A method for synthesizing a nucleophilically substituted aromatic decalin compound from isoprene

Abstract

The present application relates to a kind of method for synthesizing nucleophilic substitution aromatic carbon ten compounds by isoprene.The specific is, with isoprene, nitrogen-containing aromatic heterocycle as raw material, under the condition of carbene nickel and iodine tandem catalysis, realize the construction of nucleophilic substitution aromatic carbon ten compounds.The present application has the following advantages, raw material isoprene and nitrogen-containing aromatic heterocycle are commercially available and cheap, wide substrate range, good selectivity and yield.

Description

Technical Field

[0001] This invention relates to a method for synthesizing nucleophilically substituted aromatic carbon-10 compounds from isoprene. Specifically, using isoprene and nitrogen-containing aromatic heterocycles as starting materials, nucleophilically substituted aromatic carbon-10 compounds are constructed under tandem catalysis of carbene nickel and iodine. This invention offers the following advantages: the starting materials, isoprene and nitrogen-containing aromatic heterocycles, are commercially available and inexpensive; it provides a broad substrate range; and it exhibits good selectivity and yield. Background Technology

[0002] Over hundreds of millions of years of evolution, nature has produced a wide variety of monoterpenoid compounds. C10 compounds, represented by monoterpenes, are widely studied due to their physiological activities such as anti-inflammatory, analgesic, and antitumor effects. In recent years, the development of renewable energy and the synthesis of steroidal drugs using them as raw materials have also progressed. In the biosynthesis of monoterpenoid derivatives, isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) are first condensed under the action of geranyl pyrophosphate synthase (GPPase) to form geranyl diphosphate (GPP). Then, through a key intermediate (geranyl cation), cyclic or acyclic monoterpenoid compounds are synthesized from GPP under enzymatic catalysis. Finally, under the catalysis of specific enzymes, these monoterpenoid compounds can be further converted into monoterpenoid derivatives. However, biosynthetic pathways often have limitations; biomimetic catalysis can overcome these bottlenecks and achieve complementarity.

[0003] Isoprene is an inexpensive and readily available bulk chemical, and its use as a C5 synthon to simulate biological processes for constructing sesquiterpenes or terpenoid derivatives is of great significance and promise. The coupling of metal-catalyzed nucleophiles with isoprene to achieve different types of isoprene-based polymerization reactions has a well-established research foundation, while nucleophilic telomerization reactions involving the programmed combination of a single nucleophile with multiple isoprene units are still in their nascent stage. The Beller, Finn, Réau, Navarro, Carbó, and Chen Qing'an research groups have conducted related research on linear nucleophilic telomerization reactions based on isoprene; in comparison, nucleophilic cyclic telomerization reactions of isoprene are rarely reported. We envision constructing nucleophilically substituted aromatic C10 compounds through isoprene, which inevitably faces several challenges: 1. Controlling the number of isoprene monomers and the telomerization mode; 2. Controlling the reactivity of isoprene in direct addition and its nucleophilic telomerization; 3. Controlling various chemical selectivity, regioselectivity, and redox selectivity.

[0004] This method overcomes these challenges, enabling the construction of nucleophilically substituted aromatic C10 compounds from isoprene. This not only provides a framework for the precise nucleophilic telomerization reaction of isoprene but also bridges the gap in the synthesis of aromatic C10 compounds from C5.

[0005]

[0006] Formula 1. Synthesis of nucleophilically substituted aromatic carbon-10 compounds from isoprene Summary of the Invention

[0007] The purpose of this invention is to precisely construct nucleophilic substituted aromatic carbon-10 compounds by achieving telomerization and nucleophilic aromatic aromatization of isoprene and nitrogen-containing aromatic heterocycles through the tandem action of nickel carbene reagent and iodine.

[0008] This invention is achieved through the following technical solution:

[0009] A method for synthesizing nucleophilically substituted aromatic carbon-10 compounds from isoprene

[0010] Using isoprene and nitrogen-containing aromatic heterocycles as raw materials, telomerization and nucleophilic aromatic aromatization reactions were rapidly achieved in excellent yields under tandem catalysis of nickel carbene reagent and iodine. The reaction formulas are shown below:

[0011]

[0012] The specific operating steps are as follows:

[0013] Under an argon and / or nitrogen atmosphere, nickel salt, carbene salt reagent, organic base, solvent, and isoprene are added to a reactor. The mixture is heated to 60-120℃ (preferably 100-120℃) and stirred for 6-18 h (preferably 10-14 h). Then, it is cooled to room temperature, and an acid, oxidant, iodide salt, iodine, nitrogen-containing aromatic heterocycle, and another solvent are added. The mixture is reacted at 80-140℃ (preferably 80-100℃) for 12-48 h (preferably 20-36 h) to generate the target product 3. The reaction system is monitored by TLC. After the reaction is complete, the solvent is evaporated, and the mobile phase for column chromatography is petroleum ether / ethyl acetate (volume ratio 20:1-2:1).

[0014] The reactant, a nitrogen-containing aromatic heterocyclic compound (Formula 1), can be one or more of indole, indazole, and pyrrole, with substituent R. 1 It can be one or more of hydrogen, fluorine, chlorine, bromine, iodine, nitro, and methoxy groups, with substituent R. 2 It can be one or both of hydrogen and methyl.

[0015] The nickel salt used is one or more of the following: nickel dicyclooctadiene, nickel chloride, nickel bromide, nickel iodide, nickel trifluoromethanesulfonate, or nickel di(acetylacetone); wherein the molar ratio of the nickel salt to the nitrogen-containing aromatic heterocycle is 0.01-0.2, preferably 0.02-0.08.

[0016] The carbene salt reagent used is one or more of the following formulas L1, L2, L3, L4, L5, and L6: (the structural formulas are as follows L1, L2, L3, L4, L5, and L6), and the molar ratio of the carbene salt reagent to the nitrogen-containing aromatic heterocycle is 0.01-0.2, preferably 0.02-0.08.

[0017]

[0018] Solvent A is one or more of the following: methanol, ethanol, isopropanol, tert-butanol, acetonitrile, toluene, n-hexane, cyclohexane, tetrahydrofuran, 2-methyltetrahydrofuran, ethylene glycol dimethyl ether, methyl tert-butyl ether, dichloromethane, dichloroethane, 1,4-dioxane, ethyl acetate, N,N-dimethylformamide, N-methylpyrrolidone, and dimethyl sulfoxide. Solvent B is one or more of the following: methanol, ethanol, isopropanol, tert-butanol, acetonitrile, toluene, n-hexane, cyclohexane, tetrahydrofuran, 2-methyltetrahydrofuran, ethylene glycol dimethyl ether, methyl tert-butyl ether, dichloromethane, dichloroethane, 1,4-dioxane, ethyl acetate, N,N-dimethylformamide, N-methylpyrrolidone, and dimethyl sulfoxide. The solvent is preferably one or more of tetrahydrofuran, n-hexane, toluene, 1,4-dioxane, and acetonitrile. Solvent A is different from solvent B. The concentration of nitrogen-containing aromatic heterocycles in the solvent is in the range of 0.01-1.5 mol / L, preferably 0.05-1 mol / L.

[0019] The amount of isoprene used is between 3 and 10 times the molar amount of nitrogen-containing aromatic heterocycles, preferably between 5 and 8 times.

[0020] The organic base is one or more of sodium tert-butoxide, potassium tert-butoxide, or sodium methoxide, and the molar ratio of the organic base to the nitrogen-containing heteroaromatic ring is 0.01-0.2, preferably 0.02-0.15.

[0021] The iodized salt reagent is one or more of potassium iodide, sodium iodide, or cuprous iodide, and the molar ratio of the iodized salt to the nitrogen-containing heteroaromatic ring is 0.01-0.2, preferably 0.02-0.15.

[0022] The acid is one or more of benzoic acid, benzenesulfonic acid, adamantane carboxylic acid or diphenyl phosphate, and the molar ratio of the acid to the nitrogen-containing heteroaromatic ring is 0.01-0.2, preferably 0.02-0.15.

[0023] The oxidant is one or more of potassium persulfate, ammonium persulfate, sodium persulfate, peroxytert-butanol, dimethyl sulfoxide, or benzoquinone, and the oxidant is 1.5 to 10 times the molar amount of the nitrogen-containing heteroaromatic ring, preferably 2 to 5 times.

[0024] The molar ratio of iodine dosage to nitrogen-containing aromatic heterocycles is 0.1-0.8, with a preferred range of 0.1-0.4.

[0025] The present invention has the following advantages:

[0026] The present invention has the following advantages: the raw materials are isoprene and nitrogen-containing aromatic heterocycles, which are commercially available and inexpensive; a broad substrate range; and good selectivity and yield. Attached image description:

[0027] Figure 1 For compound 3a 1 H NMR and 13 C NMR spectrum;

[0028] Figure 2 For compound 3b 1 H NMR and 13 C NMR spectrum;

[0029] Figure 3 For compound 3c 1 H NMR and 13 C NMR spectrum;

[0030] Figure 4 For compound 3d 1 H NMR and 13 C NMR spectrum;

[0031] Figure 5 For compound 3e 1 H NMR and 13 C NMR spectrum;

[0032] Figure 6 For compound 3f 1 H NMR and 13 C NMR spectrum;

[0033] Figure 7 3g of compound 1 H NMR and 13 C NMR spectrum;

[0034] Figure 8 For compound 3h 1 H NMR and 13 C NMR spectrum;

[0035] Figure 9 For compound 3i 1 H NMR and 13 C NMR spectrum;

[0036] Figure 10 For compound 4a 1 H NMR and 13 C NMR spectrum; Detailed Implementation

[0037] The present invention will be described below with specific embodiments, but the scope of protection of the present invention is not limited to these examples.

[0038] 1. Synthesis of nucleophilically substituted aromatic carbon-10 compounds from isoprene

[0039] Under a nitrogen atmosphere, in a 4.0 mL pressure-resistant tube (pressure-resistant reaction tube), nickel dicyclooctadiene (2.8 mg, 5 mol% relative to indole), carbene salt reagent L (5 mol% relative to indole), organic base (10 mol% relative to indole), solvent A 0.5 mL, and isoprene (120 μL, 6 times the molar amount of indole) were added sequentially. The mixture was heated to 100 °C and stirred for 12 h. After cooling to room temperature, acid (10 mol% relative to indole), sodium persulfate (0.4 mmol, 108.1 mg, 2 times the molar amount of indole), potassium iodide (3.3 mg, 10 mol% relative to indole), indole (0.2 mmol, 23.4 mg), iodine (10.2 mg, 20 mol% relative to indole), and solvent B were added. 0.5 mL was added and reacted at 100 °C for 24 h. The reaction system was monitored by TLC. After the reaction was completed, mesitylene was added as an internal standard. The yield of the target product was detected by GC-FID. See the table below.

[0040]

[0041] Table. Effects of ligands, solvents, and additives on the reaction

[0042]

[0043]

[0044] 2. Substrate type

[0045]

[0046] Table 1

[0047]

[0048]

[0049] Example 1

[0050] Under a nitrogen atmosphere, in a 4.0 mL pressure-resistant tube (pressure-resistant reaction tube), nickel dicyclooctadiene (2.8 mg, nickel salt relative to 5 mol% of the nitrogen-containing aromatic heterocycle), carbene salt reagent L2 (4.3 mg, carbene salt ligand relative to 5 mol% of the nitrogen-containing aromatic heterocycle), sodium tert-butoxide (1.9 mg, 10 mol% of the nitrogen-containing aromatic heterocycle), 0.5 mL of n-hexane (solvent A), and isoprene (1.2 mmol, 120 μL, 6 times the molar amount of the nitrogen-containing aromatic heterocycle) were added sequentially. The mixture was heated to 100 °C and stirred for 12 h (the reaction was carried out on the first reaction). (First step reaction), then cooled to room temperature, and added diphenyl phosphate (5.0 mg relative to 10 mol% of the nitrogen-containing aromatic heterocycle), sodium persulfate (0.4 mmol, 108.1 mg relative to twice the molar amount of the nitrogen-containing aromatic heterocycle, oxidant), potassium iodide (3.3 mg relative to 10 mol% of the nitrogen-containing aromatic heterocycle, iodine salt), nitrogen-containing aromatic heterocycle (0.2 mmol), iodine (10.2 mg relative to 20 mol% of the nitrogen-containing aromatic heterocycle), and tetrahydrofuran 0.5 mL (solvent B). The reaction was carried out at 100 °C for 24 h (second step reaction). After the reaction was completed, the solvent was evaporated, and the mobile phase for column chromatography was petroleum ether / ethyl acetate (volume ratio 20:1).

[0051] HRMS calculated for C 18 H 20 N[M+H] + 250.1590, found 250.1596.

[0052] Product 3a is a known compound (Reference: Song, H.; Zhou, H.; Shen, Y.; Wang, H.; Song, H.; Cai, X.; Xu, C. Hfip as protonation reagent and solvent for regioselective alkylation of indoles with all-carbon centers. J. Org. Chem. 2022, 87, 1086.)

[0053] Example 2:

[0054] The operation process and conditions are the same as in Example 1. The difference from Example 1 is that, except for the difference in raw material 2 described in Table 1, the nickel salt used for the catalyst is changed to di(acetylacetone) nickel (10 mol% relative to nitrogen-containing aromatic heterocycles).

[0055] HRMS calculated for C 19 H 22 [M+H] + 264.1747, found 264.1756.

[0056] Example 3:

[0057] The operation and conditions are the same as in Example 1, except that, apart from the difference in raw material 2 described in Table 1, the carbene salt ligand is changed to L4 (5 mol% relative to nitrogen-containing aromatic heterocycles).

[0058] 3.76(s,3H),3.37(s,3H),2.31(s,3H),1.77(s,6H); 13 C NMR(175MHz,Chloroform-d)δ154.13,149.24,139.84,133.75,128.17,125.98,125. 43,124.99,122.48,117.10,102.36,100.10,54.58,39.08,33.01,31.61,21.04.HRMS calculated for C 20 H 24 NO[M+H] + 294.1852, found 294.1851.

[0059] Example 4:

[0060] The operation process and conditions are the same as in Example 1. The difference from Example 1 is that, except for the difference in raw material 2 described in Table 1, solvent B is changed to 1,4-dioxane (1.0 mL).

[0061]

[0062] MHMS calculated forC 18 H 19 Cl 35 N[M+H] + 284.1201, found 284.1199; C 18 H 19 Cl 37 N[M+H] + 286.1171, found 286.1167.

[0063] Example 5:

[0064] The operation process and conditions are the same as in Example 1. The difference from Example 1 is that, except for the difference in raw material 2 described in Table 1, solvent A is replaced with toluene (0.5 mL).

[0065]

[0066] Chloroform-d)δ146.41,135.83,135.25,128.96,127.88,126.22,126.09,124.62,123.80,121.90,112.59,112.29,38.59,30.74,21.05.HRMS calculated forC 18 H 19 Br 79 N[M+H] + 328.0695, found 328.0696; C 18 H 19 Br 81 N[M+H] + 330.0675, 330.0677.

[0067] Example 6:

[0068] The operation process and conditions are the same as in Example 1. The difference from Example 1 is that, except for the difference in raw material 2 described in Table 1, the iodized salt is replaced with sodium iodide (relative to 20 mol% of nitrogen-containing aromatic heterocycles).

[0069]

[0070] 1H), 2.34(s, 3H), 1.75(s, 6H); 13 C NMR(175MHz,Chloroform-d)δ146.40,136.25,135.25,130.10,130.09,128.9 4,128.71,126.22,125.81,121.50,113.15,82.70,38.59,30.77,21.06.HRMS calculated for C 18 H 19 IN[M+H] + 376.0557, found 376.0550.

[0071] Example 7:

[0072] The operation process and conditions are the same as in Example 1. The difference from Example 1 is that, except for the difference in raw material 2 described in Table 1, the oxidant is changed to ammonium persulfate (3 times the molar amount of nitrogen-containing aromatic heterocycles).

[0073] MHz, DMSO-d6)δ146.26,140.37,139.65,134.60,128.73,126.94,125.87,125.48,124.65,116.98,116.20,111.99,38.09,30.57,20.50.HRMS calculated for C 18 H 19 N₂O₂[M+H] + 295.1441, found 295.1437.

[0074] Example 8:

[0075] The operation process and conditions are the same as in Example 1. The difference from Example 1 is that, except for the difference in raw material 2 described in Table 1, the reaction temperature of the first and second steps is changed to 120°C.

[0076] HRMS calculated for C 17 H 19 N2[M+H] + 251.1543, found 251.1545.

[0077] Example 9:

[0078] The operation process and conditions are the same as in Example 1. The difference from Example 1 is that, except for the difference in raw material 2 described in Table 1, the reaction time of the first step reaction is changed to 12h and the reaction time of the first step reaction is 30h.

[0079] 6.01(d,J=2.7Hz,2H),2.30(s,6H),1.59(s,12H); 13 C NMR(100MHz,Chloroform-d)δ146.67,139.77,135.52,128.88,126.19,103.65,39.18,30.30,20.99.HRMS calculated for C 24 H 30 N[M+H] + 332.2373, found 332.2378.

[0080] Comparative Example 1:

[0081] The operation process and conditions were the same as in Example 1, except that the catalyst was changed to nickel oxide (10 mol% relative to nitrogen-containing aromatic heterocycles), and no product 3a was generated.

[0082] Comparative Example 2:

[0083] The operation process and conditions were the same as in Example 1, except that the carbene salt ligand was replaced with triphenylphosphine (10 mol% relative to the nitrogen-containing aromatic heterocycle), and the yield of 3a was 5%.

[0084] Product application examples:

[0085]

[0086] In a 4.0 mL pressure-resistant tube (pressure-resistant reaction tube), product 3a (0.2 mmol, 49.9 mg), NaH (1.5 equiv, 12.0 mg), and tetrahydrofuran solvent (1.0 mL) were added sequentially under ice bath conditions. The mixture was stirred at room temperature for 15 min, and then isopentenyl bromide (1.5 equiv, 35 μL) was added. After reacting at room temperature for 8 h, the mixture was evaporated to dryness and separated by column chromatography. The mobile phase was petroleum ether / ethyl acetate (volume ratio 50:1) to obtain the target product 4a with a yield of 94% and 59.8 mg.

[0087]

[0088] NMR(100 MHz,Chloroform-d)δ147.28,137.16,135.75,134.87,128.78,126.78,126.41,124.71,124.18,121.60,121.04,120.57,118.33,109.49,44.26,38.72,30.99,25.83,21.08,18.22.HRMS calculated for C 23 H 28 N[M+H] + 318.2216,found 318.2217.

Claims

1. A method for synthesizing nucleophilically substituted aromatic carbon-10 compounds from isoprene, characterized in that: Isoprene and nitrogen-containing aromatic heterocycles undergo telomerization and nucleophilic aromatic aromatization reactions through the tandem action of nickel carbene reagent and iodine. The reaction equation is shown in Equation 1 below: ， Formula 1. Synthesis of nucleophilically substituted aromatic carbon-10 compounds from isoprene The reactant, nitrogen-containing aromatic heterocyclic compound 2, is indole, with substituent R. 1 It can be hydrogen, fluorine, chlorine, bromine, iodine, nitro or methoxy, with substituent R. 2 It is hydrogen or methyl. The specific steps are as follows: In an argon and / or nitrogen atmosphere, nickel salt, carbene salt reagent, organic base, solvent A, and isoprene are added to a reactor. The mixture is heated to 60-120 °C and stirred for 6-18 h to carry out the first step of the reaction. Then, it is cooled to room temperature, and acid, oxidant, iodide salt, iodine, nitrogen-containing aromatic heterocycle, and solvent B are added. The mixture is then reacted at 80-140 °C for 12-48 h to carry out the second step of the reaction, generating the target product. The carbene salt reagent used is one or more of the following formulas: L1, L2, L3, L4, L5, and L6, with the following structural formulas: 。 2. The method according to claim 1, characterized in that: The specific steps are as follows: In an argon and / or nitrogen atmosphere, nickel salt, carbene salt reagent, organic base, solvent A, and isoprene are added to a reactor. The mixture is heated to 100-120 °C and stirred for 10-14 h to carry out the first step of the reaction. Then, the mixture is cooled to room temperature, and acid, oxidant, iodide salt, iodine, nitrogen-containing aromatic heterocycle, and solvent B are added. The mixture is then reacted at 80-100 °C for 20-36 h to carry out the second step of the reaction, yielding the target product.

3. The method according to claim 1, characterized in that: The reaction system was monitored by TLC. After the reaction was completed in 12-48 h, the solvent was evaporated and the mixture was separated by column chromatography. The mobile phase for column chromatography was petroleum ether / ethyl acetate with a volume ratio of 20:1-2:

1.

4. The method according to claim 1, characterized in that: The nickel salt used is one or more of the following: nickel dicyclooctadiene, nickel chloride, nickel bromide, nickel iodide, nickel trifluoromethanesulfonate, or nickel di(acetylacetone); wherein the molar ratio of nickel to nitrogen-containing aromatic heterocycle is 0.01-0.

2.

5. The method according to claim 1, characterized in that: The molar ratio of carbene salt reagent to nitrogen-containing aromatic heterocycle is 0.01-0.

2.

6. The method according to claim 1, 4, or 5, characterized in that: The molar ratio of nickel to nitrogen-containing aromatic heterocycles is 0.02-0.08, and the molar ratio of carbene salt reagent to nitrogen-containing aromatic heterocycles is 0.02-0.

08.

7. The method according to claim 1, characterized in that: Solvent A used is methanol, ethanol, isopropanol, tert-butanol, acetonitrile, toluene, n-hexane, cyclohexane, tetrahydrofuran, 2-methyltetrahydrofuran, ethylene glycol dimethyl ether, methyl tert-butyl ether, dichloromethane, dichloroethane, 1,4-dioxane, ethyl acetate. N,N One or more of dimethylformamide, N-methylpyrrolidone, and dimethyl sulfoxide are used as solvents; Solvent B used is methanol, ethanol, isopropanol, tert-butanol, acetonitrile, toluene, n-hexane, cyclohexane, tetrahydrofuran, 2-methyltetrahydrofuran, ethylene glycol dimethyl ether, methyl tert-butyl ether, dichloromethane, dichloroethane, 1,4-dioxane, ethyl acetate. N,N - One or more of dimethylformamide, N-methylpyrrolidone, and dimethyl sulfoxide are used as solvents; Solvent A and solvent B may be different or the same, and the volume ratio of solvent A to solvent B is 1:1-4; The concentration range of nitrogen-containing aromatic heterocycles in solvents is 0.01-1.5 mol / L.

8. The method according to claim 1 or 7, characterized in that: Solvent B is one or more of tetrahydrofuran, n-hexane, toluene, 1,4-dioxane, and acetonitrile. Solvent A differs from solvent B in that the concentration range of nitrogen-containing aromatic heterocycles in the solvent is 0.05-1 mol / L.

9. The method according to claim 1, characterized in that: The amount of isoprene used is 3-10 times the molar amount of nitrogen-containing aromatic heterocycles. The first step of the reaction is carried out at a temperature of 60-120 °C for 6-18 h. The second step of the reaction is carried out at a temperature of 80-140 °C for 12-48 h.

10. The method according to claim 1 or 9, characterized in that: The amount of isoprene used is 5-8 times the molar amount of nitrogen-containing aromatic heterocycles; the first step of the reaction is carried out at a temperature of 100-120 ℃ for 10-14 h; the second step of the reaction is carried out at a temperature of 80-100 ℃ for 20-36 h.

11. The method according to claim 1, characterized in that: The organic base is one or more of sodium tert-butoxide, potassium tert-butoxide, or sodium methoxide, and the molar ratio of the organic base to the nitrogen-containing heteroaromatic ring is 0.01-0.

2. The iodized salt reagent is one or more of potassium iodide, sodium iodide, or cuprous iodide, and the molar ratio of iodized salt to nitrogen-containing heteroaromatic ring is 0.01-0.

2.

12. The method according to claim 1, characterized in that: The molar ratio of organic base to nitrogen-containing heteroaromatic ring is 0.02-0.15; the molar ratio of iodized salt to nitrogen-containing heteroaromatic ring is 0.02-0.

15.

13. The method according to claim 1, characterized in that: The acid is one or more of benzoic acid, benzenesulfonic acid, adamantane carboxylic acid or diphenyl phosphate, and the molar ratio of the acid to the nitrogen-containing heteroaromatic ring is 0.01-0.

2.

14. The method according to claim 1, characterized in that: The oxidizing agent is one or more of potassium persulfate, ammonium persulfate, sodium persulfate, tert-butanol peroxide, dimethyl sulfoxide, or benzoquinone, and the molar amount of the oxidizing agent is between 1.5 and 10 times that of the nitrogen-containing heteroaromatic ring. The molar ratio of iodine dosage to nitrogen-containing aromatic heterocycles is 0.1-0.

8.

15. The method according to claim 1, 13, or 14, characterized in that: The molar ratio of acid to nitrogen-containing heteroaromatic ring is 0.02-0.15, and the oxidant is 2-5 times the molar amount of nitrogen-containing heteroaromatic ring; the molar ratio of iodine to nitrogen-containing heteroaromatic ring is 0.1-0.4.

Images