JP2001328983A - Method for producing disubstituted nitroguanidine - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing a disubstituted nitroguanidine industrially easily in high yield. SOLUTION: This method for producing a disubstituted nitroguanidine of the general formula (2) (wherein, R1 is a 1-3C alkyl) comprises the following process: the corresponding monosubstituted nitroguanidine as raw material is subjected to triazine cyclization in water followed by alkylation in an organic solvent and then triazine splitting reaction in an organic solvent; wherein the above reactions are carried out continuously without any intermediate isolation operations.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a novel method for producing disubstituted nitroguanidines. More specifically, equation (1)

[0002]

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Using a monosubstituted nitroguanidine represented by the following formula as a raw material, a triazine cyclization reaction in water, an alkylation reaction in an organic solvent, and a triazine decomposition reaction in an organic solvent are performed to obtain a compound represented by the general formula (2).

[0004]

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In the method for producing a disubstituted nitroguanidine represented by the formula (1) wherein R1 represents a saturated or unsaturated alkyl group having 1 to 3 carbon atoms, a compound represented by the formula (1) General formula (3) formed by a triazine cyclization reaction

[0006]

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(Wherein R 2 represents an alkyl group having 1 to 6 carbon atoms), and a compound represented by the general formula (3) produced by an alkylation reaction of a compound represented by the general formula (3): 4)

[0008]

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(Wherein R1 and R2 have the same meanings as described above)
This is a method for producing a disubstituted nitroguanidine represented by the general formula (2) by a continuous reaction.

[0010]

2. Description of the Related Art It is well known that certain nitroguanidines are useful as pesticides (especially insecticides) or intermediates thereof (JP-A-2-288860,
JP-A-3-109374, JP-A-3-15730
No. 8, JP-A-7-179448, etc.).

The compounds represented by the formulas (1), (2), (3) and (4) are disclosed in
Japanese Patent Application Laid-Open Nos. 045739, 10-0475555, 9-227532 and 11-23
It is manufactured by a method described in JP-A-6381.

The disubstituted nitroguanidine represented by the general formula (2) can be obtained by the following method. A triazine cyclization reaction is performed using the monosubstituted nitroguanidine represented by the formula (1) as a raw material to synthesize a disubstituted triazine represented by the general formula (3), and an alkylation reaction of the obtained disubstituted triazine is performed. A trisubstituted triazine represented by the general formula (4) is synthesized. Subsequently, the obtained trisubstituted triazine is synthesized by decomposition using an acidic aqueous solution or ammonia, a primary or secondary amine, or a salt thereof. In the case where the disubstituted nitroguanidine represented by the general formula (2) is produced by the method shown above, the trisubstituted triazine represented by the general formula (4), which is an intermediate, is prepared by reacting with water and a basic substance. The reaction solution containing the trisubstituted triazine represented by the general formula (4) contains water generated by the alkylation reaction and a surplus base of the reaction. Normal,
The trisubstituted triazine represented by the general formula (4) can be easily isolated as a crystal by concentrating the reaction solvent, but is caused by decomposition due to the influence of water and a base present in the reaction solution during the isolation operation. As a result, the isolation yield is reduced, and in the decomposition reaction, the nitroimino group is also decomposed in addition to the decomposition of the triazine ring, so that the mass balance of the reaction system is deteriorated.

[0013]

The problem to be solved by the present invention is to use monosubstituted nitroguanidine as a raw material.
In a three-step reaction of triazine cyclization, alkylation and triazine decomposition via 1,5-disubstituted-2-nitroiminohexahydrotriazine and 1,3,5-trisubstituted-2-nitroiminohexahydrotriazine, It is an object of the present invention to provide a method capable of industrially easily producing a substituted nitroguanidine in high yield.

[0014]

Means for Solving the Problems The inventors of the present invention have used 1,5-disubstituted-2-nitroiminohexahydrotriazine, 1,3,5-trisubstituted-2-nitro as starting materials for monosubstituted nitroguanidine. Triazine cyclization, alkylation, and triazine decomposition via iminohexahydrotriazine
As a result of intensive studies on a method for producing a disubstituted nitroguanidine by a step reaction, the 1,5
By unifying the solvent used for the purification of disubstituted-2-nitroiminohexahydrotriazine, the alkylation reaction, and the solvent used for the triazine decomposition reaction, the isolation operation of the intermediate di- and tri-substituted triazines can be performed. Finding a method to carry out three reactions continuously without performing it, economically,
In addition, they have found that a high-quality object can be obtained, and have completed the present invention.

That is, the present invention provides:

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Using a monosubstituted nitroguanidine represented by the following formula as a raw material, a triazine cyclization reaction in water, an alkylation reaction in an organic solvent, and a triazine decomposition reaction in an organic solvent are performed to obtain a compound represented by the general formula (2).

[0017]

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(In the formula, R1 represents a saturated or unsaturated alkyl group having 1 to 3 carbon atoms.) In a method for producing a disubstituted nitroguanidine represented by the formula: A method for producing a disubstituted nitroguanidine represented by the general formula (2) by a continuous reaction without performing an intermediate isolation operation by using the same solvent for the alkylation reaction and the triazine decomposition reaction To provide.

[0019]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail.
In a specific embodiment of the present invention, three reactions are carried out, for example, by the following methods to produce a disubstituted nitroguanidine without performing an operation of isolating a disubstituted and trisubstituted triazine intermediate.

1) The first step of the triazine cyclization of the monosubstituted nitroguanidine is performed in water, and the disubstituted triazine crystals generated by the reaction are subjected to solvent extraction. The solution of the disubstituted triazine obtained is used in step 2).

2) A second-stage alkylation reaction is performed by adding an alkylating agent and a base to the disubstituted triazine solution.
The obtained trisubstituted triazine solution is used in operation 3).

3) A decomposition reaction of the trisubstituted triazine solution is performed, and a disubstituted nitroguanidine is isolated from the obtained reaction solution to obtain an intended product.

R1 in the above general formulas (2), (3) and (4) is a saturated or unsaturated alkyl group having 1 to 3 carbon atoms, such as a methyl group, an ethyl group or an n-propyl group. ,
An allyl group or a propargyl group, and R2 has 1 carbon atom.
To 6 alkyl groups, for example, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group,
And a cyclohexyl group.

The three-step reaction can be carried out in more detail by the following method. Reaction I. Triazine cyclization reaction In the triazine cyclization reaction of the monosubstituted nitroguanidine represented by the formula (1), water is used as a reaction solvent and amines are reacted with formaldehyde. After completion of the reaction, the generated disubstituted triazine represented by the general formula (3) is extracted using a solvent, and the next step is performed using the obtained extract.

The amines used in the reaction are represented by the general formula (5)

Embedded image (Wherein, R 2 has the same meaning as described above), and specific examples include methylamine, ethylamine, n-propylamine, isopropylamine, n-butylamine, and cyclohexylamine.

The number of equivalents of the amines used in the reaction is usually at least 1 equivalent, preferably 1 to 2 equivalents, more preferably 1 to 1 equivalent to the monosubstituted nitroguanidine represented by the formula (1). 5 equivalents.

The number of equivalents of the formaldehyde used is usually at least 2 equivalents, preferably 2 to 4 equivalents, more preferably 2 to 3 equivalents to the monosubstituted nitroguanidine represented by the formula (1).

Although formaldehyde is usually used in the form of an aqueous solution, it may be used after increasing the concentration by adding methanol. Usually 25 to 40% is used.

The order of addition is not limited, but it is preferable to add amines dropwise because the reaction is exothermic.

Water is usually used as a reaction solvent. The amount to be used may be any amount as long as stirring is possible, but usually the formula (1)
1 to 50 relative to the monosubstituted nitroguanidine represented by
The weight is 1 times, preferably 1 to 10 times the weight.

The reaction temperature and the reaction temperature can be varied over a wide range. Generally, the reaction temperature is 0 to 50 ° C, preferably 10 to 40 ° C. The reaction time is generally from 0.01 to 50 hours, preferably from 0.1 to 24 hours.

The solvent used for the extraction can be used as long as it can be separated from water and can dissolve the disubstituted triazine represented by the general formula (3), which is the reaction product. Aliphatic halogenated hydrocarbon solvents are preferred in view of the solubility of the disubstituted triazine represented by (3) and suitability as a solvent for the subsequent reaction. As the aliphatic halogenated hydrocarbon solvent, one having 1 to 2 carbon atoms is usually used. Specifically, dichloromethane, chloroform, carbon tetrachloride, 1,2
-Dichloroethane and the like, preferably dichloromethane.

Since the surplus amine used in the reaction remains in the reaction solution, the amine is mixed in the extract obtained by the extraction, which affects the second-stage alkylation reaction of the disubstituted triazine. Sometimes. In such a case, by extracting the amines to the aqueous layer side by adjusting the pH of the reaction solution using an acidic aqueous solution at the time of extraction, it is possible to prevent amines from being mixed into the extract. . Examples of the acidic aqueous solution used for pH adjustment include an aqueous solution of a mineral acid, specifically, aqueous sulfuric acid, aqueous hydrochloric acid, aqueous phosphoric acid, and the like. When performing the extraction operation, sodium chloride,
By adding inorganic salts such as sodium sulfate, the extraction efficiency can be increased.

Reaction II. Alkylation reaction In the alkylation reaction of the disubstituted triazine represented by the general formula (3), a base and an alkylating agent are used using the extract of the disubstituted triazine obtained by the reaction I as a raw material. Using the trisubstituted triazine solution represented by the general formula (4) obtained by the reaction, the reaction of the next step is performed in a solution state without performing an isolation operation.

As the base used in the reaction, alkali metal hydroxides are used. Specifically, lithium hydroxide,
Examples include sodium hydroxide and potassium hydroxide. The alkali metal hydroxide used is usually at least 1 equivalent, preferably 1 to 3 equivalents, more preferably 1 equivalent to the disubstituted triazine represented by the general formula (3).
To 2 equivalents.

Specific examples of the alkylating agent include dimethyl sulfate, diethyl sulfate, methyl methanesulfonate, ethyl methanesulfonate, methyl ethanesulfonate, ethyl ethanesulfonate, methyl trifluoromethanesulfonate, and trifluoromethanesulfonate. Ethyl, methyl propanesulfonate, methyl isopropylsulfonate, methyl isopropylsulfonate, methyl isopropylsulfonate, methyl benzenesulfonate, n-propyl benzenesulfonate, methyl 4-chlorophenylsulfonate, and the like.

The amount of the alkylating agent used is determined by the general formula (3)
Is usually 1 to 2 equivalents, more preferably 1 to 1.5 equivalents, to the disubstituted triazine represented by

The order of addition of the base and the alkylating agent is not limited, but it is preferable to use the last one because of the properties of the base and the alkylating agent.

The reaction temperature and the reaction temperature can be varied over a wide range. Generally, the reaction temperature is from -30 to 50C, preferably from -15 to 40C. The reaction time is generally from 0.01 to 50 hours, preferably from 0.1 to 2 hours.
4 hours. The operation of isolating the trisubstituted triazine represented by the general formula (4) from the reaction solution is not performed, but salts produced as a by-product of the reaction can be removed by filtration or the like.

Reaction III. Triazine Decomposition Reaction The decomposition of the trisubstituted triazine represented by the general formula (4) is carried out by using a reaction solution containing the trisubstituted triazine obtained in Reaction II or a washing solution obtained by filtration thereof as a raw material, using ammonia, primary, secondary, This is performed by a decomposition reaction using a secondary amine or a salt thereof. These may be used in combination of two or more. The reaction can be carried out by adding a reaction assistant to the reaction solution.

As the reactant, ammonia, aliphatic linear amine and aliphatic cyclic amine are preferred, and ammonia is particularly preferred.

Specific examples of primary and secondary amines used include methylamine, ethylamine, n-propylamine, isopropylamine, n-butylamine, cyclohexylamine, benzylamine, allylamine, aniline, phenethylamine, toluidine, Examples include ethylenediamine, benzylmethylamine, pyrrolidine, piperidine, piperazine, morpholine and the like. Ammonia or amines can be used as mineral salts such as hydrochloric acid, sulfuric acid, phosphoric acid, etc., organic carboxylate salts such as formic acid and acetic acid, sulfonic acid salts such as methanesulfonic acid and toluenesulfonic acid. Both anhydrous and hydrated can be used.

The amount of ammonia and amine used is based on the amount of trisubstituted nitroguanidine represented by the general formula (4).
It is usually at least 0.1 molar equivalent, preferably at least 0.5 molar equivalent.

The reaction can be carried out at normal pressure or under pressure. The reaction temperature is usually 0 ° C. or higher, preferably 70 ° C.
C. to 100.degree. The reaction time is generally between 0.1 hour and 7 days, preferably between 1 hour and 24 hours.

As the reaction aid, water and alcohols can be used. Examples of alcohols to be used include methanol, ethanol, n-propyl alcohol, isopropyl alcohol, n-butanol and the like, and preferably methanol.

The amount of alcohol and water to be added to the reaction system as a reaction aid is usually 0.1 mole equivalent or more, preferably 0.5 mole, relative to the trisubstituted nitroguanidine represented by the general formula (4). Equivalent to 1.0 molar equivalent.

The post-treatment after the reaction can be carried out according to a conventional method. For example, after washing the reaction solution with water as needed, a crystallization operation can be performed to take out the target product. Further, if necessary, after removing salts by filtration or the like, the target substance can be taken out using silica gel column chromatography or the like. Purification such as water washing, activated carbon treatment, ion exchange resin treatment, recrystallization and the like can be performed as necessary to obtain a highly purified product.

Formula (1), General formulas (2), (3), (4)
The compound having a nitroimino group represented by is syn-,
It can exist as an anti-structural isomer as well as a tautomer. Formulas (1), (2), (3), and (4) have an asymmetric carbon derived from a 3-tetrahydrofuryl group, and can exist as an optically active substance, a racemate, and a mixture in any ratio. . The present invention is also applicable to all isomers and tautomers of this type, and mixtures thereof in any proportion.

The method of the present invention has the following advantages as compared with the prior art method for producing disubstituted nitroguanidine via disubstituted triazine and trisubstituted triazine using monosubstituted nitroguanidine as a raw material. 1) In the prior art, in order to carry out the isolation operation of the trisubstituted triazine, water existing in the reaction solution at the time of solvent concentration and crystallization operation,
Decomposition occurs due to the influence of the base, resulting in a decrease in the isolation yield and a deterioration in the material balance. In the present invention, by performing the reaction without performing the isolation operation, it is possible to reduce the loss of the trisubstituted triazine due to the isolation operation.

2) Since the disubstituted triazine is a reaction in an aqueous solvent, the disubstituted triazine produced by the reaction is precipitated as crystals. The precipitated crystals can be removed by filtration, but the water solubility of the disubstituted triazine cannot be isolated. In the present invention, by performing solvent extraction, it is possible to reduce disubstituted triazine in wastewater. In addition, when the extract is concentrated and the crystallization is isolated after the solvent extraction, there is a loss in the crystallization filtrate. Therefore, in the present invention, crystallization loss can be reduced by not performing crystallization.

3) In the present invention, since the di-substituted triazine and the tri-substituted triazine are not isolated, the operation can be simplified, which is advantageous as an industrial production method, and the working time can be reduced. Example 1 and Comparative Example 3 for item 1)
Thus, item 2) can be confirmed by Example 1, Comparative Example 1, and Comparative Example 2, and item 3) can be confirmed by Example and Comparative Example 1, Comparative Example 2, Comparative Example 3, and Comparative Example 4.

[0052]

EXAMPLES The present invention will be specifically described below with reference to examples and comparative examples. Example 1 Reaction I) To a suspension of (3-tetrahydrofuryl) methylnitroguanidine (169.4 g) in water (60 g) was added 3
A 7% aqueous solution of formalin (160.7 g) was added and mixed with stirring. Then, isopropylamine (58.5 g) was added dropwise at 35 ° C. over 1 hour with stirring. After reacting at 35 ° C. for 3 hours, the reaction solution was cooled to 20 ° C. Dichloromethane (1110 g) was added to the reaction solution, and the mixture was stirred and mixed, and the pH was measured to be 9.9. The pH of the mixture was adjusted to 7.4 using 20% aqueous sulfuric acid, and the mixture was stirred for 1 hour. After separation, the aqueous layer obtained was extracted with dichloromethane (278 g), and the obtained extract and the organic layer obtained by the first liquid separation were mixed, and 1- (3-tetrahydrofuryl) methyl- 5-isopropyl-2-nitroiminohexahydro-1,3,5-hexahydrotriazine (concentration 14.1)
%, A content of 239.9 g) in dichloromethane solution (1699 g) was obtained (reaction yield: 98.7%).

Reaction II) 1- (3-
Tetrahydrofuryl) methyl-5-isopropyl-2-
A dichloromethane solution (1699 g) containing nitroiminohexahydro-1,3,5-hexahydrotriazine (concentration 14.1%, content 239.9 g) was cooled to 0 ° C., and dimethyl sulfate (133.2 g) was added. 0 ° C under stirring
, 95% potassium hydroxide (17.3 g) was added four times at 30 minute intervals. After the completion of the addition of potassium hydroxide, the reaction was carried out at 0 ° C. for 3 hours. After completion of the reaction, crystals of monomethylpotassium sulfate produced as a by-product were removed by filtration, and the filtration residue was washed with dichloromethane (360 g). The resulting filtrate,
The washings were mixed and 1- (3-tetrahydrofuryl) methyl-3-methyl-5-isopropyl-2-nitroimino-
1,3,5-hexahydrotriazine (concentration 13.1)
%, A content of 243.7 g) in a dichloromethane solution (18
55 g) (reaction yield: 97.1%).

Reaction III) 1- (3-
Methanol (8.7) was added to a dichloromethane solution (500 g) of tetrahydrofuryl) methyl-3-methyl-5-isopropyl-2-nitroimino-1,3,5-hexahydrotriazine (concentration 13.1%, content 70.6 g). 0
g), and after replacing the reactor with nitrogen, ammonia (3.
0 g) and reacted at 85 ° C. for 6 hours. The obtained reaction solution (488 g) contained 49.7 g of 1- (3-tetrahydrofuryl) methyl-3-methyl-2-nitroguanidine, which was the target substance (reaction yield: 98.4).
%). The reaction solution was washed with 20% aqueous sulfuric acid (225 g) and re-extracted four times with dichloromethane (750 g).
A dichloromethane solution containing 48.1 g of the desired product was added to 39
14 g were obtained (extraction yield 96.7%). The obtained dichloromethane solution was concentrated until the concentration of the target substance became about 35%, ethyl acetate (193 g) was added at 40 ° C., and seed crystals (0.3 g) were added, followed by stirring for 2 hours. Thereafter, the crystallization mass was cooled to 5 ° C., and further stirred for 1 hour. The resulting crystals were filtered, washed with ethyl acetate (77 g), and dried under reduced pressure to obtain 45.0 g of the desired product as white crystals (purity: 99.2%, crystallization yield: 93.1). %, Process isolation yield: 88.6%, reaction I to III total yield: 84.9
%).

Example 2 Reaction I) Wet wet crystals of (3-tetrahydrofuryl) methylnitroguanidine (27.5 g, content 85.3%,
37% in a suspension of water (130 g) having a pure content of 23.5 kg).
After adding a formalin aqueous solution (23.1 g) and stirring and mixing,
At 35 ° C., isopropylamine (8.5 g) was added dropwise with stirring. After reacting at 35 ° C. for 3 hours, the reaction solution was added for 20 hours.
Cooled to ° C. Dichloromethane (160 g) was added to the reaction solution.
Was added and stirred and mixed, and the pH was measured to be 9.6. The mixture was adjusted to pH 7.1 using 20% aqueous sulfuric acid and stirred for 1 hour. The aqueous layer obtained after the separation was extracted with dichloromethane (40 g), and the obtained extract was mixed with the organic layer obtained by the first liquid separation.
-Tetrahydrofuryl) methyl-5-isopropyl-2
A dichloromethane solution (226 g) containing -nitroiminohexahydro-1,3,5-hexahydrotriazine (concentration 14.7%, content 33.2 g) was obtained (reaction yield 98.2%).

Reaction II) 1- (3-) obtained in Reaction I
Tetrahydrofuryl) methyl-5-isopropyl-2-
After cooling a dichloromethane solution (226 g) containing nitroiminohexahydro-1,3,5-hexahydrotriazine (concentration: 14.7%, content: 33.2 g) to 0 ° C., dimethyl sulfate (18.5 g) was added. 95% at 0 ° C with stirring
Potassium hydroxide (2.5 g) was added four times at 30 minute intervals. After the completion of the addition of potassium hydroxide, the reaction was carried out at 0 ° C. for 2 hours. After completion of the reaction, crystals of monomethylpotassium sulfate produced as a by-product were removed by filtration, and the filtration residue was filtered with dichloromethane (5 mL
0 g). The obtained filtrate and washing liquid are mixed, and 1- (3-tetrahydrofuryl) methyl-3-methyl-5-isopropyl-2-nitroimino-1,3,5.
-Hexahydrotriazine (concentration 12.9%, content 3
4.5 g) of a dichloromethane solution (267.7 g) was obtained (reaction yield: 98.9%).

Reaction III) 1- (3-) obtained in Reaction II
Methanol (3.5 g) was added to a dichloromethane solution (268 g) of tetrahydrofuryl) methyl-3-methyl-5-isopropyl-2-nitroimino-1,3,5-hexahydrotriazine (concentration: 12.9%, content: 34.5 g). 9
g) were mixed, the reactor was replaced with nitrogen, and then ammonia (1.
7 g) was added and reacted at 85 ° C. for 6 hours. The obtained reaction liquid (270 g) contained 23.9 g of 1- (3-tetrahydrofuryl) methyl-3-methyl-2-nitroguanidine, which was the target substance (reaction yield: 97.8).
%). The reaction solution was washed with 20% aqueous sulfuric acid (123 g) and re-extracted four times with dichloromethane (410 g).
A dichloromethane solution containing 23.4 g of the desired product was 18
15 g was obtained (extraction yield 97.9%). The obtained dichloromethane solution was concentrated until the concentration of the target substance became about 33%, ethyl acetate (92 g) was added at 40 ° C., and seed crystals (0.1 g) were added, followed by stirring for 2 hours. Thereafter, the crystallization mass was cooled to 5 ° C., and further stirred for 1 hour. The resulting crystals were filtered, washed with ethyl acetate (37 g), and dried under reduced pressure to obtain 20.8 g of the desired product as white crystals (purity: 99.5%, crystallization yield: 87.2). %, Process isolation yield 85.2%, reaction I to III total yield 82.7%).

Example 3 Reaction I) A suspension of (3-tetrahydrofuryl) methylnitroguanidine (36.1 g) in water (192 g) was added
A 7% aqueous formalin solution (43.2 g) was added and mixed with stirring, and then isopropylamine (12.5 g) was added dropwise at 35 ° C. over 1 hour with stirring. After reacting at 35 ° C. for 3 hours, the reaction solution was cooled to 20 ° C. Dichloromethane (291 g) and sodium chloride (43 g) were added to the reaction solution, and the mixture was stirred and mixed, and the pH was measured to be 9.5.
The pH of the mixture was adjusted to 7.5 using 50% aqueous sulfuric acid, and the mixture was stirred for 1 hour, liquids were separated, and 1- (3-tetrahydrofuryl) methyl-5-isopropyl-2-nitroiminohexahydro- was added. A dichloromethane solution (351 g) containing 1,3,5-hexahydrotriazine (concentration 14.5%, content 50.5 g) was obtained (reaction yield 97.8).
%).

Reaction II) 1- (3-
Tetrahydrofuryl) methyl-5-isopropyl-2-
After cooling a dichloromethane solution (319 g) containing nitroiminohexahydro-1,3,5-hexahydrotriazine (concentration 14.5%, content 46.2 g) to 0 ° C.,
5% potassium hydroxide (11.5 g) was added, and the mixture was stirred at 0 ° C.
Then, dimethyl sulfate (24.6 g) was added dropwise. After the completion of the addition of potassium hydroxide, the mixture was reacted at 0 ° C. for 3 hours. Another 95
% Potassium hydroxide (2.1 g) was added, and then dimethyl sulfate (4.5 g) was further added. After the completion of the reaction, by-product crystals of monomethyl potassium sulfate were removed by filtration,
The filtration residue was washed with dichloromethane (20 g). The obtained filtrate and washing solution are mixed, and 1- (3-tetrahydrofuryl) methyl-3-methyl-5-isopropyl-
A dichloromethane solution (348 g) of 2-nitroimino-1,3,5-hexahydrotriazine (concentration: 13.7%, content: 47.8 g) was obtained (reaction yield: 98.0%).

Reaction III) 1- (3-
To a solution of tetrahydrofuryl) methyl-3-methyl-5-isopropyl-2-nitroimino-1,3,5-hexahydrotriazine (concentration 13.7%, content 20.9 g) in dichloromethane (152.4 g) was added methanol (152.4 g). 2.
After 3 g) were mixed and the reactor was replaced with nitrogen, ammonia (0.9 g) was added and reacted at 85 ° C. for 6 hours (reaction yield: 95.8%). The obtained reaction solution was washed with 20% aqueous sulfuric acid (32.4 g) containing 5% sodium sulfate, and re-extracted twice with dichloromethane (69 g) to give a dichloromethane solution containing 48.1 g of the desired product. 289
g was obtained (extraction yield 97.0%). The obtained dichloromethane solution was concentrated until the concentration of the target substance became about 35%, ethyl acetate (53 g) was added at 25 ° C., and the mixture was stirred for 2 hours. Thereafter, the crystallization mass was cooled to 5 ° C.
Stirred for hours. After filtration of the formed crystals, ethyl acetate (2
1g), and dried under reduced pressure to obtain the desired product.
2.3 g of white crystals (purity 99.1%, crystallization yield 94.1%, process isolation yield 83.1%, reaction I ~
III overall yield 79.6%).

Example 4 Reaction I) To a suspension of (3-tetrahydrofuryl) methylnitroguanidine (71.5 g) in water (253 g) was added 3
A 7% aqueous formalin solution (160.7 g) was added and mixed with stirring, and then isopropylamine (63.9 g) was added dropwise at 35 ° C. over 1 hour under stirring. After reacting at 35 ° C. for 3 hours, the reaction solution was cooled to 20 ° C. Dichloromethane (437 g) was added to the reaction solution, and the mixture was stirred and mixed, and the pH was measured to be 9.6. The pH of the mixture was adjusted to 7.5 using 50% aqueous sulfuric acid, and the mixture was stirred for 1 hour. After liquid separation, the obtained aqueous layer was extracted with dichloromethane (109 g), and the obtained extract and the organic layer obtained by the first liquid separation were mixed, and 1- (3-tetrahydrofuryl) methyl- 5-isopropyl-2-nitroiminohexahydro-
1,3,5-hexahydrotriazine (concentration 14.9
%, A content of 94.9 g) in a dichloromethane solution (6%).
37 g) (reaction yield 98.9%).

Reaction II) 1- (3-
Tetrahydrofuryl) methyl-5-isopropyl-2-
A dichloromethane solution (637.0 g) containing nitroiminohexahydro-1,3,5-hexahydrotriazine (concentration 14.9%, content 94.9 g) was cooled to 0 ° C., and then 95% potassium hydroxide (28%). .4 g), and dimethyl sulfate (59.8 g) was added dropwise at 0 ° C. with stirring. After the completion of the addition of dimethyl sulfate, the reaction was carried out at 0 ° C. for 3 hours. After completion of the reaction, crystals of monomethylpotassium sulfate produced as a by-product were removed by filtration, and the filtration residue was washed with dichloromethane (50 g). The obtained filtrate and washing solution were mixed, and 1- (3
(Tetrahydrofuryl) methyl-3-methyl-5-isopropyl-2-nitroimino-1,3,5-hexahydrotriazine (concentration 14.4%, content 98.7 g) in dichloromethane solution (684 g) was obtained ( Reaction yield 9
8.9%).

Reaction III) 1- (3-
Methanol (3.0 g) was added to a dichloromethane solution (224 g) of tetrahydrofuryl) methyl-3-methyl-5-isopropyl-2-nitroimino-1,3,5-hexahydrotriazine (concentration: 14.4%, content: 32.3 g). 5
g) were mixed, the reactor was replaced with nitrogen, and then ammonia (1.
3 g) was added and reacted at 85 ° C. for 7 hours (reaction yield 95.7%). The obtained reaction solution was treated with a 20% sulfuric acid aqueous solution (112%).
g) and washed with dichloromethane (112 g) for 4 hours.
Re-extraction was performed twice to obtain 685 g of a dichloromethane solution containing 21.9 g of the desired product (extraction yield: 90.0%).
The obtained dichloromethane solution was diluted with the target substance to a concentration of about 32.
%, And ethyl acetate (88 g) was added at 40 ° C., followed by stirring for 2 hours. Thereafter, the crystallization mass was cooled to 5 ° C., and further stirred for 1 hour. The resulting crystals were filtered, washed with ethyl acetate (35 g), and dried under reduced pressure.
The target product was obtained as 18.5 g of white crystals (purity: 99.5 g).
0%, crystallization yield 92.6%, process isolation yield 80.8
%, Total yield of reactions I to III 79.0%).

Comparative Example 1 Reaction I) To a suspension of crystals (634.0 g) of (3-tetrahydrofuryl) methylnitroguanidine in water (3150 g) was added a 37% aqueous formalin solution (599.0 g), and the mixture was stirred and mixed. Isopropylamine (217.
8g) was added dropwise with stirring. After reacting at 35 ° C for 3 hours, the reaction solution was cooled to 20 ° C (content 897.9).
g, reaction yield 98.2%). The crystals generated by the reaction were filtered and washed with water. The obtained crystals were dried under reduced pressure to give 1- (3-tetrahydrofuryl) methyl-5-isopropyl-2-nitroiminohexahydro-1,3,5-hexahydrotriazine (880.3
g) was obtained as white crystals (crystallization yield: 98.1%, isolation yield: 96.3%).

Comparative Example 2 Reaction I) To a suspension of (3-tetrahydrofuryl) methylnitroguanidine (5.0 g) in water (25 g) was added a 37% formalin aqueous solution (4.8 g), and the mixture was stirred and mixed.
At room temperature, isopropylamine (1.7 g) was added dropwise with stirring. After reacting at 35 ° C. for 3 hours, sodium chloride (5.6 g) was added, extracted with 50 g of dichloromethane, and 1- (3-tetrahydrofuryl) methyl-5-isopropyl-2-nitroiminohexahydro-1, 3,5
A solution (50 g) containing hexahydrotriazine (6.92 g) was obtained (reaction yield: 96.0%). The obtained solution was concentrated under reduced pressure, and crystallized by adding diethyl ether (100 g) to obtain the desired product (6.8 g) as white crystals (crystallization yield: 98.6%, isolation yield). 94.7
%).

Comparative Example 3 Reaction II) 1- (3-tetrahydrofuryl) methyl-5-isopropyl-2-nitroiminohexahydro-1,3,5-hexahydrotriazine (155. 8g) was dissolved in dichloromethane (900g), cooled to 0 ° C, and then 95% potassium hydroxide (39.6).
g) and dimethyl sulfate (86.2 g) at 0 ° C. with stirring.
Was added dropwise. After the completion of the addition of dimethyl sulfate, the reaction was carried out at 0 ° C. for 3 hours. Further, at 0 ° C., 95% potassium hydroxide (7.2
g) and dimethyl sulfate (15.4 g) were added at 0 ° C.
For 2 hours. After completion of the reaction, crystals of monomethylpotassium sulfate produced as a by-product were removed by filtration, and the filtration residue was washed with dichloromethane (100 g). The obtained filtrate and washing solution are mixed, and 1- (3-tetrahydrofuryl) methyl-3-methyl-5-isopropyl-2-nitroimino-1,3,5-hexahydrotriazine (concentration 13.
3%, content 153.3 g) in dichloromethane solution (1
156 g) (reaction yield 94.2%). The obtained dichloromethane solution was concentrated under reduced pressure (a decomposition rate by a concentration operation of 3.0%) to obtain a yellow oily substance (258.8 g) containing 148.7 g of the desired product. Isopropyl alcohol (200 g) was added to the obtained oil at 40 ° C.
After dissolution with stirring, the mixture was stirred at 5 ° C. for 1 hour. The precipitated crystals were filtered, washed with cooled isopropyl alcohol (50 g), and dried under reduced pressure to obtain white crystals (126.0 g) (crystallization yield: 82.2%, isolation yield: 77.0 g). 4
%).

Comparative Example 4 Reaction III) 1- (3-tetrahydrofuryl) methyl-3-methyl-5-isopropyl- obtained in Comparative Example 3
After mixing and dissolving 2-nitroimino-1,3,5-hexahydrotriazine (30.3 g) in dichloromethane (194 g), methanol (3.4 g) was mixed, the reactor was purged with nitrogen, and ammonia (1. 3g) and 85 ° C
For 7 hours (reaction yield 95.6%). The obtained reaction solution was washed with a 20% aqueous sulfuric acid solution (112 g) and re-extracted four times with dichloromethane (112 g) to obtain 682 g of a dichloromethane solution containing 18.5 g of the desired product (extraction yield: 90%). .3%). The obtained dichloromethane solution was concentrated until the concentration of the target substance became about 33%, and ethyl acetate (86 g) was added at 40 ° C., followed by stirring for 2 hours. Thereafter, the crystallization mass was cooled to 5 ° C., and further stirred for 1 hour. The resulting crystals were filtered, washed with ethyl acetate (35 g), and dried under reduced pressure to obtain 17.1 g of the desired product as white crystals (purity 99.0%, crystallization yield 92.0%).
6%, process isolation yield 79.9%). The total yield of Comparative Example 1 (Reaction I), Comparative Example 3 (Reaction II), and Comparative Example 4 (Reaction III) was 59.6%.

[0068]

As described above, according to the method of the present invention, it is possible to produce a substituted nitroguanidine derivative useful as an agrochemical (particularly an insecticide) or an intermediate thereof by a simple method with high purity. Excellent as a manufacturing method. The method of the present invention is very effective in producing a compound used as an agricultural chemical (particularly an insecticide) or an intermediate thereof.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Kenichi Sato 30 Asamuta-cho, Omuta-shi, Fukuoka Mitsui Chemicals, Inc. F-term (reference) 4C037 CA10

Claims (5)

[Claims] (1) Formula (1) Using a monosubstituted nitroguanidine represented by the following formula as a raw material, a triazine cyclization reaction in water, an alkylation reaction in an organic solvent, and a triazine decomposition reaction in an organic solvent are performed to obtain a compound represented by the general formula (2). (In the formula, R1 represents a saturated or unsaturated alkyl group having 1 to 3 carbon atoms.) In a method for producing a disubstituted nitroguanidine represented by the formula: a solvent used for a purification operation after a triazine cyclization reaction; A method for producing a disubstituted nitroguanidine represented by the general formula (2) by a continuous reaction without using an intermediate for isolating the solvent used in the alkylation reaction and the triazine decomposition reaction. 2. The method according to claim 2, wherein the decomposition reaction of the triazine ring is carried out by using ammonia,
The method according to claim 1, wherein a primary or secondary amine or a salt thereof is used. 3. The method according to claim 1, wherein ammonia is used for the decomposition reaction of the triazine ring. 4. The method according to claim 1, wherein the solvent used for the purification operation after the triazine cyclization reaction, the solvent used for the alkylation reaction of the triazine, and the solvent used for the decomposition reaction of the triazine ring are aliphatic halogenated hydrocarbon solvents. . 5. The method according to claim 1, wherein the solvent used for the purification operation after the triazine cyclization reaction, the solvent used for the alkylation reaction of the triazine, and the decomposition reaction for the triazine ring are dichloromethane.