阅读说明：本技术 一种制备β-羰基膦酸酯类化合物的方法 (Method for preparing beta-carbonyl phosphonate compound ) 是由 刘开建 欧金花 胡波年 于 2021-10-07 设计创作，主要内容包括：一种制备β-羰基膦酸酯类化合物的方法,先将2-苯乙烯基膦酸酯类化合物溶于有机溶剂中,有机溶剂为乙酸乙酯、甲醇、乙醇、丙酮、乙醚、氯仿、二氯甲烷、四氢呋喃中的一种或由其中两种或两种以上所组成的混合溶剂；之后于敞开体系中在甲基苯基亚膦酸酯催化下利用氧气作为氧化剂和氧源进行反应,反应产物经分离纯化即得所述β-羰基膦酸酯类化合物。与现有的方法相比,该方法反应温度更低、不需要使用有机金属催化剂,对环境更加友好,同时反应周期更短,且其所采用的反应工艺条件稳定,操作简单,产率更高,更适合在工业化生产中进行应用。(A method for preparing beta-carbonyl phosphonate compounds comprises dissolving 2-styryl phosphonate compounds in an organic solvent, wherein the organic solvent is one or a mixed solvent of two or more of ethyl acetate, methanol, ethanol, acetone, diethyl ether, chloroform, dichloromethane and tetrahydrofuran; and then reacting with an oxygen source in an open system under the catalysis of methyl phenyl phosphonite by using oxygen as an oxidant, and separating and purifying reaction products to obtain the beta-carbonyl phosphonate compounds. Compared with the existing method, the method has the advantages of lower reaction temperature, no need of using an organic metal catalyst, environmental friendliness, shorter reaction period, stable reaction process conditions, simple operation and higher yield, and is more suitable for application in industrial production.)

1. A method for preparing a beta-carbonyl phosphonate compound, which is characterized by comprising the following steps:

dissolving 2-styryl phosphonate compounds in an organic solvent; the organic solvent is one or a mixed solvent consisting of two or more of ethyl acetate, methanol, ethanol, acetone, diethyl ether, chloroform, dichloromethane and tetrahydrofuran;

then, reacting in an open system by using oxygen as an oxidant and an oxygen source under the catalysis of methyl phenyl phosphonite, and separating and purifying a reaction product to obtain the beta-carbonyl phosphonate compound with the structural general formula shown as I:

I ；

wherein R is₁Is a substituted monocyclic aryl radical, said R₁The substituent on the substituent is one of methyl, methoxy, bromo, chloro, fluoro, acetoxy, cyclohexenyl and hydrogen atoms; r₂Is one of methyl, ethyl, isopropyl, n-butyl and benzyl.

2. The process for preparing β -carbonyl phosphonate ester compound according to claim 1, wherein: the proportion of the 2-styryl phosphonate compound and the organic solvent is that every 0.1g of the 2-styryl phosphonate compound is dissolved in 5-30ml of the organic solvent.

3. The process for preparing β -carbonyl phosphonate ester compound according to claim 1, wherein: the molar ratio of the 2-styryl phosphonate compounds to the methyl phenyl phosphonite is 1 (0.1-1.5).

4. The process for preparing β -carbonyl phosphonate ester compound according to claim 1, wherein: the reaction is carried out in pure oxygen or air environment.

5. The process for preparing β -carbonyl phosphonate ester compound according to claim 1, wherein: the reaction temperature is normal temperature or 30-90 ℃; wherein the stirring reaction time under the normal temperature condition is 4-8h, and the stirring reaction time under the condition of 30-90 ℃ is 2-7 h.

6. The method of claim 1, wherein the 2-styrylphosphonate compound has the general structural formula ii:

Ⅱ；

wherein R is₃Is a substituted monocyclic aryl radical, said R₃The substituent is one of methyl, methoxy, bromo, chloro, fluoro, acetoxy, cyclohexenyl and hydrogen atom.

7. The process for preparing β -carbonyl phosphonate ester compound according to claim 6, wherein: the molar ratio of the 2-styryl phosphonate compounds to the methyl phenyl phosphonite is 1: 1.

8. the process for preparing β -carbonyl phosphonate ester compound according to claim 7, wherein: the organic solvent is ethyl acetate, and the ratio of the 2-styryl phosphonate compounds to the ethyl acetate is that each mmol of 2-styryl phosphonate compounds is dissolved in 30ml of ethyl acetate.

9. The process for preparing β -carbonyl phosphonate ester compound according to claim 1, wherein: the separation and purification of the reaction product comprises the following steps: and after the reaction is stopped, washing with saturated saline solution, separating an organic layer, sequentially drying, filtering and concentrating under reduced pressure to obtain an oily crude product, washing the oily crude product with an eluent, and performing flash column chromatography to obtain a light yellow oily substance, wherein the light yellow oily substance is the beta-carbonyl phosphonate compound shown in the structural general formula I.

10. The process for preparing β -carbonyl phosphonate ester compound according to claim 9, wherein: in the separation and purification process of the reaction product, anhydrous magnesium sulfate is used as a drying agent, and the eluent is a mixed eluent composed of petroleum ether and ethyl acetate.

Technical Field

The invention relates to the technical field of organic compound synthesis, in particular to a method for preparing a beta-carbonyl phosphonate compound.

Background

Beta-carbonyl phosphonates (beta-Ketophosphonates) are very valuable carbonyl compounds and are widely applied to organic synthesis as important synthesis intermediates, particularly to synthesis of alpha, beta-unsaturated carbonyl compounds, chiral beta-amino and chiral beta-hydroxy phosphonic acid compounds by HWE (Horner-Wadsworth-Emmons) reaction. In addition, the beta-carbonyl phosphonate and further products thereof have various biological activities (such as anti-tumor, anti-oxidation, enzyme activity inhibition, plant virus resistance, hyperosteogeny resistance, lactamase inhibition, etc.), and are abundantly present in natural products and drug molecules.

Chinese patent document CN102924511A discloses a method for preparing β -carbonyl phosphonate ester compounds, which uses olefin, hydrogen-phosphite ester and oxygen as starting materials, and prepares β -carbonyl phosphonate ester by using oxygen as an oxidant and an oxygen source in the presence of an organic transition metal catalyst and alkali. Although the above method has advantages of mild reaction conditions and environmental friendliness as compared with the conventional method for preparing β -carbonyl phosphonate ester, it still has disadvantages of requiring the use of an organometallic catalyst and requiring a long reaction time, and thus is not suitable for popularization and application in industrial production.

Disclosure of Invention

The invention aims to provide a method for preparing beta-carbonyl phosphonate compounds, which does not need to use metal catalysts, has lower reaction temperature and shorter reaction duration.

In order to achieve the purpose, the invention adopts the following technical scheme: a method for preparing beta-carbonyl phosphonate compounds, which comprises the following steps:

dissolving 2-styryl phosphonate compounds in an organic solvent; the organic solvent is one or a mixed solvent consisting of two or more of ethyl acetate, methanol, ethanol, acetone, diethyl ether, chloroform, dichloromethane and tetrahydrofuran;

then, reacting in an open system by using oxygen as an oxidant and an oxygen source under the catalysis of methyl phenyl phosphonite, and separating and purifying a reaction product to obtain the beta-carbonyl phosphonate compound with the structural general formula shown as I:

wherein R is₁Is a substituted monocyclic aryl radical, said R₁The substituent on the substituent is one of methyl, methoxy, bromo, chloro, fluoro, acetoxy, cyclohexenyl and hydrogen atoms; r₂Is methyl, ethyl, isopropyl, n-butylOne of the group and benzyl.

Wherein the proportion of the 2-styryl phosphonate compound to the organic solvent is that every 0.1g of the 2-styryl phosphonate compound is dissolved in 5-30ml of the organic solvent.

Wherein the molar ratio of the 2-styryl phosphonate compound to the methyl phenyl phosphonite is 1 (0.1-1.5).

Further, the reaction is carried out in a pure oxygen or air environment.

Preferably, the reaction temperature is normal temperature or 30-90 ℃; wherein the stirring reaction time under the normal temperature condition is 4-8h, and the stirring reaction time under the condition of 30-90 ℃ is 2-7 h.

In the embodiment of the invention, the structural general formula II of the 2-styryl phosphonate compound is as follows:

wherein R is₃Is a substituted monocyclic aryl radical, said R₃The substituent is one of methyl, methoxy, bromo, chloro, fluoro, acetoxy, cyclohexenyl and hydrogen atom.

Preferably, the molar ratio of the 2-styryl phosphonate compounds to the methyl phenyl phosphonite is 1: 1.

wherein the organic solvent is ethyl acetate, and the ratio of the 2-styryl phosphonate compounds to the ethyl acetate is that 2-styryl phosphonate compounds are dissolved in 30ml of ethyl acetate per mmol.

In the embodiment of the present invention, the reaction product separation and purification comprises the following steps: and after the reaction is stopped, washing with saturated saline solution, separating an organic layer, sequentially drying, filtering and concentrating under reduced pressure to obtain an oily crude product, washing the oily crude product with an eluent, and performing flash column chromatography to obtain a light yellow oily substance, wherein the light yellow oily substance is the beta-carbonyl phosphonate compound shown in the structural general formula I.

Further, in the separation and purification process of the reaction product, anhydrous magnesium sulfate is used as a drying agent, and the eluent is a mixed eluent composed of petroleum ether and ethyl acetate.

The beta-carbonyl phosphonate is prepared by the brand new preparation method which is adopted by the invention by using oxygen as an oxidant and an oxygen source under the catalysis of methyl phenyl phosphinate for 2-styryl phosphonate compounds. Compared with the existing method, the method has the advantages of lower reaction temperature, no need of using an organic metal catalyst, environmental friendliness, shorter reaction period, stable reaction process conditions, higher yield and suitability for application in industrial production.

Detailed Description

In order to facilitate the understanding of those skilled in the art, the present invention will be further described with reference to the following examples, which are not intended to limit the present invention.

Example 1: diisopropyl (2-phenethyl-2-oxo) phosphonate

In this example, diisopropyl 2-styrylphosphonate was catalyzed by methyl phenyl phosphonite to prepare the corresponding β -carbonyl phosphonate using oxygen as the oxidant and oxygen source:

the method comprises the following specific steps: diisopropyl 2-styrylphosphonate (1.072g, 4mmol), methylphenyl phosphonite (0.624g,4mmol) and ethyl acetate (120ml) are added in sequence into a 250ml three-neck flask, the mixture is stirred for about 5 hours at normal temperature, the reaction is stopped, the mixture is washed by 80ml saturated saline solution, an organic layer is separated, dried by anhydrous magnesium sulfate, filtered, concentrated under reduced pressure to obtain an oily crude product, finally, the oily crude product is washed by a mixed eluent of petroleum ether and ethyl acetate, and the column chromatography is carried out to obtain 0.98g of a light yellow oily substance with the yield of 86.3%.

¹H NMR(400MHz,CDCl₃):δ8.00(d,J＝7.7Hz,2H),7.58(t,J＝7.3Hz,1H),7.48(t,J＝7.7Hz,2H),4.74-4.69(m,2H),3.58(d,J＝23.1Hz,2H),1.27(t,J＝5.1Hz,12H)；¹³C NMR(100MHz,CDCl₃):δ192.1,136.8,133.4,129.2,128.5,71.6(d,J_C-P＝6.8Hz),39.8(d,J_C-P＝130.0Hz),23.8,23.6；HRMS calc.for C₁₄H₂₁O₄NaP(M+Na)⁺,307.1075；found,307.1068。

Example 2: diisopropyl [2- (4' -methylphenylethyl) -2-oxo ] phosphonate

This example is the preparation of the corresponding beta-carbonylphosphonate from diisopropyl 2- (4' -methylstyryl) phosphonate catalyzed by methyl phenyl phosphinate using oxygen as the oxidant and source of oxygen:

the method comprises the following specific steps: diisopropyl 2- (4' -methylstyryl) phosphonate (1.128g, 4mmol), methylphenyl phosphonite (0.624g,4mmol) and ethyl acetate (120ml) are added in sequence to a 250ml three-neck flask, the reaction is stopped after the system is opened and stirred for about 5h at normal temperature, 80ml saturated saline solution is used for washing, an organic layer is separated, anhydrous magnesium sulfate is used for drying, filtering and decompression concentration are carried out to obtain an oily crude product, finally a mixed eluent of petroleum ether and ethyl acetate is used for washing, and flash column chromatography is carried out to obtain 1.08g of a light yellow oily substance with the yield of 90.6%.

¹H NMR(400MHz,CDCl₃):δ7.93(d,J＝8.0Hz,2H),7.25(d,J＝8.0Hz,2H),4.74-4.68(m,2H),3.57(d,J＝22.7Hz,2H),2.42(s,3H),1.27(t,J＝5.9Hz,12H)；¹³CNMR(100MHz,CDCl₃):δ191.5,144.5,134.4,129.2,129.3,71.5(d,J_C-P＝6.8Hz),39.8(d,J_C-P＝128.9Hz),23.8(d,J_C-P＝3.4Hz),23.6(d,J_C-P＝5.7Hz),21.8；HRMS calc.for C₁₅H₂₃O₄NaP(M+Na)⁺,321.1232；found,321.1242。

Example 3: diisopropyl [2- (4' -methoxyphenylethyl) -2-oxo ] phosphonate

This example is the preparation of the corresponding beta-carbonylphosphonate from diisopropyl 2- (4' -methoxystyryl) phosphonate catalyzed by methyl phenyl phosphinate using oxygen as the oxidant and source of oxygen:

diisopropyl 2- (4' -methoxystyryl) phosphonate (1.192g, 4mmol), methylphenyl phosphonite (0.624g,4mmol) and ethyl acetate (120ml) are added in sequence to a 250ml three-neck flask, the reaction is stopped after the system is opened and stirred for about 6 hours at normal temperature, 80ml saturated saline solution is used for washing, an organic layer is separated, anhydrous magnesium sulfate is used for drying, filtering and decompression concentration are carried out to obtain an oily crude product, finally, a mixed eluent of petroleum ether and ethyl acetate is used for washing, and flash column chromatography is carried out to obtain 1.18g of a light yellow oily substance, and the yield is 93.9%.

¹H NMR(400MHz,CDCl₃):δ7.97(d,J＝8.8Hz,2H),6.88(d,J＝8.8Hz,2H),4.71-4.66(m,2H),3.82(s,3H),3.48(d,J＝23.2Hz,2H),1.25(t,J＝6.1Hz,12H)；¹³C NMR(100MHz,CDCl₃):δ190.4(d,J_C-P＝6.9Hz),163.7,131.6,129.7,113.5,71.4(d,J_C-P＝6.8Hz),55.5,39.7(d,J_C-P＝130.0Hz),23.8(d,J_C-P＝3.4Hz),23.6(d,J_C-P＝4.6Hz)；HRMS calc.for C₁₅H₂₄O₅P(M+H)⁺,315.1361；found,315.1365。

Example 4: diisopropyl [2- (3' -methylphenylethyl) -2-oxo ] phosphonate

This example is the preparation of the corresponding beta-carbonylphosphonate from diisopropyl 2- (4' -methylstyryl) phosphonate catalyzed by methyl phenyl phosphinate using oxygen as the oxidant and source of oxygen:

the method comprises the following specific steps: diisopropyl 2- (4' -methylstyryl) phosphonate (1.128g, 4mmol), methylphenyl phosphonite (0.624g,4mmol) and ethyl acetate (120ml) are added in sequence to a 250ml three-neck flask, the reaction is stopped after the open system is stirred for about 5h at normal temperature, 80ml saturated saline solution is used for washing, an organic layer is separated, anhydrous magnesium sulfate is used for drying, filtering and decompression concentration are carried out to obtain an oily crude product, finally a mixed eluent of petroleum ether and ethyl acetate is used for washing, and flash column chromatography is carried out to obtain 1.10g of a light yellow oily substance with the yield of 92.2%.

¹H NMR(400MHz,CDCl₃):δ7.83(d,J＝8.0Hz,2H),7.38(d,J＝7.7Hz,1H),7.37(t,J＝7.5Hz,1H),4.75-4.70(m,2H),3.59(d,J＝22.7Hz,2H),2.43(s,3H),1.28(d,J＝2.9Hz,6H,overlap),1.28(d,J＝2.9Hz,6H,overlap)；¹³C NMR(100MHz,CDCl₃):δ192.3(d,J_C-P＝6.8Hz),138.3,136.8,134.1,129.7,128.5,126.4,71.3(d,J_C-P＝6.8Hz),39.8(d,J_C-P＝130.0Hz),23.8(d,J_C-P＝3.4Hz),23.8(d,J_C-P＝4.6Hz),21.3；HRMS calc.for C₁₅H₂₃O₄NaP(M+Na)⁺,321.1232；found,321.1231。

Example 5: diisopropyl [2- (4' -bromophenylethyl) -2-oxo ] phosphonate

This example is the preparation of the corresponding β -carbonyl phosphonate from diisopropyl 2- (4' -bromostyryl) phosphonate catalyzed by methylphenyl phosphinate using oxygen as the oxidant and source of oxygen:

the method comprises the following specific steps: diisopropyl 2- (4' -bromostyryl) phosphonate (1.384g, 4mmol), methylphenyl phosphonite (0.624g,4mmol) and ethyl acetate (120ml) are added in sequence to a 250ml three-necked flask, the reaction is stopped by stirring the open system at normal temperature for about 5.5h, an organic layer is separated by washing with 80ml of saturated brine, the organic layer is dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain an oily crude product, and finally the crude product is washed with a mixed eluent of petroleum ether and ethyl acetate and subjected to flash column chromatography to obtain 1.33g of a pale yellow oily substance with a yield of 91.8%.

¹H NMR(400MHz,CDCl₃):δ7.88(d,J＝8.5Hz,2H),7.62(br.t,J＝8.4Hz,2H),4.76-4.70(m,2H),3.54(d,J＝22.7Hz,2H),1.28(d,J＝3.3Hz,6H,overlap),1.29(d,J＝3.3Hz,6H,overlap)；¹³C NMR(100MHz,CDCl₃):δ191.2(d,J_C-P＝6.8Hz),135.3,131.9,130.7,128.9,71.5(d,J_C-P＝6.8Hz),39.8(d,J_C-P＝128.9Hz),23.8(d,J_C-P＝3.4Hz),23.7(d,J_C-P＝4.6Hz)；HRMS calc.for C₁₄H₂₀O₄NaPBr(M+Na)⁺,385.0180；found,385.0188。

Example 6: diisopropyl [2- (4' -chlorophenethyl) -2-oxo ] phosphonate

This example is the preparation of the corresponding beta-carbonylphosphonate from diisopropyl 2- (4' -chlorostyryl) phosphonate under the catalysis of methyl phenyl phosphinate using oxygen as oxidant and oxygen source:

the specific implementation steps are as follows: diisopropyl 2- (4' -chlorostyryl) phosphonate (1.208g, 4mmol), methylphenyl phosphonite (0.624g,4mmol) and ethyl acetate (120ml) were added in this order to a 250ml three-necked flask, the mixture was stirred at room temperature for about 5 hours, the reaction was stopped, the mixture was washed with 80ml of saturated brine, the organic layer was separated, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give an oily crude product, and finally washed with a mixed eluent of petroleum ether and ethyl acetate, and flash column chromatography was performed to give 1.14g of a pale yellow oily substance with a yield of 89.6%.

¹H NMR(400MHz,CDCl₃):δ7.97-7.95(m,2H),7.46-7.44(m,2H),4.74-4.68(m,2H),3.56(d,J＝22.7Hz,2H),1.28(d,J＝3.3Hz,6H,overlap),1.29(d,J＝3.3Hz,6H,overlap)；¹³C NMR(100MHz,CDCl₃):δ190.8(d,J_C-P＝5.7Hz),140.1,135.1,130.5,128.7,71.7(d,J_C-P＝6.8Hz),39.8(d,J_C-P＝128.9Hz),23.8(d,J_C-P＝3.4Hz),23.8(d,J_C-P＝5.7Hz)；HRMS calc.for C₁₄H₂₁O₄PCl(M+H)⁺,319.0866；found,319.0866。

Example 7: diisopropyl [2- (4' -fluorophenethyl) -2-oxo ] phosphonate

This example utilizes diisopropyl 2- (4' -fluorophenylethenyl) phosphonate to produce the corresponding beta-carbonylphosphonate ester using oxygen as the oxidant and oxygen source, catalyzed by methylphenyl phosphinate:

the specific operation steps are as follows: diisopropyl 2- (4' -fluorophenylvinyl) phosphonate (1.144g, 4mmol), methylphenyl phosphonite (0.624g,4mmol) and ethyl acetate (120ml) are added in sequence to a 250ml three-necked flask, the mixture is stirred at normal temperature for about 6 hours, the reaction is stopped, the mixture is washed with 80ml of saturated brine, an organic layer is separated, dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure to obtain an oily crude product, finally washed with a mixed eluent of petroleum ether and ethyl acetate, and subjected to flash column chromatography to obtain 1.12g of a pale yellow oily substance with a yield of 92.7%.

¹H NMR(400MHz,CDCl₃):δ8.08-8.06(m,2H),7.18-7.14(m,2H),4.75-4.70(m,2H),3.58(d,J＝23.1Hz,2H),1.31(d,J＝3.7Hz,6H,overlap),1.28(d,J＝3.7Hz,6H,overlap)；¹³C NMR(100MHz,CDCl₃):δ190.4(d,J_C-P＝6.8Hz),166.8,165.2,133.1,132.1,131.8,115.7,115.6,71.5(d,J_C-P＝6.8Hz),39.8(d,J_C-P＝128.9Hz),23.8(d,J_C-P＝3.4Hz),23.8(d,J_C-P＝4.6Hz)；HRMS calc.for C₁₄H₂₀O₄NaPF(M+Na)⁺,325.0981；found,325.0978。

Example 8: diisopropyl [2- (4' -acetoxyphenethyl) -2-oxo ] phosphonate

This example utilizes diisopropyl 2- (4' -acetoxystyryl) phosphonate to prepare the corresponding beta-carbonylphosphonate ester using oxygen as the oxidant and source of oxygen in the presence of methylphenyl phosphinate catalyst:

the specific operation mode is as follows: diisopropyl 2- (4' -acetoxystyryl) phosphonate (1.304g, 4mmol), methylphenyl phosphonite (0.624g,4mmol) and ethyl acetate (120ml) are added in sequence to a 250ml three-neck flask, the reaction is stopped after the system is opened and stirred for about 5h at normal temperature, 80ml saturated saline is used for washing, an organic layer is separated, anhydrous magnesium sulfate is used for drying, filtering and decompression concentrating to obtain an oily crude product, finally a mixed eluent of petroleum ether and ethyl acetate is used for washing, and flash column chromatography is carried out to obtain 1.27g of a light yellow oily substance, and the yield is 92.8%.

¹H NMR(400MHz,CDCl₃):δ8.05(d,J＝8.5Hz,2H),7.22(d,J＝8.4Hz,2H),4.74-4.69(m,2H),3.58(d,J＝22.7Hz,2H),2.33(s,3H),1.28(d,J＝2.9Hz,6H,overlap),1.27(d,J＝2.6Hz,6H,overlap)；¹³C NMR(100MHz,CDCl₃):δ190.7(d,J_C-P＝6.8Hz),168.8,154.8,134.2,130.7,121.8,71.7(d,J_C-P＝6.8Hz),39.8(d,J_C-P＝128.9Hz),23.8(d,J_C-P＝4.6Hz),23.6(d,J_C-P＝4.6Hz),21.2；HRMS calc.for C₁₆H₂₃O₆NaP(M+Na)⁺,365.1130；found,365.1133。

Example 9: [2- (3' -bromophenylethyl) -2-oxo ] phosphonic acid diethyl ester

This example utilizes diethyl 2- (3' -bromostyryl) phosphonate to prepare the corresponding β -carbonylphosphonate ester using oxygen as the oxidant and source of oxygen in the presence of methylphenyl phosphinate catalyst:

the specific operation steps are as follows: diethyl 2- (3' -bromostyryl) phosphonate (1.272g, 4mmol), methyl phenyl phosphonite (0.624g,4mmol) and ethyl acetate (120ml) are added into a 250ml three-neck flask in sequence, the mixture is stirred for about 6 hours at normal temperature, the reaction is stopped, 80ml saturated saline solution is used for washing, an organic layer is separated, anhydrous magnesium sulfate is used for drying, filtering and decompression concentration are carried out, an oily crude product is obtained, finally, a mixed eluent of petroleum ether and ethyl acetate is used for washing, and fast column chromatography is carried out to obtain 1.29g of light yellow oily matter, and the yield is 96.5%.

¹H NMR(400MHz,CDCl₃)δ8.12(t,J＝2.0Hz,1H),7.93(dt,J＝8.0Hz,1.2Hz,1H),7.70-7.67(m,1H),7.32(t,J＝8.0Hz,1H),4.13-4.05(m,4H),3.58(d,J_H-P＝22.4Hz,2H),1.26(t,J＝7.2Hz,6H)；¹³C NMR(100MHz,CDCl₃)δ190.55(d,J_C-P＝6.5Hz),138.09,136.36,131.88,130.08,127.56,122.81,62.66(d,J_C-P＝6.5Hz),38.56(d,J_C-P＝128.3Hz),16.13(d,J_C-P＝5.8Hz)；HRMS calc.for C₁₂H₁₆BrO₄P(M+H)⁺,333.9968；found 333.9964。

Example 10: diisopropyl [2- (4' -acetoxyphenethyl) -2-oxo ] phosphonate

This example utilizes diisopropyl 2- (2' -methylstyryl) phosphonate to produce the corresponding beta-carbonylphosphonate ester using oxygen as the oxidant and source of oxygen in the presence of methylphenyl phosphinate catalyst:

the specific operation steps are as follows: diisopropyl 2- (2' -methylstyryl) phosphonate (1.128g, 4mmol), methylphenyl phosphonite (0.624g,4mmol) and ethyl acetate (120ml) are added in sequence to a 250ml three-neck flask, the reaction is stopped after the open system is stirred for about 5h at normal temperature, 80ml saturated saline solution is used for washing, an organic layer is separated, anhydrous magnesium sulfate is used for drying, filtering and reduced pressure concentration are carried out to obtain an oily crude product, finally, a mixed eluent of petroleum ether and ethyl acetate is used for washing, and the light yellow oily product is obtained by flash column chromatography, wherein the yield is 91.4%.

¹H NMR(400MHz,CDCl₃):δ7.72(d,J＝7.7Hz,1H),7.38(t,J＝7.5Hz,1H),7.27-7.22(m,2H),4.74-7.69(m,2H),3.55(d,J＝22.7Hz,2H),2.52(s,3H),1.27(d,J＝6.2Hz,6H,overlap),1.25(d,J＝6.2Hz,6H,overlap)；¹³C NMR(100MHz,CDCl₃):δ195.2(d,J_C-P＝6.9Hz),138.8,137.8,131.9,131.5,129.5,125.6,71.2(d,J_C-P＝6.8Hz),42.4(d,J_C-P＝128.9Hz),23.8(d,J_C-P＝3.4Hz),23.6(d,J_C-P＝5.7Hz),21.2；HRMS calc.for C₁₅H₂₃O₄NaP(M+Na)⁺,321.1232；found,321.1230。

Example 11: [2- (2' -bromophenylethyl) -2-oxo ] phosphonic acid diethyl ester

This example is a preparation of the corresponding β -carbonylphosphonate from diethyl 2- (2' -bromostyryl) phosphonate catalyzed by methylphenyl phosphinate using oxygen as the oxidant and source of oxygen:

the specific operation steps are as follows: diethyl 2- (2' -bromostyryl) phosphonate (1.272g, 4mmol), methyl phenyl phosphonite (0.624g,4mmol) and ethyl acetate (120ml) are added into a 250ml three-neck flask in sequence, the mixture is stirred for about 5 hours at normal temperature, the reaction is stopped, 80ml saturated saline solution is used for washing, an organic layer is separated, anhydrous magnesium sulfate is used for drying, filtering and decompression concentration are carried out, an oily crude product is obtained, finally, a mixed eluent of petroleum ether and ethyl acetate is used for washing, and fast column chromatography is carried out to obtain 1.28g of light yellow oily matter, and the yield is 95.8%.

¹H NMR(400MHz,CDCl₃)δ8.11(t,J＝2.0Hz,1H),7.93(dt,J＝8.0Hz,1.2Hz,1H),7.70-7.67(m,1H),7.33(t,J＝8.0Hz,1H),4.14-4.06(m,4H),3.57(d,J_H-P＝22.4Hz,2H),1.26(t,J＝7.2Hz,6H)；¹³C NMR(100MHz,CDCl₃)δ190.55(d,J_C-P＝6.5Hz),138.09,136.36,131.88,130.08,127.56,121.81,62.66(d,J_C-P＝6.5Hz),38.56(d,J_C-P＝128.3Hz),16.13(d,J_C-P＝5.8Hz)；HRMS calc.for C₁₂H₁₆BrO₄P(M+H)⁺,333.9965,found 333.9964。

Example 12: [2- (3',4' -methylenedioxyphenethyl) -2-oxo ] phosphonic acid diethyl ester

This example utilizes diethyl 2- (3',4' -methylenedioxystyryl) phosphonate to prepare the corresponding β -carbonylphosphonate ester using oxygen as the oxidant and source of oxygen, catalyzed by methylphenyl phosphinate:

the method comprises the following specific steps: diethyl 2- (3',4' -methylenedioxystyryl) phosphonate (1.136g, 4mmol), methylphenylphosphinate (0.624g,4mmol) and ethyl acetate (120ml) were added in this order to a 250ml three-necked flask, and the mixture was stirred at room temperature for about 8 hours to stop the reaction, washed with 80ml of saturated brine, the organic layer was separated, dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure to give an oily crude product, finally washed with a mixed eluent of petroleum ether and ethyl acetate, and subjected to flash column chromatography to give 1.08g of a pale yellow oily substance with a yield of 90.0%.

¹H NMR(400MHz,CDCl₃)δ7.58(d,J＝8.4Hz,1H),7.42(s,1H),6.83(d,J＝8.4Hz,1H),6.02(s,2H),4.15-4.07(m,4H),3.53(d,J_H-P＝22.8Hz,2H),1.24(t,J＝7.2Hz,6H)；¹³C NMR(100MHz,CDCl₃)δ189.72(d,J_C-P＝6.6Hz),152.26,148.18,131.32,125.97,108.36,107.75,101.93,62.58(d,J_C-P＝6.6Hz),38.24(d,J_C-P＝129.8Hz),16.16(d,J_C-P＝6.6Hz)；³¹P NMR(162MHz,CDCl₃)δ20.22；HRMS calc.for C₁₃H₁₇O₆P(M+H)⁺,300.0765,found 300.0759。

Example 13: (2-phenethyl-2-oxo) phosphonic acid diethyl ester

This example utilizes diethyl 2-styrylphosphonate to prepare the corresponding β -carbonylphosphonate ester using oxygen as the oxidant and source of oxygen in the presence of methylphenyl phosphinate catalyst:

the specific operation steps are as follows: diethyl 2-styrylphosphonate (0.96g, 4mmol), methylphenylphosphonate (0.624g,4mmol) and ethyl acetate (120ml) were added in this order to a 250ml three-necked flask, the mixture was stirred at room temperature for about 4 hours, the reaction was stopped, the mixture was washed with 80ml of saturated brine, the organic layer was separated, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to give an oily crude product, and finally washed with a mixed eluent of petroleum ether and ethyl acetate, and flash column chromatography was performed to give 0.98g of a pale yellow oily substance with a yield of 95.7%.

¹H NMR(400MHz,CDCl₃):δ8.01(d,J＝8.1Hz,2H),7.59(t,J＝7.4Hz,1H),7.48(t,J＝7.7Hz,2H),4.18-4.12(m,4H),3.64(d,J＝22.7Hz,2H),1.27(t,J＝7.1Hz,6H)；¹³C NMR(100MHz,CDCl₃):δ191.9(d,J_C-P＝6.8Hz),136.7,133.5,129.1,128.7,62.7(d,J_C-P＝5.7Hz),38.6(d,J_C-P＝128.9Hz),16.1(d,J_C-P＝5.7Hz)；HRMS calc.for C₁₂H₁₈O₄P(M+H)⁺,257.0943；found,257.0947。

Example 14: (2-phenethyl-2-oxo) phosphonic acid dimethyl ester

This example is a preparation of the corresponding beta-carbonylphosphonate from dimethyl 2-styrylphosphonate using oxygen as oxidant and oxygen source under the catalysis of methylphenyl phosphinate:

the method comprises the following specific steps: dimethyl 2-styrylphosphonate (0.848g, 4mmol), methylphenyl phosphonite (0.624g,4mmol) and ethyl acetate (120ml) were added in this order to a 250ml three-necked flask, the mixture was stirred at room temperature for about 4.5 hours, the reaction was stopped, the mixture was washed with 80ml of saturated brine, the organic layer was separated, dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure to give an oily crude product, and finally washed with a mixed eluent of petroleum ether and ethyl acetate, and column chromatography was carried out to give 0.86g of a pale yellow oily substance in 94.2% yield.

¹H NMR(400MHz,CDCl₃)δ8.01(d,J＝8.6Hz,2H),7.58(t,J＝7.4Hz,1H),7.47(t,J＝7.4Hz,2H),3.76(d,J＝11.2Hz,6H),3.65(d,J＝22.6Hz,2H)；¹³C NMR(100MHz,CDCl₃)δ191.8(d,J_C-P＝6.6Hz),136.4(d,J_C-P＝2.3Hz),133.9,129.1,128.8,53.2(d,J_C-P＝6.5Hz),37.6(d,J_C-P＝131.2Hz)；HRMS calc.for C₁₀H₁₄O₄P(M+H)⁺,229.0630；found,229.0635。

Example 15: (2-phenethyl-2-oxo) phosphonic acid di-n-butyl ester

This example utilizes di-n-butyl 2-styrylphosphonate to prepare the corresponding β -carbonylphosphonate ester using oxygen as the oxidant and source of oxygen in the presence of methylphenyl phosphinate catalyst:

the specific implementation steps are as follows: 2-styrylphosphonic acid di-n-butyl ester (1.184g, 4mmol), methylphenyl phosphonite (0.624g,4mmol) and ethyl acetate (120ml) were added in this order to a 250ml three-necked flask, the mixture was stirred at room temperature for about 5 hours, the reaction was stopped, the mixture was washed with 80ml of saturated brine, the organic layer was separated, dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure to give an oily crude product, and finally washed with a mixed eluent of petroleum ether and ethyl acetate and subjected to flash column chromatography to give 1.19g of a pale yellow oily substance with a yield of 95.3%.

¹H NMR(400MHz,CDCl₃):δ8.02(d,J＝7.7Hz,2H),7.59(t,J＝7.5Hz,1H),7.48(t,J＝7.7Hz,2H),4.11-4.03(m,4H),3.62(d,J＝22.7Hz,2H),1.63-1.57(m,4H),1.35-1.28(m,4H),0.89(t,J＝7.5Hz,6H)；¹³C NMR(100MHz,CDCl₃):δ191.8,136.7,133.5,129.1,128.7,66.2(d,J_C-P＝6.8Hz),38.5(d,J_C-P＝128.9Hz),32.2(d,J_C-P＝5.7Hz),18.5,13.6；HRMS calc.for C₁₆H₂₆O₄P(M+H)⁺,313.1569；found,313.1573。

Example 16: (2-phenethyl-2-oxo) phosphonic acid dibenzyl ester

This example is a preparation of the corresponding β -carbonylphosphonate from di-n-benzyl 2-styrylphosphonate using oxygen as the oxidant and oxygen source under the catalysis of methylphenylphosphinate:

the method comprises the following specific steps: di-n-benzyl 2-styrylphosphonate (1.456g, 4mmol), methylphenyl phosphonite (0.624g,4mmol) and ethyl acetate (120ml) were added in this order to a 250ml three-necked flask, the mixture was stirred at room temperature for about 5 hours, the reaction was stopped, the mixture was washed with 80ml of saturated brine, the organic layer was separated, dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure to give an oily crude product, and finally washed with a mixed eluent of petroleum ether and ethyl acetate, and column chromatography was performed to give 1.43g of a pale yellow oily substance with a yield of 94.1%.

¹H NMR(400MHz,CDCl₃)δ7.86-7.83(m,2H),7.46-7.42(m,1H),7.34-7.31(m,2H),7.23-7.17(m,10H),5.01-4.90(m,4H),3.54(d,J_H-P＝22.8Hz,2H)；¹³C NMR(100MHz,CDCl₃)δ191.25(d,J_C-P＝6.6Hz),136.31(d,J_C-P＝2.2Hz),135.75(d,J_C-P＝5.8Hz),133.55,128.88,128.48,128.42,128.34,127.87,67.91(d,J_C-P＝6.6Hz),38.50(d,J_C-P＝130.5Hz)；HRMS calcd for C₂₂H₂₁O₄P(M+H)⁺380.1179,found380.1172。

It should be noted that, in the above embodiment, the reaction temperature may also be adjusted to 30-90 ℃, and it should be noted that, in this temperature range, the reaction time is shortened with the increase of the reaction temperature, and the stirring reaction time under the condition of 30-90 ℃ is about 2-7 h. In addition, besides the reaction in the air environment, the oxidation reaction process in the above embodiment can also be performed in a pure oxygen environment, and the reaction time can be further shortened under the pure oxygen environment.

Examples 1-16 above all produced β -carbonyl phosphonate esters by catalyzing 2-styrylphosphonate compounds with methylphenyl phosphinate using oxygen as both the oxidant and the source of oxygen. From the experimental results, the reaction temperature used in each example was low, and it was more environmentally friendly since it did not require the use of an organometallic catalyst. Meanwhile, in each embodiment, the reaction duration is short, the reaction process conditions are stable, the yield is high, the operation steps are simple, and the method is suitable for application in industrial production.