CN118086931A - Method for electrocatalytic synthesis of organic phosphoric acid compound and application thereof - Google Patents

Method for electrocatalytic synthesis of organic phosphoric acid compound and application thereof Download PDF

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CN118086931A
CN118086931A CN202410218523.7A CN202410218523A CN118086931A CN 118086931 A CN118086931 A CN 118086931A CN 202410218523 A CN202410218523 A CN 202410218523A CN 118086931 A CN118086931 A CN 118086931A
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梁雨锋
王天璋
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Shandong University
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    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
    • C25B3/00—Electrolytic production of organic compounds
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds
    • A61K31/662—Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
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Abstract

The invention relates to a method for electrocatalytic synthesis of an organic phosphate compound and application thereof. The method for synthesizing the organic phosphoric acid under the electrocatalytic strategy has the advantages of easily available raw materials, simple operation, mild conditions, no need of additional metal catalysts or additives to participate in the reaction, very good atomic economy and accord with sustainable green chemical concepts.

Description

Method for electrocatalytic synthesis of organic phosphoric acid compound and application thereof
Technical Field
The invention relates to the field of organic synthesis, in particular to a method for electrocatalytic synthesis of an organic phosphate compound and application thereof.
Background
Among various organic acids, organic phosphoric acid is an important structural motif in various bioactive substances such as glycolipids and nucleic acids, as an important class of organic acids. In pharmaceutical studies, it has been found that the incorporation of phosphate moieties can increase solubility, thereby modulating the distribution and bioavailability of the parent drug/prodrug molecule. Meanwhile, the organic acid is used as an effective chelating agent for removing heavy metals in industrial wastewater, and is paid attention to due to the simple process and short adsorption time, and the organic acid is biologically degraded, so that the organic acid has the advantages of good ecological friendliness, very small ecological pressure on the environment and the like, and has important research significance and application prospect in the fields of metal ion adsorption, medical molecule synthesis and the like. As the demand for waste metal ion recovery has increased in recent years, the chelating ability of organic phosphoric acid is better than that of other types of organic acids, such as carboxylic acids like ethylenediamine tetraacetic acid; the phosphate group has stronger electron donating ability, is favorable for dissolving metal ions precipitated in an insoluble salt form, and has been well embodied in practical application. Phosphinic acids can be divided into two forms, mono-alkyl substituents and di-alkyl substituents. The monoalkyl phosphinic acid is mainly used in the field of biological preparation intermediates, and the dialkyl phosphinic acid has important application value in the fields of organic phosphorus compound substituent effect, structure-activity relationship research and solvent extraction separation. At present, the products are completely imported from European and American national company, so that the development of a method for synthesizing the organic phosphine compound has very important economic value and social significance.
The organic phosphoric acid compound can be used as a reaction raw material to participate in organic chemical reactions such as cross coupling and nucleophilic substitution reaction. The preparation method is usually synthesized by substitution reaction generated between phosphoryl halide or phosphoric acid and alcohol, and chemists also develop coupling reaction with Grignard reagent, artherton-Todd cross hetero dehydrogenation coupling reaction and phosphoryl oxydation free radical addition reaction with unsaturated framework participation on alkene or alkyne and the like. For example: CN103613614a discloses an α -hydroxy unsaturated alkylphosphonic acid compound, its preparation and application method, 2-ethyl-2-hexenal and hypophosphorous acid or hypophosphite undergo addition reaction in the presence of acidic catalyst to produce 1-hydroxy-2-ethyl-2-hexene-1-phosphinic acid, 1-hydroxy-2-ethyl-2-hexene-1-phosphinic acid is reacted with oxidant to produce 1-hydroxy-2-ethyl-2-hexene-1-phosphonic acid, 1-hydroxy-2-ethyl-2-hexene-1-phosphonic acid is used as flotation collector of bauxite, ilmenite, rutile, scheelite, rare earth ore, tin ore, fluorite or lithium ore. However, these methods generally require metal catalysts and/or stoichiometric alkali additives, so that the development of a method for synthesizing organic phosphoric acid compounds, which is mild, simple, convenient to operate and has a high economic added value, has wide application prospects and research significance. Many other synthetic methods have been developed based on this, for example: CN109776606a discloses an organic phosphoric acid compound, its synthesis method and application as chalcopyrite collector, the organic carboxylic acid compound and phosphorous acid are condensed under the action of phosphorus pentoxide, the condensation reaction product is hydrolyzed by water vapor, and separated and purified to obtain the final product. Among them, one of the most widespread strategies is the free radical addition reaction, which is characterized by the ability to rapidly frame highly complex polycyclic molecular frameworks with fewer synthetic steps. The radical reaction is generally mild in condition, excellent in functional group compatibility, and in addition, since the radical reaction has good steric and enantiomer control, many radical cascade reactions with high stereoselectivity have been developed in recent years, and are successfully applied to synthesis of natural products and material molecules.
Mechanochemistry is an emerging discipline for facilitating chemical transformations with electric current, and is one of the most green, efficient methods for constructing valuable molecules. Electrochemical strategies are generally characterized by mild reaction conditions, high selectivity and ease of flow technology extension. In recent years, the development of electromechanical synthesis has received increasing attention and interest in the last few years, and the electrochemically driven free radical process will react in combination with environmental sustainability and selectivity, leading to the discovery of new transformations not achievable by many traditional non-electrochemical methods. Electrochemical reactions are typically carried out in undivided cells, with controlled current being the most convenient method of preparing electrolysis. The electrolytic cell adopts a double electrode structure, and a three-necked round bottom flask or a beaker-type glass flask is used according to the reaction scale. The anode material is selected from reticular glass carbon (RVC) with good chemical corrosion resistance and high specific surface area, and the cathode material is selected from metal Pt with good hydrogen evolution electrocatalytic activity, so the selection of the electrode material in electrochemistry is particularly important. Since the current density tends to affect the efficiency of the preparation electrolysis, how to select the appropriate current magnitude also has a significant impact on the reaction.
At present, the electrocatalytic synthesis of the organic phosphate compound is not reported. For this purpose, the present invention is proposed.
Disclosure of Invention
In view of the above-mentioned prior art, the present inventors have conducted intensive and extensive studies on electrochemically promoted coupling reactions, and have found that the reaction mode of electrocatalytic free radicals is more advantageous for synthesizing an organophosphorus compound, and not only is simple to operate, mild in conditions, free of additional metal catalysts or additives, and has good economic effects and application prospects, but also an organophosphine compound having various functional groups can be efficiently constructed, thereby facilitating the later-stage modification. The present invention has been completed based on the above findings.
To this end, a first object of the present invention is to provide a method for electrocatalytic synthesis of organic phosphate compounds. The method solves the technical problems of high synthesis reaction cost, low reaction stability and complex reaction of the organic phosphate compound in the prior art.
It is a second object of the present invention to provide an organic phosphoric acid compound produced by the above synthetic method.
The third object of the present invention is to provide the use of the organic phosphate compound obtained by the above synthesis method in medicine and/or material.
In order to achieve the above object, the technical scheme of the present invention can be summarized as follows:
A method for electrocatalytic synthesis of an organophosphate compound, comprising the steps of:
In an inert solvent, under the action of an electrode and an electrolyte, adding or not adding an additive, and carrying out electrocatalytic reaction on a compound of the formula (I) and a compound of the formula (II) to obtain a compound of the formula (III), namely an organic phosphoric acid compound;
wherein R 1 is selected from saturated or unsaturated alkyl, phenyl, substituted phenyl, O-containing heterocyclic substituted alkyl, condensed ring aryl, saturated or unsaturated linear alkyl or cyclic alkyl containing halogen, ester, carbonyl, amino, nitro, cyano, sulfonyl and acyl;
r 2 is selected from hydrogen, sodium, potassium, lithium, saturated or unsaturated hydrocarbon groups, phenyl, substituted phenyl, O-containing heterocyclic substituted hydrocarbon groups, condensed ring aryl groups, saturated or unsaturated linear hydrocarbon groups or cyclic hydrocarbon groups containing halogen, ester groups, carbonyl groups, amino groups, nitro groups, cyano groups, sulfonyl groups and acyl groups.
According to the invention, preferably, the compounds of formula (I) are styrene, substituted styrene, alkyl alkene, substituted alkyl alkene, phenylacetylene, substituted phenylacetylene, alkyl alkyne or substituted alkyl alkyne;
More preferably, the compound of formula (I) is an alkyl olefin or a substituted alkyl olefin.
According to the invention, preferably, the compound of formula (II) is hypophosphorous acid or hypophosphite;
More preferably, the compound of formula (II) is a sodium, potassium, lithium salt of hypophosphorous acid.
According to the invention, preferably, the compound of formula (III), i.e. the organophosphate compound, is selected from the following compounds:
Bis (2, 4-trimethylpentyl) phosphonic acid, diphenylethyl phosphonic acid, bis (4-phenylbut-3-en-1-yl) phosphonic acid, bis (4-phenylbut-3-yn-1-yl) phosphonic acid, bis (cyclohexylmethyl) phosphonic acid.
According to the invention, it is preferred that the molar ratio of the compound of formula (I) to the compound of formula (II) is from 20:1 to 1:20;
further preferably (0.5 to 10): 1.
According to the invention, preferably, the electrolyte is selected from ammonium, lithium, sodium, potassium, zinc, aluminum or magnesium salts;
further preferably, the electrolyte is tetrabutylammonium iodide, tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium fluoride; more preferably, the electrolyte is tetrabutylammonium bromide.
According to the invention, preferably, the electrode is selected from metallic or non-metallic electrodes; further preferably, the metal electrode is a copper electrode, an iron electrode, an aluminum electrode, a platinum electrode, a gold electrode or a zinc electrode, and the nonmetal electrode is a carbon electrode; more preferably, the electrode is a platinum electrode or a carbon electrode.
According to the present invention, the size of the electrode is preferably 1X 10mm to 100X 100mm.
According to the present invention, it is preferable that the electric current of the electrocatalytic reaction is 0.1mA to 100mA; more preferably, the current is 0.5mA to 50mA.
According to the invention, preferably, the inert solvent is selected from toluene, tetrahydrofuran, 1, 4-dioxane, N '-dimethylformamide, N' -dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, acetonitrile, 1, 2-dichloroethane; more preferably, the inert solvent is N, N' -dimethylformamide.
According to the invention, preferably, the additive is one or more of sodium acetate, lithium carbonate, potassium carbonate, cesium carbonate or potassium acetate.
According to the present invention, the catalytic reaction temperature is preferably from 0 to 120 ℃, further preferably from 5 to 60 ℃;
preferably, the catalytic reaction time is 3-24 hours.
According to the present invention, preferably, after the reaction is completed, the method further comprises a separation and purification step of:
preferably, the separation and purification steps are as follows:
Cooling to room temperature after the reaction is finished, filtering by diatomite, and concentrating to obtain a crude product; separating the crude product by chromatography with silica gel plate to obtain the product; the developing agent or eluent adopted by the chromatographic separation is petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 20:1.
The invention also provides the organic phosphoric acid compound prepared by the synthesis method.
The invention also provides application of the organic phosphate compound obtained by the synthesis method in the field of medicines and/or materials. For example: the method is applied to the fields of medicine molecule synthesis, metal ion adsorption materials and the like.
The beneficial effects of the invention are as follows:
1. the method for synthesizing the organic phosphoric acid under the electrocatalytic strategy has the advantages of easily available raw materials, simple operation, mild conditions, no need of additional metal catalysts or additives to participate in the reaction, very good atomic economy and accord with sustainable green chemical concepts.
2. The substrate has wide application range and good chemical selectivity, can efficiently construct the organic phosphine compound with various functional groups, can be well compatible with the functional groups with large steric hindrance in the reaction, and provides convenience for subsequent conversion, such as various coupling reactions, so as to obtain the derivative with more functional groups. The synthesized organic phosphate compound can be widely applied to the fields of medicines and materials.
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In order to more clearly illustrate the embodiments of the invention or the technical solutions of the prior art, the drawings which are used in the description of the embodiments or the prior art will be briefly described, it being obvious that the drawings in the description below are only some embodiments of the invention, and that other drawings can be obtained from these drawings without inventive faculty for a person skilled in the art.
FIG. 1 is a chart showing nuclear magnetic resonance 1H of bis (2, 4-trimethylpentyl) phosphonic acid (3 a) provided in example 1 of the present invention;
FIG. 2 is a chart showing the nuclear magnetic resonance 13C spectrum of bis (2, 4-trimethylpentyl) phosphonic acid (3 a) provided in example 1 of the present invention;
FIG. 3 is a nuclear magnetic resonance 31 P spectrum of bis (2, 4-trimethylpentyl) phosphonic acid (3 a) provided in example 1 of the present invention.
Detailed Description
Organic phosphate compounds have a wide range of applications in the pharmaceutical and/or material field, for example: bis (2, 4-trimethyl amyl) phosphonic acid is widely used as a high-selectivity and high-efficiency metal ion separation extractant for extracting metal elements such as nickel, cobalt, rare earth and the like from large-scale resources such as seawater and the like. ( See: heteroatom Chemistry,1993,4,23-31; journal of Molecular Liquids,2015,209,203-208 )
The invention provides a method for electrocatalytic synthesis of an organic phosphate compound, which comprises the following steps:
In an inert solvent, under the action of an electrode and an electrolyte, adding or not adding an additive, and carrying out electrocatalytic reaction on a compound of the formula (I) and a compound of the formula (II) to obtain a compound of the formula (III), namely an organic phosphoric acid compound;
wherein R 1 is selected from saturated or unsaturated alkyl, phenyl, substituted phenyl, O-containing heterocyclic substituted alkyl, condensed ring aryl, saturated or unsaturated linear alkyl or cyclic alkyl containing halogen, ester, carbonyl, amino, nitro, cyano, sulfonyl and acyl;
R 2 is selected from hydrogen, sodium, potassium, lithium and other metal ions.
The reaction mechanism of the invention for synthesizing the organic phosphate compound by adopting the electrocatalytic method is as follows:
In one or more preferred embodiments of the invention, the electrocatalytic reaction is carried out in an undivided cell, which employs a double electrode structure, i.e. an anode and a cathode.
In one or more preferred embodiments, the compound of formula (I) is styrene, substituted styrene, alkyl alkene, substituted alkyl alkene, phenylacetylene, substituted phenylacetylene, alkyl alkyne, or substituted alkyl alkyne;
More preferably, the compound of formula (I) is an alkyl olefin or a substituted alkyl olefin.
In one or more preferred embodiments, the compound of formula (II) is hypophosphorous acid or hypophosphite;
More preferably, the compound of formula (II) is a sodium, potassium, lithium salt of hypophosphorous acid.
In one or more preferred embodiments, the compound of formula (III), i.e. the organophosphate compound, is selected from the following compounds:
R 1 is alkyl, such as bis (2, 4-trimethylpentyl) phosphonic acid; r 1 is aryl, such as diphenylethyl phosphonic acid; r 1 is an unsaturated linear hydrocarbyl group, such as bis (4-phenylbut-3-en-1-yl) phosphonic acid, bis (4-phenylbut-3-yn-1-yl) phosphonic acid; r 1 is a cyclic hydrocarbon group, such as bis (cyclohexylmethyl) phosphonic acid.
In one or more preferred embodiments, the molar ratio of the compound of formula (I) to the compound of formula (II) is from 20:1 to 1:20;
Further preferably (0.5 to 10): 1, for example: 1:1, 2: 1. 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1.
In one or more preferred embodiments, the electrolyte is selected from the group consisting of ammonium, lithium, sodium, potassium, zinc, aluminum, or magnesium salts;
further preferably, the electrolyte is tetrabutylammonium iodide, tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium fluoride; more preferably, the electrolyte is tetrabutylammonium bromide.
The selection of anode and cathode materials for electrocatalytic reaction is particularly important for electrochemical reaction, the anode materials can be selected from Reticular Vitreous Carbon (RVC) and the like with good chemical corrosion resistance and high specific surface area, and the cathode materials can be selected from metal Pt and the like with good hydrogen evolution electrocatalytic activity.
In one or more preferred embodiments, the electrode is selected from a metal electrode, which is a copper electrode, an iron electrode, an aluminum electrode, a platinum electrode, a gold electrode, or a zinc electrode, or a non-metal electrode, which is a carbon electrode; more preferably, the electrode is a platinum electrode or a carbon electrode. In the invention, the platinum electrode and the carbon electrode are two types of commercial materials, can be widely obtained, saves the cost of reaction and can be repeatedly used.
In one or more preferred embodiments, the size of the electrodes is 1×10mm to 100×100mm; more preferably, the size of the electrode material is 4X 50mm.
Since the current density tends to affect the efficiency of the preparation electrolysis, how to select the appropriate current magnitude also has a significant impact on the reaction.
In one or more preferred embodiments, the electrocatalytic reaction has a current level of 0.1mA to 100mA; more preferably, the current is 0.5mA-50mA, for example: 1mA, 2mA, 4mA, 5mA, 8mA, 10mA, 15mA, 20mA, 30mA, 40mA.
In one or more preferred embodiments, the inert solvent is selected from toluene, tetrahydrofuran, 1, 4-dioxane, N '-dimethylformamide, N' -dimethylacetamide, N-methylpyrrolidone, dimethylsulfoxide, acetonitrile, 1, 2-dichloroethane; more preferably, the inert solvent is N, N' -dimethylformamide;
In one or more preferred embodiments, the inert solvent is used in an amount of 0.5mL to 5mL; more preferably, the inert solvent is used in an amount of 4mL.
In one or more preferred embodiments, the additive is one or more of sodium acetate, lithium carbonate, potassium carbonate, cesium carbonate, or potassium acetate.
In one or more preferred embodiments, the catalytic reaction temperature is from 0 ℃ to 120 ℃, further preferably from 5 ℃ to 60 ℃; for example: 10 ℃, 15 ℃, 20 ℃, 25 ℃, 30 ℃, 40 ℃;
preferably, the catalytic reaction time is 3-24 hours.
In one or more preferred embodiments, after the reaction is completed, the method further comprises a separation and purification step:
preferably, the separation and purification steps are as follows:
Cooling to room temperature after the reaction is finished, filtering by diatomite, and concentrating to obtain a crude product; separating the crude product by chromatography with silica gel plate to obtain the product; the developing agent or eluent adopted by the chromatographic separation is petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 20:1.
The invention also provides the organic phosphoric acid compound prepared by the synthesis method.
The invention also provides application of the organic phosphate compound obtained by the synthesis method in the field of medicines and/or materials. For example: the method is applied to the fields of medicine molecule synthesis, metal ion adsorption materials and the like.
The technical solutions of the present invention will be clearly and completely described in conjunction with the embodiments of the present invention, and it is apparent that the described examples are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, other embodiments that may be obtained by those of ordinary skill in the art without making any inventive effort are within the scope of the present invention.
The organic phosphate compound, the synthesis method thereof and the raw materials and reagents used in the application can be purchased from the market.
Example 1: bis (2, 4-trimethylpentyl) phosphonic acid (3 a)
A dry 5-mL vial fitted with a polytetrafluoroethylene-coated magnetic stir bar (10 mm. Times.3 mm) was charged to a glove box, and then 2, 4-trimethylpentene (112.0 mg,1.0 mmol), sodium hypophosphite (17.6 mg,0.2 mmol), tetrabutylammonium bromide (64.4 mg,0.2 mmol) was added to the reaction vial in sequence. Anhydrous and degassed DMF (2.0 mL) was added via syringe. Then, the reaction flask was closed with an aluminum sheet (4X 50 mm) as the anode and stainless steel (4X 50 mm) as the cathode using a Teflon cap. The reaction mixture was stirred and was electrolyzed at room temperature at a constant current of 4mA overnight.
After the reaction was completed, the mixture was transferred to a 50mL round bottom flask, and the electrode was washed with ethyl acetate. Water (20 mL) was then added and the mixture was extracted three times with ethyl acetate (20 mL). The combined organic layers were washed with water (20 mL) and brine (20 mL). The organic layer was dried over anhydrous sodium sulfate and then concentrated in vacuo. Purifying the product by using n-hexane/ethyl acetate as an eluent and adopting a silica gel column chromatography, wherein the volume ratio of petroleum ether to ethyl acetate is 200 as the selected developing agent or eluent: 1, to obtain the product bis (2, 4-trimethylpentyl) phosphonic acid (3 a): colorless liquid, yield 98% (56.8 mg).
The determination result of the nuclear magnetic resonance hydrogen spectrum of the bis (2, 4-trimethylpentyl) phosphonic acid (3 a) is ：1H NMR(400MHz,CDCl3)δ11.53(brs,1H),2.13-2.03(m,2H),1.81-1.71(m,2H),1.62-1.53(m,2H),1.39-1.34(m,2H),1.25-1.19(m,2H),1.14-1.10(m,6H),0.93(s,9H);
The nuclear magnetic resonance carbon spectrum measurement result of the bis (2, 4-trimethylpentyl) phosphonic acid (3 a) is as follows: 13C NMR(100MHz,CDCl3 ) Delta 53.2,53.1,39.9,31.2,30.1,24.3;
The determination result of the nuclear magnetic resonance phosphine spectrum of the bis (2, 4-trimethylpentyl) phosphonic acid (3 a) is as follows: 31P NMR(121MHz,CDCl3 ) Delta 58.84,58.78.
Example 2: diphenylethyl phosphonic acid (3 b)
A dry 5-mL vial fitted with a polytetrafluoroethylene-coated magnetic stirring bar (10 mm. Times.3 mm) was charged to a glove box, and then styrene (208.2 mg,2.0 mmol), potassium hypophosphite (20.8 mg,0.2 mmol), tetrabutylammonium bromide (193.2 mg,0.6 mmol) were added to the reaction vial in sequence. Anhydrous and degassed DMF (3.0 mL) was added via syringe. Then, the reaction flask was closed with an aluminum sheet (4X 50 mm) as the anode and stainless steel (4X 50 mm) as the cathode using a Teflon cap. The reaction mixture was stirred and electrolyzed at 30℃for 16h with a constant current of 6 mA.
After the reaction was completed, the mixture was transferred to a 50mL round bottom flask, and the electrode was washed with ethyl acetate. Water (20 mL) was then added and the mixture was extracted three times with ethyl acetate (20 mL). The combined organic layers were washed with water (20 mL) and brine (20 mL). The organic layer was dried over anhydrous sodium sulfate and then concentrated in vacuo. Purifying the product by using n-hexane/ethyl acetate as an eluent and adopting a silica gel column chromatography, wherein the volume ratio of petroleum ether to ethyl acetate is 50:1, to obtain the product diphenyl ethyl phosphonic acid (3 b): colorless liquid, yield 94% (51.5 mg).
The determination result of the nuclear magnetic resonance hydrogen spectrum of the diphenyl ethyl phosphonic acid (3 b) is ：1H NMR(400MHz,CDCl3)δ7.32-7.28(m,2H),7.26-7.22(m,4H),7.20-7.19(m,2H),7.14-7.09(m,2H),3.02(t,J＝6.4Hz,4H),1.96(t,J＝7.6Hz,4H);
The nuclear magnetic resonance carbon spectrum of the diphenyl ethyl phosphonic acid (3 b) is determined as follows: 13C NMR(100MHz,CDCl3 ) Delta 142.3,130.2,129.7,128.6,36.2,26.1;
The determination result of the nuclear magnetic resonance phosphine spectrum of the diphenyl ethyl phosphonic acid (3 b) is as follows: 31P NMR(121MHz,CDCl3 ) Delta 56.14,56.12.
Example 3: bis (4-phenylbut-3-en-1-yl) phosphonic acid (3 c)
A dry 10-mL vial fitted with a polytetrafluoroethylene-coated magnetic stirring bar (10 mm. Times.3 mm) was charged to a glove box, and then 1-benzene-1, 3-butadiene (65.1 mg,0.5 mmol), hypophosphorous acid (12.8 mg,0.2 mmol), tetrabutylammonium bromide (386.4 mg,1.2 mmol) was added to the reaction vial in sequence. Anhydrous and degassed DMF (4.0 mL) was added via syringe. Then, the reaction flask was closed with an aluminum sheet (4X 50 mm) as the anode and stainless steel (4X 50 mm) as the cathode using a Teflon cap. The reaction mixture was stirred and was electrolyzed at room temperature for 3h at a constant current of 8 mA.
After the reaction was completed, the mixture was transferred to a 50mL round bottom flask, and the electrode was washed with ethyl acetate. Water (20 mL) was then added and the mixture was extracted three times with ethyl acetate (20 mL). The combined organic layers were washed with water (20 mL) and brine (20 mL). The organic layer was dried over anhydrous sodium sulfate and then concentrated in vacuo. Purifying the product by using n-hexane/ethyl acetate as an eluent and adopting a silica gel column chromatography, wherein the selected developing agent or eluent is petroleum ether and ethyl acetate in a volume ratio of 30:1 to give the product bis (4-phenylbut-3-en-1-yl) phosphonic acid (3 c): colorless liquid, yield 89% (58.1 mg).
The determination result of the nuclear magnetic resonance hydrogen spectrum of the bis (4-phenylbut-3-en-1-yl) phosphonic acid (3 c) is ：1H NMR(400MHz,CDCl3)δ7.33-7.29(m,6H),7.27-7.26(m,2H),6.62(d,J＝8.0Hz,2H),6.59-6.48(m,2H),6.46-6.40(m,2H),2.62(m,4H),1.89(m,4H);
The determination result of the nuclear magnetic resonance carbon spectrum of the bis (4-phenylbut-3-en-1-yl) phosphonic acid (3 c) is as follows: 13C NMR(100MHz,CDCl3 ) Delta 138.4,128.6,128.5,128.1,127.6,127.4,122.2,35.6,22.0;
The determination result of the nuclear magnetic resonance phosphine spectrum of the bis (4-phenylbut-3-en-1-yl) phosphonic acid (3 c) is as follows: 31P NMR(121MHz,CDCl3 ) Delta 57.10,57.09.
Example 4: bis (4-phenylbut-3-yn-1-yl) phosphonic acid (3 d)
A dry 10-mL vial fitted with a polytetrafluoroethylene-coated magnetic stirring bar (10 mm. Times.3 mm) was charged to a glove box, and then 3-butene-1-ynylbenzene (38.4 mg,0.3 mmol), lithium hypophosphite (14.4 mg,0.2 mmol), tetrabutylammonium bromide (515.2 mg,1.6 mmol) was added to the reaction vial in sequence. Anhydrous and degassed DMF (4.0 mL) was added via syringe. Then, the reaction flask was closed with an aluminum sheet (4X 50 mm) as the anode and stainless steel (4X 50 mm) as the cathode using a Teflon cap. The reaction mixture was stirred and was subjected to electrolytic reaction at 60℃for 8 hours at a constant current of 20 mA.
After the reaction was completed, the mixture was transferred to a 50mL round bottom flask, and the electrode was washed with ethyl acetate. Water (20 mL) was then added and the mixture was extracted three times with ethyl acetate (20 mL). The combined organic layers were washed with water (20 mL) and brine (20 mL). The organic layer was dried over anhydrous sodium sulfate and then concentrated in vacuo. Purifying the product by using n-hexane/ethyl acetate as an eluent and adopting a silica gel column chromatography, wherein the selected developing agent or eluent is petroleum ether and ethyl acetate in a volume ratio of 20:1 to obtain the product bis (4-phenylbut-3-yn-1-yl) phosphonic acid (3 d): colorless liquid, yield 78% (50.2 mg).
The determination result of the nuclear magnetic resonance hydrogen spectrum of the bis (4-phenylbut-3-yn-1-yl) phosphonic acid (3 d) is ：1H NMR(400MHz,CDCl3)δ7.44-7.41(m,4H),7.29-7.22(m,6H),2.29(t,J＝6.0Hz,4H),1.82-1.78(m,4H);
The determination result of the nuclear magnetic resonance carbon spectrum of the bis (4-phenylbut-3-yn-1-yl) phosphonic acid (3 d) is as follows: 13C NMR(100MHz,CDCl3 ) Delta 128.6,128.2,126.5,124.8,101.9,82.0,32.8,3.0;
The determination result of the nuclear magnetic resonance phosphine spectrum of the bis (4-phenylbut-3-yn-1-yl) phosphonic acid (3 d) is as follows: 31P NMR(121MHz,CDCl3 ) Delta 59.12,59.11.
Example 5: bis (cyclohexylmethyl) phosphonic acid (3 e)
A dry 5-mL vial fitted with a polytetrafluoroethylene-coated magnetic stirring bar (10 mm. Times.3 mm) was charged to a glove box, and then 3-butene-1-alkynylbenzene (22.0 mg,0.2 mmol), hypophosphorous acid (19.2 mg,0.3 mmol), tetrabutylammonium bromide (96.6 mg,0.3 mmol) was added to the reaction vial in sequence. Anhydrous and degassed DMF (1.0 mL) was added via syringe. Then, the reaction flask was closed with an aluminum sheet (4X 50 mm) as the anode and stainless steel (4X 50 mm) as the cathode using a Teflon cap. The reaction mixture was stirred and was subjected to electrolytic reaction at 45℃for 4 hours at a constant current of 40 mA.
After the reaction was completed, the mixture was transferred to a 50mL round bottom flask, and the electrode was washed with ethyl acetate. Water (20 mL) was then added and the mixture was extracted three times with ethyl acetate (20 mL). The combined organic layers were washed with water (20 mL) and brine (20 mL). The organic layer was dried over anhydrous sodium sulfate and then concentrated in vacuo. Purifying the product by using n-hexane/ethyl acetate as an eluent and adopting a silica gel column chromatography, wherein the selected developing agent or eluent is petroleum ether and ethyl acetate in a volume ratio of 20:1, to obtain the product bis (cyclohexylmethyl) phosphonic acid (3 e): colorless liquid, yield 84% (43.3 mg).
The determination result of the nuclear magnetic resonance hydrogen spectrum of the bis (cyclohexylmethyl) phosphonic acid (3 e) is ：1H NMR(400MHz,CDCl3)δ1.52-1.48(m,4H),1.44-1.42(m,4H),1.41-1.39(m,2H),1.39-1.35(m,4H),1.30-1.16(m,6H),1.09-1.02(m,6H);
The nuclear magnetic resonance carbon spectrum of the bis (cyclohexylmethyl) phosphonic acid (3 e) is determined as follows: 13C NMR(100MHz,CDCl3 ) Delta 40.6,38.5,37.4,35.0,29.2,25.8,25.4,23.0,22.4,20.0,14.0;
The determination result of the nuclear magnetic resonance phosphine spectrum of the bis (cyclohexylmethyl) phosphonic acid (3 e) is as follows: 31P NMR(121MHz,CDCl3 ) Delta 63.12,63.10.
The above embodiments are only for illustrating the technical solution of the present invention, and not for limiting the same; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims (10)

1. A method for electrocatalytic synthesis of an organophosphate compound, comprising the steps of:
In an inert solvent, under the action of an electrode and an electrolyte, adding or not adding an additive, and carrying out electrocatalytic reaction on a compound of the formula (I) and a compound of the formula (II) to obtain a compound of the formula (III), namely an organic phosphoric acid compound;
wherein R 1 is selected from saturated or unsaturated alkyl, phenyl, substituted phenyl, O-containing heterocyclic substituted alkyl, condensed ring aryl, saturated or unsaturated linear alkyl or cyclic alkyl containing halogen, ester, carbonyl, amino, nitro, cyano, sulfonyl and acyl;
r 2 is selected from hydrogen, sodium, potassium, lithium, saturated or unsaturated hydrocarbon groups, phenyl, substituted phenyl, O-containing heterocyclic substituted hydrocarbon groups, condensed ring aryl groups, saturated or unsaturated linear hydrocarbon groups or cyclic hydrocarbon groups containing halogen, ester groups, carbonyl groups, amino groups, nitro groups, cyano groups, sulfonyl groups and acyl groups.
2. The method of electrocatalytic synthesis of an organic phosphoric acid compound according to claim 1, wherein the compound of formula (I) is styrene, substituted styrene, alkyl alkene, substituted alkyl alkene, phenylacetylene, substituted phenylacetylene, alkyl alkyne or substituted alkyl alkyne.
3. The method for electrocatalytic synthesis of an organic phosphate compound according to claim 1, wherein the compound of formula (II) is hypophosphorous acid or hypophosphite.
4. The method for electrocatalytic synthesis of an organic phosphate compound according to claim 1, wherein the compound of formula (III), i.e. the organic phosphate compound, is selected from the following compounds:
Bis (2, 4-trimethylpentyl) phosphonic acid, diphenylethyl phosphonic acid, bis (4-phenylbut-3-en-1-yl) phosphonic acid, bis (4-phenylbut-3-yn-1-yl) phosphonic acid, bis (cyclohexylmethyl) phosphonic acid.
5. The method for electrocatalytic synthesis of an organic phosphate compound according to claim 1, wherein the molar ratio of the compound of formula (I) to the compound of formula (II) is 20:1-1:20.
6. The method of electrocatalytic synthesis of an organic phosphate compound according to claim 1, wherein the electrolyte is selected from ammonium, lithium, sodium, potassium, zinc, aluminum or magnesium salts; preferably, the electrolyte is tetrabutylammonium iodide, tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium fluoride;
Preferably, the electrode is selected from a metal electrode or a non-metal electrode; further preferably, the metal electrode is a copper electrode, an iron electrode, an aluminum electrode, a platinum electrode, a gold electrode or a zinc electrode, and the nonmetal electrode is a carbon electrode;
preferably, the inert solvent is selected from toluene, tetrahydrofuran, 1, 4-dioxane, N '-dimethylformamide, N' -dimethylacetamide, N-methylpyrrolidone, dimethylsulfoxide, acetonitrile, 1, 2-dichloroethane.
7. The method for electrocatalytic synthesis of an organic phosphate compound according to claim 1, wherein the magnitude of the electrocatalytic reaction current is 0.1mA to 100mA.
8. The method for electrocatalytic synthesis of an organic phosphate compound according to claim 1, wherein the catalytic reaction temperature is 0-120 ℃;
preferably, the catalytic reaction time is 3-24 hours.
9. An organic phosphoric acid compound produced by the method for electrocatalytic synthesis of an organic phosphoric acid compound according to any one of claims 1 to 8.
10. Use of the organophosphate compound according to claim 9, in the pharmaceutical and/or material field.
CN202410218523.7A 2024-02-28 2024-02-28 Method for electrocatalytic synthesis of organic phosphoric acid compound and application thereof Pending CN118086931A (en)

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