JP2014037380A - 4-(2-thienyl)imidazole compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a novel 4-(2-thienyl)imidazole compound.SOLUTION: A 4-(2-thienyl)imidazole compound is represented by the following formula, the compound being synthesized by causing a 2-alkyl halide-2-thienyl ketone compound and an amidine compound to be thermally reacted with one another in the presence of a dehydrohalogenation agent in an organic solvent.

Description

  The present invention relates to a novel 4- (2-thienyl) imidazole compound.

  As an imidazole compound similar to the present invention, for example, Non-Patent Document 1 and Non-Patent Document 2 disclose 2-phenyl-4- (2-thienyl) imidazole represented by the chemical formula (III). However, these documents do not disclose the imidazole compound of the present invention.

Russian Journal of Applied Chemistry, 83 (6), 1027-1031 (2010). Zeitschrift fuer Chemie, 8 (9), 339-340 (1968).

  An object of the present invention is to provide a novel 4- (2-thienyl) imidazole compound.

  As a result of intensive studies to solve the above-mentioned problems, the present inventors have been able to synthesize a novel 4- (2-thienyl) imidazole compound represented by the chemical formula (I) or the chemical formula (II). Acknowledgment has led to the completion of the present invention. In the imidazole compound, the 2-thienyl group is bonded to the 4-position of the imidazole ring.

  The 4- (2-thienyl) imidazole compound of the present invention is used as an antioxidant on the surface of metals, particularly copper (including copper alloys), as a curing agent or curing accelerator for epoxy resins, and as an intermediate raw material in the field of medicine and agrochemicals. It is also useful.

Hereinafter, the present invention will be described in detail.
The 4- (2-thienyl) imidazole compound of the present invention is
5-methyl-2-phenyl-4- (2-thienyl) imidazole,
5-methyl-2,4-di (2-thienyl) imidazole,
2- (2,4-dichlorobenzyl) -5-methyl-4- (2-thienyl) imidazole and 2- (2,4-dichlorobenzyl) -4- (2-thienyl) imidazole.

  The 4- (2-thienyl) imidazole compound of the present invention can be synthesized according to a known method. For example, as shown in the reaction formula (A), a 2-position halogenated alkyl-2-thienyl ketone compound and an amidine compound are synthesized by heating in an organic solvent in the presence of a dehydrohalogenating agent. Can do.

（式中、Ａは前記と同様であり、Ｒは水素原子又はメチル基を表し、Ｘは塩素原子、臭素原子又はヨウ素原子を表す。）

(In the formula, A is the same as above, R represents a hydrogen atom or a methyl group, and X represents a chlorine atom, a bromine atom, or an iodine atom.)

  In the above reaction, the amount of the amidine compound used is preferably 0.8 to 1.5 times, more preferably 0.9 to 1.1 times the mol of the 2-position halogenated alkyl-2-thienyl ketone compound. A mole ratio may be used. The amount of the dehydrohalogenating agent used is preferably a ratio of 1 to 10 equivalents with respect to the 2-position halogenated alkyl-2-thienyl ketone compound.

  Examples of the 2-position halogenated alkyl-2-thienyl ketone compound include 2- (2-chloroacetyl) thiophene, 2- (2-bromoacetyl) thiophene, 2- (2-iodoacetyl) thiophene, 2- (2 -Chloropropionyl) thiophene, 2- (2-bromopropionyl) thiophene and 2- (2-iodopropionyl) thiophene.

  These 2-position halogenated alkyl-2-thienyl ketone compounds can be synthesized by halogenating the 2-position of the alkyl-2-thienyl ketone compound. Among the 2-position halogenations, 2-position chlorination and 2-position iodination are possible, but 2-position bromination in which 1 mole of bromine is reacted with 1 mole of alkyl-2-thienyl ketone compound is the simplest. .

  Examples of the alkyl-2-thienyl ketone compound include 2-acetylthiophene and 2-propionylthiophene. These are known compounds, and those commercially available as reagents can be used.

  The amidine compound can be synthesized according to a known method. That is, as shown in the reaction formula (B), the precursor nitrile compound is reacted with a lower alcohol such as hydrogen chloride gas and ethanol, converted into an imidate / hydrochloride compound, and further reacted with ammonia to form an amidine compound. Can be synthesized.

（式中、Ａは前記と同様である。）

(In the formula, A is as defined above.)

  Examples of the amidine compound include benzamidine, 2-thiophenecarboximidamide, (2,4-dichlorophenyl) acetamidine, and organic acid salts such as acetates and inorganic acid salts such as hydrochlorides thereof. Of these, benzamidine hydrochloride may be one that is commercially available as a reagent.

  Examples of the nitrile compound include benzonitrile, 2-cyanothiophene, and 2,4-dichlorobenzyl cyanide. These are known compounds, and those commercially available as reagents can be used.

  Any known dehydrohalogenating agent can be used without limitation. Examples of such a dehydrohalogenating agent include inorganic alkalis such as sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, triethylamine, 1,8 -Organic bases such as diazabicyclo [5,4,0] -7-undecene (DBU), metal alkoxides such as sodium methoxide and potassium tert-butoxide, and the like.

  Any known organic solvent can be used without limitation as long as it can dissolve the 2-position halogenated alkyl-2-thienyl ketone compound and amidine compound and does not participate in the reaction. Examples of such solvents include alcohols such as isopropyl alcohol and tert-butanol, hydrocarbons such as hexane and toluene, halogenated hydrocarbons such as chloroform and chlorobenzene, esters such as ethyl acetate, and nitriles such as acetonitrile. , Ethers such as tetrahydrofuran, dioxane, ethylene glycol dimethyl ether, amides such as N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAC), dimethyl sulfoxide (DMSO), and the like. A combination of solvents may be used.

  The reaction temperature is preferably room temperature to reflux temperature, and the reaction time is preferably 1 to 10 hours. The reaction may be usually performed under atmospheric pressure.

The 4- (2-thienyl) imidazole compound produced under the above reaction conditions can be isolated by ordinary post-treatment.
For example, the reaction mixture after completion of the reaction is divided into an aqueous layer and an organic solvent layer, and a crude 4- (2-thienyl) imidazole compound that precipitates as crystals can be obtained by washing the organic solvent layer with water. It can be purified by a recrystallization operation or the like.

  EXAMPLES Hereinafter, the present invention will be specifically described with reference to examples, but the present invention is not limited to these examples. Reference examples 1 and 2 show synthesis examples of 2- (2-bromopropionyl) thiophene and 2-thiophenecarboximidamide hydrochloride.

[Reference Example 1]
<Preparation of 2- (2-bromopropionyl) thiophene / toluene solution>
To a solution composed of 25.2 g (0.180 mol) of 2-propionylthiophene and 29 g of methanol, 28.7 g (0.180 mol) of bromine was added dropwise at 30 to 35 ° C. over 30 minutes. Next, the reaction solution was cooled and then concentrated under reduced pressure until the concentrate became 43 g. The concentrate was partitioned between 80 ml of toluene and 80 ml of brine, and the toluene layer was washed with 100 ml of brine and then dried over sodium sulfate to give brown transparent 2- (2-bromopropionyl) thiophene (0.180 mol) / toluene. A solution was obtained.

[Reference Example 2]
<Synthesis of 2-thiophenecarboximidamide hydrochloride>
To a solution consisting of 110.8 g (1.015 mol) of 2-cyanothiophene, 49.4 g (1.072 mol) of dehydrated ethanol and 55 g of dehydrated dichloromethane, 54.8 g (1. 22 mol) was blown and stirred for 5 hours, and then left in a refrigerator at 4 ° C./3 days to precipitate a solid. The reaction suspension was dried under reduced pressure to obtain 194.9 g (1.017 mol, yield: 100%) of 2-thiophenimidic acid ethyl hydrochloride as a red pink crystalline solid.
The solid was pulverized, and a solution consisting of 32.0 g (1.88 mol) of ammonia and 177 g of dehydrated ethanol was added little by little while shaking under ice cooling, followed by stirring for 4 hours, returning to room temperature and further overnight. Stir. This suspension was concentrated under reduced pressure to obtain 184 g of a candy-like concentrate. To the concentrate, 380 ml of a hexane / dichloromethane solution (2: 1 volume ratio) was added and stirred to precipitate crystals. The crystals were collected by filtration, washed with a hexane / dichloromethane solution, and then dried under reduced pressure to give 147.0 g (0.904 mol, yield 89.1%) of 2-thiophenecarboximidamide hydrochloride in the form of a peach white powder. Got.

[Example 1]
<Synthesis of 5-methyl-2-phenyl-4- (2-thienyl) imidazole>
Benzamidine hydrochloride 28.2 g (0.180 mol) was dissolved in N, N-dimethylacetamide 60 g by heating at 35 ° C., potassium carbonate 82 g (0.593 mol) was added, and the mixture was stirred at 53 to 57 ° C./40 minutes. The 2- (2-bromopropionyl) thiophene / toluene solution prepared in Reference Example 1 was added dropwise at 57 to 69 ° C. over 55 minutes. After completion of dropping, the mixture was stirred at 68 to 70 ° C./2 hours 30 minutes.
Next, the reaction suspension was cooled, stirred with 500 ml of water, and the separated organic layer was washed with 500 ml of water to precipitate crystals. The crystals were collected by filtration and dispersed and washed with toluene and then with hot water to obtain a wet pale yellow powder. The powder was recrystallized from acetonitrile to obtain 25.5 g of a yellowish white powder.

The melting point of the obtained powder, Rf value of thin layer chromatography, ¹ H NMR and mass spectrum data were as follows.
・ Mp202-206 ℃
・ TLC (silica gel, acetone): Rf = 0.69
¹ H NMR (DMSO-d ₆ ): δ = 2.46 (s, 3H), 7.09-7.95 (m, 8H).
MS (EI): m / z (%) = 240 (M ⁺ , 100), 207 (2), 195 (2), 171 (3), 136 (5), 120 (3), 110 (8) 103 (3), 95 (6), 77 (4).
From these spectrum data, the obtained powder was identified as 5-methyl-2-phenyl-4- (2-thienyl) imidazole represented by the chemical formula (IV). Yield 58.9%.

[Example 2]
<Synthesis of 5-methyl-2,4-di (2-thienyl) imidazole>
A synthetic test was conducted according to the method of Example 1 in place of the benzamidine hydrochloride of Example 1 instead of 2-thiophenecarboxamide amide hydrochloride prepared in Reference Example 2, and a light beige powder was obtained.

The melting point of the obtained powder, Rf value of thin layer chromatography, ¹ H NMR and mass spectrum data were as follows.
・ Mp199-203 ℃
・ TLC (silica gel, acetone): Rf = 0.70
¹ H NMR (DMSO-d ₆ ): δ = 2.43 (s, 3H), 7.08-7.51 (m, 6H).
MS (EI): m / z (%) = 246 (M ⁺ , 100), 213 (2), 201 (2), 178 (5), 136 (6), 123 (3), 110 (12) 96 (7).
From these spectral data, the obtained powder was identified to be 5-methyl-2,4-di (2-thienyl) imidazole represented by the chemical formula (V). Yield 36.0%.

Example 3
<Synthesis of 2- (2,4-dichlorobenzyl) -4- (2-thienyl) imidazole>
First, a 2- (2-bromoacetyl) thiophene / toluene solution was prepared according to the method of Reference Example 1 by replacing 2-propionylthiophene of Reference Example 1 with 2-acetylthiophene, and 2- (2,4-Dichlorophenyl) acetamidine hydrochloride was prepared according to the method of Reference Example 2 by replacing cyanothiophene with 2,4-dichlorobenzyl cyanide.
Subsequently, the benzamidine hydrochloride of Example 1 was replaced with (2,4-dichlorophenyl) acetamidine hydrochloride, and the 2- (2-bromopropionyl) thiophene / toluene solution was replaced with the 2- (2-bromoacetyl) thiophene / toluene solution. Instead of the above, a synthetic test was conducted in accordance with the method of Example 1 to obtain milky white fine crystals.

The melting point of the obtained crystal, Rf value of thin layer chromatography, ¹ H NMR and mass spectral data were as follows.
・ Mp147-149 ℃
・ TLC (silica gel, acetone): Rf = 0.69
¹ H NMR (DMSO-d ₆ ): δ = 4.10 (s, 2H), 7.00-7.61 (m, 7H).
MS (EI): m / z (%) = 310 (M + 2, 40), 308 (M ⁺ , 57), 273 (100), 238 (52), 210 (2), 159 (7), 136 (5), 119 (8), 109 (5),
96 (13).
From these spectral data, the obtained crystal was identified as 2- (2,4-dichlorobenzyl) -4- (2-thienyl) imidazole represented by the chemical formula (VI). Yield 38.5%.

Example 4
First, a 4- (2-thienyl) imidazole compound synthesized in Examples 1 to 3 and a copper antioxidant containing 2-phenylimidazole (2PZ, manufactured by Shikoku Kasei Kogyo Co., Ltd.) as an active ingredient are prepared separately. did. Next, a chemical conversion film was formed on the surface of copper by bringing the inhibitor into contact with copper. And the wetting time of the molten solder with respect to copper was measured, and the antioxidant performance to the copper surface on which an imidazole compound acts was evaluated. In this case, it is determined that the shorter the wet time of the molten solder, the better the antioxidant performance of the imidazole compound.
The details of the evaluation test are as follows.
(1) Preparation of antioxidant After dissolving an imidazole compound, an acid, a metal salt, and a halogen compound in ion-exchanged water so as to have the composition shown in Table 1, the pH is adjusted with ammonia water to thereby add an antioxidant. Prepared.
(2) Surface treatment method A test piece (copper plate of 5 mm × 50 mm × 0.3 mm) made of metallic copper is degreased, then soft-etched, and immersed in an antioxidant at a predetermined temperature for a predetermined time to obtain a copper surface. After the chemical conversion film was formed on, it was washed with water and dried.
(3) Measurement of wetting time The surface-treated test piece is immersed in post-flux (JS-64MSS, manufactured by Hiroki) and solder wetted using a solder wettability tester (SAT-2000, manufactured by Resuka). Time (seconds) was measured. The solder used was tin-lead eutectic solder (H63A-B20, manufactured by Senju Metal Industry), and the measurement conditions were a solder temperature of 240 ° C., an immersion depth of 2 mm, and an immersion speed of 16 mm / second.
In addition, the test piece which measured the solder wetting time includes (A) a sample immediately after the surface treatment, (B) a sample left in a constant temperature and humidity chamber at a temperature of 40 ° C. and a humidity of 90% RH for 96 hours, and (C ) Further heated at 200 ° C. for 10 minutes.
The test results obtained were as shown in Table 1.

  According to the test results shown in Table 1, the antioxidant containing the 4- (2-thienyl) imidazole compound of the present invention as an active ingredient forms a chemical conversion film excellent in moisture resistance and heat resistance on the surface of copper. Therefore, it is useful for preventing oxidation of the copper surface.

  According to the present invention, 4- (2) useful as an antioxidant for the surface of metals, particularly copper (including copper alloys), as a curing agent or accelerator for epoxy resins, and as an intermediate material in the field of medicine and agrochemicals. -Thienyl) imidazole compounds can be provided.

Claims (1)

A 4- (2-thienyl) imidazole compound represented by the chemical formula (I) or the chemical formula (II).