Preparation and use of organophosphorus oxides

Abstract

The application discloses preparation and application of an organic phosphine oxide compound and belongs to the technical field of organic synthesis. 1 R 2 P(O)‑C(OH)R 3 R 4 The starting material alpha-hydroxy phosphine oxide compound R 1 R 2 P(0)A is reacted with a reaction reagent A-B, and after the reaction is completed, the organic phosphine oxide compound R 1 R 2 Each of R and R is independently an aromatic or aliphatic substituent, R 3 R 4 Each of R and R is independently an aliphatic long-chain alkyl substituent, A-B is an aryl alkyne, an alkyl alkyne, acetylene, and an aromatic or aliphatic halogenated alkane, and the obtained organic phosphine oxide compound R 1 R 2 P(0)A is stable in property, high in yield, and has various functions, and is suitable for the fields of high-efficiency flame retardant, functional material, metal extractant, medicine and homogeneous catalysis.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and more specifically, to the preparation and use of an organophosphorus oxide compound. Background Technology

[0002] Organophosphine oxides have wide applications in high-efficiency flame retardants, functional materials, metal extractants, pharmaceuticals, and homogeneous catalysis. Currently, the preparation of phosphine oxides mainly relies on phosphine chloride R2PCl and dialkylphosphine oxide R2P(O)H (secondary phosphine oxide, abbreviated as SPO) as raw materials. However, phosphine chloride R2PCl is chemically reactive and sensitive to water and oxygen, generating large amounts of chloride solid waste and acidic substances during the reaction, causing serious pollution and increasing recycling costs. Dialkylphosphine oxide R2P(O)H, taking diphenylphosphine oxide Ph2P(O)H as an example, has poor crystallinity, is difficult to purify, and under normal storage conditions, it absorbs moisture and gradually oxidizes, leading to the formation of impurities containing diphenylphosphonic acid Ph2P(O)OH. More importantly, dialkylphosphine oxide SPO suffers from instability and the potential to poison metal catalysts. Because dialkylphosphine oxides R2P(O)H... 1 R 2 P(O)H tautomer R 1 R 2 P-OH is a trivalent P(III) atom with a lone pair of electrons, which readily coordinates with transition metals with empty d orbitals. When used as a metal catalyst, it can easily lead to the deactivation of the metal catalyst. The reaction formula is shown below.

[0003]

[0004] To date, no organophosphorus oxide has been found that is stable, has weak coordination with transition metal M, does not poison transition metal catalysts, and possesses various functionalities. Summary of the Invention

[0005] 1. Technical problems to be solved

[0006] In view of the problems existing in the prior art, the purpose of the present invention is to provide a method for preparing an organophosphorus oxide compound that can maintain high selectivity and yield and has various functionalities, as well as the use of the organophosphorus oxide compound.

[0007] 2. Technical Solution

[0008] To solve the above problems, the present invention adopts the following technical solution.

[0009] The preparation of an organophosphorus oxide compound includes the following steps:

[0010] The first step is to use the starting material α-hydroxyphosphine oxide R 1 R 2 p(0)-C(OH)R 3 R 4 Add reaction reagent AB to the mixture to obtain a mixture, wherein AB is an aryl alkyne, alkyl alkyne, acetylene, or haloalkane, and the haloalkane is aliphatic or aromatic.

[0011] The second step involves adding one or more of a catalyst, ligand, additive, and reaction solvent to the mixture obtained in the first step to initiate a reaction. After the reaction is complete, the mixture is purified to obtain organophosphorus oxide R. 1 R 2 P(O)A:

[0012] R 1 R 2 Each independently represents a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group, and a substituted or unsubstituted heterocyclic aryl group containing N, O, or S atoms. R 3 R 4 Each can independently represent a long-chain or straight-chain alkyl group.

[0013] Furthermore, organophosphorus oxides R 1 R 2 When P(0)A is a martensitic addition alkenylphosphine, AB is a terminal alkyne. A catalyst, phosphine ligand, diphenylphosphonic acid as an additive, and a reaction solvent are added to the mixture obtained in the first step. In the second step, the reaction temperature is 50℃-150℃ and the reaction time is 5h-24h.

[0014] Furthermore, organophosphorus oxides R 1 R 2 When P(O)A is an alkenylphosphine undergoing anti-Markovnikov addition, AB is a terminal alkyne. A catalyst and a reaction solvent are added to the mixture obtained in the first step. In the second step, the reaction temperature is 50℃-150℃ and the reaction time is 5h-24h.

[0015] Furthermore, organophosphorus oxides R 1 R 2 When P(O)A is diphenyl(aryl)phosphine oxide and AB is a haloaromatic hydrocarbon, a catalyst, a phosphine ligand, a base as an additive, and a reaction solvent are added to the mixture obtained in the first step. In the second step, the reaction temperature is 50℃-150℃ and the reaction time is 5h-24h.

[0016] Furthermore, organophosphorus oxides R i R 2When P(0)A is diphenyl(alkyl)phosphine oxide and AB is a haloalkane, an alkali and a reaction solvent are added as additives to the mixture obtained in the first step. In the second step, the reaction temperature is 0℃-60℃ and the reaction time is 5h-24h.

[0017] Furthermore, the catalyst is selected from tris(dibenzylacetone)palladium Pd2(dba)3, tetra(triphenylphosphine)palladium Pd(Ph3P)4, palladium acetate Pd(OAc)2, and palladium chloride PdCl2, and the amount of catalyst used is 0.005-0.05 equivalents.

[0018] Furthermore, the ligand is selected from 1,2-bis(diphenylphosphine)ethane dppe, 1,2-bis(diphenylphosphine)propane dppp, 1,2-bis(diphenylphosphine)butane dppb, triphenylphosphine Ph3P, diphenylcyclohexylphosphine Ph2PCy, or bis(diphenylphosphine)ferrocene dppf, and the amount of ligand used is 0.005-0.05 equivalents.

[0019] Furthermore, the alkali is selected from potassium carbonate, sodium carbonate, lithium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, sodium tert-butoxide, potassium tert-butoxide, lithium tert-butoxide, and triethylamine, and the amount of alkali used is 0.5-3.0 equivalents.

[0020] Furthermore, the amount of diphenylphosphonic acid Ph2P(O)OH used is 4% equivalent.

[0021] Furthermore, the reaction solvent is selected from DMF, DMSO, DMAc, toluene, benzene, xylene, tetrahydrofuran, dioxane, and dichloroethane.

[0022] Furthermore, the organophosphorus oxide R 1 R 2 When p(0)A is a Marvibate addition alkenylphosphine, the catalyst is tris(dibenzylideneacetone)dipalladiumPd2(dba)3, the ligand is 1,2-bis(diphenylphosphine)ethanedppe, the additive is diphenylphosphonic acid Ph2P(O)OH, and the reaction solvent is toluene.

[0023] Furthermore, the organophosphorus oxide R 1 R 2 When P(O)A is a martensitic addition alkenylphosphine, the catalyst is 0.01 equivalents, the ligand is 0.02 equivalents, the reaction temperature is 100℃, and the reaction time is 18h.

[0024] Furthermore, the organophosphorus oxide R 1 R 2 When P(O)A is an alkenylphosphine undergoing anti-Markovnikov addition, the catalyst is tetrakis(triphenylphosphine)palladium Pd(Ph3P)4, and the reaction solvent is toluene.

[0025] Furthermore, the organophosphorus oxide R 1 R 2 When P(0)A is an alkenylphosphine undergoing anti-Markovnikov addition, the catalyst is 0.05 equivalents, the reaction temperature is 100℃, and the reaction time is 18h.

[0026] Furthermore, the organophosphorus oxide R 1 R 2 P(O)A is diphenyl(aryl)phosphine oxide, the catalyst is palladium acetate Pd(OAc)2, the ligand is bis(diphenylphosphine ferrocene dppf, the base is potassium carbonate or cesium carbonate, and the reaction solvent is DMF.

[0027] Furthermore, the organophosphorus oxide R 1 R 2 P(0)A is diphenyl(aryl)phosphine oxide, the catalyst is 0.01 equivalent, the ligand is 0.02 equivalent, the base is 1.5 equivalent, the reaction temperature is 120℃, and the reaction time is 8h.

[0028] Furthermore, the organophosphorus oxide R 1 R 2 P(0)A is diphenyl(alkyl)phosphine oxide, the base is potassium tert-butoxide, the reaction solvent is tetrahydrofuran, and the reaction temperature is 0℃-25℃.

[0029] Furthermore, the organophosphorus oxide R 1 R 2 P(O)A is diphenyl(alkyl)phosphine oxide, the base is 1.0 equivalent, and the reaction time is 18 h.

[0030] Furthermore, the catalyst includes, but is not limited to, Rh, Ni, Cu, or Pd; the ligand is selected from 1,2-bis(diphenylphosphine)ethane dppe or bisdiphenylphosphine ferrocene dppf; the additive is selected from diphenylphosphonic acid Ph₂P(O)OH or potassium carbonate; and the reaction solvent is selected from toluene, THF, or DMF. Furthermore, R... 1 R 2 It is a phenyl group, R 3 R 4 It is a methyl group.

[0031] Furthermore, the method for preparing the starting material is as follows: under an inert gas atmosphere, dialkylphosphine oxide compound R... 1 R 2 P(0)H and ketone compound R 3 C(0)R 4 The mixture was stirred at a reaction temperature of 30℃~50℃ to obtain a precipitate, which was then filtered, washed with a washing solvent, and dried for 2 hours to obtain α-hydroxyphosphine oxide R. 1 R 2 P(0)-C(0H)R3 R 4 .

[0032] Furthermore, the stirring time is 6 to 20 hours.

[0033] Furthermore, the washing solvent used is acetone rinsing.

[0034] Furthermore, the secondary phosphine oxide compound R 1 R 2 P(0)H and ketone compound R 3 C(0)R 4 The molar ratio is 1:3-6.

[0035] Furthermore, the starting material α-hydroxyphosphine oxide R 1 R 2 P(0)-C(OH)R 3 R 4 The structural formula is

[0036] Furthermore, the preparation of phosphine oxide R 1 R 2 The chemical reaction equation for P(O)A is:

[0037]

[0038] Uses of an organophosphorus oxide in the fields of high-efficiency flame retardants, functional materials, metal extractants, pharmaceuticals, and homogeneous catalysis.

[0039] Furthermore, the organophosphorus oxide is used as a metal extractant or homogeneous catalysis, and the organophosphorus oxide is one or more of alkenylphosphorus oxide, arylphosphorus oxide, and alkylphosphorus oxide.

[0040] 3. Beneficial effects

[0041] Compared with the prior art, the advantages of this invention are:

[0042] (1) The starting material d-hydroxyphosphonic acid compound R 1 R 2 P(O)-C(OH)R 3 R 4 Compared to dialkylphosphine oxide R 1 R 2 P(O)H is easier to purify, store, and chemically stable, and slowly releases R during the reaction. 1 R 2 P(O)H participates in the reaction and has the excellent characteristic of not poisoning transition metal catalysts, compared with the direct use of R 1 R 2Using P(O)H as a raw material can improve the reaction efficiency in transition metal catalytic reactions.

[0043] (2) The starting material α-hydroxyphosphine oxide R used in this invention 1 R 2 P(O)-C(OH)R 3 R 4 Under specific reaction conditions, organophosphorus compounds with a wide variety of functions can be efficiently prepared, which can replace dialkylphosphorus compounds. 1 R 2 P(O)H participates in various organic reactions to prepare organophosphorus oxides with high yields, good applicability, and wide range of applications. Detailed Implementation

[0044] The present invention will be further described below with reference to specific embodiments, but the scope of protection of the present invention is not limited thereto.

[0045] Example 1:

[0046] Synthetic raw material HDPO: Under nitrogen protection, diphenylphosphine oxide (10 mmol) was mixed with acetone (50 mmol) and stirred at 40 °C for 12 h to precipitate a white solid; the reaction solution was filtered, the filter cake was washed with acetone, and dried under vacuum for 2 h to obtain (α-hydroxy-2-propyl)diphenylphosphine oxide (HDPO) (7.8 mmol), with a yield of 78%.

[0047] The specific reaction is shown in the following formula.

[0048]

[0049] Example 2:

[0050] Synthesis of diphenyl(1-phenylvinyl)phosphonoxide (Markovnikov addition product) from HDPO: Under a nitrogen atmosphere, tris(dibenzylacetone)dipalladium Pd2(dba)3 (0.01 mmol), 1,2-bis(diphenylphosphine)ethane dppe (0.02 mmol), and diphenylphosphonic acid Ph2P(O)OH (0.04 mmol) were added to a 25 mL Schleck tube. Then, 5 mL of toluene was added, and the mixture was stirred at room temperature for 10 min. HDPO (1.0 mmol) and phenylacetylene (1.0 mmol) were added, the tube was capped, and the mixture was heated to 100 °C until the reaction was complete. The product was purified by column chromatography to obtain diphenyl(1-phenylvinyl)phosphonoxide (0.95 mmol) in 95% yield.

[0051] The specific reaction is shown in the following formula.

[0052]

[0053] Comparative Example 1: Under the same conditions as Example 2, using DPO as the raw material, the yield was 91%.

[0054] Example 3:

[0055] Synthesis of (1-octen-2-yl)diphenylphosphine oxide (Markovnikov addition product) from HDPO: Under a nitrogen atmosphere, tris(dibenzylacetone)dipalladium Pd2(dba)3 (0.01 mmol), 1,2-bis(diphenylphosphine)ethane dppe (0.02 mmol), and diphenylphosphonic acid Ph2P(O)OH (0.04 mmol) were added to a 25 mL Schleck tube, followed by the addition of 5 mL of toluene. The mixture was stirred at room temperature for 10 min, then HDPO (1.0 mmol) and 1-octyne (1.0 mmol) were added. The tube was capped and heated to 100 °C until the reaction was complete. The product was purified by column chromatography to obtain (1-octen-2-yl)diphenylphosphine oxide (0.72 mmol), with a yield of 92%.

[0056] The specific reaction is shown in the following formula.

[0057]

[0058] Comparative Example 2: Under the same conditions as Example 3, using DPO as the raw material, the yield was 86%.

[0059] Example 4:

[0060] Synthesis of (E)-diphenyl(styryl)phosphine oxide (anti-Markovnikov addition product) from HDPO: Under a nitrogen atmosphere, tetrakis(triphenylphosphine)palladium Pd(Ph3P)4 (0.05 mmol) and toluene (5 ml) were added to a 25 ml Schleck tube. The mixture was stirred at room temperature for 2 min, and then HDPO (1.0 mmol) and phenylacetylene (1.0 mmol) were added. The tube was sealed and heated to 100 °C until the reaction was complete. The product was purified by column chromatography to obtain (E)-diphenyl(styryl)phosphine oxide (0.88 mmol) in 88% yield.

[0061] The specific reaction is shown in the following formula.

[0062]

[0063] Comparative Example 3: Under the same conditions as Example 4, using DPO as the raw material, the yield was 88%.

[0064] Example 5:

[0065] Synthesis of 1,2-bis(diphenylphosphoxy)ethane from HDPO: Under a nitrogen atmosphere, 1.0 mmol of HDPO, 0.1 mol of potassium tert-butoxide, and 5 ml of ultra-dry toluene were introduced and stirred at 80 °C for 12 h. A large amount of white solid precipitated. After filtration, washing with toluene and water, and drying, 0.96 mmol of 1,2-bis(diphenylphosphoxy)ethane was obtained with a yield of 96%.

[0066] The specific reaction is shown in the following formula.

[0067]

[0068] Comparative Example 4: Under the same conditions as Example 5, using DPO as the raw material, the yield was 79%.

[0069] Example 6:

[0070] Synthesis of (1-n-butyl)diphenylphosphine oxide from HDPO and haloalkanes RX: Under a nitrogen atmosphere, HDPO (1.0 mmol), potassium tert-butoxide (1.0 mmol), and THF (2 mL) were added to a 25 mL Schleck tube. The mixture was stirred at 0 °C for 1 h, then butyl bromide (1 mmol) was added. The tube was sealed and the reaction was continued at 0 °C until complete. The product was purified by column chromatography to obtain (1-n-butyl)diphenylphosphine oxide (0.98 mmol), with a yield of 98%.

[0071] The specific reaction is shown in the following formula.

[0072]

[0073] Comparative Example 5, under the same conditions as Example 6, used DPO as the raw material, with a yield of 92%.

[0074] Example 7:

[0075] Synthesis of (2-naphthyl)diphenylphosphine oxide from HDPO and haloalkanes RX: Under a nitrogen atmosphere, palladium acetate Pd(OAc)2 (0.01 mmol), bis(diphenylphosphine)ferrocene dppf (0.01 mol), and DMF (4 mL) were stirred at room temperature for 10 min. Then, potassium carbonate (1.5 mmol), HDPO (1.0 mmol), and 2-bromonaphthalene (1.0 mmol) were added. The mixture was sealed and reacted at 120 °C for 8 h. After the reaction was complete, (2-naphthyl)diphenylphosphine oxide (0.93 mmol) was obtained by column chromatography with a yield of 93%.

[0076] The specific reaction is shown in the following formula.

[0077]

[0078] Comparative Example 6: Under the same conditions as Example 7, using DPO as the raw material, the yield was 88%.

[0079] Example 8:

[0080] Synthesis of (4-methoxyphenyl)diphenylphosphine oxide from HDPO and haloalkanes RX: Under a nitrogen atmosphere, palladium acetate Pd(OAc)2 (0.01 mmol), bis(diphenylphosphine)ferrocene dppf (0.01 mol), and DMF (4 ml) were stirred at room temperature for 10 min. Then, potassium carbonate (1.5 mmol), HDPO (1.0 mmol), and 4-bromoanisole (1.0 mmol) were added. The mixture was capped and reacted at 120 °C for 8 h. After the reaction was complete, (4-methoxyphenyl)diphenylphosphine oxide (0.97 mmol) was obtained by column chromatography with a yield of 97%.

[0081] The specific reaction is shown in the following formula.

[0082]

[0083] Comparative Example 7: Under the same conditions as Example 8, using DPO as the raw material, the yield was 89%.

[0084] Example 9:

[0085] Synthesis of (4-trifluoromethylphenyl)diphenylphosphine oxide from HDPO and haloalkanes RX: Under a nitrogen atmosphere, palladium acetate Pd(OAc)2 (0.01 mmol), bis(diphenylphosphine)ferrocene dppf (0.01 mol), and DMF (4 ml) were stirred at room temperature for 10 min. Then, potassium carbonate (1.5 mmol), HDPO (1.0 mmol), and 1-bromo-4-(trifluoromethyl)benzene (1.0 mmol) were added. The mixture was capped and reacted at 120 °C for 8 h. After the reaction was complete, (4-trifluoromethylphenyl)diphenylphosphine oxide (0.91 mmol) was obtained by column chromatography with a yield of 91%.

[0086] The specific reaction is shown in the following formula.

[0087]

[0088] Comparative Example 8: Under the same conditions as Example 9, using DPO as the raw material, the yield was 85%.

Claims

1. A method for preparing an organophosphorus oxide compound, characterized in that: Includes the following steps: The first step is to use the starting material α-hydroxyphosphine oxide R 1 R 2 P(O)-C(OH)R 3 R 4 Adding reagent AB yields a mixture, wherein AB is an aryl alkyne, an alkyl alkyne, or a haloalkanes, and the aryl alkyne or alkyl alkyne is a terminal alkyne. The haloalkane is aliphatic or aromatic; The second step involves adding one or more of a catalyst, ligand, additive, and reaction solvent to the mixture obtained in the first step to initiate a reaction. After the reaction is complete, the mixture is purified to obtain organophosphorus oxide R. 1 R 2 P(O)A; R 1 R 2 Each independently represents phenyl and naphthyl, R 3 R 4 Each independently represents a straight-chain alkyl group; Organophosphorus oxides R 1 R 2 When P(O)A is a martensitic addition alkenylphosphine, AB is a terminal alkyne. A catalyst, phosphine ligand, diphenylphosphonic acid as an additive, and a reaction solvent are added to the mixture obtained in the first step. Organophosphorus oxides R 1 R 2 When P(O)A is an alkenylphosphine undergoing anti-Markovnikov addition, AB is a terminal alkyne. A catalyst and a reaction solvent are added to the mixture obtained in the first step. Organophosphorus oxides R 1 R 2 When P(O)A is a phosphonium oxide and AB is a haloaromatic hydrocarbon, a catalyst, a phosphonium ligand, a base as an additive, and a reaction solvent are added to the mixture obtained in the first step. Organophosphorus oxides R 1 R 2 When P(O)A is a phosphonooxy and AB is a haloalkanes, a base and a reaction solvent are added as additives to the mixture obtained in the first step. The catalyst is selected from tris(dibenzylacetone)palladium Pd2(dba)3, tetra(triphenylphosphine)palladium Pd(Ph3P)4, palladium acetate Pd(OAc)2, and palladium chloride PdCl2; The ligands are selected from 1,2-bis(diphenylphosphine)ethane dppe, 1,2-bis(diphenylphosphine)propane dppp, 1,2-bis(diphenylphosphine)butane dppb, triphenylphosphine Ph3P, diphenylcyclohexylphosphine Ph2PCy, or bis(diphenylphosphine)ferrocene dppf.

2. The preparation method of an organophosphorus oxide according to claim 1, characterized in that: Organophosphorus oxides R 1 R 2 When P(O)A is a martensitic addition alkenylphosphine, the reaction temperature in the second step is 50℃-150℃ and the reaction time is 5h-24h. Organophosphorus oxides R 1 R 2 When P(O)A is an alkenylphosphine undergoing anti-Markovnikov addition, the reaction temperature in the second step is 50℃-150℃, and the reaction time is 5h-24h. Organophosphorus oxides R 1 R 2 When P(O)A is diphenyl(aryl)phosphine oxide, the reaction temperature in the second step is 50℃-150℃, and the reaction time is 5h-24h. Organophosphorus oxides R 1 R 2 When P(O)A is diphenyl(alkyl)phosphine oxide, the reaction temperature in the second step is 0℃-60℃, and the reaction time is 5h-24h.

3. The preparation method of an organophosphorus oxide according to claim 2, characterized in that: The alkali is selected from potassium carbonate, sodium carbonate, lithium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, sodium tert-butoxide, potassium tert-butoxide, lithium tert-butoxide, and triethylamine, and the amount of alkali used is 0.5-3.0 equivalents; The reaction solvent is selected from DMF, DMSO, DMAc, toluene, benzene, xylene, tetrahydrofuran, dioxane, and dichloroethane.

4. The preparation method of an organophosphorus oxide according to claim 3, characterized in that: The organophosphorus oxide R 1 R 2 When P(O)A is a martensitic addition alkenylphosphine, the catalyst is tris(dibenzylacetone)dipalladiumPd2(dba)3, the ligand is 1,2-bis(diphenylphosphine)ethanedppe, the additive is diphenylphosphonic acid Ph2P(O)OH, and the reaction solvent is toluene.

5. The preparation method of an organophosphorus oxide according to claim 3, characterized in that: The organophosphorus oxide R 1 R 2 When P(O)A is an alkenylphosphine undergoing anti-Markovnikov addition, the catalyst is tetrakis(triphenylphosphine)palladium Pd(Ph3P)4, and the reaction solvent is toluene.

6. The preparation of an organophosphorus oxide according to claim 3, characterized in that: The organophosphorus oxide R 1 R 2 P(O)A is diphenyl(aryl)phosphine oxide, the catalyst is palladium acetate Pd(OAc)2, the ligand is bis(diphenylphosphine ferrocene dppf, the base is potassium carbonate or cesium carbonate, and the reaction solvent is DMF.

7. The preparation of an organophosphorus oxide according to claim 3, characterized in that: The organophosphorus oxide R 1 R 2 P(O)A is diphenyl(alkyl)phosphine oxide, the base is potassium tert-butoxide, the reaction solvent is tetrahydrofuran, and the reaction temperature is 0℃-25℃.

8. The preparation of an organophosphorus oxide according to claim 1, characterized in that: The ligand is selected from 1,2-bis(diphenylphosphine)ethane dppe or bisdiphenylphosphine ferrocene dppf, the additive is selected from diphenylphosphonic acid Ph2P(O)OH or potassium carbonate, and the reaction solvent is selected from toluene, THF or DMF.

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