JPS61145165A - Production of benzimidazole derivative - Google Patents

Abstract

PURPOSE:To produce the titled compound useful as cocatalyst, medicinal drug and their intermediate, efficiently by a simple method, by using an easily available benzimidazole compound having excellent stability as a raw material, and heating the compound together with an aldehyde. CONSTITUTION:The benzimidazole derivative of formula III [e.g. 1-ethyl-2-(alpha- hydroxybenzyl)benzimidazole] is produced by reacting the benzimidazole compound of formula I (R<1> is 1-3C alkyl, R<2> and R<3> are H or methyl) (e.g. 1- methylbenzimidazole) with the aldehyde of formula II (R<4> is H, methyl or phenyl) (e.g. formaldehyde) at room temperature -300 deg.C, preferably under heating at 50-250 deg.C, especially about 100-200 deg.C. The unreacted raw material can be reused. USE:Cocatalyst of a ruthenium catalyst for the production of an oxygen-containing compound such as ethylene glycol from CO and H2.

Description

DETAILED DESCRIPTION OF THE INVENTION The raw material benzimidazole compound used in the present invention is represented by general formula (1).

However, R1 is a C1-3 alkyl group, such as a methyl group,
They are ethyl group, inflovir group, etc., and R2 and R3 represent the same or different substituents and are hydrogen or methyl group.゛Specific examples of compounds represented by general formula (1) include 1
-Methylbenzimidazole, 1-ethylbenzimidazole, 1-n-propylbenzimidazole, 1-isopropylbenzimidazole, 1,5.6-)limethylbenzimidazole, 1-ethyl-5,6-dimethylpenzimidazole, 1-n-propyl-5,6-dimethylbenzimidazole, 1-isopropyl-5,6-
Dimethylpenzimidazole, 1,5-dimethylbenzimidazole, 1,6-dimethylbenzimidazole,
1-Ethyl-5-methylbenzimidazole, 1-ethyl-6-methylbenzimidazole, 1-n-propyl-5-methylbenzimidazole, 1-n-propyl-
6-methylbenzimidazole, 1-isopropyl-5
-Methylbenzimidazole, 1-isopropyl-6-
Examples include methylbenzimidazole.

Other raw materials, aldehyde compounds, have the general formula (II), R
'-CHO...(II), R4
represents a hydrogen atom, a methyl group or a phenyl group. General formula (
Specific examples of the compound represented by If) include formaldehyde, acetaldehyde, benzaldehyde, etc. In the case of formaldehyde where R4 is a hydrogen atom,
Any material that can generate formaldehyde in the reaction system can be used, such as an aqueous solution or paraformaldehyde.

The reaction is carried out in a solvent or without solvent. When using a solvent, use hydrocarbons such as hexane, octane, decane, dodecane, toluene, and xylene, ethers such as diptyl ether, diglyme, triglyme, and tetraglyme, and esters such as ethyl acetate, butyl acetate, and butyl butyrate. Although not particularly limited to lactones such as , gamma-butyrolactone, and delta-valerolactone, compounds that cause a thermal reaction with the raw material aldehyde are not preferred.

In the method of the present invention, there is no need to use a solvent when the raw materials benzimidazoles and aldehydes become liquid at the reaction temperature.

The reaction in the method of the present invention can be carried out simply by mixing and heating the above raw material compounds. The reaction proceeds slowly even at room temperature, so it is usually carried out under heating.

The reaction temperature is room temperature to 300°C, preferably 50 to 250°C.
, particularly preferably from Filoo to 200°C.

Separation and purification of the target product from the reaction mixture can be carried out by conventional distillation, extraction, crystallization, chromatographic separation, etc.

Moreover, unreacted raw materials after separation of the target product can be reused.

Experimental Examples Example 1 (Production of 1-ethyl-2-(α-hydroxybenzyl)benzimidazole) 1.46 g of 1-ethylbenzimidazole;
mmol) and 10.6 grams (100 mmol) of benzaldehyde.
mmol) in a glass ampoule and placed on an oil bath for 15
The reaction was carried out at 0°C for 17 hours. After bringing the ampoule to room temperature,
The contents were removed and concentrated under reduced pressure to approximately 3d. The oil containing this white solid was recrystallized from a hot hexane/ethanol system, and the resulting white solid was subjected to silica gel column chromatography (liquid phase dichloromethane:acetone = 3
= 1), white crystals with Rf = 0.73 were obtained.
．． 958 grams were obtained. When this was analyzed by IR and nmr spectroscopy, it was found to be 1-ethyl-2-(α-hydroxybenzyl)benzimidazole. Raw material 1
-Yield based on ethylbenzimidazole is 38 mol%
Met.

Example 2 (1-methyl-2-(α-hydroxybenzyl)-5,
Production of 6-dimethylbenzimidazole) 1.5.6-
Trimethylbenzimidazole 1.60 grams (10
mmol) and 10.6 grams (100 mmol) of benzaldehyde.
The reaction was carried out in the same manner as in Example 1, except that IJ mol) was used, and the concentrated solution was directly purified by silica gel chromatography to obtain 1.15 g of white crystals. IR this.

When analyzed by nmr spectrum, 1-methyl-2-
(α-hydroxybenzyl)-5,6-dimethylbenzimidazole. The yield was 43 mol% based on the raw material 1,5,6-trimethylbenzimidazole.

Example 3 (Production of 1-ethyl-2- and droxymethylbenzimidazole) 1.46 g (10 mmol) of 1-ethylbenzimidazole and 1.6 g of a 37% formalin aqueous solution (20 mmol as formaldehyde) were placed in a glass ampoule. and reacted on an oil bath at 150°C for 3 hours. After the reaction was completed, the contents of the ampoule were taken out after cooling to room temperature, and quantitative analysis by gas chromatography revealed that 1-ethyl-2-hydroxymethylbenzimidazole was 70 mol based on the charged 1-ethylbenzimidazole. % yield.

Saturated brine 10- was added to this reaction solution, extracted with dichloromethane, and the extract was dried over anhydrous sodium sulfate.
The solvent was distilled off and the residue was recrystallized from hot toluene to obtain 0.774 g of 1-ethyl-2-hydroxymethylbenzimidazole as white crystals. Raw material 1
-Yield based on ethylbenzimidazole is 44 mol%
Met.

Example 4 (Production of 1-isopropyl-2-(α-hydroxyethyl)benzimidazole) 1.60 grams of 1-isopropylbenzimidazole (
10 mmol) and acetaldehyde 2.20 durams (5
0 mmol) was sealed in a glass ampoule and placed on an oil bath for 15 min.
The reaction was carried out at 0°C for 3 hours. After the reaction was completed and cooled to room temperature, the contents of the ampoule were quantitatively analyzed by gas chromatography, and it was found that 1-isopropyl-2-(α
-hydroxyethyl)benzimidazole was produced. The yield Vi was 70 mol% based on the raw material 1-isopropylbenzimidazole.

Claims (1)

[Claims] (1) General formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼... (I) (Here, R^1 is an alkyl group of C_1 to_3, and R^2 and R^3 are the same or different, respectively. A compound represented by the general formula (II), R^4CHO...(II) (where R^4 represents a hydrogen atom, a methyl group, or a phenyl group) ) General formula (III), which is characterized by a thermal reaction with an aldehyde represented by 3 and R^4 are the same as above).