Method for synthesizing acetal compound through light promotion

Abstract

The invention belongs to the technical field of organic synthesis, and discloses a method for synthesizing an acetal compound through light promotion, which comprises the following steps: taking an alcohol compound as shown in a formula I and tetrahydrofuran as raw materials, taking ferric chloride or ferrous chloride as a catalyst, and reacting at room temperature under an illumination condition and an air atmosphere to obtain the acetal compound as shown in a formula II. Under the photocatalysis condition, alcohol and tetrahydrofuran are subjected to dehydrogenation coupling to obtain acetal, the substrate application range is wide, no photosensitizer or ligand needs to be added, the reaction can be carried out under the room temperature condition, and the method is green, environmentally friendly, high in yield and easy to industrialize.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis and relates to a method for light-promoted synthesis of acetal compounds. Background Art

[0002] Acetals are useful molecular fragments in organic synthesis and other fields. Acetals are generally obtained by acid-catalyzed condensation of aldehydes and alcohols, or by noble metal-catalyzed dehydration coupling of alcohols and alcohols. With the development of photocatalytic technology, there are also reports on the multiphase synthesis of acetals using titanium dioxide photocatalysis of alcohols and alcohols, but the product yield is not high. In recent years, Vincent's group (Chem. Commun. 2017, 53, 12708-12711) and Hashmi's group (Org. Lett. 2020, 22, 5844-5849) reported C(sp 3 )-H bonds with alcohols to form transient fluorinated ethers from N-fluorobisbenzamide (NSFI) and ArI, respectively, in the presence of a base. Despite these advances, further development of C(sp 3 )-H function to accommodate more substrates. Summary of the invention

[0003] In view of the above technical problems, the present invention provides a method for light-promoted synthesis of acetal compounds. The method uses alcohol compounds and tetrahydrofuran as raw materials, ferric chloride or ferrous chloride as a catalyst, and dehydrogenation coupling occurs under light conditions to obtain acetals. The substrate has a wide range of applications, does not require the addition of any photosensitizer or ligand, can react at room temperature, is green and environmentally friendly, has a high yield, and is easy to industrialize.

[0004] To achieve the above object, the present invention adopts the following technical solutions:

[0005] The present invention provides a method for light-promoted synthesis of acetal compounds, comprising the following steps: using an alcohol compound shown in formula I and tetrahydrofuran as raw materials, using ferric chloride or ferrous chloride as a catalyst, and reacting at room temperature under light conditions and air atmosphere to obtain an acetal compound shown in formula II; the reaction equation is as follows:

[0006]

[0007] Wherein: R is selected from aryl, alkyl, alkenyl, alkynyl, heterocyclic group, aralkyl, aralkenyl, aralkynyl, fused heterocyclic group, fused heterocycloalkyl, fused heterocycloalkenyl, fused heterocycloalkynyl.

[0008] The usage ratio of the alcohol compound represented by formula I and tetrahydrofuran in the above technical solution is 0.4mmol:2mL.

[0009] The amount of the catalyst added in the above technical solution is 20 mol% of the compound shown in formula I.

[0010] The illumination condition in the above technical solution is blue light with a wavelength of 450nm.

[0011] Compared with the prior art, the present invention has the following beneficial effects:

[0012] The invention uses alcohol compounds and tetrahydrofuran as raw materials, ferric chloride or ferrous chloride as catalyst, and dehydrogenation coupling is carried out under light conditions to obtain acetal, which is completely different from the reaction mechanism of obtaining acetal by alcohol and alcohol catalytic dehydration coupling.

[0013] The reaction of the invention does not need to add any photosensitizer or ligand, can react at room temperature, is green and environmentally friendly, and has high yield; the tetrahydrofuran of the invention can react with various alcohols, has a wide substrate range, and the raw materials are cheap and easily available, and the cost is low; the operation is simple, does not require excessive treatment, does not require heating, and is easy to realize industrialization. DETAILED DESCRIPTION

[0014] The following examples are used to illustrate the present invention, but are not intended to limit the scope of the present invention. Unless otherwise specified, the technical means used in the examples are conventional means known to those skilled in the art. The test methods in the following examples are conventional methods unless otherwise specified.

[0015] Example 1

[0016] Take a glass test tube, add a magnetic stirrer, then add 0.08mmol of ferric chloride, 2mL of tetrahydrofuran (THF), and finally add 0.4mmol of 4-pentene-1-ol. Then place it under 450nm blue light at room temperature for 12h, and the reaction is completed. The final product is detected by TLC, and finally separated by column chromatography to obtain the final product: 2-(pent-4-ene-1-yloxy)tetrahydrofuran, with a yield of 81%.

[0017] The reaction equation for the above reaction is as follows:

[0018]

[0019] The nuclear magnetic resonance hydrogen spectrum of 2-(pent-4-en-1-yloxy)tetrahydrofuran is characterized as follows: 1H NMR (400MHz, CDCl3) δ6.01-5.72(m,1H),5.15-5.07(m,1H),5.06-4.90(m,2H),4.03-3.79(m,2H) ,3.74-3.57(m,1H),3.47-3.29(m,1H),2.24-2.04(m,2H),2.04-1.74(m,4H),1.76-1.55(m,2H).

[0020] The carbon NMR spectrum of 2-(pent-4-en-1-yloxy)tetrahydrofuran is characterized as follows: 13 C NMR (100MHz, CDCl3) δ138.2, 114.5, 103.7, 66.6, 66.4, 32.2, 30.3, 28.9, 23.4.

[0021] Example 2

[0022] Take a glass test tube, add a magnetic stirrer, then add 0.08mmol of ferric chloride, 2mL of tetrahydrofuran (THF), and finally add 0.4mmol of 2-alkyne-1-pentanol. Then place it under 450nm blue light at room temperature for 12h, and the reaction is completed. The final product is detected by TLC, and finally separated by column chromatography to obtain the final product: 2-(pent-2-alkyne-1-yloxy)tetrahydrofuran, with a yield of 77%.

[0023] The reaction equation for the above reaction is as follows:

[0024]

[0025] The nuclear magnetic resonance hydrogen spectrum of 2-(pent-2-yn-1-yloxy)tetrahydrofuran is characterized as follows: 1 H NMR(400MHz, CDCl3)δ5.40-5.17(m,1H),4.35-4.05(m,2H),3.99-3.75(m,2H), 2.41-2.15(m,2H),2.10-1.90(m,3H),1.90-1.70(m,1H),1.13(t,J=7.5Hz,3H).

[0026] The carbon NMR spectrum of 2-(pent-2-yn-1-yloxy)tetrahydrofuran is characterized as follows: 13 C NMR (100MHz, CDCl3) δ102.0,87.6,75.0,67.0,54.3,32.1,23.2,13.6,12.4.

[0027] Example 3

[0028] Take a glass test tube, add a magnetic stirrer, then add 0.08mmol of ferric chloride, 2mL of tetrahydrofuran (THF), and finally add 0.4mmol of but-3-yn-1-ol. Then place it under 450nm blue light at room temperature for 12h, and the reaction is completed. The final product is detected by TLC, and finally separated by column chromatography to obtain the final product: 2-(but-3-yn-1-yloxy)tetrahydrofuran, with a yield of 84%.

[0029] The reaction equation for the above reaction is as follows:

[0030]

[0031] The nuclear magnetic resonance hydrogen spectrum of 2-(but-3-yn-1-yloxy)tetrahydrofuran is characterized as follows: 1 H NMR (400MHz, CDCl3) δ5.22-5.02(m,1H),4.02-3.79(m,2H),3.79-3.68(m,1H),3.61-3.42(m,1H),2.65-2.33(m,2H),2.14-1.66(m,5H).

[0032] The carbon NMR spectrum of 2-(but-3-yn-1-yloxy)tetrahydrofuran is characterized as follows: 13 C NMR (100MHz, CDCl3) δ103.6,81.2,69.0,66.6,64.9,32.1,23.1,19.7.

[0033] Example 4

[0034] Take a glass test tube, add a magnetic stirrer, then add 0.08mmol of ferric chloride, 2mL of tetrahydrofuran (THF), and finally add 0.4mmol of 3-phenyl-2-propyn-1-ol. Then place it under 450nm blue light and react at room temperature for 12h, and the reaction ends. The final product is detected by TLC, and finally separated by column chromatography to obtain the final product: 2-((3-phenylprop-2-yn-1-yl)oxy)tetrahydrofuran, with a yield of 95%.

[0035] The reaction equation for the above reaction is as follows:

[0036]

[0037] The nuclear magnetic resonance hydrogen spectrum of 2-((3-phenylprop-2-yn-1-yl)oxy)tetrahydrofuran is characterized as follows: 1H NMR (400MHz, CDCl3) δ7.59-7.35(m,2H),7.37-7.21(m,3H),5.47-5.24(m,1H),4.63-4.28(m,2H),4.11-3.76(m,2H),2.30-1.62(m,4H).

[0038] The carbon NMR spectrum of 2-((3-phenylprop-2-yn-1-yl)oxy)tetrahydrofuran is characterized as follows: 13 C NMR (100MHz, CDCl3) δ131.7,128.3,128.1,122.6,102.2,85.6,85.1,67.2,54.5,32.2,23.2.

[0039] Example 5

[0040] Take a glass test tube, add a magnetic stirrer, then add 0.08mmol of ferric chloride, 2mL of tetrahydrofuran (THF), and finally add 0.4mmol of prop-2-yn-1-ol. Then place it under 450nm blue light at room temperature for 12h, and the reaction is completed. The final product is detected by TLC, and finally separated by column chromatography to obtain the final product: 2-(prop-2-yn-1-yloxy)tetrahydrofuran, with a yield of 83%.

[0041] The reaction equation for the above reaction is as follows:

[0042]

[0043] The nuclear magnetic resonance hydrogen spectrum of 2-(prop-2-yn-1-yloxy)tetrahydrofuran is characterized as follows: 1 H NMR (400MHz, CDCl3) δ5.27 (t, J = 2.9 Hz, 1H), 4.36-4.06 (m, 2H), 3.96-3.76 (m, 2H), 2.39 (t, J = 2.4 Hz, 1H), 2.17-1.71 (m, 4H).

[0044] The carbon NMR spectrum of 2-(prop-2-yn-1-yloxy)tetrahydrofuran is characterized as follows: 13 C NMR (100MHz, CDCl3) δ102.0,79.6,73.6,66.9,53.4,32.0,23.0.

[0045] Example 6

[0046] Take a glass test tube, add a magnetic stirrer, then add 0.08mmol of ferric chloride, 2mL of tetrahydrofuran (THF), and finally add 0.4mmol of 5-methylisoxazole-3-ol. Then place it under 450nm blue light for 12h at room temperature, and the reaction is completed. The final product is detected by TLC, and finally separated by column chromatography to obtain the final product: 5-methyl-3-((tetrahydrofuran-2-yl)oxy)isoxazole, with a yield of 86%.

[0047] The reaction equation for the above reaction is as follows:

[0048]

[0049] The nuclear magnetic resonance hydrogen spectrum of 5-methyl-3-((tetrahydrofuran-2-yl)oxy)isoxazole is characterized as follows: 1 H NMR (400MHz, CDCl3) δ6.06-5.89(m,1H),5.45(s,1H),4.27-3.94(m,1H),3.93-3.78(m,1H),2.55-2.08(m,6H),2.06-1.85(m,1H).

[0050] The carbon NMR spectrum of 5-methyl-3-((tetrahydrofuran-2-yl)oxy)isoxazole is characterized as follows: 13 C NMR (100MHz, CDCl3) δ171.2,169.5,98.5,84.7,69.1,28.4,24.9,13.5.

[0051] Example 7

[0052] Take a glass test tube, add a magnetic stirrer, then add 0.08mmol of ferric chloride, 2mL of tetrahydrofuran (THF), and finally add 0.4mmol of (E)-3,7-dimethyl-2,6-octadien-1-ol. Then place it under 450nm blue light at room temperature for 12h, and the reaction is completed. The final product is detected by TLC, and finally separated by column chromatography to obtain the final product: (E)-2-((3,7-dimethyl-2,6-octadien-1-yl)oxy)tetrahydrofuran, with a yield of 92%.

[0053] The reaction equation for the above reaction is as follows:

[0054]

[0055] The nuclear magnetic resonance hydrogen spectrum of (E)-2-((3,7-dimethyl-2,6-octadien-1-yl)oxy)tetrahydrofuran is characterized as follows: 1H NMR (400MHz, CDCl3) δ5.43-5.26(m,1H),5.21-5.12(m,1H),5.13-5.03(m,1H),4. 35-4.10(m,1H),4.04-3.71(m,3H),2.24-1.78(m,8H),1.67(s,6H),1.59(s,3H).

[0056] The carbon NMR spectrum of (E)-2-((3,7-dimethyl-2,6-octadien-1-yl)oxy)tetrahydrofuran is characterized as follows: 13 C NMR (100MHz, CDCl3) δ140.3,131.5,124.0,120.5,102.9,66.8,63.4,39.6,32.3,26.3,25.6,23.5,17.6,16.4.

[0057] Example 8

[0058] Take a glass test tube, add a magnetic stirrer, then add 0.08mmol of ferric chloride, 2mL of tetrahydrofuran (THF), and finally add 0.4mmol of pyridine-2-methanol. Then place it under 450nm blue light at room temperature for 12h, and the reaction is completed. The final product is detected by TLC, and finally separated by column chromatography to obtain the final product: 2-(((tetrahydrofuran-2-yl)oxy)methyl)pyridine, with a yield of 91%.

[0059] The reaction equation for the above reaction is as follows:

[0060]

[0061] Example 9

[0062] Take a glass test tube, add a magnetic stirrer, then add 0.08mmol of ferric chloride, 2mL of tetrahydrofuran (THF), and finally add 0.4mmol of benzyl alcohol. Then place it under 450nm blue light at room temperature for 12h, and the reaction is completed. The final product is detected by TLC, and finally separated by column chromatography to obtain the final product: 2-benzyloxytetrahydrofuran, with a yield of 91%.

[0063] The reaction equation for the above reaction is as follows:

[0064]

[0065] Example 10

[0066] Take a glass test tube, add a magnetic stirrer, then add 0.08mmol of ferric chloride, 2mL of tetrahydrofuran (THF), and finally add 0.4mmol of 3-phenyl-1-propanol. Then place it under 450nm blue light at room temperature for 12h, and the reaction is completed. The final product is detected by TLC, and finally separated by column chromatography to obtain the final product: 2-(3-phenylpropoxy)tetrahydrofuran, with a yield of 94%.

[0067] The reaction equation for the above reaction is as follows:

[0068]

[0069] Embodiment 11

[0070] Take a glass test tube, add a magnetic stirrer, then add 0.08mmol of ferric chloride, 2mL of tetrahydrofuran (THF), and finally add 0.4mmol of (E)-3-phenyl-2-propene-1-ol. Then place it under 450nm blue light at room temperature for 12h, and the reaction is completed. The final product is detected by TLC, and finally separated by column chromatography to obtain the final product: 2-(cinnamyloxy)tetrahydrofuran, with a yield of 82%.

[0071] The reaction equation for the above reaction is as follows:

[0072]

[0073] Example 12

[0074] Take a glass test tube, add a magnetic stirrer thereto, then add 0.08mmol of ferric chloride, 2mL of tetrahydrofuran (THF), and finally add 0.4mmol of 2-(naphthalene-1-yl) ethoxy) tetrahydrofuran. Then place it under 450nm blue light for room temperature reaction for 12h, and the reaction ends. The final product is detected by TLC, and finally separated by column chromatography to obtain the final product: 2-(2-(naphthalene-1-yl) ethoxy) tetrahydrofuran, with a yield of 96%.

[0075] The reaction equation for the above reaction is as follows:

[0076]

[0077] Example 13

[0078] Take a glass test tube, add a magnetic stirrer, then add 0.08mmol of ferric chloride, 2mL of tetrahydrofuran (THF), and finally add 0.4mmol of 2-(3-hydroxypropyl)isoindoline-1,3-dione. Then place it under 450nm blue light and react at room temperature for 12h, and the reaction is completed. The final product is detected by TLC, and finally separated by column chromatography to obtain the final product: 2-(3-((tetrahydrofuran-2-yl)oxy)propyl)isoindoline-1,3-dione, with a yield of 90%.

[0079] The reaction equation for the above reaction is as follows:

[0080]

[0081] Embodiment 14

[0082] Take a glass test tube, add a magnetic stirrer, then add 0.08mmol of ferric chloride, 2mL of tetrahydrofuran (THF), and finally add 0.4mmol of furan-2-methanol. Then place it under 450nm blue light at room temperature for 12h, and the reaction is completed. The final product is detected by TLC, and finally separated by column chromatography to obtain the final product: 2-(((tetrahydrofuran-2-yl)oxy)methyl)furan, with a yield of 62%.

[0083] The reaction equation for the above reaction is as follows:

[0084]

[0085] Examples 15 to 24

[0086] Examples 15 to 24 are basically the same as Example 11, except that the catalysts are different. The product yields under different catalyst conditions are shown in Table 1.

[0087] Table 1 Product yields under different catalyst conditions

[0088]

[0089]

[0090] As can be seen from Table 1, under different catalyst conditions, for substrates (E)-3-phenyl-2-propene-1-ol and tetrahydrofuran (THF), products can only be obtained when ferric chloride and ferrous chloride are used as catalysts, and ferric chloride is the best catalyst.

[0091] Embodiments 25 to 29

[0092] Examples 25 to 29 are substantially the same as Example 11, except that the amount of ferric chloride used is different. The yields of the product 2-(cinnamyloxy)tetrahydrofuran at different alcohol:ferric chloride molar ratios are shown in Table 2.

[0093] Table 2 Yield of product under different alcohol:ferric chloride molar ratio conditions

[0094] Example light source Alcohol: Ferric chloride molar ratio Yield Embodiment 25 450nm 1：0.01 23％ Embodiment 26 450nm 1：0.05 46％ Embodiment 27 450nm 1：0.1 77％ Embodiment 28 450nm 1：0.5 79％ Embodiment 29 450nm 1：1 76％

[0095] It can be seen from Table 2 that under different alcohol:ferric chloride molar ratio conditions, for the substrate (E)-3-phenyl-2-propene-1-ol and tetrahydrofuran (THF), the alcohol:ferric chloride molar ratio = 1:0.2 is the best ratio.

[0096] The embodiments described above are only preferred embodiments of the present invention and are only used to explain the present invention, not to limit the scope of implementation of the present invention. For those skilled in the art, other implementation methods can certainly be easily made by replacement or modification based on the technical contents disclosed in this specification. Therefore, all changes and improvements made on the principles of the present invention should be included in the scope of the patent application of the present invention.

Claims

1. A method for light-promoted synthesis of acetal compounds, characterized in that: The following steps are involved: The alcohol compound shown in formula I and tetrahydrofuran are used as raw materials, ferric chloride or ferrous chloride is used as a catalyst, and the acetal compound shown in formula II is obtained by reaction at room temperature under light conditions and air atmosphere; the reaction equation is as follows: Wherein: R is selected from aryl, alkyl, alkenyl, alkynyl, heterocyclic group, aralkyl, aralkenyl, aralkynyl, fused heterocyclic group, fused heterocycloalkyl, fused heterocycloalkenyl, fused heterocycloalkynyl.

2. The method according to claim 1, characterized in that: The usage ratio of the alcohol compound represented by formula I and tetrahydrofuran is 0.4 mmol:2 mL.

3. The method according to claim 1, characterized in that The amount of the catalyst added is 20 mol% of the compound shown in Formula I.

4. The method according to claim 1, characterized in that: The illumination condition is blue light with a wavelength of 450nm.

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