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

Method for preparing beta-carbonyl phosphonate derivatives Download PDF

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CN104341449A
CN104341449A CN201410518132.3A CN201410518132A CN104341449A CN 104341449 A CN104341449 A CN 104341449A CN 201410518132 A CN201410518132 A CN 201410518132A CN 104341449 A CN104341449 A CN 104341449A
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邹建平
李大鹏
刘奎
周少方
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Suzhou University
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Suzhou University
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Abstract

The invention discloses a method for preparing beta-carbonyl phosphonate derivatives. The method comprises the specific steps: dissolving an ethylene derivative, a phosphorus reagent and manganese acetate into a solvent, and reacting at the temperature of 20-100 DEG C, so as to prepare a beta-carbonyl phosphonate derivative; and enabling the beta-carbonyl phosphonate derivative to react in the presence of sodium hydroxide or sodium iodide, so as to obtain a beta-carbonyl sodium mono-phosphonate derivative. According to the method, an aryl ethylene derivative is used as an initiator, and the raw materials are easily obtained and are great in variety; products obtained by using the method disclosed by the invention are diverse in type, can be used directly and can also be applied to other further reactions; and meanwhile, the synthetic route is short, the reaction conditions are mild, the reaction operation and aftertreatment process are simple, and the yield is relatively high, so that the method is applicable to large-scale production.

Description

The preparation method of a kind of β-carbonylic phosphonic acid ester derivative
Technical field
The invention belongs to organic synthesis field, be specifically related to the preparation method of a kind of β-carbonylic phosphonic acid ester derivative.
Background technology
β-carbonylic phosphonic acid ester has biological activity and metal-complexing ability, has application at biological chemistry, inorganic chemistry; Also be a kind of widely used synthetic intermediate in organic chemistry, it can react with aldehydes or ketones and generate beta-unsaturated carbonyl compounds in HWE reaction.β-carbonylic phosphonic acid ester can obtain β-carbonylic phosphonic acid monoesters sodium through selective hydrolysis, and they are important beta-lactam inhibitor; β-carbonylic phosphonic acid ester is also the important source material of synthesis beta-hydroxy phosphonic acid ester, beta-amino phosphonic acid ester and acid.The similar of beta-amino phosphonic acids is in beta-amino acids, there is physiologically active widely, as the effect such as metabolism and growth, pain relieving, adjustment blood pressure, coordinate plant growth that is antibacterial, the cell that excites nerve, affects, therefore can as uses such as medicine, agricultural chemicals, antagonist, anthocyanidin synthetic inhibitors.
In prior art, the synthetic method of β-carbonylic phosphonic acid ester mainly contains following three kinds:
1, under synthesis exists, methyl benzoate and dimethyl methyl phosphonate are obtained by reacting β-carbonylic phosphonic acid ester (see Milburn, Robert R. Tetrahedron Lett., 2009,50,870-872); In the method, synthesis is very active, causes severe reaction conditions; This reaction equation is:
2, bromoacetophenone and trimethyl phosphite back flow reaction obtain β-carbonylic phosphonic acid ester (see Taber, Douglass F. Tetrahedron Lett., 2008,49,6904-6906); In the method, bromoacetophenone is difficult to obtain, and synthetic route is long, will use bromine in synthesis, causes very large corrosion and pollution), limit substrate source, and long reaction time, feed stock conversion is low, and by product is many; This reaction equation is:
3, vinylbenzene and phosphorous acid diisopropyl ester are at CuBr 2/ FeBr 3β-carbonylic phosphonic acid ester is obtained by reacting (see Wei Wei and Jian-Xin Ji under catalysis, Angew. Chem. Int. Ed. 2011,50,9097 – 9099), the method overcome the some shortcomings in traditional method, but in the method, need the triethylamine of equivalent as additive, need by high polarity, high boiling dimethyl sulfoxide (DMSO) as reaction solvent, catalyst system is complicated, causes aftertreatment loaded down with trivial details; Reaction needed is carried out in oxygen atmosphere, and long reaction time, the substrate scope of application is narrower; This reaction equation is:
β-carbonylic phosphonic acid ester is widely used in the field such as organic synthesis, biological chemistry, and therefore people are devoted to the novel method developing synthesis β-carbonylic phosphonic acid ester; But there is substrate applicability difference in existing method, yield is low, cost is high, the shortcoming of severe reaction conditions.Therefore reaction conditions method that is gentle, applied widely, that meet synthesis β-carbonylic phosphonic acid ester that Green Chemistry requires is developed extremely important.
Summary of the invention
The object of the invention is to provide the preparation method of a kind of β-carbonylic phosphonic acid ester derivative.
To achieve the above object of the invention, the technical solution used in the present invention is: the preparation method of a kind of β-carbonylic phosphonic acid ester derivative, comprise the following steps: ethene derivatives, phosphorus reagent, manganese acetate are dissolved in solvent, react at 20 ~ 100 DEG C, obtained β-carbonylic phosphonic acid ester derivative;
The chemical structure of general formula of described ethene derivatives is , wherein R is the one in following group:
、 、 、 、 、 ，
Described R 1, R 2, R 3, R 4and R 5selection take one of following scheme:
(1) R 1for the one in hydrogen, methyl, trifluoromethyl, methoxyl group, fluorine, chlorine, bromine, cyano group, formyl radical, methyl-formiate base or nitro, R 2, R 3, R 4and R 5be all hydrogen;
(2) R 2for the one in methyl, trifluoromethyl, methoxyl group, fluorine, chlorine, bromine, cyano group, formyl radical, methyl-formiate base or nitro, R 1, R 3, R 4and R 5be all hydrogen;
(3) R 3for the one in methyl, trifluoromethyl, methoxyl group, fluorine, chlorine, bromine, cyano group, formyl radical, methyl-formiate base, nitro and phenyl, R 1, R 2, R 4and R 5be all hydrogen;
(4) R 1, R 2, R 3, R 4and R 5for fluorine;
The chemical structure of general formula of described phosphorus reagent is:
，
Wherein R 6one in following group:
、 、 、 、 、 ；
Described solvent is selected from: the one in methyl alcohol, ethanol, acetonitrile, acetic acid, chloroform, methylene dichloride, toluene;
The chemical structural formula of described β-carbonylic phosphonic acid ester derivative is:
。
In technique scheme, described ethene derivatives is selected from vinylbenzene, 2-methyl styrene, 3-methoxy styrene, 4-methoxy styrene, 2-chloro-styrene, 3-chloro-styrene, 4-chloro-styrene, 4-cyano-styrene, 3-methyl-formiate base vinylbenzene, 4-acetylbenzene ethene, 3-nitrostyrolene, 3-trifluoromethyl styrene, 4-xenyl ethene, pentafluorostyrene, 2-vinyl furans, 2-vinyl thiophene, 2-vinyl pyrrole, 3-vinyl pyridine, 3-(2-chloro-phenyl-)-5-methylisoxazole-4-base) one in ethene.
In technique scheme, in molar ratio, ethene derivatives: phosphorus reagent: manganese acetate is 1: (1 ~ 2): (1 ~ 3); Be preferably 1: 1.5: 1.5.
The present invention, in preparation β-carbonylic phosphonic acid ester derivative, utilizes thin-layer chromatography to follow the tracks of reaction until terminate completely; Carry out purification processes after the completion of reaction, be specially, after reaction terminates, the solvent in concentrated removing reaction solution obtains residue, and namely residue obtains β-carbonylic phosphonic acid ester derivative through column chromatography for separation.
Utilize β of the present invention-carbonylic phosphonic acid ester derivative can prepare β-carbonylic phosphonic acid monoesters sodio-derivative, be specially and the β-carbonylic phosphonic acid ester derivative of preparation and sodium salt are reacted, obtain β-carbonylic phosphonic acid monoesters sodio-derivative; β-carbonylic phosphonic acid monoesters sodium can be used as beta-lactam inhibitor.
The chemical structural formula of described β-carbonylic phosphonic acid monoesters sodio-derivative is:
。
The reaction process of technique scheme can be expressed as:
Due to the utilization of technique scheme, the present invention compared with prior art has following advantages:
1. the present invention uses aryl ethylene derivative for initiator, and raw material is easy to get, kind is a lot; Product β-carbonylic phosphonic acid ester derivative the type prepared thus is various, not only directly can use, but also may be used for other and further react.
2. disclosed by the inventionly prepare in the method for β-carbonylic phosphonic acid ester derivative, raw material is stablized, and without the need to the reaction conditions of harshness, reaction promotor system is simple, and without the need to additive, by product is few, and yield is high, is conducive to the purification of final product.
3. the present invention in atmosphere, uses aryl ethylene derivative to be initiator, without the need to oxygen, prepared β-carbonylic phosphonic acid ester derivative simply, efficiently, overcome the defect that prior art needs oxygen, makes operation steps simplification, safety.
4. preparation method's wide application range of substrates disclosed by the invention, has high transformation efficiency to multiple substituent aryl ethylene derivative, has enriched the structure of β-carbonylic phosphonic acid ester derivative, expanded the application of β-carbonylic phosphonic acid ester derivative.
5. preparation method's reaction conditions gentleness disclosed by the invention, operation and last handling process are simple, reaction process is stablized controlled, and catalytic efficiency is high, greatly reduces the consumption of reagent and reacts generation and the discharge of refuse, product yield is high, is suitable for scale production.
Embodiment
Below in conjunction with embodiment, the invention will be further described:
Embodiment one: the synthesis of dimethyl 2-oxo-2-phenylethylphosphonic ester
With vinylbenzene, dimethyl phosphite for raw material, its reaction formula and experimental procedure as follows:
(1) in reaction flask, vinylbenzene (0.1 g, 1 mmol) is added, dimethyl phosphite (0.11 g, 1.0 mmol), manganese acetate (0.41 g, 1.5 mmol) and 10 mL acetonitriles, react on 50 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(2) reaction solution concentrates to obtain residue, obtains dimethyl 2-oxo-2-phenylethylphosphonic ester (productive rate 60%) through column chromatography for separation;
(3) add in reaction flask by dimethyl 2-oxo-2-phenylethylphosphonic ester (0.11 g of (2) gained, 0.5 mmol), sodium hydroxide solution (0.08 g, 2.0 mmol are dissolved in 1mL water) and 10 mL 1,4 dioxane, react on 25 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(4) the most of solvent of the concentrated removing of reaction solution obtains residue, after hcl acidifying, is extracted with ethyl acetate.Solvent in removing extraction liquid, in residue, add sodium hydrogen carbonate solution (0.042 g, 0.5 mmol are dissolved in 1 mL water), reaction solution obtains methyl 2-oxo-2-phenylethylphosphonic ester sodium (productive rate 68%) through freeze-dried.
The analytical data of dimethyl 2-oxo-2-phenylethylphosphonic ester is as follows: 1h NMR (400 MHz, CDCl 3): δ7.97-8.02 (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); The analytical data of methyl 2-oxo-2-phenylethylphosphonic ester sodium is as follows: 1h NMR (300 MHz, D 2o): 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).
Embodiment two: the synthesis of diethyl 2-oxo-2-phenylethylphosphonic ester
With vinylbenzene, diethyl phosphite for raw material, its reaction formula and experimental procedure as follows:
(1) in reaction flask, vinylbenzene (0.1 g, 1 mmol) is added, diethyl phosphite (0.21 g, 1.5 mmol), manganese acetate (0.41 g, 1.5 mmol) and 10 mL methyl alcohol, react on 20 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(2) reaction solution concentrates to obtain residue, obtains diethyl 2-oxo-2-phenylethylphosphonic ester (productive rate 83%) through column chromatography for separation;
(3) add in reaction flask by diethyl 2-oxo-2-phenylethylphosphonic ester (0.18 g of (2) gained, 0.5 mmol), sodium hydroxide solution (0.08 g, 2.0 mmol are dissolved in 1mL water) and 10 mL 1,4 dioxane, react on 25 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(4) the most of solvent of the concentrated removing of reaction solution obtains residue, after hcl acidifying, is extracted with ethyl acetate.Solvent in removing extraction liquid, in residue, add sodium hydrogen carbonate solution (0.042 g, 0.5 mmol are dissolved in 1 mL water), reaction solution obtains ethyl 2-oxo-2-phenylethylphosphonic ester sodium (productive rate 67%) through freeze-dried.
The analytical data of diethyl 2-oxo-2-phenylethylphosphonic ester is as follows: 1h NMR (400 MHz, CDCl 3): δ8.00-8.06 (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); The analytical data of ethyl 2-oxo-2-phenylethylphosphonic ester sodium is as follows: 1h NMR (400 MHz, D 2o): δ7.96-8.02 (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).
Embodiment three: the synthesis of di-isopropyl 2-oxo-2-phenylethylphosphonic ester
With vinylbenzene, diisopropyl phosphite for raw material, its reaction formula and experimental procedure as follows:
(1) in reaction flask, vinylbenzene (0.1 g, 1 mmol) is added, di-isopropyl phosphoric acid ester (0.25 g, 1.5 mmol), manganese acetate (0.27 g, 1.0 mmol) and 10 mL ethanol, react on 20 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(2) reaction solution concentrates to obtain residue, obtains di-isopropyl 2-oxo-2-phenylethylphosphonic ester (productive rate 52%) through column chromatography for separation;
(3) add in reaction flask by di-isopropyl 2-oxo-2-phenylethylphosphonic ester (0.14 g of (2) gained, 0.5 mmol), sodium hydroxide solution (0.08 g, 2.0 mmol are dissolved in 1mL water) and 10 mL 1,4 dioxane, react on 25 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(4) the most of solvent of the concentrated removing of reaction solution obtains residue, after hcl acidifying, is extracted with ethyl acetate.Solvent in removing extraction liquid, in residue, add sodium hydrogen carbonate solution (0.042 g, 0.5 mmol are dissolved in 1 mL water), reaction solution obtains sec.-propyl 2-oxo-2-phenylethylphosphonic ester sodium (productive rate 65%) through freeze-dried.
The analytical data of di-isopropyl 2-oxo-2-phenylethylphosphonic ester is as follows: 1h NMR (CDCl 3, 600 MHz): δ8.01 (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); The analytical data of sec.-propyl 2-oxo-2-phenylethylphosphonic ester sodium is as follows: 1h NMR (600 MHz, D 2o): 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).
Embodiment four: the synthesis of phenylbenzene 2-oxo-2-phenylethylphosphonic ester
With vinylbenzene, diphenylphosphite for raw material, its reaction formula and experimental procedure as follows:
(1) in reaction flask, vinylbenzene (0.1 g, 1 mmol) is added, diphenylphosphite (0.35 g, 1.5 mmol), manganese acetate (0.55 g, 2.0 mmol) and 10 mL acetic acid, react on 30 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(2) reaction solution concentrates to obtain residue, obtains phenylbenzene 2-oxo-2-phenylethylphosphonic ester (productive rate 81%) through column chromatography for separation;
(3) add in reaction flask by phenylbenzene 2-oxo-2-phenylethylphosphonic ester (0.17 g of (2) gained, 0.5 mmol), sodium hydroxide solution (0.08 g, 2.0 mmol are dissolved in 1mL water) and 10 mL 1,4 dioxane, react on 25 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(4) the most of solvent of the concentrated removing of reaction solution obtains residue, after hcl acidifying, is extracted with ethyl acetate.Solvent in removing extraction liquid, in residue, add sodium hydrogen carbonate solution (0.042 g, 0.5 mmol are dissolved in 1 mL water), reaction solution obtains phenyl 2-oxo-2-phenylethylphosphonic ester sodium (productive rate 64%) through freeze-dried.
The analytical data of phenylbenzene 2-oxo-2-phenylethylphosphonic ester is as follows: 1h NMR (400 MHz, CDCl 3): δ8.05 (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-phenylethylphosphonic ester sodium is as follows: 1h NMR (300 MHz, D 2o): δ7.89 (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).
Embodiment five: dimethyl 2-oxo-2-(2-tolyl) synthesis of ethyl phosphonate
With 2-methyl styrene, dimethyl phosphite for raw material, its reaction formula and experimental procedure as follows:
(1) in reaction flask, 2-methyl styrene (0.1 g, 1 mmol) is added, dimethyl phosphite (0.23 g, 2.0 mmol), manganese acetate (0.55 g, 2.0 mmol) and 10 mL chloroforms, react on 40 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(2) reaction solution concentrates to obtain residue, obtains dimethyl 2-oxo-2-(2-tolyl through column chromatography for separation) ethyl phosphonate (productive rate 80%);
(3) add in reaction flask by the dimethyl 2-oxo-2-(2-tolyl of (2) gained) ethyl phosphonate (0.12 g, 0.5 mmol), sodium hydroxide solution (0.08 g, 2.0 mmol are dissolved in 1mL water) and 10 mL 1,4 dioxane, react on 25 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(4) the most of solvent of the concentrated removing of reaction solution obtains residue, after hcl acidifying, is extracted with ethyl acetate.Solvent in removing extraction liquid, in residue, add sodium hydrogen carbonate solution (0.042 g, 0.5 mmol are dissolved in 1 mL water), reaction solution obtains methyl 2-oxo-2-(2-tolyl through freeze-dried) ethyl phosphonate sodium (productive rate 66%).
Dimethyl 2-oxo-2-(2-tolyl) analytical data of ethyl phosphonate is as follows: 1h NMR (400 MHz, CDCl 3): δ7.97-8.02 (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-tolyl) analytical data of ethyl phosphonate sodium is as follows: 1h NMR (400 MHz, D 2o): δ7.82-7.89 (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).
Embodiment six: phenylbenzene 2-oxo-2-(3-p-methoxy-phenyl) synthesis of ethyl phosphonate
With 3-methoxy styrene, diphenylphosphite for raw material, its reaction formula and experimental procedure as follows:
(1) in reaction flask, add 3-methoxy styrene (0.13 g, 1 mmol), diphenylphosphite (0.47 g, 2 mmol), manganese acetate (0.68 g, 2.5 mmol) and 10 mL methylene dichloride, react on 40 DEG C and carry out, TLC follows the tracks of reaction until terminate;
(2) reaction solution concentrates to obtain residue, obtains phenylbenzene 2-oxo-2-(3-p-methoxy-phenyl through column chromatography for separation) ethyl phosphonate (productive rate 83%);
(3) add in reaction flask by the phenylbenzene 2-oxo-2-(3-p-methoxy-phenyl of (2) gained) ethyl phosphonate (0.19 g, 0.5 mmol), sodium hydroxide solution (0.08 g, 2.0 mmol are dissolved in 1mL water) and 10 mL 1,4 dioxane, react on 25 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(4) the most of solvent of the concentrated removing of reaction solution obtains residue, after hcl acidifying, is extracted with ethyl acetate.Solvent in removing extraction liquid, sodium hydrogen carbonate solution (0.042 g is added in residue, 0.5 mmol is dissolved in 1 mL water), reaction solution obtains phenyl 2-oxo-2-(3-p-methoxy-phenyl through freeze-dried) ethyl phosphonate sodium (productive rate 67%).
Phenylbenzene 2-oxo-2-(3-p-methoxy-phenyl) analytical data of ethyl phosphonate is as follows: 1h NMR (400 MHz, CDCl 3): δ8.09 – 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); Phenyl 2-oxo-2-(3-p-methoxy-phenyl) analytical data of ethyl phosphonate sodium is as follows: 1h NMR (300 MHz, D 2o): δ8.04 – 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).
Embodiment seven: dimethyl 2-oxo-2-(4-p-methoxy-phenyl) synthesis of ethyl phosphonate
With 4-methoxy styrene, dimethyl phosphite for raw material, its reaction formula and experimental procedure as follows:
(1) in reaction flask, 4-methoxy styrene (0.13 g, 1 mmol) is added, dimethyl phosphite (0.23 g, 2 mmol), manganese acetate (0.82 g, 3 mmol) and 10 mL toluene, react on 50 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(2) reaction solution concentrates to obtain residue, obtains dimethyl 2-oxo-2-(4-p-methoxy-phenyl through column chromatography for separation) ethyl phosphonate (productive rate 81%);
(3) add in reaction flask by the dimethyl 2-oxo-2-(4-p-methoxy-phenyl of (2) gained) ethyl phosphonate (0.13 g, 0.5 mmol), sodium hydroxide solution (0.08 g, 2.0 mmol are dissolved in 1mL water) and 10 mL 1,4 dioxane, react on 25 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(4) the most of solvent of the concentrated removing of reaction solution obtains residue, after hcl acidifying, is extracted with ethyl acetate.Solvent in removing extraction liquid, sodium hydrogen carbonate solution (0.042 g is added in residue, 0.5 mmol is dissolved in 1 mL water), reaction solution obtains methyl 2-oxo-2-(4-p-methoxy-phenyl through freeze-dried) ethyl phosphonate sodium (productive rate 62%).
Dimethyl 2-oxo-2-(4-p-methoxy-phenyl) analytical data of ethyl phosphonate is as follows: 1h NMR (400 MHz, CDCl 3): δ7.25 (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-oxo-2-(4-p-methoxy-phenyl) analytical data of ethyl phosphonate sodium is as follows: 1h NMR (400 MHz, D 2o): δ7.14 (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).
Embodiment eight: dimethyl 2-oxo-2-(2-chloro-phenyl-) synthesis of ethyl phosphonate
With 2-chloro-styrene, dimethyl phosphite for raw material, its reaction formula and experimental procedure as follows:
(1) in reaction flask, 2-chloro-styrene (0.14 g, 1 mmol) is added, dimethyl phosphite (0.17 g, 1.5 mmol), manganese acetate (0.82 g, 3 mmol) and 10 mL toluene, react on 60 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(2) reaction solution concentrates to obtain residue, obtains dimethyl 2-oxo-2-(2-chloro-phenyl-through column chromatography for separation) ethyl phosphonate (productive rate 82%);
(3) add in reaction flask by the dimethyl 2-oxo-2-(2-chloro-phenyl-of (2) gained) ethyl phosphonate (0.13 g, 0.5 mmol), sodium hydroxide solution (0.08 g, 2.0 mmol are dissolved in 1mL water) and 10 mL 1,4 dioxane, react on 25 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(4) the most of solvent of the concentrated removing of reaction solution obtains residue, after hcl acidifying, is extracted with ethyl acetate.Solvent in removing extraction liquid, in residue, add sodium hydrogen carbonate solution (0.042 g, 0.5 mmol are dissolved in 1 mL water), reaction solution obtains methyl 2-oxo-2-(2-chloro-phenyl-through freeze-dried) ethyl phosphonate sodium (productive rate 68%).
Dimethyl 2-oxo-2-(2-chloro-phenyl-) analytical data of ethyl phosphonate is as follows: 1h NMR (400 MHz, CDCl 3): δ7.89-7.79 (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-chloro-phenyl-) analytical data of ethyl phosphonate sodium is as follows: 1h NMR (400 MHz, D 2o): δ7.78-7.66 (m, 2H), 7.32-7.20 (m, 2H), 3.56 (d, j=11.2 Hz, 3H), 3.41 (d, j=22.8 Hz, 2H).
Embodiment nine: dimethyl 2-oxo-2-(3-chloro-phenyl-) synthesis of ethyl phosphonate
With 3-chloro-styrene, dimethyl phosphite for raw material, its reaction formula and experimental procedure as follows:
(1) in reaction flask, 3-chloro-styrene (0.14 g, 1 mmol) is added, dimethyl phosphite (0.11 g, 1 mmol), manganese acetate (0.82 g, 3 mmol) and 10 mL toluene, react on 70 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(2) reaction solution concentrates to obtain residue, obtains dimethyl 2-oxo-2-(3-chloro-phenyl-through column chromatography for separation) ethyl phosphonate (productive rate 62%);
(3) add in reaction flask by the dimethyl 2-oxo-2-(3-chloro-phenyl-of (2) gained) ethyl phosphonate (0.13 g, 0.5 mmol), sodium hydroxide solution (0.08 g, 2.0 mmol are dissolved in 1mL water) and 10 mL 1,4 dioxane, react on 25 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(4) the most of solvent of the concentrated removing of reaction solution obtains residue, after hcl acidifying, is extracted with ethyl acetate.Solvent in removing extraction liquid, in residue, add sodium hydrogen carbonate solution (0.042 g, 0.5 mmol are dissolved in 1 mL water), reaction solution obtains methyl 2-oxo-2-(3-chloro-phenyl-through freeze-dried) ethyl phosphonate sodium (productive rate 60%).
Dimethyl 2-oxo-2-(3-chloro-phenyl-) analytical data of ethyl phosphonate is as follows: 1h NMR (400 MHz, CDCl 3): δ7.90-7.84 (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-chloro-phenyl-) analytical data of ethyl phosphonate sodium is as follows: 1h NMR (400 MHz, D 2o): δ7.75-7.64 (m, 2H), 7.30-7.21 (m, 2H), 3.57 (d, j=11.2 Hz, 3H), 3.43 (d, j=22.8 Hz, 2H).
Embodiment ten: phenylbenzene 2-oxo-2-(4-chloro-phenyl-) synthesis of ethyl phosphonate
With 4-chloro-styrene, diphenylphosphite for raw material, its reaction formula and experimental procedure as follows:
(1) in reaction flask, 4-chloro-styrene (0.14 g, 1 mmol) is added, diphenylphosphite (0.35 g, 1.5 mmol), manganese acetate (0.82 g, 3 mmol) and 10 mL toluene, react on 80 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(2) reaction solution concentrates to obtain residue, obtains phenylbenzene 2-oxo-2-(4-chloro-phenyl-through column chromatography for separation) ethyl phosphonate (productive rate 85%);
(3) add in reaction flask by the phenylbenzene 2-oxo-2-(4-chloro-phenyl-of (2) gained) ethyl phosphonate (0.19 g 0.5 mmol), sodium hydroxide solution (0.08 g, 2.0 mmol are dissolved in 1mL water) and 10 mL 1,4 dioxane, react on 25 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(4) the most of solvent of the concentrated removing of reaction solution obtains residue, after hcl acidifying, is extracted with ethyl acetate.Solvent in removing extraction liquid, in residue, add sodium hydrogen carbonate solution (0.042 g, 0.5 mmol are dissolved in 1 mL water), reaction solution obtains phenyl 2-oxo-2-(4-chloro-phenyl-through freeze-dried) ethyl phosphonate sodium (productive rate 64%).
Phenylbenzene 2-oxo-2-(4-chloro-phenyl-) analytical data of ethyl phosphonate is as follows: 1h NMR (400 MHz, CDCl 3): δ8.09 (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-oxo-2-(4-chloro-phenyl-) analytical data of ethyl phosphonate sodium is as follows: 1h NMR (300 MHz, D 2o): δ8.01 (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).
Embodiment 11: phenylbenzene 2-oxo-2-(3-methyl-formiate base phenyl) synthesis of ethyl phosphonate
With 3-methyl-formiate base vinylbenzene, diphenylphosphite for raw material, its reaction formula and experimental procedure as follows:
(1) in reaction flask, add 3-methyl-formiate base vinylbenzene (0.16 g, 1 mmol), diphenylphosphite (0.35 g, 1.5 mmol), manganese acetate (0.68 g, 2.5 mmol) and 10 mL toluene, react on 90 DEG C and carry out, TLC follows the tracks of reaction until terminate;
(2) reaction solution concentrates to obtain residue, obtains phenylbenzene 2-oxo-2-(3-methyl-formiate base phenyl through column chromatography for separation) ethyl phosphonate (productive rate 84%);
(3) add in reaction flask by the phenylbenzene 2-oxo-2-(3-methyl-formiate base phenyl of (2) gained) ethyl phosphonate (0.21 g, 0.5 mmol), sodium hydroxide solution (0.08 g, 2.0 mmol are dissolved in 1mL water) and 10 mL 1,4 dioxane, react on 25 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(4) the most of solvent of the concentrated removing of reaction solution obtains residue, after hcl acidifying, is extracted with ethyl acetate.Solvent in removing extraction liquid, sodium hydrogen carbonate solution (0.042 g is added in residue, 0.5 mmol is dissolved in 1 mL water), reaction solution obtains phenyl 2-oxo-2-(3-methyl-formiate base phenyl through freeze-dried) ethyl phosphonate sodium (productive rate 65%).
Phenylbenzene 2-oxo-2-(3-methyl-formiate base phenyl) analytical data of ethyl phosphonate is as follows: 1h NMR (400 MHz, CDCl 3): δ8.29 – 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); Phenyl 2-oxo-2-(3-methyl-formiate base phenyl) analytical data of ethyl phosphonate sodium is as follows: 1h NMR (300 MHz, D 2o): δ8.21 – 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).
Embodiment 12: phenylbenzene 2-oxo-2-(4-acetylphenyl) synthesis of ethyl phosphonate
With 4-acetylbenzene ethene, diphenylphosphite for raw material, its reaction formula and experimental procedure as follows:
(1) in reaction flask, add 4-acetylbenzene ethene (0.15 g, 1 mmol), diphenylphosphite (0.35 g, 1.5 mmol), manganese acetate (0.55 g, 2 mmol) and 10 mL toluene, react on 100 DEG C and carry out, TLC follows the tracks of reaction until terminate;
(2) reaction solution concentrates to obtain residue, obtains phenylbenzene 2-oxo-2-(4-acetylphenyl through column chromatography for separation) ethyl phosphonate (productive rate 85%);
(3) add in reaction flask by the phenylbenzene 2-oxo-2-(4-acetylphenyl of (2) gained) ethyl phosphonate (0.2 g, 0.5 mmol), sodium hydroxide solution (0.08 g, 2.0 mmol are dissolved in 1mL water) and 10 mL 1,4 dioxane, react on 25 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(4) the most of solvent of the concentrated removing of reaction solution obtains residue, after hcl acidifying, is extracted with ethyl acetate.Solvent in removing extraction liquid; sodium hydrogen carbonate solution (0.042 g is added in residue; 0.5 mmol is dissolved in 1 mL water), reaction solution obtains phenyl 2-oxo-2-(4-acetylphenyl through freeze-dried) ethyl phosphonate sodium (productive rate 62%).
Phenylbenzene 2-oxo-2-(4-acetylphenyl) analytical data of ethyl phosphonate is as follows: 1h NMR (400 MHz, CDCl 3): δ8.56 (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); Phenyl 2-oxo-2-(4-acetylphenyl) analytical data of ethyl phosphonate sodium is as follows: 1h NMR (300 MHz, D 2o): δ8.49 (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).
Embodiment 13: phenylbenzene 2-oxo-2-(4-cyano-phenyl) synthesis of ethyl phosphonate
With 4-cyano-styrene, diphenylphosphite for raw material, its reaction formula and experimental procedure as follows:
(1) in reaction flask, add 4 cyano-styrenes (0.13 g, 1 mmol), diphenylphosphite (0.35 g, 1.5 mmol), manganese acetate (0.41 g, 1.5 mmol) and 10 mL ethanol, react on 40 DEG C and carry out, TLC follows the tracks of reaction until terminate;
(2) reaction solution concentrates to obtain residue, obtains phenylbenzene 2-oxo-2-(4-cyano-phenyl through column chromatography for separation) ethyl phosphonate (productive rate 81%);
(3) add in reaction flask by the phenylbenzene 2-oxo-2-(4-cyano-phenyl of (2) gained) ethyl phosphonate (0.19 g, 0.5 mmol), sodium hydroxide solution (0.08 g, 2.0 mmol are dissolved in 1mL water) and 10 mL 1,4 dioxane, react on 25 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(4) the most of solvent of the concentrated removing of reaction solution obtains residue, after hcl acidifying, is extracted with ethyl acetate.Solvent in removing extraction liquid, sodium hydrogen carbonate solution (0.042 g is added in residue, 0.5 mmol is dissolved in 1 mL water), reaction solution obtains phenyl 2-oxo-2-(4-cyano-phenyl through freeze-dried) ethyl phosphonate sodium (productive rate 67%).
Phenylbenzene 2-oxo-2-(4-cyano-phenyl) analytical data of ethyl phosphonate is as follows: 1h NMR (400 MHz, CDCl 3): δ8.25 (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-oxo-2-(4-cyano-phenyl) analytical data of ethyl phosphonate sodium is as follows: 1h NMR (300 MHz, D 2o): δ8.16 (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).
Embodiment 14: phenylbenzene 2-oxo-2-(3-nitrophenyl) synthesis of ethyl phosphonate
With 3-nitrostyrolene, diphenylphosphite for raw material, its reaction formula and experimental procedure as follows:
(1) in reaction flask, add 3-nitrostyrolene (0.15 g, 1 mmol), diphenylphosphite (0.35 g, 1.5 mmol), manganese acetate (0.41 g, 1.5 mmol) and 10 mL acetonitriles, react on 20 DEG C and carry out, TLC follows the tracks of reaction until terminate;
(2) reaction solution concentrates to obtain residue, obtains phenylbenzene 2-oxo-2-(3-nitrophenyl through column chromatography for separation) ethyl phosphonate (productive rate 83%);
(3) add in reaction flask by the phenylbenzene 2-oxo-2-(3-nitrophenyl of (2) gained) ethyl phosphonate (0.2 g, 0.5 mmol), sodium hydroxide solution (0.08 g, 2.0 mmol are dissolved in 1mL water) and 10 mL 1,4 dioxane, react on 25 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(4) the most of solvent of the concentrated removing of reaction solution obtains residue, after hcl acidifying, is extracted with ethyl acetate.Solvent in removing extraction liquid, sodium hydrogen carbonate solution (0.042 g is added in residue, 0.5 mmol is dissolved in 1 mL water), reaction solution obtains phenyl 2-oxo-2-(3-nitrophenyl through freeze-dried) ethyl phosphonate sodium (productive rate 58%).
Phenylbenzene 2-oxo-2-(3-nitrophenyl) analytical data of ethyl phosphonate is as follows: 1h NMR (400 MHz, CDCl 3): δ8.81-8.70 (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-(3-nitrophenyl) analytical data of ethyl phosphonate sodium is as follows: 1h NMR (300 MHz, D 2o): δ8.74-8.66 (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).
Embodiment 15: dimethyl 2-oxo-2-(3-trifluoromethyl) synthesis of ethyl phosphonate
With 3-trifluoromethyl styrene, dimethyl phosphite for raw material, its reaction formula and experimental procedure as follows:
(1) in reaction flask, 3-trifluoromethyl styrene (0.17 g, 1 mmol) is added, dimethyl phosphite (0.17 g, 1.5 mmol), manganese acetate (0.41 g, 1.5 mmol) and 10 mL acetonitriles, react on 30 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(2) reaction solution concentrates to obtain residue, obtains dimethyl 2-oxo-2-(3-trifluoromethyl through column chromatography for separation) ethyl phosphonate (productive rate 80%);
(3) add in reaction flask by the dimethyl 2-oxo-2-(3-trifluoromethyl of (2) gained) ethyl phosphonate (0.15 g, 0.5 mmol), sodium hydroxide solution (0.08 g, 2.0 mmol are dissolved in 1mL water) and 10 mL 1,4 dioxane, react on 25 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(4) the most of solvent of the concentrated removing of reaction solution obtains residue, after hcl acidifying, is extracted with ethyl acetate.Solvent in removing extraction liquid, sodium hydrogen carbonate solution (0.042 g is added in residue, 0.5 mmol is dissolved in 1 mL water), reaction solution obtains methyl 2-oxo-2-(3-trifluoromethyl through freeze-dried) ethyl phosphonate sodium (productive rate 63%).
Dimethyl 2-oxo-2-(3-trifluoromethyl) analytical data of ethyl phosphonate is as follows: 1h NMR (400 MHz, CDCl 3): δ8.25 (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); Methyl 2-oxo-2-(3-trifluoromethyl) analytical data of ethyl phosphonate sodium is as follows: 1h NMR (400 MHz, D 2o): δ8.11 (s, 1 H), 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).
Embodiment 16: dibenzyl 2-oxo-2-(furans-2-base) synthesis of ethyl phosphonate
With 2-vinyl furans, dibenzyl phosphite for raw material, its reaction formula and experimental procedure as follows:
(1) in reaction flask, add 2-vinyl furans (0.1 g, 1 mmol), dibenzyl phosphite (0.39 g, 1.5 mmol), manganese acetate (0.41 g, 1.5 mmol) and 10 mL acetonitriles, react on 40 DEG C and carry out, TLC follows the tracks of reaction until terminate;
(2) reaction solution concentrates to obtain residue, obtains dibenzyl 2-oxo-2-(furans-2-base through column chromatography for separation) ethyl phosphonate (productive rate 82%);
(3) add in reaction flask by the dibenzyl 2-oxo-2-(furans-2-base of (2) gained) ethyl phosphonate (0.18 g, 0.5 mmol), sodium hydroxide solution (0.08 g, 2.0 mmol are dissolved in 1mL water) and 10 mL 1,4 dioxane, react on 25 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(4) the most of solvent of the concentrated removing of reaction solution obtains residue, after hcl acidifying, is extracted with ethyl acetate.Solvent in removing extraction liquid, in residue, add sodium hydrogen carbonate solution (0.042 g, 0.5 mmol are dissolved in 1 mL water), reaction solution obtains benzyl 2-oxo-2-(furans-2-base through freeze-dried) ethyl phosphonate sodium (productive rate 61%).
Dibenzyl 2-oxo-2-(furans-2-base) analytical data of ethyl phosphonate is as follows: 1h NMR (400 MHz, CDCl 3): δ7.77 (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-(furans-2-base) analytical data of ethyl phosphonate sodium is as follows: 1h NMR (300 MHz, D 2o): δ7.58 (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).
Embodiment 17: phenylbenzene 2-oxo-2-(thiophene-2-base) synthesis of ethyl phosphonate
With 2-vinyl thiophene, diphenylphosphite for raw material, its reaction formula and experimental procedure as follows:
(1) in reaction flask, add 2-vinyl thiophene (0.11 g, 1 mmol), diphenylphosphite (0.35 g, 1.5 mmol), manganese acetate (0.41 g, 1.5 mmol) and 10 mL acetic acid, react on 30 DEG C and carry out, TLC follows the tracks of reaction until terminate;
(2) reaction solution concentrates to obtain residue, obtains phenylbenzene 2-oxo-2-(thiophene-2-base through column chromatography for separation) ethyl phosphonate (productive rate 79%);
(3) add in reaction flask by the phenylbenzene 2-oxo-2-(thiophene-2-base of (2) gained) ethyl phosphonate (0.18 g, 0.5 mmol), sodium hydroxide solution (0.08 g, 2.0 mmol are dissolved in 1mL water) and 10 mL 1,4 dioxane, react on 25 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(4) the most of solvent of the concentrated removing of reaction solution obtains residue, after hcl acidifying, is extracted with ethyl acetate.Solvent in removing extraction liquid, in residue, add sodium hydrogen carbonate solution (0.042 g, 0.5 mmol are dissolved in 1 mL water), reaction solution obtains phenyl 2-oxo-2-(thiophene-2-base through freeze-dried) ethyl phosphonate sodium (productive rate 59%).
Phenylbenzene 2-oxo-2-(thiophene-2-base) analytical data of ethyl phosphonate is as follows: 1h NMR (400 MHz, CDCl 3): δ8.00-8.02 (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); Phenyl 2-oxo-2-(thiophene-2-base) analytical data of ethyl phosphonate sodium is as follows: 1h NMR (400 MHz, D 2o): δ7.95-7.88 (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).
Embodiment 18: dimethyl 2-oxo-2-(pyridin-3-yl) synthesis of ethyl phosphonate
With 3-vinyl pyridine, dimethyl phosphite for raw material, its reaction formula and experimental procedure as follows:
(1) in reaction flask, add 3-vinyl pyridine (0.1 g, 1 mmol), dimethyl phosphite (0.17 g, 1.5 mmol), manganese acetate (0.41 g, 1.5 mmol) and 10 mL acetic acid, react on 20 DEG C and carry out, TLC follows the tracks of reaction until terminate;
(2) reaction solution concentrates to obtain residue, obtains dimethyl 2-oxo-2-(pyridin-3-yl through column chromatography for separation) ethyl phosphonate (productive rate 78%);
(3) add in reaction flask by the dimethyl 2-oxo-2-(pyridin-3-yl of (2) gained) ethyl phosphonate (0.11 g, 0.5 mmol), sodium hydroxide solution (0.08 g, 2.0 mmol are dissolved in 1mL water) and 10 mL 1,4 dioxane, react on 25 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(4) the most of solvent of the concentrated removing of reaction solution obtains residue, after hcl acidifying, is extracted with ethyl acetate.Solvent in removing extraction liquid, in residue, add sodium hydrogen carbonate solution (0.042 g, 0.5 mmol are dissolved in 1 mL water), reaction solution obtains methyl 2-oxo-2-(pyridin-3-yl through freeze-dried) ethyl phosphonate sodium (productive rate 62%).
Dimethyl 2-oxo-2-(pyridin-3-yl) analytical data of ethyl phosphonate is as follows: 1h NMR (400 MHz, CDCl 3): δ8.97 (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); Methyl 2-oxo-2-(pyridin-3-yl) analytical data of ethyl phosphonate sodium is as follows: 1h NMR (400 MHz, D 2o): δ8.85 (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).
Embodiment 19: the synthesis of dibenzyl 2-oxo-2-phenylethylphosphonic ester
With vinylbenzene, dibenzyl phosphite for raw material, its reaction formula and experimental procedure as follows:
(1) in reaction flask, vinylbenzene (0.1 g, 1 mmol) is added, dibenzyl phosphite (0.39 g, 1.5 mmol), manganese acetate (0.41 g, 1.5 mmol) and 10 mL methylene dichloride, react on 20 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(2) reaction solution concentrates to obtain residue, obtains dibenzyl 2-oxo-2-phenylethylphosphonic ester (productive rate 85%) through column chromatography for separation;
(3) add in reaction flask by dibenzyl 2-oxo-2-phenylethylphosphonic ester (0.19 g of (2) gained, 0.5 mmol), sodium iodide (0.09 g, 0.6 mmol) and 10 mL 2-butanone, react on 80 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(4) reaction solution concentrated removing 2-butanone obtains residue, and through ice-cold washing with acetone, suction filtration obtains thick product, obtains benzyl 2-oxo-2-phenylethylphosphonic ester sodium (productive rate 62%) with ethyl alcohol recrystallization.
The analytical data of dibenzyl 2-oxo-2-phenylethylphosphonic ester is as follows: 1h NMR (400 MHz, CDCl 3): δ7.97 (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); The analytical data of benzyl 2-oxo-2-phenylethylphosphonic ester sodium is as follows: 1h NMR (300 MHz, D 2o): δ7.78 (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).
Embodiment 20: the synthesis of biphenyl methyl 2-oxo-2-phenylethylphosphonic ester
With vinylbenzene, dibiphenylyl methylisothiouronium methylphosphite ester for raw material, its reaction formula and experimental procedure as follows:
(1) in reaction flask, add vinylbenzene (0.1 g, 1 mmol), dibiphenylyl methylisothiouronium methylphosphite ester (0.61 g, 1.5 mmol), manganese acetate (0.41 g, 1.5 mmol) and 10 mL methylene dichloride, react on 30 DEG C and carry out, TLC follows the tracks of reaction until terminate;
(2) reaction solution concentrates to obtain residue, obtains biphenyl methyl 2-oxo-2-phenylethylphosphonic ester (productive rate 67%) through column chromatography for separation;
(3) add in reaction flask by biphenyl methyl 2-oxo-2-phenylethylphosphonic ester (0.27 g of (2) gained, 0.5 mmol), sodium iodide (0.09 g, 0.6 mmol) and 10 mL 2-butanone, react on 80 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(4) reaction solution concentrated removing 2-butanone obtains residue, and through ice-cold washing with acetone, suction filtration obtains thick product, with methyl alcohol: water (1:4) recrystallization obtains Biphenylmethyl 2-oxo-2-phenylethylphosphonic ester sodium (productive rate 65%).
The analytical data of biphenyl methyl 2-oxo-2-phenylethylphosphonic ester is as follows: 1h NMR (400 MHz, CDCl 3): δ7.98 (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); The analytical data of Biphenylmethyl 2-oxo-2-phenylethylphosphonic ester sodium is as follows: 1h NMR (400 MHz, D 2o): δ7.78 (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).
Embodiment 21: phenylbenzene 2-oxo-2-(xenyl-4-base) synthesis of ethyl phosphonate
With distyryl, diphenylphosphite for raw material, its reaction formula and experimental procedure as follows:
(1) in reaction flask, distyryl (0.18 g, 1 mmol) is added, diphenylphosphite (0.35 g, 1.5 mmol), manganese acetate (0.41 g, 1.5 mmol) and 10 mL methylene dichloride, react on 20 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(2) reaction solution concentrates to obtain residue, obtains phenylbenzene 2-oxo-2-(xenyl-4-base through column chromatography for separation) ethyl phosphonate (productive rate 70%);
(3) add in reaction flask by the phenylbenzene 2-oxo-2-(xenyl-4-base of (2) gained) ethyl phosphonate (0.21 g 0.5 mmol), sodium hydroxide solution (0.08 g, 2.0 mmol are dissolved in 1mL water) and 10 mL 1,4 dioxane, react on 25 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(4) the most of solvent of the concentrated removing of reaction solution obtains residue, after hcl acidifying, is extracted with ethyl acetate.Solvent in removing extraction liquid, sodium hydrogen carbonate solution (0.042 g is added in residue, 0.5 mmol is dissolved in 1 mL water), reaction solution obtains phenyl 2-oxo-2-(xenyl-4-base through freeze-dried) ethyl phosphonate sodium (productive rate 55%).
Phenylbenzene 2-oxo-2-(xenyl-4-base) analytical data of ethyl phosphonate is as follows: 1h NMR (400 MHz, CDCl 3): δ8.12 (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); Phenyl 2-oxo-2-(xenyl-4-base) analytical data of ethyl phosphonate sodium is as follows: 1h NMR (400 MHz, D 2o): δ7.92 (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).
Embodiment 22: dibenzyl 2-oxo-2-(xenyl-4-base) synthesis of ethyl phosphonate
With distyryl, dibenzyl phosphite for raw material, its reaction formula and experimental procedure as follows:
(1) in reaction flask, distyryl (0.18 g, 1 mmol) is added, dibenzyl phosphite (0.39 g, 1.5 mmol), manganese acetate (0.41 g, 1.5 mmol) and 10 mL chloroforms, react on 30 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(2) reaction solution concentrates to obtain residue, obtains dibenzyl 2-oxo-2-(xenyl-4-base through column chromatography for separation) ethyl phosphonate (productive rate 65%);
(3) add in reaction flask by the dibenzyl 2-oxo-2-(xenyl-4-base of (2) gained) ethyl phosphonate (0.23 g, 0.5 mmol), sodium iodide (0.09 g, 0.6 mmol) and 10 mL2-butanone, react on 80 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(4) reaction solution concentrated removing 2-butanone obtains residue, and through ice-cold washing with acetone, suction filtration obtains thick product, with ethanol: water (1:1) recrystallization obtains benzyl 2-oxo-2-(xenyl-4-base) ethyl phosphonate sodium (productive rate 60%).
Dibenzyl 2-oxo-2-(xenyl-4-base) analytical data of ethyl phosphonate is as follows: 1h NMR (400 MHz, CDCl 3): δ8.01 (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); Benzyl 2-oxo-2-(xenyl-4-base) analytical data of ethyl phosphonate sodium is as follows: 1h NMR (300 MHz, DMSO-d 6): δ8.13 (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).
Embodiment 23: dibiphenylyl methyl 2-oxo-2-(xenyl-4-base) synthesis of ethyl phosphonate
With distyryl, dibiphenylyl methylisothiouronium methylphosphite ester for raw material, its reaction formula and experimental procedure as follows:
(1) in reaction flask, distyryl (0.18 g, 1 mmol) is added, dibiphenylyl methylisothiouronium methylphosphite ester (0.62 g, 1.5 mmol), manganese acetate (0.41 g, 1.5 mmol) and 10 mL chloroforms, react on 20 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(2) reaction solution concentrates to obtain residue, obtains dibiphenylyl methyl 2-oxo-2-(xenyl-4-base through column chromatography for separation) ethyl phosphonate (productive rate 62%);
(3) add in reaction flask by the dibiphenylyl methyl 2-oxo-2-(xenyl-4-base of (2) gained) ethyl phosphonate (0.30 g, 0.5 mmol), sodium iodide (0.09 g, 0.6 mmol) and 10 mL 2-butanone, react on 80 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(4) reaction solution concentrated removing 2-butanone obtains residue, through ice-cold washing with acetone, suction filtration obtains thick product, with ethanol: water (1:1) recrystallization obtains diphenylmethyl 2-oxo-2-(xenyl-4-base) ethyl phosphonate sodium (productive rate 54%).
Dibiphenylyl methyl 2-oxo-2-(xenyl-4-base) analytical data of ethyl phosphonate is as follows: 1h NMR (400 MHz, CDCl 3): δ8.03 (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); Diphenylmethyl 2-oxo-2-(xenyl-4-base) analytical data of ethyl phosphonate sodium is as follows: 1h NMR (300 MHz, DMSO-d 6): δ7.95 (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).
Embodiment 24: phenylbenzene 2-oxo-2-(pentafluorophenyl group) synthesis of ethyl phosphonate
With pentafluorostyrene, diphenylphosphite for raw material, its reaction formula and experimental procedure as follows:
(1) in reaction flask, pentafluorostyrene (0.19 g, 1 mmol) is added, diphenylphosphite (0.35 g, 1.5 mmol), manganese acetate (0.41 g, 1.5 mmol) and 10 mL acetonitriles, react on 30 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(2) reaction solution concentrates to obtain residue, obtains phenylbenzene 2-oxo-2-(pentafluorophenyl group through column chromatography for separation) ethyl phosphonate (productive rate 60%);
(3) add in reaction flask by the phenylbenzene 2-oxo-2-(pentafluorophenyl group of (2) gained) ethyl phosphonate (0.22 g, 0.5 mmol), sodium hydroxide solution (0.08 g, 2.0 mmol are dissolved in 1mL water) and 10 mL 1,4 dioxane, react on 25 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(4) the most of solvent of the concentrated removing of reaction solution obtains residue, after hcl acidifying, is extracted with ethyl acetate.Solvent in removing extraction liquid, in residue, add sodium hydrogen carbonate solution (0.042 g, 0.5 mmol are dissolved in 1 mL water), reaction solution obtains phenyl 2-oxo-2-(pentafluorophenyl group through freeze-dried) ethyl phosphonate sodium (productive rate 50%).
Phenylbenzene 2-oxo-2-(pentafluorophenyl group) analytical data of ethyl phosphonate is as follows: 1h NMR (300 MHz, DMSO-d 6): δ7.32 (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-(pentafluorophenyl group) analytical data of ethyl phosphonate sodium is as follows: 1h NMR (300 MHz, DMSO-d 6): δ7.35 (t, j=7.2Hz, 2H), 7.09 – 7.19 (m, 3H), 3.72 (d, j=21.6 Hz, 2H).
Embodiment 25: phenylbenzene 2-oxo-2-(3-(2-chloro-phenyl-)-5-methylisoxazole-4-base) synthesis of ethyl phosphonate
With 3-(2-chloro-phenyl-)-5-methylisoxazole-4-base) ethene, diphenylphosphite be raw material, its reaction formula and experimental procedure as follows:
(1) in reaction flask, 3-(2-chloro-phenyl-is added)-5-methylisoxazole-4-base) ethene (0.22 g, 1 mmol), diphenylphosphite (0.35 g, 1.5 mmol), manganese acetate (0.41 g, 1.5 mmol) and 10 mL acetonitriles, react on 30 DEG C and carry out, TLC follows the tracks of reaction until terminate;
(2) reaction solution concentrates to obtain residue, obtains phenylbenzene 2-oxo-2-(3-(2-chloro-phenyl-through column chromatography for separation)-5-methylisoxazole-4-base) ethyl phosphonate (productive rate 80%);
(3) add in reaction flask by the phenylbenzene 2-oxo-2-(3-(2-chloro-phenyl-of (2) gained)-5-methylisoxazole-4-base) ethyl phosphonate (0.24 g, 0.5 mmol), sodium iodide (0.09 g, 0.6 mmol) and 10 mL 2-butanone, react on 80 DEG C to carry out, TLC follows the tracks of reaction until terminate;
(4) reaction solution concentrated removing 2-butanone obtains residue, and through ice-cold washing with acetone, suction filtration obtains thick product,
With ethanol: water (1:1) recrystallization obtains phenyl 2-oxo-2-(3-(2-chloro-phenyl-)-5-methylisoxazole-4-base) ethyl phosphonate sodium (productive rate 50%).
Phenylbenzene 2-oxo-2-(3-(2-chloro-phenyl-)-5-methylisoxazole-4-base) analytical data of ethyl phosphonate is as follows: 1h NMR (400 MHz, DMSO-d 6): δ12.15 (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-chloro-phenyl-)-5-methylisoxazole-4-base) analytical data of ethyl phosphonate sodium is as follows: 1h NMR (300 MHz, D 2o): δ7.37 – 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).
The synthesis of embodiment 26: 2-amino-2-phenylethylphosphonic
With diethyl 2-oxo-2-phenylethylphosphonic ester for raw material, its reaction formula and experimental procedure as follows:
(1) in reaction flask, diethyl 2-oxo-2-phenylethylphosphonic ester (0.52 g, 2 mmol) is added, 7 mL ethanol, the ethanolic soln of hydroxylamine hydrochloride (0.276 g, 4 mmol), mixture is in 25 DEG C of stirring reactions, TLC follows the tracks of reaction until terminate, and filters to obtain solid;
(2) add in reaction flask by gained solid in (1), add 10 mL methyl alcohol and 2 mL ammoniacal liquor, 0.2 g Raney Ni, passes into hydrogen, and mixture is in 25 DEG C of stirring reactions, and TLC follows the tracks of reaction until terminate;
(3) reaction solution concentrates, and is extracted with ethyl acetate, organic over anhydrous dried over sodium sulfate, concentrated; In enriched material, add 10 mL 20% hydrochloric acid, mixture reflux, TLC follows the tracks of reaction until terminate; Reaction solution is concentrated into dry, obtains 2-amino-2-phenylethylphosphonic (productive rate 60%) with methyl alcohol/propylene oxide recrystallization.
The analytical data of 2-amino-2-phenylethylphosphonic is as follows: 1h NMR (300 MHz, D 2o): δ7.20-7.40 (m, 5H ),4.11-4.31 (m, 1H ), 1.60-1.80 (m, 2H ).
Embodiment 27: 2-amino-2-(4-chloro-phenyl-) synthesis of ethylphosphonic acid
With diethyl 2-oxo-2-(4-chloro-phenyl-) ethyl phosphonate for raw material, its reaction formula and experimental procedure as follows:
(1) in reaction flask, add diethyl 2-oxo-2-(4-chloro-phenyl-) ethyl phosphonate (0.58 g, 2 mmol), 7 mL ethanol, hydroxylamine hydrochloride (0.276 g, 4 mmol) ethanolic soln, mixture is in 25 DEG C of stirring reactions, and TLC follows the tracks of reaction until terminate, and filters to obtain solid;
(2) add in reaction flask by gained solid in (1), add 10 mL methyl alcohol and 2 mL ammoniacal liquor, 0.2 g Raney Ni, passes into hydrogen, and mixture is in 25 DEG C of stirring reactions, and TLC follows the tracks of reaction until terminate;
(3) reaction solution concentrates, and is extracted with ethyl acetate, organic over anhydrous dried over sodium sulfate, concentrated; In enriched material, add 10 mL 20% hydrochloric acid, mixture reflux, TLC follows the tracks of reaction until terminate; Reaction solution is concentrated into dry, obtains 2-amino-2-(4-chloro-phenyl-with methyl alcohol/propylene oxide recrystallization) ethylphosphonic acid (productive rate 58%).
2-amino-2-(4-chloro-phenyl-) analytical data of ethylphosphonic acid is as follows: 1h NMR (300 MHz, D 2o): δ7.30-7.70 (m, 4H ),4.12-4.30 (m, 1H ), 1.60-1.85 (m, 2H ).
Embodiment 28: 2-amino-2-(4-tolyl) synthesis of ethylphosphonic acid
With diethyl 2-oxo-2-(4-tolyl) ethyl phosphonate for raw material, its reaction formula and experimental procedure as follows:
(1) in reaction flask, add diethyl 2-oxo-2-(4-tolyl) ethyl phosphonate (0.54 g, 2 mmol), 7 mL ethanol, hydroxylamine hydrochloride (0.276 g, 4 mmol) ethanolic soln, mixture is in 25 DEG C of stirring reactions, and TLC follows the tracks of reaction until terminate, and filters to obtain solid;
(2) add in reaction flask by gained solid in (1), add 10 mL methyl alcohol and 2 mL ammoniacal liquor, 0.2 g Raney Ni, passes into hydrogen, and mixture is in 25 DEG C of stirring reactions, and TLC follows the tracks of reaction until terminate;
(3) reaction solution concentrates, and is extracted with ethyl acetate, organic over anhydrous dried over sodium sulfate, concentrated; In enriched material, add 10 mL 20% hydrochloric acid, mixture reflux, TLC follows the tracks of reaction until terminate; Reaction solution is concentrated into dry, obtains 2-amino-2-(4-tolyl with methyl alcohol/propylene oxide recrystallization) ethylphosphonic acid (productive rate 62%).
2-amino-2-(4-tolyl) analytical data of ethylphosphonic acid is as follows: 1h NMR (300 MHz, D 2o): δ7.20-7.40 (m, 4H ),4.11-4.31 (m, 1H ), 2.35 (s, 3H), 1.60-1.80 (m, 2H ).
Embodiment 29: 2-amino-2-(4-fluorophenyl) synthesis of ethylphosphonic acid
With diethyl 2-oxo-2-(4-fluorophenyl) ethyl phosphonate for raw material, its reaction formula and experimental procedure as follows:
(1) in reaction flask, add diethyl 2-oxo-2-(4-fluorophenyl) ethyl phosphonate (0.55 g, 2 mmol), 7 mL ethanol, hydroxylamine hydrochloride (0.276 g, 4 mmol) ethanolic soln, mixture is in 25 DEG C of stirring reactions, and TLC follows the tracks of reaction until terminate, and filters to obtain solid;
(2) add in reaction flask by gained solid in (1), add 10 mL methyl alcohol and 2 mL ammoniacal liquor, 0.2 g Raney Ni, passes into hydrogen, and mixture is in 25 DEG C of stirring reactions, and TLC follows the tracks of reaction until terminate;
(3) reaction solution concentrates, and is extracted with ethyl acetate, organic over anhydrous dried over sodium sulfate, concentrated; In enriched material, add 10 mL 20% hydrochloric acid, mixture reflux, TLC follows the tracks of reaction until terminate; Reaction solution is concentrated into dry, obtains 2-amino-2-(4-fluorophenyl with methyl alcohol/propylene oxide recrystallization) ethylphosphonic acid (productive rate 59%).
2-amino-2-(4-fluorophenyl) analytical data of ethylphosphonic acid is as follows: 1h NMR (300 MHz, D 2o): δ7.20-7.40 (m, 4H ),4.11-4.31 (m, 1H ), 1.60-1.90 (m, 2H ).
Embodiment 30: 2-amino-2-(4-p-methoxy-phenyl) synthesis of ethylphosphonic acid
With diethyl 2-oxo-2-(4-p-methoxy-phenyl) ethyl phosphonate for raw material, its reaction formula and experimental procedure as follows:
(1) in reaction flask, add diethyl 2-oxo-2-(4-p-methoxy-phenyl) ethyl phosphonate (0.57 g, 2 mmol), 7 mL ethanol, hydroxylamine hydrochloride (0.276 g, 4 mmol) ethanolic soln, mixture is in 25 DEG C of stirring reactions, and TLC follows the tracks of reaction until terminate, and filters to obtain solid;
(2) add in reaction flask by gained solid in (1), add 10 mL methyl alcohol and 2 mL ammoniacal liquor, 0.2 g Raney Ni, passes into hydrogen, and mixture is in 25 DEG C of stirring reactions, and TLC follows the tracks of reaction until terminate;
(3) reaction solution concentrates, and is extracted with ethyl acetate, organic over anhydrous dried over sodium sulfate, concentrated; In enriched material, add 10 mL 20% hydrochloric acid, mixture reflux, TLC follows the tracks of reaction until terminate; Reaction solution is concentrated into dry, obtains 2-amino-2-(4-p-methoxy-phenyl with methyl alcohol/propylene oxide recrystallization) ethylphosphonic acid (productive rate 64%).
2-amino-2-(4-p-methoxy-phenyl) analytical data of ethylphosphonic acid is as follows: 1h NMR (300 MHz, D 2o): δ6.80-7.20 (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-carbonylic phosphonic acid ester derivative, is characterized in that, comprise the following steps: be dissolved in solvent by ethene derivatives, phosphorus reagent, manganese acetate, react at 20 ~ 100 DEG C, obtained β-carbonylic phosphonic acid ester derivative;
The chemical structure of general formula of described ethene derivatives is , wherein R is the one in following group:
、 、 、 、 、 ，
Described R 1, R 2, R 3, R 4and R 5selection take one of following scheme:
(1) R 1for the one in hydrogen, methyl, trifluoromethyl, methoxyl group, fluorine, chlorine, bromine, cyano group, formyl radical, methyl-formiate base, nitro, R 2, R 3, R 4and R 5be all hydrogen;
(2) R 2for the one in methyl, trifluoromethyl, methoxyl group, fluorine, chlorine, bromine, cyano group, formyl radical, methyl-formiate base, nitro, R 1, R 3, R 4and R 5be all hydrogen;
(3) R 3for the one in methyl, trifluoromethyl, methoxyl group, fluorine, chlorine, bromine, cyano group, formyl radical, methyl-formiate base, nitro, phenyl, R 1, R 2, R 4and R 5be all hydrogen;
(4) R 1, R 2, R 3, R 4and R 5for fluorine;
The chemical structure of general formula of described phosphorus reagent is:
Wherein R 6one in following group:
CH 3-、 、 、 、 、 ；
Described solvent is selected from: the one in methyl alcohol, ethanol, acetonitrile, acetic acid, chloroform, methylene dichloride, toluene;
The chemical structural formula of described β-carbonylic phosphonic acid ester derivative is:
。
2. the preparation method of β-carbonylic phosphonic acid ester derivative according to claim 1, it is characterized in that: described ethene derivatives is selected from vinylbenzene, 2-methyl styrene, 3-methoxy styrene, 4-methoxy styrene, 2-chloro-styrene, 3-chloro-styrene, 4-chloro-styrene, 4-cyano-styrene, 3-methyl-formiate base vinylbenzene, 4-acetylbenzene ethene, 3-nitrostyrolene, 3-trifluoromethyl styrene, 4-xenyl ethene, pentafluorostyrene, 2-vinyl furans, 2-vinyl thiophene, 2-vinyl pyrrole, 3-vinyl pyridine, 3-(2-chloro-phenyl-)-5-methylisoxazole-4-base) one in ethene.
3. the preparation method of β-carbonylic phosphonic acid ester derivative according to claim 1, is characterized in that: utilize thin-layer chromatography to follow the tracks of reaction until terminate completely.
4. the preparation method of β-carbonylic phosphonic acid ester derivative according to claim 1, is characterized in that: in molar ratio, ethene derivatives: phosphorus reagent: manganese acetate is 1: (1 ~ 2): (1 ~ 3).
5. the preparation method of β-carbonylic phosphonic acid ester derivative according to claim 4, is characterized in that: in molar ratio, ethene derivatives: phosphorus reagent: manganese acetate equals 1: 1.5: 1.5.
6. the preparation method of β-carbonylic phosphonic acid ester derivative according to claim 1, is characterized in that: also comprise purification step, is specially, and after reaction terminates, namely obtains β-carbonylic phosphonic acid ester derivative after reaction solution is concentrated through column chromatography for separation.
CN201410518132.3A 2014-09-30 2014-09-30 Method for preparing beta-carbonyl phosphonate derivatives Pending CN104341449A (en)

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CN105017312A (en) * 2015-06-26 2015-11-04 苏州大学 Preparation method of beta-aminoethylphosphonyl derivatives
CN105017312B (en) * 2015-06-26 2017-05-10 苏州大学 Preparation method of beta-aminoethylphosphonyl derivatives
CN106892942A (en) * 2015-06-26 2017-06-27 苏州大学 A kind of preparation method of β amidos ethylphosphonic acid derivative
CN106892942B (en) * 2015-06-26 2019-01-04 苏州大学 A kind of preparation method of beta-amido ethylphosphonic acid derivative
CN105837625A (en) * 2016-04-06 2016-08-10 浙江大学 Preparation method of beta-ketone substituted phosphate ester compound
CN106279274A (en) * 2016-08-01 2017-01-04 河南省科学院化学研究所有限公司 A kind of preparation method by alkene synthesis β carbonylic phosphonic acid ester derivant
CN106432329A (en) * 2016-09-09 2017-02-22 苏州大学 Beta-cyano phosphoryl derivatives as well as preparation method and application thereof
CN106432329B (en) * 2016-09-09 2018-07-31 苏州大学 A kind of beta-cyano phosphono analog derivative and the preparation method and application thereof
CN107573378A (en) * 2017-09-08 2018-01-12 江苏强盛功能化学股份有限公司 A kind of β hydroxyls imido grpup phosphono analog derivative and preparation method thereof
CN108329347A (en) * 2018-01-15 2018-07-27 苏州大学 A method of preparing β-chloro alkenyl phosphono analog derivative
CN113773345A (en) * 2021-10-07 2021-12-10 湖南科技学院 Method for preparing beta-carbonyl phosphonate compound
CN113773345B (en) * 2021-10-07 2024-05-03 湖南科技学院 Method for preparing beta-carbonyl phosphonate compound

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