A method for preparing difluoromethyl arene compounds based on palladium-catalyzed decarbonyl coupling

Abstract

The application belongs to the technical field of medicine, chemical industry and related chemistry, and discloses a preparation method of difluoromethyl arene compound based on palladium catalytic decarbonylation coupling. The method uses aryl boronic acid as a raw material, uses N, N-disubstituted difluoroacetamide compound as a difluoromethylation reagent, and prepares difluoromethyl arene compound under the catalysis of palladium, so that the green and efficient synthesis is realized. The method has the advantages of easy preparation and storage of the difluoromethylation reagent, high reaction selectivity, good functional group compatibility, wide substrate application range, environmental friendliness and the like. Since the difluoromethyl arene compound is an important functional molecular skeleton structure, the compound has very wide application in the fields of fine chemical industry and pharmacy, so that the application has great application value and social and economic benefits.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical and chemical intermediates and related chemical technologies, and relates to a method for preparing difluoromethyl aromatic hydrocarbons using arylboronic acid compounds and N,N-disubstituted difluoroacetamide compounds as raw materials. Background Technology

[0002] Fluoroalkyl organic compounds, especially those containing trifluoromethyl groups, possess unique physicochemical properties or physiological activities and are widely used as pharmaceutical and functional material molecules. Difluoromethyl aromatics are an important class of skeletal structures for synthetic drugs or functional molecules, with very wide applications in organic synthesis. Since the synthesis of arylboronic acids, organic chemists have conducted diverse studies on their synthesis and functionalization reactions. Among these, the difluoromethylation of arylboronic acids has shown great potential in the synthesis of pharmaceuticals and pesticides.

[0003] The synthesis of difluoromethyl aromatics is currently a research hotspot. With increasing attention to sustainable development and human health, green chemistry, characterized by high efficiency, low pollution, and atom economy, has gained widespread importance. Therefore, efficient and green synthetic methods for difluoromethyl aromatics are of great interest. Existing technologies utilize common difluoromethylating reagents, such as difluorochloromethane, difluorobromomethane, difluoroiodomethane, trimethyl(difluoromethyl)silane, trimethyl(ethyl difluorobromoacetate)silane, difluoroacetylfluoride, difluoromethylsilver, and difluoromethyltin. However, these reagents are gaseous, making them difficult to store and use, and are expensive, requiring complex preparation methods. Current research has not reported any studies on the decarbonylation and coupling of arylboronic acid compounds with N,N-disubstituted difluoroacetamide compounds to synthesize difluoromethyl aromatics. Summary of the Invention

[0004] To address the problems existing in the prior art, this invention provides a method for synthesizing difluoromethyl aromatics by reacting arylboronic acid compounds with N,N-disubstituted difluoroacetamide compounds. This method features high selectivity and yield, mild reaction conditions, high atom economy, and good catalytic effect, and is of significant importance. The method uses arylboronic acid compounds and N,N-disubstituted difluoroacetamide compounds as raw materials to achieve palladium-catalyzed synthesis of difluoromethyl aromatics. This method has advantages such as a simple catalytic system, good selectivity, mild conditions, good atom economy, environmental friendliness, and ease of industrialization. The difluoromethylating reagents used are solids at room temperature, making them easy to store and use. The raw materials, difluoroacetic acid or difluoroacetic anhydride, are inexpensive and readily available, and the method is scalable, allowing the synthesis of other fluoroalkyl reagents using the same approach. This invention has significant application value and socio-economic benefits.

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

[0006] A class of difluoromethyl aromatic hydrocarbons, with the following general structural formula:

[0007]

[0008] Wherein: R = hydrogen, straight-chain or branched alkyl, cycloalkyl, aryl, amino, alkoxy, phenoxy, trifluoromethyl, trifluoromethoxy, halogen, nitro, cyano, acyl, alkoxycarbonyl, alkylthio, carbazole, alkylsulfonyl, pyridinyl, one or a combination of two of these.

[0009] A method for preparing difluoromethyl aromatic compounds based on palladium-catalyzed decarbonylation coupling is disclosed. Using arylboronic acid compounds and N,N-disubstituted difluoroacetamide compounds as raw materials, a series of difluoromethyl aromatics are synthesized through a palladium-catalyzed decarbonylation coupling reaction between arylboronic acid compounds and N,N-disubstituted difluoroacetamide compounds. The synthetic route is as follows:

[0010]

[0011] Wherein: R = hydrogen, straight-chain or branched alkyl, cycloalkyl, aryl, amino, alkoxy, phenoxy, trifluoromethyl, trifluoromethoxy, halogen, nitro, cyano, acyl, alkoxycarbonyl, alkylthio, carbazole, alkylsulfonyl, pyridinyl; R 1 = Straight-chain or branched alkyl, aryl, benzyl, straight-chain or branched acyl, straight-chain or branched alkoxycarbonyl, benzyloxycarbonyl, benzoyl, straight-chain or branched alkylsulfonyl, benzylsulfonyl, p-toluenesulfonyl;

[0012] The specific steps are as follows:

[0013] (1) Arylboronic acid compound 1, palladium catalyst, ligand, N,N-disubstituted difluoroacetamide compound 2, base and organic solvent are added sequentially to a reactor and reacted at 25-160℃ for 4-48 h; wherein, the molar ratio of arylboronic acid compound to N,N-disubstituted difluoroacetamide compound is 1:1-1:5, the molar ratio of arylboronic acid compound to base is 1:0.5-1:5, the molar ratio of arylboronic acid compound to palladium catalyst is 1:0.01-1:0.4, the molar ratio of arylboronic acid compound to ligand is 1:0.01-1:0.4, and the concentration of arylboronic acid compound 1 in the reaction system is 0.05-0.3 mol / L;

[0014] (2) After the reaction was completed, the solvent was removed by vacuum distillation, and the solvent was separated by silica gel column separation with eluent to obtain difluoromethyl aromatic hydrocarbon 3.

[0015] The arylboronic acid compound 1 includes phenylboronic acid, linear or branched alkylphenylboronic acid, cycloalkylphenylboronic acid, biphenylboronic acid, morpholinophenylboronic acid, alkoxyphenylboronic acid, phenoxyphenylboronic acid, trifluoromethylphenylboronic acid, trifluoromethoxyphenylboronic acid, halogenated phenylboronic acid, nitrophenylboronic acid, cyanophenylboronic acid, acylphenylboronic acid, alkoxyformylphenylboronic acid, alkylthiophenylboronic acid, carbazolephenylboronic acid, alkylsulfonylphenylboronic acid, pyridylphenylboronic acid, naphthaleneboronic acid, linear or branched alkylnaphthaleneboronic acid, methoxynaphthaleneboronic acid, anthraquinoneboronic acid, phenanthreneboronic acid, fluoreneboronic acid, pyreneboronic acid, and indoleboronic acid; the N,N-disubstituted difluoroacetamide compound 2 includes N-methyl-N-phenyldifluoroacetamide. N-Ethyl-N-phenyldifluoroacetamide, N-Isopropyl-N-phenyldifluoroacetamide, N-tert-Butyl-N-phenyldifluoroacetamide, N-Phenylene-N-acetyldifluoroacetamide, N-Phenylene-N-propionyldifluoroacetamide, N-Phenylene-N-benzoyldifluoroacetamide, N-Phenylene-N-methoxycarbonyldifluoroacetamide, N-Phenylene-N-ethoxycarbonyldifluoroacetamide, N-Phenylene-N-tert-butoxycarbonyldifluoroacetamide, N-Phenylene-N-methanesulfonyldifluoroacetamide, N-Phenylene-N-benzenesulfonyldifluoroacetamide, N-Phenylene-N-p-toluenesulfonyldifluoroacetamide.

[0016] The reaction temperature range is 25–160℃, preferably 80–130℃.

[0017] The reaction time ranges from 4 to 48 hours, preferably from 8 to 24 hours.

[0018] The palladium catalyst is selected from palladium chloride, palladium acetate, palladium trifluoroacetate, palladium trifluoromethanesulfonate, palladium / carbon, palladium hydroxide / carbon, bis(acetylacetone)palladium, bis(benzylideneacetone)palladium, tri(benzylideneacetone)dipalladium, bis(triphenylphosphine)dichloride, tetra(triphenylphosphine)palladium, and (1,5-cyclooctadiene)dichloride.

[0019] The ligand is selected from triphenylphosphine, tris(2-tolyl)phosphine, tris(dimethylamino)phosphine, tricyclohexylphosphine, diphenylcyclohexylphosphine, tri-(1-adamantyl)phosphine, 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl, tris(4-trifluorotolyl)phosphine, 2-diphenylphosphine-2'-(N,N-dimethylamino)biphenyl, 2-dicyclohexylphosphine-2',6'-dimethoxybiphenyl, tris(2-furanyl)phosphine, etc. Phosphorus, 2-diphenylphosphine-2',4',6'-triisopropylbiphenyl, (2-methoxyphenyl)diphenylphosphine, 4,5-bis(dicyclohexylphosphine)-9,9-dimethyloxanthracene, 1,2-bis(diphenylphosphine)ethane, 1,3-bis(diphenylphosphine)propane, bis(2-(diphenylphosphine)phenyl)ether, 2,2'-bipyridine, 1,10-phenanthroline, 4,7-diphenyl-1,10-phenanthroline.

[0020] The base used is selected from lithium carbonate, potassium carbonate, cesium carbonate, potassium bicarbonate, sodium bicarbonate, sodium formate, potassium acetate, sodium pentovanate, potassium pentovanate, sodium phosphate, potassium phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, and potassium tert-butoxide.

[0021] The amount of organic solvent is 1 to 1000 mL, and the organic solvent is selected from n-butyl ether, methyl tert-butyl ether, tetrahydrofuran 1,4-dioxane, carbon tetrachloride, 1,2-dichloroethane, cyclohexane, dimethyl sulfoxide, N,N-dimethylformamide, acetonitrile, benzene, toluene, xylene, fluorobenzene, trifluorotoluene, and dimethyl carbonate.

[0022] The beneficial effects of this invention are as follows: This invention relates to a method for preparing difluoromethyl aromatic compounds based on palladium-catalyzed decarbonylation coupling, which has the advantages of easy preparation and storage of difluoromethylating reagents, high reaction selectivity, good functional group compatibility, wide substrate applicability, and environmental friendliness. Specifically:

[0023] (1) This method is for the decarbonylation coupling reaction of arylboronic acid compounds with N,N-disubstituted difluoroacetamide compounds. Existing techniques have disadvantages such as difficulty in preparing and storing difluoromethylating reagents, low reaction yields, and harsh reaction conditions. In this application, N,N-disubstituted difluoroacetamide compounds are used as difluoromethylating reagents to synthesize difluoromethyl aromatics through a decarbonylation coupling reaction with arylboronic acids. This method has advantages such as ease of preparation and storage, simple reaction system, and mild reaction conditions.

[0024] (2) The difluoromethylating reagents used in this method are easy to prepare and store. The difluoromethylating reagents used in the prior art, such as difluorochloromethane, difluorobromomethane, difluoroiodomethane, trimethyl(difluoromethyl)silane, trimethyl(ethyl difluorobromoacetate)silane, difluoroacetylfluoride, difluoromethylsilver, and difluoromethyltin, have disadvantages such as being gaseous and difficult to store and use, being expensive, and having complex preparation methods.

[0025] (3) The catalyst exhibits high catalytic efficiency, resulting in both high reaction selectivity and yield. In summary, this method is an effective way to prepare difluoromethyl aromatics with readily available and easily stored difluoromethylating reagents, high catalytic efficiency, good reaction selectivity, and high product yield. Since difluoromethyl aromatics are an important functional molecular skeleton structure with wide applications in medicine, pesticides, and materials, this invention has significant application value and socio-economic benefits. Attached Figure Description

[0026] Figure 1 For compound 3a 1 H-NMR.

[0027] Figure 2 For compound 3a 13C-NMR.

[0028] Figure 3 For compound 3a 19 F-NMR.

[0029] Figure 4 For compound 3b 1 H-NMR.

[0030] Figure 5 For compound 3b 13 C-NMR.

[0031] Figure 6 For compound 3b 19 F-NMR.

[0032] Figure 7 For compound 3c 1 H-NMR.

[0033] Figure 8 For compound 3c 13 C-NMR.

[0034] Figure 9 For compound 3c 19 F-NMR.

[0035] Figure 10 For compound 3d 1 H-NMR.

[0036] Figure 11 For compound 3d 13 C-NMR.

[0037] Figure 12 For compound 3d 19 F-NMR.

[0038] Figure 13 For compound 3e 1 H-NMR.

[0039] Figure 14 For compound 3e 13 C-NMR.

[0040] Figure 15 For compound 3e 19 F-NMR.

[0041] Figure 16 For compound 3f 1 H-NMR.

[0042] Figure 17 For compound 3f 13 C-NMR.

[0043] Figure 18 For compound 3f 19 F-NMR. Detailed Implementation

[0044] The specific embodiments of the present invention will be further described below with reference to the accompanying drawings and technical solutions.

[0045] The method for preparing difluoromethyl aromatic hydrocarbons described in this invention has the advantages of easy preparation and storage of difluoromethylating reagents, high catalytic efficiency, good reaction selectivity, and high product yield, showing good application prospects.

[0046] The preparation method of difluoromethyl aromatic hydrocarbon is as follows:

[0047] (1) Arylboronic acid compound 1, palladium catalyst, N,N-disubstituted difluoroacetamide compound 2, base and organic solvent are added sequentially to a reactor and reacted at 25-160℃ for 4-48h; the molar ratio of arylboronic acid compound to N,N-disubstituted difluoroacetamide compound is 1:1 to 1:5, the molar ratio of arylboronic acid compound to base is 1:0.5 to 1:5, and the molar ratio of arylboronic acid compound to palladium catalyst is 1:0.01 to 1:0.4;

[0048] (2) After the reaction was completed, the solvent was removed by vacuum distillation, and the solvent was separated by silica gel column separation with eluent to obtain difluoromethyl aromatic hydrocarbon 3.

[0049]

[0050]

[0051] Examples 1 to 6 were carried out using the above methods. The detailed preparation processes of only a few representative compounds are listed below:

[0052] Example 1: Synthesis of 4-phenyldifluorotoluene (3a)

[0053]

[0054] Accurately weigh 0.20 g (1.0 mmol) of 4-phenylphenylboronic acid, 0.22 g (1.2 mmol) of N-methyl-N-phenyldifluoroacetamide, 5.6 mg (0.025 mmol) of palladium acetate, 13.4 mg (0.05 mmol) of triphenylphosphine, and 0.14 g (1.0 mmol) of potassium carbonate, and add them sequentially to a 50 mL Schlenk flask. Add 6.0 mL of N,N-dimethylformamide and react in an oil bath at 130 °C for 20 h. After the reaction is complete, remove the solvent by vacuum distillation. Use petroleum ether / ethyl acetate (v / v 50:1) as eluent and separate by silica gel column chromatography. The yield of 4-phenyldifluorotoluene is 87%. 1 H NMR (400MHz, CDCl3) δ7.67 (d, J = 8.1Hz, 2H), 7.61–7.57 (m, 4H), 7.48–7.44 (m, 2H), 7.40–7.37 (m, 1H), 6.69 (t, J = 56.5Hz, 1H). 13 C NMR(101MHz,CDCl3)δ143.7(t,J C-F =2.0Hz), 140.2, 133.2(t,J) C-F =22.7Hz),129.0,127.9,127.5,127.3,126.1(t,J C-F =6.0Hz), 114.8(t,J C-F =239.5Hz). 19 F NMR (376MHz, CDCl3) δ-110.3 (s, 2F).

[0055] Example 2: Synthesis of 4-nitrodifluorotoluene (3b)

[0056]

[0057] Accurately weigh 0.33 g (2.0 mmol) of 4-nitrophenylboronic acid, 0.69 g (3.0 mmol) of N-phenyl-N-methoxycarbonyl difluoroacetamide, 8.8 mg (0.05 mmol) of palladium chloride, 2-dicyclohexylphosphine-2′,6′-dimethoxy-biphenyl (20.5 mg (0.05 mmol)) and 0.64 g (3.0 mmol) of potassium phosphate, and add them sequentially to a 50 mL Schlenk flask. Add 6.0 mL of dimethyl sulfoxide and react in an oil bath at 105 °C for 16 h. After the reaction is complete, remove the solvent by vacuum distillation. Use petroleum ether / ethyl acetate (v / v 30:1) as eluent and separate by silica gel column chromatography. The yield of 4-nitrodifluorotoluene is 97%. 1H NMR (600MHz, CDCl3) δ8.33(d,J=8.6Hz,2H),7.72(d,J=8.5Hz,2H),6.75(t,J=55.8Hz,1H). 13 C NMR(151MHz,CDCl3)δ149.4,140.2(t,J C-F =22.9Hz), 126.9(t,J C-F =6.0Hz), 124.0, 113.2(t,J) C-F =241.3Hz). 19 F NMR (565MHz, CDCl3) δ-113.0 (s, 2F).

[0058] Example 3: Synthesis of 3-benzyloxydifluorotoluene (3c)

[0059]

[0060] Accurately weigh 1.14 g (5.0 mmol) of 3-benzyloxyphenylboronic acid, 1.65 g (6.0 mmol) of N-phenyl-N-benzoyl difluoroacetamide, 114 mg (10 wt%) of palladium on carbon, 20.6 mg (0.05 mmol) of 1,3-bis(diphenylphosphine)propane, and 1.20 g (12.0 mmol) of potassium bicarbonate, and add them sequentially to a 100 mL Schlenk flask. Add toluene (20.0 mL) and react in an oil bath at 110 °C for 18 h. After the reaction is complete, remove the solvent by vacuum distillation. Use petroleum ether / ethyl acetate (v / v 50:1) as eluent and separate by silica gel column chromatography. The yield of 3-benzyloxydifluorotoluene is 98%. 1 H NMR(600MHz, CDCl3)δ7.41(d,J=7.0Hz,2H),7.39–7.36(m,2H),7.35–7.31(m,2H) ,7.11(s,1H),7.06(dd,J=13.2,8.0Hz,2H),6.58(t,J=56.5Hz,1H),5.05(s,2H). 13 C NMR(151MHz,CDCl3)δ159.0,136.5,135.8(t,J C-F =22.3Hz),130.0,128.7,128.1,127.5,118.1(t,J C-F =6.2Hz), 117.3, 114.5(t,J) C-F =239.2Hz), 111.8(t,J C-F =6.1Hz), 70.1. 19F NMR (565MHz, CDCl3) δ-110.6 (s, 2F).

[0061] Example 4: Synthesis of 1-difluoromethylnaphthalene (3d)

[0062]

[0063] Accurately weigh 1-naphtholic boric acid (0.52 g, 3.0 mmol), N-phenyl-N-p-toluenesulfonyl difluoroacetamide (1.30 g, 4.0 mmol), bis(acetylacetone)palladium (15.2 mg, 0.05 mmol), (2-methoxyphenyl)diphenylphosphine (29.2 mg, 0.10 mmol), and cesium carbonate (0.65 g, 2.0 mmol) and add them sequentially to a 50 mL Schlenk flask. Add 1,4-dioxane (10.0 mL) and react in an oil bath at 140 °C for 24 h. After the reaction is complete, remove the solvent by vacuum distillation. Use petroleum ether / ethyl acetate (v / v 50:1) as eluent and separate by silica gel column chromatography. The yield of 1-difluoromethylnaphthalene is 87%. 1 H NMR(600MHz, CDCl3)δ8.21(d,J=8.0Hz,1H),8.03–7.92(m,2H),7.73(dd,J=7 .0,0.8Hz,1H),7.66–7.56(m,2H),7.55–7.52(m,1H),7.17(t,J=55.2Hz,1H). 13 C NMR (151MHz, CDCl3) δ133.8,131.5,129.7,129.6(t,J C-F =20.9Hz),128.8,127.2,126.4,124.8(t,J C-F =8.7Hz),124.7,123.6,115.5(t,J C-F =238.8Hz), 113.9. 19 F NMR (565MHz, CDCl3) δ-110.9 (s, 2F).

[0064] Example 5: Synthesis of 9-difluoromethylphenanthrene (3e)

[0065]

[0066] Accurately weigh 0.22 g (1.0 mmol) of 9-phenanthroline, 0.40 g (1.5 mmol) of N-phenyl-N-ethanesulfonyl difluoroacetamide, 28.8 mg (0.05 mmol) of di(benzyleneacetone)palladium, 9.0 mg (0.05 mmol) of 1,10-phenanthroline, and 0.27 g (2.0 mmol) of potassium dihydrogen phosphate, and add them sequentially to a 50 mL Schlenk flask. Add 5.0 mL of xylene and react in an oil bath at 80 °C for 36 h. After the reaction is complete, remove the solvent by vacuum distillation. Use petroleum ether / ethyl acetate (v / v 50:1) as eluent and separate by silica gel column chromatography. The yield of 9-difluoromethylphenanthrene is 88%. 1 H NMR (600MHz, CDCl3) δ8.72 (dd, J=37.0, 8.2Hz, 2H), 8.26 (dd, J=8.1, 1.1Hz, 1H), 7.99 (s, 1H),7.95(d,J=7.9Hz,1H),7.80–7.69(m,3H),7.68–7.65(m,1H),7.18(t,J=55.1Hz,1H). 13 C NMR (151MHz, CDCl3) δ131.4,130.9,130.2,129.5,128.3,128.0(t,J C-F =20.4Hz),127.9,127.24,127.16,127.1,126.9(t,J C-F =9.3Hz),124.5,123.3,122.7,115.7(t,J C-F =238.7Hz). 19 FNMR(565MHz, CDCl3)δ-111.7(s,2F).

[0067] Example 6: Synthesis of 9,9-dimethyl-2-difluoromethylfluorene (3f)

[0068]

[0069] Accurately weigh 0.36 g (1.5 mmol) of 9,9-dimethyl-2-fluoreneboronic acid, 0.50 g (2.0 mmol) of N-phenyl-N-methanesulfonyl difluoroacetamide, 5.5 mg (0.025 mmol) of palladium trifluoroacetate, 14.0 mg (0.05 mmol) of tricyclohexylphosphine, and 0.29 g (3.0 mmol) of potassium acetate, and add them sequentially to a 50 mL Schlenk flask. Add 5.0 mL of methyl tert-butyl ether and react in an oil bath at 110 °C for 30 h. After the reaction is complete, remove the solvent by vacuum distillation. Use petroleum ether / ethyl acetate (v / v 50:1) as eluent and separate by silica gel column chromatography. The product 9,9-dimethyl-2-difluoromethylfluorene is obtained in 97% yield. 1 H NMR (600MHz, CDCl3) δ7.88–7.79(m,2H),7.66(s,1H),7.58–7.50(m,2H),7.48–7.38(m,2H),6.79(td,J=56.7,2.0Hz,1H),1.57(d,J=1.9Hz,6H). 13 C NMR (151MHz, CDCl3) δ154.1,141.8,138.2,133.2(t,J C-F =21.9Hz),128.2,127.2,124.8(t,J C-F =6.2Hz),122.8,120.6,120.2,119.9(t,J C-F =5.8Hz), 115.3(t,J C-F =238.5Hz), 47.1, 27.0. 19 F NMR (565MHz, CDCl3) δ-108.9 (s, 2F).

[0070] The examples show that when the R group is a substituent with electron-withdrawing or electron-donating properties, the reaction yield is high, and it is applicable to the difluoromethylation of naphthylboronic acid, phenanthreneboronic acid, fluorenylboronic acid, etc.

Claims

1. A method for preparing difluoromethyl aromatic compounds based on palladium-catalyzed decarbonylation coupling, characterized in that, With arylboronic acid compounds and N,N Using disubstituted difluoroacetamide compounds as raw materials, palladium-catalyzed arylboronic acid compounds react with... N, N Decarbonylation coupling of disubstituted difluoroacetamide compounds to synthesize a series of difluoromethyl aromatics; The specific steps are as follows: (1) Arylboronic acid compounds, palladium catalysts, ligands, N,N Disubstituted difluoroacetamide compounds, alkali, and organic solvents are added sequentially to the reactor, and the reaction is carried out at 25–160 °C for 4–48 h; among which, arylboronic acid compounds and N,N The molar ratio of disubstituted difluoroacetamide compounds is 1:1 to 1:5; the molar ratio of arylboronic acid compounds to base is 1:0.5 to 1:5; the molar ratio of arylboronic acid compounds to palladium catalyst is 1:0.01 to 1:0.4; the molar ratio of arylboronic acid compounds to ligand is 1:0.01 to 1:0.4; and the concentration of arylboronic acid compounds in the reaction system is 0.05 to 0.3 mol / L. (2) After the reaction was completed, the solvent was removed by vacuum distillation, and the product was separated by silica gel column chromatography with eluent to obtain difluoromethyl aromatic hydrocarbons; The arylboronic acid compounds are phenylboronic acid, biphenylboronic acid, morpholinophenylboronic acid, phenoxyphenylboronic acid, trifluoromethylphenylboronic acid, trifluoromethoxyphenylboronic acid, halophenylboronic acid, nitrophenylboronic acid, cyanophenylboronic acid, carbazolephenylboronic acid, pyridylphenylboronic acid, naphthaleneboronic acid, methoxynaphthaleneboronic acid, anthraquinoneboronic acid, phenanthreneboronic acid, fluoreneboronic acid, pyreneboronic acid, or indoleboronic acid; N,N -Disubstituted difluoroacetamide compounds are N -methyl- N -Phenylon difluoroacetamide, N -Ethyl- N -Phenylon difluoroacetamide, N -Isopropyl- N -Phenylon difluoroacetamide, N -Terbutyl- N -Phenylon difluoroacetamide, N -phenyl- N - Acetyl difluoroacetamide, N -phenyl- N -Propionyl difluoroacetamide, N -phenyl- N -benzoyl difluoroacetamide, N -phenyl- N -Methoxycarbonyl difluoroacetamide, N -phenyl- N -Ethoxycarbonyl difluoroacetamide, N -phenyl- N -tert-Butyloxycarbonyl difluoroacetamide, N -phenyl- N -Methanesulfonyl difluoroacetamide, N -phenyl- N -Ethylenesulfonyl difluoroacetamide, N -phenyl- N -benzenesulfonyl difluoroacetamide or N -phenyl- N -p-Toluenesulfonyl difluoroacetamide; The palladium catalyst is selected from palladium chloride, palladium acetate, palladium trifluoroacetate, palladium trifluoromethanesulfonate, palladium / carbon, palladium hydroxide / carbon, bis(acetylacetone)palladium, bis(benzylidene acetone)palladium, tri(benzylidene acetone)palladium, bis(triphenylphosphine)palladium dichloride, tetra(triphenylphosphine)palladium, and (1,5-cyclooctadiene)palladium dichloride. The ligand is selected from triphenylphosphine, tris(2-tolyl)phosphine, tris(dimethylamino)phosphine, tricyclohexylphosphine, diphenylcyclohexylphosphine, tri-(1-adamantyl)phosphine, 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl, tris(4-trifluorotolyl)phosphine, 2-diphenylphosphine-2'-( N , N (-Dimethylamino)biphenyl, 2-dicyclohexylphosphine-2',6'-dimethoxybiphenyl, tris(2-furanyl)phosphine, 2-diphenylphosphine-2',4',6'-triisopropylbiphenyl, (2-methoxyphenyl)diphenylphosphine, 4,5-bis(dicyclohexylphosphine)-9,9-dimethyloxanthracene, 1,3-bis(diphenylphosphine)propane, 2,2'-bipyridine, 1,10-phenanthroline, 4,7-diphenyl-1,10-phenanthroline.

2. The method for preparing difluoromethyl aromatic compounds based on palladium-catalyzed decarbonylation coupling according to claim 1, characterized in that, The base used is selected from lithium carbonate, potassium carbonate, cesium carbonate, potassium bicarbonate, sodium bicarbonate, sodium formate, potassium acetate, sodium pentovanate, potassium pentovanate, sodium phosphate, potassium phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, and potassium tert-butoxide.

3. The method for preparing difluoromethyl aromatic compounds based on palladium-catalyzed decarbonylation coupling according to claim 1, characterized in that, The organic solvent is selected from n-butyl ether, methyl tert-butyl ether, tetrahydrofuran, 1,4-dioxane, carbon tetrachloride, 1,2-dichloroethane, cyclohexane, acetonitrile, benzene, toluene, xylene, fluorobenzene, trifluorotoluene, and dimethyl carbonate.

Images