JP3042122B2 - Method for producing N-cyanoacetamidine derivative - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a compound of the formula (III)

[0002]

Embedded image

Wherein R and R ′ are the same or different and each represents a lower alkyl group, and X represents hydrogen or halogen, and relates to a method for producing an N-cyanoacetamidine derivative. Compound (III) is a very useful compound as an insecticide.

[0004]

2. Description of the Prior Art and Problems

[0005]

Embedded image (In the formula, R and X have the same meanings as described above.)

The compound (I) represented by the general formula (III)

[0007]

Embedded image (In the formula, R, R ′ and X have the same meanings as described above.)

As a method for producing the compound (III) represented by the formula, after treating the compound (I) in a DMF solvent with NaH,
Methods for reacting with alkyl iodides are known and are described in WO 91/04965.

[0009] However, such a conventional method requires a D
It uses a relatively expensive solvent such as MF and a complicated recovery operation, uses a raw material that is difficult to handle such as NaH and an expensive alkylating agent such as alkyl iodide, and has a low yield. It cannot be said that this is an advantageous production method.

[0010]

SUMMARY OF THE INVENTION The present invention relates to a method for preparing a compound (I) using an inexpensive alkylating agent and an inexpensive and easily recoverable solvent using an inexpensive caustic alkali as a deoxidizing agent and an inexpensive and easily recoverable solvent. Thus, it is an object of the present invention to establish a method for producing the compound (III) by an efficient and industrially easy method.

[0011]

The present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, decomposed caustic alkali in water and a poorly water-soluble organic solvent in the presence of a quaternary ammonium salt. By reacting compound (I) with dialkyl sulfate as an acid agent, it has been found that compound (III) can be obtained remarkably in good yield and easily as compared with the conventional method, and the present invention has been completed. That is, the present invention provides a compound of the formula (I)

[0012]

Embedded image (In the formula, R and X have the same meanings as described above.)

Compound (I) represented by the general formula (I)
_{I) R '2 SO 4 (} II) ( wherein, R' and dialkyl sulfate represented by having.) As defined above, the caustic in the presence of a quaternary ammonium salt as a deoxidizer, water And a reaction in a poorly water-soluble organic solvent, general formula (III)

[0014]

Embedded image (In the formula, R, R ′ and X have the same meanings as described above.)

A method for producing the compound (III) represented by the formula:

Next, according to the present invention, for example, a quaternary ammonium salt is added as a catalyst to a mixture of a poorly water-soluble organic solvent and a compound (I) as a catalyst, and then dialkyl sulfate is added. By reacting by dropping the aqueous solution, or after adding the aqueous solution of caustic,
The compound (III) can be obtained in good yield by dropping and reacting a dialkyl sulfate under cooling and stirring, or by simultaneously dropping an aqueous solution of a dialkyl sulfate and a caustic alkali solution. As the quaternary ammonium salt used in the present invention, for example, tetraethylammonium chloride, tetrabutylammonium chloride, triethylbenzylammonium chloride, triethylbenzylammonium chloride, tetraethylammonium bromide, tetrabutylammonium bromide, triethylbenzylammonium bromide, triethylbenzylammonium Aliphatic quaternary ammonium salts such as bromide, tetraethylammonium iodide, tetrabutylammonium iodide, triethylbenzylammonium iodide, and triethylbenzylammonium iodide can be used. The purpose can be sufficiently achieved by use. When the quaternary ammonium salt is not added to the reaction system, the reaction progresses much slower than in the case where the quaternary ammonium salt is added, and the yield is extremely low.The reaction proceeds smoothly only by adding the quaternary ammonium salt. The desired product can be obtained with good efficiency.

As the caustic alkali used as the deoxidizing agent, for example, caustic soda or caustic potash can be used. The use of 1.1 to 1.4 equivalents to 1 equivalent of the compound (I) can sufficiently achieve the purpose. Further, the aqueous solution of caustic alkali needs to be concentrated, and is preferably 40 wt% or more, and usually 50 wt% or more.
% Aqueous solution is used. When the concentration of caustic is low, the reaction rate of the target reaction becomes extremely slow,
The yield often decreases significantly due to the progress of side reactions.

The dialkyl sulfate includes, for example, dimethyl sulfate and diethyl sulfate. Sufficiently good results can be obtained by using 1.05 to 1.2 equivalents to 1 equivalent of the compound (I). As the solvent, it is preferable to use a relatively strong solvent which can dissolve the compound (III) among the poorly water-soluble organic solvents inert to the reaction reagents and products, for example, methylene chloride, chloroform, 1, and the like. Chlorine organic solvents such as 2-dichloroethane and ketone organic solvents such as methyl isobutyl ketone can be used. The reaction temperature is in the range from 0 ° C. to the boiling point of the solvent to be used.
A range from 10C to 30C is preferred. Compound (III) obtained by the method of the present invention is obtained by adding water after the completion of the reaction, and separating and removing monomethyl sulfate produced as a by-product.
By subjecting a solution of a poorly water-soluble organic solvent containing (III) to ordinary treatment such as concentration and recrystallization, it can be easily obtained with good efficiency and high purity.

The compound (III) according to the present invention has the following syn and anti isomers:

[0020]

Embedded image (In the formula, R, R ′ and X have the same meanings as described above.)

The ratio changes depending on the existence or conditions of instrument analysis.

[0022]

The following examples illustrate the present invention and do not limit the present invention in any way.

Example 1 N-cyano-N '-(2-chloro-5-pyridylmethyl) -N'-methylacetamidine

[0024]

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Compound (I) in 100 ml of chloroform
20.87 g (0.1 mol) and 1.81 g (0.004 mol) of a 50% aqueous solution of triethylbenzylammonium chloride
And cooled to 15 ° C., and 13.87 g (0.
11 mol). Then, while maintaining the temperature at 15 ° C. under cooling and stirring, 10.00 g of a 50% aqueous solution of caustic soda (0.12 g) was added.
5 mol) was added dropwise over 30 minutes, and the mixture was further stirred at the same temperature for 3 hours. After the completion of the reaction, 40 ml of water was added, and the sodium salt of monomethyl sulfate produced as a by-product was separated and removed.
Recrystallized from a mixed solution of methanol and water, filtered, washed with water and dried to obtain 19.69 g of the desired product having a melting point of 100 to 101 ° C.
I got Yield 88.4%. ¹ H-NMR spectrum (CDCl ₃ ) δ ppm: 2.4
_{6,2.68 (3H, s, CH 3} -C = N) 3.09,3.1
1 (3H, s, CH ₃ N) 4.63, 4.71 (2H, s,
_{N CH 2) 7.27~8.31 (3H,} m, aromati
c).

Example 2 N-cyano-N '-(2-chloro-5-pyridylmethyl) -N'-methylacetamidine

[0027]

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Compound (I) in 100 ml of chloroform
20.87 g (0.1 mol) and 1.81 g (0.004 mol) of a 50% aqueous solution of triethylbenzylammonium chloride
And cooled to 15 ° C., and 13.87 g (0.
11 mol). Then, while maintaining the temperature at 15 ° C. under cooling and stirring, 10.00 g of a 50% aqueous solution of caustic soda (0.12 g) was added.
5 mol) was added dropwise over 45 minutes, and the mixture was further stirred at the same temperature for 2.5 hours. After the completion of the reaction, 40 ml of water was added, and the by-produced sodium salt of monomethyl sulfate was separated and removed. The chloroform solution containing the target product obtained by the liquid separation was analyzed by high performance liquid chromatography and found to contain 21.49 g of the target product. 96.5% yield.

Example 3 N-cyano-N '-(2-chloro-5-pyridylmethyl) -N'-methylacetamidine

[0030]

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Compound (I) in 650 ml of chloroform
208.7 g (1.0 mol) and 1.81 g (0.04 mol) of a 50% aqueous solution of triethylbenzylammonium chloride were added, and the mixture was cooled to 15 ° C, and 100.0 g of 50% caustic soda was added while stirring and maintaining the same temperature. (1.25 mol) and 138.7 g (1.1 mol) of dimethyl sulfate were simultaneously added dropwise over 2 hours, and the mixture was further stirred at the same temperature for 3 hours. Two hours after the addition, the reaction solution was analyzed by high performance liquid chromatography, and it was found that the residual amount of compound (I) was 1% or less of the target product. After completion of the reaction, 400 ml of water and 3.87 g (0.05 mol) of a 40% aqueous solution of dimethylamine were added to give 1
After stirring for an hour, liquid separation was performed. The aqueous layer is chloroform 350
Extracted with water and combined with the chloroform layer
0 ml was added, and chloroform was distilled off under stirring until the internal temperature reached 100 ° C. After cooling the residual liquid to 55 ° C., 320 ml of methanol was added, and further cooled to 35 ° C. with stirring to precipitate crystals. Then, 440 ml of water was added dropwise over 1 hour, and then cooled to 15 ° C. to further crystallize. Was precipitated.
The obtained crystals were filtered and dried to obtain 203.7 g of the desired product having a melting point of 100 to 101 ° C. As a result of analysis by high performance liquid chromatography, the purity of the target product was 99.5%. Yield 91.0%.

Example 4 N-cyano-N '-(2-chloro-5-pyridylmethyl) -N'-ethylacetamidine

[0033]

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Compound (I) in 100 ml of chloroform
20.87 g (0.1 mol) and 1.81 g (0.004 mol) of a 50% aqueous solution of triethylbenzylammonium chloride
, And cooled to 20 ° C.
11 mol). Then, while maintaining the temperature at 20 ° C. under cooling and stirring, 10.00 g of a 50% aqueous solution of caustic soda (0.12 g) was added.
5 mol) was added dropwise over 30 minutes, and the mixture was further stirred at the same temperature for 3 hours. After completion of the reaction, 40 ml of water was added to remove the by-produced monomethyl sulfate, and the chloroform solution containing the desired product was concentrated.
The crystals were recrystallized from a water mixture, filtered, washed with water and dried to obtain 20.60 g of the desired product having a melting point of 99 to 100 ° C. Yield 87.0
%. ¹ H-NMR spectrum (CDCl ₃ ) δ ppm: 1.1
_{8,1.25 (3H, t, CH 3} CH 2) 2.42,2.48
_{(3H, s, CH 3 -C} = N) 3.43,3.56 (2H
, Q, CH ₃ CH ₂ ) 4.62, 4.71 (2H, s, N
_{CH 2), 7.28~8.32 (3H,} m, aromati
c).

[0035]

As is clear from the above examples, the production method of the present invention uses raw materials which are inexpensive and easy to handle as compared with the conventional method, and is easy not only in the reaction operation but also in the post-treatment operation. This is an industrially superior production method in which the target substance is obtained with remarkably high efficiency.

────────────────────────────────────────────────── ─── Continuation of front page (56) References JP-A-5-178834 (JP, A) International Publication No. 91/4965 (WO, A1) (58) Fields investigated (Int. Cl. ⁷ , DB name) C07D 213/00-213/61 CA (STN) REGISTRY (STN)

Claims (1)

(57) [Claims] 1. A compound of the formula (I) (Wherein R represents a lower alkyl group, X represents hydrogen or halogen), and a compound represented by the general formula (II): R ′ ₂ SO ₄ (II) (wherein R ′ represents a lower alkyl group) A dialkyl sulfate represented by the general formula (III) in the presence of a quaternary ammonium salt, in the presence of a caustic alkali as a deoxidizing agent, in water or a water-insoluble organic solvent. Embedded image (Wherein, R, R ′ and X have the same meanings as described above).