JPH0399065A - Preparation of imidazole compound - Google Patents

Abstract

PURPOSE:To prepare a 2-cyanoimidazole compound useful as a raw material for agricultural chemicals, drugs, etc., by reacting a 2-bromoimidazole compound with a metal cyanide. CONSTITUTION:A compound of formula I (R is F, Cl, Br or alkyl; (n) is 0-5; X is Cl or Br) is reacted with a bromination agent in a solvent such as methylene chloride at -50 to 100 deg.C to prepare a 2-bromoimidazole compound of formula II, which is reacted with a metal cyanide (e.g. cuprous cyanide) in a solvent such as dimethylformaldehyde at 80-250 deg.C to provide the objective compound of formula III. The bromination agent and the metal cyanide are used in amounts of 1.0-1.5mol and 0.5-3.0mol, respectively, per mol of the compound of formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Application Field) The present invention relates to a new industrially advantageous method for producing imidazole compounds that are useful as raw materials for a-drugs, pharmaceuticals, and the like.

(Disclosure of the Invention) The present invention involves reacting a 2-bromo ξdazole compound represented by the general formula (III) (wherein Rsn and X are as described above) with a metal cyanide, (l.) (where R, n and X
is as described above. A method for producing a 2-cyanoi ξdazole compound, the method comprising producing a 2-cyanoi ξdazole compound represented by:

(wherein, R is a fluorine atom, a chlorine atom, a bromine atom, or an alkyl group, n is an integer of O to 5, and X is a chlorine atom or a bromine atom) and a brominating agent. A method for producing a 2-bromoimidazole compound represented by the general formula (II) (in which R, n and A method for producing a 2-cyanoimidazole compound represented by the general formula (1) (wherein R, n and The present invention relates to a method of carrying out a second cyanation step after the cyanation step and the bromination step.

In the general formulas (1), (■) and (IIIi), the alkyl group represented by 1 is one having 1 to 6 carbon atoms, such as a methyl group, an ethyl group, a proyl group, a butyl group, a benzyl group, and a hexyl group. etc., which may be linear or have a side chain.Furthermore, when n is 2 or more, R may be the same or different.

In the bromination step, examples of the brominating agent include bromine, N-promosuccinimide, an aqueous solution of sodium hypobromite, and hydrogen bromide or an aqueous solution thereof may be used in combination with aqueous hydrogen peroxide. The amount used is determined by the general formula of the raw material (I
Usually 1.0 to 1.0% per mole of the compound represented by I).
5 mol, preferably 1. The amount is 0 to 1.2 moles. The reaction temperature in this step is usually -50 to 100°C, preferably 0 to 70°C, and the reaction time is usually 0.1 to 24 hours, preferably 0.1 to 3 hours. Further, this step may be carried out in the presence of a diluent, a neutralizing agent, etc. The diluent may be any one as long as it is inert to the brominating agent.
Examples include methylene chloride, chloroform, carbon tetrachloride, methanol, ethanol, acetic acid, aqueous solutions of mineral acids, and water. Examples of neutralizing agents include sodium bicarbonate, sodium acetate, and sodium hydroxide.

In the cyanation step, metal cyanides include cuprous cyanide, sodium cyanide, potassium cyanide, and the like, and two or more of these metal cyanides may be used in a mixture. In the cyanation step, when a metal cyanide other than cuprous cyanide is used, it is practically preferable to use a catalyst in combination. Examples of this catalyst include monovalent copper catalysts such as cuprous chloride, cuprous bromide, and cuprous oxide. Even when cuprous cyanide is used as the metal cyanide, the monovalent copper catalyst described above may be used in combination. In addition, cuprous cyanide itself also acts as a catalyst, so if a metal cyanide other than cuprous cyanide is used, it can be used in combination as a catalyst. .

The amount of metal cyanide to be used is usually 0.00 to 1 mole of the compound represented by general formula (II) as a raw material. 5 to 3.0 mol, preferably 1. It is 0 to 1.5 moles. The amount of catalyst used is usually 0.05 to 2 mol per 1 mol of the compound represented by general formula (n) as a raw material. The reaction temperature in the cyanation step is usually 80 to 250°C, preferably 120 to 250°C.
The reaction time is usually 0.5 to 20 hours, preferably 1 to 10 hours.

Also, this cyanation step is usually carried out in the presence of a solvent,
Examples of the medium include aprotic polar solvents such as dimethynolephonolemamide, dimethylacetamide, dimethylsulfoxide, dimethylsulfone, N-methylpyrrolidone, and hexamethylphosphorifuctriamide; pyridine, β
- Pyridines such as vicolin and ethylmethylpyridine;
Nitrile necks such as benzonitrile; aromatic hydrocarbon necks such as toluene and xylene; and the like.

The compound represented by the general formula (1) can be produced, for example, by the following method.

(In the formula, Rsn and X are as described above.) Examples of the brominating agent in the above reaction include those similar to those used in the bromination step. Chlorinating agents include chlorine gas, N-chlorosucciniide, and sodium hypochlorite.
An aqueous solution of hydrogen chloride or an aqueous solution thereof may be used in combination with a hydrogen peroxide solution. The chlorination or bromination reaction is carried out in the presence of a diluent, a neutralizing agent, etc., if necessary. The diluent may be any one as long as it is inert to the chlorinating agent or the brominating agent, such as those similar to those used in the bromination step, and the neutralizing agent may also be used in the bromination step. Examples include those similar to those used in .

The compound represented by the general formula (IV) is a known compound or can be produced by the method described in JP-A-1-131163.

The general formula (compounds represented by eyes are JP-A-1-13)
As described in Japanese Patent No. 1163, compounds useful as pest control agents can be further derived.

Next, examples of the present invention will be described.

[Bromination process]

Example! (1) 4 (5) Monophenyl hydrazole 17.2
Dissolve g in 64ml of 35% aqueous hydrochloric acid solution, and add 33ml of 30% hydrogen peroxide aqueous solution to the solution.2. Drop 4 g,
Stirring was carried out for 1 hour while maintaining the reaction temperature at about 40°C.

After the reaction was completed, the reaction solution was poured into 600 mJ of water, and 2
Neutralize by adding 0% aqueous sodium hydroxide solution, filter the precipitated crystals and dry them to obtain 4(5)-1chloro-5(4)
18.63 g of monophenylimidazole was obtained. When a part of it was recrystallized with ethyl acetate and its melting point was measured, it was found to be 23
The temperature was 4-236°C.

[2] 4(5)-1chloro-5 obtained in the above (1)
(4) 5.4 g of monophenylimidazole was suspended in 63 g of a 5% aqueous hydrobromic acid solution, and 4.4 g of a 30% aqueous hydrogen peroxide solution was added dropwise thereto. After that, the reaction temperature was increased to 40~
The temperature was maintained at 45°C and stirring was performed for 3 hours.

After the reaction is complete, add 300mj of water to the reaction solution! put it into
The precipitated crystals were collected by filtration and dried to give 2-bromo-4(5)-chloro-5(4)-phenylicotasol (compound ft
l) 7.05g was obtained. A part of it was recrystallized from ethyl acetate and the melting point was measured, and it was 201-205°C.

Example 2 (1) 4 (5)- (4-lophenyl)
8.0 g imidazole and 6 N-chlorosuccinimide
．． 58 g was added to 80 ml of methanol and stirred at 60°C for 1 hour.

After the reaction was completed, the reaction solution was poured into 400 rnl of water, and the precipitated crystals were collected by filtration and dried to give 4 (5) one chloro5
(4)-(4-chlorophenyl)imidazole 8.4
1g was obtained. A part of it was recrystallized from ethyl acetate and the melting point was measured to be 241-243°C.

[2] 4(5)-1chloro-5 obtained in [1] above
(4)-(4-chlorophenyl)imidazole8.
0 g and 3.7 g of sodium acetate were added to 50 ml of acetic acid, and 6.6 g of bromine was added dropwise thereto, followed by stirring at 40°C for 1 hour. After the reaction was completed, the reaction mixture was poured into 400 ml of water.
The precipitated crystals were collected by filtration and dried to obtain 8.34 g of 2-promo4(5)-chloro5(4)-(4-chlorophenyl)imidazole (compound 1IkL2). When a part of it was recrystallized with ethyl acetate and the melting point was measured, it was found that 1
The temperature was 90-194°C.

Example 3 (1) 4 (5)- (4-methylphenyl)imidazole 7.9 g and N-chlorosuccinimide 7
．． 34 g was added to 80 ml of methanol, and the reaction and post-treatment were carried out in the same manner as in Example 2 [1].
5) Monochloro5 (4)- (4-methylphenyl)
8.27 g of imidazole was obtained. When a part of it was recrystallized with ethyl acetate and the melting point was measured, it was found to be 220-223℃.
Met.

[2] 4(5)-1chloro-5 obtained in (1) above
(4)-(4-methylphenyl)imidazole 8.0
g and 4.1 g of sodium acetate were added to 50 ml of acetic acid, 7.3 g of bromine was added dropwise thereto, and the reaction and post-treatment were carried out in the same manner as in Example 2 [2].
)1-chloro5 (4)-(4methylphenyl)igodazole (compound 1th3)9. 97 g was obtained. A part of it was recrystallized from ethyl acetate and the melting point was measured, and it was 206-209°C.

Example 4 (1) 4 (5)-(3-Chloro-4-medylphenyl)imidazole [α-bromo-3-chloro-4-methylacetylated phenone obtained by promoacetylating 2-chlorotoluene was further subjected to form accumulation. 2.5 g of N-chlorosuccinimide (obtained by reacting with 4 (5
) 2.76 g of chloro-5(4)-(3-chloro-4-methylphenyl)-dazole was obtained. When a part of it was recrystallized with ethyl acetate and the melting point was measured, it was found to be 252-2.
The temperature was 54°C.

[2] 4(5)-1chloro-5 obtained in [1] above
(4)-(3-chloro4-methylphenyl)imidazole 1.96 g and sodium acetate 0. 8 g was added to 15 ml of acetic acid, 1.5 g of bromine was added dropwise thereto, and the reaction and post-treatment were carried out in the same manner as in Example 2 [2] to obtain 2-bromo-4(5)-1chloro-5 (4). - (3-
chloro-4-methylphenyl)imidazole (compound N
a4) 2.38g was obtained. A part of it was recrystallized from ethyl acetate and the melting point was measured to be 230-234°C.

The compounds represented by the general formula (n) include novel compounds. Representative examples of these new compounds include the compounds shown in Table 1.

No. 1 table The reaction was carried out at ℃ for 463 hours.

After the reaction is complete, let it cool to room temperature, then add 10 ethanol.
After adding 0 ml and stirring, the precipitated insoluble matter was filtered off, diluted hydrochloric acid was added to make it acidic, and the mixture was extracted with ethyl acetate. The solvent in the extract was distilled off, and 2% aqueous sodium hydroxide solution 2 was added to the residue.
After adding 0.0 0 mit and stirring thoroughly, insoluble matter was filtered off. 35% hydrochloric acid was added to the filtrate to adjust the pH to 1. The precipitated crystals were collected by filtration and dried to give 4(5)-1chloro-2-cyano5(4)-phenylimidazole5.
Obtained 0g.

A part of it was recrystallized from ethyl acetate and the melting point was measured to be 173-176°C.

[Cyanation process]

Example 5

Claims (1)

[Claims] 1. General formula (III) ▲There are mathematical formulas, chemical formulas, tables, etc.▼...(III) (In the formula, R is a fluorine atom, chlorine atom, bromine atom or an alkyl group, and n is 0 An integer of ~5 and X is a chlorine atom or a bromine atom) is reacted with a brominating agent to produce the general formula (II) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼...(II) ( A 2-bromoimidazole compound represented by the formula (wherein R, n and
) ▲There are mathematical formulas, chemical formulas, tables, etc.▼...(I) 2 characterized by producing a 2-cyanoimidazole compound represented by (in the formula, R, n and X are as described above) - A method for producing a cyanoimidazole compound. 2. General formula (III) ▲There are mathematical formulas, chemical formulas, tables, etc.▼...(III) (In the formula, R is a fluorine atom, chlorine atom, bromine atom or an alkyl group, and n is an integer from 0 to 5. , X is a chlorine atom or a bromine atom) is reacted with a brominating agent to produce 2- A method for producing a 2-bromoimidazole compound, the method comprising producing a bromoimidazole compound. 3. General formula (II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼...(II) 2-bromoimidazole compound and metal cyanide represented by (in the formula, R, n, and X are as described above) A 2-cyanoimidazole compound represented by the general formula (I) ▲Mathematical formula, chemical formula, table, etc.▼...(I) (in the formula, R, n, and X are as described above) is produced by reacting with A method for producing a 2-cyanoimidazole compound.