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

Abstract

The invention discloses a method for synthesizing 9H-tribenzo[B,D,F]azepine, and relates to the technical field of chemical synthesis of organic luminescent materials. The method aims to solve the problem that most existing synthesis methods require a Pd catalyst and are not simple and efficient. The method comprises the following steps: using 9,10-triphenylene 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 and nitrogenation under aromatic group migration; and obtaining a 9H-tribenzo[B,D,F]azepine product through separation and purification. The method has low raw material price, simple and easy operation of the synthesis steps, mild and easy-to-control reaction conditions, a low-cost and low-toxic catalyst, and an environmentally friendly preparation process. The yield of the 9H-tribenzo[B,D,F]azepine product is high, and the method is suitable for industrial application.

Description

Technical Field

[0001] The present 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 biologically active natural product molecular backbone. Similar to carbazole, it also possesses a larger conjugated system, a more rigid structure, and an ideal three-dimensional conformation, attracting increasing attention in the field of optoelectronic materials. Furthermore, due to its secondary amine properties, coupling strategies can also be used to form C-N bonds, further expanding its molecular structure and unlocking its potential applications in optoelectronic molecular rings. Therefore, the efficient synthesis of medium-sized seven-membered nitrogen heterocycles has been a hot topic of research.

[0003] There are currently three reported approaches to the synthesis of 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, by Cann et al. (J.Org.Chem., 1991, 56, 3906.). Using dibenzo[b,f]azepine derivatives as the seven-membered ring matrix, the in situ generation of benzylene species was followed by cycloaddition (DA reaction), followed by dehydration aromatization to obtain 9H-tribenzo[B,D,F]azepine. The second approach is to report the synthesis of 9H-tribenzo[B,D,F]azepine by Martin et al. 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 Zhang Yanghui's group reported a new method for the Pd-catalyzed tandem cyclization synthesis of 9H-tribenzo[B,D,F]azepine (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 synthetic routes, the first one mainly uses expensive dibenzo[b,f]azepine derivatives as initial substrates, which has a low cost-effectiveness. In addition, the steps are lengthy, the relative yield is low, and the feasibility of industrialization is poor. The second one mainly relies on Pd catalysis to achieve the ring closure process. This step requires a large amount of catalyst Pd, which is expensive. In addition, due to the presence of multiple C-H bonds, there are regioselectivity issues, which further exacerbates 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, it requires an amide solvent and high temperature and long reaction time, which will produce a large amount of tar species. In addition, this substance has poor solubility, making it difficult to obtain a high-purity off-white solid in 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 problems that most existing synthesis methods require Pd catalysts and are not simple and efficient enough.

[0006] To achieve the above-mentioned object, the present invention provides the following technical solution: a method for synthesizing 9H-tribenzo[B,D,F]azepine, comprising the following specific contents: using 9,10-triphenylene 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 group migration, and obtaining a 9H-tribenzo[B,D,F]azepine product through separation and purification.

[0007] Preferably, the reaction is carried out in 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 to monitor whether the reaction is complete during the reaction.

[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 and ring expansion modification can be achieved under mild conditions without harsh reaction conditions. The steps are simple, avoiding lengthy reaction routes and the need for expensive pre-modified substrates. Through a simple cascade one-pot method, double C-H bond activation and double C-N bond construction can be simultaneously and efficiently achieved, and the synthesis cost is easily controlled. Compared with existing synthetic methods, no inert gas protection is required, the operability is stronger, and the system compatibility is better. The use of cheap and low-toxic iron, copper or cobalt salts as catalysts avoids the use of expensive metal catalyst 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 of in situ nitrogen carbene species to activate double C-H bonds, followed by nitrogen insertion and ring expansion. It is more stable and safer, and the reaction conditions avoid the problem of difficult tar purification in a high-temperature atmosphere, further reducing the generation of three wastes, making it more environmentally friendly and embodying the essence of green chemistry. The method has a high yield, simple steps, mild conditions and easy control, making it suitable for industrial application. DETAILED DESCRIPTION

[0019] The present invention uses 9,10-triphenylene as a basic reaction raw material, a hydroxylamine derivative as an amine source (nitrogen source), and 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 through separation and purification.

[0020] The reaction conditions required by the present invention are mild and can be completed in a general environment. However, for reference, the reaction can be carried out under air atmosphere. The reaction temperature is preferably controlled between -20°C and rt, and the reaction time is 4 to 6 hours, with -20°C being the preferred reaction condition.

[0021] In the reactants of this method, the molar ratio of 9,10-triphenylene to the hydroxylamine derivative is preferably controlled to be 1:(1-1.5), preferably with a slight excess of 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 completed 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 limiting the scope of the above subject matter of the present invention to the following embodiments.

[0025] Example 1

[0026] Under air atmosphere, 11.4 g 9,10-triphenylene (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 mixture was reacted at room temperature 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 purified by flash column chromatography to obtain 3.89 g 9H-tribenzo[B,D,F]azepine in a yield of 31.8%.

[0027] Example 2

[0028] Under 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] Under 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] Under 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] Under 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] Under 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 twice with water. 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 few of the numerous embodiments of the present invention, but the scope of protection of the present invention is not limited thereto. Any changes or substitutions that can be easily conceived by a person skilled in the art within the technical scope disclosed in the present invention should be included in the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be based on the scope of protection defined by the claims.

[0038] Any matters not described in detail in the present invention are well-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; the hydroxylamine derivative is selected from MsONH3OTf and PivONH3OTf, and the reaction solvent is selected from tetrahydrofuran, acetonitrile, and dichloromethane.

2. A method for synthesizing 9H-tribenzo[b,d,f]azepine according to claim 1, characterized in that: The reaction is carried out under 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 was -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. The method for synthesizing 9H-tribenzo[b,d,f]azepine according to claim 1, wherein: The method further comprises, before separation and purification, quenching the organic layer with water and then washing it with water several times.

6. A method for synthesizing 9H-tribenzo[b,d,f]azepine according to claim 5, characterized in that: The separation and purification adopts rapid column chromatography after removing the solvent from the organic layer.

7. The method for synthesizing 9H-tribenzo[b,d,f]azepine according to claim 1, wherein: During the reaction, thin layer chromatography was used to monitor whether the reaction was complete.