CN115403623A - Method for preparing 2-pyrrolyl substituted phosphine oxide compound - Google Patents
Method for preparing 2-pyrrolyl substituted phosphine oxide compound Download PDFInfo
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
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Abstract
The invention provides a method for efficiently and selectively synthesizing 2-pyrrolyl substituted phosphine oxide compounds with different substituted functional groups, which adopts eosin Y as a catalyst, 2- (2-oxo-2-aryl ethyl) malononitrile and diaryl substituted phosphorus-oxygen compounds as reaction substrates, a 10W blue LED lamp as a light source, and alkali and an organic solvent added into a reaction system. The method has the advantages that: the auxiliary agent 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 high. The method overcomes the defects of poor reaction selectivity, complicated reaction steps, low yield, high cost, the need of using reagents harmful to the environment and the like in the traditional synthesis of the 2-pyrrolyl substituted phosphine oxide compound, and has good industrial application prospect. The invention also provides corresponding 2-pyrrolyl substituted phosphine oxide derivatives containing different substituted functional groups.
Description
Technical Field
The invention relates to the field of catalytic synthesis of organic phosphonate compounds, in particular to a synthesis method for preparing 2-pyrrolyl substituted phosphine oxide compounds by cyclization-tandem reaction of 2- (2-oxo-2-aryl ethyl) malononitrile and diaryl substituted phosphorus oxide compounds under photocatalysis.
Background
The organic phosphonate is an important organic synthesis intermediate, and the organic phosphonate is widely applied to the fields of medical intermediates, pesticides, biological agents, photoelectric materials, efficient flame retardants, catalyst ligands and the like.
The tetradentate organophosphorus reagent can be converted into a tridentate organophosphorus compound through intramolecular tautomeric transformation during the phosphorylation reaction, namely, a phosphoryl group with high bond energy (P = O) is converted into a P-OH bond with a P-H bond. During the reaction process, the pentacoordinate phosphorus compound is often used as an intermediate or transition state, and due to the mutual transformation between the compounds with different coordination numbers, the organophosphorus reagent is widely applied to organic synthesis and becomes an important component of organic phosphorus chemistry, especially organic synthesis chemistry.
The method for synthesizing the 2-pyrrolyl substituted phosphine oxide compound reported in the literature mainly comprises the following steps: (1)Friedel-CraftsReaction: firstly, protecting an N-H bond of a pyrrole compound by using a protecting group, then catalyzing a P (O) -X (X = F, cl, br) compound and the protected pyrrole compound to perform electrophilic substitution reaction by using Lewis acid (aluminum trichloride and the like), and finally performing deprotection reaction to prepare a corresponding target product; (2) cross-coupling reaction: catalyzing the cross coupling reaction of the P (O) -H compound and the 2-halogenopyrrole compound or the 2-boric acid pyrrole compound by adopting the P (O) -H compound in the presence of reagents such as transition metal (iron, copper, nickel, palladium and the like), alkali and the like; (3) nucleophilic substitution reaction: firstly, protecting an N-H bond of a 2-halogenated pyrrole compound by using a protecting group, and further preparing the compound into a corresponding format reagent; the Grignard reagent can generate nucleophilic substitution reaction with P (O) -X (X = F, cl, br) compounds under the condition of low-temperature reaction to prepare corresponding target products. However, the above methods generally employ air-sensitive reagents (Grignard reagents, phosphoryl chloride, etc.), special ligands (phosphine ligands, ferrocene ligands, carbene ligands, etc.), and further have complicated experimental procedures (pre-protection and deprotection strategies, etc.), expensive catalysts and low costDifficult recycling, harsh reaction conditions, cross-compatibility of substrates, low yield, great pollution to the environment and the like.
So far, the high-efficiency synthesis of 2-pyrrolyl substituted phosphine oxide compounds has the problems of raw material quality, production safety (phosphorus oxychloride and other compounds have strong corrosivity, poor water-oxygen stability of a format reagent and the like) and product stability and purity and the like, the synthesis technology is difficult, only a few companies in the United states, germany, british and Japan are used for production at present, and the current situation of high-end or special organic phosphonate products in China mainly depends on import.
Aiming at the defects of the existing heterocyclic group substituted organic phosphonate compound synthesis process, the industry is focusing on developing a new method for synthesizing a corresponding 2-pyrrolyl substituted phosphine oxide compound by using stable, cheap and easily obtained diaryl phosphorus oxide as a phosphorylation reagent by utilizing a cheap catalyst or an auxiliary agent for high-efficiency catalysis.
Disclosure of Invention
The invention aims to provide a novel method for synthesizing a corresponding 2-pyrrolyl substituted phosphine oxide compound by taking cheap and easily-obtained 2- (2-oxo-2-aryl ethyl) malononitrile and diaryl substituted phosphorus oxide compounds as raw materials through a photocatalytic cyclization-tandem reaction with high efficiency and high selectivity so as to overcome the defects in the prior art.
The invention comprises the following steps: taking reaction amount of 2- (2-oxo-2-arylethyl) malononitrile, diaryl substituted phosphorus oxygen, alkali, catalyst and organic solvent, placing the mixture in a reaction container under nitrogen environment, mixing, and irradiating by a 10W blue LED lamp at 60W o C, stirring and reacting for 1 hour to obtain the corresponding 2-pyrrolyl substituted phosphine oxide compounds containing different substituted functional groups. The specific reaction formula is as follows:
wherein the content of the first and second substances,
the catalyst is eosin Y, the alkali is sodium tert-butoxide, and the organic solvent is acetonitrile;
Ar 1 is selected from phenyl, 4-methylphenyl, 3-methylphenyl, 4-ethylphenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 2-hydroxyphenyl, 2, 5-dimethoxyphenyl, 4-fluorophenyl, 2-fluorophenyl, 4-chlorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 3-nitrophenyl, 4-cyanophenyl, 4-trifluoromethylphenyl, 2-naphthyl;
Ar 2 is selected from phenyl, 4-methylphenyl, 3-methylphenyl, 4-ethylphenyl, 3, 5-dimethylphenyl, 2, 5-dimethylphenyl, 3-methoxyphenyl, 4-butylphenyl, 4-tert-butylphenyl, 3-fluorophenyl, 4-chlorophenyl, 1-naphthyl, 2-naphthyl, 3-phenylphenyl;
Ar 3 is selected from phenyl, 4-methylphenyl, 3-methylphenyl, 4-ethylphenyl, 3, 5-dimethylphenyl, 2, 5-dimethylphenyl, 3-methoxyphenyl, 4-butylphenyl, 4-tert-butylphenyl, 3-fluorophenyl, 4-chlorophenyl, 1-naphthyl, 2-naphthyl, 3-phenylphenyl and 4-phenylphenyl.
In the above method for synthesizing a 2-pyrrolyl-substituted phosphine oxide compound from 2- (2-oxo-2-arylethyl) malononitrile and a diaryl-substituted phosphine oxide compound, 2- (2-oxo-2-arylethyl) malononitrile is selected from 2- (2-oxo-2-phenyl) malononitrile, 2- (2-oxo-2- (4-methylphenyl)) malononitrile, 2- (2-oxo-2- (3-methylphenyl)) malononitrile, 2- (2-oxo-2- (4-ethylphenyl)) malononitrile, 2- (2-oxo-2- (4-tert-butylphenyl)) malononitrile, 2- (2-oxo-2- (4-methoxyphenyl)) malononitrile, 2- (2-oxo-2- (2-hydroxyphenyl)) malononitrile, 2- (2-oxo-2- (2, 5-dimethoxyphenyl)) malononitrile, 2- (2-oxo-2- (4-fluorophenyl)) malononitrile, 2- (2-oxo-2- (2-fluorophenyl)) malononitrile, 2- (2-oxo-2- (4-chlorophenyl)) malononitrile, 2- (2-oxo-2-fluorophenyl)) malononitrile, 2- (2-oxo-2-chlorophenyl)) malononitrile, 2- (2-oxo-chlorophenyl)) malononitrile, 2-chlorophenyl) malononitrile, 2- (4-chlorophenyl) propanedinitrile, 2- (2-oxo-2- (3-chlorophenyl)) malononitrile, 2- (2-oxo-2- (4-bromophenyl)) malononitrile, 2- (2-oxo-2- (4-iodophenyl)) malononitrile, 2- (2-oxo-2- (3-nitrophenyl)) malononitrile, 2- (2-oxo-2- (4-cyanophenyl)) malononitrile, 2- (2-oxo-2- (4-trifluoromethylphenyl)) malononitrile, 2- (2-oxo-2- (2-naphthyl)) malononitrile.
In the method for synthesizing the 2-pyrrolyl substituted phosphine oxide compound by using the 2- (2-oxo-2-aryl ethyl) malononitrile and the diaryl substituted phosphorus oxide compound, the diaryl-substituted phosphorus-oxygen compound is selected from diphenylphosphinophosphoxy, bis (4-methylphenyl) phosphine-oxy, bis (3-methylphenyl) phosphine-oxy, bis (4-ethylphenyl) phosphine-oxy, bis (3, 5-dimethylphenyl) phosphine-oxy, bis (2, 5-dimethylphenyl) phosphine-oxy, bis (3-methoxyphenyl) phosphine-oxy, bis (4-butylphenyl) phosphine-oxy, bis (4-tert-butylphenyl) phosphine-oxy, bis (3-fluorophenyl) phosphine-oxy, bis (4-chlorophenyl) phosphine-oxy, bis (1-naphthyl) phosphine-oxy, bis (2-naphthyl) phosphine-oxy, bis (3-phenylphenyl) phosphine-oxy, phenyl (3-methoxyphenyl) phosphine-oxy, phenyl (4-tert-butylphenyl) phosphine-oxy, phenyl (4-butylphenyl) phosphine-oxy, phenyl (2, 5-dimethylphenyl) phosphine-oxy, phenyl (4-phenylphenyl) phosphine-oxy, phenyl (3-phenylphenyl) phosphine-oxy, phenyl (4-chlorophenyl) phosphine-oxy, and (4-chlorophenyl) phosphine-oxy.
The molar ratio of the 2- (2-oxo-2-arylethyl) malononitrile to the diaryl substituted phosphorus-oxygen compound is 1: [1.0 to 1.2], most preferably 1:1; the molar ratio of 2- (2-oxo-2-arylethyl) malononitrile to sodium tert-butoxide is 1: [0.1 to 2.0], most preferably 1:1; the molar ratio of 2- (2-oxo-2-arylethyl) malononitrile to eosin Y is 1: [0.01 to 0.2], most preferably 1:0.03.
the method for efficiently and selectively synthesizing the 2-pyrrolyl substituted phosphine oxide compound from the 2- (2-oxo-2-aryl ethyl) malononitrile and the diaryl substituted phosphorus oxide compound under the photocatalytic reaction condition has mild and easily controlled reaction process. The method is simple and feasible while obtaining higher yield and 100% selectivity, and the used auxiliary agent is cheap and easy to obtain, and the preparation is simple, thereby having good industrial application prospect.
Drawings
FIG. 1 is a single crystal diffraction analysis chart of the structure of the target product of example 31.
[ detailed description ] embodiments
The invention is further illustrated below with reference to examples of the invention:
1. testing and analysis
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 target product selectivity and yield were analyzed using a Bruker Avance-III 500 NMR Analyzer, manufactured by Bruker, inc.
2. Examples of the invention
Example 1
92 mg (0.5 mmol) of 2- (2-oxo-2-phenyl) malononitrile, 101 mg (0.5 mmol) of diphenylphosphine oxide and 48 mg (0.5 mmol) of sodium tert-butoxide are added under nitrogen to a Schlenk tube, 1.0 mL of acetonitrile are added under nitrogen protection, and 60 mL of acetonitrile are added o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified by column chromatography, and the yield of the target product is 97%.
Example 2
99 mg (0.5 mmol) of 2- (2-oxo-2- (4-methylphenyl)) malononitrile, 101 mg (0.5 mmol) of diphenylphosphine oxide and 48 mg (0.5 mmol) of sodium tert-butoxide are added under nitrogen to a Schlenk tube, and 1.0 mL of acetonitrile are added under nitrogen protection at 60 o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified by column chromatography, and the yield of the target product is 93%.
Example 3
99 mg (0.5 mmol) of 2- (2-oxo-2- (3-methylphenyl)) malononitrile, 101 mg (0.5 mmol) of diphenylphosphineoxy and 48 mg (0.5 mmol) of sodium tert-butoxide are added to a Schlenk tube under nitrogen, and 1.0 mL of acetonitrile is added under nitrogen protection, and 60 mL of acetonitrile is added o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, separating and purifying by column chromatographyThe yield of the desired product was 95%.
Example 4
106 mg (0.5 mmol) of 2- (2-oxo-2- (4-ethylphenyl)) malononitrile, 101 mg (0.5 mmol) of diphenylphosphineoxy and 48 mg (0.5 mmol) of sodium tert-butoxide are added under nitrogen to a Schlenk tube, and 1.0 mL of acetonitrile is added under nitrogen protection at 60% o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified by column chromatography, and the yield of the target product is 92%.
Example 5
120 mg (0.5 mmol) of 2- (2-oxo-2- (4-tert-butylphenyl)) malononitrile, 101 mg (0.5 mmol) of diphenylphosphineoxy and 48 mg (0.5 mmol) of sodium tert-butoxide are introduced into a Schlenk tube under nitrogen, and 1.0 mL of acetonitrile are added under nitrogen protection, and 60 mL of acetonitrile are added o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified through column chromatography, and the yield of the target product is 97%.
Example 6
107 mg (0.5 mmol) of 2- (2-oxo-2- (4-methoxyphenyl)) malononitrile, 101 mg (0.5 mmol) of diphenylphosphine oxide and 48 mg (0.5 mmol) of sodium tert-butoxide are added to a Schlenk tube under nitrogen, and 1.0 mL of acetonitrile is added under nitrogen protection at 60% o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified through column chromatography, and the yield of the target product is 96%.
Example 7
100 mg (0.5 mmol) of 2- (2-oxo-2- (2-hydroxyphenyl)) malononitrile, 101 mg (0.5 mmol) of diphenylphosphine oxide and 48 mg (0.5 mmol) of sodium tert-butoxide are added to a Schlenk tube under nitrogen, and 1.0 mL of acetonitrile is added under nitrogen protection, and 60 mL of acetonitrile is added o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified through column chromatography, and the yield of the target product is 86%.
Example 8
122 mg (0.5 mmol) of 2- (2-oxo-2- (2, 5-dimethoxyphenyl)) propanediylNitrile, 101 mg (0.5 mmol) of diphenylphosphineoxy and 48 mg (0.5 mmol) of sodium tert-butoxide are added under nitrogen to a Schlenk tube, and 1.0 mL of acetonitrile and 60 g of acetonitrile are added under nitrogen protection o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified by column chromatography, and the yield of the target product is 91%.
Example 9
101 mg (0.5 mmol) of 2- (2-oxo-2- (4-fluorophenyl)) malononitrile, 101 mg (0.5 mmol) of diphenylphosphine oxide and 48 mg (0.5 mmol) of sodium tert-butoxide are added to a Schlenk tube under nitrogen, and 1.0 mL of acetonitrile is added under nitrogen protection at 60% o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified through column chromatography, and the yield of the target product is 96%.
Example 10
101 mg (0.5 mmol) of 2- (2-oxo-2- (2-fluorophenyl)) malononitrile, 101 mg (0.5 mmol) of diphenylphosphine oxide and 48 mg (0.5 mmol) of sodium tert-butoxide are added to a Schlenk tube under nitrogen, and 1.0 mL of acetonitrile is added under nitrogen protection, and 60 mL of acetonitrile is added o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified by column chromatography, and the yield of the target product is 92%.
Example 11
109 mg (0.5 mmol) of 2- (2-oxo-2- (4-chlorophenyl)) malononitrile, 101 mg (0.5 mmol) of diphenylphosphineoxy and 48 mg (0.5 mmol) of sodium tert-butoxide are added under nitrogen to a Schlenk tube, 1.0 mL of acetonitrile are added under nitrogen protection, 60 mL of acetonitrile are added o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified through column chromatography, and the yield of the target product is 91%.
Example 12
109 mg (0.5 mmol) of 2- (2-oxo-2- (2-chlorophenyl)) malononitrile, 101 mg (0.5 mmol) of diphenylphosphine oxide and 48 mg (0.5 mmol) of sodium tert-butoxide are added to a Schlenk tube under nitrogen, and 1.0 mL of acetonitrile is added under nitrogen protection, and 60 mL of acetonitrile is added o C is in 10W blue light LED lamp and shineThe reaction was stirred for 1 hour. After the reaction is finished, the target product is separated and purified by column chromatography, and the yield of the target product is 86%.
Example 13
109 mg (0.5 mmol) of 2- (2-oxo-2- (3-chlorophenyl)) malononitrile, 101 mg (0.5 mmol) of diphenylphosphine oxide and 48 mg (0.5 mmol) of sodium tert-butoxide are added to a Schlenk tube under nitrogen, and 1.0 mL of acetonitrile is added under nitrogen protection, and 60 mL of acetonitrile is added o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified through column chromatography, and the yield of the target product is 89%.
Example 14
131 mg (0.5 mmol) of 2- (2-oxo-2- (4-bromophenyl)) malononitrile, 101 mg (0.5 mmol) of diphenylphosphine oxide and 48 mg (0.5 mmol) of sodium tert-butoxide are added to a Schlenk tube under nitrogen, and 1.0 mL of acetonitrile is added under nitrogen protection, and 60 mL of acetonitrile is added o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified by column chromatography, and the yield of the target product is 89%.
Example 15
155 mg (0.5 mmol) of 2- (2-oxo-2- (4-iodophenyl)) malononitrile, 101 mg (0.5 mmol) of diphenylphosphineoxide and 48 mg (0.5 mmol) of sodium tert-butoxide are added to a Schlenk tube under nitrogen, 1.0 mL of acetonitrile are added under nitrogen protection, and 60 mL of acetonitrile are added o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified by column chromatography, and the yield of the target product is 87%.
Example 16
114.5 mg (0.5 mmol) of 2- (2-oxo-2- (3-nitrophenyl)) malononitrile, 101 mg (0.5 mmol) of diphenylphosphineoxide and 48 mg (0.5 mmol) of sodium tert-butoxide are added to a Schlenk tube under nitrogen, 1.0 mL of acetonitrile are added under nitrogen protection, and 60 mL of acetonitrile are added o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified by column chromatography, and the yield of the target product is 82%.
Example 17
104.5 mg (0.5 mmol) of 2- (2-oxo-2- (4-cyanophenyl)) malononitrile, 101 mg (0.5 mmol) of diphenylphosphine oxide and 48 mg (0.5 mmol) of sodium tert-butoxide are added under nitrogen to a Schlenk tube, and 1.0 mL of acetonitrile are added under nitrogen protection at 60% o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified by column chromatography, and the yield of the target product is 88%.
Example 18
126 mg (0.5 mmol) of 2- (2-oxo-2- (4-trifluoromethylphenyl)) malononitrile, 101 mg (0.5 mmol) of diphenylphosphineoxy and 48 mg (0.5 mmol) of sodium tert-butoxide are added to a Schlenk tube under nitrogen, 1.0 mL of acetonitrile are added under nitrogen protection, and 60 mL of acetonitrile are added o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified by column chromatography, and the yield of the target product is 91%.
Example 19
117 mg (0.5 mmol) of 2- (2-oxo-2- (2-naphthyl)) malononitrile, 101 mg (0.5 mmol) of diphenylphosphine oxide and 48 mg (0.5 mmol) of sodium tert-butoxide are added under nitrogen to a Schlenk tube, and 1.0 mL of acetonitrile is added under nitrogen protection at 60% o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified through column chromatography, and the yield of the target product is 95%.
Example 20
92 mg (0.5 mmol) of 2- (2-oxo-2-phenyl) malononitrile, 115 mg (0.5 mmol) of bis (4-methylphenyl) phosphorus oxide and 48 mg (0.5 mmol) of sodium tert-butoxide are added under nitrogen to a Schlenk tube, 1.0 mL of acetonitrile are added under nitrogen protection, and 60 mL of acetonitrile are added o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified through column chromatography, and the yield of the target product is 95%.
Example 21
92 mg (0.5 mmol) of 2- (2-oxo-2-phenyl) malononitrile, 115 mg (0.5 mmol) of bis (3-methylphenyl) phosphorus oxygen and 48 mg (0.5 mmol) of sodium tert-butoxide are added under nitrogen to a Schlenk tube under nitrogenUnder the protection condition, 1.0 mL of acetonitrile is added, and then the mixture is put into a reactor at 60 DEG o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified by column chromatography, and the yield of the target product is 93%.
Example 22
92 mg (0.5 mmol) of 2- (2-oxo-2-phenyl) malononitrile, 129 mg (0.5 mmol) of bis (4-ethylphenyl) phosphorus oxy and 48 mg (0.5 mmol) of sodium tert-butoxide are added under nitrogen to a Schlenk tube, 1.0 mL of acetonitrile are added under nitrogen protection, 60 mL of acetonitrile are added o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified by column chromatography, and the yield of the target product is 96%.
Example 23
92 mg (0.5 mmol) of 2- (2-oxo-2-phenyl) malononitrile, 129 mg (0.5 mmol) of bis (3, 5-dimethylphenyl) phosphine oxide and 48 mg (0.5 mmol) of sodium tert-butoxide are added under nitrogen to a Schlenk tube, 1.0 mL of acetonitrile is added under nitrogen protection, and 60 mL of acetonitrile is added o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified by column chromatography, and the yield of the target product is 91%.
Example 24
92 mg (0.5 mmol) of 2- (2-oxo-2-phenyl) malononitrile, 129 mg (0.5 mmol) of bis (2, 5-dimethylphenyl) phosphorus-oxygen and 48 mg (0.5 mmol) of sodium tert-butoxide are added under nitrogen to a Schlenk's tube, 1.0 mL of acetonitrile are added under nitrogen protection, 60 mL of acetonitrile are added o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified through column chromatography, and the yield of the target product is 89%.
Example 25
92 mg (0.5 mmol) of 2- (2-oxo-2-phenyl) malononitrile, 131 mg (0.5 mmol) of bis (3-methoxyphenyl) phosponic oxygen and 48 mg (0.5 mmol) of sodium tert-butoxide are added under nitrogen to a Schlenk tube, 1.0 mL of acetonitrile are added under nitrogen protection, and 60 mL of acetonitrile are added o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified by column chromatographyThe yield was 92%.
Example 26
92 mg (0.5 mmol) of 2- (2-oxo-2-phenyl) malononitrile, 131 mg (0.5 mmol) of bis (4-methoxyphenyl) phosponic oxygen and 48 mg (0.5 mmol) of sodium tert-butoxide are added under nitrogen to a Schlenk tube, 1.0 mL of acetonitrile are added under nitrogen protection, and 60 mL of acetonitrile are added o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified by column chromatography, and the yield of the target product is 94%.
Example 27
92 mg (0.5 mmol) of 2- (2-oxo-2-phenyl) malononitrile, 157 mg (0.5 mmol) of bis (4-butylphenyl) phosporic acid and 48 mg (0.5 mmol) of sodium tert-butoxide are introduced into a Schlenk tube under nitrogen, 1.0 mL of acetonitrile are added under nitrogen protection, and 60 mL of acetonitrile are added o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified through column chromatography, and the yield of the target product is 98%.
Example 28
92 mg (0.5 mmol) of 2- (2-oxo-2-phenyl) malononitrile, 157 mg (0.5 mmol) of bis (4-tert-butylphenyl) phosporic acid and 48 mg (0.5 mmol) of sodium tert-butoxide are introduced into a Schlenk tube under nitrogen, 1.0 mL of acetonitrile are added under nitrogen protection, and 60 mL of acetonitrile are added o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified through column chromatography, and the yield of the target product is 93%.
Example 29
92 mg (0.5 mmol) of 2- (2-oxo-2-phenyl) malononitrile, 119 mg (0.5 mmol) of bis (3-fluorophenyl) phosphorus oxy and 48 mg (0.5 mmol) of sodium tert-butoxide are added under nitrogen to a Schlenk tube, and 1.0 mL of acetonitrile are added under nitrogen protection at 60% o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified by column chromatography, and the yield of the target product is 87%.
Example 30
92 mg (0.5 mmol) of 2- (2-oxo-2-phenyl) malononitrile, 119 mg (0.5 mmol) of bis (4-fluorophenyl) ester) Phosphorus oxygen and 48 mg (0.5 mmol) of sodium tert-butoxide are added into a Schlenk tube under nitrogen atmosphere, 1.0 mL of acetonitrile is added under nitrogen protection, and the mixture is stirred at 60 DEG o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified through column chromatography, and the yield of the target product is 90%.
Example 31
92 mg (0.5 mmol) of 2- (2-oxo-2-phenyl) malononitrile, 151 mg (0.5 mmol) of di (1-naphthyl) phosphine oxide and 48 mg (0.5 mmol) of sodium tert-butoxide are added to a Schlenk tube under nitrogen, 1.0 mL of acetonitrile are added under nitrogen protection, and 60 mL of acetonitrile are added o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified by column chromatography, and the yield of the target product is 93%.
Example 32
92 mg (0.5 mmol) of 2- (2-oxo-2-phenyl) malononitrile, 151 mg (0.5 mmol) of di (2-naphthyl) phosphine oxide and 48 mg (0.5 mmol) of sodium tert-butoxide are added to a Schlenk tube under nitrogen, 1.0 mL of acetonitrile are added under nitrogen protection, and 60 mL of acetonitrile are added o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified by column chromatography, and the yield of the target product is 90%.
Example 33
92 mg (0.5 mmol) of 2- (2-oxo-2-phenyl) malononitrile, 177 mg (0.5 mmol) of bis (3-phenylphenyl) phosphorus oxy and 48 mg (0.5 mmol) of sodium tert-butoxide are added under nitrogen to a Schlenk tube, 1.0 mL of acetonitrile are added under nitrogen protection, 60 mL of acetonitrile are added o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified through column chromatography, and the yield of the target product is 94%.
Example 34
92 mg (0.5 mmol) of 2- (2-oxo-2-phenyl) malononitrile, 116 mg (0.5 mmol) of phenyl (3-methoxyphenyl) phosporium oxide and 48 mg (0.5 mmol) of sodium tert-butoxide are added under nitrogen to a Schlenk tube, 1.0 mL of acetonitrile are added under nitrogen protection, 60 mL of acetonitrile are added o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp.After the reaction is finished, the target product is separated and purified by column chromatography, and the yield of the target product is 95%.
Example 35
92 mg (0.5 mmol) of 2- (2-oxo-2-phenyl) malononitrile, 129 mg (0.5 mmol) of phenyl (4-tert-butylphenyl) phosporxy and 48 mg (0.5 mmol) of sodium tert-butoxide are introduced under nitrogen into a Schlenk tube, 1.0 mL of acetonitrile are added under nitrogen protection, 60 mL of acetonitrile are added o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified by column chromatography, and the yield of the target product is 95%.
Example 36
92 mg (0.5 mmol) of 2- (2-oxo-2-phenyl) malononitrile, 129 mg (0.5 mmol) of phenyl (4-butylphenyl) phosporic acid and 48 mg (0.5 mmol) of sodium tert-butoxide are introduced under nitrogen into a Schlenk tube, 1.0 mL of acetonitrile are added under nitrogen protection, 60 mL of acetonitrile are added o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified by column chromatography, and the yield of the target product is 98%.
Example 37
92 mg (0.5 mmol) of 2- (2-oxo-2-phenyl) malononitrile, 115 mg (0.5 mmol) of phenyl (2, 5-dimethylphenyl) phosphine oxide and 48 mg (0.5 mmol) of sodium tert-butoxide are added under nitrogen to a Schlenk tube, 1.0 mL of acetonitrile are added under nitrogen protection, and 60 mL of acetonitrile are added o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified by column chromatography, and the yield of the target product is 88%.
Example 38
92 mg (0.5 mmol) of 2- (2-oxo-2-phenyl) malononitrile, 139 mg (0.5 mmol) of phenyl (4-phenylphenyl) phosphorus oxy and 48 mg (0.5 mmol) of sodium tert-butoxide are added under nitrogen to a Schlenk tube, 1.0 mL of acetonitrile are added under nitrogen protection, 60 mL of acetonitrile are added o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified by column chromatography, and the yield of the target product is 97%.
Example 39
Will 92mg (0.5 mmol) of 2- (2-oxo-2-phenyl) malononitrile, 139 mg (0.5 mmol) of phenyl (3-phenylphenyl) phosphorus-oxygen and 48 mg (0.5 mmol) of sodium tert-butoxide are added under nitrogen to a Schlenk tube, 1.0 mL of acetonitrile are added under nitrogen protection, 60 mL of acetonitrile are added o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified through column chromatography, and the yield of the target product is 94%.
Example 40
92 mg (0.5 mmol) of 2- (2-oxo-2-phenyl) malononitrile, 110 mg (0.5 mmol) of phenyl (3-fluorophenyl) phosphorus oxide and 48 mg (0.5 mmol) of sodium tert-butoxide are added under nitrogen to a Schlenk tube, 1.0 mL of acetonitrile are added under nitrogen protection, 60 mL of acetonitrile are added o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified through column chromatography, and the yield of the target product is 92%.
EXAMPLE 41
92 mg (0.5 mmol) of 2- (2-oxo-2-phenyl) malononitrile, 118 mg (0.5 mmol) of phenyl (4-chlorophenyl) phosporic acid and 48 mg (0.5 mmol) of sodium tert-butoxide are added under nitrogen to a Schlenk tube, and 1.0 mL of acetonitrile are added under nitrogen protection at 60% o C, stirring and reacting for 1 hour under the irradiation of a 10W blue LED lamp. After the reaction is finished, the target product is separated and purified by column chromatography, and the yield of the target product is 91%.
Example 42
92 mg (0.5 mmol) of 2- (2-oxo-2-phenyl) malononitrile, 101 mg (0.5 mmol) of diphenylphosphine oxide and 48 mg (0.5 mmol) of sodium tert-butoxide are added to a Schlenk tube under nitrogen, 1.0 mL of acetonitrile are added under nitrogen protection, and 60 mL of acetonitrile are added o C, stirring and reacting for 1 hour under the irradiation of a 5W blue LED lamp. After the reaction is finished, the target product is separated and purified through column chromatography, and the yield of the target product is 55%.
Example 43
92 mg (0.5 mmol) of 2- (2-oxo-2-phenyl) malononitrile, 101 mg (0.5 mmol) of diphenylphosphine oxide and 48 mg (0.5 mmol) of sodium tert-butoxide are introduced under nitrogen into a Schlenk tube, and 1.0 mL of acetonitrile are added under nitrogen protectionIn 60 o C the reaction was stirred for 1 hour. After the reaction is finished, the target product is separated and purified through column chromatography, and the yield of the target product is 14%.
It can be seen from the above examples that the method for preparing the corresponding 2-pyrrolyl substituted phosphine oxide compound containing different substituted functional groups by efficiently reacting 2- (2-oxo-2-arylethyl) malononitrile with diaryl substituted phosphine oxide compound 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 and the like, and provides a method for efficiently synthesizing the 2-pyrrolyl substituted phosphine oxide compounds containing different substituted functional groups.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is specific and detailed, but not to be understood 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 should be subject to the appended claims.
Claims (4)
1. A compound with structural formula prepared by the reaction of 2- (2-oxo-2-aryl ethyl) malononitrile with diaryl substituted phosphorus-oxygen compound（I）The preparation method of the middle 2-pyrrolyl substituted phosphine oxide compound has the following specific reaction formula:
the method is characterized by comprising the following steps:
taking reaction amount of 2- (2-oxo-2-aryl ethyl) malononitrile, diaryl substituted phosphorus oxygen, alkali, catalyst and organic solvent, placing the mixture in a reaction container under nitrogen environment, mixing, and irradiating by a 10W blue LED lamp at 60W o C, stirring and reacting for 1 hour to obtain corresponding 2-pyrrolyl substituent containing different substituent functional groupsA phosphine oxide compound;
wherein the content of the first and second substances,
the catalyst is eosin Y, the alkali is sodium tert-butoxide, and the organic solvent is acetonitrile;
Ar 1 is selected from phenyl, 4-methylphenyl, 3-methylphenyl, 4-ethylphenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 2-hydroxyphenyl, 2, 5-dimethoxyphenyl, 4-fluorophenyl, 2-fluorophenyl, 4-chlorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 3-nitrophenyl, 4-cyanophenyl, 4-trifluoromethylphenyl, 2-naphthyl;
Ar 2 is selected from phenyl, 4-methylphenyl, 3-methylphenyl, 4-ethylphenyl, 3, 5-dimethylphenyl, 2, 5-dimethylphenyl, 3-methoxyphenyl, 4-butylphenyl, 4-tert-butylphenyl, 3-fluorophenyl, 4-chlorophenyl, 1-naphthyl, 2-naphthyl, 3-phenylphenyl;
Ar 3 is selected from phenyl, 4-methylphenyl, 3-methylphenyl, 4-ethylphenyl, 3, 5-dimethylphenyl, 2, 5-dimethylphenyl, 3-methoxyphenyl, 4-butylphenyl, 4-tert-butylphenyl, 3-fluorophenyl, 4-chlorophenyl, 1-naphthyl, 2-naphthyl, 3-phenylphenyl, 4-phenylphenyl.
2. The process according to claim 1, wherein the 2- (2-oxo-2-arylethyl) malononitrile is selected from the group consisting of 2- (2-oxo-2-phenyl) malononitrile, 2- (2-oxo-2- (4-methylphenyl)) malononitrile, 2- (2-oxo-2- (3-methylphenyl)) malononitrile, 2- (2-oxo-2- (4-ethylphenyl)) malononitrile, 2- (2-oxo-2- (4-tert-butylphenyl)) malononitrile, 2- (2-oxo-2- (4-methoxyphenyl)) malononitrile, 2- (2-oxo-2- (2-hydroxyphenyl)) malononitrile, 2- (2-oxo-2- (2, 5-dimethoxyphenyl)) malononitrile, 2- (2-oxo-2- (4-fluorophenyl)) malononitrile, 2- (2-oxo-2- (2-fluorophenyl)) malononitrile, 2- (2-oxo-2- (4-chlorophenyl)) malononitrile, 2- (2-oxo-2-chlorophenyl)) malononitrile, 2- (3-oxo-chlorophenyl)) malononitrile, 2- (2-chlorophenyl)) malononitrile, 2-oxo-2-chlorophenyl) malononitrile, 2- (3-chlorophenyl)) malononitrile, 2-chlorophenyl) malononitrile, 2- (2-oxo-chlorophenyl)) malononitrile, 2-chlorophenyl) malononitrile, and 2- (2-chlorophenyl) malononitrile, 2- (2-oxo-2- (4-bromophenyl)) malononitrile, 2- (2-oxo-2- (4-iodophenyl)) malononitrile, 2- (2-oxo-2- (3-nitrophenyl)) malononitrile, 2- (2-oxo-2- (4-cyanophenyl)) malononitrile, 2- (2-oxo-2- (4-trifluoromethylphenyl)) malononitrile, 2- (2-oxo-2- (2-naphthyl)) malononitrile.
3. The method according to claim 1, wherein the diaryl substituted phosphorus-oxygen compound is selected from the group consisting of diphenylphosphine oxide, bis (4-methylphenyl) phosphorus oxide, bis (3-methylphenyl) phosphorus oxide, bis (4-ethylphenyl) phosphorus oxide, bis (3, 5-dimethylphenyl) phosphorus oxide, bis (2, 5-dimethylphenyl) phosphorus oxide, bis (3-methoxyphenyl) phosphorus oxide, bis (4-butylphenyl) phosphorus oxide, bis (4-tert-butylphenyl) phosphorus oxide, bis (3-fluorophenyl) phosphorus oxide, bis (4-chlorophenyl) phosphorus oxide, bis (1-naphthyl) phosphorus oxide, bis (2-naphthyl) phosphorus oxide, bis (3-phenylphenyl) phosphorus oxide, phenyl (3-methoxyphenyl) phosphorus oxide, phenyl (4-tert-butylphenyl) phosphorus oxide, phenyl (4-butylphenyl) phosphorus oxide, phenyl (2, 5-dimethylphenyl) phosphorus oxide, phenyl (4-phenylphenyl) phosphorus oxide, phenyl (3-methoxyphenyl) phosphorus oxide, and phenyl (4-fluorophenyl) phosphorus oxide.
4. The method according to claim 1, wherein the molar ratio of the 2- (2-oxo-2-arylethyl) malononitrile to the diaryl-substituted phosphorus-oxygen compound is 1: [1.0 to 1.2], most preferably 1:1; the molar ratio of 2- (2-oxo-2-arylethyl) malononitrile to sodium tert-butoxide is 1: [0.1 to 2.0], most preferably 1:1; the molar ratio of 2- (2-oxo-2-arylethyl) malononitrile to eosin Y is 1: [0.01 to 0.2], most preferably 1:0.03.
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