CN107827829A - Preparation method of 5 amide groups, 1,4,5 trisubstituted 1,2,3 triazole in aqueous phase and Biomedia - Google Patents

Abstract

The invention belongs to the technical field of organic synthesis, and relates to a preparation method of 5-amido-1,4,5-trisubstituted 1,2,3-triazole in aqueous phase and biological medium, in a solvent, in 1 , under the action of 5-cyclooctadiene iridium chloride dimer catalyst, catalyzed alkyne amine compound and azide to prepare 5-amido-1,4,5-trisubstituted 1,2,3-triazole. The preparation method of the 5-amido-1,4,5-trisubstituted 1,2,3-triazole products in the present invention has mild reaction conditions, and the product yield is not lower than 80%. The preparation method has mild reaction conditions, green, high reaction efficiency, and potential biological application value, and the prepared 5-amido-1,4,5-trisubstituted 1,2,3-triazole compounds have potential biological activity.

Description

5-amido-1,4,5-trisubstituted 1,2,3-triazoles in aqueous and biological media The preparation method in

technical field

The invention belongs to the technical field of organic synthesis and relates to a preparation method of novel 5-amido-1,4,5-trisubstituted 1,2,3-triazole in aqueous phase and biological medium.

Background technique

The alkyne-azido cycloaddition reaction is one of the most important methods for the preparation of 1,2,3-triazoles. In recent years, a series of documents or patents have reported the preparation methods of 1,2,3-triazole compounds.

In 2001, the Medal research group and the Sharpless research group respectively reported the copper-catalyzed terminal alkyne-azide cycloaddition reaction (J.Org.Chem., 2002, 67, 3057 and Angew.Chem.Int.Ed., 2002, 41, 2596). Subsequently, this reaction has been extensively studied and paid attention to. However, there is no report on the transition metal-catalyzed alkyne amine-azide cycloaddition reaction in aqueous phase. How to realize the alkyne amine-azido cycloaddition reaction in aqueous phase is the focus of our attention. If this cycloaddition can be achieved in aqueous phase to give 5-amido-1,4,5-trisubstituted 1,2,3-triazole products, we will further investigate the potential of this reaction using various biological media. application value in the biological field. 5-amido-1,4,5-trisubstituted 1,2,3-triazole compounds have potential physiological activities, so it is of great significance to study their preparation methods.

The present invention adopts various alkyne amines as raw materials, uses 2.5mol% [Ir(COD)Cl] ₂ as a catalyst, and obtains 5-amido-1 with a yield of 80% to 87% under mild conditions at 23°C. 4,5-trisubstituted 1,2,3-triazole compounds.

Contents of the invention

The technical problem to be solved by the present invention is to provide a method for synthesizing 5-amido-1,4,5-trisubstituted 1,2,3-triazole compounds in aqueous phase and biological medium.

Technical scheme of the present invention:

A preparation method of novel 5-amido-1,4,5-trisubstituted 1,2,3-triazole in aqueous phase and biological medium, the steps are as follows:

In a solvent, under the action of 1,5-cyclooctadiene iridium chloride dimer ([Ir(COD)Cl] ₂ ) catalyst, catalyzed alkyne amine compound and azide to prepare 5-amido-1,4 ,5-trisubstituted 1,2,3-triazole, the reaction formula is as follows:

Wherein, R ¹ and R ² are hydrogen atom, alkyl, alkoxy or aryl, R ¹ and R ² are the same or different;

R ³ is an alkyl group, an alkoxyl group or an aryl group;

R ⁴ is alkyl or aryl;

I is acetylene amine compound;

The reaction temperature is -15°C to 25°C, the reaction time is 8h to 16h, and the yield of 5-amido-1,4,5-trisubstituted 1,2,3-triazole is not less than 70%. .

The molar ratio of the acetylenic amine compound to azide is 1:1, and the concentration of the acetylenic amine compound is 0.01-0.1 mmol/ml.

The amount of [Ir(COD)Cl] ₂ is 0.5-50 mol% of the acetylene amine compound.

Described solvent is water, phosphate buffered saline solution (pH=1～14), DMEM cell culture fluid, HeLa cell lysate, normal mouse serum (concentration is 50%～100%), normal human serum (concentration is 50%) %～100%), the preferred solvent is water or phosphate buffered saline (pH=5.7).

Beneficial effects of the present invention: the preparation method of 5-amido-1,4,5-trisubstituted 1,2,3-triazole products in the present invention has mild reaction conditions and the product yield is not less than 80%. The preparation method has mild reaction conditions, green, high reaction efficiency, and potential biological application value, and the prepared 5-amido-1,4,5-trisubstituted 1,2,3-triazole compounds have potential biological activity.

Detailed ways

The specific implementation manners of the present invention will be further described below in conjunction with the technical solutions.

Example 1: Preparation of 1-benzyl-4-phenyl-5-(pyrazolin 2-one group)-1H-1,2,3-triazole

Under air, 3-phenylethynyl-pyrazolin 2-one (0.2 mmol, 37.4 mg) was added to water (2 mL), followed by benzyl azide (0.3 mmol, 40.2 mg) and [Ir( COD)Cl] ₂ (0.005mmol, 3.3mg), the reaction mixture was stirred at room temperature, and reacted for 12h. After the reaction was completed, it was extracted with ethyl acetate, and the solvent was selected and separated by column chromatography to obtain 54.4mg of a yellow solid product with a yield of 85%.

Example 2: Preparation of 1-benzyl-4-p-methoxyphenyl-5-(pyrazolin 2-one)-1H-1,2,3-triazole

3-p-Methoxyphenylethynyl-pyrazolin 2-one (0.2 mmol, 43.4 mg) was added to water (2 mL) followed by benzyl azide (0.3 mmol, 40.2 mg) under air And [Ir(COD)Cl] ₂ (0.005mmol, 3.3mg), the reaction mixture was stirred at room temperature, and reacted for 12h. After the reaction, it was extracted with ethyl acetate, and the solvent was selected and separated by column chromatography to obtain 60.9mg of a yellow liquid product. The rate is 87%.

Example 3: Preparation of 1-benzyl-4-p-chlorophenyl-5-(pyrazolin 2-one)-1H-1,2,3-triazole

Under air, 3-p-chlorophenylethynyl-pyrazolin 2-one (0.2 mmol, 44.2 mg) was added to water (2 mL), followed by benzyl azide (0.3 mmol, 40.2 mg) and [ Ir(COD)Cl] ₂ (0.005mmol, 3.3mg), stirred the reaction mixture at room temperature, reacted for 12h, extracted with ethyl acetate after the reaction, selected dry solvent, separated by column chromatography to obtain 56.7mg of white solid product, yield 80 %.

Example 4: Preparation of 1-p-chlorobenzyl-4-phenyl-5-(pyrazolin 2-one)-1H-1,2,3-triazole

3-Phenylethynyl-pyrazolin 2-one (0.2 mmol, 37.4 mg) was added to water (2 mL) under air, followed by p-chlorobenzyl azide (0.3 mmol, 50.1 mg) and [ Ir(COD)Cl] ₂ (0.005mmol, 3.3mg), stirred the reaction mixture at room temperature, reacted for 12h, extracted with ethyl acetate after the reaction, selected dry solvent, and separated by column chromatography to obtain 60.1mg of white solid product, yield 85 %.

Example 5: Preparation of 1-p-methylbenzyl-4-phenyl-5-(pyrazolin 2-one)-1H-1,2,3-triazole

Under air, 3-phenylethynyl-pyrazolin 2-one (0.2mmol, 37.4mg) was added to water (2mL), followed by p-methylbenzyl azide (0.3mmol, 44.1mg) and [Ir(COD)Cl] ₂ (0.005mmol, 3.3mg), stirred the reaction mixture at room temperature, reacted for 12h, extracted with ethyl acetate after the reaction, selected dry solvent, and separated by column chromatography to obtain 54.9mg of white liquid product, the yield was 82%.

Claims (8)

1. a kind of 5- amide groups-Isosorbide-5-Nitrae, 5- trisubstituted 1, preparation method of 2, the 3- triazoles in aqueous phase and Biomedia, its It is characterised by, step is as follows：

In a solvent, under 1,5- cyclo-octadiene iridium chloride dimer catalyst actions, catalysis alkynes aminated compounds and nitrine system Standby 5- amide groups-Isosorbide-5-Nitrae, 5- trisubstituted 1,2,3- triazoles, reaction equation are as follows：

Wherein, R¹And R²For hydrogen atom, alkyl, alkoxy or aryl, R¹And R²It is identical or different；

R³For alkyl, alkoxy or aryl；

R⁴For alkyl or aryl；

I is alkynes aminated compounds；

Reaction temperature be -15 DEG C~25 DEG C, the reaction time be 8h~16h, be prepared yield be not less than 70% 5- amide groups - The trisubstituted 1,2,3- triazoles of 1,4,5-.

2. the trisubstituted 1,2,3- triazoles of 5- amide groups -1,4,5- according to claim 1 are in aqueous phase and Biomedia In preparation method, it is characterised in that described alkynes aminated compounds and the mol ratio of nitrine are 1:1, alkynes aminated compounds Concentration 0.01-0.1mmol/ml.

3. the trisubstituted 1,2,3- triazoles of 5- amide groups -1,4,5- according to claim 1 or 2 are situated between in aqueous phase and biology Preparation method in matter, it is characterised in that described 1,5- cyclo-octadiene iridium chloride dimers catalyst amount is ynamine class 0.5~50mol% of compound.

4. the trisubstituted 1,2,3- triazoles of 5- amide groups -1,4,5- according to claim 1 or 2 are situated between in aqueous phase and biology Preparation method in matter, it is characterised in that described solvent is water, phosphate buffered saline solution, DMEM cell culture fluids, HeLa thin The mice serum or mass percent concentration that cellular lysate liquid, mass percent concentration are 50%~100% are 50%~100% Human serum.

5. the trisubstituted 1,2,3- triazoles of 5- amide groups -1,4,5- according to claim 3 are in aqueous phase and Biomedia In preparation method, it is characterised in that described solvent be water, phosphate buffered saline solution, DMEM cell culture fluids, HeLa cells The people that the mice serum or mass percent concentration that lysate, mass percent concentration are 50%~100% are 50%~100% Serum.

6. the trisubstituted 1,2,3- triazoles of 5- amide groups -1,4,5- according to claim 1,2 or 5 are in aqueous phase and biology Preparation method in medium, it is characterised in that described solvent is water or phosphate buffered saline solution.

7. the trisubstituted 1,2,3- triazoles of 5- amide groups -1,4,5- according to claim 3 are in aqueous phase and Biomedia In preparation method, it is characterised in that described solvent is water or phosphate buffered saline solution.

8. the trisubstituted 1,2,3- triazoles of 5- amide groups -1,4,5- according to claim 4 are in aqueous phase and Biomedia In preparation method, it is characterised in that described solvent is water or phosphate buffered saline solution.