CN114349684A - Synthetic method of benzo [ c, d ] indole imine derivative - Google Patents

Synthetic method of benzo [ c, d ] indole imine derivative Download PDF

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CN114349684A
CN114349684A CN202210060255.1A CN202210060255A CN114349684A CN 114349684 A CN114349684 A CN 114349684A CN 202210060255 A CN202210060255 A CN 202210060255A CN 114349684 A CN114349684 A CN 114349684A
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张莲鹏
杜官本
杨龙
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Southwest Forestry University
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Abstract

The invention discloses a synthesis method of a polysubstituted benzo [ c, d ] indole imine derivative, which comprises the steps of firstly placing an 8-halogen-1-naphthylamine compound, an isonitrile derivative, a catalyst and an additive into a reaction vessel, then adding a solvent into the reaction vessel until the 8-halogen-1-naphthylamine compound is completely dissolved, then heating the mixture in a nitrogen atmosphere for reaction, and carrying out post-treatment after the reaction is finished to obtain the polysubstituted benzo [ c, d ] indole imine derivative. The invention adopts a one-pot one-step method to synthesize the polysubstituted benzo [ c, d ] indole imine derivative, uses high-efficiency transition metal as a catalyst, has simple reaction conditions, convenient operation, wide substrate universality, simple and easily obtained reaction raw materials and low production cost, is not only suitable for small-scale preparation in a laboratory, but also suitable for industrialized large-scale production. The reaction is favorable for establishing a polysubstituted benzo [ c, d ] indole imine derivative compound library, and provides a simple and convenient method for screening activities of resisting tumors, resisting bacteria, treating cardiovascular and cerebrovascular diseases and the like.

Description

Synthetic method of benzo [ c, d ] indole imine derivative
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a synthesis method of a benzo [ c, d ] indole imine derivative.
Background
Benzo [ c, d ] indoles are important heterocyclic compounds, and the compounds are widely applied to biological medicines (J.Med.chem.1991,34,1925; bioorg.Med.chem.2012,20,789; J.Med.chem.1992,35,663.), fluorescent Dyes (Org.Lett.2015,17,278.), organic ligands (Tetrahedron 1996,52,7277.), materials (dye Pies Pigm.2016,129, 163; dye Pigm.2017,141,457.) and the like due to good biological activity and optical performance. Benzo [ c, d ] indole imine derivatives are a special benzo [ c, d ] indole compound, have good activity and selectivity for inhibiting tumor cell proliferation (Chinese invention patent, 101602707,16Dec 2009.), and are also used as cardiovascular and cerebrovascular drugs (eur. Pat. appl.,446603,18Sep 1991).
There are two main methods for constructing benzo [ c, d ] indole imine derivatives: the benzo [ c, d ] indole-2-ketone is used as a raw material, nitrogen atoms are subjected to group modification, then the benzo [ c, d ] indole-2-thioketone derivative is generated by reacting with phosphorus pentasulfide, and finally the benzo [ c, d ] indole-2-thioketone derivative is generated by reacting with a primary amine compound under the catalysis of mercuric oxide or mercuric acetate. The reaction has many steps, uses a highly toxic catalyst and has certain hazard. The other method is also to take benzo [ c, d ] indole-2-ketone as a raw material, take phosphorus oxychloride as a dehydrating agent, firstly carry out dehydration condensation reaction with primary amine compounds to form imine, and finally carry out group modification on nitrogen atoms to obtain the polysubstituted benzo [ c, d ] indole imine derivative. Through the two methods, the inherent structure of benzo [ c, d ] indole-2-ketone is not easy to modify, so that the number of benzo [ c, d ] indole imine derivatives reported at present is small. Therefore, the invention aims to invent a simple method for preparing a novel benzo [ c, d ] indole imine derivative by using a high-efficiency metal as a catalyst.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provides a synthetic method of a benzo [ c, d ] indole imine derivative.
The purpose of the invention is realized by the following technical scheme: a synthetic method of benzo [ c, d ] indole imine derivatives comprises the following steps: under the action of a catalyst and an additive, 8-halogen-1-naphthylamine compound and an isonitrile derivative react in a solvent under nitrogen atmosphere at a certain temperature, and the benzo [ c, d ] indole imine derivative is obtained after post-treatment after the reaction;
the structure of the 8-halogen-1-naphthylamine compound is shown as the formula (I):
Figure BDA0003477968200000021
the structure of the isonitrile derivative is shown as the formula (II):
R4-NC (II)
the structure of the benzo [ c, d ] indole imine derivative is shown as a formula (III):
Figure BDA0003477968200000022
in the formulae (I) to (III), R1Selected from H, aryl, alkyl, sulfonic acid or acyl;
R2selected from H, alkyl, acyl, nitro or amino;
R3selected from H, alkyl, acyl, nitro or amino; or R2、R3And the carbon on the naphthalene ring connected with the naphthalene ring form a five-membered ring or a six-membered ring;
R4selected from alkyl, phenyl or naphthyl;
x is selected from halogen atoms;
wherein the substituent on the phenyl is selected from C1～C4Alkyl radical, C1～C4Alkoxy, nitro or halogen.
Preferably, R1Selected from H, phenyl, methyl, ethyl, n-butyl, phenylsulfonyl, naphthalenesulfonyl, thiophenesulfonyl or benzoyl;
R2selected from H, nitro or amino;
R3selected from H, nitro or amino; or R2、R3Are both methylene groups, and the two methylene groups are connected by a chemical bond; or R2、R3Both formyl groups and both formyl groups are chemically bonded to nitrogen to form caprolactam;
R4selected from the group consisting of tert-butyl, cyclohexyl, n-butyl, phenyl, naphthyl, p-tolyl, p-nitrophenyl, p-chlorophenyl,P-fluorophenyl, 3, 4-dichlorophenyl, p-methoxyphenyl or o-chlorophenyl;
x is selected from iodine and bromine.
The method specifically comprises the following steps: taking 8-halogen-1-naphthylamine compounds, isonitrile derivatives, catalysts and additives according to the molar ratio of 1: 1.0-2.0: 0.05-0.2: 1.0-3.0, putting the 8-halogen-1-naphthylamine compounds, the isonitrile derivatives, the catalysts and the additives into a reaction vessel, and adding a solvent into the reaction vessel until the 8-halogen-1-naphthylamine compounds are completely dissolved; placing the reaction vessel in nitrogen atmosphere at 25-120 ℃ for stirring reaction for 0-24h, cooling to room temperature, adding water with volume 5 times of that of the solvent, and extracting for 2-4 times by using ethyl acetate; combining the filtrates, and distilling under reduced pressure to remove solvent; separating by silica gel chromatographic column, and distilling under reduced pressure to obtain the product, namely the polysubstituted benzo [ c, d ] indole imine derivative.
Further, the 8-halo-1-naphthylamine compound can be 8-iodo-1-naphthylamine compound (i.e. X is iodine) or 8-bromo-1-naphthylamine compound (i.e. X is bromine); the solvent is an aprotic solvent.
Further, the aprotic solvent is acetonitrile, toluene, tetrahydrofuran, dichloromethane, 1, 2-dichloroethane, N-dimethylformamide, N-dimethylacetamide, N-methylpyrrolidone, hexamethylphosphoramide, or dimethylsulfoxide.
Further, the aprotic solvent is 1, 2-dichloroethane.
Further, the catalyst is Pd (OAc)2、Pd(PPh)4、PdCl2、Pd(PPh3)2Cl2、Pd(TFA)2Or Pd2(dba)3The catalyst is preferably Pd (TFA)2。
Further, the additive is triphenylphosphine and Cs2CO3、K2CO3、KOH、K3PO4、Na2CO3、NaHCO3One or more of NaOAc, NaOH, DBU, piperidine, and pyridine.
The additive is preferably K2CO3。
Further, the reaction temperature may be 25 ℃, 30 ℃, 40 ℃, 50 ℃, 60 ℃, 70 ℃, 80 ℃, 90 ℃, 100 ℃, 110 ℃ or 120 ℃.
The reaction temperature is preferably 70 ℃.
Further, the molar ratio of the 8-halogen-1-naphthylamine compound to the isonitrile derivative to the catalyst to the additive is 1.0:1.5:0.1: 2.0.
Compared with the prior art, the invention has the beneficial effects that: is beneficial to the establishment of a polysubstituted benzo [ c, d ] indole imine derivative compound library, and provides a simple and convenient method for screening the activities of resisting tumors, resisting bacteria, treating cardiovascular and cerebrovascular diseases and the like. The invention adopts a one-pot one-step method to synthesize the polysubstituted benzo [ c, d ] indole imine derivative, the reaction raw materials are simple and easy to obtain, high-efficiency transition metal is used as a catalyst, the reaction conditions are simple, the operation is convenient, the catalytic amount of the catalyst can obtain excellent yield, the substrate universality is wide, the production cost is low, and the method is not only suitable for small-scale preparation in a laboratory, but also suitable for industrial large-scale production. Furthermore, the polysubstituted benzo [ c, d ] indole imine derivative can be converted into more molecules with medicinal value and biological activity.
Detailed Description
The structure of the polysubstituted benzo [ c, d ] indole imine derivative is shown as follows:
Figure BDA0003477968200000041
wherein: r1＝CH3,R2＝H,R3＝H,R4＝t-Bu；R1＝Et,R2＝H,R3＝H,R4＝t-Bu；R1＝p-toluenesulfonyl,R2＝H,R3＝H,R4＝t-Bu；R1＝p-chlorobenzenesulfonyl,R2＝H,R3＝H,R4＝t-Bu；R1＝p-fluorobenzenesulfonyl,R2＝H,R3＝H,R4＝t-Bu；R1＝p-nitrobenzenesulfonyl,R2＝H,R3＝H,R4＝t-Bu；R1＝o-bromobenzenesulfonyl,R2＝H,R3＝H,R4＝t-Bu；R1＝2-naphthalenesulfonyl,R2＝H,R3＝H,R4＝t-Bu；R1＝2-thiophenesulfonyl,R2＝H,R3＝H,R4＝t-Bu；R1＝H,R2＝H,R3＝H,R4＝t-Bu；R1＝H,R2＝CH2,R3＝CH2,R4＝t-Bu；R1＝p-toluenesulfonyl,R2＝CH2,R3＝CH2,R4＝t-Bu；R1＝p-toluenesulfonyl,R2＝NO2,R3＝H,R4＝t-Bu；R1＝p-toluenesulfonyl,R2＝NO2,R3＝NO2,R4＝t-Bu；R1＝p-toluenesulfonyl,R2＝H,R3＝H,R4＝cyclohexyl；R1＝p-toluenesulfonyl,R2＝H,R3＝H,R4＝n-Bu；R1＝p-toluenesulfonyl,R2＝H,R3＝H,R4＝p-nitrophenyl；R1＝H,R2＝H,R3＝H,R4＝p-nitrophenyl；R1＝p-toluenesulfonyl,R2＝H,R3＝H,R4＝phenyl；R1＝p-toluenesulfonyl,R2＝H,R3＝H,R4＝2-naphthyl；R1＝p-toluenesulfonyl,R2＝H,R3＝H,R4＝3,4-dichlorophenyl；R1＝p-toluenesulfonyl,R2＝H,R3＝H,R4＝p-tolyl；R1＝p-toluenesulfonyl,R2＝H,R3＝H,R4＝p-chlorophenyl；R1＝p-toluenesulfonyl,R2＝H,R3＝H,R4＝p-methoxyphenyl；R1＝p-toluenesulfonyl,R2＝H,R3＝H,R4＝p-methoxyphenyl；R1＝p-toluenesulfonyl,R2＝H,R3＝H,R4＝o-chlorophenyl.
The synthesis method adopts a one-pot one-step synthesis mode, and specifically comprises the following steps: taking 8-halogen-1-naphthylamine compounds, isonitrile derivatives, catalysts and additives according to the molar ratio of 1.0:1.5:0.1:2.0, putting the 8-halogen-1-naphthylamine compounds, the isonitrile derivatives, the catalysts and the additives into a reaction vessel, and adding a solvent into the reaction vessel until the 8-halogen-1-naphthylamine compounds are completely dissolved; placing the reaction vessel in nitrogen atmosphere at 25-120 ℃ for stirring reaction for 0-24h, cooling to room temperature, adding water with volume 5 times of that of the solvent, and extracting for 2-4 times by using ethyl acetate; combining the filtrates, and distilling under reduced pressure to remove solvent; separating by silica gel chromatographic column, and distilling under reduced pressure to obtain the product, namely the polysubstituted benzo [ c, d ] indole imine derivative.
In the synthesis method, the 8-halogen-1-naphthylamine compound can be 8-iodine-1-naphthylamine compound and 8-bromine-1-naphthylamine compound; the solvent may be an aprotic solvent such as one or more of acetonitrile, toluene, tetrahydrofuran, dichloromethane, 1, 2-dichloroethane, N-dimethylformamide, N-dimethylacetamide, N-methylpyrrolidone, hexamethylphosphoramide or dimethylsulfoxide. Of these, 1, 2-dichloroethane is particularly preferable. The catalyst can be Pd (OAc)2、Pd(PPh)4、PdCl2、Pd(PPh3)2Cl2、Pd(TFA)2Or Pd2(dba)3Among the most preferred catalysts are Pd (TFA)2. The additive can be triphenylphosphine and Cs2CO3、K2CO3、KOH、K3PO4、Na2CO3、NaHCO3One or more of NaOAc, NaOH, DBU, piperidine and pyridine, wherein the most preferred additive is K2CO3. The mol ratio of the 8-halogen-1-naphthylamine compound to the isonitrile derivative to the catalyst to the additive is 1.0:1.5:0.1: 2.0.
Figure BDA0003477968200000051
The invention is further illustrated by the following specific examples, which are not intended to limit the invention thereto.
Table 1 shows the structures of the polysubstituted benzo [ c, d ] indolimine derivatives of examples 1-5.
Figure BDA0003477968200000052
TABLE 1 Structure of polysubstituted benzo [ c, d ] indolimine derivatives of examples 1-5
Figure BDA0003477968200000053
Figure BDA0003477968200000061
The starting materials of examples 1 to 6 were prepared from the known compound 8-iodo (bromo) -1-naphthylamine derivative by reacting with a sulfonyl chloride compound in one step.
Example 1
N-Ts-8-iodonaphthylamine (0.5mmol), t-butylisonitrile (0.75mmol), Pd (TFA) were added sequentially to a round-bottomed flask at room temperature2(0.05mmol), potassium carbonate (1.0mmol) and DCE (3ml), followed by stirring the reaction at 70 ℃ under a nitrogen atmosphere until the N-Ts-8-iodonaphthylamine reaction was complete. After the reaction is finished, cooling to room temperature, adding water with the volume 5 times that of the solvent, and extracting for 2-4 times by using ethyl acetate; combining the filtrates, and distilling under reduced pressure to remove solvent; separating with silica gel chromatographic column, and distilling under reduced pressure to obtain the product with yield of 87%. The identification result is as follows:
yellow solid.
1H NMR(400MHz,CDCl3)δ7.97–7.85(m,5H),7.62(t,J＝7.8Hz,1H),7.53(d,J＝4.2Hz,2H),7.21(d,J＝8.3Hz,2H),2.38(s,3H),1.40(s,9H)；13C{1H}NMR(100MHz,CDCl3)δ148.1,143.8,138.3,137.0,130.6,128.9,128.7,128.6,128.5,128.2,127.8,126.4,122.9,119.9,109.0,54.4,28.7,21.6；IR(neat)3132,1645,1340,1170,781cm-1；HRMS(ESI-TOF)m/z:[M+H]+Calcd for C22H23N2O2S 379.1480；Found 379.1478.
Example 2
8-iodonaphthylamine (0.3mmol), t-butylisonitrile (0.3mmol), Pd (OAc) were added successively to a round-bottomed flask at room temperature2(0.06mmol), cesium carbonate (0.9mmol) and CH3CN (2ml), then the reaction was stirred at 100 ℃ under nitrogen atmosphere until the 8-iodonaphthylamine reaction was complete. After the reaction is finished, cooling to room temperature, adding water with the volume 5 times that of the solvent, and extracting for 2-4 times by using ethyl acetate; combining the filtrates, and distilling under reduced pressure to remove solvent; separating with silica gel chromatographic column, and distilling under reduced pressure to obtain the product with yield of 78%. The identification result is as follows:
yellow solid.
1H NMR(400MHz,CDCl3)δ7.88(d,J＝8.4Hz,1H),7.69(d,J＝7.4Hz,1H),7.58–7.50(m,1H),7.49–7.35(m,2H),7.32(d,J＝6.3Hz,1H),1.63(s,9H)；13C{1H}NMR(100MHz,CDCl3)δ133.0,131.2,129.9,129.2,129.1,128.9,127.0,124.3,120.0,119.8,114.5,52.8,29.2；IR(neat)3312,3129,1651,752cm-1；HRMS(ESI-TOF)m/z:[M+H]+Calcd for C15H17N2225.1392；Found 225.1395.
Example 3
Sequentially adding 8-bromo-3, 4-cycloethyl-1-naphthylamine (1.0mmol), tert-butyl isonitrile (1.2mmol) and PdCl into a reaction bottle at room temperature2(0.05mmol), sodium carbonate (1.0mmol) and DMF (4ml) were then stirred at 120 ℃ under nitrogen until the reaction of 8-bromo-3, 4-cycloethyl-1-naphthylamine was complete. After the reaction is finished, cooling to room temperature, adding water with the volume 5 times that of the solvent, and extracting for 2-4 times by using ethyl acetate; combining the filtrates, and distilling under reduced pressure to remove solvent; separating with silica gel chromatographic column, and distilling under reduced pressure to obtain the product with yield of 71%. The identification result is as follows:
yellow solid.
1H NMR(400MHz,CDCl3)δ7.75(d,J＝6.7Hz,1H),7.39–7.27(m,2H),7.18(d,J＝6.8Hz,1H),3.50–3.37(m,4H),1.62(s,9H)；13C{1H}NMR(100MHz,CDCl3)δ162.8,159.3,149.0,138.6,136.6,127.3,123.3,121.4,120.6,119.0,115.6,52.8,33.3,32.0,29.2；IR(neat)3315,3128,1653,1471,762cm-1；HRMS(ESI-TOF)m/z:[M+H]+Calcd for C17H19N2251.1548；Found 251.1546.
Example 4
N-Ts-8-bromonaphthylamine (0.2mmol), cyclohexylisonitrile (0.26mmol), Pd (PPh) were added sequentially to a round-bottomed flask at room temperature4(0.04mmol), NaOH (0.5mmol) and DMAc (3ml), followed by stirring the reaction at 110 ℃ under a nitrogen atmosphere until the N-Ts-8-bromonaphthylamine reaction was complete. After the reaction is finished, cooling to room temperature, adding water with the volume 5 times that of the solvent, and extracting for 2-4 times by using ethyl acetate; combining the filtrates, and distilling under reduced pressure to remove solvent; separating with silica gel chromatographic column, and distilling under reduced pressure to obtain the product with yield of 65%. The identification result is as follows:
yellow solid.
1H NMR(400MHz,CDCl3)δ7.91(d,J＝8.1Hz,2H),7.85(d,J＝8.2Hz,1H),7.81(d,J＝7.2Hz,1H),7.55(t,J＝7.5Hz,1H),7.52–7.44(m,2H),7.24–7.13(m,3H),3.73(t,J＝6.7Hz,2H),2.32(s,3H),1.71–1.62(m,2H),1.38–1.28(m,2H),0.89(t,J＝7.3Hz,3H)；13C{1H}NMR(100MHz,CDCl3)δ151.5,144.3,138.5,136.2,130.5,129.1,129.0,128.8,128.6,128.2,127.1,124.8,124.1,120.1,109.3,50.7,33.3,21.6,20.6,14.0；IR(neat)3128,1635,1346,1176,755cm-1；HRMS(ESI-TOF)m/z:[M+H]+Calcd for C24H25N2O2S 405.1637；Found 405.1639.
Example 5
Sequentially adding N-Ts-4-nitro-8-iodonaphthylamine (0.6mmol), tert-butylisonitrile (1.2mmol) and Pd in a reaction bottle at room temperature2(dba)3(0.09mmol)，NaHCO3(1.8mmol) and DMSO (3ml), followed by stirring at 90 ℃ under a nitrogen atmosphere until the N-Ts-4-nitro-8-iodonaphthylamine reacted completely. After the reaction is finished, cooling to room temperature, adding water with the volume 5 times that of the solvent, and extracting for 2-4 times by using ethyl acetate; combining the filtrates, and distilling under reduced pressure to remove solvent; separating with silica gel chromatographic column, and distilling under reduced pressure to obtain the product with yield of 72%. The identification result is as follows:
yellow solid.
1H NMR(400MHz,CDCl3)δ8.50(d,J＝7.6Hz,1H),8.33(d,J＝7.8Hz,1H),8.10(d,J＝6.7Hz,1H),6.79–6.66(m,1H),4.24–4.08(m,2H),4.04–3.83(m,2H),1.75–1.65(m,4H),1.58(s,9H),1.48–1.33(m,4H),1.00–0.97(m,2H),0.97–0.93(m,4H)；13C{1H}NMR(100MHz,CDCl3)δ163.9,163.8,161.8,135.5,130.9,130.7,130.6,129.4,128.8,127.8,126.3,126.2,126.0,40.9,40.0,30.5,30.2,29.7,29.4,20.4,20.1,13.9,13.8；IR(neat)3129,1632,1535,1345,1163,756cm-1；HRMS(ESI-TOF)m/z:[M+H]+Calcd for C22H22N3O4S 424.1331；Found 424.1330.
Example 6
Sequentially adding 8-iodonaphthylamine (0.4mmol), p-nitrophenylisonitrile (0.7mmol) and Pd (PPh) into a reaction flask at room temperature3)2Cl2(0.06mmol)，K2CO3(0.7mmol) and DMSO (2ml), followed by stirring the reaction at 100 ℃ under nitrogen atmosphere until the 8-iodonaphthylamine reaction is complete. After the reaction is finished, cooling to room temperature, adding water with the volume 5 times that of the solvent, and extracting for 2-4 times by using ethyl acetate; combining the filtrates, and distilling under reduced pressure to remove solvent; separating with silica gel chromatographic column, and distilling under reduced pressure to obtain the product with yield of 56%. The identification result is as follows:
yellow solid.
1H NMR(400MHz,d6-DMSO)δ9.10(s,1H),8.58–8.37(m,3H),8.34–7.84(m,5H),7.81–7.66(m,1H),7.66–7.36(m,1H)；13C{1H}NMR(100MHz,d6-DMSO)δ157.6,144.6,141.4,133.0,129.9,129.6,129.4,128.3,127.3,126.8,125.6,125.4,123.6,122.8,112.8；IR(neat)3130,1636,1351,758cm-1；HRMS(ESI-TOF)m/z:[M+H]+Calcd for C17H12N3O2290.0930, respectively; found 290.0929, CAS number: 1203674-69-4.
The above-described embodiments are intended to illustrate rather than to limit the invention, and any modifications and variations of the present invention are within the spirit of the invention and the scope of the appended claims.

Claims (9)

1. A synthetic method of a benzo [ c, d ] indole imine derivative is characterized by comprising the following steps: under the action of a catalyst and an additive, 8-halogen-1-naphthylamine compound and an isonitrile derivative react in a solvent under the atmosphere of nitrogen, and the benzo [ c, d ] indole imine derivative is obtained after post-treatment after the reaction;
the structure of the 8-halogen-1-naphthylamine compound is shown as the formula (I):
Figure FDA0003477968190000011
the structure of the isonitrile derivative is shown as the formula (II):
R4-NC (II)
the structure of the benzo [ c, d ] indole imine derivative is shown as a formula (III):
Figure FDA0003477968190000012
in the formulae (I) to (III), R1Selected from H, aryl, alkyl, sulfonic acid or acyl;
R2selected from H, alkyl, acyl, nitro or amino;
R3selected from H, alkyl, acyl, nitro or amino; or R2、R3And the carbon on the naphthalene ring connected with the naphthalene ring form a five-membered ring or a six-membered ring;
R4selected from alkyl, substituted or unsubstituted phenyl or naphthyl;
x is selected from halogen atoms;
wherein the substituent on the phenyl is selected from C1～C4Alkyl radical, C1～C4Alkoxy, nitro or halogen.
2. Benzo [ c, d ] according to claim 1]Indoleimine derivativesA method of biosynthesis, characterized in that R1Selected from H, phenyl, methyl, ethyl, n-butyl, phenylsulfonyl, naphthalenesulfonyl, thiophenesulfonyl or benzoyl;
R2selected from H, nitro or amino;
R3selected from H, nitro or amino; or R2、R3Are both methylene groups, and the two methylene groups are connected by a chemical bond; or R2、R3Both formyl groups and both formyl groups are chemically bonded to nitrogen to form caprolactam;
R4selected from tert-butyl, cyclohexyl, n-butyl, phenyl, naphthyl, p-tolyl, p-nitrophenyl, p-chlorophenyl, p-fluorophenyl, 3, 4-dichlorophenyl, p-methoxyphenyl or o-chlorophenyl;
x is selected from iodine and bromine.
3. The method for synthesizing benzo [ c, d ] indole imine derivative according to claim 1, wherein the 8-halo-1-naphthylamine compound is 8-iodo-1-naphthylamine compound or 8-bromo-1-naphthylamine compound.
4. The method for synthesizing a benzo [ c, d ] indolimine derivative according to claim 1, wherein the solvent is an aprotic solvent.
5. The method for synthesizing a benzo [ c, d ] indolimine derivative according to claim 4, wherein the aprotic solvent is acetonitrile, toluene, tetrahydrofuran, dichloromethane, 1, 2-dichloroethane, N-dimethylformamide, N-dimethylacetamide, N-methylpyrrolidone, hexamethylphosphoramide, or dimethylsulfoxide.
6. Benzo [ c, d ] according to claim 1]The synthesis method of the indole imine derivative is characterized in that the catalyst is Pd (OAc)2、Pd(PPh)4、PdCl2、Pd(PPh3)2Cl2、Pd(TFA)2、Pd2(dba)3One or more of (a).
7. Benzo [ c, d ] according to claim 1]The synthesis method of the indole imine derivative is characterized in that the additive is triphenylphosphine and Cs2CO3、K2CO3、KOH、K3PO4、Na2CO3、NaHCO3One or more of NaOAc, NaOH, DBU, piperidine, and pyridine.
8. The method for synthesizing benzo [ c, d ] indolimine derivative according to claim 1, wherein the reaction temperature is 25-120 ℃.
9. The synthesis method of the benzo [ c, d ] indole imine derivative according to claim 1, wherein the molar ratio of the 8-halo-1-naphthylamine compound, the isonitrile derivative, the catalyst and the additive is 1.0: 1.0-2.0: 0.05-0.2: 1.0-3.0.
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