JPS58170764A - Preparation of n-substituted imidazole - Google Patents

Abstract

PURPOSE:To prepare the titled substance having antibacterial activity, easily, in high yield and purity, from chemically stable raw materials, by reacting a triphenylmethanol compound with imidazole in the presence of sulfuric anhydride. CONSTITUTION:The titled compound is prepared by reacting a triphenylmethanol compound with imidazole in an inert organic solvent such as methylene chloride, dichloroethane, chloroform, trichloroethane, etc., in the presence of sulfuric anhydride, if necessary in the presence of an acid acceptor, at -50- +140 deg.C, preferably -20--80 deg.C. The amount of the sulfuric anhydride is preferably 0.2-5pts.wt. per 1pt.wt. of the triphenylmethanol compound used as a raw material. The acid acceptor is preferably imidazole used in excess.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing l-triphenylmethylimidazole, which is characterized by reacting triphenylmethanol and imidazole in the presence of sulfuric anhydride.

The triphenylmethanols include triphenylmethanol having a substituted or unsubstituted phenyl group. As a substituent for a substituted phenyl group.

Halogen atoms such as chlorine and bromine, methyl and ethyl.

Examples include lower alkyl groups such as propyl, alkoxy groups such as methoxy, ethoxy, propoxy, and aryl groups. Specific substituted phenyl groups include m-methylphenyl, 0-chlorophenyl, P-methoxyphenyl, P-nitrophenyl, etc. It will be done.

The 1-triphenylmethylimidazole obtained in the present invention is known to have antibacterial properties (
Chew, Ber, 93 P, 576 (+9
60) ;Special Publication No. 47-18752, Special Publication No. 4
Various methods are known for producing 1-triphenylmethylimidazole. That is,
(A)) Method of reacting liphenylmethyl halides with imidazole compounds (for example, Japanese Patent Publication No. 48-1530
No. 7; Special Publication No. 18752 of 1972; Japanese Patent Publication No. 15 of 1972
No. 1970; JP-A-54-17741).

(B) Triphenylmethanols and imidazole or an activated imidazole compound, such as tri(1
A method of reacting with -imidazolyl)phosphin, venter(l-imidazolyl)phosphorane, or imidazole magnesium halide (for example,
20015; Japanese Patent Publication No. 47-32982; Japanese Patent Publication No. 1973
-157561; JP-A-55-2644).

(C) A method in which triphenylmethanols and imidazole are reacted in the presence of a reaction accelerator, such as a phosphorus oxyacid ester.

Titanium chloride, aluminum chloride (JP-A-55-6206
No. 7; JP-A No. 55-62068) is known.

However, the method (A) uses halide as a raw material and is stable in handling. Moreover, it has a first-class drawback that requires special consideration in terms of hygiene management. (B),
Method (C) has the advantage of not using triphenylmethyl halide as a raw material. However, since the raw material is triphenylmethanol, which is inert compared to halides, high temperatures are generally required. On the other hand, converting imidazole into an active derivative requires complicated operations. Furthermore, even when a reaction accelerator is added, the reaction temperature is high.

Moreover, it has drawbacks such as the production of by-products in addition to the desired product, 1-triphenylmethylimidazole, and a poor purification yield.

For these reasons, there has been a desire for the development of an easy-to-implement, high-yield method that uses chemically stable raw materials and does not require special considerations for factory hygiene control.

The present inventors have overcome the drawbacks of the above-mentioned conventional methods.

In order to develop a process for producing 1-triphenylmethylimidazole that can be easily carried out with good yield on an industrial scale.

I did various research. As a result, triphenylmethanols and sulfuric anhydride were reacted in an inert organic solvent.

Then, by applying imidazole, high quality 1
It has been found that -triphenylmethylimidazoles can be produced easily and with good yield.

The present invention was completed based on this knowledge.

The present invention will be explained in more detail below.

In the present invention, triphenylmethanol is dissolved in an inert organic solvent and sulfuric anhydride is added. Then, imidazole is reacted. At this time, if necessary, the reaction may be carried out in the presence of an acid binder.

The amount of sulfuric anhydride to be used can be arbitrarily selected depending on the type of solvent or reaction temperature, but it is preferably 0.2 to 5 times the weight of the raw material triphenylmethanol.

As the inert organic solvent used as the reaction solvent, methylene chloride, dichloroethane, chloroform, trichloroethane, trichlene, etc. are advantageously used in the craft industry. A preferred acid binder optionally used in the reaction is imidazole in excess.

The reaction temperature is 411! of the reaction solvent! Although it varies depending on the amount of tl or sulfuric anhydride used, it can be selected in the range of -50°C to 140'C, but preferably -20°C to -80°C.
It is.

When the target substance, 1-triphenylmethylimidazole, is obtained from the reaction solution thus obtained, it can be obtained, for example, by the following method.

is added and then chloroform or methylene chloride is added to extract the product. By concentrating the extract, crude l-triphenylmethylimidazole can be obtained. Next, recrystallize this material using, for example, acetonitrile.

Alternatively, a highly pure target substance can be obtained by purification by column chromatography or the like.

Examples are shown below.

Example 1: Triphenylmethanol 5.
Dissolve 21 g (0.02 mol) at room temperature and add 3 ml of anhydrous sulfuric acid.
．． 20g, then 5.45g imidazole (0,
08 mol) and reacted for 15 minutes. After the reaction is completed, the organic layer is washed with water 501 and separated, and then the organic layer is distilled off under reduced pressure. Ethanol 451 is added to the remaining residue for crystallization. After filtration and washing with water, 4.84 g of ukl triphenylmethylimidazole are obtained (yield 78%).

If the obtained crystals are recrystallized with ethanol, 1, p, 22
1-triphenylmethylimidazole is obtained at 6°C (literature value 226-227°C).

Elemental analysis value CH,N Calculated value 85.13% 5.84% 9.02%
Actual value 85.10% 5.65% 9.00%
Example 2 In the same manner as in Example 1, 5.90 g (0.02 mol) of 0-chlorophenyldiphenylmethanol is used instead of triphenylmethanol. After the reaction is completed, the organic layer is washed with 50 liters of water and branched, and then the organic layer is distilled off under reduced pressure, and 20 l of acetonitrile is added to the residue for crystallization. After filtering and washing with water, 5.19 g of 1-[0-chlorophenyldiphenylmethylcoimidazole is obtained (yield 7.53%).
. If the obtained crystals are recrystallized with ethanol, -, p,
1- of 142-143℃ (literature value -142-145℃)
(O-chlorophenyldiphenylmethylcoimidazole is obtained.

Elemental analysis value CHN Calculated value 76.63% 4.97% 8.12%
Actual value 76.60% 4.82% 8.01%
Proceeding Amendment Written Patent No. 2g, J. 1980 (c) Director-General of the Agency 1. Indication of matter P1, Patent Application No. 53242 of 1982, 2. Title of invention: Process for producing N-substituted imidazoles 3. Amendment. Relationship with the patent applicant's case Postal code 100 Address No. 6-1, Otemachi-cho, Chiyoda-ku, Tokyo Name (102) Kyowa Hakko Kogyo Co., Ltd. Column 5 of the detailed description of the invention in the specification, M Masaru (as shown in the attached sheet) In the specification page 4, line 20, "~-80°C" is corrected to "~+80'CJ."

(2) Above the first line of page 5 of the specification, ``The solvent is distilled off from the reaction solution under reduced pressure, and water is added to the residue''.

(3) Page 5, line 16 of the specification rl) "Riphenylmethy" is corrected to "4-triphenylmethy".

(4) "(Yield 7.53%)" on page 6, line 9 of the specification is corrected to "(yield 75.3%)."

Claims (1)

[Claims] A method for producing 1-triphenylmethylimidazole, which comprises reacting triphenylmethanol and imidazole in the presence of sulfuric anhydride.