JPH05178833A - Production of n-cyanoacetamidine derivative - Google Patents

Abstract

PURPOSE:To easily obtain the subject compound on an industrial scale in high yield by N-alkylating a compound corresponding to the subject compound using an easily handleable inexpensive caustic alkali as an acid acceptor in combination with an inexpensive alkylation agent and an easily recoverable inexpensive solvent CONSTITUTION:The objective N-cyanoacetamidine derivative of formula III [e.g. N-cyano-N'-(2-chloro-5-pyridylmethyl)-N'-methylacetamidine of formula IV] can be produced by N-alkylating a compound of formula I (R is lower alkyl; X is H or halogen) (e.g. the compound of formula II) with a dialkyl sulfate of the formula R'2SO4 (R' is alkyl) (e.g. dimethyl sulfate) using a caustic alkali as an acid acceptor in water and a scarcely water-soluble organic solvent in the presence of a quaternary ammonium salt. The process is industrially advantageous because it uses an easily handleable inexpensive raw material, the post-treatment as well as the reaction operation can easily be carried out and the objective compound can be produced in remarkably high yield.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention has the general formula (III)

[0002]

[Chemical 3]

(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 process for producing an N-cyanoacetamidine derivative. Compound (III) is a very useful compound as an insecticide.

[0004]

Prior Art and Problems: Formula (I)

[0005]

[Chemical 4] (In the formula, R and X have the same meanings as described above.)

The compound of the general formula (III) is obtained by alkylating the N-position of the compound (I) represented by

[0007]

[Chemical 5] (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 (I), after treating the compound (I) in DMF solvent with NaH,
Methods for reacting with alkyl iodides are known and these are described in WO 91/04965.

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

[0010]

DISCLOSURE OF THE INVENTION In the present invention, a caustic alkali which is easy to handle and inexpensive is used as a deoxidizing agent, and an inexpensive alkylating agent and an inexpensive and easily recoverable solvent are used to convert the compound (I) into an N-alkyl. Is to establish a method for producing compound (III) by a highly efficient and industrially easy method.

[0011]

Means for Solving the Problems As a result of intensive studies to solve the above problems, the present inventors have found that caustic alkali is removed in the presence of a quaternary ammonium salt in water and a poorly water-soluble organic solvent. The present invention has been completed by finding that by reacting compound (I) with a dialkylsulfuric acid as an acid agent, compound (III) can be easily obtained with a remarkably good yield as compared with the conventional method. That is, the present invention has the formula (I)

[0012]

[Chemical 6] (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 characterized by reacting in a water-insoluble organic solvent, the general formula (III)

[0014]

[Chemical 7] (In the formula, R, R ′ and X have the same meanings as described above.)

A method for producing the compound (III) represented by

Next, in the present invention, for example, a quaternary ammonium salt as a catalyst is added to a mixed solution of a poorly water-soluble organic solvent and compound (I), and then dialkyl sulfuric acid is added, and then caustic alkali is added under cooling and stirring. After dropping the aqueous solution to react or after adding the aqueous solution of caustic,
The compound (III) can be obtained in good yield by dropping a dialkyl sulfuric acid under cooling and stirring for reaction, or by adding a dialkyl sulfuric acid and an aqueous solution of caustic alkali at the same time. Examples of the quaternary ammonium salt used in the present invention include 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, and the amount thereof is 1 to 5% of the compound (I). The purpose can be achieved by using it. When such a quaternary ammonium salt is not added to the reaction system, the reaction proceeds much slower than in the case where it is added, and the yield is extremely low.The addition of the quaternary ammonium salt allows the reaction to proceed smoothly. The target 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, and the use of 1.1 to 1.4 equivalents relative to 1 equivalent of the compound (I) can sufficiently achieve the purpose. In addition, a caustic alkali aqueous solution needs to be concentrated, and preferably 40 wt% or more, usually 50 wt.
% Aqueous solution is used. When the concentration of caustic is low, the reaction speed of the target reaction becomes extremely slow,
The yield often decreases significantly due to the progress of side reactions.

Examples of the dialkylsulfate include dimethylsulfate and diethylsulfate. Use of 1.05 to 1.2 equivalents relative to 1 equivalent of the compound (I) gives sufficiently good results. As the solvent, it is preferable to use a relatively polar solvent capable of dissolving the compound (III) among the poorly water-soluble organic solvents inert to the reaction reagent and the product. For example, methylene chloride, chloroform, 1, A chlorine-based organic solvent such as 2-dichloroethane or a ketone-based organic solvent such as methyl isobutyl ketone can be used. The reaction temperature is in the range of 0 ° C. to the boiling point of the solvent used, but at a high temperature, decomposition of raw materials or products or side reaction may occur,
The range of 10 ° C to 30 ° C is preferable. The compound (III) obtained by the method of the present invention is a compound obtained by adding water after the reaction to remove the by-produced monomethylsulfate and separating it.
A solution of a poorly water-soluble organic solvent containing (III) can be easily obtained with good efficiency and high purity by subjecting it to ordinary treatments such as concentration and recrystallization.

The compound (III) according to the present invention has the syn and anti isomers shown below.

[0020]

[Chemical 8] (In the formula, R, R ′ and X have the same meanings as described above.)

The ratio varies depending on the existence or the condition of instrumental analysis.

[0022]

EXAMPLES The following examples illustrate the present invention, but the present invention is not limited thereto.

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

[0024]

[Chemical 9]

Compound (I) was added to 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
Was added, and the mixture was cooled to 15 ° C and 13.87 g (0.8%) of dimethylsulfate was added.
11 mol) was added. Then, while maintaining the temperature at 15 ° C. under cooling and stirring, 10.00 g (0.12 g) of a 50% aqueous solution of caustic soda was prepared.
(5 mol) was added dropwise over 30 minutes, and the mixture was further stirred at the same temperature for 3 hours. After the reaction was completed, 40 ml of water was added to remove the sodium salt of by-produced monomethylsulfate, and the resulting chloroform solution containing the target compound was concentrated to obtain a residue of 36 wt.
% 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.
Got Yield 88.4%. ¹ H-NMR spectrum (CDCl ₃ ) δppm: 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]

[Chemical 10]

Compound (I) was added to 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
Was added, and the mixture was cooled to 15 ° C and 13.87 g (0.8%) of dimethylsulfate was added.
11 mol) was added. Then, while maintaining the temperature at 15 ° C. under cooling and stirring, 10.00 g (0.12 g) of a 50% aqueous solution of caustic soda was prepared.
(5 mol) was added dropwise over 45 minutes, and the mixture was further stirred at the same temperature for 2 hours and a half. After completion of the reaction, 40 ml of water was added to remove by-produced sodium salt of monomethylsulfate. The chloroform solution containing the target substance obtained by liquid separation was analyzed by high performance liquid chromatography, and it was found that the target substance contained 21.49 g. Yield 96.5%.

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

[0030]

[Chemical 11]

Compound (I) was added to 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., while maintaining the same temperature under stirring and cooling, 50% caustic soda 100.0 g (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 dropping, the reaction liquid was analyzed by high performance liquid chromatography, and it was found that the residual amount of the compound (I) was 1% or less of the target product. After the reaction was completed, 400 ml of water and 3.87 g (0.05 mol) of a 40% dimethylamine aqueous solution were added to 1
After stirring for an hour, the layers were separated. Chloroform 350 in water layer
It was extracted with ml and combined with the previous chloroform layer, water 45
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 the mixture was 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 deposited.
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]

[Chemical 12]

Compound (I) was added to 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
Was added, and the mixture was cooled to 20 ° C. and 16.95 g of dimethyl sulfate (0.
11 mol) was added. Then, while maintaining the temperature at 20 ° C. under cooling and stirring, 10.00 g (0.12 g) of a 50% aqueous solution of caustic soda was prepared.
(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 monomethylsulfate, and the resulting chloroform solution containing the desired product was concentrated.
Recrystallization from a mixture of water, filtration, washing with water and drying gave 20.60 g of the desired product having a melting point of 99-100 ° C. Yield 87.0
%. ¹ H-NMR spectrum (CDCl ₃ ) δppm: 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 apparent from the above-mentioned examples, the production method of the present invention uses a raw material which is cheaper and easier to handle than the conventional method, and is easy to carry out not only the reaction operation but also the post-treatment operation. It is an industrially excellent manufacturing method in that the desired product can be obtained with excellent efficiency.

Claims (1)

[Claims] 1. Formula (I): (Wherein R represents a lower alkyl group and X represents hydrogen or halogen), and a compound of the general formula (II) R ′ ₂ SO ₄ (II) (wherein R ′ is a lower alkyl group). A dialkylsulfuric acid represented by the formula (1) in the presence of a quaternary ammonium salt in the presence of a caustic alkali as a deoxidizing agent in water and a poorly water-soluble organic solvent. [Chemical 2] (In the formula, R, R'and X have the same meanings as described above.) A method for producing an N-cyanoacetamidine derivative.