CN106749396B - Method for preparing organic phosphonate compound by efficiently esterifying compound containing P (O) -OH and alcohol - Google Patents

Method for preparing organic phosphonate compound by efficiently esterifying compound containing P (O) -OH and alcohol Download PDF

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CN106749396B
CN106749396B CN201611136064.XA CN201611136064A CN106749396B CN 106749396 B CN106749396 B CN 106749396B CN 201611136064 A CN201611136064 A CN 201611136064A CN 106749396 B CN106749396 B CN 106749396B
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熊碧权
唐课文
张盼良
刘宇
许卫凤
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Hunan Institute of Science and Technology
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    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
    • C07F9/32—Esters thereof
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Abstract

The invention provides a method for efficiently and selectively synthesizing organic phosphonate derivatives containing different substituted functional groups, which adopts a polypeptide catalyst as a condensation reagent, takes a compound containing P (O) -OH and alcohol as reaction substrates, and adds an organic solvent 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 organic phosphonate compounds, and has good industrial application prospect. The invention also provides corresponding organic phosphonate derivatives containing different substituted functional groups.

Description

Method for preparing organic phosphonate compound by efficiently esterifying compound containing P (O) -OH and alcohol
[ technical field ] A method for producing a semiconductor device
The invention relates to the field of application catalytic synthesis of organic phosphonate compounds, in particular to a preparation method for preparing organic phosphonate derivatives by efficiently esterifying P (O) -OH-containing compounds and alcohol.
[ background of the invention ]
The organic phosphonate compounds are important organic compounds in organic synthesis, and have good catalytic activity, optical activity and biological activity, so that the organic phosphonate compounds have wide application in the aspects of biological, medical and optical active materials, asymmetric catalytic synthesis and the like. Phosphorus and organic phosphorus compounds are known to be important substrates in life, such as ADP, ATP, RNA, organic phospholipid bilayers and the like in human bodies. However, it is difficult to find a natural organic phosphonate compound in nature, and most of phosphorus exists in nature in the form of inorganic salt, and most of the organic phosphonate compounds known at present are synthesized by chemical methods.
In recent years, with the continuous expansion of the application field of organic phosphonate (especially as organic ligand), the market demand is also increasing, and the development of new synthesis technology of the compounds is also receiving more and more attention. The synthesis method of the organic phosphonate compounds reported in the literature at present mainly comprises the following steps: (1) Atherton-Todd reaction: catalyzing a P (O) -H bond compound to perform cross coupling reaction with a nucleophilic reagent (alcohol, phenol, amine compound and the like) in the presence of reagents such as carbon tetrachloride, triethylamine and the like; (2) nucleophilic substitution reaction: the compound containing P (O) -H or P (O) -OH reacts with a halogenating agent to prepare a corresponding compound containing P (O) -Cl, and then the compound and a nucleophilic reagent (alcohol, phenol, amine compound and the like) are subjected to cross coupling reaction; (3) arbuzov reaction: the trialkyl phosphite is used as a nucleophilic reagent to react with alkyl halide to prepare the dialkyl alkylphosphonate. (4) And (3) cross-coupling reaction: noble metal catalysts (palladium, silver, copper, nickel) are used for catalyzing the cross coupling reaction of nucleophiles such as P (O) -H and the like and compounds such as R-X/Ar-X and the like. However, the above methods generally employ air-sensitive reagents (p (o) -H compounds, carbon tetrachloride, sulfonyl chloride, etc.), and have the disadvantages of complicated experimental steps, expensive catalyst, difficult recycling, harsh reaction conditions, cross-reactivity of substrates, low yield, and great environmental pollution.
So far, the high-efficiency synthesis of organic phosphonate compounds has the problems of raw material quality, production safety (the compounds such as phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride and the like have strong corrosiveness) and stability, purity and the like of products, the synthesis technology has great difficulty, only a plurality of companies in the countries of America, Japan and the like are used for production at present, 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.
[ summary of the invention ]
The invention aims to provide a method for efficiently and selectively synthesizing corresponding organic phosphonate compounds containing different substituted functional groups by using cheap and easily-obtained P (O) -OH compounds and alcohol compounds as raw materials so as to overcome the defects in the prior art.
The invention aims to provide a method for synthesizing a P (O) -OH-containing compound and an alcohol compound with high efficiency and high selectivity by using a cheap and easily-obtained compoundThe method for preparing the organic phosphonate compound comprises the following steps: taking reaction amount of compound containing P (O) -OH, alcohol, alkali and organic solvent in N2Or placing the mixture in a reaction vessel under the protection of inert gas for mixing, and reacting for 3-12 hours at 25-80 ℃ under stirring to obtain the corresponding organic phosphonate derivatives containing different substituted functional groups. The specific reaction formula is as follows:
Figure GDA0002657604730000021
taking reaction amount of compound containing P (O) -OH, alcohol, alkali, condensation reagent and organic solvent in N2Putting the mixture into a reaction container under protection, mixing, and reacting for 3-12 hours at 25-80 ℃ under stirring to obtain corresponding organic phosphonate derivatives containing different substituted functional groups;
wherein,
the structural formula of the compound containing P (O) -OH is shown as
Figure GDA0002657604730000022
The base is triethylamine;
the organic solvent is dichloroethane;
the condensation reagent is 2- (1H-benzotriazo L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate (TBTU);
the alcohol is R-OH and is selected from benzyl alcohol, methanol, ethanol, n-butyl alcohol, isobutyl alcohol, cyclohexanol, cyclopentanol, trifluoroethanol, 3- (trimethylsilyl) -propiolic alcohol, 3-buten-1-ol, 2-butyn-1-ol, 3-butyn-2-ol, isopropanol, tert-butyl alcohol, 9-fluorenol, 4-bromobenzyl alcohol, 4-nitrobenzyl alcohol and 4-methoxybenzyl alcohol;
R1selected from phenyl, 4-methylphenyl, 4-trifluoromethylphenyl, 2-ethyl-hexyl;
R2selected from phenyl, ethoxy, 4-methylphenyl, 4-trifluoromethylphenyl, 2-ethyl-hexyloxy;
when the P (O) -OH compound is a cyclic phosphonic acid compound, R1And R2Together are a 9, 10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxo substituent.
In the method for synthesizing the organic phosphonate compound from the P (O) -OH compound and the alcohol, the P (O) -OH-containing compound is selected from diphenyl phosphonic acid, bis (4-methyl-phenyl) phosphonic acid, bis (4-trifluoromethyl-phenyl) phosphonic acid, phenyl ethoxy phosphonic acid, 2-ethylhexyl phosphonic acid mono 2-ethylhexyl ester, and 9, 10-dihydro-9-oxa-10-phosphaphenanthrene-10-phosphonic acid.
In the method for synthesizing the organic phosphonate compound by the P (O) -OH compound and the alcohol, the molar ratio of the P (O) -OH compound to the alcohol is 1: 1.0-2.0.
In the method for synthesizing the organic phosphonate compound by the P (O) -OH compound and the alcohol, the molar ratio of the P (O) -OH compound to the alkali is 1: 1.0-5.0.
In the method for synthesizing the organic phosphonate compound by the P (O) -OH compound and the alcohol, the molar ratio of the P (O) -OH compound to the condensation reagent is 1: 1.0-2.0.
The method for synthesizing the organic phosphonate ester compound from the compound containing P (O) -OH and the alcohol compound with high efficiency and high selectivity has mild and easily controlled reaction process. The method is simple and easy to implement while obtaining higher yield and 100 percent 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 GC7820A, 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
109mg (0.5mmol) of diphenylphosphonic acid, 40.5uL (1.0mmol) of methanol, 138uL (1.0mmol) of triethylamine and 161mg (0.5mmol) of 2- (1H-benzotriazol L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate (TBTU) were charged into a Schlenk tube under a nitrogen atmosphere, 1.0mL of an organic solvent (dichloromethane, dichloroethane, tetrahydrofuran, acetonitrile, toluene, N-dimethylformamide, ethyl acetate) was added under a nitrogen atmosphere, and the mixture was stirred at room temperature for 12 hours. The reaction was carried out in 99% yield with dichloroethane as the reaction solvent, as determined by GC analysis.
Example 2
109mg (0.5mmol) of diphenylphosphonic acid, 40.5uL (1.0mmol) of methanol, 1.0mmol of a base (triethylamine, 1, 8-diazabicycloundecen-7-ene, N-dimethylaniline, N-diethylaniline, N-dimethylbenzylamine, diisopropylethylamine, sodium hydrogen carbonate, potassium carbonate, sodium carbonate, cesium carbonate, sodium tert-butoxide, potassium phosphate) and 161mg (0.5mmol) of 2- (1H-benzotriazol L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate (TBTU) were charged into a Schlenk tube under a nitrogen atmosphere, 1.0mL of dichloroethane were added under a nitrogen atmosphere, and the reaction was stirred at room temperature for 12 hours. The reaction was carried out in 99% yield with triethylamine as base, as determined by GC. The efficiency of organic bases in this system is significantly higher than that of inorganic bases, mainly because inorganic bases are prone to the formation of the corresponding phosphonates from p (o) -OH compounds.
Example 3
109mg (0.5mmol) of diphenylphosphonic acid, 40.5uL (1.0mmol) of methanol, 138uL (1.0mmol) of triethylamine and 0.5mmol of a condensation reagent (TBTU: 2- (1H-benzotriazol L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate, COMU: (1-cyano-2-ethoxy-2-oxyethyleneaminoxy) dimethylamino-morpholinyl-carbenium hexafluorophosphate, HATU: O- (7-azabenzotriazole) -N, N, N ', N' -tetramethyluronium hexafluorophosphate, Cartesian condensation agent) were added to a Schlenk tube under nitrogen atmosphere, 1.0mL of dichloroethane was added under nitrogen atmosphere, and the reaction was stirred at room temperature for 12 hours. Analysis by GC detection, at TBTU: when 2- (1H-benzotriazol L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate is used as a condensation reagent of the reaction, the yield of the reaction can reach 99 percent.
Example 4
109mg (0.5mmol) of diphenylphosphonic acid, 40.5uL (1.0mmol) of methanol, 138uL (1.0mmol) of triethylamine and different molar ratios of TBTU: 2- (1H-benzotriazol L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate (0 mol%, 5 mol%, 10 mol%, 20 mol%, 50 mol%, 100 mol%) was charged into a Schlenk tube under a nitrogen atmosphere, and 1.0mL of dichloroethane was added under a nitrogen atmosphere, and the reaction was stirred at room temperature for 12 hours. Analysis by GC detection, only in TBTU: when the using amount of the 2- (1H-benzotriazol L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate is one time of reaction equivalent, the yield of the reaction can reach 99 percent.
Example 5
109mg (0.5mmol) of diphenylphosphonic acid, methanol (0.5mmol, 0.6mmol, 0.75mmol, 1.0mmol, 1.5mmol) in various molar ratios, 138uL (1.0mmol) of triethylamine and 161mg (0.5mmol) of 2- (1H-benzotriazol L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate were charged into a Schlenk tube under a nitrogen atmosphere, and 1.0mL of dichloroethane was charged under a nitrogen atmosphere and stirred at room temperature for 12 hours. The reaction yield reached 99% only when the amount of methanol was 1.0mmol, i.e., twice the reaction equivalent, as determined by GC.
Example 6
109mg (0.5mmol) of diphenylphosphonic acid, 40.5uL (1.0mmol) of methanol, 138uL (1.0mmol) of triethylamine and 161mg (0.5mmol) of 2- (1H-benzotriazol L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate were charged into a Schlenk tube under a nitrogen atmosphere, dichloroethane (0.5mL, 1.0mL, 2.0mL, 5.0mL) was added under a nitrogen atmosphere, and the reaction was stirred at room temperature for 12 hours. The reaction was carried out in 99% yield by GC analysis only at 1.0mL of dichloroethane. The yield of the reaction gradually decreased with increasing amount of solvent.
Example 7
Preparation of O-ethyl-phenyl-phenylphosphinate: 109mg (0.5mmol) of diphenylphosphonic acid, 58.3uL (1.0mmol) of ethanol, 138uL (1.0mmol) of triethylamine and 161mg (0.5mmol) of 2- (1H-benzotriazol L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate were put into a Schlenk tube under a nitrogen atmosphere, and 1.0mL of dichloroethane was added under a nitrogen atmosphere, followed by stirring at room temperature for 12 hours. After the reaction is finished, the O-ethyl-phenyl-phenylphosphinate with the separation yield of 97% can be obtained by column chromatography separation and purification.
Example 8
Preparation of O-butyl-phenyl-phenylphosphinate: 109mg (0.5mmol) of diphenylphosphonic acid, 91.5uL (1.0mmol) of n-butanol, 138uL (1.0mmol) of triethylamine and 161mg (0.5mmol) of 2- (1H-benzotriazol L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate were put into a Schlenk tube under a nitrogen atmosphere, and 1.0mL of dichloroethane was added under a nitrogen atmosphere, followed by stirring at room temperature for 12 hours. After the reaction is finished, the O-ethyl-phenyl-phenylphosphinate with 93% separation yield can be obtained by column chromatography separation and purification.
Example 9
Preparation of O-isobutyl-phenyl-phenylphosphinate: 109mg (0.5mmol) of diphenylphosphonic acid, 92.4uL (1.0mmol) of isobutanol, 138uL (1.0mmol) of triethylamine and 161mg (0.5mmol) of 2- (1H-benzotriazol L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate were charged into a Schlenk tube under a nitrogen atmosphere, and 1.0mL of dichloroethane was added under a nitrogen atmosphere, followed by stirring at room temperature for 12 hours. After the reaction is finished, the O-isobutyl-phenyl-phenylphosphinate with the separation yield of 96% can be obtained by column chromatography separation and purification.
Example 10
Preparation of O-benzyl-phenyl-phenylphosphinate: 109mg (0.5mmol) of diphenylphosphonic acid, 103.8uL (1.0mmol) of benzyl alcohol, 138uL (1.0mmol) of triethylamine and 161mg (0.5mmol) of 2- (1H-benzotriazol L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate were put into a Schlenk tube under a nitrogen atmosphere, and 1.0mL of dichloroethane was added under a nitrogen atmosphere, followed by stirring at room temperature for 12 hours. After the reaction is finished, the O-benzyl-phenyl-phenylphosphinate with 89% separation yield can be obtained by column chromatography separation and purification.
Example 11
Preparation of O-cyclohexyl-phenyl-phenylphosphinate: 109mg (0.5mmol) of diphenylphosphonic acid, 104uL (1.0mmol) of cyclohexanol, 138uL (1.0mmol) of triethylamine and 161mg (0.5mmol) of 2- (1H-benzotriazol L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate were charged into a Schlenk tube under a nitrogen atmosphere, and 1.0mL of dichloroethane was charged under a nitrogen atmosphere, and the mixture was stirred at room temperature for 12 hours. After the reaction is finished, the O-cyclohexyl-phenyl-phenylphosphinate with the separation yield of 97 percent can be obtained by column chromatography separation and purification.
Example 12
Preparation of O-cyclopentyl-phenyl-phenylphosphinate: 109mg (0.5mmol) of diphenylphosphonic acid, 90.7uL (1.0mmol) of cyclopentanol, 138uL (1.0mmol) of triethylamine and 161mg (0.5mmol) of 2- (1H-benzotriazol L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate were charged into a Schlenk tube under a nitrogen atmosphere, and 1.0mL of dichloroethane was added under a nitrogen atmosphere, followed by stirring at room temperature for 12 hours. After the reaction is finished, the O-cyclopentyl-phenyl-phenylphosphinate with the separation yield of 91% can be obtained by column chromatography separation and purification.
Example 13
Preparation of O-trifluoroethyl-phenyl-phenylphosphinate: 109mg (0.5mmol) of diphenylphosphonic acid, 72.4uL (1.0mmol) of trifluoroethanol, 138uL (1.0mmol) of triethylamine and 161mg (0.5mmol) of 2- (1H-benzotriazol L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate were put into a Schlenk tube under a nitrogen atmosphere, and 1.0mL of dichloroethane was added under a nitrogen atmosphere, followed by stirring at room temperature for 12 hours. After the reaction is finished, the O-trifluoroethyl-phenyl-phenylphosphinate with the separation yield of 98% can be obtained by column chromatography separation and purification.
Example 14
Preparation of O-3- (trimethylsilyl) -propynyl-phenyl-phenylphosphinate: 109mg (0.5mmol) of diphenylphosphonic acid, 148.3uL (1.0mmol) of 3- (trimethylsilyl) -propiolic alcohol, 138uL (1.0mmol) of triethylamine and 161mg (0.5mmol) of 2- (1H-benzotriazol L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate were added to a Schlenk's tube under a nitrogen atmosphere, 1.0mL of dichloroethane was added under a nitrogen atmosphere, and the reaction was stirred at room temperature for 12 hours. After the reaction is finished, the O-3- (trimethylsilyl) -propynyl-phenyl-phenylphosphinate with the separation yield of 85 percent can be obtained by column chromatography separation and purification.
Example 15
Preparation of O-3-butenyl-phenyl-phenylphosphinate: 109mg (0.5mmol) of diphenylphosphonic acid, 148.3uL (1.0mmol) of 3-buten-1-ol, 138uL (1.0mmol) of triethylamine and 161mg (0.5mmol) of 2- (1H-benzotriazol L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate were charged into a Schlenk's tube under a nitrogen atmosphere, and 1.0mL of dichloroethane was charged under a nitrogen atmosphere and stirred at room temperature for 12 hours. After the reaction is finished, the O-3-butenyl-phenyl-phenylphosphinate with 93% separation yield can be obtained by column chromatography separation and purification.
Example 16
Preparation of O-2-butynyl-phenyl-phenylphosphinate: 109mg (0.5mmol) of diphenylphosphonic acid, 74.8uL (1.0mmol) of 2-butyn-1-ol, 138uL (1.0mmol) of triethylamine and 161mg (0.5mmol) of 2- (1H-benzotriazol L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate were charged into a Schlenk's tube under a nitrogen atmosphere, and 1.0mL of dichloroethane was added under a nitrogen atmosphere and stirred at room temperature for reaction for 12 hours. After the reaction is finished, the O-2-butynyl-phenyl-phenylphosphinate with 93 percent of separation yield can be obtained by column chromatography separation and purification.
Example 17
Preparation of O-1-methyl-2-propynyl-phenyl-phenylphosphinate: 109mg (0.5mmol) of diphenylphosphonic acid, 78.4uL (1.0mmol) of 3-butyn-2-ol, 138uL (1.0mmol) of triethylamine and 161mg (0.5mmol) of 2- (1H-benzotriazol L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate were charged into a Schlenk's tube under a nitrogen atmosphere, and 1.0mL of dichloroethane was added under a nitrogen atmosphere and stirred at room temperature for reaction for 12 hours. After the reaction is finished, the O-1-methyl-2-propynyl-phenyl-phenylphosphinate with the separation yield of 87% can be obtained by column chromatography separation and purification.
Example 18
Preparation of O-isopropyl-phenyl-phenylphosphinate: 109mg (0.5mmol) of diphenylphosphonic acid, 76.5uL (1.0mmol) of isopropanol, 138uL (1.0mmol) of triethylamine and 161mg (0.5mmol) of 2- (1H-benzotriazol L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate were charged into a Schlenk tube under a nitrogen atmosphere, and 1.0mL of dichloroethane was added under a nitrogen atmosphere, followed by stirring at room temperature for 12 hours. After the reaction is finished, the O-isopropyl-phenyl-phenylphosphinate with the separation yield of 96% can be obtained by column chromatography separation and purification.
Example 19
Preparation of O-tert-butyl-phenyl-phenylphosphinate: 109mg (0.5mmol) of diphenylphosphonic acid, 76.5uL (1.0mmol) of tert-butanol, 138uL (1.0mmol) of triethylamine and 161mg (0.5mmol) of 2- (1H-benzotriazol L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate were charged into a Schlenk tube under a nitrogen atmosphere, and 1.0mL of dichloroethane was added under a nitrogen atmosphere, followed by stirring at room temperature for 12 hours. After the reaction is finished, the O-tert-butyl-phenyl-phenylphosphinate with the separation yield of 92% can be obtained by column chromatography separation and purification.
Example 20
Preparation of O-4-bromo-benzyl-phenyl-phenylphosphinate: 109mg (0.5mmol) of diphenylphosphonic acid, 187mg (1.0mmol) of 4-bromobenzyl alcohol, 138uL (1.0mmol) of triethylamine and 161mg (0.5mmol) of 2- (1H-benzotriazol L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate were charged into a Schlenk tube under a nitrogen atmosphere, and 1.0mL of dichloroethane was added under a nitrogen atmosphere, followed by stirring at room temperature for 12 hours. After the reaction is finished, the O-4-bromine-benzyl-phenyl-phenylphosphinate with the separation yield of 89% can be obtained by column chromatography separation and purification.
Example 21
Preparation of O-4-nitro-benzyl-phenyl-phenylphosphinate: 109mg (0.5mmol) of diphenylphosphonic acid, 153mg (1.0mmol) of 4-nitrobenzyl alcohol, 138uL (1.0mmol) of triethylamine and 161mg (0.5mmol) of 2- (1H-benzotriazol L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate were charged into a Schlenk's tube under a nitrogen atmosphere, and 1.0mL of dichloroethane was added under a nitrogen atmosphere, followed by stirring at room temperature for 12 hours. After the reaction is finished, the O-4-nitro-benzyl-phenyl-phenylphosphinate with 83% separation yield can be obtained by column chromatography separation and purification.
Example 22
Preparation of O-4-methoxy-benzyl-phenyl-phenylphosphinate: 109mg (0.5mmol) of diphenylphosphonic acid, 124.1uL (1.0mmol) of 4-methoxybenzyl alcohol, 138uL (1.0mmol) of triethylamine and 161mg (0.5mmol) of 2- (1H-benzotriazol L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate were put into a Schlenk tube under a nitrogen atmosphere, and 1.0mL of dichloroethane was added under a nitrogen atmosphere, followed by stirring at room temperature for 12 hours. After the reaction is finished, separating and purifying by column chromatography to obtain O-4-methoxy-benzyl-phenyl-phenylphosphinate with 83% separation yield.
Example 23
Preparation of O-9-fluorenyl-benzyl-phenyl-phenylphosphinate: 109mg (0.5mmol) of diphenylphosphonic acid, 182.2mg (1.0mmol) of 9-fluorenol, 138uL (1.0mmol) of triethylamine and 161mg (0.5mmol) of 2- (1H-benzotriazol L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate were put into a Schlenk tube under a nitrogen atmosphere, and 1.0mL of dichloroethane was added under a nitrogen atmosphere, followed by stirring at room temperature for 12 hours. After the reaction is finished, the O-9-fluorenyl-benzyl-phenyl-phenylphosphinate with 81 percent of separation yield can be obtained by column chromatography separation and purification.
Example 24
Preparation of O-methyl- (bis 4-methylphenyl) -phosphinate: 123mg (0.5mmol) of bis (4-methylphenyl) phosphonic acid, 40.5uL (1.0mmol) of methanol, 138uL (1.0mmol) of triethylamine and 161mg (0.5mmol) of 2- (1H-benzotriazol L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate were charged into a Schlenk's tube under a nitrogen atmosphere, and 1.0mL of dichloroethane was charged under a nitrogen atmosphere and stirred at room temperature for 12 hours. After the reaction is finished, the O-methyl- (bi 4-methylphenyl) -phosphinic acid ester with the separation yield of 96 percent can be obtained by column chromatography separation and purification.
Example 25
Preparation of O-methyl- (bis 4-trifluoromethylphenyl) -phosphinite: 177mg (0.5mmol) of bis (4-trifluoromethylphenyl) phosphonic acid, 40.5uL (1.0mmol) of methanol, 138uL (1.0mmol) of triethylamine and 161mg (0.5mmol) of 2- (1H-benzotriazol L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate were added to a Schlenk's tube under a nitrogen atmosphere, and 1.0mL of dichloroethane was added under a nitrogen atmosphere, and the mixture was stirred at room temperature for 12 hours. After the reaction is finished, the O-methyl- (bis 4-trifluoromethylphenyl) -phosphinic acid ester with the separation yield of 92 percent can be obtained by column chromatography separation and purification.
Example 26
Preparation of O-methyl-phenyl-ethoxy-phosphinic acid ester: 93mg (0.5mmol) of phenylethoxyphosphonic acid, 40.5uL (1.0mmol) of methanol, 138uL (1.0mmol) of triethylamine and 161mg (0.5mmol) of 2- (1H-benzotriazol L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate were charged into a Schlenk tube under a nitrogen atmosphere, and 1.0mL of dichloroethane was added under a nitrogen atmosphere, and the mixture was stirred at room temperature for 12 hours. After the reaction is finished, the O-methyl-phenyl-ethoxy-phosphinic acid ester with the separation yield of 67 percent can be obtained by column chromatography separation and purification.
Example 26
Preparation of O-methyl-2-ethylhexyl phosphonic acid mono 2-ethylhexyl ester: 105mg (0.5mmol) of 2-ethylhexyl phosphonic acid mono 2-ethylhexyl ester, 40.5uL (1.0mmol) of methanol, 138uL (1.0mmol) of triethylamine and 161mg (0.5mmol) of 2- (1H-benzotriazol L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate were added to a Schlenk tube under a nitrogen atmosphere, 1.0mL of dichloroethane were added under a nitrogen atmosphere, and the mixture was stirred at room temperature for 12 hours. After the reaction is finished, the O-methyl-2-ethylhexyl phosphonic acid mono-2-ethylhexyl ester with 55 percent of separation yield can be obtained by column chromatography separation and purification.
Example 27
Preparation of O-methyl-9, 10-dihydro-9-oxa-10-phosphaphenanthrene-10-phosphonate: 116mg (0.5mmol) of 9, 10-dihydro-9-oxa-10-phosphaphenanthrene-10-phosphonic acid, 40.5uL (1.0mmol) of methanol, 138uL (1.0mmol) of triethylamine and 161mg (0.5mmol) of 2- (1H-benzotriazol L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate were introduced into a Schlenk tube under nitrogen atmosphere, 1.0mL of dichloroethane was introduced under nitrogen atmosphere, and the mixture was stirred at room temperature for 12 hours. After the reaction is finished, the O-methyl-9, 10-dihydro-9-oxa-10-phosphaphenanthrene-10-phosphonate with 92 percent separation yield can be obtained by column chromatography separation and purification.
It can be seen from the above examples that the method for preparing corresponding organic phosphonate derivatives containing different substituted functional groups by using the condensation reaction of the compound containing p (o) -OH and the alcohol compound, which is adopted by the invention, has the advantages of mild reaction conditions, cheap and easily available catalyst, simple preparation and the like. In addition, the method also has the advantages of wide substrate applicability, high yield, high selectivity (100%) and the like, and provides a method for efficiently synthesizing the organic phosphonate derivatives containing different substituted functional groups.
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 (5)

1. A process for preparing the compound with structural formula (I) by esterifying P (O) -OH compound with alcohol（I）The preparation method of the organic phosphonate ester derivative comprises the following steps:
Figure DEST_PATH_IMAGE002
（I）
the method is characterized by comprising the following steps:
taking reaction amount of compound containing P (O) -OH, alcohol, alkali, condensation reagent and organic solvent in N2Putting the mixture into a reaction container under protection, mixing, and reacting for 3-12 hours at 25-80 ℃ under stirring to obtain corresponding organic phosphonate derivatives containing different substituted functional groups;
wherein,
the structural formula of the compound containing P (O) -OH is shown as
Figure DEST_PATH_IMAGE004
；
The base is triethylamine;
the organic solvent is dichloroethane;
the condensation reagent is 2- (1H-benzotriazo L-1-yl) -1,1,3, 3-tetramethyluronium tetrafluoroborate (TBTU);
the alcohol is R-OH and is selected from benzyl alcohol, methanol, ethanol, n-butyl alcohol, isobutyl alcohol, cyclohexanol, cyclopentanol, trifluoroethanol, 3- (trimethylsilyl) -propiolic alcohol, 3-buten-1-ol, 2-butyn-1-ol, 3-butyn-2-ol, isopropanol, tert-butyl alcohol, 9-fluorenol, 4-bromobenzyl alcohol, 4-nitrobenzyl alcohol and 4-methoxybenzyl alcohol;
R1selected from phenyl, 4-methylphenyl, 4-trifluoromethylphenyl, 2-ethyl-hexyl;
R2selected from phenyl, ethoxy, 4-methylphenyl, 4-trifluoromethylphenyl, 2-ethyl-hexyloxy;
when the P (O) -OH compound is a cyclic phosphonic acid compound, R1And R2Together are a 9, 10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxo substituent.
2. The method according to claim 1, wherein the P- (O) -OH-containing compound is selected from diphenyl phosphonic acid, bis (4-methyl-phenyl) phosphonic acid, bis (4-trifluoromethyl-phenyl) phosphonic acid, phenyl ethoxy phosphonic acid, 2-ethylhexyl phosphonic acid mono 2-ethylhexyl ester, 9, 10-dihydro-9-oxa-10-phosphaphenanthrene-10-phosphonic acid.
3. The method according to claim 1, wherein the molar ratio of the P- (O) -OH-containing compounds to the alcohol is 1: [1.0 to 2.0 ].
4. The method according to claim 1, wherein the molar ratio of the P- (O) -OH-containing compound to the base is 1: [1.0 to 5.0 ].
5. The method according to claim 1, wherein the molar ratio of the P- (O) -OH-containing compound to the condensation reagent is 1: [1.0 to 2.0 ].
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* Cited by examiner, † Cited by third party
Title
TBTU促进合成杂环及酯的有机反应;石伟;《中国优秀硕士学位论文数据库工程科技I辑》;20140815(第08期);B014-129 *

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