Method of selectively synthesizing 2-alkyl acylated-4-aryl-1,2,3-triazole compound

Abstract

The invention relates to a method of selectively synthesizing a 2-alkyl acylated-4-aryl-1,2,3-triazole compound. The method comprises the following steps: (a) introducing a bromine atom to a carbon atom at #5 site of 4-aryl-1,2,3-triazole by means of a bromination reagent to obtain 4,5-di-substituted-NH-1,2,3,-triazole; (b) finishing nitrogen site-2 selective alkyl acylation of the 4,5-di-substituted-NH-1,2,3,-triazole under the joint action of a metal catalyst, an oxidant and alkali; and (c) removing the introduced bromine atom under catalysis of the metal catalyst to obtain the 2-alkyl acylated-4-aryl-1,2,3-triazole compound. By taking cheap metal salt as the catalyst, the system is open, the yield is high, and the 2-alkyl acylated-4-aryl-1,2,3-triazole compound can be selectively synthesized.

Description

technical field

[0001] The invention relates to a method for selectively synthesizing 2-alkanoyl-4-aryl-1,2,3-triazole compounds through multi-step reactions, and belongs to the technical field of organic and pharmaceutical synthesis. technical background

[0002] 1,2,3-Triazole compounds are a class of nitrogen-containing heterocyclic compounds with important physiological activities, widely used in preservatives, pesticides, optical materials, dyes, HIV-1 inhibitors, antibiotics, selective β 3 - Adrenal antagonists, antivirals and anticonvulsants.

[0003] However, the triazole compounds need to be functionalized in the application of triazoles, and there are few studies on nitrogen-diposition-selective functionalization of triazoles. In 2002, Kamijo et al. reported the synthesis of nitrogen two-position allyl group under the catalysis of tris(dibenzylideneacetone) dipalladium with alkyne, azidotrimethylsilane and allyl methyl carbonate as raw materials. 1,2,3-Triazole, ...

Examples

Embodiment 1

[0025] A method for selectively synthesizing 2-alkanoylation-4-aryl-1,2,3-triazole compounds, the specific steps are:

[0026] Step (a): In a round bottom flask (50ml), add 4-phenyl-NH-1,2,3 triazole (1mmol), NBS (1.1mmol, 1.1 equiv), join in ethyl acetate, in open Under the system, the reaction was performed under magnetic stirring at 50°C for 10 h, and the solvent was evaporated under reduced pressure to obtain the crude product which was directly used in step (b).

[0027] Step (b): In a round bottom flask (50ml), add 4-bromo-5-o-bromophenyl-NH-1,2,3 triazole (1mmol), TBHP (2 mmol, 2equiv), CuCl (0.2equiv ), K 2 CO 3 (1.1 equiv), added to DMF, under the open system, magnetic stirring reaction at 80 ° C for 10 h, the extraction reaction solution was extracted with ethyl acetate, the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and reduced pressure The solvent was evaporated to obtain the crude product which was directly used in step ...

Embodiment 2

[0031] A method for selectively synthesizing 2-alkanoylation-4-aryl-1,2,3-triazole compounds, the specific steps are:

[0032] Step (a): In a round bottom flask (50ml), add 4-phenyl-NH-1,2,3 triazole (1mmol), NBS (1.1mmol, 1.1 equiv), join in ethyl acetate, in open Under the system, the reaction was performed under magnetic stirring at 50°C for 10 h, and the solvent was evaporated under reduced pressure to obtain the crude product which was directly used in step (b).

[0033] Step (b): In a round bottom flask (50ml), add 4-bromo-5-o-bromophenyl-NH-1,2,3 triazole (1mmol), TBHP (2 mmol, 2equiv), CuBr (0.2equiv ), NaOAc (1.1 equiv), were added to DMA, and in an open system, magnetically stirred at 80°C for 10 h, extracted the reaction solution with ethyl acetate, washed the organic layer with saturated brine, and dried over anhydrous sodium sulfate , The solvent was evaporated under reduced pressure to obtain the crude product which was directly used in step (c).

[0034] Step ...

Embodiment 3

[0037] A method for selectively synthesizing 2-alkanoylation-4-aryl-1,2,3-triazole compounds, the specific steps are:

[0038] Step (a): In a round bottom flask (50ml), add 4-phenyl-NH-1,2,3 triazole (1mmol), NBS (1.1mmol, 1.1 equiv), join in ethyl acetate, in open Under the system, magnetically stirred at 30°C for 8 hours, and the solvent was evaporated under reduced pressure to obtain the crude product which was directly used in step (b).

[0039] Step (b): In a round bottom flask (50ml), add 4-bromo-5-o-bromophenyl-NH-1,2,3 triazole (1mmol), K 2 S 2 o 8 (2 mmol, 2 equiv), CuCl (0.2 equiv), K 2 CO 3 (1.1 equiv), was added to DMF, and under the open system, magnetically stirred at 95°C for 10 h, extracted the reaction solution with ethyl acetate, washed the organic layer with saturated brine, dried over anhydrous sodium sulfate, and decompressed The solvent was evaporated to obtain the crude product which was directly used in step (c).

[0040] Step (c): In a Schlenk bo...

technical field

[0001] The invention relates to a method for selectively synthesizing 2-alkanoyl-4-aryl-1,2,3-triazole compounds through multi-step reactions, and belongs to the technical field of organic and pharmaceutical synthesis. technical background

[0002] 1,2,3-Triazole compounds are a class of nitrogen-containing heterocyclic compounds with important physiological activities, widely used in preservatives, pesticides, optical materials, dyes, HIV-1 inhibitors, antibiotics, selective β 3 - Adrenal antagonists, antivirals and anticonvulsants.

[0003] However, the triazole compounds need to be functionalized in the application of triazoles, and there are few studies on nitrogen-diposition-selective functionalization of triazoles. In 2002, Kamijo et al. reported the synthesis of nitrogen two-position allyl group under the catalysis of tris(dibenzylideneacetone) dipalladium with alkyne, azidotrimethylsilane and allyl methyl carbonate as raw materials. 1,2,3-Triazole, ...

Examples

Embodiment 1

[0025] A method for selectively synthesizing 2-alkanoylation-4-aryl-1,2,3-triazole compounds, the specific steps are:

[0026] Step (a): In a round bottom flask (50ml), add 4-phenyl-NH-1,2,3 triazole (1mmol), NBS (1.1mmol, 1.1 equiv), join in ethyl acetate, in open Under the system, the reaction was performed under magnetic stirring at 50°C for 10 h, and the solvent was evaporated under reduced pressure to obtain the crude product which was directly used in step (b).

[0027] Step (b): In a round bottom flask (50ml), add 4-bromo-5-o-bromophenyl-NH-1,2,3 triazole (1mmol), TBHP (2 mmol, 2equiv), CuCl (0.2equiv ), K 2 CO 3 (1.1 equiv), added to DMF, under the open system, magnetic stirring reaction at 80 ° C for 10 h, the extraction reaction solution was extracted with ethyl acetate, the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and reduced pressure The solvent was evaporated to obtain the crude product which was directly used in step ...

Embodiment 2

[0031] A method for selectively synthesizing 2-alkanoylation-4-aryl-1,2,3-triazole compounds, the specific steps are:

[0032] Step (a): In a round bottom flask (50ml), add 4-phenyl-NH-1,2,3 triazole (1mmol), NBS (1.1mmol, 1.1 equiv), join in ethyl acetate, in open Under the system, the reaction was performed under magnetic stirring at 50°C for 10 h, and the solvent was evaporated under reduced pressure to obtain the crude product which was directly used in step (b).

[0033] Step (b): In a round bottom flask (50ml), add 4-bromo-5-o-bromophenyl-NH-1,2,3 triazole (1mmol), TBHP (2 mmol, 2equiv), CuBr (0.2equiv ), NaOAc (1.1 equiv), were added to DMA, and in an open system, magnetically stirred at 80°C for 10 h, extracted the reaction solution with ethyl acetate, washed the organic layer with saturated brine, and dried over anhydrous sodium sulfate , The solvent was evaporated under reduced pressure to obtain the crude product which was directly used in step (c).

[0034] Step ...

Embodiment 3

[0037] A method for selectively synthesizing 2-alkanoylation-4-aryl-1,2,3-triazole compounds, the specific steps are:

[0038] Step (a): In a round bottom flask (50ml), add 4-phenyl-NH-1,2,3 triazole (1mmol), NBS (1.1mmol, 1.1 equiv), join in ethyl acetate, in open Under the system, magnetically stirred at 30°C for 8 hours, and the solvent was evaporated under reduced pressure to obtain the crude product which was directly used in step (b).

[0039] Step (b): In a round bottom flask (50ml), add 4-bromo-5-o-bromophenyl-NH-1,2,3 triazole (1mmol), K 2 S 2 o 8 (2 mmol, 2 equiv), CuCl (0.2 equiv), K 2 CO 3 (1.1 equiv), was added to DMF, and under the open system, magnetically stirred at 95°C for 10 h, extracted the reaction solution with ethyl acetate, washed the organic layer with saturated brine, dried over anhydrous sodium sulfate, and decompressed The solvent was evaporated to obtain the crude product which was directly used in step (c).

[0040] Step (c): In a Schlenk bo...

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