A monofluoro / difluorooxoallyl ester compound and a preparation method thereof

Abstract

The present invention relates to a monofluoro / difluorooxoallyl ester compound and a preparation method thereof. The chemical structural formula of the compound is: wherein, R 1 includes phenyl or substituted phenyl, R 2 is a substituted phenyl, R f includes monofluoro or difluoro; The method includes the following steps: respectively adding compound 3, a catalyst and an oxidant and mixing them, then taking compound 1 or 2, dissolving it in a solvent and adding it, stirring and reacting, and then cooling to room temperature; The obtained reaction solution is subjected to extraction and separation to obtain compound 4, namely the monofluoro / difluorooxoallyl ester compound; The chemical equation is: Compared with the prior art, the present invention synthesizes a series of monofluoro / difluorooxoallyl ester compounds, which have the advantages of high efficiency, high yield, mild conditions, environmental friendliness, etc.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis and relates to a monofluoro / difluorooxoallyl ester compound and a preparation method thereof. Background Art

[0002] The molecular skeleton of α-halo-α′,β′-unsaturated ketones, especially those modified with fluorine, as a key intermediate structure for synthesizing bioactive target drugs, has begun to receive extensive attention in the patent literature. For example, in 2019, Ning Jun et al. disclosed a synthesis method of a 4-oxo-trans-2-hexenal analog in patent CN112094181A, and a 5,5-difluoro-4-oxo-trans-2-hexenal analog therein can be used as a new type of insecticide with slow release, long-lasting efficacy, strong sex attractant ability, and environmental friendliness.

[0003]

[0004] Through literature research, it can be found that introducing fluorine atoms or fluorine-containing groups into organic compound molecules can significantly improve the physical, chemical, and physiological properties of organic compounds or drugs compared to their parent molecules. Selectively introducing fluorine or fluorinated groups into candidate drugs has been considered a powerful strategy in drug design and screening. Indiummediated barbier-type allylation: Synthesis of highly functionalizedhomoallylic difluorohydrins has successfully synthesized a series of building blocks that can be used as substrates. Summary of the Invention

[0005] The purpose of the present invention is to provide a monofluoro / difluorooxoallyl ester compound and a preparation method thereof to overcome at least one defect of the above-mentioned existing technologies. The present invention uses the synthesized α-hydroxyiodo gem-monofluoro / difluoromethyl compound building blocks as substrates, and under the promotion of transition metals and oxidants, synthesizes a series of monofluoro / difluorooxoallyl ester compounds, which have the advantages of high efficiency, high yield, mild conditions, and environmental friendliness.

[0006] The purpose of the present invention can be achieved by the following technical solutions:

[0007] One of the technical solutions of the present invention is to provide a monofluoro / difluorooxoallyl ester compound, and the chemical structural formula of the compound is:

[0008]

[0009] Wherein, R 1 includes phenyl or substituted phenyl, R2 is a substituted phenyl group, R f includes mono-fluorine or di-fluorine.

[0010] Furthermore, the said R 1 is a substituted phenyl group, and the substituents in the substituted phenyl group are selected from one or more of phenyl, hydrogen, fluorine, chlorine, bromine, methoxy, methyl, and trifluoromethyl;

[0011] The said R 2 is a substituted phenyl group, and the substituents in the substituted phenyl group are selected from one or more of nitro, hydrogen, fluorine, chlorine, bromine, methoxy, methylene, methyl, and trifluoromethyl.

[0012] Furthermore, the said mono-fluorinated oxoallyl esters include (E)-5-fluoro-4-oxo-5-phenyl-penta-2-en-1-yl 4,5-difluoro-2-nitrobenzoate, (E)-5-fluoro-4-oxo-5-phenyl-penta-2-en-1-yl 2-(5-fluoro-2-nitrophenyl)acetate, (E)-5-fluoro-4-oxo-5-phenyl-penta-2-en-1-yl 2-(4-bromo-2-nitrophenyl)acetate, or (E)-5-fluoro-4-oxo-5-phenyl-penta-2-en-1-yl 2-(2-nitro-4-(trifluoromethyl)phenyl)acetate.

[0013] Further, the difluorooxoallyl ester compounds include (E)-5,5-difluoro-4-oxo-5-phenylpent-2-en-1-yl 2-nitrobenzoate, (E)-5,5-difluoro-5-(4-methoxyphenyl)-4-oxo-pent-2-en-1-yl 2-nitrobenzoate, (E)-5,5-difluoro-5-(3-methoxyphenyl)-4-oxo-pent-2-en-1-yl 2-nitrobenzoate, (E)-5,5-difluoro-5-(2-methoxyphenyl)-4-oxo-pent-2-en-1-yl 2-nitrobenzoate, (E)-5,5-difluoro-5-(4-fluorophenyl)-4-oxo-pent-2-en-1-yl 2-nitrobenzoate, (E)-5-(3-chlorophenyl)-5,5-difluoro-4-oxo-pent-2-en-1-yl 2-nitrobenzoate, (E)-5,5-difluoro-5-(naphthalen-2-yl)-4-oxo-pent-2-en-1-yl 2-nitrobenzoate, (E)-5,5-difluoro-4-oxo-5-phenylpent-2-en-1-yl 4-methoxy-2-nitrobenzoate, (E)-5,5-difluoro-4-oxo-5-phenylpent-2-en-1-yl 4-fluoro-2-nitrobenzoate, (E)-5,5-difluoro-4-oxo-5-phenylpent-2-en-1-yl 3-chloro-2-nitrobenzoate, (E)-5,5-difluoro-4-oxo-5-phenylpent-2-en-1-yl 5-bromo-2-nitrobenzoate, (E)-5,5-difluoro-5-(4-fluorophenyl)-4-oxo-pent-2-en-1-yl 4-methoxy-2-nitrobenzoate, (E)-5,5-difluoro-5-(4-fluorophenyl)-4-oxo-pent-2-en-1-yl 4,5-dimethoxy-2-nitrobenzoate, (E)-5,5-difluoro-4-oxo-5-phenylpent-2-en-1-yl 2-(2-nitrophenyl)acetate, (E)-5,5-difluoro-4-oxo-5-(o-tolyl)pent-2-en-1-yl 2-nitrobenzoate, (E)-5-(2-chlorophenyl)-5,5-difluoro-4-oxopent-2-en-1-yl 2-nitrobenzoate, (E)-5,5-difluoro-4-oxo-5-(4-trifluoromethylphenyl)pent-2-en-1-yl 2-nitrobenzoate, (E)-5,5-difluoro-4-oxo-5-phenylpent-2-en-1-yl 4-methyl-2-nitrobenzoate, (E)-5,5-difluoro-4-oxo-5-phenylpent-2-en-1-yl 5-methyl-2-nitrobenzoate, (E)-5,5-difluoro-4-oxo-5-phenylpent-2-en-1-yl 2-methyl-6-nitrobenzoate, (E)-5,5-difluoro-4-oxo-5-phenylpent-2-en-1-yl 5-chloro-2-nitrobenzoate or (E)-5,5-difluoro-4-oxo-5-phenylpent-2-en-1-yl 2-nitro-4-(trifluoromethyl)benzoate.

[0014] One of the technical solutions of the present invention is to provide a method for preparing monofluoro / difluorooxoallyl esters, which method comprises the following steps:

[0015] (1) Compounds 3, a catalyst and an oxidant are added and mixed respectively, then Compound 1 or 2 is dissolved in a solvent and added, and the mixture is stirred until the reaction is complete, and then cooled to room temperature;

[0016] (2) The obtained reaction solution is subjected to extraction and separation to obtain Compound 4, namely monofluoro / difluorooxoallyl esters;

[0017] The chemical equation is:

[0018]

[0019] Further, in step (1), the catalyst is selected from one or more of palladium(II) acetate, palladium(II) bis(triphenylphosphine) acetate, palladium(II) tetra(acetonitrile) tetrafluoroborate, palladium(II) 1,2-bis(benzenesulfinyl)ethyl diacetate, palladium(II) hexafluoroacetylacetonate, palladium(II) (2,2'-bipyridine) dichloride, palladium(II) bis(triphenylphosphine) dichloride, palladium(II) dichloride and palladium(0) tetrakis(triphenylphosphine);

[0020] The oxidant is selected from one or more of silver(I) oxide, silver(I) trifluoromethanesulfonate, silver(I) acetate, silver(I) trifluoroacetate, silver(I) fluoride and silver(I) carbonate;

[0021] The solvent is selected from one or more of hexafluoroisopropanol (HFIP), tert-butanol (TBA), isopropanol (IPA), trifluoroethanol (TFE), ethanol (EtOH), dimethyl ketone (DMK), acetonitrile (ACN), tetrahydrofuran (THF), dimethylformamide (DMF) and dimethyl sulfoxide (DMSO).

[0022] Further, in step (1), the molar ratio of Compound 1 or 2, Compound 3 to the oxidant is (0.15 - 0.5):(0.35 - 0.7):(0.005 - 0.5), and the dosage of the catalyst is 10 - 20 mmol% of Compound 1 or 2.

[0023] Further, in step (1), the reaction temperature is 20 - 80 °C and the time is 8 - 12 h.

[0024] Further, in step (2), the extraction is carried out using an extraction liquid, the extraction liquid is ethyl acetate, the volume ratio of the extraction liquid to the reaction solution is 1:(1 - 1.5), and the number of extraction times is 3 - 4 times.

[0025] Further, in step (2), the separation is carried out by purification with an eluent in a chromatography column. The eluent is a mixture of petroleum ether and ethyl acetate with a volume ratio of (1 - 200):1, and the elution time is 1 - 2 h.

[0026] Compared with the prior art, the present invention has the following advantages:

[0027] (1) The preparation method of the present invention has the advantages of easily available raw materials, high efficiency, high yield, mild conditions, and environmental friendliness through a radical-induced rearrangement reaction, and has great application potential in the fields of medicine and pesticides;

[0028] (2) The present invention uses the synthesized α-hydroxy iodinated geminal mono-fluoro / difluoromethyl compound building blocks as raw materials, adds a catalyst and an oxidant, greatly shortens the reaction time, has mild reaction conditions, and a high yield;

[0029] (3) The mono-fluoro / difluorooxoallyl esters prepared by the present invention have the molecular skeletons of α-fluoro-unsaturated ketones or α,α-difluoro-unsaturated ketones, can be used as general building blocks for synthesizing pharmaceutical intermediates, have potential biological activities, and are easy to operate, which is beneficial to industrial production. Specific embodiments

[0030] The present invention will be described in detail below with reference to specific embodiments. These embodiments are implemented on the premise of the technical solution of the present invention, and detailed implementation manners and specific operation processes are given. However, the protection scope of the present invention is not limited to the following embodiments.

[0031] Unless otherwise specified, the equipment used in the following embodiments represents conventional equipment in the art; unless otherwise specified, the reagents used represent commercially available products or are prepared by conventional methods in the art. Those not described in detail in the following embodiments can be achieved by conventional experimental means in the art.

[0032] In this embodiment, a mild palladium-catalyzed radical-induced rearrangement reaction method of α-hydroxy iodinated geminal mono-fluoro / difluoromethyl compounds (compounds 1 and 2 are successfully synthesized building blocks, and the specific preparation method can refer to the article: Indium mediated barbier-type allylation: Synthesis of highly functionalized homoallylic difluorohydrins) and o-nitrobenzoic acid and its derivatives is adopted to synthesize a series of mono-fluoro / difluorooxoallyl esters. The chemical equation is as follows:

[0033]

[0034] Example 1:

[0035] (E)-5,5-difluoro-4-oxo-5-phenyl-2-en-1-yl-2-nitrobenzoate compound and its preparation method, the specific steps are as follows:

[0036] (1) In a 10 mL reaction tube dried in an oven and equipped with a magnetic stir bar, add 2-nitrobenzoic acid (0.45 mmol, 1.5 equiv), palladium(II) acetate (Pd(OAc) 2 , 20 mmol%), and silver(I) oxide (Ag 2 O, 0.225 mmol, 0.75 equiv); then take 1,1-difluoro-1-iodo-2-phenyl-4-en-2-ol (0.30 mmol, 1.0 equiv), dissolve it in hexafluoroisopropanol (HFIP, 1.5 mL), add it to the reaction tube, cover the reaction tube with a rubber stopper, and stir at 50 °C for 12 h; react until the raw materials are completely reacted as monitored by thin-layer chromatography (TLC), and then cool to room temperature;

[0037] (2) Filter by suction with diatomaceous earth, extract with an extraction solution, the extraction solution is ethyl acetate, the volume ratio of the extraction solution to the reaction solution is 1:(1 - 1.5), the number of extraction times is 3 - 4 times, the combined organic phase is dried with anhydrous sodium sulfate (Na 2 SO 4 ), concentrated under 0.6 - 0.8 kPa, separated and purified by an eluent in a chromatography column, the eluent is petroleum ether and ethyl acetate with a volume ratio of (5 - 20):1, the elution time is 1 - 2 h, and finally a pale yellow oily liquid (82.38 mg, yield 76%) is obtained, namely (E)-5,5-difluoro-4-oxo-5-phenyl-2-en-1-yl-2-nitrobenzoate compound, and its chemical structural formula is:

[0038]

[0039] The basic parameters of this compound are as follows:

[0040] 1 H NMR (500 MHz, CDCl 3 ) δ = 7.94 (d, J = 10.0 Hz, 1H), 7.77 (d, J = 10.0 Hz, 1H), 7.71 (q, J = 10.0 Hz, 2H), 7.57 (d, J = 10.0 Hz, 2H), 7.49 - 7.46 (m, 3H), 7.16 (dd, J = 20.0, 4.0 Hz, 1H), 6.76 (d, J = 10.0 Hz, 1H), 5.05 - 5.02 (m, 2H);

[0041] 1313C NMR(125MHz,CDCl 3 )δ=187.54(t, 2 J C-F =40.0Hz),164.69,148.37,143.58,133.12,132.39,131.92(t, 2 J C-F =31.25Hz),131.14,130.15,128.94,126,71,125.77(t, 3 J C-F =8.75Hz),124.13,122.28,116.12(t, 1 J C-F =315.0Hz),64.52;

[0042] 19 19F NMR(376MHz,CDCl 3 )δ=-106.89(s,2F);

[0043] HRMS(ESI-TOF):m / z[M+Na] + calcd for C 18 H 13 O 5 NF 2 :384.0654;found:384.0656.

[0044] Example 2:

[0045] A compound of (E)-5,5-difluoro-5-(4-methoxyphenyl)-4-oxo-2-en-1-yl 2-nitrobenzoate and its preparation method are substantially the same as those in Example 1, except that Compound 2 is 1,1-difluoro-1-iodo-2-(4-methoxyphenyl)pent-4-en-2-ol, and finally a pale yellow oily liquid (102.14 mg, yield 87%) is obtained, namely the compound of (E)-5,5-difluoro-5-(4-methoxyphenyl)-4-oxo-2-en-1-yl 2-nitrobenzoate, and the chemical structural formula is:

[0046]

[0047] The basic parameters of this compound are as follows:

[0048] 1 1H NMR(500MHz,CDCl 3) δ = 7.94 (d, J = 10.0 Hz, 1H), 7.77 - 7.76 (m, 1H), 7.73 - 7.68 (m, 2H), 7.49 (d, J = 5.0 Hz, 2H), 7.16 - 7.11 (m, 1H), 6.95 (d, J = 5.0 Hz, 2H), 6.73 (d, J = 15.0 Hz, 1H), 5.02 (d, J = 5.0 Hz, 2H), 3.82 (s, 3H);

[0049] 13 C NMR (125 MHz, CDCl 3 ) δ = 187.58 (t, 2 J C-F = 32.5 Hz), 164.65, 161.70, 148.30, 143.25, 133.07, 132.54, 132.33, 130.10, 127.33 (t, 3 J C-F = 6.25 Hz), 126.67, 124.07, 122.36, 116.28 (t, 1 J C-F = 252.5 Hz), 114.32, 64.50, 55.41;

[0050] 19 F NMR (376 MHz, CDCl 3 ) δ = -104.68 (s, 2F);

[0051] HRMS (ESI-TOF): m / z [M+Na] + calcd for C 19 H 15 O 6 NF 2 : 414.0760; found: 414.0754.

[0052] Example 3:

[0053] An (E)-5,5-difluoro-5-(3-methoxyphenyl)-4-oxo-2-en-1-yl-2-nitrobenzoate compound and its preparation method are substantially the same as in Example 1, except that Compound 2 is 1,1-difluoro-1-iodo-2-(3-methoxyphenyl)pent-4-en-2-ol, and finally a pale yellow oily liquid (97.44 mg, yield 83%) is obtained, which is the (E)-5,5-difluoro-5-(3-methoxyphenyl)-4-oxo-2-en-1-yl-2-nitrobenzoate compound, and its chemical structural formula is:

[0054]

[0055] The basic parameters of the compound are as follows:

[0056] 1 H NMR(500MHz,CDCl 3 )δ=7.93(d,J=5.0Hz,1H),7.76 - 7.75(m,1H),7.72 - 7.66(m,2H),7.37 - 7.34(m,1H),7.17 - 7.13(m,2H),7.07(s,1H),7.00(d,J=10.0Hz,1H),6.75(d,J=15.0Hz,1H),5.02(d,J=5.0Hz,2H),3.80(s,3H);

[0057] 13 C NMR(125MHz,CDCl 3 )δ=187.33(t, 2 J C-F =31.25Hz),164.62,159.91,148.30,143.63,133.19(t,2 J C-F =25.0Hz),133.09,132.37,130.14,130.10,126.61,124.05,122.15,117.89(t, 3 J C-F =6.25Hz),117.08,115.91(t, 1 J C-F =252.5Hz),110.85,64.45,55.44;

[0058] 19 F NMR(376MHz,CDCl 3 )δ= - 104.90(s,2F);

[0059] HRMS(ESI - TOF):m / z[M + Na] + calcd for C 19 H 15 O 6 NF 2 :414.0760;found:414.0756.

[0060] Example 4:

[0061] An (E)-5,5-difluoro-5-(2-methoxyphenyl)-4-oxo-2-en-1-yl-2-nitrobenzoate compound and its preparation method are basically the same as those in Example 1, except that Compound 2 is 1,1-difluoro-1-iodo-2-(2-methoxyphenyl)pent-4-en-2-ol, and finally a pale yellow oily liquid (93.92 mg, yield 80%) is obtained, namely the (E)-5,5-difluoro-5-(2-methoxyphenyl)-4-oxo-2-en-1-yl-2-nitrobenzoate compound, and its chemical structural formula is:

[0062]

[0063] The basic parameters of this compound are as follows:

[0064] 1 H NMR (500 MHz, CDCl 3 ) δ = 7.95 (d, J = 10.0 Hz, 1H), 7.76 - 7.74 (m, 1H), 7.72 - 7.68 (m, 2H), 7.63 (d, J = 10.0 Hz, 1H), 7.40 - 7.38 (m, 1H), 7.32 - 7.29 (m, 1H), 7.25 - 7.18 (m, 2H), 6.73 (d, J = 15.0 Hz, 1H), 5.05 (d, J = 5.0 Hz, 2H), 2.35 (s, 3H);

[0065] 13 C NMR (125 MHz, CDCl 3 ) δ = 186.86 (t, 2 J C-F = 32.5 Hz), 164.66, 148.24, 143.28, 136.94 (t, 3 J C-F = 3.75 Hz), 133.10, 132.33, 132.07, 131.03, 130.10 (t, 2 J C-F = 22.5 Hz), 130.02, 126.67, 126.30 (t, 3 J C-F = 10.0 Hz), 126.12, 124.08, 122.58, 116.66 (t, 1 J C-F = 252.5 Hz), 64.45, 19.89;

[0066] 19 F NMR (376 MHz, CDCl 3 ) δ = -102.76 (s, 2F);

[0067] HRMS(ESI-TOF): m / z [M+Na] + calcd for C 19 H 15 O 6 NF 2 : 414.0760;found: 414.0757.

[0068] Example 5:

[0069] A (E)-5,5-difluoro-5-(4-fluorophenyl)-4-oxo-2-en-1-yl-2-nitrobenzoate compound and its preparation method are basically the same as those in Example 1, except that Compound 2 is 2,2-difluoro-2-iodo-1-(4-methoxyphenyl)ethan-1-one (0.3121 g, 1 mmol), and finally a pale yellow oily liquid (85.34 mg, yield 75%) is obtained, namely the (E)-5,5-difluoro-5-(4-fluorophenyl)-4-oxo-2-en-1-yl-2-nitrobenzoate compound, and its chemical structural formula is:

[0070]

[0071] The basic parameters of this compound are as follows:

[0072] 1 H NMR(500 MHz, CDCl 3 ) δ=7.94 (d, J=5.0 Hz, 1H), 7.78 - 7.77 (m, 1H), 7.73 - 7.68 (m, 2H), 7.58 - 7.56 (m, 2H), 7.18 - 7.12 (m, 3H), 6.75 (d, J=15.0 Hz, 1H), 5.04 (d, J=5.0 Hz, 2H);

[0073] 13 C NMR(125 MHz, CDCl 3 ) δ=187.29 (t, 2 J C-F =32.5 Hz), 164.60 (t, 1 J C-F =157.5 Hz), 148.36, 143.87, 133.06, 132.40, 130.17, 128.14, 128.07, 126.56, 124.06, 121.95, 116.19, 116.01, 115,75 (t, 1 J C-F =252.5 Hz), 64.44;

[0074] 19 F NMR (376 MHz, CDCl 3 ) δ = -60.76 (s, 2F), -102.66 (s, 1F);

[0075] HRMS (ESI-TOF): m / z [M+Na] + calcd for C 18 H 12 O 5 NF 3 : 402.0560; found: 402.0558..

[0076] Example 6:

[0077] A compound of (E)-5-(3-chlorophenyl)-5,5-difluoro-4-oxo-2-en-1-yl-2-nitrobenzoate and its preparation method are basically the same as those in Example 1, except that Compound 2 is 2-(3-chlorophenyl)-1,1-difluoro-1-iodo-4-en-2-ol, and finally a pale yellow oily liquid (104.48 mg, yield 88%) is obtained, namely the compound of (E)-5-(3-chlorophenyl)-5,5-difluoro-4-oxo-2-en-1-yl-2-nitrobenzoate, and its chemical structural formula is:

[0078]

[0079] The basic parameters of this compound are as follows:

[0080] 1 H NMR (500 MHz, CDCl 3 ) δ = 7.95 (d, J = 5.0 Hz, 1H), 7.79 - 7.77 (m, 1H), 7.74 - 7.68 (m, 2H), 7.57 (s, 1H), 7.46 - 7.45 (m, 2H), 7.41 - 7.28 (m, 1H), 7.18 (d, J = 2.0 Hz, 1H), 6.77 (d, J = 15.0 Hz, 1H), 5.04 (d, J = 5.0 Hz, 2H);

[0081] 13 C NMR (125 MHz, CDCl 3 ) δ = 186.95 (t, 2 J C-F = 32.5 Hz), 164.60, 148.36, 144.18, 135.03, 133.96, 133.75, 133.07, 132.39, 131.32, 130.28, 130.14, 126.56, 126.03 (t,3 J C-F = 6.25 Hz), 124.07 (t, 3 J C-F = 6.25 Hz), 121.81, 115.25 (t, 1 J C-F = 252.5 Hz), 64.42;

[0082] 19 19F NMR (376 MHz, CDCl 3 ) δ = -104.89 (s, 2F);

[0083] HRMS (ESI-TOF): m / z [M+Na] + calcd for C 18 H 12 ClO 5 NF 2 : 418.0264; found: 418.0267.

[0084] Example 7:

[0085] An (E)-5,5-difluoro-5-(naphthalen-2-yl)-4-oxo-2-en-1-yl 2-nitrobenzoate compound and its preparation method are basically the same as those in Example 1, except that Compound 2 is 1,1-difluoro-1-iodo-2-(naphthalen-2-yl)pent-4-en-2-ol, and finally a pale yellow oily liquid (90.09 mg, yield 73%) is obtained, namely the (E)-5,5-difluoro-5-(naphthalen-2-yl)-4-oxo-2-en-1-yl 2-nitrobenzoate compound, and its chemical structural formula is:

[0086]

[0087] The basic parameters of this compound are as follows:

[0088] 1 1H NMR (500 MHz, CDCl 3 ) δ = 8.14 (s, 1H), 7.93 (d, J = 5.0 Hz, 3H), 7.87 (d, J = 5.0 Hz, 1H), 7.74 - 7.73 (m, 1H), 7.67 - 7.65 (m, 2H), 7.61 (d, J = 5.0 Hz, 1H), 7.57 - 7.55 (m, 2H), 7.18 (d, J = 2.0 Hz, 1H), 6.84 (d, J = 15.0 Hz, 1H), 5.02 (d, J = 5.0 Hz, 2H);

[0089] 1313C NMR (125 MHz, CDCl 3 ) δ = 187.50 (t, 2 J C-F = 32.5 Hz), 164.63, 148.31, 143.66, 134.30, 133.05, 132.60, 132.33, 130.11, 129.10, 128.78, 127.86, 127.82, 127.02, 126.60, 126.22 (t, 3 J C-F = 7.5 Hz), 124.05, 122.26, 122.00 (t, 3 J C-F = 6.25 Hz), 116.34 (t, 1 J C-F = 252.5 Hz), 64.47;

[0090] 19 19F NMR (376 MHz, CDCl 3 ) δ = -104.77 (s, 2F);

[0091] HRMS (ESI-TOF): m / z [M+Na] + calcd for C 22 H 15 O 5 NF 2 : 434.0811; found: 434.0802.

[0092] Example 8:

[0093] A compound of (E)-5,5-difluoro-4-oxo-5-phenyl-2-en-1-yl 4-methoxy-2-nitrobenzoate and its preparation method are basically the same as those in Example 1, except that Compound 2 is 1,1-difluoro-1-iodo-2-phenyl-4-en-2-ol, and finally a pale yellow oily liquid (99.79 mg, yield 85%) is obtained, namely the compound of (E)-5,5-difluoro-4-oxo-5-phenyl-2-en-1-yl 4-methoxy-2-nitrobenzoate, and its chemical structural formula is:

[0094]

[0095] The basic parameters of this compound are as follows:

[0096] 1 1H NMR (500 MHz, CDCl 3) δ = 7.84 (d, J = 10.0 Hz, 2H), 7.61 (d, J = 5.0 Hz, 2H), 7.51 - 7.46 (m, 3H), 7.28 - 7.27 (m, 1H), 7.18 - 7.15 (m, 2H), 6.79 (d, J = 15.0 Hz, 1H), 5.00 (d, J = 5.0 Hz, 2H), 3.94 (s, 3H);

[0097] 13 C NMR (125 MHz, CDCl 3 ) δ = 187.50 (t, 2 J C-F = 31.5 Hz), 163.63, 162.84, 150.94, 143.82, 132.45, 131.91 (t, 2 J C-F = 25.0 Hz), 131.07, 128.88, 125.72 (t, 3 J C-F = 6.25 Hz), 121.96, 117.39, 116.77, 116.10 (t, 1 J C-F = 252.5 Hz), 109.46, 64.17, 56.27;

[0098] 19 F NMR (376 MHz, CDCl 3 ) δ = -104.54 (s, 2F);

[0099] HRMS (ESI-TOF): m / z [M+Na] + calcd for C 19 H 15 O 6 NF 2 : 414.0706; found: 414.0764.

[0100] Example 9:

[0101] A compound of (E)-5,5-difluoro-4-oxo-5-phenyl-2-en-1-yl 4-fluoro-2-nitrobenzoate and its preparation method are substantially the same as those in Example 1, except that Compound 2 is 1,1-difluoro-1-iodo-2-phenyl-4-en-2-ol, and finally a pale yellow oily liquid (88.75 mg, yield 78%) is obtained, namely the compound of (E)-5,5-difluoro-4-oxo-5-phenyl-2-en-1-yl 4-fluoro-2-nitrobenzoate, and its chemical structural formula is:

[0102]

[0103] The basic parameters of the compound are as follows:

[0104] 1 H NMR(500MHz,CDCl 3 )δ=7.86 - 7.83(m,1H),7.60 - 7.56(m,3H),7.50 - 7.45(m,3H),7.42 - 7.39(m,1H),7.14(d,J=15.0Hz,1H),6.75(d,J=15.0Hz,1H),5.01(d,J=5.0Hz,2H);

[0105] 13 C NMR(125MHz,CDCl 3 )δ=187.43(t, 2 J C-F =32.5Hz),163.41(t, 1 J C-F =180.0Hz),143.32,132,67,132.60,131.12,129.17,128.90,125.70(t, 3 J C-F =7.5Hz),122.25,120.06,119.88,116.07(t, 1 J C-F =252.5Hz),112.25,112.04,64.60;

[0106] 19 F NMR(376MHz,CDCl 3 )δ= - 104.88(s,2F), - 155.64(s,1F);

[0107] HRMS(ESI - TOF):m / z[M + Na] + calcd for C 18 H 12 O 5 NF 3 :402.0560;found:402.0565.

[0108] Example 10:

[0109] An (E)-5,5-difluoro-4-oxo-5-phenyl-2-en-1-yl 3-chloro-2-nitrobenzoate compound and its preparation method are basically the same as those in Example 1, except that Compound 2 is 1,1-difluoro-1-iodo-2-phenyl-4-en-2-ol, and finally a pale yellow oily liquid (91.42 mg, yield 77%) is obtained, namely the (E)-5,5-difluoro-4-oxo-5-phenyl-2-en-1-yl 3-chloro-2-nitrobenzoate compound, and its chemical structural formula is:

[0110]

[0111] The basic parameters of this compound are as follows:

[0112] 1 H NMR(500MHz,CDCl 3 )δ=8.01(d,J=10.0Hz,1H),7.76(d,J=10.0Hz,1H),7.61-7.55(m,3H),7.49-7.46(m,3H),7.12(d,J=20.0Hz,1H),6.80(d,J=15.0Hz,1H),5.01(d,J=5.0Hz,2H);

[0113] 13 C NMR(125MHz,CDCl 3 )δ=187.48(t, 2 J C-F =31.25Hz),161.48,148.78,142.94,135.31,131.12,130.92,130.01,129.27,128.91,126.52,125.74(t, 3 J C-F =6.25Hz),123.69,122.23,116.09(t, 1 J C-F =252.5Hz),64.75;

[0114] 19 F NMR(376MHz,CDCl 3 )δ=-104.53(s,2F);

[0115] HRMS(ESI-TOF):m / z[M+Na] + calcd for C 18 H 12 ClO 5 NF 2 :418.0264;found:418.0268.

[0116] Example 11:

[0117] A compound of (E)-5,5-difluoro-4-oxo-5-phenyl-2-en-1-yl-5-bromo-2-nitrobenzoate and its preparation method are basically the same as those in Example 1, except that Compound 2 is 1,1-difluoro-1-iodo-2-phenyl-4-en-2-ol, and finally a pale yellow oily liquid (110.93 mg, yield 84%) is obtained, namely the compound of (E)-5,5-difluoro-4-oxo-5-phenyl-2-en-1-yl-5-bromo-2-nitrobenzoate, and its chemical structural formula is:

[0118]

[0119] The basic parameters of this compound are as follows:

[0120] 1 H NMR(500MHz,CDCl 3 )δ=7.86 - 7.84(m,2H),7.81 - 7.79(m,1H),7.57 - 7.55(m,2H),7.49 - 7.44(m,2H),7.41 - 7.37(m,1H),7.13(d,J=15.0Hz,1H),6.74(d,J=20.0Hz,1H),5.03(d,J=5.0Hz,2H);

[0121] 13 C NMR(125MHz,CDCl 3 )δ=187.38(t, 2 J C-F =32.5Hz),163.44,149.06,143.12,135.19,132.90,131.13,129.32,128.92,128.66,127.07,125.70,125.62,122.46,116.05(t, 1 J C-F =252.5Hz),64.78;

[0122] 19 F NMR(376MHz,CDCl 3 )δ=-104.88(s,2F);

[0123] HRMS(ESI-TOF):m / z[M+Na] + calcd for C 18 H 12 BrO 5 NF 2: 461.9759; found: 461.9760.

[0124] Example 12:

[0125] A (E)-5,5-difluoro-5-(4-fluorophenyl)-4-oxo-2-en-1-yl-4-methoxy-2-nitrobenzoate compound and its preparation method are basically the same as those in Example 1, except that Compound 2 is 1,1-difluoro-2-(4-fluorophenyl)-1-iodopent-4-en-2-ol, and finally a pale yellow oily liquid (98.24 mg, yield 80%) is obtained, namely the (E)-5,5-difluoro-5-(4-fluorophenyl)-4-oxo-2-en-1-yl-4-methoxy-2-nitrobenzoate compound, and its chemical structural formula is:

[0126]

[0127] The basic parameters of this compound are as follows:

[0128] 1 H NMR (500 MHz, CDCl 3 ) δ = 7.82 (d, J = 10.0 Hz, 1H), 7.59 - 7.56 (m, 2H), 7.24 - 7.23 (m, 1H), 7.16 - 7.11 (m, 4H), 6.75 (d, J = 15.0 Hz, 1H), 4.98 (d, J = 5.0 Hz, 2H), 3.91 (s, 3H);

[0129] 13 C NMR (125 MHz, CDCl 3 ) δ = 187.31 (t, 2 J C-F = 32.5 Hz), 163.59 (t, 1 J C-F = 216.25 Hz), 162.88, 150.95, 144.18, 132.53, 128.14, 128.07, 121.64, 117.36, 116.64, 116.16, 115.99, 115.77 (t, 1 J C-F = 252.5 Hz), 109.44, 64.15, 56.26;

[0130] 19 F NMR (376 MHz, CDCl 3 ) δ = -60.98 (s, 1F), -104.88 (s, 2F);

[0131] HRMS(ESI-TOF): m / z [M+Na] + calcd for C 19 H 14 O 6 NF 3 : 432.0665;found: 432.0666.

[0132] Example 13:

[0133] A (E)-5,5-difluoro-5-(4-fluorophenyl)-4-oxo-2-enyl-4,5-dimethoxy-2-nitrobenzoate compound and its preparation method are basically the same as those in Example 1, except that Compound 2 is 1,1-difluoro-1-iodo-2-phenyl-4-en-2-ol, and finally a pale yellow oily liquid (115.99 mg, yield 88%) is obtained, namely the (E)-5,5-difluoro-5-(4-fluorophenyl)-4-oxo-2-enyl-4,5-dimethoxy-2-nitrobenzoate compound, and its chemical structural formula is:

[0134]

[0135] The basic parameters of this compound are as follows:

[0136] 1 H NMR(500 MHz, CDCl 3 ) δ = 7.55 - 7.53 (m, 2H), 7.44 (s, 1H), 7.13 - 7.09 (m, 4H), 6.74 (d, J = 15.0 Hz, 1H), 5.00 (d, J = 5.0 Hz, 2H), 3.96 (s, 6H);

[0137] 13 C NMR(125 MHz, CDCl 3 ) δ = 187.28 (t, 2 J C-F = 32.5 Hz), 164.95, 163.30 (t, 1 J C-F = 248.75 Hz), 152.49, 150.90, 144.18, 141.56, 128.11, 128.04, 121.83, 120.30, 116.15, 115.98, 115.75 (t, 1 J C-F = 252.5 Hz), 111.03, 107.03, 64.37, 56.65 (t, J = 3.75 Hz);

[0138] 19F NMR (376 MHz, CDCl 3 ) δ = -61.65 (s, 1F), -104.89 (s, 2F);

[0139] HRMS (ESI-TOF): m / z [M+Na] + calcd for C 20 H 16 O 7 NF 3 : 462.0771; found: 462.0768.

[0140] Example 14:

[0141] A compound of (E)-5,5-difluoro-4-oxo-5-phenyl-2-en-1-yl 2-(2-nitrophenyl) acetate and its preparation method are basically the same as those in Example 1, except that Compound 2 is 1,1-difluoro-1-iodo-2-phenyl-4-en-2-ol, and finally a pale yellow oily liquid (85.58 mg, yield 76%) is obtained, namely the compound of (E)-5,5-difluoro-4-oxo-5-phenyl-2-en-1-yl 2-(2-nitrophenyl) acetate, and its chemical structural formula is:

[0142]

[0143] The basic parameters of this compound are as follows:

[0144] 1 H NMR (400 MHz, CDCl 3 ) δ = 8.16 (d, J = 8.0 Hz, 1H), 7.66 - 7.62 (m, 1H), 7.56 - 7.52 (m, 3H), 7.50 - 7.46 (m, 3H), 7.39 (d, J = 8.0 Hz, 1H), 7.10 (dt, J = 16.0, 8.0 Hz, 1H), 6.66 (d, J = 16.0 Hz, 1H), 4.84 - 4.82 (m, 2H), 4.10 (s, 2H);

[0145] 13 C NMR (125 MHz, CDCl 3 ) δ = 187.61 (t, 2 J C-F = 32.0 Hz), 169.30, 148.59, 144.69, 133.96, 133.56, 131.94 (t, 2 J C-F = 25.0 Hz), 131.15, 129.35, 129.06, 128.69, 125.75 (t,3 J C-F = 6.0 Hz), 125.55, 121.60, 116.11 (t, 1 J C-F = 252.0 Hz), 63.41, 39.80;

[0146] 19 F NMR (376 MHz, CDCl 3 ) δ = -106.89 (s, 2F);

[0147] HRMS (ESI-TOF): m / z [M+Na] + calcd for C 19 H 15 O 5 NF 2 : 398.0668; found: 398.0665.

[0148] Example 15:

[0149] A compound of (E)-5,5-difluoro-4-oxo-5-(o-tolyl)pent-2-en-1-yl 2-nitrobenzoate and its preparation method are basically the same as those in Example 1, except that Compound 2 is 1,1-difluoro-1-iodo-2-(o-tolyl)but-4-en-2-ol, and finally a pale yellow oily liquid (86.70 mg, yield 77%) is obtained, namely the compound of (E)-5,5-difluoro-4-oxo-5-(o-tolyl)pent-2-en-1-yl 2-nitrobenzoate, and its chemical structural formula is:

[0150]

[0151] The basic parameters of this compound are as follows:

[0152] 1 H NMR (500 MHz, CDCl 3 ) δ = 7.95 (d, J = 10.0 Hz, 1H), 7.76 - 7.69 (m, 3H), 7.63 (d, J = 10.0 Hz, 1H), 7.40 - 7.38 (m, 1H), 7.32 - 7.29 (m, 1H), 7.25 - 7.19 (m, 2H), 6.73 (d, J = 20.0 Hz, 1H), 5.05 (s, 2H), 2.36 (s, 3H);

[0153] 13 C NMR (125 MHz, CDCl 3 ) δ = 186.86 (t, 2 J C-F= 32.5 Hz), 164.62, 148.34, 143.41, 136.93 (t, 3 J C-F = 3.75 Hz), 133.10, 132.34, 132.12, 131.03, 130.11 (t, 2 J C-F = 22.5 Hz), 130.03, 126.70, 126.33 (t, 3 J C-F = 10.0 Hz), 126.11, 124.14, 122.60, 116.73 (t, 1 J C-F = 252.5 Hz), 64.41, 19.90;

[0154] 19 F NMR (376 MHz, CDCl 3 ) δ = -102.61 (s, 2F);

[0155] HRMS (ESI-TOF): m / z [M+Na] + calcd for C 19 H 15 O 5 NF 2 : 398.0811;found: 398.0809.

[0156] Example 16:

[0157] A compound of (E)-5-(2-chlorophenyl)-5,5-difluoro-4-oxopent-2-en-1-yl 2-nitrobenzoate and its preparation method are basically the same as those in Example 1, except that Compound 2 is 2-(2-chlorophenyl)-1,1-difluoro-1-iodo-4-en-2-ol, and finally a pale yellow oily liquid (93.79 mg, yield 79%) is obtained, namely the compound of (E)-5-(2-chlorophenyl)-5,5-difluoro-4-oxopent-2-en-1-yl 2-nitrobenzoate, and its chemical structural formula is:

[0158]

[0159] The basic parameters of this compound are as follows:

[0160] 1 H NMR (500 MHz, CDCl 3) δ = 7.96 (d, J = 5.0 Hz, 1H), 7.80 - 7.70 (m, 4H), 7.45 - 7.42 (m, 3H), 7.28 - 7.23 (m, 1H), 6.90 (d, J = 20.0 Hz, 1H), 5.11 - 5.10 (m, 2H);

[0161] 13 C NMR (125 MHz, CDCl 3 ) δ = 186.64 (t, 2 J C-F = 32.5 Hz), 164.71, 148.23, 143.48, 133.10, 132.33, 132.10, 130.87, 130.70, 130.04, 129.61, 127.94 (t, 3 J C-F = 8.75 Hz), 127.04, 126.90, 124.13, 122.52, 114.69 (t, 1 J C-F = 252.5 Hz), 64.53;

[0162] 19 F NMR (376 MHz, CDCl 3 ) δ = -102.32 (s, 2F);

[0163] HRMS (ESI-TOF): m / z [M+Na] + calcd for C 18 H 12 ClO 5 NF 2 : 418.0264; found: 418.0263.

[0164] Example 17:

[0165] A compound of (E)-5,5-difluoro-4-oxo-5-(4-trifluoromethylphenyl)pent-2-en-1-yl 2-nitrobenzoate and its preparation method are substantially the same as those in Example 1, except that Compound 2 is 1,1-difluoro-1-iodo-2-(4-trifluoromethylphenyl)pent-4-en-2-ol, and finally a pale yellow oily liquid (105.61 mg, yield 82%) is obtained, which is the compound of (E)-5,5-difluoro-4-oxo-5-(4-trifluoromethylphenyl)pent-2-en-1-yl 2-nitrobenzoate, and its chemical structural formula is:

[0166]

[0167] The basic parameters of this compound are as follows:

[0168] 1 1H NMR (500 MHz, CDCl 3 ) δ = 7.95 - 7.94 (m, 1H), 7.80 - 7.78 (m, 1H), 7.73 - 7.70 (m, 6H), 7.21 - 7.17 (m, 1H), 6.80 (d, J = 15.0 Hz, 1H), 5.05 - 5.06 (m, 2H);

[0169] 13 13C NMR (125 MHz, CDCl 3 ) δ = 186.91 (t, 2 J C-F = 32.5 Hz), 164.63, 148.40, 144.43, 135.58, 133.29, 133.03, 132.42, 130.21, 126.54 (t, 3 J C-F = 6.25 Hz), 125.88 (q, 1 J C-F = 3.75 Hz), 124.60, 124.13, 122.51, 121.72, 115.43 (t, 1 J C-F = 252.5 Hz), 64.4;

[0170] 19 19F NMR (376 MHz, CDCl 3 ) δ = -60.91 (s, 3F), -104.88 (s, 2F);

[0171] HRMS (ESI-TOF): m / z [M+Na] + calcd for C 19 H 12 O 5 NF 5 : 452.0528; found: 452.0526.

[0172] Example 18:

[0173] A compound of (E)-5,5-difluoro-4-oxo-5-phenylpent-2-en-1-yl 4-methyl-2-nitrobenzoate and its preparation method are basically the same as those in Example 1, except that Compound 3 is 4-methyl-2-nitrobenzoic acid, and finally a pale yellow oily liquid (85.58 mg, yield 76%) is obtained, namely the compound of (E)-5,5-difluoro-4-oxo-5-phenylpent-2-en-1-yl 4-methyl-2-nitrobenzoate, and its chemical structural formula is:

[0174]

[0175] The basic parameters of this compound are as follows:

[0176] 1 H NMR(500MHz,CDCl 3 )δ=7.68(d,J=10.0Hz,2H),7.57(d,J=10.0Hz,2H),7.48 - 7.45(m,4H),7.17 - 7.12(m,1H),6.76(d,J=15.0Hz,1H),4.99(s,2H),2.48(s,3H);

[0177] 13 C NMR(125MHz,CDCl 3 )δ=187.49(t, 2 J C-F =32.5Hz),164.44,148.81,144.08,143.83,133.30,131.90(t, 2 J C-F =25.0Hz),131.13,130.31,128.94,125.70(t, 3 J C-F =6.25Hz),124.33,123.21,122.07,116.12(t, 1 J C-F =252.5Hz),64.31,21.33;

[0178] 19 F NMR(376MHz,CDCl 3 )δ= - 104.94(s,2F);

[0179] HRMS(ESI - TOF):m / z[M+Na] + calcd for C 19 H 15 O 5 NF 2 :398.0811;found:398.0815.

[0180] Example 19:

[0181] An (E)-5,5-difluoro-4-oxo-5-phenylpent-2-en-1-yl 5-methyl-2-nitrobenzoate compound and its preparation method are basically the same as those in Example 1, except that Compound 3 is 5-methyl-2-nitrobenzoic acid, and finally a pale yellow oily liquid (102.47 mg, yield 91%) is obtained, namely the (E)-5,5-difluoro-4-oxo-5-phenylpent-2-en-1-yl 5-methyl-2-nitrobenzoate compound, and its chemical structural formula is:

[0182]

[0183] The basic parameters of this compound are as follows:

[0184] 1 H NMR(500MHz,CDCl 3 )δ=7.91-7.89(m,1H),7.59(s,2H),7.51-7.48(m,5H),7.20-7.16(m,1H),6.79(d,J=15.0Hz,1H),5.04(s,2H),2.50(s,3H);

[0185] 13 C NMR(125MHz,CDCl 3 )δ=187.51(t, 2 J C-F =32.5Hz),165.10,145.72,144.93,143.77,132.42,131.86(t, 2 J C-F =25.0Hz),131.10,130.21,128.87,127.24,125.70(t, 3 J C-F =6.25Hz),124.28,122.33,116.14(t, 1 J C-F =252.5Hz),64.40,21.41;

[0186] 19 F NMR(376MHz,CDCl 3 )δ=-104.67(s,2F);

[0187] HRMS(ESI-TOF):m / z[M+Na] + calcd for C 19 H 15 O 5 NF 2: 398.0811; found: 398.0817.

[0188] Example 20:

[0189] A (E)-5,5-difluoro-4-oxo-5-phenylpent-2-en-1-yl 2-methyl-6-nitrobenzoate compound and its preparation method are basically the same as those in Example 1, except that Compound 3 is 6-methyl-2-nitrobenzoic acid, and finally a pale yellow oily liquid (86.70 mg, yield 77%) is obtained, namely the (E)-5,5-difluoro-4-oxo-5-phenylpent-2-en-1-yl 2-methyl-6-nitrobenzoate compound, and its chemical structural formula is:

[0190]

[0191] The basic parameters of this compound are as follows:

[0192] 1 H NMR (500 MHz, CDCl 3 ) δ = 8.04 - 8.03 (m, 1H), 7.58 - 7.57 (m, 3H), 7.51 - 7.48 (m, 3H), 7.24 - 7.20 (m, 1H), 6.79 (d, J = 10.0 Hz, 1H), 5.10 (s, 2H), 2.43 - 2.42 (m, 3H);

[0193] 13 C NMR (125 MHz, CDCl 3 ) δ = 187.51 (t, 2 J C-F = 32.5 Hz), 165.73, 146.30, 143.88, 137.71, 136.19, 131.93 (t, 2 J C-F = 25.0 Hz), 131.11, 130.23, 128.94, 128.50, 125.69 (t, 3 J C-F = 6.25 Hz), 122.53, 122.01, 116.14 (t, 1 J C-F = 252.5 Hz), 64.27, 19.22;

[0194] 19 F NMR (376 MHz, CDCl 3 ) δ = -104.65 (s, 2F);

[0195] HRMS (ESI-TOF): m / z [M+Na]+ Calculated for C 19 H 15 O 5 NF 2 : 398.0811; found: 398.0813.

[0196] Example 21:

[0197] A (E)-5,5-difluoro-4-oxo-5-phenylpent-2-en-1-yl 5-chloro-2-nitrobenzoate compound and its preparation method are basically the same as those in Example 1, except that Compound 3 is 5-chloro-2-nitrobenzoic acid, and finally a pale yellow oily liquid (92.60 mg, yield 78%) is obtained, namely (E)-5,5-difluoro-4-oxo-5-phenylpent-2-en-1-yl 5-chloro-2-nitrobenzoate compound, and its chemical structural formula is:

[0198]

[0199] The basic parameters of this compound are as follows:

[0200] 1 H NMR (500 MHz, CDCl 3 ) δ = 7.95 (d, J = 5.0 Hz, 1H), 7.70 (d, J = 5.0 Hz, 1H), 7.65 - 7.63 (m, 1H), 7.57 - 7.56 (m, 2H), 7.49 - 7.46 (m, 3H), 7.17 - 7.12 (m, 1H), 6.75 (d, J = 15.0 Hz, 1H), 5.03 - 5.04 (m, 2H);

[0201] 13 C NMR (125 MHz, CDCl 3 ) δ = 187.43 (t, 2 J C-F = 32.5 Hz), 163.61, 149.07, 146.23, 143.11, 139.87, 132.14, 131.12, 130.04, 128.92, 128.66 (t, 3 J C-F = 12.5 Hz), 127.11, 125.74 (t, 3 J C-F = 12.5 Hz), 122.52, 116.01 (t, 1 J C-F = 252.5 Hz), 64.83;

[0202] 1919F NMR (376 MHz, CDCl 3 ) δ = -104.90 (s, 2F);

[0203] HRMS (ESI-TOF): m / z [M+Na] + calcd for C 18 H 12 ClO 5 NF 2 : 418.0264; found: 418.0264.

[0204] Example 22:

[0205] A compound of (E)-5,5-difluoro-4-oxo-5-phenyl-2-en-1-yl-2-nitro-4-(trifluoromethyl) benzoate and its preparation method are basically the same as those in Example 1, except that compound 3 is 2-nitro-4-(trifluoromethyl) benzoic acid, and finally a pale yellow oily liquid (105.61 mg, yield 82%) is obtained, namely the compound of (E)-5,5-difluoro-4-oxo-5-phenyl-2-en-1-yl-2-nitro-4-(trifluoromethyl) benzoate, and its chemical structural formula is:

[0206]

[0207] The basic parameters of this compound are as follows:

[0208] 1 1H NMR (500 MHz, CDCl 3 ) δ = 8.25 (s, 1H), 7.98 - 7.90 (m, 2H), 7.56 (s, 2H), 7.48 (s, 3H), 7.16 - 7.13 (m, 1H), 6.75 (d, J = 15.0 Hz, 1H), 5.06 (s, 2H);

[0209] 13 13C NMR (125 MHz, CDCl 3 ) δ = 187.43 (t, 2 J C-F = 32.5 Hz), 163.61, 148.08, 142.91, 134.70, 134.43, 131.81 (t, 2 J C-F = 26.25 Hz), 131.13, 130.91, 130.03 (t, 3 J C-F = 5.0 Hz), 128.91, 125.70 (t, 3 J C-F= 6.25 Hz), 123.33, 122.58, 121.61 (t, 3 J C-F = 3.75 Hz), 116.03 (t, 1 J C-F = 252.5 Hz), 64.91;

[0210] 19 F NMR (376 MHz, CDCl 3 ) δ = -61.19 (s, 3F), -102.83 (s, 2F);

[0211] HRMS (ESI-TOF): m / z [M+Na] + calcd for C 19 H 12 O 5 NF 5 : 452.0528;found: 452.0525.

[0212] Example 23:

[0213] A (E)-5-fluoro-4-oxo-5-phenyl-2-en-1-yl-4,5-difluoro-2-nitrobenzoate compound and its preparation method are basically the same as those in Example 1, except that compound 3 is 4,5-difluoro-2-nitrobenzoic acid and compound 1 is 1-fluoro-1-iodo-2-phenyl-4-en-2-ol. Finally, a pale yellow oily liquid (83.06 mg, yield 73%) was obtained, namely the (E)-5-fluoro-4-oxo-5-phenyl-2-en-1-yl-4,5-difluoro-2-nitrobenzoate compound, and its chemical structural formula is:

[0214]

[0215] The basic parameters of this compound are as follows:

[0216] 1 H NMR (500 MHz, CDCl 3 ) δ = 7.86 - 7.83 (m, 1H), 7.61 - 7.55 (m, 2H), 7.50 - 7.45 (m, 3H), 7.15 - 7.11 (m, 1H), 6.73 (d, J = 20.0 Hz, 1H), 5.03 - 5.02 (m, 2H);

[0217] 13 C NMR (125 MHz, CDCl 3 ) δ = 187.41 (t, 2 J C-F= 32.5 Hz), 162.72, 153.63 (t, 3 J C-F = 11.25 Hz), 152.27 (t, 2 J C-F = 12.5 Hz), 151.03 (t, 3 J C-F = 11.25 Hz), 150.21 (t, 2 J C-F = 12.5 Hz), 144.23 (t, 3 J C-F = 7.5 Hz), 142.89, 131.80 (t, 2 J C-F = 25.0 Hz), 131.13, 128.91, 125.74 (t, 3 J C-F = 6.25 Hz), 122.61, 119.43 (t, 1 J C-F = 21.25 Hz), 116.03 (t, 1 J C-F = 252.5 Hz), 114.81 (t, 1 J C-F = 22.5 Hz), 64.90;

[0218] 19 F NMR (376 MHz, CDCl 3 ) δ = -123.99--125.02 (m, 2F), -155.84 (d, J = 48.5 Hz, 1F);

[0219] HRMS (ESI-TOF): m / z [M+Na] + calcd for C 18 H 11 O 5 NF 3 : 398.0811; found: 398.0810.

[0220] Example 24:

[0221] An (E)-5-fluoro-4-oxo-5-phenylpent-2-en-1-yl 2-(5-fluoro-2-nitrophenyl)acetate compound and its preparation method are basically the same as those in Example 1, except that Compound 3 is 2-(5-fluoro-2-nitrophenyl)acetic acid and Compound 1 is 1-fluoro-1-iodo-2-phenyl-4-en-2-ol. Finally, a pale yellow oily liquid (91.21 mg, yield 81%) was obtained, namely the (E)-5-fluoro-4-oxo-5-phenylpent-2-en-1-yl 2-(5-fluoro-2-nitrophenyl)acetate compound, and its chemical structural formula is:

[0222]

[0223] The basic parameters of this compound are as follows:

[0224] 1 H NMR (500 MHz, CDCl 3 ) δ=8.23 - 8.21 (m, 1H), 7.66 - 7.62 (m, 1H), 7.55 (s, 2H), 7.48 - 7.41 (m, 3H), 7.19 - 7.18 (m, 1H), 7.10 - 7.08 (m, 2H), 6.68 (d, J=15.0 Hz, 1H), 4.84 (s, 2H), 4.09 - 4.08 (m, 2H);

[0225] 13 C NMR (125 MHz, CDCl 3 ) δ=187.53 (t, 2 J C-F =32.5 Hz), 168.71, 165.94, 163.81, 144.43, 132.78 (t, 2 J C-F =8.75 Hz), 131.92 (t, 2 J C-F =25.0 Hz), 131.07, 128.91, 128.43 (t, 3 J C-F =5.0 Hz), 125.70 (t, 3 J C-F =6.25 Hz), 121.83, 120.41 (t, 1 J C-F =23.75 Hz), 116.02 (t, 1 J C-F =252.0 Hz), 115.88 (t, 2 J C-F =11.25 Hz), 63.52, 39.80;

[0226] 19 F NMR (376 MHz, CDCl 3 ) δ = -100.97 (s, 1F), -155.86 (d, J = 48.5 Hz, 1F);

[0227] HRMS (ESI-TOF): m / z [M+Na] + calcd for C 19 H 14 O 5 NF 2 : 398.0810; found: 398.0799.

[0228] Example 25:

[0229] A compound of (E)-5-fluoro-4-oxo-5-phenylpent-2-en-1-yl 2-(4-bromo-2-nitrophenyl)acetate and its preparation method are basically the same as those in Example 1, except that compound 3 is 2-(4-bromo-2-nitrophenyl)acetic acid and compound 1 is 1-fluoro-1-iodo-2-phenylbut-4-en-2-ol. Finally, a pale yellow oily liquid (102.08 mg, yield 78%) was obtained, which is the compound of (E)-5-fluoro-4-oxo-5-phenylpent-2-en-1-yl 2-(4-bromo-2-nitrophenyl)acetate. The chemical structural formula is:

[0230]

[0231] The basic parameters of this compound are as follows:

[0232] 1 H NMR (500 MHz, CDCl 3 ) δ = 8.31 (s, 1H), 7.78 - 7.76 (m, 1H), 7.59 - 7.57 (m, 2H), 7.52 - 7.49 (m, 3H), 7.29 - 7.28 (m, 1H), 7.13 - 7.09 (m, 1H), 6.69 (d, J = 15.0 Hz, 1H), 4.85 - 4.85 (m, 2H), 4.07 (s, 2H);

[0233] 13 C NMR (125 MHz, CDCl 3 ) δ = 187.52 (t, 2 J C-F = 31.25 Hz), 168.70, 149.01, 144.27, 136.80, 134.73, 131.91, 131.09, 128.92, 128.40, 128.22, 125.66 (t,3 J C-F = 6.25 Hz), 122.10, 121.83, 116.01 (t, 1 J C-F = 252.0 Hz), 63.48, 39.22;

[0234] 19 F NMR (376 MHz, CDCl 3 ) δ = -155.82 (d, J = 48.5 Hz, 1F);

[0235] HRMS (ESI-TOF): m / z [M+Na] + calcd for C 19 H 14 BrO 5 NF: 458.0010; found: 458.0098.

[0236] Example 26:

[0237] A compound of (E)-5-fluoro-4-oxo-5-phenylpent-2-en-1-yl 2-(2-nitro-4-(trifluoromethyl)phenyl)acetate and its preparation method are basically the same as those in Example 1, except that Compound 3 is 2-(2-nitro-4-trifluoromethyl)phenylacetic acid, Compound 1 is 1-fluoro-1-iodo-2-phenyl-4-en-2-ol, and finally a pale yellow oily liquid (105.91 mg, yield 83%) is obtained, namely the compound of (E)-5-fluoro-4-oxo-5-phenylpent-2-en-1-yl 2-(2-nitro-4-(trifluoromethyl)phenyl)acetate, and its chemical structural formula is:

[0238]

[0239] The basic parameters of this compound are as follows:

[0240] 1 H NMR (500 MHz, CDCl 3 ) δ = 8.45 - 8.44 (m, 1H), 7.91 - 7.90 (m, 1H), 7.58 - 7.58 (m, 3H), 7.51 - 7.50 (m, 3H), 7.14 - 7.11 (m, 1H), 6.73 - 6.69 (m, 1H), 4.87 (s, 2H), 4.21 - 4.19 (m, 2H);

[0241] 13 C NMR (125 MHz, CDCl 3 ) δ = 187.50 (t, 2 J C-F= 32.5 Hz), 168.46, 148.71, 144.23, 134.41, 133.10, 131.93, 131.58, 131.14, 130.22, 128.90, 125.73 (t, 3 J C-F = 5.0 Hz), 123.81, 122.69, 121.22, 116.01 (t, 1 J C-F = 251.25 Hz), 63.63, 39.54;

[0242] 19 F NMR (376 MHz, CDCl 3 ) δ = -61.08 (s, 3F), -155.87 (d, J = 48.5 Hz, 1F);

[0243] HRMS (ESI-TOF): m / z [M+Na] + calcd for C 20 H 14 O 5 NF 4 : 448.0779;found: 448.0778.

[0244] The above description of the embodiments is for the convenience of those of ordinary skill in the art to understand and use the invention. It is obvious that those skilled in the art can easily make various modifications to these embodiments and apply the general principles described herein to other embodiments without creative efforts. Therefore, the present invention is not limited to the above embodiments, and the improvements and modifications made by those skilled in the art without departing from the scope of the present invention should be within the protection scope of the present invention.

Claims

1. A method for preparing a mono-fluoro / difluoro oxoallyl ester compound, characterized in that, the method comprises the following steps: (1) Add compound 3, a catalyst and an oxidant respectively and mix them, then dissolve compound 1 or 2 in a solvent and add it, stir the reaction, and then cool to room temperature; (2) The obtained reaction solution is subjected to extraction and separation to obtain compound 4, namely the mono-fluoro / difluoro oxoallyl ester compound; The chemical equation is: ， Among them, R 1 is phenyl or substituted phenyl, R 2 is substituted phenyl, R f is mono-fluoro or di-fluoro; The described R 1 When it is a substituted phenyl group, the substituents in the substituted phenyl group are selected from one or more of phenyl, fluorine, chlorine, bromine, methoxy, methyl and trifluoromethyl; The described R 2 When it is a substituted phenyl group, the substituents in the substituted phenyl group are selected from one or more of nitro, fluorine, chlorine, bromine, methoxy, methyl and trifluoromethyl; In step (1), the catalyst used is palladium(II) acetate; The oxidant used is silver(I) oxide; The solvent used is hexafluoroisopropanol.

2. The method for preparing a mono-fluoro / difluoro oxoallyl ester compound according to claim 1, characterized in that, the mono-fluoro oxoallyl ester compound includes (E)-5-fluoro-4-oxo-5-phenyl-2-en-1-yl 4,5-difluoro-2-nitrobenzoate.

3. The method for preparing a mono-fluoro / difluoro oxoallyl ester compound according to claim 1, characterized in that, The described difluorooxoallyl ester compounds include (E)-5,5-difluoro-4-oxo-5-phenylpent-2-en-1-yl 2-nitrobenzoate, (E)-5,5-difluoro-5-(4-methoxyphenyl)-4-oxo-pent-2-en-1-yl 2-nitrobenzoate, (E)-5,5-difluoro-5-(3-methoxyphenyl)-4-oxo-pent-2-en-1-yl 2-nitrobenzoate, (E)-5,5-difluoro-5-(2-methoxyphenyl)-4-oxo-pent-2-en-1-yl 2-nitrobenzoate, (E)-5,5-difluoro-5-(4-fluorophenyl)-4-oxo-pent-2-en-1-yl 2-nitrobenzoate, (E)-5-(3-chlorophenyl)-5,5-difluoro-4-oxo-pent-2-en-1-yl 2-nitrobenzoate, (E)-5,5-difluoro-4-oxo-5-phenylpent-2-en-1-yl 4-methoxy-2-nitrobenzoate, (E)-5,5-difluoro-4-oxo-5-phenylpent-2-en-1-yl 4-fluoro-2-nitrobenzoate, (E)-5,5-difluoro-4-oxo-5-phenylpent-2-en-1-yl 3-chloro-2-nitrobenzoate, (E)-5,5-difluoro-4-oxo-5-phenylpent-2-en-1-yl 5-bromo-2-nitrobenzoate, (E)-5,5-difluoro-5-(4-fluorophenyl)-4-oxo-pent-2-en-1-yl 4-methoxy-2-nitrobenzoate, (E)-5,5-difluoro-5-(4-fluorophenyl)-4-oxo-pent-2-en-1-yl 4,5-dimethoxy-2-nitrobenzoate, (E)-5,5-difluoro-4-oxo-5-(o-tolyl)pent-2-en-1-yl 2-nitrobenzoate, (E)-5-(2-chlorophenyl)-5,5-difluoro-4-oxopent-2-en-1-yl 2-nitrobenzoate, (E)-5,5-difluoro-4-oxo-5-(4-trifluoromethylphenyl)pent-2-en-1-yl 2-nitrobenzoate, (E)-5,5-difluoro-4-oxo-5-phenylpent-2-en-1-yl 4-methyl-2-nitrobenzoate, (E)-5,5-difluoro-4-oxo-5-phenylpent-2-en-1-yl 5-methyl-2-nitrobenzoate, (E)-5,5-difluoro-4-oxo-5-phenylpent-2-en-1-yl 2-methyl-6-nitrobenzoate, (E)-5,5-difluoro-4-oxo-5-phenylpent-2-en-1-yl 5-chloro-2-nitrobenzoate or (E)-5,5-difluoro-4-oxo-5-phenylpent-2-en-1-yl 2-nitro-4-(trifluoromethyl)benzoate.

4. The preparation method of a monofluoro / difluorooxoallyl ester compound according to claim 1, characterized in that In step (1), the molar ratio of compound 1 or 2, compound 3 to the oxidant is (0.15 - 0.5):(0.35 - 0.7):(0.005 - 0.5), and the dosage of the catalyst is 10 - 20 mmol% of compound 1 or 2.

5. A method for preparing a monofluoro / difluorooxoallyl ester compound according to claim 1, characterized in that, in step (1), the reaction temperature is 20 - 80 °C and the time is 8 - 12 h.

6. A method for preparing a monofluoro / difluorooxoallyl ester compound according to claim 1, characterized in that, in step (2), extraction is carried out using an extraction solution, the extraction solution is ethyl acetate, the volume ratio of the extraction solution to the reaction solution is 1:(1 - 1.5), and the number of extraction times is 3 - 4 times.

7. A method for preparing a monofluoro / difluorooxoallyl ester compound according to claim 1, characterized in that, in step (2), separation is carried out by purification in a chromatography column using an eluent, the eluent is petroleum ether and ethyl acetate with a volume ratio of (1 - 200):1, and the elution time is 1 - 2 h.

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