JPH107645A - Production of alkylnitroguanidine derivatives - Google Patents

Abstract

PROBLEM TO BE SOLVED: To selectively obtain a alkylnitroguanidine in one step useful for organic intermediates, medicines, agrochemicals, especially penetrative insecticides by alkylating nitroguanidine derivatives with an alkylating agent. SOLUTION: According to this method 2-nitroguanidine derivatives of formula II (R is an 1-4C alkyl) are capable of obtaining by alkylation of (A) nitroguanidine derivatives of formula I (A is a (substituted) heterocyclic ring or phenyl) in the presence of a base or an acid and base, in a solvent by an alkylating agent (preferably an 1-4C dialkylsulfuric acid). For example, 1- methyl-2-nitro-3-[(tetrahydro-3-franyl)methyl]guanidine is obtained by carrying out the reaction using 3-tetrahydrofurylmethylnitroguanidine as component A and dimethyl sulfuric acid as component B in the presence of sodium hydroxide, in dimethylformamide as solvent.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a compound of the formula (2) useful as an organic intermediate, a pharmaceutical or a pesticide, particularly a systemic insecticide.

[0002]

Embedded image A 2-nitroguanidine derivative represented by the formula (1)

[0003]

Embedded image The present invention relates to a method for producing from a nitroguanidine derivative represented by the formula:

[0004]

2. Description of the Related Art There are many known methods for producing a nitroguanidine derivative represented by the formula (1) (JP-A-2-28859, JP-A-7-278094, and European Patent Publication No. 0383091). . However, the substitution reaction is non-selective due to the presence of three reactive hydrogen atoms in the monosubstituted 2-nitroguanidine which is the starting material for these reactions, resulting in undesired substitution products. . Further, Japanese Patent Application Laid-Open No. 3-279359 and Japanese Patent Application Laid-Open
In JP-A-109374, JP-A-5-310650, etc., as a method for producing 1,3-disubstituted 2-nitroguanidine, a method of reacting a monosubstituted nitroisothiourea with a primary amine is described. Have been.
However, these nitroisothiourea compounds as starting materials are difficult to obtain. Further, a method of obtaining a target product by synthesizing a cyclic nitroguanidine once, followed by alkylation and hydrolysis is disclosed in JP-A-4-3304.
No. 9 is described. However, this method requires more reaction steps than the aforementioned method, and is disadvantageous when industrially performed.

[0005]

Accordingly, the present invention provides
An object of the present invention is to selectively perform alkylation of a 2-nitroguanidine derivative in one step without passing through a cyclic nitroguanidine.

[0006]

The present inventors have solved the above-mentioned problems.
As a result of intensive studies to solve the problem, the nit
Loganidine derivative in a solvent in the presence of a base or acid
And in the presence of a base, C ₁-C_FourReacted with alkylating agents
To form a 2-nitroguanidine derivative represented by the formula (2).
A manufacturing method was found, and the present invention was completed.

That is, the present invention relates to a compound of the formula (1)

[0008]

Embedded image (Wherein A represents a heterocyclic ring which may be substituted or a phenyl group which may be substituted.) A nitroguanidine derivative represented by the following formula: in a solvent in the presence of a base or in the presence of an acid and a base, Formula (2) wherein the alkylation is carried out using an alkylating agent.

[0009]

Embedded image (Wherein, A represents an optionally substituted heterocyclic ring or an optionally substituted phenyl group, and R represents a C ₁ -C ₄ alkyl group). It is a manufacturing method of.

[0010]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Solvents used in the production method of the present invention include alcohols such as methanol, ethanol, propanol and butanol, aromatic hydrocarbons such as benzene, toluene and xylene, hexane, heptane and petroleum benzine. Aprotic polar solvents such as aliphatic hydrocarbons, dimethylformamide, dimethylacetamide, dimethylsulfoxide, 1,3-dimethyl-2-imidazolidinone, 1-methyl-2-pyrrolidinone,
Ethyl ether, diisopropyl ether, 1,3-dimethoxyethane, tetrahydrofuran, dioxane, etc., ethers, acetonitrile, propionitrile, etc., nitriles, acetone, diisopropyl ketone, etc., ketones, water alone or in any ratio They can be used in combination. Preferred are nitriles such as acetonitrile and propionitrile, and ketones such as acetone and diisopropyl ketone, and more preferred are acetonitrile and acetone.

Examples of the alkylating agent include alkyl halides such as methyl iodide, ethyl iodide, methyl bromide and ethyl bromide, dialkyl sulfates such as dimethyl sulfate and diethyl sulfate, methanesulfonic acid methyl ester, and methanesulfonic acid. Methanesulfonic acid esters such as ethyl ester,
Carbonic acid esters such as dimethyl carbonic acid, and phosphoric acid esters such as trimethyl phosphoric acid, preferably methyl iodide,
Alkyl halides such as ethyl iodide, methyl bromide and ethyl bromide, and dialkyl sulfates such as dimethyl sulfate and diethyl sulfate, and more preferably dialkyl sulfates such as dimethyl sulfate and diethyl sulfate.

As the base, hydrides of alkali metals such as sodium hydride and potassium hydride, hydroxides of alkali metals such as sodium hydroxide and potassium hydroxide, carbonates of alkali metals such as sodium carbonate and potassium carbonate,
Tertiary amines such as triethylamine, pyridine and the like, alkali metal phosphates such as trisodium phosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate, tripotassium phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate,
Preferably sodium hydroxide, alkali metal hydroxides such as potassium hydroxide, sodium carbonate, alkali metal carbonates such as potassium carbonate, trisodium phosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate, tripotassium phosphate, Alkali metal phosphates such as dipotassium monohydrogen phosphate and potassium dihydrogen phosphate, more preferably tripotassium phosphate.

The addition amounts of the base or acid and the base are not particularly limited, but are preferably 1 equivalent or more and 4 equivalents or less relative to the nitroguanidine derivative, and more preferably 1.
It is 5 equivalents or more and 2.5 equivalents or less. The method for adding the base or the acid and the base to the reaction system for the alkylation reaction is not particularly limited, but it may be added as a solid, or may be added after being dissolved or suspended in a solvent.

The reaction temperature and reaction time of the alkylation reaction can be varied over a wide range, but generally the reaction temperature is 0 to 200 ° C., preferably 50 to 80 ° C., and the reaction time is 0.01 to 50 hours. , Preferably 0.1 to 5 hours. The reaction pressure is not particularly limited, but is preferably normal pressure.

After completion of the reaction, the reaction solution is subjected to ordinary post-treatments such as concentration and filtration to obtain the desired compound.
If necessary, it can be further purified by operations such as column chromatography, distillation, recrystallization and the like.

[0016]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples and the like, but the present invention is not limited to these Examples. The obtained reaction mixture was quantified by an internal standard method using high performance liquid chromatography.

Example 1 1-methyl-2-nitro-3
Production of-{(tetrahydro-3-furanyl) methyl} guanidine 3-tetrahydrofurylmethylnitroguanidine 1.
0 g, dimethyl sulfate 0.8 g, sodium hydride
21 g and dimethylformamide 20 ml at 80 ° C.
After stirring for an hour, the desired product was obtained in a yield of 15%.

Example 2 1-methyl-2-nitro-3
Production of-{(tetrahydro-3-furanyl) methyl} guanidine 3-tetrahydrofurylmethylnitroguanidine 1.
1. g, dimethylsulfuric acid 1.42 g, tripotassium phosphate
When 28 g and acetonitrile 20 ml were stirred at 80 ° C. for 1 hour, the target product was obtained in a yield of 60%.

Example 3 1-methyl-2-nitro-3
Production of-{(tetrahydro-3-furanyl) methyl} guanidine 3-tetrahydrofurylmethylnitroguanidine 1.
1. g, dimethylsulfuric acid 1.42 g, tripotassium phosphate
When 28 g and acetone 20 ml were stirred at 80 ° C. for 1 hour, the target product was obtained in a yield of 57%.

Example 4 1-ethyl-2-nitro-3
Production of-{(tetrahydro-3-furanyl) methyl} guanidine 3-tetrahydrofurylmethylnitroguanidine 1.
0 g, 1.63 g of diethyl sulfate, and tri-potassium phosphate
When 28 g and acetonitrile 20 ml were stirred at 80 ° C. for 1 hour, the target product was obtained in a yield of 57%.

Example 5 Preparation of 1- (6-chloro-3-pyridylmethyl) -1-methyl-2-nitroguanidine 1.0 g of 1- (6-chloro-3-pyridylmethyl) -2-nitroguanidine, When 1.13 g of dimethyl sulfate, 1.87 g of tripotassium phosphate and 20 ml of acetonitrile were stirred at 80 ° C. for 1 hour, the target product was obtained in a yield of 35%.

Example 6 1-methyl-2-nitro-3
Preparation of-{(tetrahydro-3-furanyl) methyl} guanidine 3-tetrahydrofurylmethylnitroguanidine
5 g, methyl iodide 0.52 g, potassium hydroxide
When 16 g and acetonitrile 20 ml were stirred at 80 ° C. for 3 hours, the target product was obtained in a yield of 10%.

[0023]

According to the method of the present invention, a nitroguanidine derivative represented by the formula (2) or (4), which is useful as an organic intermediate, a pharmaceutical or a pesticide, particularly a systemic insecticide, is converted into a compound represented by the formula (1) or (5). ) Can be selectively produced in one step from the nitroguanidine derivative.

 ──────────────────────────────────────────────────続 き Continued on front page (72) Inventor Kenji Odaka 1144 Togo, Mobara-shi, Chiba Mitsui Toatsu Chemicals Co., Ltd.

Claims (6)

[Claims] (1) Formula (1) (Formula 1) (Wherein A represents a heterocyclic ring which may be substituted or a phenyl group which may be substituted.) A nitroguanidine derivative represented by the following formula: in a solvent in the presence of a base or in the presence of an acid and a base, Formula (2) wherein alkylation is carried out using an alkylating agent. (Wherein, A represents an optionally substituted heterocyclic ring or an optionally substituted phenyl group, and R represents a C ₁ -C ₄ alkyl group). Manufacturing method. 2. The nitroguanidine derivative according to claim 1, wherein A is a 5- or 6-membered ring, and is a heterocyclic ring which may be substituted and contains at least one of N, S and O. method for producing a 2-nitroguanidine derivative according to claim 1, characterized in that to alkylation with dialkyl sulfate of C ₁ -C _4. 3. The method according to claim 2, wherein A is a nitroguanidine derivative represented by an optionally substituted thiazole ring, an optionally substituted pyridine ring, or an optionally substituted tetrahydrofuran ring. A method for producing a 2-nitroguanidine derivative according to claim 2, characterized in that: 4. The compound according to claim 3, wherein A is a nitroguanidine derivative represented by an optionally substituted tetrahydrofuran ring. (Wherein, R represents a C ₁ -C ₄ alkyl group, X represents a halogen or a C ₁ -C ₄ alkyl group, and n represents 0 to 3)
Represents an integer. The method for producing a 2-nitroguanidine derivative according to claim 3, which is represented by the formula: 5. The method according to claim 1, wherein the alkylation is carried out in the presence of a phosphate or phosphoric acid and a base.
-A method for producing a nitroguanidine derivative. 6. The method for producing a 2-nitroguanidine derivative according to claim 1, wherein the solvent is acetonitrile or acetone.