A fluorine-containing azide derivative and its preparation method and application

Abstract

The present invention relates to a fluorinated azide derivative, its preparation method, and application. The fluorinated azide derivative is represented by the following general structural formula I or II: wherein R1, R2, and R3 are each selected from any one or more of phenyl, substituted aryl, alkyl, heterocyclic, or hydrogen. The fluorinated azide derivative is obtained by reacting a fluoroalkyl iodide derivative, an azidating agent, a catalyst, a free radical initiator, and an organic solvent. Compared with existing technologies, the present invention has the advantages of high efficiency, i.e., short reaction time, high yield (over 90%), and mild reaction conditions.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthetic chemistry, and in particular to a fluorine-containing azide derivative and a preparation method and application thereof. Background Art

[0002] Azide compounds have a long history of research and are widely used in fields such as synthetic chemistry, medicinal chemistry, and materials science. For example, azide compounds were the first anti-AIDS drug approved by the US Food and Drug Administration (FDA). A thymidine analog, with an azide group replacing the hydroxyl group at the 3' position of the ribose sugar structure, has been shown to competitively inhibit HIV reverse transcriptase, thereby terminating viral DNA synthesis. Azidocillin, another clinically used azide drug, is a penicillin derivative found to have significant bactericidal activity against Gram-positive bacteria such as Streptococcus and Staphylococcus. The booming development of "click chemistry" in recent decades has further highlighted the value of azides. Furthermore, azide compounds, as important precursors for organic synthesis, serve as raw materials for classic organic chemical reactions such as the Staudinger reaction, Curtius rearrangement, click reaction, Schmidt rearrangement, and 1,3-dipolar addition reaction. The preparation of azide compounds requires azidating reagents. Most azidating reagents are explosive and toxic. For example, silver azide (AgN3), lead azide (PbN6), and sodium azide (NaN3) are highly explosive, making the search for alternatives essential. Among them, trimethylsilyl azide (TMSN3) is a colorless, transparent liquid with a boiling point of 95°C. It is a commercially available azidating reagent. Compared to hydrazoic acid and sodium azide, it is less explosive and has high thermal stability, decomposing very slowly even at temperatures reaching 200°C. TMSN3 is miscible with most organic solvents, such as toluene, dichloromethane, and diethyl ether, and can react in many organic solvents, making it easier to work with and yielding better results. Therefore, TMSN3 can serve as an ideal alternative to metal azidating reagents. In addition, the various advantages of azide compounds have attracted chemists to study them. However, in recent years, research on the preparation of azides using carbon-halogen bonds has been rare, especially research on carbon-iodine bonds. In addition, with the continuous development of fluorine-containing organic chemical synthesis methodologies, chemists have effectively introduced fluorine atoms or fluorine-containing groups into organic compound molecules and developed a variety of fluorine-related reactions, resulting in organic compounds or drugs with significantly improved physical, chemical, and physiological properties compared to their parent molecules. Therefore, exploring and developing economical and highly reactive fluorine-containing azide building blocks and establishing effective synthetic methodologies using fluorine-containing azide building blocks is of paramount importance.

[0003] In 1990, Archibald et al. reported that difluorochloroalkyl ketone derivatives reacted in a dimethyl sulfoxide solution of sodium azide to generate fluorinated azide derivatives. As shown in the following formula:

[0004]

[0005] In 2011, Lwasa et al. reported that monofluorochloroalkyl ketone derivatives reacted in a dimethyl sulfoxide solution of sodium azide to generate monofluoroazidoalkyl ketone derivatives. As shown in the following formula:

[0006]

[0007] In 2021, Chung et al. reported that monofluorochloroaryl ketone derivatives reacted in a 1,2-dichloroethane solution of tetrabutylammonium azide to generate monofluoroazidoaryl ketone derivatives. As shown in the following formula:

[0008] Summary of the Invention

[0009] The present invention aims to provide a fluorine-containing azide derivative using a fluoroalkyl iodide derivative as a precursor, and a preparation method and application thereof, so as to achieve mild reaction conditions, simple operation, and high yield preparation of the target product.

[0010] The purpose of the present invention can be achieved by the following technical solutions:

[0011] One of the technical solutions of the present invention is to provide a fluorine-containing azide derivative represented by the following structural formula I or II:

[0012]

[0013] wherein R1, R2, and R3 are all selected from any one or more of phenyl, substituted aryl, alkyl, heterocycle, or hydrogen;

[0014] The substituents in the substituted aryl group are selected from any one or more of phenyl, hydrogen, fluorine, bromine, chlorine, iodine, C1-C4 alkyl, nitro, p-methoxy, methyl ethyl ether, trifluoromethyl, trifluoromethoxy, p-tert-butoxy, p-diphenyl ether, p-1,3-benzodioxole, p-halogen-substituted benzene or benzyl;

[0015] The heterocyclic ring is selected from any one or more of thiophene, furan, indole, pyrrole, thiophene homologues, furan homologues, indole homologues, pyrrole homologues or oxazole rings.

[0016] In some specific embodiments, the fluorine-containing azide derivative is selected from any one or more of compounds 1-31 represented by the following structural formulas:

[0017]

[0018]

[0019] A second technical solution of the present invention is to provide a method for preparing a fluorinated azide derivative as described in one of the above technical solutions, comprising: reacting a fluoroalkyl iodide derivative, an azidation reagent, a catalyst, a free radical initiator, and an organic solvent; and extracting and separating and purifying the fluorinated azide derivative after the reaction.

[0020] The fluoroalkyl iodide derivative is selected from the following compounds of the general structural formula III or IV:

[0021]

[0022] In some embodiments, the azidation reagent is selected from any one or more of ethyl azidoacetate (AAE), trimethylsilyl azide, or diphenylphosphoryl azide (DPPA).

[0023] The trimethylsilyl azide is also preferably TMSA or TMSN3.

[0024] In some specific embodiments, the catalyst is selected from any one or more of FeCl2, FeCl3, Fe(OAc)2, Fe(OTf)2, and Fe(OTf)3.

[0025] In some specific embodiments, the free radical initiator is selected from any one or more of tert-butyl perbenzoate (TBPB), azobisisobutyronitrile (AIBN), dilauroyl peroxide (LPO), dibenzoyl peroxide (BPO), 2,2′-bis(diphenylphosphine)benzophenone (DPBP), tert-butyl peroxide or tert-butyl hydroperoxide.

[0026] In some specific embodiments, the organic solvent is selected from any one or more of ethylene glycol dimethyl ether, tetrahydrofuran, dichloromethane, methanol, 1,4-dioxane, dimethyl sulfoxide, diethyl ether, cyclopentyl methyl ether or acetonitrile.

[0027] In some specific embodiments, the ratio of the fluoroalkyl iodide derivative to the organic solvent is 1 g:10 mL.

[0028] In some specific embodiments, the equivalent ratio of the fluoroalkyl iodide derivative, catalyst, azidation reagent, and free radical initiator is 1:(0.2-0.4):(1.1-1.3):(0.9-1.2).

[0029] In some specific embodiments, the reaction temperature during the reaction is 25° C.-80° C., and the reaction time is 0.5-12 h.

[0030] Furthermore, in some specific embodiments, the extract in the extraction process is selected from a mixture of ethyl acetate and water, and the volume ratio of ethyl acetate to water is (0.8-1.0):1.0;

[0031] Column chromatography was used for separation and purification, and the eluent of the column chromatography was petroleum ether.

[0032] The reaction formula of the fluorine-containing azide derivative is:

[0033]

[0034] A third technical solution of the present invention is to provide an application of the fluorine-containing azide derivative as described in one of the above technical solutions, wherein the fluorine-containing azide derivative is used as a fluorine-containing building block in an organic synthesis reaction.

[0035] Compared with the prior art, the present invention has the following beneficial effects:

[0036] The method for preparing fluorinated azide derivatives of the present invention has the advantages of high efficiency (i.e., short reaction time), high yield (over 90%), and mild conditions. It has good prospects for industrial production and strong application potential in the pharmaceutical and pesticide fields. Furthermore, the prepared fluorinated azide derivatives can be used as azide-containing building blocks in various organic synthesis reactions. DETAILED DESCRIPTION

[0037] The present invention is described in detail below with reference to specific embodiments. This embodiment is implemented based on the technical solution of the present invention, and provides a detailed implementation method and specific operation process, but the protection scope of the present invention is not limited to the following embodiments.

[0038] In the following examples, unless otherwise specified, raw materials or processing techniques are conventional commercially available raw materials or conventional processing techniques in the art.

[0039] The fluoroalkyl iodide derivatives with the general structural formula Ⅲ can be synthesized by reference to the literature: doi:10.1016 / j.cclet.2015.07.007.

[0040] The fluoroalkyl iodide derivatives shown in the general structural formula IV, and their synthesis methods can be found in the literature: doi: 10.1002 / ejoc.202200137.

[0041] Example 1: Compound 1 (2-azido-2,2-difluoro-1-phenylethane-1-one) and its preparation method

[0042] Add Fe(OTf)2 (0.2123 g, 0.6 mmol, 0.3 equiv) to a dry, clean reaction tube. Evacuate the tube and backfill with nitrogen (repeat three times). Then, add 2-iodo-2,2-difluoroacetophenone derivative III-1 (0.5000 g, 1.69 mmol, 1.0 equiv), TMSN3 (0.2336 g, 2.027 mmol, 1.2 equiv), and TBPB (0.3281 g, 1.77 mmol, 1.0 equiv) dissolved in 1,4-dioxane (5.0 mL) to the reaction tube. Stir the reaction mixture at 25°C for 0.5 h. Reaction proceeds until the starting material is completely reacted, as monitored by TLC. After the reaction is completed, 1,4-dioxane is first removed by rotary evaporation under reduced pressure. After the rotary evaporation is completed, ethyl acetate (10 mL) and water (10 mL) are added to the reaction system and extracted three times; after the extraction is completed, the aqueous layer is extracted twice with ethyl acetate (20 mL); the aqueous layer is discarded, the organic layers are combined, and anhydrous sodium sulfate (5 g) is added to dry (about 0.5 h); after drying, the mixture is filtered, the organic solvent in the filtrate is removed by rotary evaporation, and column chromatography is performed with petroleum ether as eluent (1 h) to obtain a colorless oil, namely compound 1: 2-azido-2,2-difluoro-1-phenylethane-1-one, whose structural formula is shown below, and the yield is 98%.

[0043]

[0044] The NMR data of 2-azido-2,2-difluoro-1-phenylethane-1-one prepared in this example are as follows:

[0045] 1 H NMR (400MHz, CDCl3): δ8.10 (d, J = 8.0 Hz, 2H), 7.69 (t, J = 8.0 Hz, 1H), 7.53 (t, J = 8.0 Hz, 2H).

[0046] 13 C NMR (100MHz, CDCl3): δ183.25(t,J C-F =34.0Hz), 135.17, 130.42 (t, J = 3.0Hz), 128.91, 128.57, 115.47 (t, J = 372.0Hz).

[0047] 19 F NMR (376MHz, CDCl3): δ-78.02 (s, 2F).

[0048] HRMS (APCI-QE, m / z) [M+H] +Calcd.for C8H5F2N3O+H,198.1403; found,198.1402.

[0049] Example 2: Compound 2 (2-azido-2,2-difluoro-1-(p-tolyl)ethane-1-one) and its preparation method

[0050] Compared with Example 1, most of the methods are the same, except that the raw materials are: Fe(OTf)2 (0.1793 g, 0.5 mmol, 0.3 equiv), 1,4-dioxane (5.0 mL), 2-iodo-2,2-difluoroacetophenone derivative III-2 (0.5000 g, 1.69 mmol, 1.0 equiv), TMSN3 (0.2452 g, 2.13 mmol, 1.2 equiv) and TBPB (0.3444 g, 1.77 mmol, 1.0 equiv).

[0051] Finally, a colorless oily substance was obtained, namely compound 2: 2-azido-2,2-difluoro-1-(p-tolyl)ethane-1-one, the structural formula of which is shown below. The yield was 99%.

[0052]

[0053] The NMR data of 2-azido-2,2-difluoro-1-(p-tolyl)ethane-1-one prepared in this example are as follows:

[0054] 1 H NMR (400MHz, CDCl3): δ7.44 (d, J = 8.0 Hz, 2H), 6.72 (d, J = 7.8 Hz, 2H), 2.41 (s, 3H).

[0055] 13 C NMR (100MHz, CDCl3): δ196.6(t,J C-F =35.0Hz),170,142.8,133.7,128.9,128.9,128.7,128.7,21.3.

[0056] 19 F NMR (376MHz, CDCl3): δ-77.02 (s, 2F).

[0057] HRMS (APCI-QE, m / z) [M+H] + Calcd.for C9H7F2N3O+H,212.3206; found,212.3208.

[0058] Example 3: Compound 3 (2-azido-2,2-difluoro-1-(o-tolyl)ethane-1-one) and its preparation method

[0059] Compared with Example 1, most of the methods are the same, except that the raw materials are: Fe(OTf)2 (0.1793 g, 0.5 mmol, 0.3 equiv), 1,4-dioxane (5.0 mL), 2-iodo-2,2-difluoroacetophenone derivative III-3 (0.5000 g, 1.69 mmol, 1.0 equiv), TMSN3 (0.2452 g, 2.13 mmol, 1.2 equiv) and TBPB (0.3444 g, 1.77 mmol, 1.0 equiv).

[0060] Finally, a colorless oil was obtained, namely compound 3: 2-azido-2,2-difluoro-1-(o-tolyl)ethane-1-one, the structural formula of which is shown below. The yield was 97%.

[0061]

[0062] The NMR data of 2-azido-2,2-difluoro-1-(o-tolyl)ethane-1-one prepared in this example are as follows:

[0063] 1 H NMR (400MHz, CDCl3): δ7.17-7.75 (m, 4H), 2.48 (s, 3H).

[0064] 13 C NMR (100MHz, CDCl3): δ196.5(t,J C-F =35.0Hz),170,137.3,134.8,131.3,133.0,127.5,125.6,18.6.

[0065] 19 F NMR (376MHz, CDCl3): δ-78.12 (s, 2F).

[0066] HRMS (APCI-QE, m / z) [M+H] + Calcd.for C9H7F2N3O+H,212.2106; found,212.2110.

[0067] Example 4: Compound 4 (2-azido-2,2-difluoro-1-(m-tolyl)ethane-1-one) and its preparation method

[0068] Compared with Example 1, most of the methods are the same, except that the raw materials are: Fe(OTf)2 (0.1793 g, 0.5 mmol, 0.3 equiv), 1,4-dioxane (5.0 mL), 2-iodo-2,2-difluoroacetophenone derivative III-4 (0.5000 g, 1.69 mmol, 1.0 equiv), TMSN3 (0.2452 g, 2.13 mmol, 1.2 equiv) and TBPB (0.3444 g, 1.77 mmol, 1.0 equiv).

[0069] Finally, a colorless oil was obtained, namely compound 4: 2-azido-2,2-difluoro-1-(m-tolyl)ethane-1-one, the structural formula of which is shown below. The yield was 97%.

[0070]

[0071] The NMR data of 2-azido-2,2-difluoro-1-(m-tolyl)ethane-1-one prepared in this example are as follows:

[0072] 1 H NMR (400MHz, CDCl3): δ7.25-7.90 (m, 4H), 2.42 (s, 3H).

[0073] 13 C NMR (100MHz, CDCl3): δ196.5(t,J C-F =35.0Hz),170,138.3,136.6,133.4,128.5,127.0,125.8,21.3.

[0074] 19 F NMR (376MHz, CDCl3): δ-78.10 (s, 2F).

[0075] HRMS (APCI-QE, m / z) [M+H] + Calcd.for C9H7F2N3O+H,212.2506; found,212.2500.

[0076] Example 5: Compound 5 (2-azido-1-(4-chlorophenyl)-2,2-difluoroethane-1-one) and its preparation method

[0077] Compared with Example 1, most of the methods are the same, except that the raw materials are: Fe(OTf)2 (0.1793 g, 0.5 mmol, 0.3 equiv), 1,4-dioxane (5.0 mL), 2-iodo-2,2-difluoroacetophenone derivative III-5 (0.5000 g, 1.58 mmol, 1.0 equiv), TMSN3 (0.2188 g, 1.90 mmol, 1.2 equiv) and TBPB (0.3074 g, 1.58 mmol, 1.0 equiv).

[0078] Finally, a colorless oil was obtained, namely compound 5: 2-azido-1-(4-chlorophenyl)-2,2-difluoroethane-1-one, whose structural formula is shown below. The yield was 96%.

[0079]

[0080] The NMR data of 2-azido-1-(4-chlorophenyl)-2,2-difluoroethane-1-one prepared in this example are as follows:

[0081] 1 H NMR (400MHz, CDCl3): δ8.05 (d, J = 8.0Hz, 2H), 7.63 (t, J = 8.25Hz, 2H).

[0082] 13 C NMR (100MHz, CDCl3): δ195.8(t,J C-F =36.87Hz),171,138.9,135.8,130.5,130.5,128.9,128.9.

[0083] 19 F NMR (376MHz, CDCl3): δ-79.32 (s, 2F).

[0084] HRMS (APCI-QE, m / z) [M+H] + Calcd.for C8H4ClF2N3O+H,232.8900; found,232.8901.

[0085] Example 6: Compound 6 (2-azido-1-(4-bromophenyl)-2,2-difluoroethane-1-one) and its preparation method

[0086] Compared with Example 1, most of the methods are the same, except that the raw materials are: Fe(OTf)2 (0.1475 g, 0.4 mmol, 0.3 equiv), 1,4-dioxane (5.0 mL), 2-iodo-2,2-difluoroacetophenone derivative III-6 (0.5000 g, 1.39 mmol, 1.0 equiv), TMSN3 (0.1924 g, 1.67 mmol, 1.2 equiv) and TBPB (0.2700 g, 1.39 mmol, 1.0 equiv).

[0087] Finally, a colorless oil was obtained, namely compound 6: 2-azido-1-(4-bromophenyl)-2,2-difluoroethane-1-one, whose structural formula is shown below. The yield was 97%.

[0088]

[0089] The NMR data of 2-azido-1-(4-bromophenyl)-2,2-difluoroethane-1-one prepared in this example are as follows:

[0090] 1 H NMR (400MHz, CDCl3): δ8.10 (d, J = 8.10Hz, 2H), 7.53 (t, J = 8.32Hz, 2H).

[0091] 13 C NMR (100MHz, CDCl3): δ196.25(t,J C-F =36.96Hz),171,135.7,130.42,128.91,128.91,128.57,128.57.

[0092] 19 F NMR (376MHz, CDCl3): δ-79.02 (s, 2F).

[0093] HRMS (APCI-QE, m / z) [M+H] + Calcd.for C8H4BrF2N3O+H,275.4595; found,275.4596.

[0094] Example 7: Compound 7 (2-azido-1-(4-iodophenyl)-2,2-difluoroethane-1-one) and its preparation method

[0095] Compared with Example 1, most of the methods are the same, except that the raw materials are: Fe(OTf)2 (0.1475 g, 0.4 mmol, 0.3 equiv), 1,4-dioxane (5.0 mL), 2-iodo-2,2-difluoroacetophenone derivative III-7 (0.5000 g, 1.23 mmol, 1.0 equiv), TMSN3 (0.1695 g, 1.47 mmol, 1.2 equiv) and TBPB (0.2389 g, 1.23 mmol, 1.0 equiv).

[0096] Finally, a colorless oily substance was obtained, namely compound 7: 2-azido-1-(4-iodophenyl)-2,2-difluoroethane-1-one, whose structural formula is shown below. The yield was 96%.

[0097]

[0098] The NMR data of 2-azido-1-(4-iodophenyl)-2,2-difluoroethane-1-one prepared in this example are as follows:

[0099] 1 H NMR (400MHz, CDCl3): δ7.89 (d, J = 8.02Hz, 2H), 7.66 (t, J = 8.20Hz, 2H).

[0100] 13 C NMR (100MHz, CDCl3): δ197.8(t,J C-F =37.87Hz),171,138.5,138.5,135.7,130.5,130.5,98.7.

[0101] 19 F NMR (376MHz, CDCl3): δ-80.02 (s, 2F).

[0102] HRMS (APCI-QE, m / z) [M+H] + Calcd.for C8H4F2IN3O+H,323.5894; found,323.5895.

[0103] Example 8: Compound 8 (2-azido-1-(4-ethylphenyl)-2,2-difluoroethane-1-one) and its preparation method

[0104] Compared with Example 1, most of the methods are the same, except that the raw materials are: Fe(OTf)2 (0.1712 g, 0.5 mmol, 0.3 equiv), 1,4-dioxane (5.0 mL), 2-iodo-2,2-difluoroacetophenone derivative III-8 (0.5000 g, 1.61 mmol, 1.0 equiv), TMSN3 (0.2230 g, 1.94 mmol, 1.2 equiv) and TBPB (0.3133 g, 1.61 mmol, 1.0 equiv).

[0105] Finally, a colorless oil was obtained, namely Compound 8: 2-azido-1-(4-ethylphenyl)-2,2-difluoroethane-1-one, the structural formula of which is shown below. The yield was 96%.

[0106]

[0107] The NMR data of 2-azido-1-(4-ethylphenyl)-2,2-difluoroethane-1-one prepared in this example are as follows:

[0108] 1 H NMR (400MHz, CDCl3): δ6.77-6.93 (m, 4H), 2.72 (q, J = 8.0Hz, 2H), 1.18 (t, J = 7.8Hz, 3H).

[0109] 13 C NMR (100MHz, CDCl3): δ196.5(t,J C-F =35.0Hz),170,148.7,133.9,128.7,128.7,127.6,127.6,28.2,14.5.

[0110] 19 F NMR (376MHz, CDCl3): δ-78.03 (s, 2F).

[0111] HRMS (APCI-QE, m / z) [M+H] + Calcd.for C 10 H9F2N3O+H,226.2307; found,226.2308.

[0112] Example 9: Compound 9 (2-azido-2,2-difluoro-1-(4-methoxyphenyl)ethane-1-one) and its preparation method

[0113] Compared with Example 1, most of the methods are the same, except that the raw materials are: Fe(OTf)2 (0.1712 g, 0.5 mmol, 0.3 equiv), 1,4-dioxane (5.0 mL), 2-iodo-2,2-difluoroacetophenone derivative III-9 (0.5000 g, 1.61 mmol, 1.0 equiv), TMSN3 (0.2230 g, 1.94 mmol, 1.2 equiv) and TBPB (0.3133 g, 1.61 mmol, 1.0 equiv).

[0114] Finally, a colorless oily substance was obtained, namely compound 9: 2-azido-2,2-difluoro-1-(4-methoxyphenyl)ethane-1-one, whose structural formula is shown below. The yield was 99%.

[0115]

[0116] The NMR data of 2-azido-2,2-difluoro-1-(4-methoxyphenyl)ethane-1-one prepared in this example are as follows:

[0117] 1 H NMR (400MHz, CDCl3): δ7.08-7.91 (m, 4H), 3.81 (s, 3H).

[0118] 13 C NMR (100MHz, CDCl3): δ196.5(t,J C-F =35.0Hz),170,165.0,129.8,129.8,129.1,115.2,115.2,55.9.

[0119] 19 F NMR (376MHz, CDCl3): δ-80.10 (s, 2F).

[0120] HRMS (APCI-QE, m / z) [M+H] + Calcd.for C9H7F2N3O2+H,228.2205; found,228.2206.

[0121] Example 10: Compound 10 (2-azido-1-(4-(tert-butoxy)phenyl)-2,2-difluoroethane-1-one) and its preparation method

[0122] Compared with Example 1, most of the methods are the same, except that the raw materials are: Fe(OTf)2 (0.1475 g, 0.4 mmol, 0.3 equiv), 1,4-dioxane (5.0 mL), 2-iodo-2,2-difluoroacetophenone derivative III-10 (0.5000 g, 1.41 mmol, 1.0 equiv), TMSN3 (0.1949 g, 1.69 mmol, 1.2 equiv) and TBPB (0.2739 g, 1.41 mmol, 1.0 equiv).

[0123] Finally, a colorless oil was obtained, namely Compound 10: 2-azido-1-(4-(tert-butoxy)phenyl)-2,2-difluoroethane-1-one, the structural formula of which is shown below. The yield was 99%.

[0124]

[0125] The NMR data of 2-azido-1-(4-(tert-butoxy)phenyl)-2,2-difluoroethane-1-one prepared in this example are as follows:

[0126] 1 H NMR (400MHz, CDCl3): δ7.01-7.93(m,4H),1.43(s,9H).

[0127] 13 C NMR (100MHz, CDCl3): δ196.5(t,J C-F =35.0Hz),170,162.8,129.5,129.5,128.1,114.2,114.2,86.5,27.9,27.9,27.9.

[0128] 19 F NMR (376MHz, CDCl3): δ-81.01 (s, 2F).

[0129] HRMS (APCI-QE, m / z) [M+H] + Calcd.for C 12 H 13 F2N3O2+H,270.1011; found,270.1112.

[0130] Example 11: Compound 11 (2-azido-2,2-difluoro-1-(naphthalen-2-yl)ethane-1-one) and its preparation method

[0131] Compared with Example 1, most of the methods are the same, except that the raw materials are: Fe(OTf)2 (0.1599 g, 0.45 mmol, 0.3 equiv), 1,4-dioxane (5.0 mL), 2-iodo-2,2-difluoroacetophenone derivative III-11 (0.5000 g, 1.51 mmol, 1.0 equiv), TMSN3 (0.2085 g, 1.81 mmol, 1.2 equiv) and TBPB (0.2933 g, 1.51 mmol, 1.0 equiv).

[0132] Finally, a colorless oily substance was obtained, namely Compound 11: 2-azido-2,2-difluoro-1-(naphthalen-2-yl)ethan-1-one, the structural formula of which is shown below. The yield was 95%.

[0133]

[0134] The NMR data of 2-azido-2,2-difluoro-1-(naphthalen-2-yl)ethane-1-one prepared in this example are as follows:

[0135] 1 H NMR (400MHz, CDCl3) δ=8.52(s,1H),7.94(d,J=9.0Hz,1H),7.86(d,J=8.5Hz,1H),7.78(d,J=9.0H z, 1H), 7.75 (d, J = 8.5Hz, 1H), 7.54 (td, J = 7.0Hz, J = 1.0Hz, 1H), 7.46 (td, J = 8.0Hz, J = 1.0Hz, 1H).

[0136] 13 C NMR (100MHz, CDCl3) δ = 182.1 (t, J F-C =34.0Hz),135.3,132.4(t,J F-C =3.8Hz),131.1,129.1,128.8,127.8,126.8,126.4,126.2,123.5,114.6(t,J F-C =273.4Hz).

[0137] 19 F NMR (376MHz, CDCl3) δ = -77.3 (s, 2F).

[0138] HRMS (APCI-QE, m / z) [M+H] + Calcd.for C 12 H7F2N3O+H,248.0646; found,248.0702.

[0139] Example 12: Compound 12 (2-azido-2,2-difluoro-1-(4-(trifluoromethyl)phenyl)ethane-1-one) and its preparation method

[0140] Compared with Example 1, most of the methods are the same, except that the raw materials are: Fe(OTf)2 (0.1475 g, 0.4 mmol, 0.3 equiv), 1,4-dioxane (5.0 mL), 2-iodo-2,2-difluoroacetophenone derivative III-12 (0.5000 g, 1.41 mmol, 1.0 equiv), TMSN3 (0.1949 g, 1.69 mmol, 1.2 equiv) and TBPB (0.2739 g, 1.41 mmol, 1.0 equiv).

[0141] Finally, a colorless oil was obtained, namely Compound 12: 2-azido-2,2-difluoro-1-(4-(trifluoromethyl)phenyl)ethan-1-one, the structural formula of which is shown below. The yield was 94%.

[0142]

[0143] The NMR data of 2-azido-2,2-difluoro-1-(4-(trifluoromethyl)phenyl)ethane-1-one prepared in this example are as follows:

[0144] 1 H NMR (400MHz, CDCl3): δ7.58 (d, J = 8.0 Hz, 2H), 6.70 (d, J = 7.8 Hz, 2H).

[0145] 13 C NMR (100MHz, CDCl3): δ196.5(t,J C-F =24.9Hz),170.0,140.0(t,J C-F =33.4Hz),135.4,129.1,129.1,125.0,125.0,124.1(t,J=325.8.0Hz).

[0146] 19 F NMR (376MHz, CDCl3): δ-56.28(s,2F),-63.12(s,3F).

[0147] HRMS (APCI-QE, m / z) [M+H] + Calcd.for C9H4F5N3O+H,266.0312; found,266.0311.

[0148] Example 13: Compound 13 (1-([1,1'-biphenyl]-4-yl)-2-azido-2,2-difluoroethane-1-one) and its preparation method

[0149] Compared with Example 1, most of the methods are the same, except that the raw materials are: Fe(OTf)2 (0.1475 g, 0.4 mmol, 0.3 equiv), 1,4-dioxane (5.0 mL), 2-iodo-2,2-difluoroacetophenone derivative III-13 (0.5000 g, 1.40 mmol, 1.0 equiv), TMSN3 (0.1935 g, 1.68 mmol, 1.2 equiv) and TBPB (0.2719 g, 1.41 mmol, 1.0 equiv).

[0150] Finally, a colorless oily substance was obtained, namely Compound 13: 1-([1,1'-biphenyl]-4-yl)-2-azido-2,2-difluoroethane-1-one, the structural formula of which is shown below. The yield was 93%.

[0151]

[0152] The NMR data of 1-([1,1'-biphenyl]-4-yl)-2-azido-2,2-difluoroethane-1-one prepared in this example are as follows:

[0153] 1 H NMR (400MHz, CDCl3): δ8.00 (d, J=9.0Hz, 2H), 7.75-7.80 (m, 4H), 7.41-7.49 (m, 3H).

[0154] 13 C NMR (100MHz, CDCl3): δ196.5(t,J C-F =23.4Hz),170.0,145.2,140.8,135.6,129.3,129.3,129.3,129.3,127.9,127.9,127.8,127.8,127.8.

[0155] 19 F NMR (376MHz, CDCl3): δ-55.78 (s, 2F).

[0156] HRMS (APCI-QE, m / z) [M+H] + Calcd.for C 14 H9F2N3O+H,274.0712; found,274.0713.

[0157] Example 14: Compound 14 (2-azido-2,2-difluoro-1-(4-phenoxyphenyl)ethane-1-one) and its preparation method

[0158] Compared with Example 1, most of the methods are the same, except that the raw materials are: Fe(OTf)2 (0.1475 g, 0.4 mmol, 0.3 equiv), 1,4-dioxane (5.0 mL), 2-iodo-2,2-difluoroacetophenone derivative III-14 (0.5000 g, 1.34 mmol, 1.0 equiv), TMSN3 (0.1843 g, 1.6 mmol, 1.2 equiv) and TBPB (0.2603 g, 1.34 mmol, 1.0 equiv).

[0159] Finally, a colorless oil was obtained, namely Compound 14: 2-azido-2,2-difluoro-1-(4-phenoxyphenyl)ethane-1-one, whose structural formula is shown below. The yield was 92%.

[0160]

[0161] The NMR data of 2-azido-2,2-difluoro-1-(4-phenoxyphenyl)ethane-1-one prepared in this example are as follows:

[0162] 1 H NMR (400MHz, CDCl3): δ7.87 (d, J = 9.0Hz, 2H), 7.42 (td, J = 7.6, 1.9Hz, 2H), 7.17-7.18 (m, 3H), 7.08 (t, J = 9.0Hz, 2H).

[0163] 13 C NMR (100MHz, CDCl3): δ196.5(t,J C-F =23.6Hz),170.0,161.4,157.0,129.8,128.5,128.5,128.4,128.4,121.8,118.9,118.9,117.4,117.4.

[0164] 19 F NMR (376MHz, CDCl3): δ-53.56 (s, 2F).

[0165] HRMS (APCI-QE, m / z) [M+H] + Calcd.for C 14 H9F2N3O2+H,290.0712; found,290.0711.

[0166] Example 15: Compound 15 (2-azido-1-(benzo[d][1,3]dihydroxy-5-yl)-2,2-difluoroethane-1-one) and its preparation method

[0167] Compared with Example 1, most of the methods are the same, except that the raw materials are: Fe(OTf)2 (0.1628 g, 0.46 mmol, 0.3 equiv), 1,4-dioxane (5.0 mL), 2-iodo-2,2-difluoroacetophenone derivative III-15 (0.5000 g, 1.53 mmol, 1.0 equiv), TMSN3 (0.2115 g, 1.84 mmol, 1.2 equiv) and TBPB (0.2972 g, 1.53 mmol, 1.0 equiv).

[0168] Finally, a colorless oil was obtained, namely Compound 15: 2-azido-1-(benzo[d][1,3]dihydroxy-5-yl)-2,2-difluoroethane-1-one, the structural formula of which is shown below. The yield was 93%.

[0169]

[0170] The NMR data of 2-azido-1-(benzo[d][1,3]dihydroxy-5-yl)-2,2-difluoroethane-1-one prepared in this example are as follows:

[0171] 1 H NMR (400MHz, CDCl3): δ7.59 (d, J = 8.3Hz, 1H), 7.40 (d, J = 8.52Hz.1H), 7.09 (d, J = 8.52Hz, 1H), 6.08 (s, 1H).

[0172] 13 C NMR (100MHz, CDCl3): δ196.5(t,J C-F =23.6Hz),170.0,161.4,157.0,129.8,128.5,128.5,128.4,128.4,121.8,118.9,118.9,117.4,117.4.

[0173] 19 F NMR (376MHz, CDCl3): δ-53.56 (s, 2F).

[0174] HRMS (APCI-QE, m / z) [M+H] + Calcd.for C9H5F2N3O3+H,242.0304; found,242.0305.

[0175] Example 16: Compound 16 (2-azido-1-(2-ethoxy-4-methoxyphenyl)-2,2-difluoroethane-1-one) and its preparation method

[0176] Compared with Example 1, most of the methods are the same, except that the raw materials are: Fe(OTf)2 (0.1946 g, 0.55 mmol, 0.3 equiv), 1,4-dioxane (5.0 mL), 2-iodo-2,2-difluoroacetophenone derivative III-16 (0.5000 g, 1.84 mmol, 1.0 equiv), TMSN3 (0.2544 g, 2.21 mmol, 1.2 equiv) and TBPB (0.3574 g, 1.84 mmol, 1.0 equiv).

[0177] Finally, a colorless oil was obtained, namely Compound 16: 2-azido-1-(2-ethoxy-4-methoxyphenyl)-2,2-difluoroethane-1-one, the structural formula of which is shown below. The yield was 95%.

[0178]

[0179] The NMR data of 2-azido-1-(2-ethoxy-4-methoxyphenyl)-2,2-difluoroethane-1-one prepared in this example are as follows:

[0180] 1 H NMR (400MHz, CDCl3): δ7.65 (d, J = 8.3Hz, 1H), 6.67 (d, J = 8.52Hz, 1H), 6.66 (s, 1H), 4.01-4.05 (m, 2H), 3.84 (s, 3H), 1.34 (s, 3H).

[0181] 13 C NMR (100MHz, CDCl3): δ196.5(t,J C-F =23.6Hz),170.0,165.6,163.4,130.4,112.6,105.8,101.4,64.6,55.8,14.8.

[0182] 19 F NMR (376MHz, CDCl3): δ-56.56 (s, 2F).

[0183] HRMS (APCI-QE, m / z) [M+H] + Calcd.for C 11 H 11 F2N3O3+H,272.0855; found,282.0856.

[0184] Example 17: Compound 17 (2-azido-2,2-difluoro-1-(4-(trifluoromethoxy)phenyl)ethane-1-one) and its preparation method

[0185] Compared with Example 1, most of the methods are the same, except that the raw materials are: Fe(OTf)2 (0.1889 g, 0.53 mmol, 0.3 equiv), 1,4-dioxane (5.0 mL), 2-iodo-2,2-difluoroacetophenone derivative III-17 (0.5000 g, 1.78 mmol, 1.0 equiv), TMSN3 (0.2465 g, 2.14 mmol, 1.2 equiv) and TBPB (0.3558 g, 1.78 mmol, 1.0 equiv).

[0186] Finally, a colorless oil was obtained, namely Compound 17: 2-azido-2,2-difluoro-1-(4-(trifluoromethoxy)phenyl)ethan-1-one, the structural formula of which is shown below. The yield was 94%.

[0187]

[0188] The NMR data of 2-azido-2,2-difluoro-1-(4-(trifluoromethoxy)phenyl)ethane-1-one prepared in this example are as follows:

[0189] 1 H NMR (400MHz, CDCl3): δ7.91 (d, J = 8.3Hz, 2H), 7.04 (d, J = 8.52Hz, 2H).

[0190] 13 C NMR (100MHz, CDCl3): δ196.5(t,J C-F =23.6Hz),170.0,155.0,129.8,129.8,129.7,129.0,114.2,114.2.

[0191] 19 F NMR (376MHz, CDCl3): δ-56.56 (s, 2F).

[0192] HRMS (APCI-QE, m / z) [M+H] + Calcd.for C9H4F5N3O2+H,282.0223; found,282.0324.

[0193] Example 18: Compound 18 (2-azido-2-fluoro-1-phenylethane-1-one) and its preparation method

[0194] Compared with Example 1, most of the methods are the same, except that the raw materials are: Fe(OTf)2 (0.2017 g, 0.57 mmol, 0.3 equiv), 1,4-dioxane (5.0 mL), 2-iodo-2-fluoroacetophenone derivative III-18 (0.5000 g, 1.89 mmol, 1.0 equiv), TMSN3 (0.2613 g, 2.268 mmol, 1.2 equiv) and TBPB (0.3671 g, 1.89 mmol, 1.0 equiv).

[0195] Finally, a colorless oil was obtained, namely Compound 18: 2-azido-2-fluoro-1-phenylethane-1-one, whose structural formula is shown below. The yield was 98%.

[0196]

[0197] The NMR data of 2-azido-2-fluoro-1-phenylethane-1-one prepared in this example are as follows:

[0198] 1 H NMR (400MHz, CDCl3): δ7.55-8.00 (m, 5H), 4.8 (d, J = 56.0Hz, 1H).

[0199] 13 C NMR (100MHz, CDCl3): δ188.31(d,J C-F =27.0Hz),134.96,132.57,129.38(d,J C-F =43.0Hz),97.52,97.52,77.16,77.16.

[0200] 19 F NMR (376MHz, CDCl3): δ-144.41 (s, 1F).

[0201] HRMS (APCI-QE, m / z) [M+H] + Calcd.for C8H6FN3O+H,180.0554; found,182.0453.

[0202] Example 19: Compound 19 (2-azido-2-fluoro-1-(p-tolyl)ethane-1-one) and its preparation method

[0203] Compared with Example 1, most of the methods are the same, except that the raw materials are: Fe(OTf)2 (0.1911 g, 0.54 mmol, 0.3 equiv), 1,4-dioxane (5.0 mL), 2-iodo-2-fluoroacetophenone derivative IV-1 (0.5000 g, 1.8 mmol, 1.0 equiv), TMSN3 (0.2487 g, 2.16 mmol, 1.2 equiv) and TBPB (0.3496 g, 1.8 mmol, 1.0 equiv).

[0204] Finally, a colorless oil was obtained, namely Compound 19: 2-azido-2-fluoro-1-(p-tolyl)ethan-1-one, the structural formula of which is shown below. The yield was 99%.

[0205]

[0206] The NMR data of 2-azido-2-fluoro-1-(p-tolyl)ethane-1-one prepared in this example are as follows:

[0207] 1 H NMR (400MHz, CDCl3): δ7.44 (d, J = 8.0 Hz, 2H), 6.72 (d, J = 7.8 Hz, 2H), 4.8 (d, J = 54.5 Hz, 1H), 2.41 (s, 3H).

[0208] 13 C NMR (100MHz, CDCl3): δ196.5(t,J C-F =35.0Hz),142.8,133.7,129,128.9,128.9,128.7,128.7,21.3.

[0209] 19 F NMR (376MHz, CDCl3): δ-145.6 (s, 1F).

[0210] HRMS (APCI-QE, m / z) [M+H] + Calcd.for C9H8FN3O+H,194.0706; found,194.0605.

[0211] Example 20: Compound 20 (2-azido-2-fluoro-1-(o-tolyl)ethane-1-one) and its preparation method

[0212] Compared with Example 1, most of the methods are the same, except that the raw materials are: Fe(OTf)2 (0.1911 g, 0.54 mmol, 0.3 equiv), 1,4-dioxane (5.0 mL), 2-iodo-2-fluoroacetophenone derivative IV-2 (0.5000 g, 1.8 mmol, 1.0 equiv), TMSN3 (0.2487 g, 2.16 mmol, 1.2 equiv) and TBPB (0.3496 g, 1.8 mmol, 1.0 equiv).

[0213] Finally, a colorless oil was obtained, namely Compound 20: 2-azido-2-fluoro-1-(o-tolyl)ethan-1-one, whose structural formula is shown below. The yield was 98%.

[0214]

[0215] The NMR data of 2-azido-2-fluoro-1-(o-tolyl)ethane-1-one prepared in this example are as follows:

[0216] 1 H NMR (400MHz, CDCl3): δ7.17-7.75 (m, 4H), 4.8 (d, J = 54.7Hz, 1H), 2.48 (s, 3H).

[0217] 13 C NMR (100MHz, CDCl3): δ196.5(t,J C-F =35.0Hz),137.3,134.8,133.0,131.3,129,127.5,125.6,18.6.

[0218] 19 F NMR (376MHz, CDCl3): δ-145.8 (s, 1F).

[0219] HRMS (APCI-QE, m / z) [M+H] + Calcd.for C9H8FN3O+H,194.0703; found,194.0804.

[0220] Example 21: Compound 21 (2-azido-2-fluoro-1-(m-tolyl)ethane-1-one) and its preparation method

[0221] Compared with Example 1, most of the methods are the same, except that the raw materials are: Fe(OTf)2 (0.1911 g, 0.54 mmol, 0.3 equiv), 1,4-dioxane (5.0 mL), 2-iodo-2-fluoroacetophenone derivative IV-3 (0.5000 g, 1.8 mmol, 1.0 equiv), TMSN3 (0.2487 g, 2.16 mmol, 1.2 equiv) and TBPB (0.3496 g, 1.8 mmol, 1.0 equiv).

[0222] Finally, a colorless oil was obtained, namely Compound 21: 2-azido-2-fluoro-1-(m-tolyl)ethan-1-one, the structural formula of which is shown below. The yield was 97%.

[0223]

[0224] The NMR data of 2-azido-2-fluoro-1-(m-tolyl)ethane-1-one prepared in this example are as follows:

[0225] 1 H NMR (400MHz, CDCl3): δ7.25-7.90 (m, 4H), 4.8 (d, J = 54.7Hz, 1H), 2.42 (s, 3H).

[0226] 13 C NMR (100MHz, CDCl3): δ196.5(t,J C-F =35.0Hz),138.3,136.6,133.4,129,128.5,127.0,125.8,21.3.

[0227] 19 F NMR (376MHz, CDCl3): δ-145.7 (s, 1F).

[0228] HRMS (APCI-QE, m / z) [M+H] + Calcd.for C9H8FN3O+H,194.1812; found,194.1813.

[0229] Example 22: Compound 22 (2-azido-2-fluoro-1-(4-methoxyphenyl)ethane-1-one) and its preparation method

[0230] Compared with Example 1, most of the methods are the same, except that the raw materials are: Fe(OTf)2 (0.1804 g, 0.51 mmol, 0.3 equiv), 1,4-dioxane (5.0 mL), 2-iodo-2-fluoroacetophenone derivative IV-4 (0.5000 g, 1.7 mmol, 1.0 equiv), TMSN3 (0.2350 g, 2.04 mmol, 1.2 equiv) and TBPB (0.3302 g, 1.7 mmol, 1.0 equiv).

[0231] Finally, a colorless oil was obtained, namely Compound 22: 2-azido-2-fluoro-1-(4-methoxyphenyl)ethan-1-one, whose structural formula is shown below. The yield was 99%.

[0232]

[0233] The NMR data of 2-azido-2-fluoro-1-(4-methoxyphenyl)ethane-1-one prepared in this example are as follows:

[0234] 1 H NMR (400MHz, CDCl3): δ7.08-7.91 (m, 4H), 4.8 (d, J = 54.7Hz, 1H), 3.81 (s, 3H).

[0235] 13 C NMR (100MHz, CDCl3): δ196.5(t,J C-F =36.0Hz),165.0,129.8,129.8,129.0,129.0,114.2,114.2,55.8.

[0236] 19 F NMR (376MHz, CDCl3): δ-146.5 (s, 1F).

[0237] HRMS (APCI-QE, m / z) [M+H] + Calcd.for C9H8FN3O2+H,210.0602; found,210.0701.

[0238] Example 23: Compound 23 (2-azido-1-(4-(tert-butoxy)phenyl)-2-fluoroethane-1-one) and its preparation method

[0239] Compared with Example 1, most of the methods are the same, except that the raw materials are: Fe(OTf)2 (0.1592 g, 0.45 mmol, 0.3 equiv), 1,4-dioxane (5.0 mL), 2-iodo-2-fluoroacetophenone derivative IV-5 (0.5000 g, 1.5 mmol, 1.0 equiv), TMSN3 (0.2074 g, 2.04 mmol, 1.2 equiv) and TBPB (0.3496 g, 1.8 mmol, 1.0 equiv).

[0240] Finally, a colorless oil was obtained, namely Compound 23: 2-azido-1-(4-(tert-butoxy)phenyl)-2-fluoroethane-1-one, the structural formula of which is shown below. The yield was 97%.

[0241]

[0242] The NMR data of 2-azido-1-(4-(tert-butoxy)phenyl)-2-fluoroethane-1-one prepared in this example are as follows:

[0243] 1 H NMR (400MHz, CDCl3): δ7.04-7.91 (m, 4H), 4.8 (d, J = 54.7Hz, 1H), 1.42 (s, 9H).

[0244] 13 C NMR (100MHz, CDCl3): δ196.5(t,J C-F =36.0Hz),161.8,129.4,129.4,129,128.3,114.3,114.3,86.0,27.8,27.8,27.8.

[0245] 19 F NMR (376MHz, CDCl3): δ-146.7 (s, 1F).

[0246] HRMS (APCI-QE, m / z) [M+H] + Calcd.for C 12 H 14 FN3O2+H,252.1102; found,252.1201.

[0247] Example 24: Compound 24 (2-azido-1-(4-chlorophenyl)-2-fluoroethane-1-one) and its preparation method

[0248] Compared with Example 1, most of the methods are the same, except that the raw materials are: Fe(OTf)2 (0.1783 g, 0.5 mmol, 0.3 equiv), 1,4-dioxane (5.0 mL), 2-iodo-2-fluoroacetophenone derivative IV-6 (0.5000 g, 1.68 mmol, 1.0 equiv), TMSN3 (0.2322 g, 2.01 mmol, 1.2 equiv) and TBPB (0.3263 g, 1.68 mmol, 1.0 equiv).

[0249] Finally, a colorless oily substance was obtained, namely Compound 24: 2-azido-1-(4-chlorophenyl)-2-fluoroethane-1-one, whose structural formula is shown below. The yield was 96%.

[0250]

[0251] The NMR data of 2-azido-1-(4-chlorophenyl)-2-fluoroethane-1-one prepared in this example are as follows:

[0252] 1 H NMR (400MHz, CDCl3): δ8.03 (d, J = 8.0Hz, 2H), 7.63 (t, J = 8.25Hz, 2H), 4.8 (d, J = 55.0Hz, 1H).

[0253] 13 C NMR (100MHz, CDCl3): δ196.5(t,J C-F =38.0Hz),138.7,134.8,130.2,130.2,129,128.7,128.7.

[0254] 19 F NMR (376MHz, CDCl3): δ-145.6 (s, 1F).

[0255] HRMS (APCI-QE, m / z) [M+H] + Calcd.for C8H5ClFN3O+H,214.0113; found,214.0112.

[0256] Example 25: Compound 25 (2-azido-1-(4-bromophenyl)-2-fluoroethane-1-one) and its preparation method

[0257] Compared with Example 1, most of the methods are the same, except that the raw materials are: Fe(OTf)2 (0.1557 g, 0.44 mmol, 0.3 equiv), 1,4-dioxane (5.0 mL), 2-iodo-2-fluoroacetophenone derivative IV-7 (0.5000 g, 1.46 mmol, 1.0 equiv), TMSN3 (0.2018 g, 1.75 mmol, 1.2 equiv) and TBPB (0.2836 g, 1.46 mmol, 1.0 equiv).

[0258] Finally, a colorless oil was obtained, namely Compound 25: 2-azido-1-(4-chlorophenyl)-2-bromoethane-1-one, whose structural formula is shown below. The yield was 95%.

[0259]

[0260] The NMR data of 2-azido-1-(4-bromophenyl)-2-fluoroethane-1-one prepared in this example are as follows:

[0261] 1 H NMR (400MHz, CDCl3): δ7.95 (d, J = 9.05Hz, 2H), 7.78 (t, J = 8.52Hz, 2H), 4.8 (d, J = 55.0Hz, 1H).

[0262] 13 C NMR (100MHz, CDCl3): δ196.5(t,J C-F =38.0Hz),135.7,131.5,131.5,129.8,129.8,129,127.5.

[0263] 19 F NMR (376MHz, CDCl3): δ-145.7 (s, 1F).

[0264] HRMS (APCI-QE, m / z) [M+H] + Calcd.for C8H5BrFN3O+H,257.9601; found,257.9702.

[0265] Example 26: Compound 26 (2-azido-1-(4-iodophenyl)-2-fluoroethane-1-one) and its preparation method

[0266] Compared with Example 1, most of the methods are the same, except that the raw materials are: Fe(OTf)2 (0.1359 g, 0.38 mmol, 0.3 equiv), 1,4-dioxane (5.0 mL), 2-iodo-2-fluoroacetophenone derivative IV-8 (0.5000 g, 1.28 mmol, 1.0 equiv), TMSN3 (0.1769 g, 1.54 mmol, 1.2 equiv) and TBPB (0.2486 g, 1.28 mmol, 1.0 equiv).

[0267] Finally, a colorless oily substance was obtained, namely Compound 26: 2-azido-1-(4-chlorophenyl)-2-iodoethane-1-one, whose structural formula is shown below. The yield was 96%.

[0268]

[0269] The NMR data of 2-azido-1-(4-iodophenyl)-2-fluoroethane-1-one prepared in this example are as follows:

[0270] 1 H NMR (400MHz, CDCl3): δ7.88 (d, J = 8.12Hz, 2H), 7.67 (t, J = 8.22Hz, 2H), 4.8 (d, J = 55.0Hz, 1H).

[0271] 13 C NMR (100MHz, CDCl3): δ196.5(t,J C-F =38.0Hz),137.5,137.5,135.6,130.4,130.4,129,98.7.

[0272] 19 F NMR (376MHz, CDCl3): δ-145.8 (s, 1F).

[0273] HRMS (APCI-QE, m / z) [M+H] + Calcd.for C8H5FIN3O+H,305.9512; found,305.9611.

[0274] Example 27: Compound 27 (2-azido-2-fluoro-1,2-diphenylethane-1-one) and its preparation method

[0275] Compared with Example 1, most of the methods are the same, except that the raw materials are: Fe(OTf)2 (0.1560 g, 0.44 mmol, 0.3 equiv), 1,4-dioxane (5.0 mL), 2-iodo-2-fluoroacetophenone derivative IV-9 (0.5000 g, 1.47 mmol, 1.0 equiv), TMSN3 (0.2032 g, 1.76 mmol, 1.2 equiv) and TBPB (0.2855 g, 1.47 mmol, 1.0 equiv).

[0276] Finally, a colorless oily substance was obtained, namely compound 27: 2-azido-2-fluoro-1,2-diphenylethane-1-one, the structural formula of which is shown below, and the yield was 92%.

[0277]

[0278] The NMR data of 2-azido-2-fluoro-1,2-diphenylethane-1-one prepared in this example are as follows:

[0279] 1 H NMR (400MHz, CDCl3): δ7.98-7.95(m,2H),7.60-7.37(m,8H).

[0280] 13 C NMR (100MHz, CDCl3): δ190.0 (d, J = 30.7Hz), 134.4 (d, J = 25.9Hz), 134.1, 132.6 (d, J = 1.9 Hz), 130.7 (d, J = 3.8Hz), 130.5, 129.3, 128.7, 125.5 (d, J = 5.7Hz), 107.2 (d, J = 227.2Hz).

[0281] 19 F NMR (376MHz, CDCl3): δ-119.8 (s, 1F).

[0282] HRMS (APCI-QE, m / z) [M+H] + Calcd.for C 14 H 10 FN3O,256.2503; found,256.2504.

[0283] Example 28: Compound 28 (1-azido-1-fluoro-3,3-dimethyl-1-phenylbutan-2-one) and its preparation method

[0284] Compared with Example 1, most of the methods are the same, except that the raw materials are: Fe(OTf)2 (0.1656 g, 0.47 mmol, 0.3 equiv), 1,4-dioxane (5.0 mL), 2-iodo-2-fluoroacetophenone derivative IV-10 (0.5000 g, 1.56 mmol, 1.0 equiv), TMSN3 (0.2157 g, 1.87 mmol, 1.2 equiv) and TBPB (0.3030 g, 1.56 mmol, 1.0 equiv).

[0285] Finally, a colorless oily substance was obtained, namely Compound 28: 1-azido-1-fluoro-3,3-dimethyl-1-phenylbutan-2-one, the structural formula of which is shown below. The yield was 94%.

[0286]

[0287] The NMR data of 1-azido-1-fluoro-3,3-dimethyl-1-phenylbutan-2-one prepared in this example are as follows:

[0288] 1 H NMR (400MHz, CDCl3): δ7.53-7.43 (m, 5H), 1.12 (d, J = 1.2Hz, 9H).

[0289] 13 C NMR (100MHz, CDCl3): δ205.7 (d, J = 30.7Hz), 134.2 (d, J = 25.9Hz), 130.2, 129.0, 125.6(d,J=7.7Hz), 108.6(d,J=231.0Hz), 44.9(d,J=3.8Hz), 26.8(d,J=3.8Hz).

[0290] 19 F NMR (376MHz, CDCl3): δ-129.8 (s, 1F).

[0291] HRMS (APCI-QE, m / z) [M+H] + Calcd.for C 12 H 14 FN3O,236.2622; found,236.2623.

[0292] Example 29: Compound 29 (2-azido-2-fluoro-1-phenylpropan-1-one) and its preparation method

[0293] Compared with Example 1, most of the methods are the same, except that the raw materials are: Fe(OTf)2 (0.1911 g, 0.54 mmol, 0.3 equiv), 1,4-dioxane (5.0 mL), 2-iodo-2-fluoroacetophenone derivative IV-11 (0.5000 g, 1.80 mmol, 1.0 equiv), TMSN3 (0.2489 g, 2.16 mmol, 1.2 equiv) and TBPB (0.3496 g, 1.80 mmol, 1.0 equiv).

[0294] Finally, a colorless oily substance was obtained, namely compound 29: 2-azido-2-fluoro-1-phenylpropan-1-one, whose structural formula is shown below. The yield was 99%.

[0295]

[0296] The NMR data of 2-azido-2-fluoro-1-phenylpropan-1-one prepared in this example are as follows:

[0297] 1 H NMR (400MHz, CDCl3): δ1.91 (d, J = 19.7Hz, 3H), 7.49 (t, J = 8.0Hz, 2H), 7.60-7.65 (m, 1H), 8.12 (d, J = 8.0Hz, 2H).

[0298] 13 C NMR (100MHz, CDCl3): δ22.1(d,J C-F =26.8Hz),105.8(d,J C-F =223.3Hz),128.6,130.4(d,J C-F =4.8Hz),132.2(d,J C-F =2.9Hz),134.1,190.8(d,J C-F =30.7Hz).

[0299] 19 F NMR (376MHz, CDCl3): δ-111.5(q,J H-F =19.3Hz).

[0300] HRMS (APCI-QE, m / z) [M+H] + Calcd.for C9H8FN3O,194.0730, found 194.0740.

[0301] Example 30: Compound 30 (2-azido-2-fluoro-1-phenylbutan-1-one) and its preparation method

[0302] Compared with Example 1, most of the methods are the same, except that the raw materials are: Fe(OTf)2 (0.1815 g, 0.51 mmol, 0.3 equiv), 1,4-dioxane (5.0 mL), 2-iodo-2-fluoroacetophenone derivative IV-12 (0.5000 g, 1.71 mmol, 1.0 equiv), TMSN3 (0.2364 g, 2.05 mmol, 1.2 equiv) and TBPB (0.3321 g, 1.80 mmol, 1.0 equiv).

[0303] Finally, a colorless oily substance was obtained, namely Compound 30: 2-azido-2-fluoro-1-phenylbutan-1-one, whose structural formula is shown below. The yield was 96%.

[0304]

[0305] The NMR data of 2-azido-2-fluoro-1-phenylbutan-1-one prepared in this example are as follows:

[0306] 1 H NMR (400MHz, CDCl3): δ1.01(t,J=7.6Hz,3H),2.08-2.27(m,2H),7.49(t,J=7.8Hz,2H),7.61-7.65(m,1H),8.11(d,J=8.7Hz,2H).

[0307] 13 C NMR (100 MHz, CDCl3): δ 7.0 (d, J C-F =4.8Hz),29.7(d,J C-F =24.9Hz),108.2(d,J C-F =225.2Hz),128.7,130.1(d,J C-F =4.8Hz),132.9(d,J C-F =2.9Hz),134.0,191.6(d,J C-F =30.7Hz).

[0308] 19 F NMR (376MHz, CDCl3): δ-122.4(d,J F-H =34.7Hz).

[0309] HRMS (APCI-QE, m / z) [M+H] + Calcd.for C 10 H 10FN3O,208.0882,found208.0983.

[0310] Example 31: Compound 31 (4-azido-1-(4,5-diphenyloxazol-2-yl)-4-fluoropentan-3-one) and its preparation method

[0311] Compared with Example 1, most of the methods are the same, except that the raw materials are: Fe(OTf)2 (0.1178 g, 0.33 mmol, 0.3 equiv), 1,4-dioxane (5.0 mL), 2-iodo-2-fluoroacetophenone derivative IV-13 (0.5000 g, 1.11 mmol, 1.0 equiv), TMSN3 (0.1535 g, 1.33 mmol, 1.2 equiv) and TBPB (0.2156 g, 1.11 mmol, 1.0 equiv).

[0312] Finally, a colorless oil was obtained, namely Compound 31: 4-azido-1-(4,5-diphenyloxazol-2-yl)-4-fluoropentan-3-one, the structural formula of which is shown below. The yield was 90%.

[0313]

[0314] The NMR data of 4-azido-1-(4,5-diphenyloxazol-2-yl)-4-fluoropentan-3-one prepared in this example are as follows:

[0315] 1 H NMR (400MHz, CDCl3): δ1.76 (d, J = 19.2Hz, 3H), 3.16-3.35 (m, 4H), 7.30-7.38 (m, 6H), 7.55-7.58 (m, 2H), 7.60-7.62 (m, 2H);

[0316] 13 C NMR (100 MHz, CDCl3) δ 20.9 (d, J C-F =25Hz),21.6,33.3,104.8(d,J C-F =225Hz),126.5,127.8,128.1,128.5,128.5,128.6,128.9,132.4,135.1,145.6,161.4,200.6(d,J C-F =12.5Hz).

[0317] 19 F NMR(376MHz,CDCl3)δ-119.3(q,J F-H =19.0Hz).

[0318] HRMS (APCI-QE, m / z) [M+H] + Calcd.for C 20 H 17 FN4O2,365.1433,found365.1332.

[0319] The above description of the embodiments is intended to facilitate understanding and use of the invention by those skilled in the art. It will be apparent that those skilled in the art can readily make various modifications to these embodiments and apply the general principles described herein to other embodiments without requiring inventive effort. Therefore, the present invention is not limited to the above-described embodiments. Improvements and modifications made by those skilled in the art based on the disclosure of the present invention, without departing from the scope of the present invention, should be within the scope of protection of the present invention.

Claims

1. A method for preparing a fluorinated azide derivative, comprising: reacting a fluoroalkyl iodide derivative, an azidating agent, a catalyst, a free radical initiator, and an organic solvent; and after the reaction, extracting, separating, and purifying the fluorinated azide derivative. The fluorine-containing azide derivative is selected from any one or more of compounds 1-17, 19 to 26 represented by the following structural formulas: Corresponding to fluorine-containing azide derivatives, the fluoroalkyl iodide derivatives are selected from any one or more of the following structural formulas: The azidation reagent is trimethylsilyl azide, the catalyst is Fe(OTf)2, and the free radical initiator is tert-butyl perbenzoate.

2. The method for preparing a fluorine-containing azide derivative according to claim 1, wherein The organic solvent is selected from any one or more of ethylene glycol dimethyl ether, tetrahydrofuran, dichloromethane, methanol, 1,4-dioxane, dimethyl sulfoxide, diethyl ether, cyclopentyl methyl ether or acetonitrile.

3. The method for preparing a fluorine-containing azide derivative according to claim 1, wherein The equivalent ratio of the fluoroalkyl iodide derivative, the catalyst, the azidation reagent, and the free radical initiator is 1:(0.2-0.4):(1.1-1.3):(0.9-1.2).

4. The method for preparing a fluorine-containing azide derivative according to claim 1, wherein The reaction temperature during the reaction is 25°C-80°C, and the reaction time is 0.5-12h.

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