CN110437280B - Novel method for preparing 2 '-iodo [1, 1' -biaryl ] -2-organic phosphonate compound - Google Patents

Novel method for preparing 2 '-iodo [1, 1' -biaryl ] -2-organic phosphonate compound Download PDF

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CN110437280B
CN110437280B CN201910372819.3A CN201910372819A CN110437280B CN 110437280 B CN110437280 B CN 110437280B CN 201910372819 A CN201910372819 A CN 201910372819A CN 110437280 B CN110437280 B CN 110437280B
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biphenyl
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CN110437280A (en
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熊碧权
王刚
唐课文
刘宇
许卫凤
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Hunan Institute of Science and Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
    • C07F9/40—Esters thereof
    • C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/4021—Esters of aromatic acids (P-C aromatic linkage)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
    • C07F9/40—Esters thereof
    • C07F9/4071—Esters thereof the ester moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/4084—Esters with hydroxyaryl compounds

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Abstract

The invention provides a novel method for efficiently and selectively synthesizing 2 '-iodo [1, 1' -biaryl ] -2-organic phosphonate compounds containing different substituted functional groups, which adopts cheap transition metal copper salt as a catalyst, takes a compound containing P (O) -OH and biaryl trifluoromethanesulfonic acid high-iodine salt as reaction substrates, and adds an organic solvent and alkali into a reaction system. The method has the advantages that: the catalyst is cheap and easy to obtain; the substrate applicability is high; the reaction condition is mild, safe and reliable; the selectivity of the obtained target product is close to 100 percent, and the yield is up to more than 90 percent. The method overcomes the defects of poor reaction selectivity, complicated reaction steps, low yield, the need of using reagents harmful to the environment and the like in the traditional synthesis of the 2 '-iodo [1, 1' -biaryl ] -2-organic phosphonate compound, and has good industrial application prospect. The invention also provides corresponding 2 '-iodo [1, 1' -biaryl ] -2-organic phosphonate derivatives containing different functional group substitutions.

Description

Novel method for preparing 2 '-iodo [1, 1' -biaryl ] -2-organic phosphonate compound
Technical Field
The invention relates to the field of application catalytic synthesis of 2 '-iodo [1, 1' -biaryl ] -2-organic phosphonate compounds, in particular to a novel method for preparing 2 '-iodo [1, 1' -biaryl ] -2-organic phosphonate compounds by copper-catalyzed cross-coupling reaction of P (O) -OH compounds and biaryl trifluoromethanesulfonic acid high-iodine salts.
Background
The 2 '-halogenated [1, 1' -biaryl ] -2-organic phosphonate compound is an important organic compound and an organic intermediate building block in organic synthesis, and the compound has good catalytic activity, optical activity and biological activity. Especially, the iodide compound has high reaction activity, so that the iodide compound can be selectively modified aiming at the compound, and the iodide compound also has wide application in the aspects of biological, medical, optical active materials, asymmetric catalytic synthesis and the like. In addition, phosphorus element and organic phosphorus compound are indispensable in living bodies, such as ADP, ATP, RNA, organic phospholipid bilayer, etc. in the human body. However, it is difficult to find a natural organic phosphate compound in nature, and most of phosphorus exists in nature in the form of inorganic salt, and most of organic phosphate compounds known at present are synthesized by a chemical method.
In recent years, with the continuous expansion of the application field of organic phosphonate (especially as organic ligand and organic functional block), the market demand is also increasing, and the development of new, green and environment-friendly synthesis technology with high atom economic benefit is also receiving more and more attention. The most common method for synthesizing 2 '-halogenated [1, 1' -biaryl ] -2-organic phosphonate compounds at present mainly comprises the following steps: (a) Atherton-Todd reaction: directly halogenating a P (O) -H compound by carbon tetrachloride, and further carrying out cross coupling reaction with an alpha-halohydrin compound under the catalysis of triethylamine; (b) oxidative dehydrogenation coupling reaction: adopting a P (O) -H compound as a phosphorylation reagent, and promoting the oxidative dehydrogenation reaction of the P (O) -H compound and an alpha-halogenated alcohol compound by using an oxidant (oxygen, tert-butyl peroxide and the like) in the presence of a catalyst such as transition metal palladium, nickel and the like; (c) and (3) cross-coupling reaction: the cross-coupling reaction of P (O) -OH and alpha, beta-dihaloalkane compound is catalyzed by noble metal catalyst (palladium, silver, rhodium, ruthenium, etc.) under the action of alkali. However, the above methods generally employ air-sensitive reagents (p (o) -H compounds, carbon tetrachloride, etc.) and expensive transition metal catalysts (palladium, silver, rhodium, ruthenium, etc.), and have disadvantages of complicated experimental steps, expensive and difficult catalyst recycling, severe reaction conditions, cross-reactivity of substrates, low yield, and great environmental pollution.
So far, the high-efficiency synthesis of organic phosphonate compounds still has the problems of raw material quality, production safety, product stability, product purity and the like, and the synthesis technology has great difficulty. Few companies producing refined products of organic phosphonate in Shandong, Henan and the like in China face technical and environmental problems and are subjected to restrictive production. At present, only a few companies in the countries of America, Japan and the like are in production, and the current situation of high-end organic phosphonate products in China mainly depends on import.
Aiming at the defects of the existing organic phosphonate ester synthesis process, the industry is focusing on developing a method for efficiently and selectively synthesizing the corresponding organic phosphonate ester compound by using a stable, cheap and easily obtained P (O) -OH-containing compound as a raw material.
Disclosure of Invention
The invention aims to provide a synthetic method for preparing a 2 '-iodo [1, 1' -biaryl ] -2-organic phosphonate compound by using a cheap and easily-obtained P (O) -OH compound as a phosphorylation reagent and using a cheap transition metal copper salt to catalyze the cross-coupling reaction between the phosphorylation reagent and biaryl trifluoromethanesulfonic acid high-iodine salt, so as to overcome the defects in the prior art.
An object of the invention is to provide a method for efficiently and selectively synthesizing a corresponding 2 '-iodo [1, 1' -biaryl ] -2-organic phosphonate compound from a cheap and easily available P (O) -OH-containing compound and biaryl trifluoromethanesulfonic acid high-iodine salt under the catalysis of copper salt, which comprises the following steps: putting a reaction amount of a compound containing P (O) -OH, a biaryl trifluoromethanesulfonic acid high-iodine salt, alkali and an organic solvent in a reaction container under the protection of nitrogen, mixing, and reacting for 6-12 hours at 25-100 ℃ under stirring to obtain corresponding 2 '-iodo [1, 1' -biaryl ] -2-organic phosphonate derivatives containing different functional group substitutions;
Figure DEST_PATH_IMAGE001
wherein the content of the first and second substances,
R1is selected from hydrogen atom, methyl, methoxyl, fluorine atom, chlorine atom, trifluoromethyl;
R2is selected from hydrogen atom, methyl, methoxyl, fluorine atom, chlorine atom, trifluoromethyl;
R3is phenyl, 3-methylphenyl, 4-methylphenyl, 3, 5-dimethylphenyl, 3-fluorophenyl, 4-methoxyphenyl, 1-naphthyl, 2-naphthyl;
R4is phenyl, 3-methylphenyl, 4-methylphenyl, 3, 5-dimethylphenyl, 3-fluorophenyl, 4-methoxyphenyl, 1-naphthyl, 2-naphthyl, methyl;
the above-mentioned P (O) -OH compound and biaryl trifluoromethanesulfoneSynthesis of 2 '-iodo [1, 1' -biaryl group from acid periodate]-2-organic phosphonate compound, wherein in the reacting step the base is selected from the group consisting of diisopropylethylamine, 1, 8-diazabicycloundec-7-ene,N,N-dimethylaniline,N,N-diethylaniline,N,N-dimethylbenzylamine, triethylamine, potassium carbonate, sodium carbonate, potassium phosphate, potassium hydroxide, sodium hydroxide or cesium carbonate.
In the above method for synthesizing a 2 '-iodo [1, 1' -biaryl ] -2-organophosphonate compound from a p (o) -OH compound and a biaryltrifluoromethanesulfonic acid periodate, the p (o) -OH compound is selected from diphenyl phosphoric acid, bis (3-methyl-phenyl) phosphoric acid, bis (4-methyl-phenyl) phosphoric acid, bis (3, 5-dimethyl-phenyl) phosphoric acid, bis (3-fluoro-phenyl) phosphoric acid, bis (4-methoxy-phenyl) phosphoric acid, bis (1-naphthyl) phosphoric acid, bis (2-naphthyl) phosphoric acid, and methylphenyl phosphoric acid.
In the above method for synthesizing 2 ' -iodo [1,1 ' -biaryl ] -2-organophosphonate from a P (O) -OH compound and a biaryl trifluoromethanesulfonic acid periodate, the biaryl trifluoromethanesulfonic acid periodate is selected from the group consisting of 4,4 ' -dimethyl- [1,1 ' -biphenyl ] -2,2 ' -trifluoromethanesulfonic acid periodate, 5 ' -difluoro- [1,1 ' -biphenyl ] -2,2 ' -trifluoromethanesulfonic acid periodate, 4 ' -dichloro- [1,1 ' -biphenyl ] -2,2 ' -trifluoromethanesulfonic acid periodate, a salt thereof, and a salt thereof, 4-hydro-4 ' -fluoro- [1,1 ' -biphenyl ] -2,2 ' -trifluoromethanesulfonic acid periodate, 4-hydro-4 ' -chloro-5 ' -fluoro- [1,1 ' -biphenyl ] -2,2 ' -trifluoromethanesulfonic acid periodate, 5-hydro-5 ' -trifluoromethyl- [1,1 ' -biphenyl ] -2,2 ' -trifluoromethanesulfonic acid periodate, 5-hydro-5 ' -methoxy- [1,1 ' -biphenyl ] -2,2 ' -trifluoromethanesulfonic acid periodate, and a salt thereof, 5-methoxy-5 '-trifluoromethyl- [1, 1' -biphenyl ] -2,2 '-trifluoromethane sulfonic acid high iodide salt, 6-hydrogen-6' -methoxy- [1,1 '-biphenyl ] -2, 2' -trifluoromethane sulfonic acid high iodide salt.
The synthesis of 2 '-iodo [1, 1' -biaryl by P (O) -OH compound and biaryl trifluoromethanesulfonic acid periodate]-2-organic phosphonate compound, wherein the organic solvent is selected from the group consisting of toluene, tetrahydrofuran, dichloromethane, dichloroethane, mixtures thereof,N,N-dimethylformamide, 1, 4-dioxane, acetone, ethyl acetate, acetonitrile.
In the above method for synthesizing 2 '-iodo [1, 1' -biaryl ] -2-organophosphonate compound from p (o) -OH compound and biaryl trifluoromethanesulfonic acid periodate, the copper salt is selected from cuprous chloride, cuprous bromide, cuprous iodide, cupric oxide, cuprous oxide, copper powder, cupric chloride, cupric bromide, cupric acetate, copper trifluoromethanesulfonate, and cupric sulfate.
In the above method for synthesizing 2 '-iodo [1, 1' -biaryl ] -2-organophosphonate compound from p (o) -OH compound and biaryl trifluoromethanesulfonic acid periodate, the molar ratio of p (o) -OH compound to biaryl trifluoromethanesulfonic acid periodate is 1: [1.0 to 2.0], wherein the molar ratio of the P (O) -OH compound to the base is 1: [1.0 to 2.0], wherein the molar ratio of the P (O) -OH compound to the copper salt is 1: [0.01 to 0.5 ].
The method for synthesizing the 2 '-iodo [1, 1' -biaryl ] -2-organic phosphonate compound from the P (O) -OH compound and the biaryl trifluoromethanesulfonic acid high-iodine salt with high efficiency and high selectivity, which is provided by the invention, has the advantages of mild and easily controlled reaction process. The method is simple and feasible while obtaining high yield and high selectivity, and the used catalyst is cheap and easy to obtain, is simple to prepare and has good industrial application prospect.
[ detailed description ] embodiments
The invention is further illustrated below with reference to examples of the invention:
first, testing and analyzing
The structural analysis of the reaction products in the following examples of the present invention employed GC/MS (6890N/5973N) gas-mass spectrometer equipped with HP-5MS capillary chromatography column (30 m.times.0.45 mm.times.0.8 μm) manufactured by Agilent and Bruker Avance-III 500 NMR analyzer manufactured by Bruker. The selectivity and yield of the target product were analyzed by Agilent GC 7820A, a gas chromatograph equipped with a hydrogen flame detector, AB-FFAP capillary chromatography column (30 m. times.0.25 mm. times.0.25 μm), manufactured by Agilent.
Second, example
Example 1
109 mg (0.5 mmol) of diphenylphosphoric acid, 215 mg (0.5 mmol) of diiphenyl trifluoromethanesulfonic acid periodate, 0.5 mmol of triethylamine and 7.2 mg (0.05 mmol) of cuprous bromide were added under a nitrogen atmosphere with 2.0 mL of an organic solvent (toluene, tetrahydrofuran, dichloromethane, dichloroethane, dichloromethane, methanol, ethanol, etc.),N,N-dimethylformamide, 1, 4-dioxane, acetone, ethyl acetate, acetonitrile) in 100oC stirring the reaction for 12 hours. The yield of the coupling reaction was 86% when tetrahydrofuran was used as the reaction solvent, as analyzed by GC assay.
Example 2
109 mg (0.5 mmol) of diphenylphosphoric acid, 215 mg (0.5 mmol) of diiphenyl trifluoromethanesulfonic acid periodate, 0.5 mmol of a base (diisopropylethylamine, 1, 8-diazabicycloundece-7-ene, n-diisopropylethylamine, n-diisopropylundec-7-ene, n-diisopropylethylamine, n-isopropyliden-7-ene,N,N-dimethylaniline,N,N-diethylaniline,N,NDimethylbenzylamine, triethylamine, potassium carbonate, sodium carbonate, potassium phosphate, potassium hydroxide, sodium hydroxide or cesium carbonate) with 7.2 mg (0.05 mmol) of cuprous bromide, 2.0 mL of tetrahydrofuran under nitrogen, 100oC stirring the reaction for 12 hours. The yield of the coupling reaction was 86% when triethylamine was used as the base, as analyzed by GC detection.
Example 3
109 mg (0.5 mmol) of diphenylphosphoric acid, 215 mg (0.5 mmol) of biphenyltrifluoromethanesulfonic acid periodate, 0.5 mmol of triethylamine and 0.05 mmol of copper salt (cuprous chloride, cuprous bromide, cuprous iodide, cupric oxide, cuprous oxide, copper powder, cupric chloride, cupric bromide, cupric acetate, trifluoromethanesulfonic acid copper, cupric sulfate) were added with 2.0 mL of tetrahydrofuran under a nitrogen-protected atmosphere, and the mixture was poured into a 100-mL flaskoC stirring the reaction for 12 hours. The yield of the coupling reaction was 92% when cuprous iodide was used as the catalyst, as analyzed by GC assay.
Example 4
109 mg (0.5 mmol) of diphenylphosphoric acid, 258 mg (0.6 mmol) of diiphenyl trifluoromethanesulfonic acid periodate, (0.5 mmol, 0.6 mmol, 0) were added.75 mmol, 1.0 mmol) of triethylamine and 9.6 mg (0.05 mmol) of cuprous iodide under nitrogen atmosphere are added 2.0 mL of tetrahydrofuran, 100oC stirring the reaction for 12 hours. The yield of the coupling reaction was 96% when the amount of triethylamine was 0.75 mmol as determined by GC assay.
Example 5
109 mg (0.5 mmol) of diphenylphosphoric acid, different molar ratios (0.5 mmol, 0.6 mmol, 0.75 mmol, 1.0 mmol) of diiphenyl trifluoromethanesulfonic acid periodate, 0.75 mmol of triethylamine and 9.6 mg (0.05 mmol) of cuprous iodide were added under a nitrogen atmosphere with 2.0 mL of tetrahydrofuran, 100 mg (100 mmol) of tetrahydrofuranoC stirring the reaction for 12 hours. The yield of the coupling reaction was 99% when the amount of the diiodo salt of biphenyltrifluoromethanesulfonic acid was 0.6 mmol as determined by GC.
Example 6
109 mg (0.5 mmol) of diphenylphosphoric acid, 258 mg (0.6 mmol) of diiphenyl trifluoromethanesulfonic acid periodate, 0.75 mmol of triethylamine and cuprous iodide in different molar ratios (0.005 mmol, 0.01 mmol, 0.02 mmol, 0.05 mmol, 0.1 mmol, 0.2 mmol) were added under nitrogen protection to 2.0 mL of tetrahydrofuran in 100 goC stirring the reaction for 12 hours. The yield of the coupling reaction was 99% at 0.05 mmol of cuprous iodide, as determined by GC assay.
Example 7
2 ' -iodo-4, 4 ' -dimethyl- [1,1 ' -biphenyl]Preparation of 2-diphenylphosphonate: 0.5 mmol of diphenylphosphoric acid and 0.6 mmol of 4,4 '-dimethyl- [1, 1' -biphenyl]2.0 mL of tetrahydrofuran in 100 under a nitrogen atmosphere with high iodide salt of (2, 2' -trifluoromethane sulfonic acid), 0.75 mmol of triethylamine and 9.6 mg (0.05 mmol) of cuprous iodideoC stirring the reaction for 12 hours. After the reaction is finished, the 2 ' -iodine-4, 4 ' -dimethyl- [1,1 ' -biphenyl ] with 88 percent of separation yield can be obtained by column chromatography separation and purification]-2-diphenylphosphonate.
Example 8
2 ' -iodo-5, 5 ' -dimethyl- [1,1 ' -biphenyl]Preparation of 2-diphenylphosphonate: 0.5 mmol of diphenyl phosphoric acid and 0.6 mmol of 5, 5'-dimethyl- [1, 1' -biphenyl]2.0 mL of tetrahydrofuran in 100 under a nitrogen atmosphere with high iodide salt of (2, 2' -trifluoromethane sulfonic acid), 0.75 mmol of triethylamine and 9.6 mg (0.05 mmol) of cuprous iodideoC stirring the reaction for 12 hours. After the reaction is finished, 2 ' -iodine-5, 5 ' -dimethyl- [1,1 ' -biphenyl ] with 84 percent of separation yield can be obtained by column chromatography separation and purification]-2-diphenylphosphonate.
Example 9
2 ' -iodo-5, 5 ' -difluoro- [1,1 ' -biphenyl]Preparation of 2-diphenylphosphonate: 0.5 mmol of diphenylphosphoric acid and 0.6 mmol of 5,5 '-difluoro- [1, 1' -biphenyl]2.0 mL of tetrahydrofuran in 100 under a nitrogen atmosphere with high iodide salt of (2, 2' -trifluoromethane sulfonic acid), 0.75 mmol of triethylamine and 9.6 mg (0.05 mmol) of cuprous iodideoC stirring the reaction for 12 hours. After the reaction is finished, the 2 ' -iodine-5, 5 ' -difluoro- [1,1 ' -biphenyl ] with 92 percent separation yield can be obtained by column chromatography separation and purification]-2-diphenylphosphonate.
Example 10
2 ' -iodo-4, 4 ' -dichloro- [1,1 ' -biphenyl]Preparation of 2-diphenylphosphonate: 0.5 mmol of diphenylphosphoric acid and 0.6 mmol of 4,4 '-dichloro- [1, 1' -biphenyl]2.0 mL of tetrahydrofuran in 100 under a nitrogen atmosphere with high iodide salt of (2, 2' -trifluoromethane sulfonic acid), 0.75 mmol of triethylamine and 9.6 mg (0.05 mmol) of cuprous iodideoC stirring the reaction for 12 hours. After the reaction is finished, the 2 ' -iodine-5, 5 ' -difluoro- [1,1 ' -biphenyl ] with 85 percent of separation yield can be obtained by column chromatography separation and purification]-2-diphenylphosphonate.
Example 11
2 ' -iodo-4-hydro-4 ' -fluoro- [1,1 ' -biphenyl]Preparation of 2-diphenylphosphonate: 0.5 mmol of diphenylphosphoric acid and 0.6 mmol of 4-hydro-4 '-fluoro- [1, 1' -biphenyl]2.0 mL of tetrahydrofuran in 100 under a nitrogen atmosphere with high iodide salt of (2, 2' -trifluoromethane sulfonic acid), 0.75 mmol of triethylamine and 9.6 mg (0.05 mmol) of cuprous iodideoC stirring the reaction for 12 hours. After the reaction is finished, the 2 ' -iodine-4-hydrogen-4 ' -fluorine- [1,1 ' -bi-component with 43 percent of separation yield can be obtained by column chromatography separation and purificationPhenyl radical]-2-diphenylphosphonate.
Example 12
2 ' -iodo-4-hydro-4 ' -chloro- [1,1 ' -biphenyl]Preparation of 2-diphenylphosphonate: 0.5 mmol of diphenylphosphoric acid and 0.6 mmol of 4-hydro-4 '-chloro- [1, 1' -biphenyl]2.0 mL of tetrahydrofuran in 100 under a nitrogen atmosphere with high iodide salt of (2, 2' -trifluoromethane sulfonic acid), 0.75 mmol of triethylamine and 9.6 mg (0.05 mmol) of cuprous iodideoC stirring the reaction for 12 hours. After the reaction is finished, the 2 ' -iodine-4-hydrogen-4 ' -chlorine- [1,1 ' -biphenyl ] with 39 percent of separation yield can be obtained by column chromatography separation and purification]-2-diphenylphosphonate.
Example 13
2 '-iodo-4' -chloro-5 '-fluoro- [1, 1' -biphenyl]Preparation of 2-diphenylphosphonate: 0.5 mmol of diphenylphosphoric acid and 0.6 mmol of 4-hydro-4 ' -chloro-5 ' -fluoro- [1,1 ' -biphenyl]2.0 mL of tetrahydrofuran in 100 under a nitrogen atmosphere with high iodide salt of (2, 2' -trifluoromethane sulfonic acid), 0.75 mmol of triethylamine and 9.6 mg (0.05 mmol) of cuprous iodideoC stirring the reaction for 12 hours. After the reaction is finished, the 2 '-iodine-4' -chlorine-5 '-fluorine- [1, 1' -biphenyl ] with the separation yield of 42 percent can be obtained by column chromatography separation and purification]-2-diphenylphosphonate.
Example 14
2 ' -iodo-5-hydro-5 ' -trifluoromethyl- [1,1 ' -biphenyl]Preparation of 2-diphenylphosphonate: 0.5 mmol of diphenylphosphoric acid, 0.6 mmol of 5-hydro-5 '-trifluoromethyl- [1, 1' -biphenyl]2.0 mL of tetrahydrofuran in 100 under a nitrogen atmosphere with high iodide salt of (2, 2' -trifluoromethane sulfonic acid), 0.75 mmol of triethylamine and 9.6 mg (0.05 mmol) of cuprous iodideoC stirring the reaction for 12 hours. After the reaction is finished, the 2 ' -iodine-5-hydrogen-5 ' -trifluoromethyl- [1,1 ' -biphenyl ] with the separation yield of 44 percent can be obtained by column chromatography separation and purification]-2-diphenylphosphonate.
Example 15
2 ' -iodo-5-hydro-5 ' -methoxy- [1,1 ' -biphenyl]Preparation of 2-diphenylphosphonate: 0.5 mmol of diphenylphosphoric acid and 0.6 mmol of 5-hydro-5 '-methoxy- [1, 1' -biphenyl]-2, 2' -trifluoromethylAlkane sulfonic acid high iodine salt, 0.75 mmol triethylamine and 9.6 mg (0.05 mmol) cuprous iodide, adding 2.0 mL tetrahydrofuran under nitrogen protection, 100%oC stirring the reaction for 12 hours. After the reaction is finished, the 2 ' -iodine-5-hydrogen-5 ' -methoxy- [1,1 ' -biphenyl ] with 39 percent of separation yield can be obtained by column chromatography separation and purification]-2-diphenylphosphonate.
Example 16
2 ' -iodo-5-methoxy-5 ' -trifluoromethyl- [1,1 ' -biphenyl]Preparation of 2-diphenylphosphonate: 0.5 mmol of diphenylphosphoric acid and 0.6 mmol of 5-methoxy-5 '-trifluoromethyl- [1, 1' -biphenyl]2.0 mL of tetrahydrofuran in 100 under a nitrogen atmosphere with high iodide salt of (2, 2' -trifluoromethane sulfonic acid), 0.75 mmol of triethylamine and 9.6 mg (0.05 mmol) of cuprous iodideoC stirring the reaction for 12 hours. After the reaction is finished, the 2 ' -iodine-5-hydrogen-5 ' -methoxy- [1,1 ' -biphenyl ] with 36 percent of separation yield can be obtained by column chromatography separation and purification]-2-diphenylphosphonate.
Example 17
2 ' -iodo-6-hydro-6 ' -methoxy- [1,1 ' -biphenyl]Preparation of 2-diphenylphosphonate: 0.5 mmol of diphenylphosphoric acid and 0.6 mmol of 6-hydro-6 '-methoxy- [1, 1' -biphenyl]2.0 mL of tetrahydrofuran in 100 under a nitrogen atmosphere with high iodide salt of (2, 2' -trifluoromethane sulfonic acid), 0.75 mmol of triethylamine and 9.6 mg (0.05 mmol) of cuprous iodideoC stirring the reaction for 12 hours. After the reaction is finished, the 2 ' -iodine-6-hydrogen-6 ' -methoxy- [1,1 ' -biphenyl ] with 39 percent of separation yield can be obtained by column chromatography separation and purification]-2-diphenylphosphonate.
Example 18
2 '-iodo- [1, 1' -biphenyl]Preparation of 2-bis (3-methyl-phenyl) phosphonate: 0.5 mmol of bis (3-methyl-phenyl) phosphoric acid, 0.6 mmol of [1, 1' -biphenyl]2.0 mL of tetrahydrofuran in 100 under a nitrogen atmosphere with high iodide salt of (2, 2' -trifluoromethane sulfonic acid), 0.75 mmol of triethylamine and 9.6 mg (0.05 mmol) of cuprous iodideoC stirring the reaction for 12 hours. After the reaction is finished, the 2' -iodine- [1 ] with 88 percent of separation yield can be obtained by column chromatography separation and purification1' -Biphenyl radical]-2-bis (3-methyl-phenyl) phosphonate.
Example 19
2 '-iodo- [1, 1' -biphenyl]Preparation of 2-bis (4-methyl-phenyl) phosphonate: 0.5 mmol of bis (4-methyl-phenyl) phosphoric acid, 0.6 mmol of [1, 1' -biphenyl]2.0 mL of tetrahydrofuran in 100 under a nitrogen atmosphere with high iodide salt of (2, 2' -trifluoromethane sulfonic acid), 0.75 mmol of triethylamine and 9.6 mg (0.05 mmol) of cuprous iodideoC stirring the reaction for 12 hours. After the reaction is finished, the 2 '-iodine- [1, 1' -biphenyl ] with 81 percent of separation yield can be obtained by column chromatography separation and purification]-2-bis (4-methyl-phenyl) phosphonate.
Example 20
2 '-iodo- [1, 1' -biphenyl]Preparation of 2-bis (3, 5-dimethyl-phenyl) phosphonate: 0.5 mmol of bis (3, 5-dimethyl-phenyl) phosphoric acid, 0.6 mmol of [1, 1' -biphenyl]2.0 mL of tetrahydrofuran in 100 under a nitrogen atmosphere with high iodide salt of (2, 2' -trifluoromethane sulfonic acid), 0.75 mmol of triethylamine and 9.6 mg (0.05 mmol) of cuprous iodideoC stirring the reaction for 12 hours. After the reaction is finished, the 2 '-iodine- [1, 1' -biphenyl ] with the separation yield of 85 percent can be obtained by column chromatography separation and purification]-2-bis (3, 5-dimethyl-phenyl) phosphonate.
Example 21
2 '-iodo- [1, 1' -biphenyl]-preparation of 2-bis (3-fluoro-phenyl) phosphonate: 0.5 mmol of bis (3-fluoro-phenyl) phosphoric acid, 0.6 mmol of [1, 1' -biphenyl]2.0 mL of tetrahydrofuran in 100 under a nitrogen atmosphere with high iodide salt of (2, 2' -trifluoromethane sulfonic acid), 0.75 mmol of triethylamine and 9.6 mg (0.05 mmol) of cuprous iodideoC stirring the reaction for 12 hours. After the reaction is finished, the 2 '-iodine- [1, 1' -biphenyl ] with 69 percent of separation yield can be obtained by column chromatography separation and purification]-2-bis (3-fluoro-phenyl) phosphonate.
Example 22
2 '-iodo- [1, 1' -biphenyl]Preparation of 2-bis (4-methoxy-phenyl) phosphonate: 0.5 mmol of bis (4-methoxy-phenyl) phosphoric acid, 0.6 mmol of [1, 1' -biphenyl]-2, 2' -trifluoromethane sulfonic acid iodoniumSalt, 0.75 mmol of triethylamine and 9.6 mg (0.05 mmol) of cuprous iodide, 2.0 mL of tetrahydrofuran under nitrogen atmosphere, 100oC stirring the reaction for 12 hours. After the reaction is finished, the 2 '-iodine- [1, 1' -biphenyl ] with 78 percent of separation yield can be obtained by column chromatography separation and purification]-2-bis (4-methoxy-phenyl) phosphonate.
Example 23
2 '-iodo- [1, 1' -biphenyl]Preparation of 2-di (1-naphthyl) phosphonate: 0.5 mmol of bis (1-naphthyl) phosphoric acid and 0.6 mmol of [1, 1' -biphenyl]2.0 mL of tetrahydrofuran in 100 under a nitrogen atmosphere with high iodide salt of (2, 2' -trifluoromethane sulfonic acid), 0.75 mmol of triethylamine and 9.6 mg (0.05 mmol) of cuprous iodideoC stirring the reaction for 12 hours. After the reaction is finished, the 2 '-iodine- [1, 1' -biphenyl ] with 78 percent of separation yield can be obtained by column chromatography separation and purification]-2-di (1-naphthyl) phosphonate.
Example 24
2 '-iodo- [1, 1' -biphenyl]Preparation of 2-di (2-naphthyl) phosphonate: 0.5 mmol of bis (2-naphthyl) phosphoric acid and 0.6 mmol of [1, 1' -biphenyl]2.0 mL of tetrahydrofuran in 100 under a nitrogen atmosphere with high iodide salt of (2, 2' -trifluoromethane sulfonic acid), 0.75 mmol of triethylamine and 9.6 mg (0.05 mmol) of cuprous iodideoC stirring the reaction for 12 hours. After the reaction is finished, 2 '-iodine- [1, 1' -biphenyl ] with 82% separation yield can be obtained by column chromatography separation and purification]-2-di (2-naphthyl) phosphonate.
Example 25
2 '-iodo- [1, 1' -biphenyl]Preparation of 2-methylphenylphosphonate: 0.5 mmol of methylphenyl phosphoric acid and 0.6 mmol of [1, 1' -biphenyl group]2.0 mL of tetrahydrofuran in 100 under a nitrogen atmosphere with high iodide salt of (2, 2' -trifluoromethane sulfonic acid), 0.75 mmol of triethylamine and 9.6 mg (0.05 mmol) of cuprous iodideoC stirring the reaction for 12 hours. After the reaction is finished, the 2 '-iodine- [1, 1' -biphenyl ] with 75 percent of separation yield can be obtained by column chromatography separation and purification]-2-methylphenyl phosphonate.
It can be seen from the above examples that the method for synthesizing 2 '-iodo [1, 1' -biaryl ] -2-organophosphonate compound with high efficiency and high selectivity by using p (o) -OH compound and biaryl trifluoromethanesulfonic acid high-iodine salt adopted by the present invention has the advantages of mild reaction conditions, cheap and easily available catalyst, simple reaction steps, etc. In addition, the method also has the advantages of wide substrate applicability, high yield, high selectivity and the like, and provides a method for efficiently synthesizing the 2 '-iodo [1, 1' -biaryl ] -2-organic phosphonate derivative.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the present invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.

Claims (6)

1. A copper-catalyzed P (O) -OH compound and biaryl trifluoromethanesulfonic acid high-iodine salt are used to prepare the compound with structural formula（I）2 '-iodo [1, 1' -biaryl]-2-organic phosphonate compound, as follows:
Figure 986981DEST_PATH_IMAGE001
（I）
the method is characterized by comprising the following steps:
putting a reaction amount of a compound containing P (O) -OH, a biaryl trifluoromethanesulfonic acid high-iodine salt, alkali and an organic solvent in a reaction container under the protection of nitrogen, mixing, and reacting for 6-12 hours at 25-100 ℃ under stirring to obtain corresponding 2 '-iodo [1, 1' -biaryl ] -2-organic phosphonate derivatives containing different functional group substitutions;
wherein the content of the first and second substances,
the catalyst is cuprous iodide, the organic solvent is tetrahydrofuran, and the base is triethylamine;
R1is selected from hydrogen atom, methyl, methoxyl, fluorine atom, chlorine atom, trifluoromethyl;
R2is selected from hydrogen atom, methyl, methoxyl, fluorine atom, chlorine atom, trifluoromethyl;
R3is phenyl, 3-methylphenyl, 4-methylphenyl, 3, 5-dimethylphenyl, 3-fluorophenyl, 4-methoxyphenyl, 1-naphthyl, 2-naphthyl;
R4is phenyl, 3-methylphenyl, 4-methylphenyl, 3, 5-dimethylphenyl, 3-fluorophenyl, 4-methoxyphenyl, 1-naphthyl, 2-naphthyl or methyl.
2. The method according to claim 1, wherein the P- (O) -OH-containing compound is selected from diphenyl phosphate, bis (3-methyl-phenyl) phosphate, bis (4-methyl-phenyl) phosphate, bis (3, 5-dimethyl-phenyl) phosphate, bis (3-fluoro-phenyl) phosphate, bis (4-methoxy-phenyl) phosphate, bis (1-naphthyl) phosphate, bis (2-naphthyl) phosphate, and methylphenyl phosphate.
3. The method according to claim 1, wherein the bisaryl triflate periodate is selected from the group consisting of 4,4 '-dimethyl- [1, 1' -biphenyl ] -2,2 '-triflate periodate, 5' -difluoro- [1,1 '-biphenyl ] -2, 2' -triflate periodate, 4 '-dichloro- [1, 1' -biphenyl ] -2,2 '-triflate periodate, 4-hydro-4' -fluoro- [1,1 '-biphenyl ] -2, 2' -triflate periodate, 4-hydro-4 '-chloro- [1, 1' -biphenyl ] -2,2 '-trifluoromethanesulfonic acid periodate, 4-hydro-4' -chloro-5 '-fluoro- [1, 1' -biphenyl ] -2,2 '-trifluoromethanesulfonic acid periodate, 5-hydro-5' -trifluoromethyl- [1,1 '-biphenyl ] -2, 2' -trifluoromethanesulfonic acid periodate, 5-hydro-5 '-methoxy- [1, 1' -biphenyl ] -2,2 '-trifluoromethanesulfonic acid periodate, 5-methoxy-5' -trifluoromethyl- [1,1 '-biphenyl ] -2, 2' -trifluoromethanesulfonic acid periodate, and a salt thereof, 6-hydrogen-6 ' -methoxy- [1,1 ' -biphenyl ] -2,2 ' -trifluoromethane sulfonic acid high iodine salt.
4. The process according to claim 1, wherein the molar ratio of the P (O) -OH compound to the bisaryl trifluoromethanesulfonic acid periodate is 1: [1.0 to 2.0 ].
5. The method according to claim 1, wherein the molar ratio of the P (O) -OH compound to the catalyst is 1: [0.01 to 0.5 ].
6. The process according to claim 1, wherein the molar ratio of the P (O) -OH compound to the base is 1: [1.0 to 2.0 ].
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CN107082789A (en) * 2017-03-06 2017-08-22 湖南理工学院 A kind of method to prepare organophosphorus ester compound containing P (O) OH classes compound and the efficient esterification of phenol
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CN107082789A (en) * 2017-03-06 2017-08-22 湖南理工学院 A kind of method to prepare organophosphorus ester compound containing P (O) OH classes compound and the efficient esterification of phenol
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