CN114181214A

CN114181214A - Non-activated alkane C (sp)3) -H-functional initiated radical cyclization reaction process

Info

Publication number: CN114181214A
Application number: CN202111472712.XA
Authority: CN
Inventors: 郑滟男; 魏文廷; 汪子颖
Original assignee: Ningbo University
Current assignee: Ningbo University
Priority date: 2021-11-24
Filing date: 2021-11-24
Publication date: 2022-03-15

Abstract

The invention relates to a C (sp) of naphthenic hydrocarbon or toluene compound in an aqueous phase metal-free system³) -H bond functionalization initiated radical cyclization of 2-arylbenzimidazoles to benzimidazoloisoquinolinones. The method comprises the steps of adding a naphthenic hydrocarbon or toluene compound, a 2-aryl benzimidazole compound, an oxidant, a phase transfer agent and a solvent into a Schlenk reaction bottle, and stirring and reacting at a certain temperature under an air atmosphere to obtain the benzimidazolyl isoquinolone compound.

Description

Non-activated alkane C (sp)3) -H-functional initiated radical cyclization reaction process

Technical Field

The application belongs to the field of organic synthesis, and particularly relates to unactivated alkane C (sp) in an aqueous phase metal-free system³) -H-functional initiated radical cyclisation of 2-arylbenzimidazoles to give benzimidazoloisoquinolinones.

Background

As an important component of life, water plays an immobile role in green solvents. It is well known that water is non-toxic, low cost and readily available. The high heat capacity of water makes it an ideal medium for carrying out large scale exothermic reactions, while the insolubility of organic compounds in water makes the product easy to extract and purify. On the other hand, metal-free conversion is easier to purify, and compared to these processes involving metal catalysis, it eliminates the disadvantages of metal catalysts, such as high cost, poor durability, and the need for strong bases or complex ancillary ligands. By comprehensively considering all the factors, the development of organic reactions in an aqueous medium under a metal-free system has important significance and urgency.

Carbon radicals are widely used for the radical cyclisation of 2-arylbenzimidazoles for the synthesis of a variety of benzimidazoles [2, 1-a ]]Isoquinolin-6 (5H) -ones, corresponding C-central radicalsIs prepared from C-X, C-C, C-N, C-B or C (sp)²) -H bond cleavage. In sharp contrast, only one case will generate a carbon-centered free radical through C (sp)³) -H bond cleavage. However, to our knowledge, the conversion between the non-activated alkane and the 2-arylbenzimidazole has not been reported, which may be attributed to the non-activated C (sp)³) High Bond Dissociation Energy (BDE) and low polarity of the H bond. Since unactivated alkanes are available natural resources, their unactivated C (sp)³) The direct functionalization of the-H bonds would expand the range of applications for various products. Based on these, we propose in the present invention a highly efficient and green metal-free radical cyclization of 2-arylbenzimidazoles with unactivated alkanes using di-tert-butyl peroxide (DTBP) to promote C (sp)³) Functionalization of the-H bond, resulting in a series of valuable benzimidazoles [2, 1-a ] in aqueous media]Isoquinoline-6 (5H) -ketone compounds.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provides a method for preparing benzimidazolyl isoquinolone compounds by cyclization reaction of 2-arylbenzimidazole compounds and naphthene compounds or toluene compounds, which is green, efficient and low in cost.

The cyclization reaction method provided by the invention takes 2-aryl benzimidazole compound and naphthene or toluene compound as raw materials, and is prepared by the following steps:

adding an N-methacryloyl-2-phenylbenzimidazole compound shown in a formula 1, a naphthenic hydrocarbon compound shown in a formula 2 or a toluene compound shown in a formula 3, an oxidant, a phase transfer agent and a solvent into a reactor, placing the reactor at a certain temperature, stirring for reaction, monitoring the reaction process by TLC or GC until the raw materials are completely reacted, and carrying out post-treatment to obtain the benzimidazolyl isoquinolone compound shown in the formula I or the formula II.

The chemical reaction formula of the method for preparing the benzimidazolono compound by cyclizing the 2-arylbenzimidazole compound and the naphthenic hydrocarbon or toluene compound can be expressed as (see formula I):

the post-processing operation is as follows: extracting the reaction solution after the reaction is finished with ethyl acetate, drying an organic phase with anhydrous sodium sulfate, filtering, concentrating under reduced pressure to remove a solvent, and separating the residue by column chromatography, wherein the elution solvent is: ethyl acetate/n-hexane to obtain the benzimidazol isoquinolinone compound (I) or (II).

In the compounds represented by the formulae 1, 2, 3, formula I and formula II, R¹Selected from hydrogen, halogen, C₁-C₁₀Alkyl radical, C₆-C₂₀An aryl group;

R²selected from hydrogen, halogen, cyano, C₁-C₁₀Alkyl, substituted or unsubstituted C₆-C₂₀An aryl group;

R³is selected from C₁-C₁₀Alkyl, substituted or unsubstituted C₆-C₂₀An aryl group;

R⁴is selected from C₁-C₁₀Alkyl radical, C₆-C₂₀An aryl group;

is represented by C₃-C₁₂A cycloalkyl group;

R⁵selected from hydrogen, halogen, C₁-C₁₀An alkyl group;

wherein the substituents in the substituted or unsubstituted group are selected from halogen, C₁-C₁₀Alkyl radical, C₁-C₁₀Alkoxy radical, C₆-C₂₀An aryl group;

preferably, R¹Selected from hydrogen, halogen, C₁-C₆An alkyl group;

R²selected from hydrogen, halogen, cyano, C₁-C₆Alkyl, substituted or unsubstituted C₆-C₁₀An aryl group;

R³is selected from C₁-C₆Alkyl, substituted or unsubstituted C₆-C₁₀An aryl group;

R⁴is selected from C₁-C₆Alkyl radical, C₆-C₁₂An aryl group;

is represented by C₃-C₁₂A cycloalkyl group;

R⁵selected from hydrogen, halogen, C₁-C₆An alkyl group;

wherein the substituted or unsubstituted substituents are selected from the group consisting of fluoro, chloro, bromo, iodo, methyl, ethyl, tert-butyl, methoxy, cyano.

Most preferably, in the compounds represented by formulas 1, 2, 3 and formula I, II, R¹Selected from hydrogen, methyl, chlorine;

R²selected from hydrogen, methyl, methoxy, fluoro, chloro, bromo, cyano, naphthyl;

selected from the group consisting of cyclopentyl, cyclohexyl, 1-methylcyclopentyl, 1, 4-dimethylcyclohexyl, cycloheptyl, cyclooctyl, cyclododecyl, adamantyl, sec-hexyl;

R³selected from methyl, benzyl;

R⁴selected from methyl, phenyl;

R⁵selected from hydrogen, methyl, chlorine.

In the reaction of the present invention, the oxidizing agent is selected from potassium persulfate (K)₂S₂O₈) The compound is any one or a mixture of more of di-tert-butyl peroxide (DTBP), tert-butyl hydroperoxide (TBHP), dibenzoyl peroxide (BPO) and tert-butyl peroxybenzoate (TBPB), and is preferably di-tert-butyl peroxide (DTBP).

In the reaction of the present invention, the di-tert-butyl hydroperoxide (DTBP) is used in an amount of 1.2 to 2.0 molar equivalents, preferably 1.2 molar equivalents.

In the reaction of the present invention, the certain temperature is 80 to 100 ℃, preferably 90 ℃.

In the reaction of the present invention, the solvent is selected from H₂O/cyclohexane 1.5mL/0.5mL-1.9mL/0.1mL, preferably H₂O/cyclohexane was 1.8mL/0.2 mL.

The invention has the beneficial effects that: an unactivated alkane C (sp)³) A process for the preparation of benzimidazolone compounds by free radical cyclisation of-H-functional initiated 2-arylbenzimidazoles, which is carried out in a metal-free aqueous system in high yields to give a series of desired products. The method has the advantages of wide reaction substrate application range, greenness and high efficiency, and is particularly suitable for industrial production.

Detailed Description

The present invention will be described in further detail with reference to specific examples, but the present invention is not limited thereto.

The experimental methods described in the following examples are all conventional methods unless otherwise specified; the reagents and starting materials, if not otherwise specified, are commercially available and/or may be prepared according to known methods.

Examples 1-10 reaction conditions optimization experiments.

Example 1

2-Arylbenzimidazole 1a (52.4mg, 0.2mmol), cyclohexane 2a (0.2mL), di-tert-butyl hydroperoxide (DTBP, 35.1mg, 0.24mmol), sodium dodecyl sulfate (SDS, 11.5mg, 0.04mmol) and H were added to a Schlenk tube₂O (1.8 mL). The reaction was then stirred at 90 ℃ and sealed in air until complete consumption of the starting material (24 hours reaction time) as monitored by TLC or GC-MS analysis. After the reaction was completed, it was extracted three times with ethyl acetate. Organic layer in Na₂SO₄Dried, solvent filtered and evaporated. Concentrating the solution under reduced pressure, and mixingPurifying the compound by flash column chromatography to obtain a target product I-1 (86% yield);¹H NMR(500MHz，CDCl₃)δ：8.50-8.49(m，1H)，8.39-8.38(m，1H)， 7.84-7.83(m，1H)，7.58-7.55(m，1H)，7.49-7.41(m，4H)，2.50-2.46(m，1H)， 2.08-2.04(m，1H)，1.66(s，3H)，1.47-1.39(m，3H)，1.27-1.24(m，1H)，1.19-1.14 (m，1H)，1.00-0.88(m，3H)，0.84-0.77(m，3H)；¹³C NMR(125MHz，CDCl₃)δ： 173.4，149.8，144.0，141.8，131.6，131.4，127.5，126.5，125.9，125.8，125.4，122.5， 119.7，115.7，48.8，48.3，34.9，34.2，32.9，31.7，25.9(2)，25.8。

example 2

The oxidant used tert-butyl hydroperoxide (TBHP) instead of di-tert-butyl hydroperoxide (DTBP) and the rest of the conditions were the same as in example 1, and the yield of the target product I-1 was 75%.

Example 3

The oxidant used was tert-butyl perbenzoate (TBPB) in place of di-tert-butyl hydroperoxide (DTBP), and the same procedure as in example 1 was repeated except for changing the reaction conditions to give the desired product I-1 in a yield of 67%.

Example 4

The oxidizing agent is Benzoyl Peroxide (BPO) instead of di-tert-butyl hydroperoxide (DTBP), and the rest conditions are the same as

Example 1 gave the desired product I-1 in a yield of 63%.

Example 5

Potassium persulfate (K) as oxidant₂S₂O₈) The desired product I-1 was not obtained under the same conditions as in example 1 except that di-t-butylhydroperoxide (DTBP) was replaced.

Example 6

The amount of the oxidant di-tert-butyl hydroperoxide (DTBP) was 2.0 equivalents, and the other conditions were the same as in example 1, giving the target product I-1 a yield of 87%.

Example 7

The reaction temperature is reduced to 80 ℃ for reaction, the rest conditions are the same as the example 1, and the yield of the target product I-1 is 81 percent.

Example 8

The reaction temperature is raised to 100 ℃ for reaction, the rest conditions are the same as in example 1, and the yield of the target product I-1 is 88%.

Example 9

The amount of water and n-hexane used was 1.5mL/0.5mL, and the other conditions were the same as in example 1, whereby the yield of the objective product I-1 was 87%.

Example 10

The amount of water and n-hexane used was 1.9mL/0.1mL, and the other conditions were the same as in example 1, whereby the yield of the objective product I-1 was 49%.

As can be seen from the above examples 1 to 10, the optimum reaction conditions were those of example 1, i.e., di-t-butyl hydroperoxide (DTBP) in an amount of 1.2 equivalents as an oxidizing agent, Sodium Dodecyl Sulfate (SDS) in an amount of 0.2 equivalents as a phase transfer agent, and water (1.8mL) as a solvent were reacted in a reactor at 90 ℃ for 24 hours. On the basis of obtaining the optimal reaction condition, the inventor further selects 2-aryl benzimidazole with different substituents under the optimal reaction condition, and the non-activated alkane is used as a raw material to pass through C (sp)³) -H-functionalized metal-free radical cyclization.

Example 11

2-Arylbenzimidazole 1a (52.4mg, 0.2mmol), cyclopentane 2b (0.2mL), di-tert-butyl hydroperoxide (DTBP, 35.1mg, 0.24mmol), sodium dodecyl sulfate (SDS, 11.5mg, 0.04mmol) and H were added to a Schlenk tube₂O (1.8 mL). The reaction was then stirred at 90 ℃ and sealed in air until complete consumption of the starting material (24 hours reaction time) as monitored by TLC or GC-MS analysis. After the reaction was completed, it was extracted three times with ethyl acetate. Organic layer in Na₂SO₄Dried, solvent filtered and evaporated. The solution was concentrated under reduced pressure, and the mixture was purified by flash column chromatography to give the target product I-2 (85% yield);¹H NMR(500MHz，CDCl₃)δ：8.49(d，J＝7.5Hz，1H)，8.40-8.38(m，1H)， 7.83(d，J＝7.0Hz，1H)，7.57(t，J＝8.0Hz，1H)，7.48-7.41(m，4H)，2.55-2.51(m， 1H)，2.20-2.17(m；1H)，1.73(s，3H)，1.42-1.37(m，2H)，1.30-1.18(m，5H)， 0.99-0.93(m，1H)，0.83-0.78(m，1H)；¹³C NMR(125MHz，CDCl₃)δ：173.6，149.9， 144.1，142.1，131.6，131.4，127.6，126.6，125.9，125.8，125.5，122.8，119.7，115.8， 49.2，49.1，37.5，33.6，32.4，30.1，24.9，24.6。

example 12

2-Arylbenzimidazole 1a (52.4mg, 0.2mmol), methylcyclopentane 2c (0.2mL), di-tert-butyl hydroperoxide (DTBP, 35.1mg, 0.24mmol), sodium dodecyl sulfate (SDS, 11.5mg, 0.04mmol) and H were added to a Schlenk tube₂O (1.8 mL). The reaction was then stirred at 90 ℃ and sealed in air until complete consumption of the starting material (24 hours reaction time) as monitored by TLC or GC-MS analysis. After the reaction was completed, it was extracted three times with ethyl acetate. Organic layer in Na₂SO₄Dried, solvent filtered and evaporated. The solution was concentrated under reduced pressure and the mixture was purified by flash column chromatography to give the desired products I-3, I-4 and I-5 (81% yield, 2: 1, d.r. > 20: 1);¹H NMR(500MHz，CDCl₃)δ： 8.51-8.47(m，1H)，8.40-8.38(m，1H)，7.83(d，J＝7.5Hz，1H)，7.54-7.41(m，5H)， 2.74(d，J＝14.0Hz，0.4H)，2.67-2.63(m，0.2H)，2.55-2.46(m，0.4H)，2.33-2.30(m， 0.2H)，2.23(d，J＝14.5Hz，0.4H)，2.17-2.09(m，0.4H)，1.75(s，0.6H)，1.72(s， 2.4H)，1.59-1.35(m，3H)，1.29-1.16(m，2H)，1.13-0.83(m，3H)，0.74-0.63(m，2H)， 0.34(s，1H)；¹³C NMR(125MHz，CDCl₃)δ：173.5(2)，173.3，150.0，149.9，149.8， 144.1(3)，142.4，142.1，142.0，131.7，131.6(2)，131.5，131.4，131.3，131.1，127.6 (3)，127.0，126.6(2)，126.3，125.8(2)，125.5，123.0，122.9，122.7，122.5，119.7(2)， 115.8(2)，115.7，55.0，49.9，49.8，49.4，49.1，48.9，48.8，48.0，47.6，45.2，44.2，43.4， 43.2，41.4，41.2，40.5(2)，40.2，37.8，37.7，35.9，34.8，34.4，34.2，33.6，33.4，33.0， 32.9，32.4(2)，31.4，29.9，29.7，24.2，23.4，23.2，22.5，21.2，20.8，18.4，18.2；HRMS m/z(ESI)calcd for C₂₃H₂₅N₂O([M+H]⁺)345.1961，found 345.1957。

example 13

2-Arylbenzimidazole 1a (52.4mg, 0.2mmol), 1, 4-dimethylcyclohexane 2d (0.2mL), di-tert-butylhydroperoxide (DTBP, 35.1mg, 0.24mmol), sodium dodecyl sulfate (SDS, 11.5mg, 0.04mmol) and H were added to a Schlenk tube₂O (1.8 mL). The reaction was then stirred at 90 ℃ and sealed in air until complete consumption of the starting material (24 hours reaction time) as monitored by TLC or GC-MS analysis. After the reaction was completed, it was extracted three times with ethyl acetate. Organic layer in Na₂SO₄Dried, solvent filtered and evaporated. The solution was concentrated under reduced pressure and the mixture was purified by flash column chromatography to give the desired products I-6 and I-7 (82% yield, 2: 1, d.r. > 20: 1);¹H NMR(400MHz，CDCl₃)δ： 8.50-8.46(m，1H)，8.40-8.35(m，1H)，7.84-7.82(m，1H)，7.57-7.49(m，2H)， 7.47-7.40(m，3H)，2.63-2.57(m，0.7H)，2.44-2.39(m，0.3H)，2.34-2.13(m，1H)， 1.76-1.72(m，2H)，1.70(d，J＝3.6Hz，1H)，1.26-1.13(m，3H)，1.09-1.00(m，3H)， 0.89-0.81(m，3H)，0.75-0.63(m，3H)，0.52-0.46(m，1H)，0.40(d，J＝4.8Hz，1H)， 0.32(d，J＝6.0Hz，1H)；¹³C NMR(100MHz，CDCl₃)δ：173.6，173.5，149.8，144.1， 142.3，142.2，131.5，131.1，127.7，127.6，127.3，126.9，126.7，125.8，125.5，122.3， 122.2，119.7(2)，115.8，115.6，57.9，49.2，49.0，48.4，47.9，47.6，47.3，43.3，41.5， 41.2，40.8，39.1，38.4，35.6，35.5，34.7，34.3，33.5，33.2，30.3(2)，27.2，27.0，22.3， 21.9，20.0，19.3；HRMS m/z(ESI)calcd for C₂₅H₂₉N₂O([M+H]⁺)373.2274，found 373.2278。

example 14

2-Arylbenzimidazole 1a (52.4mg, 0.2mmol), cycloheptane 2e (0.2mL), di-t-butyl hydroperoxide (DTBP, 35.1mg, 0.24mmol), sodium dodecyl sulfate (SDS, 11.5mg, 0.04mmol) and H were added to a Schlenk tube₂O (1.8 mL). The reaction was then stirred at 90 ℃ and sealed in air until complete consumption of the starting material (24 hours reaction time) as monitored by TLC or GC-MS analysis. After the reaction was completed, it was extracted three times with ethyl acetate. Organic layer in Na₂SO₄Dried, solvent filtered and evaporated. The solution was concentrated under reduced pressure and the mixture was purified by flash column chromatography to give the desired product I-8 (78% yield);¹H NMR(400MHz，CDCl₃)δ：8.49(d，J＝8.0Hz，1H)，8.39-8.37(m，1H)， 7.84-7.82(m，1H)，7.59-7.55(m，1H)，7.49-7.42(m，4H)，2.54-2.48(m，1H)， 2.06-2.02(m，1H)，1.69(s，3H)，1.34-1.26(m，8H)，1.22-1.18(m，2H)，1.05-0.93 (m，3H)；¹³C NMR(100MHz，CDCl₃)δ：173.6，149.9，144.1，141.8，131.6，131.4， 127.6，126.6，125.9，125.8，125.5，122.8，119.7，115.7，50.0，48.9，36.4，35.6，33.9， 30.9，28.4，28.3，25.6，25.5；HRMS m/z(ESI)calcd for C₂₄H₂₇N₂O([M+H]⁺) 359.2118，found 359.2112。

example 15

2-Arylbenzimidazole 1a (52.4mg, 0.2mmol), cyclooctane 2f (0.2mL), di-tert-butyl hydroperoxide (DTBP, 35.1mg, 0.24mmol), dodecyl group, were added to a Schlenk tubeSodium sulfate (SDS, 11.5mg, 0.04mmol) and H₂O (1.8 mL). The reaction was then stirred at 90 ℃ and sealed in air until complete consumption of the starting material (24 hours reaction time) as monitored by TLC or GC-MS analysis. After the reaction was completed, it was extracted three times with ethyl acetate. Organic layer in Na₂SO₄Dried, solvent filtered and evaporated. The solution was concentrated under reduced pressure, and the mixture was purified by flash column chromatography to give the desired product I-9 (72% yield);¹H NMR(500MHz，CDCl₃)δ：8.49(d，J＝8.0Hz，1H)，8.38(d，J＝7.5Hz， 1H)，7.83(d，J＝6.5Hz，1H)，7.57(t，J＝7.5Hz，1H)，7.49-7.40(m，4H)，2.53-2.48 (m，1H)，2.03-1.99(m，1H)，1.70(s，3H)，1.43-1.30(m，5H)，1.26-1.15(m，6H)， 1.12-1.01(m，3H)，0.98-0.92(m，1H).¹³C NMR(125MHz，CDCl₃)δ：173.5，149.9， 144.1，141.9，131.6，131.4，127.6，126.6，125.9，125.8，125.5，122.8，119.7，115.7， 49.8，48.7，34.3，32.8，31.2，30.8，27.2(2)，26.0，24.8，24.5；HRMS m/z(ESI)calcd for C₂₅H₂₉N₂O([M+H]⁺)373.2274，found 373.2272。

example 16

2-Arylbenzimidazole 1a (52.4mg, 0.2mmol), cyclododecane 2g (336.6mg, 2mmol), di-tert-butylhydroperoxide (DTBP, 35.1mg, 0.24mmol), sodium dodecyl sulfate (SDS, 11.5mg, 0.04mmol), H, were added to a Schlenk tube₂O (1.8mL) and toluene (0.2mL) and then the reaction was stirred at 90 ℃ and sealed in air until complete consumption of the starting material (24 hours reaction time) as monitored by TLC or GC-MS analysis. After the reaction was completed, it was extracted three times with ethyl acetate. Organic layer in Na₂SO₄Dried, solvent filtered and evaporated. The solution was concentrated under reduced pressure, and the mixture was purified by flash column chromatography to give the target product I-10 (70% yield);¹H NMR(400MHz，CDCl₃)δ： 8.49-8.47(m，1H)，8.38-8.35(m，1H)，7.82-7.80(m，1H)，7.58-7.54(m，1H)， 7.49-7.45(m，2H)，7.44-7.39(m，2H)，2.35-2.30(m，1H)，1.99-1.94(m，1H)，1.77 (s，3H)，1.34-1.25(m，2H)，1.11-0.92(m，15H)，0.82-0.73(m，3H)，0.65-0.46(m， 3H)；¹³C NMR(100MHz，CDCl₃)δ：173.7，149.9，144.1，142.0，131.6，131.4， 127.6，126.7，125.8(2)，125.5，123.1，119.7，115.7，49.7，48.7，30.9，30.5，29.4，28.7， 24.2，23.8，23.2，23.1，23.0，22.7，22.2，22.1，21.5；HRMS m/z(ESI)calcd for C₂₉H₃₇N₂O([M+H]⁺)429.2900，found 429.2892。

example 17

2-Arylbenzimidazole 1a (52.4mg, 0.2mmol), amantadine 2H (302.4mg, 2mmol), di-tert-butyl hydroperoxide (DTBP, 35.1mg, 0.24mmol), sodium dodecyl sulfate (SDS, 11.5mg, 0.04mmol), H, were added to a Schlenk tube₂O (1.8mL) and toluene (0.2mL) and then the reaction was stirred at 90 ℃ and sealed in air until complete consumption of the starting material (24 hours reaction time) as monitored by TLC or GC-MS analysis. After the reaction was completed, it was extracted three times with ethyl acetate. Organic layer in Na₂SO₄Dried, solvent filtered and evaporated. The solution was concentrated under reduced pressure, and the mixture was purified by flash column chromatography to give the target product I-11 (72% yield);¹H NMR(500MHz，CDCl₃)δ： 8.51-8.47(m，1H)，8.41-8.35(m，1H)，7.86-7.82(m，1H)，7.55-7.51(m，2H)， 7.48-7.43(m，3H)，2.51(d，J＝14.5Hz，1H)，2.07(d，J＝14.5Hz，1H)，1.66(s， 3H)，1.63-1.56(m，2H)，1.49-1.40(m，3H)，1.32-1.26(m，4H)，1.16-1.08(m，6H)；¹³C NMR(125MHz，CDCl₃)δ：173.4，149.8，144.1，142.3，131.5，131.1，127.6， 127.5，125.9，125.8，125.5，122.1，119.7，115.9，56.2，46.9，43.5，41.6，36.5，34.2， 33.7，32.3，28.4。

example 18

2-Arylbenzimidazole 1a (52.4mg, 0.2mmol), n-hexane 2i (0.2mL), di-tert-butylhydroperoxide (DTBP, 35.1mg, 0.24mmol), sodium dodecyl sulfate (SDS, 11.5mg, 0.04mmol) and H were added to a Schlenk tube₂O (1.8 mL). The reaction was then stirred at 90 ℃ and sealed in air until complete consumption of the starting material (24 hours reaction time) as monitored by TLC or GC-MS analysis. After the reaction was completed, it was extracted three times with ethyl acetate. Organic layer in Na₂SO₄Dried, solvent filtered and evaporated. The solution was concentrated under reduced pressure and the mixture was purified by flash column chromatography to give the desired products I-12 and I-13 (43% yield, 2: 1, d.r. > 20: 1); 1H NMR (500MHz, CDCl)₃)δ：8.50-8.47(m， 1H)，8.39-8.36(m，1H)，7.82(d，J＝7.5Hz，1H)，7.59-7.55(m，1H)，7.49-7.40(m， 4H)，2.52-2.48(m，0.3H)，2.43-2.35(m，0.7H)，2.18-2.14(m，0.3H)，2.03-1.92(m， 0.7H)，1.77-1.74(m，1H)，1.73-1.70(m，2H)，1.34-1.26(m，1H)，1.17-1.03(m，3H)，0.97-0.84(m，4H)，0.79-0.75(m，1H)，0.65-0.45(m，4H)；13C NMR(125MHz， CDCl₃)δ：173.7，173.5，149.9，149.8，144.1，141.9，141.7，131.6(2)，127.6(2)， 126.7(2)，126.6，125.9(3)，125.8，125.5，123.0，122.9，119.8，115.8，115.7，50.1， 48.8(2)，47.2，46.9，37.7，36.7，35.8，35.7，31.2，30.0，28.7，28.4，26.4，25.8，22.7， 22.5，20.7，19.7，19.1，18.7，14.1，14.0，13.8，10.4，10.0；HRMS m/z(ESI)calcd for C₂₃H₂₇N₂O([M+H]⁺)347.2118，found 347.2114。

Example 19

Adding 2-aryl into Schlenk tubePhenylbenzimidazole Compound 1b (62.2mg, 0.2mmol), cyclohexane 2a (0.2mL), Di-tert-butylhydroperoxide (DTBP, 35.1mg, 0.24mmol), sodium dodecyl sulfate (SDS, 11.5mg, 0.04mmol) and H₂O (1.8 mL). The reaction was then stirred at 90 ℃ and sealed in air until complete consumption of the starting material (24 hours reaction time) as monitored by TLC or GC-MS analysis. After the reaction was completed, it was extracted three times with ethyl acetate. Organic layer in Na₂SO₄Dried, solvent filtered and evaporated. The solution was concentrated under reduced pressure, and the mixture was purified by flash column chromatography to give the desired product I-14 (86% yield);¹H NMR(400MHz，CDCl₃)δ：8.42-8.39(m，1H)， 8.23-8.19(m，1H)，7.70-7.60(m，1H)，7.46-7.42(m，2H)，7.29-7.27(m，1H)，2.54 (s，3H)，2.49-2.44(m，1H)，2.03-1.97(m，1H)，1.65(s，3H)，1.48-1.37(m，3H)， 1.23-1.13(m，2H)，0.96-0.78(m，6H)；¹³C NMR(100MHz，CDCl3)δ：172.8， 148.4，143.4，142.0，137.6，136.2，131.5，128.2，127.3，127.2，126.7，119.2，115.9， 115.2，48.8，48.4，34.9，34.2，32.9，31.7，30.2，25.9，21.9，21.7；HRMS m/z(ESI) calcd for C₂₄H₂₆ClN₂O([M+H]⁺)393.1728，found 393.1722。

example 20

To a Schlenk tube were added 2-arylbenzimidazole compound 1c (66.4mg, 0.2mmol), cyclohexane 2a (0.2mL), di-t-butylhydroperoxide (DTBP, 35.1mg, 0.24mmol), sodium dodecyl sulfate (SDS, 11.5mg, 0.04mmol) and H₂O (1.8 mL). The reaction was then stirred at 90 ℃ and sealed in air until complete consumption of the starting material (24 hours reaction time) as monitored by TLC or GC-MS analysis. After the reaction was completed, it was extracted three times with ethyl acetate. Organic layer in Na₂SO₄Dried, solvent filtered and evaporated. The solution was concentrated under reduced pressure, and the mixture was purified by flash column chromatography to give the desired product I-15 (88% yield)；¹H NMR(500MHz，CDCl₃)δ：8.39-8.36(m，1H)，8.24-8.21(m，1H)，7.69-7.60(m，1H)，7.50-7.45(m，2H)，7.27-7.21(m，1H)，2.53 (s，3H)，2.48-2.44(m，1H)，2.06-2.03(m，1H)，1.66(s，3H)，1.49-1.44(m，1H)，1.38 (s，9H)，1.34-1.22(m，4H)，0.98-0.88(m，3H)，0.85-0.76(m，3H).¹³C NMR(125 MHz，CDCl₃)δ：173.9，154.9，149.2，144.5，141.5，135.7，127.0，126.4，125.6， 124.8，123.4，119.6，119.1，115.2，49.0，48.6，35.2，35.0，34.3，33.2，31.7，31.5，31.2， 26.0，25.9，21.7；HRMS m/z(ESI)calcd for C₂₈H₃₅N₂O([M+H]⁺)415.2744，found 415.2748。

Example 21

To a Schlenk tube were added 2-arylbenzimidazole compound 1d (58.0mg, 0.2mmol), cyclohexane 2a (0.2mL), di-t-butylhydroperoxide (DTBP, 35.1mg, 0.24mmol), sodium dodecyl sulfate (SDS, 11.5mg, 0.04mmol) and H₂O (1.8 mL). The reaction was then stirred at 90 ℃ and sealed in air until complete consumption of the starting material (24 hours reaction time) as monitored by TLC or GC-MS analysis. After the reaction was completed, it was extracted three times with ethyl acetate. Organic layer in Na₂SO₄Dried, solvent filtered and evaporated. The solution was concentrated under reduced pressure, and the mixture was purified by flash column chromatography to give the target product I-16 (89% yield);¹H NMR(400MHz，CDCl₃)δ：8.47-8.44(m，1H)，8.17(s， 1H)，7.59(s，1H)，7.56-7.52(m，1H)，7.47-7.43(m，2H)，2.50-2.44(m，1H)，2.43(s， 3H)，2.41(s，3H)，2.07-2.02(m，1H)，1.65(s，3H)，1.50-1.36(m，3H)，1.26-1.17(m， 2H)，0.97-0.77(m，6H)；¹³C NMR(100MHz，CDCl₃)δ：173.5，149.1，142.5，141.6， 134.8(2)，131.2，129.8，127.5，126.5，125.7，122.8，119.9，116.1，48.8，48.2，34.9， 34.3，32.9，31.8，26.0，25.9(2)，20.5(2)。

example 22

To a Schlenk tube were added 2-arylbenzimidazole compound 1e (66.0mg, 0.2mmol), cyclohexane 2a (0.2mL), di-t-butylhydroperoxide (DTBP, 35.1mg, 0.24mmol), sodium dodecyl sulfate (SDS, 11.5mg, 0.04mmol) and H₂O (1.8 mL). The reaction was then stirred at 90 ℃ and sealed in air until complete consumption of the starting material (24 hours reaction time) as monitored by TLC or GC-MS analysis. After the reaction was completed, it was extracted three times with ethyl acetate. Organic layer in Na₂SO₄Dried, solvent filtered and evaporated. The solution was concentrated under reduced pressure, and the mixture was purified by flash column chromatography to give the desired product I-17 (81% yield); 1H NMR (400MHz, CDCl)₃)δ：8.51(s，1H)，8.45-8.43(m， 1H)，7.89(s，1H)，7.63-7.59(m，1H)，7.51-7.46(m，2H)，2.49-2.44(m，1H)， 2.09-2.04(m，1H)，1.67(s，3H)，1.49-1.38(m，3H)，1.27-1.23(m，2H)，0.96-0.77 (m，6H)；¹³C NMR(125MHz，CDCl₃)δ：173.5，149.9，141.9，131.7，131.5，127.6， 126.6，126.0，125.9，125.5，122.6，119.8，115.8，48.9，48.4，35.0，34.3，33.0，31.8， 26.0(2)，25.9。

Example 23

To a Schlenk tube were added 2-arylbenzimidazole compound 1f (58.4mg, 0.2mmol), cyclohexane 2a (0.2mL), di-t-butylhydroperoxide (DTBP, 35.1mg, 0.24mmol), sodium dodecyl sulfate (SDS, 11.5mg, 0.04mmol) and H₂O (1.8 mL). The reaction was then stirred at 90 ℃ and sealed in air until complete consumption of the starting material (24 hours reaction time) as monitored by TLC or GC-MS analysis. After the reaction was completed, it was extracted three times with ethyl acetate. Organic layer in Na₂SO₄Dried, solvent filtered and evaporated. The solution was concentrated under reduced pressure, and the mixture was purified by flash column chromatography to give the desired product I-18 (88% yield);¹H NMR(500MHz，CDCl₃)δ：8.43(d，J＝8.5Hz，1H)， 8.35(d，J＝7.5Hz，1H)，7.78(d，J＝7.5Hz，1H)，7.43-7.37(m，2H)，7.03(d，J＝ 8.5Hz，1H)，6.93(s，1H)，3.91(s，3H)，2.49-2.45(m，1H)，2.02-1.99(m，1H)，1.65 (s，3H)，1.49-1.38(m，3H)，1.29-1.16(m，2H)，1.05-0.93(m，3H)，0.86-0.78(m， 3H)；¹³C NMR(125MHz，CDCl₃)δ：173.5，162.4，150.0，144.2，144.0，131.4， 127.9，125.7，125.0，119.3，115.6(2)，113.3，112.2，55.5，49.0，48.5，34.9，34.3，33.0， 31.9，26.0，25.9(2)。

example 24

To a Schlenk tube were added 1g (55.2mg, 0.2mmol) of a 2-arylbenzimidazole compound, cyclohexane 2a (0.2mL), di-t-butylhydroperoxide (DTBP, 35.1mg, 0.24mmol), sodium dodecylsulfate (SDS, 11.5mg, 0.04mmol) and H₂O (1.8 mL). The reaction was then stirred at 90 ℃ and sealed in air until complete consumption of the starting material (24 hours reaction time) as monitored by TLC or GC-MS analysis. After the reaction was completed, it was extracted three times with ethyl acetate. Organic layer in Na₂SO₄Dried, solvent filtered and evaporated. The solution was concentrated under reduced pressure, and the mixture was purified by flash column chromatography to give the desired product I-19 (87% yield);¹H NMR(400MHz，CDCl₃)δ：8.38-8.35(m，2H)， 7.82-7.80(m，1H)，7.46-7.40(m，2H)，7.31-7.28(m，1H)，7.24(s，1H)，2.48(s，3H)， 2.47-2.43(m，1H)，2.06-2.01(m，1H)，1.65(s，3H)，1.47-1.40(m，3H)，1.28-1.25 (m，3H)，0.98-0.92(m，2H)，0.83-0.78(m，3H).¹³C NMR(100MHz，CDCl₃)δ： 173.7，150.1，144.1，142.1，141.9，131.4，128.7，126.9，125.9，125.7，125.2，119.9， 119.5，115.7，48.9，48.2，34.9，34.3，32.9，31.7，26.0，25.9(2)，22.0。

example 25

A Schlenk flask was charged with 2-arylbenzimidazole compound represented by formula 1H (53.2mg, 0.2mmol), cyclohexane represented by formula 2a (0.2mL), di-tert-butylhydroperoxide (DTBP, 35.1mg, 0.24mmol), sodium dodecyl sulfate (SDS, 11.5mg, 0.04mmol), and H₂O (1.8mL), then the reactor was stirred at 90 ℃ under an air atmosphere for reaction, and the progress of the reaction was monitored by TLC or GC-MS until the disappearance of the starting material (reaction time 24 hours). After completion of the reaction, the reaction solution was extracted 3 times with ethyl acetate. Drying the organic phase with anhydrous sodium sulfate, filtering, concentrating under reduced pressure to remove solvent, and separating the residue by column chromatography (eluting solvent is ethyl acetate/n-hexane) to obtain target product I-20 (78% yield);¹H NMR(400 MHz，CDCl₃)δ：8.52-8.48(m，1H)，8.39-8.35(m，1H)，7.81(d，J＝6.4Hz，1H)， 7.46-7.41(m，2H)，7.20-7.14(m，2H)，2.52-2.47(m，1H)，2.01-1.97(m，1H)，1.66 (s，3H)，1.49-1.39(m，3H)，1.22-1.15(m，2H)，1.04-0.93(m，2H)，0.88-0.81(m， 4H)；¹³C NMR(100MHz，CDCl₃)δ：172.9，164.9(d，J_C-F＝250.9Hz)，149.0， 144.8，144.0，131.3，128.5(d，J_C-F＝9.1Hz)，125.8(d，J_C-F＝38.1Hz)，119.7，119.1，115.8(2)，115.6，113.5(d，J_C-F＝22.8Hz)，48.8，48.5，34.9，34.2，32.9，31.4， 30.2，25.9(2)；¹⁹F NMR(471MHz，CDCl₃)δ：-106.6。

example 26

A Schlenk flask was charged with a 2-arylbenzimidazole compound represented by formula 1i (59.2mg, 0.2mmol), cyclohexane represented by formula 2a (0.2mL),di-tert-butyl hydroperoxide (DTBP, 35.1mg, 0.24mmol), sodium dodecyl sulfate (SDS, 11.5mg, 0.04mmol) and H₂O (1.8mL), then the reactor was stirred at 90 ℃ under an air atmosphere for reaction, and the progress of the reaction was monitored by TLC or GC-MS until the disappearance of the starting material (reaction time 24 hours). After completion of the reaction, the reaction solution was extracted 3 times with ethyl acetate. Drying the organic phase with anhydrous sodium sulfate, filtering, concentrating under reduced pressure to remove solvent, and separating the residue by column chromatography (eluting solvent is ethyl acetate/n-hexane) to obtain target product I-21 (77% yield);¹H NMR(400 MHz，CDCl₃)δ：8.44-8.42(m，1H)，8.37(d，J＝7.2Hz，1H)，7.82(d，J＝6.8Hz， 1H)，7.47-7.43(m，4H)，2.51-2.46(m，1H)，2.03-1.98(m，1H)，1.66(s，3H)， 1.49-1.39(m，3H)，1.30-1.25(m，1H)，1.20-1.12(m，1H)，1.01-0.94(m，3H)， 0.85-0.81(m，3H)；¹³C NMR(100MHz，CDCl₃)δ：172.7，148.9，144.0，143.6， 137.9，131.4，128.2，127.4，126.7，126.0，125.7，121.2，119.8，115.8，48.8，48.4， 34.9，34.2，32.9，31.6，31.4，25.9(2)。

example 27

A Schlenk flask was charged with a 2-arylbenzimidazole compound represented by formula 1j (68.0mg, 0.2mmol), cyclohexane represented by formula 2a (0.2mL), di-tert-butylhydroperoxide (DTBP, 35.1mg, 0.24mmol), sodium dodecyl sulfate (SDS, 11.5mg, 0.04mmol), and H₂O (1.8mL), then the reactor was stirred at 90 ℃ under an air atmosphere for reaction, and the progress of the reaction was monitored by TLC or GC-MS until the disappearance of the starting material (reaction time 24 hours). After completion of the reaction, the reaction solution was extracted 3 times with ethyl acetate. Drying the organic phase with anhydrous sodium sulfate, filtering, concentrating under reduced pressure to remove solvent, and separating the residue by column chromatography (eluting solvent is ethyl acetate/n-hexane) to obtain target product I-22 (77% yield);¹H NMR(400 MHz，CDCl₃)δ：8.37-8.34(m，2H)，7.83-7.81(m，1H)，7.63-7.59(m，2H)， 7.45-7.43(m，2H)，2.50-2.45(m，1H)，2.03-1.98(m，1H)，1.66(s，3H)，1.49-1.39 (m，3H)，1.26-1.16(m，2H)，1.01-0.79(m，6H)；¹³C NMR(100MHz，CDCl₃)δ： 172.6，148.9，144.0，143.8，131.4，131.1，129.7，127.4，126.3，126.0，125.8，121.6， 119.8，115.8，48.9，48.4，34.9，34.2，32.9，31.6，31.4，25.9(2)。

example 28

A Schlenk flask was charged with a 2-arylbenzimidazole compound represented by formula 1k (57.4mg, 0.2mmol), cyclohexane represented by formula 2a (0.2mL), di-tert-butylhydroperoxide (DTBP, 35.1mg, 0.24mmol), sodium dodecyl sulfate (SDS, 11.5mg, 0.04mmol), and H₂O (1.8mL), then the reactor was stirred at 90 ℃ under an air atmosphere for reaction, and the progress of the reaction was monitored by TLC or GC-MS until the disappearance of the starting material (reaction time 24 hours). After completion of the reaction, the reaction solution was extracted 3 times with ethyl acetate. Drying the organic phase with anhydrous sodium sulfate, filtering, concentrating under reduced pressure to remove the solvent, and separating the residue by column chromatography (eluting solvent is ethyl acetate/n-hexane) to obtain target product I-23 (72% yield);¹H NMR(400 MHz，CDCl₃)δ：8.60(d，J＝8.4Hz，1H)，8.40-8.37(m，1H)，7.87-7.85(m，1H)， 7.78-7.32(m，2H)，7.51-7.48(m，2H)，2.57-2.51(m，1H)，2.07-2.02(m，1H)，1.69 (s，3H)，1.50-1.40(m，3H)，1.26-1.10(m，2H)，0.98-0.81(m，6H)；¹³C NMR(100 MHz，CDCl₃)δ：172.1，147.7，144.0，142.7，131.4，130.8，130.7，126.7，126.6(2)， 126.3，120.3，118.2，115.9，114.8，48.7，48.4，35.0，34.2，32.8，31.6，25.9，25.8(2)。

example 29

To a Schlenk flask was added a solution of the formula 1l2-Arylbenzimidazole compound (58.4mg, 0.2mmol), cyclohexane represented by formula 2a (0.2mL), di-t-butylhydroperoxide (DTBP, 35.1mg, 0.24mmol), sodium dodecyl sulfate (SDS, 11.5mg, 0.04mmol) and H₂O (1.8mL), then the reactor was stirred at 90 ℃ under an air atmosphere for reaction, and the progress of the reaction was monitored by TLC or GC-MS until the disappearance of the starting material (reaction time 24 hours). After completion of the reaction, the reaction solution was extracted 3 times with ethyl acetate. Drying the organic phase with anhydrous sodium sulfate, filtering, concentrating under reduced pressure to remove solvent, and separating the residue by column chromatography (eluting solvent is ethyl acetate/n-hexane) to obtain target products 1-24 and 1-25 (83% yield, 6.5: 1);¹H NMR(500MHz，CDCl₃)δ：8.39(d，J＝7.0Hz，1H)，7.94(d，J＝2.5Hz，1H)， 7.84(d，J＝7.0Hz，1H)，7.47-7.43(m，2H)，7.35(d，J＝9.0Hz，1H)，7.15-7.09(m， 1H)，3.97(s，2.6H)，3.93(s，0.4H)，2.47-2.43(m，1H)，2.03-1.99(m，1H)，1.75(s， 0.4H)，1.63(s，2.6H)，1.48-1.38(m，3H)，1.23-1.16(m，2H)，1.01-0.92(m，3H)， 0.84-0.76(m，3H)；¹³C NMR(125MHz，CDCl₃)δ：174.6，173.8，158.7，157.6， 150.0，149.9，144.2，144.0，134.2，131.5(2)，128.8，127.9，125.8，125.5，125.4， 124.2，123.5，120.4，119.7，118.7，115.9，115.8，114.1，107.7，55.7，55.5，48.9，48.7， 47.9，45.5，35.7，34.9，34.3，34.0，32.9，31.8，31.4，31，27.2，26.0(2)，25.9(3)。

example 30

A Schlenk flask was charged with a 2-arylbenzimidazole compound represented by formula 1m (55.2mg, 0.2mmol), cyclohexane represented by formula 2a (0.2mL), di-tert-butylhydroperoxide (DTBP, 35.1mg, 0.24mmol), sodium dodecyl sulfate (SDS, 11.5mg, 0.04mmol), and H₂O (1.8mL), then the reactor was stirred at 90 ℃ under an air atmosphere for reaction, and the progress of the reaction was monitored by TLC or GC-MS until the disappearance of the starting material (reaction time 24 hours). After the reaction is completed, the reaction solution is usedThe ethyl acetate was extracted 3 times. Drying the organic phase with anhydrous sodium sulfate, filtering, concentrating under reduced pressure to remove solvent, and separating the residue by column chromatography (eluting solvent is ethyl acetate/n-hexane) to obtain target product I-26 (80% yield);¹H NMR(500 MHz，CDCl₃)δ：8.42-8.40(m，1H)，7.85-7.83(m，1H)，7.43-7.39(m，3H)， 7.33-7.29(m，2H)，3.07(s，3H)，2.49-2.45(m，1H)，2.05-2.02(m，1H)，1.65(s，3H)， 1.47-1.34(m，4H)，1.20-1.15(m，1H)，1.02-0.92(m，3H)，0.84-0.78(m，3H)；¹³C NMR(125MHz，CDCl₃)δ：173.7，150.1，144.2，143.0，139.7，130.8，130.7，130.3， 125.5(2)，124.5，121.3，120.0，115.8，49.2，48.2，34.8，34.3，32.9，32.2，26.0(2)， 25.9，24.7。

example 31

A Schlenk flask was charged with a 2-arylbenzimidazole compound represented by formula 1n (59.6mg, 0.2mmol), cyclohexane represented by formula 2a (0.2mL), di-tert-butylhydroperoxide (DTBP, 35.1mg, 0.24mmol), sodium dodecyl sulfate (SDS, 11.5mg, 0.04mmol), and H₂O (1.8mL), then the reactor was stirred at 90 ℃ under an air atmosphere for reaction, and the progress of the reaction was monitored by TLC or GC-MS until the disappearance of the starting material (reaction time 24 hours). After completion of the reaction, the reaction solution was extracted 3 times with ethyl acetate. Drying the organic phase with anhydrous sodium sulfate, filtering, concentrating under reduced pressure to remove solvent, and separating the residue by column chromatography (eluting solvent is ethyl acetate/n-hexane) to obtain target products I-27 and I-28 (78% yield, 5: 1);¹H NMR(400MHz，CDCl₃)δ：8.66-8.64(m，1H)，8.55-8.52(m，1H)，8.43-8.41(m， 1H)，7.97-7.93(m，2H)，7.88-7.86(m，1H)，7.60-7.57(m，2H)，7.48-7.45(m，2H)， 2.92-2.87(m，1H)，2.77-2.72(m，1H)，2.05(s，2.5H)，1.77(s，0.5H)，1.20-1.05(m， 4H)，0.89-0.64(m，7H)；¹³C NMR(100MHz，CDCl₃)δ：174.9，173.5，150.3，149.9， 144.4，144.2，138.1，138.0，134.8，132.1，131.7，131.3，130.9，130.3，129.7，128.8， 128.0，127.8，127.0，126.6，126.0(2)，125.6，125.5，122.6，121.3，120.6，119.8， 119.7，115.9，50.5，49.6，48.5，48.4，35.4，34.9，34.4，33.7，33.0，32.8，32.4，29.6， 26.0，25.9(2)，25.8，25.7。

example 32

A Schlenk flask was charged with a 2-arylbenzimidazole compound represented by formula 1o (67.6mg, 0.2mmol), cyclohexane represented by formula 2a (0.2mL), di-tert-butylhydroperoxide (DTBP, 35.1mg, 0.24mmol), sodium dodecyl sulfate (SDS, 11.5mg, 0.04mmol), and H₂O (1.8mL), then the reactor was stirred at 90 ℃ under an air atmosphere for reaction, and the progress of the reaction was monitored by TLC or GC-MS until the disappearance of the starting material (reaction time 24 hours). After completion of the reaction, the reaction solution was extracted 3 times with ethyl acetate. Drying the organic phase with anhydrous sodium sulfate, filtering, concentrating under reduced pressure to remove solvent, and separating the residue by column chromatography (eluting solvent is ethyl acetate/n-hexane) to obtain target product I-29 (70% yield);¹H NMR(400 MHz，CDCl₃)δ：8.37-8.34(m，1H)，8.28-8.26(m，1H)，7.68-7.55(m，3H)， 7.49-7.45(m，1H)，7.39-7.37(m，2H)，6.82(t，J＝7.2Hz，1H)，6.73(t，J＝7.6Hz，2H)，6.46-6.42(m，2H)，3.50(d，J＝12.8Hz，1H)，3.10(d，J＝12.8Hz，1H)，2.74-2.69(m，1H)，2.30-2.26(m，1H)，1.44-1.40(m，2H)，1.25-1.16(m，4H)， 1.01-0.74(m，5H)；¹³C NMR(100MHz，CDCl₃)δ：172.4，149.4，143.6，139.2， 134.3，131.3，130.9，128.9，127.7，127.6，127.0，125.7，125.6，125.3，124.5，124.0， 119.5，115.5，54.7，52.6，46.6，34.9，34.4，32.8，31.5，30.2，26.0；HRMS m/z(ESI) calcd for C₂₉H₂₉N₂O([M+H]⁺)421.2274，found 421.2270。

example 33

A Schlenk flask was charged with a 2-arylbenzimidazole compound represented by formula 1p (67.4mg, 0.2mmol), cyclohexane represented by formula 2a (0.2mL), di-tert-butylhydroperoxide (DTBP, 35.1mg, 0.24mmol), sodium dodecyl sulfate (SDS, 11.5mg, 0.04mmol), and H₂O (1.8mL), then the reactor was stirred at 90 ℃ under an air atmosphere for reaction, and the progress of the reaction was monitored by TLC or GC-MS until the disappearance of the starting material (reaction time 24 hours). After completion of the reaction, the reaction solution was extracted 3 times with ethyl acetate. Drying the organic phase with anhydrous sodium sulfate, filtering, concentrating under reduced pressure to remove solvent, and separating the residue by column chromatography (eluting solvent is ethyl acetate/n-hexane) to obtain target product I-30 (89% yield);¹H NMR(400 MHz，CDCl₃)δ：8.67(d，J＝8.4Hz，1H)，7.56-7.48(m，5H)，7.44-7.36(m，3H)， 7.32-7.27(m，2H)，7.25-7.22(m，1H)，6.99(t，J＝7.8Hz，1H)，2.46-2.40(m，1H)， 1.98-1.94(m，1H)，1.68(s，3H)，1.48-1.42(m，3H)，1.33-1.26(m，2H)，1.14-1.08 (m，1H)，1.00-0.94(m，2H)，0.87-0.80(m，3H)；¹³C NMR(100MHz，CDCl₃)δ： 173.7，139.2，134.3，132.3，130.3，129.8，129.3，128.2，128.1，126.7，126.4，125.8， 125.3，125.2，124.5，120.0，119.4，116.8，49.4，47.7，34.9，34.5，33.2，30.8，26.2， 26.1。

example 34

A Schlenk flask was charged with a 2-arylbenzimidazole compound represented by formula 1q (61.8mg, 0.2mmol), cyclohexane represented by formula 2a (0.2mL), di-tert-butylhydroperoxide (DTBP, 35.1mg, 0.24mmol), sodium dodecyl sulfate (SDS, 11.5mg, 0.04mmol), and H₂O (1.8mL), then the reactor was stirred at 90 ℃ under an air atmosphere for reaction, and the progress of the reaction was monitored by TLC or GC-MS until the disappearance of the starting material (reaction time 24 hours). After the reaction is completed, the reaction solution is added,the reaction solution was extracted 3 times with ethyl acetate. Drying the organic phase with anhydrous sodium sulfate, filtering, concentrating under reduced pressure to remove the solvent, and separating the residue by column chromatography (eluting solvent is ethyl acetate/n-hexane) to obtain target product I-31 (78% yield);¹H NMR(400 MHz，CDCl₃)δ：8.60(d，J＝7.2Hz，1H)，7.95(d，J＝8.8Hz，1H)，7.61-7.59(m， 1H)，7.42-7.34(m，4H)，2.64(s，3H)，2.44-2.39(m，1H)，1.92-1.87(，1H)，1.61(s， 3H)，1.48-1.37(m，3H)，1.25-1.19(m，2H)，0.99-0.76(m，6H)；¹³C NMR(100MHz， CDCl₃)δ：173.6，142.6，137.7，134.9，133.7，129.7，129.1，128.5，128.4，128.1， 127.4，127.2，123.3，118.9，114.6，45.4，44.9，35.7，31.4，30.6，27.2，27.0，25.9，24.7，23.5。

example 35

A Schlenk flask was charged with a 2-arylbenzimidazole compound represented by formula 1a (52.4mg, 0.2mmol), toluene (0.2mL) represented by formula 3a, di-tert-butylhydroperoxide (DTBP, 35.1mg, 0.24mmol), sodium dodecyl sulfate (SDS, 11.5mg, 0.04mmol), and H₂O (1.8mL), then the reactor was stirred at 90 ℃ under an air atmosphere for reaction, and the progress of the reaction was monitored by TLC or GC-MS until the disappearance of the starting material (reaction time 24 hours). After completion of the reaction, the reaction solution was extracted 3 times with ethyl acetate. Drying the organic phase with anhydrous sodium sulfate, filtering, concentrating under reduced pressure to remove the solvent, and separating the residue by column chromatography (the eluting solvent is ethyl acetate/n-hexane) to obtain the target product II-1 (81% yield);¹H NMR(400 MHz，CDCl₃)δ：8.52(d，J＝8.0Hz，1H)，8.33-8.31(m，1H)，7.83-7.81(m，1H)， 7.64-7.60(m，1H)，7.54-7.50(m，2H)，7.46-7.39(m，2H)，7.10(t，J＝8.0Hz，2H)， 7.01(t，J＝6.0Hz，1H)，6.94-6.92(m，2H)，2.86-2.78(m，1H)，2.35-2.17(m，3H)， 1.75(s，3H)；¹³C NMR(100MHz，CDCl₃)δ：173.0，149.8，144.0，141.4，140.3， 132.0，131.3，128.3，128.2，127.9，126.1，126.0(2)，125.9，125.5，123.2，119.7， 115.7，49.3，44.2，31.6，29.5。

example 36

A Schlenk flask was charged with a 2-arylbenzimidazole compound represented by formula 1a (52.4mg, 0.2mmol), mesitylene represented by formula 3b (0.2mL), di-t-butylhydroperoxide (DTBP, 35.1mg, 0.24mmol), sodium dodecyl sulfate (SDS, 11.5mg, 0.04mm0l), and H₂O (1.8mL), then the reactor was stirred at 90 ℃ under an air atmosphere for reaction, and the progress of the reaction was monitored by TLC or GC-MS until the disappearance of the starting material (reaction time 24 hours). After completion of the reaction, the reaction solution was extracted 3 times with ethyl acetate. Drying the organic phase with anhydrous sodium sulfate, filtering, concentrating under reduced pressure to remove the solvent, and separating the residue by column chromatography (the eluting solvent is ethyl acetate/n-hexane) to obtain the target product H-2 (83% yield);¹H NMR (400MHz，CDCl₃)δ：8.51(d，J＝8.0Hz，1H)，8.29(d，J＝7.6Hz，1H)，7.80(d，J＝ 7.6Hz，1H)，7.64-7.60(m，1H)，7.54-7.49(m，2H)，7.45-7.37(m，2H)，6.56(s，1H)， 6.49(s，2H)，2.85-2.78(m，1H)，2.32-2.26(m，1H)，2.23-2.14(m，2H)，2.11(s，6H)，1.73(s，3H)；¹³C NMR(100MHz，CDCl₃)δ：173.0，149.7，144.0，141.4，139.7， 137.7，131.9，131.3，127.8，127.7，126.2，126.1，125.9，125.8，125.4，123.3，119.7， 115.7，49.1，44.2，31.5，29.6，21.1；HRMS m/z(ESI)calcd for C₂₆H₂₅N₂O([M+H]⁺) 381.1961，found 381.1953。

example 37

To a Schlenk flask was added a 2-arylbenzimidazole compound represented by formula 1a (52.4mg, 0.2mmol), p-chlorobenzoyl represented by formula 3cBenzene (0.2mL), di-tert-butyl hydroperoxide (DTBP, 35.1mg, 0.24mmol), sodium dodecyl sulfate (SDS, 11.5mg, 0.04mmol) and H₂O (1.8mL), then the reactor was stirred at 90 ℃ under an air atmosphere for reaction, and the progress of the reaction was monitored by TLC or GC-MS until the disappearance of the starting material (reaction time 24 hours). After completion of the reaction, the reaction solution was extracted 3 times with ethyl acetate. Drying the organic phase with anhydrous sodium sulfate, filtering, concentrating under reduced pressure to remove the solvent, and separating the residue by column chromatography (eluting solvent is ethyl acetate/n-hexane) to obtain target product II-3 (76% yield);¹H NMR (400MHz，CDCl₃)δ：8.53-8.51(m，1H)，8.30-8.27(m，1H)，7.83-7.81(m，1H)， 7.65-7.61(m，1H)，7.55-7.51(m，2H)，7.45-7.40(m，2H)，7.04-7.02(m，2H)， 6.85-6.82(m，2H)，2.83-2.76(m，1H)，2.33-2.26(m，1H)，2.24-2.18(m，2H)，1.75 (s，3H)；¹³C NMR(100MHz，CDCl₃)δ：172.9，149.6，144.0，141.1，138.5，132.0， 131.9，131.2，129.5，128.3，127.9，126.0(3)，125.6，123.2，119.8，115.7，49.1，44.0， 31.0，29.6。

example 38

A Schlenk flask was charged with a 2-arylbenzimidazole compound represented by formula 1r (62.0mg, 0.2mmol), toluene (0.2mL) represented by formula 2a, di-tert-butylhydroperoxide (DTBP, 35.1mg, 0.24mmol), sodium dodecyl sulfate (SDS, 11.5mg, 0.04mmol), and H₂O (1.8mL), then the reactor was stirred at 90 ℃ under an air atmosphere for reaction, and the progress of the reaction was monitored by TLC or GC-MS until the disappearance of the starting material (reaction time 24 hours). After completion of the reaction, the reaction solution was extracted 3 times with ethyl acetate. Drying the organic phase with anhydrous sodium sulfate, filtering, concentrating under reduced pressure to remove solvent, and separating the residue by column chromatography (eluting solvent is ethyl acetate/n-hexane) to obtain target products II-4 and II-5 (80% yield, 1.5: 1);¹H NMR(400MHz，CDCl₃)δ：8.43-8.40(m，1H)，8.17-8.13(m，1H)， 7.69-7.59(m，1H)，7.50-7.46(m，2H)，7.26-7.21(m，1H)，7.13-7.09(m，2H)， 7.04-7.00(m，1H)，6.93(t，J＝5.8Hz，2H)，2.83-2.76(m，1H)，2.53(s，1.2H)，2.52 (s，1.8H)，2.28-2.19(m，3H)，1.74(s，3H)；¹³C NMR(100MHz，CDCl₃)δ：172.3， 172.0，148.8，148.3，144.3，143.0，142.0，139.9(2)，138.0，137.9，136.2，136.1， 131.4，128.4，128.3，128.2，127.3，127.2(2)，127.0，126.3(2)，126.1(2)，122.0， 131.9，119.8，119.3，115.9，115.2，49.3，49.2，44.2，44.1，31.6，29.7，29.3，21.9，21.7； HRMS m/z(ESI)calcd for C₂₅H₂₂ClN₂O([M+H]⁺)401.1415，found 401.1411。

example 39

To a Schlenk flask were added a 2-arylbenzimidazole compound represented by formula 1s (67.4mg, 0.2mmol), toluene represented by formula 2a (0.2mL), di-t-butylhydroperoxide (DTBP, 35.1mg, 0.24mmol), sodium dodecyl sulfate (SDS, 11.5mg, 0.04mmol) and H₂O (1.8mL), then the reactor was stirred at 90 ℃ under an air atmosphere for reaction, and the progress of the reaction was monitored by TLC or GC-MS until the disappearance of the starting material (reaction time 24 hours). After completion of the reaction, the reaction solution was extracted 3 times with ethyl acetate. Drying the organic phase with anhydrous sodium sulfate, filtering, concentrating under reduced pressure to remove the solvent, and separating the residue by column chromatography (the eluting solvent is ethyl acetate/n-hexane) to obtain the target product H-6 (83% yield);¹H NMR(400MHz， CDCl₃)δ：8.66(d，J＝8.4Hz，1H)，7.58-7.49(m，5H)，7.47-7.39(m，3H)， 7.33-7.28(m，3H)，7.16(t，J＝7.2Hz，2H)，7.09-7.02(m，4H)，2.79-2.72(m，1H)， 2.42-2.37(m，1H)，2.30-2.21(m，2H)，1.75(s，3H)；¹³C NMR(100MHz，CDCl₃)δ： 173.1，141.3，138.7，134.2，132.3130.3，129.7，129.3，128.6，128.3(2)，128.1， 126.7，126.1，125.9，125.7，125.4，124.6，120.2，119.4，116.7，48.7，44.5，31.6，28.9； HRMS m/z(ESI)calcd for C₃₁H₂₆NO([M+H]⁺)428.2009，found 428.2007。

example 40 reaction mechanism control experiment

To further verify the mechanism of this reaction, the following three sets of control experiments were performed. When 3.0 equivalents of 2, 2, 6, 6-tetramethylpiperidine-1-oxyl (TEMPO) or Butylhydroxytoluene (BHT) or 1, 1-Diphenylethylene (DPE) as a radical scavenger were added to the reaction of example 1, the process was completely inhibited and Nuclear Magnetic Resonance (NMR) analysis could detect the product III-1 in which TEMPO binds to cyclohexyl radicals. The above results indicate that the reaction involves a free radical process.

It is understood that the possible reaction mechanism of the present invention can be derived as shown in the following formula:

the embodiments described above are only preferred embodiments of the invention and are not exhaustive of the possible implementations of the invention. Any obvious modifications to the above would be obvious to those of ordinary skill in the art, but would not bring the invention so modified beyond the spirit and scope of the present invention.

Claims

1. Non-activated alkane C (sp) in aqueous phase metal-free system³) -H-functional initiated radical cyclisation of 2-arylbenzimidazoles, characterised in that it comprises the following steps:

adding a 2-aryl benzimidazole compound shown in a formula 1, a naphthenic hydrocarbon compound shown in a formula 2 or a toluene compound shown in a formula 3, an oxidant, a phase transfer agent and a solvent into a reactor, placing the reactor at a certain temperature, stirring for reaction, monitoring the reaction process by TLC or GC until the raw materials react completely, and carrying out aftertreatment to obtain a benzimidazolyl isoquinolone compound shown in a formula I or a formula II; the reaction formula is as follows:

R⁴is selected from C₁-C₁₀Alkyl radical, C₆-C₂₀An aryl group;

is represented by C₃-C₁₂A cycloalkyl group;

R⁵selected from hydrogen, halogen, C₁-C₁₀An alkyl group;

wherein the substituted or unsubstituted substituents are selected from halogen, C₁-C₁₀Alkyl radical, C₁-C₁₀Alkoxy radical, C₆-C₂₀An aryl group;

the oxidant is selected from potassium persulfate (K)₂S₂O₈) Any one or a mixture of more of di-tert-butyl peroxide (DTBP), tert-butyl peroxide (TBHP), dibenzoyl peroxide (BPO) and tert-butyl peroxybenzoate (TBPB).

2. The method of claim 1, wherein R is¹Selected from hydrogen, halogen, C₁-C₆An alkyl group;

R²selected from hydrogen, halogen, cyano, and,C₁-C₆Alkyl, substituted or unsubstituted C₆-C₁₀An aryl group;

R⁴is selected from C₁-C₆Alkyl radical, C₆-C₁₂An aryl group;

is represented by C₃-C₁₂A cycloalkyl group;

R⁵selected from hydrogen, halogen, C₁-C₆An alkyl group;

3. The method of claim 2, wherein R is¹Selected from hydrogen, methyl, chlorine;

R²selected from hydrogen, methyl, methoxy, tert-butyl, fluoro, chloro, bromo, cyano, naphthyl;

R³selected from methyl, benzyl;

R⁴selected from methyl, phenyl;

R⁵selected from hydrogen, methyl, chlorine.

4. A process according to any one of claims 1 to 3, wherein the oxidant is selected from potassium persulphate (K)₂S₂O₈) Di-tert-butyl hydroperoxide (DTBP), tert-butyl peroxide (TBHP), peroxylAny one or a mixture of dibenzoyl (BPO) and tert-butyl peroxybenzoate (TBPB), and is preferably di-tert-butyl hydroperoxide (DTBP).

5. The process according to claims 1 to 4, wherein the di-tert-butyl hydroperoxide (DTBP) is used in an amount of 1.2 to 2.0 molar equivalents, preferably 1.2 molar equivalents.

6. A method according to any one of claims 1 to 5, characterised in that the defined temperature is 80-100 ℃, preferably 90 ℃.

7. The method according to any one of claims 1 to 6, wherein the solvent is used in a ratio selected from H₂O/cyclohexane 1.5mL/0.5mL-1.9mL/0.1mL, preferably H₂O/cyclohexane was 1.8mL/0.2 mL.

8. The method according to any of claims 1-7, characterized in that the post-processing operation is as follows: extracting the reaction solution after the reaction is finished with ethyl acetate, drying an organic phase with anhydrous sodium sulfate, filtering, concentrating under reduced pressure to remove a solvent, and separating the residue by column chromatography, wherein the elution solvent is: ethyl acetate/n-hexane to obtain the benzimidazol isoquinolinone compound shown in the formula I or the formula II.