Method for preparing 2-formyl aryl (hypophosphite) / phosphamide compound
By performing a ring-opening-coupling reaction with aryl[c]isoxazole and hydrogen phosphine compounds under copper catalysis, the synthesis problem of 2-formylaryl(second)phosphine/phosphineamide compounds in the prior art was solved. , realizes efficient and selective synthesis methods and has good industrial application prospects.
Patent Information
- Application Number
- CN202411572055.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-11-06
- Publication Date
- 2025-02-14
Smart Images
Figure CN119431439A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the field of catalytic synthesis of organic (hypo)phosphine / phosphoramide compounds, and more particularly to a method for preparing 2-formylaryl (hypo)phosphine / phosphoramide compounds by ring-opening-coupling reaction of aromatic [c] isoxazole and phosphorus hydrogen compounds (dialkyl phosphites, aryl alkyl phosphates and diaryl phosphine oxides) under copper catalysis. Background Art
[0002] Organic (secondary) phosphine / phosphoramide compounds are an important class of organic synthesis intermediates. They are widely used in the fields of pharmaceutical intermediates, pesticides, biological preparations, optoelectronic materials, high-efficiency flame retardants and catalyst ligands.
[0003] From the analysis of the types and basic properties of phosphating agents, tetracoordinated organophosphorus reagents can be transformed into tricoordinated organophosphorus compounds through intramolecular tautomerism during the phosphating reaction, that is, the high-bond energy phosphoryl group (P=O) and PH bond are transformed into P-OH bond. It is precisely because of this mutual conversion between compounds with different coordination numbers that organophosphorus reagents are widely used in organic synthesis and become an important part of organophosphorus chemistry, especially organic synthetic chemistry.
[0004] The synthesis of 2-formylaryl (secondary) phosphine / phosphoramide compounds reported in the literature mainly includes: (1) (oxidative) dehydrogenation coupling reaction: first, 2-aminobenzaldehyde and phosphine compounds are used as raw materials, and then a transition metal (iron, copper, nickel, palladium, etc.), an organic ligand (phosphine, nitrogen, carbene, etc.) and (or) an oxidant are used to catalyze the (oxidative) dehydrogenation coupling reaction between them; however, in the above reaction, the formyl group in 2-aminobenzaldehyde is very easy to react with PH compounds. In addition, the formyl group The CH bond in the reaction is also prone to side reactions during the oxidative dehydrogenation coupling reaction; therefore, the reaction selectivity and functional group tolerance of the above system are poor; (2) Cross-coupling reaction: 2-aminobenzaldehyde and phosphoryl chloride compounds are used to undergo cross-coupling reaction under the promotion of base; (3) Formylation reaction: first, aniline and phosphorus hydrogen compounds are used to obtain aromatic (secondary) phosphine / phosphoramide compounds through cross-coupling reaction, and then the corresponding target product is obtained through formylation reaction under the synergistic action of transition metal and base. However, the above methods generally use special reaction reagents (difficult to prepare, expensive, etc.) and special ligands (phosphine ligands, ferrocene ligands, carbene ligands, etc.), and there are also defects such as cumbersome experimental steps, expensive catalysts that are difficult to recycle, harsh reaction conditions, cross-substrate applicability, low selectivity and yield, and greater environmental pollution.
[0005] So far, the efficient synthesis of 2-formylaryl phosphines / phosphoramide compounds has several problems, such as raw material quality, production safety (phosphoryl chloride compounds and formylating agents have strong corrosiveness and physiological toxicity, oxidants have poor safety and stability, etc.), and product stability and purity. The synthesis technology is quite difficult. Currently, only a few companies in the United States, Germany, the United Kingdom and Japan are producing them. At present, my country's high-end or special aryl phosphines / phosphoramide compound products mainly rely on imports.
[0006] In view of the shortcomings of the existing synthesis process of 2-formylarylphosphines / phosphoramides, the industry is focusing on developing new methods for synthesizing corresponding 2-formylarylphosphines / phosphoramides using stable, cheap and readily available phosphine hydrogen compounds as phosphating agents by using inexpensive catalysts or auxiliary agents for efficient catalysis. Summary of the invention
[0007] The object of the present invention is to provide a novel method for efficiently and selectively synthesizing the corresponding 2-formylaryl (secondary) phosphine / phosphoramide compounds by using cheap and readily available aromatic [c] isoxazoles and phosphine hydrogen compounds (dialkyl phosphites, aryl alkyl phosphates and diaryl phosphine oxides) as raw materials through a ring-opening-coupling reaction, so as to overcome the above-mentioned defects in the prior art.
[0008] The present invention comprises the following steps: taking a reaction amount of aromatic [c] isoxazole, a phosphorus hydrogen compound (dialkyl phosphite, aryl alkyl phosphate and diaryl phosphorus oxide), a catalyst, a base and an organic solvent, placing them in a reaction container under a nitrogen atmosphere for mixing, and stirring and reacting at 25-100° C. for 1-6 hours to obtain the corresponding 2-formyl aryl (secondary) phosphine / phosphoramide compounds containing different substituted functional groups. The specific reaction formula is as follows:
[0009]
[0010] Wherein, the catalyst is cuprous chloride, the base is potassium carbonate, and the organic solvent is acetonitrile;
[0011] R 1 is selected from hydrogen, 5-methoxy, 6-methoxy, 6-fluoro, 5-chloro, 6-chloro, 5-bromo, 4-bromo, 6-nitro, 5-phenoxy;
[0012] R 2 is selected from phenyl, 4-methylphenyl, 3-methylphenyl, 3,5-dimethylphenyl, 2,5-dimethylphenyl, 2,4,6-trimethylphenyl, 4-n-butylphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-phenylphenyl, 1-naphthyl, 2-naphthyl, methoxy, ethoxy, isopropoxy, phenoxy;
[0013] R3 is selected from phenyl, 4-methylphenyl, 3-methylphenyl, 3,5-dimethylphenyl, 2,5-dimethylphenyl, 2,4,6-trimethylphenyl, 4-n-butylphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-phenylphenyl, 1-naphthyl, 2-naphthyl, methoxy, ethoxy, isopropoxy, phenoxy, and 4-tert-butylphenyl.
[0014] In the above method for synthesizing 2-formylarylphosphine / phosphamide compounds from aromatic [c] isoxazoles and phosphorus hydrogen compounds, the aromatic [c] isoxazoles are selected from benzo [c] isoxazole, 5-methoxybenzo [c] isoxazole, 6-methoxybenzo [c] isoxazole, 6-fluorobenzo [c] isoxazole, 5-chlorobenzo [c] isoxazole, 6-chlorobenzo [c] isoxazole, 5-bromobenzo [c] isoxazole, 4-bromobenzo [c] isoxazole, 6-nitrobenzo [c] isoxazole, and 5-phenoxybenzo [c] isoxazole.
[0015] In the above method for synthesizing 2-formylaryl (secondary) phosphine / phosphoramide compounds from aryl[c]isoxazoles and phosphine hydrogen compounds, the phosphine hydrogen compounds are selected from diphenyl phosphine oxide, di(4-methylphenyl)phosphine oxide, di(3-methylphenyl)phosphine oxide, di(3,5-dimethylphenyl)phosphine oxide, di(2,5-dimethylphenyl)phosphine oxide, di(2,4,6-trimethylphenyl)phosphine oxide, di(4-n-butylphenyl)phosphine oxide, di(4-fluorophenyl)phosphine oxide, di(4-chlorophenyl)phosphine oxide, di(4-phenylphenyl)phosphine oxide, di(1-naphthyl)phosphine oxide, di(2-naphthyl)phosphine oxide, dimethyl phosphite, diethyl phosphite, diisopropyl phosphite, diphenyl phosphite, phenyl(4-tert-butylphenyl)phosphine oxide, phenyl(4-phenylphenyl)phosphine oxide, phenyl(4-fluorophenyl)phosphine oxide, phenyl(4-chlorophenyl)phosphine oxide, and ethyl phenylphosphonate.
[0016] In the method for synthesizing 2-formylarylphosphine / phosphoramide compounds from aromatic [c] isoxazoles and phosphine compounds, the molar ratio of aromatic [c] isoxazoles to phosphine compounds is 1: [1.0-2.0]; the molar ratio of aromatic [c] isoxazoles to cuprous chloride is 1: [0.1-0.3]; and the molar ratio of aromatic [c] isoxazoles to potassium carbonate is 1: [1.0-2.0].
[0017] The present invention provides a method for efficiently and selectively synthesizing 2-formylaryl (secondary) phosphine / phosphoramide compounds from aromatic [c] isoxazoles and phosphorus hydrogen compounds (dialkyl phosphites, aryl alkyl phosphates and diaryl phosphorus oxides) under copper catalytic reaction conditions. The reaction process is mild and easy to control. While obtaining a high yield and 100% selectivity, the method is simple and easy to operate, and the auxiliary agents used are cheap and easy to obtain, the preparation is simple, and the method has good industrial application prospects. BRIEF DESCRIPTION OF THE DRAWINGS
[0018] Figure 1 This is the single crystal diffraction analysis diagram of the target product in Example 31. DETAILED DESCRIPTION
[0019] The present invention will be further described below in conjunction with embodiments of the present invention:
[0020] 1. Testing and Analysis
[0021] The structural analysis of the reaction products in the following examples of the present invention was performed using a gas phase-mass spectrometer GC / MS (6890N / 5973N) equipped with an HP-5MS capillary chromatographic column (30m×0.45mm×0.8μm) produced by Agilent and a Bruker Avance-III500 nuclear magnetic resonance analyzer produced by Bruker. The selectivity and yield of the target product were analyzed using a Bruker Avance-III 500 nuclear magnetic resonance analyzer produced by Bruker.
[0022] 2. Embodiment
[0023] Example 1
[0024] 23.8 mg (0.2 mmol) of benzo[c]isoxazole, 40.4 mg (0.2 mmol) of diphenylphosphine, 27.6 mg (0.2 mmol) of potassium carbonate and 2.0 mg (0.02 mmol) of cuprous chloride were added to a Schlenk tube under nitrogen atmosphere, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 80° C. for 2 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 92%.
[0025] Example 2
[0026] 29.8 mg (0.2 mmol) of 5-methoxybenzo[c]isoxazole, 40.4 mg (0.2 mmol) of diphenylphosphine, 27.6 mg (0.2 mmol) of potassium carbonate and 2.0 mg (0.02 mmol) of cuprous chloride were added to a Schlenk tube under nitrogen atmosphere, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 80° C. for 2 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 91%.
[0027] Example 3
[0028] 29.8 mg (0.2 mmol) of 6-methoxybenzo[c]isoxazole, 40.4 mg (0.2 mmol) of diphenylphosphine, 27.6 mg (0.2 mmol) of potassium carbonate and 2.0 mg (0.02 mmol) of cuprous chloride were added to a Schlenk tube under nitrogen atmosphere, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 80° C. for 2 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 94%.
[0029] Example 4
[0030] 27.4 mg (0.2 mmol) of 6-fluorobenzo[c]isoxazole, 40.4 mg (0.2 mmol) of diphenylphosphine oxide, 27.6 mg (0.2 mmol) of potassium carbonate and 2.0 mg (0.02 mmol) of cuprous chloride were added to a Schlenk tube under nitrogen atmosphere, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 80° C. for 2 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 92%.
[0031] Example 5
[0032] 30.6 mg (0.2 mmol) of 5-chlorobenzo[c]isoxazole, 40.4 mg (0.2 mmol) of diphenylphosphine, 27.6 mg (0.2 mmol) of potassium carbonate and 2.0 mg (0.02 mmol) of cuprous chloride were added to a Schlenk tube under nitrogen atmosphere, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 80° C. for 2 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 91%.
[0033] Example 6
[0034] 30.6 mg (0.2 mmol) of 6-chlorobenzo[c]isoxazole, 40.4 mg (0.2 mmol) of diphenylphosphine oxide, 27.6 mg (0.2 mmol) of potassium carbonate and 2.0 mg (0.02 mmol) of cuprous chloride were added to a Schlenk tube under nitrogen atmosphere, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 80° C. for 2 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 81%.
[0035] Example 7
[0036] 39.6 mg (0.2 mmol) of 5-bromobenzo[c]isoxazole, 40.4 mg (0.2 mmol) of diphenylphosphine, 27.6 mg (0.2 mmol) of potassium carbonate and 2.0 mg (0.02 mmol) of cuprous chloride were added to a Schlenk tube under nitrogen atmosphere, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 80° C. for 2 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 93%.
[0037] Example 8
[0038] 39.6 mg (0.2 mmol) of 4-bromobenzo[c]isoxazole, 40.4 mg (0.2 mmol) of diphenylphosphine oxide, 27.6 mg (0.2 mmol) of potassium carbonate and 2.0 mg (0.02 mmol) of cuprous chloride were added to a Schlenk tube under nitrogen atmosphere, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 80° C. for 2 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 85%.
[0039] Example 9
[0040] 32.8 mg (0.2 mmol) of 6-nitrobenz[c]isoxazole, 40.4 mg (0.2 mmol) of diphenylphosphine, 27.6 mg (0.2 mmol) of potassium carbonate and 2.0 mg (0.02 mmol) of cuprous chloride were added to a Schlenk tube under nitrogen atmosphere, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 80° C. for 2 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 92%.
[0041] Example 10
[0042] 42.2 mg (0.2 mmol) of 5-phenoxybenzo[c]isoxazole, 40.4 mg (0.2 mmol) of diphenylphosphine, 27.6 mg (0.2 mmol) of potassium carbonate and 2.0 mg (0.02 mmol) of cuprous chloride were added to a Schlenk tube under nitrogen atmosphere, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 80° C. for 2 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 87%.
[0043] Embodiment 11
[0044] 23.8 mg (0.2 mmol) of benzo[c]isoxazole, 46.0 mg (0.2 mmol) of di(4-methylphenyl)phosphine oxide, 27.6 mg (0.2 mmol) of potassium carbonate and 2.0 mg (0.02 mmol) of cuprous chloride were added to a Schlenk tube under nitrogen atmosphere, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 80° C. for 2 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 94%.
[0045] Example 12
[0046] 23.8 mg (0.2 mmol) of benzo[c]isoxazole, 46.0 mg (0.2 mmol) of di(3-methylphenyl)phosphine, 27.6 mg (0.2 mmol) of potassium carbonate and 2.0 mg (0.02 mmol) of cuprous chloride were added to a Schlenk tube under nitrogen atmosphere, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 80° C. for 2 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 90%.
[0047] Example 13
[0048] 23.8 mg (0.2 mmol) of benzo[c]isoxazole, 51.6 mg (0.2 mmol) of di(3,5-dimethylphenyl)phosphine, 27.6 mg (0.2 mmol) of potassium carbonate and 2.0 mg (0.02 mmol) of cuprous chloride were added to a Schlenk tube under nitrogen atmosphere, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 80° C. for 2 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 92%.
[0049] Embodiment 14
[0050] 23.8 mg (0.2 mmol) of benzo[c]isoxazole, 51.6 mg (0.2 mmol) of di(2,5-dimethylphenyl)phosphine, 27.6 mg (0.2 mmol) of potassium carbonate and 2.0 mg (0.02 mmol) of cuprous chloride were added to a Schlenk tube under nitrogen atmosphere, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 80° C. for 2 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 87%.
[0051] Embodiment 15
[0052] 23.8 mg (0.2 mmol) of benzo[c]isoxazole, 57.2 mg (0.2 mmol) of di(2,4,6-trimethylphenyl)phosphine, 27.6 mg (0.2 mmol) of potassium carbonate and 2.0 mg (0.02 mmol) of cuprous chloride were added to a Schlenk tube under nitrogen atmosphere, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 80° C. for 2 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 76%.
[0053] Example 16
[0054] 23.8 mg (0.2 mmol) of benzo[c]isoxazole, 62.8 mg (0.2 mmol) of di(4-n-butylphenyl)phosphine, 27.6 mg (0.2 mmol) of potassium carbonate and 2.0 mg (0.02 mmol) of cuprous chloride were added to a Schlenk tube under nitrogen atmosphere, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 80° C. for 2 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 95%.
[0055] Embodiment 17
[0056] 23.8 mg (0.2 mmol) of benzo[c]isoxazole, 47.6 mg (0.2 mmol) of di(4-fluorophenyl)phosphine, 27.6 mg (0.2 mmol) of potassium carbonate and 2.0 mg (0.02 mmol) of cuprous chloride were added to a Schlenk tube under nitrogen atmosphere, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 80° C. for 2 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 91%.
[0057] Embodiment 18
[0058] 23.8 mg (0.2 mmol) of benzo[c]isoxazole, 54.2 mg (0.2 mmol) of di(4-chlorophenyl)phosphine, 27.6 mg (0.2 mmol) of potassium carbonate and 2.0 mg (0.02 mmol) of cuprous chloride were added to a Schlenk tube under nitrogen atmosphere, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 80° C. for 2 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 89%.
[0059] Embodiment 19
[0060] 23.8 mg (0.2 mmol) of benzo[c]isoxazole, 70.8 mg (0.2 mmol) of di(4-phenylphenyl)phosphine oxide, 27.6 mg (0.2 mmol) of potassium carbonate and 2.0 mg (0.02 mmol) of cuprous chloride were added to a Schlenk tube under nitrogen atmosphere, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 80° C. for 2 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 85%.
[0061] Embodiment 20
[0062] 23.8 mg (0.2 mmol) of benzo[c]isoxazole, 60.4 mg (0.2 mmol) of di(1-naphthyl)phosphine oxide, 27.6 mg (0.2 mmol) of potassium carbonate and 2.0 mg (0.02 mmol) of cuprous chloride were added to a Schlenk tube under nitrogen atmosphere, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 80° C. for 2 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 92%.
[0063] Embodiment 21
[0064] 23.8 mg (0.2 mmol) of benzo[c]isoxazole, 60.4 mg (0.2 mmol) of di(2-naphthyl)phosphine oxide, 27.6 mg (0.2 mmol) of potassium carbonate and 2.0 mg (0.02 mmol) of cuprous chloride were added to a Schlenk tube under nitrogen atmosphere, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 80° C. for 2 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 93%.
[0065] Embodiment 22
[0066] 23.8 mg (0.2 mmol) of benzo[c]isoxazole, 22.0 mg (0.2 mmol) of dimethyl phosphite, 27.6 mg (0.2 mmol) of potassium carbonate and 2.0 mg (0.02 mmol) of cuprous chloride were added to a Schlenk tube under nitrogen atmosphere, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 80° C. for 2 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 83%.
[0067] Embodiment 23
[0068] 23.8 mg (0.2 mmol) of benzo[c]isoxazole, 27.6 mg (0.2 mmol) of diethyl phosphite, 27.6 mg (0.2 mmol) of potassium carbonate and 2.0 mg (0.02 mmol) of cuprous chloride were added to a Schlenk tube under nitrogen atmosphere, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 80° C. for 2 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 86%.
[0069] Embodiment 24
[0070] 23.8 mg (0.2 mmol) of benzo[c]isoxazole, 33.2 mg (0.2 mmol) of diisopropyl phosphite, 27.6 mg (0.2 mmol) of potassium carbonate and 2.0 mg (0.02 mmol) of cuprous chloride were added to a Schlenk tube under nitrogen atmosphere, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 80° C. for 2 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 93%.
[0071] Embodiment 25
[0072] 23.8 mg (0.2 mmol) of benzo[c]isoxazole, 46.8 mg (0.2 mmol) of diphenyl phosphite, 27.6 mg (0.2 mmol) of potassium carbonate and 2.0 mg (0.02 mmol) of cuprous chloride were added to a Schlenk tube under nitrogen atmosphere, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 80° C. for 2 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 75%.
[0073] Embodiment 26
[0074] 23.8 mg (0.2 mmol) of benzo[c]isoxazole, 51.6 mg (0.2 mmol) of phenyl(4-tert-butylphenyl)phosphine, 27.6 mg (0.2 mmol) of potassium carbonate and 2.0 mg (0.02 mmol) of cuprous chloride were added to a Schlenk tube under nitrogen atmosphere, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 80° C. for 2 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 89%.
[0075] Embodiment 27
[0076] 23.8 mg (0.2 mmol) of benzo[c]isoxazole, 55.6 mg (0.2 mmol) of phenyl (4-phenylphenyl) phosphine, 27.6 mg (0.2 mmol) of potassium carbonate and 2.0 mg (0.02 mmol) of cuprous chloride were added to a Schlenk tube under nitrogen atmosphere, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 80° C. for 2 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 92%.
[0077] Embodiment 28
[0078] 23.8 mg (0.2 mmol) of benzo[c]isoxazole, 44.0 mg (0.2 mmol) of phenyl(4-fluorophenyl)phosphine, 27.6 mg (0.2 mmol) of potassium carbonate and 2.0 mg (0.02 mmol) of cuprous chloride were added to a Schlenk tube under nitrogen atmosphere, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 80° C. for 2 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 91%.
[0079] Embodiment 29
[0080] 23.8 mg (0.2 mmol) of benzo[c]isoxazole, 47.2 mg (0.2 mmol) of phenyl(4-chlorophenyl)phosphine, 27.6 mg (0.2 mmol) of potassium carbonate and 2.0 mg (0.02 mmol) of cuprous chloride were added to a Schlenk tube under nitrogen atmosphere, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 80° C. for 2 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 88%.
[0081] Embodiment 30
[0082] 23.8 mg (0.2 mmol) of benzo[c]isoxazole, 34.0 mg (0.2 mmol) of ethyl phenylphosphonate, 27.6 mg (0.2 mmol) of potassium carbonate and 2.0 mg (0.02 mmol) of cuprous chloride were added to a Schlenk tube under nitrogen atmosphere, and then 1.0 mL of acetonitrile was added, and the mixture was stirred at 80° C. for 2 hours. After the reaction was completed, the mixture was separated and purified by column chromatography, and the yield of the target product was 86%.
[0083] As can be seen from the above examples, the method of preparing the corresponding 2-formylaryl (secondary) phosphine / phosphoramide compounds containing different substituted functional groups by efficiently reacting aromatic [c] isoxazoles with phosphorus hydrogen compounds (dialkyl phosphites, aryl alkyl phosphates and diaryl phosphorus oxides) adopted in the present invention has the advantages of mild reaction conditions, cheap and easy to obtain catalysts, and simple preparation. In addition, the method also has the advantages of wide substrate applicability and high yield, and provides a method for efficiently synthesizing 2-formylaryl (secondary) phosphine / phosphoramide compounds containing different substituted functional groups.
[0084] The above-mentioned embodiments only express several implementation methods of the present invention, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the scope of the patent of the present invention. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, which all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.
Claims
1. A method for preparing 2-formylaryl (secondary) phosphine / phosphoramide compounds, characterized in that: The method comprises the following steps: taking a reaction amount of aromatic [c] isoxazole, a phosphorus hydrogen compound, a catalyst, a base and an organic solvent, placing them in a reaction container under a nitrogen atmosphere for mixing, and stirring and reacting at 25-100° C. for 1-6 hours to obtain the corresponding 2-formyl aryl (secondary) phosphine / phosphoramide compounds containing different substituted functional groups; the specific reaction formula is as follows: Wherein, the catalyst is cuprous chloride, the base is potassium carbonate, and the organic solvent is acetonitrile; R 1 is selected from hydrogen, 5-methoxy, 6-methoxy, 6-fluoro, 5-chloro, 6-chloro, 5-bromo, 4-bromo, 6-nitro, 5-phenoxy; R 2 is selected from phenyl, 4-methylphenyl, 3-methylphenyl, 3,5-dimethylphenyl, 2,5-dimethylphenyl, 2,4,6-trimethylphenyl, 4-n-butylphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-phenylphenyl, 1-naphthyl, 2-naphthyl, methoxy, ethoxy, isopropoxy, phenoxy; R 3 is selected from phenyl, 4-methylphenyl, 3-methylphenyl, 3,5-dimethylphenyl, 2,5-dimethylphenyl, 2,4,6-trimethylphenyl, 4-n-butylphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-phenylphenyl, 1-naphthyl, 2-naphthyl, methoxy, ethoxy, isopropoxy, phenoxy, and 4-tert-butylphenyl.
2. The method according to claim 1, characterized in that The aromatic [c] isoxazole is selected from benzo [c] isoxazole, 5-methoxybenzo [c] isoxazole, 6-methoxybenzo [c] isoxazole, 6-fluorobenzo [c] isoxazole, 5-chlorobenzo [c] isoxazole, 6-chlorobenzo [c] isoxazole, 5-bromobenzo [c] isoxazole, 4-bromobenzo [c] isoxazole, 6-nitrobenzo [c] isoxazole, 5-phenoxybenzo [c] isoxazole.
3. The method according to claim 1, characterized in that The phosphine hydrogen compound is selected from diphenylphosphine oxide, di(4-methylphenyl)phosphine oxide, di(3-methylphenyl)phosphine oxide, di(3,5-dimethylphenyl)phosphine oxide, di(2,5-dimethylphenyl)phosphine oxide, di(2,4,6-trimethylphenyl)phosphine oxide, di(4-n-butylphenyl)phosphine oxide, di(4-fluorophenyl)phosphine oxide, di(4-chlorophenyl)phosphine oxide, di(4-phenylphenyl)phosphine oxide, di(1-naphthyl)phosphine oxide, di(2-naphthyl)phosphine oxide, dimethyl phosphite, diethyl phosphite, diisopropyl phosphite, diphenyl phosphite, phenyl(4-tert-butylphenyl)phosphine oxide, phenyl(4-phenylphenyl)phosphine oxide, phenyl(4-fluorophenyl)phosphine oxide, phenyl(4-chlorophenyl)phosphine oxide, and ethyl phenylphosphonate.
4. The method according to claim 1, characterized in that: The molar ratio of the aromatic [c] isoxazole to the phosphine compound is 1: [1.0-2.0]; the molar ratio of the aromatic [c] isoxazole to cuprous chloride is 1: [0.1-0.3]; and the molar ratio of the aromatic [c] isoxazole to potassium carbonate is 1: [1.0-2.0].