A method for photocatalytic conversion of a benzyl chloride compound to an aldehyde or ketone

Abstract

The application belongs to the technical field of organic synthesis and specifically relates to a method for photocatalytic conversion of a benzyl chloride compound into an aldehyde or a ketone, which comprises the following steps: S1, adding the benzyl chloride compound and 5-bromoindole potassium xanthate into a reaction container, and then adding triethylamine, acetonitrile and water to obtain a reaction mixture; S2, performing a photocatalytic reaction on the reaction mixture in step S1 under blue light irradiation, and obtaining a photocatalytic product after the reaction is completed; and S3, extracting the photocatalytic product obtained in step S2 with ethyl acetate, drying the organic phase, concentrating the organic phase, and then obtaining a benzaldehyde or a phenylacetone product through column chromatography. The application uses low-toxicity and degradable xanthate as a catalyst, and provides a benzyl chloride compound oxidation method which is mild in reaction condition, environmentally friendly, high in selectivity and strong in universality.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for the photocatalytic conversion of benzyl chloride compounds into aldehydes or ketones. Background Technology

[0002] Aldehydes and ketones are important classes of organic compounds widely used in medicine, pesticides, fragrances, dyes, and other fields. The conversion of benzyl chloride compounds into aldehydes or ketones is a crucial reaction in organic synthesis. Through the tireless efforts of chemists, a technical system combining traditional chemical oxidation and modern green catalysis has been developed, including the Krohnke reaction, the Kornblum reaction and its various variants, cuprous chloride / diatomaceous earth, selenium compounds, potassium carbonate / dimethyl sulfoxide, manganese dioxide, bismuth nitrate pentahydrate / tetrabutylammonium fluoride, sodium periodate / dimethylformamide, pyridine N-oxide, sodium periodate, vanadium pentoxide / trioctylmethylammonium chloride / hydrogen peroxide, bromate exchange resins, 3,6-bis(triphenylphosphine)cyclohexene peroxydisulfate, and magnesium aluminum hydrotalcite / dimethyl sulfoxide, etc. These oxidation systems are quite practical for small-scale reactions, but most methods require the use of dangerous, expensive, or toxic reagents, or require long-term reactions at high temperatures.

[0003] Photocatalytic oxidation reactions have attracted widespread attention due to their mild conditions and environmental friendliness. While some photocatalytic systems attempt to utilize clean energy, their low efficiency is limited by insufficient catalyst activity, making it difficult to effectively activate the relatively inert C-Cl bonds in benzyl chloride compounds. Furthermore, some methods have narrow substrate applicability, failing to achieve selective oxidation of benzyl chloride compounds with different structures, thus hindering the diverse needs of complex organic synthesis. In addition, traditional radical generation strategies often suffer from difficulties in radical initiation and poor reaction controllability when dealing with inert benzyl chloride substrates, further restricting the development of aldehyde and ketone synthesis technologies. The strong electron-withdrawing ability and the ability to induce absorption shift changes in sulfhydryl anions endow their application in photocatalysis with unique catalytic modes. Therefore, developing a benzyl chloride oxidation method using sulfhydryl anions as catalysts, with mild reaction conditions, environmental friendliness, high selectivity, and broad applicability, has become an urgent need to overcome traditional technological bottlenecks and promote innovative development in the field of aldehyde and ketone synthesis. Summary of the Invention

[0004] To address the problems existing in the prior art, this invention provides a method for the photocatalytic conversion of benzyl chloride compounds into aldehydes or ketones, using low-toxicity, biodegradable xanthate as a catalyst, and providing a benzyl chloride compound oxidation method with mild reaction conditions, environmental friendliness, high selectivity, and broad applicability.

[0005] The specific technical solution adopted in this invention is as follows:

[0006] A method for photocatalytic conversion of benzyl chloride compounds into aldehydes or ketones includes the following steps:

[0007] S1. Add benzyl chloride compound and potassium 5-bromoindole xanthate to a reaction vessel, then add triethylamine, acetonitrile and water to obtain a reaction mixture;

[0008] S2. The reaction mixture in step S1 is subjected to a photocatalytic reaction under blue light irradiation. After the reaction is completed, the photocatalytic product is obtained.

[0009] S3. Extract the photocatalytic product obtained in step S2 with ethyl acetate. After drying and concentrating the organic phase, obtain the product benzaldehyde or acetophenone by column chromatography.

[0010] The chemical structural formula of the benzyl chloride compound is as follows: or .

[0011] The benzyl chloride compound includes any one of benzyl chloride, 4-tert-butylbenzyl chloride, 4-methoxybenzyl chloride, 4-chlorobenzyl chloride, 4-methylbenzyl chloride, and α-methylbenzyl chloride.

[0012] The amount of potassium 5-bromoindole xanthate used is 18-22 mol of the number of moles of the benzyl chloride compound.

[0013] The molar ratio of the benzyl chloride compound, triethylamine, and water is 1:1-1.4:8-10.

[0014] For every mmol of the benzyl chloride, add 10-12 mL of acetonitrile.

[0015] The specific steps of photocatalysis in step S2 are as follows: at room temperature, the reaction vessel containing the reaction mixture is placed on a stirrer, the reaction vessel is open and a 36W blue LED is placed next to the reaction vessel, the distance between the reaction vessel and the light source is 0.8-1.2cm, the reaction is stirred for 20-28 h, and the photocatalytic product is obtained.

[0016] The eluent used for column chromatography is a mixture of ethyl acetate and petroleum ether in a volume ratio of 1:20-50.

[0017] The beneficial effects of this invention are:

[0018] 1. This invention uses low-toxicity, biodegradable xanthate as a catalyst, which can greatly reduce environmental pollution compared with traditional toxic heavy metal catalysts, and is in line with the concept of green chemistry.

[0019] Furthermore, the thioanion of xanthate has unique electronic effects and steric hindrance matching, which can accurately identify and directionally activate the methylene group (-CH2Cl) of benzyl chloride, generating benzaldehyde with high selectivity, reducing byproducts and improving the yield of the target product.

[0020] 2. Traditional methods often require high temperatures (80-150℃) and high pressures (closed reactors), while the reaction conditions in this invention are mild, requiring only open conditions at room temperature and normal pressure. No special pressure- and temperature-resistant equipment is needed, reducing energy consumption and equipment costs. The open design also allows direct use of oxygen from the air as a green oxidant, avoiding the cost of adding expensive oxidants as required by traditional methods, while also reducing the risk of pressure runaway that may occur in closed systems.

[0021] 3. The synthesis method of this invention is novel and is a photocatalytic strategy for generating free radicals based on different physical properties of the substrates, providing a new tool for the activation of inert substrates in classical free radical generation strategies. Attached Figure Description

[0022] Figure 1 The reaction equation of this invention is as follows;

[0023] Figure 2 The structural formulas and yields of the aldehyde or ketone products obtained in Examples 1-6 are shown below.

[0024] Figure 3 The 1H NMR spectrum of product 3a from Example 1;

[0025] Figure 4 The carbon spectrum of product 3a from Example 1;

[0026] Figure 5 The 3b proton NMR spectrum of the product from Example 2;

[0027] Figure 6 The 3b carbon spectrum of the product from Example 2;

[0028] Figure 7 The 3c proton spectrum of the product in Example 3;

[0029] Figure 8 The 3C carbon spectrum of the product in Example 3;

[0030] Figure 9 The 3e proton spectrum of the product in Example 4;

[0031] Figure 10 The 3e carbon spectrum of the product in Example 4;

[0032] Figure 11 The 3f proton NMR spectrum of the product from Example 5;

[0033] Figure 12 The 3f carbon spectrum of the product from Example 5;

[0034] Figure 13 The product 3a from Example 1 is a high-resolution mass spectrometer (HRMS) of mass spectrometer. Detailed Implementation

[0035] The present invention will be further described below with reference to the accompanying drawings and specific embodiments: I. Specific Implementation Methods

[0037] Example 1

[0038] S1. In a dried 10 mL reaction tube, add 0.3 mmol of 4-tert-butylbenzyl chloride, 0.06 mmol of 5-bromoindole xanthate potassium, 0.36 mmol of triethylamine, 3 mL of acetonitrile and 2.4 mmol of water in sequence, and stir until homogeneous to obtain the reaction mixture;

[0039] S2. At room temperature, the reaction tube containing the reaction mixture was placed open next to a 36 W LED lamp emitting blue light, with the reaction tube 1 cm away from the lamp. The reaction was stirred for 24 h to obtain the photocatalytic product.

[0040] S3. The photocatalytic product was extracted with ethyl acetate, the organic phase was dried with anhydrous Na2SO4, concentrated under reduced pressure, and then subjected to column chromatography (ethyl acetate / petroleum ether = 1 / 50-20 as a gradient eluent) to obtain 4-(tert-butyl)benzaldehyde.

[0041] Example 2

[0042] S1. In a dried 10 mL reaction tube, add 0.3 mmol of 4-methoxybenzyl chloride, 0.06 mmol of 5-bromoindole xanthate potassium, 0.36 mmol of triethylamine, 3 mL of acetonitrile and 2.4 mmol of water in sequence, and stir until homogeneous to obtain the reaction mixture;

[0043] S2. At room temperature, the reaction tube containing the reaction mixture was placed open next to a 36 W LED lamp emitting blue light, with the reaction tube 1 cm away from the lamp. The reaction was stirred for 24 h to obtain the photocatalytic product.

[0044] S3. The photocatalytic product was extracted with ethyl acetate, the organic phase was dried with anhydrous Na2SO4, concentrated under reduced pressure, and then 4-methoxybenzaldehyde was obtained by column chromatography (ethyl acetate / petroleum ether = 1 / 50-20 as a gradient eluent).

[0045] Example 3

[0046] S1. In a dried 10 mL reaction tube, add 0.3 mmol of 4-chlorobenzyl chloride, 0.06 mmol of 5-bromoindole xanthate potassium, 0.36 mmol of triethylamine, 3 mL of acetonitrile and 2.4 mmol of water in sequence, and stir until homogeneous to obtain the reaction mixture;

[0047] S2. At room temperature, the reaction tube containing the reaction mixture was placed open next to a 36W LED lamp emitting blue light, with the reaction tube 1 cm away from the lamp. The reaction was stirred for 24 h to obtain the photocatalytic product.

[0048] S3. The photocatalytic product was extracted with ethyl acetate, the organic phase was dried with anhydrous Na2SO4, concentrated under reduced pressure, and then 4-chlorobenzaldehyde was obtained by column chromatography (ethyl acetate / petroleum ether = 1 / 50-20 as a gradient eluent).

[0049] Example 4

[0050] S1. In a dried 10 mL reaction tube, add 0.3 mmol of 4-methylbenzyl chloride, 0.06 mmol of potassium 5-bromoindole xanthate, 0.36 mmol of triethylamine, 3 mL of acetonitrile and 2.4 mmol of water in sequence, and stir until homogeneous to obtain the reaction mixture;

[0051] S2. At room temperature, the reaction tube containing the reaction mixture was placed open next to a 36 W LED lamp emitting blue light, with the reaction tube 1 cm away from the lamp. The reaction was stirred for 24 h to obtain the photocatalytic product.

[0052] S3. The photocatalytic product was extracted with ethyl acetate, the organic phase was dried with anhydrous Na2SO4, concentrated under reduced pressure, and then 4-methylbenzaldehyde was obtained by column chromatography (ethyl acetate / petroleum ether = 1 / 50-20 as a gradient eluent).

[0053] Example 5

[0054] S1. In a dried 10 mL reaction tube, add 0.3 mmol α-methylbenzyl chloride, 0.06 mmol 5-bromoindole xanthate potassium, 0.36 mmol triethylamine, 3 mL acetonitrile and 2.4 mmol water in sequence, and stir until homogeneous to obtain the reaction mixture;

[0055] S2. At room temperature, the reaction tube containing the reaction mixture was placed open next to a 36 W LED lamp emitting blue light, with the reaction tube 1 cm away from the lamp. The reaction was stirred for 24 h to obtain the photocatalytic product.

[0056] S3. The photocatalytic product was extracted with ethyl acetate, the organic phase was dried with anhydrous Na2SO4, concentrated under reduced pressure, and then acetophenone was obtained by column chromatography (ethyl acetate / petroleum ether = 1 / 50-20 as a gradient eluent).

[0057] II. Component Analysis

[0058] The reaction equations for the synthesis methods in Examples 1-5 are shown below. Figure 1 The structural formulas and yields of the aldehyde or ketone products are shown in [reference needed]. Figure 2 Nuclear magnetic resonance (NMR) spectrum Figure 1 See H NMR and 13C NMR Figure 3-12 The high-resolution mass spectrometry (HRMS) of product 3a from Example 1 is shown in [reference needed]. Figure 13 .

[0059] The characterization data of the compound obtained in Example 1 are as follows:

[0060] 4-(Tert-butyl)benzaldehyde (3a) Colorless oil.

[0061] 1H NMR (400 MHz, CDCl3) δ / ppm = 9.98 (s, 1H), 7.84 - 7.81 (m, 2H), 7.57 - 7.54 (m, 2H), 1.35 (s, 9H).

[0062] 13C NMR (101 MHz, CDCl3) δ = 192.0, 158.4, 134.1, 129.7, 126.0, 35.3,31.1.

[0063] The characterization data of the compound obtained in Example 2 are as follows:

[0064] 4-Methoxybenzaldehyde (3b) Colorless oil.

[0065] 1H NMR (400 MHz, CDCl3) δ / ppm = 9.81 (s, 1H), 7.83 - 7.74 (m, 2H), 6.94 (d, J = 8.8 Hz, 2H), 3.81 (s, 3H).

[0066] 13C NMR (150 MHz, CDCl3) δ / ppm = 190.7, 164.6, 131.9, 129.9, 114.2,55.5.

[0067] The characterization data of the compound obtained in Example 3 are as follows:

[0068] 4-Chlorobenzaldehyde (3c) Colorless oil.

[0069] 1H NMR (400 MHz, CDCl3) δ / ppm = 9.97 (s, 1H), 7.83 - 7.79 (m, 2H), 7.52 - 7.48 (m, 2H).

[0070] 13C NMR (101 MHz, CDCl3) δ = 190.9, 141.0, 134.7, 130.9, 129.5.

[0071] The characterization data of the compound obtained in Example 4 are as follows:

[0072] 4-Methylbenzaldehyde (3e) Colorless oil.

[0073] 1H NMR (400 MHz, CDCl3) δ / ppm = 9.96 (s, 1H), 7.79 - 7.76 (m, 2H), 7.34 - 7.32 (m, 2H), 2.44 (s, 3H).

[0074] 13C NMR (101 MHz, CDCl3) δ = 192.0, 145.6, 134.2, 129.9, 129.7, 21.9.

[0075] The characterization data of the compound obtained in Example 5 are as follows:

[0076] Acetophenone (3f) Colorless oil.

[0077] 1H NMR (400 MHz, CDCl3) δ / ppm = 7.96 – 7.91 (m, 2H), 7.56 – 7.50 (m,1H), 7.43 (t, J = 7.6 Hz, 2H), 2.57 (s, 3H).

[0078] 13C NMR (150 MHz, CDCl3) δ / ppm = 198.1, 137.1, 133.1, 128.5, 128.3,26.5.

[0079] In one example, after reacting benzyl chloride as a raw material for 24 hours, the product contained only trace amounts of benzaldehyde for 3 days.

Claims

1. A method for the photocatalytic conversion of benzyl chloride compounds into aldehydes or ketones, characterized in that, Includes the following steps: S1. Add benzyl chloride compound and potassium 5-bromoindole xanthate to a reaction vessel, then add triethylamine, acetonitrile and water to obtain a reaction mixture; S2. The reaction mixture in step S1 is subjected to a photocatalytic reaction under blue light irradiation. After the reaction is completed, the photocatalytic product is obtained. S3. Extract the photocatalytic product obtained in step S2 with ethyl acetate. After drying and concentrating the organic phase, obtain the product benzaldehyde or acetophenone by column chromatography.

2. The method for photocatalytic conversion of benzyl chloride compounds into aldehydes or ketones according to claim 1, characterized in that, The chemical structural formula of the benzyl chloride compound is as follows: or .

3. The method for photocatalytic conversion of benzyl chloride compounds into aldehydes or ketones according to claim 1, characterized in that, The benzyl chloride compound includes any one of benzyl chloride, 4-tert-butylbenzyl chloride, 4-methoxybenzyl chloride, 4-chlorobenzyl chloride, 4-methylbenzyl chloride, and α-methylbenzyl chloride.

4. The method for photocatalytic conversion of benzyl chloride compounds into aldehydes or ketones according to claim 1, characterized in that, The amount of potassium 5-bromoindole xanthate used is 18-22 mol of the number of moles of the benzyl chloride compound.

5. The method for photocatalytic conversion of benzyl chloride compounds into aldehydes or ketones according to claim 1, characterized in that, The molar ratio of the benzyl chloride compound, triethylamine, and water is 1:1-1.4:8-10.

6. The method for photocatalytic conversion of benzyl chloride compounds into aldehydes or ketones according to claim 1, characterized in that, For every mmol of the benzyl chloride, add 10-12 mL of acetonitrile.

7. The method for photocatalytic conversion of benzyl chloride compounds into aldehydes or ketones according to claim 1, characterized in that, The specific steps of photocatalysis in step S2 are as follows: at room temperature, the reaction vessel containing the reaction mixture is placed on a stirrer, the reaction vessel is open and a 36W blue LED is placed next to the reaction vessel, the distance between the reaction vessel and the light source is 0.8-1.2 cm, the reaction is stirred for 20-28 h, and the photocatalytic product is obtained.

8. The method for photocatalytic conversion of benzyl chloride compounds into aldehydes or ketones according to claim 1, characterized in that, The eluent used for column chromatography is a mixture of ethyl acetate and petroleum ether in a volume ratio of 1:20-50.

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