CN107082788A - It is a kind of that the synthetic method that P (O) OH classes compound is efficiently esterified with alcohol is catalyzed with imines - Google Patents

It is a kind of that the synthetic method that P (O) OH classes compound is efficiently esterified with alcohol is catalyzed with imines Download PDF

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CN107082788A
CN107082788A CN201710127845.0A CN201710127845A CN107082788A CN 107082788 A CN107082788 A CN 107082788A CN 201710127845 A CN201710127845 A CN 201710127845A CN 107082788 A CN107082788 A CN 107082788A
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alcohol
phenyl
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phosphate
dicyclohexylcarbodiimide
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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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    • C07F9/02—Phosphorus compounds
    • 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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    • C07F9/32—Esters thereof
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    • C07F9/32—Esters thereof
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    • C07F9/3288—Esters with arylalkanols
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    • 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
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    • C07F9/40—Esters thereof
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    • C07F9/6571—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms
    • C07F9/657163—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms the ring phosphorus atom being bound to at least one carbon atom
    • C07F9/657172—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms the ring phosphorus atom being bound to at least one carbon atom the ring phosphorus atom and one oxygen atom being part of a (thio)phosphinic acid ester: (X = O, S)
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Abstract

The invention provides a kind of method of organophosphorus ester analog derivative of efficient, high selectivity containing different substitution functional groups, it is usedN,N’‑Dicyclohexylcarbodiimide catalyst is as condensation reagent, so that containing P (O) OH classes compound, as reaction substrate, alcohol adds organic solvent as esterifying reagent, reaction system.The advantage of this method：Catalyst is cheap and easy to get；Substrate applicability is high；Reaction condition is gentle, safe and reliable；The selectivity of gained target product is close to 100%, and yield is up to more than 90%.The reaction selectivity that this method solve conventional synthesis organophosphorus ester compound is poor, reactions steps are cumbersome, low yield and need to use to deficiencies such as environment harmful reagents, with good prospects for commercial application.The present invention additionally provides the corresponding organophosphorus ester analog derivative containing different substitution functional groups simultaneously.

Description

Synthesis method for efficiently esterifying P (O) -OH compounds and alcohol by using imine as catalyst
Technical Field
The invention relates to the field of application catalytic synthesis of organic phosphate compounds, in particular to a preparation method for preparing organic phosphate derivatives by efficiently catalyzing selective esterification reaction of P (O) -OH-containing compounds and alcohol by using imine.
Background
The organic phosphonate is an important organic compound, has wide application prospect in the fields of functional materials, pesticides, auxiliaries, additives, organic ligands, asymmetric catalysis and the like, and part of chiral phosphonate also shows unique biological activity in the fields of life science, medicine 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 out 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.
The traditional synthetic method of organic phosphonate mainly adopts P-Cl compounds, trialkoxy phosphonate and other air-sensitive phosphorylation reagents as starting raw materials, and has the defects of harsh conditions, poor reaction selectivity, poor functional group applicability and the like; and it is difficult to find a pure natural compound having a phosphorus chiral center in nature. With the development of modern organic synthetic chemistry, high atom economy and chemical selectivity have become the focus of attention of chemists. However, the conventional method generally adopts air-sensitive reagents (P (O) -H compounds, carbon tetrachloride, sulfonyl chloride and the like), and has the defects of complicated experimental steps, expensive catalyst, difficult recycling, harsh reaction conditions, cross-reactivity of substrates, low yield, great environmental pollution and the like. Therefore, the method for preparing the (chiral) organic phosphonate by researching a high-efficiency, high-stereoselectivity, economic and environment-friendly synthetic route has important significance.
So far, the efficient synthesis of organic phosphate 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 few companies in the countries of America, Japan and the like are in production at present, and the current situation of high-end organic phosphate products in China mainly depends on import.
Aiming at the defects of the existing organic phosphate synthesis process, the industry is focusing on developing a method for efficiently and selectively synthesizing corresponding organic phosphate compounds by taking stable, cheap and easily obtained P (O) -OH-containing compounds as raw materials.
Disclosure of Invention
The object of the present invention is to provide a method for producing a polymer with low cost and easy availabilityN, N’The dicyclohexylcarbodiimide condensing agent catalyzes the high-efficiency esterification reaction of the P (O) -OH compounds and alcohol to synthesize the corresponding organophosphorus containing different substituted functional groups with high selectivityThe method of acid ester compound, in order to overcome the above-mentioned defect in the prior art.
The esterification reaction comprises the following steps: taking reaction amount of P (O) -OH compound, alcohol,N, N’Dicyclohexylcarbodiimide 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 phosphate derivatives containing different substituted functional groups. The specific reaction formula is as follows:
wherein,
r is selected from benzyl, methyl, ethyl, n-butyl, isobutyl, cyclohexyl, cyclopentyl, trifluoroethyl, 3- (trimethylsilyl) -propyne, 3-butenyl, 2-butynyl, 1-methyl-2-propynyl, isopropyl, tert-butyl, 9-fluorenyl, 4-bromobenzyl, 4-nitrobenzyl, 4-methoxybenzyl;
R1is phenyl, 4-methylphenyl, 4-trifluoromethylphenyl, 2-ethyl-hexyl, 9, 10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxyl;
R2is phenyl, ethoxy, 4-methylphenyl, 4-trifluoromethylphenyl, 2-ethyl-hexyloxy.
In the method for synthesizing the organophosphate compound by efficiently esterifying the P (O) -OH compound with the alcohol, the base in the reaction step is selected from triethylamine, 1, 8-diazabicycloundec-7-ene, and,N, N-dimethylaniline,N, N-diethylaniline,N, N-dimethylbenzylamine, diisopropylethylamine, sodium bicarbonate, potassium carbonate, sodium carbonate, cesium carbonate, sodium tert-butoxide, potassium tert-butoxide or potassium phosphate.
In the method for synthesizing the organic phosphate compound by efficiently esterifying the P (O) -OH compound and the alcohol, the P (O) -OH compound is selected from diphenyl phosphoric acid, bis (4-methyl-phenyl) phosphoric acid, bis (4-trifluoromethyl-phenyl) phosphoric acid, phenyl ethoxy phosphoric acid, 2-ethylhexyl phosphoric acid mono-2-ethylhexyl ester and 9, 10-dihydro-9-oxa-10-phosphaphenanthrene-10-phosphoric acid.
In the method for synthesizing the organic phosphate compound by efficiently esterifying the P (O) -OH compound and the alcohol, the alcohol compound is selected from benzyl alcohol, methanol, ethanol, n-butanol, isobutanol, cyclohexanol, cyclopentanol, trifluoroethanol, 3- (trimethylsilyl) -propiolic alcohol, 3-buten-1-ol, 2-butyn-1-ol, 3-butyn-2-ol, isopropanol, tert-butanol, 9-fluorenol, 4-bromobenzyl alcohol, 4-nitrobenzyl alcohol and 4-methoxybenzyl alcohol.
In the method for synthesizing the organic phosphate compound by efficiently esterifying the P (O) -OH compound and the alcohol, the organic solvent refers to dichloromethane, dichloroethane, tetrahydrofuran, acetonitrile, toluene,N, N-dimethylformamide, ethyl acetate.
In the method for synthesizing the organic phosphate compound by efficiently esterifying the P (O) -OH compound and the alcohol, the condensing agent isN, N’-dicyclohexylcarbodiimide.
In the above method for synthesizing an organic phosphate ester compound from a p (o) -OH compound and an alcohol, the molar ratio of the p (o) -OH containing compound to the alcohol is 1: [ 1.0-2.0 ] wherein the molar ratio of the compound containing P (O) -OH to the condensation reagent is 1: [1.0 to 2.0 ].
The method for synthesizing the organic phosphate compound by efficiently esterifying the compound containing P (O) -OH and the alcohol compound 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 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 (0.5mmol) of diphenylphosphoric acid, 40.5 uL (1.0 mmol) of methanol and 103 mg (0.5mmol)N, N’Dicyclohexylcarbodiimide (DCC) was added to a Schlenk tube under nitrogen atmosphere, and 1.0 mL of an organic solvent (dichloromethane, dichloroethane, tetrahydrofuran, acetonitrile, toluene, methanol, ethanol,N, N-dimethylformamide, ethyl acetate) and the reaction stirred at room temperature for 12 hours. The coupling reaction was carried out in 98% yield using acetonitrile as the reaction solvent, as determined by GC assay.
Example 2
109 mg (0.5mmol) of diphenylphosphoric acid, 40.5 uL (1.0 mmol) of methanol and various molar ratiosN, N’-Dicyclohexylcarbodiimide (DCC): (0 mol%, 5 mol%, 10 mol%, 20 mol%, 50 mol%, 100mol%, 200 mol%) in a Schlenk tube under a nitrogen atmosphere, and under a nitrogen atmosphere1.0 mL of acetonitrile, and the reaction was stirred at room temperature for 12 hours. Analysis by GC detection was only performed in CDI:N, N’the yield of the coupling reaction can reach 98% when the amount of dicyclohexylcarbodiimide is one reaction equivalent.
Example 3
109 mg (0.5mmol) of diphenylphosphoric acid, different molar ratios of methanol (0.5mmol, 0.6 mmol,0.75 mmol, 1.0 mmol) and 103 mg (0.5mmol)N, N’Dicyclohexylcarbodiimide (DCC), added to a Schlenk tube under nitrogen atmosphere, added to 1.0 mL of acetonitrile under nitrogen atmosphere, and stirred at room temperature for 12 hours. The coupling reaction yield reached 98% only at 1.0 mmol of methanol, i.e. twice the reaction equivalent, as determined by GC.
Example 4
109 mg (0.5mmol) of diphenylphosphoric acid, 40.5 uL (1.0 mmol) of methanol and 103 mg (0.5mmol)N, N’Dicyclohexylcarbodiimide (DCC), added to a Schlenk tube under nitrogen atmosphere, added to acetonitrile (0.5 mL, 1.0 mL, 2.0 mL, 5.0 mL) under nitrogen atmosphere, and stirred at room temperature for reaction for 12 hours. The coupling reaction was carried out in 98% yield by GC assay only with acetonitrile at 1.0 mL. The yield of the reaction gradually decreased with increasing amount of solvent.
Example 5
OPreparation of ethyl-phenyl-phenylphosphinate: 109 mg (0.5mmol) of diphenylphosphoric acid, 58.3 uL (1.0 mmol) of ethanol and 103 mg (0.5mmol)N, N’Dicyclohexylcarbodiimide (DCC), Schle addition under nitrogen atmosphereIn a nk tube, 1.0 mL of acetonitrile was added under a nitrogen atmosphere, and the reaction was stirred at room temperature for 12 hours. After the reaction is finished, the 95 percent separation yield can be obtained by column chromatography separation and purificationO-ethyl-phenyl-phenylphosphinate.
Example 6
OPreparation of-butyl-phenyl-phenylphosphinate: 109 mg (0.5mmol) of diphenylphosphoric acid, 91.5 uL (1.0 mmol) of n-butanol and 103 mg (0.5mmol)N, N’Dicyclohexylcarbodiimide (DCC), added to a Schlenk tube under nitrogen atmosphere, added to 1.0 mL of acetonitrile under nitrogen atmosphere, and stirred at room temperature for 12 hours. After the reaction is finished, the 96 percent separation yield can be obtained by column chromatography separation and purificationO-ethyl-phenyl-phenylphosphinate.
Example 7
OPreparation of isobutyl-phenyl-phenylphosphinate: 109 mg (0.5mmol) of diphenylphosphoric acid, 92.4 uL (1.0 mmol) of isobutanol and 103 mg (0.5mmol)N, N’Dicyclohexylcarbodiimide (DCC), added to a Schlenk tube under nitrogen atmosphere, added to 1.0 mL of acetonitrile under nitrogen atmosphere, and stirred at room temperature for 12 hours. After the reaction is finished, the 92 percent separation yield can be obtained by column chromatography separation and purificationO-isobutyl-phenyl-phenylphosphinate.
Example 8
OPreparation of-benzyl-phenyl-phenylphosphinate: 109 mg (0.5mmol) of diphenylphosphoric acid, 103.8 uL (1.0 mmol) of benzyl alcohol and 103 mg (0.5mmol)N, N’Dicyclohexylcarbodiimide (DCC), Schlen's addition under nitrogen atmosphereInto 1.0 mL of acetonitrile was added under a nitrogen atmosphere in a k-tube, and the reaction was stirred at room temperature for 12 hours. After the reaction is finished, the 87 percent separation yield can be obtained by column chromatography separation and purificationO-benzyl-phenyl-phenylphosphinate.
Example 9
OPreparation of-cyclohexyl-phenyl-phenylphosphinate: 109 mg (0.5mmol) of diphenylphosphoric acid, 104 uL (1.0 mmol) of cyclohexanol were admixed with 103 mg (0.5mmol)N, N’Dicyclohexylcarbodiimide (DCC), added to a Schlenk tube under nitrogen atmosphere, added to 1.0 mL of acetonitrile under nitrogen atmosphere, and stirred at room temperature for 12 hours. After the reaction is finished, the separation and purification by column chromatography can obtain the product with the separation yield of 91 percentO-cyclohexyl-phenyl-phenylphosphinate.
Example 10
OPreparation of-cyclopentyl-phenyl-phenylphosphinate: 109 mg (0.5mmol) of diphenylphosphoric acid, 90.7 uL (1.0 mmol) of cyclopentanol and 103 mg (0.5mmol)N, N’Dicyclohexylcarbodiimide (DCC), added to a Schlenk tube under nitrogen atmosphere, added to 1.0 mL of acetonitrile under nitrogen atmosphere, and stirred at room temperature for 12 hours. After the reaction is finished, the 88 percent separation yield can be obtained by column chromatography separation and purificationO-cyclopentyl-phenyl-phenylphosphinate.
Example 11
OPreparation of-trifluoroethyl-phenyl-phenylphosphinate: 109 mg (0.5mmol) of diphenylphosphoric acid, 72.4uL (1.0 mmol) of trifluoroethanol and 103 mg (0.5mmol)N, N’Dicyclohexylcarbodiimide (DCC), added to a Schlenk tube under nitrogen atmosphere, added to 1.0 mL of acetonitrile under nitrogen atmosphere, and stirred at room temperature for 12 hours. After the reaction is finished, the 95 percent separation yield can be obtained by column chromatography separation and purificationO-trifluoroethyl-phenyl-phenylphosphinate.
Example 12
OPreparation of (E) -3- (trimethylsilyl) -propynyl-phenyl-phenylphosphinate: 109 mg (0.5mmol) of diphenylphosphoric acid, 148.3uL (1.0 mmol) of 3- (trimethylsilyl) -propiolic alcohol and 103 mg (0.5mmol)N, N’Dicyclohexylcarbodiimide (DCC), added to a Schlenk tube under nitrogen atmosphere, added to 1.0 mL of acetonitrile under nitrogen atmosphere, and stirred at room temperature for 12 hours. After the reaction is finished, the 86 percent separation yield can be obtained by column chromatography separation and purificationO-3- (trimethylsilyl) -propynyl-phenyl-phenylphosphinate.
Example 13
OPreparation of-3-butenyl-phenyl-phenylphosphinate: 109 mg (0.5mmol) of diphenylphosphoric acid, 148.3uL (1.0 mmol) of 3-buten-1-ol and 103 mg (0.5mmol)N, N’Dicyclohexylcarbodiimide (DCC), added to a Schlenk tube under nitrogen atmosphere, added to 1.0 mL of acetonitrile under nitrogen atmosphere, and stirred at room temperature for 12 hours. After the reaction is finished, the separation and purification by column chromatography can obtain the product with the separation yield of 91 percentO-3-butenyl-phenyl-phenylphosphinate.
Example 14
OPreparation of-2-butynyl-phenyl-phenylphosphinate: 109 mg (0.5mmol) of diphenylphosphoric acid, 74.8uL (1.0 mmol) of but-2-yn-1-ol and 103 mg (0.5mmol)N, N’Dicyclohexylcarbodiimide (DCC), added to a Schlenk tube under nitrogen atmosphere, added to 1.0 mL of acetonitrile under nitrogen atmosphere, and stirred at room temperature for 12 hours. After the reaction is finished, the 94 percent separation yield can be obtained by column chromatography separation and purificationO-2-butynyl-phenyl-phenylphosphinate.
Example 15
OPreparation of 1-methyl-2-propynyl-phenyl-phenylphosphinate: 109 mg (0.5mmol) of diphenylphosphoric acid, 78.4 uL (1.0 mmol) of 3-butyn-2-ol and 103 mg (0.5mmol)N, N’Dicyclohexylcarbodiimide (DCC), added to a Schlenk tube under nitrogen atmosphere, added to 1.0 mL of acetonitrile under nitrogen atmosphere, and stirred at room temperature for 12 hours. After the reaction is finished, the 83 percent separation yield can be obtained by column chromatography separation and purificationO-1-methyl-2-propynyl-phenyl-phenylphosphinate.
Example 16
OPreparation of isopropyl-phenyl-phenylphosphinate: 109 mg (0.5mmol) of diphenylphosphoric acid, 76.5uL (1.0 mmol) of isopropanol and 103 mg (0.5mmol)N, N’Dicyclohexylcarbodiimide (DCC), added to a Schlenk tube under nitrogen atmosphere, added to 1.0 mL of acetonitrile under nitrogen atmosphere, and stirred at room temperature for 12 hours. After the reaction is finished, the 92 percent separation yield can be obtained by column chromatography separation and purificationO-isopropyl-phenyl-phenylphosphinate.
Example 17
OPreparation of tert-butyl-phenyl-phenylphosphinate: 109 mg (0.5mmol) of diphenylphosphoric acid, 76.5uL (1.0 mmol) of tert-butanol and 103 mg (0.5mmol)N, N’Dicyclohexylcarbodiimide (DCC), added to a Schlenk tube under nitrogen atmosphere, added to 1.0 mL of acetonitrile under nitrogen atmosphere, and stirred at room temperature for 12 hours. After the reaction is finished, the separation and purification by column chromatography can obtain the product with 63 percent of separation yieldO-tert-butyl-phenyl-phenylphosphinate.
Example 18
OPreparation of 4-bromo-benzyl-phenyl-phenylphosphinate: 109 mg (0.5mmol) of diphenylphosphoric acid, 187mg (1.0 mmol) of 4-bromobenzyl alcohol and 103 mg (0.5mmol)N, N’Dicyclohexylcarbodiimide (DCC), added to a Schlenk tube under nitrogen atmosphere, added to 1.0 mL of acetonitrile under nitrogen atmosphere, and stirred at room temperature for 12 hours. After the reaction is finished, the 82 percent separation yield can be obtained by column chromatography separation and purificationO-4-bromo-benzyl-phenyl-phenylphosphinate.
Example 19
OPreparation of 4-nitro-benzyl-phenyl-phenylphosphinate: 109 mg (0.5mmol) of diphenylphosphoric acid, 153 mg (1.0 mmol) of 4-nitrobenzol and 103 mg (0.5mmol)N, N’Dicyclohexylcarbodiimide (DCC), added to a Schlenk tube under nitrogen atmosphere, added to 1.0 mL of acetonitrile under nitrogen atmosphere, and stirred at room temperature for 12 hours. After the reaction is finished, the 79 percent separation yield can be obtained by column chromatography separation and purificationO-4-nitro-benzyl-phenyl-phenylphosphinate.
Example 20
OPreparation of 4-methoxy-benzyl-phenyl-phenylphosphinate: 109 mg (0.5mmol) of diphenylphosphoric acid, 124.1 ul (1.0 mmol) of 4-methoxybenzyl alcohol and 103 mg (0.5mmol)N, N’Dicyclohexylcarbodiimide (DCC), added to a Schlenk tube under nitrogen atmosphere, added to 1.0 mL of acetonitrile under nitrogen atmosphere, and stirred at room temperature for 12 hours. After the reaction is finished, the 86 percent separation yield can be obtained by column chromatography separation and purificationO-4-methoxy-benzyl-phenyl-phenylphosphinate.
Example 21
OPreparation of-9-fluorenyl-benzyl-phenyl-phenylphosphinate: 109 mg (0.5mmol) of diphenylphosphoric acid, 182.2 mg (1.0 mmol) of 9-fluorenol and 103 mg (0.5mmol)N, N’Dicyclohexylcarbodiimide (DCC), added to a Schlenk tube under nitrogen atmosphere, added to 1.0 mL of acetonitrile under nitrogen atmosphere, and stirred at room temperature for 12 hours. After the reaction is finished, the 87 percent separation yield can be obtained by column chromatography separation and purificationO-9-fluorenyl-benzyl-phenyl-phenylphosphinate.
Example 22
OPreparation of-methyl- (bis 4-methylphenyl) -phosphinate ester: 123 mg (0.5mmol) of bis (4-methylphenyl) phosphoric acid, 40.5 uL (1.0 mmol) of methanol and 103 mg (0.5mmol)N, N’Dicyclohexylcarbodiimide (DCC), added to a Schlenk tube under nitrogen atmosphere, added to 1.0 mL of acetonitrile under nitrogen atmosphere, and stirred at room temperature for 12 hours. After the reaction is finished, the 95 percent separation yield can be obtained by column chromatography separation and purificationO-first of allRadical- (bis 4-methylphenyl) -phosphinic acid ester.
Example 23
OPreparation of (E) -methyl- (bis 4-trifluoromethylphenyl) -phosphinite: 177 mg (0.5mmol) of bis (4-trifluoromethylphenyl) phosphate, 40.5 uL (1.0 mmol) of methanol and 103 mg (0.5mmol)N, N’Dicyclohexylcarbodiimide (DCC), added to a Schlenk tube under nitrogen atmosphere, added to 1.0 mL of acetonitrile under nitrogen atmosphere, and stirred at room temperature for 12 hours. After the reaction is finished, the 93 percent separation yield can be obtained by column chromatography separation and purificationO-methyl- (bis 4-trifluoromethylphenyl) -phosphinate.
Example 24
OPreparation of methyl-phenyl-ethoxy-phosphinic acid ester: 93 mg (0.5mmol) of phenylethoxyphosphoric acid, 40.5 uL (1.0 mmol) of methanol and 103 mg (0.5mmol)N, N’Dicyclohexylcarbodiimide (DCC), added to a Schlenk tube under nitrogen atmosphere, added to 1.0 mL of acetonitrile under nitrogen atmosphere, and stirred at room temperature for 12 hours. After the reaction is finished, the 81 percent separation yield can be obtained by column chromatography separation and purificationO-methyl-phenyl-ethoxy-phosphinic acid ester.
Example 25
OPreparation of mono 2-ethylhexyl-methyl-2-ethylhexyl phosphate: 105 mg (0.5mmol) of 2-ethylhexyl phosphate mono 2-ethylhexyl ester, 40.5 uL (1.0 mmol) of methanol and 103 mg (0.5mmol)N, N’Dicyclohexylcarbodiimide (DCC), added to a Schlenk tube under nitrogen atmosphere, protected with nitrogenAdd to 1.0 mL acetonitrile at ambient temperature and stir the reaction at room temperature for 12 hours. After the reaction is finished, the product can be separated and purified by column chromatography to obtain the product with the separation yield of 62 percentO-methyl-2-ethylhexyl phosphate mono 2-ethylhexyl ester.
Example 26
OPreparation of methyl-9, 10-dihydro-9-oxa-10-phosphaphenanthrene-10-phosphate: 116 mg (0.5mmol) of 9, 10-dihydro-9-oxa-10-phosphaphenanthrene-10-phosphoric acid, 40.5 uL (1.0 mmol) of methanol and 103 mg (0.5mmol)N, N’Dicyclohexylcarbodiimide (DCC), added to a Schlenk tube under nitrogen atmosphere, added to 1.0 mL of acetonitrile under nitrogen atmosphere, and stirred at room temperature for 12 hours. After the reaction is finished, the 94 percent separation yield can be obtained by column chromatography separation and purificationO-methyl-9, 10-dihydro-9-oxa-10-phosphaphenanthrene-10-phosphate.
It can be seen from the above examples that the method for preparing corresponding organophosphate derivatives containing different substituted functional groups by efficiently catalyzing esterification of a compound containing p (o) -OH and an alcohol compound with imine 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 phosphate 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 (7)

1. A method for preparing organic phosphate derivatives by efficiently catalyzing P (O) -OH compounds and alcohol esterification by imine comprises the following steps:
the method is characterized by comprising the following steps:
taking reaction amount of P (O) -OH compound, alcohol,N, N’Dicyclohexylcarbodiimide and organic solvent in N2Or inert gasesPutting the mixture into a reaction vessel under protection, mixing, and reacting for 3-12 hours at 25-80 ℃ under stirring to obtain corresponding organic phosphate derivatives containing different substituted functional groups;
wherein,
r is selected from benzyl, methyl, ethyl, n-butyl, isobutyl, cyclohexyl, cyclopentyl, trifluoroethyl, 3- (trimethylsilyl) -propyne, 3-butenyl, 2-butynyl, 1-methyl-2-propynyl, isopropyl, tert-butyl, 9-fluorenyl, 4-bromobenzyl, 4-nitrobenzyl, 4-methoxybenzyl;
R1is phenyl, 4-methylphenyl, 4-trifluoromethylphenyl, 2-ethyl-hexyl, 9, 10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxyl;
R2is phenyl, ethoxy, 4-methylphenyl, 4-trifluoromethylphenyl, 2-ethyl-hexyloxy.
2. The method according to claim 1, wherein the P (O) -OH-containing compound is selected from diphenyl phosphate, bis (4-methyl-phenyl) phosphate, bis (4-trifluoromethyl-phenyl) phosphate, phenyl ethoxy phosphate, mono-2-ethylhexyl phosphate, 9, 10-dihydro-9-oxa-10-phosphaphenanthrene-10-phosphate.
3. The method according to claim 1, wherein the alcohol is selected from benzyl alcohol, methanol, ethanol, n-butanol, isobutanol, cyclohexanol, cyclopentanol, trifluoroethanol, 3- (trimethylsilyl) -propiolic alcohol, 3-buten-1-ol, 2-butyn-1-ol, 3-butyn-2-ol, isopropanol, t-butanol, 9-fluorenol, 4-bromobenzyl alcohol, 4-nitrobenzyl alcohol, and 4-methoxybenzyl alcohol.
4. The method according to claim 1, wherein the organic solvent is dichloromethane, dichloroethane, tetrahydrofuran, acetonitrile, toluene, or a mixture thereof,N, N-dimethylformamide, ethyl acetate.
5. The method of claim 1, wherein the condensing agent isN, N’-dicyclohexylcarbodiimide.
6. 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 ].
7. 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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