An electrochemical organic synthesis method for benzyl alcohol fluorination product using sulfur hexafluoride as a fluorination reagent

Abstract

The application discloses an electrochemical organic synthesis method of benzyl alcohol fluorination product using sulfur hexafluoride as a fluorination reagent, comprising the following steps: uniformly mixing benzyl alcohol, an electrolyte, a solvent and an alkali, introducing sulfur hexafluoride, performing an electrolysis reaction in a sulfur hexafluoride gas atmosphere with zinc as an anode and tin as a cathode, and obtaining the benzyl alcohol fluorination product after post-treatment; wherein the benzyl alcohol is a mixture of one or more of diphenyl carbinol, (2-chlorophenyl)-benzyl alcohol, (3,4-dichlorophenyl)-benzyl alcohol, 3-(trifluoromethyl)diphenyl carbinol, (4-cyanophenyl)benzyl alcohol, 1,3-diphenyl-1-propanol and 1-(4-fluorophenyl)-3-phenyl-1-propanol. The application provides a novel benzyl alcohol dehydroxylation fluorination conversion method which is safe, inexpensive, mild and good in substrate compatibility, and solves the problems of excessively high reagent activity, harsh reaction conditions, dangerous operation and excessively high cost in the existing benzyl alcohol dehydroxylation fluorination method.

Description

Technical Field

[0001] This invention relates to the field of electrochemical synthesis technology, specifically to an electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorinating agent. Background Technology

[0002] In 2022, Pavel Nagorny et al. reported the electrochemical synthesis of 17 six-membered cyclic hemiacetal fluorides using sulfur hexafluoride gas as the fluorinating agent, with yields ranging from 73% to 98% and reaching a scale of 5 g. Mechanistic studies, including cyclic voltammetry, showed a correspondence between the cathodic reduction of sulfur hexafluoride and the anode oxidation of zinc. Under these reducing conditions, sulfur hexafluoride produces reactive fluorinated species such as sulfur tetrafluoride, and byproducts containing sulfur and fluorine combine with zinc ions to form easily removable salts. This work opened up the field of applying sulfur hexafluoride to organic electrosynthesis, but the substrates remain limited to pyranose glucoside derivatives.

[0003] In the same year, Lutz Ackermann et al. used a graphite felt anode paired with a platinum cathode, and triethylamine hydrofluoric acid as the fluorine source, to achieve C(sp... 3 Nucleophilic electrochemical fluorination of the 1H-bond. This reaction exhibits good chemo and site selectivity, avoiding the use of electrophilic fluorine sources and stoichiometric oxidants. The reaction is well-tolerant to functional groups and can be used for the late-stage functionalization of bioactive drugs. Electrolysis experiments powered by sunlight further confirmed the practicality of this method. Mechanistic studies revealed the key role of hexafluoroisopropanol in promoting proton-coupled electron transfer. However, the introduction of excessive (12 stoichiometric) fluorinating agents indicates that the reaction efficiency of the system still needs to be improved.

[0004] In 2023, Kwangmin Shin et al. reported a palladium-electrocatalyzed nucleophilic fluorination reaction of olefins using styrene derivatives as raw materials, enabling the conversion of various substrates, including more challenging α,β-unsaturated carbonyl derivatives. Mechanistic studies showed that anodic oxidation to generate a high-valent palladium intermediate is a key step in the electrocatalytic hydrofluorination reaction. However, the application of excess triethylamine hydrofluoric acid salts introduced drawbacks similar to those in the previous example.

[0005] In 2024, Alastair JJ Lennox achieved the fluorination of the 4-benzyl C(sp3)-H bond in biphenyl alkyl compounds using a double platinum electrode system. Unlike traditional direct current electrolysis strategies, pulsed electrolysis provides a favorable environment for the generation and stabilization of benzyl cations. By introducing a cutoff period, the electrical bilayer of the pulsed current can improve mass transfer and limit over-oxidation, further enhancing its application value in the field of organic electrosynthesis. However, this research is limited by the novel electrolysis strategy and has not made significant progress in substrate expansion.

[0006] Chinese patent application CN117486661A discloses a method for preparing fluorinated diphenylmethane compounds using sulfur hexafluoride as a fluorinating agent. By selecting a certain ratio of raw materials and catalysts, fluorinated diphenylmethane compounds are efficiently prepared using sulfur hexafluoride as the fluorinating agent. The raw materials are inexpensive, the preparation process is safe and mild, has good substrate compatibility, and the preparation efficiency is high. However, it uses a photocatalytic method, which has a long reaction time and low reaction efficiency.

[0007] Chinese patent application CN117398818A discloses a method for the degradation of sulfur hexafluoride (SF6) gas under electrochemical conditions. In this method, at room temperature, triphenylphosphine and SF6 are reacted with an electrode, an electrolyte, and an alkali to degrade SF6 via an electrochemical reaction. The positive electrode is zinc (Zn), the negative electrode is tin (Sn), the electrolyte is tetrabutylammonium tetrafluoroborate, and the alkali is triethylamine. This method is characterized by mild conditions, readily available and inexpensive raw materials, and simple operation, making it highly valuable. However, it focuses on the degradation of SF6, addressing the problems of difficult SF6 degradation, complex operation, and high degradation costs. Summary of the Invention

[0008] The technical problem to be solved by this invention is how to use sulfur hexafluoride to electrochemically prepare benzyl alcohol fluoride products.

[0009] The present invention solves the above-mentioned technical problems through the following technical means:

[0010] An electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorinating agent includes the following steps: mixing benzyl alcohol, electrolyte, solvent, and alkali uniformly, introducing sulfur hexafluoride, and carrying out an electrolytic reaction in a sulfur hexafluoride gas atmosphere with zinc as the anode and tin as the cathode, followed by post-treatment to obtain the benzyl alcohol fluorination product; wherein the benzyl alcohol is one or a mixture of diphenylmethanol, (2-chlorophenyl)-benzyl alcohol, (3,4-dichlorophenyl)-benzyl alcohol, 3-(trifluoromethyl)diphenylmethanol, (4-cyanophenyl)benzyl alcohol, 1,3-diphenyl-1-propanol, and 1-(4-fluorophenyl)-3-phenyl-1-propanol.

[0011] Preferably, the electrolyte is one or a mixture of tetrabutylammonium perchlorate, tetrabutylammonium tetrafluoroborate, and tetrabutylammonium hexafluorophosphate.

[0012] Preferably, the solvent is one or a mixture of tetrahydrofuran, dichloromethane, and dichloroethane.

[0013] Preferably, the base is one or a mixture of two of N,N-diisopropylethylamine, triethylamine, and 4-dimethylaminopyridine.

[0014] Preferably, the electrolyte is tetrabutylammonium perchlorate; the solvent is tetrahydrofuran; and the base is triethylamine.

[0015] Preferably, the benzyl alcohol is diphenylethanol or (2-chlorophenyl)-phenylethanol.

[0016] Preferably, the molar ratio of benzyl alcohol to electrolyte is 1:4.5.

[0017] Preferably, the ratio of benzyl alcohol to solvent is 0.1 mmol: 3 mL.

[0018] Preferably, the molar ratio of benzyl alcohol to base is 1:3.

[0019] Preferably, during the electrolysis reaction, the maximum voltage of the power supply is set to 30V, the constant current is 7.5-15mA, the electrolysis time is 1-4h, and the electrochemical equivalent is 5.6F / mol.

[0020] Preferably, electrolysis is carried out for 1-2 hours.

[0021] Preferably, the constant current is 15mA, and the electrolysis time is 1 hour.

[0022] Preferably, the electrolysis reaction is stirred at a speed of 750 rpm.

[0023] Preferably, the post-treatment includes washing the product after the electrolytic reaction with ethyl acetate, then adding water and dilute hydrochloric acid, taking the organic phase and washing it with saturated sodium bicarbonate solution, collecting the organic phase and removing the solvent to obtain the benzyl alcohol fluorinated product.

[0024] The advantages of this invention are:

[0025] In this invention, sulfur hexafluoride is used as a safe and inexpensive fluorinating reagent to react with specific alcohols under electrolytic conditions to prepare high-value-added organic fluorinated small molecules. This electrochemical method overcomes the disadvantage of traditional chemical methods in providing sufficient redox potential, offering a safe, inexpensive, mild, and substrate-compatible novel method for the dehydroxylation and fluorination of benzyl alcohol. It solves the problems of excessively high reagent activity, harsh reaction conditions, dangerous operation, and high cost in existing benzyl alcohol dehydroxylation and fluorination methods. Furthermore, compared with photocatalysis, electrocatalysis significantly improves reaction efficiency, shortening the reaction time to within 1-2 hours while achieving near-yield. Attached Figure Description

[0026] Figure 1 The product of Example 1 of this invention 1 H NMR yield;

[0027] Figure 2 The product of Example 1 of this invention 1Pure H NMR spectrum;

[0028] Figure 3 The product of Example 1 of this invention 13 Pure C NMR spectrum;

[0029] Figure 4 The product of Example 8 of this invention 1 H NMR yield;

[0030] Figure 5 The product of Example 8 of this invention 1 Pure H NMR spectrum;

[0031] Figure 6 The product of Example 8 of this invention 13 Pure C NMR spectrum;

[0032] Figure 7 The product of Example 9 of this invention 1 H NMR yield;

[0033] Figure 8 The product of Example 9 of this invention 1 Pure H NMR spectrum;

[0034] Figure 9 The product of Example 9 of this invention 13 Pure C NMR spectrum;

[0035] Figure 10 The product of Example 10 of this invention 1 H NMR yield;

[0036] Figure 11 The product of Example 10 of this invention 1 Pure H NMR spectrum;

[0037] Figure 12 The product of Example 10 of this invention 13 Pure C NMR spectrum;

[0038] Figure 13 The product of Example 11 of this invention 1 H NMR yield;

[0039] Figure 14 The product of Example 11 of this invention 1 Pure H NMR spectrum;

[0040] Figure 15 The product of Example 11 of this invention 13 Pure C NMR spectrum;

[0041] Figure 16The product of Example 12 of this invention 1 H NMR yield;

[0042] Figure 17 The product of Example 12 of this invention 1 Pure H NMR spectrum;

[0043] Figure 18 The product of Example 12 of this invention 13 Pure C NMR spectrum;

[0044] Figure 19 The product of Example 13 of this invention 1 H NMR yield;

[0045] Figure 20 The product of Example 13 of this invention 1 Pure H NMR spectrum;

[0046] Figure 21 The product of Example 13 of this invention 13 C10 NMR pure spectrum. Detailed Implementation

[0047] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0048] Unless otherwise specified, all test materials and reagents used in the following examples are commercially available.

[0049] Unless otherwise specified in the embodiments, the techniques or conditions described in the literature in this field or in accordance with the product manual may be followed.

[0050] Example 1

[0051] An electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorinating agent includes the following steps:

[0052] (1) Preparation of the electrocatalytic system solution: Add benzyl alcohol (0.1 mmol, 0.0184 g) and tetrabutylammonium perchlorate (4.5 equiv., 0.1539 g) to a 5 mL cylindrical glass bottle. Add tetrahydrofuran (3 mL, water content ≤ 30 ppm), shake for 5 s, and sonicate for 10 s to completely dissolve the components. Use a 100 μL microsyringe to add triethylamine (3.0 equiv., 0.0304 g) to the glass bottle, shake for 5 s to ensure uniform dissolution. Place an A5 (3 × 5 mm) polytetrafluoroethylene magnetic stir bar in the solution for later use.

[0053] (2) Setup: Place the double-layered gasket inside the cylindrical glass bottle cap and tighten the cap. Drill holes in the cap and insert the anode zinc wire (3×50mm) and cathode tin wire (3×50mm), taking care not to interfere with the normal operation of the magnetic stirrer. Connect the sulfur hexafluoride gas to two gas throttle valves connected in series via a gas delivery tube, and then connect a stainless steel long syringe needle about 10cm long to deliver the sulfur hexafluoride gas. Insert the needle for delivering the sulfur hexafluoride gas to the bottom of the solution in the glass bottle. Take a 1mL syringe needle, insert it into the cap through the gasket, and leave it above the liquid surface as a gas venting channel. All components should be securely fixed above a room-temperature magnetic stirrer with a rotation speed of 750rpm. The setup of the device can be referenced in P. Nagorny et al., Org. Lett. 2022, 24, 2294-2298;

[0054] (3) Electrolysis reaction: Sulfur hexafluoride gas is introduced. After waiting for 1 minute for the sulfur hexafluoride gas to enter the solution, the positive terminal of the adjustable DC regulated power supply is connected to the zinc wire at the anode and the negative terminal is connected to the tin wire at the cathode. The power supply is turned on and the maximum voltage is set to 30V. The constant current is 15mA. Electrolysis is carried out for 1 hour. The electrochemical equivalent is 5.6F / mol.

[0055] (4) Post-treatment: After the electrolysis reaction is complete, stop the power supply, turn off the adjustable DC regulated power supply, and remove the electrodes. Wash the reaction mixture in the glass bottle with ethyl acetate (30 mL) into a separatory funnel, ensuring thorough cleaning of the electrodes and bottle cap. Add water (20 mL) and dilute hydrochloric acid (1 M, 3 mL) and shake until the dark gray metallic residue is completely dissolved. Retain the organic phase and wash with saturated sodium bicarbonate solution (20 mL) to remove excess hydrochloric acid. Collect the organic phase and remove the solvent using a rotary evaporator. Determine the yield of the product using 1H NMR spectroscopy with dibromomethane (1 equiv., 0.01738 g) as an internal standard.

[0056] Reaction results: diphenylethanol was produced at 78%... 1 H-NMR yielded the dehydroxylated fluorinated product, namely the benzyl alcohol fluorinated product, and its NMR spectrum is shown below. Figure 1-3 As shown.

[0057] Example 2

[0058] An electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorinating agent, differs from Example 1 only in that dichloromethane is used instead of tetrahydrofuran in step (1) of Example 1, while the remaining steps are the same as in Example 1.

[0059] Reaction results: diphenylethanol was produced at 37%... 1 H-NMR yielded the dehydroxylated fluorinated product, namely the benzyl alcohol fluorinated product.

[0060] Example 3

[0061] An electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorinating agent differs from Example 1 only in that dichloroethane is used instead of tetrahydrofuran in step (1) of Example 1, while the remaining steps are the same as in Example 1.

[0062] Reaction results: benzyl alcohol was produced at 40%... 1 H-NMR yielded the dehydroxylated fluorinated product, namely the benzyl alcohol fluorinated product.

[0063] Example 4

[0064] An electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorinating agent differs from Example 1 only in that tetrabutylammonium tetrafluoroborate (4.5 equiv., 0.1482 g) is used instead of tetrabutylammonium perchlorate (4.5 equiv., 0.1539 g) in step (1) of Example 1, while the remaining steps are the same as in Example 1.

[0065] Reaction results: benzyl alcohol was produced at 59%... 1 H-NMR yielded the dehydroxylated fluorinated product, namely the benzyl alcohol fluorinated product.

[0066] Example 5

[0067] An electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorinating agent differs from Example 1 only in that tetrabutylammonium hexafluorophosphate (4.5 equiv., 0.1743 g) is used instead of tetrabutylammonium perchlorate (4.5 equiv., 0.1539 g) in step (1) of Example 1, while the other steps are the same as in Example 1.

[0068] Reaction results: diphenylethanol at 27% 1 H-NMR yielded the dehydroxylated fluorinated product, namely the benzyl alcohol fluorinated product.

[0069] Example 6

[0070] An electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorinating agent differs from Example 2 only in that N,N-diisopropylethylamine (3.0 equiv., 0.0388 g) is used instead of triethylamine (3.0 equiv., 0.0304 g) in step (1) of Example 2, while the other steps are the same as in Example 2.

[0071] Reaction results: diphenylethanol was produced at 47%... 1 H-NMR yielded the dehydroxylated fluorinated product, namely the benzyl alcohol fluorinated product.

[0072] Example 7

[0073] An electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorinating agent differs from Example 2 only in the following aspects: (1) Preparation of the electrocatalytic system solution: Add benzyl alcohol (0.1 mmol, 0.0184 g) and tetrabutylammonium perchlorate (4.5 equiv., 0.1539 g) to a cylindrical glass bottle with a volume of 5 mL. Add dichloromethane (3 mL, water content ≤ 30 ppm) to the bottle, shake for 5 s, and sonicate for 10 s to completely dissolve the components. Weigh 4-dimethylaminopyridine (3.0 equiv., 0.0367 g) and add it to the glass bottle, shake for 5 s to dissolve evenly. Place an A5 (3 × 5 mm) polytetrafluoroethylene magnetic stir bar in the solution for later use.

[0074] The remaining steps are the same as in Example 2.

[0075] Reaction results: diphenylethanol was produced at 37%... 1 H-NMR yielded the dehydroxylated fluorinated product, namely the benzyl alcohol fluorinated product.

[0076] Example 8

[0077] An electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorinating agent differs from Example 1 only in that (2-chlorophenyl)-benzyl alcohol (0.1 mmol, 0.0218 g) is used instead of diphenylethanol (0.1 mmol, 0.0184 g) in step (1) of Example 1, while the other steps are the same as in Example 1.

[0078] Reaction results: (2-chlorophenyl)-benzyl alcohol yielded 74% 1 H-NMR yielded the dehydroxylated fluorinated product, namely the benzyl alcohol fluorinated product, and its NMR spectrum is shown below. Figure 4-6 As shown.

[0079] Example 9

[0080] An electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorinating agent differs from Example 1 only in that (3,4-dichlorophenyl)-benzyl alcohol (0.1 mmol, 0.0253 g) is used instead of dibenzyl alcohol (0.1 mmol, 0.0184 g) in step (1) of Example 1, while the other steps are the same as in Example 1.

[0081] Reaction results: (3,4-dichlorophenyl)-benzyl alcohol was produced at 41%... 1 H-NMR yielded the dehydroxylated fluorinated product, namely the benzyl alcohol fluorinated product, and its NMR spectrum is shown below. Figure 7-9 As shown.

[0082] Example 10

[0083] An electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorinating agent differs from Example 1 only in that 3-(trifluoromethyl)diphenylmethanol (0.1 mmol, 0.0252 g) is used instead of diphenylmethanol (0.1 mmol, 0.0184 g) in step (1) of Example 1, while the other steps are the same as in Example 1.

[0084] Reaction results: 3-(trifluoromethyl)diphenylmethanol at 44% 1 H-NMR yielded the dehydroxylated fluorinated product, namely the benzyl alcohol fluorinated product, and its NMR spectrum is shown below. Figure 10-12 As shown.

[0085] Example 11

[0086] An electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorinating agent differs from Example 1 only in that (4-cyanophenyl)benzyl alcohol (0.1 mmol, 0.0209 g) is used instead of diphenylethanol (0.1 mmol, 0.0184 g) in step (1) of Example 1, while the other steps are the same as in Example 1.

[0087] Reaction results: (4-cyanophenyl)benzyl alcohol produced 43% 1 H-NMR yielded the dehydroxylated fluorinated product, namely the benzyl alcohol fluorinated product, and its NMR spectrum is shown below. Figure 13-15 As shown.

[0088] Example 12

[0089] An electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorinating agent differs from Example 1 only in that 1,3-diphenyl-1-propanol (0.1 mmol, 0.0212 g) is used instead of benzyl alcohol (0.1 mmol, 0.0184 g) in step (1) of Example 1, while the other steps are the same as in Example 1.

[0090] Reaction results: 1,3-Diphenyl-1-propanol was produced at 41%... 1 H-NMR yielded the dehydroxylated fluorinated product, namely the benzyl alcohol fluorinated product, and its NMR spectrum is shown below. Figure 16-18 As shown.

[0091] Example 13

[0092] An electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorinating agent differs from Example 1 only in that: 1-(4-fluorophenyl)-3-phenyl-1-propanol (0.1 mmol, 0.0230 g) is used instead of diphenylmethanol (0.1 mmol, 0.0184 g) in step (1) of Example 1, while the other steps are the same as in Example 1.

[0093] Reaction results: 1-(4-fluorophenyl)-3-phenyl-1-propanol was produced at 51% concentration. 1 H-NMR yielded the dehydroxylated fluorinated product, namely the benzyl alcohol fluorinated product, and its NMR spectrum is shown below. Figure 19-21 As shown.

[0094] Comparative Example 1

[0095] Compared with the previously reported literature Chem. Eur. J., 2022, 28, e202201654 (doi:10.1002 / chem.202201654), alkyl compounds were used in the comparative preparation of benzyl alcohol fluorination products.

[0096] (1) Procedure: Under an inert gas atmosphere, diphenylmethane (1.0 equiv., 0.50 mmol) and triethylamine hydrofluoric acid (1.0 mL) were dissolved in a mixed solvent of dichloroethane (2.0 mL) and hexafluoroisopropanol (1.0 mL) in a 10 mL electrochemical reactor. A graphite felt (GF) anode (25 × 10 × 6.0 mm) and a platinum cathode (25 × 10 × 0.125 mm) were connected to an electrode holder assembled on an electrolytic cell. Electrosynthesis was carried out at a constant current of 8.0 mA at room temperature until 2.5 F / mol passed (4.2 h). After electrolysis, the reaction mixture was filtered through a silicon plug. The platinum cathode and graphite felt anode were cleaned with EtOAc (Pt: 1 × 5.0 mL; C: 3 × 10 mL), and the resulting solution was filtered through the same silicon plug. After rinsing the silicon plug with an additional n-hexane / ethyl acetate mixture (75 mL), the solvent was removed under vacuum. CH2Br2 (36 μL, 0.50 mmol) and PhCF3 (62 μL, 0.50 mmol) were used as internal standards for the following experiments: 1 H-NMR and 19 F-NMR analysis.

[0097] (2) Effect: The substrate diphenylmethane achieved 64% 1 H-NMR yielded the fluorinated product of benzyl alcohol.

[0098] (3) Comparison: From the operation steps and effects, it can be seen that the operation of this invention is simpler, does not require an inert gas atmosphere protection, has a higher yield (78%) and reagent utilization rate, is applicable to a variety of substrates, and the solvent tetrahydrofuran is easier to separate than hexafluoroisopropanol. The comparative example uses alkyl compounds that are more difficult to convert as substrates, which easily triggers a series of free radical side reactions, resulting in slightly worse selectivity and yield.

[0099] Comparative Example 2

[0100] The only difference from Example 1 is that an unsuitable substrate, 1-(4-bromophenyl)-1-ethanol, is used; that is, 1-(4-bromophenyl)-1-ethanol (0.1 mmol, 0.0201 g) is used instead of diphenylmethanol (0.1 mmol, 0.0184 g) in step (1) of Example 1. All other steps are the same as in Example 1.

[0101] Reaction results: 1-(4-bromophenyl)-1-ethanol at 7% 1 The dehydroxylated fluorinated product was obtained by H-NMR yield.

[0102] In contrast, this reaction system is not suitable for methylphenyl alcohols.

[0103] Comparative Example 3

[0104] The only difference from Example 1 is that an unsuitable substrate is used: 1-(4-tert-butylphenyl)ethane-1-ol; that is, 1-(4-tert-butylphenyl)ethane-1-ol (0.1 mmol, 0.0178 g) is used instead of diphenylethanol (0.1 mmol, 0.0184 g) in step (1) of Example 1. All other steps are the same as in Example 1.

[0105] Reaction results: 1-(4-tert-butylphenyl)ethane-1-ol was produced at 3% concentration. 1 The dehydroxylated fluorinated product was obtained by H-NMR yield.

[0106] In contrast, this reaction system is not suitable for methylphenyl alcohols.

[0107] Example 14

[0108] The only difference from Example 1 is that in (3), the constant current is 7.5mA and the electrolysis time is 4h, while the other steps are the same as in Example 1.

[0109] Reaction results: diphenylethanol at 27% 1 The dehydroxylated fluorinated product was obtained by H-NMR yield.

[0110] In contrast, this reaction system requires a specific combination of current and time to achieve the optimal yield.

[0111] The structural formulas and yields of the raw materials and products in Examples 1 and 8-13 are shown in the table below:

[0112]

[0113] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. An electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorinating agent, characterized in that: Includes the following steps: Benzyl alcohol, electrolyte, solvent, and alkali are mixed uniformly, and sulfur hexafluoride is introduced. An electrolytic reaction is carried out in a sulfur hexafluoride gas atmosphere using zinc as the anode and tin as the cathode. After post-treatment, the fluorinated benzyl alcohol product is obtained. The benzyl alcohol is, in this case, diphenylethanol, (2-chlorophenyl)-benzylethanol, (3,4-dichlorophenyl)-benzylethanol, 3-(trifluoromethyl)diphenylethanol, (4-cyanophenyl)benzylethanol, 1,3-diphenyl-1-propanol, or 1-(4-fluorophenyl)-3-phenylethanol. The electrolyte is one or more of the following: 1-propanol; the solvent is one or more of the following: tetrabutylammonium perchlorate, tetrabutylammonium tetrafluoroborate, and tetrabutylammonium hexafluorophosphate; the solvent is one or more of the following: tetrahydrofuran, dichloromethane, and dichloroethane; the base is one or a mixture of two of the following: N,N-diisopropylethylamine, triethylamine, and 4-dimethylaminopyridine; during the electrolysis reaction, the constant current is 7.5-15 mA, and the electrolysis time is 1-4 h.

2. The electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorinating agent according to claim 1, characterized in that: The electrolyte is tetrabutylammonium perchlorate; the solvent is tetrahydrofuran; and the base is triethylamine.

3. The electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorinating agent according to claim 1, characterized in that: The benzyl alcohol is diphenylethanol or (2-chlorophenyl)-phenylethanol.

4. The electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorinating agent according to claim 1, characterized in that: The molar ratio of benzyl alcohol to electrolyte is 1:4.

5.

5. The electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorinating agent according to claim 1, characterized in that: The ratio of benzyl alcohol to solvent is 0.1 mmol: 3 mL.

6. The electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorinating agent according to claim 1, characterized in that: The molar ratio of benzyl alcohol to base is 1:

3.

7. The electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorinating agent according to claim 1, characterized in that: During the electrolysis reaction, the maximum power supply voltage was set to 30V, and the electrochemical equivalent was 5.6F / mol.

8. The electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorinating agent according to claim 1, characterized in that: The constant current is 15mA, and the electrolysis time is 1 hour.

9. The electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorinating agent according to claim 1, characterized in that: The electrolysis reaction was stirred at a speed of 750 rpm.

10. The electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorinating agent according to any one of claims 1-9, characterized in that: The post-processing includes washing the product after electrolysis with ethyl acetate, then adding water and dilute hydrochloric acid, taking the organic phase and washing it with saturated sodium bicarbonate solution, collecting the organic phase and removing the solvent to obtain the benzyl alcohol fluorinated product.

Images