Copper difluorocarbene reagent, and preparation method and application thereof

A difluorocarbene and copper reagent technology, applied in the difluorocarbene copper reagent and its preparation and application fields, can solve the problems of limited wide use, general reactivity, inconvenient operation, etc., and achieve low production cost, simple and convenient reaction operation, good The effect of industrial application prospect

Inactive Publication Date: 2015-09-16
FUZHOU UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

So far, the most economical and effective difluorocarbene precursor is Fre0n22 gas (HCF2Cl), but it has a very large destructive effect on the atmospheric ozone layer, and its reactivity is general, and the required amount larger
Moreover, the reagent is a gas, and the laboratory operation is inconvenient, which limits its wide use

Method used

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  • Copper difluorocarbene reagent, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Under the protection of nitrogen, add a polytetrafluoroethylene magnetic stirring bar to the reactor, add 10.00 mmol cuprous chloride to it, add 10 mL tetrahydrofuran solvent and mix well, then add dropwise 55 mL containing 12.00 mmol tert-butyl The tetrahydrofuran solution of sodium alkoxide was stirred at room temperature for 25 minutes, filtered to obtain a light yellow clear solution, and 15 mL of tetrahydrofuran solution containing 14.00 mmol o-phenanthroline was added dropwise to obtain a dark reddish-brown solution. Slowly add 10 mL of tetrahydrofuran solution containing 7.00 mmol of difluorochloroacetic acid dropwise into the solution. After the dropwise addition, continue stirring at room temperature for 5 minutes; filter out the resulting precipitate, and wash the resulting precipitate with ether to obtain a dark reddish-brown solid After recrystallization, reddish-brown granular crystals were obtained, namely 1,10-phenanthroline-difluorochloroacetic acid cupro...

Embodiment 2

[0022] Under the protection of nitrogen, add a polytetrafluoroethylene magnetic stirring bar to the reactor, add 10.00 mmol cuprous chloride to it, add 10 mL tetrahydrofuran solvent and mix well, then add dropwise 55 mL containing 12.00 mmol tert-butyl The tetrahydrofuran solution of sodium alkoxide was stirred at room temperature for 25 minutes, filtered to obtain a light yellow clear solution, and 15 mL of tetrahydrofuran solution containing 14.00 mmol 2,2-bipyridine was added dropwise to obtain a dark reddish-brown solution. Slowly add 10 mL of tetrahydrofuran solution containing 7.00 mmol difluorochloroacetic acid dropwise into the reddish-brown solution. After the dropwise addition, continue to stir for 5 minutes at room temperature; Brown solid, reddish-brown granular crystals obtained after recrystallization, that is, 2,2-bipyridine difluorochloroacetic acid cuprous(I) complex (bpy)Cu(O 2 CCF 2 Cl), productive rate 75%, 1 H-NMR (400 MHz, DMSO- d 6 ) δ: 8.66 (d, J ...

Embodiment 3

[0024]Under the protection of nitrogen, add a polytetrafluoroethylene magnetic stirring bar to the reactor, add 10.00 mmol cuprous chloride to it, add 10 mL tetrahydrofuran solvent and mix well, then add dropwise 55 mL containing 12.00 mmol tert-butyl Sodium alkoxide solution in tetrahydrofuran, stirred at room temperature for 25 minutes, filtered to obtain a light yellow clear solution, dropwise added 15 mL of tetrahydrofuran solution containing 14.00 mmol 2,9-dimethyl-phenanthroline to obtain a dark reddish-brown solution, used once Slowly add 10 mL of tetrahydrofuran solution containing 7.00 mmol of difluorochloroacetic acid into the above dark reddish-brown solution with a syringe, and after the addition, continue to stir for 5 minutes at room temperature; After washing, a dark reddish brown solid was obtained, and after recrystallization, a reddish brown granular crystal was obtained, which was 2,9-dimethyl-phenanthroline-difluorochloroacetic acid cuprous (I) complex (2,9-...

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Abstract

The invention discloses a copper difluorocarbene reagent, and a preparation method and an application thereof. The structural formula of the reagent is shown in the specification; and in the formula, a bidentate nitrogen and nitrogen ligand can be one of substances with the structures also shown in the specification, and R1 and R2 are independently selected from H or alkyl groups. The preparation method of the reagent comprises the following steps: reacting cuprous chloride, sodium tert-butoxide and the bidentate nitrogen and nitrogen ligand in a tetrahydrofuran solvent, adding difluorochloroacetic acid, reacting, and separating and purifying to obtain the copper difluorocarbene reagent. The reagent can react with oxygen, sulfur, selenium,hetero atoms of amine, or a reactive hydrogen-containing compound at the end of terminal alkyne to generate corresponding difluoromethylation derivative products. The preparation method has the advantages of simplicity, and cheap and easily available raw materials, and the obtained copper difluorocarbene reagent has good selectivity, can promote fast and efficient process of a difluoromethylation reaction, and has good industrial application prospect.

Description

technical field [0001] The invention belongs to the field of organic synthesis, and in particular relates to a difluorocarbene copper reagent and its preparation and application. Background technique [0002] Compounds containing difluoromethyl groups have very important applications in the fields of medicine, pesticides and materials. The introduction of difluoromethyl groups into drug molecules can change its pharmacokinetic parameters, such as improving its cell membrane permeability, bioavailability, binding affinity, metabolic stability, and lipophilicity. Therefore, in isosteric-based drug design, it is often considered to add difluoromethyl to the molecule. Drugs currently on the market, such as eflornithine, pantoprazole, and garefloxacin, as well as some pesticides, such as sulfentrazone and mefentrazone, all contain difluoromethyl groups. So far, the most cost-effective difluorocarbene precursor is Fre0n22 gas (HCF 2 Cl), but it has a great destructive effect on...

Claims

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Application Information

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IPC IPC(8): C07F1/08C07C201/12C07C205/37C07C253/30C07C255/54C07C41/01C07C43/225
Inventor 翁志强林晓希黄扬杰
Owner FUZHOU UNIVERSITY
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