Technical field
The invention specifically relates to a copper (I) trifluoroacetate reagent and its application in trifluoromethylation reaction.
technical background
[0002] Fluorine-containing compounds have many unique physical and chemical properties, and have very important application values in biochemistry, medicine, pesticides, functional materials and other fields. Therefore, it is of great research value and practical significance to develop new synthesis methods of fluorine-containing compounds. Among the functional groups containing fluorine atoms, trifluoromethyl (-CF 3), especially as an aromatic functional group, has attracted more and more attention because of its strong electronegativity and strong lipophilicity. Many drugs contain trifluoromethyl, such as fluoxetine and sorafenib. However, at present, the transition metal-catalyzed trifluoromethylation reaction needs expensive catalysts, ligands and trifluoromethylation reagents, which is difficult to be popularized in industry. Therefore, it is very necessary to invent an economical and feasible trifluoromethylation reagent to promote the trifluoromethylation reaction efficiently and quickly.
Summary of the invention
[0003] The purpose of the present invention is to provide a copper (I) trifluoroacetate reagent and its application in the trifluoromethylation reaction. The reagent takes trifluoroacetic acid which is cheap and easily available in industry as the main raw material, chelates with bidentate nitrogen ligands, can be stably stored, and can efficiently promote the trifluoromethylation reaction of halogenated aromatic hydrocarbons or halogenated heterocyclic compounds.
[0004] In order to achieve the above purpose, the invention adopts the following technical scheme: copper (I) trifluoroacetate reagent, the structural formula of which is:
Sovereignty terms
1. A copper trifluoroacetate reagent, which is characterized by its structural formula:
Wherein Rp R2 is independently selected from h or alkyl.
2. The copper (I) trifluoroacetate reagent according to claim 1, characterized in that R2 is H in the structural formula.
3. The copper (I) trifluoroacetate reagent according to claim 1, characterized in that in the structural formula, R2 with the length of R is alkyl.
4. The copper (I) trifluoroacetate reagent according to claim 1, wherein R2 is alkyl in the structural formula R 1S H.
5. The copper (I) trifluoroacetate reagent according to claim 1, wherein in its structural formula, R is independently selected from H or any alkyl group with 1-4 carbon atoms.
6. The preparation method of copper (I) trifluoroacetate reagent according to claim 1 comprises the following steps: 1) adding cuprous chloride and tetrahydrofuran solvent into the reactor, dropwise adding tetrahydrofuran solution of sodium tert-butoxide, stirring at room temperature for 15 minutes, and filtering to obtain cuprous tert-butoxide solution; 2) dropwise adding the tetrahydrofuran solution of bidentate nitrogen ligand into the obtained cuprous tert-butyl alcohol solution to obtain a dark reddish brown solution, dropwise adding the tetrahydrofuran solution of trifluoroacetic acid into the dark reddish brown solution at 0 DEG C, stirring at room temperature for 65,438+/-0.5 minutes, filtering, removing the solvent in the filtrate in vacuum, washing the obtained solid with diethyl ether, and recrystallizing to obtain the copper (I) trifluoroacetate reagent; The molar ratio of cuprous chloride, sodium tert-butoxide, bidentate nitrogen ligand and trifluoroacetic acid is1:1:1.
7. The preparation method of copper (I) trifluoroacetate reagent according to claim 6, characterized in that the structural formula of bidentate nitrogen ligand in step 2) is:
Wherein, RJPR2 is independently selected from h or alkyl.
8. The application of copper trifluoroacetate reagent in trifluoromethylation reaction according to claim 1, characterized in that the copper trifluoroacetate reagent reacts with compound R-X in N, N- dimethylformamide solvent to generate trifluoromethylation product R-CF 3 in the presence of NaF, wherein X is Br or CF 3.
9. The application of copper trifluoroacetate reagent in trifluoromethylation reaction according to claim 8, characterized by the following specific steps: adding copper trifluoroacetate reagent, compounds R-X and NaF, adding N, N- dimethylformamide solvent, stirring in a closed system at 65438 040℃ for 8 hours, and cooling to room temperature. Wherein, copper (I) trifluoroacetate reagent, compound R-X and NaFN are added according to the molar ratio of1:1:3, and the amount of N- dimethylformamide is 20-30ml per millimole of copper (I) trifluoroacetate reagent.
The invention discloses a copper trifluoroacetate reagent and its application in trifluoromethylation reaction. The structural formula is as follows: cuprous chloride, sodium tert-butoxide and bidentate nitrogen ligand react in tetrahydrofuran solvent, then trifluoroacetic acid is added for reaction, and finally copper (I) trifluoroacetate reagent is obtained by separation and purification; The reagent can be decarboxylated with halogenated aromatic hydrocarbons or halogenated heterocyclic compounds to carry out trifluoromethylation reaction to form corresponding trifluoromethylation derivative products. The preparation process of the invention is simple, the raw materials are cheap and easily available, and the obtained copper (I) trifluoroacetate reagent has good selectivity, can quickly and efficiently promote the trifluoromethylation reaction, and has a good industrial application prospect.
IPC classification C07C 17-32, C07C22-08, C07B37-04, C07F 1-08.
Publication number: cn104530101
The application number is cn 201510041619.
Inventors Weng Zhiqiang, Hou Chuanqi, Zhang
Applicant Fuzhou University
Open day 2065438+April 22, 2005
Date of application: 2015 65438+128 October.
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This technology has been patented. For study and research only. If used for commercial purposes, please contact the technology owner.
Technical R&D personnel: Weng Zhiqiang; Huang Yangjie; Hou Chuanqi; Zhang;
Technical director: Fuzhou University;