WO2004035529A1 - Process for producing n-(2-amino-1,2-dicyanovinyl)formamidine - Google Patents

Abstract

An industrially advantageous process for producing N-(2-amino-1,2-dicyanovinyl)formamidine (AMD), which is represented by the formula (I) and useful as an intermediate for agricultural chemicals and medicines. (I) Diaminomaleonitrile (DAMN) is reacted with hydrogen chloride and hydrogen cyanide in an organic solvent to obtain AMD hydrochloride in a high yield.

Description

 Specification

TECHNICAL FIELD The present invention relates to a compound of the formula (1) useful as an agrochemical intermediate: (1) A method for producing N- (2-amino-1,2-dicyanovinyl) formamidine

で表される N- (ァミノ- 1,2—ジシァノビニル） ホルムアミジン （AMD) の製造 方法に関する。 従来の技術：

The present invention relates to a method for producing N- (amino-1,2-disocyanovinyl) formamidine (AMD) represented by the formula: Conventional technology:

AMD was obtained by reacting diaminomaleonitrile (DAMN) with formamidine (NH = CHNH) (J.O.C. Vol. 44 No. 25 (1979) 4532 4536).

However, this method is not preferable as an industrial production method because formamidine as a raw material is expensive.

Further, as a reaction similar to the present invention, Japanese Patent Application Laid-Open No. 2001-158776 discloses a method for producing an amidine derivative represented by the following reaction formula.

しかし で表される置換基はアルキル基等であり本発明の が水素の化合物 は開示されていない。 この反応は、 中間体としてシァノ化合物と塩化水素が反 応したイミドイルクロリドを経由するものと考えられるが、 が水素の化合物、 即ちシアン化水素の場合、 対応するイミドイルクロリドが生成するか、 また生 成したイミドイルクロリドが安定か否かわからず AMD の製法としては全く知 られていなかった。 発明の開示： 本発明は、 AMDの工業的に優れた製造方法を提供することをその目的とする。 本発明者等は、 AMDの工業的製法に関し鋭意研究した結果、 ジォキサン等のェ 一テル系の溶媒で反応させることにより高収率で目的物が得られることを見出 し本発明を完成した。 即ち、 本発明は、 D AMNと塩化水素とシアン化水素と を有機溶媒中で反応させることを特徴とする AMDの製造方法である。

However, the substituent represented by is an alkyl group or the like, and the compound of the present invention is not disclosed. This reaction is thought to be via an imidoyl chloride obtained by reacting a cyano compound with hydrogen chloride as an intermediate.When is a compound of hydrogen, that is, hydrogen cyanide, the corresponding imidoyl chloride is produced or It was not known whether the imidoyl chloride formed was stable or not, and it was not known at all as an AMD manufacturing method. DISCLOSURE OF THE INVENTION The object of the present invention is to provide an industrially superior method for producing AMD. The present inventors have conducted intensive studies on the industrial production process of AMD and found that the desired product can be obtained in high yield by reacting with an ether-based solvent such as dioxane, and completed the present invention. . That is, the present invention is a method for producing AMD, which comprises reacting DAMN, hydrogen chloride, and hydrogen cyanide in an organic solvent.

The reaction is carried out by dissolving hydrogen cyanide in an organic solvent and blowing hydrogen chloride, and then adding DAMN. The organic solvent used in the reaction is not particularly limited as long as it is a solvent inert to the reaction, and examples thereof include ether solvents such as dioxane and tetrahydrofuran, and halogen solvents such as chloroform, and methylene chloride. Solvents are preferred, and cyclic ethers such as dioxane are particularly preferred.

The reaction temperature is between −20 and 30 ° C., preferably between 0 and 10 ° C. — If the temperature is lower than 20 ° C, the reaction speed becomes slow. If the temperature is higher than 30 ° C, generated AMD is decomposed and hydrogen cyanide escapes out of the system, which is not preferable.

The amount of the solvent used in the reaction is not particularly limited, but is 0.5 to 5 liters, preferably 1 to 2 liters per mole of DAMN.

The number of moles of the reaction is 1 to 5 moles, preferably 1.1 to 1.3 moles, of hydrogen cyanide per mole of DAMN, and hydrogen chloride is 2 to 3 moles, preferably 2 to 2.4 moles, based on hydrogen cyanide.

The reaction is usually completed in 1 to 10 hours. After the reaction is completed, the slurry is removed and dried to obtain the hydrochloride salt of AMD.However, when dioxane or the like is used, the solvent is incorporated into the crystals, so the crude crystals containing the solvent are once converted to alcohol, etc. After dissolving in water, the solvent is distilled off to obtain a high-purity AMD hydrochloride.

 When it is desired to obtain a free form of AMD, it can be obtained by dissolving the obtained hydrochloride in water and neutralizing with sodium hydrogen carbonate or the like. It is also possible to neutralize the hydrochloride with caustic soda or the like and use it as it is in the next reaction.

AMD can be a raw material for various compounds as shown below. 1. Synthesis of 4 (5) -amino-5 (4) -cyanoimidazole (AICN)

 (AMD hydrochloride) (AICN)

When reacting with AMD hydrochloride, the desired product can be obtained in high yield by suspending the mixture in an organic solvent or an aqueous solvent and dropping an aqueous solution of sodium hydroxide such as aqueous sodium hydroxide.

The organic solvent used in the reaction is not particularly limited as long as it is a solvent inert to the reaction, and the same solvents as those used in the production of AMD can be used. In particular, when the reaction is carried out without isolating AMD hydrochloride, it is advantageous to use the solvent used for producing AMD as it is.

The reaction temperature is -20 to 30 ° C, preferably 10 to 20 ° C. If the temperature is lower than -20 ° C, the reaction speed will be slow.

The amount of the solvent used in the reaction is not particularly limited, but is 0.5 to 5 liters, preferably:! To 2 liters per mole of AMD hydrochloride.

The number of moles of the reaction is 3 to 5 moles, preferably 3.2 to 3.8 moles of alkali per mole of AMD hydrochloride.

The reaction is usually completed in 1 to 5 hours. After completion of the reaction, the product is neutralized with an acid, extracted with an organic solvent, and concentrated to obtain crude crystalline AICN.

2.1 Synthesis of 1Η-4 (5) -aminoimidazole-5 (4) -carpoxamide (AICA)

 (AMD hydrochloride) (AICA)

After cooling in an organic solvent of AMD hydrochloride and adding dropwise an aqueous solution of sodium hydroxide or the like, the target product can be obtained in high yield by heating to reflux.

The number of moles of the reaction is 4 to 10 moles, preferably 5 moles per mole of AMD hydrochloride. ~ 6 moles.

The reaction is usually completed in several hours to ten and several hours. After completion of the reaction, crude crystals AICA can be obtained by neutralizing with an acid and extracting with an organic solvent, or concentrating as it is.

3. Synthesis of 4,5-dicyanimidazole (DCI)

 (DCI) The target compound can be obtained in high yield by heating and refluxing the AMD hydrochloride dissolved or suspended in an organic solvent.

 When reacting without isolation of AMD hydrochloride, the amount of hydrochloric acid used to produce AMD hydrochloride is 2.5 to 3.5 moles per mole of DAMN, which is higher than the usual AMD manufacturing conditions, so that it can be manufactured in one pot. Is possible.

When AMD is isolated, DCI can also be obtained by heating in a polar solvent such as acetic acid. BEST MODE FOR CARRYING OUT THE INVENTION Next, the present invention will be described in more detail with reference to examples.

Example 1: Synthesis of AMD hydrochloride

 (AMD hydrochloride)

To 3 L of dioxane cooled to 10 ° C., 97.3 g (3.6 Omo 1) of HCN was added. After injecting 275.9 g (7.56mo1) of HC1 there, 324.3g (3.0 Omo1) of DAMN was added, and the mixture was stirred at 25 ° C for 8 hours. The slurry was cooled to 3 ° C and filtered to remove AMD hydrochloride containing dioxane. 3. O g was obtained. 30.1 g of the crystal was taken, dissolved in 210 ml of methanol, concentrated and dried to remove dioxane, thereby obtaining 25.4 g of AMD hydrochloride (purity: 96.7%). (Yield 98.5%) Melting point 129 ° C (decomposition)

Example 1 Synthesis of AICN

 (AICN)

To dioxane 2 Om 1 cooled to 10 ° C, 1.62 g (0.060 mo 1) of HCN was added. Thereto was added a solution obtained by dissolving 14.60 g (0.126 mo 1) of HC in 3 Om 1 dioxane. To this, 5.41 g (0.050 mol 1) of DAMN was added, and the mixture was stirred at 25 ° C for 8 hours to synthesize AMD. The solution was cooled to 3 ° C., and 38.00 g (0.238 mol) of a 25% aqueous NaOH solution was gradually added dropwise, followed by stirring at 10 ° C. for 1.5 hours. The mixture was neutralized by adding 1.50 g (0.11 Omo 1) of 35% hydrochloric acid, and extracted with THF to obtain a solution of AICN. (Yield 94.7%)

Reference Example 2 Synthesis of AICN

To THF 40 Om1 cooled to 3 ° C., 32.4 g (1.2 Omo1) of HCN was added. Thereto was added a solution prepared by dissolving 148.2 g (1.32 mol) of HC in 600 ml of THF. To this, 108.1 g (1.0 Omo 1) of DAMN was added, and the mixture was stirred at 25 ° C. for 17 hours to synthesize AMD. The mixture was cooled to 3 and 625 g (3.9 lmo 1) of a 25% NaOH aqueous solution was gradually added dropwise, followed by stirring at 25 ° C for 2 hours. After adding and neutralizing 275 g (2.64 mol) of 35% hydrochloric acid, the mixture was extracted with THF to obtain a solution of AICN. The solution was concentrated to 990.2 g, and 420.O g was collected. After concentration, 1.1 1 L of water and 7.40 g of activated carbon were added, and the mixture was stirred at 25 ° C for 1 hour and filtered. The aqueous solution was concentrated to 14 Oml, cooled to 5 ° C., crystallized, and filtered to obtain 32.6 g of AICN. (Yield 71%) Reference Example 3 Synthesis of AICA

 (AICA)

To 40 ml of dioxane cooled to 10 ° C., 3.24 g (0.12 Omo 1) of HCN was added. Thereto was added a solution obtained by dissolving 9.20 g (0.252 mo 1) of HC in 6 Om 1 of dioxane. To this, 10.81 g (0.100 mo 1) of DAMN was added and stirred at 25 ° C for 8 hours to synthesize AMD. The solution was cooled to 3 ° C, and 76.00 g (0.480 mol) of a 25% aqueous NaOH solution was gradually added dropwise, followed by stirring at 10 for 1.5 hours to obtain AICN. The solution was heated to 84 ° C, 101.3 g of the solvent was distilled off, and then 16 g (0.10 Omo 1) of 25% NaOH was added.The mixture was refluxed for 12 hours to obtain an aqueous solution of AICA. . (Yield 93.4%)

Reference example 4 DCI synthesis

 (DCI)

To THF 2 Om1 cooled to 5 ° C., 1.62 g (0.06 Omo1) of HCN was added. To this was added a solution of 6.57 g (0.18 Omo 1) of HCl in 30 ml of THF. To this, 5.41 g (0.05 Omo 1) of DAMN was added, and the mixture was refluxed for 48 hours to obtain a THF solution of DCI. (Yield: 76.9%) The analysis conditions of HP LC used for quantification in the above Examples and Reference Examples are as follows.

産業上の利用可能性 本発明の製造方法は、 前記参考例からも明らかなように種々の農医薬中間体と 成り得る AMDが温和な条件でしかも高収率で得られるので、 工業的に優れた 製造方法である。 HPLC analysis conditions / column: Mightysil RP-18GP Aqua 250-4.6 (5 m), mobile phase: 4% CH3CN in Buffer (wt%), Buffer: 3 mM sodium 1-octanesulfonate, _{40mM KH2PO4, 24mM 85% H 3} PO4, column temperature 40 ° (:, UV: 230nm ,

INDUSTRIAL APPLICABILITY The production method of the present invention is, as is clear from the above-mentioned Reference Examples, capable of producing AMD which can be used as various agrochemical intermediates under mild conditions and in a high yield, and thus is industrially excellent. It is a manufacturing method.

Claims

O 2004 Cafe 529 Claims 1. A method for producing N- (2-amino-1,2-dichanovinyl) formamidine, which comprises reacting diaminomaleonitrile with hydrogen chloride and hydrogen cyanide in an organic solvent. 2. The method according to claim 1, wherein the organic solvent is an ether solvent.