Method for synthesizing 9H-tribenzo [B, D, F] azepine

Abstract

The invention discloses a method for synthesizing 9H-tribenzo [B, D, F] azepine, relates to the technical field of chemical synthesis of organic light-emitting materials, and aims to solve the problems that most of existing synthesis methods need a Pd catalyst and are not simple and efficient enough. The method comprises the following steps: by taking 9, 10-benzophenanthrene as a basic reaction raw material, a hydroxylamine derivative as an amine source and FeBr3, CuBr2 or CoBr2 as a catalyst, reacting in a reaction solvent to realize ring-expanding nitridation under aryl migration, and separating and purifying to obtain a 9H-tribenzo [B, D, F] azepine product; the method has the advantages of low raw material price, simple and easily operated synthesis steps, mild and easily controlled reaction conditions, low price and low toxicity of the used catalyst, green and environment-friendly whole preparation process, and high yield of the 9H-tribenzo [B, D, F] azepine product, and is suitable for industrial application.

Description

Technical Field

[0001] The invention relates to the technical field of chemical synthesis of organic luminescent materials, in particular to a method for synthesizing 9H-tribenzo[B,D,F]azepine. Background Art

[0002] 9H-Tribenzo[B,D,F]azepine, an important nitrogen-containing seven-membered heterocyclic ring, is a natural product molecular skeleton with biological activity. In addition, similar to carbazole, it also has a larger conjugated system, a better rigid structure and an ideal three-dimensional spatial conformation, so it has attracted more and more attention in the field of optoelectronic materials. In addition, based on its secondary amine characteristics, the CN bond can also be realized with the help of coupling ideas, further expanding the molecular structure and further releasing its application prospects in optoelectronic molecular rings. Therefore, how to efficiently realize the synthesis of medium-ring-seven-membered nitrogen heterocycles has always been a hot topic of research.

[0003] There are currently three reported synthetic approaches to 9H-tribenzo[B,D,F]azepine. The first approach is to construct a seven-membered nitrogen heterocycle by multiple steps such as the Diels-Alder reaction (J.Org.Chem., 1991, 56, 3906.), using dibenzo[b,f]azepine derivatives as the seven-membered ring matrix, generating benzyne species in situ, further realizing cycloaddition (DA reaction), and further dehydration aromatization to obtain 9H-tribenzo[B,D,F]azepine. The second approach is to report the Martin group. One example is the Buchwald-Hartwig coupling to achieve intramolecular coupling to synthesize 9H-tribenzo[B,D,F]azepine (J.Org.Chem.,2009,74,4490.), which mainly involves the cyclization process of the C-halogen bond; the other is that Zhang Yanghui's group reported a new method for the synthesis of 9H-tribenzo[B,D,F]azepine by tandem cyclization under Pd catalysis (Org.Lett.,2021,23,1239.), involving in situ generated cyclic Pd species, assisted by halogenated aniline to achieve the synthesis of seven-membered heterocycles.

[0004] Among the above-mentioned synthetic routes, the first one mainly uses expensive dibenzo[b,f]azepine derivatives as initial substrates, which has low cost performance, and the steps are lengthy, the relative yield is low, and the feasibility of industrialization is poor; the second one mainly uses Pd catalysis to achieve the cyclization process. This step requires a high amount of catalyst Pd, so the cost is high. In addition, due to the presence of multiple CH bonds, there are problems of regional selectivity, which further aggravates the difficulty of purification, reduces the overall yield, and is not conducive to industrial production; the third one also faces the problem of high Pd catalyst usage. In addition, amide solvents are required for high-temperature and long-term reactions, which will generate a large amount of tar species. In addition, this substance has poor solubility, and it is difficult to obtain a high-purity off-white solid with high yield. In summary, a method for synthesizing 9H-tribenzo[B,D,F]azepine is urgently needed to solve this problem. Summary of the invention

[0005] The purpose of the present invention is to provide a method for synthesizing 9H-tribenzo[B,D,F]azepine, so as to solve the problem that most of the existing synthesis methods require Pd catalyst and the methods are not simple and efficient enough.

[0006] To achieve the above-mentioned purpose, the present invention provides the following technical scheme: a method for synthesizing 9H-tribenzo[B,D,F]azepine, comprising the following specific contents: using 9,10-phenylene as a basic reaction raw material, using a hydroxylamine derivative as an amine source, using FeBr3, CuBr2 or CoBr2 as a catalyst, reacting in a reaction solvent, realizing ring expansion nitrogenation under aromatic migration, and obtaining a 9H-tribenzo[B,D,F]azepine product through separation and purification.

[0007] Preferably, the reaction is carried out in an air atmosphere, the reaction temperature is -20°C to rt, and the reaction time is 4 to 6 hours.

[0008] In the above preferred embodiment, the reaction temperature is preferably -20°C.

[0009] Preferably, the molar ratio of 9,10-triphenylene to the hydroxylamine derivative is 1:(1-1.5).

[0010] Preferably, the hydroxylamine derivative is selected from O-methylsulfonylhydroxylamine trifluoromethanesulfonate (ie, MsONH3OTf) or O-pivaloylhydroxylamine (PivONH3OTf).

[0011] Preferably, the reaction solvent is selected from tetrahydrofuran, acetonitrile and dichloromethane.

[0012] Preferably, the above method further comprises, before separation and purification, quenching the organic layer with water and then washing it with water several times.

[0013] Preferably, separation and purification are performed by removing the solvent from the organic layer and then performing rapid column chromatography.

[0014] Preferably, thin layer chromatography (TLC) is used during the reaction to monitor whether the reaction is complete.

[0015] Preferably, the yield of 9H-tribenzo[B,D,F]azepine product can reach more than 80%.

[0016] Compared with the prior art, the present invention has the following beneficial effects:

[0017] 1. The method for synthesizing 9H-tribenzo[B,D,F]azepine has a wide range of substrate sources and uses readily available 9,10-phenylene industrial chemicals as synthetic precursors. The raw material price is low, high value-added transformation is achieved, the competitiveness of the production process is enhanced, and the economy is good; precise and selective ortho-position nitrogen insertion ring expansion modification can be achieved under mild conditions, without harsh reaction conditions, the steps are simple, and a lengthy reaction route is avoided. No expensive pre-modified substrate is required, and double CH bond activation and double CN bond construction can be simultaneously and efficiently achieved through a simple series one-pot method, and the synthesis cost is easy to control; compared with existing synthetic methods, no inert gas protection is required, the operability is stronger, and the system compatibility is better; cheap and low-toxic iron, copper or cobalt salts are used as catalysts, avoiding the use of expensive metal catalysts Pd in ​​subsequent coupling, further reducing the reaction cost.

[0018] 2. The method for synthesizing 9H-tribenzo[B,D,F]azepine is based on metal complexation in situ nitrogen carbene species, activates double CH bonds, and then completes nitrogen insertion ring expansion. It is more stable and safer, and the reaction conditions avoid the problem of difficult purification of tar under high temperature atmosphere, further reducing the generation of three wastes, being more green and environmentally friendly, and meeting the essence of composite green chemistry. The method has a high yield, simple steps, mild conditions and easy control, and is suitable for industrial application. DETAILED DESCRIPTION

[0019] The present invention uses 9,10-triphenylene as a basic reaction raw material, uses a hydroxylamine derivative as an amine source (nitrogen source), and uses FeBr3, CuBr2 or CoBr2 as a catalyst. No expensive Pd catalyst is used. The reaction is carried out in a reaction solvent to achieve ring expansion nitrogenation under aromatic migration. For reference, the reaction solvent can be tetrahydrofuran, acetonitrile or dichloromethane. After the reaction is completed, the 9H-tribenzo[B,D,F]azepine product can be obtained by separation and purification.

[0020] The reaction conditions required by the present invention are mild and can be completed in a general environment, but for reference, it can be controlled to be carried out in an air atmosphere, the reaction temperature is preferably controlled at -20°C ~ rt, and the reaction time is 4 to 6h, wherein -20°C is a more preferred reaction condition.

[0021] In the reactants of the method, the molar ratio of 9,10-phenylene to the hydroxylamine derivative is preferably controlled to be 1:(1-1.5), preferably with a slight excess of the nitrogen source; for reference, the hydroxylamine derivative can be selected from O-methylsulfonylhydroxylamine trifluoromethanesulfonate (MsONH3OTf) or O-pivaloylhydroxylamine (PivONH3OTf).

[0022] In the above method, it is further preferred that the organic layer is quenched with water and then washed with water several times, for example, twice, before separation and purification. The separation and purification can be carried out by removing the solvent from the organic layer and then performing rapid column chromatography.

[0023] In addition, in order to accurately understand the reaction dynamics, thin layer chromatography (TLC) can be used to monitor whether the reaction is complete during the reaction.

[0024] In order to make the purpose, technical solutions and advantages of the present invention clearer, the above contents of the present invention are further described in detail below in conjunction with embodiments, but this should not be understood as the scope of the above subject matter of the present invention being limited to the following embodiments.

[0025] Example 1

[0026] In an air atmosphere, 11.4 g 9,10-phenylene (Mr = 228.3, 99%, 0.05 mol), 13.1 g MsONH3OTf (Mr = 261.0, 99%, 0.05 mol), 1.1 g CuBr2 (Mr = 223.4, 99%, 0.005 mol) were added to a 250 mL four-necked flask, and 100 mL tetrahydrofuran was added. After the addition, the reaction was carried out at room temperature for 6 h and monitored by thin layer chromatography (TLC). After the reaction was completed, the organic layer was quenched with water and washed with water twice. The organic layer was freed from the solvent and flash column chromatography was performed to obtain 3.89 g 9H-tribenzo[B,D,F]azepine with a yield of 31.8%.

[0027] Example 2

[0028] In an air atmosphere, 11.4 g 9,10-phenylene (Mr = 228.3, 99%, 0.05 mol), 16.0 g PivONH3OTf (Mr = 267.0, 99%, 0.06 mol), 1.4 g FeBr3 (Mr = 295.6, 99%, 0.005 mol) were added to a 250 mL four-necked flask, and 100 mL acetonitrile was added. After the addition, the mixture was reacted at -10 ° C for 6 h and monitored by thin layer chromatography (TLC). After the reaction, the organic layer was quenched with water and washed twice with water. The organic layer was freed from the solvent and flash column chromatography was performed to obtain 9.12 g 9H-tribenzo[B,D,F]azepine with a yield of 75.1%.

[0029] Example 3

[0030] In an air atmosphere, 11.4 g 9,10-phenylene (Mr = 228.3, 99%, 0.05 mol), 16.0 g PivONH3OTf (Mr = 267.0, 99%, 0.06 mol), 1.1 g CoBr2 (Mr = 218.7, 99%, 0.005 mol) were added to a 250 mL four-necked flask, and 100 mL of dichloromethane was added. After the addition, the mixture was reacted at -10 ° C for 6 h and monitored by thin layer chromatography (TLC). After the reaction, the organic layer was quenched with water and washed twice with water. The organic layer was freed from the solvent and flash column chromatography was performed to obtain 2.81 g 9H-tribenzo[B,D,F]azepine with a yield of 23.1%.

[0031] Example 4

[0032] In an air atmosphere, 11.4 g 9,10-phenylene (Mr = 228.3, 99%, 0.05 mol), 19.6 g MsONH3OTf (Mr = 261.0, 99%, 0.075 mol), 1.4 g FeBr3 (Mr = 295.6, 99%, 0.005 mol) were added to a 250 mL four-necked flask, and 100 mL acetonitrile was added. After the addition, the mixture was reacted at -20 ° C for 6 h and monitored by thin layer chromatography (TLC). After the reaction, the organic layer was quenched with water and washed twice with water. The organic layer was freed from the solvent and flash column chromatography was performed to obtain 10.29 g 9H-tribenzo[B,D,F]azepine with a yield of 84.6%.

[0033] Example 5

[0034] In an air atmosphere, 11.4 g 9,10-phenylene (Mr = 228.3, 99%, 0.05 mol), 19.6 g MsONH3OTf (Mr = 261.0, 99%, 0.075 mol), 1.1 g CuBr2 (Mr = 223.4, 99%, 0.005 mol) were added to a 250 mL four-necked flask, and 100 mL acetonitrile was added. After the addition, the mixture was reacted at -20 ° C for 6 h and monitored by thin layer chromatography (TLC). After the reaction, the organic layer was quenched with water and washed twice with water. The organic layer was freed from the solvent and flash column chromatography was performed to obtain 6.53 g 9H-tribenzo[B,D,F]azepine with a yield of 53.7%.

[0035] Example 6

[0036] In an air atmosphere, 11.4 g 9,10-phenylene (Mr = 228.3, 99%, 0.05 mol), 13.1 g MsONH3OTf (Mr = 261.0, 99%, 0.05 mol), 1.4 g FeBr3 (Mr = 295.6, 99%, 0.005 mol) were added to a 250 mL four-necked flask, and 100 mL acetonitrile was added. After the addition, the mixture was reacted at -20 ° C for 6 h and monitored by thin layer chromatography (TLC). After the reaction, the organic layer was quenched with water and washed with water twice. The organic layer was freed from the solvent and flash column chromatography was performed to obtain 5.00 g 9H-tribenzo[B,D,F]azepine with a yield of 41.2%.

[0037] The above are only a small part of the numerous embodiments of the present invention, but the protection scope of the present invention is not limited thereto. Any changes or substitutions that can be easily thought of by a person skilled in the art within the technical scope disclosed by the present invention should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention should be based on the protection scope defined by the claims.

[0038] The matters not described in detail in the present invention are all known technologies to those skilled in the art.

Claims

1. A method for synthesizing 9H-tribenzo[B,D,F]azepine, characterized in that: The method includes the following specific contents: using 9,10-phenylene as a basic reaction raw material, a hydroxylamine derivative as an amine source, and FeBr3, CuBr2 or CoBr2 as a catalyst, reacting in a reaction solvent to achieve ring expansion nitrogenation under aromatic migration, and obtaining a 9H-tribenzo[B,D,F]azepine product through separation and purification.

2. A method for synthesizing 9H-tribenzo[B,D,F]azepine according to claim 1, characterized in that: The reaction is carried out in an air atmosphere, the reaction temperature is -20°C to rt, and the reaction time is 4 to 6 hours.

3. A method for synthesizing 9H-tribenzo[B,D,F]azepine according to claim 2, characterized in that: The reaction temperature is -20°C.

4. A method for synthesizing 9H-tribenzo[B,D,F]azepine according to claim 1, characterized in that: The molar ratio of the 9,10-triphenylene to the hydroxylamine derivative is 1:(1-1.5).

5. A method for synthesizing 9H-tribenzo[B,D,F]azepine according to claim 4, characterized in that: The hydroxylamine derivative is selected from O-methylsulfonylhydroxylamine trifluoromethanesulfonate (ie, MsONH3OTf) or O-pivaloylhydroxylamine (PivONH3OTf).

6. A method for synthesizing 9H-tribenzo[B,D,F]azepine according to claim 1, characterized in that: The reaction solvent is selected from tetrahydrofuran, acetonitrile and dichloromethane.

7. A method for synthesizing 9H-tribenzo[B,D,F]azepine according to claim 1, characterized in that: The method further comprises, before separation and purification, quenching the organic layer with water and then washing it with water several times.

8. A method for synthesizing 9H-tribenzo[B,D,F]azepine according to claim 7, characterized in that: The separation and purification adopts rapid column chromatography after removing the solvent from the organic layer.

9. A method for synthesizing 9H-tribenzo[B,D,F]azepine according to claim 1, characterized in that: During the reaction, thin layer chromatography (TLC) was used to monitor whether the reaction was complete.

10. A method for synthesizing 9H-tribenzo[B,D,F]azepine according to claim 1, characterized in that: The yield of the 9H-tribenzo[B,D,F]azepine product can reach more than 80%.