JPH1045711A - Production of dithiocarbonimide derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To simply obtain the subject derivative having excellent plant disease control effect by reacting a ketoester compound with a dithiocarbamate compound in the presence of a base and passing through a ketoester derivative and a ketoamide derivative as reaction intermediates. SOLUTION: A ketoester compound represented by formula II (X is a halogen) is reacted with a dithiocarbamate compound represented by formula III in the presence of a base (e.g. potassium tert.-butoxy) in a solvent (e.g. tetrahydrofuran), normally at -10 to 60 deg.C for 0.5-10hr to provide the objective dithiocarbonimide derivative represented by formula I (R<1> is a 1-6C alkyl; R<2> and R<3> are each H, a 1-6C alkyl, a 1-6C alkoxy, etc.; Z is CH or N). The raw materials (compounds of formulas II and III) and the base are preferably used at an equimolar ratio.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a dithiocarbonimide derivative.

2. Description of the Related Art

 General formula 8

Embedded image [Wherein, R ² and R ³ are the same or different and each represent a hydrogen atom, a C1-C6 alkyl group, a halogen atom,
6 alkoxy group, C1-C6 haloalkyl group or C1
~C6 represent a haloalkoxy group, or represents R ² and R ³ and at which may be a methylenedioxy group substituted with a fluorine atom. Z represents a CH group or a nitrogen atom. ]
It has been described in JP-A-8-73424 that dithiocarbonimide derivatives and the like represented by the formula (1) have an excellent plant disease controlling effect, and it is desired to develop an advantageous production method of the compound.

[0002]

Means for Solving the Problems In view of the above situation, the present inventors have conducted intensive studies on a method for advantageously producing the dithiocarbonimide derivative represented by the above-mentioned general formula (8), and as a result, have shown the following general formula (9). By reacting the ketoester compound represented by the general formula (10) with a dithiocarbamate compound represented by the general formula (10) to form a ketoester derivative represented by the general formula (11), and then reacting the ketoester derivative with methylamine; After the ketoamide derivative represented by the general formula 12, the ketoamide derivative and O-
The present inventors have found that a dithiocarbonimide derivative represented by the general formula (8) can be easily produced by reacting with methylhydroxylamine or a salt thereof, thereby completing the present invention. That is, the present invention provides a compound represented by the general formula:

Embedded image [In the formula, X represents a halogen atom, and R ¹ represents a C1-C6 alkyl group. And a general formula

Embedded image [Wherein, R ² and R ³ are the same or different and each represent a hydrogen atom, a C1-C6 alkyl group, a halogen atom,
6 alkoxy group, C1-C6 haloalkyl group or C1
~C6 represent a haloalkoxy group, or represents R ² and R ³ and at which may be a methylenedioxy group substituted with a fluorine atom. Z represents a CH group or a nitrogen atom. ]
Is reacted with a dithiocarbamate compound represented by the following formula (hereinafter referred to as reaction 1) to give a compound represented by the general formula
1

Embedded image Wherein R ¹ , R ² , R ³ and Z have the same meaning as described above. And then reacting the ketoester derivative with methylamine (hereinafter referred to as reaction 2) to obtain a compound of the general formula

Embedded image Wherein R ² , R ³ and Z have the same meaning as described above. And then reacting the ketoamide derivative with O-methylhydroxylamine or a salt thereof (e.g., a salt with an inorganic acid such as a hydrochloride or a sulfate) (hereinafter referred to as reaction 3). ), Which provides a method for producing a dithiocarbonimide derivative represented by the above general formula (8). The present invention further provides a ketoester derivative represented by the above general formula 11 and a ketoamide derivative represented by the following general formula 12, which are useful as an intermediate for producing the dithiocarbonimide derivative represented by the above general formula 8.

[0003]

DETAILED DESCRIPTION OF THE INVENTION In the present invention, the halogen atom represented by X, refers to bromine, chlorine or iodine atom, examples of C1~C6 alkyl group represented by R ^1, a methyl group, an ethyl group , An isopropyl group, and the like. Examples of the C1-C6 alkyl group represented by R ² and R ³ include a methyl group and an ethyl group, and examples of the halogen atom include a fluorine atom and a chlorine atom.
Examples of the C1 to C6 alkoxy group include a methoxy group and an ethoxy group. Examples of the C1 to C6 haloalkyl group include a trifluoromethyl group. Examples of the C1 to C6 haloalkoxy group include a trifluoromethoxy group and the like. can give. In the present invention, preferred examples of X include a bromine atom and a chlorine atom, and examples of R ¹ include a methyl group, an ethyl group and an isopropyl group;
Examples of R ² include a methyl group, an ethyl group and a trifluoromethyl group, and examples of R ³ include a hydrogen atom.
Examples of Z include a CH group.

Hereinafter, Reaction 1 will be described in detail. Examples of the base used include alkoxides of alkali metals (potassium, sodium, etc.) such as potassium tert-butoxide, sodium methoxide, sodium ethoxide, sodium isopropoxide (eg, te)
C1 such as rt-butoxide, methoxide, ethoxide, etc.
Alkali metal hydrides such as C5 alkoxide) and sodium hydride; and alkali metal hydroxides such as sodium hydroxide and potassium hydroxide. The reaction is usually performed in a solvent, and the solvent used depends on the base used and the like. Examples thereof include ether solvents such as tetrahydrofuran (hereinafter referred to as THF), diethyl ether and dibutyl ether, methanol, ethanol and isopropanol. Alcohol solvents, aromatic hydrocarbon solvents such as toluene, xylene, and benzene; halogenated aromatic hydrocarbon solvents such as chlorobenzene and dichlorobenzene; aliphatic hydrocarbon solvents such as hexane and heptane;
Examples thereof include N-dimethylformamide, water and the like, or a mixed solvent thereof. The reaction temperature is usually −10 to 60 ° C., the reaction time is usually 0.5 to 10 hours, and the ratio of the starting materials and the base used for the reaction is equimolar or close to it (usually 1: 0.8 to 0. 8 to 1.0).
The reaction solution after the reaction is usually treated with, for example, water, aqueous ammonium chloride or dilute hydrochloric acid, and then the organic layer is concentrated, and if necessary, further purified by chromatography or the like to obtain the desired general formula. The ketoester derivative shown in 11 can be isolated. Examples of the ketoester derivative represented by the general formula 11 thus produced include N- (4-methylphenyl) -S-methyl-S- [2-
(Α-oxo-α-methoxycarbonyl) methyl] phenylmethyldithiocarbonimide N- (4-ethylphenyl) -S-methyl-S- [2-
(Α-oxo-α-methoxycarbonyl) methyl] phenylmethyldithiocarbonimide N- (4-trifluoromethylphenyl) -S-methyl-S- [2- (α-oxo-α-methoxycarbonyl)
Methyl] phenylmethyldithiocarbonimide N- (4-methylphenyl) -S-methyl-S- [2-
(Α-oxo-α-ethoxycarbonyl) methyl] phenylmethyldithiocarbonimide N- (4-ethylphenyl) -S-methyl-S- [2-
(Α-oxo-α-ethoxycarbonyl) methyl] phenylmethyldithiocarbonimide N- (4-trifluoromethylphenyl) -S-methyl-S- [2- (α-oxo-α-ethoxycarbonyl)
Methyl] phenylmethyldithiocarbonimide N- (4-methylphenyl) -S-methyl-S- [2-
(Α-oxo-α-isopropoxycarbonyl) methyl] phenylmethyldithiocarbonimide N- (4-ethylphenyl) -S-methyl-S- [2-
(Α-oxo-α-isopropoxycarbonyl) methyl] phenylmethyldithiocarbonimide N- (4-trifluoromethylphenyl) -S-methyl-S- [2- (α-oxo-α-isopropoxycarbonyl) methyl Phenylmethyldithiocarbonimide, etc.

The ketoester compound represented by the general formula 9 used as a starting compound in the reaction 1 includes, for example, methyl 2- (bromomethyl) benzoylformate ethyl 2- (bromomethyl) benzoylformate 2-isopropyl (bromomethyl) benzoylformate Methyl 2- (chloromethyl) benzoyl formate 2- (chloromethyl) benzoyl formate Ethyl 2- (chloromethyl) benzoyl formate and the like. These compounds are described, for example, in the following scheme.

Embedded image [Wherein, NXS represents N-halogenosuccinimide (N-bromosuccinimide, N-chlorosuccinimide or N-iodosuccinimide), and RI represents benzoyl peroxide (BPO) or azobisisobutyronitrile. Represents a radical initiator, and R ¹ has the same meaning as described above. ].

Examples of the dithiocarbamate compound represented by the general formula 10 used as the other starting compound in Reaction 1 include, for example, methyl 4-methylphenyldithiocarbamate 4-methylphenyldithiocarbamate 4-trifluoromethylphenyl Methyl dithiocarbamate and the like. These compounds are described, for example, in the following scheme.

Embedded image Wherein R ² , R ³ and Z have the same meaning as described above. ].

Hereinafter, Reaction 2 will be described in detail. The reaction is usually performed in a solvent. Examples of the solvent used include alcohol solvents such as methanol, ethanol and isopropanol, ether solvents such as THF, diethyl ether and dibutyl ether, and aromatic hydrocarbon solvents such as toluene, xylene and benzene. , Chlorobenzene, dichlorobenzene and the like, halogenated aromatic hydrocarbon solvents such as hexane, heptane and the like, N, N-dimethylformamide, water and the like, or a mixed solvent thereof. The reaction temperature is usually −10 to 60 ° C., the reaction time is usually 0.5 to 10 hours, and the ratio of methylamine used in the reaction is usually 1 to 10 mol per 1 mol of the ketoester derivative represented by the general formula (11). Is the ratio of The reaction solution after the reaction is usually concentrated, and if necessary, further purified operations such as recrystallization and chromatography can isolate the desired ketoamide derivative represented by the general formula (12). General formula produced in this way
As an example of the ketoamide derivative represented by Chemical formula 12, N- (4-methylphenyl) -S-methyl-S- {2-}
[Α-oxo-α- (N-methylcarbamoyl)] methyl} phenylmethyldithiocarbonimide N- (4-ethylphenyl) -S-methyl-S- {2-
[Α-oxo-α- (N-methylcarbamoyl)] methyl} phenylmethyldithiocarbonimide N- (4-trifluoromethylphenyl) -S-methyl-S- {2- [α-oxo-α- (N -Methylcarbamoyl)] methyl} phenylmethyldithiocarbonimide.

Hereinafter, Reaction 3 will be described in detail. The reaction is usually performed in a solvent. Examples of the solvent used include alcohol solvents such as pyridine, methanol, ethanol and isopropanol, THF, diethyl ether, and the like.
Ether solvents such as dibutyl ether; aromatic hydrocarbon solvents such as toluene, xylene and benzene; halogenated aromatic hydrocarbon solvents such as chlorobenzene and dichlorobenzene; aliphatic hydrocarbon solvents such as hexane and heptane;
Examples thereof include N-dimethylformamide, water and the like, or a mixed solvent thereof. The reaction temperature is usually −10 to 60 ° C., the reaction time is generally 0.5 to 10 hours, and the ratio of O-methylhydroxylamine or a salt thereof used in the reaction is based on 1 mol of the ketoamide derivative represented by the general formula. , Usually 1 to 2 moles. When a salt of O-methylhydroxylamine is used in the reaction, the salt 1
One or more moles of base are used per mole. Examples of such a base include organic bases such as pyridine and sodium acetate, and inorganic bases such as sodium carbonate, potassium carbonate and sodium hydrogen carbonate. The reaction solution after the reaction is usually treated with, for example, water, aqueous ammonium chloride or dilute hydrochloric acid, and then the organic layer is concentrated.If necessary, recrystallization, chromatography, and other purification operations are performed to obtain the desired solution. The dithiocarbonimide derivative represented by the general formula 8 can be isolated. Examples of the dithiocarbonimide derivative represented by the general formula 8 produced as described above include N- (4-methylphenyl) -S-methyl-S- ｛2-
[Α-methoxyimino-α- (N-methylcarbamoyl)] methyl} phenylmethyldithiocarbonimide N- (4-ethylphenyl) -S-methyl-S- {2-
[Α-methoxyimino-α- (N-methylcarbamoyl)] methyl} phenylmethyldithiocarbonimide N- (4-trifluoromethylphenyl) -S-methyl-S- {2- [α-methoxyimino-α- (N-methylcarbamoyl)] methyl} phenylmethyldithiocarbonimide.

[0009]

The present invention will be described in more detail with reference to the following production examples.
However, the present invention is not limited to only these examples.
No. Production Example 1 (1) Ethyl 2- (bromomethyl) benzoylformate
(5.0 g) in a THF solution (50 ml).
Methyl enyldithiocarbamate (3.9 g) was added.
Was. Under ice cooling, add potassium tert-butoxide
(2.2 g) was added slowly, and the mixture was stirred for 1 hour under ice cooling.
Thereafter, it was further heated at 50 ° C. for 1 hour. Bring reaction to room temperature
After cooling, water and ethyl acetate were added thereto, and the layers were separated. Organic
After washing the layer with water, drying over anhydrous magnesium sulfate and concentration
An oil was obtained. This is a silica gel column chromatograph
(Eluent: hexane: ethyl acetate = 10: 1)
And the desired N- (4-ethylphenyl) -S-methyl
Ru-S- [2- (α-oxo-α-ethoxycarboni
Ru) methyl] phenylmethyldithiocarbonimide
(5.8 g, 78% yield).¹ H-NMR (CDCl_Three/ TMS, 300MH_z,δ (ppm)) 1.23 (3H, t, J = 8H
 _z), 1.40 (3H, t, J = 7H_z), 2.43 (3H, s), 2.63 (2
H, q, J = 8H_z), 4.42 (2H, q, J = 7H_z), 4.70 (2H, s),
 6.76 (2H, d, J = 8H_z), 7.17 (2H, d, J = 8H_z ), 7.3-7.
8 (4H, m) (2) N- (4-ethylphenyl) -S-methyl-S
-(2- (α-oxo-α-ethoxycarbonyl) methyl
R) phenylmethyldithiocarbonimide (4.0 g)
40% methylamine solution in methanol solution (20 ml)
A ethanol solution (3.9 g) was added, and the mixture was stirred at room temperature for 2 hours.
Was. The reaction solution was concentrated under reduced pressure to obtain an oil. This
Ricagel column chromatography (eluent; hexa
And ethyl acetate = 2: 1) to give the desired N- (4
-Ethylphenyl) -S-methyl-S- {2- [α-O
Oxo-α- (N-methylcarbamoyl)] methyldiphenyl
Nylmethyldithiocarbonimide (3.3 g, yield 87)
%).¹ H-NMR (CDCl_Three/ TMS, 300MH_z,δ (ppm)) 1.22 (3H, t, J = 7.5H
_z), 2.40 (3H, s), 2.61 (2H, q, J = 7.5H_z), 2.87
(3H, d, J = 5H_z), 4.55 (2H, s), 6.74 (2H, d, J = 8H _z),
 7.08 (1H, brs), 7.13 (2H, d, J = 8H_z ), 7.3 to 8.0 (4H,
m) (3) O-methylhydroxylamine hydrochloride (0.8
7g) in a pyridine solution (5 ml) at room temperature.
Tylphenyl) -S-methyl-S- ｛2- [α-oxo
-Α- (N-methylcarbamoyl)] methyldiphenyl
Methyldithiocarbonimide (2.0 g) was added all at once.
And stirred at room temperature for 2 hours. PH becomes acidic in the reaction solution
1N aqueous hydrochloric acid was added until the mixture was added.
did. After washing the organic layer with saline, anhydrous magnesium sulfate
And concentrated under reduced pressure to give a yellow oil. this
To silica gel column chromatography (eluent;
Sun: ethyl acetate = 2: 1) to give the desired N-
(4-ethylphenyl) -S-methyl-S- {2- [α
-Methoxyimino-α- (N-methylcarbamoyl)]
Methyl diphenylmethyldithiocarbonimide (1.1
g, yield 52%) from a mixture of E-form: Z-form = about 9: 4
As obtained.¹ H-NMR (CDCl_Three/ TMS, 300MH_z,δ (ppm)) E-form: 1.21 (3H, t, J = 8H_z), 2.42 (3H, s), 2.63
(2H, q, J = 8H_z), 2.84 (3H, d, J = 6H_z), 3.90 (3H,
s), 4.18 (2H, s), 6.69 (2H, d, J = 8H_z), 7.13 (2H, d,
J = 8H_z ), 7.2 to 7.7 (5H, m) Z-form: 1.21 (3H, t, J = 7.5H)_z), 2.46 (3H, s), 2.6
0 (2H, q, J = 7.5H_z), 2.75 (3H, d, J = 5H_z), 4.01 (3H,
s), 4.54 (2H, s), 6.73 (2H, d, J = 8H_z), 7.13 (2H, d,
J = 8H_z ), 7.2 to 7.7 (5H, m).
-(4-ethylphenyl) -S-methyl-S-Ｓ2-
[Α-oxo-α- (N-methylcarbamoyl)] methyl
Ruphenylphenyldithiocarbonimide (0.9 g; 4
3%).

Next, an example of the production of a ketoester compound represented by the general formula 9 and used as one of the starting compounds in Reaction 1 will be described. Reference Production Example 1 A solution of diethyl oxalate (30 g) in anhydrous THF (300 ml) was cooled to −30 ° C., and a THF solution of o-tolylmagnesium chloride (1 M, 140 ml) was added at a reaction solution temperature of −20 ° C. or lower. After stirring at −30 ° C. for 30 minutes, the temperature was raised to 0 ° C., and an aqueous ammonium chloride solution was added. This was concentrated under reduced pressure, and water and diethyl ether were added to the residue to carry out liquid separation. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated to obtain a yellow oil. This was subjected to silica gel column chromatography (eluent; hexane: ethyl acetate = 10: 1) to give the desired 2
-Ethyl methylbenzoylformate (18 g, 87% yield)
I got ¹ H-NMR (CDCl ₃ / TMS, 300 MHz _, δ (ppm)) 1.42 (3H, t, J = 6H
_{z), 2.62 (3H, s} ), 4.45 (2H, q, J = 6H z), 7.2~
8.2 (4H, m) N-bromosuccinimide (1) was added to a solution of ethyl 2-methylbenzoylformate (10 g) in carbon tetrachloride (200 ml).
0 g) and 25% aqueous benzoyl peroxide (1 g) were added, and the mixture was heated under reflux for 2 hours. The reaction solution was cooled with ice water and filtered through celite. The filtrate was concentrated under reduced pressure to give a yellow oil. This was subjected to silica gel column chromatography (eluent; hexane: ethyl acetate = 20: 1),
Thus, ethyl 2- (bromomethyl) benzoylformate (6.1 g, yield 43%) was obtained. ¹ H-NMR (CDCl ₃ / TMS, 300 MHz _, δ (ppm)) 1.42 (3H, t, J = 6H
_{z), 4.44 (2H, q} , J = 6H z), 4.88 (2H, s), 7.2~8.
2 (4H, m) In addition, by further eluting with the above eluate, 2
-Ethyl methylbenzoyl formate (4 g; 40%) was recovered. Reference Production Example 2 A chlorobenzene solution (50 ml) of ethyl 2-methylbenzoylformate (10 g) was heated to 60 ° C., and a chlorobenzene solution (20 ml) of bromine (10 g) was added thereto.
A chlorobenzene suspension (10 ml) of 5% aqueous benzoyl peroxide (1 g) was added over 2 hours, and the mixture was further heated under reflux for 1 hour. The reaction solution was concentrated under reduced pressure to obtain a yellow oil. This was subjected to silica gel column chromatography (eluent; hexane: ethyl acetate = 20: 1) to obtain ethyl 2- (bromomethyl) benzoylformate (1.4 g, yield 10%). In addition, by further eluting with the above eluate, ethyl 2-methylbenzoylformate (6.3 g; 63%) as a raw material was recovered.

Next, a production example of a dithiocarbamate compound represented by the general formula (10), which is used as the other starting compound in Reaction 1, is shown. Carbon disulfide (6 g) and triethylamine (13 g) were added to a diethyl ether solution (40 ml) of 4-ethylaniline (7.8 g). After stirring at room temperature for 2 hours, the precipitated crystals were taken out by filtration and dried. The crystals (16 g) were added to methanol (100 ml).
And methyl iodide (7.6 g) was added dropwise thereto. After stirring at room temperature for 2 hours, 1N hydrochloric acid was added to make the mixture acidic (pH: about 2), and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a solid. Hexane was added thereto, and the mixture was pulverized, filtered and dried to obtain the desired methyl 4-ethylphenyldithiocarbamate (9.5 g, yield 67%). mp 78 ° C

Claims (6)

[Claims] 1. A compound represented by the general formula: [In the formula, X represents a halogen atom, and R ¹ represents a C1-C6 alkyl group. And a ketoester compound represented by the general formula: [Wherein, R ² and R ³ are the same or different and each represent a hydrogen atom, a C1-C6 alkyl group, a halogen atom,
6 alkoxy group, C1-C6 haloalkyl group or C1
~C6 represent a haloalkoxy group, or represents R ² and R ³ and at which may be a methylenedioxy group substituted with a fluorine atom. Z represents a CH group or a nitrogen atom. ]
Is reacted in the presence of a base with a dithiocarbamate compound represented by the general formula 3 Wherein R ¹ , R ² , R ³ and Z have the same meaning as described above. And then reacting the keto ester derivative with methylamine to obtain a keto ester derivative represented by the general formula: Wherein R ² , R ³ and Z have the same meaning as described above. Wherein the ketoamide derivative is reacted with O-methylhydroxylamine or a salt thereof, wherein the ketoamide derivative is reacted with O-methylhydroxylamine or a salt thereof. Wherein R ² , R ³ and Z have the same meaning as described above. ] The method for producing a dithiocarbonimide derivative represented by the formula: (2) R ¹ is a methyl group, an ethyl group or an isopropyl group, R ² is a methyl group, an ethyl group or a trifluoromethyl group, R ³ is a hydrogen atom, and Z is
The method according to claim 1, which is an H group. 3. A compound represented by the general formula: [Wherein, R ¹ represents a C1-C6 alkyl group, R ² and R ³ are the same or different and are each a hydrogen atom, C1-C6
Alkyl group, halogen atom, C1-C6 alkoxy group,
It represents a C1 to C6 haloalkyl group or a C1 to C6 haloalkoxy group, or a methylenedioxy group which may be substituted with a fluorine atom for R ² and R ³ .
Z represents a CH group or a nitrogen atom. And a ketoester derivative represented by the formula: 4. R ¹ is methyl, ethyl or isopropyl, R ² is methyl, ethyl or trifluoromethyl, R ³ is hydrogen, Z is C
The ketoester derivative according to claim 3, which is an H group. 5. A compound represented by the general formula: [Wherein, R ² and R ³ are the same or different and each represent a hydrogen atom, a C1-C6 alkyl group, a halogen atom,
6 alkoxy group, C1-C6 haloalkyl group or C1
~C6 represent a haloalkoxy group, or represents R ² and R ³ and at which may be a methylenedioxy group substituted with a fluorine atom. Z represents a CH group or a nitrogen atom. ]
A ketoamide derivative represented by the formula: (6) R ² is a methyl group, an ethyl group or a trifluoromethyl group, R ³ is a hydrogen atom, and Z is CH
The ketoamide derivative according to claim 5, which is a group.