Method for preparing benzyl carboxylic acid compound by taking carbon dioxide as raw material

Abstract

The invention relates to a method for preparing a benzyl carboxylic acid compound by taking carbon dioxide as a raw material. The method comprises the following steps: synthesizing benzyl alcohol into a pinacol borate compound in one step at room temperature, and then adding the pinacol borate compound, electrolyte and alkali into a solvent to obtain a mixed solution; and introducing carbon dioxide into the mixed solution, and electrifying to electrolyze the mixed solution to obtain the benzyl carboxylic acid compound. The benzyl carboxylic acid compound is constructed through a simple, convenient, efficient and green method, carbon dioxide serves as a reaction carbon source, the problem of carbon dioxide emission is well solved, and the method is a thought of carbon neutralization; the gram-level reaction can be realized through electrolysis at room temperature, the yield is high, and high efficiency is embodied; the reaction is economical and environment-friendly, and metal catalysts, ligands and high-temperature and high-pressure conditions are not needed. The method has the advantages of convenient operation, mild reaction conditions, simple and easily available raw materials, and huge potential large-scale application value.

Description

Technical Field

[0001] The invention relates to the technical field of catalytic synthesis, and in particular to a method for preparing a benzylic acid compound by taking carbon dioxide as a raw material. Background Art

[0002] Since the Industrial Revolution, due to the extensive use of fossil fuels, carbon dioxide (CO2) emissions have increased day by day, resulting in a continuous increase in the concentration of CO2 in the atmosphere. As a key component of the earth's carbon cycle, CO2 has an important impact on climate change. This greenhouse gas has brought about environmental problems such as global warming. Therefore, how to convert the large amount of CO2 generated in industry into resources has become a key research direction.

[0003] Carbon dioxide (CO2) is an important component in the air and is also a widely existing, cheap, easy to obtain, non-toxic, stable, renewable and recyclable "carbon one" (C1) resource. A large number of environmental protection companies incinerate CO2 because CO2 has high thermodynamic and kinetic stability and low reaction activity. CO2 activation is a huge challenge and is widely used in the synthesis of important fine chemicals. Aromatic acid is widely present in many drug molecules and is an important class of carboxylic acid molecules.

[0004] Benzylic alcohol compounds are commercially available and inexpensive, making them ideal substrates for the synthesis of arylic acids. Therefore, the synthesis of arylic acids using benzylic alcohol compounds and CO2 as raw materials is very attractive. The traditional synthesis method of arylic acids requires the pre-preparation of benzyl halides into water- and oxygen-sensitive benzylic metal reagents, which are then reacted with CO2 for carboxylation. However, due to poor compatibility and cumbersome operation, practical applications are limited. In addition, transition metal-catalyzed carboxylation reactions of benzylic halides with CO2 have made great progress, but there are also problems such as limited substrate range, poor functional group compatibility, the use of metal reducing agents, and the presence of heavy metal pollution.

[0005] Therefore, seeking a method that is mild, green, efficient, simple and easy to operate to synthesize benzyl carboxylic acid compounds is a key issue that needs to be solved urgently. Summary of the invention

[0006] The present invention aims to solve the technical problem that the existing synthesis method requires metal catalysts, ligands and high-temperature heating, which leads to difficulty in preparation, and provides a method for preparing benzyl carboxylic acid compounds using carbon dioxide as a raw material.

[0007] A method for preparing a benzylic acid compound using carbon dioxide as a raw material comprises the following steps:

[0008] 1. In an air atmosphere and at room temperature, the synthesized pinacol borate, base and electrolyte are added to a solvent to obtain a mixed solution;

[0009] 2. Place two electrodes into the mixed solution obtained in step 1, connect to a power source, and electrolyze the mixed solution for 8-12 hours;

[0010] 3. After the electrolysis reaction in step 2 is completed, the product obtained is acidified with dilute hydrochloric acid, washed with brine, extracted with ethyl acetate, and the solvent is removed by rotary evaporation. Then, it is separated and purified by thin layer chromatography to obtain a benzyl carboxylic acid compound, thereby completing the preparation.

[0011] The invention firstly uses benzylic alcohol to synthesize pinacol borate, and a single electron transfer process occurs under electrochemical conditions to obtain a benzylic free radical, which is then further reduced at a cathode to obtain a benzylic anion. The benzylic anion undergoes a nucleophilic reaction with carbon dioxide to finally obtain a benzylic carboxylic acid compound.

[0012] The beneficial effects of the present invention are:

[0013] Compared with the prior art, the present invention constructs benzyl carboxylic acid compounds by a simple, green and efficient method, which has the following advantages:

[0014] (1) The carbon source used in the reaction is carbon dioxide, which can not only solve the problem of atmospheric ozone layer damage, but also solve the company's carbon emission problem;

[0015] (2) The alcohol, electrolyte, and base used in the catalytic system are simple, cheap, and readily available commercial compounds. The substrate synthesis is also very simple, and the reaction substrates in the reaction have good universality. The entire reaction system is economical and efficient.

[0016] (3) The reaction system is an electrochemical reaction system, which does not require heating, nor does it require the ligands and metal catalysts commonly used in traditional carboxylic acid synthesis reactions. It only requires the addition of a small amount of electrolyte to maintain the conductivity of the solution and a small amount of alkali to maintain the pH value of the solution to obtain the benzylic carboxylic acid product;

[0017] (4) The catalytic system has a wide range of substrate applications and is very green and mild. It can achieve a good yield when powered on at room temperature, demonstrating high efficiency. It does not use ligands and metal catalysts, which reflects the energy-saving and environmentally friendly nature of the reaction and has potential application value.

[0018] The invention is used for preparing benzyl carboxylic acid compounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 It is the mechanism process diagram of the reaction;

[0020] Figure 2 The benzyl carboxylic acid compound-1 obtained in Example 1 1 H NMR spectrum;

[0021] Figure 3The benzyl carboxylic acid compound-1 obtained in Example 1 13 C NMR spectrum. DETAILED DESCRIPTION

[0022] The technical solution of the present invention is not limited to the specific implementation modes listed below, but also includes any combination of the specific implementation modes.

[0023] The following examples and comparative experiments are used to verify the beneficial effects of the present invention:

[0024] Embodiment 1:

[0025] This embodiment provides a method for preparing a benzylic carboxylic acid compound by reacting a benzylic alcohol compound with carbon dioxide under electrochemical conditions, the method comprising the following steps:

[0026] 1. Under nitrogen protection, 2 mmol of p-methylphenylethanol and 2 mmol of triethylamine were added to a pressure tube with a magnet, and 1 mL of anhydrous tetrahydrofuran was added as a solvent. Then 3 mmol of pinacol borane was added to the tube, and stirred at room temperature, and the reaction progress was monitored by a TLC plate. After the reaction was completed, the solvent was dried by a rotary evaporator, and the pinacol borate compound was separated by column chromatography.

[0027] 2. Install an iron electrode and a nickel electrode on the left and right sides of the three-necked flask respectively. In an air atmosphere, add 0.3 mmol of the pinacol borate compound obtained in the previous step into the flask, add 0.2 mmol of electrolyte nBu4NPF6 and 1 mmol of triethylamine, and finally add 5 mL of DMF solvent into the three-necked flask to obtain a mixed solution.

[0028] 3. Insert a rubber stopper into the middle mouth of the three-necked flask and seal it with sealing glue. At room temperature, connect the iron electrode to the anode and the nickel electrode to the cathode. Use a constant potential meter as the power supply, adjust it to the constant current mode, control the current intensity to 10 mA, and electrolyze the mixed solution for 6 hours. Monitor the reaction progress by TLC.

[0029] 4. The product obtained after the electrolysis reaction in step 3 is acidified with dilute hydrochloric acid and mixed with saturated brine, and then extracted three times with ethyl acetate, and the organic phases are mixed, evaporated with a rotary evaporator, and then separated and purified by thin layer chromatography using a petroleum ether / ethyl acetate mixed solvent as an eluent to obtain a benzyl carboxylic acid compound, thereby completing the preparation.

[0030] The cis-olefin compound prepared in this example was identified as benzylic acid compound-1 by H-NMR spectrum, C-NMR spectrum, and mass spectrum, and its structural formula is:

[0031]

[0032] Purity 99%, yield 71%; its NMR data analysis is: 1 HNMR (400MHz, CDCl3) δ12.35(s,1H),7.19(d,J=7.2Hz,2H),7.12(d,J=7.2Hz,2H),3.55(s,2H),2.29(s,3H)

[0033] 13 C NMR (100MHz, CDCl3) δ137.3, 136.1, 132.4, 129.7, 129.3, 40.9, 21.0.

[0034] Embodiment 2:

[0035] This embodiment provides a method for preparing a benzylic carboxylic acid compound by reacting a benzylic alcohol compound with carbon dioxide under electrochemical conditions, the method comprising the following steps:

[0036] 1. Under nitrogen protection, 2 mmol of p-iodophenylethanol and 2 mmol of triethylamine were added to a pressure tube with a magnet, and 1 mL of anhydrous tetrahydrofuran was added as a solvent. Then 3 mmol of pinacol borane was added to the tube, and stirred at room temperature, and the reaction progress was monitored by a TLC plate. After the reaction was completed, the solvent was dried by a rotary evaporator, and the pinacol borate compound was separated by column chromatography.

[0037] 2. Install an iron electrode and a nickel electrode on the left and right sides of the three-necked flask respectively. In an air atmosphere, add 0.3 mmol of the pinacol borate compound obtained in the previous step into the flask, add 0.2 mmol of electrolyte nBu4NPF6 and 1 mmol of triethylamine, and finally add 5 mL of DMF solvent into the three-necked flask to obtain a mixed solution.

[0038] 3. Insert a rubber stopper into the middle mouth of the three-necked flask and seal it with sealing glue. At room temperature, connect the iron electrode to the anode and the nickel electrode to the cathode. Use a constant potential meter as the power supply, adjust it to the constant current mode, control the current intensity to 10 mA, and electrolyze the mixed solution for 6 hours. Monitor the reaction progress by TLC.

[0039] 4. The product obtained after the electrolysis reaction in step 3 is acidified with dilute hydrochloric acid and mixed with saturated brine, and then extracted three times with ethyl acetate, and the organic phases are mixed, evaporated with a rotary evaporator, and then separated and purified by thin layer chromatography using a petroleum ether / ethyl acetate mixed solvent as an eluent to obtain a benzyl carboxylic acid compound, thereby completing the preparation.

[0040] The cis-olefin compound prepared in this example was identified as benzylic acid compound-2 by H-NMR spectrum, C-NMR spectrum, and mass spectrum, and its structural formula is:

[0041]

[0042] Purity 99%, yield 92%; its NMR data analysis is: 1 HNMR(400MHz,DMSO)δ12.39(s,1H),7.66(d,J=8.2Hz,2H),7.08(d,J=8.2Hz,2H),3.54(s,2H)

[0043] 13 C NMR (100MHz, DMSO) δ172.7, 137.4, 135.4, 132.3, 92.9.

[0044] Embodiment three:

[0045] This embodiment provides a method for preparing a benzylic carboxylic acid compound by reacting a benzylic alcohol compound with carbon dioxide under electrochemical conditions, the method comprising the following steps:

[0046] 1. Under nitrogen protection, add 2mmol of p-bromophenethanol and 2mmol of triethylamine to a pressure tube with a magnet, and add 1mL of anhydrous tetrahydrofuran as a solvent. Then add 3mmol of pinacol borane to the tube, stir at room temperature, and monitor the reaction progress with a TLC plate. After the reaction is completed, the solvent is dried with a rotary evaporator and separated by column chromatography to obtain pinacol borate compounds.

[0047] 2. Install an iron electrode and a nickel electrode on the left and right sides of the three-necked flask respectively. In an air atmosphere, add 0.3 mmol of the pinacol borate compound obtained in the previous step into the flask, add 0.2 mmol of electrolyte nBu4NPF6 and 1 mmol of triethylamine, and finally add 5 mL of DMF solvent into the three-necked flask to obtain a mixed solution.

[0048] 3. Insert a rubber stopper into the middle mouth of the three-necked flask and seal it with sealing glue. At room temperature, connect the iron electrode to the anode and the nickel electrode to the cathode. Use a constant potential meter as the power supply, adjust it to the constant current mode, control the current intensity to 10 mA, and electrolyze the mixed solution for 6 hours. Monitor the reaction progress by TLC.

[0049] 4. The product obtained after the electrolysis reaction in step 3 is acidified with dilute hydrochloric acid and mixed with saturated brine, and then extracted three times with ethyl acetate, and the organic phases are mixed, evaporated with a rotary evaporator, and then separated and purified by thin layer chromatography using a petroleum ether / ethyl acetate mixed solvent as an eluent to obtain a benzyl carboxylic acid compound, thereby completing the preparation.

[0050] The cis-olefin compound prepared in this example was identified as benzylic acid compound-3 by H-NMR spectrum, C-NMR spectrum, and mass spectrum, and its structural formula is:

[0051]

[0052] Purity 99%, yield 77%; its NMR data analysis is: 1 H NMR (400MHz, CDCl3) δ10.04(s,1H),7.45(d,J=8.4Hz,2H),7.14(d,J=8.4Hz,2H),3.59(s,2H)

[0053] 13 C NMR (101MHz, CDCl3) δ177.5,132.2,131.9,131.1,121.5,40.4.

[0054] Embodiment 4:

[0055] This embodiment provides a method for preparing a benzylic carboxylic acid compound by reacting a benzylic alcohol compound with carbon dioxide under electrochemical conditions, the method comprising the following steps:

[0056] 1. Under nitrogen protection, 2 mmol of 3-methoxyphenylethanol and 2 mmol of triethylamine are added to a pressure-resistant tube with a magnet, and 1 mL of anhydrous tetrahydrofuran is added as a solvent. Then 3 mmol of pinacol borane is added to the tube, and stirred at room temperature, and the reaction progress is monitored by a TLC plate. After the reaction is completed, the solvent is dried by a rotary evaporator, and separated by column chromatography to obtain a pinacol borate compound.

[0057] 2. Install an iron electrode and a nickel electrode on the left and right sides of the three-necked flask respectively. In an air atmosphere, add 0.3 mmol of the pinacol borate compound obtained in the previous step into the flask, add 0.2 mmol of electrolyte nBu4NPF6 and 1 mmol of triethylamine, and finally add 5 mL of DMF solvent into the three-necked flask to obtain a mixed solution.

[0058] 3. Insert a rubber stopper into the middle mouth of the three-necked flask and seal it with sealing glue. At room temperature, connect the iron electrode to the anode and the nickel electrode to the cathode. Use a constant potential meter as the power supply, adjust it to the constant current mode, control the current intensity to 10 mA, and electrolyze the mixed solution for 6 hours. Monitor the reaction progress by TLC.

[0059] 4. The product obtained after the electrolysis reaction in step 3 is acidified with dilute hydrochloric acid and mixed with saturated brine, and then extracted three times with ethyl acetate, and the organic phases are mixed, evaporated with a rotary evaporator, and then separated and purified by thin layer chromatography using a petroleum ether / ethyl acetate mixed solvent as an eluent to obtain a benzyl carboxylic acid compound, thereby completing the preparation.

[0060] The cis-olefin compound prepared in this example was identified as benzylic acid compound-4 by H-NMR spectrum, C-NMR spectrum, and mass spectrum, and its structural formula is:

[0061]

[0062] Purity 99%, yield 82%; its NMR data analysis is: 1 H NMR (400MHz, CDCl3) δ9.39 (s, 1H), 7.23 (t, J = 7.5Hz, 1H), 6.87-6.81 (m, 3H), 3.78 (s, 3H), 3.60 (s, 2H)

[0063] 13 C NMR (101MHz, CDCl3) δ177.7,159.8,134.7,129.6,121.7,115.1,112.9,55.2,41.1.

Claims

1. A method for preparing a benzylic acid compound using carbon dioxide as a raw material, characterized in that: The method comprises the following steps:

1. In an air atmosphere and at room temperature, the synthesized pinacol borate, base and electrolyte are added to a solvent to obtain a mixed solution; 2. Place two electrodes in the mixed solution obtained in step 1, introduce carbon dioxide gas into the solution system through an external carbon dioxide balloon, connect it to a power source, and electrolyze the mixed solution for 8-12 hours; 3. After the electrolysis reaction in step 2 is completed, the product obtained is acidified with dilute hydrochloric acid, washed with brine, extracted with ethyl acetate, and the solvent is removed by rotary evaporation. Then, it is separated and purified by thin layer chromatography to obtain a benzyl carboxylic acid compound, thereby completing the preparation.

2. The method for preparing a benzylic acid compound according to claim 1, wherein The synthesis method of pinacol borate is as follows: Under nitrogen protection, 2 mmol of phenylethanol and 2 mmol of triethylamine were added to a pressure tube with a magnet, and 1 mL of anhydrous tetrahydrofuran was added as a solvent; then 3 mmol of pinacol borane was added to the tube, and stirred at room temperature, and the reaction progress was monitored by a TLC plate; after the reaction was completed, the solvent was dried by a rotary evaporator, and the pinacol borate compounds were separated by column chromatography.

3. The method for preparing a benzylic acid compound according to claim 1, wherein The raw materials of the pinacol borate in step 1 are p-methoxyphenylethanol, 2-chlorophenylethanol, 3-chlorophenylethanol, 4-chlorophenylethanol, 2-phenylpropanol, 4-cyanophenylethanol, p-methylphenylethanol, and 4-fluorophenylethanol.

4. The method for preparing a benzylic acid compound according to claim 1, characterized in that: In step 1, the base is triethylamine.

5. The method for preparing a benzylic acid compound according to claim 1, characterized in that: The electrolyte in step 1 is nBu4NBF4.

6. The method for preparing a benzylic acid compound according to claim 1, characterized in that: The solvent in step 1 is N,N-dimethylacetamide.

7. The method for preparing a benzylic acid compound according to claim 1, characterized in that: In step 1, the ratio of the pinacol borate to the solvent is 0.1 mmol:1 mL; The usage ratio of the base to the solvent is 0.2mmol:1mL; The usage ratio of the electrolyte to the solvent is 0.2 mmol:1 mL.

8. The method for preparing a benzylic acid compound according to claim 1, characterized in that: The power supply described in step 2 is a constant current power supply.

9. The method for preparing a benzylic acid compound according to claim 1, characterized in that: In step 2, the electrode anode is an iron sheet electrode and the cathode is a nickel sheet electrode; the size of the iron sheet electrode is 10mm×10mm×0.15mm, and the size of the nickel sheet electrode is 10mm×10mm×0.15mm.

10. The method for preparing a benzylic acid compound according to claim 1, characterized in that: Step 2: Control the current intensity to 7mA.

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