Preparation method for electrocatalytic synthesis of polyfluorinated biaryl
The method for synthesizing polyfluoroaromatics by electrocatalysis solves the problem of relying on metal nucleophiles or photocatalysts in existing technologies, achieves highly selective functionalization of polyfluoroaromatics, and provides a cheap and efficient synthetic route.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- GUIZHOU MINZU UNIV
- Filing Date
- 2026-01-21
- Publication Date
- 2026-04-10
AI Technical Summary
Existing methods for synthesizing complex polyfluoroaryl compounds from polyfluoroaromatics rely on metal nucleophiles or photocatalysts, which limits their application.
A method for the electrocatalytic synthesis of polyfluoroalkyl aromatics (PFA) was adopted. The PFA was constructed by mixing PFA, aromatic hydrocarbons, tetrabutylammonium bromide, ferrocene and potassium hydroxide in an organic solvent at room temperature, followed by electrochemical reaction, vacuum distillation and silica gel column chromatography.
This method achieves highly selective functionalization of unconventional CF reaction sites in polyfluoroaromatics, opening up a new approach for the synthesis of polyfluorobiaromatics. Moreover, it does not require precious metal photocatalysts and can be completed with only inexpensive bases and low current.
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Figure CN121826740A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of organic synthesis. Background Technology
[0002] Polyfluoroaromatics (PFA) are a class of organic compounds containing multiple fluorine atoms on their aromatic rings. Due to the unique properties of fluorine atoms, these compounds have significant applications in medicine, pesticides, and materials science. The strong electron-withdrawing effect of PFAs can significantly lower the HOMO and LUMO energy levels of their compounds, promoting π-π interactions between electron-rich and electron-deficient PFAs, thereby improving the conductivity and oxidation resistance of optoelectronic materials and giving them the properties of n-type semiconductor materials. In terms of synthetic methods, traditional strategies mainly include CH or CX bond fluorination, but these methods usually require the pre-introduction of multiple functional groups or directing groups, which has significant limitations when applied to PFA synthesis. Therefore, using inexpensive and readily available PFA chemicals as raw materials, direct defluorination functionalization strategies have become an effective way to synthesize complex polyfluoroaryl compounds (such as compounds 1, 2, and 3). These strategies include aryl nucleophilic substitution (SNAr) strategies, photocatalytic single-electron reduction strategies, and metal-catalyzed CF bond activation strategies.
[0003]
[0004] However, most existing methods rely on the use of metal nucleophiles such as organolithium and Grignard reagents, or on the redox capabilities of photocatalysts, which limits their application range to some extent. Summary of the Invention
[0005] This invention aims to address the problem that existing methods for synthesizing complex polyfluoroaryl compounds from polyfluoroaromatics often rely on the use of metal nucleophiles or the redox capabilities of photocatalysts, and thus provides a method for the electrocatalytic synthesis of polyfluoroaryl compounds.
[0006] A method for the electrocatalytic synthesis of polyfluorinated aromatic hydrocarbons, comprising the following steps:
[0007] Polyfluoroaromatics, aromatic hydrocarbons, tetrabutylammonium bromide, ferrocene, potassium hydroxide and organic solvent were mixed evenly under room temperature and stirring conditions. Then, an electrochemical reaction was carried out under room temperature and stirring conditions. The solvent was removed by vacuum distillation and then purified by silica gel column chromatography to obtain polyfluoroaromatics.
[0008] The general structural formula of the polyfluoroaromatic hydrocarbon is as follows: , where R is methyl, methoxy, ester, or cyano;
[0009] The general structural formula of the aromatic hydrocarbon is as follows: Ar represents aryl groups with different structures.
[0010] The beneficial effects of this invention are:
[0011] This invention employs a greener electrocatalytic synthesis method to achieve highly selective functionalization of unconventional CF reaction sites in polyfluoroaromatics, opening up new methods for the synthesis of polyfluorobiaromatics.
[0012] Unlike existing technologies, this method uses an electrocatalytic approach, eliminating the need for precious metal photocatalysts. It can achieve the construction of polyfluoroalkyl hydrocarbons (PANA) using only inexpensive alkalis, additives, and low current. Attached Figure Description
[0013] Figure 1 The polyfluoroalkyl hydrocarbons prepared in Example 1 1 H NMR spectrum. Detailed Implementation
[0014] Specific Implementation Method 1: This implementation method describes a method for preparing polyfluoroalkyl aromatic hydrocarbons through electrocatalytic synthesis, which is carried out according to the following steps:
[0015] Polyfluoroaromatics, aromatic hydrocarbons, tetrabutylammonium bromide, ferrocene, potassium hydroxide and organic solvent were mixed evenly under room temperature and stirring conditions. Then, an electrochemical reaction was carried out under room temperature and stirring conditions. The solvent was removed by vacuum distillation and then purified by silica gel column chromatography to obtain polyfluoroaromatics.
[0016] The general structural formula of the polyfluoroaromatic hydrocarbon is as follows: , where R is methyl, methoxy, ester, or cyano;
[0017] The general structural formula of the aromatic hydrocarbon is as follows: Ar represents aryl groups with different structures.
[0018] The beneficial effects of this embodiment are:
[0019] This embodiment employs a greener electrocatalytic synthesis method, achieving highly selective functionalization of unconventional CF reaction sites in polyfluoroaromatics, thus opening up new methods for the synthesis of polyfluorobiaromatics.
[0020] Unlike existing technologies, this method uses an electrocatalytic approach, eliminating the need for precious metal photocatalysts. It can achieve the construction of polyfluoroalkyl hydrocarbons (PANA) using only inexpensive alkalis, additives, and low current.
[0021] Specific Implementation Method Two: This implementation method differs from Specific Implementation Method One in that: the molar ratio of the polyfluoroaromatic hydrocarbon to the aromatic hydrocarbon is 1:(1.5~3); the molar ratio of the polyfluoroaromatic hydrocarbon to tetrabutylammonium bromide is 1:(1.5~3); the molar ratio of the polyfluoroaromatic hydrocarbon to ferrocene is 1:(1.5~3); and the molar ratio of the polyfluoroaromatic hydrocarbon to potassium hydroxide is 1:(1.5~3). Everything else is the same as in Specific Implementation Method One.
[0022] Specific Implementation Method Three: This implementation method differs from Specific Implementation Method One or Two in that the organic solvent used is acetonitrile, toluene, N,N-dimethylformamide, or dimethyl sulfoxide. Everything else is the same as in Specific Implementation Method One or Two.
[0023] Specific Implementation Method Four: This implementation method differs from Specific Implementation Methods One to Three in that the molar ratio of the polyfluoroaromatic hydrocarbon to the volume of the organic solvent is 1 mmol:(10~20) mL. Everything else is the same as in Specific Implementation Methods One to Three.
[0024] Specific Implementation Method Five: This implementation method differs from Specific Implementation Methods One to Four in that: under the conditions of room temperature and a stirring speed of 600 r / min to 800 r / min, polyfluoroaromatics, aromatics, tetrabutylammonium bromide, ferrocene, potassium hydroxide, and organic solvent are mixed evenly. Everything else is the same as in Specific Implementation Methods One to Four.
[0025] Specific Implementation Method Six: This implementation method differs from Specific Implementation Methods One to Five in that the electrochemical reaction is carried out at room temperature, with a stirring speed of 600 r / min to 800 r / min and a current of 5 mA to 30 mA for 5 h to 24 h. Everything else is the same as Specific Implementation Methods One to Five.
[0026] Specific Implementation Method Seven: This implementation method differs from Specific Implementation Methods One to Six in that the solvent used for silica gel column chromatography separation and purification is a mixed solvent of petroleum ether and ethyl acetate. Everything else is the same as in Specific Implementation Methods One to Six.
[0027] Specific Implementation Method Eight: This implementation method differs from Specific Implementation Methods One to Seven in that the volume ratio of petroleum ether to ethyl acetate is (30~80):1. Everything else is the same as in Specific Implementation Methods One to Seven.
[0028] Specific Implementation Method Nine: This implementation method differs from Specific Implementation Methods One through Eight in that the general structural formula of the polyfluorohydroaromatics is: Wherein R is methyl, methoxy, ester, or cyano. Other aspects are the same as in embodiments one through eight.
[0029] Specific Implementation Method Ten: This implementation method differs from Specific Implementation Methods One to Nine in that the structural formula of the polyfluoroaromatic hydrocarbon is: or The structural formula of the aromatic hydrocarbon is as follows: or The structural formula of the polyfluoroalkylene is as follows: or The rest is the same as in specific implementation methods one through nine.
[0030] The beneficial effects of the present invention are verified using the following embodiments:
[0031] Example 1:
[0032] A method for the electrocatalytic synthesis of polyfluorinated aromatic hydrocarbons, comprising the following steps:
[0033] At room temperature and with a stirring speed of 750 r / min, 63.0 mg (0.2 mmol) of polyfluoroaromatics, 48.3 mg (0.3 mmol) of aromatics, 128.8 mg (0.4 mmol) of tetrabutylammonium bromide, 74.4 mg (0.4 mmol) of ferrocene, 22.4 mg (0.4 mmol) of potassium hydroxide and 2 mL of acetonitrile were mixed evenly. Then, the mixture was electrochemically reacted for 24 h at room temperature, with a stirring speed of 750 r / min and a current of 15 mA. The solvent was removed by vacuum distillation, and the mixture was then purified by silica gel column chromatography to obtain polyfluoroalkyl aromatics.
[0034] The polyfluoroaromatic hydrocarbon mentioned is pentafluoroacetophenone, with the structural formula as follows: ;
[0035] The aromatic hydrocarbon is 1-benzylpyrrolidine, with the structural formula as follows: .
[0036] The solvent used for silica gel column chromatography separation and purification is a mixture of petroleum ether and ethyl acetate.
[0037] The volume ratio of petroleum ether to ethyl acetate is 50:1.
[0038] The structural formula of the polyfluoroalkylene is as follows: .
[0039] The reaction route in this embodiment is as follows:
[0040] .
[0041] The polyfluoroalkyl hydrocarbons prepared in Example 1 were tested and found to have a purity of 99% and a yield of 93%.
[0042] Figure 1 The polyfluoroalkyl hydrocarbons prepared in Example 1 1 H NMR spectrum. NMR data analysis is as follows: 1¹H NMR (400MHz, CDCl₃) δ H 7.26 (s, 2H), 7.19 (s, 2H), 3.73 (s, 2H), 2.69 (s, 2H), 2.60(t, J = 7.0 Hz, 2H), 2.54 (t, J = 1.9 Hz, 3H), 1.56 (ddd, J = 14.6, 8.1, 3.9Hz, 4H).
[0043] Example 2:
[0044] A method for the electrocatalytic synthesis of polyfluorinated aromatic hydrocarbons, comprising the following steps:
[0045] At room temperature and with a stirring speed of 750 r / min, 31.4 mg (0.2 mmol) of polyfluoroaromatics, 50.4 mg (0.3 mmol) of aromatics, 128.8 mg (0.4 mmol) of tetrabutylammonium bromide, 74.4 mg (0.4 mmol) of ferrocene, 22.4 mg (0.4 mmol) of potassium hydroxide and 2 mL of acetonitrile were mixed evenly. Then, the mixture was electrochemically reacted for 24 h at room temperature, with a stirring speed of 750 r / min and a current of 15 mA. The solvent was removed by vacuum distillation, and the mixture was then purified by silica gel column chromatography to obtain polyfluoroalkyl aromatics.
[0046] The polyfluoroaromatic hydrocarbon is 3,4,5-trifluorobenzonitrile, with the structural formula as follows: ;
[0047] The aromatic hydrocarbon is 1,3,5-trimethoxybenzene, with the structural formula as follows: .
[0048] The solvent used for silica gel column chromatography separation and purification is a mixture of petroleum ether and ethyl acetate.
[0049] The volume ratio of petroleum ether to ethyl acetate is 50:1.
[0050] The structural formula of the polyfluoroalkylene is as follows: .
[0051] The reaction route in this embodiment is as follows:
[0052] .
[0053] The purity of the polyfluoroalkyl aromatic hydrocarbons in Example 1 was tested to be 96%, and the yield was 68%.
[0054] The NMR data analysis of the polyfluorinated biaromatics prepared in Example 2 is as follows: 1 H NMR (400 MHz, CDCl3) δH 7.24(d, J = 5.3 Hz, 2H), 3.89(s, 3H), 3.78(s, 6H).
[0055] 19 F NMR (376 MHz, DMSO-d6): δ -106.40 (s, 2F).
Claims
1. A method for preparing polyfluoroalkyl aromatic hydrocarbons by electrocatalytic synthesis, characterized in that... It is done in the following steps: Polyfluoroaromatics, aromatic hydrocarbons, tetrabutylammonium bromide, ferrocene, potassium hydroxide and organic solvent were mixed evenly under room temperature and stirring conditions. Then, an electrochemical reaction was carried out under room temperature and stirring conditions. The solvent was removed by vacuum distillation and then purified by silica gel column chromatography to obtain polyfluoroaromatics. The general structural formula of the polyfluoroaromatic hydrocarbon is as follows: , where R is methyl, methoxy, ester, or cyano; The general structural formula of the aromatic hydrocarbon is as follows: Ar represents aryl groups with different structures.
2. The method for preparing polyfluoroalkyl aromatic hydrocarbons by electrocatalytic synthesis according to claim 1, characterized in that... The molar ratio of the polyfluoroaromatic hydrocarbon to the aromatic hydrocarbon is 1:(1.5~3); the molar ratio of the polyfluoroaromatic hydrocarbon to tetrabutylammonium bromide is 1:(1.5~3); the molar ratio of the polyfluoroaromatic hydrocarbon to ferrocene is 1:(1.5~3); and the molar ratio of the polyfluoroaromatic hydrocarbon to potassium hydroxide is 1:(1.5~3).
3. The method for preparing polyfluoroalkyl hydrocarbons by electrocatalytic synthesis according to claim 1, characterized in that... The organic solvent is acetonitrile, toluene, N,N-dimethylformamide, or dimethyl sulfoxide.
4. The method for preparing polyfluoroalkyl hydrocarbons by electrocatalytic synthesis according to claim 1, characterized in that... The molar ratio of the polyfluoroaromatic hydrocarbon to the volume ratio of the organic solvent is 1 mmol:(10~20) mL.
5. The method for preparing polyfluoroalkyl hydrocarbons by electrocatalytic synthesis according to claim 1, characterized in that... Under conditions of room temperature and a stirring speed of 600 r / min to 800 r / min, polyfluoroaromatics, aromatics, tetrabutylammonium bromide, ferrocene, potassium hydroxide and organic solvent are mixed evenly.
6. The method for preparing polyfluoroalkyl hydrocarbons by electrocatalytic synthesis according to claim 1, characterized in that... The electrochemical reaction was carried out at room temperature, with a stirring speed of 600 r / min to 800 r / min and a current of 5 mA to 30 mA for 5 h to 24 h.
7. The method for preparing polyfluoroalkyl hydrocarbons by electrocatalytic synthesis according to claim 1, characterized in that... The solvent used for silica gel column chromatography separation and purification is a mixture of petroleum ether and ethyl acetate.
8. The method for preparing polyfluoroalkyl hydrocarbons by electrocatalytic synthesis according to claim 7, characterized in that... The volume ratio of petroleum ether to ethyl acetate is (30~80):
1.
9. The method for preparing polyfluoroalkyl hydrocarbons by electrocatalytic synthesis according to claim 1, characterized in that... The general structural formula of the polyfluoroalkylene is: ; where R is methyl, methoxy, ester or cyano.
10. The method for preparing polyfluoroalkyl aromatic hydrocarbons by electrocatalytic synthesis according to claim 1, characterized in that... The structural formula of the polyfluoroaromatic hydrocarbon is as follows: or The structural formula of the aromatic hydrocarbon is as follows: or The structural formula of the polyfluoroalkylene is as follows: or .