JP2966041B2 - Method for chlorination of imidazole ring - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a method for efficiently chlorinating an imidazole ring.

BACKGROUND OF THE INVENTION Chlorimidazole compounds are used in pharmaceuticals, photographic materials,
It is a compound useful as a dye intermediate or the like.

To chlorinate a compound, a chlorinating agent (eg, N
-Chlorosuccinimide, sulfuryl chloride, chlorine, etc.) and directly introducing a chloro group into the compound is generally used.

In particular, chlorination with N-chlorosuccinimide (hereinafter referred to as NCS) has a small number of side reactions and is easy to perform post-treatment. Therefore, chlorination to an active methylene compound or another heterocyclic compound (for example, a tetrazole compound or the like) is performed. Often used to introduce

NCS is a highly reactive compound, and the reaction with the various active methylene compounds and other heterocyclic compounds is often completed in a few minutes to several hours at room temperature.

However, when trying to introduce a chloro group into the imidazole ring using NCS, the reactivity is extremely low,
Often it takes days to weeks to complete the reaction.

The use of another chlorinating agent is not preferred because side reactions occur, the reaction stops halfway, or post-treatment is extremely troublesome.

OBJECTS OF THE INVENTION It is therefore an object of the present invention to provide an improved method of chlorination of the imidazole ring.

[Constitution of the Invention] When the imidazole ring is chlorinated using NCS, the reaction is remarkably accelerated by the presence of hydrochloric acid in the reaction system during the reaction, and the object of the present invention is sufficiently achieved. I found something to be done.

Examples of the imidazole ring that can be chlorinated by the method of the present invention include an imidazole ring of a compound represented by the following general formula [I].

General formula [I] In the formula, A, B and C each represent a hydrogen atom or a substituent. At least one of A, B and C is a hydrogen atom.

In the compound represented by the general formula [I], the substituent is an alkyl group, an aryl group, a heterocyclic group, a cyano group,
Such as an acyl group, an organic group bonded to the imidazole ring via a carbon atom, an acylamino group, an alkoxycarbonylamino group, an aryloxycarbonylamino group, a sulfonamide group, an anilino group, an ureido group, an amino group, a heterocyclic group, etc. An organic group, an alkylthio, an arylthio, a heterocyclic thio group, etc., which is bonded to an imidazole ring via an oxygen atom, such as an organic group, an alkoxy group, an aryloxy group, a heterocyclic oxy group bonded to a imidazole ring via a nitrogen atom An organic group bonded to an imidazole ring via a sulfur atom is preferable because chlorinated compounds are useful as various intermediates and the like.

According to the chlorination method of the present invention, in the compound represented by the general formula [I], when A, B and C are hydrogen atoms, the positions thereof are chlorinated.

In the present invention, the chlorination of the imidazole ring is preferably performed in an organic solvent. The organic solvent is not particularly limited as long as it does not react with NCS, and a solvent generally used for an organic reaction can be used. For example, chloroform, ethyl acetate, acetic acid, dimethylformamide, acetonitrile and the like are particularly useful.

The hydrochloric acid used in the reaction may be concentrated hydrochloric acid or diluted hydrochloric acid, and the amount added is not more than an equimolar amount of the imidazole compound, but may be added more.

Next, specific examples of chlorimidazole obtained by the chlorination method of the present invention will be described.

The compounds obtained by the chlorination method of the present invention are not limited to these compounds.

[Examples] In order to specifically illustrate the chlorination method of the present invention, both examples and comparative examples are described below, but the present invention is not limited to these examples.

Synthesis of Exemplified Compound 3 Comparative Example- 1 8.0 g of raw material 1 was dissolved in 150 ml of chloroform, and NCS 1.48 was dissolved.
g was added and reacted at room temperature. The reaction was carried out while checking the reactivity by TLC.
Was completely consumed and the reaction was completed. After the chloroform was distilled off, the residue was purified by column chromatography to obtain 6.05 g of a candy-like target product.

Comparative Example-2 In Comparative Example-1, chlorination was carried out in exactly the same manner except that the reaction was carried out by heating and refluxing on a hot water bath. The number of days required for the reaction did not change, and the yield was 5.2 g. As a result, the yield was deteriorated.

Example- 1 8.0 g of raw material 1 and 1.48 g of NCS were dissolved in 150 ml of chloroform, and a few drops of concentrated hydrochloric acid were added thereto while stirring at room temperature.
The reaction was complete after 1 hour. Post-treatment was carried out in the same manner as in Comparative Example 1 to obtain 6.9 g of the desired product.

The structure of the target compound was confirmed by NMR and Mass spectra.

From the above results, it can be seen that the method of the present invention is extremely excellent as a method for producing a chlorimidazole compound.

[Effects of the Invention] According to the present invention, the imidazole compound can be chlorinated in a short time, the yield is high, and the side reaction is small.

Continuation of the front page (58) Field surveyed (Int. Cl. ⁶ , DB name) C07D 233/68 CA (STN)

Claims (1)

(57) [Claims] 1. A method for chlorinating an imidazole ring, comprising chlorinating N-chlorosuccinimide as a chlorinating agent in the presence of hydrochloric acid.