Synthesis method of 7-bromine-5, 6-bis (benzyloxy) benzopyrrole and derivative dimer of 7-bromine-5, 6-bis (benzyloxy) benzopyrrole

Abstract

The invention discloses a synthetic method of 7-bromo-5, 6-bis (benzyloxy) benzopyrrole and a derivative dimer of the 7-bromo-5, 6-bis (benzyloxy) benzopyrrole. The synthetic method of the 7-bromo-5, 6-bis (benzyloxy) benzopyrrole comprises the following steps: 1) 2-methoxy-5-nitrophenol is subjected to a bromination reaction through NBS (N-bromosuccinimide), and a compound A is obtained; 2) demethylating the compound A to obtain a compound B; 3) performing benzyl protection on two phenolic hydroxyl groups of the compound B to obtain a compound C; and 4) the compound C is subjected to a Baltorry reaction under the action of vinyl magnesium bromide, and the compound is obtained. The invention relates to a synthesis method of 7, 7 '-dimer, which is characterized in that 7-bromo-5, 6-bis (benzyloxy) benzopyrrole is taken as an initial raw material, and the 7, 7'-dimer is obtained through two-step reaction, the synthesis of the 7, 7 '-dimer is reported for the first time, and the synthesis method has the advantages that the raw material is cheap and easy to obtain, the steps are few, the final product is convenient to purify and easy to stably preserve and the like, and the synthesis method of the 2, 7'-dimer is obviously optimized.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and specifically relates to a method for synthesizing 7-bromo-5,6-bis(benzyloxy)benzopyrrole and a derivative dimer thereof. Background Art

[0002] The structures of 7-bromo-5,6-bis(benzyloxy)benzopyrrole, 5,5',6,6'-tetrahydroxy-7,7'-benzopyrrole dimer (7,7'-dimer) and 5,5',6,6'-tetrahydroxy-2,7'-benzopyrrole dimer (2,7'-dimer) are shown below:

[0003]

[0004] 5,6-Dihydroxybenzopyrrole can quickly oxidize and polymerize in vivo or in a weakly alkaline environment to form complex dark macromolecular melanin. Melanin, a naturally occurring pigment, has very unique physical and chemical properties, such as wide-band UV-visible absorption, strong antioxidant properties, antibacterial properties, free radical scavenging ability, conductivity, and biocompatibility. These properties make it have great application potential in many fields [Paulin JV, Batagin-Neto A, Naydenov B, et al. High-field / high-frequency EPR spectroscopy on synthetic melanin: On the origin of carbon-centered radicals [J]. Materials Advances, 2021, 2 (19): 6297-6305.].

[0005] 7,7'-dimer and 2,7'-dimer are dimer forms formed during the self-polymerization of 5,6-dihydroxybenzopyrrole. The self-assembly process of 5,6-dihydroxybenzopyrrole polymerization is extremely complex, and the product uniformity is low. This is a bottleneck for its application in some important fields. Self-polymerization using specific dimers as starting materials is expected to greatly improve its uniformity during polymerization. However, it is very difficult to obtain high-purity, specific, and uniform dimers by separating the mixture of self-polymerization reactions. Therefore, it is of great significance to establish a method for efficiently obtaining 7,7'-dimer and 2,7'-dimer.

[0006] Christina LLChai et al. reported the synthesis of 7-bromo-5,6-dimethoxybenzopyrrole in 2008 [Huleatt PB, Choo SS, Chua S, et al. Expedient routes to valuable bromo-5,6-dimethoxyindole building blocks [J]. Tetrahedron Letters, 2008, 49 (36): 5309-5311.]. 2-methoxy-5-nitrophenol was used as the starting material, and the phenolic hydroxyl group was protected by methyl after bromination, and then subjected to the Bartoli reaction with vinyl magnesium bromide to obtain 7-bromo-5,6-dimethoxybenzopyrrole. The reaction process is as follows:

[0007]

[0008] In the same year, it was reported that 7-bromo-5,6-dimethoxybenzopyrrole undergoes Suzuki-Miyaura reaction to self-couple to generate 5,5',6,6'-tetramethoxy-7,7'-benzopyrrole dimer [Duong HA, Chua S, Huleatt PB, et al. Synthesis of biindolyls via palladium-catalyzed reactions [J]. The Journal of Organic Chemistry, 2008, 73 (22): 9177-9180.]. The reaction flow is as follows:

[0009]

[0010] Although Christina LLChai et al. have established a synthetic method for synthesizing 5,5',6,6'-tetramethoxy-7,7'-benzopyrrole dimer. However, the demethylation operation of 5,5',6,6'-tetramethoxy-7,7'-benzopyrrole dimer is a very difficult problem. 5,5',6,6'-tetramethoxy-7,7'-benzopyrrole dimer needs to be treated with a large excess of boron tribromide to completely remove the four methyl groups, and 7,7'-dimer is very unstable during the subsequent boron tribromide quenching, post-treatment and purification process. Therefore, it is difficult to scale up the production of 7,7'-dimer on an industrial scale.

[0011] Marco d'Ischia et al. reported the synthesis of hydroxyl fully acetylated 2,7'-dimer in 2009 [Capelli L, Manini P, Pezzella A, et al. Efficient synthesis of 5,6-dihydroxyindoledimers, key eumelanin building blocks, by a unified o-ethynylaniline-based strategy for the construction of 2-linked biindolyl scaffolds [J]. The Journal of Organic Chemistry, 2009, 74 (18): 7191-7194.]. The synthesis process comprises: 1) using 4-nitrocatechol as a starting material, and using acetic anhydride and pyridine system to protect the phenolic hydroxyl group to obtain compound 1; 2) compound 1 is subjected to 20 atmospheres of hydrogen and palladium carbon conditions to reduce the nitro group to obtain compound 2; 3) compound 2 is subjected to diiodine substitution through sodium iodide, sodium chlorite and hydrochloric acid system to obtain compound 3; 4) compound 3 is subjected to Sonogashira coupling with trimethylsilyl acetylene to obtain compound 4; 5) compound 4 is subjected to potassium fluoride to remove trimethylsilyl group to obtain compound 5; 6) compound 5 is subjected to ring closure under the condition of cuprous iodide and toluene reflux to obtain compound 6 (7-iodo-5,6-dimethoxybenzopyrrole); 7) compound 4 is subjected to zinc powder and acetic acid conditions to deiodinate to obtain compound 7; 8) compound 7 is subjected to potassium fluoride to remove trimethylsilyl group to obtain compound 8; 9) compound 8 is subjected to Sonogashira coupling with compound 6 to obtain compound 9; 10) compound 9 is subjected to ring closure under the condition of aluminum trichloride and toluene reflux to obtain compound 10. The reaction process is as follows:

[0012]

[0013] Although Marcod's method achieves the synthesis of acetyl-protected 2,7'-dimer, this synthetic route has the following shortcomings: 1) the synthesis steps are long and the operation is cumbersome, 2) the yields of reactions such as the iodination reaction of 4-amino-1,2-benzenediacetate and the ring closure of alkynes and amino groups are low, and 3) the removal of the acetyl group requires alkaline conditions, which can easily lead to instability of the final product 2,7'-dimer. Summary of the invention

[0014] In view of the shortcomings of the current synthesis methods of 7,7'-dimer and 2,7'-dimer, the purpose of the present invention is to develop a low-cost, simple and efficient method for preparing 7,7'-dimer and 2,7'-dimer.

[0015] Based on this, the present invention provides a method for efficiently synthesizing 7-bromo-5,6-bis(benzyloxy)benzopyrrole and using it as an important intermediate to synthesize 7,7'-dimer and 2,7'-dimer.

[0016] The synthesis method of 7-bromo-5,6-bis(benzyloxy)benzopyrrole provided by the present invention comprises the following steps:

[0017] 1) Using 2-methoxy-5-nitrophenol as a starting material, a bromination reaction is carried out by using N-bromosuccinimide (NBS) to obtain compound A;

[0018] 2) demethylating the compound A obtained in step 1) under the action of boron tribromide to obtain compound B;

[0019] 3) performing benzyl protection on the two phenolic hydroxyl groups of the compound B obtained in step 2) to obtain compound C;

[0020] 4) subjecting the compound C obtained in step 3) to a Bartoli reaction under the action of vinylmagnesium bromide to obtain the target compound 7-bromo-5,6-bis(benzyloxy)benzopyrrole;

[0021]

[0022] In step 1) of the above method, the bromination reaction is carried out in the presence of NBS, and the molar ratio of the 2-methoxy-5-nitrophenol to NBS can be 1:1.

[0023] In step 1) of the above method, the bromination reaction is carried out in a solvent, and the solvent may be dichloromethane (DCM).

[0024] The conditions of the bromination reaction are: the reaction temperature is 25° C. to 35° C. at room temperature, and the reaction time is 1 to 3 hours.

[0025] In step 2) of the above method, the demethylation reaction is carried out in the presence of boron tribromide, and the molar ratio of compound A to boron tribromide can be 1:2.

[0026] In step 2) of the above method, the demethylation reaction is carried out in a solvent, and the solvent may be dichloromethane (DCM).

[0027] In step 2) of the above method, the reaction conditions of the demethylation reaction are: carried out under the protection of inert gas nitrogen (or argon), the reaction temperature is naturally increased from -25°C to 25°C room temperature and maintained, and the reaction time is 1 to 3 hours.

[0028] In step 3) of the above method, the benzyl protection of the phenolic hydroxyl group is carried out under alkaline conditions, and the alkaline conditions can be provided by a base such as potassium carbonate, cesium carbonate, sodium carbonate, etc.

[0029] In step 3) of the above method, the protecting group reagent used for protecting the phenolic hydroxyl group can be selected from at least one of the following: benzyl bromide (BnBr), allyl bromide (Allyl bromide), p-methoxybenzyl chloride (PMBCl) or other ether protecting group reagents.

[0030] When benzyl bromide (BnBr) is used as the protecting group reagent, the molar ratio of the compound B to benzyl bromide is 1:3.

[0031] In step 3) of the above method, the benzyl protection of the phenolic hydroxyl group is carried out in a solvent, and the solvent may be acetone or N,N-dimethylformamide.

[0032] In step 3) of the above method, the benzyl protection of the phenolic hydroxyl group is carried out under heating reflux conditions at 60° C. to 80° C., and the reaction time is 0.5 to 2 hours.

[0033] In step 4) of the above method, the Bartoli reaction is carried out in the presence of vinyl magnesium bromide, and the molar ratio of the compound C to vinyl magnesium bromide is 1:3.

[0034] In step 4) of the above method, the Bartoli reaction is carried out in a solvent, and the solvent may be tetrahydrofuran;

[0035] In step 4) of the above method, the Bartoli reaction is carried out under the protection of an inert gas, nitrogen (or argon), at a reaction temperature of -25°C and a reaction time of 1 to 3 hours.

[0036] Another object of the present invention is to provide a method for synthesizing 7,7'-dimer.

[0037] The synthesis method of 7,7'-dimer provided by the present invention is to obtain 7-bromo-5,6-bis(benzyloxy)benzopyrrole as an intermediate through a two-step reaction, which specifically comprises the following steps (reaction flow chart as shown in Figure 3 shown):

[0038] a) allowing 7-bromo-5,6-bis(benzyloxy)benzopyrrole to undergo Suzuki-Miyaura coupling reaction under the action of bis-pinacol borate, tris(dibenzylideneacetone)dipalladium and 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl to generate compound D;

[0039] b) removing the benzyl group from the compound D obtained in step a) to obtain the target product 7,7'-dimer.

[0040]

[0041] In step a) of the above method, the Suzuki-Miyaura coupling reaction needs to be carried out under alkaline conditions, the alkaline conditions can be provided by potassium phosphate, and the molar ratio of 7-bromo-5,6-bis(benzyloxy)benzopyrrole to potassium phosphate can be 1:4;

[0042] In step a) of the above method, the Suzuki-Miyaura coupling reaction is carried out in the presence of bis-pinacol borate, tris[dibenzylideneacetone]dipalladium and 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl, and the molar ratio of the compound 7-bromo-5,6-bis(benzyloxy)benzopyrrole to bis-pinacol borate, tris[dibenzylideneacetone]dipalladium and 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl is 1:0.55:0.1:0.4 respectively;

[0043] In step a) of the above method, the Suzuki-Miyaura coupling reaction is carried out in a solvent, and the solvent is a mixed solvent of dioxane and water, wherein the volume ratio of dioxane to water can be 15:1 to 4:1;

[0044] In step a) of the above method, the Suzuki-Miyaura coupling reaction is carried out under the protection of an inert gas, and the inert gas may be nitrogen or argon; the reaction temperature of the Suzuki-Miyaura coupling reaction may be 90° C. to 110° C., and the reaction time may be 0.5 to 2 hours;

[0045] In step b) of the above method, the removal of the benzyl group is carried out in a hydrogen atmosphere with a hydrogen pressure of 15 psi.

[0046] In step b) of the above method, the hydrogenolysis of the benzyl group can be carried out in the presence of at least one of the following catalysts: palladium carbon, Raney Ni, platinum carbon, palladium dichloride and palladium hydroxide;

[0047] When palladium carbon (specifically, wet palladium carbon with a palladium content of 5%) is used as a catalyst, the molar ratio of the compound D to palladium carbon may be 1:0.05;

[0048] In step b) of the above method, the removal of the benzyl group is carried out in a solvent, and the solvent may be a mixed solvent of ethyl acetate and ethanol, wherein the volume ratio of ethyl acetate to ethanol may be 10:1 to 2:1;

[0049] In step b) of the above method, the removal of the benzyl group is carried out under weakly acidic conditions, and the weakly acidic conditions can be provided by acetic acid or dilute hydrochloric acid;

[0050] In step b) of the above method, the reaction temperature for removing the benzyl group is 25° C. to 35° C., and the reaction time is 1 to 8 hours.

[0051] Another object of the present invention is to provide a method for synthesizing 2,7'-dimer.

[0052] The synthesis method of 2,7'-dimer provided by the present invention is to obtain 7-bromo-5,6-bis(benzyloxy)benzopyrrole as an intermediate through a five-step reaction, which specifically comprises the following steps (reaction flow chart as shown in FIG. Figure 4 shown):

[0053] A) allowing the compound 7-bromo-5,6-bis(benzyloxy)benzopyrrole to undergo Sonogashira coupling with trimethylsilyl acetylene to obtain compound 1;

[0054] B) removing the trimethylsilyl group from the compound 1 obtained in step A) under the action of tetrabutylammonium fluoride to obtain compound 2;

[0055] C) subjecting the compound 2 obtained in step B) to Sonogashira coupling with compound III to obtain compound 4;

[0056] D) Compound 4 obtained in step C) is first reacted with pyrrolidine, and then subjected to nitro reduction and intramolecular ring closure under the action of zinc powder and ferrous chloride to obtain compound 5.

[0057] E) debenzylating the compound 5 obtained in step D) under the action of hydrogen and palladium on carbon to obtain the final product 2,7'-dimer.

[0058]

[0059] In step A) of the above method, the Sonogashira coupling is carried out in the presence of cuprous iodide and bistriphenylphosphine palladium dichloride, and the molar ratios of the 7-bromo-5,6-bis(benzyloxy)benzopyrrole to trimethylsilyl acetylene, cuprous iodide, and bistriphenylphosphine palladium dichloride are 1:1.5:0.2:0.1, respectively;

[0060] In step A) of the above method, the Sonogashira coupling is carried out under alkaline conditions, and the alkaline conditions can be provided by triethylamine;

[0061] In step A) of the above method, the Sonogashira coupling is carried out in a solvent, which may be toluene;

[0062] In step A) of the above method, the reaction conditions of the Sonogashira coupling are: carried out under the protection of inert gas nitrogen, the reaction temperature is 50° C., and the reaction time is 0.5 to 3 hours.

[0063] In step B) of the above method, the detrimethylsilylation of compound 1 is carried out in the presence of tetrabutylammonium fluoride, and the molar ratio of compound 2 to tetrabutylammonium fluoride is 1:2;

[0064] In step B) of the above method, the detrimethylsilylation of compound 1 is carried out in a solvent, and the solvent may be tetrahydrofuran;

[0065] In step B) of the above method, the reaction temperature for detrimethylsilylation of compound 1 may be 25° C., and the reaction time may be 0.5 to 2 hours.

[0066] In step C) of the above method, the Sonogashira coupling is carried out in the presence of cuprous iodide and bistriphenylphosphine palladium dichloride, and the molar ratios of compound 2 to compound III, cuprous iodide and bistriphenylphosphine palladium dichloride are 1:1.2:0.2:0.1, respectively;)

[0067] In step C) of the above method, the Sonogashira coupling is carried out under alkaline conditions, and the alkaline conditions can be provided by triethylamine;

[0068] In step C) of the above method, the Sonogashira coupling is carried out in a solvent, and the solvent may be toluene;

[0069] In step C) of the above method, the reaction conditions of the Sonogashira coupling are: carried out under the protection of an inert gas, nitrogen (or argon), at a reaction temperature of 80° C. and a reaction time of 0.5 to 3 hours.

[0070] In step D) of the above method, the molar ratio of compound 4 to pyrrolidine may be 1:20;

[0071] In step D) of the above method, the reaction temperature of the compound 4 and pyrrolidine may be 80° C., and the reaction time may be 0.5 to 2 hours;

[0072] In step D) of the above method, the nitro reduction and intramolecular ring closure can be carried out in the presence of zinc powder (or iron powder) and ferrous chloride, and the solvent is ethanol;

[0073] In step D) of the above method, the reaction conditions for the nitro reduction and intramolecular ring closure are: carried out under the protection of inert gas nitrogen (or argon), the reaction temperature is 85° C., and the reaction time is 0.5 to 2 hours.

[0074] In step E) of the above method, the reduction of the benzyl group can be carried out in the presence of at least one of the following catalysts: palladium carbon, Raney Ni, platinum carbon, palladium dichloride and palladium hydroxide.

[0075] When palladium carbon is used as a catalyst, the molar ratio of the compound 5 to palladium carbon can be 1:0.05.

[0076] In step E) of the above method, the removal of the benzyl group is carried out in a hydrogen atmosphere, and the pressure of the hydrogen is 15 psi;

[0077] In step E) of the above method, the removal of the benzyl group is carried out in a solvent, which is a mixed solvent of ethyl acetate and ethanol, wherein the volume ratio of ethyl acetate to ethanol can be 10:1 to 2:1;

[0078] In step E) of the above method, the removal of the benzyl group is carried out under weakly acidic conditions, and the weakly acidic conditions can be provided by acetic acid; or by dilute hydrochloric acid.

[0079] In step E) of the above method, the reaction temperature for removing the benzyl group may be 25° C. to 35° C., and the reaction time may be 1 to 8 hours.

[0080] The self-oxidative polymerization of 5,6-dihydroxybenzopyrrole is a very important form of melanin formation [d'IschiaM, NapolitanoA, PezzellaA.5,6-Dihydroxyindole chemistry:unexploredopportunities beyond eumelanin[J].EuropeanJournalofOrganicChemistry,2011,2011(28):5501-5516.]. However, the polymerization process has the problems of slow reaction speed, complex self-assembly process and poor product uniformity. Using a single dimer as the starting material can improve the above problems to a great extent. However, due to the active nature of this type of compound, it is very easy to undergo oxidative polymerization under alkaline conditions, and it has been difficult to prepare stably so far.

[0081] The inventors of the present invention have established a method for efficiently synthesizing 7-bromo-5,6-bis(benzyloxy)benzopyrrole through repeated exploration and using it as an important intermediate to synthesize 7,7'-dimer and 2,7'-dimer.

[0082] The present invention has the following beneficial effects:

[0083] 1) The present invention uses 2-methoxy-5-nitrophenol as a starting material, which is cheap and readily available;

[0084] 2) The process is short, and the final product is easy to separate and purify and to store stably;

[0085] 3) The synthesis and preparation of 7,7'-dimer is reported for the first time, and has the advantages of cheap and readily available raw materials, fewer steps, and easy purification and stable storage of the final product;

[0086] 4) The synthetic route of 2,7'-dimer has great advantages over the methods previously reported in the literature in terms of synthetic steps, overall yield and separation and purification of the final product. BRIEF DESCRIPTION OF THE DRAWINGS

[0087] Figure 1 The structures of 7-bromo-5,6-bis(benzyloxy)benzopyrrole, 7,7'-dimer and 2,7'-dimer are shown;

[0088] Figure 2 The synthetic flow chart of 7-bromo-5,6-bis(benzyloxy)benzopyrrole provided by the present invention;

[0089] Figure 3 The synthetic flow chart of 7,7'-dimer provided by the present invention;

[0090] Figure 4 The synthetic flow chart of 2,7'-dimer provided by the present invention;

[0091] Figure 5 is the hydrogen nuclear magnetic resonance spectrum of 2-bromo-6-methoxy-3-nitrophenol (Compound A);

[0092] Figure 6 is the hydrogen nuclear magnetic resonance spectrum of 3,4-bis(benzyloxy)-2-bromo-nitrobenzene (compound C);

[0093] Figure 7 is the carbon NMR spectrum of 3,4-bis(benzyloxy)-2-bromo-nitrobenzene (Compound C);

[0094] Figure 8 is the hydrogen nuclear magnetic resonance spectrum of 7-bromo-5,6-bis(benzyloxy)benzopyrrole;

[0095] Fig. 9 The carbon NMR spectrum of 7-bromo-5,6-bis(benzyloxy)benzopyrrole

[0096] Fig.10 LCMS chart of 7-bromo-5,6-bis(benzyloxy)benzopyrrole;

[0097] Fig.11 is the hydrogen nuclear magnetic resonance spectrum of 5,5',6,6'-tetrakis(benzyloxy)-7,7'-benzopyrrole dimer (Compound D);

[0098] Fig.12is the carbon NMR spectrum of 5,5',6,6'-tetrakis(benzyloxy)-7,7'-benzopyrrole dimer (Compound D);

[0099] Fig.13 LCMS chart of 5,5',6,6'-tetrakis(benzyloxy)-7,7'-benzopyrrole dimer (Compound D);

[0100] Fig.14 is the H NMR spectrum of compound 7,7'-dimer;

[0101] Fig.15 is the carbon NMR spectrum of compound 7,7'-dimer;

[0102] Fig.16 is the LCMS chart of compound 7,7'-dimer;

[0103] Fig.17 is the hydrogen nuclear magnetic resonance spectrum of 1,2-bis(benzyloxy)benzene (Compound I);

[0104] Fig.18 is the hydrogen nuclear magnetic resonance spectrum of 2-nitro-4,5-bis(benzyloxy)iodobenzene (Compound III);

[0105] Fig.19 is the carbon NMR spectrum of 2-nitro-4,5-bis(benzyloxy)iodobenzene (Compound III);

[0106] Fig. 20 is the hydrogen nuclear magnetic resonance spectrum of 5,6-bis(benzyloxy)-7-((trimethylsilyl)ethynyl)-benzopyrrole (Compound 1);

[0107] Fig.21 is the carbon NMR spectrum of 5,6-bis(benzyloxy)-7-((trimethylsilyl)ethynyl)-benzopyrrole (Compound 1);

[0108] Fig. 22 LCMS chart of 5,6-bis(benzyloxy)-7-ethynyl-benzopyrrole (Compound 2);

[0109] Fig.23 The H NMR spectrum of 5,6-bis(benzyloxy)-7-((4,5-bis(benzyloxy)-2-nitrophenyl)ethynyl)benzopyrrole (Compound 4);

[0110] Fig.24 The carbon NMR spectrum of 5,6-bis(benzyloxy)-7-((4,5-bis(benzyloxy)-2-nitrophenyl)ethynyl)benzopyrrole (Compound 4);

[0111] Fig.25LCMS chart of 5,6-bis(benzyloxy)-7-((4,5-bis(benzyloxy)-2-nitrophenyl)ethynyl)benzopyrrole (Compound 4);

[0112] Fig.26 is the H NMR spectrum of 5,5',6,6'-tetrakis(benzyloxy)-2,7'-bisbenzopyrrole (Compound 5);

[0113] Fig. 27 The carbon NMR spectrum of 5,5',6,6'-tetrakis(benzyloxy)-2,7'-bisbenzopyrrole (Compound 5);

[0114] Fig.28 LCMS chart of 5,5',6,6'-tetrakis(benzyloxy)-2,7'-bisbenzopyrrole (Compound 5);

[0115] Fig.29 is the hydrogen nuclear magnetic resonance spectrum of compound 2,7'-dimer;

[0116] Fig.30 is the carbon NMR spectrum of compound 2,7'-dimer;

[0117] Fig.31 is the H-HCOSY spectrum of compound 2,7'-dimer;

[0118] Fig.32 is the HSQC spectrum of compound 2,7'-dimer;

[0119] Fig.33 is the HMBC spectrum of compound 2,7'-dimer;

[0120] Fig.34 This is the LCMS chart of compound 2,7'-dimer. DETAILED DESCRIPTION

[0121] The present invention is further described below in conjunction with specific examples, but the present invention is not limited to the following examples. The methods described are conventional methods unless otherwise specified. The raw materials described can be obtained from public commercial channels unless otherwise specified.

[0122] Example 1. Preparation of 2-bromo-6-methoxy-3-nitrophenol (Compound A)

[0123]

[0124] Weigh 2-methoxy-5-nitrophenol (60g, 354.7mmol) and dissolve in dichloromethane (300mL), slowly add N-bromosuccinimide (63g, 354.7mmol) in batches. The reaction system reacts for 3 hours at 25°C room temperature, and the TLC spot plate detection reaction is good. Add dichloromethane (300mL) to dilute the reaction system, then use water (300mL X3), saturated brine (200mL) to wash, anhydrous sodium sulfate drying, filter and decompress and spin-dry. The obtained crude product is first preliminarily purified using a silica gel column, and then pure crystallization operation is performed using ethyl acetate and petroleum ether to obtain a light yellow solid compound A (38g, yield 43.2%). 1 H NMR (500 MHz, DMSO-d6) δ 10.39 (s, 1H), 7.55 (d, J = 8.9 Hz, 1H), 7.13 (d, J = 9.0 Hz, 1H), 3.93 (s, 3H). The H NMR spectrum of 2-bromo-6-methoxy-3-nitrophenol (Compound A) is shown in Figure 5 shown.

[0125] Example 2, Preparation of 3-bromo-4-nitro-1,2-diphenol (Compound B)

[0126]

[0127] Weigh compound A (37g, 149.2mmol) and dissolve in anhydrous dichloromethane (200mL), slowly drip boron tribromide (2M dichloromethane solution, 149.2mL) into the system under -25℃ nitrogen protection, then naturally raise the temperature to 25℃ room temperature.React for 2 hours at 25℃, TLC spot plate monitoring, raw material disappears, and the reaction is good.Cryogenic decompression removes most of boron tribromide, then adds dichloromethane (400mL), and slowly pours the system into an ice-water bath (200mL).The organic phase is washed with water (200mL X 3) and saturated brine (100mL) in turn, dried over anhydrous sodium sulfate, filtered and spin-dried to obtain 33g crude product.The crude product is directly used in the next step reaction.

[0128] Example 3. Preparation of 3,4-bis(benzyloxy)-2-bromo-nitrobenzene (Compound C)

[0129]

[0130] Weigh compound B (33 g, 141.0 mmol) and dissolve it in acetone (160 mL), then add potassium carbonate (78 g, 564.1 mmol) and benzyl bromide (72.4 g, 423.1 mmol). Reflux at 60 ° C for 1 hour. TLC spot plate monitoring, the reaction is good. Add methanol (30 mL) and continue stirring for 10 minutes. After filtering, the filtrate is directly purified by silica gel column by spin drying, and methanol is used for recrystallization. White solid compound C (35 g, two-step reaction yield 56.6%) is obtained. 1 H NMR (500MHz, DMSO-d6) δ7.89(d,J=9.1Hz,1H),7.56-7.49(m,2H),7.42(ddt,J=11.4,9.0,4.4Hz,6H),7.36-7.30(m,3H),5.33(s,2H),5.02(s,2H). 13 C NMR (126 MHz, DMSO-d6) δ 156.28, 146.00, 143.61, 136.68, 136.17, 129.04, 129.01, 128.82, 128.78, 128.72, 128.50, 122.80, 113.31, 111.62, 74.77, 71.37. The hydrogen nuclear magnetic resonance spectrum of 3,4-bis(benzyloxy)-2-bromo-nitrobenzene (Compound C) is as follows Figure 6 As shown, the carbon NMR spectrum is Figure 7 shown.

[0131] Example 4. Preparation of 7-bromo-5,6-bis(benzyloxy)benzopyrrole

[0132]

[0133] Weigh compound C (17 g, 41.0 mmol) and dissolve it in tetrahydrofuran (100 mL). Slowly add vinylmagnesium bromide (123 mL, 1 M tetrahydrofuran solution) under nitrogen protection at -25 ° C. The system reacts at -25 ° C for 2 hours. TLC spot plate monitoring shows a good reaction. Add saturated ammonium chloride solution (50 ml) to quench the reaction. Add ethyl acetate (600 mL) to dilute the reaction solution, wash with water (300 mL X 3) and saturated brine (200 mL) in turn, dry with anhydrous sodium sulfate, filter and spin dry, and purify with a silica gel column. A light yellow semi-solid compound 7-bromo-5,6-bis(benzyloxy)benzopyrrole (7.6 g, yield 45.4%) is obtained. 1H NMR(500MHz,DMSO-d6)δ11.08(s,1H),7.51(d,J=7.2Hz,2H),7.49-7.45(m,2H),7.40(dd,J=8.2,6.6Hz,2H) ,7.35(dd,J=7.9,2.5Hz,4H),7.30(d,J=3.4Hz,2H),6.46(dd,J=3.0,1.8Hz,1H),5.17(s,2H),4.98(s,2H). 13 C NMR(126MHz,DMSO-d6)δ147.35,141.90,137.76,137.68,130.05,128.84,128.82,128.64,128.42,128.26,128 .14,126.85,126.81,124.39,104.55,104.51,102.70,102.64,100.10,75.09,71.35.LC-MS(m / z)=408.03(M+H + ). The H NMR spectrum of 7-bromo-5,6-bis(benzyloxy)benzopyrrole is as follows Figure 8 As shown, the carbon NMR spectrum is Fig. 9 As shown, LC-MS Fig.10 shown.

[0134] Example 5. Preparation of 5,5',6,6'-tetrakis(benzyloxy)-7,7'-benzopyrrole dimer (Compound D)

[0135]

[0136] Weigh the compound 7-bromo-5,6-bis(benzyloxy)benzopyrrole (6 g, 14.7 mmol) and dissolve it in a mixed solvent of dioxane (120 mL) and water (12 mL). Add diboric acid pinacol ester (2.05 g, 8.08 mmol), tris[dibenzylideneacetone]dipalladium (1.35 g, 1.47 mmol), 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl (2.8 g, 5.88 mmol), and potassium phosphate (12.5 g, 58.8 mmol) in sequence under nitrogen protection. The reaction mixture was reacted at 100°C for 1 hour, and the reaction was well monitored by TLC spot plate. Ethyl acetate (300 mL) was added to dilute the reaction solution, and it was washed with water (150 mL X 3) and saturated brine (100 mL) in sequence, dried over anhydrous sodium sulfate, filtered and dried, and then purified by silica gel column. An off-white solid compound D (2.7 g, yield 56.0%) was obtained. 1H NMR(500MHz,DMSO-d6)δ10.37(t,J=2.3Hz,2H),7.58-7.49(m,4H),7.46-7.37(m,6H),7.37-7.30(m,2H),7.18-7.10 (m,4H),7.06(t,J=7.5Hz,4H),6.76-6.65(m,4H),6.44(dd,J=3.0,1.9Hz,2H),5.29-5.17(m,4H),4.82-4.65(m,4H). 13 C NMR (126MHz, DMSO-d6) δ147.28,143.55,138.34,130.72,128.79,128.78,128.24,128.06,128.04,127 .88,127.86,127.75,125.87,123.90,113.12,104.93,101.42,74.89,71.34.LC-MS(m / z)=657.28(M+H + ). The H NMR spectrum of 5,5',6,6'-tetra(benzyloxy)-7,7'-benzopyrrole dimer (Compound D) is as follows Fig.11 As shown, the carbon NMR spectrum is Fig.12 As shown, LC-MS Fig.13 shown.

[0137] Example 6. Preparation of 5,5',6,6'-tetrahydroxy-7,7'-benzopyrrole dimer (7,7'-dimer)

[0138]

[0139] Weigh compound D (2.7 g, 4.11 mmol) and dissolve it in a mixed solvent of ethyl acetate (40 mL) and ethanol (10 mL). Add palladium carbon (875 mg, palladium content 5%) and acetic acid (~50 mg) under hydrogen environment. React for 3 hours at room temperature and 15 psi in a hydrogen environment. LCMS monitoring shows a good reaction. Filter using diatomaceous earth and mercapto silica gel, dry under reduced pressure in the dark, and recrystallize using methyl tert-butyl ether and petroleum ether to obtain an off-white solid 7,7'-dimer (1.1 g, yield 90.3%). 1 H NMR (500MHz, DMSO-d6) δ9.51 (s, 2H), 8.72 (s, 2H), 7.47 (s, 2H), 6.94 (s, 2H), 6.87 (t, J = 2.8Hz, 2H), 6.19 (dd, J = 3.0, 1.9Hz, 2H). 13C NMR(126MHz,DMSO-d6)δ140.74,140.62,130.01,123.30,120.19,105.52,104.01,100.56.LC-MS(m / z)=297.09(M+H + ). The H NMR spectrum of 5,5',6,6'-tetrahydroxy-7,7'-benzopyrrole dimer (7,7'-dimer) is as follows Fig.14 As shown, the carbon NMR spectrum is Fig.15 As shown, LC-MS Fig.16 shown.

[0140] Example 7. Preparation of 1,2-bis(benzyloxy)benzene (Compound I)

[0141]

[0142] Weigh catechol (10 g, 90.8 mmol) and dissolve it in DMF (100 mL), and add potassium carbonate (50.2 g, 363 mmol) and benzyl bromide (46 g, 272 mmol) in sequence. React at 80 ° C for 12 h under nitrogen protection. TLC spot plate monitoring shows a good reaction. Add methanol (20 mL) to quench the remaining benzyl bromide. Cool to room temperature, add 500 mL of ethyl acetate to dilute the reaction solution, wash with water (300 mLX 3) and saturated brine in sequence, dry with anhydrous sodium sulfate, filter and spin dry. Use ethanol (60 mL) for recrystallization to obtain white solid 1,2-bis(benzyloxy)benzene (22 g, yield 83%). 1 H NMR (500 MHz, DMSO-d6) δ7.48-7.41 (m, 4H), 7.40-7.34 (m, 4H), 7.34-7.27 (m, 2H), 7.05 (dd, J = 6.0, 3.6 Hz, 2H), 6.87 (dd, J = 6.0, 3.6 Hz, 2H), 5.11 (s, 4H). The hydrogen nuclear magnetic resonance spectrum of 1,2-bis(benzyloxy)benzene (Compound I) is as follows Fig.17 shown.

[0143] Example 8. Preparation of 4-iodo-1,2-bis(benzyloxy)benzene (Compound II)

[0144]

[0145] Weigh catechol (10 g, 34.4 mmol) and dissolve it in a mixed solvent of dichloromethane (70 mL) and ethanol (70 mL), and add silver sulfate (10.5 g, 51.7 mmol) and iodine (5.3 g, 20.7 mmol) in sequence. Stir the reaction at room temperature for 2 hours. TLC spot plate monitoring shows a good reaction. Filter through diatomaceous earth, and the filtrate is spin-dried to obtain a crude product (14 g). The next step of the reaction is carried out directly without further purification.

[0146] Example 9. Preparation of 2-nitro-4,5-bis(benzyloxy)iodobenzene (Compound III)

[0147]

[0148] Weigh 4-iodo-1,2-bis(benzyloxy)benzene (10 g, 24.0 mmol) and dissolve it in a mixed solution of acetic acid (50 mL) and water (5 mL), and slowly add 70% nitric acid (15.3 mL, 240 mmol). Stir the reaction at 40°C for 2 hours. TLC spot plate monitoring shows a good reaction. Add water (100 mL) and a large amount of yellow solid will precipitate. Collect the yellow solid by filtration and use ethanol for recrystallization to obtain a yellow solid (8.5 g, yield 77%). 1 H NMR (500MHz, DMSO-d6) δ7.73 (d, J = 1.7Hz, 1H), 7.64 (d, J = 1.7Hz, 1H), 7.46-7.24 (m, 10H), 5.24 (s, 2H), 5.19 (s, 2H). 13 C NMR (126MHz, DMSO-d6) δ152.30, 148.24, 145.84, 136.52, 136.41, 128.95, 128.92, 128.59, 128.53, 128.08, 128.07, 124.92, 111.53, 79.64, 71.02, 70.86. The hydrogen nuclear magnetic resonance spectrum of 2-nitro-4,5-bis(benzyloxy)iodobenzene (Compound III) is as follows Fig.18 As shown, the carbon NMR spectrum is Fig.19 shown.

[0149] Example 10. Preparation of 5,6-bis(benzyloxy)-7-((trimethylsilyl)ethynyl)-benzopyrrole (Compound 1)

[0150]

[0151] Weigh 7-bromo-5,6-bis(benzyloxy)benzopyrrole (4g, 9.8mmol) and dissolve it in toluene (50mL). Add bistriphenylphosphine palladium dichloride (688mg, 980umol), cuprous iodide (373mg, 1.96mmol), triethylamine (4.96g, 49.0mmol) and trimethylsilyl acetylene (1.92g, 19.6mmol) in sequence under nitrogen protection. Stir the reaction at 50°C for 2 hours. TLC spot plate monitoring shows good reaction. Add ethyl acetate (200mL) to dilute the reaction solution, wash with water (100mLX 3) and saturated brine (60mL) in sequence, and dry over anhydrous sodium sulfate. Filter and spin dry, then purify using a silica gel column to obtain a colorless oily product (2.48g, yield 59%). 1 H NMR(500MHz,DMSO-d6)δ10.89(s,1H),7.57-7.45(m,4H),7.38(dd,J=8.3,6.7Hz,2H),7.36-7.29( m,5H),7.26(t,J=2.8Hz,1H),6.38(dd,J=3.1,1.8Hz,1H),5.13(s,2H),5.04(s,2H),0.27(s,9H). 13 C NMR (126MHz, DMSO-d6) δ147.02, 146.44, 138.04, 137.93, 131.50, 128.81, 128.64, 128.53, 128.30, 128.18, 128.06, 126.39, 123.65, 107.40, 102.31, 102.25, 101.15, 98.72, 75.47, 71.37, 0.46.5, the nuclear magnetic resonance hydrogen spectrum of 6-bis(benzyloxy)-7-((trimethylsilyl)ethynyl)-benzopyrrole (Compound 1) is as follows Fig. 20 As shown, the carbon NMR spectrum is Fig.21 shown.

[0152] Example 11. Preparation of 5,6-bis(benzyloxy)-7-ethynyl-benzopyrrole (Compound 2)

[0153]

[0154] Weigh 5,6-bis(benzyloxy)-7-((trimethylsilyl)ethynyl)-benzopyrrole (2.2 g, 5.17 mmol) and dissolve it in tetrahydrofuran (30 mL). Slowly add 1 mol / L tetrabutylammonium fluoride solution in tetrahydrofuran (10 mL, 10.3 mmol). Stir at room temperature for 1 hour. LCMS monitoring showed a good reaction. The crude product (2.3 g) was obtained by spin drying and used directly in the next step. LC-MS (m / z) = 354.99 (M+H+ ). The LCMS of 5,6-bis(benzyloxy)-7-ethynyl-benzopyrrole (Compound 2) is as follows Fig. 22 shown.

[0155] Example 12: Preparation of 5,6-bis(benzyloxy)-7-((4,5-bis(benzyloxy)-2-nitrophenyl)ethynyl)benzopyrrole (Compound 4)

[0156]

[0157] Weigh 2-nitro-4,5-bis(benzyloxy)iodobenzene (2.35 g, 5.09 mmol) and dissolve it in toluene (20 mL). Add bistriphenylphosphine palladium dichloride (298 mg, 424 umol), cuprous iodide (162 mg, 849 umol), triethylamine (2.15 g, 21.2 mmol) and 5,6-bis(benzyloxy)-7-ethynyl-benzopyrrole (1.5 g, 4.24 mmol) in sequence under nitrogen protection. React at 80 ° C for 3 hours, TLC monitoring, the reaction is good. Add dichloromethane (200 mL) to dilute the reaction solution, wash with water (100 mLX 3) and saturated brine (60 mL) in sequence, and dry over anhydrous sodium sulfate. Filter and spin dry, then purify using a silica gel column to obtain an orange-red solid (1.9 g, yield 65%). 1 H NMR (500MHz, DMSO-d6) δ10.96 (t, J = 2.4Hz, 1H), 7.90 (s, 1H), 7.60 (s, 1H), 7.50-7.47 (m, 8H), 7.44-7. 30(m,11H),7.30-7.17(m,3H),6.50-6.33(m,1H),5.32(s,2H),5.31(s,2H),5.16(s,2H),5.15(s,2H). 13 C NMR(126MHz,DMSO-d6)δ152.63,148.45,146.66,146.56,142.39,138.03,137.82 ,136.56,136.36,131.56,129.03,128.97,128.83,128.80,128.71,128.58,128. 44,128.23,128.20,128.11,126.40,123.65,118.18,112.46,110.42,107.77,10 2.51,100.87,92.96,89.43,75.79,71.36,71.18,70.96.LC-MS(m / z)=687.22(M+H +The H NMR spectrum of 5,6-bis(benzyloxy)-7-((4,5-bis(benzyloxy)-2-nitrophenyl)ethynyl)benzopyrrole (Compound 4) is as follows Fig.23 As shown, the carbon NMR spectrum is Fig.24 As shown in LCMS Fig.25 shown.

[0158] Example 13, 5,5',6,6'-Tetrakis(benzyloxy)-2,7'-bisbenzopyrrole (Compound 5)

[0159]

[0160] Weigh 5,6-bis(benzyloxy)-7-((4,5-bis(benzyloxy)-2-nitrophenyl)ethynyl)benzopyrrole (1.5 g, 2.18 mmol) and dissolve it in acetonitrile (15 mL), and add pyrrolidine (3.1 g, 43.7 mmol). Reflux at 80°C for 30 minutes, and the solution changes from orange-red to bright crimson. TLC spot plate monitoring shows that all the raw materials have reacted, and the newly generated spots are slightly less polar than the raw materials. Directly decompress and spin dry to obtain a crimson residue. Add ethanol (150 mL) to dissolve the residue, and then add ferrous chloride (277 mg, 2.18 mmol) and zinc powder (1.43 g, 21.84 mmol) in sequence. React at 85°C under nitrogen protection for 1 h (or stop heating when the solution becomes clear). LCMS monitoring shows that the reaction is good. Filter through diatomaceous earth and spin dry. Purify on a silica gel column to obtain a white solid (1.07 g, yield 75%). 1 H NMR (500MHz, DMSO-d6) δ11.02(d,J=2.2Hz,1H),10.71(s,1H),7.54(dq,J=7.6,2.0Hz,6H),7.40(qd,J=6.8,3.0Hz,6H),7.37-7.32(m,3H) ,7.30(s,1H),7.27-7.20(m,3H),7.20-7.10(m,5H),6.70(d,J=2.1Hz,1H),6.43(t,J=2.4Hz,1H),5.20(s,4H),5.18(s,2H),4.76(s,2H). 13C NMR(126MHz,DMSO-d6)δ147.06,146.37,144.32,142.24,138.51,138.21,138 .17,137.90,131.96,130.52,129.15,128.79,128.76,128.41,128.13,128.0 8,128.03,128.01,127.90,126.37,124.24,122.10,112.24,105.98,104.79, 102.28,101.86,98.33,75.32,71.57,71.21,71.18.LC-MS(m / z)=657.24(M+H + ). The H NMR spectrum of 5,5',6,6'-tetrakis(benzyloxy)-2,7'-bisbenzopyrrole (Compound 5) is as follows Fig.26 As shown, the carbon NMR spectrum is Fig. 27 As shown in LCMS Fig.28 shown.

[0161] Example 14: Preparation of 5,5',6,6'-tetrahydroxy-2,7'-bisbenzopyrrole dimer (2,7'-dimer)

[0162]

[0163] Weigh 5,5',6,6'-tetra(benzyloxy)-2,7'-bisbenzopyrrole (900mg, 1.37mmol) and dissolve it in a mixed solvent of ethyl acetate (15mL) and ethanol (3mL), then add 5% wet palladium carbon (325mg) and 1 drop of acetic acid. Use hydrogen replacement three times and react in a hydrogen environment at 35°C for 3 hours. LCMS monitoring shows a good reaction. Filter through diatomaceous earth and mercapto silica gel and dry under reduced pressure. Use petroleum ether (8mL) and ethyl acetate (2mL) for pulping operation, pour off the supernatant after centrifugation, and dry under reduced pressure to obtain a brick red solid (335mg, yield is 82%). 1 HNMR(500MHz,DMSO-d6)δ10.44(s,1H),10.27(s,1H),8.43(brs,4H),7.06(t,J= 2.8Hz,1H),6.92(s,2H),6.91(s,1H),6.62(s,1H),6.26(dd,J=3.0,1.8Hz,1H). 13C NMR(126MHz,DMSO-d6)δ142.94,140.89,140.69,139.80,130.97,128.19,123.92,121 .33,120.86,104.69,104.50,104.07,101.21,100.56,97.83.LC-MS(m / z)=297.09(M+H + ).

[0164] The H NMR spectrum of 5,5',6,6'-tetrahydroxy-2,7'-bisbenzopyrrole dimer (2,7'-dimer) is as follows Fig.29 As shown, the carbon NMR spectrum is Fig.30 As shown, H-HCOSY Fig.31 As shown, HSQC Fig.32 As shown, HMBC Fig.33 As shown in LCMS Fig.34 shown.

Claims

1. A method for synthesizing 7-bromo-5,6-bis(benzyloxy)benzopyrrole, comprising the following steps: 1) Using 2-methoxy-5-nitrophenol as a starting material, a bromination reaction is carried out by using N-bromosuccinimide to obtain compound A; 2) demethylating the compound A obtained in step 1) under the action of boron tribromide to obtain compound B; 3) performing benzyl protection on the two phenolic hydroxyl groups of the compound B obtained in step 2) to obtain compound C; 4) subjecting the compound C obtained in step 3) to a Bartoli reaction under the action of vinylmagnesium bromide to obtain the target compound 7-bromo-5,6-bis(benzyloxy)benzopyrrole; 2. The synthesis method according to claim 1, characterized in that: In the step 1), the bromination reaction is carried out in the presence of N-bromosuccinimide, and the molar ratio of the 2-methoxy-5-nitrophenol to N-bromosuccinimide is 1:1; In the step 1), the bromination reaction is carried out in a solvent, and the solvent is dichloromethane; In the step 1), the conditions of the bromination reaction are: the reaction temperature is 25° C. to 35° C. at room temperature, and the reaction time is 1 to 3 hours.

3. The synthesis method according to claim 1 or 2, characterized in that: In the step 2), the demethylation reaction is carried out in the presence of boron tribromide, and the molar ratio of compound A to boron tribromide is 1:2; In the step 2), the demethylation reaction is carried out in a solvent, and the solvent is dichloromethane; In the step 2), the reaction conditions of the demethylation reaction are: carried out under the protection of an inert gas such as nitrogen or argon, the reaction temperature is naturally raised from -25°C to 25°C room temperature and maintained, and the reaction time is 1 to 3 hours.

4. The synthesis method according to any one of claims 1 to 3, characterized in that: In the step 3), the benzyl protection of the phenolic hydroxyl group is carried out under alkaline conditions, and the alkaline conditions are provided by potassium carbonate, cesium carbonate, and sodium carbonate; In the step 3), the protecting group reagent used for protecting the phenolic hydroxyl group is selected from at least one of the following: benzyl bromide, allyl bromide, p-methoxybenzyl chloride or other ether protecting group reagents; when benzyl bromide is used as the protecting group reagent, the molar ratio of the compound B to benzyl bromide is 1:3; In the step 3), the benzyl protection of the phenolic hydroxyl group is carried out in a solvent, and the solvent may be acetone or N,N-dimethylformamide; In the step 3), the benzyl protection of the phenolic hydroxyl group is carried out under heating reflux at 60° C. to 80° C., and the reaction time is 0.5 to 2 hours.

5. The synthesis method according to any one of claims 1 to 4, characterized in that: In the step 4), the Bartoli reaction is carried out in the presence of vinyl magnesium bromide, and the molar ratio of the compound C to vinyl magnesium bromide is 1:3; In the step 4), the Bartoli reaction is carried out in a solvent, and the solvent is tetrahydrofuran; In the step 4), the Bartoli reaction is carried out under the protection of an inert gas, nitrogen or argon, at a reaction temperature of -25°C and a reaction time of 1 to 3 hours.

6. A method for synthesizing 7,7'-dimer, comprising the following steps: aa) preparing 7-bromo-5,6-bis(benzyloxy)benzopyrrole according to the synthesis method according to any one of claims 1 to 5; a) allowing 7-bromo-5,6-bis(benzyloxy)benzopyrrole to undergo Suzuki-Miyaura coupling reaction under the action of bis-pinacol borate, tris(dibenzylideneacetone)dipalladium and 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl to generate compound D; b) removing the benzyl group from the compound D obtained in step a) to obtain the target product 7,7'-dimer; 7. The synthesis method according to claim 6, characterized in that: In the step a), the Suzuki-Miyaura coupling reaction needs to be carried out under alkaline conditions, the alkaline conditions are provided by potassium phosphate, and the molar ratio of 7-bromo-5,6-bis(benzyloxy)benzopyrrole to potassium phosphate is 1:4; Or, in the step a), the Suzuki-Miyaura coupling reaction is carried out in the presence of bis-pinacol borate, tris[dibenzylideneacetone]dipalladium and 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl, and the molar ratio of the compound 7-bromo-5,6-bis(benzyloxy)benzopyrrole to bis-pinacol borate, tris[dibenzylideneacetone]dipalladium and 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl is 1:0.55:0.1:0.4 respectively; Or, in the step a), the Suzuki-Miyaura coupling reaction is carried out in a solvent, the solvent is a mixed solvent of dioxane and water, wherein the volume ratio of dioxane to water is 15:1 to 4:1; Alternatively, in the step a), the Suzuki-Miyaura coupling reaction is carried out under the protection of an inert gas, which may be nitrogen or argon; the reaction temperature of the Suzuki-Miyaura coupling reaction is 90° C. to 110° C., and the reaction time may be 0.5 to 2 hours.

8. The synthesis method according to claim 6 or 7, characterized in that: In the step b), the removal of the benzyl group is carried out in a hydrogen atmosphere, and the pressure of the hydrogen is 15 psi; Or, in the step b), the hydrogenolysis of the benzyl group is carried out in the presence of at least one of the following catalysts: palladium carbon, Raney Ni, platinum carbon, palladium dichloride and palladium hydroxide; When palladium carbon is used as a catalyst, the molar ratio of the compound D to palladium carbon is 1:0.05; Or, in the step b), the removal of the benzyl group is carried out in a solvent, the solvent is a mixed solvent of ethyl acetate and ethanol, wherein the volume ratio of ethyl acetate to ethanol is 10:1 to 2:1; Or, in the step b), the removal of the benzyl group is carried out under weak acidic conditions, and the weak acidic conditions are provided by acetic acid or dilute hydrochloric acid; Alternatively, in the step b), the reaction temperature for removing the benzyl group is 25° C. to 35° C., and the reaction time is 1 to 8 hours.

9. A method for synthesizing 2,7'-dimer, comprising the following steps: AA) preparing 7-bromo-5,6-bis(benzyloxy)benzopyrrole according to the synthesis method of any one of claims 1 to 5; A) allowing the compound 7-bromo-5,6-bis(benzyloxy)benzopyrrole to undergo Sonogashira coupling with trimethylsilyl acetylene to obtain compound 1; B) removing the trimethylsilyl group from the compound 1 obtained in step A) under the action of tetrabutylammonium fluoride to obtain compound 2; C) subjecting the compound 2 obtained in step B) to Sonogashira coupling with compound III to obtain compound 4; D) allowing the compound 4 obtained in step C) to react with pyrrolidine first, and then undergo nitro reduction and intramolecular ring closure under the action of zinc powder and ferrous chloride to obtain compound 5; E) debenzylating the compound 5 obtained in step D) under the action of hydrogen and palladium on carbon to obtain the final product 2,7'-dimer; 10. The synthesis method according to claim 9, characterized in that: In the step A), the Sonogashira coupling is carried out in the presence of cuprous iodide and bistriphenylphosphine palladium dichloride, and the molar ratios of the 7-bromo-5,6-bis(benzyloxy)benzopyrrole to trimethylsilyl acetylene, cuprous iodide, and bistriphenylphosphine palladium dichloride are 1:1.5:0.2:0.1, respectively; Or, in the step A), the Sonogashira coupling is carried out under alkaline conditions, and the alkaline conditions are provided by triethylamine; Or, in the step A), the Sonogashira coupling is carried out in a solvent, and the solvent is toluene; Or, in method step A), the reaction conditions of the Sonogashira coupling are: carried out under the protection of inert gas nitrogen, the reaction temperature is 50° C., and the reaction time is 0.5 to 3 hours.

11. The synthesis method according to claim 9 or 10, characterized in that: In the step B), the detrimethylsilylation of the compound 1 is carried out in the presence of tetrabutylammonium fluoride, and the molar ratio of the compound 2 to the tetrabutylammonium fluoride is 1:2; Or, in the step B), the detrimethylsilylation of compound 1 is carried out in a solvent, and the solvent may be tetrahydrofuran; Alternatively, in the step B), the reaction temperature for detrimethylsilylation of compound 1 may be 25° C., and the reaction time may be 0.5 to 2 hours.

12. The synthesis method according to any one of claims 9 to 11, characterized in that: In the step C), the Sonogashira coupling is carried out in the presence of cuprous iodide and bistriphenylphosphine palladium dichloride, and the molar ratios of compound 2 to compound III, cuprous iodide and bistriphenylphosphine palladium dichloride are 1:1.2:0.2:0.1, respectively; Or, in the step C), the Sonogashira coupling is carried out under alkaline conditions, and the alkaline conditions are provided by triethylamine; Or, in the step C), the Sonogashira coupling is carried out in a solvent, and the solvent is toluene; Or, in the step C), the reaction conditions of the Sonogashira coupling are: carried out under the protection of an inert gas such as nitrogen or argon, the reaction temperature is 80° C., and the reaction time is 0.5 to 3 hours.

13. The synthesis method according to any one of claims 9 to 12, characterized in that: In the step D), the molar ratio of compound 4 to pyrrolidine is 1:20; Or, in the step D), the reaction temperature of the compound 4 and pyrrolidine may be 80° C., and the reaction time may be 0.5 to 2 hours; Or, in the step D), the nitro reduction and intramolecular ring closure can be carried out in the presence of zinc powder (or iron powder) and ferrous chloride, and the solvent is ethanol; Or, in the step D), the reaction conditions of the nitro reduction and intramolecular ring closure are: carried out under the protection of an inert gas such as nitrogen or argon, the reaction temperature is 85° C., and the reaction time is 0.5 to 2 hours.

14. The synthesis method according to any one of claims 9 to 13, characterized in that: In the step E), the reduction of the benzyl group is carried out in the presence of at least one of the following catalysts: palladium carbon, Raney Ni, platinum carbon, palladium dichloride and palladium hydroxide; when palladium carbon is used as a catalyst, the molar ratio of the compound 5 to palladium carbon is 1:0.05; Or, in the step E), the removal of the benzyl group is carried out in a hydrogen atmosphere, and the pressure of the hydrogen is 15 psi; Or, in the step E), the removal of the benzyl group is carried out in a solvent, the solvent is a mixed solvent of ethyl acetate and ethanol, wherein the volume ratio of ethyl acetate to ethanol is 10:1 to 2:1; Or, in the step E), the removal of the benzyl group is carried out under weakly acidic conditions, and the weakly acidic conditions are provided by acetic acid or dilute hydrochloric acid; Alternatively, in the step E), the reaction temperature for removing the benzyl group is 25° C. to 35° C., and the reaction time is 1 to 8 hours.

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