reaction may be appropriately selected from the range of -80 ° C to 200 ° C, and the reaction is preferably performed in the range of 0 ° C to 100 ° C. The reaction time of this reaction is not fixed depending on the reaction scale, the reaction temperature and the like, but it is sufficient that this reaction is completed, and is in the range of several minutes to 48 hours. After completion of the reaction, 3- (3-pyridylmethylamino) represented by the general formula (I), which is the desired product, is obtained according to a conventional method.
The -3,4-dihydro-2 (1H) -quinazolinone derivative may be isolated, and a purification operation can be performed if necessary.

[0010] 2. Structural formula (IV) → General formula (II) This reaction is carried out by reacting a compound represented by Structural formula (IV) with a compound represented by General formula (V) in the presence of an inert solvent and a base. The compound represented by the general formula (II) can be produced. In this reaction, the compound represented by the general formula (II) can be produced by carrying out the reaction according to Production method 1. The obtained compound represented by the general formula (II) can be isolated from the reaction system or can be subjected to the next reaction without isolation. 3. General formula (VII) → General formula (II) This reaction is produced by reacting a compound represented by general formula (VII) with a compound represented by general formula (VI) in the presence of an inert solvent and a catalyst. can do. As the inert solvent used in this reaction, for example, the inert solvent used in Production Method 1 can be used.

As the catalyst used in this reaction, for example, inorganic acids such as hydrochloric acid and sulfuric acid, and organic acids such as acetic acid and p-toluenesulfonic acid can be used. It can be used by selecting from the range.
Since this reaction is an equimolar reaction, the compound represented by the general formula (VII) and the compound represented by the general formula (VI) may be used in equimolar amounts, but any one of the reactants is used in excess. You can also. The reaction temperature is in the range of room temperature to the boiling point of the inert solvent used, and preferably in the range of room temperature to 90 ° C. Although the reaction time is not fixed depending on the reaction scale, the reaction temperature, and the like, the reaction may be performed within a range of several minutes to 48 hours. After the completion of the reaction, the desired product can be isolated from the reaction system by a conventional method, and if necessary, the desired product can be produced by a purification operation or the like. After completion of the reaction, the target product can be subjected to the next reaction without isolation from the reaction system.

4. General formula (VIII) → General formula (VII) This reaction is carried out by reacting a compound represented by the general formula (VIII) with a compound represented by the general formula (IX) in the presence of an inert solvent and a base. The compound represented by the general formula (VII) can be produced. This reaction can be carried out in the same manner as in Production Method 1 to produce a compound represented by the general formula (VII). The obtained compound represented by the general formula (VII) can be subjected to the next reaction without isolation from the reaction system. The general formula (I) produced by production methods 2 and 3
The compound represented by the formula (I) can be prepared by the production method described in JP-A-8-325239.
Pyridylmethylamino) -3,4-dihydro-2 (1
H) -Quinazolinone derivatives can be produced.
The compounds represented by the structural formulas (III), (IV) and (VIII), which are the starting compounds of the present production method, are disclosed in
It can be produced by the production method described in JP-A-325239.

[0013]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, typical examples of the present invention will be described, but the present invention is not limited to these examples. Example 1

Embedded image

113 mg (4.73 mmol) of sodium hydride is suspended in 5 ml of dimethylacetamide, and 3- (3-pyridylmethylamino) -3,4-
1 g of dihydro-2- (1H) -quinazolinone (3.94
Mmol) and stirred at 50 ° C. for 30 minutes. After cooling the reaction solution on ice, 4-nitrophenylpropionate 883m
g (4.53 mmol) was added and the reaction was carried out with stirring for 30 minutes. After completion of the reaction, the reaction solution was poured into water, and the target substance was extracted with ethyl acetate. The extract was washed with water and saturated saline, dried over sodium sulfate, and the solvent was distilled off. The residual crude crystals were washed (toluene-n-hexane 1: 1) to obtain 915 mg of the desired product. Physical properties: m. p. 107-108 ° C Yield 75%

Examples 2 to 14 The desired product was obtained in the same manner as in Example 1 except that the base, the inert solvent and the reactant used in Example 1 were changed. The results are shown in Table 1.

[0016]

[Table 1]

[0017]

[Table 2]

Embodiment 15

Embedded image 189 mg of powdered sodium hydroxide in 15 ml of toluene
(4.73 mmol) was suspended in the suspension, and 3- (3
-Pyridylmethylamino) -3,4-dihydro-2-
1 g (3.94 mmol) of (1H) -quinazolinone was added and heated to reflux. The reflux liquid is molecular sieves 4A
(2 g) and returned to the reaction system, and reacted for 5 hours. After cooling the reaction solution with ice, 563 mg (4.33 mmol) of propionic anhydride was added, and the reaction was carried out with stirring for 30 minutes. After completion of the reaction, the reaction solution was poured into water, and the target substance was extracted with ethyl acetate. The extract was washed with water and saturated saline, dried over anhydrous sodium sulfate, the solvent was distilled off, and the residue was recrystallized (isopropanol-N-heptane 1: 2) to obtain 915 mg of the desired product. Obtained. Physical properties: m. p. 107-108 ° C Yield 75%

Embodiment 16

Embedded image 1 g (3.97 mmol) of 3- (3-pyridylmethylideneamino) -3,4-dihydro-2- (1H) -quinazolinone was dissolved in 35 ml of dimethylacetamide, and 100 mg (4.17 mmol) of sodium hydride was added. In addition, the mixture was stirred at room temperature for 1 hour. Propionic anhydride 5 was added to the reaction mixture.
A solution in which 40 mg (4.17 mmol) of dimethylacetamide was dissolved in 5 ml of dimethylacetamide was added, and the reaction was carried out with stirring for 30 minutes. After completion of the reaction, the reaction solution was poured into water, and the target substance was extracted with toluene. The extract was washed with water and saturated saline,
After drying over sodium sulfate, the solvent was distilled off, and the crude crystals of the residue were washed with ether to obtain 820 mg of the desired product. Yield: 67% Examples 17 to 25 The desired product was obtained in the same manner as in Example 16 except that the inert solvent or the reactant used in Example 16 was changed. The results are shown in Table 2.

[0020]

[Table 3]

[0021]

[Table 4]

Embodiment 26

Embedded image . 3- (1-methoxyethylideneamino) -3,4-
1 g (4.5 mmol) of dihydro-2- (1H) -quinazolinone was dissolved in 10 ml of toluene, and 220 mg (5.5 mmol) of sodium hydride was added.
Stir for a minute. After allowing the reaction mixture to cool, propionic anhydride 71
0 mg (5.5 mmol) were added and then again
The reaction was carried out with stirring for 0 minutes. After completion of the reaction, the reaction solution was poured into water, and the desired product was extracted with ethyl acetate.
After washing with saturated saline and drying with sodium sulfate, the solvent is distilled off, and the crude crystals of the residue are washed with n-hexane to give 3- (1-methoxyethylideneamino) -1-propionyl-3 which is the desired product. 1.16 g of 2,4-dihydro-2- (1H) -quinazolinone was obtained. (Yield 92%)

[0023] The obtained 3- (1-methoxyethylideneamino) -1-propionyl-3,4-dihydro-2
-(1H) -quinazolinone is converted to t-butyl alcohol 10
nicotinaldehyde (500 mg, 4.6 mg).
(Mmol) and 100 mg of concentrated hydrochloric acid, and the mixture was reacted under heating and reflux for 60 minutes. After completion of the reaction, the reaction solution is allowed to cool,
Toluene was added to the residue obtained by concentration under reduced pressure to extract the desired product. The extract was washed with water and saturated saline, dried over sodium sulfate, and the solvent was distilled off to give 3- (3) as a target compound.
-Pyridylmethylideneamino) -1-propionyl-
3,4-dihydro-2- (1H) -quinazolinone was added to 1.
17 g were obtained. Physical properties: m. p. 129 ° C Yield 83%

Examples 27 to 33 The reaction was carried out in the same manner as in Example 26 except that the reaction conditions in Example 26 were changed as shown in Tables 3 and 4. The results are shown in Tables 3 and 4. Reaction of

[Table 5]

Reaction

[Table 6]

 ──────────────────────────────────────────────────の Continued on the front page (72) Inventor Michihiko Kawaguchi 3-7-5-503, Kishimachi, Tondabayashi-shi, Osaka (72) Inventor Noboru Abe 10-3-A102, Shoei-cho, Kawachinagano-shi, Osaka (72) Invention Person Akira Seo 2-3-19 Kimigaoka, Hashimoto City, Wakayama Prefecture

Claims (4)

[Claims] (1) Structural formula (III) And a quinazolinone derivative represented by the general formula (V): R-CO-ZR ₁ (V) (wherein R is a hydrogen atom, a (C ₁ -C ₈ ) alkyl group or a (C _1-
C ₈ ) represents an alkoxy group; Z represents an oxygen atom or a sulfur atom; R ₁ represents a (C ₁ -C ₈ ) alkyl group, a phenyl group which may have a substituent or —CO—R ₂ (wherein , R ₂ are a hydrogen atom, a (C ₁ -C ₈ ) alkyl group, a (C ₁ -C ₈ ) alkoxy group or Is shown. ). Wherein the compound is reacted with a compound represented by the general formula (I): (Wherein, R is the same as above.) 3- (3-pyridylmethylamino) -3,4-dihydro-2 (1H)-
A method for producing a quinazolinone derivative. 2. Structural formula (IV) And a compound represented by the general formula (V): R-CO-ZR ₁ (V) (wherein R is a hydrogen atom, a (C ₁ -C ₈ ) alkyl group or a (C _1-
C ₈ ) represents an alkoxy group; Z represents an oxygen atom or a sulfur atom; R ₁ represents a (C ₁ -C ₈ ) alkyl group, a phenyl group which may have a substituent or —CO—R ₂ (wherein , R ₂ are a hydrogen atom, a (C ₁ -C ₈ ) alkyl group, a (C ₁ -C ₈ ) alkoxy group or Is shown. ). Wherein the compound is represented by the general formula (II): (Wherein R is as defined above) 3- (3-pyridylmethylideneamino) -3,4-dihydro-2 (1
H) A method for producing a quinazolinone derivative. 3. A compound of the general formula (VII) (Wherein, R is a hydrogen atom, a (C ₁ -C ₈ ) alkyl group or a (C _1-
C ₈ ) represents an alkoxy group, R ₂ and R ₃ may be the same or different, represents a (C ₁ -C ₈ ) alkyl group or a (C ₁ -C ₈ ) alkoxy group, and R ₂ and R ₃ are to become and - (CH ₂₎
n- (where n represents an integer of 2 to 5) can also be shown. ) And a compound represented by the structural formula (VI): A general formula characterized by reacting with a compound represented by the formula:
(II) (Wherein R is as defined above) 3- (3-pyridylmethylideneamino) -3,4-dihydro-2 (1
H) A method for producing a quinazolinone derivative. 4. A compound of the general formula (VIII) (Wherein R ₂ and R ₃ may be the same or different, and (C _1-
C ₈₎ an alkyl group or (C ₁ -C ₈₎ alkoxy group, R ₂
And R ₃ together - (CH ₂₎ n- (wherein, n represents an integer of 2-5.) It may also indicate. ) And a compound represented by the general formula (IX): R-CO-X (IX) (wherein R is a hydrogen atom, a (C ₁ -C ₈ ) alkyl group or a (C _1-
C ₈ ) represents an alkoxy group, and X represents a halogen atom or -Z-
R ₁ (wherein, Z represents an oxygen atom or a sulfur atom, and R ₁ is
(C ₁ -C ₈₎ alkyl group, in a phenyl group or a -CO-R ₂ (Formula may have a substituent, R ₂ is a hydrogen atom, (C ₁ -C ₈₎ alkyl groups, (C ₁ - C ₈ ) an alkoxy group or Is shown. ). Wherein the compound is reacted with a compound represented by the general formula (VII): (In the formula, R, R ₂ and R ₃ are the same as described above.) A method for producing a quinazolinone derivative.