A class of dibenzo[c,e]azepines and their derivatives and a nickel-catalyzed synthesis method thereof

Abstract

The present invention discloses a class of dibenzo[c,e]azepines and their derivatives and a nickel-catalyzed synthesis method thereof. The method uses a dibromoaniline compound as a raw material, nickel bromide as a catalyst, 3,4,7,8-tetramethyl-1,10-phenanthroline as a ligand, potassium dihydrogen phosphate as an additive, manganese powder as a reducing agent, N,N-dimethylformamide as a solvent, and reacts at 120 °C to synthesize a series of dibenzo[c,e]azepines. The reaction has good functional group tolerance and medium to excellent yields. For drug molecules such as celecoxib, pregabalin, and osimertinib analogs, the corresponding ring-closed products can be synthesized on a gram scale, and it has wide applications in the fields of synthetic drugs and natural products.

Description

Technical Field

[0001] The present invention belongs to the field of catalytic organic synthesis, and particularly relates to a class of dibenzo[c,e]azepines and their derivatives and a nickel-catalyzed synthesis method thereof. Background Art

[0002] Dibenzo[c,e]azepine compounds have broad application prospects in production and life. The core structural units of many drug molecules, bioactive substances, and natural products contain a seven-membered nitrogen heterocyclic skeleton. In addition, due to the rapid development of catalytic chemistry, such skeletons are often found in the auxiliary ligands of transition metal catalysts and organic catalysts. Based on this, how to develop an efficient synthesis method for benzoazepine compounds is one of the important research contents in the field of synthetic chemistry. The synthesis of such compounds usually requires multiple steps, with harsh reaction conditions and high costs for skeleton functionalization, thus restricting the synthesis and development of new ligands, organic catalysts, and bioactive molecules.

[0003] The construction of carbon-carbon bonds is a central topic in synthetic organic chemistry because it is of great significance for the synthesis of various structurally important molecules (including biological entities or natural products) from simple and readily available molecules. For a long time, the formation of carbon-carbon bonds has been a research topic of interest to scientists, and many strategies have been developed to solve this problem. In the past, the research on carbon-carbon bond construction mainly focused on the use of organometallic compounds containing alkali metals, while the past decade has witnessed great progress in transition metal-catalyzed cross-coupling strategies. Among them, the in-situ direct reductive coupling of haloaryl compounds (without the need to pre-prepare organometallic reagents) is one of the most convenient and rapid methods for preparing biaryls. In recent years, nickel-catalyzed reductive coupling reactions have made rapid progress in synthesis, application, and mechanism research. Their reaction conditions are mild, providing advantages for traditional cross-coupling reactions. For example, the reductive coupling reaction does not require the pre-preparation of organometallic reagents, providing an attractive strategy for intramolecular cyclization reactions. Therefore, we hope to synthesize dibenzo[c,e]azepines and their derivatives through this strategy. Summary of the Invention

[0004] The present invention discloses a class of dibenzo[c,e]azepines and their derivatives and a nickel-catalyzed synthesis method thereof. The method uses a dibromoaniline compound as a raw material, nickel bromide as a catalyst, 3,4,7,8-tetramethyl-1,10-phenanthroline as a ligand, potassium dihydrogen phosphate as an additive, manganese powder as a reducing agent, and N,N-dimethylformamide as a solvent, and reacts at 120 °C to synthesize a series of dibenzo[c,e]azepines. This scheme has the advantages of mild conditions, a broad substrate scope, good functional group tolerance, high yield, and easy operation, which lays a foundation for the synthesis of functionalized benzazepines. For drug molecules such as celecoxib, pregabalin, and osimertinib analogs, the corresponding ring-closed products can be synthesized on a gram scale, which is conducive to realizing their industrial production.

[0005] To achieve the above invention purpose, the present invention proposes the following technical solutions:

[0006] A class of dibenzo[c,e]azepines and their derivatives and a nickel-catalyzed synthesis method thereof, wherein the structural formula of the product is as Figure 1 shown.

[0007] Among them, the catalytic synthesis method of dibenzo[c,e]azepine is characterized in that using dibromoaniline 1 (0.2 mmol) as a raw material, nickel bromide (10 mol%) as a catalyst, 3,4,7,8-tetramethyl-1,10-phenanthroline as a ligand, 2.0 equivalents of potassium dihydrogen phosphate as an additive, 2.0 equivalents of manganese powder as a reducing agent, N,N-dimethylformamide as a solvent, reacting at 120 °C for 12 hours in a nitrogen atmosphere to obtain dibenzo[c,e]azepine compounds 2a-2z, 2aa-2ae, 3a-3z and 5a-5l with a yield of 70-97%.

[0008] The specific reaction principle of the Ullmann-type reductive coupling of the dibromoaniline in the present invention: The oxidative addition of aryl bromide 1 and Ni(0) substance produces a Ni(II) substance A, which is reduced by stoichiometric Mn. The generated Ni(I) intermediate B undergoes a second oxidative addition with another bromine atom of itself to form a Ni(III) substance C, which then undergoes reductive elimination to provide the desired product 2, while regenerating the Ni(0) catalyst through Mn reduction, as Figure 2 shown. Description of the Drawings

[0009] Figure 1 is a schematic diagram of the structural formula of the product;

[0010] Figure 2 is a schematic diagram of the principle of regenerating the Ni(0) catalyst through Mn reduction. Detailed Embodiments

[0011] To make the above features, advantages and objectives of the present invention more clearly understandable, the following provides a detailed description of the present invention in conjunction with specific embodiments. Many specific details have been set forth in the above description to facilitate a full understanding of the present invention. However, the present invention can be implemented in many other ways different from those described herein, and those skilled in the art can make similar improvements without departing from the connotation of the present invention. Therefore, the present invention is not limited by the specific embodiments disclosed below.

[0012] For the reaction raw materials and catalysts involved in the following examples, unless otherwise specified, they are all conventional commercially available reagents on the market.

[0013] Preparation Examples 1 - 70 of Dibenz[c,e]azepine

[0014] Example 1

[0015] Add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as a solvent into a 10 mL reaction tube. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, the dibenz[c,e]azepine compound 2a is obtained by column chromatography separation. It is a white solid with a yield of 85%.

[0016] The structural characterization of the dibenz[c,e]azepine compound 2a is as follows:

[0017] 1 H NMR(400MHz,Chloroform - d)δ7.59(d,J=7.6Hz,2H),7.56–7.44(m,4H),7.42–7.33(m,4H),7.01(d,J=8.5Hz,2H),4.22(s,4H). 13 C NMR(101MHz,CDCl 3 )δ151.30,140.56,134.36,129.58,128.62,128.27,127.96,126.55(q,J=3.7Hz),125.00(q,J=270.5Hz),119.04(q,J=32.7Hz),113.39,51.61. 19 F NMR(376MHz,CDCl 3 )δ - 60.99.

[0018] Example 2

[0019] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, the dibenzo[c,e]azepine compound 2b is obtained by column chromatography separation. It is a white solid with a yield of 92%.

[0020] Example 3

[0021] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, the dibenzo[c,e]azepine compound 2c is obtained by column chromatography separation. It is a white solid with a yield of 97%.

[0022] Example 4

[0023] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, the dibenzo[c,e]azepine compound 2d is obtained by column chromatography separation. It is a white solid with a yield of 90%.

[0024] Example 5

[0025] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, the dibenzo[c,e]azepine compound 2e is obtained by column chromatography separation. It is a white solid with a yield of 91%.

[0026] Example 6

[0027] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, separate by column chromatography to obtain dibenzo[c,e]azepine compound 2f, which is an oily liquid with a yield of 89%.

[0028] Example 7

[0029] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, separate by column chromatography to obtain dibenzo[c,e]azepine compound 2g, which is a white solid with a yield of 70%.

[0030] Example 8

[0031] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, separate by column chromatography to obtain dibenzo[c,e]azepine compound 2h, which is a colorless liquid with a yield of 89%.

[0032] Example 9

[0033] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, separate by column chromatography to obtain dibenzo[c,e]azepine compound 2i, which is a white solid with a yield of 95%.

[0034] Example 10

[0035] In a 10 mL reaction tube, 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent were added. Under a nitrogen atmosphere, the reaction was carried out at 120 °C for 12 hours. After the reaction was completed, the dibenzo[c,e]azepine compound 2j was obtained by column chromatography separation. It was a white solid with a yield of 77%.

[0036] Example 11

[0037] In a 10 mL reaction tube, 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent were added. Under a nitrogen atmosphere, the reaction was carried out at 120 °C for 12 hours. After the reaction was completed, the dibenzo[c,e]azepine compound 2k was obtained by column chromatography separation. It was a white solid with a yield of 94%.

[0038] Example 12

[0039] In a 10 mL reaction tube, 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent were added. Under a nitrogen atmosphere, the reaction was carried out at 120 °C for 12 hours. After the reaction was completed, the dibenzo[c,e]azepine compound 2l was obtained by column chromatography separation. It was an oily liquid with a yield of 92%.

[0040] Example 13

[0041] In a 10 mL reaction tube, 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent were added. Under a nitrogen atmosphere, the reaction was carried out at 120 °C for 12 hours. After the reaction was completed, the dibenzo[c,e]azepine compound 2m was obtained by column chromatography separation. It was a white solid with a yield of 85%.

[0042] Example 14

[0043] In a 10 mL reaction tube, 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent were added. Under a nitrogen atmosphere, the reaction was carried out at 120 °C for 12 hours. After the reaction, the dibenzo[c,e]azepine compound 2n was obtained by column chromatography separation. It was an oily liquid with a yield of 92%.

[0044] Example 15

[0045] In a 10 mL reaction tube, 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent were added. Under a nitrogen atmosphere, the reaction was carried out at 120 °C for 12 hours. After the reaction, the dibenzo[c,e]azepine compound 2o was obtained by column chromatography separation. It was a white solid with a yield of 86%.

[0046] Example 16

[0047] In a 10 mL reaction tube, 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent were added. Under a nitrogen atmosphere, the reaction was carried out at 120 °C for 12 hours. After the reaction, the dibenzo[c,e]azepine compound 2p was obtained by column chromatography separation. It was a yellow solid with a yield of 87%.

[0048] Example 17

[0049] In a 10 mL reaction tube, 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent were added. Under a nitrogen atmosphere, the reaction was carried out at 120 °C for 12 hours. After the reaction, the dibenzo[c,e]azepine compound 2q was obtained by column chromatography separation. It was a white solid with a yield of 86%.

[0050] Example 18

[0051] In a 10 mL reaction tube, 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent were added. Under a nitrogen atmosphere, the reaction was carried out at 120 °C for 12 hours. After the reaction was completed, the dibenzo[c,e]azepine compound 2r was obtained by column chromatography separation. It was a yellow solid with a yield of 77%.

[0052] Example 19

[0053] In a 10 mL reaction tube, 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent were added. Under a nitrogen atmosphere, the reaction was carried out at 120 °C for 12 hours. After the reaction was completed, the dibenzo[c,e]azepine compound 2s was obtained by column chromatography separation. It was a colorless liquid with a yield of 75%.

[0054] Example 20

[0055] In a 10 mL reaction tube, 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent were added. Under a nitrogen atmosphere, the reaction was carried out at 120 °C for 12 hours. After the reaction was completed, the dibenzo[c,e]azepine compound 2t was obtained by column chromatography separation. It was a yellow solid with a yield of 74%.

[0056] Example 21

[0057] In a 10 mL reaction tube, 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent were added. Under a nitrogen atmosphere, the reaction was carried out at 120 °C for 12 hours. After the reaction was completed, the dibenzo[c,e]azepine compound 2u was obtained by column chromatography separation. It was a white solid with a yield of 85%.

[0058] Example 22

[0059] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, the dibenzo[c,e]azepine compound 2v is obtained by column chromatography separation. It is a white solid with a yield of 89%.

[0060] Example 23

[0061] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, the dibenzo[c,e]azepine compound 2w is obtained by column chromatography separation. It is a white solid with a yield of 79%.

[0062] Example 24

[0063] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, the dibenzo[c,e]azepine compound 2x is obtained by column chromatography separation. It is a white solid with a yield of 90%.

[0064] Example 25

[0065] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, the dibenzo[c,e]azepine compound 2y is obtained by column chromatography separation. It is a white solid with a yield of 92%.

[0066] Example 26

[0067] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, the dibenzo[c,e]azepine compound 2z is obtained by column chromatography separation. It is a white solid with a yield of 78%.

[0068] Example 27

[0069] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, the dibenzo[c,e]azepine compound 2aa is obtained by column chromatography separation. It is a white solid with a yield of 94%.

[0070] Example 28

[0071] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, the dibenzo[c,e]azepine compound 2ab is obtained by column chromatography separation. It is a yellow solid with a yield of 90%.

[0072] Example 29

[0073] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, the dibenzo[c,e]azepine compound 2ac is obtained by column chromatography separation. It is a white solid with a yield of 90%.

[0074] Example 30

[0075] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, the dibenzo[c,e]azepine compound 2ad is obtained by column chromatography separation. It is a white solid with a yield of 93%.

[0076] Example 31

[0077] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, the dibenzo[c,e]azepine compound 2ae is obtained by column chromatography separation. It is a white solid with a yield of 85%.

[0078] Example 32

[0079] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, the dibenzo[c,e]azepine compound 3a is obtained by column chromatography separation. It is a colorless liquid with a yield of 94%.

[0080] Example 33

[0081] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, the dibenzo[c,e]azepine compound 3b is obtained by column chromatography separation. It is a colorless liquid with a yield of 91%.

[0082] Example 34

[0083] In a 10 mL reaction tube, 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder were added, and 2.0 mL of N,N - dimethylformamide was used as the solvent. Under a nitrogen atmosphere, the reaction was carried out at 120 °C for 12 hours. After the reaction was completed, the dibenzo[c,e]azepine compound 3c was obtained by column chromatography separation. It was a colorless liquid with a yield of 89%.

[0084] Example 35

[0085] In a 10 mL reaction tube, 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder were added, and 2.0 mL of N,N - dimethylformamide was used as the solvent. Under a nitrogen atmosphere, the reaction was carried out at 120 °C for 12 hours. After the reaction was completed, the dibenzo[c,e]azepine compound 3d was obtained by column chromatography separation. It was a colorless liquid with a yield of 90%.

[0086] Example 36

[0087] In a 10 mL reaction tube, 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder were added, and 2.0 mL of N,N - dimethylformamide was used as the solvent. Under a nitrogen atmosphere, the reaction was carried out at 120 °C for 12 hours. After the reaction was completed, the dibenzo[c,e]azepine compound 3e was obtained by column chromatography separation. It was a colorless liquid with a yield of 92%.

[0088] Example 37

[0089] In a 10 mL reaction tube, 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder were added, and 2.0 mL of N,N - dimethylformamide was used as the solvent. Under a nitrogen atmosphere, the reaction was carried out at 120 °C for 12 hours. After the reaction was completed, the dibenzo[c,e]azepine compound 3f was obtained by column chromatography separation. It was a colorless liquid with a yield of 96%.

[0090] Example 38

[0091] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, 3 g of dibenzo[c,e]azepine compound is obtained by column chromatography separation. It is an oily liquid with a yield of 93%.

[0092] Example 39

[0093] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, 3 h of dibenzo[c,e]azepine compound is obtained by column chromatography separation. It is an oily liquid with a yield of 93%.

[0094] Example 40

[0095] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, 3 i of dibenzo[c,e]azepine compound is obtained by column chromatography separation. It is a colorless liquid with a yield of 92%.

[0096] Example 41

[0097] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, 3 j of dibenzo[c,e]azepine compound is obtained by column chromatography separation. It is a white solid with a yield of 90%.

[0098] Example 42

[0099] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, the dibenzo[c,e]azepine compound 3k is obtained by column chromatography separation. It is a colorless liquid with a yield of 94%.

[0100] Example 43

[0101] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, the dibenzo[c,e]azepine compound 3l is obtained by column chromatography separation. It is a colorless liquid with a yield of 87%.

[0102] Example 44

[0103] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, the dibenzo[c,e]azepine compound 3m is obtained by column chromatography separation. It is a colorless liquid with a yield of 92%.

[0104] Example 45

[0105] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, the dibenzo[c,e]azepine compound 3n is obtained by column chromatography separation. It is a colorless liquid with a yield of 85%.

[0106] Example 46

[0107] In a 10 mL reaction tube, 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent were added. Under a nitrogen atmosphere, the reaction was carried out at 120 °C for 12 hours. After the reaction was completed, the dibenzo[c,e]azepine compound 3o was obtained by column chromatography separation. It was an oily liquid with a yield of 86%.

[0108] Example 47

[0109] In a 10 mL reaction tube, 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent were added. Under a nitrogen atmosphere, the reaction was carried out at 120 °C for 12 hours. After the reaction was completed, the dibenzo[c,e]azepine compound 3p was obtained by column chromatography separation. It was a colorless liquid with a yield of 92%.

[0110] Example 48

[0111] In a 10 mL reaction tube, 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent were added. Under a nitrogen atmosphere, the reaction was carried out at 120 °C for 12 hours. After the reaction was completed, the dibenzo[c,e]azepine compound 3q was obtained by column chromatography separation. It was a white solid with a yield of 84%.

[0112] Example 49

[0113] In a 10 mL reaction tube, 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent were added. Under a nitrogen atmosphere, the reaction was carried out at 120 °C for 12 hours. After the reaction was completed, the dibenzo[c,e]azepine compound 3r was obtained by column chromatography separation. It was a colorless liquid with a yield of 83%.

[0114] Example 50

[0115] In a 10 mL reaction tube, 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8-tetramethyl-1,10-phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N-dimethylformamide as the solvent were added. Under a nitrogen atmosphere, the reaction was carried out at 120 °C for 12 hours. After the reaction was completed, the dibenzo[c,e]azepine compound 3s was obtained by column chromatography separation. It was an oily liquid with a yield of 87%.

[0116] Example 51

[0117] In a 10 mL reaction tube, 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8-tetramethyl-1,10-phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N-dimethylformamide as the solvent were added. Under a nitrogen atmosphere, the reaction was carried out at 120 °C for 12 hours. After the reaction was completed, the dibenzo[c,e]azepine compound 3t was obtained by column chromatography separation. It was a white solid with a yield of 86%.

[0118] Example 52

[0119] In a 10 mL reaction tube, 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8-tetramethyl-1,10-phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N-dimethylformamide as the solvent were added. Under a nitrogen atmosphere, the reaction was carried out at 120 °C for 12 hours. After the reaction was completed, the dibenzo[c,e]azepine compound 3u was obtained by column chromatography separation. It was a white solid with a yield of 92%.

[0120] Example 53

[0121] In a 10 mL reaction tube, 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8-tetramethyl-1,10-phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N-dimethylformamide as the solvent were added. Under a nitrogen atmosphere, the reaction was carried out at 120 °C for 12 hours. After the reaction was completed, the dibenzo[c,e]azepine compound 3v was obtained by column chromatography separation. It was an oily liquid with a yield of 87%.

[0122] Example 54

[0123] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, the dibenzo[c,e]azepine compound 3w is obtained by column chromatography separation. It is a white solid with a yield of 90%.

[0124] Example 55

[0125] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, the dibenzo[c,e]azepine compound 3x is obtained by column chromatography separation. It is an oily liquid with a yield of 95%.

[0126] Example 56

[0127] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, the dibenzo[c,e]azepine compound 3y is obtained by column chromatography separation. It is an oily liquid with a yield of 90%.

[0128] Example 57

[0129] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.02 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, the dibenzo[c,e]azepine compound 3z is obtained by column chromatography separation. It is a yellow liquid with a yield of 84%.

[0130] Example 58

[0131] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.04 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.8 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, the dibenzo[c,e]azepine compound 5a is obtained by column chromatography separation. It is a white solid with a yield of 84%.

[0132] Example 59

[0133] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.04 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.8 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, the dibenzo[c,e]azepine compound 5b is obtained by column chromatography separation. It is a white solid with a yield of 87%.

[0134] Example 60

[0135] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.04 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.8 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, the dibenzo[c,e]azepine compound 5c is obtained by column chromatography separation. It is a white solid with a yield of 86%.

[0136] Example 61

[0137] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.04 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.8 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, the dibenzo[c,e]azepine compound 5d is obtained by column chromatography separation. It is a white solid with a yield of 90%.

[0138] Example 62

[0139] In a 10 mL reaction tube, 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.04 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.8 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent were added. Under a nitrogen atmosphere, the reaction was carried out at 120 °C for 12 hours. After the reaction was completed, the dibenzo[c,e]azepine compound 5e was obtained by column chromatography separation. It was a white solid with a yield of 86%.

[0140] Example 63

[0141] In a 10 mL reaction tube, 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.04 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.8 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent were added. Under a nitrogen atmosphere, the reaction was carried out at 120 °C for 12 hours. After the reaction was completed, the dibenzo[c,e]azepine compound 5f was obtained by column chromatography separation. It was a white solid with a yield of 82%.

[0142] Example 64

[0143] In a 10 mL reaction tube, 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.04 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.8 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent were added. Under a nitrogen atmosphere, the reaction was carried out at 120 °C for 12 hours. After the reaction was completed, the dibenzo[c,e]azepine compound 5g was obtained by column chromatography separation. It was a white solid with a yield of 94%.

[0144] Example 65

[0145] In a 10 mL reaction tube, 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.04 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.8 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent were added. Under a nitrogen atmosphere, the reaction was carried out at 120 °C for 12 hours. After the reaction was completed, the dibenzo[c,e]azepine compound 5h was obtained by column chromatography separation. It was a white solid with a yield of 92%.

[0146] Example 66

[0147] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.04 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.8 mmol of potassium dihydrogen phosphate, 0.4 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, separate by column chromatography to obtain dibenzo[c,e]azepine compound 5i as a white solid with a yield of 90%.

[0148] Example 67

[0149] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.04 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.2 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, separate by column chromatography to obtain dibenzo[c,e]azepine compound 5j as a white solid with a yield of 84%.

[0150] Example 69

[0151] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.04 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.2 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, separate by column chromatography to obtain dibenzo[c,e]azepine compound 5k as a colorless liquid with a yield of 70%.

[0152] Example 70

[0153] In a 10 mL reaction tube, add 10.2 mmol of dibromoaniline, 0.02 mmol of nickel bromide, 0.04 mmol of 3,4,7,8 - tetramethyl - 1,10 - phenanthroline, 0.4 mmol of potassium dihydrogen phosphate, 0.2 mmol of manganese powder, and 2.0 mL of N,N - dimethylformamide as the solvent. Under a nitrogen atmosphere, react at 120 °C for 12 hours. After the reaction is completed, separate by column chromatography to obtain dibenzo[c,e]azepine compound 5l as a white solid with a yield of 75%.

[0154] The above-described embodiments merely represent several implementation manners of the present invention. The description is relatively specific and detailed, but it should not be construed as a limitation on the scope of the patent for the present invention. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present invention, several modifications and improvements can still be made, and these all fall within the protection scope of the present invention. Therefore, the protection scope of the patent for the present invention shall be defined by the appended claims.

Claims

1. A synthetic method of a class of dibenzo[c,e]azepine derivatives 2, characterized in that, using 0.2 mmol of aniline compound 1 as the raw material, 10 mol% nickel bromide as the catalyst, 10 mol% 3,4,7,8-tetramethyl-1,10-phenanthroline as the ligand, 2.0 equivalents of potassium dihydrogen phosphate as the additive, 2.0 equivalents of manganese powder as the reducing agent, N,N-dimethylformamide as the solvent, reacting at 120 °C for 12 hours under a nitrogen atmosphere to obtain dibenzo[c,e]azepine derivatives 2, and the dibenzo[c,e]azepine derivatives 2 are 2a-2z, 2aa-2ae and 3a-3z;

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