Benzyl alcohol fluorinated product electrochemical organic synthesis method using sulfur hexafluoride as fluorinating reagent

Abstract

The invention discloses a benzyl alcohol fluorinated product electrochemical organic synthesis method using sulfur hexafluoride as a fluorination reagent, which comprises the following steps: uniformly mixing benzyl alcohol, an electrolyte, a solvent and alkali, introducing sulfur hexafluoride, carrying out an electrolytic reaction in a sulfur hexafluoride gas atmosphere by using zinc as an anode and tin as a cathode, and carrying out post-treatment to obtain the benzyl alcohol fluorinated product, wherein the benzyl alcohol is one or a mixture of more of diphenyl carbinol, (2-chlorphenyl)-benzyl alcohol, (3, 4-dichlorophenyl)-benzyl alcohol, 3-(trifluoromethyl) diphenyl carbinol, (4-cyanophenyl) benzyl alcohol, 1, 3-diphenyl-1-propyl alcohol and 1-(4-fluorophenyl)-3-phenyl-1-propyl alcohol. The invention provides a novel benzyl alcohol dehydroxylation fluorination conversion method which is safe, cheap, mild and good in substrate compatibility, and solves the problems of over-high reagent activity, harsh reaction conditions, dangerous operation, over-high cost and the like in the existing benzyl alcohol dehydroxylation fluorination method.

Description

Technical Field

[0001] The invention relates to the technical field of electrochemical synthesis, and in particular to an electrochemical organic synthesis method of benzyl alcohol fluorination products using sulfur hexafluoride as a fluorination reagent. Background Art

[0002] In 2022, Pavel Nagorny and others used sulfur hexafluoride gas as a fluorination reagent and reported the electrochemical synthesis of 17 six-membered cyclic hemiacetal fluorides with a yield of 73-98% and a 5g scale. Mechanistic studies such as cyclic voltammetry showed that the cathode reduction of sulfur hexafluoride corresponds to the oxidation of the zinc anode. Under this reduction condition, sulfur hexafluoride produces active fluorinated species such as sulfur tetrafluoride, and by-products with sulfur and fluorine elements combine with zinc ions to form easily removable salts. This work has opened up the field of applying sulfur hexafluoride to organic electrosynthesis, but the substrates are still limited to pyranose glucopyranose derivatives.

[0003] In the same year, Lutz Ackermann et al. used a graphite felt anode with a platinum cathode and triethylamine hydrofluoride as a fluorine source to achieve C(sp 3 )-H bonds. The reaction has good chemical and site selectivity, avoiding the use of electrophilic fluorine sources and chemically equivalent oxidants. The reaction tolerates functional groups well and can be used for later functionalization of bioactive drugs. Electrolysis experiments using sunlight as energy 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 too much (12 equivalents) fluorination reagent 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, making the conversion of various substrates such as more challenging α,β-unsaturated carbonyl derivatives possible. Mechanistic studies have shown that the generation of high-valent palladium intermediates by anodic oxidation is a key step in the electrocatalytic hydrofluorination reaction. However, the use of excess triethylamine hydrofluoride brings similar shortcomings as in the above example.

[0005] In 2024, Alastair JJLennox used a double platinum electrode system to achieve the fluorination reaction of the 4-benzyl C(sp3)-H bond of biphenyl alkyl compounds. Unlike the traditional DC electrolysis strategy, pulse electrolysis provides a favorable environment for the generation and stabilization of benzyl cations. By introducing a cut-off period, the electrical double layer 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 to new electrolysis strategies and has not made significant progress in substrate expansion.

[0006] A Chinese patent application document with publication number CN117486661A discloses a method for preparing fluorinated diphenylmethane compounds using sulfur hexafluoride as a fluorination agent. The method uses sulfur hexafluoride as a fluorination agent, selects raw materials and catalysts in a certain ratio, and efficiently prepares fluorinated diphenylmethane compounds. The reaction raw materials are cheap, the preparation process is safe and mild, the substrate compatibility is good, and the preparation efficiency is high. However, the method adopts a photocatalytic method, the reaction time is long, and the reaction efficiency is low.

[0007] A Chinese patent application document with publication number CN117398818A discloses a method for degrading sulfur hexafluoride gas under electrochemical conditions, wherein at room temperature, triphenylphosphine and sulfur hexafluoride are subjected to an electrochemical reaction under the action of electrodes, electrolytes and alkalis to degrade sulfur hexafluoride; wherein the positive electrode is zinc Zn, the negative electrode is tin Sn, the electrolyte is tetrabutylammonium tetrafluoroborate; and the alkali is triethylamine; the method has mild conditions, simple and readily available raw materials, low price, simple operation, and high application value, but it focuses on the degradation of sulfur hexafluoride, and solves the problems of difficult degradation of SF6, complex operation, and high degradation cost. Summary of the invention

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

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

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

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

[0012] Preferably, the solvent is a mixture of one or more 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 benzhydrol or (2-chlorophenyl)-benzyl alcohol.

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

[0017] Preferably, the usage 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 is 1-4h, and the electrochemical equivalent is 5.6F / mol.

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

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

[0022] Preferably, stirring treatment is performed during the electrolysis reaction, and the stirring speed is 750 rpm.

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

[0024] The advantages of the present invention are:

[0025] In the present invention, sulfur hexafluoride is used as a safe and cheap fluorination reagent to react with specific alcohol substances under electrolytic conditions to prepare high-value-added organic fluorine-containing small molecule substances. The electrochemical method is used as a tool to overcome the disadvantage that traditional chemical methods cannot provide sufficient redox potential, and a new benzyl alcohol dehydroxylation fluorination conversion method with safety, cheapness, mildness and good substrate compatibility is provided, which 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. Compared with the photocatalytic method, the electrocatalytic method significantly improves the reaction efficiency, shortens the reaction time to within 1-2 hours, and obtains a similar yield. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 For the product in Example 1 of the present invention 1 H NMR yield;

[0027] Figure 2 For the product in Example 1 of the present invention 1H NMR pure spectrum;

[0028] Figure 3 For the product in Example 1 of the present invention 13 C NMR pure spectrum;

[0029] Figure 4 For the product in Example 8 of the present invention 1 H NMR yield;

[0030] Figure 5 For the product in Example 8 of the present invention 1 H NMR pure spectrum;

[0031] Figure 6 For the product in Example 8 of the present invention 13 C NMR pure spectrum;

[0032] Figure 7 For the product in Example 9 of the present invention 1 H NMR yield;

[0033] Figure 8 For the product in Example 9 of the present invention 1 H NMR pure spectrum;

[0034] Fig. 9 For the product in Example 9 of the present invention 13 C NMR pure spectrum;

[0035] Fig.10 For the product in Example 10 of the present invention 1 H NMR yield;

[0036] Fig.11 For the product in Example 10 of the present invention 1 H NMR pure spectrum;

[0037] Fig.12 For the product in Example 10 of the present invention 13 C NMR pure spectrum;

[0038] Fig.13 For the product in Example 11 of the present invention 1 H NMR yield;

[0039] Fig.14 For the product in Example 11 of the present invention 1 H NMR pure spectrum;

[0040] Fig.15 For the product in Example 11 of the present invention 13 C NMR pure spectrum;

[0041] Fig.16For the product in Example 12 of the present invention 1 H NMR yield;

[0042] Fig.17 For the product in Example 12 of the present invention 1 H NMR pure spectrum;

[0043] Fig.18 For the product in Example 12 of the present invention 13 C NMR pure spectrum;

[0044] Fig.19 For the product in Example 13 of the present invention 1 H NMR yield;

[0045] Fig. 20 For the product in Example 13 of the present invention 1 H NMR pure spectrum;

[0046] Fig.21 For the product in Example 13 of the present invention 13 C NMR pure spectrum. DETAILED DESCRIPTION

[0047] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be clearly and completely described in combination with the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0048] Unless otherwise specified, the test materials and reagents used in the following examples can be obtained from commercial sources.

[0049] If no specific techniques or conditions are specified in the examples, they can be carried out according to the techniques or conditions described in the literature in the art or according to the product instructions.

[0050] Example 1

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

[0052] (1) Preparation of electrocatalytic system solution: Add benzhydrol (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, take tetrahydrofuran (3 mL, water ≤ 30 ppm) and add it to the bottle, oscillate for 5 seconds, and ultrasonicate for 10 seconds to completely dissolve the components. Use a 100 μL microinjector to draw triethylamine (3.0 equiv., 0.0304 g) and add it to the glass bottle, oscillate for 5 seconds to make it evenly dissolved. Put an A5 (3×5 mm) polytetrafluoroethylene magnetic stirrer in the solution and set aside.

[0053] (2) Device construction: Place the double-layer gasket in the cap of the above-mentioned cylindrical glass bottle and tighten the cap. Punch a hole in the bottle cap and insert the anode zinc wire (3×50mm) and the cathode tin wire (3×50mm). Care should be taken not to affect the normal operation of the magnetic stirrer. Connect the sulfur hexafluoride gas through the gas duct to two gas throttle valves in series, and then connect a stainless steel long syringe needle about 10 cm long to deliver sulfur hexafluoride gas. Insert the needle for delivering sulfur hexafluoride gas to the bottom of the solution in the glass bottle, take a 1mL syringe metal needle, insert it into the bottle cap, pass through the gasket and stay above the liquid surface as a gas exhaust pipe. All parts should be firmly fixed above a room temperature magnetic stirrer with a rotation speed of 750rpm. The construction of the device can refer to the literature P.Nagorny et al., Org.Lett.2022,24,2294-2298;

[0054] (3) Electrolysis reaction: introduce sulfur hexafluoride gas, wait for 1 minute after the sulfur hexafluoride gas is introduced into the solution, connect the positive electrode of the adjustable DC regulated power supply to the anode zinc wire, and the negative electrode to the cathode tin wire, turn on the power supply and set the maximum voltage to 30 V, the constant current to 15 mA, and electrolyze for 1 hour. The electrochemical equivalent is 5.6 F / mol.

[0055] (4) Subsequent treatment: After the electrolysis reaction is completed, stop the power supply, turn off the adjustable DC regulated power supply, and remove the electrode. Wash the reaction mixture in the glass bottle into a separatory funnel with ethyl acetate (30 mL), and thoroughly clean the residue on the electrode and the bottle cap. Add water (20 mL) and dilute hydrochloric acid (1 M, 3 mL) and shake until the black-gray metal residue is completely dissolved. Leave the organic phase and wash it with saturated sodium bicarbonate solution (20 mL) to remove excess hydrochloric acid. Collect the organic phase and remove the solvent using a rotary evaporator. The product hydrogen spectrum yield is determined using dibromomethane (1 equiv., 0.01738 g) as an internal standard.

[0056] Reaction results: Benzhydrol was 78% 1 The dehydroxylation product, i.e., the benzyl alcohol fluorination product, is obtained by H-NMR yield, and its NMR spectrum is as follows Figure 1-3 shown.

[0057] Example 2

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

[0059] Reaction results: Benzhydrol was 37% 1 The dehydroxyfluorination product, i.e., the benzyl alcohol fluorination product, was obtained by H-NMR yield.

[0060] Example 3

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

[0062] Reaction results: Benzhydrol with 40% 1 The dehydroxyfluorination product, i.e., the benzyl alcohol fluorination product, was obtained by H-NMR yield.

[0063] Example 4

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

[0065] Reaction results: Benzhydrol was 59% 1 The dehydroxyfluorination product, i.e., the benzyl alcohol fluorination product, was obtained by H-NMR yield.

[0066] Example 5

[0067] An electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorination agent, which is different from Example 1 only in that tetrabutylammonium hexafluorophosphate (4.5 equiv., 0.1743 g) is used to replace tetrabutylammonium perchlorate (4.5 equiv., 0.1539 g) in step (1) of Example 1, and the remaining steps are the same as those of Example 1.

[0068] Reaction results: Benzhydrol with 27% 1 The dehydroxyfluorination product, i.e., the benzyl alcohol fluorination product, was obtained by H-NMR yield.

[0069] Example 6

[0070] An electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorination agent, which is different from Example 2 only in that N,N-diisopropylethylamine (3.0 equiv., 0.0388 g) is used to replace triethylamine (3.0 equiv., 0.0304 g) in step (1) of Example 2, and the remaining steps are the same as those of Example 2.

[0071] Reaction results: Benzhydrol was 47% 1 The dehydroxyfluorination product, i.e., the benzyl alcohol fluorination product, was obtained by H-NMR yield.

[0072] Example 7

[0073] An electrochemical organic synthesis method of benzyl alcohol fluorination products using sulfur hexafluoride as a fluorination agent, which is different from Example 2 only in that: (1) Preparation of electrocatalytic system solution: Add benzhydrol (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, take dichloromethane (3 mL, water ≤ 30 ppm) and add it to the bottle, oscillate for 5 seconds, and ultrasonicate for 10 seconds to completely dissolve the components. Weigh 4-dimethylaminopyridine (3.0 equiv., 0.0367 g) and add it to the glass bottle, oscillate for 5 seconds to make it evenly dissolved. Put an A5 (3×5 mm) type polytetrafluoroethylene magnetic stirrer in the solution and set aside.

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

[0075] Reaction results: Benzhydrol was 37% 1 The dehydroxyfluorination product, i.e., the benzyl alcohol fluorination product, was obtained by H-NMR yield.

[0076] Example 8

[0077] An electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorination agent, which is different from Example 1 only in that (2-chlorophenyl)-benzyl alcohol (0.1 mmol, 0.0218 g) is used to replace dibenzhydrol (0.1 mmol, 0.0184 g) in step (1) of Example 1, and the remaining steps are the same as Example 1.

[0078] Reaction results: (2-chlorophenyl)-benzyl alcohol with 74% 1 The dehydroxylation product, i.e., the benzyl alcohol fluorination product, is obtained by H-NMR yield, and its NMR spectrum is as follows Figure 4-6 shown.

[0079] Example 9

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

[0081] Reaction results: (3,4-dichlorophenyl)-benzyl alcohol with 41% 1 The dehydroxylation product, i.e., the benzyl alcohol fluorination product, is obtained by H-NMR yield, and its NMR spectrum is as follows Figure 7-9 shown.

[0082] Example 10

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

[0084] Reaction results: 3-(trifluoromethyl)diphenylmethanol with 44% 1 The dehydroxylation product, i.e., the benzyl alcohol fluorination product, is obtained by H-NMR yield, and its NMR spectrum is as follows Figure 10-12 shown.

[0085] Embodiment 11

[0086] An electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorination agent, which is different from Example 1 only in that (4-cyanophenyl)benzyl alcohol (0.1 mmol, 0.0209 g) is used to replace dibenzyl alcohol (0.1 mmol, 0.0184 g) in step (1) of Example 1, and the remaining steps are the same as Example 1.

[0087] Reaction results: (4-cyanophenyl)benzyl alcohol with 43% 1 The dehydroxylation product, i.e., the benzyl alcohol fluorination product, is obtained by H-NMR yield, and its NMR spectrum is as follows Figure 13-15 shown.

[0088] Example 12

[0089] An electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorination agent, which is different from Example 1 only in that 1,3-diphenyl-1-propanol (0.1 mmol, 0.0212 g) is used to replace dibenzhydrol (0.1 mmol, 0.0184 g) in step (1) of Example 1, and the remaining steps are the same as those of Example 1.

[0090] Reaction results: 1,3-diphenyl-1-propanol was 41% 1 The dehydroxylation product, i.e., the benzyl alcohol fluorination product, is obtained by H-NMR yield, and its NMR spectrum is as follows Figure 16-18 shown.

[0091] Example 13

[0092] An electrochemical organic synthesis method for benzyl alcohol fluorination products using sulfur hexafluoride as a fluorination agent, which is different from Example 1 only in that 1-(4-fluorophenyl)-3-phenyl-1-propanol (0.1 mmol, 0.0230 g) is used to replace dibenzhydrol (0.1 mmol, 0.0184 g) in step (1) of Example 1, and the remaining steps are the same as Example 1.

[0093] Reaction results: 1-(4-fluorophenyl)-3-phenyl-1-propanol was 51% 1 The dehydroxylation product, i.e., the benzyl alcohol fluorination product, is obtained by H-NMR yield, and its NMR spectrum is as follows Figure 19-21 shown.

[0094] Comparative Example 1

[0095] Compared with the reported literature Chem.Eur.J., 2022, 28, e202201654 (doi: 10.1002 / chem.202201654), the comparative example uses an alkyl compound to prepare the benzyl alcohol fluorination product.

[0096] (1) Operational procedures: Under an inert gas atmosphere, diphenylmethane (1.0 equiv., 0.50 mmol) and triethylamine hydrofluoride (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 the electrolytic cell. The electrosynthesis was carried out at room temperature at a constant current of 8.0 mA until 2.5 F / mol passed (4.2 h). After electrolysis, the reaction mixture was filtered on a silica plug. The platinum cathode and graphite felt anode were washed with EtOAc (Pt: 1 × 5.0 mL; C: 3 × 10 mL), and the resulting solution was filtered on the same silica plug. After rinsing the silica plug with additional n-hexane / ethyl acetate mixture (75 mL), the solvent was removed in vacuo. CH2Br2 (36 μL, 0.50 mmol) and PhCF3 (62 μL, 0.50 mmol) were used as internal standards. 1 H-NMR and 19 F-NMR analysis.

[0097] (2) Effect: The substrate diphenylmethane is 64% 1 The benzyl alcohol fluorination product was obtained by H-NMR.

[0098] (3) Comparison: From the operation steps and effects, it can be seen that the present invention is simpler to operate, does not require inert gas atmosphere protection, has higher yield (78%) and reagent utilization, is applicable to a variety of substrates, and the solvent tetrahydrofuran is easier to separate than hexafluoroisopropanol. The comparative example uses an alkyl compound that is more difficult to convert as a substrate, which easily triggers a series of free radical side reactions, and has slightly poor 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 benzhydrol (0.1 mmol, 0.0184 g) in step (1) of Example 1, and the remaining steps are the same as those of Example 1.

[0101] Reaction results: 1-(4-bromophenyl)-1-ethanol with 7% 1 The dehydroxyfluorinated product was obtained by H-NMR.

[0102] Comparison: This reaction system is not suitable for methylphenyl alcohol compounds.

[0103] Comparative Example 3

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

[0105] Reaction results: 1-(4-tert-butylphenyl)ethane-1-ol was added with 3% 1 The dehydroxyfluorinated product was obtained by H-NMR.

[0106] Comparison: This reaction system is not suitable for methylphenyl alcohol compounds.

[0107] Embodiment 14

[0108] The only difference from Example 1 is that in (3), the constant current is 7.5 mA and the electrolysis is carried out for 4 hours. The remaining steps are the same as in Example 1.

[0109] Reaction results: Benzhydrol with 27% 1 The dehydroxyfluorinated product was obtained by H-NMR.

[0110] Comparison: This reaction system requires a specific combination of current and time to achieve the best yield.

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

[0112]

[0113] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features thereof may be replaced by equivalents. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. An electrochemical organic synthesis method of benzyl alcohol fluorination products using sulfur hexafluoride as a fluorination agent, characterized in that: The following steps are involved: Benzyl alcohol, electrolyte, solvent and alkali are uniformly mixed, sulfur hexafluoride is introduced, and electrolysis reaction is carried out in a sulfur hexafluoride gas atmosphere with zinc as an anode and tin as a cathode, and the benzyl alcohol fluorination product is obtained after post-treatment; wherein the benzyl alcohol is a mixture of one or more of benzhydrol, (2-chlorophenyl)-benzyl alcohol, (3,4-dichlorophenyl)-benzyl alcohol, 3-(trifluoromethyl)benzhydrol, (4-cyanophenyl)benzyl alcohol, 1,3-diphenyl-1-propanol and 1-(4-fluorophenyl)-3-phenyl-1-propanol.

2. The electrochemical organic synthesis method of benzyl alcohol fluorination product using sulfur hexafluoride as a fluorination agent according to claim 1, characterized in that: The electrolyte is a mixture of one or more of tetrabutylammonium perchlorate, tetrabutylammonium tetrafluoroborate and tetrabutylammonium hexafluorophosphate.

3. The electrochemical organic synthesis method of benzyl alcohol fluorination product using sulfur hexafluoride as a fluorination agent according to claim 1, characterized in that: The solvent is a mixture of one or more of tetrahydrofuran, dichloromethane and dichloroethane.

4. The electrochemical organic synthesis method of benzyl alcohol fluorination product using sulfur hexafluoride as a fluorination agent according to claim 1, characterized in that: The base is one of N,N-diisopropylethylamine, triethylamine and 4-dimethylaminopyridine or a mixture of two thereof.

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

6. The electrochemical organic synthesis method of benzyl alcohol fluorination product using sulfur hexafluoride as a fluorination agent according to claim 1, characterized in that: The benzyl alcohol is benzhydrol or (2-chlorophenyl)-benzyl alcohol.

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

5.

8. The electrochemical organic synthesis method of benzyl alcohol fluorination product using sulfur hexafluoride as a fluorination agent according to claim 1, characterized in that: The usage ratio of the benzyl alcohol and the solvent is 0.1 mmol:3 mL.

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

3.

10. The electrochemical organic synthesis method of benzyl alcohol fluorination products using sulfur hexafluoride as a fluorination agent according to claim 1, characterized in that: During the electrolysis reaction, the maximum voltage of the power supply was set to 30 V, the constant current was 7.5-15 mA, the electrolysis was performed for 1-4 h, and the electrochemical equivalent was 5.6 F / mol.

11. The electrochemical organic synthesis method of benzyl alcohol fluorination product using sulfur hexafluoride as a fluorination agent according to claim 10, characterized in that: The constant current was 15 mA and the electrolysis was performed for 1 h.

12. The electrochemical organic synthesis method of benzyl alcohol fluorination products using sulfur hexafluoride as a fluorination agent according to claim 1, characterized in that: During the electrolysis reaction, stirring was performed at a speed of 750 rpm.

13. The electrochemical organic synthesis method of benzyl alcohol fluorination product using sulfur hexafluoride as a fluorination agent according to any one of claims 1 to 12, characterized in that: The post-treatment includes washing the product after the electrolysis reaction with ethyl acetate, then adding water and dilute hydrochloric acid, taking the organic phase and washing it with a saturated sodium bicarbonate solution, collecting the organic phase and removing the solvent to obtain the benzyl alcohol fluorination product.

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