CN104341449A - Method for preparing beta-carbonyl phosphonate derivatives - Google Patents

Abstract

The invention discloses a preparation method of β-carbonyl phosphonate derivatives. Specifically, ethylene derivatives, phosphorus reagents, and manganese acetate are dissolved in a solvent, and the reaction is carried out at 20-100°C to prepare β-carbonyl phosphonic acid Ester derivatives; β-carbonyl phosphonic acid ester derivatives can be obtained under the action of sodium hydroxide or sodium iodide to obtain β-carbonyl phosphonic acid monoester sodium derivatives. The present invention uses aryl vinyl derivatives as starting materials, and the raw materials are easy to obtain and have many types; the products obtained by the method of the present invention are of various types, which can be used directly or for other further reactions; meanwhile, the synthetic route is short , mild reaction conditions, simple reaction operation and post-treatment process, high yield, suitable for large-scale production.

Description

A kind of preparation method of β-carbonyl phosphonate derivative

technical field

The invention belongs to the field of organic synthesis, and in particular relates to a preparation method of beta-carbonyl phosphonate derivatives.

Background technique

β-carbonyl phosphonate has biological activity and metal coordination ability, and has applications in biochemistry and inorganic chemistry; it is also a widely used synthetic intermediate in organic chemistry, which can be produced by reacting with aldehydes or ketones in HWE reactions Unsaturated carbonyl compounds. β-carbonyl phosphonate can be selectively hydrolyzed to obtain β-carbonyl phosphonic acid monoester sodium, which is an important β-lactam inhibitor; β-carbonyl phosphonate is also used to synthesize β-hydroxy phosphonate, β-amino An important raw material for phosphonates and acids. The structure of β-aminophosphonic acid is similar to that of β-amino acid, and has a wide range of physiological activities, such as antibacterial, stimulating nerves, affecting cell growth and metabolism, analgesic, regulating blood pressure, regulating plant growth, etc., so it can be used as medicine, pesticide, Antagonists, anthocyanin synthesis inhibitors, etc. are used.

In the prior art, the synthetic method of β-carbonyl phosphonate mainly contains following three kinds:

1. In the presence of metal lithium reagent, methyl benzoate and dimethyl methyl phosphonate react to obtain β-carbonyl phosphonate (see: Milburn, Robert R. Tetrahedron Lett., 2009, 50, 870-872); Metal lithium reagent is very active in this method, causes harsh reaction condition; This reaction equation is:

2. Refluxing reaction of bromoacetophenone and trimethyl phosphite to obtain β-carbonyl phosphonate (see: Taber, Douglass F. Tetrahedron Lett., 2008, 49, 6904-6906); in this method, bromoacetophenone Ketones are difficult to obtain, the synthesis route is long, and bromine is used in the synthesis, which causes great corrosion and pollution), which limits the source of substrates, and the reaction time is long, the conversion rate of raw materials is low, and there are many by-products; the reaction equation is:

3. Reaction of styrene and diisopropyl phosphite under the catalysis of CuBr ₂ /FeBr ₃ to obtain β-carbonyl phosphonate (see: Wei Wei and Jian-Xin Ji, Angew. Chem. Int. Ed. 2011, 50 , 9097–9099), this method overcomes some shortcomings in the traditional method, but in this method, an equivalent amount of triethylamine is required as an additive, and dimethyl sulfoxide with a high polarity and a high boiling point is used as a reaction solvent to catalyze The system is complex, resulting in cumbersome post-treatment; the reaction needs to be carried out in an oxygen atmosphere, and the reaction time is long, and the scope of substrate application is narrow; the reaction equation is:

β-carbonyl phosphonates are widely used in fields such as organic synthesis and biochemistry, so people are devoting themselves to developing new methods for the synthesis of β-carbonyl phosphonates; however, the existing methods have poor substrate applicability, low yield, high cost, The disadvantage of harsh reaction conditions. Therefore, it is very important to develop a method for synthesizing β-carbonyl phosphonate with mild reaction conditions, wide application range and meeting the requirements of green chemistry.

Contents of the invention

The purpose of the present invention is to provide a preparation method of β-carbonyl phosphonate derivatives.

In order to achieve the above-mentioned purpose of the invention, the technical scheme adopted in the present invention is: a preparation method of β-carbonyl phosphonate derivatives, comprising the following steps: dissolving vinyl derivatives, phosphorus reagents, and manganese acetate in a solvent, Reaction at 100°C to obtain β-carbonyl phosphonate derivatives;

The general chemical structure formula of the ethylene derivative is , where R is one of the following groups:

, , , , , ,

The selection of R ¹ , R ² , R ³ , R ⁴ and R ⁵ adopts one of the following schemes:

(1) R ¹ is one of hydrogen, methyl, trifluoromethyl, methoxy, fluorine, chlorine, bromine, cyano, formyl, methyl formate or nitro, R ² , R ³ , R ⁴ and R ⁵ are both hydrogen;

(2) R ² is one of methyl, trifluoromethyl, methoxy, fluorine, chlorine, bromine, cyano, formyl, methyl formate or nitro, R ¹ , R ³ , R ⁴ and R are ^both hydrogen;

(3) R ³ is one of methyl, trifluoromethyl, methoxy, fluorine, chlorine, bromine, cyano, formyl, methyl formate, nitro and phenyl, R ¹ , R ² , R ⁴ and R ⁵ are all hydrogen;

(4) R ¹ , R ² , R ³ , R ⁴ and R ⁵ are fluorine;

The chemical structural general formula of described phosphorus reagent is:

,

Wherein ^R is one of the following groups:

, , , , , ;

Described solvent is selected from: the one in methanol, ethanol, acetonitrile, acetic acid, chloroform, methylene chloride, toluene;

The chemical structural formula of the β-carbonyl phosphonate derivative is:

.

In the above technical scheme, the ethylene derivative is selected from styrene, 2-methylstyrene, 3-methoxystyrene, 4-methoxystyrene, 2-chlorostyrene, 3-chlorostyrene, 4-chlorostyrene, 4-cyanostyrene, 3-methylcarboxystyrene, 4-acetylstyrene, 3-nitrostyrene, 3-trifluoromethylstyrene, 4-biphenyl Ethylene, pentafluorostyrene, 2-vinylfuran, 2-vinylthiophene, 2-vinylpyrrole, 3-vinylpyridine, 3-(2-chlorophenyl)-5-methylisoxazole-4 -base) one of vinyl.

In the above technical scheme, the molar ratio of ethylene derivative: phosphorus reagent: manganese acetate is 1: (1-2): (1-3); preferably 1:1.5:1.5.

In the preparation of β-carbonyl phosphonate derivatives, the present invention uses thin-layer chromatography to track the reaction until it is completely completed; after the reaction is completed, purification treatment is carried out, specifically, after the reaction is completed, the solvent in the reaction solution is concentrated and removed to obtain a residue, The residue was separated by column chromatography to obtain the β-carbonyl phosphonate derivative.

The β-carbonyl phosphonate derivatives of the present invention can be used to prepare β-carbonyl phosphonic acid monoester sodium derivatives. Specifically, the prepared β-carbonyl phosphonic acid ester derivatives are reacted with sodium salts to obtain β-carbonyl phosphonic acid monoester derivatives. Sodium ester derivatives; sodium β-carbonyl phosphonic acid monoester can be used as a β-lactam inhibitor.

The chemical structural formula of the β-carbonyl phosphonic acid monoester sodium derivative is:

.

The reaction process of above-mentioned technical scheme can be expressed as:

Due to the application of the above-mentioned technical solution, the present invention has the following advantages compared with the prior art:

1. The present invention uses aryl vinyl derivatives as starting materials, and the raw materials are easy to obtain and have many types; the product β-carbonyl phosphonate derivatives prepared therefrom are of various types, which can be used directly or in other further reactions.

2. In the method for preparing β-carbonyl phosphonate derivatives disclosed in the present invention, the raw materials are stable, no harsh reaction conditions are required, the reaction accelerator system is simple, no additives are required, there are very few by-products, and the yield is high, which is beneficial to the final product of purification.

3. In the air, the present invention uses aryl vinyl derivatives as starting materials without oxygen, and prepares β-carbonyl phosphonate derivatives simply and efficiently. Simplify and secure.

4. The preparation method disclosed in the present invention has a wide range of substrates, and has a high conversion rate for aryl vinyl derivatives of various substituents, enriches the structure of β-carbonyl phosphonate derivatives, and expands the range of β-carbonyl phosphonate derivatives. Use of phosphonate derivatives.

5. The preparation method disclosed by the invention has mild reaction conditions, simple reaction operation and post-treatment process, stable and controllable reaction process, high catalytic efficiency, greatly reduced reagent consumption and generation and discharge of reaction waste, high product yield, and is suitable for large-scale production. Production.

Detailed ways

The present invention will be further described below in conjunction with embodiment:

Example 1: Synthesis of dimethyl 2-oxo-2-phenylethylphosphonate

Using styrene and dimethyl phosphite as raw materials, the reaction formula and experimental steps are as follows:

    

(1) Add styrene (0.1 g, 1 mmol), dimethyl phosphite (0.11 g, 1.0 mmol), manganese acetate (0.41 g, 1.5 mmol) and 10 mL of acetonitrile into the reaction flask, and react at 50°C Carry out, TLC follow-up reaction until the end;

(2) The reaction solution was concentrated to obtain a residue, which was separated by column chromatography to obtain dimethyl 2-oxo-2-phenylethylphosphonate (yield 60%);

(3) Add dimethyl 2-oxo-2-phenylethylphosphonate (0.11 g, 0.5 mmol) obtained in (2) into the reaction flask, and sodium hydroxide solution (0.08 g, 2.0 mmol in 1mL water) and 10 mL 1,4-dioxane, the reaction was carried out at 25°C, and the reaction was followed by TLC until the end;

(4) The reaction solution was concentrated to remove most of the solvent to obtain a residue, acidified with hydrochloric acid, and extracted with ethyl acetate. Remove the solvent in the extract, add sodium bicarbonate solution (0.042 g, 0.5 mmol dissolved in 1 mL water) to the residue, and freeze-dry the reaction solution to obtain methyl 2-oxo-2-phenylethylphosphonic acid Sodium ester (68% yield).

The analytical data for dimethyl 2-oxo-2-phenylethylphosphonate are as follows: ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.97-8.02 (m, 2H), 7.56-7.62 (m, 1H) , 7.45-7.52 (m, 2H), 3.77 (d, J = 11.2 Hz, 6H), 3.64 (d, J = 22.8 Hz, 2H); sodium methyl 2-oxo-2-phenylethylphosphonate The analytical data for are as follows: ¹ H NMR (300 MHz, D ₂ O): 7.83-7.92 (m, 2H), 7.43-7.56 (m, 1H), 7.35-7.44 (m, 2H), 3.56 (d, J = 11.2 Hz, 3H), 3.41 (d, J = 22.8 Hz, 2H).

Example two: Synthesis of diethyl 2-oxo-2-phenylethylphosphonate

With styrene and diethyl phosphite as raw materials, its reaction formula and experimental steps are as follows:

        

(1) Add styrene (0.1 g, 1 mmol), diethyl phosphite (0.21 g, 1.5 mmol), manganese acetate (0.41 g, 1.5 mmol) and 10 mL methanol into the reaction flask, and react at 20°C Carry out, TLC follow-up reaction until the end;

(2) The reaction solution was concentrated to obtain a residue, which was separated by column chromatography to obtain diethyl 2-oxo-2-phenylethylphosphonate (yield 83%);

(3) Add the diethyl 2-oxo-2-phenylethylphosphonate (0.18 g, 0.5 mmol) obtained in (2) into the reaction flask, and sodium hydroxide solution (0.08 g, 2.0 mmol is dissolved in 1mL water) and 10 mL 1,4-dioxane, the reaction was carried out at 25°C, and TLC followed the reaction until the end;

(4) The reaction solution was concentrated to remove most of the solvent to obtain a residue, acidified with hydrochloric acid, and extracted with ethyl acetate. Remove the solvent in the extract, add sodium bicarbonate solution (0.042 g, 0.5 mmol dissolved in 1 mL water) to the residue, and freeze-dry the reaction solution to obtain ethyl 2-oxo-2-phenylethylphosphonic acid Sodium ester (67% yield).

The analytical data of diethyl 2-oxo-2-phenylethylphosphonate are as follows: ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.00-8.06 (m, 2H), 7.58-7.65 (m, 1H) , 7.47-7.53 (m, 2H), 4.10-4.22 (m, 4H), 3.66 (d, J = 22.7 Hz, 2H), 1.30 (t, J = 7.0 Hz, 6H); ethyl 2-oxo- The analytical data for sodium 2-phenylethylphosphonate are as follows: ¹ H NMR (400 MHz, D ₂ O): δ 7.96-8.02 (m, 2H), 7.56-7.64 (m, 1H), 7.44-7.54 (m , 2H), 4.01-4.12 (m, 2H), 3.47 (d, J = 22.7 Hz, 2H), 1.19 (t, J = 4.7 Hz, 3H).

Example three: Synthesis of diisopropyl 2-oxo-2-phenylethylphosphonate

Taking styrene and diisopropyl phosphite as raw materials, its reaction formula and experimental steps are as follows:

    

(1) Add styrene (0.1 g, 1 mmol), diisopropyl phosphate (0.25 g, 1.5 mmol), manganese acetate (0.27 g, 1.0 mmol) and 10 mL of ethanol into the reaction flask, and react at 20°C Carry out, TLC follow-up reaction until the end;

(2) The reaction solution was concentrated to obtain a residue, which was separated by column chromatography to obtain diisopropyl 2-oxo-2-phenylethylphosphonate (yield 52%);

(3) Add diisopropyl 2-oxo-2-phenylethylphosphonate (0.14 g, 0.5 mmol) obtained in (2) into the reaction flask, sodium hydroxide solution (0.08 g, 2.0 mmol in 1mL water) and 10 mL 1,4-dioxane, the reaction was carried out at 25°C, and the reaction was followed by TLC until the end;

(4) The reaction solution was concentrated to remove most of the solvent to obtain a residue, acidified with hydrochloric acid, and extracted with ethyl acetate. Remove the solvent in the extract, add sodium bicarbonate solution (0.042 g, 0.5 mmol dissolved in 1 mL water) to the residue, and freeze-dry the reaction solution to obtain isopropyl 2-oxo-2-phenylethylphosphine Na ester (65% yield).

The analytical data of diisopropyl 2-oxo-2-phenylethylphosphonate are as follows: ¹ H NMR (CDCl ₃ , 600 MHz): δ 8.01 (d, J = 7.7 Hz, 2H), 7.57 (t, J = 7.3 Hz, 1H), 7.47 (t, J = 7.7 Hz, 2H), 4.75-4.70 (m, 2H), 3.59 (m, 2H), 1.27 (m, 12H); isopropyl 2-oxo - The analytical data for sodium 2-phenylethylphosphonate are as follows: ¹ H NMR (600 MHz, D ₂ O): 7.88 (d, J = 7.7 Hz, 2H), 7.45 (t, J = 7.3 Hz, 1H) , 7.33 (t, J = 7.7 Hz, 2H), 4.54-4.46 (m, 2H), 3.42 (m, 1H), 1.14 (m, 6H).

Example four: Synthesis of diphenyl 2-oxo-2-phenylethylphosphonate

Using styrene and diphenyl phosphite as raw materials, the reaction formula and experimental steps are as follows:

   

(1) Add styrene (0.1 g, 1 mmol), diphenyl phosphite (0.35 g, 1.5 mmol), manganese acetate (0.55 g, 2.0 mmol) and 10 mL of acetic acid into the reaction flask, and react at 30°C Carry out, TLC follow-up reaction until the end;

(2) The reaction solution was concentrated to obtain a residue, which was separated by column chromatography to obtain diphenyl 2-oxo-2-phenylethylphosphonate (yield 81%);

(3) Add the diphenyl 2-oxo-2-phenylethylphosphonate (0.17 g, 0.5 mmol) obtained in (2) into the reaction flask, and sodium hydroxide solution (0.08 g, 2.0 mmol in 1mL water) and 10 mL 1,4-dioxane, the reaction was carried out at 25°C, and the reaction was followed by TLC until the end;

(4) The reaction solution was concentrated to remove most of the solvent to obtain a residue, acidified with hydrochloric acid, and extracted with ethyl acetate. Remove the solvent in the extract, add sodium bicarbonate solution (0.042 g, 0.5 mmol dissolved in 1 mL water) to the residue, and freeze-dry the reaction solution to obtain phenyl 2-oxo-2-phenylethylphosphonic acid Sodium ester (64% yield).

The analytical data for diphenyl 2-oxo-2-phenylethylphosphonate are as follows: ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.05 (d, J = 7.2 Hz, 2H), 7.62 (t, J = 7.2 Hz, 1H), 7.50 (t, J = 7.8 Hz, 2H), 7.30 (t, J = 7.8 Hz, 4H), 7.14–7.21 (m, 6H), 3.93 (d, J = 23.1Hz, 2H ); the analytical data of phenyl 2-oxo-2-phenylethylphosphonate sodium are as follows: ¹ H NMR (300 MHz, D ₂ O): δ 7.89 (d, J = 7.8 Hz, 2H), 7.55 ( t, J = 7.5 Hz, 1H), 7.41-7.45 (m, 2H), 7.20 (t, J = 7.8 Hz, 2H), 7.03 (t, J = 7.5 Hz, 1H), 6.91 (d, J = 8.7 Hz, 2H), 3.61 (d, J = 22.2 Hz, 2H).

Example five: Synthesis of dimethyl 2-oxo-2-(2-tolyl)ethylphosphonate

Taking 2-methylstyrene and dimethyl phosphite as raw materials, its reaction formula and experimental steps are as follows:

(1) Add 2-methylstyrene (0.1 g, 1 mmol), dimethyl phosphite (0.23 g, 2.0 mmol), manganese acetate (0.55 g, 2.0 mmol) and 10 mL chloroform into the reaction flask, The reaction was carried out at 40°C, and TLC followed the reaction until the end;

(2) The reaction solution was concentrated to obtain a residue, which was separated by column chromatography to obtain dimethyl 2-oxo-2-(2-tolyl)ethylphosphonate (yield 80%);

(3) Add dimethyl 2-oxo-2-(2-tolyl) ethyl phosphonate (0.12 g, 0.5 mmol) and sodium hydroxide solution (0.08 g , 2.0 mmol dissolved in 1 mL water) and 10 mL 1,4-dioxane, the reaction was carried out at 25 ° C, and TLC followed the reaction until the end;

(4) The reaction solution was concentrated to remove most of the solvent to obtain a residue, acidified with hydrochloric acid, and extracted with ethyl acetate. Remove the solvent in the extract, add sodium bicarbonate solution (0.042 g, 0.5 mmol dissolved in 1 mL water) to the residue, and freeze-dry the reaction solution to obtain methyl 2-oxo-2-(2-tolyl ) Sodium ethylphosphonate (66% yield).

The analytical data for dimethyl 2-oxo-2-(2-tolyl)ethylphosphonate are as follows: ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.97-8.02 (m, 1H), 7.45-7.52 (m, 3H), 3.77 (d, J = 11.2 Hz, 6H), 3.64 (d, J = 22.8 Hz, 2H), 2.20 (s, 3H); methyl 2-oxo-2-(2-toluene The analytical data for sodium ethylphosphonate are as follows: ¹ H NMR (400 MHz, D ₂ O): δ 7.82-7.89 (m, 1H), 7.35-7.44 (m, 3H), 3.56 (d, J = 11.2 Hz, 3H), 3.41 (d, J = 22.8 Hz, 2H), 2.20 (s, 3H).

Example 6: Synthesis of diphenyl 2-oxo-2-(3-methoxyphenyl)ethylphosphonate

With 3-methoxystyrene and diphenyl phosphite as raw materials, its reaction formula and experimental steps are as follows:

(1) Add 3-methoxystyrene (0.13 g, 1 mmol), diphenyl phosphite (0.47 g, 2 mmol), manganese acetate (0.68 g, 2.5 mmol) and 10 mL di Chloromethane, the reaction was carried out at 40°C, and TLC followed the reaction until the end;

(2) The reaction solution was concentrated to obtain a residue, which was separated by column chromatography to obtain diphenyl 2-oxo-2-(3-methoxyphenyl) ethyl phosphonate (yield 83%);

(3) Add diphenyl 2-oxo-2-(3-methoxyphenyl) ethyl phosphonate (0.19 g, 0.5 mmol) obtained in (2) into the reaction flask, sodium hydroxide solution (0.08 g, 2.0 mmol dissolved in 1 mL of water) and 10 mL of 1,4-dioxane, the reaction was carried out at 25 ° C, TLC followed the reaction until the end;

(4) The reaction solution was concentrated to remove most of the solvent to obtain a residue, acidified with hydrochloric acid, and extracted with ethyl acetate. Remove the solvent in the extract, add sodium bicarbonate solution (0.042 g, 0.5 mmol dissolved in 1 mL water) to the residue, and freeze-dry the reaction solution to obtain phenyl 2-oxo-2-(3-methoxy phenyl) ethyl phosphonate sodium (yield 67%). the

The analytical data for diphenyl 2-oxo-2-(3-methoxyphenyl)ethylphosphonate are as follows: ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.09–8.00 (m, 2H), 7.50-7.54 (m, 2H), 7.31 (t, J = 7.8 Hz, 4H), 7.14–7.21 (m, 6H), 3.93 (d, J = 23.1Hz, 2H); 3.77 (s, 3H); benzene The analytical data for sodium 2-oxo-2-(3-methoxyphenyl)ethylphosphonate are as follows: ¹ H NMR (300 MHz, D ₂ O): δ 8.04–7.96 (m, 2H), 7.48-7.40 (m, 2H), 7.22 (t, J = 7.8 Hz, 2H), 7.14–7.21 (m, 3H), 3.62 (d, J = 23.1Hz, 2H); 3.77 (s, 3H).

Example 7: Synthesis of Dimethyl 2-oxo-2-(4-methoxyphenyl)ethylphosphonate

Taking 4-methoxystyrene and dimethyl phosphite as raw materials, its reaction formula and experimental steps are as follows:

     

(1) Add 4-methoxystyrene (0.13 g, 1 mmol), dimethyl phosphite (0.23 g, 2 mmol), manganese acetate (0.82 g, 3 mmol) and 10 mL toluene into the reaction flask , the reaction was carried out at 50°C, and TLC followed the reaction until the end;

(2) The reaction solution was concentrated to obtain a residue, which was separated by column chromatography to obtain dimethyl 2-oxo-2-(4-methoxyphenyl)ethylphosphonate (yield 81%);

(3) Add dimethyl 2-oxo-2-(4-methoxyphenyl) ethyl phosphonate (0.13 g, 0.5 mmol) obtained in (2) into the reaction flask, sodium hydroxide solution (0.08 g, 2.0 mmol dissolved in 1 mL of water) and 10 mL of 1,4-dioxane, the reaction was carried out at 25 ° C, TLC followed the reaction until the end;

(4) The reaction solution was concentrated to remove most of the solvent to obtain a residue, acidified with hydrochloric acid, and extracted with ethyl acetate. Remove the solvent in the extract, add sodium bicarbonate solution (0.042 g, 0.5 mmol dissolved in 1 mL water) to the residue, and freeze-dry the reaction solution to obtain methyl 2-oxo-2-(4-methoxy phenyl) ethyl phosphonate sodium (yield 62%).

The analytical data for dimethyl 2-oxo-2-(4-methoxyphenyl)ethylphosphonate are as follows: ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.25 (d, J = 8.0 Hz, 2H), 6.91 (d, J = 8.0 Hz, 2H), 3.79 (d, J = 11.2 Hz, 6H), 3.62 (d, J = 22.8 Hz, 2H), 3.87 (s, 3H); methyl 2- The analytical data for sodium oxo-2-(4-methoxyphenyl)ethylphosphonate are as follows: ¹ H NMR (400 MHz, D ₂ O): δ 7.14 (d, J = 8.0 Hz, 2H), 6.82 (d, J = 8.0 Hz, 2H), 3.56 (d, J = 11.2 Hz, 3H), 3.41 (d, J = 22.8 Hz, 2H), 3.85 (s, 3H).

Example 8: Synthesis of dimethyl 2-oxo-2-(2-chlorophenyl)ethylphosphonate

Taking 2-chlorostyrene and dimethyl phosphite as raw materials, its reaction formula and experimental steps are as follows:

(1) Add 2-chlorostyrene (0.14 g, 1 mmol), dimethyl phosphite (0.17 g, 1.5 mmol), manganese acetate (0.82 g, 3 mmol) and 10 mL toluene into the reaction flask, and react Carried out at 60°C, followed by TLC until the end of the reaction;

(2) The reaction solution was concentrated to obtain a residue, which was separated by column chromatography to obtain dimethyl 2-oxo-2-(2-chlorophenyl)ethylphosphonate (yield 82%);

(3) Add dimethyl 2-oxo-2-(2-chlorophenyl) ethyl phosphonate (0.13 g, 0.5 mmol) obtained in (2) into the reaction flask, sodium hydroxide solution (0.08 g, 2.0 mmol dissolved in 1 mL of water) and 10 mL of 1,4-dioxane, the reaction was carried out at 25 ° C, and TLC followed the reaction until the end;

(4) The reaction solution was concentrated to remove most of the solvent to obtain a residue, acidified with hydrochloric acid, and extracted with ethyl acetate. Remove the solvent in the extract, add sodium bicarbonate solution (0.042 g, 0.5 mmol dissolved in 1 mL water) to the residue, and freeze-dry the reaction solution to obtain methyl 2-oxo-2-(2-chlorobenzene base) sodium ethylphosphonate (68% yield).

The analytical data for dimethyl 2-oxo-2-(2-chlorophenyl)ethylphosphonate are as follows: ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.89-7.79 (m, 2H), 7.44- 7.33 (m, 2H), 3.79 (d, J = 11.2 Hz, 6H), 3.62 (d, J = 22.8 Hz, 2H); methyl 2-oxo-2-(2-chlorophenyl)ethylphosphine The analytical data of sodium esters are as follows: ¹ H NMR (400 MHz, D ₂ O): δ 7.78-7.66 (m, 2H), 7.32-7.20 (m, 2H), 3.56 (d, J = 11.2 Hz, 3H) , 3.41 (d, J = 22.8 Hz, 2H).

Example 9: Synthesis of Dimethyl 2-oxo-2-(3-chlorophenyl)ethylphosphonate

Taking 3-chlorostyrene and dimethyl phosphite as raw materials, its reaction formula and experimental steps are as follows:

(1) Add 3-chlorostyrene (0.14 g, 1 mmol), dimethyl phosphite (0.11 g, 1 mmol), manganese acetate (0.82 g, 3 mmol) and 10 mL toluene into the reaction flask, and react Carried out at 70°C, TLC followed the reaction until the end;

(2) The reaction solution was concentrated to obtain a residue, which was separated by column chromatography to obtain dimethyl 2-oxo-2-(3-chlorophenyl)ethylphosphonate (yield 62%);

(3) Add dimethyl 2-oxo-2-(3-chlorophenyl) ethyl phosphonate (0.13 g, 0.5 mmol) obtained in (2) into the reaction flask, sodium hydroxide solution (0.08 g, 2.0 mmol dissolved in 1 mL of water) and 10 mL of 1,4-dioxane, the reaction was carried out at 25 ° C, and TLC followed the reaction until the end;

(4) The reaction solution was concentrated to remove most of the solvent to obtain a residue, acidified with hydrochloric acid, and extracted with ethyl acetate. Remove the solvent in the extract, add sodium bicarbonate solution (0.042 g, 0.5 mmol dissolved in 1 mL water) to the residue, and freeze-dry the reaction solution to obtain methyl 2-oxo-2-(3-chlorobenzene base) sodium ethyl phosphonate (yield 60%).

The analytical data for dimethyl 2-oxo-2-(3-chlorophenyl)ethylphosphonate are as follows: ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.90-7.84 (m, 2H), 7.46- 7.38 (m, 2H), 3.79 (d, J = 11.2 Hz, 6H), 3.62 (d, J = 22.8 Hz, 2H); methyl 2-oxo-2-(3-chlorophenyl)ethylphosphine The analytical data of sodium esters are as follows: ¹ H NMR (400 MHz, D ₂ O): δ 7.75-7.64 (m, 2H), 7.30-7.21 (m, 2H), 3.57 (d, J = 11.2 Hz, 3H) , 3.43 (d, J = 22.8 Hz, 2H).

Example 10: Synthesis of diphenyl 2-oxo-2-(4-chlorophenyl)ethylphosphonate

Taking 4-chlorostyrene and diphenyl phosphite as raw materials, its reaction formula and experimental steps are as follows:

(1) Add 4-chlorostyrene (0.14 g, 1 mmol), diphenyl phosphite (0.35 g, 1.5 mmol), manganese acetate (0.82 g, 3 mmol) and 10 mL toluene into the reaction flask, and react Carried out at 80°C, TLC followed the reaction until the end;

(2) The reaction solution was concentrated to obtain a residue, which was separated by column chromatography to obtain diphenyl 2-oxo-2-(4-chlorophenyl) ethyl phosphonate (yield 85%);

(3) Add diphenyl 2-oxo-2-(4-chlorophenyl) ethyl phosphonate (0.19 g 0.5 mmol) obtained in (2) and sodium hydroxide solution (0.08 g , 2.0 mmol dissolved in 1 mL water) and 10 mL 1,4-dioxane, the reaction was carried out at 25 ° C, and TLC followed the reaction until the end;

(4) The reaction solution was concentrated to remove most of the solvent to obtain a residue, acidified with hydrochloric acid, and extracted with ethyl acetate. Remove the solvent in the extract, add sodium bicarbonate solution (0.042 g, 0.5 mmol dissolved in 1 mL water) to the residue, and freeze-dry the reaction solution to obtain phenyl 2-oxo-2-(4-chlorobenzene base) sodium ethylphosphonate (64% yield).

The analytical data for diphenyl 2-oxo-2-(4-chlorophenyl)ethylphosphonate are as follows: ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.09 (d, J = 7.2 Hz, 2H) , 7.82 (d, J = 7.2 Hz, 2H), 7.30 (t, J = 7.8 Hz, 4H), 7.12–7.23 (m, 6H), 3.93 (d, J = 23.1Hz, 2H); phenyl 2- The analytical data of sodium oxo-2-(4-chlorophenyl)ethylphosphonate are as follows: ¹ H NMR (300 MHz, D ₂ O): δ 8.01 (d, J = 7.2 Hz, 2H), 7.74 ( d, J = 7.2 Hz, 2H), 7.22 (t, J = 7.8 Hz, 2H), 7.09–7.19 (m, 3H), 3.63 (d, J = 23.1Hz, 2H).

Example 11: Synthesis of diphenyl 2-oxo-2-(3-formylmethylphenyl)ethylphosphonate

With 3-formic acid methyl styrene and diphenyl phosphite as raw materials, its reaction formula and experimental steps are as follows:

(1) Add 3-carboxymethylstyrene (0.16 g, 1 mmol), diphenyl phosphite (0.35 g, 1.5 mmol), manganese acetate (0.68 g, 2.5 mmol) and 10 mL Toluene, the reaction was carried out at 90°C, and TLC followed the reaction until the end;

(2) The reaction solution was concentrated to obtain a residue, which was separated by column chromatography to obtain diphenyl 2-oxo-2-(3-formic acid methyl phenyl) ethyl phosphonate (yield 84%);

(3) Add diphenyl 2-oxo-2-(3-formic acid methyl phenyl) ethyl phosphonate (0.21 g, 0.5 mmol) obtained in (2) into the reaction flask, sodium hydroxide solution (0.08 g, 2.0 mmol dissolved in 1 mL of water) and 10 mL of 1,4-dioxane, the reaction was carried out at 25 ° C, and TLC followed the reaction until the end;

(4) The reaction solution was concentrated to remove most of the solvent to obtain a residue, acidified with hydrochloric acid, and extracted with ethyl acetate. Remove the solvent in the extract, add sodium bicarbonate solution (0.042 g, 0.5 mmol dissolved in 1 mL water) to the residue, and freeze-dry the reaction solution to obtain phenyl 2-oxo-2-(3-formic acid methyl Ethyl phenyl) ethyl phosphonate sodium (65% yield).

The analytical data for diphenyl 2-oxo-2-(3-carboxymethylphenyl)ethylphosphonate are as follows: ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.29–8.20 (m, 2H) , 8.03-7.94 (m, 2H), 7.31 (t, J = 7.8 Hz, 4H), 7.14–7.21 (m, 6H), 3.93 (d, J = 23.1Hz, 2H); 3.89 (s, 3H); The analytical data for sodium phenyl 2-oxo-2-(3-carboxymethylphenyl)ethylphosphonate are as follows: ¹ H NMR (300 MHz, D ₂ O): δ 8.21–8.13 (m, 2H ), 7.96-7.88 (m, 2H), 7.21 (t, J = 7.8 Hz, 2H), 7.10–7.18 (m, 3H), 3.61 (d, J = 23.1Hz, 2H); 3.89 (s, 3H) .

Example 12: Synthesis of diphenyl 2-oxo-2-(4-acetylphenyl)ethylphosphonate

With 4-acetyl styrene and diphenyl phosphite as raw materials, its reaction formula and experimental steps are as follows:

     

(1) Add 4-acetylstyrene (0.15 g, 1 mmol), diphenyl phosphite (0.35 g, 1.5 mmol), manganese acetate (0.55 g, 2 mmol) and 10 mL toluene into the reaction flask, The reaction was carried out at 100°C, and TLC followed the reaction until the end;

(2) The reaction solution was concentrated to obtain a residue, which was separated by column chromatography to obtain diphenyl 2-oxo-2-(4-acetylphenyl) ethyl phosphonate (yield 85%);

(3) Add diphenyl 2-oxo-2-(4-acetylphenyl) ethyl phosphonate (0.2 g, 0.5 mmol) obtained by (2) in the reaction flask, sodium hydroxide solution ( 0.08 g, 2.0 mmol (dissolved in 1 mL water) and 10 mL 1,4-dioxane, the reaction was carried out at 25 ° C, and TLC followed the reaction until the end;

(4) The reaction solution was concentrated to remove most of the solvent to obtain a residue, acidified with hydrochloric acid, and extracted with ethyl acetate. Remove the solvent in the extract, add sodium bicarbonate solution (0.042 g, 0.5 mmol dissolved in 1 mL water) to the residue, and freeze-dry the reaction solution to obtain phenyl 2-oxo-2-(4-acetyl phenyl) sodium ethylphosphonate (62% yield).

The analytical data for diphenyl 2-oxo-2-(4-acetylphenyl)ethylphosphonate are as follows: ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.56 (d, J = 7.2 Hz, 2H ), 8.48 (d, J = 7.2 Hz, 2H), 7.30 (t, J = 7.8 Hz, 4H), 7.14–7.21 (m, 6H), 3.93 (d, J = 23.1Hz, 2H), 2.03 (s , 3H); the analytical data of sodium phenyl 2-oxo-2-(4-acetylphenyl)ethylphosphonate are as follows: ¹ H NMR (300 MHz, D ₂ O): δ 8.49 (d, J = 7.2 Hz, 2H), 8.40 (d, J = 7.2 Hz, 2H), 7.22 (t, J = 7.8 Hz, 2H), 7.14–7.20 (m, 3H), 3.60 (d, J = 23.1Hz, 2H ), 2.03 (s, 3H).

Example 13: Synthesis of diphenyl 2-oxo-2-(4-cyanophenyl)ethylphosphonate

With 4-cyanostyrene and diphenyl phosphite as raw materials, its reaction formula and experimental steps are as follows:

  

(1) Add 4-cyanostyrene (0.13 g, 1 mmol), diphenyl phosphite (0.35 g, 1.5 mmol), manganese acetate (0.41 g, 1.5 mmol) and 10 mL of ethanol into the reaction flask, and react Carried out at 40°C, followed by TLC until the end of the reaction;

(2) The reaction solution was concentrated to obtain a residue, which was separated by column chromatography to obtain diphenyl 2-oxo-2-(4-cyanophenyl) ethyl phosphonate (yield 81%);

(3) Add diphenyl 2-oxo-2-(4-cyanophenyl) ethyl phosphonate (0.19 g, 0.5 mmol) obtained by (2) in the reaction flask, sodium hydroxide solution ( 0.08 g, 2.0 mmol (dissolved in 1 mL water) and 10 mL 1,4-dioxane, the reaction was carried out at 25 ° C, and TLC followed the reaction until the end;

(4) The reaction solution was concentrated to remove most of the solvent to obtain a residue, acidified with hydrochloric acid, and extracted with ethyl acetate. Remove the solvent in the extract, add sodium bicarbonate solution (0.042 g, 0.5 mmol dissolved in 1 mL water) to the residue, and freeze-dry the reaction solution to obtain phenyl 2-oxo-2-(4-cyano phenyl) sodium ethylphosphonate (67% yield).

The analytical data for diphenyl 2-oxo-2-(4-cyanophenyl)ethylphosphonate are as follows: ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.25 (d, J = 7.2 Hz, 2H ), 8.04 (d, J = 7.2 Hz, 2H), 7.30 (t, J = 7.8 Hz, 4H), 7.14–7.21 (m, 6H), 3.93 (d, J = 23.1Hz, 2H); phenyl 2 The analytical data for sodium oxo-2-(4-cyanophenyl)ethylphosphonate are as follows: ¹ H NMR (300 MHz, D ₂ O): δ 8.16 (d, J = 7.2 Hz, 2H), 7.95 (d, J = 7.2 Hz, 2H), 7.24 (t, J = 7.8 Hz, 2H), 7.13–7.22 (m, 3H), 3.60 (d, J = 23.1Hz, 2H).

Example 14: Synthesis of diphenyl 2-oxo-2-(3-nitrophenyl)ethylphosphonate

With 3-nitrostyrene and diphenyl phosphite as raw materials, its reaction formula and experimental steps are as follows:

(1) Add 3-nitrostyrene (0.15 g, 1 mmol), diphenyl phosphite (0.35 g, 1.5 mmol), manganese acetate (0.41 g, 1.5 mmol) and 10 mL of acetonitrile into the reaction flask, The reaction was carried out at 20°C, and TLC followed the reaction until the end;

(2) The reaction solution was concentrated to obtain a residue, which was separated by column chromatography to obtain diphenyl 2-oxo-2-(3-nitrophenyl) ethyl phosphonate (yield 83%);

(3) Add diphenyl 2-oxo-2-(3-nitrophenyl) ethyl phosphonate (0.2 g, 0.5 mmol) obtained by (2) in the reaction flask, sodium hydroxide solution ( 0.08 g, 2.0 mmol (dissolved in 1 mL water) and 10 mL 1,4-dioxane, the reaction was carried out at 25 ° C, and TLC followed the reaction until the end;

(4) The reaction solution was concentrated to remove most of the solvent to obtain a residue, acidified with hydrochloric acid, and extracted with ethyl acetate. Remove the solvent in the extract, add sodium bicarbonate solution (0.042 g, 0.5 mmol dissolved in 1 mL water) to the residue, and freeze-dry the reaction solution to obtain phenyl 2-oxo-2-(3-nitro phenyl) sodium ethylphosphonate (58% yield).

The analytical data for diphenyl 2-oxo-2-(3-nitrophenyl)ethylphosphonate are as follows: ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.81-8.70 (m, 2H), 8.15 -8.06 (m, 2H), 7.31 (t, J = 7.8 Hz, 4H), 7.14–7.21 (m, 6H), 3.93 (d, J = 23.1Hz, 2H); phenyl 2-oxo-2- The analytical data for sodium (3-nitrophenyl)ethylphosphonate are as follows: ¹ H NMR (300 MHz, D ₂ O): δ 8.74-8.66 (m, 2H), 8.07-7.98 (m, 2H), 7.24 (t, J = 7.8 Hz, 2H), 7.10–7.21 (m, 3H), 3.65 (d, J = 23.1Hz, 2H).

Example 15: Synthesis of Dimethyl 2-oxo-2-(3-trifluoromethylphenyl)ethylphosphonate

Taking 3-trifluoromethylstyrene and dimethyl phosphite as raw materials, its reaction formula and experimental steps are as follows:

(1) Add 3-trifluoromethylstyrene (0.17 g, 1 mmol), dimethyl phosphite (0.17 g, 1.5 mmol), manganese acetate (0.41 g, 1.5 mmol) and 10 mL Acetonitrile, the reaction was carried out at 30°C, and TLC followed the reaction until the end;

(2) The reaction solution was concentrated to obtain a residue, which was separated by column chromatography to obtain dimethyl 2-oxo-2-(3-trifluoromethylphenyl)ethylphosphonate (yield 80%);

(3) Add dimethyl 2-oxo-2-(3-trifluoromethylphenyl) ethyl phosphonate (0.15 g, 0.5 mmol) obtained in (2) into the reaction flask, sodium hydroxide solution (0.08 g, 2.0 mmol dissolved in 1 mL of water) and 10 mL of 1,4-dioxane, the reaction was carried out at 25 ° C, and TLC followed the reaction until the end;

(4) The reaction solution was concentrated to remove most of the solvent to obtain a residue, acidified with hydrochloric acid, and extracted with ethyl acetate. Remove the solvent in the extract, add sodium bicarbonate solution (0.042 g, 0.5 mmol dissolved in 1 mL water) to the residue, and freeze-dry the reaction solution to obtain methyl 2-oxo-2-(3-trifluoro methylphenyl) sodium ethylphosphonate (63% yield).

The analytical data for dimethyl 2-oxo-2-(3-trifluoromethylphenyl)ethylphosphonate are as follows: ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.25 (s, 1 H), 8.18 (d, J = 7.9 Hz, 1H), 7.84 (d, J = 7.8 Hz, 1H), 7.58-7.66 (m, 1H), 3.80 (d, J = 11.3 Hz, 6H), 3.68 (d, J = 22.8 Hz, 2H); the analytical data for sodium methyl 2-oxo-2-(3-trifluoromethylphenyl)ethylphosphonate are as follows: ¹ H NMR (400 MHz, D ₂ O): δ 8.11 (s, 1H), 8.04 (d, J = 7.9 Hz, 1H), 7.72 (d, J = 7.8 Hz, 1H), 7.45-7.56 (m, 1H), 3.62 (d, J = 11.3 Hz, 3H), 3.44 (d, J = 22.8 Hz, 2H).

Example 16: Synthesis of dibenzyl 2-oxo-2-(furan-2-yl)ethylphosphonate

Using 2-vinylfuran and dibenzyl phosphite as raw materials, the reaction formula and experimental steps are as follows:

     

(1) Add 2-vinylfuran (0.1 g, 1 mmol), dibenzyl phosphite (0.39 g, 1.5 mmol), manganese acetate (0.41 g, 1.5 mmol) and 10 mL of acetonitrile into the reaction flask, and react Carried out at 40°C, followed by TLC until the end of the reaction;

(2) The reaction solution was concentrated to obtain a residue, which was separated by column chromatography to obtain dibenzyl 2-oxo-2-(furan-2-yl)ethylphosphonate (yield 82%);

(3) Dibenzyl 2-oxo-2-(furan-2-yl) ethyl phosphonate (0.18 g, 0.5 mmol) obtained from (2), sodium hydroxide solution (0.08 g, 2.0 mmol dissolved in 1 mL of water) and 10 mL of 1,4-dioxane, the reaction was carried out at 25 ° C, and TLC followed the reaction until the end;

(4) The reaction solution was concentrated to remove most of the solvent to obtain a residue, acidified with hydrochloric acid, and extracted with ethyl acetate. Remove the solvent in the extract, add sodium bicarbonate solution (0.042 g, 0.5 mmol dissolved in 1 mL water) to the residue, and freeze-dry the reaction solution to obtain benzyl 2-oxo-2-(furan-2- base) sodium ethylphosphonate (61% yield).

The analytical data for dibenzyl 2-oxo-2-(furan-2-yl)ethylphosphonate are as follows: ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.77 (d, J = 7.5 Hz, 2H) , 7.15-7.24 (m, 2H), 7.30–7.34 (m, 10H), 4.99–5.12 (m, 4H), 3.67 (d, J = 22.8 Hz, 2H); benzyl 2-oxo-2-( The analytical data for sodium furan-2-yl)ethylphosphonate are as follows: ¹ H NMR (300 MHz, D ₂ O): δ 7.58 (d, J = 7.5 Hz, 2H), 7.104-7.13 (m, 2H) , 7.13–7.22 (m, 3H), 7.02–7.11 (m, 2H), 4.62 (d, J = 10.2 Hz, 2H), 3.44 (d, J = 21.6 Hz, 2H).

Example 17: Synthesis of diphenyl 2-oxo-2-(thiophen-2-yl)ethylphosphonate

Using 2-vinylthiophene and diphenyl phosphite as raw materials, the reaction formula and experimental steps are as follows:

(1) Add 2-vinylthiophene (0.11 g, 1 mmol), diphenyl phosphite (0.35 g, 1.5 mmol), manganese acetate (0.41 g, 1.5 mmol) and 10 mL of acetic acid in a reaction flask, and react Carried out at 30°C, followed by TLC until the end of the reaction;

(2) The reaction solution was concentrated to obtain a residue, which was separated by column chromatography to obtain diphenyl 2-oxo-2-(thiophen-2-yl)ethylphosphonate (yield 79%);

(3) Add diphenyl 2-oxo-2-(thiophen-2-yl) ethyl phosphonate (0.18 g, 0.5 mmol) obtained in (2) into the reaction flask, sodium hydroxide solution (0.08 g, 2.0 mmol dissolved in 1 mL of water) and 10 mL of 1,4-dioxane, the reaction was carried out at 25 ° C, and TLC followed the reaction until the end;

(4) The reaction solution was concentrated to remove most of the solvent to obtain a residue, acidified with hydrochloric acid, and extracted with ethyl acetate. Remove the solvent in the extract, add sodium bicarbonate solution (0.042 g, 0.5 mmol dissolved in 1 mL water) to the residue, and freeze-dry the reaction solution to obtain phenyl 2-oxo-2-(thiophene-2- base) sodium ethyl phosphonate (yield 59%).

The analytical data for diphenyl 2-oxo-2-(thiophen-2-yl)ethylphosphonate are as follows: ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.00-8.02 (m, 1H), 7.93- 7.95 (m, 1H), 7.65-7.68 (m, 2H), 7.60-7.69 (m, 4H), 7.32-7.40 (m, 4H), 7.20–7.28 (m, 2H), 3.84 (d, J = 23.4 Hz, 2H); the analytical data of phenyl 2-oxo-2-(thiophen-2-yl)ethylphosphonate sodium are as follows: ¹ H NMR (400 MHz, D ₂ O): δ 7.95-7.88 (m , 1H), 7.80-7.72 (m, 1H), 7.62-7.54 (m, 2H), 7.54-7.64 (m, 2H), 7.23-7.35 (m, 2H), 7.11–7.20 (m, 1H), 3.53 (d, J = 23.4 Hz, 2H).

Example 18: Synthesis of Dimethyl 2-oxo-2-(pyridin-3-yl)ethylphosphonate

With 3-vinylpyridine and dimethyl phosphite as raw materials, its reaction formula and experimental steps are as follows:

(1) Add 3-vinylpyridine (0.1 g, 1 mmol), dimethyl phosphite (0.17 g, 1.5 mmol), manganese acetate (0.41 g, 1.5 mmol) and 10 mL of acetic acid in a reaction flask, and react Carried out at 20°C, TLC followed the reaction until the end;

(2) The reaction solution was concentrated to obtain a residue, which was separated by column chromatography to obtain dimethyl 2-oxo-2-(pyridin-3-yl)ethylphosphonate (yield 78%);

(3) Dimethyl 2-oxo-2-(pyridin-3-yl) ethyl phosphonate (0.11 g, 0.5 mmol) obtained from (2), sodium hydroxide solution (0.08 g, 2.0 mmol dissolved in 1 mL of water) and 10 mL of 1,4-dioxane, the reaction was carried out at 25 ° C, and TLC followed the reaction until the end;

(4) The reaction solution was concentrated to remove most of the solvent to obtain a residue, acidified with hydrochloric acid, and extracted with ethyl acetate. Remove the solvent in the extract, add sodium bicarbonate solution (0.042 g, 0.5 mmol dissolved in 1 mL water) to the residue, and freeze-dry the reaction solution to obtain methyl 2-oxo-2-(pyridine-3- base) sodium ethylphosphonate (62% yield). the

The analytical data for dimethyl 2-oxo-2-(pyridin-3-yl)ethylphosphonate are as follows: ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.97 (d, J = 1.8 Hz, 2 H ), 8.56 (dd, J = 4.8, 1.6 Hz, 1 H), 8.06-8.0 (m, 1 H), 7.23 (dd, J = 4.8, 0.6 Hz, 1 H), 3.55 (d, J = 11.3 Hz , 6H), 3.50 (d, J = 22.6 Hz, 2 H); the analytical data for methyl 2-oxo-2-(pyridin-3-yl)ethylphosphonate sodium are as follows: ¹ H NMR (400 MHz , D ₂ O): δ 8.85 (d, J = 1.8 Hz, 2 H), 8.41 (dd, J = 4.8, 1.6 Hz, 1 H), 7.87-7.97 (m, 1 H), 7.04 (dd, J = 4.8, 0.6 Hz, 1 H), 3.36 (d, J = 11.3 Hz, 3H), 3.28 (d, J = 22.6 Hz, 2 H).

Example 19: Synthesis of Dibenzyl 2-oxo-2-phenylethylphosphonate

Using styrene and dibenzyl phosphite as raw materials, the reaction formula and experimental steps are as follows:

     

(1) Add styrene (0.1 g, 1 mmol), dibenzyl phosphite (0.39 g, 1.5 mmol), manganese acetate (0.41 g, 1.5 mmol) and 10 mL of dichloromethane into the reaction flask, react in Carried out at 20°C, TLC followed the reaction until the end;

(2) The reaction solution is concentrated to obtain a residue, which is separated by column chromatography to obtain dibenzyl 2-oxo-2-phenylethylphosphonate (yield 85%);

(3) Add dibenzyl 2-oxo-2-phenylethylphosphonate (0.19 g, 0.5 mmol), sodium iodide (0.09 g, 0.6 mmol) and 10 mL 2-butanone, the reaction was carried out at 80°C, and the reaction was followed by TLC until the end;

(4) The reaction solution was concentrated to remove 2-butanone to obtain a residue, which was washed with ice-cold acetone and suction filtered to obtain a crude product, which was recrystallized with ethanol to obtain benzyl 2-oxo-2-phenylethylphosphonate sodium (product rate of 62%).

The analytical data for dibenzyl 2-oxo-2-phenylethylphosphonate are as follows: ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.97 (d, J = 7.5 Hz, 2H), 7.59 (t, J = 7.5 Hz, 1H), 7.44 (t, J = 7.8 Hz, 2H), 7.30– 7.34 (m, 10H), 4.99–5.12 (m, 4H), 3.67 (d, J = 22.8 Hz, 2H); benzyl The analytical data of sodium 2-oxo-2-phenylethylphosphonate are as follows: ¹ H NMR (300 MHz, D ₂ O): δ 7.78 (d, J = 7.2 Hz, 2H), 7.47 (t, J = 7.2 Hz, 1H), 7.31 (t, J = 7.8 Hz, 2H), 7.12–7.21 (m, 3H), 7.03–7.10 (m, 2H), 4.63 (d, J = 10.2 Hz, 2H), 3.43 (d, J = 21.6 Hz, 2H).

Example 20: Synthesis of biphenylmethyl 2-oxo-2-phenylethylphosphonate

Taking styrene and bisphenylmethyl phosphite as raw materials, its reaction formula and experimental steps are as follows:

    

(1) Add styrene (0.1 g, 1 mmol), bisphenylmethyl phosphite (0.61 g, 1.5 mmol), manganese acetate (0.41 g, 1.5 mmol) and 10 mL of dichloromethane into the reaction flask , the reaction was carried out at 30°C, and TLC followed the reaction until the end;

(2) The reaction solution was concentrated to obtain a residue, which was separated by column chromatography to obtain biphenylmethyl 2-oxo-2-phenylethylphosphonate (67% yield);

(3) Add biphenylmethyl 2-oxo-2-phenylethylphosphonate (0.27 g, 0.5 mmol) and sodium iodide (0.09 g, 0.6 mmol) obtained in (2) into the reaction flask and 10 mL of 2-butanone, the reaction was carried out at 80°C, and the reaction was followed by TLC until the end;

(4) The reaction solution was concentrated to remove 2-butanone to obtain a residue, which was washed with ice-cold acetone and suction-filtered to obtain a crude product, which was recrystallized with methanol: water (1:4) to obtain biphenylmethyl 2-oxo-2- Sodium phenethylphosphonate (65% yield).

The analytical data for bisphenylmethyl 2-oxo-2-phenylethylphosphonate are as follows: ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.98 (d, J = 7.2Hz, 2H), 7.53–7.57 (m, 9H), 7.44 (t, J = 7.9 Hz, 6H), 7.35–7.37 (m, 6H), 5.06–5.18 (m, 4H), 3.71 (d, J = 22.5 Hz, 2H); biphenyl The analytical data of sodium methyl 2-oxo-2-phenylethylphosphonate are as follows: ¹ H NMR (400 MHz, D ₂ O): δ 7.78 (d, J = 8.4Hz, 2H), 7.54 (d, J = 8.1 Hz, 2H), 7.45 (d, J = 7.8 Hz, 3H), 7.38 (t, J = 7.8Hz, 2H), 7.31 (t, J = 8.4 Hz, 3H), 7.17 (d, J = 7.5 Hz, 2H), 4.73 (d, J = 7.2Hz, 2H), 3.47 (d, J = 21 Hz, 2H).

Example 21: Synthesis of diphenyl 2-oxo-2-(biphenyl-4-yl)ethylphosphonate

Using distyrene and diphenyl phosphite as raw materials, the reaction formula and experimental steps are as follows:

(1) Add distyryl (0.18 g, 1 mmol), diphenyl phosphite (0.35 g, 1.5 mmol), manganese acetate (0.41 g, 1.5 mmol) and 10 mL of dichloromethane in the reaction flask, and react Carried out at 20°C, TLC followed the reaction until the end;

(2) The reaction solution was concentrated to obtain a residue, which was separated by column chromatography to obtain diphenyl 2-oxo-2-(biphenyl-4-yl)ethylphosphonate (yield 70%);

(3) Add diphenyl 2-oxo-2-(biphenyl-4-yl) ethyl phosphonate (0.21 g 0.5 mmol) obtained by (2) in the reaction flask, sodium hydroxide solution ( 0.08 g, 2.0 mmol (dissolved in 1 mL water) and 10 mL 1,4-dioxane, the reaction was carried out at 25 ° C, and TLC followed the reaction until the end;

(4) The reaction solution was concentrated to remove most of the solvent to obtain a residue, acidified with hydrochloric acid, and extracted with ethyl acetate. Remove the solvent in the extract, add sodium bicarbonate solution (0.042 g, 0.5 mmol dissolved in 1 mL water) to the residue, and freeze-dry the reaction solution to obtain phenyl 2-oxo-2-(biphenyl- 4-yl) sodium ethylphosphonate (55% yield).

The analytical data for diphenyl 2-oxo-2-(biphenyl-4-yl)ethylphosphonate are as follows: ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.12 (d, J = 8.7 Hz, 2H), 7.71 (d, J = 8.1 Hz, 2H), 7.63 (d, J = 6.6 Hz, 2H), 7.41–7.51 (m, 3H), 7.31 (t, J = 6.9 Hz, 4H), 7.15– 7.20 (m, 6H), 3.96 (d, J = 23 Hz, 2H); The analytical data for sodium phenyl 2-oxo-2-(biphenyl-4-yl)ethylphosphonate are as follows: ¹ H NMR (400 MHz, D ₂ O): δ 7.92 (d, J = 8.1 Hz, 2H), 7.63 (t, J = 8.4 Hz, 4H), 7.40 (t , J = 7.2 Hz, 2H), 7.33 (d , J = 7.5 Hz,1H), 7.16 (t, J = 7.8 Hz, 2H), 6.99 (t, J = 7.2 Hz, 1H), 6.88 (d, J = 8.4 Hz, 2H), 3.60 (d, J = 22.2 Hz, 2H).

Example 22: Synthesis of dibenzyl 2-oxo-2-(biphenyl-4-yl)ethylphosphonate

Using distyrene and dibenzyl phosphite as raw materials, the reaction formula and experimental steps are as follows:

(1) Add distyryl (0.18 g, 1 mmol), dibenzyl phosphite (0.39 g, 1.5 mmol), manganese acetate (0.41 g, 1.5 mmol) and 10 mL chloroform into the reaction flask, and react at 30 ℃, TLC tracking reaction until the end;

(2) The reaction solution was concentrated to obtain a residue, which was separated by column chromatography to obtain dibenzyl 2-oxo-2-(biphenyl-4-yl)ethylphosphonate (65% yield);

(3) Add dibenzyl 2-oxo-2-(biphenyl-4-yl)ethylphosphonate (0.23 g, 0.5 mmol) obtained in (2) into the reaction flask, sodium iodide ( 0.09 g, 0.6 mmol) and 10 mL 2-butanone, the reaction was carried out at 80°C, and the reaction was followed by TLC until the end;

(4) The reaction solution was concentrated to remove 2-butanone to obtain a residue, which was washed with ice-cold acetone and suction-filtered to obtain a crude product, which was recrystallized with ethanol: water (1:1) to obtain benzyl 2-oxo-2-( phenyl-4-yl) sodium ethylphosphonate (60% yield).

The analytical data of dibenzyl 2-oxo-2-(biphenyl-4-yl)ethylphosphonate are as follows: ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.01 (d , J = 8.0 Hz, 2H), 7.64 (d, J = 8.0 Hz, 2H), 7.61 (d,

J = 8.0 Hz, 2H), 7.48 (t, J = 8.0 Hz, 2H), 7.43 (t, J = 8.0 Hz, 1H), 7.40-7.20 (m, 10H), 5.07 (dq, J = 9.6, 13.6 Hz, 4H), 3.69 (d, J = 24.5 Hz, 2H); the analytical data for benzyl 2-oxo-2-(biphenyl-4-yl)ethylphosphonate sodium are as follows: ¹ H NMR ( 300 MHz, DMSO-d ₆ ): δ 8.13 (d, J = 7.5 Hz, 2H), 7.71 (2d , J = 7.5 Hz, 4H), 7.48 (t, J = 7.5 Hz, 2H), 7.39 (t, J = 7.5 Hz, 1H), 7.28 (m, 5H), 4.69 (d, J = 6.9 Hz, 2H), 3.26 (d, J = 20.9 Hz, 2H).

Example 23: Synthesis of Biphenylmethyl 2-oxo-2-(biphenyl-4-yl)ethylphosphonate

With distyrene and bisphenylmethyl phosphite as raw materials, its reaction formula and experimental steps are as follows:

(1) Add distyryl (0.18 g, 1 mmol), bisphenylmethyl phosphite (0.62 g, 1.5 mmol), manganese acetate (0.41 g, 1.5 mmol) and 10 mL chloroform into the reaction flask, The reaction was carried out at 20°C, and TLC followed the reaction until the end;

(2) The reaction solution was concentrated to obtain a residue, which was separated by column chromatography to obtain bis-biphenylmethyl 2-oxo-2-(biphenyl-4-yl)ethylphosphonate (yield 62%);

(3) Add bisphenylmethyl 2-oxo-2-(biphenyl-4-yl)ethylphosphonate (0.30 g, 0.5 mmol) obtained in (2) into the reaction flask, iodine Sodium chloride (0.09 g, 0.6 mmol) and 10 mL 2-butanone, the reaction was carried out at 80°C, and the reaction was followed by TLC until the end;

(4) The reaction solution was concentrated to remove 2-butanone to obtain a residue, which was washed with ice-cold acetone and suction filtered to obtain a crude product, which was recrystallized with ethanol: water (1:1) to obtain biphenylmethyl 2-oxo-2 Sodium -(biphenyl-4-yl)ethylphosphonate (54% yield).

The analytical data of bisphenylmethyl 2-oxo-2-(biphenyl-4-yl)ethylphosphonate are as follows: ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.03 (d, J = 8.7 Hz, 2H), 7.52–7.65 (m, 12H), 7.33–7.47 (m, 13H), 5.07–5.20 (m, 4H), 3.74 (d, J = 22.5 Hz, 2H); biphenylmethyl The analytical data of sodium 2-oxo-2-(biphenyl-4-yl)ethylphosphonate are as follows: ¹ H NMR (300 MHz, DMSO-d ₆ ): δ 7.95 (d, J = 8.0 Hz, 2H), 7.63 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 8.0 Hz, 2H), 7.45 (d, J = 7.6 Hz, 5H), 7.17–7.31 (m, 7H), 4.95– 4.98 (m, 2H), 3.92 (d, J = 22.4 Hz, 2H).

Example 24: Synthesis of diphenyl 2-oxo-2-(pentafluorophenyl)ethylphosphonate

Using pentafluorostyrene and diphenyl phosphite as raw materials, the reaction formula and experimental steps are as follows:

(1) Add pentafluorostyrene (0.19 g, 1 mmol), diphenyl phosphite (0.35 g, 1.5 mmol), manganese acetate (0.41 g, 1.5 mmol) and 10 mL of acetonitrile into the reaction flask, react in Carried out at 30°C, TLC followed the reaction until the end;

(2) The reaction solution was concentrated to obtain a residue, which was separated by column chromatography to obtain diphenyl 2-oxo-2-(pentafluorophenyl) ethyl phosphonate (60% yield);

(3) Add diphenyl 2-oxo-2-(pentafluorophenyl) ethyl phosphonate (0.22 g, 0.5 mmol) obtained in (2) into the reaction flask, sodium hydroxide solution (0.08 g , 2.0 mmol dissolved in 1 mL water) and 10 mL 1,4-dioxane, the reaction was carried out at 25 ° C, and TLC followed the reaction until the end;

(4) The reaction solution was concentrated to remove most of the solvent to obtain a residue, acidified with hydrochloric acid, and extracted with ethyl acetate. Remove the solvent in the extract, add sodium bicarbonate solution (0.042 g, 0.5 mmol dissolved in 1 mL water) to the residue, and freeze-dry the reaction solution to obtain phenyl 2-oxo-2-(pentafluorophenyl ) Sodium ethylphosphonate (50% yield).

The analytical data of diphenyl 2-oxo-2-(pentafluorophenyl)ethylphosphonate are as follows: ¹ H NMR (300 MHz, DMSO-d ₆ ): δ 7.32 (t, J = 7.8 Hz, 4H ), 7.19 (t, J = 7.2 Hz, 2H), 7.13 (d, J = 8.1 Hz, 4H), 3.87 (d, J = 22.5 Hz, 2H); phenyl 2-oxo-2-(pentafluoro The analytical data for sodium phenyl)ethylphosphonate are as follows: ¹ H NMR (300 MHz, DMSO-d ₆ ): δ 7.35 (t, J = 7.2Hz, 2H), 7.09–7.19 (m, 3H), 3.72 (d, J = 21.6 Hz, 2H).

Example 25: Synthesis of diphenyl 2-oxo-2-(3-(2-chlorophenyl)-5-methylisoxazol-4-yl)ethylphosphonate

Using 3-(2-chlorophenyl)-5-methylisoxazol-4-yl)ethylene and diphenyl phosphite as raw materials, the reaction formula and experimental steps are as follows:

(1) Add 3-(2-chlorophenyl)-5-methylisoxazol-4-yl)ethylene (0.22 g, 1 mmol), diphenyl phosphite (0.35 g, 1.5 mmol), manganese acetate (0.41 g, 1.5 mmol) and 10 mL of acetonitrile, the reaction was carried out at 30°C, and the reaction was followed by TLC until the end;

(2) The reaction solution was concentrated to obtain a residue, which was separated by column chromatography to obtain diphenyl 2-oxo-2-(3-(2-chlorophenyl)-5-methylisoxazol-4-yl)ethyl Phosphonate (yield 80%);

(3) Add the diphenyl 2-oxo-2-(3-(2-chlorophenyl)-5-methylisoxazol-4-yl)ethylphosphine obtained in (2) into the reaction flask Ester (0.24 g, 0.5 mmol), sodium iodide (0.09 g, 0.6 mmol) and 10 mL 2-butanone, the reaction was carried out at 80°C, and the reaction was followed by TLC until the end;

(4) The reaction solution was concentrated to remove 2-butanone to obtain the residue, washed with ice-cold acetone, and suction filtered to obtain the crude product,

Recrystallization from ethanol:water (1:1) gave phenyl 2-oxo-2-(3-(2-chlorophenyl)-5-methylisoxazol-4-yl)ethylphosphonate sodium (Yield 50%).

The analytical data for diphenyl 2-oxo-2-(3-(2-chlorophenyl)-5-methylisoxazol-4-yl)ethylphosphonate are as follows: ¹ H NMR (400 MHz, DMSO-d ₆ ): δ 12.15 (br s, 1H), 8.00 (s, 1H), 7.97 (d, J = 8.1 Hz, 1H), 7.39 (t, J = 7.8 Hz, 4H), 7.23 (d, J = 8.0 Hz, 2H), 7.13–7.19 (m, 5H), 4.35 (d, J = 23.0 Hz, 2H), 2.51 (s, 3H); phenyl 2-oxo-2-(3-(2 The analytical data for sodium -chlorophenyl)-5-methylisoxazol-4-yl)ethylphosphonate are as follows: ¹ H NMR (300 MHz, D ₂ O): δ 7.37–7.45 (m, 2H) , 7.20–7.33 (m, 5H), 7.05–7.08 (m, 2H), 4.55 (d, J = 6.9 Hz, 2H), 2.51 (s, 3H).

Example 26: Synthesis of 2-amino-2-phenylethylphosphonic acid

Taking diethyl 2-oxo-2-phenylethyl phosphonate as raw material, its reaction formula and experimental steps are as follows:

(1) Add diethyl 2-oxo-2-phenylethylphosphonate (0.52 g, 2 mmol), 7 mL ethanol, and ethanol solution of hydroxylamine hydrochloride (0.276 g, 4 mmol) in the reaction flask , the mixture was stirred and reacted at 25°C, followed by TLC until the end of the reaction, and a solid was obtained by filtration;

(2) Put the solid obtained in (1) into the reaction flask, add 10 mL of methanol and 2 mL of ammonia water, 0.2 g of Raney Ni, pass in hydrogen, stir the mixture at 25°C, and follow the reaction by TLC until the end;

(3) The reaction solution was concentrated, extracted with ethyl acetate, the organic layer was dried over anhydrous sodium sulfate, and concentrated; 10 mL of 20% hydrochloric acid was added to the concentrate, the mixture was heated to reflux, and the reaction was tracked by TLC until the end; the reaction solution was concentrated to dryness , recrystallized from methanol/propylene oxide to obtain 2-amino-2-phenethylphosphonic acid (60% yield).

The analytical data of 2-amino-2-phenylethylphosphonic acid are as follows: ¹ H NMR (300 MHz, D ₂ O): δ 7.20-7.40 (m, 5H ), 4.11-4.31 (m, 1H ) , 1.60-1.80 (m, 2H ) .

Example 27: Synthesis of 2-amino-2-(4-chlorophenyl)ethylphosphonic acid

Using diethyl 2-oxo-2-(4-chlorophenyl) ethyl phosphonate as raw material, its reaction formula and experimental steps are as follows:

(1) Add diethyl 2-oxo-2-(4-chlorophenyl) ethyl phosphonate (0.58 g, 2 mmol), 7 mL ethanol, hydroxylamine hydrochloride (0.276 g, 4 mmol) ethanol solution, the mixture was stirred and reacted at 25°C, followed by TLC until the end of the reaction, and the solid was obtained by filtration;

(2) Put the solid obtained in (1) into the reaction flask, add 10 mL of methanol and 2 mL of ammonia water, 0.2 g of Raney Ni, pass in hydrogen, stir the mixture at 25°C, and follow the reaction by TLC until the end;

(3) The reaction solution was concentrated, extracted with ethyl acetate, the organic layer was dried over anhydrous sodium sulfate, and concentrated; 10 mL of 20% hydrochloric acid was added to the concentrate, the mixture was heated to reflux, and the reaction was tracked by TLC until the end; the reaction solution was concentrated to dryness , recrystallized from methanol/propylene oxide to obtain 2-amino-2-(4-chlorophenyl)ethylphosphonic acid (yield 58%).

The analytical data of 2-amino-2-(4-chlorophenyl)ethylphosphonic acid are as follows: ¹ H NMR (300 MHz, D ₂ O): δ 7.30-7.70 (m, 4H ), 4.12-4.30 (m, 1H ) , 1.60-1.85 (m, 2H ) .

Example 28: Synthesis of 2-amino-2-(4-methylphenyl)ethylphosphonic acid

Using diethyl 2-oxo-2-(4-tolyl)ethyl phosphonate as raw material, the reaction formula and experimental steps are as follows:

(1) Add diethyl 2-oxo-2-(4-methylphenyl) ethyl phosphonate (0.54 g, 2 mmol), 7 mL ethanol, hydroxylamine hydrochloride (0.276 g, 4 mmol) ethanol solution, the mixture was stirred and reacted at 25°C, followed by TLC until the end of the reaction, and the solid was obtained by filtration;

(2) Put the solid obtained in (1) into the reaction flask, add 10 mL of methanol and 2 mL of ammonia water, 0.2 g of Raney Ni, pass in hydrogen, stir the mixture at 25°C, and follow the reaction by TLC until the end;

(3) The reaction solution was concentrated, extracted with ethyl acetate, the organic layer was dried over anhydrous sodium sulfate, and concentrated; 10 mL of 20% hydrochloric acid was added to the concentrate, the mixture was heated to reflux, and the reaction was tracked by TLC until the end; the reaction solution was concentrated to dryness , recrystallized from methanol/propylene oxide to give 2-amino-2-(4-methylphenyl)ethylphosphonic acid (62% yield).

The analytical data of 2-amino-2-(4-methylphenyl)ethylphosphonic acid are as follows: ¹ H NMR (300 MHz, D ₂ O): δ 7.20-7.40 (m, 4H ), 4.11-4.31 (m, 1H ) , 2.35 (s, 3H), 1.60-1.80 (m, 2H ) .

Example 29: Synthesis of 2-amino-2-(4-fluorophenyl)ethylphosphonic acid

Using diethyl 2-oxo-2-(4-fluorophenyl)ethylphosphonate as raw material, the reaction formula and experimental steps are as follows:

(1) Add diethyl 2-oxo-2-(4-fluorophenyl) ethyl phosphonate (0.55 g, 2 mmol), 7 mL ethanol, hydroxylamine hydrochloride (0.276 g, 4 mmol) ethanol solution, the mixture was stirred and reacted at 25°C, followed by TLC until the end of the reaction, and the solid was obtained by filtration;

(2) Put the solid obtained in (1) into the reaction flask, add 10 mL of methanol and 2 mL of ammonia water, 0.2 g of Raney Ni, pass in hydrogen, stir the mixture at 25°C, and follow the reaction by TLC until the end;

(3) The reaction solution was concentrated, extracted with ethyl acetate, the organic layer was dried over anhydrous sodium sulfate, and concentrated; 10 mL of 20% hydrochloric acid was added to the concentrate, the mixture was heated to reflux, and the reaction was tracked by TLC until the end; the reaction solution was concentrated to dryness , recrystallized from methanol/propylene oxide to give 2-amino-2-(4-fluorophenyl)ethylphosphonic acid (yield 59%).

The analytical data of 2-amino-2-(4-fluorophenyl)ethylphosphonic acid are as follows: ¹ H NMR (300 MHz, D ₂ O): δ 7.20-7.40 (m, 4H ), 4.11-4.31 (m, 1H ) , 1.60-1.90 (m, 2H ) .

Example 30: Synthesis of 2-amino-2-(4-methoxyphenyl)ethylphosphonic acid

Using diethyl 2-oxo-2-(4-methoxyphenyl) ethyl phosphonate as raw material, the reaction formula and experimental steps are as follows:

(1) Add diethyl 2-oxo-2-(4-methoxyphenyl)ethylphosphonate (0.57 g, 2 mmol), 7 mL ethanol, hydroxylamine hydrochloride (0.276 g, 4 mmol) in ethanol solution, the mixture was stirred and reacted at 25°C, followed by TLC until the end of the reaction, and the solid was obtained by filtration;

(2) Put the solid obtained in (1) into the reaction flask, add 10 mL of methanol and 2 mL of ammonia water, 0.2 g of Raney Ni, pass in hydrogen, stir the mixture at 25°C, and follow the reaction by TLC until the end;

(3) The reaction solution was concentrated, extracted with ethyl acetate, the organic layer was dried over anhydrous sodium sulfate, and concentrated; 10 mL of 20% hydrochloric acid was added to the concentrate, the mixture was heated to reflux, and the reaction was tracked by TLC until the end; the reaction solution was concentrated to dryness , recrystallized from methanol/propylene oxide to give 2-amino-2-(4-methoxyphenyl)ethylphosphonic acid (64% yield).

The analytical data of 2-amino-2-(4-methoxyphenyl)ethylphosphonic acid are as follows: ¹ H NMR (300 MHz, D ₂ O): δ 6.80-7.20 (m, 4H ), 4.11-4.31 ( m, 1H ) , 3.83 (s, 3H), 1.60-1.90 (m, 2H ) .

Claims (6)

1. A preparation method for β-carbonyl phosphonate derivatives, characterized in that it comprises the following steps: dissolving ethylene derivatives, phosphorus reagents, and manganese acetate in a solvent, and reacting at 20 to 100°C to obtain β - carbonyl phosphonate derivatives; The general chemical structure formula of the ethylene derivative is , where R is one of the following groups: , , , , , , The selection of R ¹ , R ² , R ³ , R ⁴ and R ⁵ adopts one of the following schemes: (1) R ¹ is one of hydrogen, methyl, trifluoromethyl, methoxy, fluorine, chlorine, bromine, cyano, formyl, methyl formate, nitro, R ² , R ³ , R ⁴ and R ⁵ are both hydrogen; (2) R ² is one of methyl, trifluoromethyl, methoxy, fluorine, chlorine, bromine, cyano, formyl, methyl formate, nitro, R ¹ , R ³ , R ⁴ and R are ^both hydrogen; (3) R ³ is one of methyl, trifluoromethyl, methoxy, fluorine, chlorine, bromine, cyano, formyl, methyl formate, nitro, phenyl, R ¹ , R ² , R ⁴ and R ⁵ are all hydrogen; (4) R ¹ , R ² , R ³ , R ⁴ and R ⁵ are fluorine; The general chemical structure formula of described phosphorus reagent is: Wherein R is ^one of the following groups: _CH3- , , , , , ; Described solvent is selected from: the one in methanol, ethanol, acetonitrile, acetic acid, chloroform, methylene chloride, toluene; The chemical structural formula of the β-carbonyl phosphonate derivative is: . 2. according to the preparation method of the described β-carbonyl phosphonate derivative of claim 1, it is characterized in that: described vinyl derivative is selected from styrene, 2-methylstyrene, 3-methoxystyrene, 4 -Methoxystyrene, 2-chlorostyrene, 3-chlorostyrene, 4-chlorostyrene, 4-cyanostyrene, 3-formylmethylstyrene, 4-acetylstyrene, 3- Nitrostyrene, 3-trifluoromethylstyrene, 4-biphenylethylene, pentafluorostyrene, 2-vinylfuran, 2-vinylthiophene, 2-vinylpyrrole, 3-vinylpyridine, One of 3-(2-chlorophenyl)-5-methylisoxazol-4-yl)ethylene. 3. according to the preparation method of the described β-carbonyl phosphonate derivative of claim 1, it is characterized in that: utilize thin-layer chromatography to follow up reaction until completely finishing. 4. according to the preparation method of the described β-carbonyl phosphonate derivative of claim 1, it is characterized in that: in molar ratio, ethylene derivative: phosphorus reagent: manganese acetate is 1: (1～2): (1～3 ). 5. according to the preparation method of the described β-carbonyl phosphonate derivative of claim 4, it is characterized in that: by molar ratio, ethylene derivative: phosphorus reagent: manganese acetate is equal to 1: 1.5: 1.5. 6. according to the preparation method of the described β-carbonyl phosphonate derivative of claim 1, it is characterized in that: also comprise purification step, specifically, after reaction finishes, reaction solution is concentrated and separated by column chromatography to obtain β-carbonyl Phosphonate derivatives.