CN115093372A - Synthesis method of imidazole derivative - Google Patents

Synthesis method of imidazole derivative Download PDF

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CN115093372A
CN115093372A CN202210679449.XA CN202210679449A CN115093372A CN 115093372 A CN115093372 A CN 115093372A CN 202210679449 A CN202210679449 A CN 202210679449A CN 115093372 A CN115093372 A CN 115093372A
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imidazole derivative
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imidazole
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CN115093372B (en
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徐绘
章辉
王贻蓓
刘全
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Anhui Polytechnic University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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    • Y02P20/00—Technologies relating to chemical industry
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Abstract

The invention relates to a method for synthesizing an imidazole derivative, which comprises the following steps: mixing aurone or its derivative I, benzamidine or its derivative II, iodine and alkali, adding a solvent, and heating for reaction; after the reaction is finished, cooling to room temperature, washing, extracting, drying and decompressing and concentrating the reaction liquid, and then carrying out chromatographic separation to obtain the product imidazole derivative III. The raw materials used in the invention are conventional, cheap and easily available, and the accelerator iodine is cheap, safe and nontoxic; the reaction efficiency is improved by utilizing a domino reaction strategy, and the separation and purification operations are reduced; the reaction selectivity is good, the side reaction is less, and the product yield is high; the synthesis of the imidazole derivative with a conjugated structure is realized by utilizing a spiro ring opening strategy, so that a large amount of chemical oxidants are avoided, and the pollution is low; can effectively solve the problems of difficult raw material synthesis or high price, high catalyst toxicity, high oxidant demand, harsh reaction conditions, poor selectivity, complex product separation and low yield existing in the conventional imidazole derivative synthesis method.

Description

Synthesis method of imidazole derivative
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a synthesis method of an imidazole derivative.
Background
Imidazole as an important five-membered nitrogen-containing heterocyclic compound has a skeleton which is widely present in natural products and drug molecules and shows remarkable biological activity. Imidazole derivatives are also important organic synthesis intermediates of medicines, pesticides, dyes and the like, and are widely applied to the fields of ionic liquids, proton exchange materials, organic luminescent materials and the like.
In view of this, a great deal of research has been conducted on the synthesis of imidazole derivatives, and the following synthetic methods have been developed: (1) the Debus synthesis method is characterized in that alpha-diketone, aldehyde and ammonia are used as raw materials to carry out condensation reaction, and imidazole derivatives are generated through ring closure; (2) an alpha-aminoacetal method which utilizes the cyclization reaction of alpha-aminoacetal and amide to form imidazole derivative; (3) synthesizing ethylenediamine, namely reacting substituted ethylenediamine with carboxylic acid, ester or anhydride to obtain an imidazole derivative; (4) the acetonitrile method is characterized in that 3-bromo-2-acetonitrile methyl ester and primary amine react under the action of an alkaline reagent to generate an imidazole product; (5) an imidazoline oxidation method for oxidizing imidazoline into an imidazole derivative having a conjugated structure by using a large amount of an oxidizing agent; (6) in the Claisen rearrangement reaction method, in the reaction of amidoxime and propiolic acid ester, water molecules are removed through the Claisen rearrangement reaction to form an imidazole ring compound.
Although these methods are capable of synthesizing a wide variety of pyrrole derivatives, they all have some disadvantages: for example, the Debus synthesis method has more byproducts, lower product yield and more troublesome product separation and purification; other methods also have the problems of difficult synthesis of raw materials or high price, high catalyst toxicity, need of using a large amount of oxidant, prefabrication or separation of reaction intermediates, harsh reaction conditions, poor reaction selectivity, complicated product separation and purification, low yield and the like.
Disclosure of Invention
The invention aims to provide a method for synthesizing an imidazole derivative, which can effectively solve the problems of difficult raw material synthesis or high price, high catalyst toxicity, high oxidant demand, harsh reaction conditions, poor selectivity, complex product separation and low yield existing in the conventional method for synthesizing the imidazole derivative.
In order to solve the technical problems, the invention adopts the following technical scheme:
a method for synthesizing an imidazole derivative has the following reaction general formula:
Figure BDA0003697738330000011
in the formula: r 1 Is aryl, alkyl or heterocyclyl; r 2 Is aryl or alkyl; r 3 Aryl, benzyl or alkyl.
The synthesis method of the imidazole derivative comprises the following steps:
(a) mixing aurone or its derivative I, benzamidine or its derivative II, iodine and alkali, adding solvent and heating to react;
(b) after the reaction is finished, cooling to room temperature, washing, extracting, drying and decompressing and concentrating the reaction liquid, and then carrying out chromatographic separation to obtain the product imidazole derivative III.
Wherein, the ratio of the amount of the aurone or the derivatives thereof, the benzamidine or the derivatives thereof, the iodine and the alkali in the step (a) is 1: 1.2-1.8: 1-1.5: 1; the base is sodium acetate, potassium carbonate, sodium hydroxide, sodium ethoxide, triethylamine, 4-dimethylaminopyridine or 1, 8-diazabicyclo [5.4.0] undec-7-ene; the solvent is 1, 2-dichloroethane, acetonitrile, toluene, chlorobenzene, 1, 4-dioxane, dimethyl sulfoxide or N, N-dimethylformamide, and the volume of the solvent is 10-12 times of the total mass of the raw materials.
In the step (a), the reaction temperature is 80-130 ℃, and the reaction time is 5-10 h.
Wherein the solution adopted in the washing step in the step (b) is a sodium thiosulfate aqueous solution; the extractant adopted in the extraction step is ethyl acetate; the drying step is drying using anhydrous sodium sulfate; the chromatographic conditions of the chromatographic separation step are as follows: 200-300-mesh silica gel column, wherein the eluent is a mixture of ethyl acetate and petroleum ether, and the volume ratio of the ethyl acetate to the petroleum ether is 1: 6-10.
When R is 1 Is phenyl, R 2 Is phenyl, R 3 In the case of benzyl, the synthesis mechanism of the imidazole derivative is:
Figure BDA0003697738330000021
according to the synthesis method of the imidazole derivative, firstly, aza-Michael addition reaction is carried out on aurone I and N-phenyl benzamidine II under the induction of iodine to obtain a ketone intermediate A, the A can be converted into an enol intermediate B, the A and the iodine are subjected to substitution reaction to generate an intermediate C, the C is subjected to intramolecular nucleophilic substitution reaction to generate a spiro intermediate D, the D is subjected to elimination reaction similar to E2 type under the action of alkali 4-dimethylaminopyridine to form an oxyanion intermediate E, and the E immediately takes a molecule of proton to generate a final target product III.
Compared with the prior art, the technical scheme of the invention has the following beneficial effects: the adopted raw materials are conventional, cheap and easily available, and are suitable for substrates substituted by various functional groups; the adopted accelerator iodine is a cheap, safe and nontoxic reagent; the reaction efficiency is greatly improved by utilizing a domino reaction strategy, the separation and purification operations are reduced, and the cost is reduced; the reaction selectivity is good, the side reaction is less, the product yield is high, and the obtained product is a single imidazole derivative; the synthesis of the imidazole derivative with a conjugated structure is realized by utilizing a spiro ring opening strategy, the atom utilization rate is high, a large amount of chemical oxidants can be avoided, and the pollution is low. The comprehensive problems of the method in the background art are effectively solved.
Drawings
FIG. 1 shows the target product of example 1 1 H NMR spectrum;
FIG. 2 shows the target product of example 1 13 C NMR spectrogram;
FIG. 3 shows the target product of example 2 1 H NMR spectrum;
FIG. 4 shows the target product of example 2 13 C NMR spectrogram;
FIG. 5 shows the target product of example 3 1 H NMR spectrum;
FIG. 6 shows the target product of example 3 13 C NMR spectrum;
FIG. 7 shows the target product of example 4 1 H NMR spectrum;
FIG. 8 shows the target product of example 4 13 C NMR spectrum;
FIG. 9 shows the target product of example 5 1 H NMR spectrum;
FIG. 10 shows the target product of example 5 13 C NMR spectrum;
FIG. 11 shows the target product of example 6 1 H NMR spectrum;
FIG. 12 shows the target product of example 6 13 C NMR spectrogram;
FIG. 13 shows the target product of example 7 1 H NMR spectrum;
FIG. 14 shows the target product of example 7 13 C NMR spectrum;
FIG. 15 shows the target product of example 8 1 H NMR spectrum;
FIG. 16 shows the target product of example 8 13 C NMR spectrum.
Detailed Description
In order that the objects and advantages of the invention will be more clearly understood, the following description is given in conjunction with the examples. It is to be understood that the following text is merely illustrative of one or more specific embodiments of the invention and does not strictly limit the scope of the invention as specifically claimed.
Example 1
A synthetic method of 1-benzyl-2, 4-diphenyl-5-o-hydroxybenzoyl-1H-imidazole comprises the following steps:
to a 25mL reaction tube were added 44.4mg (0.2mmol) of 2-benzylidene benzofuran-3 (2H) -one, 63.0mg (0.3mmol) of N-benzylbenzamidine, 50.8mg (0.2mmol) of iodine, 24.4mg (0.2mmol) of 4-dimethylaminopyridine and 2mL of chlorobenzene, stirred at 110 ℃ for 6H, cooled to room temperature after the reaction was completed, washed with 10mL of sodium thiosulfate solution, then extracted three times with 20mL of ethyl acetate, and the separated organic phase was dried over sodium sulfate and separated by silica gel column chromatography (V ethyl acetate: V petroleum ether ═ 1:6) to give 75.1mg of the desired product in 87% yield as a yellow solid.
The nuclear magnetic resonance spectrum of the target product is shown in fig. 1 and fig. 2: 1 H NMR(600MHz,CDCl 3 )δ11.75(s,1H),7.70–7.66(m,2H),7.50–7.47(m,3H),7.46(d,J＝7.5Hz,2H),7.22–7.12(m,7H),7.08(t,J＝7.4Hz,1H),6.93(d,J＝7.6Hz,2H),6.84(d,J＝8.3Hz,1H),6.33(t,J＝7.6Hz,1H),5.50(s,2H)； 13 C NMR(125MHz,CDCl 3 )δ193.0,162.7,152.0,147.1,136.8,136.5,133.4,133.3,130.0,129.7,129.6(2C),129.0(2C),128.9(2C),128.8(2C),128.3(2C),128.0,127.9,126.6(2C),125.7,119.6,118.7,117.6,49.4；HRMS(ESI-TOF)calcd for C 29 H 23 N 2 O 2 [M+H] + 431.1760,found 431.1766。
wherein the chemical structural formula of the 1-benzyl-2, 4-diphenyl-5-o-hydroxybenzoyl-1H-imidazole is as follows:
Figure BDA0003697738330000041
the mechanism of synthesis of the imidazole derivatives of this example is as follows:
Figure BDA0003697738330000042
firstly, azi-Michael addition reaction is carried out on aurone I and N-phenyl benzamidine II under the induction of iodine to obtain a ketone intermediate A, the A can be converted into an enol intermediate B, and substitution reaction is carried out on the enol intermediate B and iodine to generate an intermediate C, the intermediate C generates a spiro intermediate D through intramolecular nucleophilic substitution reaction, the D generates an oxygen anion intermediate E similar to an E2 type elimination reaction under the action of alkali 4-dimethylaminopyridine, and the E immediately takes a molecule of proton to generate a final target product III.
Example 2
A synthetic method of 1-benzyl-2-phenyl-4-p-tolyl-5-o-hydroxybenzoyl-1H-imidazole comprises the following steps:
to a 25mL reaction tube were added 47.2mg (0.2mmol) of 2- (4-methylbenzylidene) benzofuran-3 (2H) -one, 63.0mg (0.3mmol) of N-benzylbenzamidine, 50.8mg (0.2mmol) of iodine, 24.4mg (0.2mmol) of 4-dimethylaminopyridine and 2mL of chlorobenzene, stirred at 110 ℃ for 6H, cooled to room temperature after the reaction was completed, washed with 10mL of sodium thiosulfate solution, then extracted three times with 20mL of ethyl acetate, and the separated organic phase was dried over anhydrous sodium sulfate and separated by silica gel column chromatography (V ethyl acetate: V petroleum ether ═ 1:6) to give 73.8mg of the desired product in 83% yield as a yellow solid.
The nuclear magnetic resonance spectrum of the target product is shown in fig. 3 and 4: 1 H NMR(500MHz,CDCl 3 )δ11.83(s,1H),7.70–7.65(m,2H),7.50–7.45(m,3H),7.35(d,J＝8.1Hz,2H),7.23–7.19(m,2H),7.13(t,J＝7.4Hz,2H),7.07(t,J＝7.3Hz,1H),6.96(d,J＝7.9Hz,2H),6.93(d,J＝7.3Hz,2H),6.84(d,J＝8.7Hz,1H),6.35(t,J＝7.6Hz,1H),5.49(s,2H),2.23(s,3H)； 13 C NMR(125MHz,CDCl 3 )δ193.1,162.6,151.9,147.1,137.8,136.8,136.4,133.4,130.3,129.9,129.7,129.6(2C),129.0(2C),128.9(2C),128.8(4C),127.8,126.6(2C),125.3,119.5,118.7,117.6,49.3,21.3；HRMS(ESI-TOF)calcd for C 30 H 25 N 2 O 2 [M+H] + 445.1916,found 445.1925。
wherein the chemical structural formula of the 1-benzyl-2-phenyl-4-p-tolyl-5-o-hydroxybenzoyl-1H-imidazole is as follows:
Figure BDA0003697738330000051
example 3
A synthetic method of 1-benzyl-4-o-chlorophenyl-2-phenyl-5-o-hydroxybenzoyl-1H-imidazole comprises the following steps:
to a 25mL reaction tube were added 51.4mg (0.2mmol) of 2- (2-chlorobenzylidene) benzofuran-3 (2H) -one, 63.0mg (0.3mmol) of N-benzylbenzamidine, 50.8mg (0.2mmol) of iodine, 24.4mg (0.2mmol) of 4-dimethylaminopyridine and 2mL of chlorobenzene, stirred at 110 ℃ for 6H, cooled to room temperature after completion of the reaction, washed with 10mL of sodium thiosulfate solution, then extracted three times with 20mL of ethyl acetate, and the separated organic phase was dried over anhydrous sodium sulfate and separated by silica gel column chromatography (V ethyl acetate: V petroleum ether ═ 1:6) to give 74.6mg of the desired product in a yield of 80% as a yellow solid.
The nuclear magnetic resonance spectrum of the target product is shown in fig. 5 and 6: 1 H NMR(500MHz,CDCl 3 )δ11.43(s,1H),7.71–7.66(m,2H),7.56(d,J＝7.6Hz,1H),7.50–7.44(m,3H),7.23–7.17(m,3H),7.17–7.12(m,4H),7.11–7.06(m,1H),6.98(d,J＝7.4Hz,2H),6.80(d,J＝8.7Hz,1H),6.30(t,J＝7.6Hz,1H),5.64(s,2H)； 13 C NMR(125MHz,CDCl 3 )δ191.6,162.0,152.3,145.3,137.1,136.1,133.6,133.3,132.9,132.1,130.1,129.64,129.60(2C),129.5,129.4,128.93(2C),128.90(2C),127.8,127.3,126.8,126.3(2C),119.7,118.0,117.4,49.4；HRMS(ESI-TOF)calcd for C 29 H 22 35 ClN 2 O 2 [M+H] + 465.1370,found 465.1369。
wherein the chemical structural formula of the 1-benzyl-4-o-chlorophenyl-2-phenyl-5-o-hydroxybenzoyl-1H-imidazole is as follows:
Figure BDA0003697738330000061
example 4
A synthetic method of 1-benzyl-4- (2-furyl) -2-phenyl-5-o-hydroxybenzoyl-1H-imidazole comprises the following steps:
to a 25mL reaction tube were added 42.4mg (0.2mmol) of 2- (2-furanmethylene) benzofuran-3 (2H) -one, 63.0mg (0.3mmol) of N-benzylbenzamidine, 50.8mg (0.2mmol) of iodine, 24.4mg (0.2mmol) of 4-dimethylaminopyridine and 2mL of chlorobenzene, stirred at 110 ℃ for 6H, cooled to room temperature after the reaction was completed, washed with 10mL of sodium thiosulfate solution, then extracted three times with 20mL of ethyl acetate, and the separated organic phase was dried over anhydrous sodium sulfate and separated by silica gel column chromatography (V ethyl acetate: V petroleum ether ═ 1:6) to give 60.7mg of the desired product in a yield of 72% as a yellow solid.
The nuclear magnetic resonance spectrum of the target product is shown in fig. 7 and 8: 1 H NMR(500MHz,CDCl 3 )δ11.71(s,1H),7.68–7.64(m,2H),7.50–7.46(m,3H),7.35–7.30(m,2H),7.14–7.10(m,3H),7.07(t,J＝7.3Hz,1H),6.93–6.88(m,3H),6.59–6.53(m,2H),6.28(dd,J＝3.3,1.8Hz,1H),5.43(s,2H)； 13 C NMR(125MHz,CDCl 3 )δ192.5,162.6,152.2,147.9,142.7,137.3,136.53,136.52,133.0,130.1,129.7(2C),129.5,129.0(2C),128.8(2C),128.0,126.7(2C),125.1,120.4,118.8,117.8,111.4,109.3,49.5；HRMS(ESI-TOF)calcd for C 27 H 21 N 2 O 3 [M+H] + 421.1552,found 421.1556。
wherein the chemical structural formula of the 1-benzyl-4- (2-furyl) -2-phenyl-5-o-hydroxybenzoyl-1H-imidazole is as follows:
Figure BDA0003697738330000062
example 5
A synthetic method of 1-benzyl-4-phenyl-2-m-tolyl-5-o-hydroxybenzoyl-1H-imidazole comprises the following steps:
to a 25mL reaction tube were added 44.4mg (0.2mmol) of 2-benzylidenebenzofuran-3 (2H) -one, 67.2mg (0.3mmol) of N-benzyl-3-methylbenzamidine, 50.8mg (0.2mmol) of iodine, 24.4mg (0.2mmol) of 4-dimethylaminopyridine and 2mL of chlorobenzene, stirred at 110 ℃ for 6H, cooled to room temperature after the reaction was completed, washed with 10mL of sodium thiosulfate solution, then extracted three times with 20mL of ethyl acetate, and the separated organic phase was dried over anhydrous sodium sulfate and separated by silica gel column chromatography (V ethyl acetate: V petroleum ether 1:6) to give 74.5mg of the desired product in 84% yield as a yellow solid.
The nuclear magnetic resonance spectrum of the target product is shown in fig. 9 and 10: 1 H NMR(500MHz,CDCl 3 )δ11.79(s,1H),7.54(s,1H),7.48–7.42(m,3H),7.35(t,J＝7.6Hz,1H),7.29(d,J＝7.6Hz,1H),7.22–7.12(m,7H),7.08(t,J＝7.3Hz,1H),6.94(d,J＝7.4Hz,2H),6.83(d,J＝8.3Hz,1H),6.32(t,J＝7.6Hz,1H),5.51(s,2H),2.40(s,3H)； 13 C NMR(125MHz,CDCl 3 )δ192.9,162.6,152.2,147.1,138.8,136.9,136.5,133.4,133.3,130.8,130.5,129.5,128.9(2C),128.8(2C),128.7,128.3(2C),128.0,127.8,126.6(2C),126.4,125.6,119.5,118.6,117.6,49.4,21.5；HRMS(ESI-TOF)calcd for C 30 H 25 N 2 O 2 [M+H] + 445.1916,found 445.1924。
wherein the chemical structural formula of the 1-benzyl-4-phenyl-2-m-tolyl-5-o-hydroxybenzoyl-1H-imidazole is as follows:
Figure BDA0003697738330000071
example 6
A synthetic method of 1-phenethyl-2, 4-diphenyl-5-o-hydroxybenzoyl-1H-imidazole comprises the following steps:
to a 25mL reaction tube were added 44.4mg (0.2mmol) of 2-benzylidene benzofuran-3 (2H) -one, 67.2mg (0.3mmol) of N-phenethylbenzamidine, 50.8mg (0.2mmol) of iodine, 24.4mg (0.2mmol) of 4-dimethylaminopyridine and 2mL of chlorobenzene, stirred at 110 ℃ for 6H, cooled to room temperature after the reaction was completed, washed with 10mL of sodium thiosulfate solution, then extracted three times with 20mL of ethyl acetate, and the separated organic phase was dried over anhydrous sodium sulfate and then separated by silica gel column chromatography (V ethyl acetate: V petroleum ether ═ 1:6) to obtain 78.3mg of the desired product in 88% yield as a yellow solid.
The nuclear magnetic resonance spectrum of the target product is shown in fig. 11 and 12: 1 H NMR(500MHz,CDCl 3 )δ12.03(s,1H),7.53–7.50(m,2H),7.50–7.46(m,3H),7.44–7.40(m,2H),7.34–7.27(m,2H),7.19–7.10(m,6H),6.96(d,J＝8.1Hz,1H),6.92–6.88(m,2H),6.42(t,J＝7.6Hz,1H),4.52(t,J＝7.4Hz,2H),2.85(t,J＝7.4Hz,2H)； 13 C NMR(125MHz,CDCl 3 )δ192.8,162.9,151.8,147.6,137.1,136.7,133.7,133.6,130.0,129.8,129.5(2C),129.2(2C),128.81(2C),128.76(2C),128.7(2C),128.3(2C),128.0,127.0,125.4,119.7,118.8,117.9,47.2,37.7；HRMS(ESI-TOF)calcd for C 30 H 25 N 2 O 2 [M+H] + 445.1916,found 445.1919。
wherein the chemical structural formula of the 1-phenethyl-2, 4-diphenyl-5-o-hydroxybenzoyl-1H-imidazole is as follows:
Figure BDA0003697738330000081
example 7
A method for synthesizing 1,2, 4-triphenyl-5-o-hydroxybenzoyl-1H-imidazole comprises the following steps:
to a 25mL reaction tube were added 44.4mg (0.2mmol) of 2-benzylidene benzofuran-3 (2H) -one, 58.8mg (0.3mmol) of N-phenylbenzamidine, 50.8mg (0.2mmol) of iodine, 24.4mg (0.2mmol) of 4-dimethylaminopyridine and 2mL of chlorobenzene, stirred at 110 ℃ for 6H, cooled to room temperature after the reaction was completed, washed with 10mL of sodium thiosulfate solution, then extracted three times with 20mL of ethyl acetate, and the separated organic phase was dried over sodium sulfate and separated by silica gel column chromatography (V ethyl acetate: V petroleum ether ═ 1:6) to give 72.6mg of the desired product in 87% yield as a yellow solid.
The nmr spectra of the target product are shown in fig. 13 and 14: 1 H NMR(500MHz,CDCl 3 )δ11.67(s,1H),7.57–7.53(m,2H),7.49(dd,J＝8.0,1.6Hz,1H),7.46–7.43(m,2H),7.40–7.35(m,3H),7.34–7.26(m,4H),7.25–7.18(m,5H),6.89(d,J＝8.4Hz,1H),6.51(t,J＝7.6Hz,1H)； 13 C NMR(125MHz,CDCl 3 )δ192.6,162.7,149.8,145.6,136.9,136.8,133.4,133.1,129.5(2C),129.4,129.3,129.2(2C),129.1,128.7(2C),128.45(2C),128.39(2C),128.1,127.7(3C),120.3,119.0,117.9；HRMS(ESI-TOF)calcd for C 28 H 21 N 2 O 2 [M+H] + 417.1603,found 417.1611。
wherein the chemical structural formula of the 1,2, 4-triphenyl-5-o-hydroxybenzoyl-1H-imidazole is as follows:
Figure BDA0003697738330000082
example 8
A method for synthesizing 1-p-methoxyphenyl-2, 4-diphenyl-5-o-hydroxybenzoyl-1H-imidazole comprises the following steps:
to a 25mL reaction tube were added 44.4mg (0.2mmol) of 2-benzylidene benzofuran-3 (2H) -one, 67.8mg (0.3mmol) of N-p-methoxyphenylbenzamidine, 50.8mg (0.2mmol) of iodine, 24.4mg (0.2mmol) of 4-dimethylaminopyridine and 2mL of chlorobenzene, stirred at 110 ℃ for 6H, cooled to room temperature after the reaction was completed, washed with 10mL of sodium thiosulfate solution, then extracted three times with 20mL of ethyl acetate, and the separated organic phase was dried over anhydrous sodium sulfate and separated by silica gel column chromatography (V ethyl acetate: V petroleum ether ═ 1:6) to give 76.9mg of the objective product in 86% yield as a yellow solid.
The nmr spectra of the target product are shown in fig. 15 and 16: 1 H NMR(500MHz,CDCl 3 )δ11.73(s,1H),7.56–7.53(m,2H),7.50–7.46(m,3H),7.34–7.26(m,4H),7.24–7.14(m,5H),6.89(d,J＝8.4Hz,1H),6.86(d,J＝8.9Hz,2H),6.51(t,J＝7.6Hz,1H),3.81(s,3H)； 13 C NMR(125MHz,CDCl 3 )δ192.7,162.7,159.7,150.0,145.4,136.9,133.4,133.2,129.5,129.4,129.23,129.17(2C),128.8(2C),128.7(2C),128.44(2C),128.41(2C),128.1,127.8,120.2,119.0,117.9,114.6(2C),55.5；HRMS(ESI-TOF)calcd for C 29 H 23 N 2 O 3 [M+H] + 447.1709,found 447.1713。
wherein the chemical structural formula of the 1-p-methoxyphenyl-2, 4-diphenyl-5-o-hydroxybenzoyl-1H-imidazole is as follows:
Figure BDA0003697738330000091
the embodiments of the present invention have been described in detail with reference to the examples, but the present invention is not limited to the embodiments, and those skilled in the art can make various equivalent changes and substitutions without departing from the principle of the present invention after learning the content of the present invention, and these equivalent changes and substitutions should be considered as falling within the protection scope of the present invention.

Claims (9)

1. A synthetic method of an imidazole derivative is characterized in that the reaction general formula of the synthetic method is as follows:
Figure FDA0003697738320000011
in the formula: r 1 Is aryl, alkyl or heterocyclyl; r 2 Is aryl or alkyl; r 3 Aryl, benzyl or alkyl.
2. The method for synthesizing an imidazole derivative according to claim 1, comprising the steps of:
(a) mixing aurone or its derivative I, benzamidine or its derivative II, iodine and alkali, adding solvent and heating to react;
(b) after the reaction is finished, cooling to room temperature, washing, extracting, drying and decompressing and concentrating the reaction liquid, and then carrying out chromatographic separation to obtain the product imidazole derivative III.
3. The method for synthesizing an imidazole derivative according to claim 2, wherein: the ratio of the amount of the aurone or the derivative thereof, the benzamidine or the derivative thereof, and the iodine to the amount of the alkali in the step (a) is 1: 1.2-1.8: 1-1.5: 1.
4. The method for synthesizing an imidazole derivative according to claim 2, wherein: the alkali in the step (a) is sodium acetate, potassium carbonate, sodium hydroxide, sodium ethoxide, triethylamine, 4-dimethylaminopyridine or 1, 8-diazabicyclo [5.4.0] undec-7-ene.
5. The method for synthesizing an imidazole derivative according to claim 2, wherein: in the step (a), the solvent is 1, 2-dichloroethane, acetonitrile, toluene, chlorobenzene, 1, 4-dioxane, dimethyl sulfoxide or N, N-dimethylformamide, and the volume of the solvent is 10-12 times of the total mass of the raw materials.
6. The method for synthesizing an imidazole derivative according to claim 2, wherein: in the step (a), the reaction temperature is 80-130 ℃, and the reaction time is 5-10 h.
7. The method for synthesizing an imidazole derivative according to claim 2, wherein: the solution adopted in the washing step in the step (b) is a sodium thiosulfate aqueous solution; the extractant adopted in the extraction step is ethyl acetate; the drying step is dried using anhydrous sodium sulfate.
8. The method for synthesizing an imidazole derivative according to claim 2, wherein the chromatographic conditions of the chromatographic separation step in the step (b) are as follows: 200-300-mesh silica gel column, wherein the eluent is a mixture of ethyl acetate and petroleum ether, and the volume ratio of the ethyl acetate to the petroleum ether is 1: 6-10.
9. The method for synthesizing an imidazole derivative according to claim 1, wherein R is the number of R 1 Is phenyl, R 2 Is phenyl, R 3 In the case of benzyl, the synthesis mechanism of the imidazole derivative is:
Figure FDA0003697738320000021
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