Method for synthesizing benzimidazobenzothiazole compound

Abstract

The invention provides a method for synthesizing a benzimidazobenzothiazole compound, and belongs to the technical field of fine chemical synthesis. The preparation method comprises the following steps: mixing a 2-mercapto benzimidazole compound, fluoride, alkali, an additive, a molecular sieve and dichloromethane, then adding a benzyne precursor into the mixture, and synthesizing the benzimidazobenzothiazole compound at 110 DEG C; the method has the advantages of simplicity, convenience, rapidness, no need of transition metal catalysis, wide substrate range, cheap and easily available fluorine source, no environmental pollution and the like; the method has the advantages of being simple in process, good in universality and the like, the yield of the synthesized benzimidazobenzothiazole compound is as high as 90%, and the method has extremely high industrial popularization value.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of fine chemical synthesis, and particularly relates to a method for synthesizing a benzimidazolobenzothiazole compound. BACKGROUND

[0002] The benzimidazole skeleton is an important core skeleton of many compounds and drugs, which can act on different targets and thus produce different pharmacological properties, playing a crucial role in modern drugs or other aspects. Compounds with benzimidazole and benzothiazole functional groups are an important class of benzopentaheterocyclic compounds, which not only have good biological activity, fluorescence characteristics and coordination effect, but also can be used as metal corrosion inhibitors and metal ion capture agents. Moreover, such compounds are important intermediates in organic synthesis, and have important roles in the fields of industry, agriculture and biological medicine. There are also review documents reported on the synthesis and application research of such compounds at home and abroad. Compounds with double benzimidazole or benzothiazole functional groups have become a research field of great concern in recent years due to their unique photochemical properties and coordination ability with metal ions. Therefore, it is of great academic research value and application prospect to carry out the synthesis and preparation research of such compounds.

[0003] Benzimidazolo[2,1-b]thiazole derivatives are a class of aromatic heterocyclic compounds, which have important biological and pharmaceutical activities, can be used as key structural fragments of biological active substances and drugs, and have a wide range of applications in the treatment of diseases such as diabetes, tumors and cancers, and are one of the hot topics in the current research field. This kind of compound is often synthesized by multi-step synthesis method, which has low yield and complex post-processing. Zhang et al. used 2-mercaptobenzimidazole and o-dihalogenated compounds to obtain the product at 130℃ using DMSO and base, but the yield was only 64%; Gao et al. used 2-mercaptobenzimidazole and o-dihalogenated compounds to successfully obtain the product in the presence of copper catalyst and ligand; Sk. Rasheed et al. successfully obtained the product by using 2-mercaptobenzothiazole and o-iodobenzoic acid in the presence of copper catalyst. Since the metal catalyst cannot be completely recovered and will cause certain pollution to the environment, the reaction without metal catalyst does not have this disadvantage and is more in line with the current green development concept. However, the current synthesis of benzimidazolo[1,2-b]thiazole derivatives without metal catalyst still has problems such as complex reaction system, low yield and difficult post-processing, which makes it difficult to be used for the synthesis of benzimidazolo[2,1-b]thiazole derivatives. At present, there are few reports on the preparation of imidazolo[2,1-b]thiazole derivatives with pharmaceutical activity by using a simple and convenient method with mild reaction conditions. Therefore, it is still of great significance to develop a method for synthesizing benzimidazolobenzothiazole compounds without metal catalyst, with high yield and simple operation. SUMMARY

[0004] In view of some deficiencies in the prior art, the application provides a method for synthesizing a benzimidazolobenzothiazole compound; 2-mercaptobenzimidazole compounds, fluoride, base, additive, molecular sieve and dichloromethane are mixed, then a benzyne precursor is added, and a benzimidazolobenzothiazole compound is synthesized at 110 DEG C; the method has the advantages of being simple and fast, not requiring transition metal catalysis, having a wide substrate range, using cheap and easily available fluoride sources, and not causing environmental pollution; the method has the advantages of simple process and good universality, and the synthesized benzimidazolobenzothiazole compound has a high yield of up to 90%, and has high industrial promotion value.

[0005] In order to achieve the above technical purpose, the application adopts the following technical means: The application first provides a method for synthesizing a benzimidazolobenzothiazole compound, which comprises the following steps: 2-mercaptobenzimidazole compounds, fluoride, base, additive and molecular sieve are mixed in a solvent under nitrogen protection, a benzyne precursor is added dropwise under stirring, and a mixed solution is obtained after mixing; The mixed solution is subjected to [3+2] cycloaddition reaction, the solvent is removed under reduced pressure after the reaction is completed, and a benzimidazolobenzothiazole compound is separated and obtained.

[0006] Preferably, the 2-mercaptobenzimidazole compounds comprise 2-mercaptobenzimidazole compounds with the structural formula of . In the formula, R 2 includes any one of 5-methyl, 4,5-dimethyl,, 5-ethoxy, 5-trifluoromethyl, naphthyl, 5-fluoro, 5-fluoro-6-chloro, 5-chloro, 5-bromo or 5-tert-butyl.

[0007] Preferably, the benzyne precursor comprises benzyne precursors with the structural formula of . In the formula, R 1 includes any one of hydrogen, 4,5-phenyl, pyridyl, 4,5-difluoro, 4,5-cyclopentyl, 3,6-dimethyl, 3-methoxy, 3-fluoro or 3-methyl.

[0008] Preferably, the fluoride includes one or more of potassium fluoride, cesium fluoride, tetra-n-butylammonium difluorotriphenylsilicate or tetrabutylammonium fluoride; The base includes one or more of cesium carbonate, potassium carbonate, potassium tert-butoxide or sodium bicarbonate; The molecular sieve includes 4A molecular sieve; The additive includes an iodine source and 18-crown-6; the iodine source includes one or more of iodobenzene acetate, iodine element or iodine monochloride; The solvent includes one or more of dichloromethane, tetrahydrofuran, acetonitrile or toluene.

[0009] Preferably, the ratio of the 2-mercaptobenzimidazole compound, fluoride, base, additive, molecular sieve and solvent is 0.2-0.25 mmol: 0.8-1.0 mmol: 0.2-0.3 mmol: 0.15-0.2 mmol: 0.1 g: 2.0-3.0 mL.

[0010] Preferably, the stirring speed is 300-450 r / min. When the phenylacetylene precursor is added dropwise, the dropwise addition rate should be controlled to avoid splashing and ensure rapid dispersion in the reaction system; more preferably, the dropwise addition is performed at a rate of 2-4 s / drop using a 100 μL microsyringe, which can achieve this effect.

[0011] Preferably, the molar ratio of the 2-mercaptobenzimidazole compound to the phenylacetylene precursor is 1:1.5-2.5.

[0012] Preferably, the reaction conditions of the [3+2] cycloaddition reaction are: 100-120℃ for 5-10 h in a closed environment.

[0013] The application also provides a benzimidazobenzothiazole compound synthesized by the above method, and the structural general formula of the benzimidazobenzothiazole compound is ; In the formula, R 1 includes any one of a hydrogen group, a 4,5-benzene group, a pyridine group, a 4,5-difluoro group, a 4,5-cyclopentane group, a 3,6-dimethyl group, a 3-methoxy group, a 3-fluoro group or a 3-methyl group; R 2 includes any one of a 5-methyl group, a 4,5-dimethyl group, a 5-ethoxy group, a 5-trifluoromethyl group, a naphthyl group, a 5-fluoro group, a 5-fluoro-6-chloro group, a 5-chloro group, a 5-bromo group or a 5-tert-butyl group.

[0014] Compared with the prior art, the application has the following beneficial effects: The present application mixes 2-mercaptobenzimidazole, potassium fluoride, 18-crown-6, cesium carbonate, iodobenzene acetate, 4A molecular sieve and dichloromethane, adds a phenylacetylene precursor, and obtains a benzimidazolobenzothiazole compound under the condition of 110°C. In the [3+2] cycloaddition reaction process, the fluoride ion in the fluoride attacks the trimethylsilyl group in the phenylacetylene precursor, forms a strong fluorosilicon bond with silicon, the carbon-silicon bond breaks to form a carbon anion, then the trifluoromethanesulfonic acid group is removed to form a phenylacetylene group, the cesium carbonate (Cs2CO3) is used as a base to deprotonate the mercapto group (-SH) of 2-mercaptobenzimidazole to generate a sulfur anion intermediate; then, the sulfur anion attacks the nucleophilic double bond of the highly active phenylacetylene intermediate to form a carbon-sulfur bond to generate an anion species; then, through an intramolecular cyclization process, the phenylacetylene is combined with the imidazole ring part of 2-mercaptobenzimidazole, and under the action of the iodine cation (I+) provided by iodobenzene acetate, the [3+2] cycloaddition is promoted, and finally the benzimidazolobenzothiazole product is formed, in which the hydrogen atom of the original mercapto group is replaced by a phenylacetylene, and a new heterocycle is connected to the imidazole ring.

[0015] The present application first proposes to use phenylacetylene and 2-mercaptobenzimidazole compounds to prepare benzimidazolobenzothiazole compounds, so that the atomic utilization rate of the reaction reaches 100%, and the product separation is easier. The synthesis method has the advantages of simple and fast, no transition metal catalyst, wide substrate range, cheap and easy-to-obtain fluoride source, commercially available part of the raw materials, part of the raw materials can be prepared by simple method using o-phenylenediamine and carbon disulfide reagent, and no environmental pollution.

[0016] The synthesis method has the advantages of simple process and good universality, and the benzimidazolobenzothiazole compound synthesized by the method has a yield of up to 90%, which has extremely high industrial popularization value. DETAILED DESCRIPTION

[0017] The following examples are used to further illustrate the present application, but the scope of protection of the present application is not limited thereto. In the following examples, the experimental methods not specified in the specific conditions are selected according to the conventional methods and conditions in the art, or according to the product instructions. The reagents and raw materials not specified in the following examples can be prepared by conventional methods or commercially available.

[0018] The above application is described in detail through the following examples.

[0019] Example 1 In this example, 2-mercaptobenzimidazole and phenylacetylene precursor 2-(trimethylsilyl)phenyl trifluoromethanesulfonate are used to prepare benz[d]benzo[4,5]thiazolo[2,1-b]imidazole, and the specific steps are as follows: Accurately take 0.2 mmoL 2-mercaptobenzimidazole and 0.8 mmoL potassium fluoride, 0.8 mmoL 18-crown-6, 0.2 mmol cesium carbonate, 0.2 mmol iodobenzene acetate, 0.1 g 4 Å molecular sieve and put it into a 25 mL reaction tube with a polytetrafluoroethylene cover, vacuum and nitrogen three times, add 2.0 mL dichloromethane under nitrogen protection, stir for 5 minutes at room temperature, then add 0.4 mmoL phenyl acetylide precursor 2-(trimethylsilyl)phenyl trifluoromethanesulfonate dropwise under stirring at a speed of 450 r / min, stir at 110°C for 6 hours, after the reaction is completed, remove the solvent under reduced pressure, and separate by column chromatography to obtain benzene [d] benzene [4, 5] thiazolo [2, 1-b] imidazole.

[0020] The benzene [d] benzene [4, 5] thiazolo [2, 1-b] imidazole is a white solid, with a yield of 40.3 mg and a yield of 90%. The prepared benzene [d] benzene [4, 5] thiazolo [2, 1-b] imidazole is characterized, and the characterization results are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.97 (d, J = 8.36 Hz, 2H), 7.85 (dd,J = 1.36, 1.28 Hz, 1H), 7.76 (d, J = 8 Hz, 1H), 7.54-7.58 (m, 1H), 7.37-7.46(m, 3H); 13 C NMR (101 MHz, Chloroform-d) δ 110.6 112.4 119.5 122.0 123.7 124.4124.5 126.7 129.1 130.4 133.2 147.9 155.4。

[0021] According to the above characterization results, it can be known that the benzene [d] benzene [4, 5] thiazolo [2, 1-b] imidazole prepared in the embodiment has a structural formula as shown in .

[0022] Example 2: In this embodiment, 5-methoxy-benzene [d] benzene [4, 5] thiazolo [2, 1-b] imidazole is prepared by using 2-mercaptobenzimidazole and phenyl acetylide precursor 3-methoxy-2- (trimethylsilyl) phenyl trifluoromethanesulfonate, and the specific steps are as follows: Accurately take 0.2 mmoL 2-mercaptobenzimidazole and 0.8 mmoL cesium fluoride, 0.8 mmoL 18-crown-6, 0.2 mmol cesium carbonate, 0.2 mmol iodobenzene acetate, 0.1 g 4 Å molecular sieve and put it into a 25 mL reaction tube with a polytetrafluoroethylene cover, vacuum and nitrogen three times, add 2.0 mL dichloromethane under nitrogen protection, stir for 5 minutes at room temperature, then add 0.4 mmoL phenyl acetylene precursor 3-methoxy-2-(trimethylsilyl) phenyl trifluoromethanesulfonate dropwise under stirring at 450 r / min, stir at 110℃ for 6 hours, after the reaction is completed, remove the solvent under reduced pressure, and separate by column chromatography to obtain 5-methoxy-benzo[d]benzo[4,5]thiazolo[2,1-b]imidazole.

[0023] The 5-methoxy-benzo[d]benzo[4,5]thiazolo[2,1-b]imidazole is a white solid, with a yield of 41.3 mg and a yield of 81%. The prepared 5-methoxy-benzo[d]benzo[4,5]thiazolo[2,1-b]imidazole is characterized, and the characterization results are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.89 – 7.71(m, 2H), 7.51 – 7.45(m, 1H), 7.40 (t, J = 8.1 Hz, 1H), 7.38 – 7.26 (m, 2H), 6.78 (d, J = 8.2 Hz,1H),3.94 (s, 3H); 13 C NMR (101 MHz, Chloroform-d) δ 155.0, 134.2, 127.9, 123.5, 121.8,119.5, 116.6, 110.6, 105.8, 105.3, 56.1。

[0024] According to the above characterization results, it can be known that the 5-methoxy-benzo[d]benzo[4,5]thiazolo[2,1-b]imidazole prepared in this embodiment has a structure as shown in .

[0025] Example 3: In this embodiment, 2-mercaptobenzimidazole and phenyl acetylene precursor 3-methyl-2-(trimethylsilyl) phenyl trifluoromethanesulfonate are used to prepare a mixture of 5-methyl-benzo[d]benzo[4,5]thiazolo[2,1-b]imidazole and 8-methyl-benzo[d]benzo[4,5]thiazolo[2,1-b]imidazole, and the specific steps are as follows: Accurately weigh 0.2 mmol of 2-mercaptobenzimidazole, 0.8 mmol of potassium fluoride, 0.8 mmol of 18-crown-6, 0.2 mmol of cesium carbonate, 0.2 mmol of iodobenzene acetate, and 0.1 g of 4 Å molecular sieve and place them into a 25 mL reaction tube with a polytetrafluoroethylene cap. Vacuum the tube three times and replace the nitrogen gas. Under nitrogen protection, add 2.0 mL of dichloromethane and stir at room temperature for 5 minutes. Then, stir at 450 r / min and add 0.4 mmol of 3-methyl-2-(trimethylsilyl)phenyltrifluoromethanesulfonate, a precursor of benzyne, dropwise. Stir the reaction at 110 °C for 6 hours. After the reaction is complete, remove the solvent under reduced pressure and separate the 5-methyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole and 8-methyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole by column chromatography.

[0026] Both 5-methyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole and 8-methyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole were yellow solids, with a total yield of 40.6 mg and an overall yield of 85%. The prepared 5-methyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole and 8-methyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole were characterized, and the results were as follows: 1 H NMR (400 MHz, Chloroform-d) δ 8.25 (d, J = 8.4 Hz,1H), 7.91 – 7.67 (m, 4H), 7.45 – 7.26(m, 5H), 7.19 – 7.08 (m, 4H), 3.05 (s,3H), 2.45 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 134.1, 133.0, 129.9, 129.5, 128.9, 126.6, 125.1, 124.8, 123.5, 123.4, 122.1, 121.92, 121.4, 119.5, 113.2, 110.6, 109.8, 24.2, 20.1. The product was confirmed by NMR, and the ratio of the two was 1:1.

[0027] Based on the characterization results above, it can be seen that the structure prepared in this embodiment is as follows: The examples shown are 5-methyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole and 8-methyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole.

[0028] Example 4: In this embodiment, 5,8-dimethyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole was prepared using 2-mercaptobenzimidazole and the benzoyne precursor 3,6-dimethyl-2-(trimethylsilyl)phenyltrifluoromethanesulfonate. The specific steps are as follows: Accurately weigh 0.2 mmol of 2-mercaptobenzimidazole, 0.8 mmol of potassium fluoride, 0.8 mmol of 18-crown-6, 0.2 mmol of cesium carbonate, 0.2 mmol of iodobenzene acetate, and 0.1 g of 4 Å molecular sieve and place them into a 25 mL reaction tube with a polytetrafluoroethylene cap. Vacuum the tube and replace the nitrogen gas three times. Under nitrogen protection, add 2.0 mL of dichloromethane and stir at room temperature for 5 minutes. Then, stir at 450 r / min and add 0.4 mmol of 3,6-dimethyl-2-(trimethylsilyl)phenyltrifluoromethanesulfonate, a benzyne precursor, dropwise. Stir the reaction at 110 °C for 6 hours. After the reaction is complete, remove the solvent under reduced pressure and separate the product by column chromatography to obtain 5,8-dimethyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole.

[0029] The 5,8-dimethyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole was a yellow solid with a yield of 41.6 mg and a yield of 82%. The prepared 5,8-dimethyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole was characterized, and the characterization results were as follows: 1 H NMR (400 MHz, Chloroform-d) δ 8.26 (d, J = 8.5 Hz, 1H), 7.72 (d, J= 8.1 Hz, 1H), 7.30 (t, J = 7.5 Hz, 1H), 7.19 (t, J = 7.5 Hz, 1H), 7.09 (d, J =7.6 Hz, 1H), 6.99 (d,J = 7.6 Hz, 1H), 3.02 (s, 3H), 2.39 (s, 3H); 13 C NMR (101 MHz, Chloroform-d) δ 133.8, 131.2, 129.9, 129.5, 125.4, 123.4, 121.4, 120.7, 119.5, 113.3, 23.9, 19.9.

[0030] Based on the characterization results above, it can be seen that the structure prepared in this embodiment is as follows: The 5,8-dimethyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazolium shown is an example.

[0031] Example 5: In this embodiment, benzo[d]benzo[4,5]-2,3-dihydro-1H-inden-5-yltrifluoromethanesulfonate, a precursor of 2-mercaptobenzimidazole and benzoyne, was prepared to produce benzo[d]benzo[4,5]-2,3-dihydro-1H-inden[5,6-d]thiazo[2,1-b]imidazole. The specific steps are as follows: Accurately weigh 0.2 mmol of 2-mercaptobenzimidazole, 0.8 mmol of potassium fluoride, 0.8 mmol of 18-crown-6, 0.3 mmol of cesium carbonate, 0.2 mmol of iodobenzene acetate, and 0.1 g of 4 Å molecular sieve and place them into a 25 mL reaction tube with a polytetrafluoroethylene cap. Vacuum the tube three times and replace the nitrogen gas. Under nitrogen protection, add 2.0 mL of dichloromethane and stir at room temperature for 5 minutes. Then, stir at 450 r / min and add dropwise 0.4 mmol of the benzyne precursor 6-(trimethylsilyl)-2,3-dihydro-1H-inden-5-yltrifluoromethanesulfonate. Stir the reaction at 110 °C for 6 hours. After the reaction is complete, remove the solvent under reduced pressure and separate the product by column chromatography to obtain benzo[d]benzo[4,5]-2,3-dihydro-1H-inden[5,6-d]thiazo[2,1-b]imidazole.

[0032] The benzo[d]benzo[4,5]-2,3-dihydro-1H-inda[5,6-d]thiazo[2,1-b]imidazole was a yellow solid with a yield of 39.6 mg and a yield of 75%. The prepared benzo[d]benzo[4,5]-2,3-dihydro-1H-inda[5,6-d]thiazo[2,1-b]imidazole was characterized, and the results were as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.89 – 7.61 (m, 3H), 7.39 – 7.12 (m,3H), 3.01 (t, J = 7.4 Hz, 2H), 2.94 (t, J = 7.4 Hz, 2H), 2.13 (p, J = 7.5 Hz,2H); 13C NMR (101 MHz, Chloroform-d) δ 155.8, 143.7, 141.0, 131.7, 126.6,123.3, 122.1, 121.7, 121.4, 121.1, 119.8, 119.30, 110.6, 108.6, 33.1, 32.7,25.9.

[0033] Based on the characterization results above, it can be seen that the structure prepared in this embodiment is as follows: The benzo[d]benzo[4,5]-2,3-dihydro-1H-indo[5,6-d]thiazo[2,1-b]imidazolium shown is a benzo[d]benzo[4,5]-2,3-dihydro-1H-indo[5,6-d]thiazo[2,1-b]imidazolium.

[0034] Example 6: In this embodiment, benzo[d]naphtho[4,5]thiazo[2,1-b]imidazole was prepared using 2-mercaptobenzimidazole and the benzoyne precursor 3-(trimethylsilyl)naphth-2-yltrifluoromethanesulfonate. The specific steps are as follows: Accurately weigh 0.2 mmol of 2-mercaptobenzimidazole, 0.9 mmol of potassium fluoride, 0.9 mmol of 18-crown-6, 0.2 mmol of cesium carbonate, 0.25 mmol of iodobenzene acetate, and 0.1 g of 4 Å molecular sieve and place them into a 25 mL reaction tube with a polytetrafluoroethylene cap. Vacuum the tube and replace the nitrogen gas three times. Under nitrogen protection, add 2.0 mL of dichloromethane and stir at room temperature for 5 minutes. Then, stir at 450 r / min and add 0.4 mmol of 3-(trimethylsilyl)naphthyl-2-yltrifluoromethanesulfonate, a precursor of benzyne, dropwise. Stir the reaction at 110 °C for 6 hours. After the reaction is complete, remove the solvent under reduced pressure and separate the product by column chromatography to obtain benzo[d]naphtho[4,5]thiazo[2,1-b]imidazole.

[0035] The benzo[d]naphtho[4,5]thiazo[2,1-b]imidazole was a brown solid with a yield of 47.1 mg and a yield of 86%. The prepared benzo[d]naphtho[4,5]thiazo[2,1-b]imidazole was characterized, and the characterization results were as follows: 1H NMR (400 MHz, Chloroform-d) δ 8.07 (s, 1H), 8.01 (s, 1H), 7.93(dd, J = 6.0, 3.2 Hz, 1H), 7.88 (d, J = 8.2 Hz, 1H), 7.79 – 7.71(m, 2H), 7.45(dddd, J = 23.1, 8.2, 6.8, 1.4 Hz, 2H), 7.40 – 7.29 (m, 2H); 13 C NMR (101 MHz, Chloroform-d) δ 155.5, 148.4, 131.8, 130.8, 130.4,128.9 127.7, 127.2, 126.9, 125.9, 123.7, 123.1, 122.3, 119.6, 110.6, 108.8.

[0036] Based on the characterization results above, it can be seen that the structure prepared in this embodiment is as follows: The benzo[d]naphtho[4,5]thiazo[2,1-b]imidazolium shown is an example of benzo[d]naphtho[4,5]thiazo[2,1-b]imidazolium.

[0037] Example 7: In this embodiment, 6,7-difluoro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole was prepared using 2-mercaptobenzimidazole and the benzoyne precursor 4,5-difluoro-2-(trimethylsilyl)phenyltrifluoromethanesulfonate. The specific steps are as follows: Accurately weigh 0.2 mmol of 2-mercaptobenzimidazole, 0.8 mmol of potassium fluoride, 0.8 mmol of 18-crown-6, 0.2 mmol of cesium carbonate, 0.2 mmol of iodobenzene acetate, and 0.1 g of 4 Å molecular sieve and place them into a 25 mL reaction tube with a polytetrafluoroethylene cap. Vacuum the tube three times and replace the nitrogen gas. Under nitrogen protection, add 2.0 mL of dichloromethane and stir at room temperature for 5 minutes. Then, stir at 450 r / min and add 0.4 mmol of 4,5-difluoro-2-(trimethylsilyl)phenyltrifluoromethanesulfonate, a benzyne precursor, dropwise. Stir the reaction at 110 °C for 6 hours. After the reaction is complete, remove the solvent under reduced pressure and separate to obtain 6,7-difluoro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole.

[0038] The 6,7-difluoro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole was a white solid with a yield of 39.5 mg and a yield of 76%. The prepared 6,7-difluoro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole was characterized, and the results were as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.77 (ddd, J = 7.2, 5.3, 1.7 Hz, 2H), 7.68 (dd, J = 9.6, 6.4 Hz, 1H), 7.50 (dd, J = 9.2, 7.2 Hz, 1H), 7.40 –7.29 (m, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 155.5, 148.9, 148.0, 146.4, 130.1, 124.0, 122.4, 119.8, 113.2, 112.9, 110.1, 102.1, 101.9.

[0039] Based on the characterization results above, it can be seen that the structure prepared in this embodiment is as follows: The 6,7-difluoro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazolium shown is an example.

[0040] Example 8: In this embodiment, 5-fluoro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole was prepared using 2-mercaptobenzimidazole and the benzoyne precursor 3-fluoro-2-(trimethylsilyl)phenyltrifluoromethanesulfonate. The specific steps are as follows: Accurately weigh 0.2 mmol of 2-mercaptobenzimidazole, 0.8 mmol of potassium fluoride, 0.8 mmol of 18-crown ether-6, 0.2 mmol of cesium carbonate, 0.2 mmol of iodobenzene acetate, and 0.1 g of 4 Å molecular sieve and place them into a 25 mL reaction tube with a polytetrafluoroethylene cap. Evacuate the tube three times with nitrogen. Under nitrogen protection, add 2.0 mL of dichloromethane and stir at room temperature for 5 minutes. Then, stir at 450 r / min and add 0.4 mmol of 3-fluoro-2-(trimethylsilyl)phenyltrifluoromethanesulfonate, a benzyne precursor, dropwise. Stir at 110 °C for 6 hours. After the reaction is complete, remove the solvent under reduced pressure and separate by column chromatography to obtain 5-fluoro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole.

[0041] The 5-fluoro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole was a white solid with a yield of 39.7 mg and a yield of 82%. The prepared 5-fluoro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole was characterized, and the results were as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.80 (dd, J = 7.5, 1.6 Hz, 1H), 7.77– 7.71 (m, 1H), 7.61 (dd, J = 8.1, 0.9 Hz, 1H), 7.42 (td, J = 8.2, 5.3 Hz,1H), 7.36 – 7.27 (m, 2H),7.02 (ddd, J = 9.1, 8.3, 0.8 Hz, 1H). 13 C NMR (101 MHz, Chloroform-d) δ 158.9, 156.5, 135.0, 134.9, 130.4,128.2, 128.1, 123.9, 122.3, 119.7, 111.0, 110.8, 110.6, 108.2, 108.2.

[0042] Based on the characterization results above, it can be seen that the structure prepared in this embodiment is as follows: The 5-fluoro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazolium shown is an example.

[0043] Example 9: In this embodiment, benzo[d][1,3]dioxacyclopenten-5-yltrifluoromethanesulfonate was used to prepare a benzo[d][1,3]dioxacyclopenten-5,4-b]benzo[b]thiazole compound. The specific steps are as follows: Accurately weigh 0.2 mmol of 2-mercaptobenzimidazole, 0.8 mmol of potassium fluoride, 0.8 mmol of 18-crown ether-6, 0.2 mmol of cesium carbonate, 0.2 mmol of iodobenzene acetate, and 0.1 g of 4 Å molecular sieve and place them into a 25 mL reaction tube with a polytetrafluoroethylene cap. Evacuate the tube three times with nitrogen. Under nitrogen protection, add 2.0 mL of dichloromethane and stir at room temperature for 5 minutes. Then, stir at 450 r / min and add dropwise 0.4 mmol of 6-(trimethylsilyl)benzo[d][1,3]dioxacyclopenten-5-yltrifluoromethanesulfonate, a precursor of benzyne. Stir the reaction at 110 °C for 6 hours. After the reaction, remove the solvent under reduced pressure and separate the product by column chromatography to obtain benzo[d][1,3]dioxacyclopenten[5,4-b]benzo[b]thiazole.

[0044] The benzo[d][1,3]dioxacyclopenten[5,4-b]benzo[b]thiazole was a black solid with a yield of 42.9 mg and a yield of 82%. The prepared benzo[d][1,3]dioxacyclopenten[5,4-b]benzo[b]thiazole was characterized, and the characterization results were as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.74 (ddd, J = 7.8, 4.3, 1.3 Hz, 2H), 7.45 – 7.12 (m, 4H), 6.01 (s, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 155.7, 147.9, 147.5, 145.2, 130.1, 127.3, 123.4, 121.6, 120.2, 119.4, 110.2, 104.2, 102.2, 94.8.

[0045] Based on the characterization results above, it can be seen that the structure prepared in this embodiment is as follows: The benzo[d][1,3]dioxacyclopenten[5,4-b]benzo[b]thiazole shown.

[0046] Example 10: In this embodiment, benzo[4',5']imidazo[2',1':2,3]thiazo[5,4-b]pyridine was prepared using 2-mercaptobenzimidazole and the benzoyne precursor 2-(trimethylsilyl)pyridyltrifluoromethanesulfonate. The specific steps are as follows: Accurately weigh 0.2 mmol of 2-mercaptobenzimidazole, 0.8 mmol of potassium fluoride, 0.8 mmol of 18-crown ether-6, 0.2 mmol of cesium carbonate, 0.2 mmol of iodobenzene acetate, and 0.1 g of 4 Å molecular sieve and place them into a 25 mL reaction tube with a polytetrafluoroethylene cap. Evacuate the tube three times with nitrogen. Under nitrogen protection, add 3.0 mL of dichloromethane and stir at room temperature for 5 minutes. Then, stir at 450 r / min and add 0.25 mmol of 2-(trimethylsilyl)pyridinyl trifluoromethanesulfonate, a precursor of benzyne, dropwise. Stir the reaction at 110 °C for 6 hours. After the reaction is complete, remove the solvent under reduced pressure and separate the product by column chromatography to obtain benzo[4',5']imidazo[2',1':2,3]thiazo[5,4-b]pyridine.

[0047] The benzo[4',5']imidazo[2',1':2,3]thiazo[5,4-b]pyridine was a brown solid with a yield of 25.7 mg, representing a yield of 57%. The prepared benzo[4',5']imidazo[2',1':2,3]thiazo[5,4-b]pyridine was characterized, and the results were as follows: 1 H NMR (400 MHz, Chloroform-d) δ 8.45 (dd, J = 5.0, 1.5 Hz, 1H), 8.32 (dd, J = 7.4, 1.8 Hz, 1H), 7.95 (dd, J = 8.0, 1.5 Hz, 1H), 7.78 – 7.71(m,1H), 7.35 (pd, J = 7.3, 1.4 Hz, 2H), 7.21 (dd, J = 7.9, 4.9 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 153.4, 148.1, 146.1, 132.1, 130.2, 124.3, 123.8, 122.6, 119.4, 119.2, 112.6.

[0048] Based on the characterization results above, it can be seen that the structure prepared in this embodiment is as follows: The benzo[4',5']imidazo[2',1':2,3]thiazo[5,4-b]pyridine shown.

[0049] Example 11: In this embodiment, benzo[4',5']imidazo[2',1':2,3]thiazo[5,4-b]quinoline was prepared using 2-mercaptobenzimidazole and the benzoyne precursor 2-(trimethylsilyl)quinolinyltrifluoromethanesulfonate. The specific steps are as follows: Accurately weigh 0.2 mmol of 2-mercaptobenzimidazole, 0.8 mmol of potassium fluoride, 0.8 mmol of 18-crown ether-6, 0.2 mmol of cesium carbonate, 0.2 mmol of iodobenzene acetate, and 0.1 g of 4 Å molecular sieve and place them into a 25 mL reaction tube with a polytetrafluoroethylene cap. Vacuum the tube three times and replace the nitrogen gas. Under nitrogen protection, add 2.0 mL of dichloromethane and stir at room temperature for 5 minutes. Then, stir at 450 r / min and add 0.45 mmol of 2-(trimethylsilyl)quinolinyl trifluoromethanesulfonate, a precursor of benzyne, dropwise. Stir the reaction at 115 °C for 10 hours. After the reaction is complete, remove the solvent under reduced pressure and separate to obtain benzo[4',5']imidazo[2',1':2,3]thiazo[5,4-b]quinoline.

[0050] The benzo[4',5']imidazo[2',1':2,3]thiazo[5,4-b]quinoline was a brown solid with a yield of 37.4 mg and a yield of 68%. The prepared benzo[4',5']imidazo[2',1':2,3]thiazo[5,4-b]quinoline was characterized, and the results were as follows: 1 H NMR (400 MHz, Chloroform-d) δ 8.55 – 8.41 (m, 1H), 8.32 (s, 1H), 8.11 (dd, J = 8.4, 1.1 Hz, 1H), 7.83 – 7.67 (m, 3H), 7.51 (ddd, J = 8.2, 6.9,1.2 Hz, 1H), 7.45– 7.34 (m, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 145.5, 145.4, 131.4, 130.1, 128.6, 127.2, 126.2, 125.6, 124.5, 123.4, 123.0, 119.2, 112.9.

[0051] Based on the characterization results above, it can be seen that the structure prepared in this embodiment is as follows: The benzo[4',5']imidazo[2',1':2,3]thiazo[5,4-b]quinoline is shown.

[0052] Example 12: In this embodiment, a mixture of 2-methyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole and 3-methyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole was prepared using 5-methyl-2-mercaptobenzimidazole and the benzoyne precursor 2-(trimethylsilyl)phenyltrifluoromethanesulfonate. The specific steps are as follows: Accurately weigh 0.2 mmol of 5-methyl-2-mercaptobenzimidazole, 0.8 mmol of potassium fluoride, 0.8 mmol of 18-crown ether-6, 0.2 mmol of cesium carbonate, 0.2 mmol of iodobenzene acetate, and 0.1 g of 4 Å molecular sieve and place them into a 25 mL reaction tube with a polytetrafluoroethylene cap. Evacuate the tube three times with nitrogen. Under nitrogen protection, add 2.0 mL of dichloromethane and stir at room temperature for 5 minutes. Then, stir at 450 r / min and add 0.5 mmol of 2-(trimethylsilyl)phenyltrifluoromethanesulfonate, a precursor of benzyne, dropwise. Stir and react at 115 °C for 10 hours. After the reaction, remove the solvent under reduced pressure and separate the results by column chromatography to obtain 2-methyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole and 3-methyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole.

[0053] The 2-methyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole and 3-methyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole compounds were both light yellow solids, with a total yield of 41.3 mg and an overall yield of 81%. The prepared 2-methyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole and 3-methyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole compounds were characterized, and the results were as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.75 (dd, J= 14.7, 8.0 Hz, 2H), 7.67 – 7.55 (m, 5H), 7.50 (s, 1H), 7.39 (tt, J = 7.9, 1.4Hz, 2H), 7.22 (tt, J = 7.8, 1.4 Hz, 2H), 7.08 (ddd, J = 19.9, 8.3, 1.5 Hz, 2H), 2.47 (s, 3H), 2.42 (s, 3H). 13C NMR (101 MHz, Chloroform-d) δ 155.2, 154.6, 148.5, 146.3, 133.4, 133.2, 131.9, 130.6, 128.9, 128.9, 128.5, 126.6, 126.6, 124.9, 124.2, 124.1, 123.2, 119.4, 118.9, 112.2, 112.2, 110.7, 109.9, 21.8, 21.7. The product was confirmed by NMR, and the ratio of the two was 1:1.

[0054] Based on the characterization results above, it can be seen that the structure prepared in this embodiment is as follows: The 2-methyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazolium and 3-methyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazolium shown are examples.

[0055] Example 13: In this embodiment, a mixture of 2-trifluoromethyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole and 3-trifluoromethyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole was prepared using 5-trifluoromethyl-2-mercaptobenzimidazole and the benzoyne precursor 2-(trimethylsilyl)phenyltrifluoromethanesulfonate. The specific steps are as follows: Accurately weigh 0.2 mmol of 5-trifluoromethyl-2-mercaptobenzimidazole, 0.8 mmol of potassium fluoride, 0.8 mmol of 18-crown ether-6, 0.2 mmol of cesium carbonate, 0.2 mmol of iodobenzene acetate, and 0.1 g of 4 Å molecular sieve, and place them into a 25 mL reaction tube with a polytetrafluoroethylene cap. Evacuate the tube three times with nitrogen. Under nitrogen protection, add 2.0 mL of dichloromethane and stir at room temperature for 5 minutes. Then, while stirring at 450 r / min, add 0.4 mmol dropwise. The benzoyne precursor 2-(trimethylsilyl)phenyltrifluoromethanesulfonate was stirred at 110 °C for 6 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the product was separated by column chromatography to obtain 2-trifluoromethyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole and 3-trifluoromethyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole.

[0056] The 2-trifluoromethyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole and 3-trifluoromethyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole compounds were both white solids, with a total yield of 47.9 mg and an overall yield of 82%. The prepared 2-trifluoromethyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole and 3-trifluoromethyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole compounds were characterized, and the results were as follows: 1 H NMR (400 MHz, Chloroform-d) δ 8.11 (d, J = 1.7 Hz, 2H), 7.86 (dd,J = 27.6, 8.3 Hz, 4H), 7.68 (dd, J = 8.0, 1.1 Hz, 2H), 7.60 (dd, J = 8.5, 1.7Hz, 2H), 7.51 (td,J = 7.8, 1.2 Hz, 2H), 7.34 (td,J = 7.8, 1.1 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 158.1, 150.3, 132.7, 129.8, 128.9, 127.1, 125.1, 124.5, 124.2, 123.8, 123.5, 120.7, 120.6, 120.6, 119.7, 112.6, 108.2, 108.2, 108.1, 108.1. The product was confirmed by NMR, and the ratio of the two was 1:1.

[0057] Based on the characterization results above, it can be seen that the structure prepared in this embodiment is as follows: The examples shown are 2-trifluoromethyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole and 3-trifluoromethyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole.

[0058] Example 14: In this embodiment, a mixture of 2-fluoro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole and 3-fluoro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole compounds was prepared using 5-fluoro-2-mercaptobenzimidazole and the benzoyne precursor 2-(trimethylsilyl)phenyltrifluoromethanesulfonate. The specific steps are as follows: Accurately weigh 0.2 mmol of 5-fluoro-2-mercaptobenzimidazole, 0.8 mmol of potassium fluoride, 0.8 mmol of 18-crown ether-6, 0.2 mmol of cesium carbonate, 0.2 mmol of iodobenzene acetate, and 0.1 g of 4 Å molecular sieve and place them into a 25 mL reaction tube with a polytetrafluoroethylene cap. Evacuate the tube three times with nitrogen. Under nitrogen protection, add 2.0 mL of dichloromethane and stir at room temperature for 5 minutes. Then, stir at 450 r / min and add 0.4 mmol of 2-(trimethylsilyl)phenyltrifluoromethanesulfonate, a benzyne precursor, dropwise. Stir and react at 110 °C for 6 hours. After the reaction, remove the solvent under reduced pressure and separate the results by column chromatography to obtain 2-fluoro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole and 3-fluoro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole.

[0059] Both 2-fluoro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole and 3-fluoro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole are white solids, with a total yield of 34.4 mg and an overall yield of 71%. The prepared 2-fluoro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole and 3-fluoro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole were characterized, and the results are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.88 (d, J = 8.1 Hz, 1H), 7.88 –7.79 (m, 2H), 7.73 (dd, J = 7.8, 4.6 Hz, 3H), 7.63 (dd, J = 8.4, 2.4 Hz, 1H),7.58 – 7.42 (m, 3H), 7.37 (t, J = 7.7 Hz, 2H), 7.14 (dtd, J = 17.9, 9.1, 2.3Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 132.7, 128.9, 128.8, 126.8, 126.8, 124.7, 124.6, 124.4, 120.1, 119.9, 112.3, 112.1, 111.7, 111.5, 110.8, 110.7, 110.0, 109.7, 105.9, 105.7, 98.1, 97.8. The product was confirmed by NMR, and the ratio of the two was 1:1.

[0060] Based on the characterization results above, it can be seen that the structure prepared in this embodiment is as follows: The examples shown are 2-fluoro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole and 3-fluoro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole.

[0061] Example 15: In this embodiment, 2-chloro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole was prepared using 5-chloro-2-mercaptobenzimidazole and the benzoyne precursor 2-(trimethylsilyl)phenyltrifluoromethanesulfonate. The specific steps are as follows: Accurately weigh 0.2 mmol of 5-chloro-2-mercaptobenzimidazole, 0.8 mmol of potassium fluoride, 0.8 mmol of 18-crown-6, 0.2 mmol of cesium carbonate, 0.2 mmol of iodobenzene acetate, and 0.1 g of 4 Å molecular sieve and place them into a 25 mL reaction tube with a polytetrafluoroethylene cap. Vacuum the tube and replace the nitrogen gas three times. Under nitrogen protection, add 2.0 mL of dichloromethane and stir at room temperature for 5 minutes. Then, stir at 450 r / min and add 0.4 mmol of 2-(trimethylsilyl)phenyltrifluoromethanesulfonate, a precursor of benzyne, dropwise. Stir the reaction at 110 °C for 6 hours. After the reaction is complete, remove the solvent under reduced pressure and separate the product by column chromatography to obtain 2-chloro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole.

[0062] The 2-chloro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazolium derivative was a yellow solid with a yield of 38.7 mg and a yield of 75%. The prepared 2-chloro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazolium was characterized, and the characterization results were as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.88 (d, J = 2.0 Hz, 1H), 7.83 (dd,J = 8.1, 1.2 Hz, 1H), 7.68 (dd, J = 8.1, 1.3 Hz, 2H), 7.49 (td, J = 7.8, 1.2Hz, 1H), 7.33 (td,J = 8.5, 1.6 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 129.0, 127.6, 126.9, 124.9, 124.5, 124.2, 120.2, 112.5, 110.9.

[0063] Based on the characterization results above, it can be seen that the structure prepared in this embodiment is as follows: The 2-chloro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazolium shown is an example.

[0064] Example 16: In this embodiment, 2-bromo-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole was prepared using 5-bromo-2-mercaptobenzimidazole and the benzoyne precursor 2-(trimethylsilyl)phenyltrifluoromethanesulfonate. The specific steps are as follows: Accurately weigh 0.2 mmol of 5-bromo-2-mercaptobenzimidazole, 0.8 mmol of tetra-n-butylammonium difluorotriphenylsilicate, 0.2 mmol of potassium carbonate, 0.2 mmol of iodine monochloride, and 0.1 g of 4 Å molecular sieve, and place them into a 25 mL reaction tube with a polytetrafluoroethylene cap. Vacuum the tube three times and replace the nitrogen gas. Under nitrogen protection, add 2.0 mL of acetonitrile and stir at room temperature for 5 minutes. Then, stir at 450 r / min and add 0.4 mmol of 2-(trimethylsilyl)phenyltrifluoromethanesulfonate, a benzyne precursor, dropwise. Stir the reaction at 110 °C for 6 hours. After the reaction is complete, remove the solvent under reduced pressure and separate to obtain 2-bromo-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole.

[0065] The 2-bromo-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole was a white solid with a yield of 51.2 mg, representing a yield of 85%. The prepared 2-bromo-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole was characterized, and the results were as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.98 (d, J = 1.9 Hz, 1H), 7.78 (d, J= 8.1 Hz, 1H), 7.64 (d, J = 8.0 Hz, 1H), 7.59 (d, J = 8.6 Hz, 1H), 7.50 –7.37 (m, 2H), 7.30 (t, J = 7.7 Hz, 1H). 13 C NMR (101 MHz, Chloroform-d) δ 147.1, 132.7, 131.2, 128.9, 126.9, 126.8, 124.8, 124.4, 120.6, 114.9, 113.7, 112.4.

[0066] Based on the characterization results above, it can be seen that the structure prepared in this embodiment is as follows: The 2-bromo-benzo[d]benzo[4,5]thiazo[2,1-b]imidazolium shown is an example.

[0067] Example 17: In this embodiment, 2-mercaptonaphthemidazole and the benzoyne precursor 2-(trimethylsilyl)phenyltrifluoromethanesulfonate were used to prepare naphthe[d]benzo[4,5]thiazo[2,1-b]imidazole. The specific steps are as follows: Accurately weigh 0.2 mmol of 2-mercaptonaphthezide and 0.8 mmol of tetrabutylammonium fluoride, 0.2 mmol of potassium tert-butoxide, 0.2 mmol of elemental iodine, and 0.1 g of 4 Å molecular sieve and place them into a 25 mL reaction tube with a polytetrafluoroethylene cap. Vacuum the tube three times and replace the nitrogen gas. Under nitrogen protection, add 2.0 mL of toluene and stir at room temperature for 5 minutes. Then, stir at 450 r / min and add 0.4 mmol of 2-(trimethylsilyl)phenyltrifluoromethanesulfonate, a precursor of benzoyne, dropwise. Stir the reaction at 110 °C for 5 hours. After the reaction is complete, remove the solvent under reduced pressure and separate the product by column chromatography to obtain naphtho[d]benzo[4,5]thiazo[2,1-b]imidazole.

[0068] The prepared naphtho[d]benzo[4,5]thiazo[2,1-b]imidazole was a white solid with a yield of 43.84 mg and a yield of 80%. The prepared naphtho[d]benzo[4,5]thiazo[2,1-b]imidazole was characterized, and the results were as follows: 1 H NMR (400 MHz, Chloroform-d) δ 8.17 (d, J = 12.3 Hz, 2H), 7.93 (td,J = 8.4, 7.8, 2.4 Hz, 3H), 7.63 (dd, J = 8.0, 1.2 Hz, 1H), 7.49 (td, J = 7.8,1.2 Hz, 1H), 7.48 – 7.34 (m, 2H), 7.28 (td, J = 7.8, 1.1 Hz, 1H). 13 C NMR (101 MHz, Chloroform-d) δ 159.6, 133.4, 130.7, 129.5, 128.5,128.4, 127.7, 126.9, 124.8, 124.5, 124.3, 124.2, 116.0, 112.1, 107.0.

[0069] Based on the characterization results above, it can be seen that the structure prepared in this embodiment is as follows: The example shown is naphtho[d]benzo[4,5]thiazo[2,1-b]imidazolium.

[0070] Example 18: In this embodiment, 2-tert-butyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole was prepared by using 5-tert-butyl-2-mercaptobenzimidazole and the benzoyne precursor 2-(trimethylsilyl)phenyltrifluoromethanesulfonate. The specific steps are as follows: Accurately weigh 0.2 mmol of 5-tert-butyl-2-mercaptobenzimidazole, 0.8 mmol of potassium fluoride, 0.8 mmol of 18-crown ether-6, 0.25 mmol of sodium bicarbonate, 0.2 mmol of iodine monochloride, and 0.1 g of 4 Å molecular sieve and place them into a 25 mL reaction tube with a polytetrafluoroethylene cap. Evacuate the tube three times with nitrogen. Under nitrogen protection, add 2.0 mL of tetrahydrofuran and stir at room temperature for 5 minutes. Then, stir at 450 r / min and add 0.4 mmol of 2-(trimethylsilyl)phenyltrifluoromethanesulfonate, a precursor of benzyne, dropwise. Stir at 110 °C for 6 hours. After the reaction is complete, remove the solvent under reduced pressure and separate the product by column chromatography to obtain 2-tert-butyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole.

[0071] The 2-tert-butyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole was a yellow solid with a yield of 49.3 mg and a yield of 88%. The prepared 2-tert-butyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole was characterized, and the characterization results were as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.90 – 7.83 (m, 2H), 7.70 – 7.61(m, 2H), 7.50 – 7.40 (m, 2H), 7.28 (td, J = 7.7, 1.1 Hz, 1H), 1.40 (s, 9H). 13 CNMR (101 MHz, Chloroform-d) δ 154.9, 146.1, 145.6, 133.3, 130.6, 129.0,126.6, 124.3, 124.2, 121.6, 118.8, 112.3, 107.0, 35.1, 31.9, 31.7.

[0072] Based on the characterization results above, it can be seen that the structure prepared in this embodiment is as follows: The 2-tert-butyl-benzo[d]benzo[4,5]thiazo[2,1-b]imidazolium shown is an example.

[0073] Example 19: In this embodiment, a mixture of 2-ethoxy-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole and 3-ethoxy-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole was prepared using 5-ethoxy-2-mercaptobenzimidazole and the benzoyne precursor 2-(trimethylsilyl)phenyltrifluoromethanesulfonate. The specific steps are as follows: Accurately weigh 0.25 mmol of 5-ethoxy-2-mercaptobenzimidazole, 0.8 mmol of potassium fluoride, 0.8 mmol of 18-crown ether-6, 0.2 mmol of cesium carbonate, 0.2 mmol of iodobenzene acetate, and 0.1 g of 4 Å molecular sieve, and place them into a 25 mL reaction tube with a polytetrafluoroethylene cap. Evacuate the tube three times with nitrogen. Under nitrogen protection, add 2.0 mL of dichloromethane and stir at room temperature for 5 minutes. Then, while stirring at 450 r / min, add 0.4 mmol of the mixture dropwise. The benzoyne precursor 2-(trimethylsilyl)phenyltrifluoromethanesulfonate was stirred at 110 °C for 6 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the compounds were separated by column chromatography to obtain 2-ethoxy-benzo[d]benzo[4,5]thiazo[2,1-b]imidazolium and 3-ethoxy-benzo[d]benzo[4,5]thiazo[2,1-b]imidazolium.

[0074] The 2-ethoxy-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole and 3-ethoxy-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole compounds were both white solids, with a total yield of 42.3 mg and an overall yield of 80%. The prepared 2-ethoxy-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole and 3-ethoxy-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole compounds were characterized, and the characterization results are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.85 – 7.52 (m, 6H), 7.42 (tdd, J =7.9, 2.8, 1.2 Hz, 2H), 7.34 – 7.20(m, 4H), 6.92 (ddd, J = 16.9, 8.9, 2.4 Hz,2H), 4.06 (dq, J = 16.4, 7.0 Hz, 4H), 1.41 (dt, J = 9.2, 7.0 Hz, 6H).13 C NMR(101 MHz, Chloroform-d) δ 156.2, 155.4, 155.0, 149.2, 133.1,128.8, 126.6,126.5, 125.0, 124.3, 124.2, 124.1, 119.7, 112.1, 112.1, 112.0, 111.7, 110.8,103.1, 96.5, 64.5, 64.1, 15.0, 14.9.

[0075] Based on the characterization results above, it can be seen that the structure prepared in this embodiment is as follows: The products shown are 2-ethoxy-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole and 3-ethoxy-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole. The products were confirmed by NMR, and the ratio of the two products was 1:1.

[0076] Example 20: In this embodiment, 2-fluoro-3-chloro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole and 2-chloro-3-fluoro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole were prepared using 5-fluoro-6-chloro-2-mercaptobenzimidazole and the benzoyne precursor 2-(trimethylsilyl)phenyltrifluoromethanesulfonate. The specific steps are as follows: Accurately weigh 0.2 mmol of 5-fluoro-6-chloro-2-mercaptobenzimidazole, 0.8 mmol of potassium fluoride, 0.8 mmol of 18-crown ether-6, 0.2 mmol of cesium carbonate, 0.2 mmol of iodobenzene acetate, and 0.1 g of 4 Å molecular sieve, and place them into a 25 mL reaction tube with a polytetrafluoroethylene cap. Evacuate the tube three times with nitrogen. Under nitrogen protection, add 2.0 mL of dichloromethane and stir at room temperature for 5 minutes. Then, while stirring at 450 rpm, add 0.4 mmol of the mixture dropwise. The benzoyne precursor 2-(trimethylsilyl)phenyltrifluoromethanesulfonate was stirred at 110 °C for 6 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the compounds were separated by column chromatography to obtain 2-fluoro-3-chloro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazolium and 2-chloro-3-fluoro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazolium compounds.

[0077] The 2-fluoro-3-chloro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole and 2-chloro-3-fluoro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole compounds were both yellow solids, with a total yield of 47.9 mg and an overall yield of 87%. The prepared 2-fluoro-3-chloro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole and 2-chloro-3-fluoro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole compounds were characterized, and the results were as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.80 (d, J = 6.3 Hz, 1H), 7.74 –7.60 (m, 5H), 7.57 (d, J = 8.4 Hz, 1H), 7.45 (ddt, J = 9.3, 7.7, 1.7 Hz, 3H),7.30 (td, J = 7.7, 1.1 Hz, 2H), 1.18 (d, J = 3.8 Hz,0H). 13 C NMR (101 MHz, Chloroform-d) δ 132.4, 132.3, 128.9, 128.8, 127.0, 126.9, 126.8, 125.0,124.9, 124.5, 120.3,115.5, 112.2, 112.1, 111.4, 106.7, 106.4, 98.7, 98.5.

[0078] Based on the characterization results above, it can be seen that the structure prepared in this embodiment is as follows: The products shown are 2-fluoro-3-chloro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole and 2-chloro-3-fluoro-benzo[d]benzo[4,5]thiazo[2,1-b]imidazole. The products were confirmed by NMR, and the ratio of the two products was 1:1.

[0079] In summary, this invention is the first to propose the simultaneous preparation of benzimidazole and benzothiazole compounds using benzoyne. The method is simple and rapid, requires no transition metal catalysis, has a wide substrate range, uses inexpensive and readily available fluorine sources, and does not cause environmental pollution. The method has the advantages of simple process and good versatility, and the synthesized benzimidazole and benzothiazole compounds have high yields, up to 90%, making it extremely valuable for industrial application.

[0080] The embodiments described above are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments. Any obvious improvements, substitutions or modifications that can be made by those skilled in the art without departing from the essence of the present invention shall fall within the protection scope of the present invention.

Claims

1. A method for synthesizing benzimidazole and benzothiazole compounds, characterized in that, The method includes: 2-Mercaptobenzimidazole compounds, fluorides, bases, additives, and molecular sieves are added to a solvent under nitrogen protection and mixed thoroughly. Then, under stirring, a benzyne precursor is added dropwise and mixed thoroughly to obtain a mixed solution. The mixture was subjected to a [3+2] cycloaddition reaction. After the reaction was completed, the solvent was removed under reduced pressure, and the benzimidazole-benzothiazole compound was obtained by separation.

2. The method according to claim 1, characterized in that, The 2-mercaptobenzimidazole compounds include those with the structural formula […]. 2-Mercaptobenzimidazole compounds; In the formula, R 2 It includes any one of 5-methyl, 4,5-dimethyl, 5-ethoxy, 5-trifluoromethyl, naphthyl, 5-fluoro, 5-fluoro-6-chloro, 5-chloro, 5-bromo, or 5-tert-butyl.

3. The method according to claim 1, characterized in that, The benzoyne precursor includes the structural formula: Benzyne precursor; In the formula, R 1 It includes any one of hydrogen-based, 4,5-phenyl, pyridyl, 4,5-difluoro, 4,5-cyclopentyl, 3,6-dimethyl, 3-methoxy, 3-fluoro, or 3-methyl.

4. The method according to claim 1, characterized in that, The fluoride includes one or more of potassium fluoride, cesium fluoride, tetra-n-butylammonium difluorotriphenyl silicate, or tetrabutylammonium fluoride; The alkali includes one or more of cesium carbonate, potassium carbonate, potassium tert-butoxide, or sodium bicarbonate. The molecular sieve includes a 4Å molecular sieve; The additive includes an iodine source and 18-crown-6; the iodine source includes one or more of iodobenzene acetate, elemental iodine, or iodine monochloride. The solvent includes one or more of dichloromethane, tetrahydrofuran, acetonitrile, or toluene.

5. The method according to claim 1, characterized in that, The ratio of the amount of the 2-mercaptobenzimidazole compound, fluoride, alkali, additive, molecular sieve and solvent is 0.2~0.25 mmol / L: 0.8~1.0 mmol / L: 0.2~0.3 mmol / L: 0.15~0.2 mmol / L: 0.1 g: 2.0~3.0 mL.

6. The method according to claim 1, characterized in that, The molar ratio of the 2-mercaptobenzimidazole compound to the benzoyne precursor is 1:1.5~2.

5.

7. The method according to claim 1, characterized in that, The reaction conditions for the [3+2] cycloaddition reaction are: in a closed environment, at 100~120℃ for 5~10h.

8. The benzimidazole-benzothiazole compound synthesized by the method according to any one of claims 1 to 7, characterized in that, The general structural formula of the benzimidazole-benzothiazole compound is as follows: ; In the formula, R 1 Including any one of hydrogen-based, 4,5-phenyl, pyridyl, 4,5-difluoro, 4,5-cyclopentyl, 3,6-dimethyl, 3-methoxy, 3-fluoro, or 3-methyl; R 2 It includes any one of 5-methyl, 4,5-dimethyl, 5-ethoxy, 5-trifluoromethyl, naphthyl, 5-fluoro, 5-fluoro-6-chloro, 5-chloro, 5-bromo, or 5-tert-butyl.

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