The invention relates to 3apos; , 4apos; , 5apos; synthesis method of-trifluoro-2-aminobiphenyl

Abstract

The present invention relates to the technical field of organic synthesis, and provides a 3 ', 4', 5 '-trifluoro-2-aminobiphenyl synthesis method, which comprises: carrying out a reaction on 3, 4, 5-trifluorophenylboronic acid and o-bromoaniline in the presence of a catalyst, an alkali and a solution to obtain 3', 4 ', 5'-trifluoro-2-aminobiphenyl, the catalyst comprises a supported palladium catalyst and a phase transfer catalyst, and the mass ratio of the supported palladium catalyst to the phase transfer catalyst is 1: (1-5). According to the technical scheme, the problems of low yield and low purity in the synthesis process of 3 ', 4', 5 '-trifluoro-2-aminobiphenyl in the prior art are solved.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a method for synthesizing 3',4',5'-trifluoro-2-aminobiphenyl. Background Art

[0002] In the field of organic synthetic chemistry, 3',4',5'-trifluoro-2-aminobiphenyl, as an important organic intermediate, has broad application prospects. It shows unique value in high-tech fields such as medicine and materials science. However, the synthesis of 3',4',5'-trifluoro-2-aminobiphenyl has always been a challenge in the field of chemical synthesis. Traditional synthesis methods have many problems in terms of yield and purity. On the one hand, in terms of yield, due to the problems of insufficient substrate activity and low catalyst efficiency in the reaction process, the reaction is incomplete, and a large amount of raw materials cannot be converted into the target product, making the final yield unsatisfactory. On the other hand, the purity problem also seriously troubles the synthesis process. A variety of side reactions are prone to occur during the synthesis process. The impurities generated by these side reactions are similar in nature to the target product and are difficult to remove by simple separation methods. The presence of these impurities not only affects the quality of the product, but may also have an adverse effect on the performance of the product in subsequent applications. Therefore, it is necessary to develop a method that can improve the yield and purity of 3',4',5'-trifluoro-2-aminobiphenyl synthesis. Summary of the invention

[0003] The invention provides a method for synthesizing 3',4',5'-trifluoro-2-aminobiphenyl, which solves the problems of low yield and low purity in the synthesis process of 3',4',5'-trifluoro-2-aminobiphenyl in the related art.

[0004] The technical scheme of the present invention is as follows: The present invention provides a method for synthesizing 3',4',5'-trifluoro-2-aminobiphenyl, comprising the following steps: 3,4,5-trifluorophenylboric acid and o-bromoaniline react under the conditions of a catalyst, a base and a solution to obtain 3',4',5'-trifluoro-2-aminobiphenyl; The catalyst comprises a supported palladium catalyst and a phase transfer catalyst, and the mass ratio of the supported palladium catalyst to the phase transfer catalyst is 1:1-5.

[0005] As a further technical solution, the mass ratio of the catalyst to the total mass of the 3,4,5-trifluorophenylboric acid and o-bromoaniline is 1-2:20.

[0006] As a further technical solution, the mass ratio of the supported palladium catalyst to the phase transfer catalyst is 1:3~4.

[0007] As a further technical solution, the carrier of the palladium catalyst is carbon nanotubes, and the active ingredient is palladium ions.

[0008] In the present invention, carbon nanotubes are used as carriers to load palladium ions, thereby providing abundant dispersion sites for palladium ions, effectively avoiding agglomeration of palladium ions, increasing the number of active sites of the catalyst, improving the catalytic reaction activity, accelerating the reaction process, and promoting the reaction to proceed more efficiently in the direction of generating the target product, thereby improving the yield and purity of 3',4',5'-trifluoro-2-aminobiphenyl.

[0009] As a further technical solution, the preparation method of the loaded palladium catalyst includes the following steps: dispersing the palladium ion precursor in a solvent, adding activated carbon nanotubes, stirring and loading, adding a reducing agent for reduction reaction, washing, filtering and drying to obtain the loaded palladium catalyst.

[0010] As a further technical solution, the stirring time is 3-5 hours, the reducing agent is sodium borohydride solution, the reduction reaction temperature is 2-4°C, the time is 1-2 hours, and the mass volume ratio of the carbon nanotubes to the reducing agent is 3g:20mL.

[0011] As a further technical solution, the mass ratio of the carbon nanotubes to the solvent is 1:5.

[0012] As a further technical solution, the preparation method of activated carbon nanotubes comprises the following steps: dispersing carbon nanotubes in a mixed acid solution, heating and refluxing, and drying to obtain activated carbon nanotubes.

[0013] As a further technical solution, the mixed acid solution consists of concentrated nitric acid and concentrated sulfuric acid, and the volume ratio of the concentrated nitric acid to the concentrated sulfuric acid is 1:3.

[0014] As a further technical solution, the heating temperature is 70-90° C., and the reflux time is 5-7 hours.

[0015] As a further technical solution, the precursor of the palladium ion includes one or more of palladium chloride, palladium acetate, and palladium nitrate.

[0016] As a further technical solution, the carbon nanotubes are modified carbon nanotubes, the modified carbon nanotubes are carbon nanotubes modified by a modifier, the modifier is a thiophene pyrrole compound, and the mass ratio of the modifier to the carbon nanotubes is 3-4:30.

[0017] In the present invention, thiophene pyrrole compounds are used to modify carbon nanotubes so that more palladium ions can be firmly loaded on the carbon nanotubes, thereby increasing the loading amount and dispersion of palladium, improving the catalytic efficiency, and further improving the yield and purity of 3',4',5'-trifluoro-2-aminobiphenyl.

[0018] As a further technical solution, the thiophene pyrrole compound includes one or more of 2,5-di(2-thiophene)-1H-pyrrole, 2-(thiophene-3-yl)pyrrolidine, and 4-methyl-2-(2-thiophene-yl)pyrrole.

[0019] As a further technical solution, the preparation method of the modified carbon nanotubes comprises the following steps: dispersing the modifier in a solution, adding the activated carbon nanotubes, filtering and drying after modification to obtain the modified carbon nanotubes.

[0020] As a further technical solution, the mass ratio of the activated carbon nanotubes to the solvent is 1:10.

[0021] As a further technical solution, the modification time is 6 hours.

[0022] As a further technical solution, the phase transfer catalyst includes one or both of tetrabutylammonium bromide and tetrabutylammonium chloride.

[0023] As a further technical solution, the base includes one or both of potassium carbonate and potassium hydroxide, and the solution includes one or both of benzene and toluene.

[0024] The working principle and beneficial effects of the present invention are: In the present invention, 3,4,5-trifluorophenylboric acid and o-bromoaniline are used as raw materials, a supported palladium catalyst and a phase transfer catalyst are added at the same time, and 3',4',5'-trifluoro-2-aminobiphenyl is prepared under the conditions of alkali and solvent. The synergistic effect of the supported palladium catalyst and the phase transfer catalyst is exerted to efficiently activate the reaction substrate, promote the occurrence of the reaction in the direction of the target product, reduce the occurrence of side reactions, and improve the yield and purity of 3',4',5'-trifluoro-2-aminobiphenyl. DETAILED DESCRIPTION

[0025] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0026] In the following examples and comparative examples: Carbon nanotubes: 10nm in thickness and 10μm in length; Palladium catalyst: particle size 20nm; Chromatography column: The stationary phase is silica gel.

[0027] Example 1 The preparation of the supported palladium catalyst comprises the following steps: weighing 30g of carbon nanotubes, adding into 450mL of a mixed acid of concentrated nitric acid (68wt%) and concentrated sulfuric acid (98wt%) in a volume ratio of 1:3, refluxing at 70°C for 7h, drying to obtain activated carbon nanotubes, weighing 3g of palladium chloride, adding into 150mL of hydrochloric acid (molar concentration of 2mol / L), adding the activated carbon nanotubes, stirring for 3h, adding into 200mL of sodium borohydride solution (molar concentration of 1mol / L) at 2°C, stirring for 2h, washing, filtering and drying to obtain the supported palladium catalyst; A method for synthesizing 3',4',5'-trifluoro-2-aminobiphenyl comprises the following steps: weighing 175.9 g (1 mol) of 3,4,5-trifluorophenylboric acid, 172.03 g (1 mol) of o-bromoaniline, and 138.21 g (1 mol) of potassium carbonate, adding 5% of a catalyst (based on the total mass of 3,4,5-trifluorophenylboric acid and o-bromoaniline), adding 900 g of toluene under nitrogen protection, heating to 110°C and stirring for 7 hours, rinsing three times with 400 g of water, drying with anhydrous sodium carbonate, filtering and desolventizing to obtain a crude product, and purifying with a chromatography column to obtain 212.92 g of a product, wherein the catalyst consists of a supported palladium catalyst and tetrabutylammonium bromide in a mass ratio of 1:1.

[0028] The yield was 95.4% and the purity was 98.73%.

[0029] Example 2 The preparation of the supported palladium catalyst comprises the following steps: weighing 30g of carbon nanotubes, adding into 450mL of a mixed acid of concentrated nitric acid (68wt%) and concentrated sulfuric acid (98wt%) in a volume ratio of 1:3, refluxing at 80°C for 6h, drying to obtain activated carbon nanotubes, weighing 3g of palladium acetate, adding into 150mL of hydrochloric acid (molar concentration of 2mol / L), adding the activated carbon nanotubes, stirring for 4h, adding into 200mL of sodium borohydride solution (molar concentration of 1mol / L) at 3°C, stirring for 1.5h, washing, filtering and drying to obtain the supported palladium catalyst; A method for synthesizing 3',4',5'-trifluoro-2-aminobiphenyl comprises the following steps: weighing 175.9 g (1 mol) of 3,4,5-trifluorophenylboric acid, 172.03 g (1 mol) of o-bromoaniline, and 56.1 g (1 mol) of potassium hydroxide, adding 8% of a catalyst (based on the total mass of 3,4,5-trifluorophenylboric acid and o-bromoaniline), adding 900 g of benzene under nitrogen protection, heating to 120°C and stirring for 6 hours, rinsing three times with 400 g of water, drying with anhydrous sodium carbonate, filtering and desolventizing to obtain a crude product, and purifying with a chromatography column to obtain 214.04 g of a product, wherein the catalyst consists of a supported palladium catalyst and tetrabutylammonium chloride in a mass ratio of 1:3.

[0030] The yield was 95.9% and the purity was 98.91%.

[0031] Example 3 The preparation of the supported palladium catalyst comprises the following steps: weighing 30g of carbon nanotubes, adding into 450mL of a mixed acid of concentrated nitric acid (68wt%) and concentrated sulfuric acid (98wt%) in a volume ratio of 1:3, refluxing at 90°C for 5h, drying to obtain activated carbon nanotubes, weighing 3g of palladium nitrate, adding into 150mL of hydrochloric acid (molar concentration of 2mol / L), adding the activated carbon nanotubes, stirring for 4h, adding into 200mL of sodium borohydride solution (molar concentration of 1mol / L) at 4°C, stirring for 1h, washing, filtering and drying to obtain the supported palladium catalyst; A method for synthesizing 3',4',5'-trifluoro-2-aminobiphenyl comprises the following steps: weighing 175.9 g (1 mol) of 3,4,5-trifluorophenylboric acid, 172.03 g (1 mol) of o-bromoaniline, and 138.21 g (1 mol) of potassium carbonate, adding 10% of a catalyst (based on the total mass of 3,4,5-trifluorophenylboric acid and o-bromoaniline), adding 900 g of toluene under nitrogen protection, heating to 130°C and stirring for 5 hours, rinsing three times with 400 g of water, drying with anhydrous sodium carbonate, filtering and desolventizing to obtain a crude product, and purifying with a chromatography column to obtain 214.71 g of a product, wherein the catalyst consists of a supported palladium catalyst and tetrabutylammonium bromide in a mass ratio of 1:5.

[0032] The yield was 96.2% and the purity was 99.04%.

[0033] Example 4 Compared with Example 3, the difference of Example 4 is that the catalyst consists of a supported palladium catalyst and tetrabutylammonium bromide in a mass ratio of 1:4.

[0034] 216.05 g of product was obtained, with a yield of 96.8% and a purity of 99.16%.

[0035] Example 5 The preparation method of modified carbon nanotubes comprises the following steps: weighing 30g of carbon nanotubes, adding into 450mL of a mixed acid of concentrated nitric acid (68wt%) and concentrated sulfuric acid (98wt%) in a volume ratio of 1:3, refluxing at 90°C for 5h, drying to obtain activated carbon nanotubes, weighing 3g of 4-methyl-2-(2-thienyl)pyrrole, adding into 300mL of toluene, adding the activated carbon nanotubes, stirring for 6h, filtering and drying to obtain modified carbon nanotubes; Compared with Example 4, the difference of Example 5 is that the carbon nanotubes are replaced with an equal amount of modified carbon nanotubes obtained by the above preparation method.

[0036] 217.39 g of product was obtained with a yield of 97.4% and a purity of 99.25%.

[0037] Example 6 Compared with Example 5, the difference in Example 6 is that the added amount of 4-methyl-2-(2-thienyl)pyrrole is 3.5 g.

[0038] 219.40 g of product was obtained, with a yield of 98.3% and a purity of 99.41%.

[0039] Example 7 Compared with Example 5, the difference in Example 7 is that the added amount of 4-methyl-2-(2-thienyl)pyrrole is 4 g.

[0040] 218.50 g of product was obtained, with a yield of 97.9% and a purity of 99.37%.

[0041] Example 8 Compared with Example 6, Example 8 is different in that 4-methyl-2-(2-thienyl)pyrrole is replaced by an equal amount of 2-(thien-3-yl)pyrrolidine.

[0042] 220.51 g of product was obtained with a yield of 98.8% and a purity of 99.53%.

[0043] Example 9 Compared with Example 6, Example 9 is different in that 4-methyl-2-(2-thienyl)pyrrole is replaced by an equal amount of 2,5-di(2-thiophene)-1H-pyrrole.

[0044] 221.18 g of product was obtained with a yield of 99.1% and a purity of 99.68%.

[0045] Comparative Example 1 Compared with Example 3, the difference in Comparative Example 1 is that the catalyst is a supported palladium catalyst.

[0046] 211.36 g of product was obtained, with a yield of 94.7% and a purity of 97.15%.

[0047] Comparative Example 2 Compared with Example 3, the difference in Comparative Example 2 is that the catalyst is tetrabutylammonium bromide.

[0048] 143.29 g of product was obtained, with a yield of 64.2% and a purity of 67.57%.

[0049] Comparative Example 3 Compared with Example 3, the difference of Comparative Example 3 is that the supported palladium catalyst is replaced with an equal amount of palladium catalyst.

[0050] 208.01 g of product was obtained, with a yield of 93.2% and a purity of 96.94%.

[0051] Comparative Example 4 Compared with Example 3, the difference in Comparative Example 4 is that tetrabutylammonium bromide is replaced by an equal amount of triethylamine.

[0052] 212.03 g of product was obtained with a yield of 95.0% and a purity of 97.65%.

[0053] Compared with Comparative Examples 1, 2, and 4, Example 3 simultaneously added a supported palladium catalyst and a phase transfer catalyst. As a result, the yield and purity of Example 3 were better than those of Comparative Examples 1, 2, and 4, indicating that the supported palladium catalyst and the phase transfer catalyst played a synergistic role and could improve the yield and purity of 3',4',5'-trifluoro-2-aminobiphenyl.

[0054] Compared with Comparative Example 3, Example 3 added a supported palladium catalyst. As a result, the yield and purity of Example 3 were better than those of Comparative Example 3, indicating that the supported palladium catalyst can further improve the yield and purity of 3',4',5'-trifluoro-2-aminobiphenyl.

[0055] Compared with Example 4, Examples 5 to 9 use modified carbon nanotubes modified with thiophene pyrrole compounds as carriers. As a result, the yield and purity of Examples 5 to 9 are better than those of Example 4, indicating that when modified carbon nanotubes are used as carriers, the yield and purity of 3',4',5'-trifluoro-2-aminobiphenyl can be improved.

[0056] In Examples 5 to 7, different mass ratios of modifier and carbon nanotubes were added. As a result, the yield and purity of Example 6 were better than those of Examples 5 and 7, indicating that when the mass ratio of modifier to carbon nanotubes was 7:60, the yield and purity of the obtained 3',4',5'-trifluoro-2-aminobiphenyl were higher.

[0057] In Examples 7 to 9, different types of thiophene pyrrole compounds were used to modify carbon nanotubes. As a result, the yield and purity of Example 9 were better than those of Examples 7 and 8, indicating that when the modifier used was 2,5-di(2-thiophene)-1H-pyrrole, the yield and purity of the obtained 3',4',5'-trifluoro-2-aminobiphenyl were higher.

[0058] The above are only preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for synthesizing 3',4',5'-trifluoro-2-aminobiphenyl, characterized in that: The method comprises the following steps: 3,4,5-trifluorophenylboric acid and o-bromoaniline react under the conditions of a catalyst, a base and a solution to obtain 3',4',5'-trifluoro-2-aminobiphenyl; the catalyst comprises a supported palladium catalyst and a phase transfer catalyst, and the mass ratio of the supported palladium catalyst to the phase transfer catalyst is 1:1-5.

2. The method for synthesizing 3',4',5'-trifluoro-2-aminobiphenyl according to claim 1, characterized in that: The mass ratio of the supported palladium catalyst to the phase transfer catalyst is 1:3-4.

3. The method for synthesizing 3',4',5'-trifluoro-2-aminobiphenyl according to claim 1, characterized in that: The carrier of the palladium catalyst is carbon nanotube, and the active component is palladium ion.

4. The method for synthesizing 3',4',5'-trifluoro-2-aminobiphenyl according to claim 1, characterized in that: The preparation method of the supported palladium catalyst comprises the following steps: dispersing a palladium ion precursor in a solvent, adding activated carbon nanotubes, stirring and loading, adding a reducing agent for reduction reaction, washing, filtering and drying to obtain the supported palladium catalyst.

5. The method for synthesizing 3',4',5'-trifluoro-2-aminobiphenyl according to claim 4, characterized in that: The precursor of the palladium ion includes one or more of palladium chloride, palladium acetate, and palladium nitrate.

6. The method for synthesizing 3',4',5'-trifluoro-2-aminobiphenyl according to claim 3, characterized in that: The carbon nanotubes are modified carbon nanotubes, which are obtained by modifying carbon nanotubes with a modifier, wherein the modifier is a thiophene pyrrole compound, and the mass ratio of the modifier to the carbon nanotubes is 3-4:

30.

7. The method for synthesizing 3',4',5'-trifluoro-2-aminobiphenyl according to claim 6, characterized in that: The thiophene pyrrole compound includes one or more of 2,5-di(2-thiophene)-1H-pyrrole, 2-(thiophene-3-yl)pyrrolidine, and 4-methyl-2-(2-thiophene-yl)pyrrole.

8. The method for synthesizing 3',4',5'-trifluoro-2-aminobiphenyl according to claim 6, characterized in that: The preparation method of the modified carbon nanotubes comprises the following steps: dispersing a modifier in a solvent, adding activated carbon nanotubes, filtering and drying after modification to obtain the modified carbon nanotubes.

9. The method for synthesizing 3',4',5'-trifluoro-2-aminobiphenyl according to claim 1, characterized in that: The phase transfer catalyst includes one or both of tetrabutylammonium bromide and tetrabutylammonium chloride.

10. The method for synthesizing 3',4',5'-trifluoro-2-aminobiphenyl according to claim 1, characterized in that: The base includes one or both of potassium carbonate and potassium hydroxide, and the solution includes one or both of benzene and toluene.