A phosphine carboxamide compound, a preparation method and application thereof

Abstract

This invention provides a phosphonocarboxamide compound, its preparation method, and its applications. Under inert gas protection, a highly active metal catalyst is generated in situ by a metal salt and a metal reducing agent. With the aid of a ligand, phosphonochloride undergoes cross-coupling with isocyanate or thioisocyanate to prepare phosphonocarboxamides of formula I, II, or III. The phosphonocarboxamide of formula I is then reacted with an oxidizing agent (or a sulfiding agent) to prepare oxidized (or sulfided) phosphonocarboxamides of formula IV. The phosphonocarboxamides or oxidized (or sulfided) phosphonocarboxamides provided by this invention can be used as good ligands for coupling reactions catalyzed by metal catalysts. This invention provides a method for preparing phosphonocarboxamide compounds, using an inexpensive metal salt as a catalyst and air-insensitive and relatively stable phosphonochloride as a raw material for cross-coupling with isocyanate or thioisocyanate to obtain high-value-added phosphonocarboxamides of formulas I, II, and III. The reaction conditions are mild and safe, making it easy to industrialize and apply, and it has broad prospects for industrial production.

Description

Technical Field

[0001] This invention belongs to the field of organic compound preparation technology, specifically relating to a phosphonocarboxamide compound, its preparation method, and its application. Background Technology

[0002] Organophosphine compounds have attracted widespread attention in modern chemistry due to their unique electronic and steric properties. Phosphine carboxamides, as important organophosphine molecules, contain both hard electron donors (N and O atoms) and soft electron donors (P atoms). This bidentate or multidentate coordination property of phosphine carboxamides has broad applications in catalysis chemistry, materials chemistry, and medicinal chemistry.

[0003] Reference 1 ( J. Org. Chem. 1959, 24, 1460–1462 This report describes the preparation of phosphine carboxamide compounds by reacting phenyl (or substituted phenyl) isocyanate, phosphine (PH3), and triethylamine at room temperature with benzene as a solvent. This preparation method suffers from low yield (only 13%) and long reaction time (4 days). The reaction formula is as follows: ; Reference 2 ( Organometallics 2013, 32, 1141–1149 The paper reports on the reaction of isocyanates or thioisocyanates with diphenylphosphine (Ph2PH) using lanthanum metal catalysts to obtain phosphonocarboxamides or phosphonothioamides in moderate to excellent yields (38-93%). The preparation reaction formula is as follows: Reference 3 ( Angew. Chem., Int. Ed . 2017, 56, 4845–4848 The paper reports on the iron-catalyzed reaction of isocyanates with diphenylphosphine, in which isocyanates are reacted with diphenylphosphine in the presence of catalytic amounts of (2,6-Mes2C6H3)2Fe (Mes=2,4,6-Me3C6H2) or (2,6-Tmp2C6H3)2Fe(THF) (Tmp=2,4,5-Me3C6H2) to give the corresponding phosphonocarboxamides or phosphonodicarboxamides. The preparation reaction formulas are as follows: In references 2 and 3, although the reactions showed good reactivity and chemoselectivity, they were only applicable to HPPh2 as a phosphine source, while HPPh2 is highly toxic, very sensitive to air, and prone to spontaneous combustion and oxidation.

[0004] Therefore, the development of a preparation method for the industrial production of phosphonic amides that can use stable phosphonating reagents as raw materials, has mild and efficient reaction conditions, and can achieve high conversion and yield is currently anticipated in this field. Summary of the Invention

[0005] This invention provides a phosphonocarboxamide compound, its preparation method, and its applications. The preparation method provided by this invention uses a stable phosphonating reagent as a raw material, and the reaction conditions are mild and efficient, enabling the preparation of phosphonocarboxamide compounds with high conversion and yield. The preparation method is as follows: Under nitrogen (argon or other inert gas) protection, a highly active metal catalyst is generated in situ from a metal salt and a reducing agent. Then, under the action of ligands, the raw material phosphine chloride undergoes cross-coupling with isocyanate or thioisocyanate to prepare phosphocarboxamides as shown in Formulas I, II, and III. The general formula for its preparation reaction is as follows: Where R is a substituted phenyl, a substituted biphenyl, a substituted benzyl, a substituted C1-C10 alkyl, or a substituted cycloalkyl. R -C or S -C chiral alkyl group, and the definition of other substituents R in this invention is the same as that herein.

[0006] Where X is an oxygen atom or a sulfur atom, and the definition of X is the same as here when other substituents X appear in this invention.

[0007] Wherein R' is phenyl, the same or different substituted phenyl, substituted biphenyl, substituted benzyl, substituted C1-C10 alkyl or substituted cycloalkyl, and other substituents R' in this invention are defined in the same way as here.

[0008] [cat] refers to metal salt catalysts, selected from nickel salts such as nickel chloride, nickel bromide, nickel iodide, nickel acetate, nickel acetylacetonate, bis(triphenylphosphine) chloride, nickel acetate tetrahydrate, nickel chloride hexahydrate, nickel chloride dimethoxyethane, nickel bromide dimethoxyethane, nickel chloride diethylene glycol dimethyl ether, or nickel bromide diethylene glycol dimethyl ether; and cobalt salts such as cobalt chloride, cobalt bromide, cobalt iodide, cobalt acetate, bis(acetylacetonate) cobalt, tri(acetylacetonate) cobalt, bis(triphenylphosphine) dichloride, hexaaminocobalt chloride, cobalt perchlorate hexahydrate, cobalt chloride hexahydrate, and cobalt acetate tetrahydrate. Or cobalt carbonate, chromium salts such as chromium dichloride, chromium trichloride, chromium dibromide, or chromium tribromide; bismuth salts such as bismuth chloride, bismuth bromide, bismuth iodide, or bismuth acetate; iron salts such as ferric chloride, ferric chloride, ferric dibromide, ferric tribromide, ferric acetate, or ferric acetylacetone; copper salts such as cuprous chloride, cuprous bromide, cuprous iodide, cuprous acetate, cuprous cyanide, copper thiophene-2-carboxylate, copper bromide, copper acetate, copper sulfate, copper trifluoromethanesulfonate, copper tetraacetonitrile tetrafluoroborate, copper chloride dihydrate, or copper sulfate pentahydrate; indium salts such as indium trichloride or indium dichloride; preferably nickel acetate tetrahydrate; [cat] In the synthesis of the phosphonocarboxamides shown in Formula I, the amount used is at least 0.1-20 mol% equivalent of isocyanate or thioisocyanate, preferably 10 mol% equivalent; in the synthesis of the phosphonocarboxamides shown in Formulas II and III, the amount used is at least 0.1-20 mol% equivalent of phosphine chloride, preferably 10 mol% equivalent.

[0009] It should be specifically noted that in the above general formula for preparation, the molar ratio of phosphine chloride to isocyanate or thioisocyanate is 3:1-1:5; in the synthesis of phosphine carboxamide shown in Formula I, the molar ratio of phosphine chloride to isocyanate or thioisocyanate is 3:1-1:3, preferably 2:1; in the synthesis of phosphine carboxamide shown in Formula II, the molar ratio of phosphine chloride to isocyanate or thioisocyanate is 1:1.5-1:5, preferably 1:2; and in the synthesis of phosphine carboxamide shown in Formula III, the molar ratio of phosphine chloride to isocyanate or thioisocyanate is 1:1.5-1:5, preferably 1:2.

[0010] M is a metal reducing agent, selected from zinc or manganese. In the synthesis of the phosphonocarboxamide shown in Formula I, the amount used is at least 1-4 molar equivalents of isocyanate or thioisocyanate, preferably 2.5-3 molar equivalents. In the synthesis of the phosphonocarboxamides shown in Formulas II and III, the amount used is at least 1-4 molar equivalents of phosphine chloride, preferably 2.5-3 molar equivalents.

[0011] L is a ligand selected from monodentate, bidentate, or tridentate nitrogen ligands, such as substituted 2,2'-bipyridine, substituted 1,10-phenanthroline, or substituted terpyridine, preferably 1,10-phenanthroline. In the synthesis of the phosphonocarboxamide shown in Formula I, the amount used is at least 0.15-30 mol% equivalent of isocyanate or thioisocyanate, preferably 15 mol% equivalent. In the synthesis of the phosphonocarboxamides shown in Formulas II and III, the amount used is at least 0.15-30 mol% equivalent of phosphine chloride, preferably 15 mol% equivalent.

[0012] The reaction solvent is selected from N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, tetrahydrofuran (THF), 1,4-dioxane, acetone or acetonitrile; preferably N,N-dimethylformamide; the amount used is isocyanate or thioisocyanate in a concentration of 0.1M-10M, preferably 1M (M: 1mol / L).

[0013] The reaction temperature is from -20°C to 180°C; preferably 60-100°C; more preferably 80°C.

[0014] The reaction time is 1h-24h, preferably 14-18h, and more preferably 16h.

[0015] It should be noted that this reaction needs to be carried out under nitrogen (argon or other inert gas) protection, using inexpensive metal salts such as nickel salts as catalysts, and using dialkylphosphine chloride or diarylphosphine chloride, which are insensitive to air, relatively stable, widely available and inexpensive, as raw materials to directly construct NCP bonds with isocyanates. This method has the advantages of high yield (up to 95%), convenient operation, good selectivity and easy industrial production.

[0016] The phosphonocarboxamide compounds or oxidized (or sulfidated) phosphonocarboxamide compounds prepared according to the preparation method of the present invention are preferably the following compounds: The phosphonocarboxamide prepared by the above method as shown in Formula I can be further reacted with an oxidizing agent (or a sulfurizing agent) to obtain the oxidized (or sulfurized) phosphonocarboxamide as shown in Formula IV. The preparation reaction formula is as follows: [O] or S (i.e., oxidizing agent or sulfiding agent) is selected from hydrogen peroxide or sulfur powder.

[0017] It is worth mentioning that the phosphonocarboxamide compounds or oxidized (or sulfided) phosphonocarboxamide compounds prepared by this invention can be used as ligands in coupling reactions catalyzed by metal catalysts, especially as ligands in Suzuki coupling reactions catalyzed by metal catalysts.

[0018] Surprisingly, the phosphonocarboxamide compounds prepared in this invention exhibit better performance than conventional phosphonic ligands such as triphenylphosphine. They show higher yields when used to synthesize important intermediates for fungicides such as fluopyram, bifenazate, cyazofamid, and benzymediazon, including nitrobiphenyl or aminobiphenyl (e.g., under the same reaction conditions, compound 3ah, as a ligand, achieves a 96% yield in the synthesis of fluopyram intermediate compound 7, while using triphenylphosphine as a ligand yields only 80%). This is likely due to the tunable coordination atoms of these compounds. The phosphonocarboxamide compounds prepared in this invention have potential applications in constructing bidentate or multidentate ligands for metal catalysis, chiral synthesis, and other fields.

[0019] This invention provides a method for preparing phosphonocarboxamide compounds. Under the catalysis of a metal salt catalyst, air-insensitive and relatively stable phosphonium chloride is used as a starting material for cross-coupling with isocyanates or thioisocyanates to obtain high-value-added phosphonocarboxamides represented by formulas I, II, and III. The reaction conditions are mild, safe, and easy for industrial production, overcoming the problems of instability, high toxicity, or low reaction yield of phosphonides or diphenylphosphonides. This reaction utilizes a metal catalyst, exhibiting good functional group compatibility, allowing phosphonium chloride to react smoothly with aryl / alkyl / heterocyclic isocyanates or thioisocyanates, achieving rapid preparation of phosphonocarboxamides. It can also modify amino acid derivatives or complex bioactive molecules with phosphonocarboxamides. Furthermore, these phosphonocarboxamides or oxidized (or sulfided) phosphonocarboxamides can serve as excellent ligands in metal-catalyzed reactions, providing new candidate compounds for research fields such as catalysis chemistry, materials chemistry, and medicinal chemistry. Detailed Implementation

[0020] The technical solution of the present invention will be further illustrated below through specific embodiments. Those skilled in the art should understand that the embodiments described are merely illustrative of the present invention and should not be construed as limiting the invention in any way.

[0021] In the following examples, the shift data for the 1H NMR, 1C NMR, phosphorus (P) NMR, and fluorine (F) NMR spectra of the compounds were all obtained by dissolving the corresponding samples in deuterated chloroform and measuring them sequentially using NMR spectra at 400 MHz, 101 MHz, 162 MHz, and 376 MHz. All units are in ppm. The purity of the raw materials is expressed as mass content. The yields are measured using quantitative NMR spectroscopy with 1,3,5-trimethoxybenzene as an internal standard. In Examples 1 and 4, the feed equivalents are relative to the equivalents of the feed isocyanate or thioisocyanate. In Examples 2 and 3, the feed equivalents are relative to the equivalents of the feed phosphine chloride.

[0022] Example 1: NSynthesis of 1,1-(4-methoxyphenyl)-1,1-diphenylphosphine carboxamide (3aa) Procedure: Under a nitrogen atmosphere, add Ph₂PCl (1 mmol, 2.0 equiv, 98% purity), 4-methoxyphenyl isocyanate (0.5 mmol, 1.0 equiv), Ni(OAc)₂·4H₂O (10 mol%, 98% purity), 1,10-phenanthroline (15 mol%, 98% purity), Zn (1.25 mmol, 2.5 equiv, 99.9% purity), and 2.0 mL DMF (99.5% purity) to a dry 25 mL Schlenk tube. Heat the reaction mixture in an oil bath at 80 °C. o The reaction mixture was stirred at C for 16 hours. After the reaction was complete, the reaction solution was diluted with 10 mL of ethyl acetate and filtered through a funnel with a thin layer of silica. The solution was washed with ethyl acetate. The combined organic phases were washed three times with saturated NH4Cl aqueous solution, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was purified by rapid silica gel column chromatography to give the corresponding white solid compound 3aa (112.3 mg), in 67% yield.

[0023] Other compounds besides compound 3aa in Table 1 were prepared according to the method in Example 1, and the general reaction formula is as follows: Table 1 Example 2: Preparation of 1,1-diphenyl-N-(2-(thiophen-2-yl)ethyl)-N-((2-(phenyl-2-yl)ethyl)carbamoyl)phosphonoformamide (3cd) Procedure: Under a nitrogen atmosphere, add Ph₂PCl (0.5 mmol, 1.0 equiv), 2-(2-isocyanatoethyl)thiophene (1.0 mmol, 2.0 equiv), Ni(OAc)₂·4H₂O (10 mol%), 1,10-phenanthroline (15 mol%), Zn (1.25 mmol, 2.5 equiv), and 2.0 mL DMF to a dry 25 mL Schlenk tube. Heat the reaction mixture in an oil bath at 80 °C. o The reaction mixture was stirred at C for 16 hours. After the reaction was complete, the reaction solution was diluted with 10 mL of ethyl acetate and filtered through a funnel with a thin layer of silica. The filter cake was washed with ethyl acetate. The combined organic phases were washed three times with saturated NH4Cl aqueous solution, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was purified by rapid silica gel column chromatography to give the corresponding white solid compound 3 cd (150.1 mg), in 61% yield.

[0024] 3CD spectral characterization data of the compound: 1 H NMR δ 8.08 (s, 1H), 7.90 – 7.80 (m, 4H), 7.61 – 7.52 (m, 2H), 7.52 – 7.43 (m, 4H), 7.15 – 7.08 (m, 2H), 6.95 – 6.83(m, 2H), 6.82 – 6.75 (m, 2H), 3.70 – 3.61 (m, 2H), 3.39 (t, J = 6.7 Hz, 2H), 3.08 (t, J = 7.0 Hz, 2H), 2.96 (t, J = 6.7 Hz, 2H). 13 C NMR δ 169.8 (d, J =121.2 Hz), 158.3, 141.7, 140.4, 132.8 (d, J = 4.0 Hz), 131.8 (d, J = 10.1Hz), 129.1 (d, J = 101 Hz), 128.8 (d, J = 10.1 Hz), 127.8, 127.1 (d, J = 4.0Hz), 125.7, 125.4, 124.2, 123.9, 41.9, 41.0 (d, J= 4.0 Hz), 30.7, 29.7. 31 PNMR δ 15.40. Example 3: Preparation of N,N'-di-tert-butyl-1-phenylphosphine diamide (3ce) Procedure: Under a nitrogen atmosphere, add Ph₂PCl (0.5 mmol, 1.0 equiv), tert-butyl isocyanate (1.0 mmol, 2.0 equiv), Ni(OAc)₂·4H₂O (10 mol%), 1,10-phenanthroline (15 mol%), Zn (1.25 mmol, 2.5 equiv), and 2.0 mL DMF to a dry 25 mL Schlenk tube. Heat the reaction mixture in an oil bath at 80 °C. o The reaction mixture was stirred at C for 16 hours. After the reaction was complete, the reaction solution was diluted with 10 mL of ethyl acetate and filtered through a funnel lined with a thin layer of silica. The filter cake was washed with ethyl acetate. The combined organic phases were washed three times with saturated NH4Cl aqueous solution, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was purified by rapid silica gel column chromatography to give the corresponding white solid compound 3ce (95.5 mg), in 62% yield.

[0025] 3ce spectral characterization data of compound: 1 H NMR δ 8.01 – 7.96 (m, 2H), 7.61 (t, J = 8.0Hz, 1H), 7.54 – 7.49 (m, 2H), 7.38 (s, 2H), 1.39 (s, 18H). 13 C NMR δ 167.0 (d, J = 111.1 Hz), 133.2, 131.3 (d, J = 10.1 Hz), 128.9 (d, J = 10.1 Hz), 126.4 (d, J = 101 Hz), 53.7 (d, J = 4.0 Hz), 28.5. 31 P NMR δ -3.52. Example 4: Preparation of 1-(diphenylphosphonothio)-N-(4-methoxyphenyl)formamide (4aa) Procedure: Under a nitrogen atmosphere, add Ph₂PCl (1 mmol, 2.0 equiv), 1-isocyanate-4-methoxybenzene (0.5 mmol, 1.0 equiv), Ni(OAc)₂·4H₂O (10 mol%), 1,10-phenanthroline (15 mol%), Zn (1.25 mmol, 2.5 equiv), and 2.0 mL DMF to a dry 25 mL Schlenk tube. Heat the reaction mixture in an oil bath at 80 °C. o The reaction mixture was stirred at C for 16 hours. Sulfur powder (2.5 mmol, 5.0 equiv) was then added, and the mixture was stirred at room temperature for 12 hours. After the reaction was complete, the reaction solution was diluted with 10 mL of ethyl acetate and filtered through a funnel fitted with a thin layer of silica. The solution was washed with ethyl acetate. The combined organic phases were washed three times with saturated NH4Cl aqueous solution, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was purified by rapid silica gel column chromatography to give the corresponding yellow solid compound 4aa (159.7 mg, 87% yield).

[0026] Other compounds were prepared following the procedure in Example 4, using hydrogen peroxide or sulfur powder to obtain the corresponding phosphonic oxycarboxamides or phosphonic sulfide carboxamides (Formula IV), with the general reaction formulas as follows. The results are shown in Table 2. Table 2 Example 5: Application of phosphonocarboxamide in Suzuki coupling: Synthesis of the intermediate 3',4',5'-trifluoro-2-nitrobenzene (compound 7) for fluopyram General operating procedure: Under nitrogen atmosphere, 0.5 mmol of 2-nitrochlorobenzene 5, 0.5 mmol of 3,4,5-trifluorophenylboronic acid 6, Pd(OAc)2 (5 mol%), ligand L (10 mol%) and 1.0 mmol of K2CO3 were placed in a 25 mL sealed tube, and then 3.0 mL of THF / H2O (1.5 mL / 1.5 mL) was added. The mixture was stirred at 100°C for 12 hours. After the reaction was complete, the reaction mixture was filtered through a diatomaceous earth filter and washed with ethyl acetate. The solvent was removed by rotary evaporation under reduced pressure. The residue was purified by rapid silica gel column chromatography to give the corresponding 3',4',5'-trifluoro-2-nitrobiphenyl 7 (when ligand L was Ph3P: 101.2 mg of compound 7, yield 80%; when ligand L was N-(4-fluorophenyl)-1,1-diphenylphosphine carboxamide: 112.6 mg of compound 7, yield 89%; when ligand L was N-(4-cyanophenyl)-1,1-diphenylphosphine carboxamide: 121.5 mg of compound 7, yield 96%).

[0027] It is evident that the phosphonocarboxamide compounds represented by Formula I of this invention can be used as ligands in the Suzuki coupling reaction for the synthesis of the fungicide fluopyram intermediate compound 7, with a yield superior to that of traditional triphenylphosphine.

[0028] The spectral characterization data of compound 7 are as follows: 1 H NMR δ 7.94 (d, J = 8.1 Hz, 1H), 7.67 (t, J = 7.6 Hz, 1H), 7.59 – 7.55 (m, 1H), 7.40 (d, J = 7.6 Hz, 1H), 6.94 (dd, J =8.0, 6.4 Hz, 2H). 13 C NMR δ 152.2 (dd, J = 10.1, 4.1 Hz), 149.6 (dd, J = 10.1,4.2 Hz), 148.4, 140.8 (t, J = 20.2 Hz), 138.3 (t, J = 20.2 Hz), 133.3, 132.6,131.5, 129.2, 124.3, 112.5 (d, J = 10.1 Hz), 112.3 (d, J = 10.1 Hz). 19F NMR δ-133.2 (m, 2F), -160.4 (m, 1F). Example 6: Application of oxidized or sulfide phosphonocarboxamide (Formula IV) in Suzuki coupling: General procedure: Under nitrogen atmosphere, 0.5 mmol of 2-nitrochlorobenzene 5, 0.5 mmol of 3,4,5-trifluorophenylboronic acid 6, Pd(OAc)2 (5 mol%), ligand L (10 mol%), and 1.0 mmol of K2CO3 were placed in a 25 mL sealed tube, followed by the addition of 3.0 mL of THF / H2O (1.5 mL / 1.5 mL). The mixture was stirred at 100°C for 12 hours. After the reaction was complete, the reaction mixture was filtered through a diatomaceous earth filter and washed with ethyl acetate. The solvent was removed by rotary evaporation under reduced pressure. The residue was purified by rapid silica gel column chromatography to give the corresponding 3',4',5'-trifluoro-2-nitrobiphenyl 7 (when ligand L was compound 4ac: 97.1 mg of compound 7, yield 76%; when ligand L was compound 4af: 85.1 mg of compound 7, yield 67%).

[0029] The phosphonocarboxamide compounds of formula IV synthesized by the method of the present invention can also be used in the Suzuki coupling reaction for the synthesis of intermediate compound 7 of the fungicide fluopyram.

[0030] The applicant declares that this invention illustrates a phosphonocarboxamide compound, its preparation method, and its application through the above embodiments. However, this invention is not limited to the above embodiments, meaning that this invention does not necessarily rely on the above embodiments for implementation. Those skilled in the art should understand that any improvements to this invention, equivalent substitutions of raw materials, additions of auxiliary components, and selection of specific methods, etc., all fall within the protection and disclosure scope of this invention.

Claims

1. A method for preparing a phosphonocarboxamide compound, characterized in that, Under inert gas protection, a highly active metal catalyst is generated in situ from a metal salt and a metal reducing agent. Then, under the action of ligands, phosphine chloride undergoes cross-coupling with isocyanate or thioisocyanate to prepare phosphocarboxamides as shown in Formula I, II, or III, as follows: ； Wherein, R is selected from substituted phenyl, substituted biphenyl, substituted benzyl, substituted C1-C10 alkyl, substituted cycloalkyl, R -C or S -C chiral alkyl; X is selected from oxygen or sulfur atoms; R' is selected from phenyl, the same or different substituted phenyl, substituted biphenyl, substituted benzyl, substituted C1-C10 alkyl or substituted cycloalkyl; [cat] is selected from metal salt catalysts; M is selected from metal reducing agents; L is selected from ligands.

2. The preparation method according to claim 1, characterized in that, The metal salt catalyst is selected from nickel salts, cobalt salts, chromium salts, bismuth salts, iron salts, copper salts, or indium salt catalysts; The metal reducing agent is selected from zinc or manganese. The ligands are selected from monodentate, bidentate, or tripentate nitrogen ligands.

3. The preparation method according to claim 1 or 2, characterized in that, The metal salt catalysts are selected from nickel chloride, nickel bromide, nickel iodide, nickel acetate, nickel acetylacetonate, bis(triphenylphosphine) chloride, nickel acetate tetrahydrate, nickel chloride hexahydrate, nickel chloride dimethoxyethane, nickel bromide dimethoxyethane, nickel chloride diethylene glycol dimethyl ether, nickel bromide diethylene glycol dimethyl ether, cobalt chloride, cobalt bromide, cobalt iodide, cobalt acetate, bis(acetylacetonate) cobalt, tri(acetylacetonate) cobalt, bis(triphenylphosphine) dichloride, hexaaminocobalt chloride, cobalt perchlorate hexahydrate, cobalt chloride hexahydrate, and cobalt chloride tetrahydrate. Cobalt acetate, cobalt carbonate, chromium dichloride, chromium trichloride, chromium dibromide, chromium tribromide, bismuth chloride, bismuth bromide, bismuth iodide, bismuth acetate, ferric chloride, ferric trichloride, ferric dibromide, ferric tribromide, ferric acetate, ferric acetylacetone, cuprous chloride, cuprous bromide, cuprous iodide, cuprous acetate, cuprous cyanide, copper thiophene-2-carboxylate, copper bromide, copper acetate, copper sulfate, copper trifluoromethanesulfonate, copper tetraacetonitrile tetrafluoroborate, copper chloride dihydrate, copper sulfate pentahydrate, indium trichloride or indium dichloride, preferably nickel acetate tetrahydrate; The metal reducing agent is selected from zinc or manganese. The ligand is selected from substituted 2,2'-bipyridine, substituted 1,10-phenanthroline or substituted terpyridine, preferably 1,10-phenanthroline.

4. The preparation method according to claims 1-3, characterized in that, When preparing the phosphonocarboxamide of Formula I, the molar ratio of phosphonium chloride to isocyanate or thioisocyanate is 3:1-1:3, preferably 2:1; when preparing the phosphonocarboxamide of Formula II or Formula III, the molar ratio of phosphonium chloride to isocyanate or thioisocyanate is 1:1.5-1:5, preferably 1:2; When preparing the phosphonocarboxamides of Formula I, Formula II or Formula III, the amount of metal salt catalyst used is at least 0.1-20 mol% equivalent of isocyanate or thioisocyanate, preferably 10 mol% equivalent; The amount of metal reducing agent used is at least 1-4 molar equivalents of isocyanate or thioisocyanate, preferably 2.5-3 molar equivalents; The amount of ligand used is at least 0.15-30 mol% equivalent of isocyanate or thioisocyanate, preferably 15 mol% equivalent.

5. The preparation method according to claims 1-4, characterized in that, The reaction is carried out in a solvent selected from N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, tetrahydrofuran, 1,4-dioxane, acetone or acetonitrile, preferably N,N-dimethylformamide; the solvent is an isocyanate or thioisocyanate in a concentration of 0.1-10 mol / L, preferably 1 mol / L.

6. The preparation method according to claims 1-5, characterized in that, The reaction temperature is -20 to 180°C, preferably 60 to 100°C, and more preferably 80°C; the reaction time is 1 to 24 hours, preferably 14 to 18 hours, and more preferably 16 hours.

7. Phosphocarboxamides of Formula I, Formula II, or Formula III prepared by the preparation method according to claims 1-6: 。 8. An oxidized (or sulfidated) phosphonocarboxamide of formula IV, characterized in that, The oxidized (or sulfidated) phosphonocarboxamide shown in Formula IV is prepared by reacting the phosphonocarboxamide shown in Formula I with an oxidizing agent (or a sulfiding agent), as shown in the following reaction formula: ； Wherein [O] is selected from oxidizing agents, preferably hydrogen peroxide; S is selected from sulfiding agents, preferably sulfur powder.

9. The phosphonocarboxamide or oxidized (or sulfided) phosphonocarboxamide according to claims 7-8, characterized in that, The phosphonocarboxamide is selected from any one of the following compounds: 。 10. The application of the phosphonocarboxamide or oxidized (or sulfided) phosphonocarboxamide according to claims 7-9 as a ligand in coupling reactions catalyzed by metal catalysts, preferably as a ligand in the coupling reaction for preparing the intermediate nitrobiphenyl or aminobiphenyl of the fungicides fluopyram, bifenthiophanate-methyl, cyproconazole or benzylpyrazine.

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