CN102126962A - Method for preparing 2,4,6-triarylaniline compounds in aqueous phase - Google Patents

Abstract

The invention discloses a method for preparing a 2,4, 6-triarylaniline compound in an aqueous phase. The method is to prepare the 2,4, 6-triaryl aniline compound through Suzuki cross-coupling reaction of 2,4, 6-tribromoaniline and aryl boric acid. Adding 2,4, 6-tribromoaniline, arylboronic acid, alkali and catalyst into N, N-Dimethylformamide (DMF)/H according to the molar ratio of 0.25:1.125:1.25:0.0025₂O（2.7mL/1.3 mL) in air at 80 ℃, adding saturated salt solution after the reaction is finished, extracting a reaction product by using ethyl acetate, combining organic phases, concentrating, and separating by using column chromatography to obtain the analytically pure 2,4, 6-triarylaniline compound. The method has the characteristics of no need of any ligand, phase transfer agent or promoter, no need of inert gas protection, environmental friendliness, low consumption of palladium catalyst, quick reaction, high yield and simple product separation.

Description

Method for preparing 2,4,6-triarylaniline compounds in aqueous phase

technical field

The invention relates to a method for preparing 2,4,6-triarylaniline compounds in an aqueous phase, which belongs to the technical field of organic compound catalytic chemistry.

Background technique

2,4,6-triarylaniline compounds are widely used in the preparation of medicines, dyes, high-spin or magnetic materials (Bioorg. Med. Chem. Lett. 2007, 3208; Tetrahedron 2000, 5435; Macromol. Rapid Commun. 2003, 768 ; Polyhedron 2002, 1305; J. Org. Chem. 2001, 7456; J. Org. Chem. 2003, 1225; J. Org. Chem. 1991, 6638). 2,4,6-Triarylaniline compounds can be obtained by reduction of nitro compounds, but the reaction conditions are very harsh (J. Chem. Soc., Dalton Trans. 1996, 4265). Palladium-catalyzed Suzuki coupling reaction is one of the most efficient methods for preparing 2,4,6-triarylaniline structures. So far, the methods reported in the literature for the preparation of 2,4,6-triarylaniline compounds require the use of phosphine ligands that are sensitive to air and water, difficult to synthesize, expensive to facilitate, and require long reaction times (Synthesis 1995, 1419). Therefore, the development of simple, cheap, efficient and versatile preparation methods for 2,4,6-triarylaniline compounds has important application prospects.

In recent years, the literature has reported the preparation of 2,4,6-triarylaniline compounds without ligand-promoted Suzuki reaction system (Green Chem. 2003, 635; Tetrahedron Lett. 2003, 3817). However, these methods still have shortcomings such as large amount of catalyst used, low reactivity, long reaction time or low yield. So far, there is no report on the efficient activation of 2,4,6-tribromoaniline for Suzuki reaction to prepare 2,4,6-triaryl-substituted aniline derivatives without ligand promotion.

Contents of the invention

The purpose of the present invention is to provide a simple, cheap, high activity, palladium catalyzed 2,4,6-tribromoaniline and Suzuki cross-coupling reaction of aryl boronic acid to prepare 2,4,6- A new catalytic process for triarylaniline compounds.

The technical scheme adopted is: provide a kind of method for preparing 2,4,6-triarylaniline compound in water phase, in air atmosphere, 2,4,6-tribromoaniline, aryl boronic acid, alkali and palladium The catalyst is added to the N,N-dimethylformamide solution of 1 mL/3 mL-3 mL/1 mL of DMF/H ₂ O at a molar ratio of 1:4.5-6.5:4.5-5.5:0.005-0.02, Suzuki (Suzuki) cross-coupling reaction was carried out at 50-100 ° C for 15-80 minutes. After the reaction, the reaction product was extracted with ethyl acetate, the organic phases were combined, concentrated, and separated by column chromatography to obtain analytically pure 2,4,6-Triarylaniline compounds.

A preferred technical scheme of a method for preparing 2,4,6-triarylaniline compounds in water phase according to the present invention is: before extracting the reaction product with ethyl acetate, add saturated saline.

A preferred technical scheme of a method for preparing 2,4,6-triarylaniline compounds in aqueous phase according to the present invention is: the 2,4,6-tribromoaniline, arylboronic acid, alkali and palladium catalyst The molar ratio is 0.25 : 1.125 : 1.25 : 0.0025.

A preferred technical scheme of a method for preparing 2,4,6-triarylaniline compounds in the aqueous phase according to the present invention is: the DMF/H ₂ O of the N,N-dimethylformamide solution is 2.7 mL/1.3 mL.

A preferred technical proposal of a method for preparing 2,4,6-triarylaniline compounds in water phase according to the present invention is: the reaction temperature of the Suzuki cross-coupling reaction is 80°C.

A preferred technical scheme of a method for preparing 2,4,6-triarylaniline compounds in water phase according to the present invention is: the palladium catalyst is selected from palladium acetate or palladium chloride.

A preferred technical proposal of a method for preparing 2,4,6-triarylaniline compounds in water phase according to the present invention is: the base is selected from potassium phosphate heptahydrate, potassium carbonate or sodium carbonate.

According to a preferred technical scheme of a method for preparing 2,4,6-triarylaniline compounds in water phase provided by the present invention: the arylboronic acid is selected from phenylboronic acid, 4-methylphenylboronic acid, 4-methylphenylboronic acid, Oxyphenylboronic acid, 4-fluorophenylboronic acid, 3,4-difluorophenylboronic acid or 4-chlorophenylboronic acid.

The beneficial effects of the present invention are: the preparation method of this 2,4,6-triarylaniline compound does not use ligands or promoters, does not need inert gas protection, reacts under mild conditions, uses less palladium catalyst, and reacts quickly , high yield, simple product separation, and has broad application prospects in the synthesis of medicine, dyes, ligands, high-spin or magnetic materials, etc.

Detailed ways

The present invention will be described in detail below in conjunction with specific embodiments.

Example 1 2,4,6-triphenylaniline

In the air, weigh 2,4,6-tribromoaniline (0.25 mmol), phenylboronic acid (1.125 mmol), potassium phosphate heptahydrate (1.25 mmol), palladium acetate (0.0025 mmol) and transfer to 25 mL di Then add DMF/H ₂ O (2.7 mL/1.3 mL) into a 25 mL two-necked bottle. The reaction was magnetically stirred at 80 °C for 30 min, followed by TLC. After the reaction was completed, 15 mL of saturated brine was added and the reaction product was extracted with ethyl acetate (15 mL??3). The organic phases were combined and concentrated using a rotary evaporator to obtain a crude product. The target product was obtained by column chromatography. The dehydration was ethyl acetate/petroleum ether (V/V=1/200), and the structure of the product was identified by ¹ H NMR and mass spectrometry. The separation yield reached 99%.

Example 2 2,4,6-triphenylaniline

In the air, weigh 2,4,6-tribromoaniline (0.25 mmol), phenylboronic acid (1.125 mmol), potassium phosphate heptahydrate (1.25 mmol), palladium chloride (0.0025 mmol) and transfer to 25 mL Then add DMF/H ₂ O (2.7 mL/1.3 mL) into a 25 mL two-necked flask. The reaction was magnetically stirred at 80 °C for 60 min, followed by TLC. After the reaction was completed, 15 mL of saturated brine was added and the reaction product was extracted with ethyl acetate (15 mL ?? 3 ). The organic phases were combined and concentrated using a rotary evaporator to obtain a crude product with an isolation yield of 91%.

Example 3 2,4,6-triphenylaniline

In the air, weigh 2,4,6-tribromoaniline (0.25 mmol), phenylboronic acid (1.125 mmol), potassium carbonate (1.25 mmol), palladium acetate (0.0025 mmol) and transfer them to a 25 mL two-necked bottle , then add DMF/H ₂ O (2.7 mL/1.3 mL) into a 25 mL two-neck flask. The reaction was magnetically stirred at 80 °C for 60 min, followed by TLC. After the reaction was completed, 15 mL of saturated brine was added and the reaction product was extracted with ethyl acetate (15 mL??3). The organic phases were combined and concentrated using a rotary evaporator to obtain a crude product with an isolation yield of 99%.

Example 4 2,4,6-triphenylaniline

In the air, weigh 2,4,6-tribromoaniline (0.25 mmol), phenylboronic acid (1.125 mmol), sodium carbonate (1.25 mmol), palladium acetate (0.0025 mmol) and transfer them to a 25 mL two-necked bottle , then add DMF/H ₂ O (2.7 mL/1.3 mL) into a 25 mL two-neck flask. The reaction was magnetically stirred at 80 °C for 60 min, followed by TLC. After the reaction was completed, 15 mL of saturated brine was added and the reaction product was extracted with ethyl acetate (15 mL??3). The organic phases were combined and concentrated using a rotary evaporator to obtain a crude product with an isolation yield of 99%.

Example 5 2,4,6-tri(4-methylphenyl)aniline

In air, successively weigh 2,4,6-tribromoaniline (0.25 mmol), 4-methylphenylboronic acid (1.125 mmol), potassium phosphate heptahydrate (1.25 mmol), palladium acetate (0.0025 mmol) and transfer to into a 25 mL two-necked flask, and then add DMF/H ₂ O (2.7 mL/1.3 mL) into the 25 mL two-necked flask. The reaction was magnetically stirred at 80 °C for 55 min, followed by TLC. After the reaction was completed, 15 mL of saturated brine was added and the reaction product was extracted with ethyl acetate (15 mL??3). The organic phases were combined and concentrated using a rotary evaporator to obtain a crude product. The target product was obtained by column chromatography. The dehydration was ethyl acetate/petroleum ether (V/V=1/300), and the structure of the product was identified by ¹ H NMR and mass spectrometry. The separation yield was 86%.

Example 6 2,4,6-tris(4-methoxyphenyl)aniline

In air, successively weigh 2,4,6-tribromoaniline (0.25 mmol), 4-methoxyphenylboronic acid (1.125 mmol), potassium phosphate heptahydrate (1.25 mmol), palladium acetate (0.0025 mmol) and transfer to into a 25 mL two-necked flask, and then add DMF/H ₂ O (2.7 mL/1.3 mL) into the 25 mL two-necked flask. The reaction was magnetically stirred at 80 °C for 80 min, followed by TLC. After the reaction was completed, 15 mL of saturated brine was added and the reaction product was extracted with ethyl acetate (15 mL??3). The organic phases were combined and concentrated using a rotary evaporator to obtain a crude product. The target product was obtained by column chromatography. The dehydration was ethyl acetate/petroleum ether (V/V=1/10), and the structure of the product was identified by ¹ H NMR and mass spectrometry. The separation yield was 82%.

Example 7 2,4,6-tri(4-fluorophenyl)aniline

In air, successively weigh 2,4,6-tribromoaniline (0.25 mmol), 4-fluorophenylboronic acid (1.125 mmol), potassium phosphate heptahydrate (1.25 mmol), palladium acetate (0.0025 mmol) and transfer to 25 mL two-necked flask, and then add DMF/H ₂ O (2.7 mL/1.3 mL) to the 25 mL two-necked flask. The reaction was magnetically stirred at 80 °C for 40 min, followed by TLC. After the reaction was completed, 15 mL of saturated brine was added and the reaction product was extracted with ethyl acetate (15 mL??3). The organic phases were combined and concentrated using a rotary evaporator to obtain a crude product. The target product was obtained by column chromatography. The dehydration was ethyl acetate/petroleum ether (V/V=1/300), and the structure of the product was identified by ¹ H NMR and mass spectrometry. The separation yield reached 93%.

Example 8 2,4,6-tris(3,4-difluorophenyl)aniline

In air, weigh 2,4,6-tribromoaniline (0.25 mmol), 3,4-difluorophenylboronic acid (1.125 mmol), palladium acetate (0.0025 mmol), potassium phosphate heptahydrate (1.25 mmol) and Transfer to a 25 mL two-necked bottle, and then add DMF/H ₂ O (2.7 mL/1.3 mL) to the 25 mL two-necked bottle. The reaction was magnetically stirred at 80 °C for 15 min, followed by TLC. After the reaction was completed, 15 mL of saturated brine was added and the reaction product was extracted with ethyl acetate (15 mL??3). The organic phases were combined and concentrated using a rotary evaporator to obtain a crude product. The target product was obtained by column chromatography. The dehydration was ethyl acetate/petroleum ether (V/V=1/200), and the structure of the product was identified by ¹ H NMR and mass spectrometry. The separation yield was 87%.

Example 9 2,4,6-tri(4-chlorophenyl)aniline

In air, successively weigh 2,4,6-tribromoaniline (0.25 mmol), 4-chlorophenylboronic acid (1.125 mmol), palladium acetate (0.0025 mmol), potassium phosphate heptahydrate (1.25 mmol) and transfer to 25 mL two-necked flask, and then add DMF/H ₂ O (2.7 mL/1.3 mL) to the 25 mL two-necked flask. The reaction was magnetically stirred at 80 °C for 35 min, followed by TLC. After the reaction was completed, 15 mL of saturated brine was added and the reaction product was extracted with ethyl acetate (15 mL??3). The organic phases were combined and concentrated using a rotary evaporator to obtain a crude product. The target product was obtained by column chromatography. The dehydration is pure petroleum ether, and the structure of the product is identified by ¹ H NMR and mass spectrometry. The separation yield reached 96%.

The above content is a further detailed description of the present invention in combination with preferred technical solutions, and it cannot be assumed that the specific implementation of the invention is limited to these descriptions. For those of ordinary skill in the technical field to which the present invention belongs, simple deduction and substitutions can be made without departing from the concept of the present invention, which should be regarded as the protection scope of the present invention.

Claims (8)

1. one kind in aqueous phase preparation 2,4, the method for 6-triaryl aniline compound, it is characterized in that: in air atmosphere, with 2,4,6-bromamide, aryl boric acid, alkali and palladium catalyst are added to DMF/H for 1:4.5-6.5:4.5-5.5:0.005-0.02 in molar ratio ₂O is the N of 1 mL/3 mL-3 mL/1 mL, in the dinethylformamide solution, carried out Suzuki Suzuki cross-coupling reaction 15～80 minutes 50-100 ° of C stirring, reaction is used the ethyl acetate extraction reaction product after finishing, merge organic phase, concentrate, use column chromatography, make analytically pure 2,4,6-triaryl aniline compound.

2. according to claim 1 a kind of in aqueous phase preparation 2,4, the method for 6-triaryl aniline compound is characterized in that: before with the ethyl acetate extraction reaction product, add saturated aqueous common salt.

3. according to claim 1 a kind of in aqueous phase preparation 2,4, the method for 6-triaryl aniline compound is characterized in that: described 2,4,6-bromamide, aryl boric acid, alkali and palladium catalyst are 0.25: 1.125: 1.25 in molar ratio: 0.0025.

4. according to claim 1 a kind of in aqueous phase preparation 2,4, the method for 6-triaryl aniline compound is characterized in that: described N, the DMF/H of dinethylformamide solution ₂O is 2.7 mL/1.3 mL.

5. according to claim 1 a kind of in aqueous phase preparation 2,4, the method for 6-triaryl aniline compound is characterized in that: the temperature of reaction of described Suzuki cross-coupling reaction is 80 ° of C.

6. according to claim 1 a kind of in aqueous phase preparation 2,4, the method for 6-triaryl aniline compound is characterized in that: described palladium catalyst is selected from palladium or Palladous chloride.

7. according to claim 1 a kind of in aqueous phase preparation 2,4, the method for 6-triaryl aniline compound is characterized in that: described alkali is selected from seven hypophosphite monohydrate potassium, salt of wormwood or yellow soda ash.

8. according to claim 1 a kind of in aqueous phase preparation 2,4, the method of 6-triaryl aniline compound is characterized in that: described aryl boric acid is selected from phenylo boric acid, 4-methylphenylboronic acid, 4-methoxyphenylboronic acid, 4-fluorobenzoic boric acid, 3,4-two fluorobenzoic boric acids or 4-chlorobenzene boric acid.