CN112300075B - 2,4, 5-trisubstituted imidazole compound and preparation method thereof - Google Patents
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- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
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- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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Abstract
The invention discloses a 2,4, 5-trisubstituted imidazole compound and a preparation method thereofA preparation method. The imidazole compound has structural formulas shown as 3 and 3 ', and the synthesis method of the compound 3 or 3' comprises the following steps: under the protection of argon, in a dry Schlenk tube, uniformly mixing the compound 1 and the benzamide hydrochloride 2 or 2 'in a solvent, adding a proper amount of alkali, stirring at a certain temperature, and carrying out cycloaddition reaction to obtain the heterocyclic compound 3 or 3'. The invention provides a simple and feasible new method for synthesizing 2,4, 5-trisubstituted imidazole compounds; the synthesized compounds are not reported in the literature and are all novel compounds; the method provided by the invention is promoted by alkali to carry out reaction in a cycloaddition mode, and transition metal is not required to be used in a reaction system, so that heavy metal pollution does not exist in the product.
Description
Technical Field
The invention belongs to the technical field of organic compound synthesis, and particularly relates to a 2,4, 5-trisubstituted imidazole compound and a preparation method thereof.
Background
Imidazole and derivatives thereof are structural units of natural products and medicines with important biological activities, have various physiological activities such as sedation, anti-tumor, anti-bacterial, anti-virus and anti-osteoporosis in the field of medicine, have better biological activities in the aspects of treating asthma, rheumatoid arthritis and the like, and some compounds have already been put into clinical application and have better effects (J. Med. chem.,1992, 25, 324.; J. org. chem., 2001, 66, 1030.; J.org. chem.,2006,71,8641.; J. Med. chem.,2004,47, 5833.; J. Med. chem.,2007, 50, 2007.). Meanwhile, the imidazole derivatives as a novel nitrogen-containing heterocyclic pesticide show high activity and high selectivity in the aspects of disinsection, sterilization and weeding (Wangming, Zhang Yibin, research and development progress of imidazolyl bactericides, modern pesticides, 2003,2 and 36; Liu Chang. Moreover, imidazole derivatives are also useful for volume analysis, ionometric analysis, biomimetic systems, and photographic materials (Marfan's, Hu build. applications of imidazole and its derivatives. Chemicals, 1998, 20, 146.; Schering, Sudayu. progress in the study of imidazole ring biomimetic systems. chemical research and applications 1999, 11, 449.; Crystal Growth & design. 2006, 6, 1653.). Although there are many reports on the synthesis of imidazole heterocyclic compounds, it is also important to develop a simple and efficient synthetic method and a variety of such compounds in view of the diverse biological activities and wide practical applications of the compounds.
The base-catalyzed cycloaddition reaction provides an economic and efficient method for synthesizing natural products and carbon rings and heterocycles commonly existing in bioactive molecules, and various carbon rings and heterocycles (adv, Synth, Cat., 2017, 359, 3855.; J, org, chem, 2018, 83, 15178.; J, org, chem, 2016, 81, 912.) can be efficiently constructed through cyclization reactions of [3+2], [3+3] [4+1], [4+2], [4+3], and the like from simple and easily-obtained raw materials.
Disclosure of Invention
The invention aims to provide a 2,4, 5-trisubstituted imidazole compound and a preparation method thereof. According to the method, under the promotion of alkali, the compound 1 and the compound 2 are uniformly mixed in a solvent for cycloaddition reaction, and the imidazole heterocyclic compound 3 can be obtained after the reaction is finished; and uniformly mixing the compound 1 and 6-chloropyridine-3-formamidine hydrochloride 2 'in a solvent, adding a proper amount of alkali, stirring at a certain temperature, and carrying out cycloaddition reaction to obtain the 2,4, 5-trisubstituted imidazole heterocyclic compound 3'. The reaction is a [3+2] cycloaddition reaction promoted by alkali, and the synthetic route is as follows:
in the reactant neutralization product, R1Is alkyl, alkoxy, halogen, R2Alkyl, alkoxy, aryl, hydroxyl, halogen, trifluoromethyl and cyano.
In the preparation method, the alkali is at least one of triethylamine, sodium carbonate, sodium bicarbonate, pyridine, potassium bicarbonate or potassium carbonate. At least one of triethylamine, sodium carbonate, sodium bicarbonate, and potassium carbonate is preferable.
The solvent of the addition reaction can be any one of dichloromethane, ethyl acetate, tetrahydrofuran, N-dimethylformamide, N-dimethyl sulfoxide or acetonitrile. Preferably at least one of dichloromethane, ethyl acetate, tetrahydrofuran and acetonitrile.
In the preparation of compound 3, the molar ratio of the starting compounds 1 and 2 is 1:1 to 1.5, such as 1:1, 1:1.2, 1:1.5, preferably 1: 1.5; the molar amount of the base catalyst to be fed is 1.2 to 2 times, such as 1.2 times, 1.5 times, 2 times, preferably 2 times the molar amount of the compound 1 to be fed. The addition reaction time can be 5 hours to 15 hours, specifically 5 hours to 8 hours, 5 hours to 10 hours, 5 hours to 12 hours or 12 hours to 15 hours, preferably 5 hours; the reaction temperature is 25 ℃ to 80 ℃, specifically 25 ℃, 40 ℃, 60 ℃ or 80 ℃, preferably 80 ℃.
In the preparation of compound 3', the starting compounds 1 and 2 are present in a molar ratio of 1:1 to 1.5, e.g. 1:1, 1:1.2, 1:1.5, preferably 1: 1.5; the molar amount of the base catalyst to be fed is 1.2 to 2 times, such as 1.2 times, 1.5 times, 2 times, preferably 2 times the molar amount of the compound 1 to be fed. The addition reaction time can be 5 hours to 15 hours, specifically 5 hours to 8 hours, 5 hours to 10 hours, 5 hours to 12 hours or 12 hours to 15 hours, preferably 5 hours to 8 hours; the reaction temperature is 25 ℃ to 80 ℃, specifically 25 ℃, 40 ℃, 60 ℃ or 80 ℃, preferably 80 ℃.
The invention has the following advantages:
1. the invention provides a base-promoted cycloaddition reaction;
2. the [3+2] cycloaddition reaction promoted by alkali is one of few successful examples of the [3+2] cyclization under the action of inorganic alkali, and transition metal is not required to be used in a reaction system, so that heavy metal residue does not exist in a product;
3. the invention provides a new way for synthesizing new imidazole compounds with potential biological activity, and increases the diversity of the compounds.
Detailed Description
The method is applicable to, but not limited to, the following examples.
The starting compound 1 used in the following examples is reference Li, t. -r., Cheng, b. -y., Wang, y. -n., Zhang, m. -m., Lu, l. -q., Xiao, w. -J.Angew. Chem. Int. Ed.,2016, 55, 12422The method is characterized by comprising the following steps:
example 1
0.0200g (0.05mmol) of Compound 1a, 0.0078g (0.05mmol) of Compound 2a and 1mL of acetonitrile were put into a dry 10mL Schlenk tube, and 8. mu.L (0.06 mmol) of triethylamine was added thereto and mixed well to conduct cycloaddition reaction. In this reaction system, the molar ratio of compound 1a to compound 2a was 1:1, the molar amount of triethylamine was 1.2 times that of 1a, stirring was performed at 25 ℃ for 20 hours, concentration was performed under reduced pressure, and the residue was purified by column chromatography (petroleum ether: ethyl acetate =5:1, v/v) to obtain 7.1mg of product 3aa, with a yield of 30%.
Example 2
0.0200g (0.05mmol) of Compound 1a, 0.0078g (0.05mmol) of Compound 2a and 8.3mg (0.06 mmol) of potassium carbonate were put into a dry 10mL Schlenk's tube, and 1mL of acetonitrile was added thereto and mixed well to conduct cycloaddition reaction. In this reaction system, the molar ratio of the compound 1a to the compound 2a was 1:1, the molar amount of triethylamine was 1.2 times that of 1a, stirring was performed at 25 ℃ for 20 hours, concentration was performed under reduced pressure, and the residue was purified by column chromatography (petroleum ether: ethyl acetate =5:1, v/v) to obtain 9.5mg of the product 3aa with a yield of 40%.
Example 3
0.0200g (0.05mmol) of Compound 1a, 0.0078g (0.05mmol) of Compound 2a and 10.0mg (0.1 mmol) of potassium hydrogencarbonate were put into a dry 10mL Schlenk's tube, and 1mL of acetonitrile was added thereto and mixed well to conduct cycloaddition reaction. In this reaction system, the molar ratio of compound 1a to compound 2a was 1:1, the molar amount of potassium carbonate was 1.2 times that of 1a, stirring was performed at 25 ℃ for 20 hours, concentration was performed under reduced pressure, and the residue was purified by column chromatography (petroleum ether: ethyl acetate =5:1, v/v) to obtain 5.0mg of product 3aa, yield 21%.
From this, potassium carbonate is the best base.
Example 4
0.0200g (0.05mmol) of Compound 1a, 0.0117g (0.075 mmol) of Compound 2a and 13.8mg (0.1 mmol) of potassium carbonate were put into a dry 10mL Schlenk's tube, and 1mL of acetonitrile was added thereto and mixed well to conduct cycloaddition reaction. In this reaction system, the molar ratio of compound 1a to compound 2a was 1:1.5, the molar amount of potassium carbonate was twice that of 1a, stirring was performed at 80 ℃ for 5 hours, concentration was performed under reduced pressure, and the residue was purified by column chromatography (petroleum ether: ethyl acetate =5:1, v/v) to obtain 19.7mg of product 3aa, yield 83%.
Example 5
0.0200g (0.05mmol) of Compound 1a, 0.0117g (0.075 mmol) of Compound 2a and 13.8mg (0.1 mmol) of potassium carbonate were put into a dry 10mL Schlenk's tube, and 1mL of acetonitrile was added thereto and mixed well to conduct cycloaddition reaction. In this reaction system, the molar ratio of compound 1a to compound 2a was 1:1.5, the molar amount of potassium carbonate was twice that of 1a, stirring was carried out at 60 ℃ for 11 hours, concentration was carried out under reduced pressure, and the residue was purified by column chromatography (petroleum ether: ethyl acetate =5:1, v/v) to obtain 16.1mg of product 3aa, yield 68%.
Example 6
0.0200g (0.05mmol) of Compound 1a, 0.0117g (0.075 mmol) of Compound 2a and 13.8mg (0.1 mmol) of potassium carbonate were put into a dry 10mL Schlenk's tube, and 1mL of acetonitrile was added thereto and mixed well to conduct cycloaddition reaction. In this reaction system, the molar ratio of compound 1a to compound 2a was 1:1.5, the molar amount of potassium carbonate was twice that of 1a, stirring was performed at 40 ℃ for 12 hours, concentration was performed under reduced pressure, and the residue was purified by column chromatography (petroleum ether: ethyl acetate =5:1, v/v) to obtain 15.4mg of product 3aa, yield 65%.
From this, 80 ℃ was found to be the optimum reaction temperature.
1H NMR (500 MHz, Acetone-d6) δ 12.55 (brs, 1H), 11.53 (brs, 1H), 8.02 – 7.97 (m, 2H), 7.68 – 7.63 (m, 1H), 7.52 – 7.45 (m, 5H), 7.41 – 7.35 (m, 1H), 7.16 – 7.11 (m, 1H), 7.09 – 7.06 (m, 2H), 7.06 – 7.01 (m, 1H), 2.34 (s, 2H), 2.24 (s, 3H), -0.13 (s, 9H)。
13C NMR (126 MHz, Acetone-d6) δ 143.3, 142.9, 137.9, 136.1, 130.2, 129.5, 129.4, 128.8, 127.93, 127.26, 126.9, 125.2, 124.8, 123.9, 121.8, 20.8, 15.9, -1.8。
From the nuclear magnetic data listed above, the product obtained is structurally correct
Example 7
0.0265g (0.05mmol) of Compound 1a, 0.0117g (0.075 mmol) of Compound 2a and 13.8mg (0.1 mmol) of potassium carbonate were put into a dry 10mL Schlenk's tube, and 1mL of acetonitrile was added thereto and mixed well to conduct cycloaddition reaction. In this reaction system, the molar ratio of the compound 1a to the compound 2a was 1:1.5, the molar amount of potassium carbonate was twice that of 1a, stirring was performed at 80 ℃ for 5 hours, concentration was performed under reduced pressure, and the residue was purified by column chromatography (petroleum ether: ethyl acetate =5:1, v/v) to obtain 19.8mg of a product 3ba, yield 81%.
1H NMR (500 MHz, CDCl3) δ 11.70 (brs, 1H), 9.08 (brs, 1H), 7.61 – 7.57 (m, 1H), 7.52 – 7.49 (m, 1H), 7.44 – 7.39 (m, 2H), 7.27 – 7.23 (m, 1H), 7.21 – 7.15 (m, 3H), 7.10 – 7.05 (m, 1H), 6.95 (t, J = 7.8 Hz, 3H), 2.61 (s, 3H), 2.19 (s, 3H), 2.07 (s, 2H), -0.11 (s, 9H)。
13C NMR (126 MHz, CDCl3) δ 141.9, 137.7, 135.8, 134.3, 128.5,128.1, 128.0, 127.9, 126.0, 125.9, 124.3, 123.5, 122.8, 121.1, 120.9, 20.4, 20.4, 14.7, -2.4。
From the nuclear magnetic data listed above, the product obtained is structurally correct
Example 8
0.0215g (0.05mmol) of compound 1a, 0.0117g (0.075 mmol) of compound 2a and 13.8mg (0.1 mmol) of potassium carbonate were put into a dry 10mL Schlenk's tube, and 1mL of acetonitrile was added thereto and mixed well to conduct cycloaddition reaction. In this reaction system, the molar ratio of the compound 1a to the compound 2a was 1:1.5, the molar amount of potassium carbonate was twice that of 1a, stirring was performed at 80 ℃ for 5 hours, concentration was performed under reduced pressure, and the residue was purified by column chromatography (petroleum ether: ethyl acetate =5:1, v/v) to obtain 25.1mg of a product 3ba, yield 86%.
1H NMR (500 MHz, CDCl3) δ 11.65 (brs, 1H), 9.55 (brs, 1H), 7.89 – 7.83 (m, 2H), 7.65 – 7.59 (m, 1H), 7.40 – 7.34 (m, 4H), 7.34 – 7.29 (m, 1H), 6.96 – 6.93 (m, 2H), 6.83 – 6.81 (m, 1H), 6.76 – 6.72 (m, 1H), 3.77 (s, 3H), 2.24 (s, 3H), 2.06 (s, 2H), -0.02 (s, 9H)。
13C NMR (126 MHz, CDCl3) δ 156.2, 142.7, 142.5, 136.2, 128.9, 128.8, 128.7, 128.5, 126.7, 125.1, 124.5, 112.8, 111.5, 55.3, 21.1, 15.4, -1.5。
From the nuclear magnetic data listed above, the resulting product was structurally correct
Example 9
0.0200g (0.05mmol) of Compound 1a, 0.0129g (0.075 mmol) of Compound 2f and 13.8mg (0.1 mmol) of potassium carbonate were put into a dry 10mL Schlenk tube, and 1mL of acetonitrile was added thereto and mixed well to conduct the cycloaddition reaction. In this reaction system, the molar ratio of compound 1a to compound 2a was 1:1.5, the molar amount of potassium carbonate was twice that of 1a, stirring was carried out at 80 ℃ for 5 hours, concentration was carried out under reduced pressure, and the residue was purified by column chromatography (petroleum ether: ethyl acetate =2:1, v/v) to obtain 22.1mg of product 3af with a yield of 90%.
1H NMR (500 MHz, DMSO-d6) δ 13.10 (brs, 1H), 12.14 (brs, 1H), 9.80 (brs, 1H), 7.80 – 7.75 (m, 2H), 7.53 – 7.48 (m, 1H), 7.46 – 7.44 (m, 1H), 7.42 – 7.39 (m, 2H), 7.14 – 7.09 (m, 3H), 7.05 – 7.00 (m, 1H), 6.94 – 6.88 (m, 2H), 2.28 (s, 2H), 2.21 (s, 3H), -0.22 (s, 9H)。
13C NMR (126 MHz, DMSO-d6) δ 143.9, 143.4, 137.5, 135.7, 132.1, 130.4, 129.1, 127.4, 127.2, 124.9, 124.6, 121.7, 121.4, 116.8, 21.9, 16.8, -0.5。
From the nuclear magnetic data listed above, the product obtained is structurally correct
Example 10
0.0200g (0.05mmol) of Compound 1a, 0.0131 g (0.075 mmol) of Compound 2i and 13.8mg (0.1 mmol) of potassium carbonate were put into a dry 10mL Schlenk tube, and 1mL of acetonitrile was added thereto and mixed well to conduct cycloaddition reaction. In this reaction system, the molar ratio of compound 1a to compound 2a was 1:1.5, the molar amount of potassium carbonate was twice that of 1a, stirring was performed at 80 ℃ for 5 hours, concentration was performed under reduced pressure, and the residue was purified by column chromatography (petroleum ether: ethyl acetate =5:1, v/v) to obtain 17.7mg of product 3ai, yield 72%.
1H NMR (500 MHz, DMSO-d6) δ 12.37 (brs, 1H), 11.46 (brs, 1H), 7.91 (brs, 1H), 7.59 – 7.50 (m, 1H), 7.40 – 7.32 (m, 3H), 7.21 – 7.12 (m, 2H), 7.06 – 6.90 (m, 4H), 2.22 (s, 2H), 2.14 (s, 3H), -0.23 (s, 9H)。
13C NMR (126 MHz, DMSO-d6) δ 166.2(d, J = 246.6 Hz)., 164.2, 144.1, 139.8, 137.9, 131.6, 129.30, 129.26, 129.22, 129.19, 128.9, 126.8, 125.9, 118.4, 118.2, 22.8, 17.9, 0.2。
From the nuclear magnetic data listed above, the product obtained is structurally correct.
Example 11
0.0200g (0.05mmol) of Compound 1a, 0.0143g (0.075 mmol) of Compound 2j and 13.8mg (0.1 mmol) of potassium carbonate were put in a dry 10mL Schlenk tube, and 1mL of acetonitrile was added thereto and mixed to conduct the cycloaddition reaction. In this reaction system, the molar ratio of compound 1a to compound 2a was 1:1.5, the molar amount of potassium carbonate was twice that of 1a, the mixture was stirred at 80 ℃ for 5 hours, concentrated under reduced pressure, and the residue was purified by column chromatography (petroleum ether: ethyl acetate =5:1, v/v) to obtain 23.7mg of product 3af in 93% yield.
1H NMR (500 MHz, CDCl3) δ 11.52 (brs, 1H), 9.90 (brs, 1H), 8.37 – 8.30 (m, 1H), 7.73 – 7.67 (m, 1H), 7.53 – 7.47 (m, 2H), 7.46 – 7.41 (m, 2H), 7.33 – 7.29 (m, 2H), 7.22 – 7.16 (m, 1H), 7.11 – 7.04 (m, 1H), 7.04 – 7.00 (m, 2H), 2.28 (s, 3H), 2.12 (s, 2H), 0.03 (s, 9H)。
13C NMR (126 MHz, CDCl3) δ 144.2, 141.8, 138.5, 137.1, 135.0, 132.1, 131.7, 131.1, 130.8, 130.6, 129.5, 129.2, 128.9, 128.8, 128.7, 128.5, 22.9, 17.2, 0.2。
From the nuclear magnetic data listed above, the product obtained is structurally correct.
Example 12
0.0200g (0.05mmol) of Compound 1a, 0.0168 g (0.075 mmol) of Compound 2o and 13.8mg (0.1 mmol) of potassium carbonate were put into a dry 10mL Schlenk tube, and 1mL of acetonitrile was added thereto and mixed well to conduct cycloaddition reaction. In this reaction system, the molar ratio of the compound 1a to the compound 2o was 1:1.5, the molar amount of potassium carbonate was twice that of 1a, stirring was performed at 80 ℃ for 5 hours, concentration was performed under reduced pressure, and the residue was purified by column chromatography (petroleum ether: ethyl acetate =5:1, v/v) to obtain 21.2 mg of the product 3ao in 78% yield.
1H NMR (500 MHz, DMSO-d6) δ 12.65 (brs, 1H), 12.52 (brs, 1H), 7.80 – 7.76 (m, 1H), 7.72 – 7.66 (m, 1H), 7.61 – 7.54 (m, 1H), 7.52 – 7.44 (m, 2H), 7.43 – 7.36 (m, 2H), 7.27 – 7.19 (m, 1H), 7.17 – 7.08 (m, 3H), 7.06 – 7.02 (m, 1H), 2.30 (s, 2H), 2.20 (s, 3H), -0.24 (s, 9H)。
13C NMR (126 MHz, DMSO-d6) δ 164.6(d, J = 243.3 Hz), 162.7, 144.1, 141.63, 141.60, 137.4, 133.2, 132.7, 132.6, 132.4, 132.3, 130.9, 130.5, 127.8, 127.7, 127.4, 124.8, 124.6, 121.6, 121.5, 116.2, 116.0, 112.1, 111.9, 21.9, 16.7, -0.5。
From the nuclear magnetic data listed above, the product obtained is structurally correct.
Example 13
0.0200g (0.05mmol) of Compound 1a, 0.0143g (0.075 mmol) of Compound 2 'and 13.8mg (0.1 mmol) of potassium carbonate were put into a dry 10mL Schlenk's tube, and 1mL of acetonitrile was added thereto and mixed well to conduct cycloaddition reaction. In this reaction system, the molar ratio of compound 1a to compound 2a was 1:1.5, the molar amount of potassium carbonate was twice that of 1a, the mixture was stirred at 80 ℃ for 5 hours, concentrated under reduced pressure, and the residue was purified by column chromatography (petroleum ether: ethyl acetate =5:1, v/v) to obtain 18.4mg of product 3af with a yield of 72%.
1H NMR (500 MHz, CDCl3) δ 8.88 – 8.81 (m, 2H), 8.24 (dd, J = 8.3, 1.9 Hz, 1H), 8.22 – 8.17 (m, 1H), 7.57 (d, J = 8.1 Hz, 2H), 7.42 (d, J = 8.3 Hz, 1H), 7.24 – 7.15 (m, 3H), 7.14 – 7.10 (m, 2H), 2.56 (s, 2H), 2.30 (s, 3H), 1.68 (brs, 1H), 0.07 (s, 9H)。
13C NMR (126 MHz, CDCl3) δ 153.5, 152.1, 147.7, 144.5, 137.5, 136.0, 135.4, 130.2, 129.6, 129.3, 126.4, 125.48, 124.3, 123.6, 123.5, 117.9, 115.8, 21.5, 17.0, -0.8。
From the nuclear magnetic data listed above, the product obtained is structurally correct.
Claims (6)
1. A method for synthesizing 2,4, 5-trisubstituted imidazole compounds is characterized in that the reaction conditions of the method are as follows:
in the reactants and products, R1Is alkyl, alkoxy, halogen, R2Is alkyl, alkoxy, aryl, hydroxyl, halogen, trifluoromethyl, cyano;
the synthesis method of the compound 3 comprises the following steps: uniformly mixing the compound 1 and benzamidine hydrochloride 2 in a solvent, and adding alkali to perform cycloaddition reaction to obtain a 2,4, 5-trisubstituted imidazole heterocyclic compound 3;
the synthesis method of the compound 3' comprises the following steps: and uniformly mixing the compound 1 and 6-chloropyridine-3-formamidine hydrochloride 2 'in a solvent, adding alkali, stirring, and carrying out cycloaddition reaction to obtain the 2,4, 5-trisubstituted imidazole heterocyclic compound 3'.
2. The method of claim 1, wherein the base is at least one of triethylamine, sodium carbonate, sodium bicarbonate, pyridine, potassium bicarbonate, or potassium carbonate.
3. The method of claim 1, wherein the solvent is dichloromethane, ethyl acetate, tetrahydrofuran, or mixtures thereof,N,N-dimethylformamide, dimethylformamide,N,N-either dimethylsulfoxide or acetonitrile.
4. The synthesis method of claim 1, wherein the molar ratio of the compounds 1 and 2 is 1: 1-1.5; the feeding molar amount of the alkali catalyst is 1.2-2 times of that of the compound 1.
5. The synthesis of claim 1, wherein:
the cycloaddition reaction time of the compound 3 is 5 hours to 15 hours; the reaction temperature is 25-80 ℃;
the cycloaddition reaction time of the compound 3' is 5-15 hours, and the reaction temperature is 25-80 ℃.
6. Imidazoles are prepared according to the synthesis method described in one of claims 1 to 5.
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