JP2013139427A - Method of improving and synthesizing isoquinolin-4(3h)-ones - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method of producing isoquinolin-4(3H)-ones useful as a fungicide for agriculture and horticulture safely, simply, and in good yield.SOLUTION: A method of producing isoquinolin-4(3H)-ones useful as a fungicide for agriculture and horticulture includes hydrolyzing 4,4-dibromo-3,4-dihydroisoquinoline compound represented by the following general formula (II).

Description

  The present invention relates to a method for producing isoquinolin-4 (3H) -ones.

（一般式（Ｉ）中、Ｒ^１及びＲ^２は、同一若しくは異なっていてもよく、
ハロゲン原子及びＣ_１〜Ｃ_６アルコキシ基からなる群から選ばれる同一若しくは異なった１〜３個の置換基で置換されてもよいＣ_１〜Ｃ_６アルキル基を表し、
Ｘは、ハロゲン原子；
ハロゲン原子及びＣ_１〜Ｃ_６アルコキシ基からなる群から選ばれる同一若しくは異なった１〜３個の置換基で置換されてもよいＣ_１〜Ｃ_６アルキル基；又は
Ｃ_１〜Ｃ_６アルコキシ基を表し、
ｎは、０〜４の整数を表し、
ｎが２〜４の場合、Ｘは、同一若しくは異なっていてもよく、
Ｙは、ハロゲン原子、Ｃ_１〜Ｃ_６アルキル基及びＣ_１〜Ｃ_６アルコキシ基からなる群から選ばれる基を表し、
ｍは、０〜６の整数を表す。） Numerous drugs have been proposed for the purpose of controlling diseases of agricultural and horticultural crops. For example, Patent Document 1 and Patent Document 2 disclose isoquinolin-4 (3H) -ones represented by the following general formula (I), which are known to be useful as agricultural and horticultural fungicides. ing. At the same time, it is also disclosed that it is useful as a synthetic intermediate for other compounds described in Patent Document 1.

(In general formula (I), R ¹ and R ² may be the same or different,
Represent the same or different one to three optionally substituted with a substituent C ₁ -C ₆ alkyl group selected from the group consisting of halogen atom and C ₁ -C ₆ alkoxy group,
X is a halogen atom;
Or C ₁ -C ₆ alkoxy group; the same or different may be substituted with 1-3 substituents _C 1 -C ₆ alkyl group selected from the group consisting of halogen atom and _C 1 -C ₆ alkoxy group Represent,
n represents an integer of 0 to 4,
when n is 2 to 4, X may be the same or different;
Y represents a group selected from the group consisting of halogen _atom, C 1 -C ₆ alkyl and _C 1 -C ₆ alkoxy group,
m represents an integer of 0-6. )

（一般式（III）中、Ｒ^１、Ｒ^２、Ｘ、Ｙ、ｎ及びｍは、上記と同様の意味を表す） Patent Document 1 discloses the following general formula (III) also disclosed in Patent Document 1 as a specific synthesis example of isoquinolin-4 (3H) -ones represented by the above general formula (I). The chromic acid oxidation of 3,4-dihydroisoquinolines is described.

(In general formula (III), R ¹ , R ² , X, Y, n and m represent the same meaning as described above.)

However, the yield in the above examples was very poor at 6%. Further, since chromic acid having high toxicity is used as an oxidizing agent, it has a drawback that it is difficult to handle in mass production.
Against this background, it is eager to develop a production method that can synthesize isoquinolin-4 (3H) -ones safely and simply in a high yield and that can be produced on an industrial scale. It had been.

International Publication No. 2005/70917 International Publication No. 2011/77514

  An object of the present invention is to provide a method for producing isoquinolin-4 (3H) -ones safely and simply in a high yield.

  As a result of intensive studies to solve the above problems, the present inventors have used 4,4-dibromo-3,4-dihydroisoquinolines as raw materials, and by reacting them with water, isoquinoline-4 (3H)- It was found that ONs can be obtained in good yield. The present invention has been completed based on these findings.

  That is, the present invention relates to the following production method.

（式中、Ｒ^１及びＲ^２は、同一若しくは異なっていてもよく、
ハロゲン原子及びＣ_１〜Ｃ_６アルコキシ基からなる群から選ばれる同一若しくは異なった１〜３個の置換基で置換されてもよいＣ_１〜Ｃ_６アルキル基を表し、
Ｘは、ハロゲン原子；
ハロゲン原子及びＣ_１〜Ｃ_６アルコキシ基からなる群から選ばれる同一若しくは異なった１〜３個の置換基で置換されてもよいＣ_１〜Ｃ_６アルキル基；又は
Ｃ_１〜Ｃ_６アルコキシ基を表し、
ｎは、０〜４の整数を表し、
ｎが２〜４の場合、Ｘは、同一若しくは異なっていてもよく、
Ｙは、ハロゲン原子、Ｃ_１〜Ｃ_６アルキル基及びＣ_１〜Ｃ_６アルコキシ基からなる群から選ばれる基を表し、
ｍは、０〜６の整数を表す）
で表されるイソキノリン−４（３Ｈ）−オン類の製造方法であって、 <1>
Formula (I)

(Wherein R ¹ and R ² may be the same or different,
Represent the same or different one to three optionally substituted with a substituent C ₁ -C ₆ alkyl group selected from the group consisting of halogen atom and C ₁ -C ₆ alkoxy group,
X is a halogen atom;
Or C ₁ -C ₆ alkoxy group; the same or different may be substituted with 1-3 substituents _C 1 -C ₆ alkyl group selected from the group consisting of halogen atom and _C 1 -C ₆ alkoxy group Represent,
n represents an integer of 0 to 4,
when n is 2 to 4, X may be the same or different;
Y represents a group selected from the group consisting of halogen _atom, C 1 -C ₆ alkyl and _C 1 -C ₆ alkoxy group,
m represents an integer of 0 to 6)
A process for producing isoquinolin-4 (3H) -ones represented by:

（式中、Ｒ^１、Ｒ^２、Ｘ、Ｙ、ｎ及びｍは、上記と同様の意味を表す）
で表される４，４−ジブロモ−３，４−ジヒドロイソキノリン類を加水分解する方法。 The following general formula (II)

(Wherein R ¹ , R ² , X, Y, n and m represent the same meaning as described above)
A method for hydrolyzing 4,4-dibromo-3,4-dihydroisoquinolines represented by the formula:

<2>
In the general formula (I) and the general formula (II), R ¹ and R ² may represent the same or different C _{1 to} C ₆ alkyl group, X represents a halogen atom, and Y represents a halogen atom. The production method according to <1>.

  According to the production method of the present invention, isoquinolin-4 (3H) -ones useful as agricultural and horticultural fungicides can be easily obtained in high yield. In addition, there are advantages such as avoidance of reactants that cause safety problems, and significant reduction of industrial waste.

Hereinafter, the present invention will be described in detail.
The production method of isoquinolin-4 (3H) -ones represented by the following general formula (I) hydrolyzes 4,4-dibromo-3,4-dihydroisoquinolines represented by the following general formula (II). It is characterized by doing.

In which R ¹ and R ² may be the same or different;
Substituted by the same or different 1 to 3 substituents selected from the group consisting of halogen atom and C ₁ -C ₆ alkoxy group represents an C ₁ -C ₆ alkyl group.
X is a halogen atom;
Or _C 1 -C ₆ alkoxy group; the same or different may be substituted with 1-3 substituents _C 1 -C ₆ alkyl group selected from the group consisting of halogen atom and _C 1 -C ₆ alkoxy group Represent.
n represents an integer of 0 to 4, and when n is 2 to 4, X may be the same or different.
Y represents a group selected from the group consisting of halogen _atom, C 1 -C ₆ alkyl and _C 1 -C ₆ alkoxy group.
m represents an integer of 0-6.

Examples of the “C ₁ -C ₆ alkyl group” include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, s-butyl group, t-butyl group, pentyl group, isopentyl group, 2 -Methylbutyl group, neopentyl group, 1-ethylpropyl group, hexyl group, 4-methylpentyl group, 3-methylpentyl group, 2-methylpentyl group, 1-methylpentyl group, 3,3-dimethylbutyl group, 2 , 2-dimethylbutyl group, 1,1-dimethylbutyl group, 1,2-dimethylbutyl group, 1,3-dimethylbutyl group, 2,3-dimethylbutyl group, 2-ethylbutyl group, etc. 6 straight-chain or branched alkyl groups, preferably a straight-chain or branched alkyl group having 1 to 5 carbon atoms (C ₁ -C ₅ alkyl group), more preferably carbon From 1 to 4 straight-chain or branched-chain alkyl group (C ₁ -C ₄ alkyl group), even more preferably at a linear or branched alkyl group having 1 to 3 carbon atoms (C ₁ ~ C ₃ alkyl group), particularly preferably a methyl group, an ethyl group or a propyl group, and most preferably a methyl group or an ethyl group.
The “halogen atom” is a fluorine atom, a chlorine atom, a bromine atom or an iodine atom, preferably a fluorine atom, a chlorine atom or a bromine atom.
Examples of the “C ₁ -C ₆ alkoxy group” include methoxy group, ethoxy group, propoxy group, isopropoxy group, butoxy group, isobutoxy group, s-butoxy group, t-butoxy group, pentyloxy group, isopentyl group. Oxy group, 2-methylbutoxy group, neopentyloxy group, 1-ethylpropoxy group, hexyloxy group, (4-methylpentyl) oxy group, (3-methylpentyl) oxy group, (2-methylpentyl) oxy group (1-methylpentyl) oxy group, 3,3-dimethylbutoxy group, 2,2-dimethylbutoxy group, 1,1-dimethylbutoxy group, 1,2-dimethylbutoxy group, 1,3-dimethylbutoxy group, A straight or branched alkoxy group having 1 to 6 carbon atoms such as 2,3-dimethylbutoxy group and 2-ethylbutoxy group; In is a straight or branched alkoxy group having 1 to 4 carbon atoms (C ₁ -C ₄ alkoxy group), more preferably a methoxy group or an ethoxy group, and most preferably, a methoxy group It is.
The "halogen atom and C ₁ -C ₆ same or different 1-3 substituents optionally C ₁ -C ₆ alkyl group optionally substituted by a group selected from the group consisting of alkoxy group", the "C ₁ ~ “C ₆ alkyl group”, “C ₁ -C ₆ alkyl group substituted by 1 to 3 identical or different substituents selected from the group consisting of halogen atoms”, “C ₁ -C ₆ alkoxy group” The same or different C ₁ -C ₆ alkyl group substituted with 1 to 3 identical or different substituents selected from the above and “the same group selected from the group consisting of halogen atoms and the group consisting of C ₁ -C ₆ alkoxy groups” or different means C ₁ -C ₆ alkyl group "which is substituted with 2-3 substituents.
“C ₁ -C ₆ alkyl group substituted with the same or different 1 to 3 substituents selected from the group consisting of halogen atoms” includes, for example, trifluoromethyl group, trichloromethyl group, difluoromethyl group, dichloro Methyl group, dibromomethyl group, fluoromethyl group, chloromethyl group, bromomethyl group, iodomethyl group, 2,2,2-trichloroethyl group, 2,2,2-trifluoroethyl group, 2-bromoethyl group, 2 -Chloroethyl, 2-fluoroethyl, 3-chloropropyl, 3,3,3-trifluoropropyl, 4-fluorobutyl, 3-fluoro-2-methylpropyl, 3,3,3-tri 1 to 3 above-mentioned “halogen atoms” which are the same or different, such as a fluoro-2-methylpropyl group and a 6,6,6-trichlorohexyl group It is said that the more substituted "C ₁ -C ₆ alkyl group", preferably, the substituted same or different 1-3 wherein the "halogen atom" in the "C ₁ -C ₄ alkyl group" More preferably, the above-mentioned “C ₁ -C ₃ alkyl group” substituted by ₁ to ₃ “fluorine or chlorine atoms” which are the same or different, and even more preferably a chloromethyl group or A trifluoromethyl group, particularly preferably a trifluoromethyl group.
The “C ₁ -C ₆ alkyl group substituted by the same or different 1 to 3 substituents selected from the group consisting of C ₁ -C ₆ alkoxy groups” is the same or different 1 to 3 “ C ₁ -C ₆ alkoxy group "is substituted by" _C 1 -C ₆ alkyl group ", preferably substituted by identical or different 1-3 of the" _C 1 -C ₄ alkoxy group "," a C ₁ -C ₄ alkyl group ", more preferably substituted by same or different 1-3 of the" _C 1 -C ₄ alkoxy group "," _C 1 -C ₃ alkyl group ", the most A methyl group or an ethyl group substituted with 1 to 3 substituents selected from the group consisting of a methoxy group, an ethoxy group and a propoxy group is preferable.
"C ₁ -C ₆ alkyl group substituted with same or different 2-3 substituents selected from both the group consisting of the group, and C ₁ -C ₆ alkoxy group consisting of a halogen atom", 1-chloro 2-methoxyethyl group, 2-chloro-1-methoxyethyl group, 1-fluoro-2-methoxyethyl group, 2-fluoro-1-methoxyethyl group, 1-bromo-2-methoxyethyl group, 1-chloro 2-ethoxyethyl group, 2-chloro-1-ethoxyethyl group, 1-fluoro-2-ethoxyethyl group, 2-fluoro-1-ethoxyethyl group, 1-chloro-3-methoxypropyl group, 1-fluoro -3-methoxypropyl group, 1,1-difluoro-3-methoxypropyl group, 1-chloro-4-methoxybutyl group, 1,1-difluoro-4-methoxybutyl group, 1 Such as chloro-5-methoxy-pentyl group, the group consisting of the halogen atoms, and the C ₁ -C ₆ said substituted with 2-3 substituents selected from both the group consisting of alkoxy group "C ₁ -C ₆ alkyl group ", more preferably the group consisting of the halogen atoms, and the C ₁ -C ₆ said substituted with 2-3 substituents selected from both the group consisting of alkoxy group" C ₁ ~ it is a C ₃ alkyl group ".
X is preferably a halogen atom.
Since n represents an integer of 0 to 4, X may not be present on the isoquinoline ring, or may be present at 1 to 4 substitutable positions on the isoquinoline ring, and X is 2 or more. If present, they may be the same or different. n is preferably 0 to 2, more preferably 0 to 1.
Y is preferably a halogen atom.
Since m represents an integer of 0 to 6, Y may not be present on the quinoline ring, or may be present at 1 to 6 substitutable positions on the quinoline ring, and Y is 2 or more. If present, they may be the same or different. m is preferably 0 to 2, and more preferably 0 to 1.
Preferably, R ¹ and R ² may be the same or different and may be substituted with the same or different 1 to 3 substituents selected from the group consisting of a halogen atom and a C _{1 to} C ₆ alkoxy group. represents an _C 1 -C ₆ alkyl group, X and Y represents a halogen atom, n represents an integer of 0 to 4, and m represents an integer of 0 to 6. Particularly preferably, R ¹ and R ² may be the same or different and are substituted with the same or different 1 to 3 substituents selected from the group consisting of a halogen atom and a C _{1 to} C ₆ alkoxy group. Represents a C _{1 to} C ₆ alkyl group, X and Y represent a halogen atom, and n and m represent an integer of 0 to 1.

  Hereinafter, a method for producing the general formula (I) from the general formula (II) will be described.

The amount of water used as a reactant in the present invention is not particularly limited as long as it is 1 equivalent or more with respect to the compound represented by the general formula (II).
In the present invention, a solvent can be used, and in this case, the solvent used is not particularly limited as long as it does not inhibit the reaction. For example, aromatic hydrocarbons such as benzene, toluene, xylene and the like; Alcohols such as methanol, ethanol and propanol; ketones such as acetone; ethers such as dioxane, tetrahydrofuran and ethylene glycol dimethyl ether; organic acids such as formic acid, acetic acid and butyric acid; N, N-dimethylformamide, N, N-dimethyl Amides such as acetamide, N-methylpyrrolidone and hexamethylphosphoric triamide; Sulfoxides such as dimethyl sulfoxide, diethyl sulfoxide and tetramethylene sulfoxide; Sulfones such as sulfolane and dimethyl sulfone; N, N′-dimethylethyleneurea, N , N ' Ureas such as dimethyl propylene urea; or, nitriles such as acetonitrile and isobutyronitrile, and the like. These solvents can be used alone or in admixture of two or more at any ratio.
The amount of the solvent for the reaction is not particularly limited as long as the reaction proceeds, but it is preferably 3 to 50 times by weight with respect to the compound represented by the general formula (II).
The reaction temperature varies depending on the raw material compound and the solvent, but is usually 0 ° C to 120 ° C.
While the reaction time varies depending on the raw material compound, reaction reagent, solvent, reaction temperature and the like, it is generally 5 minutes to 120 hours, preferably 10 minutes to 24 hours.

In order to neutralize hydrogen bromide generated as the reaction proceeds in this step, a base can also be used in the reaction solution. In the case of using a base, the base used is not particularly limited as long as it is used as a base in a normal reaction. For example, alkali metal carbonates such as sodium carbonate and potassium carbonate; sodium hydrogen carbonate, hydrogen carbonate Alkali metal hydrogen carbonates such as potassium; alkali metal hydroxides or alkaline earth metal hydroxides such as sodium hydroxide, potassium hydroxide and barium hydroxide; sodium methoxide, sodium ethoxide, potassium t-butoxide Alkali metal alkoxides such as sodium formate, potassium formate, sodium acetate, potassium acetate and the like; triethylamine, tributylamine, diisopropylethylamine, N-methylmorpholine, pyridine, 4- (N, N-dimethyl) Amino) pyridine, , N-dimethylaniline, N, N-diethylaniline, 1,5-diazabicyclo [4.3.0] non-5-ene, 1,4-diazabicyclo [2.2.2] octane (DABCO), 1, And organic bases such as 8-diazabicyclo [5.4.0] -7-undecene (DBU).
The amount of the base used is usually 2 to 30 mol per 1 mol of compound (II).

After completion of the reaction, the target compound can be collected from the reaction mixture according to a conventional method. For example, the reaction mixture is appropriately neutralized, and if insoluble matter is present, it is removed by filtration, water and an immiscible organic solvent such as methylene chloride or toluene are added, and the organic solvent phase is washed with water, The organic layer containing the target compound is separated, dried over anhydrous magnesium sulfate and the like, and then the solvent is distilled off.
The obtained target compound can be further purified by a conventional method such as recrystallization, reprecipitation, solvent washing or chromatography if necessary.
The solvent used for recrystallization, reprecipitation, and solvent washing is not particularly limited as long as the compound represented by the general formula (I) is not decomposed.
Specific examples of solvents used for recrystallization, reprecipitation, and solvent washing include hydrocarbons such as hexane, heptane, cyclohexane, benzene, toluene, and xylene; halogenation such as dichloromethane, dichloroethane, chloroform, and tetrachloroethane. Hydrocarbons; ethers such as dioxane, diethyl ether, tetrahydrofuran, diisopropyl ether and ethylene glycol dimethyl ether; alcohols such as methanol, ethanol and isopropanol; esters such as ethyl acetate and butyl acetate; acetonitrile, isobutyronitrile and the like Nitriles; water and the like. These solvents can be used alone or in admixture of two or more at any ratio.
The amount of the solvent used may be set according to the target yield and purity, and is not particularly limited.

（式中、Ｒ^１、Ｒ^２、Ｘ、Ｙ、ｎ及びｍは、上記と同様の意味を表す） The 4,4-dibromo-3,4-dihydroisoquinoline compound represented by the general formula (II) is a compound represented by the following general formula (III) described in, for example, WO 2005/70917. It can be produced by reacting with an agent.

(Wherein R ¹ , R ² , X, Y, n and m represent the same meaning as described above)

Examples of the brominating agent include 1,3-dibromo-5,5-dimethylhydantoin and N-bromosuccinimide.
The amount of the brominating agent used is not particularly limited as long as the target reaction proceeds, and may be 2 equivalents or more in terms of bromine atoms. From an economical viewpoint, 2 equivalents or more and 4 equivalents or less are preferable in terms of bromine atoms.
When converting the compound represented by the general formula (III) to the compound represented by the general formula (II) with a brominating agent, a radical initiator such as a peracid or an azo compound or light irradiation is required. .
The radical initiator is not particularly limited as long as the intended bromination proceeds.
As peracids for radical initiators, diisobutyryl peroxide, cumylperoxyneodecanoate, di-n-propylperoxydicarbonate, diisopropylperoxydicarbonate, di-sec-butylperoxydicarbonate, 1,1 , 3,3-tetramethylbutylperoxyneodecanoate, di (4-t-butylcyclohexyl) peroxydicarbonate, di (2-ethylhexyl) peroxydicarbonate, t-hexylperoxyneodecanoate, t- Butylperoxyneodecanoate, t-butylperoxyneoheptanoate, t-hexylperoxypivalate, t-butylperoxypivalate, di (3,5,5-trimethylhexanoyl) peroxide, dilauryl peroxide, 1, 1,3,3- Tramethylbutylperoxy-2-ethylhexanoate, peroxydisuccinic acid, 2,5-dimethyl-2,5-di (2-ethylhexanoylperoxy) hexane, t-hexylperoxy-2-ethylhexanoate, Di (4-methylbenzoyl) peroxide, t-butylperoxy-2-ethylhexanoate, a mixture of di (3-methylbenzoyl) peroxide and benzoyl (3-methylbenzoyl) peroxide and dibenzoyl peroxide, dibenzoyl peroxide, 1 , 1-di (t-butylperoxy) -2-methylcyclohexane, 1,1-di (t-hexylperoxy) -3,3,5-trimethylcyclohexane and the like.
As a radical initiator azo compound, 2,2′-azobisisobutyronitrile, 2,2′-azobis (4-methoxy-2.4-dimethylvalenonitrile), 2,2′-azobis (2. 4-dimethylvalenonitrile), dimethyl 2,2′-azobis (2-methylpropionitrile), 2,2′-azobis (2-methylbutyronitrile), 1,1′-azobis (cyclohexane-1- Carbonitrile) and the like.
The amount of the radical initiator used is not particularly limited as long as the target reaction proceeds. From an economic viewpoint, 0.001 equivalent or more and 0.30 equivalent or less are preferable.
In carrying out the reaction with the brominating agent, a solvent can be used. Examples of the solvent include halogenated aromatic hydrocarbons such as chlorobenzene and dichlorobenzene; halogenated hydrocarbons such as carbon tetrachloride; hydrocarbons such as hexane, heptane, cyclohexane and methylcyclohexane; ethyl acetate and isopropyl acetate. And esters such as butyl acetate.
The amount of the solvent used for the reaction with the brominating agent is not particularly limited as long as the reaction proceeds, but it is 3 to 30 times by weight with respect to the compound represented by the general formula (III). Is preferred.
The reaction temperature with the brominating agent may be set according to the radical initiator, and is 30 ° C. or higher and 150 ° C. or lower than the boiling point of the solvent.
As a post-treatment of the reaction with the brominating agent, a by-product generated from the brominating agent (for example, 5,5-dimethylhydantoin in the case of 1,3-dibromo-5,5-dimethylhydantoin) is precipitated. In this case, the by-product can be removed by performing a filtration operation.
The reaction mixture containing the compound represented by the general formula (II) can be washed, reprecipitated or recrystallized with an appropriate solvent. Solvents used here include aromatic hydrocarbons such as toluene, xylene, benzene, chlorobenzene and dichlorobenzene; esters such as ethyl acetate, isopropyl acetate and butyl acetate; diethyl ether, diisopropyl ether and methyl-t- Examples include ethers such as butyl ether; halogenated hydrocarbons such as dichloromethane, dichloroethane, and chloroform; hydrocarbons such as hexane, heptane, cyclohexane, and methylcyclohexane. In addition, these solvents can be used alone, or two or more kinds of solvents can be mixed in an arbitrary ratio. In addition, it can be purified by column chromatography. What is necessary is just to implement suitably according to the target purity.

A compound represented by general formula (II) obtained by converting a compound represented by general formula (III) with a brominating agent is a compound represented by general formula (I) by reacting with water. Can be converted to
As described above, isoquinolin-4 (3H) -ones can be produced safely, simply and efficiently.

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

Example 1 (Production 1 of 3,3-dimethyl-1-quinolin-3-ylisoquinolin-4 (3H) -one represented by formula (I) 1)
Water (100 mL) was added to a solution of 3- (4,4-dibromo-3,3-dimethyl-3,4-dihydrotetrahydroisoquinolin-1-yl) quinoline (26.43 g, 59.5 mmol) in acetone (200 mL). The mixture was further stirred at room temperature for 3 hours. Acetone was distilled off under reduced pressure, and 10% aqueous sodium hydroxide solution was added dropwise until the remaining aqueous solution became alkaline. Extracted with methylene chloride, washed with water, and dried over anhydrous magnesium sulfate. Methylene chloride was distilled off under reduced pressure, and the resulting solid was washed with diethyl ether to obtain the title compound (15.10 g, yield 84.5%).
Physical property: mp 137 ° C.
1H-NMR (270 MHz, CDCl ₃ ) δ ppm: 1.62 (6H, s), 7.38-7.43 (1H, m), 7.58-7.68 (2H, m), 7.81 (1H, t, J = 8.2 Hz), 7.91 (1H, d, J = 7.9 Hz), 8.20 (1H, d, J = 7.1 Hz), 8.37 (1H, d, J = 2.1 Hz), 9.11 (1H, d, J = 2.1 Hz).
MS m / z: 300 (M +), 285, 271, 257, 244, 231, 216, 189, 149, 128, 107, 94.

Example 2 (Production 2 of 3,3-dimethyl-1-quinolin-3-ylisoquinolin-4 (3H) -one represented by general formula (I) 2)
Water (859 mL) was added to a solution of 3- (4,4-dibromo-3,3-dimethyl-3,4-dihydrotetrahydroisoquinolin-1-yl) quinoline (171.78 g, 386.8 mmol) in acetone (859 mL). The mixture was further stirred at room temperature for 1.5 hours. Acetone was distilled off under reduced pressure, toluene (1500 mL) and 10% aqueous sodium hydroxide solution (355 g) were added dropwise to the residue, and the mixture was stirred at room temperature for 30 minutes. After liquid separation, the aqueous layer was extracted with toluene, and the mixed toluene layer was washed with water. Toluene was distilled off under reduced pressure, and the residue was dried under reduced pressure to obtain the title compound (115.58 g, yield 97.4%).

Example 3 (Production of 1- (6-bromoquinolin-3-yl) -3,3-dimethylisoquinolin-4 (3H) -one represented by general formula (I))
A suspension of 6-bromo-3- (4,4-dibromo-3,3-dimethyl-3,4-dihydrotetrahydroisoquinolin-1-yl) quinoline (5.16 g, 9.87 mmol) in acetone (25 mL). Water (25 mL) was added to the mixture, and the mixture was stirred at room temperature for 6 hours and at 60 ° C. for 1 hour. The reaction mixture was cooled to 2 ° C., the precipitated solid was filtered, washed with water, and dried under reduced pressure to give the title compound (3.74 g, yield 99.9%).
1H-NMR (500 MHz, CDCl ₃ ) δ ppm: 1.62 (6H, s), 7.36-7.38 (1H, m), 7.71-7.73 (2H, m), 7.87 (1H, dd, J = 2.1 Hz, 8.9 Hz), 8.06-8.07 (2H, m), 8.19-8.21 (1H, m), 8.28 (1H, d, J = 2.1 Hz), 9.11 (1H, d, J = 2.1 Hz).

Reference Example (Production of 3- (4,4-dibromo-3,3-dimethyl-3,4-dihydrotetrahydroisoquinolin-1-yl) quinoline represented by general formula (II))
1,3-dibromo-5,5-dimethylhydantoin (176.83 g, 617 mmol), 3- (3,3-dimethyl-3,4-dihydrotetrahydroisoquinolin-1-yl) quinoline (166.01 g, purity 88 2,2′-azobisisobutyronitrile (4.23 g, 25.8 mmol) was added to a mixture of .9%, 515 mmol) and carbon tetrachloride (1,500 mL), and the mixture was heated to reflux for 2 hours. After standing to cool, the precipitated insoluble material was filtered off and washed with carbon tetrachloride. The filtrate was concentrated, the obtained residue was purified by silica gel column chromatography, and the obtained crystals were washed with diisopropyl ether to give the title compound (206.22 g, 464 mmol). Yield 90%.
¹ H-NMR (500 MHz, CDCl ₃ ) δ ppm: 1.38 (3H, brs), 2.09 (3H, brs), 7.24 (1H, d, J = 7.6 Hz), 7.43 ( 1H, t, J = 7.6 Hz), 7.63 (2H, t, J = 7.6 Hz), 7.81 (1H, d, J = 7.6 Hz), 7.90 (1H, d, J = 7.6 Hz), 8.22 (2H, d, J = 7.6 Hz), 8.39 (1H, s), 9.13 (1H, s).
MASS (EI) m / z: 444 (M +), 363, 316, 283, 269.

  According to the present invention, isoquinolin-4 (3H) -ones useful as agricultural and horticultural fungicides can be produced safely and simply at a high yield.

Claims (2)

Formula (I)

(Wherein R ¹ and R ² may be the same or different,
Represent the same or different one to three optionally substituted with a substituent C ₁ -C ₆ alkyl group selected from the group consisting of halogen atom and C ₁ -C ₆ alkoxy group,
X is a halogen atom;
Or C ₁ -C ₆ alkoxy group; the same or different may be substituted with 1-3 substituents _C 1 -C ₆ alkyl group selected from the group consisting of halogen atom and _C 1 -C ₆ alkoxy group Represent,
n represents an integer of 0 to 4,
when n is 2 to 4, X may be the same or different;
Y represents a group selected from the group consisting of halogen _atom, C 1 -C ₆ alkyl and _C 1 -C ₆ alkoxy group,
m represents an integer of 0 to 6)
A process for producing isoquinolin-4 (3H) -ones represented by:
The following general formula (II)

(Wherein R ¹ , R ² , X, Y, n and m represent the same meaning as described above)
A method for hydrolyzing a 4,4-dibromo-3,4-dihydroisoquinoline compound represented by the formula: In the general formula (I) and the general formula (II), R ¹ and R ² may represent the same or different C _{1 to} C ₆ alkyl group, X represents a halogen atom, and Y represents a halogen atom. The manufacturing method according to claim 1, wherein