Preparation method of trifluoromethyl-substituted chroman-4-one compound

Abstract

The invention discloses a preparation method of a trifluoromethyl substituted chroman-4-one compound, and relates to the technical field of organic matter synthesis. According to the method, a Togni's reagent is used as a trifluoromethyl source, various 2-allyloxy benzaldehyde compounds are used as substrates, and a nonmetal photosensitizer is used, so that synthesis of various trifluoromethyl substituted chroman-4-ones and derivatives thereof is realized. By optimizing the synergistic effect of the photosensitizer and the light source, substrate limitation is broken through, the reaction stability is improved, and the problems that in the prior art, substrate applicability is limited, light source dependency is high, and the substrate yield is unstable are solved.

Description

Technical Field

[0001] The present invention relates to the technical field of organic compound synthesis, and in particular to a method for preparing a trifluoromethyl-substituted chroman-4-one compound. Background Art

[0002] Due to their unique biological activities, chroman-4-one compounds have attracted much attention in the field of medicinal chemistry. In particular, the introduction of a trifluoromethyl group can significantly improve the metabolic stability and lipophilicity of the compound. Currently, the synthesis of trifluoromethyl-substituted chroman-4-one compounds mainly includes the following two technical routes:

[0003] (1) Traditional transition metal catalysis. Early methods relied on transition metal catalysts (such as copper salts) or oxidants to achieve trifluoromethylation. For example, allyl salicylaldehyde reacted with different trifluoromethyl sources in the presence of transition metal copper (Chem. Commun. 2017, 53, 6440;), peroxide (Org. Lett. 2018, 20, 6520; CN109400564A), and photocatalytic C (sp 2 The above methods generally have the problems of high cost, harsh reaction conditions (high temperature, strong oxidant), and environmental unfriendliness, which limit their industrial application.

[0004] (2) Photocatalytic metal-free method. The patent application with publication number CN119350284A proposed an improved scheme: using 2-allyloxybenzaldehyde and sodium trifluoromethanesulfinate as raw materials, direct cyclization under violet light (380-450nm) irradiation, without the need for metal catalysts or oxidants. This method has the following advantages: green and safe: avoiding the use of hazardous reagents (such as phosphorus oxychloride, fuming nitric acid); low cost: the price of sodium trifluoromethanesulfinate is significantly lower than that of Togni reagent; simple operation: room temperature reaction, one-pot synthesis. However, this technology still has the following limitations: light source dependence: requires a specific wavelength of violet light (8WLED), and other light sources (such as blue light, white light) are inefficient (yield <30%); limited substrate applicability: poor compatibility with substrates containing strong electron-withdrawing groups (such as nitro groups) or large steric hindrance substituents; no photosensitizer is introduced to regulate the reaction path, resulting in large fluctuations in the yield of some complex substrates (45-95%).

[0005] Based on the above problems, there is an urgent need to develop a more universal and efficient photocatalytic reaction system. Summary of the Invention

[0006] The present invention provides a method for preparing a trifluoromethyl-substituted chroman-4-one compound. By optimizing the synergistic effect of a photosensitizer and a light source, the method overcomes substrate limitations and improves reaction stability, thereby solving many problems of the prior art, such as limited substrate applicability, strong light source dependence, and unstable substrate yield.

[0007] The technical solution adopted in the present invention is as follows:

[0008] A method for preparing a trifluoromethyl-substituted chroman-4-one compound, as shown in Formula 1, comprises reacting compound 1 and compound 2 in a solvent under the irradiation of a photocatalyst and blue light to obtain compound 3:

[0009]

[0010] Among them, the aryl group in compound 1 is an aromatic ring or an aromatic heterocycle, R 1 There are 1 to 3 functional groups distributed at different positions of the aromatic group, and R 1 、R 2 are any one of hydrogen, halogen, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, and substituted or unsubstituted ester; X is one of O, N, S, and C; and the photocatalyst is one of metal iridium photocatalyst, metal ruthenium photocatalyst, carbazole photocatalyst, and acridine photocatalyst.

[0011] Preferably, the compound 1 is one of the following compounds:

[0012]

[0013] Preferably, the photocatalyst is one of the following structures:

[0014]

[0015] Furthermore, the usage amount of the photocatalyst is 2-4% of 1 mole of the compound.

[0016] Preferably, the wavelength of the blue light is 450-465 nm.

[0017] Preferably, the solvent is at least one of N-dimethylformamide, methanol, acetonitrile, tetrahydrofuran and dimethyl sulfoxide.

[0018] Preferably, the molar ratio of compound 1 to compound 2 is 1:0.6-1.2.

[0019] Preferably, the reaction temperature of the reaction represented by Formula 1 is room temperature.

[0020] In summary, compared with the prior art, the present invention has the following advantages and beneficial effects:

[0021] 1. The present invention uses a non-metallic photosensitizer (such as 4CzIPN) for the first time to achieve an efficient trifluoromethylation reaction under blue light (450-465nm). The use of a non-metallic photosensitizer can effectively avoid the introduction of traditional metal catalysts, and the product has no risk of metal residue, meeting the high purity requirements of pharmaceutical intermediates.

[0022] 2. The present invention successfully expands the scope of substrate application by optimizing the photocatalytic system. For example, the substituents on the benzene ring can be nitro, halogen, ester, alkoxy, etc. The number of substituents can reach 1-3, and the yield is relatively stable.

[0023] 3. The reaction of the present invention is carried out at room temperature (20-30°C), without the need for high temperature or high pressure, and omitting oxidants (such as potassium persulfate), significantly reducing the risk of side reactions; after the one-pot synthesis, only simple extraction and column chromatography purification are required, simplifying the process and making it suitable for large-scale production.

[0024] 4. The present invention uses an inexpensive trifluoromethyl source (such as Togni's reagent) and a non-metallic photosensitizer to avoid dependence on precious metal catalysts (such as iridium and ruthenium), reducing raw material costs by more than 30%, and the reaction solvents (such as DMSO and DMF) can be recycled, which is in line with the principles of green chemistry. DETAILED DESCRIPTION

[0025] The present invention will be described in detail below in conjunction with specific embodiments, and the advantages and various effects of the present invention will be more clearly presented. It should be understood by those skilled in the art that these specific embodiments and examples are for illustrating the present invention, rather than limiting the present invention.

[0026] Throughout this specification, unless otherwise specified, the terms used herein should be understood as having the same meaning as commonly used in the art. Therefore, unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In the event of any conflict, the present specification shall take precedence.

[0027] Unless otherwise specified, various raw materials, reagents, instruments and equipment used in the present invention can be purchased from the market or prepared by existing methods.

[0028] The present application will be described in detail below with reference to specific embodiments and experimental data.

[0029] Example 1

[0030] In this example, compound 3a was prepared according to the following reaction formula:

[0031]

[0032] The reaction process is as follows: In a glove box, compound 1a, compound 2, and the photosensitizer 4CzIPN (2 mol%) are weighed sequentially into an 8 mL sample vial. DMSO (2 mL) is added, and the PTFE cap is tightened. The sample vial is removed from the glove box and exposed to 450-465 nm blue light. The reaction is allowed to proceed at room temperature for 24 hours. After completion of the reaction, the product is diluted with water and extracted three times with ethyl acetate. The organic phases are combined and the solvent is removed on a rotary evaporator to obtain a crude product. Column chromatography separation and purification yield the target compound 3a.

[0033] The NMR analysis data of compound 3a are as follows:

[0034] 1 H NMR (400MHz, CDCl3) δ7.75 (dd, J=8.0, 1.2Hz, 1H), 7.36 (dd, J=7.2, 0.8Hz, 1H), 6.96-6.92 (m, 1H), 4.7 7 (dd, J=11.2, 5.2Hz, 1H), 4.23 (t, J=11.9Hz, 1H), 3.17-3.01 (m, 2H), 2.25 (s, 3H), 2.15-2.01 (m, 1H).

[0035] 13 C NMR (100MHz, CDCl3) δ191.1, 159.8, 137.2, 127.2, 127.6 (d, J=274.7Hz), 125.2 , 121.2, 119.7, 69.7 (d, J=2.5Hz), 40.4 (d, J=1.7Hz), 29.6 (q, J=29.9HZ), 15.5.

[0036] 19 F NMR(376MHz, CDCl3)δ-64.0(s).

[0037] Example 2

[0038] The reaction was basically the same as Example 1, except that compound 1b was used as the substrate. The yield of the target product, compound 3b, was 57%, and its structural formula is as follows:

[0039]

[0040] The NMR analysis data of compound 3b are as follows:

[0041] 1H NMR (400MHz, CDCl3) δ7.89 (dd, J=7.8, 1.4Hz, 1H), 7.52-7.48 (m, 1H), 7.06-7.02 (m, 1H), 6.98 (d, J=8. 4Hz, 1H), 4.71 (dd, J=11.4, 5.0Hz, 1H), 4.23 (t, J=11.6Hz, 1H), 3.19-3.01 (m, 2H), 2.15-2.00 (m, 1H).

[0042] 13 C NMR (100MHz, CDCl3) δ190.9, 161.7, 136.5, 127.7, 126.8 (q, J=274.7Hz), 121 .9, 120.2, 118.0, 69.9 (d, J=1.5Hz), 40.6 (d, J=2.0Hz), 29.7 (q, J=30.0HZ).

[0043] 19 F NMR(376MHz, CDCl3)δ-64.0(s).

[0044] Example 3

[0045] The reaction was basically the same as Example 1, except that compound 1c was used as the substrate. The yield of the target product, compound 3c, was 62%, and its structural formula is as follows:

[0046]

[0047] The NMR analysis data of compound 3c are as follows:

[0048] 1 H NMR (400MHz, CDCl3) δ7.81 (dd, J=8, 1.6Hz, 1H), 7.50 (dd, J=7.6, 1.6Hz, 1H), 7.00-6.96 (m), 4.79 (dd, J=11.0, 5.0Hz, 1H), 4.22 (t, J=11.6Hz, 1H), 3.19-3.02 (m, 2H), 2.16-2.02 (m), 1.39 (s, 9H)..

[0049] 13 C NMR (100MHz, CDCl3) δ191.4, 160.8, 139.1, 133.4, 126.7 (q, J=274.7Hz), 125.7, 121.4, 120.9, 69.3, 40.4 (d, J=1.9Hz), 34.9, 29.8 (q, J=29.8Hz).

[0050] 19 F NMR(376MHz, CDCl3)δ-64.0(s).

[0051] Example 4

[0052] The reaction was basically the same as Example 1, except that compound 1d was used as the substrate. The yield of the target product, compound 3d, was 60%, and its structural formula is as follows:

[0053]

[0054] The NMR analysis data of compound 3d are as follows:

[0055] 1 H NMR (400MHz, CDCl3) δ7.78 (d, J=8.0Hz, 1H), 6.86 (d, J=8.4Hz, 1H), 6.79 (s, 1H), 4.68 (dd, J= 11.8, 5.0Hz, 1H), 4.21 (t, J=11.6Hz, 1H), 3.14-3.00 (m, 2H), 2.36 (s, 3H), 2.13-1.99 (m, 1H).

[0056] 13 C NMR (100MHz, CDCl3) δ190.5, 161.8, 148.2, 126.8 (q, J=274.7Hz), 127.6, 12 3.4, 118.0, 69.9 (d, J=1.4HZ), 40.6 (d, J=1.9HZ), 29.8 (q, J=29.9HZ), 22.1.

[0057] 19 F NMR(376MHz, CDCl3)δ-64.0(s).

[0058] Example 5

[0059] The reaction was basically the same as Example 1, except that compound 1e was used as the substrate. The yield of the target product, compound 3e, was 48%, and its structural formula is as follows:

[0060]

[0061] The NMR analysis data of compound 3e are as follows:

[0062] 1H NMR (400MHz, CDCl3) δ7.83 (d, J=8.8Hz, 1H), 6.60 (dd, J=8.8, 2.4Hz, 1H), 6.41 (d, J=2.4Hz, 1H), 4.69 (dd, J=11.2, 4.8Hz, 1H), 4.22 (t, J=11.4Hz, 1H), 3.84 (s, 3H), 3.14-3.01 (m, 2H), 2.12-2.01 (m, 1H).

[0063] 13 C NMR (100MHz, CDCl3) δ189.4, 166.4, 163.7, 126.9 (q, J=277.5Hz), 129.5, 114.0, 110.6, 100.8, 70.2, 55.8, 40.2, 29.8 (q, J=30Hz).

[0064] 19 F NMR(376MHz, CDCl3)δ-64.0(s).

[0065] Example 6

[0066] The reaction was basically the same as Example 1, except that compound 1f was used as the substrate. The yield of the target product, compound 3f, was 49%, and its structural formula is as follows:

[0067]

[0068] The NMR analysis data of compound 3f are as follows:

[0069] 1 H NMR (400MHz, CDCl3) δ7.93 (dd, J=8.8, 6.8Hz, 1H), 6.77 (td, J=8.6, 2.4Hz, 1H), 6.68 (dd, J=9.6, 2.4 Hz, 1H), 4.74 (dd, J=11.4, 5.0Hz, 1H), 4.25 (t, J=11.8Hz, 1H), 3.18-3.02 (m, 2H), 2.14-2.00 (m, 1H).

[0070] 13C NMR (100MHz, CDCl3) δ189.5, 167.8 (dd, J=255.6Hz), 163.4 (d, J=13.6Hz), 130.4 (d, J=11.5Hz), 126.7 (q, J=274.6 Hz), 117.1 (d, J=2.4HZ), 110.5 (d, J=22.8Hz), 104.9 (d, J=22.6Hz), 70.3, 40.4 (d, J=2.0Hz), 29.6 (q, J=29.9Hz).

[0071] 19 F NMR (376MHz, CDCl3) δ-64.0 (s), -99.4 (s).

[0072] Example 7

[0073] The reaction was basically the same as Example 1, except that compound 1g was used as the substrate. The yield of the target product, compound 3g, was 52%, and its structural formula is as follows:

[0074]

[0075] The NMR analysis data of compound 3g are as follows:

[0076] 1 H NMR (400MHz, CDCl3) δ7.85-7.83 (m, 1H), 7.04 (dd, J=6.6, 1.8Hz, 2H), 4.74 (dd, J =11.2, 5.2Hz, 1H), 4.24 (t, J = 11.8Hz, 1H), 3.18-3.00 (m, 2H), 2.15-2.01 (m, 1H).

[0077] 13 C NMR (100MHz, CDCl3) δ189.8, 162.0, 142.5, 129.0, 126.7 (q, J=274.8Hz), 122.8, 118.8, 118.2, 77.2, 76.8, 126.7 (q, J=30.1Hz).

[0078] 19 F NMR(376MHz, CDCl3)δ-64.0(s).

[0079] Example 8

[0080] The reaction was basically the same as Example 1, except that compound 1h was used as the substrate. The yield of the target product, compound 3h, was 33%, and its structural formula is as follows:

[0081]

[0082] The NMR analysis data of compound 3h are as follows:

[0083] 1 H NMR (400MHz, CDCl3) δ8.09-8.06 (m, 1H), 7.86 (dd, J=6.8, 2.0Hz, 2H), 4.85 (dd, J=11.6, 5. 2Hz, 1H), 4.33 (t, J=12.0Hz, 1H), 3.29-3.22 (m, 1H), 3.18-3.04 (m, 1H), 2.19-2.04 (m, 1H).

[0084] 13 C NMR (100MHz, CDCl3) δ189.6, 161.7, 152.5, 129.4, 126.4 (q, J=274.7Hz), 123.9, 116.3, 114.0, 70.3, 40.7 (d, J=2.0Hz), 126.7 (q, J=30.3Hz).

[0085] 19 F NMR(376MHz, CDCl3)δ-64.0(s).

[0086] Example 9

[0087] The reaction was basically the same as Example 1, except that compound 1i was used as the substrate. The yield of the target product, compound 3i, was 58%, and its structural formula is as follows:

[0088]

[0089] The NMR analysis data of compound 3i are as follows:

[0090] 1 H NMR (400MHz, CDCl3) δ7.69 (d, J=1.2Hz, 1H), 7.32 (dd, J=8.4, 2.0Hz, 1H), 6.89 (d, J=8.4Hz, 1H), 4.68 (dd, J=11.0, 5.0Hz, 1H), 4.21 (t, J=11.6Hz, 1H), 3.16-3.00 (m, 2H), 2.32 (s, 3H), 2.15-2.01 (m, 1H).

[0091] 13C NMR (100MHz, CDCl3) δ191.0, 159.7, 137.5, 131.3, 127.1, 126.6 (q, J=274.6Hz), 119.7, 117.7, 69.8, 40.6, 29.7 (q, J=29.9Hz), 20.4.

[0092] 19 F NMR(376MHz, CDCl3)δ-64.0(s).

[0093] Example 10

[0094] The reaction was basically the same as Example 1, except that compound 1j was used as the substrate. The yield of the target product, compound 3j, was 55%, and its structural formula is as follows:

[0095]

[0096] The NMR analysis data of compound 3j are as follows:

[0097] 1 H NMR (400MHz, CDCl3) δ7.89 (d, J=2.4Hz, 1H), 7.57 (dd, J=8.6, 2.6Hz, 1H), 6.93 (d, J=8.8Hz, 1H), 4.68 (dd, J=11.4, 5.0Hz, 1H), 4.22 (m, J=11.8Hz, 1H), 3.16-3.00 (m, 2H), 2.15-2.01 (m, 1H), 1.31 (s, 9H).

[0098] 13 C NMR (100MHz, CDCl3) δ191.2, 159.7, 144.9, 134.3, 126.8 (q, J=274.7Hz), 123.6, 11 9.4, 117.6, 69.9 (d, J=1.3Hz), 40.7 (d, J=1.9Hz), 34.5, 31.4, 29.8 (q, J=29.9Hz).

[0099] 19 F NMR(376MHz, CDCl3)δ-64.0(s).

[0100] Example 11

[0101] The reaction was basically the same as Example 1, except that compound 1k was used as the substrate. The yield of the target product, compound 3k, was 63%, and its structural formula is as follows:

[0102]

[0103] The NMR analysis data of compound 3k are as follows:

[0104] 1 H NMR (400MHz, CDCl3) δ8.57 (d, J=2.4Hz, 1H), 8.15 (dd, J=8.8, 2.4Hz, 1H), 7.03 (d, J=8.4Hz, 1H), 4.78 (dd, J=11.6, 5.2Hz, 1H), 4.28 (t, J=11.8Hz, 1H), 3.90 (s, 3H), 3.22-3.03 (m, 2H), 2.16-2.02 (m, 1H).

[0105] 13 C NMR (100MHz, CDCl3) δ184.5, 160.6, 159.3, 131.8, 124.8, 121.3 (q, J=274.7H z), 118.9, 114.4, 113.0, 64.7, 47.0, 35.2 (d, J=1.9Hz), 24.3 (q, J=30.1Hz).

[0106] 19 F NMR(376MHz, CDCl3)δ-64.0(s).

[0107] Example 12

[0108] The reaction was basically the same as Example 1, except that compound 11 was used as the substrate. The yield of the target product, compound 31, was 69%, and its structural formula is as follows:

[0109]

[0110] The NMR analysis data of compound 3l are as follows:

[0111] 1 H NMR (400MHz, CDCl3) δ7.56 (dd, J=8.4, 3.2Hz, 1H), 7.28-7.23 (m, 1H), 7.00 (dd, J=9.0, 4.2Hz, 1 H), 4.73 (dd, J=11.2, 5.2Hz, 1H), 4.24 (t, J=11.8Hz, 1H), 3.20-3.02 (m, 2H), 2.18-2.03 (m, 1H).

[0112] 13C NMR (100MHz, CDCl3) δ190.2, 158.4 (d, J=75.4Hz), 156.3, 126.6 (q, J=274.7HZ), 124.2 (d, J=24.4Hz), 12 0.6 (d, J=6.6Hz), 119.8 (d, J=7.4Hz), 112.6 (d, J=23.3Hz), 70.1 (d, J=1.4Hz), 40.6, 29.7 (q, J=30.0Hz).

[0113] 19 F NMR (376MHz, CDCl3) δ-64.0 (s), 120.7.

[0114] Example 13

[0115] The reaction was basically the same as Example 1, except that compound 1m was used as the substrate. The yield of the target product, compound 3m, was 76%, and its structural formula is as follows:

[0116]

[0117] The NMR analysis data of compound 3m are as follows:

[0118] 1 H NMR (400MHz, CDCl3) δ7.86 (d, J=2.8Hz, 1H), 7.44 (dd, J=8.8, 2.8Hz, 1H), 6.96 (d, J=8.8Hz, 1H ), 4.74 (dd, J=11.6, 5.2Hz, 1H), 4.23 (t, J=11.8Hz, 1H), 3.18-3.00 (m, 2H), 2.16-2.01 (m, 1H).

[0119] 13 C NMR (100MHz, CDCl3) δ189.8, 160.2, 136.4, 127.6, 127.0, 126.6 (q, J=273.5H z), 121.0, 119.8, 70.0 (d, J=1.4HZ), 40.5 (d, J=1.9HZ), 29.7 (q, J=30.1Hz).

[0120] 19 F NMR(376MHz, CDCl3)δ-64.0(s).

[0121] Example 14

[0122] The reaction was basically the same as Example 1, except that compound 1n was used as the substrate. The yield of the target product, compound 3n, was 48%, and its structural formula is as follows:

[0123]

[0124] The NMR analysis data of compound 3n are as follows:

[0125] 1 H NMR (400MHz, CDCl3) δ7.30 (d, J=3.2Hz, 1H), 7.11 (dd, J=8.8, 3.2Hz, 1H), 6.92 (d, J=8.8Hz, 1H), 4.67 (dd, J=11.6, 5.2Hz, 1H), 4.20 (t, J=11.6Hz, 1H), 3.80 (s, 3H), 3.16-2.99 (m, 2H), 2.16-2.01 (m, 1H).

[0126] 13 C NMR (100MHz, CDCl3) δ191.0, 156.4, 154.5, 125.8, 125.7 (q, J=274.8Hz), 120.0, 1 19.3, 107.9, 70.0 (d, J=1.3HZ), 55.9 (s), 40.6 (d, J=1.9Hz), 29.8 (q, J=29.9HZ).

[0127] 19 F NMR(376MHz, CDCl3)δ-64.0(s).

[0128] Example 15

[0129] This example is basically the same as Example 1, except that the substrate used is compound 1 o , to obtain the target product compound 3 o The yield is 54%, and its structural formula is as follows:

[0130]

[0131] Compound 3 o The NMR analysis data are as follows:

[0132] 1 H NMR (400MHz, CDCl3) δ7.35-7.31 (m, 1H), 6.85-6.81 (m, 2H), 4.66 (dd, J=11.2, 4.8H z, 1H), 4.20 (t, J=11.6Hz, 1H), 3.15-2.97 (m, 2H), 2.62 (s, 3H), 2.14-2.00 (m, 1H).

[0133] 13C NMR (100MHz, CDCl3) δ191.1, 161.6, 141.6, 134.2, 125.9 (q, J=274.7Hz), 124.1, 117.8, 114.9, 68.2 (d, J=1.6Hz), 40.4 (d, J=1.7Hz), 28.8 (q, J=29.7Hz), 21.97.

[0134] 19 F NMR(376MHz, CDCl3)δ-64.0(s).

[0135] Example 16

[0136] The reaction was basically the same as Example 1, except that compound 1p was used as the substrate. The yield of the target product, compound 3p, was 63%, and its structural formula is as follows:

[0137]

[0138] The NMR analysis data of compound 3p are as follows:

[0139] 1 H NMR (400MHz, CDCl3) 7.41-7.37 (m, 1H), 6.58-6.52 (m, 2H), 4.64 (dd, J=11.6, 4.8H z, 1H), 4.19 (t, J=11.2Hz, 1H), 3.90 (s, 3H), 3.12-2.98 (m, 2H), 2.12-1.97 (m, 1H).

[0140] 13 C NMR (100MHz, CDCl3) δ189.1, 163.0, 161.0, 136.3, 126.8 (q, J=274.6Hz), 110.5 , 109.8, 104.1, 69.2 (d, J=1.3Hz), 56.2, 41.3 (d, J=2.0Hz), 29.6 (q, J=29.6Hz).

[0141] 19 F NMR(376MHz, CDCl3)δ-64.0(s).

[0142] Example 17

[0143] The reaction was basically the same as Example 1, except that compound 1q was used as the substrate. The yield of the target product, compound 3q, was 77%, and its structural formula is as follows:

[0144]

[0145] The NMR analysis data of compound 3q are as follows:

[0146] 1 H NMR (400MHz, CDCl3) δ7.46-7.41 (m, 1H), 6.80 (d, J=8.8Hz, 1H), 6.75-6.70 (m, 1H), 4.71 (dd, J=11.6, 5.2Hz, 1H), 4.24 (t, J=11.8Hz, 1H), 3.18-3.00 (m, 2H), 2.14-2.00 (m, 1H).

[0147] 13 C NMR (100MHz, CDCl3) δ188.2, 161.8 (d, J = 264.9Hz), 162.2 (d, J = 2.9Hz), 136.4 (d, J = 11.7Hz), 126.6 (q, J = 274.7Hz) 11 3.6 (d, J=4.0Hz), 110.3 (d, J=9.3Hz), 109.2 (d, J=10.9Hz), 69.6 (d, J=1.5Hz), 41.1 (d, J=1.8Hz), 29.4 (q, J=29.9Hz).

[0148] 19 F NMR (376MHz, CDCl3) δ-64.0 (s), -110.1 (s).

[0149] Example 18

[0150] The reaction was basically the same as Example 1, except that compound 1r was used as the substrate. The yield of the target product, compound 3r, was 85%, and its structural formula is as follows:

[0151]

[0152] The NMR analysis data of compound 3r are as follows:

[0153] 1 H NMR (400MHz, CDCl3) δ7.37-7.33 (m, 1H), 7.06 (d, J=7.6Hz, 1H), 6.91 (m, J=8.4Hz, 1H), 4. 70 (dd, J=11.2, 5.2Hz, 1H), 4.23 (t, J=11.8Hz, 1H), 3.21-2.99 (m, 2H), 2.14-2.00 (m, 1H).

[0154] 13C NMR (100MHz, CDCl3) δ188.9, 163.0, 135.3, 134.9, 126.7 (q, J=274.7Hz) 125.2, 117.6, 117.1, 69.4, 41.2 (d, J=1.9Hz), 29.7 (q, J=30.0Hz).

[0155] 19 F NMR(376MHz, CDCl3)δ-64.0(s).

[0156] Example 19

[0157] The reaction was basically the same as Example 1, except that compound 1s was used as the substrate. The yield of the target product, compound 3s, was 68%, and its structural formula is as follows:

[0158]

[0159] The NMR analysis data of compound 3s are as follows:

[0160] 1 H NMR (400MHz, CDCl3) δ7.81 (d, J=2.4Hz, 1H), 7.58 (d, J=2.4Hz, 1H), 4.75 (dd, J=11.2, 4.8Hz, 1H) , 4.21 (t, J=11.6Hz, 1H), 3.16-3.01 (m, 2H), 2.07-2.02 (m, 5.1Hz, 1H), 1.40 (s, 9H), 1.32 (s, 9H).

[0161] 13 C NMR (100MHz, CDCl3) δ191.7, 158.7, 143.8, 138.4, 131.1, 126.8 (q, J=274.7Hz), 12 1.6, 120.2, 69.3, 40.5 (d, J=1.9Hz), 35.1, 34.5, 31.3, 29.7, 29.9 (q, J=274.8Hz).

[0162] 19 F NMR(376MHz, CDCl3)δ-64.0(s).

[0163] Example 20

[0164] The reaction was basically the same as Example 1, except that compound 1t was used as the substrate. The yield of the target product, compound 3t, was 74%, and its structural formula is as follows:

[0165]

[0166] The NMR analysis data of compound 3t are as follows:

[0167] 1 H NMR (400MHz, CDCl3) δ7.81 (d, J=1.6Hz, 1H), 7.47-7.44 (m, 1H), 4.84 (dd, J=11.6, 5.2H z, 1H), 4.30 (t, J=11.8Hz, 1H), 3.24-3.00 (m, 2H), 2.18-2.04 (dp, J=15.7, 10.2Hz, 1H).

[0168] 13 C NMR (100MHz, CDCl3) δ188.6 (d, J=3.0Hz), 151.6 (d, J=253.7HZ), 149.3 (d, J=11.6Hz), 126.5 (q, J=274.8 Hz) 125.6, 125.4 (d, J=1.9Hz), 122.9, 113.2 (d, J=7.4Hz), 70.6, 40.7 (d, J=1.9HZ), 29.6 (q, J=30.3Hz).

[0169] 19 F NMR (376MHz, CDCl3) δ-64.0 (s), -131.3 (s).

[0170] Example 21

[0171] The reaction was basically the same as Example 1, except that compound 1u was used as the substrate. The yield of the target product, compound 3u, was 47%, and its structural formula is as follows:

[0172]

[0173] The NMR analysis data of compound 3u are as follows:

[0174] 1 H NMR (400MHz, CDCl3) δ7.81 (d, J=1.6Hz, 1H), 7.47-7.44 (m, 1H), 4.84 (dd, J=11.6, 5.2Hz , 1H), 4.30 (t, J=11.8Hz, 1H), 3.24-3.17 (m, 1H), 3.14-3.00 (m, 1H), 2.18-2.04 (m, 1H).

[0175] 13C NMR (100MHz, CDCl3) δ188.5 (d, J=3.0Hz), 151.4 (d, J=253.7HZ), 149.1 (d, J=11.6Hz), 125.5, 125.3 (d, J =1.9Hz), 125.2 (q, J=274.7Hz), 122.7, 113.1 (d, J=7.4Hz), 70.4, 40.5 (d, J=1.9Hz), 29.5 (q, J=30.3Hz).

[0176] 19 F NMR(376MHz, CDCl3)δ-64.0(s).

[0177] Example 22

[0178] The reaction was basically the same as Example 1, except that compound 1v was used as the substrate. The yield of the target product, compound 3v, was 87%, and its structural formula is as follows:

[0179]

[0180] The NMR analysis data of compound 3v are as follows:

[0181] 1 H NMR (400MHz, CDCl3) δ7.08 (d, J=1.6Hz, 1H), 6.95 (d, J=2.0Hz, 1H), 4.72 (dd, J= 11.6, 5.2Hz, 1H), 4.24 (t, J=11.8Hz, 1H), 3.20-2.99 (m, 2H), 3.14-2.00 (m, 1H).

[0182] 13 C NMR (100MHz, CDCl3) δ187.8, 162.9, 140.9, 135.8, 126.5 (q, J=274.7Hz) 125.3, 117.1, 116.0, 69.5 (d, J=1.4Hz), 41.0 (d, J=1.8Hz), 29.5 (q, J=30.0Hz).

[0183] 19 F NMR(376MHz, CDCl3)δ-64.0(s).

[0184] Example 23

[0185] The reaction was basically the same as Example 1, except that compound 1w was used as the substrate. The yield of the target product, compound 3w, was 42%, and its structural formula is as follows:

[0186]

[0187] The NMR analysis data of compound 3w are as follows:

[0188] 1 H NMR (400MHz, CDCl3) δ9.39 (d, J=8.4Hz, 1H), 7.95 (d, J=8.8Hz, 1H), 7.77 (d, J=8.0Hz, 1H), 7.67-7.63 (m, 1H), 7.47-7.44 ( m, 1H), 7.11 (d, J=8.8Hz, 1H), 4.79 (dd, J=11.2, 5.2Hz, 1H), 4.37 (t, J=11.6Hz, 1H), 3.27-3.06 (m, 2H), 2.24-2.10 (m, 1H).

[0189] 13 C NMR (100MHz, CDCl3) δ191.6, 163.7, 138.1, 131.6, 130.0, 129.4, 128.7, 126.9 (q, J= 274.7Hz) 125.8, 125.2, 118.6, 111.9, 69.8, 41.1 (d, J=2.0HZ), 30.1 (q, J=29.6HZ).

[0190] 19 F NMR(376MHz, CDCl3)δ-63.8(s).

[0191] Example 24

[0192] The reaction was basically the same as Example 1, except that compound 1x was used as the substrate. The yield of the target product, compound 3x, was 83%, and its structural formula is as follows:

[0193]

[0194] The NMR analysis data of compound 3x are as follows:

[0195] 1 H NMR (400MHz, CDCl3) δ8.50 (dd, J=3.8, 1.4Hz, 1H), 7.47-7.41 (m, 2H), 4.80 (dd, J=11.6, 5.2Hz, 1H), 4.32 (t, J=12.0Hz, 1H), 3.35-3.27 (m, 1H), 3.18 (m, 1H), 3.25-3.12 (m, 1H).

[0196] 13C NMR (100MHz, CDCl3) δ189.3, 159.4, 144.8, 136.1, 129.6, 126.8, 126.4 (q, J=274.7HZ), 69.9 (d, J=1.8HZ), 41.3 (d, J=2.1Hz), 29.5 (q, J=30.1Hz).

[0197] 19 F NMR(376MHz, CDCl3)δ-64.0(s).

[0198] Example 25

[0199] The reaction was basically the same as Example 1, except that compound 1y was used as the substrate. The yield of the target product, compound 3y, was 34%, and its structural formula is as follows:

[0200]

[0201] The NMR analysis data of compound 3y are as follows:

[0202] 1 H NMR (400MHz, CDCl3) δ7.91 (dd, J=7.8, 1.4Hz, 1H), 7.537.49 (m, 1H), 7.087.04 (m, 1H), 6 .99 (d, J=8.4Hz, 1H), 4.35 (q, J=11.3Hz, 2H), 2.57 (qd, J=11.6, 1.2Hz, 2H), 1.35 (s, 3H).

[0203] 13 C NMR (100MHz, CDCl3) δ193.9, 160.8, 136.2, 128.2, 126.3 (q, J=276.4Hz), 122.0, 118.9, 117.8, 73.9 (d, J=2.1Hz), 36.3 (q, J=28.6Hz), 42.6, 18.6.

[0204] 19 F NMR (376MHz, CDCl3) δ-59.5 (s).

[0205] Example 26

[0206] The reaction was basically the same as Example 1, except that compound 1z was used as the substrate. The yield of the target product, compound 3z, was 62%, and its structural formula is as follows:

[0207]

[0208] The NMR analysis data of compound 3z are as follows:

[0209] 1 H NMR (400MHz, CDCl3) δ7.91 (dd, J=8.0, 1.6Hz, 1H), 7.45-7.41 (m, 1H), 6.80-6.72 (m, 2H), 3 .61 (dd, J=12.0, 5.2Hz, 1H), 3.33 (t, J=12.4Hz, 1H), 3.15-2.97 (m, 5H), 2.14-2.00 (m, 1H).

[0210] 13 C NMR (100MHz, CDCl3) δ192.2, 152.3, 135.8, 128.6, 127.1 (q, J=274.7Hz), 118.8, 117.5, 113.2, 55.5, 41.0 (d, J=1.7Hz), 39.4.30.8 (q, J=29.3Hz).

[0211] 19 F NMR (376MHz, CDCl3) δ63.8 (s).

[0212] Example 27

[0213] The reaction was basically the same as Example 1, except that compound 1aa was used as the substrate. The yield of the target product, compound 3aa, was 58%, and its structural formula is as follows:

[0214]

[0215] The NMR analysis data of compound 3aa are as follows:

[0216] 1 H NMR (400MHz, CDCl3) δ7.90-7.86 (m, 2H), 7.55-7.49 (m, 3H), 7.22-7.49 (m, 3H), 4.68 (dd, J=14.4, 4.8H z, 1H), 3.61 (t, J=13.9Hz, 1H), 2.98-2.84 (m, 1H), 2.44-2.37 (m, 1H), 2.32 (s, 3H), 1.89-1.75 (m, 1H).

[0217] 13C NMR (100MHz, CDCl3) δ191.6, 144.9, 142.2, 136.6, 135.2, 130.3, 128.3, 127.0 (J=274.9 Hz), 126.8, 125.6, 124.3, 124.1, 50.1, 39.6 (d, J=1.9Hz), 30.8 (q, J=29.7Hz), 21.6 (s).

[0218] 19 F NMR (376MHz, CDCl3) δ63.8 (s).

[0219] Example 28

[0220] The reaction was basically the same as Example 1, except that compound 1ba was used as the substrate. The yield of the target product, compound 3ba, was 58%, and its structural formula is as follows:

[0221]

[0222] The NMR analysis data of compound 3ba are as follows:

[0223] 1 H NMR (400MHz, CDCl3) δ8.41 (d, J=2.0Hz, 1H), 8.17 (dd, J=8.6, 2.2Hz, 1H), 7.07 (d, J=8.8Hz, 1H), 4.78 (dd, J=11.6, 5.2H z, 1H), 4.37-4.32 (m, 2H), 4.32-4.26 (m, 1H), 3.23-3.04 (m, 2H), 2.75 (s, 3H), 2.18-2.04 (m, 1H), 1.38 (t, J=7.0Hz, 3H).

[0224] 13 C NMR (100MHz, CDCl3) δ188.8, 167.1, 162.2, 160.5 (d, J=115.7Hz), 133.3, 126.1, 125.5 (q, J=2 75.0Hz), 125.3, 120.9, 119.1, 117.9, 68.9, 60.3, 39.4, 30.4, 28.6 (q, J=30.1Hz), 16.4, 13.3.

[0225] 19 F NMR(376MHz, CDCl3)δ-64.0(s).

[0226] Finally, it should be noted that the terms "comprises," "comprising," or any other variations thereof are intended to encompass non-exclusive inclusion, such that a process, method, article, or apparatus comprising a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus. Although preferred embodiments of the present invention have been described, additional changes and modifications may be made to these embodiments by those skilled in the art once the basic inventive concepts are known. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments and all changes and modifications that fall within the scope of the invention.

[0227] The above-described embodiments merely represent specific implementation methods of the present application. While the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of protection of the present application. It should be noted that a person skilled in the art would be able to make numerous variations and improvements without departing from the technical concept of the present application, and all such variations and improvements fall within the scope of protection of the present application.

Claims

1. A method for preparing a trifluoromethyl-substituted chroman-4-one compound, characterized in that: The preparation method is shown in Formula 1. Under the conditions of photocatalyst and blue light irradiation, compound 1 and compound 2 react in a solvent to obtain compound 3: Among them, the aryl group in compound 1 is an aromatic ring or an aromatic heterocycle, R 1 There are 1 to 3 functional groups distributed at different positions of the aromatic group, and R 1 、R 2 are any one of hydrogen, halogen, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, and substituted or unsubstituted ester; X is one of O, N, S, and C; and the photocatalyst is one of metal iridium photocatalyst, metal ruthenium photocatalyst, carbazole photocatalyst, and acridine photocatalyst.

2. The preparation method according to claim 1, wherein The compound 1 is one of the following compounds:

3. The preparation method according to claim 1, wherein The photocatalyst is one of the following structures:

4. The preparation method according to claim 3, wherein The usage amount of the photocatalyst is 2-4% of 1 mol of the compound.

5. The preparation method according to claim 1, wherein The wavelength of the blue light is 450-465nm.

6. The preparation method according to claim 1, wherein The solvent is at least one of N,N-dimethylformamide, methanol, acetonitrile, tetrahydrofuran and dimethyl sulfoxide.

7. The preparation method according to claim 1, wherein The molar ratio of the compound 1 to the compound 2 is 1:0.6-1.

2.

8. The preparation method according to claim 1, wherein The reaction temperature of the reaction shown in Formula 1 is room temperature.

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