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A kind of method that prepares hydroxyimidazole compound by multi-component cyclization reaction

A technology of cyclization reaction and hydroxyimidazole, which is applied in the field of medicinal chemistry and can solve problems such as application influence, time-consuming, harsh preparation conditions, etc.

Active Publication Date: 2021-07-06
GUANGDONG PHARMA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The steps of this method are relatively simple and environmentally friendly, but it is necessary to use silver acetate as a catalyst, and only when a specific solvent is selected can a better yield be achieved. It also needs to be flushed with nitrogen, and the preparation conditions are relatively harsh.
In addition, the reaction needs to be reacted at 100°C for 10 hours, which takes a long time and has a certain impact on its application

Method used

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  • A kind of method that prepares hydroxyimidazole compound by multi-component cyclization reaction
  • A kind of method that prepares hydroxyimidazole compound by multi-component cyclization reaction
  • A kind of method that prepares hydroxyimidazole compound by multi-component cyclization reaction

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] As shown in the following formula, add 784.4mg (4mmol) arylamidine, 520.2mg (4mmol) alkyne aldehyde substrate and water (0.3mL) into a 25ml test tube with a stirring bar, add 5mL toluene at room temperature, and then add 688.1mg (4mmol) benzenesulfonic acid, 623.8mg (4mmol) sodium trifluoromethanesulfinate, stirred at 80°C for 4 hours, washed with water and separated by silica gel chromatography to obtain the target product with a yield of 88%.

[0029]

[0030] 1 H NMR (400MHz, CDCl3) δ7.57 (d, J = 7.6Hz, 2H), 7.40-7.32 (m, 8H), 7.30-7.28 (m, 1H), 7.25-7.20 (m, 2H), 7.16- 7.12(m,2H),6.67(s,1H),5.97(s,1H),3.34(s,1H).

[0031] 13 C NMR (100MHz, CDCl3) δ146.4, 145.2, 142.2, 138.1, 129.6, 129.4, 129.4, 128.7, 128.7, 128.6, 128.3, 128.3, 128.3, 128.2, 128.2, 127.6, 126.7, 126.7, 129.8, 129.8 .

[0032] HR-MALDI-MS m / z calcd. for C22H18N2O[M+H]+: 327.1492, found: 327.1490.

Embodiment 2

[0034] As shown in the following formula, add 45.3mg (0.2mmol) arylamidine, 26.0mg (0.2mmol) alkyne aldehyde substrate and water (0.1mL) into a 25mL test tube with a stirring bar, add 2mL toluene at room temperature, and then add 31.7 mg (0.2 mmol) of benzenesulfonic acid and 31.2 mg (0.2 mmol) of sodium trifluoromethanesulfinate were stirred at 80°C for 4 hours, washed with water and separated by silica gel chromatography to obtain the target product with a yield of 80%.

[0035]

[0036] 1 H NMR (400MHz, CDCl3) δ7.57 (d, J = 7.2Hz, 2H), 7.39-7.35 (m, 4H), 7.31-7.29 (m, 1H), 7.25-7.19 (m, 3H), 7.08- 7.05(m,2H),6.86-6.82(m,2H),6.62(s,1H),5.96(s,1H),4.20(s,1H),3.80(s,3H).

[0037] 13 C NMR (100MHz, CDCl3) δ159.1, 146.5, 145.1, 142.5, 131.2, 130.0, 128.6, 128.6, 128.4, 128.2, 128.2, 128.1, 128.1, 127.5, 127.0, 127.0, 126.7, 126.1, 128.4, 143.4 ,55.5.

[0038] HR-MALDI-MS m / z calcd. for C23H21N2O2[M+H]+: 357.1598, found: 357.1615.

Embodiment 3

[0040] As shown in the following formula, add 57.8mg (0.2mmol) aryl amidine, 26.0mg (0.2mmol) alkyne aldehyde substrate and water (0.1mL) into a 25mL test tube with a stirring bar, add 2mL toluene at room temperature, and then add 31.7mg (0.2mmol) of benzenesulfonic acid, 31.2mg (0.2mmol) of sodium trifluoromethanesulfinate, stirred at 80°C for 4 hours, washed with water and separated by silica gel chromatography to obtain the target product with a yield of 68%.

[0041]

[0042] 1 H NMR (400MHz, CDCl3) δ7.56 (d, J = 7.1Hz, 2H), 7.48–7.45 (m, 2H), 7.40-7.35 (m, 3H), 7.33-7.30 (m, 1H), 7.11- 7.10(m,2H),7.04-7.00(m,2H),6.98-6.94(m,1H),6.64(s,1H),5.95(s,1H),3.82(s,1H),2.28(s, 3H).

[0043] 13 C NMR (100MHz, CDCl3) δ146.7, 145.5, 142.1, 138.3, 137.2, 132.5, 132.5, 129.7, 129.5, 129.3, 128.3, 128.3, 128.1, 127.6, 127.2, 127.2, 126.7, 126.7, 129.7, 129.7 ,21.3.

[0044] HR-MALDI-MS m / z calcd. for C23H20BrN2O[M+H]+: 419.0754, found: 419.0754.

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Abstract

The invention discloses a method for preparing hydroxyimidazole compounds by multi-component cyclization reaction, and relates to the field of medicinal chemistry. The preparation method of the present invention takes aryl amidine, alkyne aldehyde and water as reaction substrate, protonic acid and Na 2 SO 2 CF 3 As an additive, the hydroxyimidazole compound is prepared through a cyclization reaction. The method can construct C-N and C-O bonds by a one-step reaction, the preparation method is green and environmentally friendly, the preparation process is simple and easy to operate, the reaction conditions are mild, the reaction substrate has a wide range of applications, good regioselectivity, high yield, and short preparation time It is short and can quickly synthesize various types of hydroxyimidazole compounds, and has a good application prospect.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a method for preparing hydroxyimidazole compounds by multi-component cyclization reaction. Background technique [0002] Imidazole and its derivatives, as ubiquitous nitrogen heterocyclic compounds, widely exist in the fields of natural products, functional materials, drug molecules, and carbene ligand precursors. Imidazole compounds have a wide range of biological activities, such as antibacterial, anticancer, antifungal, antagonist and phosphatase inhibitory effects. It can not only be used as a pharmaceutical intermediate to synthesize various complex drugs and imidazole drugs, such as non-prescription metronidazole, prescription drug ornidazole and prescription drug senidazole, etc. It can also be used as a raw material for many functional materials, and can also be used as an organic small molecule catalyst to catalyze some organic reactions. It is also an important compo...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D233/64
CPCC07D233/64
Inventor 曹华刘想余跃
Owner GUANGDONG PHARMA UNIV